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 immediately upon identification of clinical or physiological impairment. 1, 2

Initial Treatment Approach

• Start prednisone at immunosuppressive doses immediately when NSIP is diagnosed and clinical or physiological impairment is identified 1, 2
• The majority of NSIP patients show improvement with corticosteroid therapy, with a favorable prognosis of 15-20% mortality at 5 years 1, 2
• Treatment response is typically better in the "inflammatory type" of NSIP characterized by prominent lymphocytic inflammation on biopsy and BAL, with mixed NSIP/organizing pneumonia pattern on HRCT 3

Critical Diagnostic Prerequisite

Surgical lung biopsy (preferably video-assisted thoracoscopy) is essential before initiating treatment to definitively distinguish NSIP from usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF), as corticosteroids are contraindicated and potentially harmful in UIP/IPF 1, 2

• NSIP shows homogeneous inflammation or fibrosis with temporally uniform changes and bilateral symmetric ground-glass opacities on HRCT 1, 2
• UIP demonstrates marked fibrosis with architectural distortion, patchy involvement, fibroblastic foci, and honeycombing in subpleural distribution 1, 2
• Incorrect treatment can cause harm—corticosteroids should NOT be given to UIP/IPF patients 2

Treatment Escalation for Inadequate Response

Add cyclophosphamide when initial corticosteroid response is insufficient 4, 5

• Cyclophosphamide can be administered intravenously followed by oral maintenance when corticosteroids alone fail to produce adequate improvement 4
• In scleroderma-associated NSIP, cyclophosphamide (with or without prednisone) stabilized lung function parameters for 3 years after 1 year of therapy 5
• This combination may be particularly useful for patients showing inadequate response to corticosteroids alone 4

Factors Predicting Treatment Response

Early treatment initiation and seronegative ANA status predict better outcomes 6

• Shorter duration of respiratory symptoms at diagnosis is significantly associated with good response to treatment (p = 0.018) 6
• Seronegative anti-nuclear antibody (ANA) patients show significantly better lung function improvement compared to seropositive patients (p = 0.013) 6
• After 1 year of corticosteroid treatment, patients showed significant improvements: FVC 10.0%, FEV1 9.8%, DLco 8.4% (p < 0.001) 6

Phenotype-Specific Considerations

The "inflammatory type" versus "highly fibrotic" distinction guides treatment expectations 3:

• Inflammatory type: Prominent lymphocytic inflammation on biopsy and BAL, mixed NSIP/organizing pneumonia pattern on HRCT—tends to have better response to corticosteroids and immunosuppressive treatment 3
• Highly fibrotic type: Prominent reticular changes and traction bronchiectasis on HRCT, high fibrotic background on biopsy, no lymphocytosis on BAL—less potential to respond to immunosuppressive treatment 3

Monitoring Treatment Response

Use a combination of clinical, radiographic, and physiological parameters to assess response 1, 2

• Serial pulmonary function tests (FVC, FEV1, DLco) should be performed to evaluate treatment response 2, 6
• HRCT imaging should be repeated to assess radiographic improvement 2
• Clinical symptom assessment including dyspnea and functional status 2

Management of Progressive or Refractory Disease

Consider lung transplantation for patients with progressive deterioration despite treatment 1, 2

• Pulmonary rehabilitation and oxygen therapy for hypoxemia are important supportive measures for all patients 2
• The role of antifibrotic drugs in fibrotic, progressive, immunosuppressive treatment-refractory NSIP remains uncertain and requires further study 3

Common Pitfalls to Avoid

• Never treat presumed NSIP with corticosteroids without histopathologic confirmation, as UIP/IPF patients can be harmed by corticosteroid therapy 2
• Do not delay treatment once NSIP is confirmed—early initiation is associated with better outcomes 6
• Do not rely solely on clinical improvement with corticosteroids to confirm the diagnosis, as other ILDs like hypersensitivity pneumonitis may also improve with immunosuppressive treatment 7
• Failure to respond to corticosteroids does not exclude NSIP diagnosis, particularly in highly fibrotic subtypes 7, 3