What is the treatment for Nonspecific Interstitial Pneumonia (NSIP)?

Treatment for Nonspecific Interstitial Pneumonia (NSIP)

Corticosteroids are the first-line treatment for NSIP, with prednisone at immunosuppressive doses (typically 0.5-1 mg/kg/day) initiated at the first identification of clinical or physiological impairment. 1, 2

Initial Treatment Approach

• Start prednisone immediately when NSIP is diagnosed and clinical or physiological impairment is documented, rather than waiting for disease progression 1
• The majority of NSIP patients show clinical improvement with corticosteroid therapy 1, 2, 3
• Prognosis is favorable with treatment, showing 15-20% mortality at 5 years 1, 2

Treatment Stratification by Disease Phenotype

The response to immunosuppression varies significantly based on the radiologic-pathologic profile:

Inflammatory/Cellular NSIP (Better Prognosis)

• Characterized by prominent lymphocytic inflammation on biopsy and bronchoalveolar lavage 4
• HRCT shows mixed NSIP/organizing pneumonia pattern with ground-glass opacities 4
• These patients have excellent response to corticosteroids and may require addition of immunosuppressive agents (such as mycophenolate or azathioprine) 4, 3

Fibrotic NSIP (Guarded Prognosis)

• Prominent reticular changes and traction bronchiectasis on HRCT 4
• High fibrotic background on biopsy without significant lymphocytosis on BAL 4
• Less responsive to immunosuppressive treatment and carries marginal risk of evolution to usual interstitial pneumonia pattern 4, 5
• Consider antifibrotic therapy (though evidence is limited) for progressive, treatment-refractory cases 4

Critical Diagnostic Caveat

Surgical lung biopsy is essential before initiating treatment to definitively distinguish NSIP from usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis, as corticosteroids are contraindicated and potentially harmful in UIP 1, 2. This distinction is critical because:

• UIP should NOT receive corticosteroids 2
• NSIP responds well to corticosteroids 1, 2
• Misdiagnosis leads to inappropriate and potentially harmful treatment 2

Treatment Monitoring

Use a combination of parameters to assess response 1, 2:

• Serial pulmonary function tests (FVC, DLCO) to document stabilization or improvement 2
• Follow-up HRCT imaging to assess radiographic response 2
• Clinical symptom assessment (dyspnea, cough, exercise tolerance) 2

Additional Therapeutic Considerations

• Exclude ongoing antigen exposure before starting immunosuppression, particularly if hypersensitivity pneumonitis is in the differential diagnosis 6
• Screen for underlying connective tissue disease, as this would classify the case as secondary NSIP and may alter management (consider mycophenolate as first-line per rheumatology guidelines) 2, 7
• Pulmonary rehabilitation and oxygen therapy for hypoxemia should be implemented as supportive measures 2, 4

Management of Progressive or Refractory Disease

• Lung transplantation referral is indicated for patients with progressive deterioration despite optimal medical therapy 1, 2, 4
• Some fibrotic NSIP cases may evolve to a UIP pattern over time (16-115 months), developing honeycombing and becoming treatment-refractory 5
• The role of antifibrotic agents (pirfenidone, nintedanib) in progressive fibrotic NSIP remains uncertain and requires further study 4

Common Pitfall to Avoid

Do not assume lack of response to corticosteroids rules out NSIP—fibrotic NSIP may show limited improvement, and some cases progress despite treatment 6, 4, 5. However, complete absence of response should prompt reconsideration of the diagnosis and potential repeat biopsy to exclude evolution to UIP 5.