Diagnosa PPOK

Clin Chest Med

Pathology of interstitial lung disease

Kevin O Leslie MDab

aDepartment of Pathology Mayo Clinic College of Medicine Rochester MN USAbDepartment of Laboratory Medicine and Pathology Mayo Clinic Scottsdale 13400 East Shea Boulevard

Scottsdale AZ 85259 USA

A large and diverse group of pathologic conditions

manifests clinically and radiologically as diffuse

parenchymal lung disease In practice this group of

disorders has been categorized on the basis of clinical

dysfunction (lsquolsquorestrictive lung diseasersquorsquo) or radiologic

appearance (lsquolsquointerstitial lung disease [ILD]rsquorsquo) neither

of which accurately reflects the pathologic processes

involved [1] Diffuse ILDs encompass mainly inflam-

matory processes that involve the structural elements

of this organ Some ILDs are caused by infections but

most are the result of immunologic environmental or

toxic mechanisms These diseases are discussed

together because they have in common the tendency

to produce bilateral abnormalities on chest imaging

studies and are mainly nonneoplastic conditions [2]

Currently less morbid sampling techniques have

increased dramatically the probability that pulmo-

nologists and their general pathology colleagues will

be faced with establishing a specific and clinically

relevant diagnosis using surgical lung biopsy material

Most of the concepts presented in this article have

been established using this type of specimen

In the early years of surgical lung biopsy a small

number of diffuse inflammatory conditions came to

light that exclusively involved the lungs and did not

seem to be caused by infection toxin sarcoidosis

pneumoconiosis or neoplasm Liebow is credited

with recognizing these conditions and devising a

classification system for them These disorders came

0272-523104$ ndash see front matter D 2004 Elsevier Inc All rights

doi101016jccm200405002

Department of Laboratory Medicine and Pathology

Mayo Clinic Scottsdale 13400 East Shea Boulevard

Scottsdale AZ 85259

E-mail address lesliekevinmayoedu

to be known as the idiopathic interstitial pneumonias

[3] The original classification proposed by Liebow is

presented for historical purposes in Box 1 Much has

changed in medical science over the years and none

of the entities proposed in Liebowrsquos original classi-

fication is viewed today exactly as he described them

more than 30 years ago A recent international

consensus conference updated the classification of

idiopathic interstitial pneumonias (Box 2) [4] In this

article these lsquolsquoidiopathicrsquorsquo disorders are discussed in

the context of their dominant pathologic findings

rather than presented as a separate group of entities

(as has been traditional in past) A comparison of the

pathologic manifestations of the idiopathic ILDs is

presented in Table 1

Interpretation of lung biopsies in a patient with

ILD is best accomplished using a multidisciplinary

approach that results in a composite clinico-radio-

logic-pathologic diagnosis Unfortunately this is not

always realistic in many clinical practice settings For

diffuse lung diseases a pathologist must have some

essential information regarding the clinical and

radiologic findings to arrive at a clinically meaningful

diagnosis In many instances more extensive clinical

and radiologic consultation may be necessary The

pulmonologist who is conversant with the pathology

of ILD is a powerful ally in this process

Pattern analysis approach to surgical lung

biopsies

The concept of lsquolsquolosing the forest for the treesrsquorsquo

becomes evident in the evaluation of lung wedge

biopsies The age-old training method of requiring

25 (2004) 657 ndash 703

reserved

Box 1 Liebow classification of interstitialpneumonia (1975)

Usual interstitial pneumonia (UIP)Bronchiolitis obliterans with usual

interstitial pneumonia (BIP)Desquamative interstitial pneumonia

(DIP)Lymphoid interstitial pneumonia (LIP)Giant cell interstitial pneumonia (GIP)

Adapted from Liebow A Carrington CThe interstitial pneumonias In Simon MPotchen E LeMay M editors Frontiers ofpulmonary radiology pathophysiologicroentgenographic and radioisotopic con-siderations Orlando Grune amp Stratton1969 p 109ndash42

Box 2 International ConsensusCommittee classification of idiopathicinterstitial pneumonia (2002)

Acute interstitial pneumoniaDIPrespiratory bronchiolitisndashasso-

ciated interstitial disease (RB-ILD)Cryptogenic organizing pneumonia

(COP)Nonspecific interstitial pneumonia

fibrosis (NSIPF)a

a ProvisionalAdapted from Travis W King T Bate-man E Lynch DA Capron F Colby TVet al ATSERS international multidisci-plinary consensus classification of theidiopathic interstitial pneumonias Am JRespir Crit Care Med 2002165(2)277ndash304

KO Leslie Clin Chest Med 25 (2004) 657ndash703658

that the microscope slide be evaluated first by the

naked eye may seem overly methodical but it does

force the interpreter to see the lsquolsquobig picturersquorsquo before

getting lost in the fine details For nonneoplastic lung

diseases the scanning low power objective (2 or

4) is useful if not essential because different

diseases give rise to different architectural patterns

which may immediately raise a narrow differential

diagnosis For diffuse lung diseases several helpful

patterns emerge

Pattern 1 acute lung injury

The prototype of this pattern is diffuse alveolar

damage (DAD) with hyaline membranes classically

encountered in the clinical setting of adult respiratory

distress syndrome (ARDS) (Fig 1)

Pattern 2 fibrosis

Lung diseases that lead to the accrual of collagen

in the lung with permanent structural remodeling

are represented by this pattern (Fig 2) Idiopathic

pulmonary fibrosis (IPF) (pathologic usual intersti-

tial pneumonia [UIP]) is the prototype and is often

the diagnosis of greatest clinical concern in older

adult patients because of the dismal prognosis of

this condition

Pattern 3 cellular interstitial infiltrates

Lymphocytes plasma cells and macrophages

are present in the alveolar walls in Pattern 3 (Fig 3)

Hypersensitivity pneumonitis (extrinsic allergic al-

veolitis) is the prototype of this pattern

Pattern 4 airspace filling

This pattern is characterized by the presence of

cells or other material filling the alveolar spaces

(Fig 4) Organizing pneumonia is the prototype of

this pattern The airspace filling pattern also includes

infectious bronchopneumonias (neutrophils in the al-

veoli) classic Pneumocystis infection in the immu-

nocompromised host (foamy casts in alveoli)

pulmonary alveolar proteinosis (PAP) (proteinaceous

material in alveoli) diffuse pulmonary hemorrhage

(blood siderophages and patchy organizing pneumo-

nia in alveoli) and DIP in which lightly pigmented

lsquolsquosmokersrsquorsquo-type macrophages are the dominant intra-

alveolar element

Pattern 5 nodules

The presence of discrete nodules (Fig 5) in the

lung parenchyma raises a differential diagnosis that

includes nodular infections benign and malignant

neoplasms sarcoidosis Langerhansrsquo cell histiocyto-

sis and various bronchiolocentric diseases The

prototype is Wegenerrsquos granulomatosis (large nodular

pattern) but small (miliary) patterns of disease also

are included

Table 1

Contrasting pathologic features of idiopathic interstitial pneumonias

Features NSIP UIP DIP AIP LIP COP

Temporal appearance Uniform Variegated Uniform Uniform Uniform Uniform

Interstitial inflammation Prominent Scant Scant Scant Prominent Scant

Interstitial fibrosis (collagen) Variable diffuse Patchy Variable

diffuse

No Some cases No

Interstitial fibrosis (fibroblasts) Occasional diffuse No No Yes diffuse No No

Organizing pneumonia pattern Occasional focal Occasional

No Occasional

No Prominent

Fibroblast foci Occasional focal Typical No No No No

Honeycomb areas Rare Yes No No Sometimes No

Intra-alveolar macrophages Occasional patchy Occasional

diffuse

No Occasional

patchy

Hyaline membranes No No No Yes focal No No

Granulomas No No No No Focal poorly

formed

Abbreviation AIP acute interstitial pneumonia

Data from Katzenstein A Fiorelli R Nonspecific interstitial pneumoniafibrosis histologic features and clinical significance

Am J Surg Pathol 199418136ndash47 and Trans W Colby T Koss M Rosado-Christenson ML Muller NL King TE et al Non-

neoplastic disorders of the lower respiratory tract In King D editor Atlas of nontumor pathology Washington DC American

Registry of Pathology and the Armed Forces Institute of Pathology 2002 p 939

KO Leslie Clin Chest Med 25 (2004) 657ndash703 659

Pattern 6 near normal lung

The surgical lung biopsy that has barely discern-

ible abnormalities is often the result of diseases that

affect the airways and blood vessels of the lung The

changes may be subtle at low magnification The

prototype is small airways disease in which pruning

dilatation and generalized scarring of the small

airways occur and this may be difficult to appreciate

Fig 1 Pattern 1 acute lung injury DAD with hyaline

membranes classically encountered in the clinical setting of

ARDS is the prototype of the acute lung injury pattern

at scanning magnification Vascular diseases (eg pul-

monary hypertension) cystic diseases (eg lymphan-

gioleiomyomatosis [LAM]) and conditions with

patchy scarring also can produce subtle disease that

results in what seems to be lsquolsquonormalrsquorsquo lung from

scanning magnification (Fig 6)

Once the dominant pattern is determined addi-

tional microscopic findings help narrow the diagnos-

tic possibilities A list of these findings with their

Fig 2 Pattern 2 fibrosis Lung diseases that lead to the

accrual of collagen in the lung with permanent structural

remodeling are represented by this pattern IPF (pathologic

UIP) often is the diagnosis of greatest clinical concern

in older adult patients because of the dismal prognosis of

this condition

Fig 3 Pattern 3 cellular interstitial infiltrates Lymphocytes

plasma cells and macrophages are present in the alveolar

walls in Pattern 3 Hypersensitivity pneumonitis (extrinsic

allergic alveolitis) is the prototype of this pattern

Fig 5 Pattern 5 nodules The presence of discrete nod-

ules in the lung parenchyma raises a narrow differen-

tial diagnosis

respective differential diagnosis is presented inTable 2

Overlap between patterns occurs and may be a use-

ful clue in the differential diagnosis For example

when nearly all of the six patterns are present in the

same biopsy specimen rheumatoid arthritis is often

the correct diagnosis Acute lung injury also proceeds

through several distinctive histopathologic patterns

during the repair phase after injury If a lung biopsy is

performed in the subacute phase of DAD airspace

Fig 4 Pattern 4 airspace filling The alveolar spaces are

filled with cells or other material Organizing pneumonia is

the prototype of this pattern

organization may dominate the picture and poten-

tially cause confusion with organizing pneumonia

Acute lung injury pattern (days to weeks in

evolution rapid onset of symptoms)

The pattern of acute lung injury is characterized

by variable interstitial and alveolar edema fibrin in

airspaces and reactive type-II cell hyperplasia (Fig 7)

Hyaline membranes neutrophils necrosis eosino-

Fig 6 Pattern 6 near normal lung The surgical lung biopsy

that has barely discernible abnormalities is often the result of

diseases that affect the airways and blood vessels of the lung

or produce cysts The changes may be subtle at low

magnification The prototype is small airways disease in

which pruning dilatation and generalized scarring of the

small airways occur and may be difficult to appreciate at

scanning magnification

Table 2

Pattern-based approach to interstitial lung diseases

Acute lung injury Fibrosis Cellular interstitial pneumonia Alveolar filling Nodular Minimal change

With hyaline membranes

Infection

With variable fibrosis

(normal to HC)

UIPIPF

With lymphs and plasma cells

C-NSIP CVD

HSP drug

With macrophages

Smoking-related

Local fibrosis

With lymphoid

Follicular bronch

Wegenerrsquos

With SAD

Constrictive bronchiolitis

Drug Asbestosis Infection Lymphoma

Idiopathic RA Lymphoma

Chronic HSP

With eosinophils With honeycombing only With neutrophils With neutrophils With necrosis With vascular

AEP Diffuse Infection Infection Infections pathology

Drug Late UIP CVD DPH Tumor PHT

DAD in smoker Focal Hemorrhage Wegenerrsquos VOD

Many causes

With necrosis With diffuse fibrosis With granulomas With OP With atypical cells With cysts

Infections

Bacterial

Sarcoid (with granulomas)

Infection HSP

sarcoidberylliosis

aspiration

With focal OP

Infection drug

With eosinophilic material

Infections Ca

Lymphomas

Sarcomas

With no findings

Fungal PLCH (with stellate scars)

Infection

Infection CVD

Drug DPH

With stellate scars Sampling error

Pneumoconiosis

F-NSIP CVD CHF PAP

With siderophages With pleuritis With pleuritis With hemorrhage With OP

DPH CVD CVD CVD Infections CVD

CVD DPH Drug Wegenerrsquos

Infarct

Abbreviations AEP acute eosinophilic pneumonia bronch bronchiolitis CHF congestive heart failure C-NSIP cellular NSIP CVD collagen vascular disease DPH diffuse pulmonary

hemorrhage Drug drug toxicity F-NSIP fibrotic NSIP HC honeycomb HSP hypersensitivity pneumonitis OP organizing pneumonia PHT pulmonary hypertension PLCH

pulmonary Langerhans cell histiocytosis RA rheumatoid arthritis SAD small airways disease VOD veno-occlusive disease

KOLeslie

25(2004)657ndash703

Fig 7 Acute lung injury The pattern of acute lung injury is

characterized by variable interstitial and alveolar edema

fibrin in alveolar spaces and reactive type II cells

Box 3 Causes of diffuse alveolar damage

InfectionsPneumocystis jiroveciViruses (eg influenza cytomegalo-

virus varicella and adenovirus)Fungi (eg blastomycosis

aspergillus)Legionella sp

ToxinsInhaled toxins (eg O2 NO2

household ammonia and bleachmercury vapor)

Ingested toxins (eg paraquat)

DrugsCytotoxic (eg azothioprine

carmustine [BCNU] bleomycinbusulfan lomustin [CCNU]cyclophosphamide melphelanmethotrexate mitomycinprocarbazine teniposidevinblastin and zinostatin)

Noncytotoxic (eg amiodaroneamitriptyline colchicine goldsalts hexamethoniumnitrofurantoin penicillaminestreptokinase sulphathiozole)

Illicit (heroin)

ShockTraumaSepsisCardiogenesisRadiation

phils and siderophages are the qualifying elements to

be searched for once this pattern is identified When

hyaline membranes are present (Fig 8) the term

lsquolsquodiffuse alveolar damagersquorsquo is appropriate (see later

discussion) The differential diagnosis in the setting of

DAD always includes infection at the top of the list

but several other causes must be considered once

infection has been reasonably excluded (Box 3)

Adult respiratory distress syndrome and diffuse

alveolar damage

The clinical prototype of acute lung disease is

ARDS ARDS is a relatively common condition in

Fig 8 DAD When hyaline membranes are present the term

DAD is appropriate

MiscellaneousAcute pancreatitis

Data from Myers JL Colby TV YousemSA Common pathways and patternsof injury In Dail D Hammer S editorsPulmonary pathology 2nd edition NewYork Springer-Verlag 1994 p 59

the United States where it is estimated to occur at a

rate of 150000 cases per year The pathologic

manifestation of ARDS is DAD Although DAD is

the prototypic manifestation of ARDS pathologic

DAD does not necessarily correspond to the clinical

entity of ARDS In current practice in the United

States most cases of DAD arise as a consequence of

lung infection or immunologically mediated acute

lung injury related to drug toxicity or connective

tissue disease In the immunocompromised patient

infection dominates this picture

Infections

A complete discussion of pulmonary infections

that produce acute lung injury is beyond the scope of

this article Bacteria fungi and viruses can produce

acute lung injury and are the diagnosis of exclusion in

this setting Viruses are the most common of these

infections to cause diffuse acute lung injury The

more common viruses that cause pneumonia and their

susceptible hosts are presented in Table 3

Drugs and radiation reactions

Medications taken orally or by injection may

produce various lesions within the lung including

DAD pulmonary edema asthma eosinophilic pneu-

monia and even advanced fibrosis [56] For many

drugs acute and chronic forms of toxicity have been

reported This discussion emphasizes a few reactions

that classically manifest as acute lung disease and

highlight those that may produce chronic disease

Nitrofurantoin

Nitrofurantoin is an antimicrobial agent used in

the treatment of urinary tract infections This agent is

responsible for more cases of pulmonary toxicity than

any other drug with acute and chronic reactions

reported [78] Acute reactions are accompanied by

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

Respiratory syncytial virus

NLH (infants) ICH

adults (rare)

Hantavirus

DNA NLH NLH (children) IC

Adenovirus ICH

Herpes simplex NLH (adults) ICH

Varicella-zoster ICH

Cytomegalovirus

Abbreviations ICH immunocompromised host NLH

normal host

Data from Miller RR Muller LM Thurlbeck WM Diffuse

diseases of the lungs In Silverberg SG DeLellis RA Frable

WJ editors Silverbergrsquos principles and practice of surgical

pathology and cytopathology 3rd edition New York

Churchill-Livingstone 1997 p 1116

fever dyspnea and peripheral eosinophilia which

typically appear within 2 weeks of initiating therapy

The histopathologic findings are similar to those of

acute eosinophilic pneumonia Chronic reactions

occur in a few patients taking the drug and clinical

manifestations appear after 1 to 6 months of treat-

ment The chronic cases are more often subjected to

biopsy and show interstitial inflammation and fibrosis

accompanied by vascular sclerosis

Cytotoxic chemotherapeutic drugs

The most common group of drugs that produces

acute lung injury includes the antineoplastic agents

From a clinical standpoint some drugs (eg 5-fluoro-

uracil vinblastine cytarabine adriamycin thiotepa

azathioprine) almost never produce pulmonary dis-

ease With increasing numbers of newer antineo-

plastic agents being used pulmonary toxicity

undoubtedly will increase Excellent on-line re-

sources that provide comprehensive and up-to-date

lists of these agents are available [9]

Analgesics

Heroin [10] methadone propoxyphene and even

aspirin can produce acute lung reactions [1112]

Toxicity typically results from overdose and is

characterized by pulmonary edema sometimes com-

plicated by aspiration of gastric contents When pill

binding agents such as talc or microcrystalline

cellulose are injected with a drug intravenously a

foreign body giant cell reaction may be seen in lung

tissue in a characteristic perivascular distribution

Radiation pneumonitis

Radiation therapy was a common cause of acute

lung injury before improved technology and modi-

fications in dosing were instituted [13] Radiation

injury can be exacerbated by infection [14] and

chemotherapeutic drugs [15] Initial clinical signs and

symptoms often are absent or mild In the acute

phase chest radiographs and high-resolution CT

(HRCT) reveal ground-glass opacities or airspace

consolidation with some loss of lung volume

Acute eosinophilic lung disease

Acute lung injury that occurs in the presence of

significant numbers of tissue eosinophils is referred

to as lsquolsquoacute eosinophilic lung diseasersquorsquo Peripheral

blood and bronchoalveolar lavage eosinophils are

commonly elevated in these conditions Eosinophilia

may not be persistent throughout the disease and

eosinophilic vasculitis is not a prerequisite for the

diagnosis in lung tissue Several forms have been

Fig 9 Eosinophilic pneumonia The histopathologic features of eosinophilic pneumonia are characterized by intra-alveolar

eosinophils fibrin and plump eosinophilic macrophages surrounded by striking reactive type II cell hyperplasia (A) Low

magnification with parenchymal consolidation (B) Prominent fibrin in airspaces with eosinophils and reactive type II cells

