This patient with chronic dyspnea and cough accompanied by characteristic lung biopsy findings most likely has hypersensitivity pneumonitis (HP).  HP is an exaggerated immunologic response to an inhaled antigen; common offending agents include mold, bacteria, animal protein, and chemicals.  The condition has variable presentation that is largely dependent on the dose and chronicity of antigen exposure:

• Acute HP involves abrupt-onset and often recurring episodes of fever, chills, cough, dyspnea, and fatigue that coincide with intermittent high-dose antigen exposure.  Leukocytosis is often present.  Chest x-ray may be normal or show scattered micronodular opacification.

• Chronic HP involves persistent and gradually progressive symptoms (as in this patient) resulting from long-term, moderate-dose antigen exposure.  Patients usually have symptoms of cough, dyspnea, fatigue, and weight loss for several months or more.  Lung auscultation usually reveals fine crackles, and chest x-ray shows interstitial reticular opacities consistent with the development of pulmonary fibrosis.

The diagnosis of HP can be aided by pulmonary function testing that reveals a restrictive pattern; the restriction is worse with chronic HP and is accompanied by more severe impairments in gas exchange (eg, hypoxemia, low DLCO).  Biopsy in both acute and chronic disease reveals lymphocytic infiltrate with poorly formed noncaseating granulomas created by the walling off of inhaled antigens.  Chronic HP is associated with progressive alveolar septal fibrosis.  Removal of antigen exposure usually resolves acute disease; however, the fibrosis occurring in chronic disease is often irreversible.

(Choice A)  Asthma presents with intermittent cough and dyspnea.  Bronchiolar biopsy can reveal noncaseating granulomas, but fibrosis is not typical and eosinophilic infiltrate is expected.

(Choice B)  Chronic bronchitis presents with dyspnea and cough and is expected to cause wheezing on lung auscultation.  Lymphocytic infiltrate may be present on biopsy, but granulomas are not typical.

(Choice D)  Idiopathic pulmonary fibrosis can present quite similarly to chronic HP, but affected patients are usually older (eg, age >50) and granulomas are not expected on lung biopsy.

(Choice E)  Pulmonary tuberculosis typically presents with fever, cough, dyspnea, night sweats, and weight loss.  Lung biopsy demonstrates lymphocytic infiltrate, but caseating (rather than noncaseating) granulomas.

Educational objective:
Hypersensitivity pneumonitis involves an exaggerated immunologic response to an inhaled antigen and can have an acute or chronic presentation.  Chronic disease presents with gradually progressive cough, dyspnea, fatigue, and weight loss, and lung biopsy reveals lymphocytic infiltrate, poorly formed noncaseating granulomas, and septal fibrosis.