Frontline Assessment of Lung Cancer and Occupational Diseases

Frontline Assessment of Lung Cancer & Occupational Pulmonary Diseases

WelcomeWelcome to the Snowdrift Frontline TreatmentMonographs. The authors welcome you to this seriesof monographs that aim to disseminate worldwide newknowledge about common pulmonary disorders. Weoffer our messages to anyone who will find them usefulin the diagnosis and treatment of the many pulmonarydisorders that continue to plague mankind around theworld. We invite you to download these monographsand use them in your teaching and practice ofmedicine. We feel a fraternal connection to allpractitioners who serve the suffering. We hope that wecan move toward the prevention of disease as analternative to premature morbidity and mortality.

The Authors.

Mission StatementThe Snowdrift Pulmonary Conference is a not-for-profit corporation that is dedicated to thedissemination of knowledge about the lungs and lungdiseases. Composed of both private practicepulmonologists and academicians, the conferees havelaunched a consumer-oriented program for primarycare practitioners and the patients they serve. As aresult, the following concise and authoritativemonographs have been written.

i

Books in the Frontline Series

Frontline Treatment of COPD, 2000*

Frontline Treatment of Asthma, 1997

Frontline Treatment of Common RespiratoryInfections, 1998

Frontline Treatment of Venous Thromboembolism,1999

Frontline Assessment of Common PulmonaryPresentations, 2000*

Frontline Assessment of Lung Cancer and Occupational Pulmonary Diseases, 2001*

Frontline Pulmonary Procedures and Interventions,2001*

Frontline Cardiopulmonary Topics / Dyspnea, 2001*

Frontline Advice for COPD Patients, 2002*

* Available on the web for downloading

A Monograph for Primary Care Physicians

FrontlineAssessmentof LungCancer &OccupationalPulmonaryDiseasesThe Authors

J. Roy Duke, Jr., md West Palm Beach, FL

James T. Good, Jr., md Denver, CO

Thomas M. Hyers, md* St. Louis, MO

Michael D. Iseman, md Denver, CO

Bernard E. Levine, md Paradise Valley, AZ

Richard A. Matthay, md New Haven, CT

Thomas L. Petty, md* Denver, CO

Donald R.Rollins, md White Sulphur Springs,WV

*Co-Editors

iii

iv

Copyright ©The SnowdriftPulmonaryFoundation, Inc.2001

The SnowdriftPulmonaryConference is afunction of TheSnowdrift PulmonaryFoundation, Inc.A NonprofitCorporation

The SnowdriftPulmonaryConference,899 LoganDenver, CO 80203

All rights reserved.No part of this bookto which theSnowdrift copyrightlegally applies may bereproduced or copiedin any form or by anymeans withoutwritten permission ofThe SnowdriftPulmonaryFoundation, Inc.

Printed and bound inthe United States ofAmerica.

ISBN 0-9671809-5-3

Contents

Pearls/ 2

A. Epidemiology and Etiology / 3

B. A Practical Approach to Early Diagnosis andStaging / 12

C. New Technologies in Diagnosis / 22

D. Chemotherapy, Radiation Therapy and Other Therapies / 26

E. When to Refer to a Specialist / 34

F. Medicolegal Issues / 40


Pearls/ 44

G. Asbestosis, Lung Cancer and Mesothelioma / 46

H. Other Pneumoconioses / 55

I. Occupational Asthma / 65

J. Hypersensitivity Pneumonitis / 73

K. When to Refer to a Specialist / 84

L. Medicolegal Issues / 89

M. Postscript and Biographical Sketches of Authors / 94

Index / 104

Frontline Assessment of Occupational Pulmonary Diseases

Frontline Assessment of Lung Cancer

Preface / v

v

Frontline Assessment of Lung CancerTables

vi

Table 1. / page 9Substances Encountered in Workplace ExposuresCategorized as Causative for Bronchogenic Carcinoma

Table 2. / page 17Stage Grouping B TNM Subsets

Table 3. / page 18TNM Descriptors

Table 4. / page 27 Expectations from Current Chemotherapy Regimensfor Metastatic Non-Small-Cell Lung Cancer

Table 5. / page 29 Newer Regimens of Chemotherapy for MetastaticNon-Small-Cell Lung Cancer

Table 6. / page 31 Commonly Used Opiates for Control of Pain andDyspnea

Table 7. / page 38 Preoperative Tests For Assessing Pulmonary Risk Priorto Major Lung Resection


Table 8. / page 47 Lung Diseases and Findings Associated with AsbestosExposure

Table 9. / page 53 Other Causes of Lung Cancer

Table 10. / page 56 Occupations Associated with Silica Exposure

Table 11. / page 62 Occupations Associated with Berylliosis

Table 12. / page 66 Occupational Asthma: Examples of Workers at Riskand Causal Agents

Figures

Table 13. / page 75 Agents Associated with Hypersensitivity Pneumonitis

Table 14. / page 77 Clinical Clues Pointing to Hypersensitivity Pneumonitis

Table 15. / page 81 Common Disorders Which Can Mimic HypersensitivityPneumonitis

Table 16. / page 85 When to Refer a Patient to a Specialist



Figure 1. / page 4Age-Adjusted Cancer Death Rates, for Males by Site,US, 1930–1997

Figure 2. / page 5Age-Adjusted Cancer Death Rates, for Females by Site,US, 1930–1997

Figure 3. / page 15Algorithm for Determination of Risk of Lung Cancer inSmokers Versus Non-smokers

Figure 4. / page 16Diagnostic Approach to Lung Cancer

vii

Preface Lung cancer is the most common fatal malignancyin both men and women in the United Statestoday, and also the most common cause of cancer

death worldwide. Tobacco smoking is responsible forapproximately 90% of all lung cancers, but we are notmaking great progress in reducing the prevalence ofsmoking in this country. The worldwide prevalence ofsmoking continues to skyrocket. Thus, the epidemic oflung cancer will continue to increase.

Unfortunately, lung cancer is usually diagnosed late inits course, and mostly on the basis of symptoms ofadvanced stage or metastatic disease. Althoughscreening programs for all other major cancers areadvised, such is not the case in lung cancer. This policymust change. Today we have the knowledge andtechnology to change the outcome of lung cancer.

Occupational lung disease represents a wide spectrumof hypersensitivity, fibrotic and neoplastic diseases.Some of these occupational diseases relate to lungcancer, such as fibrotic lung diseases where lung canceris a complication. Prevention of disease initiation orprogression is the goal of medicine, and could reduce oreliminate these disorders.

The frontline practitioner encounters the great majorityof smokers who are at risk of lung cancer. A pragmaticapproach to the early diagnosis of lung cancer is criticalto improving survival. Frontline practitioners also see the majority of patients who have occupational-related lung diseases. Thus, this monograph is directed to the frontline practitioners who encounterthese patients first.

viii

Frontline Treatment of Lung Cancer & Occupational Pulmonary Diseases

As in the previous five monographs of this series, theauthors are all specialists in pulmonary medicine fromboth academia and the private practice sector. We haveprepared a practical approach to assessment of lungcancer and occupational lung diseases for the frontlinepractitioner. As with our other monographs, we do notpresent our advice as a cookbook approach or asguidelines that are set in stone. Rather, we aim to offeryou and your patients a pragmatic approach to theinitial assessment of lung cancer and occupational lungdiseases in hopes of early treatment and resolution ofthese problems. ■

The Authors

ix

x

FrontlineAssessmentof LungCancer

A Monograph for Primary Care Physicians1

2

Pearls ● Lung cancer is the most common cause of cancerdeaths in men and women.

● Smoking cessation is the only proven method toreduce the risk of lung cancer.

● Lung cancer is four to six times more common insmokers with airflow obstruction than with normalairflow, as measured by spirometry.

● Surgical resection cures greater than 80% ofpatients with stage I lung cancer.

● A second primary lung cancer will occur in 5% to20% of previously cured lung cancer patients.

● Adenocarcinoma has replaced squamous cellcarcinoma as the most common histologic type oflung cancer.

● Lung cancer occurs more commonly in non-smoking women than in non-smoking men.

● Small-cell lung cancer is primarily treated withchemotherapy. ■


A. Epidemiologyand Etiology

EpidemiologyLung cancer worldwide constitutes 16% of all

malignant tumors and accounts for 28% ofcancer deaths (35% in males and 19% in

females) and about 6% of all deaths. By the year 2000,there will be 1,331,000 deaths annually from lungcancer worldwide. The American Cancer Society (acs),projects that 169,500 new cases of lung cancer will bediagnosed in the United States (90,700 in males and78,800 in females) in 2001, and 157,400 affectedpatients will die from the disease (90,100 males and67,300 females). Although the mortality rate from mostsolid tumors has been declining in the United States, themortality rate from lung cancer has continued to riseover the past several decades (See Figures 1 and 2). Theslight drop in mortality in men is overwhelmed by themortality increase in women.

Patients with lung cancer are typically heavy tobaccosmokers in their sixth or seventh decade of life. Lessthan 5% of affected patients are under 40 years of age.Lung cancer used to be primarily a male disease.However, recently the prevalence has increased morerapidly in women (See Figures 1 and 2). The increase oflung cancer in females parallels the well-documentedincrease in the number of women smokers. In the pastfour decades, there has also been a marked increase inadenocarcinoma of the lung, which is now the mostcommonly diagnosed histologic type, followed bysquamous cell, small-cell and large-cell carcinomas.

The economic cost of lung cancer is enormous. In theUnited States alone, lung cancer-associated medicalcosts are estimated to exceed $10 billion, representing1.5% of the total cost of illness. Twenty percent of thecost is from direct health care, whereas lost wages andproductivity account for 80%.(continued)

3

4 A. Epidemiology and Etiology (continued)

Figure 1

Age-Adjusted Cancer Death Rates, for Males by Site, US, 1930–1997

Source: Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001; 51:28.

1930

1935

1940

1945

1950

1955

1960

1965

1970

1975

1980

1985

1990

1995

1997

0

10

20

30

40

50

60

70

80

Rat

e pe

r 10

0,00

Mal

e P

opul

atio

n

StomachProstatePancreasLiverLeukemiaColon & Rectum Lung & Bronchus


Figure 2

Age-Adjusted Cancer Death Rates, for Females by Site, US, 1930–1997

Source: Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001; 51:27.

5

1930

1935

1940

1945

1950

1955

1960

1965

1970

1975

1980

1985

1990

1995

1997

0

10

20

30

40

50

60

70

80

Rat

e pe

r 10

0,00

Fem

ale

Pop

ulat

ion

PancreasColon & RectumUterusOvaryStomachBreast

Lung & Bronchus


Etiology and RiskFactors

TobaccoSmoking

A vast amount of statistical evidence has incriminatedtobacco smoking, especially in the form of cigarettes, asthe main cause of the progressive rise in mortality ratesfrom lung cancer. The risk in smokers is related directlyto the number of cigarettes smoked, the duration ofsmoking in years, the age of initiation of smoking, thedepth of inhalation and the tar and nicotine levels in thecigarettes smoked. Smokers who consume one pack perday have approximately a nine- to ten-fold increasedrisk over non-smokers for developing lung cancer, whilethose who smoke two or more packs per day have atleast a ten- to 25-fold increased risk.

Cigarette smoke, a complex aerosol composed of bothgaseous and particulate compounds, reaches the lungsas either mainstream smoke, which is produced byinhalation of air through the cigarette, or sidestreamsmoke which is produced from smoldering of thecigarette between puffs. Sidestream smoke is the majorsource of environmental tobacco smoke.

Tar is the total particulate matter of cigarette smokeafter nicotine and water have been removed. Tarexposure appears to be the major link to lung cancerrisk. Mainstream smoke contains a large number ofpotential carcinogens.

1Radioactive materials

2are also

present in tobacco smoke. The tobacco-specific n-nitrosamines (tsna’s) are formed from the nitrosationof nicotine both during tobacco processing andsmoking. Of the tsna, nnk

3, appears to be the most

important cause of lung cancer. When tobacco smoke isinhaled, tsna’s are delivered directly to the lungs, andbecause they are absorbed systemically, they also reachthe lung via the pulmonary circulation.

1 Polynuclear aromatic hydrocarbons, aromatic amines, N-nitrosamines and miscellaneous organic and inorganic com-pounds such as benzene, vinyl chloride, arsenic and chromium.

2 Radon and its decay products, bismuth and polonium (radium).3 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a tobacco-

specific nitrosamine.


EnvironmentalTobacco Smoke(SecondhandSmoke)

GeneticAlterations

AirwayObstruction

The intensity of tobacco use is a function of a smoker’snicotine dependence. Although cigarettes now containless nicotine and tar than previously, to satisfy nicotineneed, smokers tend to take more puffs per minute andto inhale more deeply. With deeper inhalation, smallairways in the periphery of the lung, which lackprotective epithelium, are selectively exposed tocarcinogens, as opposed to the major bronchi. Themarked increase in adenocarcinoma of the lung, largelya peripheral tumor, has been attributed to the increaseddelivery of carcinogens such as nnk to the outerportions of the lung. Use of filters to produce smallerparticles is also a factor in the peripheral deposition ofcarcinogens and associated adenocarcinoma.

The United States Environmental Protection Agencynow classifies environmental tobacco smoke (also calledsecondhand smoke) as a lung carcinogen. In one largestudy, the relative risk of lung cancer in women withhusbands who smoke was 1.2, an increase in lungcancer incidence of 20%. The relative risk in non-smoking men with smoking wives was somewhat less,but still was elevated at 1.1.

Smoking has been shown to be associated withmutations in the p53 tumor suppressor genes, the mostcommon genetic alterations detected in human cancers.Such mutations have been associated with a history ofheavy tobacco use, but they have also been detected innon-smokers with lung cancer.

The presence of airway obstruction is also a risk factor for lung cancer after adjustment for smokinghistory. Moreover, there is a statistically significantassociation between the presence of airflow obstructionand the development of lung cancer in women whohave never smoked.(continued)

7

8

Gender

Diet

OccupationalCarcinogens

The lung cancer mortality rate has risen more than500% in women since 1950. Although most of thisincrease could be attributed to the increase in theprevalence of cigarette smoking among women sincethe 1940’s, two disturbing facts have emerged. First,women appear to be more susceptible to carcinogens incigarettes than men. Zang and Wynder showed thatodds for the development of lung cancer were 1.2- to1.7-fold higher in women than in men. Second, it alsoappears that lung cancer occurs more commonly innon-smoking women than in non-smoking men. In acase-controlled study, Zang and Wynder found thatwomen are twice as common as men in the small groupof lung cancer patients who never smoked.

Various studies in several countries have shown thatlow dietary intake of fruits and vegetables is associatedwith increased lung cancer risk and that a lower serumlevel of beta-carotene (a provitamin A occurring infruits and vegetables) is associated with risk for laterdevelopment of lung cancer. Persons in the lowestquartile of beta carotene intake have approximately a50% to 100% increase of lung cancer risk as comparedwith persons in the highest quartile. Unfortunately,large-scale epidemiological studies assessing whetherbeta carotene and vitamin E might be useful as cancerchemopreventive agents did not demonstrate areduction in the incidence of lung cancer mortality oroverall mortality.

Substances encountered in the workplace that areconsidered causative of lung cancer are listed in Table 1.

Asbestos may be the most frequent occupational causeof human lung cancer. Among asbestos workers, onedeath in five is due to lung cancer. The latency period(the interval between the beginning of exposure and theonset of lung cancer) is usually 20 years or more. Mostcases of lung cancer in occupationally exposed workersoccur in smokers with asbestosis (interstitial lung

A. Epidemiology and Etiology (continued)

Frontline Assessment of Lung Cancer9

Table 1

Substances Encountered in Workplace ExposuresCategorized as Causative for Bronchogenic Carcinoma

Substance

Arsenic

Asbestos

Bis(chloromethyl) ether and chloromethyl methyl ether

Chromium and certain chromium compounds (hexavalent chromium)

Ionizing radiation, gamma radiation (x-rays)

Man-made mineral fibers (certain kinds only)

Mustard gas

Nickel in nickel refining

Radon progency (decay products)

Soots, tars, mineral oils (polycyclic aromatic hydrocarbons)

Vinyl chloride

Adapted with permission from Beckett WS. Epidemiology and etiology oflung cancer. Clin Chest Med 1993;14:8.


disease due to asbestos), and the distribution of celltypes is about the same as that of smokers withoutasbestos exposure.

All types of radiation may be carcinogenic. There is astrong association between exposure to uranium amongminers and development of bronchogenic carcinoma,particularly small-cell lung cancer. Combining smokingand uranium exposure markedly increases the risk ofdeveloping lung cancer.

Radon is a radioactive gas which occurs naturally in theearth’s crust as part of the decay chain of uranium-238,and although concentrations of radon remain low inoutdoor air, the gas can build up inside homes. Theincidence of lung cancer increases with increasing radonconcentrations in homes. It has been recently estimatedthat occurrence of radon in people’s homes may accountfor one in 20 cases of lung cancer. ■


References

Beckett WS. Epidemiology and etiology of lung cancer.Clin Chest Med 1993;14:1-15. Excellent review.

Greenlee RT, Hill-Harmon MB, Murray T, Thun M.Cancer Statistics, 2001. CA Cancer J Clin 2001;51:15-36. Comprehensive annual review of worldwide cancerstatistics.