Fig 10 Eosinophilic pneumonia Eosinophilic microab-

scesses and eosinophilic vasculitis may be present but are

not necessary for the diagnosis

described over the years the mildest of which has

been referred to as Loeffler syndrome or simple

eosinophilic pneumonia Ascaris infestation was

documented eventually in the initial series by

Loeffler which led to the hypothesis that simple

eosinophilic pneumonia was a manifestation of

hypersensitivity to Ascaris antigens

The second form occurs commonly in patients

with asthma presumably as an allergic manifestation

to an unknown antigen The clinical course is more

chronic and typically evolves slowly over many

months Patients with the lsquolsquochronicrsquorsquo form of eosino-

philic pneumonia may have a typical clinical syn-

drome and radiographic appearance [16]

Finally a dramatic new manifestation of idio-

pathic eosinophilic lung disease has been described

that is characterized by rapid onset of breathlessness

in an otherwise healthy young adult without asthma

[17] This form may mimic DAD clinically and patho-

logically even with the presence of hyaline mem-

branes The importance of recognizing this entity lies

in its excellent prognosis and characteristic rapid

response to corticosteroid therapy

Some other well-recognized associations have

been described with eosinophilic pneumonia The

best example is that produced by sensitivity to nitro-

furantoin and other drugs Eosinophilic pneumonia in

the presence of asthma may be a manifestation of

hypersensitivity to aspergillus and other fungal organ-

isms (eg allergic bronchopulmonary fungal disease)

The histopathologic features of eosinophilic pneu-

monia include intra-alveolar eosinophils fibrin and

plump eosinophilic macrophages surrounded by

striking reactive type II cell hyperplasia (Fig 9)

Acute fibrinous pleuritis may occur Eosinophilic

microabscesses and eosinophilic vasculitis may be

present but are not necessary for the diagnosis

(Fig 10)

Acute pulmonary manifestations of the collagen

vascular diseases

The most common acute manifestation of the

collagen vascular diseases is DAD but diffuse

pulmonary hemorrhage also occurs The more com-

mon collagen vascular diseases that produce acute

manifestations are presented herein

Fig 11 Acute lupus pneumonitis is a serious complication of SLE The pattern is acute lung injury (A) with or without hyaline

membranes Diffuse pulmonary hemorrhage also may occur usually accompanied by vasculitis (B) and capillaritis

Fig 12 Acute fibrinous and organizing pneumonia This

condition typically lacks hyaline membranes but is rich in

fibrinous alveolar exudates

Rheumatoid arthritis

Nearly one-half of all patients with rheumatoid

arthritis (RA) develop one or more forms of

rheumatoid lung disease [18] and patients with more

severe joint involvement are more likely to develop

pleuropulmonary manifestations Lung disease typi-

cally follows the development of joint disease but

occasionally the lung or pleura may herald the

disease DAD is a well-recognized complication of

RA [19]

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) also com-

monly involves the lungs and pleura [18] Painful

pleuritis with or without effusion is the most common

abnormality [20] but acute lupus pneumonitis is a

potentially disastrous complication with a mortality

rate of 50 [21] Acute lupus pneumonitis is

characterized morphologically by DAD Diffuse

pulmonary hemorrhage also may occur usually

accompanied by vasculitis and capillaritis (Fig 11)

Immune complexes may be identified on capillary

basement membranes in this setting [22]

Dermatomyositis-polymyositis

DAD is not common in dermatomyositis-poly-

myositis but the clinical presentation may be

particularly dramatic Tazelaar et al [23] presented

14 patients with dermatomyositis-polymyositis who

developed lung disease Three patients developed

DAD all of whom died most frequently in the acute

episode The authors also reviewed 27 additional

cases of dermatomyositis-polymyositis lung disease

reported in the literature and found similar results

DAD may be the first clinical manifestation of

dermatomyositis-polymyositis and may precede the

clinical and serologic diagnosis of the disease by

many months

Acute fibrinous and organizing pneumonia

A new entity with some similarities to DAD

recently has been described and it is termed lsquolsquoacute

fibrinous and organizing pneumoniarsquorsquo [24] Acute

fibrinous and organizing pneumonia can be patchy

and typically lacks hyaline membranes but is rich in

fibrinous alveolar exudates (Fig 12) without evi-

Box 4 Causes of diffuse alveolarhemorrhage

Goodpasturersquos syndrome (antiglo-merular basement membraneantibody disease)

Vasculitides (especially Wegenerrsquosgranulomatosis)

Mitral stenosisIgA nephropathyBehcetrsquos syndromeCertain systemic collagen vascular dis-

eases (especially SLE)HIV infectionAntiphospholipid syndromePulmonary veno-occlusive diseaseIdiopathic pulmonary hemosiderosisDrug reactions including toxic reac-

tions and anticoagulantsAcute lung allograft rejectionUnclassified forms

Data from Leslie K Colby T Swenson SAnatomic distribution and histopathologicpatterns of interstitial lung disease InSchwarz M King TE editors Interstitiallung disease NewYork BCDecker 2003p 31ndash53

dence of infection Like DAD acute fibrinous and

organizing pneumonia can be idiopathic or associated

with several underlying or associated conditions

such as collagen vascular disease drug reaction

and occupational exposures Survival is similar to

DAD in general but the requirement for mechanical

ventilation was associated with a worse prognosis

Acute diffuse alveolar hemorrhage

Diffuse alveolar hemorrhage (DAH) is character-

ized by a triad of (1) hemoptysis (2) anemia and

(3) bilateral ground-glass opacities (or consolidation)

that rapidly wax and wane Hemorrhage and hemo-

siderin-laden macrophages in alveolar spaces are

essential to the pathologic diagnosis [25ndash27] In

practice artifactual hemorrhage can occur commonly

in lung biopsy specimens Hemosiderin-laden macro-

phages (with coarsely granular golden-brown refrac-

tile pigment) always should be present in the alveolar

spaces before one invokes the diagnosis of DAH

(Fig 13) The differential diagnosis of DAH is pre-

sented in Box 4

Antiglomerular basement membrane disease

(Goodpasturersquos syndrome)

When diffuse pulmonary hemorrhage occurs with

renal disease in the presence of circulating antibodies

against glomerular basement membranes the con-

dition is referred to as antiglomerular basement

membrane disease [28ndash31] Lung biopsy is less

desirable than kidney as a diagnostic specimen in

Fig 13 DAH Fresh blood in the lung is not sufficient

evidence for a diagnosis of DAH Hemosiderin-laden

macrophages with coarsely granular golden-brown refractile

pigment always should be present

antiglomerular basement membrane disease but

because renal disease is commonly occult at the time

of presentation the lung is often the first tissue

sample examined by the pathologist Unfortunately

the lung findings are relatively nonspecific and

consist of fresh alveolar hemorrhage hemosiderin

deposition in macrophages (siderophages) and vari-

able interstitial inflammation with delicate interstitial

fibrosis (Fig 14) The presence of capillaritis in the

alveolar wall is also helpful in distinguishing anti-

glomerular basement membrane disease from idio-

pathic pulmonary hemosiderosis (IPH) and chronic

passive lung congestion The results of immunofluo-

rescent studies on lung tissue are not as reliable as

they are on kidney tissue [30] and for cost-effective

practice we generally recommend serologic confir-

mation (radioimmunoassay or ELISA) even when

appropriately preserved lung tissue is available

Diffuse alveolar hemorrhage associated with the

systemic collagen vascular diseases

DAH may occur as a consequence of several

immune-mediated vasculitides including those that

Fig 14 Antiglomerular basement membrane disease The lung findings consist of fresh alveolar hemorrhage hemosiderin

deposition in macrophages (siderophages) and variable interstitial inflammation with delicate interstitial fibrosis (A) At higher

magnification hemosiderin-laden macrophages are present (B)

occur in the setting of collagen vascular disease

Potential causes of DAH in this setting include

microscopic polyangiitis SLE Wegenerrsquos granulo-

matosis cryoglobulinemia RA crescentic glomeru-

lonephritis and scleroderma [25272930] The

common histopathologic feature is acute capillaritis

with or without larger vessel vasculitis (Fig 15)

Idiopathic pulmonary hemosiderosis

In the absence of renal disease or demonstrable

immunologic disease DAH has been termed IPH

Fig 15 DAH in the collagen vascular diseases The common histo

disease is acute capillaritis (A) with or without larger vessel vascu

IPH occurs most commonly in children younger

than 10 years and young adults in the second and

third decades of life Anemia is accompanied by

bilateral areas of consolidation on the chest radio-

graph The sexes are equally affected in the younger

age group but men predominate in the older age

group The histopathology is similar to that of

antiglomerular basement membrane disease namely

alveolar hemorrhage and hemosiderin-laden macro-

phages but in IPH there is less interstitial inflam-

mation and more fibrosis (Fig 16) By definition

pathologic feature of DAH in the setting of connective tissue

litis (B)

Fig 16 IPH The pathologic changes seen in IPH are similar

to those of antiglomerular basement membrane disease

namely alveolar hemorrhage and hemosiderin-laden macro-

phages In IPH there tends to be less interstitial inflamma-

tion and more fibrosis

tissue immunoglobulin studies and electron micros-

copy are nondiagnostic

Idiopathic diffuse alveolar damage acute interstitial

pneumonia

The term lsquolsquoacute interstitial pneumoniarsquorsquo was first

introduced in 1986 to describe a syndrome of rapidly

evolving acute respiratory failure that occurred in

immunocompetent individuals [32] The patients

described included three men and five women (two

of whom were pregnant) who developed sudden

unexplained respiratory failure Six reported a viral-

like prodrome None of the patients was reported to

have underlying collagen vascular disease By

definition acute interstitial pneumonia is of unknown

cause and is a diagnosis of exclusion The usual

causes of ARDS must be absent (ie shock sepsis

trauma aspiration or drug toxicity)

Surgical lung biopsies show DAD in varying

stages (Fig 17) The changes observed in biopsy

specimens depend on the stage at which the biopsy is

taken and tend to be relatively diffuse throughout the

specimen Like other forms of DAD the early stages

show an exudative phase with edema and hyaline

membranes Bronchioles may show squamous meta-

plasia that extend peripherally to involve adjacent

alveolar walls Organizing arterial thrombi were seen

in five of the seven patients who died in the Kat-

zenstein series [32] In the last stages fibrosis distorts

the lung architecture

Collagen vascular disease or allergic disorders

may be responsible for many cases of acute inter-

stitial pneumonia although they may not be clinically

apparent at the time of presentation acute interstitial

pneumonia has been formally added to the classi-

fication of the idiopathic interstitial pneumonias by a

recent international consensus committee [4]

Pattern 2 interstitial lung disease dominated by

fibrosis (typically months to years in evolution)

A large number of systemic diseases inhalational

exposures toxins and drugs and even genetic

disorders are well known to cause scarring in the

lungs with permanent structural remodeling A list of

these diseases is presented in Box 5 UIP is the most

notorious of these diseases and is the diagnosis of

exclusion for patients over the age of 50 because of

the dismal prognosis of this idiopathic condition In

younger patients the systemic connective tissue

diseases figure prominently as causes of chronic lung

disease with fibrosis

Pulmonary fibrosis in the systemic connective tissue

diseases

The collagen vascular diseases as a group involve

the respiratory system frequently Each of these

diseases may involve the lung and pleura in several

different ways Although the lung morphologic

abnormalities are not specific for any one of these

diseases some features are more commonly mani-

fested than others in each of them (Table 4) A few of

the more prominent collagen vascular diseases known

to produce fibrosis are presented herein

The most common thoracic complication of RA is

pleural disease (effusion or pleuritis) which is seen in

as much as 50 of patients in autopsy studies

According to a study by Walker and Wright [33]

approximately one-third of the patients with pleural

effusions also have pulmonary manifestations of RA

in the form of nodules or interstitial disease Nodules

may be seen in the lung parenchyma and occasionally

in the walls of airways in persons with RA which

represents lymphoid hyperplasia with germinal cen-

ters in most instances (Fig 18) The interstitial

pneumonia of RA may be cellular with little fibrosis

(cellular NSIP-like see later discussion) fibrotic with

honeycomb cystic remodeling (UIP-like see later

discussion) and occasionally may have a macro-

phage-rich DIP pattern (discussed in Pattern 4) [19]

Fig 17 Acute interstitial pneumonia Surgical lung biopsies show diffuse alveolar damage in varying stages In the earliest

manifestation (A) edema in the alveolar spaces and interstitium is typical with hyaline membranes and preservation of the

alveolar spaces As the process evolves (2ndash4 days after onset) hyaline membranes become thicker and there is greater cellularity

in the interstitium as inflammatory cells begin to accrue (B) By the end of the first week (C) alveolar spaces are overwhelmed

by reparative changes with myofibroblasts that produce an organizing pneumonia pattern Over the next weeks (D) the

myofibroblasts become incorporated into the interstitium as the best outcome with reconstitution of the alveolar architecture

Similar to RA SLE also commonly involves the

respiratory system [18] Painful pleuritis with or

without effusion is the most common abnormality

[20] Noninfectious organizing pneumonia also has

been reported and advanced fibrosis with honey-

comb remodeling occurs (Fig 19) [34]

Progressive systemic sclerosis

The most notable feature of lsquolsquoscleroderma lungrsquorsquo

is the presence of extensive alveolar wall fibrosis

without much inflammation (Fig 20) [35] Some

degree of diffuse lung fibrosis occurs in nearly every

patient with pulmonary involvement [18] Patients

with longstanding progressive systemic sclerosisndash

related lung fibrosis are at high risk of developing

bronchoalveolar carcinoma Vascular sclerosis usu-

ally without true vasculitis is typical if sufficiently

severe it produces pulmonary hypertension [36]

Pleural disease is less common in progressive

systemic sclerosis than in RA or SLE

Mixed connective tissue disease

Mixed connective tissue disease is relatively

common in producing interstitial pulmonary disease

or pleural effusions [18] In many cases the

abnormalities respond well to corticosteroid therapy

but severe and progressive pulmonary disease with

Box 5 Diseases with fibrosis andhoneycombing

Idiopathic pulmonary fibrosis(idiopathic UIP)

DIPLymphocytic interstitial pneumoniaSystemic collagen vascular diseaseChronic drug reactionsPneumoconioses (eg asbestosis

berylliosis silicosis hard metalpneumoconiosis)

SarcoidosisPulmonary Langerhansrsquo cell histiocyto-

sis (PLCH histiocytosis X)Chronic granulomatous infectionsChronic aspirationChronic hypersensitivity pneumonitisOrganized chronic eosinophilic

pneumoniaOrganized and organizing DADChronic interstitial pulmonary edema

passive congestionRadiation (chronic)Healed infectious pneumonias and

other inflammatory processesNSIPF

fibrosis does occur A pattern of fibrosis that re-

sembles the pattern seen in UIP (see later discussion)

occurs and pulmonary hypertension may occur

accompanied by plexiform lesions similar to those

seen in persons with primary pulmonary hyperten-

sion [37]

DermatomyositisPolymyositis

Several forms of ILD have been reported in der-

matomyositispolymyositis and the histologic find-

ings seen on biopsy seem to be better predictors of

prognosis than clinical or radiologic features [23] A

subacute presentation with a noninfectious organizing

pneumonia pattern has been associated with the best

prognosis whereas the worst prognosis has been

associated with advanced lung fibrosis [23]

Sjogrenrsquos syndrome

The common pulmonary lesions of Sjogrenrsquos

syndrome generally evolve over weeks to months

and are analogous to the disease manifestations in the

salivary glands The range of disease patterns in

Sjogrenrsquos syndrome is broad especially when Sjog-

renrsquos syndrome is accompanied by other connective

tissue disease A hallmark of pure Sjogrenrsquos syndrome

in the lung is marked lymphoreticular infiltrates in

the submucosal glands of the tracheobronchial tree

(Fig 21) [18] Patients with Sjogrenrsquos syndrome also

are at risk for LIP and occasionally develop lympho-

proliferative disorders that involve the pulmonary

interstitium ranging from relatively low-grade extra-

nodal marginal zone lymphoma (MALToma) to a

high-grade lymphoma Advanced lung fibrosis also

occurs as pleuropulmonary manifestation in Sjogrenrsquos

syndrome (Fig 22) [3839]

Certain chronic drug reactions

Many drugs are reported to produce lung fibrosis

among them bleomycin carmustine penicillamine ni-

trofurantoin tocainide mexiletine amiodarone aza-

thioprine methotrexate melphalan and mitomycin C

Unfortunately the list of agents is growing rapidly

and the reader is referred to on-line resources such

as wwwpneumotoxcom [188] for continuously

updated information on reported drug reactions Bleo-

mycin is presented in this article because it causes sub-

acute and chronic toxicity and has been used widely

as an experimental model of pulmonary fibrosis

Bleomycin

Bleomycin is an antineoplastic agent that becomes

concentrated in skin lungs and lymphatic fluid

Pulmonary lesions may be dose-related [4041] and

prior radiotherapy seems to predispose to toxicity

[42] The initial site of injury in experimental models

seems to be the venous endothelial cell [43] but type I

cell injury allows fibrin and other serum proteins to

leak into the alveolus Type II cell hyperplasia occurs

as a regenerative phenomenon that results in atypical

enlarged forms and intra-alveolar fibroplasia occurs

(often in a subpleural distribution) eventually result-

ing in alveolar septal widening (Fig 23)

Hermansky-Pudlak syndrome

The Hermansky-Pudlak syndromes are a group of

autosomal-recessive inherited genetic disorders that

share oculocutaneous albinism platelet storage

pool deficiency and variable tissue lipofuschinosis

[44ndash46] The most common form of Hermansky-

Table 4

Lung manifestations of the collagen vascular diseases

Lung manifestations RA J-RA SLE PSS DM-PM MCTD

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

Pleural inflammation fibrosis effusions X X X X X X X X

Airway disease inflammation obstruction

lymphoid hyperplasia follicular bronchiolitis

X X X X X

Interstitial disease X X X X X X X

Acute (DAD) with or without hemorrhage X X X X X X

Subacuteorganizing (OP pattern) X X X X X

Subacute cellular X X X

Chronic cellular X X X X X X X

Eosinophilic infiltrates X

Granulomatous interstitial pneumonia X X X

Vascular diseases hypertensionvasculitis X X X X X X X

Parenchymal nodules X X

Apical fibrobullous disease X X

Lymphoid proliferation (reactive neoplastic) X X X

Abbreviations DMPM dermatomyositispolymyositis J-RA juvenile rheumatoid arthritis MCTD mixed connective

tissue disease OP organizing pneumonia PSS progressive systemic sclerosis RA rheumatoid arthritis SLE systemic

lupus erythematosus

Data from Colby T Lombard C Yousem S Kitaichi M Atlas of pulmonary surgical pathology In Bordin G editor Atlases in

diagnostic surgical pathology Philadelphia WB Saunders 1991 p 380 and Trans W Colby T Koss M Rosado-Christenson

ML Muller NL King TE et al Non-neoplastic disorders of the lower respiratory tract In King D editor Atlas of nontumor

pathology Washington DC American Registry of Pathology and the Armed Forces Institute of Pathology 2002 p 939

Pudlak syndrome arises from a 16-base pair duplica-

tion in the HPS1 gene at exon 15 on the long arm of

chromosome 10 (10q23) [47] This form is referred to

as HPS1 and is associated with progressive lethal

pulmonary fibrosis HPS1 affects between 400 and

500 individuals in northwest Puerto Rico [4849]

