Hypersensitivity pneumonitis

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


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


Insidious hypersensitivity pneumonitis. Axial high-resolution CTimages depict ill-defined centrilobular ground-glass opacities


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).


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


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


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


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


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

Health & Medicine

Hypersensitivity pneumonitis