Loeb LA, Ernster VL, Warner KE, Abbotts J, Laszlo J.Smoking and lung cancer: An overview. Cancer Res1984;44:5940-5958. Discusses the wide impact ofsmoking on lung cancer.

Murray CJ, Lopez AD (eds). The Global Burden ofDisease: A comprehensive assessment on mortality anddisability from diseases, injuries, and risk factors in1996 and projected to 2020. Worldwide deaths 1996.Harvard Press. Cambridge, MA 1996 43 p. Deathsfrom lung cancer are projected to 2020.

Zang EA, Wynder EL. Differences in lung cancer riskbetween men and women: Examination of the evidence.J Natl Cancer Inst 1996;88:183-192. Reviews theapparent increased susceptibility of women to developlung cancer.

11

12

B. A PracticalApproach toEarly Diagnosisand Staging

Early Diagnosis

In 2001, approximately 169,500 new lung cancerswill be diagnosed in the United States. Only about25% of these patients will be candidates for

resectional surgery because most lung cancer isdiagnosed in late or metastatic stages. The frontlinepractitioner can help with the diagnosis of early lungcancer by the following approach.

Ninety percent of lung cancer occurs in smokers.Unfortunately, due to the lingering effects of the carcin-ogen-induced mutations from tobacco smoke, todaymore lung cancer is diagnosed in former smokers thanin current smokers. Occupational risks for lung cancerinclude asbestos and uranium mining, and exposure tovolatile toxins such as benzene and certain forms ofindustrial ether, which are rare. Although x-rayscreening and the use of sputum cytology as case find-ing tools for lung cancer are not recommended today bythe American Cancer Society (acs), the NationalCancer Institute (nci) or any medical society, it is likelythat this dogma will be replaced by a new pragmaticapproach to screening in patients at highest risk.

Late diagnosis results in high costs for cancer care in therange of $43,758 to $52,124 per patient, and results ina five-year survival rate of approximately 13%.Prospective studies have shown that subjects who havesmoked 30 to 40 or more pack-years, and who have anydegree of airflow obstruction, have a high prevalence ofmalignant or premalignant cells in their sputum. In onestudy, 1.8% of such subjects were found to havecarcinoma in situ or invasive carcinoma; another 25%had moderate dysplasia which yielded additionalcarcinomas over the subsequent follow-up period. Thecombination of smoking with the presence of airflowobstruction results in four to six times more lung cancer than if airflow is normal, with all other riskfactors being equal.

Staging

Figure 3 is a simple algorithm which stratifies the risk ofpatients having lung cancer. Currently, we recommendthat all smokers with airflow obstruction have at least achest x-ray and sputum cytology (if a reliable cyto-pathology laboratory is available) for risk assessmentand case finding. Patients with abnormalities should beappropriately staged. According to the steps in Figure 4, patients with moderate or greater degrees ofrisk should receive at least an annual chest x-ray, orbetter, a yearly helical ct scan and sputum cytology.The low-radiation dose ct scan is emerging as moresensitive than the pa and lateral chest x-ray. Very likelya combination of ct and sputum cytology will becomethe preferred approach to early diagnosis. Currently, aprospective study is underway at the Mayo Clinicwhich will determine the cost and effectiveness of suchan approach to the early diagnosis of lung cancer.

When lung cancer is diagnosed by sputum cytology,biopsy or resection, staging is the next step. Small-cellcarcinoma is staged as central (90% of cases), orperipheral (10% of cases), and localized ordisseminated. For non-small-cell carcinoma, staging isnecessary to plan treatment and for prognosticpurposes. Recently, a new, more detailed staging systemhas been offered by Mountain. It is presented in Table 2. The descriptors used in the staging system arepresented in Table 3. The diagnostic tools used instaging are discussed in the next Section. Positronemission tomography (pet) scans and surgicalexploration (mediastinoscopy or thoracotomy) are alsoused in staging. (See Section C for a discussion of theapplication of the new tools in the diagnosis andstaging of lung cancer.)

A new healthcare initiative, known as the NationalLung Health Education Program (nlhep), proposesthat simple, handheld, accurate office spirometers beused by all primary care physicians. Patients who


B. A Practical Approach to Early Diagnosis and Staging (continued)

should have spirometry are all smokers over the age of45, patients with a family history of lung cancer orchronic obstructive pulmonary disease (copd), and anypatient with cough, inappropriate dyspnea, wheeze orexcess mucus production. All smokers, particularlythose with symptoms of airflow obstruction, should beassisted in smoking cessation. When heavy smoking andairflow obstruction are both present, the patient shouldbe evaluated for lung cancer annually by ct scanningand sputum cytology. If moderate or severe dysplasia isfound, chemoprevention should be considered. Thedetails of chemoprevention go beyond the scope of thisdiscussion. Today, clinical trials are underway to furtherevaluate the reduction in lung cancer risk from smokingcessation. Stopping smoking may result in a regressionof dysplastic changes in the bronchial epithelium. ■

14

Figure 3

Algorithm for Determination of Risk of Lung Cancer in Smokers Versus Non-smokers


Sm

oker

?

No

No

No

No

Yes

Yes

Yes

Yes

Cou

gh, W

heez

e, D

yspn

ea

No

Ris

k

Sta

ndar

d R

isk

Hig

hest

Ris

kM

oder

ate

Ris

k

Mild

Ris

k

Hig

h R

isk

Cou

gh,

Whe

eze,

Dys

pnea

Spi

rom

etry

Spi

rom

etry

Abn

orm

al

Abn

orm

al

Nor

mal

Nor

mal

Low

Ris

k

Cou

gh,

Whe

eze,

Dys

pnea

Assumes no additionalrisk; for example,asbestos exposure, uranium mining, or familyhistory of lung cancer.

15

16 B. A Practical Approach to Early Diagnosis and Staging (continued)

Figure 4

Diagnostic Approach to Lung CancerH

ighe

st R

isk:

(he

avy

smok

ing,

sym

ptom

s, a

irflow

obs

truc

tion)

Nor

mal

Spu

tum

cyt

olog

y

Nor

mal

Bro

ncho

scop

y

No

canc

er fo

und

6 m

onth

s ye

arly

follo

w-u

p by

spu

tum

cyt

olog

y an

d x-

ray

or C

T

Abn

orm

al: n

odul

e m

ass

or in

filtr

ates

Bro

ncho

scop

y an

d bi

opsy

Mar

ked

atyp

ia o

r ca

ncer

cel

ls fo

und

Can

cer

foun

d: s

urge

ry if

ope

rabl

e; r

adia

tion

ther

apy

if no

t

Che

st x

-ray

or

CT

Table 2

Stage Grouping B TNM Subsets1

Stage TNM Subset

0 Carcinoma in situ

IA T1N0M0

IB T2N0M0

IIA T1N1M0

IIB T2N1M0

T3N0M0

IIIA T3N1M0

T1N2M0

T2N2M0

T3N2M0

IIIB T4N0M0

T4N1M0

T4N2M0

T1N3M0

T2N3M0

T3N3M0

T4N3M0

IV Any T Any N M1

1 Staging is not relevant for occult carcinoma, designated TXN0M0.

Source: Mountain CF. Revisions in the International System for StagingLung Cancer. Chest 1997;111:1712,Table 3.


18

Table 3

TNM Descriptors

TX Primary tumor cannot be assessed, or tumor proven by thepresence of malignant cells in sputum or bronchial washingsbut not visualized by imaging or bronchoscopy

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor ≤ 3 cm in greatest dimension, surrounded by lung orvisceral pleura, without bronchoscopic evidence of invasionmore proximal than the lobar bronchus

1(i.e., not the

main bronchus)

T2 Tumor with any of the following features in size or extent:

> 3 cm in greatest dimension

Involves main bronchus, ≥2 cm distal to the carina

Invades the visceral pleura

Associated with atelectasis or obstructive pneumonitisthat extends to the hilar region but does not involve the entire lung

T3 Tumor of any size that directly invades any of the following:chest wall (including superior sulcus tumors), diaphragm,mediastinal pleura, parietal pericardium; or tumor in the mainbronchus <2 cm distal to the carina, but without involvementof the carina; or associated atelectasis or obstructive pneu-monitis of the entire lung

T4 Tumor of any size that invades any of the following: medi-astinum, heart, great vessels, trachea, esophagus, vertebralbody, carina; or tumor with a malignant pleural or pericardialeffusion,

2or with satellite tumor nodules(s) within the ipsilater-

al primary-tumor lobe of the lung

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilarlymph nodes, and intrapulmonary nodes involved by directextension of the primary tumor

N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s)

N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)

(continued)

B. A Practical Approach to Early Diagnosis and Staging (continued)

Primary Tumor (T)

Regional LymphNodes (N)


MX Presence of distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis present3

1 The uncommon superficial tumor of any size with its invasive compo-nent limited to the bronchial wall, which may extend proximal to the mainbronchus, is also classified T1.

2 Most pleural effusions associated with lung cancer are due to tumor.However, there are a few patients in whom multiple cytopathologic exam-inations of pleural fluid show no tumor. In these cases, the fluid is non-bloody and is not an exudate. When these elements and clinical judge-ment dictate that the effusion is not related to the tumor, the effusionshould be excluded as a staging element and the patient's diseaseshould be staged T1, T2 or T3. Pericardial effusion is classified accordingto the same rules.

3 Separate metastatic tumor nodule(s) in the ipsilateral nonprimary-tumorlobe(s) of the lung also are classified M1.

Source: Mountain CF. Revisions in the International System for StagingLung Cancer. Chest 1997;111:1711, Table 2.

Distant Metastasis (M)

20 B. A Practical Approach to Early Diagnosis and Staging (continued)

References

Bechtel JJ, Kelley WR, Petty TL, Patz DS, SaccomannoG. Outcome of 51 patients with roentgenographicallyoccult lung cancer detected by sputum cytologic testing:A community hospital program. Arch Intern Med1994;154:975-980. Results of a community-based casefinding study. Forty-six of 51 patients were candidatesfor surgery (n=27) or radiation therapy for cure (n=19). Actuarial survival including all deaths in five years was 54%.

Bechtel JJ, Petty TL, Saccomanno G. Five year survivaland later outcome of patients with x-ray occult lungcancer detected by sputum cytology. Lung Cancer2000;30:1-7. This is a follow-up of the earlier study,which includes the causes of death in all patients. Thefive-year survival in surgically resected patients was 74%.

Burns DM. Primary prevention, smoking, and smokingcessation: Implications for future trends in lung cancerprevention. Cancer 2000;89:2506-2509. This analysisshows that lung cancer diagnosis and mortality rates arehigher in former than in current smokers. After at least20 years of smoking, stopping smoking does noteliminate the risk of lung cancer. Primary preventionefforts must be increased.

Greenlee RT, Hill-Harmon MB, Murray T, Thun M.Cancer statistics, 2001. CA Cancer J Clin 2001;51:15-36. The latest lung cancer statistics for which projec-tions for the prevalence of cancer in 2001 can be made.

Henschke CI, McCauley DI, Yankelevitz DF, NaidichDP, McGuinness G, Miettinen OS, Libby DM,Pasmantier MW, Koizumi J, Altorki NK, Smith JP. EarlyLung Cancer Action Project: Overall design andfindings from baseline screening. Lancet 1999;354:99-105. Evidence that low dose ct scans can greatlyimprove the detection of small non-calcified nodules,which can represent lung cancer at an earlier stage.

Hillner BE, McDonald MK, Desch CE, Smith TJ,Penberthy LT, Maddox P, Retchin SM. Costs of careassociated with a non-small-cell lung cancer in acommercially insured cohort. J Clin Oncol1998;16:1420-1424. This is a study of the economics ofdiagnosing lung cancer by conventional methods. Thecost per patient was approximately $50,000 in 1995dollars. The two-year survival was only 27%.

Kennedy TC, Proudfoot SP, Franklin WA, Merrick TA,Saccomanno G, Corkill ME, Mumma DL, Sirgi KE,Miller YE, Archer PG, Prochazka A. Cytopathologicalanalysis of sputum in patients with airflow obstructionand significant smoking histories. Cancer Res1996;56:4673-4678. A large study which employedsputum cytology for case finding in heavy smokers. Onepoint eight percent had malignant cells. Twenty-fivepercent had moderate dysplasia.

Mountain CF. Revisions in the International System forStaging Lung Cancer. Chest 1997;111:1710-1717. Thelatest international staging system for lung cancer.

Petty TL. Lung cancer screening. Compr Ther1995;21:432-437. A pragmatic approach to lung cancer screening.

Raab SS, Hornberger J, Raffin T. The importance ofsputum cytology in the diagnosis of lung cancer. A cost-effectiveness analysis. Chest 1997;112:937-945.Sputum cytology (in a reliable laboratory) is argued tobe the most cost-effective first step in diagnosing lung cancer.

Strauss GM, Gleason RE, Sugerbaker DJ. Screening forlung cancer. Another look; A different view. Chest 1997;111:754-768. A re-analysis of the NationalCancer Institute controlled trials that showed improvedlung cancer survival with screening.


22

C. NewTechnologies inDiagnosis The early diagnosis of lung cancer remains a

difficult challenge. While newer technologies arehelping to accomplish this, the majority of lung

cancers diagnosed today are not curable at the time ofdiagnosis. Symptoms of cough and hemoptysis mayoccur with a small (curable) tumor if it is strategicallylocated in an area to produce early bronchial irritationor obstruction, but these symptoms usually only appearwith advanced disease.

Patients with symptoms of cough, dyspnea and wheeze,strong smoking histories and documented airflowobstruction are more likely to develop lung cancer thanpatients without these symptoms. This subset ofpatients is at high risk for lung cancer. Annual sputumcytologies can identify those with sputum atypia whoare at even higher risk of developing lung cancer.

The standard diagnostic techniques over the past 15years for identifying lung cancer include the chest x-ray,thoracic computed tomography (ct) and fiberopticbronchoscopy. While the chest x-ray can identifynodules greater than 1 cm in diameter, smaller lesions,and those hidden by bony, mediastinal and cardiacstructures are often missed. Once a lesion is identified,previous ct and x-ray studies should be reviewed, andappropriate consultation obtained. If the lesion is new, athree-month period of observation may be followed andthe appropriate study repeated at this time. Ifobservation seems inappropriate, then a biopsy toconfirm a tissue diagnosis should be done.

When establishing a tissue diagnosis, the approach thatis least invasive and has the highest yield should beemployed. At times, a direct surgical approach is best toprovide better staging and to eliminate sampling error.For newly diagnosed lung nodules and massesbronchoscopy, or transthoracic needle biopsy or videoassisted thoracic surgery (vats) are commonly used.(continued)

Standard diagnostictechniques over thepast 15 years toidentify lung cancerinclude the chest x-ray, CT andfiberoptic broncho-scopy. A newertechnique is low-radiation-dose CT toscreen patients athigh risk. Thetechnique is muchmore sensitive inidentifying non-calcified pulmonarynodules than thestandard chest x-ray.Because of rapidimaging capabilities itis cost-effective.


24

With smaller peripheral lesions (<2 cm) transthoracicbiopsy or vats is the procedure of choice. Whenpatients present with atelectasis or if pulmonaryinfiltrates suspicious for endobronchial obstruction aresuspected, fiberoptic bronchoscopy is indicated.

Three newer techniques merit separate discussions.First, is the use of low-radiation-dose ct to screenpatients at high risk for lung cancer. The technique ismuch more sensitive in identifying non-calcifiedpulmonary nodules than the standard chest x-ray.Because of the rapid imaging capabilities (20 secondsfor an entire study), it is cost-effective.

Second, is the use of a special bronchoscope to detectdysplasia and carcinoma in-situ by tissue auto-fluorescence. The Lung Imaging FluorescenceEndoscope (life), device takes advantage of thedifference in the autofluorescence between normal anddysplastic tissue when blue light (instead of white light)is utilized. The abnormal areas are then biopsied underdirect vision and sent for histopathologic evaluation.Currently, this technology is only being used in high-risk patients who have airflow obstruction, a heavysmoking history and sputum atypia.

Because of the high incidence of unsuspected advanced(stage II, III and IV) disease when lung cancer is initiallydiagnosed, a technique that could identify metastaticdisease would be extremely helpful. ct scans may showenlarged nodes but many times pathological correlationis not good. The pet technique is more accurate than ctfor the staging of lung cancer. Fluorodeoxyglucose(fdg) is administered to the patient and has increasedaccumulation in malignant cells. The fdg pet scanidentifies malignant nodes and metastatic disease that isunsuspected by conventional imaging. Solitarypulmonary nodules that have increased uptake of fdgare more likely to be malignant and require tissuediagnosis, while those that do not enhance may be

C. New Technologies in Diagnosis(continued)

NewTechnologies

observed for three months and then reimaged with achest x-ray or low-radiation-dose ct. The fdg pet scanlooks promising for accurate non-surgical staging oflung cancer, as well as early response to chemotherapy. ■

References

Conti PS. The clinical use of pet in lung cancer. ICPSource Book 1999, 2-16. An excellent overview of theusefulness of pet scanning in the diagnosis and stagingof lung cancer.

Henschke CI, McCauley DI, Yankelevitz DF, NaidichDP, McGuinness G, Miettinen OS, Libby DM,Pasmantier MW, Koizumi J, Altorki NK, Smith JP. EarlyLung Cancer Action Project: Overall design andfindings from baseline screening. Lancet 1999;354:99-105. This excellent study demonstrates how the use oflow-radiation-dose ct scans of the chest are much moreeffective in early detection of pulmonary nodules thanchest x-rays, and thus, can lead to earlier diagnosis oflung cancer in high-risk patients.