Pulmonary fibrosis typically begins in the fourth

Fig 18 RA Nodules of hyperplastic lymphoid tissue with germina

RA and occasionally in the walls of airways (follicular bronchiolitis

(B) the distribution may suggest UIP of idiopathic pulmonary fibr

diffuse alveolar wall fibrosis throughout the lobule

decade and results in death from respiratory failure

within 1 to 6 years of onset [50] No effective therapy

has been identified for patients with Hermansky-

Pudlak syndrome with lung fibrosis but newer

antifibrotic therapies are being explored [51] HRCT

findings include peribronchovascular thickening

ground-glass opacification and septal thickening

l centers may be seen in the lung parenchyma in persons with

) (A) When advanced fibrosis and remodeling occurs in RA

osis but typically with more chronic inflammation and more

Fig 19 SLE Advanced fibrosis with honeycomb remodel-

ing may occur in SLE No residual alveolar parenchyma is

present in the example of honeycomb remodeling

Fig 21 Sjogrenrsquos syndrome A hallmark of pure Sjogrenrsquos

syndrome in the lung is marked lymphoreticular infiltrates

in the submucosal glands of the tracheobronchial tree All

of the small blue nodules seen in this illustration are lym-

phoid follicles with germinal centers (secondary follicles)

[52] A granulomatous colitis also may occur in

patients with Hermansky-Pudlak syndrome

Histopathologically the findings in Hermansky-

Pudlak syndrome are distinctive At scanning mag-

nification broad irregular zones of fibrosis are seen

some of which are pleural based whereas others are

centered on the airways (Fig 24) Alveolar septal

thickening is present and associated with prominent

clear vacuolated type II pneumocytes (Fig 25) Con-

Fig 20 Progressive systemic sclerosis The most notable

feature of lsquolsquoscleroderma lungrsquorsquo is the presence of extensive

alveolar wall thickening by fibrosis without much inflam-

mation Like advanced fibrosis in RA the disease may

mimic UIP on occasion Note that all of the alveolar walls in

this photograph are abnormal although the walls located

centrally in the illustrated lobule are less involved than those

at the periphery

strictive bronchiolitis occurs and microscopic honey-

combing is present without a consistent distribution

Ultrastructurally numerous giant lamellar bodies can

be found in the vacuolated macrophages and type II

cells The phospholipid material in the vacuoles is

weakly positive with antibodies directed against

surfactant apoprotein by immunohistochemistry

Idiopathic nonspecific interstitial pneumonia

In the 30 years after the original Liebow clas-

sification of the idiopathic interstitial pneumonias a

lsquolsquonewrsquorsquo category of interstitial pneumonia emerged

and was informally referred to as lsquolsquounclassified or

Fig 22 Sjogrenrsquos syndrome Advanced lung fibrosis also

occurs as a pleuropulmonary manifestation in Sjogrenrsquos syn-

drome often with abundant chronic lymphoid infiltration

Fig 25 Hermansky-Pudlak syndrome Alveolar septal

thickening is present and is associated with prominent

clear vacuolated type II pneumocytes in Hermansky-

Pudlak syndromeFig 23 Bleomycin toxicity Advanced lung fibrosis may

occur after bleomycin therapy which is one of the main

reasons that bleomycin is used in experimental models

of IPF

unclassifiablersquorsquo interstitial pneumonia by some or

simple lsquolsquocellular interstitial pneumoniarsquorsquo by others In

an effort to group these lsquolsquounclassifiablersquorsquo patterns of

interstitial pneumonia Katzenstein and Fiorelli [53]

published in 1994 a review of 64 patients whose

biopsies showed diffuse interstitial inflammation or

fibrosis that did not fit Liebowrsquos classification

scheme The pathologic findings for this group of

patients were referred to as lsquolsquononspecific interstitial

pneumoniafibrosisrsquorsquo or simply NSIP NSIP was not a

Fig 24 Hermansky-Pudlak syndrome The histopathologic

findings in Hermansky-Pudlak syndrome are distinctive At

scanning magnification broad irregular zones of fibrosis are

seenmdashsome pleural based and others centered on the

airways A focus of metaplastic bone is present in the upper

left portion of this image (a nonspecific sign of chronicity in

fibrotic lung disease)

specific disease entity but likely represented several

unrelated diseases and conditions

Katzenstein and Fiorelli subdivided their cases

into three groups group I had diffuse interstitial

inflammation alone (Fig 26) group II had interstitial

inflammation and early interstitial fibrosis occurring

together (Fig 27) and group III had denser diffuse

interstitial fibrosis without significant active inflam-

mation (Fig 28) These uniform injury patterns were

judged to be separable from the lsquolsquotemporally hetero-

geneousrsquorsquo injury seen in UIP (transitions from

uninvolved lsquolsquonewrsquorsquo lung to lsquolsquooldrsquorsquo injury with fibrosis

and honeycombing) Group I NSIP (cellular NSIP) is

discussed under Pattern 3 later in this article

Fig 26 NSIP group I Katzenstein and Fiorelli subdivided

their cases into three groups Group I had diffuse interstitial

inflammation alone (without fibrosis) In this photograph

there is only mild interstitial thickening by small lympho-

cytes and a few plasma cells

Fig 27 NSIP Group II had interstitial inflammation and

early interstitial fibrosis occurring together

Several significant systemic disease associations

were identified in their population Connective tissue

disease was identified in 16 of patients including

RA SLE polymyositisdermatomyositis sclero-

derma and Sjogrenrsquos syndrome Pulmonary disease

preceded the development of systemic collagen

vascular disease in some of their casesmdasha phenome-

non well documented for some collagen vascular

diseases such as dermatomyositispolymyositis

Other autoimmune diseases that occurred in their

series included Hashimotorsquos thyroiditis glomerulo-

nephritis and primary biliary cirrhosis Beyond these

systemic associations another subset of patients was

found to have a history of chemical organic antigen

Fig 28 NSIP Group III had denser diffuse interstitial fibrosis w

inflammation may be present (B)

or drug exposures which suggested the possibility of

a hypersensitivity phenomenon Two additional

patients were status post-ARDS and two patients

had suffered pneumonia months before their biopsies

were performed

Perhaps the most important finding in the Katzen-

stein and Fiorelli study was that their population of

patients had morbidity and mortality rates signifi-

cantly different from that of UIP in which reported

mortality figures were more in the range of 90 with

median survival in the range of 3 years Only 5 of 48

patients with clinical follow-up died of progressive

lung disease (11) whereas 39 patients either

recovered or were alive with stable lung disease

For the patients with follow-up no deaths were

reported in group I patients whereas 3 patients from

group II and 2 patients from group III died

Unfortunately a significant number of patients were

lost to follow-up and mean lengths of follow-up

varied Since 1994 there have been several additional

reported series of patients with NSIP [54ndash61] with

variable reported survival rates (Table 5) Deaths

occurred in patients with NSIP who had fibrosis

(groups II and III) analogous to results reported by

Katzenstein and Fiorelli Nagai et al [58] restricted

the scope of NSIP to patients with idiopathic disease

primarily by excluding patients with known collagen

vascular diseases and environmental exposures Two

of 31 patients in their study (65) died of pro-

gressive lung disease both of whom had group III

disease By contrast the highest mortality rate was re-

ported in the series by Travis et al [61] in which 9 of

22 patients (41) died with group II and III disease

These deaths occurred after 5 years somewhat

ithout significant active inflammation (A) Mild interstitial

Table 5

Literature review of deaths or progression related to nonspecific interstitial pneumonia

Authors No of patients Sex Progression () Deaths (NSIP) ()

Katzenstein and Fiorelli 1994 [53] 64 26 M 38 F 13 11

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Kim et al 1998 [57] 23 1 M 22 F Not given Not given

Travis et al 2000 [61] 29 10 M 9 F 41 (at least) 41

Daniil et al 1999 [56] 15 7 M 8 F 33 13

Bjoraker et al 1998 [54] 14 8 M 6 F Not given 25 (5 yr) 35 (10 yr)

Abbreviations F female M male

different from the course of most patients with UIP

Travis et al also reported 5- and 10-year survival rates

of 90 and 35 respectively in their patients with

NSIP compared with 5- and 10-year survival rates of

43 and 15 respectively for patients with UIP

Idiopathic usual interstitial pneumonia (cryptogenic

fibrosing alveolitis)

UIP is a chronic diffuse lung disease of

unknown origin characterized by a progressive

tendency to produce fibrosis UIP has had many

names over the years including chronic Hamman-

Rich syndrome fibrosing alveolitis cryptogenic

fibrosing alveolitis idiopathic pulmonary fibrosis

widespread pulmonary fibrosis and idiopathic inter-

stitial fibrosis of the lung For Liebow UIP was the

Fig 29 Cryptogenic fibrosing alveolitis (A) At scanning magnif

peripheral fibrosis There is tractional emphysema centrally in lob

appearance of UIP in the setting of cryptogenic fibrosing alveolitis

and has a consistent tendency to leave lung fibrosis and honeycom

illustrated Note the presence of subpleural fibrosis immediately

can be seen at the lower left as paler zones of tissue

most common or lsquolsquousualrsquorsquo form of diffuse lung

fibrosis According to Liebow UIP was idiopathic

in approximately half of the patients originally

studied In the other half the disease was lsquolsquohetero-

geneous in terms of structure and causationrsquorsquo [3]

Currently UIP has been restricted to a subset of the

broad and heterogeneous group of diseases initially

encompassed by this term [114]

UIP is a disease of older individuals typically

older than 50 years [62] Men are slightly more

commonly affected than women Characteristic clini-

cal findings include distinctive end-inspiratory

crackles (lsquolsquoVelcro cracklesrsquorsquo) at the lung bases and

the eventual development of lung fibrosis with cor

pulmonale Clubbing occurs commonly with the

disease Many patients die of respiratory failure

The average duration of symptoms in one series was

ication the lung lobules are accentuated by the presence of

ules which further adds to the distinctive low magnification

The disease begins at the periphery of the pulmonary lobule

b cystic lung remodeling in its wake (B) An entire lobule is

adjacent to thin and delicate alveolar septa Fibroblast foci

Fig 30 Cryptogenic fibrosing alveolitis The renowned fibroblast focus (A) is not unique to cryptogenic fibrosing alveolitis but

is distinctive and occurs at the interface between dense peripheral fibrosis and more normal lung centrally in the lobule Another

consistent finding seen even in early examples of cryptogenic fibrosing alveolitis is microscopic honeycombing (B) This focus

was presumably an intact lobule once but was replaced by cysts partially filled with mucus No alveoli remain

Fig 31 Cryptogenic fibrosing alveolitis Smooth muscle is

typically present within areas of fibrosis

3 years [3] and the mean survival after diagnosis has

been reported as 42 years in a population-based

study [63] Different from other chronic inflamma-

tory lung diseases immunosuppressive therapy im-

proves neither survival nor quality of life for patients

with UIP [62]

HRCT has added a new dimension to the diagnosis

of UIP The abnormalities are most prominent at the

periphery of the lungs and in the lung bases

regardless of the stage [64] Irregular linear opacities

result in a reticular pattern [64] Advanced lung

remodeling with cyst formation (honeycombing) is

seen in approximately 90 of patients at presentation

[65] Ground-glass opacities can be seen in approxi-

mately 80 of cases of UIP but are seldom extensive

The gross examination of the lung often reveals a

characteristic nodular external surface (Fig 29)

Histopathologically UIP is best envisioned as a

smoldering alveolitis of unknown cause accompanied

by microscopic foci of injury repair and lung

remodeling with dense fibrosis The disease begins

at the periphery of the pulmonary lobule and has a

consistent tendency to leave lung fibrosis and honey-

comb cystic lung remodeling in its wake as it

progresses from the periphery to the center of the

lobule (Fig 30) This transition from dense fibrosis

with or without honeycombing to near normal lung

through an intermediate stage of alveolar organization

and inflammation is the histologic hallmark of so-

called lsquolsquotemporal heterogeneityrsquorsquo Thick irregular

bundles of smooth muscle typically are present within

areas of fibrosis (Fig 31) presumably arising as a

consequence of progressive parenchymal collapse

with incorporation of native airway and vascular

smooth muscle into fibrosis Less well-recognized

additional features of UIP are distortion and narrow-

ing of bronchioles together with peribronchiolar

fibrosis and inflammation This observation likely

accounts for the functional evidence of small airway

obstruction that may be found in UIP [66] Wide-

spread bronchial dilation (traction bronchiectasis)

may be present at postmortem examination in ad-

vanced disease and is evident on HRCT late in the

course of IPF

Acute exacerbation of idiopathic pulmonary fibrosis

Episodes of clinical deterioration are expected in

patients with UIP Although lsquolsquorespiratory failurersquorsquo is

the cause of death in approximately one half of

affected individuals for a small subset death is

sudden after acute respiratory failure This manifes-

tation of the disease has been termed lsquolsquoacute exa-

cerbation of IPFrsquorsquo when no infectious cause is

identified The typical history is that of a patient

being followed for IPF who suddenly develops acute

respiratory distress that often is accompanied by

fever elevation of the sedimentation rate marked

increase in dyspnea and new infiltrates that often

have an lsquolsquoalveolarrsquorsquo character radiologically For

many years this manifestation was believed to be

infectious pneumonia (possibly viral) superimposed

on a fibrotic lung with marginal reserve Because

cases are sufficiently common organisms are rarely

identified and a small percentage of patients respond

to pulse systemic corticosteroid therapy many inves-

tigators consider such exacerbation to be a form of

fulminant progression of the disease process itself

Overall acute exacerbation has a poor prognosis and

death within 1 week is not unusual Pathologically

acute lung injury that resembles DAD or organizing

pneumonia is superimposed on a background of

peripherally accentuated lobular fibrosis with honey-

combing This latter finding can be highlighted in

tissue sections using the Masson trichrome stain for

collagen (Fig 32) That acute exacerbation is a real

phenomenon in IPF is underscored by the results of a

recent large randomized trial of human recombinant

interferon gamma 1b in IPF In this study of patients

with early clinical disease (FVC 50 of predicted)

Fig 32 In acute exacerbation of cryptogenic fibrosing alveolitis ac

is superimposed on a background of peripherally accentuate lobula

highlighted in tissue sections using the Masson trichrome stain fo

44 of 330 enrolled subjects died unexpectedly within

the 48-week trial period Eighty percent of deaths in

the experimental and control groups were respiratory

in origin and without a defined cause [67]

Pattern 3 interstitial lung diseases dominated by

interstitial mononuclear cells (chronic

inflammation)

The most classic manifestation of ILD is em-

bodied in this pattern in which mononuclear in-

flammatory cells (eg lymphocytes plasma cells and

histiocytes) distend the interstitium of the alveolar

walls The pattern is common and has several

associated conditions (Box 6)

Hypersensitivity pneumonitis

Lung disease can result from inhalation of various

organic antigens In most of these exposures the

disease is immunologically mediated presumably

through a type III hypersensitivity reaction although

the immunologic mechanisms have not been well

documented in all conditions [68] The prototypic

example is so-called lsquolsquofarmerrsquos lungrsquorsquo which is

caused by hypersensitivity to thermophilic actino-

mycetes (Micromonospora vulgaris and Thermophyl-

liae polyspora) that grow in moldy hay

The radiologic appearance depends on the stage of

the disease In the acute stage airspace consolidation

is the dominant feature In the subacute stage there is

a fine nodular pattern or ground-glass opacification

The chronic stage is dominated by fibrosis with

ute lung injury that resembles DAD or organizing pneumonia

r fibrosis with honeycombing (A) This latter finding can be

r collagen (B)

Box 6 Lung diseases with diffuse cellularinterstitial infiltrates

NSIPSystemic collagen vascular diseases

that manifest in the lungHypersensitivity pneumonitisCertain toxic or hypersensitivity

drug reactionsLymphocytic interstitial pneumonia in

HIV infectionLymphoproliferative diseases

irregular linear opacities resulting in a reticular

pattern The HRCT reveals bilateral 3- to 5-mm

poorly defined centrilobular nodular opacities or

symmetric bilateral ground-glass opacities which

are often associated with lobular areas of air trapping

[69] The chronic phase is characterized by irregular

linear opacities (reticular pattern) that represent

fibrosis which are usually most severe in the mid-

lung zones [70]

Table 6

Summary of morphologic features in pulmonary biopsies of 60 fa

Morphologic criteria Present

Interstitial infiltrate 60 100

Unresolved pneumonia 39 65

Pleural fibrosis 29 48

Fibrosis interstitial 39 65

Bronchiolitis obliterans 30 50

Foam cells 39 65

Edema 31 52

Granulomas 42 70

With giant cellsb 30 50

Without giant cells 35 58

Solitary giant cells 32 53

Foreign bodies 36 60

Birefringentb 28 47

Non-birefringent 24 40

a Degree of involvement rated on an arbitrary but documentedb The discrepancy in the total numbers is caused by the fact tha

be found This discrepancy also applies with the foreign bodies

Data from Reyes C Wenzel F Lawton D Emanuel DA The pul

142ndash51

The classic histologic features of hypersensitivity

pneumonia are presented in Table 6 Because biopsy

is typically performed in the subacute phase the

picture is usually one of a chronic inflammatory

interstitial infiltrate with lymphocytes and variable

numbers of plasma cells Lung structure is preserved

and alveoli usually can be distinguished A few

scattered poorly formed granulomas are seen in the

interstitium (Fig 33) The epithelioid cells in the

lsquolsquogranulomasrsquorsquo are loosely aggregated and mixed with

lymphocytes Characteristically scattered giant cells

of the foreign body type are seen around terminal

airways and may contain cleft-like spaces or small

particles that are doubly refractile (Fig 34) Terminal

airways display chronic inflammation of their walls

(bronchiolitis) often with destruction distortion and

even occlusion Pale or lightly eosinophilic vacuo-

lated macrophages are typically found in alveolar

spaces and are a common sign of bronchiolar

obstruction Similar macrophages also are seen within

alveolar walls

In the largest series reported the inciting allergen

was not identified in 37 of patients who had

unequivocal evidence of hypersensitivity pneumo-

nitis on biopsy [71] even with careful retrospective

search [72] As the condition becomes more chronic

there is progressive distortion of the lung architecture

by fibrosis and microscopic honeycombing occa-

sionally attended by extensive pleural fibrosis At this

stage the lesions are difficult to distinguish from

rmerrsquos lung patients

Degree of involvementa

plusmn 1+ 2+ 3+

0 14 19 27

mdash mdash mdash mdash

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

scale for each criterion

t in some cases granulomas with and without giant cells may

monary pathology of farmerrsquos lung disease Chest 198281

Fig 33 Hypersensitivity pneumonitis The picture is usually one of a chronic inflammatory interstitial infiltrate (cellular

interstitial pneumonia) with lymphocytes and variable numbers of plasma cells (A) Lung structure is preserved and alveoli

usually can be distinguished A few scattered poorly formed granulomas can be seen in the interstitium (B)

other chronic lung diseases with fibrosis because the

lymphocytic infiltrate diminishes and only rare giant

cells may be evident The differential diagnosis of

hypersensitivity pneumonitis is presented in Table 7

Bioaerosol-associated atypical mycobacterial

infection

The nontuberculous mycobacteria species such

as Mycobacterium kansasii Mycobacterium avium

Fig 34 Hypersensitivity pneumonitis The epithelioid cells

in the lsquolsquogranulomasrsquorsquo are loosely aggregated and mixed with

lymphocytes Characteristically scattered giant cells of the

foreign body type are seen around terminal airways and

may contain cleft-like spaces or small particles that are

refractile in plane-polarized light

intracellulare complex and Mycobacterium xenopi

often are referred to as the atypical mycobacteria [73]

