What is the treatment for chronic hypersensitivity pneumonitis?

Treatment of Chronic Hypersensitivity Pneumonitis

The cornerstone of treatment for chronic hypersensitivity pneumonitis is immediate and complete removal of the inciting antigen, which is the single most critical intervention to alter disease trajectory and mortality; systemic corticosteroids should be added only in patients with evidence of physiologic impairment or severe disease. 1, 2

Initial Disease Classification

Before initiating treatment, classify the patient into one of two phenotypes, as this fundamentally determines prognosis and treatment approach:

• Non-fibrotic HP: Purely inflammatory disease without radiographic or histopathologic evidence of fibrosis 2
• Fibrotic HP: Presence of fibrosis on imaging or pathology, which carries significantly worse prognosis and reduced survival 1, 2

The presence or absence of fibrosis is the primary determinant of survival outcomes. 2

Antigen Identification and Complete Avoidance

Exposure Assessment Strategy

Conduct a systematic three-component evaluation to identify the inciting antigen: 2

• Exposure survey: Document all potential organic antigens, inorganic chemicals, and pharmaceutical agents 2
• Occupational history: Common sources include farming, bird exposure (pigeons, parakeets), contaminated humidifiers, indoor molds, metalworking fluids, and aerosolized water 3, 4
• Environmental history: Assess home environment for hot tubs, humidifiers, water damage, and pet birds 4, 2

For occupational exposures, immediately involve an occupational medicine specialist and certified environmental hygienist during diagnostic workup. 2

Critical Importance of Complete Antigen Removal

• Complete removal is mandatory—partial measures are insufficient and will result in continued disease progression 2
• For hot-tub lung (mycobacterial HP), the indoor hot tub must be moved outdoors or completely removed, not simply cleaned 1, 2
• Remove the patient from the suspected environment within days if the antigen source cannot be remediated 4
• If occupational disease recurs despite workplace modifications, worker removal from the exposure site is mandatory 2

Critical pitfall: Never escalate immunosuppression without ensuring complete antigen avoidance first, as continued exposure negates treatment benefits and increases mortality. 4

Pharmacological Management

Non-Fibrotic HP

For severe disease or respiratory failure: 1, 2

• Initiate prednisone at 1-2 mg/kg/day (typically 40-60 mg daily) 1, 2
• Taper over 4-8 weeks 1, 2
• Corticosteroids hasten recovery and improve gas exchange but must be combined with antigen avoidance 2
• In acute non-fibrotic HP, prednisone starting at 40 mg daily for 8 weeks showed lung function improvement at 1 month, though no difference at 5 years 4

For mycobacterial HP (hot-tub lung): 1, 2

• Antimycobacterial therapy for 3-6 months if symptoms persist after complete antigen avoidance 1, 2

Fibrotic HP

Corticosteroid approach: 1

• Higher doses may be needed for longer periods, but response is often limited 1
• Clinical improvement after antigen avoidance in fibrotic HP is associated with decreased mortality (HR 0.18; 95% CI 0.04-0.77) 1, 4

Steroid-sparing immunosuppression: 1, 4

When complete antigen avoidance cannot be achieved or disease progresses despite corticosteroids:

• Mycophenolate mofetil: 500-1000 mg/m² body surface area 4

  • Demonstrates benefit in altering the slope of FVC decline 1
  • Particularly effective in improving DLCO even when FVC improvement is limited 1
  • 66% less frequent treatment-emergent adverse events compared to prednisone alone (p=0.002) 5

• Azathioprine: Alternative steroid-sparing agent 1, 5

  • 54% less frequent treatment-emergent adverse events compared to prednisone alone (p=0.04) 5

Important caveat: Lack of improvement does not rule out HP, as fibrotic HP commonly fails to improve with any intervention. 1, 4

Monitoring and Expected Outcomes

Non-Fibrotic HP

• Clinical improvement typically manifests within 2 weeks to 3.4 months after antigen avoidance 4
• Improvement or normalization of lung function occurs on average 3.4 ± 2.4 months after antigen cessation 4
• Monitor FVC%, DLCO%, and gas exchange at baseline and at 3-4 month follow-up 1, 2
• Patients who avoid antigens for at least 2 years show significant improvement in all lung function parameters (P < .01), while continued exposure results in no improvement 4

Fibrotic HP

• Monitor for 3-4 months for improvement in FVC% and DLCO% after antigen avoidance 2
• Fibrotic HP often shows no improvement regardless of intervention 4
• Patients with unidentified inciting antigen have significantly worse survival (HR 2.08; 95% CI 1.02-4.24) compared to those with identified antigens 4, 2

Management Algorithm for Disease Worsening on Steroid Taper

1. Re-evaluate for ongoing or unidentified antigen exposure 1
2. Return to the last effective corticosteroid dose that controlled symptoms 1
3. Consider transition to steroid-sparing agents (mycophenolate mofetil or azathioprine) for patients requiring prolonged therapy 1, 5
4. Reassess disease phenotype: Determine if progression to fibrotic disease has occurred 1

Special Populations and Considerations

• Immunocompromised patients: Consider antimicrobial therapy if symptoms persist despite antigen avoidance and corticosteroids 2
• UIP-like pattern on imaging: Particularly poor prognosis; early consideration of antifibrotic therapy warranted if progressive phenotype develops 2
• Smoking: Associated with poor prognosis and should be addressed as part of comprehensive management 2

Continued Surveillance

• Perform continued surveillance for exposure at every visit 1, 2
• Reinforce patient education focused on antigen avoidance at each encounter 2
• Regular assessment of lung function (FVC%, DLCO%) is essential to monitor response to treatment 1