What are the clinical, radiologic, histologic features and etiology of nonspecific interstitial pneumonia (NSIP)?

Nonspecific Interstitial Pneumonia (NSIP): Features and Etiology

NSIP is a distinct idiopathic interstitial pneumonia characterized by temporally uniform interstitial inflammation and fibrosis, bilateral ground-glass opacities with subpleural sparing on HRCT, and a significantly better prognosis than UIP/IPF, with 5-year mortality of 15-20% when treated with corticosteroids. 1

Clinical Features

Demographics and Presentation:

• Predominantly affects middle-aged women (67% female) who are never-smokers (69%) 2
• Mean age at presentation is 52 years 2
• More than 50% of patients have never smoked 3

Symptoms:

• Dyspnea occurs in 96% of patients 2
• Cough in 87% of cases 2
• Constitutional symptoms including fever and fatigue are common 3
• Fever may be more common in NSIP compared to UIP 4
• Clubbing is less common than in UIP 4

Physical Examination:

• Mild hypoxemia 3
• Inspiratory rales on auscultation 3

Pulmonary Function Tests:

• Restrictive ventilatory defect with decreased gas transfer 3, 4
• Low diffusing capacity for carbon monoxide (DLCO) 3
• 69% demonstrate restriction 2

Radiologic Features (HRCT)

Distribution Pattern:

• Bilateral symmetric involvement 1
• Lower lung zone predominance in 92% of cases 2
• Subpleural sparing is a key distinguishing feature from UIP 1
• Peripheral distribution in 46%, diffuse in 47% 2

Characteristic Findings:

• Bilateral ground-glass opacity is the most common abnormality 1
• Irregular reticular opacities in approximately 75% of cases 1
• Traction bronchiectasis and bronchiolectasis in 75-82% 1, 2
• Volume loss in 77% 2
• Honeycombing is sparse or absent at presentation (critical distinction from UIP) 1
• Consolidation, if present, reflects organizing pneumonia component and may suggest connective tissue disease 1

Histologic Features

Pathologic Characteristics:

• Temporally uniform pattern of interstitial inflammation and/or fibrosis (distinguishes from UIP's temporal heterogeneity) 1, 3
• Alveolar and interstitial mononuclear cell inflammation 3
• Preserved underlying alveolar architecture 3
• Uniform thickening of alveolar walls 2

Histologic Subtypes:

• Most cases show predominantly fibrotic pattern 1
• Rare cases of isolated cellular NSIP 1
• Spectrum ranges from cellular to fibrosing patterns 2

Key Negative Features:

• Organizing pneumonia and honeycomb fibrosis should be inconspicuous or absent 1
• Less profusion of fibroblastic foci compared to UIP 4
• Marked fibrosis with architectural distortion (characteristic of UIP) should be absent 1

Etiology

Idiopathic NSIP:

• Diagnosis of exclusion requiring elimination of secondary causes 1, 3
• True idiopathic NSIP is rare 3

Secondary NSIP Pattern (Must Be Excluded):

The NSIP pattern occurs in multiple settings and is NOT disease-specific 1:

• Connective tissue diseases (most common secondary cause) 1, 5

  • Substantial percentage of NSIP patients have findings suggesting but not meeting criteria for defined connective tissue disease 1
  • Comprehensive autoantibody panel required (ANA, RF, anti-CCP, anti-Scl-70, anti-Jo-1, myositis antibodies) 6

• Hypersensitivity pneumonitis 1

  • Detailed exposure history essential 6

• Drug toxicity 1

  • Thorough medication history required 6

• Familial pulmonary fibrosis 1

  • Family history should be obtained in all suspected cases 1

Critical Diagnostic Requirement:

• Multidisciplinary discussion including pulmonologist(s), radiologist(s), and pathologist(s) is essential to establish diagnosis of idiopathic NSIP and improve diagnostic accuracy 3
• Surgical lung biopsy (preferably video-assisted thoracoscopy) is necessary for firm diagnosis 3, 7

Prognosis

Favorable Compared to UIP/IPF:

• 5-year mortality of 15-20% with treatment 1, 7
• 5-year survival of 82.3% 2
• Markedly better prognosis than UIP, which cannot be explained by baseline differences in physiology or radiographic features 4

Clinical Course:

• Some patients improve 1
• Others remain stable or improve on treatment 1
• Some evolve to end-stage fibrosis and die of disease 1
• Honeycombing may increase in prevalence and extent during follow-up 1

Critical Pitfalls

Distinguishing NSIP from UIP/IPF is absolutely critical because corticosteroid treatment (first-line for NSIP) can be harmful to UIP/IPF patients who require antifibrotic therapy instead 8, 7, 6. The presence of subpleural sparing, absence of honeycombing, and temporally uniform histology favor NSIP over UIP 1.