Hypersensitivity Pneumonitis Wael Batobara

Case 1 82 y Female smoker (30 pack) Seen in OPD because of 6/12 SOBE , Cough No Orthopnea , PND ,LL swelling No CP , Wheeze , Fever ,Sputum , Wt loss No similar episode in the past Able to walk 3 blocks & climb 20 stairs

History PMH : HTN , IHD ,Hypothyroidism Medication: Thyroxine , Altace , Ranitidine Ventolin PSH : Partial gastrectomy for bleeding GU Works as Cook Travel to Arizona & North ON No pets No Contact with similar case

Examination Afebrile BP 120/70 RR14 Sat93% RA No Clubbing or lymphadenopathy Chest : N BS No wheeze Fine crackles Bilaterally basally CVS : N JVP S1+S2 +0 No Signs of Pulmonary HTN Abd & LL : NAD

Investigation CBC & Coagulation N BUN , Creat & Lytes N LFT & UA N Cardiac Enzyme & EKG & 2DE N CXR & CT

Investigation ABG PH 6.42 PCO2 36 PO2 68 Hco3 24 Sat 93% PFT : Isolated decrease in DLCO 60% 6MWT : 100 m HR 115 Sat 85% Open Lung Bx  Non caseating granuloma & organizing pneumonia Sent to Mayo Clinic  Hypersensitivity Pneumonitis

Course Patient was symptomatic persistently H/O exposure To Wheat & Flour 24 lbs /week Persistent decrease DLCO & walking hypoxemia Prednisolone 40 mg was initiated Will be seen in OPD in follow up

Case 2 52 y Female Xsmoker (15pack) Seen In OPD because of 6 months H/O SOB ,Cough Cough non productive SOBE NO orthopnea ,PND No fever , night sweating , chest pain , wheeze No Wt Loss , anorexia

History NO CTD symptoms No leg pain or swelling PMH Hypothyroidism & Migraine No H/O CAP ,TB contact NO IHD risk factor Rx Thyroxine Lives in Portage la Pairie Works as animal rescue aids 25 y

Examination Afebrile BP 120/70 HR 80 RR 16 Sat 93% RA No clubbing ,lymphadenopathy JVP N Chest Bilateral fine crackles No wheeze CVS ,Abd & LL NAD No CTD signs

Investigations CBC & Coagulation N BUN , Creat , Lytes N LFT N UA N CXR , CT Chest PFT

Patient Course Seen By Allergy / Immunology +ve precipitant to avian protein Hypersensitivity pneumonitis Bird Fancier lung Advised to avoid exposure Steroids has not been started Given the mild symptoms & N exercise test

Hypersensitivity Pneumonitis Syndrome of varying presentations & natural history Immunologic reaction to an inhaled antigen mainly organic Genetic predisposition 44 Pt with HP Vs 50 Asymptomatic Vs 99 control MHC 2 & TNF alpha levels difference Am J Respir Crit Care Med 2001 Jun

Epidemiology Data from Farmers lung & Bird fancier lung Great variation because of geographical , seasonal & local practice Bird fancier prevalence 20 -20000/ 100000 Farmer 0.5-7 % Life guard in swimming pools Contaminated forced air system

Smoking Effect Less symptoms & immune response 102 pigeon breeder 1/23 smokers +ve IgG Vs 39/65 Non smokers Clin Allergy 1985 Sep 92 dairy farmers Micropolyspora faeni antibody Non smoker 27% Vs 7% smoker Am Rev Respir Dis 1989 Sep

Smoking Effect 12 smoker Vs 31 non smokers farmers No difference in age ,gender ,working environment & exposure duration Acute FLD in non smoker 58% Vs 8% Chronic insidious in Smokers 92% Vs 42% 10 y survival 91% Non Sm Vs 70% Sm Persistent symptoms & radiological findings & higher reccurent episodes in Smokers Intern Med 1995 Oct

Etiologies through droppings ,feathers Farming ,Dairy or Cattle workers Different from Organic Dust Toxic Syndrome more common than HP occur with single day exposure & non immunologic reaction Bird ,Poultry & Animal handling through droppings ,feathers processed products or serum

Etiologies Grain and flour processing and loading being colonized with organisms & easily aerosolized Contaminated Ventilation & Water Source Forced air systems , heated water reservoir Spa Hot tubs, swimming pools water damaged carpet MAC as a cause in immunocompetent Construction & Lumber milling Plastic , Painting & electronic industry

Classification Acute 6-12 hours of heavy exposure Misdiagnosed as CAP Fever ,Chills ,Cough, SOB , CP & Malaise Tachypnea & fine crackles

Classification Acute Symptoms will resolve with removal of offending agent Complete radiological resolution takes weeks Elevated ESR & Immunoglobulin +ve specific Precipitating IgG BAL  Lymphocytosis PFT  restrictive pattern

