HYPERSENSITIVE PNEUMONITIS

(Extrinsic allergic alveolitis, EAA)

Dr. Shahid PervaizDr. Shahid Pervaiz

Postgraduate Trainee Postgraduate Trainee

Pulmonology Department Pulmonology Department

Nishtar Hospital MultanNishtar Hospital Multan

Hypersensitivity pneumonitis: definition

Hypersensitivity pneumonitis is a Hypersensitivity pneumonitis is a spectrum of granulomatous, interstitial, spectrum of granulomatous, interstitial, and alveolar-filling lung diseases that and alveolar-filling lung diseases that result from repeated inhalation of and result from repeated inhalation of and sensitization to a wide variety of sensitization to a wide variety of organic dustsorganic dusts..

Hypersensitivity PneumonitisExtrinsic Allergic Alveolitis

A syndrome characterized by diffuse A syndrome characterized by diffuse inflammation of lung parenchyma inflammation of lung parenchyma

and airways in response to inhalation and airways in response to inhalation of antigens to which the patient has of antigens to which the patient has

been previously sensitizedbeen previously sensitized

Extrinsic allergic alveolitis(hypersensitivity pneumonitis, EAA)

Immunologically mediated Immunologically mediated inflammatory reaction in the inflammatory reaction in the alveoli and in the respiratory alveoli and in the respiratory bronchiolesbronchioles

Extrinsic allergic alveolitis(hypersensitivity pneumonitis, EAA)

CCausesauses- Organic Dusts (<5µm)Organic Dusts (<5µm)

- Moulds- Moulds- Foreign Proteins- Foreign Proteins

- Some ChemicalsSome Chemicals- Di-isocyanates- Di-isocyanates- Organic Acid Anhydrides- Organic Acid Anhydrides

- Often - Often Heavy, Repeated ExposureHeavy, Repeated Exposure, Most Often , Most Often At The Work PlaceAt The Work Place

Extrinsic allergic alveolitis (hypersensitivity pneumonitis)

• Chronic Chronic inflammatoryinflammatory diseasedisease• Small airwaysSmall airways• InterstitiumInterstitium• Occasional Occasional

granulomasgranulomas

• Allergic originAllergic origin• Type III Type III

hypersensitivityhypersensitivity

• Type IV Type IV hypersensitivityhypersensitivity

Hypersensitivity Pneumonitis

• Hypersensitivity reaction in the lung Hypersensitivity reaction in the lung occurs in response to inhaled organic dust.occurs in response to inhaled organic dust.

• Example is farmer’s lung.Example is farmer’s lung.• The exposure may be occupational or The exposure may be occupational or

environmental.environmental.• The disease occurs from type III and type The disease occurs from type III and type

IV hypersensitivity reactions.IV hypersensitivity reactions.• Farmer’s lung is due to Farmer’s lung is due to Thermophilic Thermophilic

ActinomycesActinomyces in moldy hay. in moldy hay.• Bird fancier’s lung is caused by avian Bird fancier’s lung is caused by avian

antigen.antigen.

EAA

• Thermophilic Thermophilic bacteria – Farmers bacteria – Farmers lunglung

• Avian proteins – Bird Avian proteins – Bird fanciers lungfanciers lung

• Fungi – Malt workers Fungi – Malt workers lunglung

• Precipitins Precipitins (antibodies) often (antibodies) often detectable in serum. detectable in serum. Unusual cases come Unusual cases come to biopsy.to biopsy.

PathologyPathology

• There is infiltration of alveolar walls There is infiltration of alveolar walls with lymphocytes, plasma cells and with lymphocytes, plasma cells and histiocytes.histiocytes.

• There are loosely formed granulomas.There are loosely formed granulomas.

• Fibrotic changes occur in advanced Fibrotic changes occur in advanced disease.disease.

EAAPathologyPathology: :

Granulomatous inflammation around Granulomatous inflammation around the alveoli and the peripheral the alveoli and the peripheral bronchioles.bronchioles.Exudates with plasma cells and Exudates with plasma cells and lymphocytes. Macrophages, lymphocytes. Macrophages, epitheloid cells and giant cells in the epitheloid cells and giant cells in the granulomas in the middle of the granulomas in the middle of the inflammation process.inflammation process.

EAA

PathologyPathology: : After the exposure ceases the After the exposure ceases the

reaction disappears in 3-4 months.reaction disappears in 3-4 months.If the exposure continues, the If the exposure continues, the

exudation organizes into fibrin and exudation organizes into fibrin and an irreversible pulmonary fibrosis an irreversible pulmonary fibrosis follows.follows.

