Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges

Abstract

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILD), that presents unique challenges for a confident diagnosis and limited therapeutic options. The disease is triggered by exposure to a wide variety of inciting antigens in susceptible individuals which results in T-cell hyperactivation and bronchioloalveolar inflammation. However, the genetic risk and the pathogenic mechanisms remain incompletely elucidated. Revised diagnostic criteria have recently been proposed, recommending to classify the disease in fibrotic and non-fibrotic HP which has strong therapeutic and outcome consequences. Confident diagnosis depends on the presence of clinical features of ILD, identification of the antigen(s), typical images on high-resolution computed tomography (HRCT), characteristic histopathological features, and lymphocytosis in the bronchoalveolar lavage. However, identifying the source of antigen is usually challenging, and HRCT and histopathology are often heterogeneous and not typical, supporting the notion that diagnosis should include a multidisciplinary assessment. Antigen removal and treating the inflammatory process is crucial in the progression of the disease since chronic persistent inflammation seems to be one of the mechanisms leading to lung fibrotic remodeling. Fibrotic HP has a few therapeutic options but evidence of efficacy is still scanty. Deciphering the molecular pathobiology of HP will contribute to open new therapeutic avenues and will provide vital insights in the search for novel diagnostic and prognostic biomarkers.

Keywords: diagnosis; hypersensitivity pneumonitis; lung fibrosis; prognostic factors; risk factors.

Figure 1

High-resolution computed tomography scan in patients with non-fibrotic HP: (A) show inspiratory phase with diffuse centrilobular nodules, (B) expiratory phase in the same patient with centrilobular nodules and air trapping in right side; (C) in inspiratory phase present subpleural reticular pattern, with mosaic attenuation which is highlighted in the expiratory phase (D).

Figure 2

High-resolution computed tomography scan in patients with fibrotic HP. In (A), it is observed bilateral subpleural reticulation and in (B) traction bronchiectasis, honey combing and discrete ground-glass opacification and volume loss in left lung; (C) show lung fibrosis and areas of low attenuation and the same patient in (D) bronchiectasis and persistence of mosaic attenuation.

Figure 3

Differential cell count in bronchoalveolar lavage fluid from a patient with hypersensitivity pneumonitis showing strong lymphocytosis. Hematoxylin and eosin staining, magnification: 40×.

Figure 4

Lung biopsy sample from a patient with non-fibrotic hypersensitivity pneumonitis showing cellular chronic interstitial pneumonia and a poorly formed non-necrotizing granuloma. Hematoxylin and eosin staining, magnification: 40×.

Figure 5

Hypersensitivity pneumonitis diagnostic algorithm. The diagnosis of HP diagnosis relies primarily on three domains: HRCT pattern (according to ATS guideline classification), antigen exposure, and BAL lymphocytosis. This approach is followed by multidisciplinary team discussion where the diagnostic confidence is made. Undetermined or Unlikely HP may require the lung biopsy to orientate to an alternative diagnosis, or occasionally, reveal a hidden HP. Diagnostic confidence: Confident (>90%), Compatible (70%-89%), Undetermined (50%-69%), Unlikely (<50%). NO BAL (Not performed, e.g., patients with comorbidities and/or very low pulmonary function tests, patient's refusal to do the procedure; BAL not available, or other reasons). HP, hypersensitivity pneumonitis; HRCT, high resolution computed tomography; BAL, bronchoalveolar lavage; MDD, multidisciplinary discussion.