Newer diagnostic procedures are emerging thatcan change the outcome of lung cancer withhigh expectations of cure of early-stage disease.

These developments are the major message of thisportion of the monograph. Improvements in lungcancer chemotherapy for advanced stages of diseasealso offer important new options in our goal to reducethe suffering of this country's most common fatalmalignancy. This Section informs the frontlinepractitioner about new strategies of chemotherapy ofadvanced stages of disease that are available to theoncologist and pulmonologist who are involved in lungcancer chemotherapy. Radiation therapy and othertreatments are briefly cited. This Section also considersmeasures to control pain and suffering in late-stage andmetastatic lung cancer.

An excellent review of chemotherapy for lung cancer,which cites new agents with significant benefit hasappeared in a special supplement. Expectations incurrent chemotherapy regimens for metastatic non-small-cell carcinoma are cited in Table 4. Table 5 citesthe newer regimens for chemotherapy for metastaticnon-small-cell carcinoma.

Differing strategies of combination chemotherapy forthe various stages of disease go beyond the scope of thisSection. Suffice it to say that the nihilism of the pastneeds to be replaced with a hopeful outlook. At leastpalliation is possible with chemotherapy. Today, there isa strong impetus to popularize the concept of the“thoracic oncologist” or pneumo-oncologist. Thisperson could be a pulmonologist, thoracic surgeon,radiation oncologist or medical oncologist who hasparticular interest and expertise in lung cancer. Verylikely, many of the complexities of managing lungcancer can be handled by such an individual, or perhapsmore realistically by a team of individuals with specialexpertise in lung cancer diagnosis and treatment inspecialized centers.(continued)

26

D.Chemotherapy,RadiationTherapy andOther Therapies

Chemotherapy

Table 4

Expectations from Current Chemotherapy Regimens for Metastatic Non-Small-Cell Lung Cancer


MeaningfulResponse Rate Average 1-Year 2-Year Relief of

Setting (>50%) Survival Survival Survival Symptoms

No therapy orfailure to respond 0% 6 months 10% 0% No

Older chemotherapy:etopiside-cisplatin,vinblastine-cisplatin 20%–30% 7–9 months 25% <5% Yes

Newer chemotherapy:paclitaxel,docetaxel, vinorelbine or gemcitabine witha platinum 40%–60% 1 year 40%–50% 10%–15% Yes

Source: Ruckdeschel JC. Chemotherapy for lung cancer: New agents with significant benefit. Prim Care & Cancer 1998;18:27S, Table 1.

27

D. Chemotherapy, Radiation Therapy and Other Therapies (continued)

RadiationTherapy

PhotodynamicTherapy

Drugs that appear to have the best activity against non-small-cell lung cancer include carboplatin, vp-16,taxines, paclitaxel and docetaxel (See Table 5). Mostcurrent regimens include carboplatin and one or moreadditional agents, such as vindesine or vp-16 (etopo-side or gemritabine). Complete and partial responserates are in the range of 30% to 50%. Toxicity can besignificant. Factors that appear to correlate best withresponse to chemotherapy are, extent of disease andperformance status. Whether any subtype of non-small-cell lung cancer (nslc) tumor may respond better tochemotherapy has not been demonstrated consistently.Currently, the most realistic recommendation is to usechemotherapy as part of a protocol in patients with areasonably modest tumor burden and good clinicalperformance.

Chemotherapy is the treatment of choice for small-celllung cancer. Survival has been increased from betweentwo and three months in untreated patients to betweeneight and 14 months and sometimes longer in patientstreated with combination chemotherapy. A variety ofdrug regimens are effective, but the most effectiveinclude cisplatin plus etoposide alternating with cyclo-phosphamide, doxorubicin and vincristine. Severalstudies have documented overall response rates in therange of 80% to 95%. However, only 10% of patientswith small-cell lung cancer will survive for five years.

In patients whose co-morbidity (e.g., copd, heartdisease, advanced age), precludes surgical resection,radiation therapy may be palliative and occasionallycurative. Co-modality therapy using chemotherapy withradiation is sometimes advocated for small-cell lungcancer. The additional effect of radiation therapy addedto chemotherapy is small.

Photodynamic therapy (pdt) using new generationprotopopphyrins may be curative for in situ carcinoma.pdt may also be used in early-stage smallendobronchial cancers which have not invaded the

28


Table 5

Newer Regimens of Chemotherapy for Metastatic Non-Small-Cell Lung Cancer

Paclitaxel (Taxol)Taxol-Cisplatin (Platinol)Taxol-Carboplatin (Paraplatin)Taxol

Vinorelbine (Navelbine)Navelbine-CisplatinNavelbine-Carboplatin

Docetaxel (Taxotere)Taxotere-CisplatinTaxotere-Carboplatin

Gemcitabine (Gemzar)Gemzar-CisplatinGemzar

Source: Ruckdeschel JC. Chemotherapy for lung cancer: New agents withsignificant benefit. Prim Care & Cancer 1998;18:30S, Table 4.Gemzar, Navelbine, Paraplatin, Platinol, Taxol and Taxotere are registered trade names.

29

bronchial cartilage and in patients who are poorcandidates for surgical resection due to advanced age,tumor location or co-morbidity.

Local approaches to the treatment of malignantendobronchial lesions have included laser therapy withor without hematoporphyrin derivative and brachy-therapy with endobronchial radioisotopic implant-ation. Endobronchial stents may be used to palliateobstruction. These treatments have been used for bothin situ lesions as well as palliative therapy for advancedendobronchial disease.

Another emerging approach under intense interest ischemoprevention of lung cancer in patients with highdegrees of dysplasia judged by sputum cytology. Theeffect of vitamin E and beta carotene and the incidenceof lung cancer and other cancers in male smokersappears to be unfavorable.

The emotional and physical trauma produced by lungcancer usually overwhelms the newly diagnosedpatient. As physicians, our first duty is to providepatient comfort. Emotional support though honest andinformative discussion is paramount. Therapeuticoptions must be openly presented and, while physiciansmust be careful not to eliminate hope, statements about“curing the disease” when it is already metastatic mustbe avoided. In some situations, supportive and pallia-tive care is all that is desired and all that is appropriate.

The most troubling symptoms associated withmetastatic lung cancer include pain, dyspnea, coughand hemoptysis. Opiates remain the most effectiveagents available to control symptoms of pain anddyspnea. The use of anti-anxiety medications and non-steroidal anti-inflammatories may have a secondaryrole. In the long-term management of pain, the use oforal agents is preferable to intravenous administrationof medications. Commonly used opiates for control ofpain and dyspnea are listed in Table 6. ■

D. Chemotherapy, Radiation Therapy and Other Therapies (continued)

30

Laser Therapy,BrachytherapyandEndobronchialProstheses

Chemo-prevention

Palliative andSupportive Care


Table 6

Commonly Used Opiates for Control of Pain and Dyspnea

Medication Dose

Hydromorphone hydrochloride 2, 4, 8 mg tablets every 4 hours(Dilaudid)

Long-acting oral morphine sulfate 15, 30, 60, 100 mg tablets(MS Contin) (dose based on pain control needs)

Immediate release oral suspension 10, 20, 30 mg/ccof morphine sulfate (Roxanol) Start at 10 mg every 4 hours and increase as needed

Fentanyl transdermal system 25, 50, 75, 100 mcg released per hour(Duragesic patches) Change patch every 72 hours

Oxycodone (Percocet and Roxicet also 5 mg of oxycodonehave 325 mg of acetominophen) 1 or 2 tablets every 4 hours

Dilaudid, Duragesic patches, Percoset and MS Contin are registered trade names. Roxanol and Roxicet are registered trademarks.

31

32 D. Chemotherapy, Radiation Therapy and Other Therapies (continued)

References

The Alpha-Tocopherol, Beta-Carotene CancerPrevention Study Group. The effect of vitamin E andbeta carotene on the incidence of lung cancer and othercancers in male smokers. N Engl J Med 1994;330:1029-1035. Evidence is cited that harm may arise fromvitamin E and beta carotene given for cancerchemoprevention.

Papadimitrakopoulou VA, Ayoub JP, Hong WK. Newdevelopments in the chemoprevention of lung cancer.Prim Care & Cancer 1998;18:51S-56S.Chemoprevention strategies to reduce the risk of cancerof the aerodigestive tract in smokers are proposed in asuccinct article.

Pritchard RS, Anthony SP. Chemotherapy plusradiotherapy compared with radiotherapy alone in thetreatment of locally advanced, unresectable, non-small-cell lung cancer. A meta-analysis. Ann Intern Med1996;125:723-729. A good study which demonstrates asmall additional benefit from chemotherapy added toradiotherapy for non-resectable carcinoma.

Ruckdeschel JC. Chemotherapy for lung cancer: Newagents with significant benefit. Prim Care & Cancer1998;18:26S-32S. A brief comprehensive review ofcancer chemotherapy for non-small-cell and small-celllung cancer. “The age of nihilism is dead.”

Slotman BJ, Njo KH, Karim AB. Curative radiotherapyfor technically operable stage I non-small-cell lungcancer. Int J Radiat Oncol Biol Phys 1994;29:33-37. A review of radiation therapy strategies for early-stagelung cancer.

Stewart LA (PORT Meta-analysis Trialists Group).Postoperative radiotherapy in non-small-cell lungcancer: Systematic review and meta-analysis ofindividual patient data from nine randomised control-led trials. Lancet 1998;352:257-263. A good review ofdata on 2,128 patients in nine randomized trials whichcompared the outcome of postoperative radiationtherapy and surgical therapy without radiation.


34

E. When to Referto a Specialist The frontline physician should partner with a

local or regional pulmonologist or oncologist toprovide improved care for patients with lung

cancer. Since patients with lung cancers that present asasymptomatic chest lesions have a much betterprognosis than those diagnosed with accompanyingsymptoms, the frontline practitioner has an importantrole in screening patients with copd and a smokinghistory for possible neoplasm.

Additionally, the frontline practitioner plays animportant role in referring patients to a pulmonaryspecialist for several specific indications to help in theirscreening, preoperative evaluation and care of post-operative complications. Assistance in the post-operative period can be helpful in shortening the lengthof hospitalization and dealing with complications ofsurgery. After discharge, the pulmonologist can helpdirect the patient’s rehabilitation to optimize pulmonaryfunction.

For patients who have resection of their cancer, a long-term surveillance program is appropriate to watch foreither recurrence of their initial lung cancer or thedevelopment of a second primary lung cancer. A newlung cancer will occur in 5% to 20% of previouslytreated patients.

Patients who undergo non-surgical treatment witheither chemotherapy or radiation therapy have specificcomplications, such as infection related to bone marrowsuppression or pulmonary fibrosis secondary toradiation therapy, which a pulmonologist can helpdiagnose and treat.

Finally, patients with malignant pleural effusions,persistent atelectasis, recurrent pneumonia or rapidlydeclining pulmonary function secondary to progressionof their underlying pulmonary disease or cancertreatment program, need the assistance of a pulmonary

The frontlinephysician shouldpartner with a local orregional pulmonol-ogist or oncologist toprovide improved carefor patients with lungcancer. When a chestx-ray is deemedsuspicious for lungcancer, the patientshould be referredimmediately to aspecialist. CT israpidly replacingchest x-ray in thediagnosis of earlystage lung cancer.


36 E. When to Refer to a Specialist (continued)

Reasons to Refer

Abnormal ChestX-ray or CT

Hemoptysis

PreoperativeEvaluation

specialist to optimize pulmonary function and toimprove quality of life.

The chest x-ray is the means by which the frontlinepractitioner usually detects lung cancer. As such, it is anextremely valuable diagnostic tool for the detection oflung cancer. When a chest x-ray is deemed suspiciousfor lung cancer, the patient should be referredimmediately to a specialist. ct is rapidly replacingchest x-ray in the diagnosis of early stage lung cancer.

Hemoptysis is a special indication for referral since itmay be the initial sign of lung cancer or other seriouspulmonary disease, such as pulmonary embolus.Patients younger than 40 years with normal findings ona chest x-ray are at very low risk of bronchogeniccarcinoma and probably can be observed closely withserial chest x-rays unless other significant risk factors,such as heavy smoking history, copd or a positivefamily history for lung cancer are present.

Since pulmonary complications are the most commonform of postoperative morbidity experienced in patientswho undergo abdominal or thoracic surgery, a carefulpreoperative risk assessment by a pulmonologist isimportant in patients who are referred for surgicaltreatment of lung cancer. In addition to pneumonia andileus, patients undergoing chest surgery are at risk forlobar collapse due to central airway mucous pluggingwith secondary atelectasis, and hypoxia, which mayresult in respiratory failure. Currently, the incidence ofpostoperative pulmonary complications afterthoracotomy and lung resection is about 30%, which isrelated to both the removal of lung tissue as well asalterations in chest wall mechanics. Pulmonary functionmeasurements (spirometry) often fall dramatically inthe postoperative period and do not return to pre-operative levels for six to eight weeks. Careful pre-operative evaluation and postoperative care by apulmonologist is an important indication for referral,especially if a previous diagnosis of copd is present.

Follow-up ofPatients AfterSurgery

Pulmonary function studies and lung scans can help topredict postoperative residual lung function after anti-cipated lung cancer resection. This is especially import-ant in patients whose preoperative spirometry makesthem borderline candidates for surgical resectionbecause of the postoperative impairment to lungfunction that will ensue after surgery. Table 7 outlinespreoperative tests which help to predict if the patient isat high risk for complications after major lung resection.

After lung cancer surgery there is a significant risk oflung cancer recurrence. Accordingly, close follow-up bya pulmonologist is appropriate. One-fourth of lungcancer diagnosed in the United States each year willundergo an attempt at cure with surgical resection. Apulmonologist can help with the evaluation andmanagement of the complications of lung cancerrecurrences when they occur. During the five years afterlung cancer surgery, recurrences will develop inapproximately 5% to 20% of patients with stage Idisease, 50% with stage II, and in 70% to 80% ofpatients with stage III disease. Early detection of eitherrecurrence or a second primary lung cancer may benefita patient by allowing an opportunity for re-resection oflocal or regional disease, or instituting non-curativemedical therapies as soon as possible to prolong life orto help manage complications at this stage of thepatient’s illness to improve quality of life.

Several leading cancer treatment centers have similarfollow-up programs to detect cancer recurrence. A systematic follow-up of this group of patientsincludes frequent chest x-rays and office visits at threeto four month intervals for the first two years, at sixmonth intervals the third and fourth postoperative yearsand annually thereafter. Further diagnostic testing isbased on patient symptoms, physical examinationfindings and any new abnormalities on the chest x-rayor ct scan.(continued)


38 E. When to Refer to a Specialist (continued)

Table 7

Preoperative Tests For Assessing Pulmonary Risk Prior to Major Lung Resection

Test Percent of Predicted or Actual Value 1

FEV1% > 60%

DLCO% > 60%

Predicted postoperative FEV1 > 800 mL

Predicted postoperative FEV1% > 40%

Predicted postoperative DLCO% > 40%

VO2 max during exercise >15 mL/kg/minute

1 These parameters are not absolute and neither guarantee a successful outcome nor rule out majorresectional surgery in individual patients.

Adapted from: Ferguson MK. Preoperative assessment of pulmonary risk. Chest 1999;115:59S.

Pleural Effusion In patients with documented lung cancer, a pleuraleffusion may be due to numerous etiologies, includingmalignancy of the pleura, pulmonary embolus,pneumonia, congestive heart failure and lung cancerrecurrence. Prompt referral to a pulmonologist foreither diagnostic thoracentesis or management of arecurrent malignant pleural effusion is appropriate.Some patients will require chemical pleurodysis tomanage their recurrent effusion. Others only requireperiodic therapeutic thoracentesis for relief of dyspnea,depending on the clinical circumstances, health andfunctional status of the patient. ■

References

Downey RJ. Follow-up of patients with completelyresected lung cancer. Chest 1999;115:1487-1489. An editorial reviewing the lung cancer follow-upprogram at Memorial Sloan-Kettering Cancer Center inNew York.

Ferguson MK. Preoperative assessment of pulmonaryrisk. Chest 1999;115:58S-63S. An excellent overview ofpreoperative risk assessment of patients beingconsidered for thoracic surgery.

Younes RN, Gross JL, Deheinzelin D. Follow-up in lungcancer. How often and for what purpose? Chest1999;115:1494-1499. An analysis of the cost-effectiveness of screening tests and clinic follow-up inpatients treated for lung cancer.


40

F. MedicolegalIssues Failure to diagnosis lung cancer is an increasingly

common cause of litigation when lung cancer ismissed on chest x-rays. When abnormalities such

as a new solitary nodule, atelectasis, mass or infiltrateare overlooked on a chest x-ray taken for any purpose,litigation may follow. All chest x-rays should have anofficial interpretation by a radiologist. Be sure to viewthe films yourself when a nodule or infiltrate is reportedby a radiologist or another specialist. When a suspiciousshadow is reported by a radiologist, you would be wiseto view all chest x-rays that you order. Review old filmsfor comparison, if they are available.

Failure to evaluate and to explain the cause ofhemoptysis is a common error. At a minimum, a chestx-ray, or better, a ct scan, sputum cytology andfiberoptic bronchoscopy are required unless there is aplausible explanation for the hemoptysis. A follow-upfilm taken at four to eight weeks should show completeclearing of any abnormality seen in the first film.