Clinical Features• The disease may occur in acute or chronic The disease may occur in acute or chronic

forms.forms.Acute HPAcute HP

• Dyspnea, fever, malaise and cough appear Dyspnea, fever, malaise and cough appear 4-6 hours after exposure.4-6 hours after exposure.

• These symptoms continue for 24-48 These symptoms continue for 24-48 hours.hours.

• Physical examination shows fine crackles Physical examination shows fine crackles throughout the lungs.throughout the lungs.

• Chest radiograph may be normal, but may Chest radiograph may be normal, but may show reticular nodular infiltration.show reticular nodular infiltration.

Acute HP• Clinical-Abrupt OnsetClinical-Abrupt Onset• Lab-ESR, IgG, RA, CRP,LDH, BAL Lab-ESR, IgG, RA, CRP,LDH, BAL

lymphocytosis, restrictive physiologylymphocytosis, restrictive physiology• CXR- micronodular interstitial, but CXR- micronodular interstitial, but

freq. normal-HRCT needed, but not freq. normal-HRCT needed, but not absoluteabsolute

• Histopathology-poorly formed, Histopathology-poorly formed, noncaseating interstitial granulomas, noncaseating interstitial granulomas, monocytes , giant cells.monocytes , giant cells.

Chronic HPChronic HP

• These patients present with progressive These patients present with progressive dyspnea.dyspnea.

• Physical examination shows bilateral Physical examination shows bilateral inspiratory crackles.inspiratory crackles.

• Chest x-ray shows reticular nodular Chest x-ray shows reticular nodular infiltration and fibrosis predominantly in infiltration and fibrosis predominantly in upper lobes.upper lobes.

• Pulmonary function tests – restrictive pattern. Pulmonary function tests – restrictive pattern.

• Gas exchange shows hypoxemia which Gas exchange shows hypoxemia which worsens on exercise.worsens on exercise.

Chronic Progressive HP

• Clinical-insidious cough, dyspnea, fatigue, Clinical-insidious cough, dyspnea, fatigue, weight loss, clubbingweight loss, clubbing

• Lab-not very helpful-BAL lymphocytosis but Lab-not very helpful-BAL lymphocytosis but ; restrictive, but usually mixed. ; restrictive, but usually mixed. DLCO always reduced, and exertional DLCO always reduced, and exertional hypoxemiahypoxemia

• CXR-may be normal, but usually CXR-may be normal, but usually progressive fibrosis; emphysema oftenprogressive fibrosis; emphysema often

• Histopathology- Granulomatous leision, Histopathology- Granulomatous leision, fibrosisfibrosis

EAA: clinical findingsStatusStatus dyspnea, cyanosis, crepitant ralesdyspnea, cyanosis, crepitant rales

chronic form^ digital glubbing chronic form^ digital glubbing

Chest X-rayChest X-ray normal or small nodules, diffuse infiltrates, groundnormal or small nodules, diffuse infiltrates, ground

glass appearance, chronic form: pulmonary fibrosisglass appearance, chronic form: pulmonary fibrosis

HRCTHRCT normal or ground glass appearancenormal or ground glass appearance

centrilobular micronodulescentrilobular micronodules

Lung functionLung function restriction, diffusing capacity decreases, hypoxemia, restriction, diffusing capacity decreases, hypoxemia,

obstruction, hyperreactivityobstruction, hyperreactivity

Lab. testsLab. tests rise of ESR, leukocytosis, neutrophiliarise of ESR, leukocytosis, neutrophilia

BALBAL lymphocytosis, T helper / T supressor cells lymphocytosis, T helper / T supressor cells

decreased decreased

EAA: HRCT, acute disease

EAA: HRCT, chronic disease

Hypersensitivity Pneumonitis(Ground glass opacity)

Ground Glass Opacity causes

• Acute Symptoms :Acute Symptoms :• Pulmonary edemaPulmonary edema

• Pneumonia.Pneumonia.

• DADDAD

• AIPAIP

• Acute Hypersensitivity Acute Hypersensitivity PneumonitisPneumonitis..

