Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease: A Systematic Review.

RATIONALE Hypersensitivity Pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation and/or fibrosis in response to an inhalational exposure. OBJECTIVE To determine the value of bronchoalveolar lavage (BAL) fluid lymphocyte cellular analysis in the detection of HP among patients with newly detected ILD. METHODS This systematic review was undertaken in the context of development of an American Thoracic Society (ATS), Japanese Respiratory Society (JRS), and Asociacion Latinoamericana del Torax (ALAT) clinical practice guideline. The clinical question was, "should patients with newly detected ILD undergo BAL fluid lymphocyte analysis to diagnose HP?" Medline, Embase, and grey literature were searched through October 2019. Studies that reported the percentage of BAL fluid lymphocytes for various ILDs were selected for inclusion. Meta-analyses compared the mean percentage of BAL fluid lymphocytes among patients with HP to that among patients with Idiopathic Pulmonary Fibrosis (IPF) or sarcoidosis. The sensitivity and specificity by which various percentages of BAL fluid lymphocytes distinguish HP from IPF and sarcoidosis were also evaluated. RESULTS Eighty-four articles were selected. No randomized trials or observational studies were identified that compared BAL fluid lymphocyte analysis to no BAL fluid lymphocyte analysis in patients with ILD. Included studies were case series describing BAL fluid cell differentials in patients with various ILDs. The percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared to IPF. Similarly, the percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared to sarcoidosis. A threshold of 20% BAL fluid lymphocytes distinguished fibrotic HP from IPF with a sensitivity and specificity of 69% and 61% respectively, and nonfibrotic HP from IPF with a sensitivity and specificity of 95% and 61% respectively. It distinguished fibrotic HP from sarcoidosis with a sensitivity and specificity of 69% and 26% respectively, and nonfibrotic HP from sarcoidosis with a sensitivity and specificity of 95% and 26% respectively. CONCLUSION The percentage of BAL fluid lymphocytes is higher in HP than IPF or sarcoidosis. However, a threshold that distinguishes HP from IPF or sarcoidosis with both high sensitivity and high specificity was not identified.