A multidisciplinary committee of international experts have released a new clinical practice guideline on the diagnosis of adult hypersensitivity pneumonitis (HP), an immune-mediated inflammatory lung and small airway disease. An abbreviated overview of the guideline summary has been published in the Annals of the American Thoracic Society.

Development of the Guideline

The guideline was developed by a team of international experts in HP appointed by American Thoracic Society (ATS), Japanese Respiratory Society (JRS) and the Asociación Latinoamericana del Tórax (ALAT). Panel members consolidated available evidence about HP clinical features, basing the new diagnostic criteria and grading recommendations on recent data. The HP guideline complements the 2018 ATS/ERS/JRS/ALAT guidance on the diagnosis of idiopathic pulmonary fibrosis (IPF).

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Diagnostic Criteria

The guideline indicated that no individual feature related to history, high-resolution computed tomography (HRCT) or histopathology is sufficient “in isolation or mandatory to make a diagnosis of HP.” Additionally, identification of the culprit exposure is not essential, as up to 50% of patients do not have an identifiable exposure culprit. Ideally, diagnosis is made through a multidisciplinary discussion. 

A new diagnostic algorithm for nonfibrotic HP (NFHP) and fibrotic HP (FHP) was proposed, including exposure identification, imaging pattern, and bronchoalveolar lavage (BAL) lymphocytosis/histopathologic findings. Exposure identification may involve assessment of clinical history, antigen specific serum immunoglobulin G (IgG), and/or specific inhalation challenge. 

Based on an approach used for fibrotic interstitial lung diseases (ILDs), the guideline uses the following level of diagnostic confidence for HP:

  • Definite confidence (≥90%)
  • High confidence (80-89%)
  • Moderate confidence (70-79%)
  • Low confidence (<69%)

A diagnosis of HP of the highest confidence is made with a culprit exposure, typical HP HRCT pattern, and BAL lymphocytosis without invasive testing. All other cases should rely on multidisciplinary discussion with or without subsequent histopathological sampling for achievement of an “acceptable” level of confidence in HP diagnosis.

Diagnostic Interventions

Questionnaires are sometimes considered a helpful component of disease assessment; however, the guideline panel made no recommendation on questionnaires for identifying potential inciting antigens in HP. This lack of guidance on questionnaire use for HP diagnosis was related to the paucity of evidence. While not providing specifics, the guideline panel noted that a questionnaire may be considered “as part of the diagnostic pathway.”

The panel suggested the use of serum IgG testing targeting potential HP-associated antigens could support an HP diagnosis in patients with newly detected ILD whose differential diagnosis includes NFHP or FHP. Serum IgG testing alone, however, is not deemed sufficient enough to either confirm or exclude an HP diagnosis. Additionally, standardization is currently lacking for serum IgG testing.

In patients with newly detected ILD whose differential diagnosis includes NFHP and FHP, the use of BAL with lymphocyte cellular analysis is recommended to assist with diagnosis. The panel noted that the evidence suggests BAL fluid cellular lymphocyte analysis can distinguish NFHP from sarcoidosis and FHP from IPF and sarcoidosis. Pooled data and collective expertise of the panel established thresholds of 20% and 30%, respectively, for BAL fluid lymphocyte count in determining HP. 

Based on very low-quality evidence, the panel suggested transbronchial forceps lung biopsy could be useful for patients with newly detected ILD whose differential diagnosis includes NFHP. The diagnostic yield of transbronchial forceps lung biopsy is suboptimal, according to the panel, and could potentially result in diagnostic misclassification. The panel wrote that the diagnostic yield may be higher in suspected NFHP, supporting the procedure’s conditional recommendation.

Additionally, the panel suggests transbronchial lung cryobiopsy could be useful in patients with newly detected ILD whose differential diagnosis includes FHP but not NFHP. The respective diagnostic yields among people with known or suspected HP, ILD, and diffuse lung disease (DLD) were 91%, 82%, and 82%, respectively, according to the data pooled by the guideline panel. The use of transbronchial lung cryobiopsy for suspected FHP, according to the experts, may result in the avoidance of surgical lung biopsy.

The panel also suggested clinicians perform surgical lung biopsy for patients with newly detected ILD whose differential diagnosis includes HP, at least after alternative diagnostic options have been exhausted. According to consensus by the panel members, the diagnostic yield by surgical lung biopsy is high with relatively low complication rates, indicating it should be used following a comprehensive multidisciplinary discussion and after all diagnostic tests have failed to reach a definitive HP diagnosis.

Future Outlook

In the summary of their guideline statement, the authors wrote that additional research is needed “to validate and standardize a questionnaire for clinical use, determine a BAL lymphocytosis threshold, identify specific HP antibodies and explore biomarkers of disease.” Additionally, the panel cited the need for “clinical and translational research, including HP-specific registries, to explore management of HP by subtype” and to provide subsequent updates to the guideline.


Koster MA, Thomson CC, Collins BF, Jenkins AR, Ruminjo JK, Raghu G. Diagnosis of hypersensitivity pneumonitis in adults, 2020 clinical practice guideline: summary for clinicians. Published online November 3, 2020. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.202009-1195CME