Interesting caseJanuary 26, 2011
A Thai 71 years-old female pt., married, Ex-govern teacher, Buddhism, Bangkok
CC: Acute dyspnea 1d PI: 3 week PTA develop progressive dyspnea with
low grade fever and dry cough within 2 d , then go to clinic and found abnormal CXR=>go to private hospital for admission
Dx:atypical pneumonia and Receive iv Levofloxacin for 1 day clinical worsening
CXR progress=>on BiPAP, add tazocin and tamiflu
Information data
Day 3 : start dexa 5 mg iv q 6 hrs.=>clinical improved within 12 hrs.
Day 4: CXR improved switch to oral pred and levofloxacin about 3d then D/C with HM 1 wk
1 week PTA develop fever with chill then return to same hospital Dx: sepsis Rx: cefazolin+maxipime *3d=>no fever (H/C:NG) HM : invanz IV OD
1d develop fever and dyspnea then go to KCMH At KCMH SpO2 room air 89-90%
Information data
U/D : HT and DLP for 2 yr No Hx of atopy, autoimmune or drug allergy No FH of autoimmune or CA No smoking She has many types of bird at home and farming
quail for 6 months
Information data
Physical examination Vital signs : BT 38.5 C, RR 24/min, PR 108 bpm, BP
100/60 mmHg GA : An old Thai female, normal consciousness, sick HEENT : not pale, no jaundice Neck : LN cannot be palpated, no neck vein engorged Heart : Tachycardia without significant murmur Lungs : bilateral basilar crackles Abdomen : no hepatosplenomegaly Extremities : no lesion, no edema Neuro : grossly intact
Information data
Lab :◦Hct 35% wbc 9840 N90 L6 E0 Plt 256,000◦BUN 14 Cr 0.6 TB 1.6 DB1.3 ALP 366 AST
574 ALT 373◦ABG pH 7.4 pO2 84 pCO2 33 (canula 5LPM)
Information data
Chest X rayday1
HRCT
Diffuse heterogeneous ground glass opacities with interlobular septal thickening scattering in both lungs
More pronounce in both upper lobes and RML
HRCT
Minimal amount of Rt. Pleural effusion
BAL◦ Wbc 410 PMN 71% Mono 29%◦ Small amount of cell composed ciliated cell, alveolar
macrophage mixed with some mixed inflammatory cell predominate mononuclear cells
Transbronchial Bx◦ Alveolar septa are mildly thickening and increase
fibroblastic stroma and mild lymphocyte inf.,mild pneumocyte proliferate,focal accumulation of alveolar macrophage, no neoplasm,no granuloma, or identified organism
Bronchoscope
After steroid Rx
12 Jan 2011 19 Jan 2011
Hypersensitivity pneumonitis
Boonthorn26 January 2011
Introdution Definition Epidemiology Diagnotic criteria Classification Investigation Pathology and pathophysiology Treatment
Outline
extrinsic allergic alveolitis occurs upon exposure to organic dust associated with farming (moldy grain or hay
handling) term “farmers lung” other most common settings
◦ contacts with birds (pigeons, parakeets)◦ humidifiers, moldy wood◦ chemical compounds (e.g. isocyanates, zinc)
Introduction
Allergy 2009: 64: 322–334
Pulmonary disease with symptoms of dyspnea and cough resulting from inhalation of Ag to which patient has been previously sensitized ( HP study group )
An inappropriate immune response to inhaled Ag that causes shortness of breath, restrictive lung defect, interstitial infiltrates seen on lung imaging caused by accumulation of large numbers of activated T lymphocytes in the lungs, characterized by episodic bouts of fever a few hours after exposure ( Cormier and Schuyler )
Definition
Allergy 2009: 64: 322–334Asthma and the workplace. New York: Marcel Dekker, 2006Am J Respir Crit Care Med 2003;168: 952–958.
