Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis (EAA), is a pulmonary delayed hypersensitivity reaction mediated mainly by cellular and humoral immune responses induced by repeated inhalation of organic and inorganic dust antigens in susceptible individuals. The pathological manifestation is characterized by chronic alveolar inflammation dominated by lymphocyte infiltration, accompanied by cellular bronchiolitis (airway-centered inflammation) and scattered non-caseous granulomas.
Pathogenesis
The pathogenesis of hypersensitivity pneumonitis has not yet been fully clarified. Some characteristics of the disease suggest that the pathogenesis of hypersensitivity pneumonitis may be closely related to certain systemic complexes. Intrinsic factors of the host (including genetic susceptibility) and changes in subsequent immune responses caused by exposure to various environmental factors in early childhood may be factors contributing to the occurrence of hypersensitivity pneumonitis. The pathogenesis of hypersensitivity pneumonitis with inflammatory response (more common in acute patients) and hypersensitivity pneumonitis with fibrotic response (common in chronic patients) may be different. Exposure to inhaled antigens may induce a proinflammatory response in respiratory epithelial cells, attracting neutrophils (producing interleukin IL-γ required for Th1 immune responses) and alveolar macrophages. Neutrophil apoptosis promotes maturation of dendritic cells and alveolar macrophages (as antigen-presenting cells). Release of IL-1, IL-12, and IL-18 promotes proliferation and differentiation of Th1 cells. In addition, circulating bone marrow-derived fibroblasts amplify inflammatory and fibrotic responses and may play a role in the pathogenesis of hypersensitivity pneumonitis.
Clinical manifestations
Currently, HP is classified into non-fibrotic HP and fibrotic HP based on the imaging and pathological manifestations. Non-fibrotic HP usually has an acute or subacute onset. Patients with acute onset generally present with chills, fever, and malaise accompanied by chest tightness, dyspnea, and cough 4 - 8 hours after exposure to antigens in the occupational or domestic environment. If the antigen exposure is removed, the condition can recover within 24 - 48 hours. If the exposure persists, recurrent acute attacks can lead to progressive dyspnea within few weeks or months, accompanied by emaciation, which is termed subacute HP. Fibrotic HP is usually caused by chronic and long-term exposure to allergens, repeated lung inflammation with abnormal repair leads to the formation of fibrosis, and the main manifestations are progressive dyspnea accompanied by cough and emaciation; end-inspiratory Velcro crackles can be heard at the base of the lungs, and some patients have clubbed fingers.
Diagnosis
On the basis of a clear history of antigen exposure, typical symptoms, chest HRCT showing characteristic manifestations such as centrilobular micronodules, patchy ground-glass opacities, mosaic sign formed by gas trapping, and pulmonary fibrosis predominant in the middle and upper lungs, and BALF examination showing significantly increased lymphocyte rate, a definite diagnosis can be established. Pathological data obtained in transbronchial lung biopsy (TBLB) and transbronchial lung cryobiopsy (TBLC) can further support the diagnosis, and open lung biopsy is usually not required.
Treatment
Identification of the pathogenic antigen and avoidance of contact with the allergen are the key to treatment. On the basis of avoidance of antigen contact, anti-inflammatory treatment (glucocorticoids alone or in combination with immunosuppressants) should be given.
Medications are effective for some patients, especially those with acute and subacute hypersensitivity pneumonitis. However, the efficacy of medications for chronic hypersensitivity pneumonitis is suboptimal.
The classic regimen is prednisolone 0.5 mg/kg.d）for 4 - 6 weeks, and then the dose is gradually reduced to a maintenance dose of 10 mg/day. It is suggested that acute and subacute hypersensitivity pneumonitis should be treated for 3 - 6 months until remission. Usually, in chronic hypersensitivity pneumonitis, glucocorticoids should be used for a longer time.