Be alert to pneumonia that fails to resolve on a chest x-ray. This is another common cause of malpracticelitigation, because the underlying abnormality may becarcinoma of the lung. ■

Reference

Quekel LG, Kessels AG, Goei R, van Engelshoven JM.Miss rate of lung cancer on the chest radiograph inclinical practice. Chest 1999;115:720-724. A large studyfrom the Netherlands which showed a 19% miss ratefor lung cancer. Delays in diagnosis were associatedwith a more advanced disease stage.


42

FrontlineAssessmentofOccupationalPulmonaryDiseases

A Monograph for Primary Care Physicians43

Pearls

Asbestosis andthe OtherPneumoconioses:

● Asbestosis typically involves the lower lung zoneswhereas silicosis and coal workers' pneumoconiosistypically involves the mid and upper lung zones.

● Continued cigarette smoking increases the progres-sion rate of asbestosis.

● Question the diagnosis of malignant mesotheliomaof the pleura if the patient is not experiencing significant chest pain.

● Mesothelioma is linked to asbestos exposure butnot to tobacco use.

● When a patient presents with interstitial pulmonaryinfiltrates and a biopsy showing non-caseatinggranuloma, take an occupational history forberyllium exposure. ■

44


Pearls

OccupationalAsthma andHypersensitivityPneumonitis:

● Suspect occupational asthma when symptoms begin shortly after a patient enters a new workenvironment.

● Occupational agents are estimated to account for5% to 10% of cases of adult asthma.

● After the diagnosis of occupational asthma orhypersensitivity pneumonitis, prompt and completeremoval of the worker from the offending agent isessential to therapy.

● Since workers with occupational asthma may besymptom-free during office visits, referral to a spe-cialist is often helpful for bronchoprovocation andother testing.

● Failure to recognize hypersensitivity pneumonitismay lead to irreversible pulmonary fibrosis.

● Asthma is characterized by cough and wheezing,whereas hypersensitivity pneumonitis is more likelyto present with fever, dry cough and pulmonaryinfiltrates. Acute hypersensitivity pneumonitis ischaracterized by fever, cough and dyspnea withinthree to 12 hours of exposure. ■

45

46

G. Asbestosis,Lung Cancer andMesothelioma

Non-malignantLung Diseases

The heat and noise abatement properties of certainmineral silicates known collectively as asbestoshave been recognized for several millennia, but

the health hazards associated with chronic exposurehave only been widely appreciated for about 50 years.Asbestos exposure results in a fibrotic lung diseasetermed asbestosis, in pleural scarring known as plaqueor thickening, and in two prominent malignancies, lungcancer and malignant mesothelioma. All of thesediseases are dependent on the amount of asbestos fibersthat are inhaled (dose-dependency) and at this time onlybegin to appear after a latency period of at least ten to15 years following first exposure.

Dose-dependency and latency are important char-acteristics of asbestos-induced lung diseases. However, itshould be noted that clinicians are currently seeing theless severely affected remnant of a large spectrum ofdisease that began with the widespread industrial use ofasbestos at the end of the nineteenth century. Patientswith more severe asbestosis and pleural disease are longsince dead. In the early part of the last century, latencyperiods for disease were considerably shorter because ofa generally larger dose of inhaled fibers.

Inhalation of asbestos fibers can lead to pleural andparenchymal lung diseases. Pleural changes generallyappear after a 10- to 15-year latency. The abnormality ismanifest on chest x-rays either by circumscribed, flatpleural plaque on the parietal pleura and diaphragm orby diffuse pleural thickening, which probably representscoalescence of multiple pleural plaques. Occasionally,linear calcification will be seen within a plaque. Thisfinding is best seen radiologically along the diaphragmon a lateral view. Rarely, pleural disease leads to pleuraleffusions that wax and wane. The effusions are usuallyexudative and may or may not contain eosinophils.Recurrent pleural effusions seem to predispose to diffusepleural thickening. Pleural plaque, the most commonpleural manifestation, is usually asymptomatic and


Table 8

Lung Diseases and Findings Associated with Asbestos Exposure

Benign Malignant

Pleural plaque Lung cancer

Pleural thickening Malignant mesothelioma

Pleural effusions

Rounded atelectasis

Asbestosis

47

G. Asbestosis, Lung Cancer and Mesothelioma (continued)

Lung Cancer

rarely progresses. Occasionally, diffuse pleuralthickening can lead to significant restrictive lungdisease. None of these pleural changes are thought topresage malignancy (See Table 8).

Pleural thickening, especially along a distal intralobarfissure, can contract and form a nodule-like lesion thatresembles a mass. This is referred to as “roundedatelectasis” and, while rare, is probably most often seenin association with asbestos-induced pleural disease.Open biopsy is sometimes necessary to rule outmalignancy, although careful examination of the ctscan will often save the patient an unneeded surgicalprocedure.

Asbestosis is characterized by a chest x-ray pattern ofsmall, non-calcified, irregular, parenchymal opacities inthe lower and mid lung fields. Today, the disease has atypical latency period of at least 20 to 25 years.Concurrent pleural disease is usually present. Thedevelopment of asbestosis generally requires inhalationof more asbestos fibers than does pleural disease.Asbestosis is more likely than pleural disease toprogress. Once exposure has ceased, continuation oftobacco smoking appears to be the major risk factor forprogression of fibrosis. Whether asbestosis itselfincreases the risk for lung cancer, remains controversial.Some authorities will not implicate asbestos exposure inthe pathogenesis of lung cancer unless asbestosis ispresent, whereas other authorities see both asbestosisand lung cancer as separate dose-dependent diseasesthat are caused by inhalation of asbestos fibers.

Lung cancer has become the most lethal malignancy inboth men and women in developed countries. As acause of lung cancer, asbestos ranks well below tobaccouse, and probably below radon gas exposure, as well.However, lung cancer induced by asbestos exposure isnearly always an occupational disease, and its causationis often complicated by heavy tobacco use in theaffected individual. The two carcinogens, asbestos and

48


tobacco smoke, act synergistically to increase the riskfor lung cancer. In this regard, smokers with significantasbestos exposure can greatly lower their risk of lungcancer with permanent smoking cessation.

Today, the combination of lung cancer and asbestos isseen most often in older construction workers who havepreviously worked in close proximity to asbestos formany years. Many of these workers have also beenheavy smokers. A latency period of at least 25 to 30years from the first exposure to asbestos to theappearance of lung cancer is usually present. Theincidence of lung cancer is crudely dependent onintensity and duration of asbestos exposure, but clinicalasbestosis need not be present to implicate asbestos incausation. Causation can also be demonstrated with asuitable exposure history and the presence of pleuralplaque or with microscopic evidence of asbestosis inresected lung tissue. Some authorities have required thatclinical asbestosis be present before asbestos can beimplicated in causation of lung cancer. This position hassome merit, primarily because other inflammatory lungdiseases such as idiopathic pulmonary fibrosis also seemto be linked to an increased risk of lung cancer.However, most authorities consider the mineral,asbestos, not the process, asbestosis, to be the propercarcinogen, and attribute the increased incidence oflung cancer seen with clinical asbestosis to the dose-response effect between asbestos exposure and bothlung cancer and clinical asbestosis.

In a person with significant asbestos exposure, therelative increase in risk for lung cancer is approximatelyfive-fold. The relative risk increase for lung cancer in anon-asbestos exposed smoker with 20 pack-years isapproximately ten-fold. The synergistic effect of the twocarcinogens is demonstrated by multiplying the tworelative risks to obtain a 50-fold increase in risk in asmoker with significant asbestos exposure.

49

The classic description of the causal link was anincrease in adenocarcinoma in the lower lobes inassociation with asbestosis in shipyard workers andinsulators. Now, it is widely recognized that all celltypes of lung cancer are increased with asbestosexposure and that the disease can appear anywhere inthe lung. Many cases are overlooked for lack of anoccupational history or a proper examination of thechest x-ray. Asbestos-containing products have not beenmanufactured in the United States for almost 25 years.Occupations most at risk today in the U.S. are end-product handlers of asbestos such as insulators,pipefitters, boilermakers, millwrights, bricklayers andgeneral laborers, all as a result of exposure thatoccurred over the previous 20 to 50 years in theworkplace.

Diagnosis and therapy are no different than with anyother lung cancer. However, in surgical cases whereasbestos is a suspected carcinogen, resected lung tissueshould be processed for asbestos bodies and uncoatedfibers.

This rare tumor (15 cases per million men and two permillion women) is linked to asbestos exposure in at least75% of patients. The disease typically appears after along latency period (>30 years) and seems to be lessdependent on asbestos dose than the other diseases.Diffuse malignant mesothelioma should not beconfused with benign localized mesothelioma, an evenmore rare condition, which is not linked to asbestosexposure.

Exposure to ionizing radiation has been implicated insporadic cases of mesothelioma. Perhaps the clearestlink to a non-asbestos cause is the association ofmesothelioma with exposure to the non-asbestiformminerals, zeolite and erionite. These fibrous mineralsare mostly concentrated in and around the nation ofTurkey, with a few deposits in New Zealand and in thestate of Oregon. The primary site for malignant

50 G. Asbestosis, Lung Cancer and Mesothelioma (continued)

DiffuseMalignantMesothelioma


mesothelioma can be either pleural or peritoneal. Thepericardium and tunica vaginalis are extremely raresites of origin. In contrast to lung cancer, tobacco usehas not been implicated in the causation of malignantmesothelioma, and should not be considered a co-carcinogen in such cases.

Chest pain, which is often pleuritic, is a prominentsymptom of malignant mesothelioma. Some authoritiesare skeptical of the diagnosis if pain is not present. On the chest x-ray, pleural mesothelioma is manifested as a unilateral pleural effusion associated with lumpythickening of the parietal pleura. Depending on cell type, mesothelioma can be confused withadenocarcinoma or sarcoma. When a diagnosticprocedure is performed, sufficient tissue should beobtained for immunohistochemical and ultrastructuralanalyses. Such an approach usually requires at least athoracoscopic biopsy. Open procedures may sometimesbe necessary.

Treatment results have been dismal. The tumorresponds poorly to traditional chemotherapy, and isusually so advanced at diagnosis that curative resectionis impossible. Most patients die within one year ofdetection. A few surgeons have recently advocatedradical extrapleural pneumonectomy for cure ofmalignant mesothelioma, but long-term survival benefithas not been demonstrated. A new potential therapeuticagent, the ribonuclease known as Onconase®, iscurrently under investigation for treatment of malignantmesothelioma. In general, we do not recommendsurgery or chemotherapy unless the patient is entering aformal research protocol.

Ionizing radiation has long been known to cause lungcancer. This link was first observed almost 500 yearsago in underground miners working in close proximityto uranium. In the last century, the link was furtherconfirmed in atomic bomb survivors. Today, chronic

Other Causes ofLung Cancer

51


exposure to radon gas is the predominant way ionizingradiation results in lung cancer.

Certain metals have been implicated in lung cancer.Arsenic exposure, particularly in copper smelting, wasone of the first substances to be identified. Nickel,chrome and coke oven workers are said to be at higherrisk of lung cancer (See Table 9). The alkylating agent,bis(chloromethyl) ether (bcme), is an intermediate inthe synthesis of organic solvents, bactericides andfungicides. bcme is linked to small-cell lung cancer andhas been declared a human carcinogen by the Occu-pational Safety and Health Administration (osha).

Whether other inorganic particles can cause lung cancercontinues to be debated. The presence of silicosis hasbeen linked to lung cancer in some epidemiologicstudies, whereas other studies have shown noassociation. In all the industrial and environmentalexposures tobacco smoking is often a major co-risk.Complete and permanent smoking cessation will greatlydecrease the risk of lung cancer for patients with anyoccupational exposure, and this therapeuticintervention should always be pursued. ■

Table 9

Other Causes of Lung Cancer

Carcinogen Where Encountered

Radon gas Home basements and underground mines

Arsenic Copper smelting

Nickel, chrome and coke Smelters, kilns and foundries

Bis(chloromethyl) ether Organic chemical synthesis

Frontline Assessment of Occupational Pulmonary Diseases53

References

Becklake MR. Asbestos-related diseases of the lung andother organs: Their epidemiology and implications forclinical practice. Am Rev Respir Dis 1976;114:187-227.An early comprehensive review of the non-malignantand malignant diseases associated with asbestosexposure.

Hammond EC, Selikoff IJ, Seidman H. Asbestosexposure, cigarette smoking and death rates. Ann N YAcad Sci 1979;330:473-490. This study illustrates thesynergistic way that asbestos exposure and cigarettesmoking increase the risk of death from lung cancer.

McDonald JC, McDonald AD. Epidemiology ofmesothelioma from estimated incidence. Prev Med1977;6:426-442. The finding that the incidence ofmesothelioma is increasing in males but not in femalesargues strongly for an occupational cause.



Pneumoconiosis has been defined as lung diseaseresulting from the chronic inhalation ofinorganic dust. This Section will focus on the

most common of the pneumoconioses, excludingasbestosis. Over the last half of the twentieth century,regulatory efforts in North America and WesternEurope have reduced exposure to coal dust, silica andother inorganic substances, and have greatly improvedmorbidity and mortality among workers. Dust-relateddiseases, however, are becoming more of a problem inthe rapidly developing industrial areas of the world.

The reaction of the lung to inhaled dust depends onmultiple factors, including the chemical nature of thedust, the size and concentration of the dust particles andthe duration of exposure. Individual susceptibility to theeffects of an inhaled substance is an important, butdifficult to quantify factor. Some workers may havesevere pulmonary impairment, while others with similarexposure are not affected. Tobacco smoking is animportant multiplying factor.

Silicosis is a parenchymal lung disease caused byinhalation of silica dust in the form of free silicadioxide. Silica is the second most common element inthe earth’s crust. As many as one million Americanshave industrial exposure in mines, quarries,sandblasting, stone finishing, foundries, ceramicsmanufacturing and a variety of other occupations (SeeTable 10). The pathogenesis of silicosis is incompletelyunderstood. Silica particles from 5u to 10u deposit inthe proximal airways and are cleared by the mucociliarydefense system. They are usually not pathogenic.Smaller particles ranging in size from .5u to 5u reachthe alveoli and are ingested by macrophages. Thiscauses the release of inflammatory mediators and aninflux of lymphocytes, polymorphonuclear leukocytesand plasma cells, which eventually leads to the classichyaline nodule, an acellular core of hyalinized collagensurrounded by macrophages, plasma cells andfibroblasts. Silica crystals may be seen at the center. The

H. OtherPneumoconioses

Silicosis

55

Table 10

Occupations Associated with Silica Exposure

Abrasive manufacture

Ceramics manufacture

Foundry workers

Quarrying

Sandblasting

Tunneling

Use of silica flour (cosmetics, abrasives and paint extenders)

Adapted from: Fraser RS, Muller NL, Colman N, Paré PD. Diagnosis ofDiseases of the Chest. W. B. Saunders Company, Philadelphia, PA 1999pp 1077, 2387.

56 H. Other Pneumoconioses (continued)

Clinical Features

Chronic SimpleSilicosis

ComplicatedSilicosis

Acute Silicosis

smaller nodules may coalesce forming larger massesthat may go on to cavitate.

The diagnosis of silicosis is based on the finding ofdiffuse nodular or interstitial infiltrates on the chest x-ray of exposed workers. Workers are usuallyasymptomatic, but may complain of dyspnea or chroniccough. Four clinical presentations may be seen inpatients with silica exposure: (a) chronic simplesilicosis, (b) complicated silicosis, (c) acute silicosis and(d) silicotuberculosis.

Chronic simple silicosis is diagnosed by x-rays. Chest x-rays show small rounded densities with sharpmargins, primarily in the upper lobes, measuring from 2mm to 10 mm in diameter. Hilar adenopathy occursfrequently and lymph nodes may show “egg shell”calcifications. Patients are asymptomatic and havenormal to near normal pulmonary function. If furtherexposure is eliminated, the disease does not progress.

Complicated silicosis (also called conglomerate orprogressive massive fibrosis) is characterizedradiographically by nodules greater than 10 mm indiameter that may coalesce and produce mass-likedensities. Radiographic changes slowly progress overtime and retraction of the upper lobes leads tocompensatory over-expansion. Clinically, patientscomplain of cough, sputum production and progressivedyspnea. Pulmonary function tests show a restrictive ormixed restrictive and obstructive dysfunction. There isno specific treatment. Progression leads to hypoxemia,cor pulmonale and death. In the laboratory, positiveantinuclear antibody and rheumatoid factor tests arefrequently present, suggesting the presence of anautoimmune mechanism.

Acute silicosis is caused by intense exposure to silicaover a relatively short period of time. It has beenencountered in sandblasting, ceramic workers andminers who drill holes in rock for inserting explosives.




Silicotuberculosis

Treatment andPrevention

Coal Worker’sPneumoconiosis

Patients present with symptoms of dry cough, fever,dyspnea and weight loss. Chest x-rays show groundglass or fibrotic opacities in the upper lung fields. Thepathological findings on biopsy resemble those ofalveolar proteinosis. An association with tuberculosisand histoplasmosis is known to occur. Patients do notrespond to corticosteroids, and progressive respiratoryfailure often leads to death in months to years.