Population-based study (in New Mexico), estimated annual incidence of ILD = 30 per 100,000 ( HP<2% )
prevalence of farmers lung in exposed farmers from 0.5% to 3% ( complicated by geographical variables, climatic conditions and, farming practices )
Epidemiology
Allergy 2009: 64: 322–334
RadioGraphics 2009; 29:1921–1938
Diagnostic criteria
Allergy 2009: 64: 322–334
Diagnostic criteria
Allergy 2009: 64: 322–334J Allergy Clin Immunol 1989;84:839–844
Most widely used are those from Richerson et al.◦History and physical findings and pulmonary
function tests indicate an interstitial lung disease◦X-ray film is consistent◦There is exposure to a recognized cause◦There is antibody to that antigen
Diagnostic criteria
Allergy 2009: 64: 322–334Am J Respir Crit Care Med 2003;168: 952–958
HP study
Diagnostic criteria
Allergy 2009: 64: 322–334Am J Respir Crit Care Med 2003;168: 952–958
Classification Clinical description
Acute HP (farmer’s lung )
Symptoms begin 2–9 h after exposure, peak typically between 6 and 23 h, and last from hours to days.Influenza-like symptoms often predominate:chills, fever, sweating, myalgias, lassitude, headache and nausea.Respiratory symptoms, such as cough and dyspnea, are common but not universal.
Subacute HP ( pigeon breeder’s or bird fancier’s diseases )
May appear gradually over several days to weeks.Marked by cough and dyspnea, and may progress to severe dyspnea and cyanosis, leading to hospitalization.
Chronic HP Insidious onset over a period of months.Increasing cough and exertional dyspnea.Fatigue and weight loss may be prominent symptoms.
Classification of HPRicherson’s classification of HP
Allergy 2009: 64: 322–334J Allergy Clin Immunol 1989;84:839–844
Chest X-ray◦ to rule out other diseases
In acute HP◦ ground-glass infiltrates, nodular and/or striated patchy
opacities◦ Up to 20% have normal chest X-rays
In subacute HP◦ Distribution is usually diffuse but often sparing the bases.
None of these findings is specific of HP
Investigation
Allergy 2009: 64: 322–334
patchy airspace disease and multiple ill-defined lung nodules with minimal upper lung volume loss
RadioGraphics 2009; 29:1921–1938
Investigation
Allergy 2009: 64: 322–334
High-resolution CT
patterns are not specific but suggest that HP be considered in the differential diagnosis when present
Insidious hypersensitivity pneumonitis in a 39-year-old woman with history of exposure to parakeets and cockatiels. (a) HRCT demonstrates extensive ground-glass opacity with a centrilobularconcentration. (b) Axial CT image obtained after therapy and removal from exposure shows complete resolution
RadioGraphics 2009; 29:1921–1938
Insidious hypersensitivity pneumonitis. Axial high-resolution CTimages depict ill-defined centrilobular ground-glass opacities
RadioGraphics 2009; 29:1921–1938
Pulmonary function tests No discriminative properties in differentiating HP
from other interstitial lung diseases Acute HP
◦ restrictive pattern with low DLCO Chronic HP
◦ most frequent profile is obstructive defect resulting from emphysema
In HP study◦ 39 of 177 patients (22%) DLCO could be normal results
at the time of diagnosis
Investigation
Allergy 2009: 64: 322–334
Specific antibodies only 1–15% of people exposed to HP antigen
develop disease while in some cases the majority of exposed individuals have high titre of serum precipitating Ab but they remain asymptomatic
10% of people exposed to Saccharopolyspora rectivirgula, main agent for Farmer’s lung,develop Ab while only 0.3% => disease
can be useful as supportive evidence
Investigation
Allergy 2009: 64: 322–334
Specific antibodies Antigens available for testing in most centres
◦ pigeon and parakeet sera, dove feather antigen, Aspergillus sp., Penicillium, S. rectivirgula and Thermoactinomyces viridans ( pigeon breeder’s disease, bird fancier’s lung, farmer’s lung and humidifier lung )
◦ Trichosporon cutaneum (summer-type HP) determination of precipitins or total IgG Ab ( ELISA
technique lacks standardization )
Investigation
Allergy 2009: 64: 322–334
Serum precipitin Negative predictive value 81-88% and positive predictive value 71-75% for prevalence of HP 20-35%
Eur Respir J 2007; 29: 706–712
Sera were collected in Sweden and South Africa and levels of IgG antibodies specific to pigeon, budgerigar and parrot antigens were quantified using the UniCAP system
Comparison of the two methods resulted in a good concordancewith a level of agreement of 94.1% (kappa statistic = 0.83)
Int Arch Allergy Immunol 2004;134:173–178
Inhalation challenge◦ lack standardization both in inhalation protocols and
criteria defining positive response Bronchoalveolar lavage
◦ normal number of lymphocytes rules out all but residual disease
◦ alveolar lymphocytosis HP, sarcoidosis, interstitial pneumonia associated with
collagen vascular disease, silicosis, BOOP , HIV-associated pneumonitis and drug-induced pneumonitis
Investigation
Allergy 2009: 64: 322–334
Bronchoalveolar lavage◦ CD4+/CD8+ ratio depends on
Stage of disease type and dose of inhaled antigen duration of antigenic exposure
◦ CD4+/CD8+ ratio < 1 => HP (chronic)◦ high CD4+/CD8+ ratio related to sarcoidosis
Transbronchial biopsy◦ limited usefulness for diagnosis of farmer’slung
Investigation
Allergy 2009: 64: 322–334
Lung biopsy In acute stages
◦ interstitial lymphocytes infiltrates and fibrosis, edema, noncaseating granulomas, and bronchiolitis obliterans
◦ Macrophages with foamy cytoplasm in alveolar space In chronic stages
◦ widespread fibrotic reaction (prominent feature)◦ often without predominant involvement of upper lobes
with contraction◦ Emphysema
Investigation
Allergy 2009: 64: 322–334
2 most common and most characteristic histopathologic featuresof HP: lymphocytic infiltrates within the interstitium, sometimes referred to as cellular interstitial pneumonitis (arrowheads), and a poorly formed granuloma (arrow).
