Hypersensitivity PneumonitisEdit

Hypersensitivity pneumonitis (HP) is an immune-mediated form of interstitial lung disease triggered by inhaled antigens. It encompasses a spectrum from acute, self-limited reactions to chronic, fibrotic lung disease. HP is not contagious and typically arises when individuals are repeatedly exposed to organic or inorganic antigens such as molds, bird proteins, or contaminated aerosols. Commonly discussed subtypes include farmer's lung, bird fancier's lung, and humidifier lung, each tied to a distinct exposure source. The diagnosis rests on a careful history of exposure, characteristic imaging findings, and supportive laboratory data; treatment hinges on removing the causal antigen and managing inflammation when necessary.

HP sits within the broader landscape of interstitial lung diseases, and its presentation can resemble infections or other inflammatory lung conditions. Because exposure histories are central to recognition, clinicians often integrate occupational and environmental health considerations with radiologic and physiologic testing. Outcomes vary widely: many patients improve after exposure avoidance, while others progress to chronic lung injury with fibrosis if exposure continues or is not identified promptly. The discussion around HP has grown to encompass not only clinical care but also how best to regulate workplaces and consumer environments to prevent exposure, and how to interpret diagnostic tests in the context of real-world exposures.

Etiology and classification

HP results from inhalation of a wide range of antigens that provoke an immune response in susceptible individuals. Antigen exposure is typically environmental or occupational rather than infectious. The condition is often labeled by the most common exposure scenarios:

Farmers' lung: inhalation of moldy hay and organic dust containing thermophilic actinomycetes.
Bird fancier's lung: inhalation of avian proteins from feathers, droppings, and cage substrates.
Humidifier or air-conditioning-associated HP: aerosols generated by contaminated humidifiers or ventilation systems.
Woodworker's lung and other occupational forms: exposure to moldy or contaminated wood dust, farming residues, or other organic matter.

HP can present in several clinical phenotypes:

Acute HP: rapid onset of fever, cough, and dyspnea within hours of a heavy exposure, often resolving with antigen avoidance.
Subacute HP: weeks of evolving breathlessness, cough, malaise, and weight loss, with less dramatic, more prolonged exposure.
Chronic HP: ongoing exposure leading to progressive dyspnea, cough, fatigue, and sometimes signs of fibrosis.

The distinction between nonfibrotic (reversible) and fibrotic (potentially irreversible) HP is clinically meaningful, as it guides prognosis and management. See hypersensitivity pneumonitis for related terms and interstitial lung disease for the broader category.

Pathophysiology

HP reflects a combination of immune mechanisms, including immune complex (type III) formation and T-cell–mediated (type IV) responses to inhaled antigens. Repeated or persistent exposure can sustain airway and interstitial inflammation, leading to a spectrum of lung injury from edema and infiltrates to repairing processes that may culminate in fibrotic scarring. The precise balance of immune pathways likely varies by antigen, exposure pattern, and host factors, which helps explain the variability in clinical presentation and progression.

Laboratory and radiographic findings often reflect this immune activity:

Serum antibodies to inhaled antigens (precipitins) may support exposure history but are not specific for HP and can be present in exposed individuals without disease.
Bronchoalveolar lavage (BAL) frequently shows increased lymphocytes, supporting a hypersensitivity process, though BAL results are not definitive on their own.
Imaging, particularly high-resolution computed tomography (HRCT), often reveals a mosaic pattern with centrilobular nodules, ground-glass opacities, and areas of air trapping, which can evolve into fibrosis in chronic cases.

Diagnosis

Diagnosing HP requires integrating exposure history, clinical features, imaging, and, when needed, physiological testing. No single test is definitive for all cases, and misclassification can occur if exposure is overlooked or if radiologic findings overlap with other interstitial lung diseases such as idiopathic pulmonary fibrosis. Key elements include:

Exposure assessment: detailed inquiry into occupational and domestic environments, hobbies, and sources of inhaled antigens.
Imaging: HRCT findings characteristic of HP can include centrilobular nodules, ground-glass opacities, and mosaic attenuation due to air trapping; fibrosis may be present in chronic HP.
Pulmonary function tests: a restrictive pattern with reduced diffusing capacity (DLCO) is common, though variability exists.
BAL and serology: BAL lymphocytosis supports HP, while precipitating antibodies to specific antigens can aid exposure identification but are not diagnostic by themselves.
Histopathology: lung biopsy is generally reserved for uncertain cases where imaging and exposure data do not yield a confident diagnosis.

See HRCT for imaging terminology and bronchoalveolar lavage for a description of the BAL procedure and its interpretive value.

Management and treatment

The cornerstone of HP management is removing the causal antigen exposure. Without effective avoidance, medical therapy is less likely to alter the disease course, especially in chronic HP with fibrotic change. Management principles include:

Antigen avoidance: targeted changes in occupation, hobbies, and household environments, coupled with patient education and occupational health support.
Pharmacotherapy: systemic corticosteroids are used to control inflammation in acute or subacute HP and may provide symptomatic relief, but long-term benefit varies and exposure cessation remains essential. In fibrotic HP, immunosuppressive therapies have uncertain benefit and are considered on a case-by-case basis.
Supportive care: supplemental oxygen as needed, pulmonary rehabilitation, vaccination against respiratory pathogens, and management of comorbidities.
Advanced disease: in selected cases with severe fibrotic HP, evaluation for lung transplantation may be appropriate.

Prognosis hinges on the ability to halt ongoing exposure and the extent of fibrotic change at diagnosis. Early recognition and antigen avoidance are associated with better outcomes.

Controversies and debates

HP sits at the intersection of clinical care, occupational health, and public policy, where several debates remain:

Diagnostic criteria and tests: clinicians differ on how much weight to give precipitins, BAL lymphocytosis, and histologic findings. Some argue for a stringent exposure-driven framework, while others emphasize imaging and physiologic patterns. The lack of a single gold-standard test means diagnoses frequently rely on clinician judgment and multidisciplinary discussion.
Role of biopsy: lung biopsy can provide diagnostic clarity in uncertain cases but carries risks. Debates focus on when the potential diagnostic yield justifies procedural risk, especially when the exposure history and imaging are suggestive.
Distinguishing HP from other ILDs: overlaps with idiopathic interstitial pneumonias complicate classification. There is ongoing discussion about how best to categorize fibrotic HP within current ILD frameworks and how that affects treatment decisions.
Antigen avoidance versus pharmacologic therapy: while avoidance is essential, some patients experience persistent symptoms or progression despite de-escalation of exposure. The appropriate intensity and duration of pharmacologic therapy, and when to escalate to immunosuppression or antifibrotic strategies, remain debated.
Public health and regulation: from a policy perspective, some commentators stress that clear, evidence-based exposure controls in workplaces and consumer environments can reduce HP incidence without imposing unnecessary burdens on employers. Critics of broad environmental regulation argue for targeted, cost-effective measures grounded in practical risk assessment.
Woke criticisms and policy responses: proponents of broad environmental advocacy sometimes argue for aggressive public health messaging around all potential inhalational risks. Critics from a traditional clinical perspective contend that such broad framing can overwhelm patients and clinicians with unlikely scenarios, potentially diverting attention from high-yield, modifiable exposures. A measured stance emphasizes actionable, evidence-based exposure avoidance and patient-specific management rather than sweeping social campaigns; this approach aims to maximize safety and reduce unnecessary regulatory or economic burdens while still protecting health.