Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP), historically called extrinsic allergic alveolitis, is an immune-mediated interstitial lung disease caused by an exaggerated response to inhaled antigens in susceptible, usually non-atopic individuals. Depending on the intensity and duration of exposure, it can present as a more inflammatory, potentially reversible process or as chronic fibrotic disease.

Definition

Hypersensitivity pneumonitis is an immunologically mediated inflammatory disease of the lung parenchyma and small airways resulting from repeated inhalation of and sensitization to environmental antigens, classified in contemporary frameworks as non-fibrotic or fibrotic based on imaging and pathology.

Scope

This entry covers the antigen-driven immunopathogenesis of HP, the contemporary distinction between non-fibrotic and fibrotic forms, and the exposure-centered, multidisciplinary diagnostic approach. It is a reference and educational overview and does not provide individualized diagnostic or treatment guidance, including antigen-avoidance advice for specific patients.

Key concepts

• Inhaled antigen sensitization
• Extrinsic allergic alveolitis
• Non-fibrotic versus fibrotic HP
• Type III and type IV immune mechanisms
• Granulomatous inflammation
• Bronchoalveolar lavage lymphocytosis
• Antigen identification and exposure history
• Multidisciplinary diagnosis

Mechanisms

HP arises when repeated inhalation of an offending antigen, such as avian proteins or thermophilic microorganisms, sensitizes the host and provokes an exaggerated immune response in the alveoli and small airways. Both immune-complex (type III) and cell-mediated (type IV) mechanisms are implicated, the latter producing the characteristic lymphocytic alveolitis and poorly formed, non-necrotizing granulomas. With continued exposure and individual susceptibility, the inflammatory process can transition to established fibrosis, which underlies the contemporary separation of non-fibrotic from fibrotic HP because the fibrotic form behaves more like a progressive interstitial disease.

Clinical relevance

HP is a clinically important consideration because it is one of the few interstitial lung diseases with a potentially modifiable trigger, and identifying an inciting exposure is central to how it is distinguished from other fibrotic ILDs such as IPF. This entry describes the disease for reference and education; it does not provide criteria for diagnosing individuals or instructions on managing exposures, which are matters for qualified clinicians.

Epidemiology

Reported frequency varies widely with exposure setting, climate, diagnostic criteria, and the antigens prevalent in a population, so true incidence is uncertain. A substantial proportion of cases have no identifiable antigen despite investigation, and fibrotic HP is increasingly recognized within cohorts of fibrotic interstitial lung disease.

Evidence & guidelines

The 2020 ATS/JRS/ALAT clinical practice guideline provided a contemporary diagnostic framework for HP in adults, formalizing the non-fibrotic versus fibrotic distinction and the roles of exposure assessment, imaging, bronchoalveolar lavage, and multidisciplinary discussion. Review syntheses such as Vasakova and colleagues (2017) summarize how diagnosis integrates these elements. These are cited as evidence landmarks rather than as treatment instructions.

History

Recognition of lung disease caused by inhaled organic antigens dates to classic descriptions of occupational exposures such as farmer's lung and bird fancier's lung, framed as extrinsic allergic alveolitis. Understanding later shifted from acute, subacute, and chronic categories toward a clinically grounded division into non-fibrotic and fibrotic disease, which the 2020 international guideline codified alongside a structured diagnostic approach.

Debates

How should hypersensitivity pneumonitis be classified?

Older schemes divided HP into acute, subacute, and chronic forms, but contemporary frameworks favor a non-fibrotic versus fibrotic dichotomy because the presence of fibrosis better predicts behavior and prognosis; the optimal classification and diagnostic thresholds remain debated.

Key figures

• Ganesh Raghu
• Martina Vasakova
• Ferran Morell

Seminal works

• raghu-2020-hp
• vasakova-2017

Frequently asked questions

What causes hypersensitivity pneumonitis?

It is caused by an exaggerated immune response to repeatedly inhaled environmental antigens, classically avian proteins and microbial agents from sources such as moldy hay, though in many cases no specific antigen is identified.

Why are non-fibrotic and fibrotic forms distinguished?

The distinction matters because fibrotic HP behaves more like a progressive interstitial fibrosis with a different prognosis, whereas non-fibrotic disease reflects a predominantly inflammatory process; this shapes how the disease is conceptualized and studied.