There is a four- to six-fold increase in the incidence oftuberculosis among patients with silicosis. Silica is toxicto macrophages, preventing ingestion and killing ofmycobacteria. Infection with M. tuberculosis, M. aviumand M. kansasii may be encountered. Antimy-cobacterial chemotherapy is less effective in patientswith silicosis.

There is no specific treatment for silicosis. The primarygoal is prevention by reducing exposure to silica dustand screening workers regularly with pulmonaryfunction studies and chest x-rays. The incidence of lungcancer is probably not increased in non-smokingworkers exposed to silica dust. Patients with silicosisshould have annual tuberculin skin tests, and workerswith positive reactions should have a comprehensiveevaluation to rule out active tuberculosis. If studies arenegative for active disease, workers should be treatedfor four months with isoniazid and rifampin, or for 12months with isoniazid alone. Lung transplantation hasrarely been used in patients with acute silicosis.

Exposure to coal dust causes chronic bronchitis, coalworker's pneumoconiosis (cwp), and progressivemassive fibrosis (pmf). Respiratory illness in coalminers is now seen less frequently in North Americaand Western Europe due to an increase inmechanization in the mines and measures to reduceexposure to coal dust. It is still a significant healthproblem in Russia, South Africa and China.

59


RadiographicFindings

Clinical Features,Treatment andPrevention

Coal dust is composed primarily of carbon, withvarying amounts of minerals, metals and organiccompounds. Although a small amount of silica ispresent in coal dust, the development of cwp dependson the deposition of carbon in the lungs. Deposition ofcoal dust in the lungs stimulates the migration ofmacrophages, neutrophils, epithelial cells andfibroblasts into alveoli and respiratory bronchioles,causing an inflammatory reaction. This leads to thedevelopment of nodules (coal macules) ranging in sizefrom 1 mm to 5 mm. With continued exposure, thenodules enlarge and coalesce, leading to the devel-opment of macroscopic black, rubbery masses thatoccasionally cavitate.

Chest x-rays in cwp show small nodular infiltratespredominately in the upper lobes measuring from 1 mmto 10 mm in diameter. The margins are typically lesswell defined than in silicosis. The nodules rarely calcify.In pmf, the nodules are 1 cm or larger in size, and mayraise the suspicion of bronchogenic carcinoma.Cavitation due to tissue necrosis may occur with orwithout mycobacterial infection.

Chronic cough with sputum production may occur innon-smoking coal workers. A significant decrease inpulmonary function may occur in patients withprogression to pmf or who smoke tobacco. There is nospecific treatment for cwp other than eliminatingexposure to coal dust and tobacco smoke.

A number of immunological abnormalities have beenassociated with cwp, including elevated serum IgA andIgG levels, antinuclear antibodies and rheumatoidfactor, suggesting an immunological mechanisminvolved in the pathogenesis. Miners with rheumatoidarthritis may have Caplan's Syndrome, characterized bythe presence of multiple large rounded nodules in thelungs. These nodules may cavitate. Rarely do theyspontaneously disappear. Caplan's Syndrome may also

61 Frontline Assessment of Occupational Pulmonary Diseases

Siderosis

Berylliosis

be seen in rheumatoid arthritis patients exposed tosilica, asbestos, iron and aluminum powder.

Siderosis is caused by the deposition of iron (primarilyiron oxide) in the lungs. It is seen most commonly inelectric arc welders. It may also be seen in silverpolishers, iron ore miners, ocher miners, steelworkersand foundry workers. Siderosis is primarily a radiologicdiagnosis and chest x-rays show multiple smallreticular-nodular opacities scattered diffusely through-out the lungs. Under light microscopy, deposits of ironoxide are seen within macrophages in the peribronchialand perivascular lymphatics. There is no convincingevidence that iron oxide alone leads to fibrosis.

Siderosis is generally considered to be a benigncondition, and is not associated with respiratorysymptoms or significant physiological impairmentunless there is concomitant exposure to other minerals such as silica or asbestos. This has been calledinto question by investigators who recently observedmild obstructive and restrictive pulmonary dysfunctionindependent of the effect of tobacco smoking.

Beryllium is a rare metal, used as an alloy to increase thetensile strength of other materials. Exposure may occurin ceramic workers, beryllium processors, aerospaceworkers and in dental laboratory technicians (See Table11). Exposure to beryllium can cause dermatitis, acutepneumonitis and chronic beryllium disease (berylliosis).

Berylliosis is a chronic, multisystem, granulomatousdisease caused by exposure to beryllium dust or fumes.Berylliosis is clinically, histologically and radio-graphically indistinguishable from sarcoidosis. It is theresult of a delayed-type hypersensitivity reaction and ischaracterized pathologically by noncaseatinggranulomas. Not all workers exposed to berylliumbecome sensitized, and not all sensitized workers go onto develop berylliosis. There may be a latent period offrom two to 15 years before respiratory symptoms


Table 11

Occupations Associated with Berylliosis

Aerospace industry

Beryllium miners and processors

Ceramic workers

Dental laboratory technicians

Manufacture of x-ray tubes

Adapted from: Kotloff RM, Richman PS, Greenacre JK, Rossman MD.Chronic beryllium disease in a dental laboratory technician. Am Rev RespirDis 1993;147:205-207, and Balkissoon RC, Newman LS. Beryllium copperalloy (2%) causes chronic beryllium disease. J Occup Med 1999;41:304-308.

63 Frontline Assessment of Occupational Pulmonary Diseases

RadiographicFindings

Diagnosis


appear. Dyspnea on exertion and a dry, non-productivecough are usually the presenting symptoms. Physicalexamination may be normal, or crackles may be heardat the lung bases.

Radiographic abnormalities are non-specific. The mostcommon x-ray presentation is that of diffuse finegranular mottling. Poorly defined nodules of moderatesize may also be seen and may coalesce. Hilar adeno-pathy is seen less commonly than in sarcoidosis. Thin-sectioned computed tomograms (ct’s) have been shownto be more sensitive than chest x-rays in detectingchronic beryllium disease.

The clinician should consider the diagnosis of berylliosiswhen confronted with a patient with chronic cough,progressive dyspnea, a restrictive defect on pulmonaryfunction testing and x-ray and pathological findingssuggesting sarcoidosis. The employment history shouldbe reviewed in detail as to beryllium exposure. Theberyllium lymphocyte proliferation test provides areliable method of distinguishing sarcoidosis fromberylliosis. This test has been positive in over 90% ofthe cases of berylliosis.

Patients with berylliosis respond to treatment withcorticosteroids, but there is no convincing evidence thatthey are curative. Dust control is the most importantelement of prevention. Periodic chest x-rays andpulmonary function studies are recommended. Usingthe beryllium lymphocyte proliferation test will identifyworkers at risk. Approximately 50% of workers with apositive test will go on to develop chronic berylliumdisease. It is unknown whether or not removal of theworker from exposure will prevent the laterdevelopment of berylliosis. ■


References

Hnizdo E, Murray J. Risk of pulmonary tuberculosisrelative to silicosis and exposure to silica dust in SouthAfrican gold miners. Occup Environ Med 1998;55:496-502. A comprehensive study documenting exposure tosilica as a risk factor for pulmonary tuberculosis.

Newman LS. Significance of the blood berylliumlymphocyte proliferation test. Environ Health Perspect1996;104:953S-956S. A review of the use of theberyllium lymphocyte proliferation in the diagnosis ofberylliosis.

Schwartz DA, Peterson MW. Occupational lung disease.Dis Month 1998;44:41-84. An excellent overview of theapproach to the patient with occupational lung disease.

Occupational asthma has become the mostprevalent occupational lung disease indeveloped countries. The incidence of asthma

worldwide is 5% to 10%. Recent studies suggest that10% to 15% of new cases of adult asthma are due tooccupational exposure. This common disorder posesimportant health and vocational problems for workers.Individuals may develop disabling respiratory symp-toms due to agents in the workplace, and optimaltherapy requires removal of affected workers fromexposure to the causative agent. Occupational hygiene,medicolegal and disability issues also make occu-pational asthma a major concern for industry and for society.

Occupational asthma is defined as variable airflowlimitation or bronchial hyperresponsiveness associatedwith conditions in a particular work environment, andnot with stimuli outside the workplace. Asthma maydevelop for the first time due to occupational exposure,or pre-existing asthma may be aggravated in theworkplace setting. Individuals with established asthmamay develop increased symptoms due to immuneresponses to new workplace allergens, or increasedsymptoms may occur due to non-specific reactions toirritants in the work environment.

Occupational asthma due to sensitization to allergensdevelops following a latency period after exposure. A similar syndrome may develop without latencyfollowing exposure to high concentrations of irritantgases or chemicals. This type of reaction has beennamed the reactive airways dysfunction syndrome(rads) or non-immune occupational asthma.

Over 250 agents have been reported to causeimmunologic occupational asthma. Major categories ofallergens include animals and animal products, plantand wood dusts, biologic enzymes, isocyanates,anhydrides, metals, fluxes, latex, drugs and other


I. OccupationalAsthma

Etiology

65

66 I. Occupational Asthma (continued)

Table 12

Occupational Asthma: Examples of Workers at Risk and Causal Agents

Occupational Work Causal Agents

Animal handlers Urine protein, dander

Bakers Wheat, rye, buckwheat; mites, a-amylase, hemicellulas, glucoamylase, papain, soybean

Chemical workers Sulfonechloramides, azo dyes, ethylenediamine, anthraquinone

Coffee or tea workers Green coffee, tea dust

Detergent workers Bacillus subtilis, esperase

Entomologists Locusts, blowfly

Fishery workers Sea squirts, prawns, crab

Insect handlers Bee, moth, cockroach, river flies, locust, meal worm, screw worm

Insulators Urea foam

Metal processors Platinum salts, cobalt, nickel

Oil extractors, crushers Castor beans

Pharmaceutical workers Pepsin, flaviastase, penicillin, cephalosporins, phenylglycine acid chloride, spiramycin

Plastic workers Phthalic anhydride, trimellitic anhydrides, diisocyanates

Printers Arabic gum, gum acacia

Processors Prawns, hoya, egg powder, tobacco leaf

Spice and enzyme workers Garlic powder, papain, pectinase, trypsin, karaya gum, maiko

Woodworkers Quillaja bark, red cedar, Douglas fir, African zebrawood, iroko

Adapted from: Alberts WM, Brooks SM. Advances in occupational asthma.Clin Chest Med 1992;13:281-302.

Diagnosis

chemicals. Table 12 lists some occupations at risk andexamples of common agents that may lead tosensitization.

A number of specific factors have been identified thatincrease the risk of development of occupationalasthma. Both the sensitizing potential of the allergenand the degree of workplace exposure are independentrisk factors. Smokers and individuals with known atopyare known to be at increased risk in many settings.Sensitization often occurs rapidly, but may develop overmonths to years.

Non-immune asthma (rads) may develop withoutlatency following exposure to high concentrations oftoxic gases such as chlorine or ammonia, usually inaccidental circumstances. Whatever etiologies ormechanisms lead to the new onset of asthma symptoms,similar changes in pathologic findings and non-specificbronchial hyperreactivity are present.

Workplace dusts and pollutants acting as irritants mayalso increase symptoms in patients with pre-existingasthma. This complication is potentially preventablewith appropriate industrial hygiene measures.

Occupational asthma is so common that possibleworkplace origin must be considered in any adult withnew onset asthma or sudden worsening of pre-existingasthma. The diagnostic work-up must first confirm aclinical diagnosis of asthma with appropriate findingson history, physical examination and pulmonaryfunction testing. Then a careful search for potentialenvironmental allergens in both home and work isessential. The patient may work in an industry in whichasthma is known to be a common hazard and exposureis obvious (e.g., wood dust exposure in carpentry). Inother individuals, the exposure may be subtle, or theoffending agent uncommon. In these patients, a possibleworkplace etiology for symptoms may be suspected



because of the onset of symptoms that correlate with anew work environment. Improvement of asthmasymptoms during weekend and holidays with wor-sening on return to work also strongly suggests anoccupational cause. Work-related allergic nasal or eyesymptoms may be further clues that wheezing isoccupational in origin. If occupational asthma seemslikely, reference to published lists of industrial allergensand potential workplaces may then help to identify theresponsible agent.

If occupational asthma seems likely, Material SafetyData Sheets can be obtained from employers to learnwhat potential allergens exist in a specific workenvironment. The responsible agent may also beidentified through reference to comprehensive publishedlists of industrial allergens and potential workplaceswhere they may occur.

If asthma is strongly suggested by history, but thepatient is free of wheezing on examination with normalspirometry, pulmonary consultation may be of value toestablish the diagnosis of asthma and its cause. Thespirometric response to inhaled methacholine can bemeasured to demonstrate the presence of bronchialhyperreactivity, a characteristic feature of asthma. Peakflow measurements may be of value to establish anoccupational cause for asthma if patients are optimallymotivated and cooperate fully for reliable results. Peakflows measured at the beginning and end of theworkday may show significant falls after workplaceexposure. These tests may be misleading, however, asasthma symptoms may begin hours after the worker hasreturned home and may persist until the following day.An excellent means to evaluate a suspected occu-pational cause is to perform morning and evening peakflow testing during a week at the workplace, followedby a week at home.


Allergy specialists can identify potential workplaceantigens by skin testing or serum IgE antibody studies.However, these tests do not prove a cause-and-effectrelationship to asthma symptoms. For definitivediagnosis, specific bronchial hyperreactivity can betested by spirometric studies before and after inhalationchallenge to the suspected occupational allergen. Anytesting of inhaled allergens must be done in carefullycontrolled conditions, with facilities for emergencytreatment readily available.

The pharmacologic therapy of patients withoccupational asthma is no different than that of anyother asthmatic patient. The unique measure in dealingwith this disorder is control of the workplace exposure.Environmental improvements may allow employeeswith pre-existing asthma to remain in a work areawithout increased asthmatic symptoms. However, forthose individuals with allergic sensitization toworkplace antigens, any level of exposure cannot betolerated. Asthma treatment may minimize symptoms,but patients who remain in the same job and continueto be exposed to the same causal agent, generallyworsen with time. Since minimal concentrations ofallergens lead to immunologic responses, optimaltherapy for the patient with occupational asthma iscomplete removal from any antigen exposure.Unfortunately, despite removal from exposure, manypatients do not recover fully from occupational asthmaand continue with symptoms and the need formedication. Since the duration of symptoms prior toleaving the workplace is a prognostic factor in thedegree of recovery patients may achieve afterwithdrawal from exposure, early removal of patientsfrom the workplace is essential.

It is necessary for physicians, employers andgovernmental agencies to recognize occupationalasthma as a common industrial problem. Workplace



risk for all employees must be minimized to decrease the number of individuals sensitized toindustrial allergens. Employers must be sensitive toemployee needs by shifting them, if possible, to areasfree of the offending allergens and minimizingworkplace irritants to protect those with pre-existingasthma. For physicians, the challenge is to be alert forthe possibility of unsuspected occupational asthma inindividuals with new onset of respiratory symptoms,and to identify links between patient symptoms andwork exposures. Public health officials must makeinformation available to both physicians and industryrelative to known possible causes of industrial asthma.Finally, those involved in evaluation and adjudication ofdisability must understand the individual and some-times unique problems of patients with occupationalasthma, such as multiple triggering factors in asthma. ■


References

Blanc PD, Eisner MD, Israel L, Yelin EH. Theassociation between occupation and asthma in a generalmedical practice. Chest 1999;115:1259-1264. A studyof the frequency and nature of occupational asthma,viewed from a general practice perspective.

Chan-Yeung M, Malo JL. Aetiological agents inoccupational asthma. Eur Respir J 1994;7:346-371. A comprehensive listing of recognized causative agentsfor occupational asthma.

Venables KM, Chan-Yeung M. Occupational asthma.Lancet 1997;349:1465-1469. An excellent review of thebroad scope of occupational asthma with flow chartswhich are useful in the process of diagnostic evaluation.

71

72

J.HypersensitivityPneumonitis(HSP)

Pathogenesis,Etiology andRisk Factors

Hypersensitivity pneumonitis (hsp) is a clinical/pathological syndrome caused by inhalation ofagents to which the host has developed cell-

mediated sensitivity. In the United Kingdom, thisdisorder is generally referred to as extrinsic allergicalveolitis, but since the process clearly involves morethan “alveolitis,” hsp seems a preferable label.

The prototype of hsp is “farmer’s lung,” which wasdescribed in the 1930’s and found to be caused byinhalation of moldy hay contaminated with the sporesof thermophilic actinomycetes. Since that time,numerous other causal agents have been found toproduce hsp, including antigens derived from variousmicrobes, plants and animals as well as severalinorganic chemicals and elements which presumably actas haptenes.

For the clinician, awareness of hsp is critical since manycases are related to exposure at work or at home.Failure to recognize this disorder may result in disablingsymptoms, and if undiagnosed, can lead to irreversible,fibrotic lung injury.

Because precipitating antibodies to offending agentswere found in farmer’s lung, it was originally thoughtthat the pathogenetic process of hsp involved a type IIIantigen-antibody complex deposition in the injuredtissue. However, subsequent studies have indicated thatthe primary pathological process entails cell-mediatedhypersensitivity to the offending antigen, a type IVreaction. The immunopathogenesis is believed due torepeated exposure to an antigen with the eventualevolution of “hypersensitivity.” Then, upon re-exposure, an immune-mediated reaction occurs withcharacteristic clinical x-ray and physiological findings.Yet, the rapid onset of acute hsp suggests there may bemechanisms other than pure type IV delayedhypersensitivity.