• Chronic Symptoms :Chronic Symptoms :• NSIPNSIP• UIPUIP• DIPDIP• Hypersensitivity Hypersensitivity

PneumonitisPneumonitis..• Alveolar proteinosis.Alveolar proteinosis.• Sarcoidosis.Sarcoidosis.• Lipoid pneumonia.Lipoid pneumonia.• BACBAC

Centrilobular nodules • causes :causes :1.1. Endobronchial spread of Endobronchial spread of

infection (Bacteria, virus, infection (Bacteria, virus, TB, mycobacterium, TB, mycobacterium, fungus)fungus)

2.2. Endobronchial spread of Endobronchial spread of tumor (BAC)tumor (BAC)

3.3. Hypersensitivity Hypersensitivity Pneumonitis.Pneumonitis.

4.4. BOOPBOOP5.5. Silicosis and coal miner Silicosis and coal miner

pneumoconiosis pneumoconiosis

Honeycombing

• CausesCauses::

1.1. IPFIPF2.2. Collagen vascular Collagen vascular

diseases (Rh.A. - diseases (Rh.A. - scleroderma)scleroderma)

3.3. Drug related fibrosisDrug related fibrosis4.4. End stage End stage

Hypersensitivity Hypersensitivity pneumonitispneumonitis

5.5. End Stage SarcoidosisEnd Stage Sarcoidosis6.6. Radiation.Radiation.7.7. End stage ARDSEnd stage ARDS

Traction Bronchiectasis

• Causes :Causes :1.1. Non specific Non specific

intersitial pneumonia.intersitial pneumonia.2.2. UIPUIP3.3. Sarcoidosis.Sarcoidosis.4.4. Hypersensitivity Hypersensitivity

pneumonitis.pneumonitis.5.5. Radiation.Radiation.6.6. End stage ARDSEnd stage ARDS

• Corkscrewed bronchi Corkscrewed bronchi in IPFin IPF

Diagnosis ofDiagnosis of Hypersensitivity Hypersensitivity Pneumonitis Pneumonitis Lab TestsLab Tests

••May have increased May have increased inflammatory inflammatory markersmarkers (erythrocyte sedimentation rate, (erythrocyte sedimentation rate, C-reactive protein)C-reactive protein)

••Leukocytosis and increased gamma Leukocytosis and increased gamma globulins typically seenglobulins typically seen

••Specific IgG antibody to offending agent Specific IgG antibody to offending agent can be detected and checked serially to can be detected and checked serially to detect response to treatmentdetect response to treatment

Diagnosis ofDiagnosis of Hypersensitivity Hypersensitivity Pneumonitis Pneumonitis Lab TestsLab Tests

• IgG Not always present (likely because IgG Not always present (likely because many unknown antigens)many unknown antigens)

Low specificity (10% of people exposed Low specificity (10% of people exposed to farmer’s lung antigen develop to farmer’s lung antigen develop antibodies; only 0.3% show symptoms)antibodies; only 0.3% show symptoms)

••Rheumatoid factor often positive Rheumatoid factor often positive (unknown cause)(unknown cause)

••Negative blood, sputum, throat culturesNegative blood, sputum, throat cultures

Diagnosis ofDiagnosis of Hypersensitivity pneumonitis Hypersensitivity pneumonitis Lab TestsLab Tests

••Bronchoalveolar lavage (BAL)Bronchoalveolar lavage (BAL)- Acute form with neutrophils and CD4 T - Acute form with neutrophils and CD4 T

lymphocyteslymphocytes- Chronic form with high number of CD8 T - Chronic form with high number of CD8 T

lymphocyteslymphocytes- BAL may help to differentiate chronic - BAL may help to differentiate chronic

hypersensitvity Pneumonitis from sarcoid, hypersensitvity Pneumonitis from sarcoid, which has high CD8 T lymphocyteswhich has high CD8 T lymphocytes

- Neutrophilia, lymphopenia, increased ESR, C - Neutrophilia, lymphopenia, increased ESR, C reactive protein, rheumatoid factor, raised reactive protein, rheumatoid factor, raised serum immunoglobulin.serum immunoglobulin.

Diagnosis ofDiagnosis of Hypersensitivity Hypersensitivity

PneumonitisPneumonitis Chest x-rayChest x-ray

• Acute: Diffuse ground-glass infiltrates, nodular or Acute: Diffuse ground-glass infiltrates, nodular or striated patchy opacities. Up to 20% have normal CXR.striated patchy opacities. Up to 20% have normal CXR.

• Subacute: Same as acute, may have sparing of lung basesSubacute: Same as acute, may have sparing of lung bases

• Chronic: Upper lobe fibrosis, reticular opacities, volume Chronic: Upper lobe fibrosis, reticular opacities, volume loss, honeycombingloss, honeycombing

• may be normal or show patchy or dif fuse infiltrates or may be normal or show patchy or dif fuse infiltrates or discrete nodular infiltrates. There may be honey-discrete nodular infiltrates. There may be honey-combing.combing.

