Nonspecific Interstitial Pneumonia (NSIP)
Nonspecific interstitial pneumonia (NSIP) is an interstitial lung disease characterized by homogeneous alveolar wall thickening with uniform fibrosis and/or inflammation, preserving the underlying lung architecture, and typically has a better prognosis than usual interstitial pneumonia (UIP). 1
Pathologic Features
NSIP has distinctive histopathological characteristics:
- Temporally uniform pattern - unlike the temporal heterogeneity seen in UIP
- Preserved alveolar architecture - maintaining the basic lung structure
- Homogeneous appearance of either inflammation or fibrosis 1
- Two main histologic subtypes:
- Cellular NSIP: Predominant interstitial inflammation with minimal fibrosis
- Fibrotic NSIP: Predominant interstitial fibrosis with mild inflammation 2
- Rare honeycomb changes - an important distinguishing feature from UIP 1, 3
- Diffuse alveolar wall thickening by uniform fibrosis 1
- Mild interstitial inflammation may be present 1
Radiological Features
High-resolution computed tomography (HRCT) findings in NSIP include:
- Bilateral symmetric ground-glass opacities - a predominant feature 1, 4
- Lower lobe predominance with reticular abnormalities 5
- Traction bronchiectasis - indicating fibrotic changes 1, 5
- Peribronchovascular distribution - more common in NSIP than in UIP 4
- Subpleural sparing - can help differentiate from UIP 4
- Limited or absent honeycombing - a key differentiating feature from UIP 2, 4
- Lower lobe volume loss may be present 5
Clinical Presentation
Patients with NSIP typically present with:
- Dyspnea and cough developing over months to years 2
- Constitutional symptoms including fever and fatigue 2
- Female predominance (>50% of cases) 2
- Non-smokers in more than half of cases 2
- Inspiratory crackles on physical examination 6
- Mild hypoxemia at rest 2, 6
- Restrictive ventilatory defect on pulmonary function tests 2, 6
- Reduced diffusing capacity for carbon monoxide (DLCO) 2, 6
Etiology and Associations
NSIP may be:
- Idiopathic - when no underlying cause is identified
- Secondary to various conditions:
Diagnosis
Accurate diagnosis requires:
- Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists 7, 2, 5
- Surgical lung biopsy for definitive diagnosis when HRCT is not diagnostic 7
- Transbronchial lung cryobiopsy as a potential alternative to surgical biopsy 7
- Thorough exposure history to exclude secondary causes 2
- Assessment for underlying connective tissue diseases 2
Prognosis and Treatment
- Better prognosis compared to idiopathic pulmonary fibrosis (IPF) 1, 3
- Estimated 15-20% mortality in 5 years 1
- Most patients respond to corticosteroids 1, 6
- Immunosuppressive therapy is generally instituted for treatment 2, 6
- Clinical improvement or stabilization occurs in approximately 80% of patients 6
Important Distinctions from Other Interstitial Lung Diseases
- vs. UIP/IPF: NSIP shows temporal homogeneity, preserved architecture, less honeycombing, and better response to treatment 3, 4
- vs. Hypersensitivity pneumonitis: NSIP lacks centrilobular nodules and air trapping 5
- vs. Organizing pneumonia: NSIP lacks the patchy consolidation pattern typical of organizing pneumonia 1
Common Pitfalls in Diagnosis
- Overlooking underlying connective tissue disease - thorough rheumatologic evaluation is essential 2
- Confusing NSIP with UIP - attention to specific HRCT and histologic features is crucial 4, 5
- Failure to recognize mixed patterns - NSIP may coexist with other patterns like organizing pneumonia 1
- Inadequate biopsy sampling - multiple lobes should be sampled when possible 7
NSIP represents an important diagnostic entity that must be distinguished from other interstitial lung diseases due to its different management approach and generally more favorable prognosis.