The list of causes of hsp expands continuously. Ratherthan simply note all of the recognized agents, theknown causal elements are delineated according to theusual sites or modes of exposure in Table 13.

In the case of most of the microbial antigens, themicroorganism is not believed to be an "infectiouspathogen" in the classical sense. Rather, it merelyprovides an antigen which evokes the damaging"immune" process. However, in the case of some of thewater-borne mycobacterial exposures includingMycobacterium avium complex (mac), or the rapid-growing mycobacteria (rgm), the potential virulence ofthese bacilli raises the possibility of simultaneous hspand infection.

In most cases of plant-derived hsp, the etiologic agent isnot present when the crop is harvested. Rather, themicrobes proliferate when the crop is stored in a warmdamp environment.

In nearly all cases of hsp, exposure to the offendingagent occurs in an enclosed, indoor environment, whichpresumably means that a critical concentration ofantigen is necessary.

Comprehensive data on the incidence of hsp are notavailable. However, for certain industrial or othersituational exposures, rough attack-rates have beenderived. Estimates of the cumulative incidence offarmer’s lung disease among agrarian populations hasranged from 2% to 9%. By strict criteria, the annualincidence of farmer’s lung in one series was 44 per100,000. By contrast, the cumulative incidence of hspamong pigeon fanciers is higher, 6% to 15%. Amongthose who keep parakeets, 1% to 7% report findingsconsistent with hsp.(continued)

74 J. Hypersensitivity Pneumonitis (continued)

EnvironmentalRisk Factors

Table 13

Agents Associated with Hypersensitivity Pneumonitis (HSP)

Worksite-related Agents

Organic Antigens Conditions Caused by Microbes

Farmer’s lung Micropolyspora faeni

Aspergillus species

Streptomyces albus

Malt worker’s lung Aspergillus species

Wood worker’s lung Penicillium chrysogenum

Alternaria species

Merulius lacrymans

Saccharomonospora viridis

Cryptostroma corticale

Aureobasidium pullulans

Wood dust

Cheese worker’s lung Penicillium casei

Sugar cane worker’s lung (Bagassosis) Thermoactinomyces vulgaris

Detergent worker’s lung Bacillus subtilis

Cork worker’s lung Penicillium frequentens

Coffee worker’s lung Coffee bean dust

Cotton worker’s lung (Bysinnosis) Bract of cotton flower

Wheat worker’s lung Wheat weevil

Metal worker’s lung Rapid growing mycobacteria

Inorganic Antigens Associated with HSP Non-microbial

Paints, resins, plastics Diisocyanates

Insulation, polyurethane Trimellitic anhydride

Vineyard sprayer’s lung (fungicide) Copper sulfate

Pesticide/insecticide Pyrethrum

Home or Work-related Agents

Organic Antigens Microbial

Humidifier lung Acanthamoebae castellani

Acanthamoebae polyphaga

Naegleria gruberi

Thermoactinomyces candidus

Bird breeder’s lung (budgies, pigeons) Bird droppings

Rodent handler’s lung Urinary antigens, serum, pelts

Hot tub/spa lung Mycobacterium avium complex

Inorganic Antigens Associated with HSP Non-microbial

Polyurethane foam insulation Diisocyanates


Host RiskFactors

Diagnosis

Clinical Features

A potentially confusing aspect of hsp is that some, butnot all, persons exposed to the offending agents becomeill. While this may to some extent reflect the extent ofexposure, it is clearly more complex. Indeed, withnearly all of the well-described hsp syndromes, there isan obvious component of individual susceptibility.Although the data are variable, there is a broad patternsuggesting genetically controlled immunologicalvariables as an important element of risk. Otherseeming components of hsp vulnerability include thegeneral observation that non-smokers are at relativelygreater risk and pregnancy/parturition seems toheighten the hazard for those exposed to pigeons.

Due to obvious similarities to “infectious” pneumonia,the most important element in diagnosis of hsp isawareness. Once a clinician gives consideration to hsp,there usually are readily ascertainable clues that point tothe diagnosis. Some of the more useful elements arebriefly noted in Table 14. Various components of thediagnostic process are discussed below.

Clinical features vary according to acuity and exposure.The “acute” syndrome is thought to be associated withintense exposure following sensitization. An influenza-like illness with dry cough, dyspnea, wheezing orcongestion, fever, malaise, anorexia and/or myalgiasmay appear between three and 12 hours followingexposure. Physical findings include fever, tachypnea,tachycardia and lower zone crackles. Evidence ofconsolidation or pleural friction rubs have not been reported.

In cases of “chronic” hsp, symptoms of respiratoryinadequacy dominate over the influenza-like acutesyndrome. Chronic cough, exertional dyspnea, andwheezing or congestion may be present, even away fromexposure. In cases with extensive fibrosis, cyanosis andright heart failure (cor pulmonale) may develop. Digital



Table 14

Clinical Clues Pointing to Hypersensitivity Pneumonitis

Historical

Repeated episodes of an influenza-like illness

Episodes of an influenza-like illness in temporal relation to specific occasions or locations

Illness among workers without evidence of transmission to home contacts

Influenza-like illness without a typical prodromal pharyngitis

“Atypical pneumonia” unresponsive to antibiotics

Laboratory/Radiographical

“Atypical pneumonia” with no microbiological or serological evidence of usual pathogens

Miliary shadows on chest x-rays or CT scans in individuals not at risk for tuberculosis

Diffuse ground glass shadowing without air-bronchograms on CT scan

77


RoutineLaboratoryStudies

Special Studies

clubbing may be seen in some cases, particularly inpigeon breeder’s lung disease.

Routine laboratory studies are of limited utility. Early,the chest x-ray may be interpreted as normal.Occasionally there may be a diffuse, finely nodularpattern which is similar to “miliary” tuberculosis. Aneutrophilic leukocytosis, not eosinophilia, is common.Arterial blood gas studies typically reveal hypoxemia orwidened alveolar-arterial oxygen gradients withreduced carbon dioxide levels consistent withhyperventilation. Spirometry characteristicallydemonstrates a restrictive pattern with proportionalreductions in both the forced expiratory volume in onesecond (fev1) and the forced vital capacity (fvc).

Obviously, the constellation of findings described aboveis quite non-specific. To confirm a diagnosis of hsp, thestudies noted below may be required.

Bronchoalveolar lavage (bal) obtained via fiberopticbronchoscopy characteristically (but not diagnostically)yields highly elevated numbers and percentages of T-lymphocytes. In acute hsp, there may also be asignificant bal neutrophilia. Increased mast cells havealso been reported. Notable as well, is the absence ofpathogenic bacteria or fungi on special stains and/orculture. Therefore, there is an inability to recovermicrobes on bal points to hsp or other diffuse lungdisorders.

Although precipitating antibodies to potential offendingagents are no longer believed to play a central role in thepathogenesis of hsp (See Table 13), their presence maybe helpful in diagnosis. Serum panels are available toconfirm exposure to various microbes or antigens thatmay be involved with hsp. However, it must be stressedthat simply having precipitating antibodies to theputative etiologic agents does not confirm their role inhsp. Broadly, such tests may be seen to be quitesensitive for hsp due to a particular microorganism,

ComputedTomography(CT), Lung Scans

PulmonaryPhysiologyTesting

Lung Biopsy

(patients with hsp due to the agent always haveantibodies) but not very specific (a large number ofindividuals may have developed antibodies to the agentwithout now or previously having hsp).

Computed tomography (ct) lung scans aresubstantially more helpful than routine x-rays inidentifying hsp. Particular findings that suggest hspinclude mixed reticular and finely nodular shadows,“ground glass” opacification without prominent airbronchograms and, with repeated episodes, theappearance of interstitial fibrosis. In some cases inwhich bronchiolitis is present with hsp there may befocal areas of air trapping with hyperlucent zones. Anormal high-resolution ct scan in the presence ofclinical findings makes hsp highly unlikely. While theseradiographic findings may be typical of hsp, noparticular abnormality or constellation of findings isdiagnostic of hsp. However, in patients with classicalhistories of exposure and other findings as noted above,a characteristic ct scan may provide a presumptivediagnosis of hsp without open lung biopsy.

Pulmonary physiology testing may provide supportive,but not diagnostic evidence. In acute hsp, a restrictivepattern with reduced diffusion capacity (dlco), is seen.The resting arterial oxygen level is low, andconsiderable desaturation is seen with exercise. Airtrapping is seen in association with bronchiolitis.Airflow obstruction may be seen in some cases, usuallywith minimal or modest response to bronchodilators.

Lung biopsy may be required in cases in which theabove studies are equivocal or nondiagnostic. Due tosampling error and the relative non-specificity offindings, transbronchial biopsy is inadequate. Openlung biopsy is required, usually by video assistedthoracoscopy (vat) to confirm or exclude hsp.(continued)




The histopathology of hsp is somewhat non-specific,although the findings may be of utility either bydemonstrating another disorder or by revealing featurescharacteristic of hsp. Acute hsp is typified by amononuclear (lymphocyte/plasma cell) alveolitis in abronchocentric pattern with associated noncaseating,epithelioid granulomas. In this form it is difficult todistinguish hsp from berylliosis (a variant of hsp), orsarcoidosis. Neutrophils, eosinophils or features ofvasculitis are not typical. Birefringent foreign bodiesmay be seen in cases with various types of inorganicdust inhalation.

In chronic hsp the pathology shifts toward aninterstitial infiltrative process featuring lymphocytes,plasma cells and macrophages. There may bebronchiolar inflammation including intraluminalgranulation tissue or bronchiolitis obliterans.Granulomas tend to subside with chronicity, andinterstitial fibrosis with honeycombing develops inlongstanding cases.

The differential diagnosis for patients with suspectedHSP is extensive. A list of those conditions likely to beconfused with hsp is displayed in Table 15.

If hsp is proven or suspected, avoidance of thepresumed site or source of the offending agent is themost important element of care. However, if theexposure occurs at the workplace, e.g., farming,complete avoidance may have unacceptable financialimplications. For persons with strong attachments totheir pets/hobbies this option may be emotionallyproblematic. Clearly, the critical issue here is whethercontinued exposure will inevitably lead to progressiveconstitutional symptoms and/or respiratoryinsufficiency. In some series, farmers or pigeon fancierswho remained in or returned to these exposures havenot experienced inevitable progression in disease. Insome instances this may reflect “tolerance” associatedwith continued exposure, while in others, improved


Table 15

Common Disorders Which Can Mimic Hypersensitivity Pneumonitis

Condition Comments

Lifeguard's lung Probably contamination of aerosols by lipopolysaccharide (LPS) derived from gram-negative rods in water

Silo-filler's disease Exposure to nitrogen dioxide from fermented corn or alfalfa

Sarcoidosis An idiopathic disorder, more similar to chronic hypersensitivity pneumonitis

Berylliosis Beryllium workers may develop hypersensitivity to the metal with an illness that actually is a form of hypersensitivity pneumonitis

Eosinophilic pneumonia An acute or sub-acute process with x-ray and clinical features similar to acute hypersensitivity pneumonitis; eosinophils in peripheral blood or bronchoalveolar lavage should distinguish

Allergic bronchopulmonary Typically associated with refractory asthma, ABPA may

Aspergillosis (ABPA) have features of acute pneumonia with fever, cough and dyspneaInfectious pneumonias “Atypical pneumonias” including psittacosis, legionellosis, mycoplasma

and nontuberculous mycobacterioses

81

ventilation or the use of respiratory protective devicesmay have ameliorated the problem.

In cases with an identified source of contamination (e.g.,a humidifier, swamp cooler, air conditioner or hot tub)attempts may be made to “sterilize” the system.However, this may be difficult to achieve or sustain.Such measures should be undertaken only in concertwith environment hygienists. In general, avoidance ispreferable.

In acute hsp, the clinical x-ray physiologicabnormalities tend to subside within five to ten daysfollowing termination of exposure. With a simple acuteepisode, a return to normal may be expected. However,with repeated or protracted episodes, there is anincreasing probability of prolonged or even chronicfunctional and physiological derangements. Thus, avital issue is which patients should receivecorticosteroid therapy. Currently agreed uponindications include:

1. Acute respiratory insufficiency with hypoxemiarefractory to supplemental oxygen,

2. Patients with sub-acute disease that is notimproving despite cessation of exposure, and/or

3. Persons with chronic disordered physiologyconsistent with bronchiolitis.

Typical dosage of prednisone would be 1 mg/kg bodyweight daily for two to four weeks, with a rapid taperwhen physiological and symptomatic improvement is seen. ■


References

Embil J, Warren P, Yakrus M, Stark R, Corne S, ForrestD, Hershfield E. Pulmonary illness associated withexposure to mycobacterium-avium complex in hot tubwater. Hypersensitivity pneumonitis or infection? Chest1997;111:813-816. The authors report a case of hspassociated with exposure to M. avium complex from ahot tub. They suggest that such patients may not needantimycobacterial therapy. However, we and others feelit may be imprudent not to treat when the data areambiguous.

Kokkarinen JI, Tukiainen HO, Terho EO. Effect ofcorticosteroid treatment on the recovery of pulmonaryfunction in farmer's lung. Am Rev Respir Dis1992;145:3-5. Among a series of patients with farmer'slung, those randomly assigned to corticosteroid therapyimproved more rapidly, but at five years there was nodifference between the treated and untreated groups.The implications of these findings were thoughtfullyreviewed in an accompanying editorial (Rose C, KingTE, Jr. Controversies in hypersensitivity pneumonitis.Am Rev Respir Dis 1992;145:1-2).

Reynolds HY. Hypersensitivity pneumonitis:Correlation of cellular and immunologic changes withclinical phases of disease. Lung 1988;166:189-208. Aclassic review of clinicopathophysiologic changes atvarious stages of hsp.

Shelton BG, Flanders WD, Morris GK. Mycobacteriumsp as a possible cause of hypersensitivity pneumonitis inmachine workers. Emerg Infect Dis 1999;5:270-273.The report documents hsp among workers who usewater to cool heated metals. The steam and agitation ofthe water ostensibly liberates an aerosol containingmycobacteria which act as the agent of hsp.


84

K. When to Referto a Specialist Occupationally-related lung disorders are

frequently unrecognized because of thedifficulty in linking the patient’s physical

findings with the workplace exposure. Furthermore,many illnesses may be due to unrecognized occu-pational factors. Therefore, there are few reliableestimates of the proportion of work-related conditionsencountered in the primary care setting. A 1995 surveyof family practice physicians reported that 9% of theirtime was spent dealing with occupationally-relatedhealth problems. Because of the extremely complicatednature of occupational lung disease, including complexpatient history, physiologic impairment, work-relatedinjury, legal issues and requirements for long-termfollow-up, referral to a pulmonologist is frequentlynecessary (See Table 16).

A careful history is necessary to diagnose occupationallung disease. Referral to a pulmonologist or allergistmay assist in making this diagnosis. Specifically,occupational asthma develops after a variable period ofasymptomatic exposure to a sensitizing agent at work.Exposure in the workplace to airborne dusts, gases,vapors or fumes can result in “irritant-induced asthma.”To make this diagnosis, it is important first to confirmthat a patient does indeed have asthma. Then thesequestions must be answered: Is there a history ofchildhood allergies or asthma? Did the patient haveasthma that went into remission and now resurfacedafter workplace exposure, or was the reoccurrence ofasthma secondary to exposure to a respiratory infectionin the community? Is there a family history of asthma?Does the patient’s employment history correlate withthe onset of respiratory illness?

Pneumoconiosis (See Sections G and H) usually presentsin a subtle manner with chronic symptoms, such ascough or dyspnea and may be confused with copd.Patients with such conditions may have experiencedexposure to inorganic dusts 20 to 40 years prior to theirpresentation, making the distinction between smoking-


Table 16

When to Refer a Patient to a Specialist

Occupational asthma

Hypersensitivity pneumonitis

Persistent cough, wheeze or dyspnea associated withoccupational lung disease

Pneumoconioses

Superimposed mycobacterial infection

Asbestosis

Other work-related interstitial lung diseases, i.e., siderosis

Need for supplemental oxygen therapy

Cor pulmonale and pulmonary hypertension related to occupational lung disease

85

86 K. When to Refer to a Specialist (continued)

Etiology

Diagnosis


related copd and occupationally-related lung diseasedifficult. By contrast, symptoms of hypersensitivitypneumonitis are more readily correlated with exposureto the work environment. This association can bedelineated with a careful history and job description,(See Section J).

After it is established that a patient has asthma and anoccupational cause is suspected, it is important toidentify the specific workplace exposure which may bethe setting initiating this illness. A careful history andevaluation of workplace Material Safety Data Sheetsmay give clues to agents to which the patient has beenexposed.

Although the diagnosis of occupational lung diseasemay be inferred from the history, it must be confirmedobjectively. The diagnosis of occupational asthma, forexample, should be documented by serial measurementsof spirometry or peak flow at the workplace. Referralfor skin testing may be useful in determining the atopicstatus of the patient. Assessment of workplacesymptoms, mainly cough and dyspnea, and compli-cations such as pulmonary fibrosis or cor pulmonaleshould be evaluated by a specialist.

Interstitial lung disease and more complex pleural-parenchymal lung disease will require more thoroughevaluation, sometimes including lung or pleural biopsyfor diagnosis. Referral of these patients to a pulmonaryspecialist can expedite the evaluation when the etiologyof the patient’s illness is unclear and distinction isneeded between pre-existing copd, asthma or idio-pathic pulmonary fibrosis and a new occupationally-related lung disease.

