What is the treatment for interstitial pneumonia?

Treatment of Interstitial Pneumonia

Treatment for interstitial pneumonia depends critically on the specific histopathologic subtype, with nonspecific interstitial pneumonia (NSIP) responding well to corticosteroids while usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) should NOT be treated with corticosteroids and instead requires antifibrotic therapy or supportive care. 1

Critical First Step: Accurate Diagnosis

Surgical lung biopsy (preferably video-assisted thoracoscopic surgery) is essential to distinguish between subtypes, as treatment approaches differ dramatically and incorrect treatment can cause harm 1. High-resolution CT (HRCT) patterns help guide diagnosis but biopsy provides definitive histopathologic classification 1, 2.

Key Diagnostic Distinctions:

• NSIP: Shows homogeneous inflammation or fibrosis with temporally uniform changes; bilateral symmetric ground-glass opacities on HRCT 3, 1
• UIP/IPF: Demonstrates marked fibrosis with architectural distortion, patchy involvement, fibroblastic foci, and honeycombing in subpleural distribution 3, 1

Treatment by Subtype

Nonspecific Interstitial Pneumonia (NSIP)

Corticosteroids are first-line therapy for NSIP, with the majority of patients showing improvement 3, 1:

• Initial regimen: Prednisone at immunosuppressive doses (typically 0.5-1 mg/kg/day) 3, 1
• Start treatment at first identification of clinical or physiological impairment 1
• Prognosis is favorable: 15-20% mortality at 5 years with treatment 3, 1

For inadequate response to corticosteroids alone: Add cyclophosphamide or other immunosuppressive agents 4. One case series demonstrated dramatic improvement when cyclophosphamide was added to corticosteroids in NSIP patients with insufficient initial response 4.

Usual Interstitial Pneumonia (UIP)/Idiopathic Pulmonary Fibrosis (IPF)

Corticosteroids are NOT recommended for UIP/IPF and may cause harm 3, 1:

• Strong recommendation AGAINST corticosteroid therapy (with or without immunomodulators) except in acute exacerbations 3
• No data adequately document that corticosteroids improve survival or quality of life in IPF 1, 5
• Mean survival is approximately 3 years regardless of treatment 5

Approved antifibrotic therapy:

• Pirfenidone is FDA-approved for IPF, demonstrating reduced decline in forced vital capacity compared to placebo (mean treatment difference 193 mL at Week 52) 6
• Administered as 2,403 mg/day in three divided doses with food 6
• Alternative antifibrotic: Nintedanib (mentioned in systemic autoimmune rheumatic disease guidelines) 3

N-acetylcysteine (NAC) may be considered for some IPF patients after evaluating benefit/risk ratio, though evidence is limited 3, 1:

• Triple therapy (prednisone + azathioprine + NAC) is contraindicated: The PANTHER-IPF trial showed increased mortality and hospitalizations 3
• NAC monotherapy received a "Weak No" recommendation but may be considered if antifibrotic therapy is not indicated 3

Organizing Pneumonia Pattern (Including Post-COVID)

Corticosteroids are effective for organizing pneumonia 3:

• Initial dose: 0.5 mg/kg prednisolone for patients with persistent symptoms and CT abnormalities 6 weeks post-discharge 3
• Duration: Typically 3 weeks initially, with clinical improvement expected in >80% of cases 3
• Monitor for spontaneous recovery, as some patients improve without treatment within 12 weeks 3

Systemic Autoimmune Rheumatic Disease-Associated ILD (SARD-ILD)

Mycophenolate is the preferred first-line therapy across all SARD-ILD subtypes 3:

• Ranked highest in head-to-head comparisons for initial therapy 3
• Alternative first-line options include rituximab, calcineurin inhibitors, or nintedanib depending on disease context 3
• Long-term glucocorticoids are conditionally recommended AGAINST in most SARD-ILD 3
• Exception for systemic sclerosis: Strong recommendation AGAINST glucocorticoids due to scleroderma renal crisis risk, particularly at doses >15 mg/day prednisone equivalent 3

Rapidly Progressive Interstitial Pneumonia

For severe or rapidly progressive disease, intensive initial therapy is critical 7:

• Intravenous glucocorticoids (methylprednisolone 2-4 mg/kg/day) 2
• Add 1-2 additional immunosuppressive agents immediately: Rituximab, cyclophosphamide, IVIG, mycophenolate, or calcineurin inhibitors 3, 7
• Primary intensive approach (starting immunosuppressives simultaneously with corticosteroids) shows significantly better survival than step-up approach (P=0.030) 7
• Consider early lung transplant referral 3

Common pitfall: Waiting to add immunosuppressive drugs after corticosteroid failure results in worse outcomes; many patients fail to respond and have significantly high mortality with delayed intensification 7.

Supportive Care and Monitoring

All patients require:

• Pulmonary rehabilitation: Weak Yes recommendation for IPF, demonstrated improved walking distance, quality of life, and dyspnea in interstitial lung disease 3
• Oxygen therapy for hypoxemia 1
• Monitoring with combination of clinical, radiographic, and physiological parameters 1
• Lung transplantation referral for progressive deterioration despite treatment 1

Treatments to AVOID:

• Anticoagulation: Strong No recommendation for IPF; warfarin associated with increased mortality in ACE-IPF study 3
• Mechanical ventilation for respiratory failure due to IPF: Weak No recommendation 3

Treatment Monitoring

Clinical effect should be expected within 3 days for acute presentations 2. Use serial pulmonary function tests, HRCT imaging, and symptom assessment to evaluate response 1. Adjust therapy based on disease progression or treatment failure, considering switch to alternative agents or addition of second-line therapies 3.