Hypersensitivity Pneumonitis PDF

Hypersensitivity pneumonitis Hypersensitivity pneumonitis Extrinsic allergic alveolitis Alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction Repetitive inhalation of antigenic agents Hypersensitivity pneumonitis Antigens Microbes...

Hypersensitivity pneumonitis Hypersensitivity pneumonitis Extrinsic allergic alveolitis Alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction Repetitive inhalation of antigenic agents Hypersensitivity pneumonitis Antigens Microbes Farmer’s Lung Animal proteins Bird Fancier’s Lung Low-molecular-weight Chemical worker’s chemicals Lung Exposure settings and Risk factors Exposure Acute symptoms – intense, intermittent Subtle, insidious sypmtoms – lower, more prolonged Latency period - weeks to years Environmental risk factors Particle size and solubility Antigen type and concentration Exposure duration, frequency, intermittency Use of respiratory protection Variability in work practices Epidemiology Worldwide prevalence unknown Considered rare 🡪incidence of ~0.9 cases/100,000 person‐years (1991–2003) Between 2004 and 2013 🡪 7498 cases of HP Hypersensitivity pneumonitis Acute, subacute (intermittent), or chronic progressive. Type III hypersensitivity reaction Specific antibodies in their serum and bronchoalveolar lavage studies 🡪 high proinflammatory chemokines Pathogenesis Pathogenesis Host factors Genetic polymorphisms Non-genetic host factors HP more common in nonsmokers Cigarette smoking depress T-cell responses to inhaled antigens Nicotine – reduction in cellular reponses, lymphocyte , and total cell counts in BAL, lung tissue inflammation Smoking – increased macrophage and decrease lymphocytes and dendritic cells 🡪 clearance of antigens from terminal airways Characteristics Acute/Subacute HP Chronic HP Exposure to Intermittent high-level Continuous low-level antigen exposure exposure Symptoms 2-9hrs after exposure, days Insidious, over weeks to to weeks months Nature of Cough and dyspnea, Progressive symptoms symptoms influenza-like symptoms (dyspnea, cough, weight loss), sometimes intermittent Physical signs Fever Inspiratory crackles, cyanosis, clubbing, cor pulmonale Outcome Symptoms peak within 6-24 End-stage fibrotic disease hours after exposure, and/or emphysema. lasting hours to days, recurs Exacerbation despite on re-exposure avoidance of exposure Diagnosis High index of suspicion + careful history Respiratory disease + history of environmental or occupational setting and a clear relationship between symptoms and exposure Causative agent - identification of specific precipitating antibodies Imaging evidence of ILD without specific features to suggest an alternate diagnosis Diagnosis No gold standard test - diagnosis from combination of procedures Main goals Identify exposures Determine severity Characteristic imaging and BAL features Diagnosis remains uncertain – multidisciplinary evaluation Criteria for the diagnosis of hypersensitivity pneumonitis (HP) 1. Known exposure to offending antigen: A. History of appropriate exposure B. Aerobiologic or microbiologic investigations of the environment that confirm the presence of an inciting antigen C. The presence of specific IgG antibodies in serum 2. Compatible clinical, radiographic, or physiologic findings: A. Respiratory signs/symptoms - cough, breathlessness, febrile episodes, wheezing, weight loss, and fatigue with crackles B. Reticular, nodular, or ground glass opacities on HRCT C. Abnormal spirometry and/or lung volumes, reduced DLCO, altered gas exchange either at rest or with exercise testing 3. BAL with lymphocytosis: A. Lymphocytosis >20%, often >50% B. Positive specific immune response to the antigen by lymphocyte transformation testing 4. Positive inhalation challenge testing by: A. Reexposure to the environment B. Inhalation challenge to the suspected antigen in a hospital setting 5. Histopathology showing compatible changes: A. Poorly formed, noncaseating granulomas OR B. Mononuclear cell infiltrate Criteria for the diagnosis of hypersensitivity pneumonitis (HP) 1. Known exposure to offending antigen: A. History of appropriate exposure B. Aerobiologic or microbiologic investigations of the environment that confirm the presence of an inciting antigen C. The presence of specific IgG antibodies in serum 2. Compatible clinical, radiographic, or physiologic findings: A. Respiratory signs/symptoms - cough, breathlessness, febrile episodes, wheezing, weight loss, and fatigue with crackles B. Reticular, nodular, or ground glass opacities on HRCT C. Abnormal spirometry and/or lung volumes, reduced DLCO, altered gas exchange either at rest or with exercise testing 3. BAL with lymphocytosis: A. Lymphocytosis >20%, often >50% B. Positive specific immune response to the antigen by lymphocyte transformation testing 4. Positive inhalation challenge testing by: A. Reexposure to the environment B. Inhalation challenge to the suspected antigen in a hospital setting 5. Histopathology showing compatible changes: A. Poorly formed, noncaseating granulomas OR B. Mononuclear cell infiltrate Management of HP Mainstay - avoidance of the causative antigen Glucocorticoids Initial dose 🡪 Prednisone 0.5 mg/kg per day (up to 30 mg per day) for 4-8 weeks Symptoms, pulmonary function, and HRCT show improvement 🡪 tapered gradually to 15 mg/day Supplemental oxygen Management Additional immunosuppressive agents Azathioprine (AZA) and mycophenolate mofetil (MMF) - not responded to antigen removal and systemic glucocorticoid use Lung transplantation advanced lung disease due to HP Overall survival 🡪 good, improved compared to patients with IPF Monitoring: Follow-up Visits assess symptoms, adverse effects, and lung function (spirometry, pulse oximetry, and DLCO) 🡪 one to two month intervals Prednisone tapered to 20 mg daily, 🡪 three to six months Repeat HRCT based on symptoms and lung function 🡪 3-6 months after initiation of treatment Prognosis Predictive features Imaging Increasing global interstitial disease extent, greater severity of traction bronchiectasis and honeycombing 🡪 increased mortality  Prognosis Predictive features Histopathology Fibrotic nonspecific interstitial pneumonitis (NSIP), bronchiolocentric fibrosis, and usual interstitial pneumonitis (UIP) 🡪 poor prognosis Fibroblast foci or dense collagen fibrosis 🡪 predictors of death or lung transplant Ping Wang, MD, et.al. Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis. 152 #3 Chest September 2017 Prognosis Predictive features Pulmonary hypertension symptomatic 🡪 correlates with the severity of ILD 🡪 worse survival Summary Hypersensitivity pneumonitis (HP) is rare pulmonary disease which affects the interstitium due to a delayed allergic reaction A combination of known exposure to an antigen; clinical, radiographic, and physiologic findings; BAL lymphocytosis, inhalation challenge testing; and histopathologic findings are needed for the diagnosis of HP The management of HP is avoidance of the causative antigen and use of glucocorticoids Hypersensitivity pneumonitis has a lower predictive mortality compared to other ILDs such as Idiopathic Pulmonary Fibrosis Thank You!