After diagnosis of occupational lung disease isconfirmed, the patient should be advised to stopexposure to the offending agent. Medical therapy isoften required for asymptomatic patients with

occupational asthma, but the strategy for managementof the disease is no different from that for other patientswith asthma, i.e., removal of environmental sensitizingagents, management of airway inflammation andsymptomatic treatment with oral and inhaled broncho-dilator medication. Patients with active interstitial lungdisease may require lengthy anti-inflammatory treat-ment necessitating referral to a specialist to both initiatea therapy plan and to periodically monitor the patient’smedication use and response to therapy. In all cases,medical therapy of the patient’s disease should not beconsidered an alternative to environmental control andavoidance of the inciting agent.

The natural history of occupational asthma andhypersensitivity pneumonitis may be one of completeresolution after exposure is terminated. However, thedisease may persist as chronic asthma or interstitial lungdisease. This leads to long-term treatment and seriouslong-term consequences for the patient and the work-place. The worker is faced with either losing his/her jobor risking disability with continued exposure. There-fore, referral to a pulmonologist can help to clarify thediagnosis, the degree of impairment and to outline atreatment plan. ■


88 K. When to Refer to a Specialist

References

Alberts MW. Occupational asthma. namdrc Clinicaland Management Quarterly 1999;23:2-4. Summary ofevaluation and causes of occupational asthma.

Blanc PD, Eisner MD, Israel L, Yelin EH. Theassociation between occupation and asthma in generalmedical practice. Chest 1999;115:1259-1264. Ananalysis of the role of occupation and asthma in adults.

Epler GR (ed). Occupational lung diseases. ClinicsChest Med 1992;13:179-382. A thorough discussion onthe pathophysiology and history of occupational lungdisease.

Newman LS. Occupational illness. N Engl J Med1995;333:1128-1134. A comprehensive review of theevaluation and treatment of occupational illness.

Tarlo SM. Occupational issues for pulmonologists.Pulm Perspectives 1998;15:1-3. An overview of theapproach to evaluating the patient with possibleoccupational lung disease, with special emphasis onmanagement and possible medicolegal issues.

L. MedicolegalIssues

Asbestos-inducedLung Diseases

Asbestosis

In each of the five previous monographs of this series,this Section carried advice for the frontline physicianabout avoiding litigation concerning poor clinical

outcomes due to alleged physician negligence. Suchadvice is presented in the lung cancer portion of thismonograph.

In occupational lung disease, medical and legal issuesoften go beyond allegations of negligence by themanaging physicians and focus on industrial andoccupational liability. Thus, this Section includes abroader scope of medical and legal issues.

The diseases caused by inhalation of asbestos fibers aregenerally acknowledged to be acquired in the work-place. This link between disease and occupation oftenresults in litigation over compensation for injuriessustained. In this Section, we offer important aspects ofthis issue that will help the frontline physician inevaluating patients with possible occupationally-induced lung disease. In all cases, obtaining a carefuloccupational history is paramount. In many cases,referral to a specialist in pulmonary or occupationaldiseases will be helpful.

Compensation for asbestosis comes through productliability suits or workers’ compensation and is usuallyobtained once agreement has been reached on thediagnosis. However, diagnosis of asbestosis may bedisputed because there are many other causes ofpulmonary fibrosis. For this reason, a diagnosis basedon chest x-ray findings alone is usually not enough. Thepatient must be carefully interviewed and examined torule out other causes of pulmonary fibrosis before aconfident diagnosis of asbestosis can be made. In somecases, laboratory testing to rule out other conditions,e.g., connective tissue disease, may be necessary.The minimal requirements for the diagnosis ofasbestosis include a suitable exposure history with alatency period of at least 15 to 20 years and the


90 L. Medicolegal Issues (continued)

Lung Cancer

MalignantMesothelioma

presence of typical parenchymal opacities on chest x-raywith no other explanation for the x-ray findings. Pleuralplaque or thickening, which will be present in mostcases of asbestosis, strengthens the diagnosis. Otherauthorities require the presence of crackles on lungexamination, restrictive ventilatory defect, a lowdiffusing capacity (dlco) on pulmonary function testsand digital clubbing. In our opinion, the more stringentdefinition that includes all of the above criteria is rarelymet, and only by patients with advanced disease. Assuch, requiring all of the above criteria is not a usefulcase finding tool.

In cases of lung cancer with previous asbestos exposure,the issue of causation is nearly always complicated by ahistory of tobacco smoking, which is a more potentcarcinogen than asbestos. Consequently, mostauthorities require more than a history of occupationalexposure before they will implicate asbestos in thecausation of lung cancer. The causation link is usuallyconceded for patients with evident asbestosis whodevelop lung cancer. Assignment of causation toasbestos for patients with only pleural plaque is moredifficult and many medical authorities will not testify toa link in these cases. However, if asbestos and notasbestosis is the carcinogen, a suitable exposure historywith pleural plaque should be sufficient to assigncausation in cases of lung cancer even when tobaccosmoking has been present as a co-carcinogen. Finally,asbestos can be implicated if histopathology of resectedlung tissue shows typical fibrosis with ferruginousbodies or uncoated asbestos fibers. The latter can bestbe demonstrated with electron microscopy.

Tobacco smoking is not thought to cause diffusemalignant mesothelioma. Causation is generally easy toestablish for patients who develop this disease followingsufficient exposure to asbestos, but a contentious debateoften arises in establishing the diagnosis of malignantmesothelioma. Depending on cell type, diffusemalignant mesothelioma can be confused with

Pneumoconiosis

adenocarcinoma or sarcoma. Special immunohisto-chemistry and ultrastructural analyses of resected tissueare usually necessary and even then the diagnosis mayremain in doubt. When this happens, the clinicalpresentation and course are helpful. Malignantmesothelioma usually presents with prominent chestpain. It rarely metastasizes until late in its course, andprogresses rapidly and inexorably to death fromrespiratory failure and inanition, usually within oneyear of diagnosis.

In summary, establishing a causal link between asbestosexposure and lung cancer requires a careful occupa-tional history, a suitable latency period and someobjective evidence, either on chest x-ray or in histo-pathology, to corroborate the exposure history. In manycases tobacco use will be present as a co-carcinogen. Incases of diffuse malignant mesothelioma, the diagnosisshould be firmly established and the exposure historydocumented. Objective evidence of asbestos exposureon either chest x-ray or by histopathology is helpful, butnot always necessary, to implicate asbestos in causationof malignant mesothelioma.

Historically, workers with cwp (coal worker'spneumoconiosis or black lung disease), silicosis andasbestosis have been involved with litigation to receivecompensation for disability. The frontline physicianshould be alert to the possibility that a patient withchronic lung disease manifested by nodular and/orinterstitial chest x-ray may have a work-related illnessand be entitled to compensation. The clinician musthave a high index of suspicion, take a careful occupa-tional history and consider referral to a pulmonologistto confirm or rule out pneumoconiosis.

Chronic beryllium disease is rare, but can masqueradeas sarcoidosis. The signs, symptoms, chest x-ray,pathology and response to corticosteroid therapy areidentical, and the potential for litigation for failure to


92 L. Medicolegal Issues (continued)

OccupationalAsthma

HypersensitivityPneumonitis

diagnose and to refer to the appropriate specialist isconsiderable.

Medicolegal issues in occupational asthma concernprimarily the liability of employers for inadequateprotection of workers from potential respiratoryhazards or for insufficient employee education relativeto those hazards. Litigation may also relate to thedegree to which an industrial exposure is causative in aworker developing new or worsening asthmasymptoms. Issues of respiratory disability andappropriate compensation are also commonmedicolegal questions. Careful pulmonary specialistevaluations and appropriate lung function testing areoften central to these complex disputes.

The most common issues surrounding hsp relate tooccupation-associated situations. In these cases, aspectsof workers’ compensation, liability litigation,responsibility for remediation and return to the worksite may be of major importance. Hence, carefuldocumentation and consultation with occupational/environmental or pulmonary medicine specialists maybe indicated. ■

References

Churg A. Lung cancer cell type and asbestos exposure.JAMA 1985;253:2984-2985. Lung cancer involving allcell types is increased in workers with significantasbestos exposure.

Mossman BT, Bignon J, Corn M, Seaton A, Gee JB.Asbestos: Scientific developments and implications forpublic policy. Science 1990;247:294-301. An attempt tobalance the health risks of asbestos with the costs ofremoving it. This paper is controversial, but makesinteresting reading regardless of the point of view.


94

M. Postscript andBiographicalSketches ofAuthors

But for smoking, there would be little interest in adisease as rare as lung cancer. Lung cancer wasso unusual in the early part of this century that

it was considered a curiosity. The keen observations ofAlton Ochsner began to draw attention to smoking asthe major cause of lung cancer. In 1959, a landmarkarticle written by Doll and Hill appeared in the BritishMedical Journal, and Wynder and Graham authored aclassic article in the jama. We now recognize thattobacco smoke is responsible for apparently 90% of alllung cancers. Unfortunately, the link between smokingand lung cancer has been denied by the tobaccoindustry until recently. The continued promotion oftobacco to our youth is a sad commentary about howwe ignore the health of our future citizens.

Even occupational lung diseases may have a smokingcomponent. Some have viewed “black lung” as “adisease invented by Congress to compensate smokerswho work in mines!” Certainly, there are realworkplace health hazards. But the greatest hazard ofthe workplace is active and passive smoking.

Let us consider the following selected quotations about smoking:

More would I, but my lungs are wasted so That strength of speech is utterly devoid me.Shakespeare in King Henry IV

To cease smoking is the easiest thing I ever did; I oughtto know because I've done it a thousand times.Mark Twain

The best way to stop smoking is to carry wet matches.Anonymous

Usually we trust that nature has a master plan. Butwhat was it she expected us to do with tobacco?Bill Vaughan

Tobacco is a dirty weed. I like it,It satisfies no normal need. I like it,It makes you thin, it makes you lean,It takes the hair right off your beanIt's the worst darn stuff I've ever seen.I like it.Graham Lee Hemminger

Smoking is very bad for you and should only be donebecause it looks so good. People who don't smoke have a terrible time findingsomething polite to do with their lips.P. J. O'Rourke

As ye smoke, so shall ye reek.Anonymous

I read in the Reader's Digest that cigarettes are bad foryou. So I had to give up reading the Reader's Digest.Anonymous ■

Frontline Assessment of Lung Cancer & Occupational Pulmonary Diseases95

M. Postscript and Biographical Sketches of Authors(continued)

Co-Editor Thomas M. Hyers, MD

Dr. Hyers received his md degree from Duke Universityin 1968. He completed his medical internship atCleveland Metropolitan General Hospital in 1969 andthen served three years in the U.S. Public Health Serviceat the National Institutes of Health, where he helpedcoordinate early studies of urokinase and streptokinasein the treatment of pulmonary embolism. He did hismedical residency and chief residency at the Universityof Washington in Seattle, and then completed apulmonary fellowship at the University of Colorado inDenver. He served for five years as a faculty member atthe University of Colorado, Denver VeteransAdministration Medical Center, and then moved to St.Louis University where he was Director of the Divisionof Pulmonology and Pulmonary Occupational Medicinefrom 1982 to 1997.

Dr. Hyers has held the rank of Professor of InternalMedicine at St. Louis University since 1985. He has along-standing interest in thrombosis and anti-thrombotic therapy and has conducted clinical researchin the diagnosis, treatment and prevention of venousthromboembolism. Dr. Hyers continues to write andlecture frequently on this topic.

Since 1997, Dr. Hyers has maintained a private practicein pulmonology and pulmonary occupational medicineat St. Joseph's Hospital in Kirkwood, Missouri, asuburb of St. Louis. Recently, he developed an interestin Internet education and, with help, designed a website(www.careinternet.com) to help caregivers deliverantithrombotic therapy more effectively.

Dr. Hyers is married with two grown sons. In his sparetime, he enjoys creative writing, gardening and fishing.

96

Co-Editor Thomas L. Petty, MDThomas L. Petty received his md at the University ofColorado in 1958. He interned at Philadelphia GeneralHospital and received his residency training at theUniversity of Michigan and the University ofColorado. His pulmonary training was at theUniversity of Colorado. He is a pulmonologist andProfessor of Medicine at the University of ColoradoHealth Sciences Center in Denver and at RushUniversity in Chicago. He was previously Head of theDivision of Pulmonary Sciences at the University ofColorado and Director of the Fellowship TrainingProgram. Dr. Petty was founding President of theAssociation of Pulmonary Program Directors (appd),and has served as President of the American College of Chest Physicians. He is a former member of theBoard of Governors of the American Board of Internal Medicine.

Dr. Petty received the Distinguished Service Award ofthe American Thoracic Society (1995), was elected tothe Colorado Pulmonary Physicians' “Hall of Fame”(1995) and received the annual award for excellenceby the American Association for Respiratory andCardiovascular Rehabilitation (1995) and the designa-tion of faarc in 1999. He was elected to MasterFellow of the American College of Chest Physicians(1995). He also received the Master Award of theAmerican College of Physicians in 1996. Dr. Petty hasbeen named Chairman of the National Lung HealthEducation Program (nlhep). Its goal is the early diag-nosis of copd and lung cancer. He is also Editor-in-chief of the newsletter, Lung Cancer Frontiers.

Today, Dr. Petty also remains active in teaching,patient care and research. He enjoys fishing, smallgame hunting and playing with his three “kids” andeight grandchildren.(continued)


98 M. Postscript and Biographical Sketches of Authors(continued)

J. Roy Duke, Jr., MDDr. Duke was born in Ocala, Florida and attendedTulane University School of Medicine in New Orleans,Louisiana, obtaining his medical degree in 1960. Aftera two-year stint in the U.S. Air Force, he completed hispostgraduate training in pulmonary medicine at Tulanein 1967.

Dr. Duke joined the Palm Beach Medical Group inWest Palm Beach, Florida in 1967 and has practicedpulmonary medicine and internal medicine there to thepresent. He has served as Chief of Medicine and Chiefof Staff of Good Samaritan Hospital in West PalmBeach and is currently the Director of PulmonaryServices.

He has an interest in hyperbaric medicine, which is anextension of his hobbies of scuba diving and underwa-ter photography. He is also an avid fly fisherman andfly tier.

Dr. Duke is married to Bobbye Craig Duke and hastwo children, Denise and Christopher.

James T. Good, Jr., MD

Dr. Good received his md degree from the University ofKansas and completed a medical internship, residencyand chief medical residency at the University of Kansas.He then completed a three-year pulmonary and criticalcare medicine fellowship at the University of Colorado.The next four years he remained on the faculty at theUniversity of Colorado as an Assistant Professor ofMedicine and was Medical Director of both theRespiratory Therapy Department and the Critical CareUnit at Denver General Hospital. His scientific interestsinclude management of critical patients with acuterespiratory failure, pleural diseases and asthma. He is afellow of the American College of Physicians and theAmerican College of Chest Physicians (accp), andserved as the Governor for the states of Colorado andWyoming for the accp from 1988 to 1994.

He currently is in the private practice of pulmonary andcritical care medicine in south Denver and is MedicalDirector of the Swedish/Columbia Critical Care Unit.He remains actively involved in clinical research,teaching medical students and residents and incontinuing medical education programs.(continued)


100

Michael D. Iseman, MDMike Iseman grew up in Fremont, Nebraska, receivinghis undergraduate degree from Princeton University,where he majored in history and played football. Heattended Columbia University's College of Physiciansand Surgeons, receiving his md in 1965. He receivedhis training in internal medicine and pulmonary medi-cine in New York City between 1965 and 1972.

Joining the faculty of the University of Colorado in1972, he spent ten years at Denver General Hospital.Then he moved to National Jewish Hospital in 1982as Head of the clinical mycobacterial disease program.His primary research interests relate to drug-resistanttuberculosis and disease due to the “atypical mycobac-teria.” He currently is Professor of Medicine in theDivision of Pulmonary Medicine and InfectiousDiseases. He is also Editor-in-chief of the InternationalJournal of Tuberculosis and Lung Diseases.

M. Postscript and Biographical Sketches of Authors(continued)


Bernard E. Levine, MD

Dr. Levine graduated from the University of MichiganMedical School in 1959. He interned at the Universityof Colorado Medical Center and did an internalmedicine residency at the University of MichiganMedical Center. He then served two years at the U.S.Army Chemical Warfare Center where he was involvedin basic research in pulmonary physiology. He returnedto the University of Colorado for his pulmonaryfellowship in 1964.

Dr. Levine has been in the private practice ofpulmonary medicine in Phoenix, Arizona since 1966.He also has been the Director of the PulmonaryFellowship and Teaching Program at Good SamaritanRegional Medical Center since its inception in 1970.He has served on the clinical faculty at the Universityof Arizona School of Medicine with a current title ofClinical Professor of Internal Medicine. He is alsoMedical Director of the Sleep Disorders Center andPulmonary Laboratory at Good Samaritan MedicalCenter. He continues to participate actively in clinicalresearch in pulmonary and sleep disorders medicine.