Being inherently less pathogenic than Myobacterium

tuberculosis these organisms often flourish in the

setting of compromised immunity or enhanced

opportunity for colonization and low-grade infection

Acute pneumonia can be produced by these organ-

isms in patients with compromised immunity Chronic

airway diseasendashassociated nontuberculous mycobac-

teria pose a difficult clinical management problem

and are well known to pulmonologists A distinctive

and recently highlighted manifestation of nontuber-

culous mycobacteria may mimic hypersensitivity

pneumonitis Nontuberculous mycobacterial infection

occurs in the normal host as a result of bioaerosol

exposure (so-called lsquolsquohot tub lungrsquorsquo) [74] The

characteristic histopathologic findings are chronic

cellular bronchiolitis accompanied by nonnecrotizing

or minimally necrotizing granulomas in the terminal

airways and adjacent alveolar spaces (Fig 35)

Idiopathic nonspecific interstitial

pneumonia-cellular

A pure lsquolsquocellularrsquorsquo (chronic inflammatory) form of

NSIP (group I) was identified in Katzenstein and

Fiorellirsquos original report In the absence of fibrosis

the prognosis of NSIP seems to be good The

distinction of cellular NSIP from hypersensitivity

pneumonitis LIP (see later discussion) some mani-

festations of drug and a pulmonary manifestation of

collagen vascular disease may be difficult on histo-

pathologic grounds alone

Table 7

Differential diagnosis of hypersensitivity pneumonitis

Histologic features Hypersensitivity pneumonitis Sarcoidosis

Lymphocytic interstitial

pneumonia

Granulomas

Frequency Two thirds of open biopsies 100 5ndash10 of cases

Morphology Poorly formed Well formed Well formed or poorly formed

Distribution Mostly random some peribronchiolar Lymphangitic

peribronchiolar

perivascular

Random

Intraluminal fibrosis Two thirds of open biopsies Rare Unusual

Lymphocyte infiltrates Mild-moderate peribronchiolar Absent or minimal Extensive diffuse

Dense fibrosis In advanced cases In advanced cases Unusual

BAL lymphocytosis CD8 gt CD4 CD4 gtCD8 Usually B cells

Abbreviation BAL bronchoalveolar lavage

Data from Travis W Colby T Koss M Rosado-Christenson ML Muller NL King TE et al Non-neoplastic disorders of

the lower respiratory tract In King D editor Atlas of nontumor pathology Washington DC American Registry of Pathology

and the Armed Forces Institute of Pathology 2002 p 939

Drug reactions

Methotrexate

Methotrexate seems to manifest pulmonary tox-

icity through a hypersensitivity reaction [75] There

does not seem to be a dose relationship to toxicity

although intravenous administration has been shown

to be associated with more toxic effects Symptoms

typically begin with a cough that occurs within the

first 3 months after administration and is accompanied

by fever malaise and progressive breathlessness

Peripheral eosinophilia occurs in a significant number

of patients who develop toxicity A chronic interstitial

infiltrate is observed in lung tissue with lymphocytes

plasma cells and a few eosinophils (Fig 36) Poorly

Fig 35 Bioaerosol-associated atypical mycobacterial infection The

bronchiolitis (A) accompanied by nonnecrotizing or minimally nec

airways into adjacent alveolar spaces (B)

formed granulomas without necrosis may be seen and

scattered multinucleated giant cells are common

(Fig 37) Symptoms gradually abate after the drug

is withdrawn [76] but systemic corticosteroids also

have been used successfully

Amiodarone

Amiodarone is an effective agent used in the

setting of refractory cardiac arrhythmias It is

estimated that pulmonary toxicity occurs in 5 to

10 of patients who take this medication and older

patients seem to be at greater risk Toxicity is

heralded by slowly progressive dyspnea and dry

cough that usually occurs within months of initiating

therapy In some patients the onset of disease may

characteristic histopathologic findings are a chronic cellular

rotizing granulomas that seemingly spill out of the terminal

Fig 36 Methotrexate A chronic interstitial infiltrate is

observed in lung tissue with lymphocytes plasma cells and

a few eosinophils

mimic infectious pneumonia [77ndash80] Diffuse infil-

trates may be present on HRCT scans but basalar and

peripherally accentuated high attenuation opacities

and nonspecific infiltrates are described [8182]

Amiodarone toxicity produces a cellular interstitial

pneumonia associated with prominent intra-alveolar

macrophages whose cytoplasm shows fine vacuola-

tion [7783ndash85] This vacuolation is also present in

adjacent reactive type 2 pneumocytes Characteristic

lamellar cytoplasmic inclusions are present ultra-

structurally [86] Unfortunately these cytoplasmic

changes are an expected manifestation of the drug so

their presence is not sufficient to warrant a diagnosis

of amiodarone toxicity [83] Pleural inflammation

and pleural effusion have been reported [87] Some

patients with amiodarone toxicity develop an orga-

Fig 37 Methotrexate Poorly formed granulomas without

necrosis may be seen and scattered multinucleated giant

cells are common

nizing pneumonia pattern or even DAD [838889]

Most patients who develop pulmonary toxicity

related to amiodarone recover once the drug is dis-

continued [777883ndash85]

Idiopathic lymphoid interstitial pneumonia

LIP is a clinical pathologic entity that fits

descriptively within the chronic interstitial pneumo-

nias By consensus LIP has been included in the

current classification of the idiopathic interstitial

pneumonias despite decades of controversy about

what diseases are encompassed by this term In 1969

Liebow and Carrington [3] briefly presented a group

of patients and used the term LIP to describe their

biopsy findings The defining criteria were morphol-

ogic and included lsquolsquoan exquisitely interstitial infil-

tratersquorsquo that was described as generally polymorphous

and consisted of lymphocytes plasma cells and large

mononuclear cells (Fig 38) Several associated

clinical conditions have been described including

connective tissue diseases bone marrow transplanta-

tion acquired and congenital immunodeficiency

syndromes and diffuse lymphoid hyperplasia of the

intestine This disease is considered idiopathic only

when a cause or association cannot be identified

The idiopathic form of LIP occurs most com-

monly between the ages of 50 and 70 but children

may be affected Women are more commonly

affected than men Cough dyspnea and progressive

shortness of breath occur and often are accompanied

by weight loss fever and adenopathy Dysproteine-

Fig 38 Lymphoid interstitial pneumonia (LIP) Liebowrsquos

LIP was characterized by dense inflammation accompanied

by variable fibrosis at scanning magnification Multi-

nucleated giant cells small granulomas and cysts may

be present

Fig 39 LIP The histopathologic hallmarks of the LIP

pattern include lsquolsquoan exquisitely interstitial infiltratersquorsquo that

must be proven to be polymorphous (not clonal) and consists

of lymphocytes plasma cells and large mononuclear cells

Fig 40 Pattern 4 alveolar filling neutrophils When

neutrophils fill the alveolar spaces the disease is usually

acute clinically and bacterial pneumonia leads the differ-

ential diagnosis Neutrophils are accompanied by necrosis

(upper right)

mia with abnormalities in gamma globulin production

is reported and pulmonary function studies show

restriction with abnormal gas exchange The pre-

dominant HRCT finding is ground-glass opacifica-

tion [90] although thickening of the bronchovascular

bundles and thin-walled cysts may be seen [90]

LIP is best thought of as a histopathologic pattern

rather than a diagnosis because LIP as proposed

initially has morphologic features that are difficult to

separate accurately from other lymphoplasmacellular

interstitial infiltrates including low-grade lymphomas

of extranodal marginal zone type (maltoma) The LIP

pattern requires clinical and laboratory correlation for

accurate assessment similar to organizing pneumo-

nia NSIP and DIP The histopathologic hallmarks of

the LIP pattern include diffuse interstitial infiltration

by lymphocytes plasmacytoid lymphocytes plasma

cells and histiocytes (Fig 39) Giant cells and small

granulomas may be present [91] Honeycombing with

interstitial fibrosis can occur Immunophenotyping

shows lack of clonality in the lymphoid infiltrate

When LIP accompanies HIV infection a wide age

range occurs and it is commonly found in children

[92ndash95] These HIV-infected patients have the same

nonspecific respiratory symptoms but weight loss is

more common Other features of HIV and AIDS

such as lymphadenopathy and hepatosplenomegaly

are also more common Mean survival is worse than

that of LIP alone with adults living an average of

14 months and children an average of 32 months

[96] The morphology of LIP with or without HIV

is similar

airspace filling

A significant number of ILDs are attended or

dominated by the presence of material filling the

alveolar spaces Depending on the composition of

this airspace filling process a narrow differential

diagnosis typically emerges The prototype for the

airspace filling pattern is organizing pneumonia in

which immature fibroblasts (myofibroblasts) form

polypoid growths within the terminal airways and

alveoli Organizing pneumonia is a common and

nonspecific reaction to lung injury Other material

also can occur in the airspaces such as neutrophils in

the case of bacterial pneumonia proteinaceous

material in alveolar proteinosis and even bone in

so-called lsquolsquoracemosersquorsquo or dendritic calcification

Neutrophils

When neutrophils fill the alveolar spaces the

disease is usually acute clinically and bacterial

pneumonia leads the differential diagnosis (Fig 40)

Rarely immunologically mediated pulmonary hem-

orrhage can be associated with brisk episodes of

neutrophilic capillaritis these cells can shed into the

alveolar spaces and mimic bronchopneumonia

Organizing pneumonia

When fibroblasts fill the alveolar spaces the

appropriate pathologic term is lsquolsquoorganizing pneumo-

niarsquorsquo although many clinicians believe that this is an

automatic indictment of infection Unfortunately the

lung has a limited capacity for repair after any injury

and organizing pneumonia often is a part of this

process regardless of the exact mechanism of injury

The more generic term lsquolsquoairspace organizationrsquorsquo is

preferable but longstanding habits are hard to

change Some of the more common causes of the

organizing pneumonia pattern are presented in Box 7

One particular form of diffuse lung disease is

characterized by airspace organization and is idio-

pathic This clinicopathologic condition was previ-

ously referred to as lsquolsquoidiopathic bronchiolitis obliterans

organizing pneumoniarsquorsquo (idiopathic BOOP) The name

of this disorder recently was changed to COP

Idiopathic cryptogenic organizing pneumonia

In 1983 Davison et al [97] described a group of

patients with COP and 2 years later Epler et al [98]

described similar cases as idiopathic BOOP The pro-

cess described in these series is believed to be the

same [1] as those cases described by Liebow and

Carrington in 1969 as lsquolsquoidiopathic bronchiolitis oblit-

erans interstitial pneumoniarsquorsquo [3] Currently a rea-

Box 7 Causes of the organizingpneumonia pattern

Organizing infectionsOrganizing DADDrug and toxic reactionsCollagen vascular diseasesHypersensitivity pneumonitisChronic eosinophil pneumoniaAirway diseases (eg bronchitis and

emphysema bronchiectasis cysticfibrosis aspiration pneumoniachronic bronchiolitis) complicatedby infection

Airway obstructionPeripheral reaction around abscesses

infarcts Wegenerrsquos granulomato-sis and others

Idiopathic (likely immunologic) lungdisease (COP)

sonable consensus has emerged regarding what is

being called COP [97ndash100] King and Mortensen

[101] recently compiled the findings from 4 major

case series reported from North America adding 18

of their own cases (112 cases in all) Based on

these compiled data the following description of

COP emerges

The evolution of clinical symptoms is subacute

(4 months on average and 3 months in most) and

follows a flu-like illness in 40 of cases The average

age at presentation is 58 years (range 21ndash80 years)

and there is no sex predominance Dyspnea and

cough are present in half the patients Fever is

common and leukocytosis occurs in approximately

one fourth The erythrocyte sedimentation rate is

typically elevated [102] Clubbing is rare Restrictive

lung disease is present in approximately half of the

patients with COP and the diffusing capacity is

reduced in most Airflow obstruction is mild and

typically affects patients who are smokers

Chest radiographs show patchy bilateral (some-

times unilateral) nonsegmental airspace consolidation

[103] which may be migratory and similar to those of

eosinophilic pneumonia Reticulation may be seen in

10 to 40 of patients but rarely is predominant

[103104] The most characteristic HRCT features of

COP are patchy unilateral or bilateral areas of

consolidation which have a predominantly peribron-

chial or subpleural distribution (or both) in approxi-

mately 60 of cases In 30 to 50 of cases small

ill-defined nodules (3ndash10 mm in diameter) are seen

[105ndash108] and a reticular pattern is seen in 10 to

30 of cases

The major histopathologic feature of COP is

alveolar space organization (so-called lsquolsquoMasson

bodiesrsquorsquo) but it also extends to involve alveolar ducts

and respiratory bronchioles in which the process has

a characteristic polypoid and fibromyxoid appearance

(Fig 41) The parenchymal involvement tends to be

patchy All of the organization seems to be recent

Unfortunately the term BOOP has become one of the

most commonly misused descriptions in lung pathol-

ogy much to the dismay of clinicians Pathologists

use the term to describe nonspecific organization that

occurs in alveolar ducts and alveolar spaces of lung

biopsies Clinicians hear the term BOOP or BOOP

pattern and often interpret this as a clinical diagnosis

of idiopathic BOOP Because of this misuse there is a

growing consensus [101109] regarding use of the

term COP to describe the clinicopathologic entity for

the following reasons (1) Although COP is primarily

an organizing pneumonia in up to 30 or more of

cases granulation tissue is not present in membra-

nous bronchioles and at times may not even be seen

Box 8 Conditions associated with adesquamative interstitial pneumoniandashlikereaction

Idiopathic DIPRB-ILDPulmonary histiocytosis X (PLCH)Drug reactions (especially associated

with amiodarone)Chronic alveolar hemorrhageEosinophilic pneumonia (especially

after corticosteroid therapy)Certain pneumoconioses (especially

talcosis hard metal disease andasbestosis)

Obstructive pneumonias (with foamyalveolar macrophages)

Exogenous lipoid pneumonia and lipidstorage diseases

Infection in immunosuppressedpatients (histiocytic pneumonia)

Fig 41 Pattern 4 alveolar filling COP The major

histopathologic feature of COP is alveolar space organiza-

tion (so-called Masson bodies) but this also extends to

involve alveolar ducts and respiratory bronchioles in which

the process has a characteristic polypoid and fibromyxoid

appearance (center)

in respiratory bronchioles [97] (2) The term lsquolsquobron-

chiolitis obliteransrsquorsquo has been used in so many

different ways that it has become a highly ambiguous

term (3) Bronchiolitis generally produces obstruction

to airflow and COP is primarily characterized by a

restrictive defect

The expected prognosis of COP is relatively good

In 63 of affected patients the condition resolves

mainly as a response to systemic corticosteroids

Twelve percent die typically in approximately

3 months The disease persists in the remaining sub-

set or relapses if steroids are tapered too quickly

Patients with COP who fare poorly frequently have

comorbid disorders such as connective tissue disease

or thyroiditis or have been taking nitrofurantoin

[110] A recent study showed that the presence of

reticular opacities in a patient with COP portended

a worse prognosis [111]

Macrophages

Macrophages are an integral part of the lungrsquos

defense system These cells are migratory and

generally do not accumulate in the lung to a

significant degree in the absence of obstruction of

the airways or other pathology In smokers dusty

brown macrophages tend to accumulate around the

terminal airways and peribronchiolar alveolar spaces

and in association with interstitial fibrosis The

cigarette smokingndashrelated airway disease known as

respiratory bronchiolitisndashassociated ILD is discussed

later in this article with the smoking-related ILDs

Beyond smoking some infectious diseases are

characterized by a prominent alveolar macrophage

reaction such as the malacoplakia-like reaction to

Rhodococcus equi infection in the immunocompro-

mised host or the mucoid pneumonia reaction to

cryptococcal pneumonia Conditions associated with

a DIP-like reaction are presented in Box 8

Eosinophilic pneumonia

Acute eosinophilic pneumonia was discussed

earlier with the acute ILDs but the acute and chronic

forms of eosinophilic pneumonia often are accom-

panied by a striking macrophage reaction in the

airspaces Different from the macrophages in a

patient with smoking-related macrophage accumula-

tion the macrophages of eosinophilic pneumonia

tend to have a brightly eosinophilic appearance and

are plump with dense cytoplasm Multinucleated

forms may occur and the macrophages may aggre-

gate in sufficient density to suggest granulomas in the

alveolar spaces When this occurs a careful search

for eosinophils in the alveolar spaces and reactive

type II cell hyperplasia is often helpful in distinguish-

ing eosinophilic lung disease from other conditions

characterized by a histiocytic reaction

Idiopathic desquamative interstitial pneumonia

In 1965 Liebow et al [112] described 18 cases of

diffuse lung diseases that differed in many respects

from UIP The striking histologic feature was the pre-

sence of numerous cells filling the airspaces Liebow

et al believed that the cells were chiefly desquamated

alveolar epithelial lining cells and coined the term

lsquolsquodesquamative interstitial pneumoniarsquorsquo It is currently

known that these cells are predominately macro-

phages however [113] DIP and the cigarette smok-

ingndashrelated disease known as RB-ILD are believed to

be similar if not identical diseases possibly repre-

senting different expressions of disease severity [115]

RB-ILD is discussed later in this article in the section

on smoking-related diffuse lung disease

The patients described by Liebow et al [112] were

on average slightly younger than patients with UIP

and their symptoms were usually milder Clubbing

was uncommon but in later series some patients with

clubbing were identified [4] Most patients have a

subacute lung disease of weeks to months of evo-

lution The predominant finding on the radiograph and

HRCT in patients with DIP consists of ground-glass

opacities particularly at the bases and at the costo-

phrenic angles [115] Some patients have mild reticu-

lar changes superimposed on ground-glass opacities

In lung biopsy the scanning magnification

appearance of DIP is striking (Fig 42) The alveolar

spaces are filled with lightly pigmented (brown)

macrophages and multinucleated cells are commonly

Fig 42 DIP The scanning magnification appearance of DIP is strik

(brown) macrophages and multinucleated cells are commonly pre

present Additional important features include the

relative preservation of lung architecture with only

mild thickening of alveolar walls and absence of

severe fibrosis or honeycombing [116ndash118] Inter-

stitial mononuclear inflammation is seen sometimes

with scattered lymphoid follicles The histologic

appearance of DIP is not specific It is commonly

present in other diffuse and localized lung diseases

including UIP asbestosis [119] and other dust-

related diseases [120] DIP-like reactions occur after

nitrofurantoin therapy [121122] and in alveolar

spaces adjacent to the nodules of PLCH (see later

section on smoking-related diseases)

Cases have been reported in which classic DIP

lsquolsquoprogressed to fibrosing alveolitisrsquorsquo [117123] It

seems clear that DIP represents a nonspecific reaction

and more commonly occurs in smokers It is critical

to distinguish between DIP and UIP especially

because these diseases are regarded as different from

one another Research has shown conclusively that

the clinical features are different the prognosis is

much better in DIP and DIP may respond to

corticosteroid administration [124] whereas UIP

does not [62]

