Executive Summary

Abstract

BACKGROUND:The purpose of this analysis is to provide evidence-based and consensusderived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability.STUDY DESIGN AND METHODS: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, and Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. RESULTS:The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations, and 2 ungraded consensus-based statements. All evidence was of very low quality.INTERPRETATION: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.

Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges

“…In general terms, the ATS/JRS/ALAT Guidelines and CHEST Guideline and Expert Panel Report 2021, show similar recommendations to classify HRCT images in the context of fibrotic or non-fibrotic HP (1,31).…”

“…HP represents a diagnostic challenge and requires a high index of suspicion by the clinician evaluating by the first time a patient with ILD (28,29). Targeted diagnostic steps should include a thorough evaluation of the ILD patient's history of occupational and environmental antigenic exposures, chest high resolution computed tomography (HRCT), serum specific IgGs for confirmation of exposure or as a screening tool, bronchioalveolar lavage (BAL), and histopathological study in some cases (1,30,31).…”

“…Increased cellularity with lymphocytosis is an important piece to improve the diagnostic likelihood of HP, where a higher percentage of lymphocytes could reflect the degree of alveolitis (Figure 3). However, the threshold proportion of BAL fluid lymphocytes that distinguishes HP from non-HP ILD is unclear and is strongly associated with the presence and extent of fibrotic changes (1,31). Important for interpretation, BAL lymphocytosis may also be influenced by several variables, including, timing relative to antigen exposure, smoking status, and others (40).…”

“…The histopathological features vary according to the phenotypes. In the case of the non-fibrotic HP, characteristic findings include bronchiolocentric cellular interstitial pneumonia and cellular bronchiolitis of lymphocytepredominant inflammatory infiltrate, as well as loosely formed granulomas and randomly scattered multinucleated giant cells within the interstitial inflammation (Figure 4) (1,31).…”

“…Fibrotic HP differs from non-fibrotic HP in that the underlying chronic interstitial pneumonia and/or bronchiolitis is complicated by fibrosis, which occasionally may overlap with a UIP pattern hindering the differential diagnosis with IPF. In other cases, interstitial pneumonia shows a more uniform and diffuse distribution mimicking fibrotic non-specific interstitial pneumonia or may display features compatible with interstitial airway-centered fibrosis (1,31,44). Findings of non-fibrotic HP may help to distinguish fibrotic HP from other fibrotic lung disorders.…”