RadioGraphics 2009; 29:1921–1938
Current Opinion in Pulmonary Medicine 2008, 14:440–454
Current Opinion in Pulmonary Medicine 2008, 14:440–454
Current Opinion in Pulmonary Medicine 2008, 14:440–454
Current Opinion in Pulmonary Medicine 2008, 14:440–454
Type III and IV hypersensitivity High titres of antigen-specific precipitating serum
IgG that can fix complement◦ Ab specific to offending agent are increased in both
serum and BAL◦ resulting C5 induces macrophages activation
cells infiltration, particularly lymphocytes, and formation of granuloma in lung
Pathology and pathophysiology
Allergy 2009: 64: 322–334
Important actors in HP: inflammatory cells Lymphocytes
◦ main cells involved in pathophysiology of HP ◦ 60–90% of BAL-recovered cells◦ CD8+ lymphocytes, CD45 RO T lymphocytes, B
lymphocytes Neutrophils
◦ Elastase break down of elastic fibres promote emphysema
◦ production of oxygen-free radicals and trigger development of fibrosis
Pathology and pathophysiology
Allergy 2009: 64: 322–334
Important actors in HP: inflammatory cells Macrophages
C5 fraction activates alveolar macrophages which release inflammatory and chemotactic factors eg. IL-8, RANTES, CCL18, MCP-1 and MIP-1α to recruitment of other cells eg. Neutrophils and macrophages
Soluble factors◦ Th1 cytokine (IL-12)◦ IL-1, IL-8, TNF, IL-6, MCP-1 and MIP-1α
◦ Surfactant Increased concentrations of phosphatidylanolamine and
phosphatidylinositol
Pathology and pathophysiology
Allergy 2009: 64: 322–334
Promoting and protective factors Aetiological agents
◦ Small slowly degradable particles◦ adjuvant effect causes release of ROS,PGs,LTs and
proteolytic compounds Viral infection
◦ could enhance HP by increasing expression of CD86 co-stimulatory molecule on APC
Genetic predispositions◦ polymorphism in TNF-α-308 promoter associated with high
production of TNF in patients with bird-fancier’s lung
Pathology and pathophysiology
Allergy 2009: 64: 322–334
Promoting and protective factors Nicotine
◦ HP and specific antibodies are more frequent in nonsmokers
◦ smoking habits affect alveolar macrophages phagocytosis and decrease capacity to produce IL-1 and TNF
◦ decrease total BAL cells like lymphocytes ,B7 co-stimulatory molecules on macrophages
◦ In smokers, viral infection not increase CD86 molecules expression on macrophages
Suppressive cells◦ tolerogenic DC able to drive differentiation of Treg cells
Pathology and pathophysiology
Allergy 2009: 64: 322–334
ideal treatment for any form of HP is contact avoidance with offending Ag
only drugs currently used for HP are oral corticosteroids◦ Dose is unclear◦ Recommend 50 mg of oral prednisolone daily◦ others suggest 20 mg would be sufficient◦ Low-dose steroids seem as effective as contact
avoidance
Treatment
Allergy 2009: 64: 322–334