Proteinaceous material

When eosinophilic material fills the alveolar

spaces the differential diagnosis includes pulmonary

edema and alveolar proteinosis

Pulmonary alveolar proteinosis

PAP (alveolar lipoproteinosis) is a rare diffuse

lung disease characterized by the intra-alveolar

ing (A) The alveolar spaces are filled with lightly pigmented

sent (B)

Fig 44 PAP Embedded clumps of dense globular granules

and cholesterol clefts are seen

accumulation of lipid-rich eosinophilic material

[125] PAP likely occurs as a result of overproduction

of surfactant by type II cells impaired clearance of

surfactant by alveolar macrophages or a combination

of these mechanisms The disease can occur as an

idiopathic form but also occurs in the settings of

occupational disease (especially dust-related) drug-

induced injury hematologic diseases and in many

settings of immunodeficiency [125ndash128] PAP is

commonly associated with exposure to inhaled

crystalline material and silica although other sub-

stances have been implicated [126] The idiopathic

form is the most common presentation with a male

predominance and an age range of 30 to 50 years

The usual presenting symptom is insidious dyspnea

sometimes with cough [129] although the clinical

symptoms are often less dramatic than the radio-

logic abnormalities

Chest radiographs show extensive bilateral air-

space consolidation that involves mainly the perihilar

regions CT demonstrates what seems to be smooth

thickening of lobular septa that is not seen on the

chest radiograph The thickening of lobular septae

within areas of ground-glass attenuation is character-

istic of alveolar proteinosis on CT and is referred to as

lsquolsquocrazy pavingrsquorsquo [130] The areas of ground-glass

attenuation and consolidation are often sharply

demarcated from the surrounding normal lung with-

out an apparent anatomic correlation [130ndash132]

Histopathologically the scanning magnification

appearance is distinctive if not diagnostic Pink

granular material fills the airspaces often with a

rim of retraction that separates the alveolar wall

slightly from the exudate (Fig 43) Embedded

clumps of dense globular granules and cholesterol

clefts are seen (Fig 44) The periodic-acid Schiff

Fig 43 PAP Pink granular material fills the airspaces in

PAP often with a rim of retraction that separates the alveolar

wall slightly from the exudate

stain reveals a diastase-resistant positive reaction in

the proteinaceous material of PAP Dramatic inflam-

matory changes should suggest comorbid infection

The idiopathic form of PAP has an excellent

prognosis Many patients are only mildly symptom-

atic In patients with severe dyspnea and hypoxemia

treatment can be accomplished with one or more

sessions of whole lung lavage which usually induces

remission and excellent long-term survival [133]

nodules

Some ILDs are dominated by or significantly

associated with nodules For most of the diffuse

ILDs the nodules are small and appreciated best

under the microscope In some instances nodules

may be sufficiently large and diffuse in distribution

that they are identified on HRCT In others cases a

few large nodules may be present in two or more

lobes or bilaterally (eg Wegener granulomatosis) For

neoplasms that diffusely involve the lung the nodular

pattern is overwhelmingly represented (eg lymphan-

gitic carcinomatosis) The differential diagnosis of the

nodular pattern is presented in Box 9

Nodular granulomas

When granulomas are present in a lung biopsy the

differential diagnosis always includes infection

sarcoidosis and berylliosis aspiration pneumonia

and some lymphoproliferative diseases Hypersensi-

tivity pneumonitis is classically grouped with lsquolsquogran-

Box 9 Diffuse lung diseases with anodular pattern

Miliary infections (bacterial fungalmycobacterial)

PLCHSarcoidosisSilicosisWegenerrsquos granulomatosisCarcinomas and sarcomasLymphomas

Box 10 Diffuse diseases associated withgranulomatous inflammation

SarcoidosisHypersensitivity pneumonitis (gener-

ally not well formed)Drug reactionsGranulomatous infectionsIntravenous talcosisPneumoconioses (eg inhalation talco-

sis berylliosis)Sjogrenrsquos syndromeAspiration pneumoniaCertain tumors especially lymphomas

ulomatous lung diseasersquorsquo but this condition rarely

produces well-formed granulomas Hypersensitivity

pneumonia is discussed under Pattern 3 because the

pattern is more one of cellular chronic interstitial

pneumonia with granulomas being subtle

Granulomatous infection

Most nodular granulomatous reactions in the lung

are of infectious origin until proven otherwise

especially in the presence of necrosis The infectious

diseases that characteristically produce well-formed

granulomas are typically caused by mycobacteria

fungi and rarely bacteria Sometimes Pneumocystis

infection produces a nodular pattern A list of the

diffuse lung diseases associated with granulomas is

presented in Box 10

Sarcoidosis

Sarcoidosis is a systemic granulomatous disease

of uncertain origin The disease commonly affects the

lungs [134135] The origin pathogenesis and

epidemiology of sarcoidosis suggest that it is a

disorder of immune regulation [136ndash138] The

observation that sarcoid granulomas recur after lung

transplantation [139ndash141] seems to underscore fur-

ther the notion that this is an acquired systemic

abnormality of immunity It also emphasizes the fact

that even profound immunosuppression (such as that

used in transplantation) may be ineffective in halting

disease progression for the subset whose condition

persists and progresses to lung fibrosis

Sarcoidosis occurs most frequently in young

adults but has been described in all ages There is a

decreased incidence of sarcoidosis in cigarette smok-

ers Many patients with intrathoracic sarcoidosis are

symptom free Systemic manifestations may be

identified (in decreasing frequency) in lymph nodes

eyes liver skin spleen salivary glands bone heart

and kidneys Breathlessness is the most common

pulmonary symptom

The chest radiographic appearance is often char-

acteristic with a combination of symmetrical bilateral

hilar and paratracheal lymph node enlargement

together with a varied pattern of parenchymal

involvement including linear nodular and ground-

glass opacities [142] In approximately 25 of the

patients the radiographic appearance is atypical and

in approximately 10 it is normal [143] Staging of

the disease is based on pattern of involvement on

plain chest radiographs only [135142]

The histopathologic hallmark of sarcoidosis is the

presence of well-formed granulomas without necrosis

(Fig 45) Granulomas are classically distributed

along lymphatic channels of the bronchovascular

bundles interlobular septa and pleura (Fig 46) The

area between granulomas is frequently sclerotic and

adjacent small granulomas tend to coalesce into larger

nodules Because of involvement of the broncho-

vascular bundles and the characteristic histology

sarcoidosis is one of the few diffuse lung diseases

that can be diagnosed with a high degree of success

by transbronchial biopsy (Fig 47) [144] Although

necrosis is not a feature of the disease sometimes

Fig 45 Sarcoidosis The histopathologic hallmark of

sarcoidosis is the presence of well-formed granulomas

without necrosis

Fig 47 Sarcoidosis Because of involvement of the

bronchovascular bundles and the characteristic histology

sarcoidosis is one of the few diffuse lung diseases that can

be diagnosed with a high degree of success by trans-

bronchial biopsy An interstitial granuloma is present at the

bifurcation of a bronchiole which makes it an excellent

target for biopsy

foci of granular eosinophilic material may be seen at

the center of the granulomas The lsquolsquodirtyrsquorsquo necrosis so

typical of mycobacterial and fungal disease granu-

lomas is not seen Distinctive inclusions may be

present within giant cells in the granulomas such as

asteroid and Schaumannrsquos bodies (Fig 48) but these

can be seen in other granulomatous diseases There

is a generally held belief that a mild interstitial inflam-

matory infiltrate accompanies granulomas in sar-

coidosis [145ndash147] If this lsquolsquointerstitial pneumoniarsquorsquo

of sarcoidosis exists it is subtle in the best example

and consists of a few lymphocytes mononuclear

cells and macrophages

The prognosis for patients with sarcoidosis is

excellent The disease typically resolves or improves

Fig 46 Sarcoidosis Granulomas are classically distributed

along lymphatic channels in sarcoidosis that involves the

bronchovascular bundles interlobular septae and pleura

with only 5 to 10 of patients developing signifi-

cant pulmonary fibrosis Most patients recover com-

pletely with minimal residual disease

Berylliosis

Occupational exposure to beryllium was first

recognized as a health hazard in fluorescent lamp

factory workers The use of beryllium in this industry

was discontinued but because of berylliumrsquos remark-

able structural characteristics it continues to be used

in metallic alloy and oxide forms in numerous

industries Berylliosis may occur as acute and chronic

forms The acute disease is usually seen in refinery

Fig 48 Sarcoidosis Distinctive inclusions may be present

within giant cells in the granulomas such as this asteroid

body These are not specific for sarcoidosis and are not seen

in every case

Fig 50 Diffuse panbronchiolitis A characteristic low-

magnification appearance is that of nodular bronchiolocen-

tric lesions

workers and produces DAD Chronic berylliosis is a

multiorgan disease but the lung is most severely

affected The radiologic findings are similar to

sarcoidosis except that hilar and mediastinal aden-

opathy is seen in only 30 to 40 of cases compared

with 80 to 90 in sarcoidosis [148149] Beryllio-

sis is characterized by nonnecrotizing lung paren-

chymal granulomas indistinguishable from those of

sarcoidosis [150]

Nodular lymphohistiocytic lesions (lymphoid cells

lymphoid follicles variable histiocytes)

Follicular bronchiolitis

When lymphoid germinal centers (secondary

lymphoid follicles) are present in the lung biopsy

(Fig 49) the differential diagnosis always includes a

lung manifestation of RA Sjogrenrsquos syndrome or

other systemic connective tissue disease immuno-

globulin deficiency diffuse lymphoid hyperplasia

and malignant lymphoma When in doubt immuno-

histochemical studies and molecular techniques may

be useful in excluding a neoplastic process

Diffuse panbronchiolitis

Diffuse panbronchiolitis can produce a dramatic

diffuse nodular pattern in lung biopsies This

condition is a distinctive form of chronic bronchi-

olitis seen almost exclusively in people of East

Asian descent (ie Japan Korea China) Diffuse

panbronchiolitis may occur rarely in individuals in

the United States [151ndash153] and in patients of non-

Asian descent

Fig 49 Follicular bronchiolitis Lymphoid germinal cen-

ters (secondary lymphoid follicles) are present around a

severely compromised bronchiole in this case of follicu-

lar bronchiolitis

Severe chronic inflammation is centered on

respiratory bronchioles early in the disease followed

by involvement of distal membranous bronchioles

and peribronchiolar alveolar spaces as the disease

progresses A characteristic low magnification ap-

pearance is that of nodular bronchiolocentric lesions

(Fig 50) The characteristic and nearly diagnostic

feature of diffuse panbronchiolitis is the accumulation

of many pale vacuolated macrophages in the walls

and lumens of respiratory bronchioles and in adjacent

airspaces (Fig 51) Japanese investigators suspect

that the condition occurs in the United States and has

been underrecognized This view was substantiated

Fig 51 Diffuse panbronchiolitis The accumulation of many

pale vacuolated macrophages in the walls and lumens of

respiratory bronchioles and in adjacent airspaces is typical of

diffuse panbronchiolitis This appearance is best appreciated

at the upper edge of the lesion

Fig 52 Lymphangitic carcinomatosis Histopathologically

malignant tumor cells are typically present in small

aggregates within lymphatic channels of the bronchovascu-

lar sheath and pleura

Box 11 Causes of a normal biopsy inclinically apparent interstitial lung disease

Subtle interstitial inflammatoryinfiltrate or early diffusealveolar damage

Small airway diseasePulmonary edemaPulmonary emboli (including

fat emboli)LAM with inconspicuous lesionsPulmonary vascular diseaseSampling error (eg histiocytosis X

lesions may not be included)

by a study of 81 US patients previously diagnosed

with cellular chronic bronchiolitis [151] On review 7

of these patients were reclassified as having diffuse

panbronchiolitis (86)

Nodules of neoplastic cells

Isolated nodules of neoplastic cells occur com-

monly as primary and metastatic cancer in the lung

When nodules of neoplastic cells are seen in the

radiologic context of ILD lymphangitic carcinoma-

tosis leads the differential diagnosis LAM also can

produce diffuse ILD typically with small nodules

and cysts LAM is discussed later in this article under

Pattern 6 PLCH also can produce small nodules and

cysts diffusely in the lung (typically in the upper lung

zones) and this entity is discussed with the smoking-

related interstitial diseases

Lymphangitic carcinomatosis

Pulmonary lymphangitic carcinomatosis (lym-

phangitis carcinomatosa) is a form of metastatic

carcinoma that involves the lung primarily within

lymphatics The disease produces a miliary nodular

pattern at scanning magnification Lymphangitic

carcinoma is typically adenocarcinoma The most

common sites of origin are breast lung and stomach

although primary disease in pancreas ovary kidney

and uterine cervix also can give rise to this

manifestation of metastatic spread Patients often

present with insidious onset of dyspnea that is

frequently accompanied by an irritating cough The

radiographic abnormalities include linear opacities

Kerley B lines subpleural edema and hilar and

mediastinal lymph node enlargement [154] The

HRCT findings are highly characteristic and accu-

rately reflect the microscopic distribution in this

disease with uneven thickening of the bronchovas-

cular bundles and lobular septa which gives them a

beaded appearance [155156]

Histopathologically malignant tumor cells are

typically present in small aggregates within lym-

phatic channels of the bronchovascular sheath and

pleura (Fig 52) Variable amounts of tumor may be

present throughout the lung in the interstitium of the

alveolar walls in the airspaces and in small muscular

pulmonary arteries This latter finding (microangio-

pathic obliterative endarteritis) may be the origin of

the edema inflammation and interstitial fibrosis that

frequently accompany the disease and likely accounts

for the clinical and radiologic impression of nonneo-

plastic diffuse lung disease [154157]

Pattern 6 interstitial lung disease with subtle

findings in surgical biopsies (chronic evolution)

A limited differential diagnosis is invoked by the

relative absence of abnormalities in a surgical lung

biopsy (Box 11) Three main categories of disease

emerge in this setting (1) diseases of the small

Fig 53 Rheumatoid bronchiolitis In this example of

rheumatoid bronchiolitis complex bronchiolar metaplasia

involves a membranous bronchiole accompanied by fol-

licular bronchiolitis Small rheumatoid nodules (similar to

those that occur around the joints) also can be seen

occasionally in the walls of airways which results in partial

or total occlusion

airways (eg constrictive bronchiolitis) (2) vasculo-

pathic conditions (eg pulmonary hypertension) and

(3) two diseases that may be dominated by cysts the

rare disease known as LAM and PLCH in the in-

active or healed phase of the disease All of these may

be dramatic in biopsy specimens but when con-

fronted with the lsquolsquonearly normalrsquorsquo lung biopsy in a pa-

tient with significant clinical disease these three

groups of diseases dominate the differential diagnosis

Small airways disease and constrictive bronchiolitis

Obliteration of the small membranous bronchioles

can occur as a result of infection toxic inhalational

exposure drugs systemic connective tissue diseases

and as an idiopathic form Outside of the setting of

lung transplantation in which so-called lsquolsquobronchio-

litis obliteransrsquorsquo (having histopathology similar to

constrictive bronchiolitis) occurs as a chronic mani-

festation of organ rejection the diagnosis presents a

challenge for pulmonologists and pathologists alike

In this section we present a few recognized forms of

nonndashtransplant-associated constrictive bronchiolitis

Irritants and infections

Many irritant gases can produce severe bronchi-

olitis This inflammatory injury may be followed by

the accumulation of loose granulation tissue and

finally by complete stenosis and occlusion of the

airways The best known of these agents are nitrogen

dioxide [158] sulfur dioxide [159] and ammonia

[160] Viral infection also can cause permanent

bronchiolar injury particularly adenovirus infection

[161] Mycoplasma pneumonia is also cited as a

potential cause [162] The course of events is similar

to that for the toxic gases Variable degrees of

bronchiectasis or bronchioloectasis may occur sec-

ondarily up- and downstream from the area of

occlusion Lung biopsy is performed rarely and then

usually because the patient is young and unusual

airflow obstruction is present Occasionally mixed

obstruction and restriction may occur presumably on

the basis of diffuse peribronchiolar scarring This

airway-associated scarring may produce CT findings

of lsquolsquointerstitialrsquorsquo disease The airway lesions are subtle

but can be recognized by variable reduction in

bronchiolar luminal diameter compared with the

adjacent pulmonary artery branch (Normally these

should be roughly equal in diameter when viewed

as cross-sections) The diagnosis depends on careful

clinical correlation and sometimes the addition of a

comparison between inspiratory and expiratory

HRCT scans which typically shows prominent

mosaic air trapping

Rheumatoid bronchiolitis

Patients with RA may develop constrictive bron-

chiolitis as a consequence of their disease In some

patients small rheumatoid nodules can be seen in the

walls of airways which results in their partial or total

occlusion (Fig 53) From a practical point of view

the lesions are focal within the airways often in small

bronchi and may not be visualized easily in the

biopsy specimen Because of the widespread recog-

nition of rheumatoid bronchiolitis biopsy is rarely

performed in these patients Morphologically scat-

tered occlusion of small bronchi and bronchioles is

observed and is associated with the presence of loose

connective tissue in their lumens

Neuroendocrine cell hyperplasia with occlusive

bronchiolar fibrosis

In 1992 Aguayo et al [163] reported six patients

with moderate chronic airflow obstruction all of

whom never smoked Diffuse neuroendocrine cell

hyperplasia of the bronchioles associated with partial

or total occlusion of airway lumens by fibrous tissue

was present in all six patients (Fig 54) Three of the

patients also had peripheral carcinoid tumors and

three had progressive dyspnea

In a study of 25 peripheral carcinoid tumors that

occurred in smokers and nonsmokers Miller and

Muller [164] identified 19 patients (76) with

neuroendocrine cell hyperplasia of the airways which

occurred mostly in bronchioles Eight patients (32)

Fig 54 Neuroendocrine cell hyperplasia with occlusive bronchiolar fibrosis (A) Diffuse neuroendocrine cell hyperplasia of the

bronchioles associated with partial or total occlusion of airway lumens by fibrous tissue is a rare cause of unexplained airflow

obstruction (B) An immunohistochemical stain for the neuroendocrine marker synaptophysin stains the hyperplastic

neuroendocrine cells red (Immuno-alkaline phosphatase method red chromogen)

Fig 55 Cryptogenic constrictive bronchiolitis is commonly

recognized as an expression of chronic organ rejection in the

setting of lung transplantation (bronchiolitis obliterans

syndrome) It also occurs on the basis of many other injuries

and exists as an idiopathic form In this photograph taken

from a biopsy in a lung transplant patient the bronchiole can

be seen at center right but the lumen is filled with loose

fibroblasts (note the adjacent pulmonary artery upper left)

were found to have occlusive bronchiolar fibrosis

Four of the 8 had mild chronic airflow obstruction

and 2 of these 4 patients were nonsmokers

An increase in neuroendocrine cells was present in

more than 20 of bronchioles examined in lung

adjacent to the tumor and in tissue blocks taken well

away from tumor Less than half of these airways

were partially or totally occluded The mildest lesion

consisted of linear zones of neuroendocrine cell

hyperplasia with focal subepithelial fibrosis The

most severely involved bronchioles showed total

luminal occlusion by fibrous tissue with few visible

neuroendocrine cells

In both of these studies most of the patients with

airway neuroendocrine hyperplasia were women Pre-

sumably fibrosis in this setting of neuroendocrine

hyperplasia is related to one or more peptides se-

creted by neuroendocrine cells possibly these cells are

more effective in stimulating airway fibrosis inwomen

Cryptogenic constrictive bronchiolitis

Unexplained chronic airflow obstruction that

occurs in nonsmokers may be a result of selective

(and likely multifocal) obliteration of the membra-

nous bronchioles (constrictive bronchiolitis) In a

study of 2094 patients with a forced expiratory

volume in the first second (FEV1) of less than

60 of predicted [165] 10 patients (9 women) were

identified They ranged in age from 27 to 60 years

Five were found to have RA and presumably

rheumatoid bronchiolitis The other 5 had airflow

obstruction of unknown cause believed to be caused

by lsquolsquobronchiolitisrsquorsquo Other studies also identified a

cryptogenic form of bronchiolar disease that produces

airflow obstruction [166167] When biopsies have

been performed constrictive bronchiolitis seems to

be the common pathologic manifestation (Fig 55)

