Hypersensitivity pneumonitis

Abstract

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by the inhalation of a variety of antigens in susceptible and sensitized individuals. These antigens are found in the environment, mostly derived from bird proteins and fungi. The prevalence and incidence of HP vary widely depending on the intensity of exposure, the geographical area and the local climate. Immunopathologically, HP is characterized by an exaggerated humoral and cellular immune response affecting the small airways and lung parenchyma. A complex interplay of genetic, host and environmental factors underlies the development and progression of HP. HP can be classified into acute, chronic non-fibrotic and chronic fibrotic forms. Acute HP results from intermittent, high-level exposure to the inducing antigen, usually within a few hours of exposure, whereas chronic HP mostly originates from long-term, low-level exposure (usually to birds or moulds in the home), is not easy to define in terms of time, and may occur within weeks, months or even years of exposure. Some patients with fibrotic HP may evolve to a progressive phenotype, even with complete exposure avoidance. Diagnosis is based on an accurate exposure history, clinical presentation, characteristic high-resolution CT findings, specific IgG antibodies to the offending antigen, bronchoalveolar lavage and pathological features. Complete antigen avoidance is the mainstay of treatment. The pharmacotherapy of chronic HP consists of immunosuppressive drugs such as corticosteroids, with antifibrotic therapy being a potential therapy for patients with progressive disease.

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Fig. 1: Pathogenesis of HP.
Fig. 2: Immunopathology in HP.
Fig. 3: HRCT of acute HP.
Fig. 4: HRCT in chronic fibrotic HP.
Fig. 5: Histopathology of acute inflammatory HP.
Fig. 6: Histopathology of chronic fibrotic HP.

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Acknowledgements

The authors thank D. Theegarten (Institute of Pathology, University Hospital Essen) for contributing Figures 5 and 6.

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Contributions

Introduction (U.C.); Epidemiology (Y.M., D.K., A.P. and M.S.); Mechanisms/pathophysiology (A.P., M.S. and D.K.); Diagnosis, screening and prevention (Y.M., D.K., F.B., J.G., C.J.R. and U.C.); Management (P.S.); Quality of life (C.J.R.); Outlook (all authors); Overview of the Primer (U.C.).

Corresponding author

Correspondence to Ulrich Costabel.

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Competing interests

Y.M. reports honoraria for lectures from Nippon Boehringer Ingelheim and AstraZeneca. F.B. reports grant funding and speaking honoraria from Boehringer Ingelheim, Galapagos and Hoffmann-La Roche that are unrelated to the current manuscript. C.J.R. reports grant funding and speaking honoraria from Boehringer Ingelheim and Hoffmann-La Roche that are unrelated to the current manuscript. M.S. reports honoraria for serving as a consultant from Boehringer and as member of an adjudication committee from Celgene that are unrelated to the current manuscript. The remaining authors declare no competing interests.

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Nature Reviews Disease Primers thanks D. Lynch, V. Poletti and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Susceptible

Increased risk of developing a disease, usually associated with genetic or host factors.

Sensitized

Presence of specific antibodies to the offending antigen.

Bronchoalveolar lavage

(BAL). A method to collect cells and fluid from the alveolar spaces for diagnostic or research purposes.

Summer-type HP

A subtype of HP mainly in Japan caused by the fungus Trichosporon asahii growing in decayed wood in housing.

House-related HP

A subtype of HP mainly caused by exposure to fungi in the home.

Granuloma

A focal collection of inflammatory cells, predominantly mature macrophages that form an aggregate in response to an antigen. It consists of a tightly formed conglomerate of epithelioid and multinucleated giant cells encircled by lymphocytes, especially CD4+ T helper cells. In hypersensitivity pneumonitis, these are small poorly formed non-necrotizing epithelioid cell granulomas.

Honeycombing

A form of lung fibrosis on high-resolution CT (HRCT) with cyst clusters having a bee honeycomb appearance.

Traction bronchiectasis

Widening of the bronchial lumen through traction exerted by shrinking fibrotic lung tissue as a sign of lung fibrosis on high-resolution CT.

Reticulation

A form of lung fibrosis on high-resolution CT with a net-like appearance.

Usual interstitial pneumonia

(UIP). A radiological and a histopathological pattern that is seen mainly in idiopathic pulmonary fibrosis but may be observed in other fibrotic lung disorders. On chest high-resolution CT, it is characterized by the presence of reticular changes, predominantly bilateral, peripheral and basal, and usually associated with traction bronchiectasis and honeycombing. Histopathologically, it is characterized by interstitial fibrosis showing spatial heterogeneity with patchy involvement of the lung parenchyma, areas of marked fibrosis, architectural distortion and microscopic honeycombing.

Non-specific interstitial pneumonia

(NSIP). A lung disease characterized by histological features of varying amounts of interstitial inflammation and fibrosis with a uniform appearance.

Auscultation

The action of listening to sounds as a part of medical diagnosis.

Ground-glass opacity

An area of mildly increased attenuation in the lung on high-resolution CT, looking like ground glass.

Bronchiolitis

Inflammation of the bronchioles, the smallest airways of the lungs.

Diffusing capacity for carbon monoxide

(DLCO). A highly sensitive method to determine the ability of the lung itself to perform normal gas exchange.

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Costabel, U., Miyazaki, Y., Pardo, A. et al. Hypersensitivity pneumonitis. Nat Rev Dis Primers 6, 65 (2020). https://doi.org/10.1038/s41572-020-0191-z

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