What are the cause, pathogenesis, management, imaging findings, and laboratory findings of Hypersensitivity Pneumonitis (HP)?

From the Guidelines

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by repeated inhalation of environmental antigens that trigger an exaggerated immune response in susceptible individuals, and its management primarily involves antigen avoidance, which is essential for preventing disease progression, as stated in the Chest guideline and expert panel report 1.

Cause and Pathogenesis

The cause of HP includes exposure to bird proteins, thermophilic actinomycetes in moldy hay, and various occupational antigens like isocyanates or metal working fluids. Pathogenesis involves both type III and type IV hypersensitivity reactions, with formation of immune complexes and T-cell mediated inflammation, leading to alveolar damage, granuloma formation, and potential progression to fibrosis.

Diagnosis

Diagnosis relies on a combination of:

• Exposure history
• Clinical presentation
• Imaging findings, typically showing ground-glass opacities, centrilobular nodules, and mosaic attenuation on HRCT in acute/subacute phases, while fibrotic changes and honeycombing may develop in chronic disease
• Sometimes lung biopsy
• Laboratory findings, including elevated serum precipitins against the offending antigen, increased inflammatory markers, lymphocytosis in bronchoalveolar lavage (BAL) with CD8+ T-cell predominance, and reduced diffusion capacity on pulmonary function tests

Management

Management primarily involves antigen avoidance, which is essential for preventing disease progression, as stated in the Chest guideline and expert panel report 1.

• Corticosteroids (typically prednisone 0.5-1 mg/kg/day with gradual taper over 2-3 months) are indicated for significant symptoms or functional impairment.
• In chronic or progressive cases, additional immunosuppressants like mycophenolate mofetil or azathioprine may be necessary.
• Supportive care includes oxygen therapy if hypoxemic, pulmonary rehabilitation, and vaccination against respiratory pathogens.
• Early diagnosis and intervention are crucial, as continued exposure can lead to irreversible fibrosis and respiratory failure, as highlighted in the American Journal of Respiratory and Critical Care Medicine 1.

Imaging and Lab Findings

Imaging typically shows:

• Ground-glass opacities
• Centrilobular nodules
• Mosaic attenuation on HRCT in acute/subacute phases
• Fibrotic changes and honeycombing may develop in chronic disease Laboratory findings may include:
• Elevated serum precipitins against the offending antigen
• Increased inflammatory markers
• Lymphocytosis in bronchoalveolar lavage (BAL) with CD8+ T-cell predominance
• Reduced diffusion capacity on pulmonary function tests, as discussed in the Journal of Allergy and Clinical Immunology 1.

From the Research

Cause of Hypersensitivity Pneumonitis

• Hypersensitivity pneumonitis (HP) is caused by an exaggerated immune response to an inhaled antigen, resulting in a complex and heterogeneous interstitial lung disease (ILD) 2.
• The disease is mediated by the immune system and caused by inhalation of a wide variety of antigens to which the individual has been previously sensitized 3.
• HP can be caused by multiple agents that are present in workplaces and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals 4.

Pathogenesis of Hypersensitivity Pneumonitis

• The pathobiology of the disease is not fully understood, but in addition to the triggers that initiate the disease, host/genetic factors are likely to be important, as only a minority of exposed individuals develop HP 3.
• HP results in mostly T cell-mediated inflammation, granuloma formation, and fibrosis in some cases 5.
• The presence of fibrosis is associated with worse outcomes, and a proportion of patients with fibrotic HP develop a progressive phenotype, characterized by worsening fibrosis, decline in lung function, and early mortality 2.

Management of Hypersensitivity Pneumonitis

• The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties in identifying the agent or because its avoidance may lead to major changes in life style or occupational settings 4.
• Therapeutic approach includes avoiding further exposure and, depending on the clinical form, the administration of a course of prednisone 6.
• Immunosuppressants are commonly used in patients with HP, but have not been shown to slow the worsening of fibrotic disease 2.
• Nintedanib, a tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for slowing the progression of chronic fibrosing ILDs with a progressive phenotype, including progressive fibrotic HP 2.

Imaging and Lab Findings of Hypersensitivity Pneumonitis

• HP is diagnosed by exposure identification, HRCT findings of ground-glass opacities, centrilobular nodules, and mosaic attenuation, with traction bronchiectasis and honeycombing in fibrotic cases 5.
• Additional testing including serum IgG testing for the presence of antigen exposure, bronchoalveolar lavage lymphocytosis, and lung biopsy demonstrating granulomas, inflammation, and fibrosis, increases the diagnostic confidence 5.
• Differential diagnosis of HP can be challenging and requires a thorough exposure history, multidisciplinary discussion of clinical and radiologic data, and, in some cases, assessment of bronchoalveolar lavage lymphocytosis and histopathologic findings 2.