It is fair to conclude that a rare but fairly distinct

clinical syndrome exists that consists of mild airflow

obstruction and usually affects middle-aged women

who manifest nonspecific respiratory symptoms

Fig 56 Vasculopathic disease Diseases that involve the small arteries and veins of the lung can be subtle when viewed from low

magnification under the microscope (A) At higher magnification scattered plexiform vascular lesions (B) are present in this

example of primary pulmonary hypertension

Fig 57 Vasculopathic disease This is not to imply that the

entities of pulmonary hypertension capillary hemangioma-

tosis and veno-occlusive disease are always subtle This

example of pulmonary veno-occlusive disease resembles an

inflammatory ILD at scanning magnification

such as cough and dyspnea It is possible that these

cryptogenic cases of constrictive bronchiolitis are

manifestations of undeclared systemic connective

tissue disease the sequelae of prior undetected

community-acquired infections (eg viral myco-

plasmal chlamydial) or exposure to toxin

Interstitial lung disease dominated by

airway-associated scarring

A form of small airway-associated ILD has been

described in recent years under the names lsquolsquoidiopathic

bronchiolocentric interstitial pneumoniarsquorsquo [168] and

lsquolsquoairway-centered interstitial fibrosisrsquorsquo [169] Affected

patients have more of a restrictive than obstructive

functional deficit and the process is characterized

histopathologically by the presence of significant

small airwayndashassociated scarring similar to that seen

in forms of chronic hypersensitivity pneumonia

certain chronic inhalational injuries (including sub-

clinical chronic aspiration pneumonia) and even

some examples of late-stage inactive PLCH (which

typically lacks characteristic Langerhansrsquo cells) This

morphologic group may pose diagnostic challenges

because of the absence of interstitial inflammatory

changes despite the radiologic and functional impres-

sion of ILD

Vasculopathic disease

Diseases that involve the small arteries and veins

of the lung can be subtle when viewed from low

magnification under the microscope (Fig 56) This is

not to imply that the entities of pulmonary hyper-

tension capillary hemangiomatosis and veno-occlu-

sive disease are always subtle (Fig 57) A complete

discussion of these disease conditions is beyond the

scope of this article however when the lung biopsy

has little pathology evident at scanning magnifica-

tion a careful evaluation of the pulmonary arteries

and veins is always in order

Lymphangioleiomyomatosis

Pulmonary LAM is a rare disease characterized by

an abnormal proliferation of smooth muscle cells in

Fig 59 LAM The walls of these spaces have variable

amounts of bundled spindled and slightly disorganized

smooth muscle cells

the pulmonary interstitium and associated with the

formation of cysts [170ndash173] The disease is

centered on lymphatic channels blood vessels and

airways LAM is a disease of women typically in

their childbearing years The disease does occur in

older women and rarely in men [174] There is a

strong association between the inherited genetic

disorder known as tuberous sclerosis complex and

the occurrence of LAM Most patients with LAM do

not have tuberous sclerosis complex but approxi-

mately one fourth of patients with tuberous sclerosis

complex have LAM as diagnosed by chest HRCT

[175] The most common presenting symptoms are

spontaneous pneumothorax and exertional dyspnea

Others symptoms include chyloptosis hemoptysis

and chest pain The characteristic findings on CT are

numerous cysts separated by normal-appearing lung

parenchyma The cysts range from 2 to 10 mm in

diameter and are seen much better with HRCT

[171176]

The appearance of the abnormal smooth muscle in

LAM is sufficiently characteristic so that once

recognized it is rarely forgotten Cystic spaces are

present at low magnification (Fig 58) The walls of

these spaces have variable amounts of bundled

spindled cells (Fig 59) The nuclei of these spindled

cells (Fig 60) are larger than those of normal smooth

muscle bundles seen around alveolar ducts or in the

walls of airways or vessels Immunohistochemical

staining is positive in these cells using antibodies

directed against the melanoma markers HMB45 and

Mart-1 (Fig 61) These findings may be useful in the

evaluation of transbronchial biopsy in which only a

Fig 58 LAM Cystic spaces are present at low

magnification

few spindled cells may be present Actin desmin

estrogen receptors and progesterone receptors also

can be demonstrated in the spindled cells of LAM

[177] Other lung parenchymal abnormalities may be

present including peculiar nodules of hyperplastic

pneumocytes (Fig 62) that lack immunoreactivity

for HMB45 or Mart-1 but show immunoreactivity for

cytokeratins and surfactant apoproteins [178] These

epithelial lesions have been referred to as lsquolsquomicro-

nodular pneumocyte hyperplasiarsquorsquo

The expected survival is more than 10 years

All of the patients who died in one large series did

Fig 60 LAM The nuclei of these spindled cells are larger

than those of normal smooth muscle bundles seen around

alveolar ducts or in the walls of airways or vessels

Fig 61 LAM Immunohistochemical staining is positive

in these cells using antibodies directed against the mela-

noma markers HMB45 and Mart-1 (immunohistochemical

stain for HMB45 immuno-alkaline phosphatase method

brown chromogen)

so within 5 years of disease onset [179] which

suggests that the rate of progression can vary widely

among patients

Interstitial lung disease related to cigarette

smoking

DIP was discussed earlier in this article as an

idiopathic interstitial pneumonia In this section we

Fig 62 Micronodular pneumocyte hyperplasia in LAM

Other lung parenchymal abnormalities may be present

including peculiar nodules of hyperplastic pneumocytes

referred to as micronodular pneumocyte hyperplasia These

cells do not show reactivity to HMB45 or MART1 but do

stain positively with antibodies directed against epithelial

markers and surfactant

present two additional well-recognized smoking-

related diseases the first of which is related to DIP

and likely represents an earlier stage or alternate

manifestation along a spectrum of macrophage

accumulation in the lung in the context of cigarette

smoking Conceptually respiratory bronchiolitis

RB-ILD DIP and PLCH can be viewed as interre-

lated components in the setting of cigarette smoking

(Fig 63)

Respiratory bronchiolitisndashassociated interstitial lung

disease

Respiratory bronchiolitis is a common finding in

the lungs of cigarette smokers and some investiga-

tors consider this lesion to be a precursor of centri-

acinar emphysema Respiratory bronchiolitis affects

the terminal airways and is characterized by delicate

fibrous bands that radiate from the peribronchiolar

connective tissue into the surrounding lung (Fig 64)

Dusty appearing tan-brown pigmented alveolar

macrophages are present in the adjacent airspaces

and a mild amount of interstitial chronic inflamma-

tion is present Bronchiolar metaplasia (extension of

terminal airway epithelium to alveolar ducts) is

usually present to some degree In the bronchioles

submucosal fibrosis may be present but constrictive

changes are not a characteristic finding When

respiratory bronchiolitis becomes extensive and

patients have signs and symptoms of ILD use of

the term RB-ILD has been suggested [180181] The

exact relationship between RB-ILD and DIP is

unclear and in smokers these two conditions are

probably part of a continuous spectrum of disease

Symptoms of RB-ILD include dyspnea excess

sputum production and cough [182] Rarely patients

may be asymptomatic Men are slightly more

Fig 63 Smoking-related ILD RB-ILD DIP and PLCH

can be viewed as interrelated components in the setting of

cigarette smoking

Fig 64 Respiratory bronchiolitis affects the terminal

airways of smokers and is characterized by delicate fibrous

bands that radiate from the peribronchiolar connective tissue

into the surrounding lung Scant peribronchiolar chronic

inflammation is typically present and brown pigmented

smokers macrophages are seen in terminal airways and

peribronchiolar alveoli

Fig 65 In RB-ILD denser aggregates of lightly pigmented

macrophages are present in the airspaces around the

terminal airways with variable bronchiolar metaplasia

and more interstitial fibrosis than seen in simple respira-

tory bronchiolitis

Fig 66 RB-ILD The relatively patchy (nonconfluent)

nature of the disease is important in differentiating RB-

ILD from DIP

commonly affected than women and the mean age of

onset is approximately 36 years (range 22ndash53 years)

The average pack year smoking history is 32 (range

7ndash75)

Most patients with respiratory bronchiolitis alone

have normal radiologic studies The most common

findings in RB-ILD include thickening of the

bronchial walls ground-glass opacities and poorly

defined centrilobular nodular opacities [183] Be-

cause most patients with RB-ILD are heavy smokers

centrilobular emphysema is common

On histopathologic examination lightly pig-

mented macrophages are present in the airspaces

around the terminal airways with variable bronchiolar

metaplasia (Fig 65) Iron stains may reveal delicate

positive staining within these cells The relatively

patchy nature of the disease is important in differ-

entiating RB-ILD from DIP (Fig 66) A spectrum of

pathologic severity emerges with isolated lesions of

respiratory bronchiolitis on one end and diffuse

macrophage accumulation in DIP on the other RB-

ILD exists somewhere in between The diagnosis of

RB-ILD should be reserved for situations in which

respiratory bronchiolitis is prominent with associated

clinical and pathologic ILD [184] No other cause for

ILD should be apparent The prognosis is excellent

and there does not seem to be evidence for pro-

gression to end-stage fibrosis in the absence of other

lung disease

Pulmonary Langerhansrsquo cell histiocytosis

PLCH (formerly known as pulmonary eosino-

philic granuloma or pulmonary histiocytosis X) is

currently recognized as a lung disease strongly

associated with cigarette smoking Proliferation of

Langerhansrsquo cells is associated with the formation of

stellate airway-centered lung scars and cystic change

in affected individuals The incidence of the disease is

unknown but it is generally considered to be a rare

complication of cigarette smoking [185]

Fig 67 PLCH The classic lsquolsquoMedusa-headrsquorsquo lesion of PLCH

is illustrated in this figure Tractional emphysema with cyst

formation is typical at the perimeter of the lesions Fig 69 PLCH The Langerhansrsquo cell has a slightly pale

basophilic nucleus with characteristic sharp nuclear folds

that resemble crumpled tissue paper

PLCH affects smokers between the ages of 20 and

40 The most common presenting symptom is cough

with dyspnea but some patients may be asymptom-

atic despite chest radiographic abnormalities Chest

pain fever weight loss and hemoptysis have been

reported to occur HRCT scan shows nearly patho-

gnomonic changes including predominately upper

and middle lung zone nodules and cysts [185186]

The classic lesion of PLCH is illustrated in

Fig 67 Characteristically the nodules have a stellate

shape and are always centered on the bronchioles

Fig 68 PLCH Immunohistochemistry using antibodies

directed against S100 protein and CD1a is helpful in

highlighting numerous positively stained Langerhansrsquo cells

within the cellular lesions (immunohistochemical stain using

antibodies directed against S100 protein) (immuno-alkaline

phosphatase method brown chromogen)

Pigmented alveolar macrophages and variable num-

bers of eosinophils surround and permeate the

lesions Immunohistochemistry using antibodies

directed against S100 proteinCD1a highlight numer-

ous positive Langerhansrsquo cells at the periphery of the

cellular lesions (Fig 68) The Langerhansrsquo cell has a

slightly pale basophilic nucleus with characteristic

sharp nuclear folds that resemble crumpled tissue

paper (Fig 69) One or two small nucleoli are usually

present Late lesions (so-called lsquolsquoinactiversquorsquo or

resolved PLCH) consist only of fibrotic centrilobular

scars [187] with a stellate configuration (Fig 70)

Microcysts and honeycombing may be present

Fig 70 PLCH Late lesions (so-called lsquolsquoinactiversquorsquo or

resolved PLCH) consist only of fibrotic centrilobular scars

with a stellate configuration

Immunohistochemistry for S-100 protein and CD1a

may be used to confirm the diagnosis but this is

usually unnecessary and even may be confounding in

late lesions in which Langerhansrsquo cells may be

sparse and the stellate scar is the diagnostic lesion

Up to 20 of transbronchial biopsies in patients

with Langerhansrsquo cell histiocytosis may have diag-

nostic changes The presence of more than 5

Langerhansrsquo cells in bronchoalveolar lavage is

considered diagnostic of Langerhansrsquo cell histiocy-

tosis in the appropriate clinical setting Unfortunately

cigarette smokers without Langerhansrsquo cell histiocy-

tosis also may have increased numbers of Langer-

hansrsquo cells in the bronchoalveolar lavage

References

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lung 2nd edition New York7 Thieme Medical

Publishers 1995 p 589ndash737

[2] Carrington CB Gaensler EA Clinical-pathologic

approach to diffuse infiltrative lung disease In

Thurlbeck W Abell M editors The lung structure

function and disease Baltimore7 Williams amp Wilkins

1978 p 58ndash67

[3] Liebow A Carrington C The interstitial pneumonias

In Simon M Potchen E LeMay M editors Fron-

tiers of pulmonary radiology pathophysiologic

roentgenographic and radioisotopic considerations

Orlando7 Grune amp Stratton 1969 p 109ndash42

[4] Travis W King T Bateman E Lynch DA Capron F

Colby TV et al ATSERS international multidisci-

plinary consensus classification of the idiopathic

interstitial pneumonias Am J Respir Crit Care Med

2002165(2)277ndash304

[5] Gillett D Ford G Drug-induced lung disease In

1978 p 21ndash42

[6] Myers JL Diagnosis of drug reactions in the lung

Monogr Pathol 19933632ndash53

[7] Sovijarvi A Lemola M Stenius B Nitrofurantoin-

induced acute subacute and chronic pulmonary re-

actions Scand J Respir Dis 19775841ndash50

[8] Cooper JAD White DA Mathay RA Drug-induced

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Dis 1986133321ndash38 488ndash502

[9] Camus PH Foucher P Bonniaud PH et al Drug-

induced infiltrative lung disease Eur Respir J Suppl

20013293sndash100s

[10] Siegel H Human pulmonary pathology associated

with narcotic and other addictive drugs Hum Pathol

1972355ndash70

[11] Rosenow E Drug-induced pulmonary disease Clin

Notes Respir Dis 1977163ndash12

[12] Davis P Burch R Pulmonary edema and salicylate

intoxication letter Ann Intern Med 197480553ndash4

[13] Abid SH Malhotra V Perry M Radiation-induced

and chemotherapy-induced pulmonary injury Curr

Opin Oncol 200113(4)242ndash8

[14] Bennett DE Million PR Ackerman LV Bilateral

radiation pneumonitis a complication of the radio-

therapy of bronchogenic carcinoma A report and

analysis of seven cases with autopsy Cancer 1969

231001ndash18

[15] Phillips T Wharham M Margolis L Modification of

radiation injury to normal tissues by chemotherapeu-

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[16] Gaensler E Carrington C Peripheral opacities in

chronic eosinophilic pneumonia the photographic

negative of pulmonary edema AJR Am J Roentgenol

19771281ndash13

[17] Buchheit J Eid N Rodgers GJ et al Acute eo-

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syndrome Am Rev Respir Dis 1992145716ndash8

[18] Hunninghake G Fauci A Pulmonary involvement in

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[19] Yousem S Colby T Carrington C Lung biopsy in

rheumatoid arthritis Am Rev Respir Dis 1985131

770ndash7

[20] Sahn S The pleura Am Rev Respir Dis 1988138

184ndash234

[21] Matthay R Schwarz M Petty T et al Pulmonary

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view of twelve cases with acute lupus pneumonitis

Medicine 197454397ndash409

[22] Myers JL Katzenstein AA Microangiitis in lupus-

induced pulmonary hemorrhage Am J Clin Pathol

198685(5)552ndash6

[23] Tazelaar HD Viggiano RW Pickersgill J et al

Interstitial lung disease in polymyositis and dermato-

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with histologic findings Am Rev Respir Dis 1990

141(3)727ndash33

[24] Beasley MB Franks TJ Galvin JR et al Acute

fibrinous and organizing pneumonia a histological

pattern of lung injury and possible variant of diffuse

alveolar damage Arch Pathol Lab Med 2002126(9)

1064ndash70

[25] Albelda SM Gefter WB Epstein DM et al Diffuse

pulmonary hemorrhage a review and classification

Radiology 1984154289ndash97

[26] Colby TV Fukuoka J Ewaskow SP et al Pathologic

approach to pulmonary hemorrhage Ann Diagn

Pathol 20015(5)309ndash19

[27] Miller R Diffuse pulmonary hemorrhage In Thurl-

beck W Churg A editors Pathology of the lung 2nd

edition New York7 Thieme Medical Publishers 1995

p 365ndash73

[28] Wilson CB Recent advances in the immunological

aspects of renal disease Fed Proc 197736(8)2171ndash5

[29] Leatherman J Davies S Hoida J Alveolar hemor-

rhage syndromes diffuse microvascular lung hemor-

rhage in immune and idiopathic disorders Medicine

(Baltimore) 198463343ndash61

[30] Leatherman J Immune alveolar hemorrhage Chest

198791891ndash7

[31] Young KJ Pulmonary-renal syndromes Clin Chest

Med 198910655ndash72

[32] Katzenstein A Myers J Mazur M Acute interstitial

pneumonia a clinicopathologic ultrastructural and

cell kinetic study Am J Surg Pathol 198610256ndash67

[33] Walker W Wright V Rheumatoid pleuritis Ann

Rheum Dis 196726467ndash73

[34] Gammon R Bridges T Al-Nezir H et al Bronchi-

olitis obliterans organizing pneumonia associated

with systemic lupus erythematosus Chest 1992102

1171ndash4

[35] Harrison N Myers A Corrin B et al Structural

features of interstitial lung disease in systemic scle-

rosis Am Rev Respir Dis 1991144706ndash13

[36] Yousem SA The pulmonary pathologic manifesta-

tions of the CREST syndrome Hum Pathol 1990

21(5)467ndash74

[37] Wiener-Kronish J Solinger A Warnock M et al Se-

vere pulmonary involvement in mixed connective tis-

sue disease Am Rev Respir Dis 1981124499ndash503

[38] Baruch HH Firooznia H Sackler JP et al Pulmonary

disorders associated with Sjogrenrsquos syndrome Rev

Interam Radiol 19772(2)77ndash81

[39] Deheinzelin D Capelozzi VL Kairalla RA et al

Interstitial lung disease in primary Sjogrenrsquos syn-

drome clinical-pathological evaluation and response

to treatment Am J Respir Crit Care Med 1996

154(3 Pt 1)794ndash9

[40] Holoye P Luna M MacKay B et al Bleomycin

hypersensitivity pneumonitis Ann Intern Med 1978

847ndash9

[41] Borzone G Moreno R Urrea R et al Bleomycin-

induced chronic lung damage does not resemble

human idiopathic pulmonary fibrosis Am J Respir

Crit Care Med 2001163(7)1648ndash53

[42] Samuels M Johnson D Holoye P et al Large-dose

bleomycin therapy and pulmonary toxicity a possible

role of prior radiotherapy JAMA 19762351117ndash20

[43] Adamson I Bowden D The pathogenesis of bleo-

mycin-induced pulmonary fibrosis in mice Am J

Pathol 197477185ndash98

[44] Davies BH Tuddenham EG Familial pulmonary

fibrosis associated with oculocutaneous albinism and

platelet function defect a new syndrome Q J Med

197645(178)219ndash32

[45] DePinho RA Kaplan KL The Hermansky-Pudlak

syndrome report of three cases and review of patho-

physiology and management considerations Medi-

cine (Baltimore) 198564(3)192ndash202

[46] Dimson O Drolet BA Esterly NB Hermansky-

Pudlak syndrome Pediatr Dermatol 199916(6)