Classification Acute Radiologically HRCT > CXR interstitial , micronodular middle &lower zones Bx  mononuclear infiltrate poorly formed non caseating granuloma peribronchial distribution

Classification Subacute , Intermittent Gradual symptoms & signs More Wt loss Improvement with removal of exposure Improvement takes longer than acute

Classification Subacute , Intermittent DLCO decreased Radiologically  Upper & middle zone Ground glass & micronodules Focal fibrosis & emphysema Bx Granuloma more formed Bronchiolitis +/- organizing Pneumonia Interstitial Fibrosis

Classification Chronic Progressive Worsening cough & SOB Removal of exposure yield partial relief ? Clubbing as bad prognosis 82 Pt followed for 5 years 16/44 +ve clubbing  worsening PFT 5/38 -ve clubbing  worsening PFT Arch Intern Med 1990 Sep

Classification Chronic Progressive PFT  Restrictive +/- obstructive Hypoxemia exertional or at rest Radiologically  Volume loss Honeycombing , Emphysema Less Ground glass Bx  difficult to differentiate from IPF

Diagnosis Exposure +ve aero/microbiological cultures History +ve aero/microbiological cultures +ve serum precipitins Compatible Clinical & Radiological Finding Symptoms appearing or worsening after exposure Reticular .nodular or ground glass Restrictive / obstructive pattern

Diagnosis +ve Inhalation challenge test Rexposure either in environment or in PFT lab BAL / Bx Lymphocytosis & Low CD4/CD8 ratio Granuloma / Mononuclear Infiltrate

Diagnosis Serum Precipitins Suggestive not diagnostic High false –ve & +ve Used to convince about hypersensitivity Smoking Effect ?!

Diagnosis Inhalation Challenge Test 2 reactions: Common  6-8 hours post challenge with fever ,malaise ,SOB neutrophilia & decreased FVC Less common  immediate wheeze & decreased FEV1 followed 6 hours later by decreased FVC & DLCO

Diagnosis Inhalation Challenge Test 17 with HP Vs 11 ILD Vs Control Challenged with pigeon serum Increase in Temp & Post Challenge decrease FVC ,PAo2 & Sat All HP & 3 ILD +ve but none of control Increase in Temp by 0.5 C  100 PPV & 85 NPV Decrease in FVC by 16%81%PPV & 83% NPV No complication were observed Am J Respir Crit Care Med 1998 Sep

Diagnosis Inhalation Challenge Test Methacholine challenge 37 dairy farmers & 11 controls 12 with FLD , 13 Asymptomatic with +Ab 12 Asymptomatic with –Ab +ve in all farmers No statistical difference in farmers subgroup in term of degree of responsiveness Am J Respir Crit Care Med. 1995 Jun

Diagnosis BAL Lymphocytosis  non specific but useful in narrowing differential Dx CD4/CD8 ? Prognostic 17 Pt study HP with fibrosis Vs no Fibrosis High CD8 acute presentation & less fibrosis High CD4  chronic & more fibrosis Chest 1993 Jul

Diagnosis Lung Bx Retrospective study 105 TBB 55 FLD Vs Control {other ILD} Gold Standard Test for FLD was not open Bx  History ,fine crackles ,Lymphocytic BAL & resolution with removal of exposure 2 pathologist reading as Probable FL ,Possible FL , non specific or alternative Dx Chest. 1997 Dec

Diagnosis Lung Bx Interobserver agreement was fair Upto 48.5% of Bxnon specific LHR for Probable FLD was 1.1-2.6 Possible FLD 1.7-2.2 Lymphocytic Infiltrates 9.1 Granuloma 1.8 Chest. 1997 Dec

Management Environmental Control Reduction of antigenic burden wetting compost & Abx use Design & Maintenance of Facilities Keeping Humidity below 60% Heating ,Ventilating & AC water shouldn’t be recirculated Early water damage control Protective devices ?

Management Environmental Control Relocation  ? If persistence of exposure will lead to disease progression 61 Pt with FLD 37 /61 continued farming 5 y follow up on PFT At 1 & 3 year reduction in DLCO,TLC more in continued exposure At 5 no statically significance difference Chest 1985 Jun

Management Steroids Accelerates initial recovery but doesn’t change long term outcome 36 Pt FLD Prospective Randomized DB 8 weeks either Prednisolone (20Pt) Vs Placebo (16Pt) At 1 month difference in DLCO At 5 years not statically significant difference in DLCO ,FEV1 At 5 years 5 of Prednisolone group had recurrence Vs 1 of Placebo Not statically significant Am Rev Respir Dis 1992 Jan

Management Steroids Prospective Randomized 3 arms 93 Pt FLD 12 weeks Vs 4 Weeks Vs Placebo Follow up 18 months No difference between 12 & 4 weeks outcomes Eur J Respir Dis 1983 May

Thank You