What is the best course of treatment for a patient with suspected hypersensitivity pneumonitis (HP), chronic cough, potential bronchospasm, reduced Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO), and newly diagnosed pulmonary fibrosis on Computed Tomography (CT) scan?

Management of Pulmonary Fibrosis with Suspected Hypersensitivity Pneumonitis

The immediate priority is to identify and completely eliminate any inciting antigen exposure while simultaneously pursuing definitive diagnosis through high-resolution CT pattern recognition, bronchoalveolar lavage, and multidisciplinary discussion, as the presence of fibrosis significantly worsens prognosis and alters treatment strategy. 1

Diagnostic Confirmation

High-Resolution CT Pattern Analysis

• Look specifically for the "three-density sign" (areas of ground-glass attenuation, normal lung, and mosaic attenuation in three or more lobes), which has 93% specificity for fibrotic HP versus IPF 1
• Identify mosaic attenuation/air-trapping more extensive than reticulation with diffuse axial distribution (90% specificity, 55% sensitivity for HP) 1
• Assess for centrilobular nodules, lobular areas with decreased attenuation, and absence of lower zone predominance—these features differentiate fibrotic HP from IPF 1
• Note that honeycombing, traction bronchiectasis, and peripheral/lower zone predominance are less common in HP than IPF 1

Antigen Identification and Exposure Assessment

• Conduct detailed exposure history focusing on: birds (including down feathers/pillows), mold/water damage, hot tubs, farming exposures, and occupational antigens 1
• Consider 2-week antigen avoidance trial with environmental assessment if exposure is identified 1, 2
• Critical caveat: Lack of clinical improvement with antigen avoidance does NOT rule out HP, especially in fibrotic disease where damage may be irreversible 1
• Serum antigen-specific IgG testing should NOT be used alone to confirm or exclude HP due to lack of standardization, but may support diagnosis when combined with typical HRCT and exposure history 1

Bronchoscopy with BAL

• Perform BAL to assess lymphocyte percentage (>20% lymphocytes supports HP diagnosis, though not required) 1
• BAL is particularly valuable when combined with multidisciplinary discussion probability assessment 1
• Consider transbronchial biopsy alongside BAL, as this substantially increases diagnostic yield, particularly in fibrotic HP 1

Tissue Diagnosis When Needed

• Pursue surgical lung biopsy or transbronchial cryobiopsy if diagnosis remains uncertain after CT, exposure assessment, and BAL 1
• Look for histologic features of typical fibrotic HP: small airway-centered fibrosis, chronic fibrosing interstitial pneumonia (NSIP or UIP pattern), and poorly formed granulomas 1
• Important distinction: A UIP pattern on biopsy does NOT exclude HP if CT shows typical HP features (three-density sign, mosaic attenuation) 1

Treatment Algorithm

For Fibrotic HP (Your Patient's Scenario)

Antigen Avoidance (First-Line)

• Immediately and completely eliminate identified antigen exposure—this is the single most important intervention 1
• Measurable improvement may not occur in established fibrosis, but continued exposure worsens outcomes 1

Immunosuppression

• Initiate oral corticosteroids (prednisone) for patients with fibrotic HP, particularly if there is evidence of active inflammation on imaging or BAL 3, 4
• Add steroid-sparing immunosuppressant such as mycophenolate mofetil or azathioprine for steroid-sparing effect and DLCO improvement 3
• Leflunomide may improve FVC in non-fibrotic or minimally fibrotic HP (8.3% FVC increase at 12 months) but shows no benefit in established fibrosis and has 40% discontinuation rate due to adverse effects 3

Antifibrotic Therapy

• Consider nintedanib or pirfenidone for progressive fibrotic HP, particularly when fibrosis extent is significant 5, 2
• Nintedanib combined with corticosteroids has been used successfully in fibrotic HP cases 2
• Pirfenidone is FDA-approved for IPF and may slow FVC decline in fibrotic interstitial lung diseases 5

Bronchodilator Therapy

• Treat bronchospasm with inhaled bronchodilators (beta-agonists and/or anticholinergics) as HP can cause small airway disease 1, 6

Prognostic Considerations

• Fibrotic HP carries significantly worse prognosis than non-fibrotic HP (HR 4.35 for death compared to non-fibrotic HP) 1
• Honeycombing on CT confers the worst prognosis, followed by non-honeycomb fibrosis 1
• Extent of fibrosis on CT (fibrosis score) independently predicts mortality or need for lung transplantation (HR 1.54 per unit increase) 1
• Unidentified antigen exposure trends toward worse survival (HR 2.07), emphasizing importance of thorough exposure assessment 1

Critical Pitfalls to Avoid

• Do NOT rely solely on lack of improvement with medical therapy to rule out HP—fibrotic HP often does not respond to treatment 1
• Do NOT use serum IgG testing alone for diagnosis—it lacks standardization and validation 1
• Do NOT assume absence of identified antigen excludes HP—up to 28-55% of fibrotic HP cases have no identified antigen 1
• Do NOT delay multidisciplinary discussion—integration of clinical, radiologic, and pathologic data is essential for accurate diagnosis 1, 7
• Do NOT confuse fibrotic HP with IPF based solely on UIP pattern—CT features (three-density sign, mosaic attenuation, mid-lung predominance) are critical differentiators 1