475ndash7

[47] Huizing M Gahl WA Disorders of vesicles of

lysosomal lineage the Hermansky-Pudlak syn-

dromes Curr Mol Med 20022(5)451ndash67

[48] Anikster Y Huizing M White J et al Mutation of a

new gene causes a unique form of Hermansky-Pudlak

syndrome in a genetic isolate of central Puerto Rico

Nat Genet 200128(4)376ndash80

[49] Hermos CR Huizing M Kaiser-Kupfer MI et al

Hermansky-Pudlak syndrome type 1 gene organiza-

tion novel mutations and clinical-molecular review of

non-Puerto Rican cases Hum Mutat 200220(6)482

[50] Okano A Sato A Chida K et al Pulmonary

interstitial pneumonia in association with Herman-

sky-Pudlak syndrome Nihon Kyobu Shikkan Gakkai

Zasshi 199129(12)1596ndash602

[51] Gahl WA Brantly M Troendle J et al Effect of

pirfenidone on the pulmonary fibrosis of Hermansky-

Pudlak syndrome Mol Genet Metab 200276(3)

234ndash42

[52] Avila NA Brantly M Premkumar A et al Herman-

sky-Pudlak syndrome radiography and CT of the

chest compared with pulmonary function tests and

genetic studies AJR Am J Roentgenol 2002179(4)

887ndash92

[53] Katzenstein A Fiorelli R Nonspecific interstitial

pneumoniafibrosis histologic features and clinical

significance Am J Surg Pathol 199418136ndash47

[54] Bjoraker JA Ryu JH Edwin MK et al Prognostic

significance of histopathologic subsets in idiopathic

pulmonary fibrosis Am J Respir Crit Care Med 1998

157(1)199ndash203

[55] Cottin V Donsbeck AV Revel D et al Nonspecific

interstitial pneumonia individualization of a clinico-

pathologic entity in a series of 12 patients Am J

Respir Crit Care Med 1998158(4)1286ndash93

[56] Daniil ZD Gilchrist FC Nicholson AG et al A

histologic pattern of nonspecific interstitial pneumo-

nia is associated with a better prognosis than usual

interstitial pneumonia in patients with cryptogenic

fibrosing alveolitis Am J Respir Crit Care Med 1999

160(3)899ndash905

[57] Kim T Lee K Chung M Kwon OJ Kim TS Hwang

JH et al Nonspecific interstitial pneumonia with

fibrosis high resolution CT and pathologic findings

Roentgenol 1998171949ndash53

[58] Nagai S Kitaichi M Itoh H et al Idiopathic non-

specific interstitial pneumoniafibrosis comparison

with idiopathic pulmonary fibrosis and BOOP Eur

Respir J 199812(5)1010ndash9

[59] Park J Lee K Kim J et al Nonspecific interstitial

pneumonia with fibrosis radiographic and CT find-

ings in 7 patients Radiology 1995195645ndash8

[60] Hartman TE Swensen SJ Hansell DM et al Non-

specific interstitial pneumonia variable appearance at

high-resolution chest CT Radiology 2000217(3)

701ndash5

[61] Travis WD Matsui K Moss J et al Idiopathic

nonspecific interstitial pneumonia prognostic signifi-

cance of cellular and fibrosing patterns Survival

comparison with usual interstitial pneumonia and

desquamative interstitial pneumonia Am J Surg

[62] American Thoracic Society Idiopathic pulmonary

fibrosis diagnosis and treatment International con-

sensus statement of the American Thoracic Society

(ATS) and the European Respiratory Society (ERS)

Am J Respir Crit Care Med 2000161(2 Pt 1)646ndash64

[63] Mapel DW Hunt WC Utton R et al Idiopathic

pulmonary fibrosis survival in population based and

hospital based cohorts Thorax 199853(6)469ndash76

[64] Muller N Miller R Webb W et al Fibrosing al-

veolitis CT-pathologic correlation Radiology 1986

160585ndash8

[65] Staples C Muller N Vedal S et al Usual interstitial

pneumonia correlations of CT with clinical func-

tional and radiologic findings Radiology 1987162

377ndash81

[66] Ostrow D Cherniack R Resistance to airflow in

patients with diffuse interstitial lung disease Am Rev

Respir Dis 1973108205ndash10

[67] Raghu G Brown KK Bradford WZ et al A placebo-

controlled trial of interferon gamma-1b in patients

with idiopathic pulmonary fibrosis N Engl J Med

2004350(2)125ndash33

[68] Bourke SJ Dalphin JC Boyd G et al Hyper-

sensitivity pneumonitis current concepts Eur Respir

J Suppl 20013281sndash92s

[69] Hansell DM High-resolution computed tomography

in chronic infiltrative lung disease Eur Radiol 1996

6(6)796ndash800

[70] Adler BD Padley SPG Muller NL et al Chronic

hypersensitivity pneumonitis high resolution CT and

radiographic features in 16 patients Radiology 1992

18591ndash5

[71] Reyes C Wenzel F Lawton B et al Pulmonary

pathology in farmerrsquos lung Chest 198281142ndash6

[72] Coleman A Colby TV Histologic diagnosis of

extrinsic allergic alveolitis Am J Surg Pathol 1988

12(7)514ndash8

[73] Marchevsky A Damsker B Gribetz A et al The

spectrum of pathology of nontuberculous mycobacte-

rial infections in open lung biopsy specimens Am J

Clin Pathol 198278695ndash700

[74] Khoor A Leslie KO Tazelaar HD et al Diffuse

pulmonary disease caused by nontuberculous myco-

bacteria in immunocompetent people (hot tub lung)

Am J Clin Pathol 2001115(5)755ndash62

[75] Clarysse AM Cathey WJ Cartwright GE et al

Pulmonary disease complicating intermittent therapy

with methotrexate JAMA 19692091861ndash4

[76] Imokawa S Colby TV Leslie KO et al Methotrexate

pneumonitis review of the literature and histopatho-

logical findings in nine patients Eur Respir J 2000

15(2)373ndash81

[77] Kennedy JI Myers JL Plumb VJ et al Amiodarone

pulmonary toxicity clinical radiologic and patho-

logic correlations Arch Intern Med 1987147(1)

50ndash5

[78] Dusman RE Stanton MS Miles WM et al Clinical

features of amiodarone-induced pulmonary toxicity

Circulation 199082(1)51ndash9

[79] Weinberg BA Miles WM Klein LS et al Five-year

follow-up of 589 patients treated with amiodarone

Am Heart J 1993125(1)109ndash20

[80] Fraire AE Guntupalli KK Greenberg SD et al

Amiodarone pulmonary toxicity a multidisciplinary

review of current status South Med J 199386(1)

67ndash77

[81] Nicholson AA Hayward C The value of computed

tomography in the diagnosis of amiodarone-induced

pulmonary toxicity Clin Radiol 198940(6)564ndash7

[82] Kuhlman JE Teigen C Ren H et al Amiodarone

pulmonary toxicity CT findings in symptomatic

patients Radiology 1990177(1)121ndash5

[83] Myers JL Kennedy JI Plumb VJ Amiodarone lung

pathologic findings in clinically toxic patients Hum

[84] Martin II WJ Rosenow III EC Amiodarone pulmo-

nary toxicity recognition and pathogenesis (part I)

Chest 198893(5)1067ndash75

nary toxicity recognition and pathogenesis (part 2)

Chest 198893(6)1242ndash8

[86] Liu FL Cohen RD Downar E et al Amiodarone

pulmonary toxicity functional and ultrastructural

evaluation Thorax 198641(2)100ndash5

[87] Gonzalez-Rothi RJ Hannan SE Hood CI et al

Amiodarone pulmonary toxicity presenting as bilat-

eral exudative pleural effusions Chest 198792(1)

179ndash82

[88] Wood DL Osborn MJ Rooke J et al Amiodarone

pulmonary toxicity report of two cases associated

with rapidly progressive fatal adult respiratory dis-

tress syndrome after pulmonary angiography Mayo

Clin Proc 198560(9)601ndash3

[89] Van Mieghem W Coolen L Malysse I et al

Amiodarone and the development of ARDS after

lung surgery Chest 1994105(6)1642ndash5

[90] Johkoh T Muller NL Pickford HA et al Lympho-

cytic interstitial pneumonia thin-section CT findings

in 22 patients Radiology 1999212(2)567ndash72

[91] Liebow AA Carrington CB Diffuse pulmonary

lymphoreticular infiltrations associated with dyspro-

teinemia Med Clin North Am 197357809ndash43

[92] Joshi V Oleske J Pulmonary lesions in children with

the acquired immunodeficiency syndrome a reap-

praisal based on data in additional cases and follow-

up study of previously reported cases Hum Pathol

198617641ndash2

[93] Joshi V Oleske J Minnefor A et al Pathologic pulmo-

nary findings in children with the acquired immuno-

deficiency syndrome Hum Pathol 198516241ndash6

[94] Solal-Celigny P Coudere L Herman D et al

Lymphoid interstitial pneumonitis in acquired immu-

nodeficiency syndrome-related complex Am Rev

[95] Grieco M Chinoy-Acharya P Lymphoid interstitial

pneumonia associated with the acquired immune

deficiency syndrome Am Rev Respir Dis 1985131

952ndash5

[96] Saldana M Mones J Lymphoid interstitial pneumo-

nia in HIV infected individuals Progress in Surgical

Pathology 199112181ndash215

[97] Davison A Heard B McAllister W et al Crypto-

genic organizing pneumonitis Q J Med 198352

382ndash94

[98] Epler GR Colby TV McLoud TC et al Bronchiolitis

obliterans organizing pneumonia N Engl J Med

1985312(3)152ndash8

[99] Guerry-Force M Muller N Wright J et al A

comparison of bronchiolitis obliterans with organiz-

ing pneumonia usual interstitial pneumonia and

small airways disease Am Rev Respir Dis 1987

135705ndash12

[100] Katzenstein A Myers J Prophet W et al Bronchi-

olitis obliterans and usual interstitial pneumonia a

comparative clinicopathologic study Am J Surg

[101] King TJ Mortensen R Cryptogenic organizing

pneumonitis Chest 19921028Sndash13S

[102] Yoshinouchi T Ohtsuki Y Kubo K et al Clinico-

pathological study on two types of cryptogenic orga-

nizing pneumonia Respir Med 199589271ndash8

[103] Muller NL Guerry-Force ML Staples CA et al

Differential diagnosis of bronchiolitis obliterans with

organizing pneumonia and usual interstitial pneumo-

nia clinical functional and radiologic findings

Radiology 1987162(1 Pt 1)151ndash6

[104] Chandler PW Shin MS Friedman SE et al Radio-

graphic manifestations of bronchiolitis obliterans with

organizing pneumonia vs usual interstitial pneumo-

nia AJR Am J Roentgenol 1986147(5)899ndash906

[105] Muller N Staples C Miller R Bronchiolitis organiz-

ing pneumonia CT features in 14 patients AJR Am J

[106] Nishimura K Itoh H High-resolution computed

tomographic features of bronchiolitis obliterans

organizing pneumonia Chest 199210226Sndash31S

[107] Bouchardy LM Kuhlman JE Ball WC et al CT

findings in bronchiolitis obliterans organizing pneu-

monia (BOOP) with radiographic clinical and his-

tologic correlation J Comput Assist Tomogr 1993

17352ndash7

[108] Lee K Kullnig P Hartman T et al Cryptogenic

organizing pneumonia CT findings in 43 patients

AJR Am J Roentgenol 199462543ndash6

[109] Myers JL Colby TV Pathologic manifestations of

bronchiolitis constrictive bronchiolitis cryptogenic

organizing pneumonia and diffuse panbronchiolitis

Clin Chest Med 199314(4)611ndash22

[110] Cohen AJ King TEJ Downey GP Rapidly pro-

gressive bronchiolitis obliterans with organizing

pneumonia Am J Respir Crit Care Med 1994149

1670ndash5

[111] Yousem SA Lohr RH Colby TV Idiopathic

bronchiolitis obliterans organizing pneumoniacryp-

togenic organizing pneumonia with unfavorable out-

come pathologic predictors Mod Pathol 199710(9)

864ndash71

[112] Liebow A Steer A Billingsley J Desquamative in-

terstitial pneumonia Am J Med 196539369ndash404

[113] Farr G Harley R Henningar G Desquamative

interstitial pneumonia an electron microscopic study

Am J Pathol 197060347ndash54

[114] Katzenstein AL Myers JL Idiopathic pulmonary

fibrosis clinical relevance of pathologic classifica-

tion Am J Respir Crit Care Med 1998157(4 Pt 1)

1301ndash15

[115] Hartman TE Primack SL Swensen SJ et al

Desquamative interstitial pneumonia thin-section

CT findings in 22 patients Radiology 1993187(3)

787ndash90

[116] Yousem S Colby T Gaensler E Respiratory bron-

chiolitis and its relationship to desquamative inter-

stitial pneumonia Mayo Clin Proc 1989641373ndash80

[117] Patchefsky A Israel H Hock W et al Desquamative

interstitial pneumonia relationship to interstitial

fibrosis Thorax 197328680ndash93

[118] Carrington C Gaensler EA et al Natural history and

treated course of usual and desquamative interstitial

pneumonia N Engl J Med 1978298801ndash9

[119] Corrin B Price AB Electron microscopic studies in

desquamative interstitial pneumonia associated with

asbestos Thorax 197227324ndash31

[120] Coates EO Watson JHL Diffuse interstitial lung

disease in tungsten carbide workers Ann Intern Med

197175709ndash16

[121] Bone RC Wolfe J Sobonya RE et al Desquamative

interstitial pneumonia following chronic nitrofuran-

toin therapy Chest 197669(Suppl 2)296ndash7

[122] Lundgren R Back O Wiman L Pulmonary lesions

and autoimmune reactions after long-term nitrofuran-

toin treatment Scand J Respir Dis 197556208ndash16

[123] McCann B Brewer D A case of desquamative in-

terstitial pneumonia progressing to honeycomb lung

J Pathol 1974112199ndash202

[124] Carrington CB Gaensler EA Coutu RE et al Natural

history and treated course of usual and desquamative

interstitial pneumonia N Engl J Med 1978298(15)

801ndash9

[125] Singh G Katyal S Bedrossian C et al Pulmonary

alveolar proteinosis staining for surfactant apoprotein

in alveolar proteinosis and in conditions simulating it

Chest 19838382ndash6

[126] Miller R Churg A Hutcheon M et al Pulmonary

alveolar proteinosis and aluminum dust exposure Am

Rev Respir Dis 1984130312ndash5

[127] Bedrossian CWM Luna MA Conklin RH et al

Alveolar proteinosis as a consequence of immuno-

suppression a hypothesis based on clinical and

pathologic observations Hum Pathol 198011(Suppl

5)527ndash35

[128] Wang B Stern E Schmidt R et al Diagnosing

pulmonary alveolar proteinosis Chest 1997111

460ndash6

[129] Davidson J MacLeod W Pulmonary alveolar protein-

osis Br J Dis Chest 19696313ndash6

[130] Murch C Carr D Computed tomography appear-

ances of pulmonary alveolar proteinosis Clin Radiol

198940240ndash3

[131] Godwin J Muller N Tagasuki J Pulmonary al-

veolar proteinosis CT findings Radiology 1989169

609ndash14

[132] Lee K Levin D Webb W et al Pulmonary al-

veolar proteinosis high resolution CT chest radio-

graphic and functional correlations Chest 1997111

989ndash95

[133] Claypool W Roger R Matuschak G Update on the

clinical diagnosis management and pathogenesis of

pulmonary alveolar proteinosis (phospholipidosis)

[134] Carrington CB Gaensler EA Mikus JP et al

Structure and function in sarcoidosis Ann N Y Acad

Sci 1977278265ndash83

[135] Hunninghake G Staging of pulmonary sarcoidosis

Chest 198689178Sndash80S

[136] Daniele R Rossman M Kern J et al Pathogenesis of

sarcoidosis Chest 198689174Sndash7S

[137] Sharma OP Alam S Diagnosis pathogenesis and

treatment of sarcoidosis Curr Opin Pulm Med 1995

1(5)392ndash400

[138] Moller DR Cells and cytokines involved in the

pathogenesis of sarcoidosis Sarcoidosis Vasc Diffuse

Lung Dis 199916(1)24ndash31

[139] Johnson B Duncan S Ohori N et al Recurrence of

sarcoidosis in pulmonary allograft recipients Am Rev

[140] Martinez FJ Orens JB Deeb M et al Recurrence of

sarcoidosis following bilateral allogeneic lung trans-

plantation Chest 1994106(5)1597ndash9

[141] Judson MA Lung transplantation for pulmonary

sarcoidosis Eur Respir J 199811(3)738ndash44

[142] Muller NL Kullnig P Miller RR The CT findings of

pulmonary sarcoidosis analysis of 25 patients AJR

Am J Roentgenol 1989152(6)1179ndash82

[143] McLoud T Epler G Gaensler E et al A radiographic

classification of sarcoidosis physiologic correlation

Invest Radiol 198217129ndash38

[144] Wall C Gaensler E Carrington C et al Comparison

of transbronchial and open biopsies in chronic

infiltrative lung disease Am Rev Respir Dis 1981

123280ndash5

[145] Judd PA Finnegan P Curran RC Pulmonary sarcoid-

osis a clinicopathological study J Pathol 1975115

191ndash8

[146] Rosen Y Athanassiades T Moon S et al Non-granu-

lomatous interstitial inflammation in sarcoidosis

relationship to development of epithelioid granulo-

mas Chest 197874122ndash5

[147] Takemura T Hiraga Y Oomechi M et al Ultra-

structural features of alveolitis in sarcoidosis Am J

Respir Crit Care Med 1995152367ndash73

[148] Aronchik JM Rossman MD Miller WT Chronic

beryllium disease diagnosis radiographic findings

and correlation with pulmonary function tests Radi-

ology 1987163677ndash8

[149] Newman L Buschman D Newell J et al Beryllium

disease assessment with CT Radiology 1994190

835ndash40

[150] Matilla A Galera H Pascual E et al Chronic

berylliosis Br J Dis Chest 197367308ndash14

[151] Iwata M Colby TV Kitaichi M Diffuse panbron-

chiolitis diagnosis and distinction from various

pulmonary diseases with centrilobular interstitial

foam cell accumulations Hum Pathol 199425(4)