CT CT scanningscanning• is diagnostic showing the details of fibrosis, and nodules.is diagnostic showing the details of fibrosis, and nodules.

studentdoctorprofessor.com.uasdp.net.ua

Diagnosis ofDiagnosis of Hypersensitivity Hypersensitivity pneumonitispneumonitis

Pulmonary function test (PFT)Pulmonary function test (PFT)

shows a restrictive or obstructive pattern, shows a restrictive or obstructive pattern, decreased lung volume, im paired diffusion decreased lung volume, im paired diffusion capacity, bronchial hyper reactivity and capacity, bronchial hyper reactivity and reversibility.reversibility.

BAL (Bronchoalveolar lavage)BAL (Bronchoalveolar lavage)

shows lymphocytic alveolitis.shows lymphocytic alveolitis.Lung biopsyLung biopsy through bronchoscopy may be diagnostic.through bronchoscopy may be diagnostic.Inhalation challengeInhalation challenge i.e. a positive response to in haled i.e. a positive response to in haled

antigen may be done for transient airflow antigen may be done for transient airflow obstruction.obstruction.studentdoctorprofessor.com.uasdp.net.ua

Diagnostics of EAA• Main criteriaMain criteria

1. Exposure to arganic dust (history, spesific IgG 1. Exposure to arganic dust (history, spesific IgG antibodies, work place measurements).antibodies, work place measurements).2. Typical symptoms2. Typical symptoms3. Chest X-ray findings3. Chest X-ray findings

• Additional criteriaAdditional criteria1. Decreased diffusion capacity1. Decreased diffusion capacity3. Hypoxia during rest or decreasing during excercise3. Hypoxia during rest or decreasing during excercise4. Restriction in spirometric values4. Restriction in spirometric values5. Lung biopsy with findings of allergic alveolitis5. Lung biopsy with findings of allergic alveolitis6. Provocation test (at work place) positive6. Provocation test (at work place) positive

All main criteria and two of the additional ones are All main criteria and two of the additional ones are needed for diagnosis.needed for diagnosis.

EAA, differential diagnostics

• Organic Dust Toxic Syndrome (ODTS)Organic Dust Toxic Syndrome (ODTS)

• SarcoidosisSarcoidosis

• Drug-induced pneumonitisDrug-induced pneumonitis

• Viral and mycoplasma pneumoniasViral and mycoplasma pneumonias

• TuberculosisTuberculosis

• Allergic bronchopulmonary aspergillosisAllergic bronchopulmonary aspergillosis

• Collagen-vascular diseasesCollagen-vascular diseases

• Lymphangitis carcinomatosaLymphangitis carcinomatosa

• Pulmonary fibrosis (DIP)Pulmonary fibrosis (DIP)

• Pneumoconioses Pneumoconioses

HP Associated with Farming

• Moldy hay, grain, silage-Farmer’s lungMoldy hay, grain, silage-Farmer’s lung

• Mold on pressed sugar cane-BagassosisMold on pressed sugar cane-Bagassosis

• Tobacco plantsTobacco plants

• Mushroom workersMushroom workers

• Potato riddlersPotato riddlers

• Cheese washersCheese washers

HP Associated with Ventilation and Water-Related Contamination

• Humidifier feverHumidifier fever

• Unventilated showerUnventilated shower

HP Associated with Birds/Poultry

• Bird fancier’s lungBird fancier’s lung

• Poultry worker’s lungPoultry worker’s lung

• Turkey handling diseaseTurkey handling disease

HP Associated with Veterinary Work and Animal Handling

• Laboratory worker’s lungLaboratory worker’s lung

• Bat lungBat lung

• Coptic lung (mummy handlers)Coptic lung (mummy handlers)