Dr. Levine and his wife, Shirley, have five children andcurrently five grandchildren. His hobbies are hiking,biking and visiting grandchildren.(continued)

102 M. Postscript and Biographical Sketches of Authors(continued)

Richard A. Matthay, MD

Richard Matthay received his ab degree from StanfordUniversity in 1963. He served as an officer in the ArmyMedical Service Corps in Texas, Louisiana and Koreafrom 1963 to 1965. In 1970, he received his md fromTufts University School of Medicine. He completedinternship, residency, and pulmonary and critical caremedicine fellowship at the University of ColoradoMedical Center between 1970 and 1975. He has beenAssociate Director and Training Director of thePulmonary and Critical Care Section at Yale UniversitySchool of Medicine since 1975. In 1994, Dr. Matthaywas awarded the Boehringer Ingelheim Chair ofMedicine at Yale.

Dr. Matthay receives enormous gratification fromteaching and mentoring medical students, residents andfellows. His primary research interests are theapplication of biomarkers in the early diagnosis of lungcancer, right ventricular function in lung disease andpulmonary manifestations of the systemic autoimmunediseases.

Dr. Matthay is an avid swimmer.

Donald R. Rollins, MD

Dr. Rollins is now consultant in Internal Medicine andPulmonary Disease at Greenbrier Clinic in WhiteSulphur Springs, West Virginia. Previously he was apulmonologist engaged in clinical practice in Loveland,Colorado, where he was Medical Director of theCardiopulmonary Department at McKee MedicalCenter. He is a Fellow of the American College of ChestPhysicians and the American College of Physicians. Hewas an Associate Clinical Professor in the PulmonaryDivision at the University of Colorado Health SciencesCenter in Denver. Dr. Rollins received his ba at St. OlafCollege and his md from the University of NorthCarolina. He did his internship, residency andpulmonary fellowship at the University of Texas.

He enjoys fishing with friends and playing string bassand guitar with his daughter Elizabeth, and wife Susan,both accomplished musicians. ■


104

AAbrasives, silica in, 56

acid chloride, asthma from, 66Acanthamoebae castellani, hypersensitivity pneumonitis, 75Acanthamoebae polyphaga, hypersensitivity pneumonitis, 75Aerospace industry, berylliosis, 62African zebrawood, asthma from, 66Airway obstruction, 7Algorithm, risk of lung cancer in smokers, 15Allergic bronchopulmonary aspergillosis, 81Alternaria species, hypersensitivity pneumonitis, 75A-amylase, asthma from, 66Animal handlers, asthma in, 66Anthraquinone, asthma from, 66Antibiotics, lack of response to, 77Arabic gum, asthma from, 66Arsenic, cause of lung cancer, 53Asbestos exposure, findings associated with, 47Asbestos-induced lung diseases, legal issues, 89Asbestosis, 44, 46-54

legal issues, 89-90referral to specialist, 85

Aspergillus species, hypersensitivity pneumonitis, 75Asthma, 45, 65-71

causal agents, 66diagnosis, 67-69etiology, 65-67legal issues, 92occupational work associated with, 66prevention, 69-70referral to specialist, 85treatment, 69-70

Atelectasis, rounded, with asbestos exposure, 47Aureobasidium pullulans, hypersensitivity pneumonitis, 75Authors, biographical sketches of, 96-103Azo dyes, asthma from, 66

BBacillus subtilis, hypersensitivity pneumonitis, 66, 75Bagassosis, 75Bakers, asthma in, 66Basements, carcinogens, 53Bee, asthma from, 66Beryllion miners, processors, berylliosis, 62Berylliosis, 61-63, 81

diagnosis, 63occupations associated with, 62prevention, 63-64radiographic findings, 63treatment, 63-64

Index

105 Frontline Assessment of Lung Cancer & Occupational Pulmonary Diseases

Beta-carotene, 8Biographical sketches of authors, 96-103Bird breeder's lung, hypersensitivity pneumonitis, 75Bird droppings, hypersensitivity pneumonitis, 75Bis(chloromethyl) ether, cause of lung cancer, 53Blowfly, occupational asthma from, 66Brachytherapy and endobronchial prostheses, 30Bronchogenic carcinoma, workplace exposures causing, 9Bronchopulmonary aspergillosis, allergic, 81Bronchoscopy, for diagnosis, 22Buckwheat, asthma from, 66Budgies, bird breeder's lung, hypersensitivity pneumonitis, 75

CCancer, death rates

in females, 5in males, 4

Carcinogens, 8-10, 53Castor beans, asthma from, 66Cephalosporins, asthma from, 66Ceramic workers, berylliosis, 62Ceramics manufacture, silica exposure, 56Cheese worker's lung, hypersensitivity pneumonitis, 75Chemical synthesis, carcinogens, 53Chemical workers, asthma in, 66Chemoprevention, 30Chemotherapy, 26-28

expectations from, 27newer regimens, 28

Chest x-rayabnormal, referral with, 36for diagnosis, 22miliary shadows, hypersensitivity pneumonitis, 77

Chrome, cause of lung cancer, 53Coal worker’s pneumoconiosis, 59-60, 90Cobalt, asthma from, 66Cockroach, asthma from, 66Coffee bean dust, hypersensitivity pneumonitis, 75Coffee green, asthma fromCoffee worker

asthma in, 66coffee worker’s lung, hypersensitivity pneumonitis, 75

Coke, cause of lung cancer, 53Computed tomography, for diagnosis, 22

abnormal, referral with, 36ground glass shadowing, hypersensitivity pneumonitis, 77miliary shadows on, hypersensitivity pneumonitis, 77

Copper smelting, carcinogens, 53Copper sulfate, hypersensitivity pneumonitis, 75Cotton flower (bract of), hypersensitivity pneumonitis, 75

106

Cor pulmonale, related to lung disease, referral to specialist, 85Cork worker's lung, hypersensitivity pneumonitis, 75Cosmetics, silica in, 56Cotton flower, hypersensitivity pneumonitis, 75Cotton worker's lung, 75Cough, persistent, referral to specialist, 85Crab, asthma from, 66Cryptostroma corticale, hypersensitivity pneumonitis, 75CT scan (Computed tomography)

abnormal, referral with, 36ground glass shadowing, hypersensitivity pneumonitis, 77miliary shadows on, hypersensitivity pneumonitis, 77

DDander, asthma from, 66Death rates, from cancer

in females, 5in males, 4

Dental laboratory technicians, berylliosis, 62Detergent workers

asthma in, 66detergent worker’s lung, hypersensitivity pneumonitis, 75

Diet, lung cancer and, 8Diffuse malignant mesothelioma, 50-51Diisocyanates

asthma from, 66hypersensitivity pneumonitis, 75occupational lung disease, 75

Douglas fir, asthma from, 66Duke, J. Roy, Jr., MD, biographical sketch, 98Dyspnea

associated with lung disease, referral to specialist, 85determinig risk, 14opiates for, 31

EEffusion, pleural, 39

with asbestos exposure, 47Egg powder, asthma from, 66Endobronchial prostheses, 30Entomologists, asthma in, 66Environmental tobacco smoke, 7Enzyme workers, asthma in, 66Eosinophilic pneumonia, 81Esperase, as causal agent, 66Ether, 53Ethylenediamine, asthma from, 66Etiology, lung cancer, 6

Index (continued)

FFarmer's lung, 73, 75Females, death rates, from cancer, 5Fiberoptic bronchoscopy, for diagnosis, 22Fishery workers, asthma in, 66Flaviastase, asthma from, 66Flour, silica, 56Fluorodeoxyglucose, for diagnosis, 24Follow-up, after surgery, 37-38Foundries, carcinogens, 53Foundry, silica exposure, 56Fruits, consumption of, lung cancer and, 8

GGarlic powder, asthma from, 66Gender

death rates, from cancer by, 4, 5, 8lung cancer and, 8

Genetic alterations, carcinogenic, 7Glucoamylase, asthma from, 66Good, James T., Jr., MD, biographical sketch, 99Green coffee, asthma from, 66Ground glass shadowing, hypersensitivity pneumonitis, CT scan, 77Gum acacia, asthma from, 66

HHemicellulas, asthma from, 66Hemoptysis, 36Home basements, carcinogens, 53Host risk factors, diagnosis, 76Hot tub/spa lung, hypersensitivity pneumonitis, 75Hoya, asthma from, 66HSI (see hypersensitivity pneumonitis)Humidifier lung, hypersensitivity pneumonitis, 75Hyers, Thomas M., MD, biographical sketch, 96Hypersensitivity pneumonitis, 45, 73-83

agents associated with, 75computed tomography (CT), 79diagnosis, 86disorders mimicking, 81environmental risk factors, 74-76etiology, 73-74, 86ground glass shadowing, without air-bronchograms, CT scan, 77host risk factors, 76inorganic antigens associated with, 75laboratory studies

routine, 78special, 78-79


Index (continued)

legal issues, 92lung biopsy, 79-80lung scan, 79miliary shadow, on x-ray, CT scan, 77pathogenesis, 73-74prevention, 80-82, 86-87pulmonary physiology testing, 79referral to specialist, 85risk factors, 73-74signs of, 77treatment, 80-82, 86-87

IInfluenza-like illness, repeated episodes of, hypersensitivitypneumonitis and, 77Insect handlers, asthma in, 66Insecticide, hypersensitivity pneumonitis, 75Insulation, hypersensitivity pneumonitis, 75Insulators, asthma in, 66Iroko, asthma from, 66Iseman, Michael D., MD, biographical sketch, 100

KKaraya gum, asthma from, 66Kilns, carcinogens, 53

LLaser therapy, 30Legal issues, 40-41, 89-93Levine, Bernard E., MD, biographical sketch, 101LIFE (see Lung imaging florescence endoscopy)Lifeguard’s lung, 81Locusts

asthma from, 66Lung cancer, 1-41, 47-54, 90

with asbestos exposure, 47diagnosis, 16legal issues, 90non-small-cell, metastatic chemotherapy

current regimens, 27newer regimens, 27-29

current chemotherapy regimens for, 26-31risk of, algorithm, 15

Lung imaging fluorescence endoscope (LIFE), 24Lung resection, prior to, pulmonary risk, 38

MMaiko, asthma from, 66Males, death rates, from cancer, 4Malignant mesothelioma

with asbestos exposure, 47

108


diffuse, 50-51legal issues, 90-91

Malt worker's lung, hypersensitivity pneumonitis, 75Matthay, Richard A., MD, biographical sketch, 102Meal worm, asthma from, 66Medicolegal issues, 40-41, 89-93Merulius lacrymans, hypersensitivity pneumonitis, 75Mesothelioma, 46-54, 50-51

with asbestos exposure, 47Metal processors, asthma in, 66Metal worker’s lung, hypersensitivity pneumonitis, 75Micropolyspora faeni, hypersensitivity pneumonitis, 75Miliary shadows, on chest X-rays, hypersensitivity pneumonitis, 77Mines, carcinogens, 53Mites, asthma from, 66Mortality, from cancer

females, 5males, 4

Moth, asthma from, 66Mycobacterial infection, superimposed, referral to specialist, 85Mycobacteria, rapid growing, hypersensitivity pneumonitis, 75Mycobacterium avium complex, hypersensitivity pneumonitis, 75

NNational Lung Health Education Program (NLHEP), 13, 97Naegleria gruberi, hypersensitivity pneumonitis, 75Nickel, cause of lung cancer, 53

asthma from, 66Non-malignant lung disease, 46-48Non-small-cell lung cancer, metastatic, chemotherapy

current regimens, 27newer regimens, 28

OOil extractors, crushers, asthma in, 66Opiates, for pain, dyspnea, 30, 31Organic chemical synthesis, carcinogens, 53Oxygen therapy, supplemental, need for, referral to specialist, 85

PPain, opiates for, 31Paint

extenders for, silica in, 56pelts, hypersensitivity pneumonitis, 75

Palliative care, 30-32Papain

asthma from, 66lung disease from, 66

Pectinase, asthma from, 66

Index (continued)

Penicillin, asthma from, 66Penicillium casei, hypersensitivity pneumonitis, 75Penicillium chrysogenum, hypersensitivity pneumonitis, 75Penicillium frequentens, hypersensitivity pneumonitis, 75Pepsin, lung disease from, 66Petty, Thomas L., MD, biographical sketch, 97Pesticides, hypersensitivity pneumonitis, 75PET, (see Positron emission tomography)Pharmaceutical workers, asthma in, 66Phenylglycine, asthma from, 66Photodynamic therapy, 28-30Phthalic anhydride, asthma from, 66Pigeons, bird breeder's lung, hypersensitivity pneumonitis, 75Plaque, pleural, with asbestos exposure, 47Plastic workers, asthma in, 66Plastics, hypersensitivity pneumonitis, 75Platinum salts, asthma from, 66Pleural effusion, 39

with asbestos exposure, 47Pleural thickening, with asbestos exposure, 47Pneumoconioses, 44, 55-64

referral to specialist, 85Pneumoconiosis

coal worker’s, 59-60legal issues, 91-92

Pneumonitis, hypersensitivity (HSP), 45, 73-83, 92agents associated with, 75computed tomography (CT), 79diagnosis, 86disorders mimicking, 81environmental risk factors, 74-76etiology, 73-74, 86ground glass shadowing, without air bronchograms, CT scan, 77host risk factors, 76inorganic antigens associated with, 75laboratory studies

routine, 78special, 78-79

lung biopsy, 79-80lung scan, 79miliary shadow, on x-ray, CT scan, 77pathogenesis, 73-74prevention, 80-82, 86-87pulmonary physiology testing, 79referral to specialist, 85risk factors, 73-74signs of, 77treatment, 80-82, 86-87

Polyurethane insulation, hypersensitivity pneumonitis, 75

110


Positron emission tomography (PET), 24Prawns, asthma from, 66Preoperative evaluation, 36-37

pulmonary risk, tests prior to lung resection, 38Printers, asthma in, 66Processors, asthma in, 66Prostheses, endobronchial, 30Pulmonary hypertension, related to lung disease, referral to specialist, 85Pulmonary physiology testing, hypersensitivity pneumonitis, 79Pulmonary risk, prior to lung resection, 38Pyrethrum, hypersensitivity pneumonitis, 75

QQuarrying, silica exposure, 56Quillaja bark, asthma from, 66

RRadiation therapy, 28Radon gas, cause of lung cancer, 53Red cedar, asthma from, 66Referral to specialist, 34-39, 84-88

hypersensitivity pneumonitis, 85Resection of lung, pulmonary risk evaluation, 38Resins, hypersensitivity pneumonitis, 75Risk factors, lung cancer, 6River flies, asthma from, 66Rodent handler’s lung, hypersensitivity pneumonitis, 75Rollins, Donald R., MD, biographical sketch, 103Rounded atelectasis, with asbestos exposure, 47Rye, asthma from, 66

SSaccharomonospora viridis, hypersensitivity pneumonitis, 75Sandblasting, silica exposure, 56Sarcoidosis, 81Screw worm, asthma from, 66Sea squirts, asthma from, 66Secondhand smoke, 7Serum, hypersensitivity pneumonitis, 75Siderosis, 61

referral to specialist, 85Silica exposure. See also Silicosis

occupations associated with, 56Silica flour, 56Silicosis, 55-57

acute, 57-59chronic, simple, 57clinical features, 57, 60-61complicated, 57

prevention, 59, 60-61radiographic findings, 60treatment, 59, 60-61

Silicotuberculosis, 59Silo-filler's disease, 81Smelting, 53

carcinogens, 53Soybean, asthma from, 66Spa lung, hypersensitivity pneumonitis, 75Specialist, referral to, 34-39, 84-88

reasons to refer, 36Spice workers, asthma in, 66Spiramycin, asthma from, 66Staging of cancer, 13-20

descriptors, 18-19grouping B TNM subsets, 17

Streptomyces albus, hypersensitivity pneumonitis, 75Sugar cane worker’s lung, hypersensitivity pneumonitis, 75Sulfonechloramides, asthma from, 66Superimposed mycobacterial infection, referral to specialist, 85Supplemental oxygen therapy, need for, referral to specialist, 85Supportive care, lung cancer, 30-32

TTea workers, asthma in, 66Technologies for diagnosis, 24-25Thermoactinomyces candidus, hypersensitivity pneumonitis, 75Thermoactinomyces vulgaris, hypersensitivity pneumonitis, 75Thickening, pleural, with asbestos exposure, 47Thoracic computed tomography, for diagnosis, 2TNM descriptors, 18-19Tobacco leaf, occupational lung disease from, 66Tobacco smoking, 6-7Trimellitic anhydride

asthma from, 66hypersensitivity pneumonitis, 75

Trypsin, lung disease from, 66Tuberculosis, 77Tunneling, silica exposure, 56

UUnderground mines, carcinogens, 53Urea foam, asthma from, 66Urinary antigens, hypersensitivity pneumonitis, 75Urine protein, asthma from, 66

VVegetables, consumption of, lung cancer and, 8Video assisted thoracic surgery, 22

112


Vineyard sprayer’s lung, hypersensitivity pneumonitis, 75Vitamin A, 8

WWheat, asthma from, 66Wheat weevil, hypersensitivity pneumonitis, 75Wheat worker's lung, 75Wheeze, associated with lung disease, referral to specialist, 85Wood dust, hypersensitivity pneumonitis, 75Woodworkers

asthma in, 66woodworker's lung, hypersensitivity pneumonitis, 75

XX-ray

abnormal, referral with, 36for diagnosis, 22miliary shadows, hypersensitivity pneumonitis, 77

X-ray tubes, manufacture of, berylliosis in, 62

Frontline Assessment of Lung Cancer and Occupational Diseases

Documents