357ndash63

[152] Randhawa P Hoagland M Yousem S Diffuse

panbronchiolitis in North America Am J Surg Pathol

19911543ndash7

[153] Baz MA Kussin PS Davis RD et al Recurrence of

diffuse panbronchiolitis after lung transplantation

Am J Respir Crit Care Med 1995151895ndash8

[154] Janower M Blennerhassett J Lymphangitic spread of

metastatic cancer to the lung a radiologic-pathologic

classification Radiology 1971101267ndash73

[155] Munk P Muller N Miller R et al Pulmonary

lymphangitic carcinomatosis CT and pathologic

findings Radiology 1988166705ndash9

[156] Stein M Mayo J Muller N et al Pulmonary lymph-

angitic spread of carcinoma appearance on CT scans

[157] Heitzman E The lung radiologic-pathologic correla-

tions St Louis7 CV Mosby 1984

[158] Horvath E DoPico G Barbee R et al Nitrogen

dioxide-induced pulmonary disease J Occup Med

197820103ndash10

[159] Woodford DM Gaensler E Obstructive lung disease

from acute sulfur-dioxide exposure Respiration

(Herrlisheim) 197938238ndash45

[160] Close LG Catlin FI Gohn AM Acute and chronic

effects of ammonia burns of the respiratory tract

Arch Otolaryngol 1980106151ndash8

[161] Becroft DMO Bronchiolitis obliterans bronchiecta-

sis and other sequelae of adenovirus type 21 infection

in young children J Clin Pathol 19712472ndash9

[162] Edwards C Penny M Newman J Mycoplasma

pneumonia Stevens-Johnson syndrome and chronic

obliterative bronchiolitis Thorax 198338867ndash9

[163] Aguayo SM Miller YE Waldron JAJ et al Brief

report idiopathic diffuse hyperplasia of pulmonary

neuroendocrine cells and airways disease N Engl J

Med 19923271285ndash8

[164] Miller R Muller N Neuroendocrine cell hyperplasia

and obliterative bronchiolitis in patients with periph-

eral carcinoid tumors Am J Surg Pathol 199519

653ndash8

[165] Turton C Williams G Green M Cryptogenic

obliterative bronchiolitis in adults Thorax 198136

805ndash10

[166] Kraft M Mortensen R Colby T et al Cryptogenic

constrictive bronchiolitis a clinicopathologic study

Am Rev Respir Dis 19921481093ndash101

[167] Edwards C Cayton R Bryan R Chronic transmural

bronchiolitis a nonspecific lesion of small airways J

[168] Yousem SA Dacic S Idiopathic bronchiolocentric

interstitial pneumonia Mod Pathol 200215(11)

1148ndash53

[169] Churg A Myers J Suarez T et al Airway-centered

interstitial fibrosis a distinct form of aggressive dif-

fuse lung disease Am J Surg Pathol 200428(1)62ndash8

[170] Carrington CB Cugell DW Gaensler EA et al

Lymphangioleiomyomatosis physiologic-pathologic-

radiologic correlations Am Rev Respir Dis 1977116

977ndash95

[171] Templeton P McLoud T Muller N et al Pulmonary

lymphangioleiomyomatosis CT and pathologic find-

ings J Comput Assist Tomogr 19891354ndash7

[172] Kitaichi M Itch H Izumi T Pulmonary lymphangio-

leiomyomatosis a report of 46 patients including a

clinicopathologic study of prognostic factors Am J

[173] Chu S Horiba K Usuki J et al Comprehensive

evaluation of 35 patients with lymphangioleiomyo-

matosis Chest 19991151041ndash52

[174] Aubry MC Myers JL Ryu JH et al Pulmonary

lymphangioleiomyomatosis in a man Am J Respir

Crit Care Med 2000162(2 Pt 1)749ndash52

[175] Costello L Hartman T Ryu J High frequency of

pulmonary lymphangioleiomyomatosis in women

with tuberous sclerosis complex Mayo Clin Proc

200075591ndash4

[176] Lenoir S Grenier P Brauner M et al Pulmonary

lymphangiomyomatosis and tuberous sclerosis com-

parison of radiographic and thin section CT Radiol-

ogy 1989175329ndash34

[177] Ohori N Yousem S Sonmez-Alpan E et al Estrogen

and progesterone receptors in lymphangioleiomyo-

matosis epithelioid hemangioendothelioma and scle-

rosing hemangioma of the lung Am J Clin Pathol

199196(4)529ndash35

[178] Muir TE Leslie KO Popper H et al Micronodular

pneumocyte hyperplasia Am J Surg Pathol 1998

22(4)465ndash72

[179] Taylor JR Ryu J Colby TV et al Lymphangioleio-

myomatosis clinical course in 32 patients N Engl J

Med 1990323(18)1254ndash60

[180] Myers J Katzenstein A Wegenerrsquos granulomatosis

presenting with massive pulmonary hemorrhage and

capillaritis Am J Surg Pathol 198711895ndash8

chiolitis-associated interstitial lung disease and its

relationship to desquamative interstitial pneumonia

Mayo Clin Proc 1989641373ndash80

[182] Myers J Veal C Shin M et al Respiratory bron-

chiolitis causing interstitial lung disease a clinico-

pathologic study of six cases Am Rev Respir Dis

1987135880ndash4

[183] Heyneman LE Ward S Lynch DA et al Respiratory

bronchiolitis respiratory bronchiolitis-associated

interstitial lung disease and desquamative interstitial

pneumonia different entities or part of the spectrum

of the same disease process AJR Am J Roentgenol

1999173(6)1617ndash22

[184] Moon J du Bois RM Colby TV et al Clinical

significance of respiratory bronchiolitis on open lung

biopsy and its relationship to smoking related inter-

stitial lung disease Thorax 199954(11)1009ndash14

[185] Vassallo R Ryu JH Colby TV et al Pulmonary

Langerhansrsquo-cell histiocytosis N Engl J Med 2000

342(26)1969ndash78

[186] Brauner M Grenier P Tijani K et al Pulmonary

Langerhansrsquo cell histiocytosis evolution of lesions on

CT scans Radiology 1997204497ndash502

[187] Basset F Soler P Wyllie L et al Langerhansrsquo cells

and lung interstitium Ann N Y Acad Sci 1976278

599ndash611

[188] Foucher P Camus P and Groupe drsquoEtudes de la

Pathologie Pulmonaire Iatrogene (GEPPI) The drug-

induced lung diseases Available at httpwww

pneumotoxcom Accessed September 24 2004

Pattern analysis approach to surgical lung biopsies
Pattern 2 fibrosis
Pattern 5 nodules
Acute lung injury pattern (days to weeks in evolution rapid onset of symptoms)
Adult respiratory distress syndrome and diffuse alveolar damage
Infections
Nitrofurantoin
Analgesics
Acute pulmonary manifestations of the collagen vascular diseases
Antiglomerular basement membrane disease (Goodpastures syndrome)
Diffuse alveolar hemorrhage associated with the systemic collagen vascular diseases
Idiopathic diffuse alveolar damage acute interstitial pneumonia
Pattern 2 interstitial lung disease dominated by fibrosis (typically months to years in evolution)
Pulmonary fibrosis in the systemic connective tissue diseases
Sjgrens syndrome
Bleomycin
Idiopathic usual interstitial pneumonia (cryptogenic fibrosing alveolitis)
Pattern 3 interstitial lung diseases dominated by interstitial mononuclear cells (chronic inflammation)
Bioaerosol-associated atypical mycobacterial infection
Idiopathic nonspecific interstitial pneumonia-cellular
Drug reactions
Methotrexate
Amiodarone
Pattern 4 interstitial lung diseases dominated by airspace filling
Neutrophils
Macrophages
Pattern 5 interstitial lung diseases dominated by nodules
Nodular granulomas
Sarcoidosis
Berylliosis
Nodular lymphohistiocytic lesions (lymphoid cells lymphoid follicles variable histiocytes)
Pattern 6 interstitial lung disease with subtle findings in surgical biopsies (chronic evolution)
Neuroendocrine cell hyperplasia with occlusive bronchiolar fibrosis
Interstitial lung disease dominated by airway-associated scarring
Interstitial lung disease related to cigarette smoking
Respiratory bronchiolitis-associated interstitial lung disease
Pulmonary Langerhans cell histiocytosis
References

Box 1 Liebow classification of interstitialpneumonia (1975)

Usual interstitial pneumonia (UIP)Bronchiolitis obliterans with usual

interstitial pneumonia (BIP)Desquamative interstitial pneumonia

(DIP)Lymphoid interstitial pneumonia (LIP)Giant cell interstitial pneumonia (GIP)

Adapted from Liebow A Carrington CThe interstitial pneumonias In Simon MPotchen E LeMay M editors Frontiers ofpulmonary radiology pathophysiologicroentgenographic and radioisotopic con-siderations Orlando Grune amp Stratton1969 p 109ndash42

Box 2 International ConsensusCommittee classification of idiopathicinterstitial pneumonia (2002)

Acute interstitial pneumoniaDIPrespiratory bronchiolitisndashasso-

ciated interstitial disease (RB-ILD)Cryptogenic organizing pneumonia

(COP)Nonspecific interstitial pneumonia

fibrosis (NSIPF)a

a ProvisionalAdapted from Travis W King T Bate-man E Lynch DA Capron F Colby TVet al ATSERS international multidisci-plinary consensus classification of theidiopathic interstitial pneumonias Am JRespir Crit Care Med 2002165(2)277ndash304

that the microscope slide be evaluated first by the

naked eye may seem overly methodical but it does

force the interpreter to see the lsquolsquobig picturersquorsquo before

getting lost in the fine details For nonneoplastic lung

diseases the scanning low power objective (2 or

4) is useful if not essential because different

diseases give rise to different architectural patterns

which may immediately raise a narrow differential

diagnosis For diffuse lung diseases several helpful

patterns emerge

The prototype of this pattern is diffuse alveolar

damage (DAD) with hyaline membranes classically

encountered in the clinical setting of adult respiratory

distress syndrome (ARDS) (Fig 1)

Pattern 2 fibrosis

Lung diseases that lead to the accrual of collagen

in the lung with permanent structural remodeling

are represented by this pattern (Fig 2) Idiopathic

pulmonary fibrosis (IPF) (pathologic usual intersti-

tial pneumonia [UIP]) is the prototype and is often

the diagnosis of greatest clinical concern in older

adult patients because of the dismal prognosis of

this condition

Lymphocytes plasma cells and macrophages

are present in the alveolar walls in Pattern 3 (Fig 3)

Hypersensitivity pneumonitis (extrinsic allergic al-

veolitis) is the prototype of this pattern

This pattern is characterized by the presence of

cells or other material filling the alveolar spaces

(Fig 4) Organizing pneumonia is the prototype of

this pattern The airspace filling pattern also includes

infectious bronchopneumonias (neutrophils in the al-

veoli) classic Pneumocystis infection in the immu-

nocompromised host (foamy casts in alveoli)

pulmonary alveolar proteinosis (PAP) (proteinaceous

material in alveoli) diffuse pulmonary hemorrhage

(blood siderophages and patchy organizing pneumo-

nia in alveoli) and DIP in which lightly pigmented

lsquolsquosmokersrsquorsquo-type macrophages are the dominant intra-

alveolar element

Pattern 5 nodules

The presence of discrete nodules (Fig 5) in the

lung parenchyma raises a differential diagnosis that

includes nodular infections benign and malignant

neoplasms sarcoidosis Langerhansrsquo cell histiocyto-

sis and various bronchiolocentric diseases The

prototype is Wegenerrsquos granulomatosis (large nodular

pattern) but small (miliary) patterns of disease also

are included

Table 1

diffuse

No Some cases No

No Occasional

No Prominent

diffuse

No Occasional

patchy

formed

this condition

tial diagnosis

Table 2

Infection

(normal to HC)

UIPIPF

C-NSIP CVD

HSP drug

With macrophages

Smoking-related

Local fibrosis

With lymphoid

Follicular bronch

Wegenerrsquos

With SAD

Chronic HSP

Many causes

Infections

Bacterial

Infection HSP

sarcoidberylliosis

aspiration

With focal OP

Infection drug

Infections Ca

Lymphomas

Sarcomas

With no findings

Infection

Infection CVD

Drug DPH

Pneumoconiosis

F-NSIP CVD CHF PAP

Infarct

KOLeslie

25(2004)657ndash703

Illicit (heroin)

alveolar damage

DAD is appropriate

Infections

Nitrofurantoin

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

NLH (infants) ICH

adults (rare)

Hantavirus

Adenovirus ICH

Cytomegalovirus

normal host

Analgesics

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Table 1

diffuse

No Some cases No

No Occasional

No Prominent

diffuse

No Occasional

patchy

formed

this condition

tial diagnosis

Table 2

Infection

(normal to HC)

UIPIPF

C-NSIP CVD

HSP drug

With macrophages

Smoking-related

Local fibrosis

With lymphoid

Follicular bronch

Wegenerrsquos

With SAD

Chronic HSP

Many causes

Infections

Bacterial

Infection HSP

sarcoidberylliosis

aspiration

With focal OP

Infection drug

Infections Ca

Lymphomas

Sarcomas

With no findings

Infection

Infection CVD

Drug DPH

Pneumoconiosis

F-NSIP CVD CHF PAP

Infarct

KOLeslie

25(2004)657ndash703

Illicit (heroin)

alveolar damage

DAD is appropriate

Infections

Nitrofurantoin

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

NLH (infants) ICH

adults (rare)

Hantavirus

Adenovirus ICH

Cytomegalovirus

normal host

Analgesics

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

tial diagnosis

Table 2

Infection

(normal to HC)

UIPIPF

C-NSIP CVD

HSP drug

With macrophages

Smoking-related

Local fibrosis

With lymphoid

Follicular bronch

Wegenerrsquos

With SAD

Chronic HSP

Many causes

Infections

Bacterial

Infection HSP

sarcoidberylliosis

aspiration

With focal OP

Infection drug

Infections Ca

Lymphomas

Sarcomas

With no findings

Infection

Infection CVD

Drug DPH

Pneumoconiosis

F-NSIP CVD CHF PAP

Infarct

KOLeslie

25(2004)657ndash703

Illicit (heroin)

alveolar damage

DAD is appropriate

Infections

Nitrofurantoin

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

NLH (infants) ICH

adults (rare)

Hantavirus

Adenovirus ICH

Cytomegalovirus

normal host

Analgesics

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Table 2

Infection

(normal to HC)

UIPIPF

C-NSIP CVD

HSP drug

With macrophages

Smoking-related

Local fibrosis

With lymphoid

Follicular bronch

Wegenerrsquos

With SAD

Chronic HSP

Many causes

Infections

Bacterial

Infection HSP

sarcoidberylliosis

aspiration

With focal OP

Infection drug

Infections Ca

Lymphomas

Sarcomas

With no findings

Infection

Infection CVD

Drug DPH

Pneumoconiosis

F-NSIP CVD CHF PAP

Infarct

KOLeslie

25(2004)657ndash703

Illicit (heroin)

alveolar damage

DAD is appropriate

Infections

Nitrofurantoin

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

NLH (infants) ICH

adults (rare)

Hantavirus

Adenovirus ICH

Cytomegalovirus

normal host

Analgesics

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Illicit (heroin)

alveolar damage

DAD is appropriate

Infections

Nitrofurantoin

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

NLH (infants) ICH

adults (rare)

Hantavirus

Adenovirus ICH

Cytomegalovirus

normal host

Analgesics

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Infections

Nitrofurantoin

Table 3

Viral pneumonias

Virus Usual patient

RNA NLH (adults)

Influenza ICH

Measles

NLH (infants) ICH

adults (rare)

Hantavirus

Adenovirus ICH

Cytomegalovirus

normal host

Analgesics

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

(Fig 10)

vascular diseases

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

RA [19]

many months

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

sented in Box 4

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

litis (B)

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

pneumonia

diseases

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

sion [37]

Bleomycin

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Table 4

Sjogrenrsquos

syndrome

Ankylosing

spondylitis

X X X X X

lupus erythematosus

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

at the periphery

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

of IPF

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

were performed

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Table 5

Nagai et al 1998 [58] 31 15 M 16 F 16 6

Cottin et al 1998 [55] 12 6 M 6 F 33 0

Park et al 1995 [59] 7 1 M 6 F 29 29

Hartman et al 2000 [60] 39 16 M 23 F 19 29

Daniil et al 1999 [56] 15 7 M 8 F 33 13

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

with UIP [62]

course of IPF

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

inflammation)

r collagen (B)

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

lung zones [70]

Table 6

Foam cells 39 65

Edema 31 52

Granulomas 42 70

Birefringentb 28 47

142ndash51

alveolar walls

plusmn 1+ 2+ 3+

0 14 19 27

10 24 5 mdash

3 mdash mdash mdash

6 24 6 3

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

infection

pneumonia-cellular

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Table 7

pneumonia

Granulomas

peribronchiolar

perivascular

Random

Drug reactions

Methotrexate

Amiodarone

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

a few eosinophils

cells are common

be present

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

(upper right)

is similar

airspace filling

Neutrophils

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

COP emerges

30 of cases

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

appearance (center)

restrictive defect

Macrophages

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

does not [62]

sent (B)

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

logic abnormalities

nodules

Nodular granulomas

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

presented in Box 10

Sarcoidosis

pulmonary symptom

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

without necrosis

target for biopsy

Berylliosis

in every case

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

tric lesions

sarcoidosis [150]

Asian descent

lar bronchiolitis

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

or total occlusion

mosaic air trapping

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

sion of ILD

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

smooth muscle cells

[171176]

magnification

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

brown chromogen)

among patients

smoking

(Fig 63)

disease

cigarette smoking

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

tory bronchiolitis

ILD from DIP

7ndash75)

lung disease

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

References

1978 p 58ndash67

2002165(2)277ndash304

1978 p 21ndash42

Dis 1986133321ndash38 488ndash502

20013293sndash100s

1972355ndash70

231001ndash18

19771281ndash13

1979119471ndash503

770ndash7

184ndash234

198685(5)552ndash6

141(3)727ndash33

1064ndash70

p 365ndash73

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

198791891ndash7

1171ndash4

21(5)467ndash74

154(3 Pt 1)794ndash9

847ndash9

197645(178)219ndash32

475ndash7

Zasshi 199129(12)1596ndash602

234ndash42

887ndash92

157(1)199ndash203

160(3)899ndash905

701ndash5

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

160585ndash8

377ndash81

2004350(2)125ndash33

6(6)796ndash800

18591ndash5

12(7)514ndash8

15(2)373ndash81

50ndash5

67ndash77

Chest 198893(5)1067ndash75

179ndash82

198617641ndash2

952ndash5

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

382ndash94

1985312(3)152ndash8

135705ndash12

17352ndash7

1670ndash5

864ndash71

1301ndash15

787ndash90

197175709ndash16

801ndash9

5)527ndash35

460ndash6

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

198940240ndash3

609ndash14

989ndash95

Sci 1977278265ndash83

1(5)392ndash400

123280ndash5

191ndash8

835ndash40

357ndash63

19911543ndash7

197820103ndash10

Med 19923271285ndash8

653ndash8

805ndash10

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

1148ndash53

977ndash95

200075591ndash4

ogy 1989175329ndash34

199196(4)529ndash35

22(4)465ndash72

Med 1990323(18)1254ndash60

1987135880ndash4

1999173(6)1617ndash22

342(26)1969ndash78

599ndash611

Pattern 2 fibrosis
Pattern 5 nodules
Infections
Nitrofurantoin
Analgesics
Sjgrens syndrome
Bleomycin
Drug reactions
Methotrexate
Amiodarone
Neutrophils
Macrophages
Nodular granulomas
Sarcoidosis
Berylliosis
References

Diagnosa PPOK

Documents

PPOK Printing

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patogenesis PPOK

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Tutorial PPOK

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