HP Associated with Grain and Flour Processing

• Grain measurer’s lungGrain measurer’s lung

• Miller’s lungMiller’s lung

• Malt worker’s diseaseMalt worker’s disease

HP Associated with Milling and Construction

• Wood dust PneumonitisWood dust Pneumonitis

• Maple bark diseaseMaple bark disease

• Wood trimmer’s diseaseWood trimmer’s disease

HP Associated with Plastics, Painting, Electronics, Etc.• Chemical HP – Toluene di-Chemical HP – Toluene di-

isocyanateisocyanate

• Detergent worker’s lungDetergent worker’s lung

• Pauli’s reagent alveolitisPauli’s reagent alveolitis

• Vineyard sprayer’s lungVineyard sprayer’s lung

• Bible printer’s lungBible printer’s lung

• Epoxy resin lungEpoxy resin lung

HP in Textile Workers

• Byssinosis (brown lung) – Byssinosis (brown lung) – cottoncotton

• ““Velvet” worker’s lungVelvet” worker’s lung

Examples of EAA Etiology

• Farmer's lungFarmer's lung mouldy haymouldy hay• Saw mill worker's lung mouldy wood dustSaw mill worker's lung mouldy wood dust• Bird fancier's lungBird fancier's lung proteins in bird droppingsproteins in bird droppings• Mushroom worker´s lung spores, mouldsMushroom worker´s lung spores, moulds• Malt worker´s lung Malt worker´s lung mouldy malt mouldy malt• Humidifier lung contaminated humidifier Humidifier lung contaminated humidifier

water water• Cheese washer's lungCheese washer's lung Penicillium casei Penicillium casei• SuberosisSuberosis cork dust mould cork dust mould

• Diisocyanate lungDiisocyanate lung polyurethane hardeners polyurethane hardeners • Hard metal worker's lungHard metal worker's lung hard metal dust, cobalthard metal dust, cobalt

HP Treatment

• Antigen avoidanceAntigen avoidance

• Corticosteroids – Corticosteroids – 0.5-1 mg/kg daily0.5-1 mg/kg daily

• Alternatives…Alternatives…

Treatment of Hypersensitivity pneumonitis

Glucocorticoids – Prednisone 1 mg/kg/day Glucocorticoids – Prednisone 1 mg/kg/day for 1-2 weeks. Maintenance dose may be for 1-2 weeks. Maintenance dose may be continued at the lowest possible dosage continued at the lowest possible dosage if symptoms recur.if symptoms recur.

Avoidance of offending antigen is Avoidance of offending antigen is primary therapy.primary therapy.• Low-dose therapy (20 mg p.o. daily) may Low-dose therapy (20 mg p.o. daily) may

be as effective as avoidancebe as effective as avoidance

HP Prevention/Avoidance

• Reduction of antigen burdenReduction of antigen burden

• Design of facilities-moisture controlDesign of facilities-moisture control

• Preventative maintenancePreventative maintenance

• Protective devices-filters, respiratorsProtective devices-filters, respirators

EAA, prevention

• Reduction of dust exposureReduction of dust exposure

• Work hygienic improvementsWork hygienic improvements

• Adequate respirators always during exposureAdequate respirators always during exposure- before any symptoms!- before any symptoms!

• Occupational health careOccupational health care

• InformationInformation

• Follow-upFollow-up

• Finding symptomatic workers in time, to Finding symptomatic workers in time, to prevent permanent loss of pulmonary prevent permanent loss of pulmonary functionfunction

HP Prognosis

• Farmer’s lung – most recover; 50% Farmer’s lung – most recover; 50% have chronic lung disease, but minor, have chronic lung disease, but minor, usually emphysematous changesusually emphysematous changes

• Bird fancier’s lung – prognosis usually Bird fancier’s lung – prognosis usually worse. Duration of exposure, older worse. Duration of exposure, older age, greater exposure, all tend toward age, greater exposure, all tend toward worsened severityworsened severity

EAA, prognosis

• Continuing exposure, relapsing disease leads Continuing exposure, relapsing disease leads to pulmonary fibrosis, permanent loss of to pulmonary fibrosis, permanent loss of pulmonary function and cor pulmonale. pulmonary function and cor pulmonale.

• When Finnish cases with farmer's lung were When Finnish cases with farmer's lung were followed for 10 years, 23% had findings of followed for 10 years, 23% had findings of pulmonary emphysema or pulmonary fibrosis.pulmonary emphysema or pulmonary fibrosis.

Conclusion• Farmer´s lung is the most usual extrinsic Farmer´s lung is the most usual extrinsic

allergic alveolitis. Chronic form leads to allergic alveolitis. Chronic form leads to severe disability. severe disability.

• Reduction of the exposure to biological Reduction of the exposure to biological dust by work hygienic improvements and dust by work hygienic improvements and using adequate respirators is important. using adequate respirators is important. The humidifiers and other sources of The humidifiers and other sources of exposure should be cleaned.exposure should be cleaned.

• Early recognition of the symptoms is Early recognition of the symptoms is essential. essential.