Epidemiology

Age

• Mean Age: 52 y/o (rangeL 26-73) (Am J Respir Crit Care Med, 2008) [MEDLINE]

Sex

• Approximately 67% of Cases are Female (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • In Contrast, IPF Has a Male Predominance

Lack of Relationship to Smoking (see Tobacco, [[Tobacco]]): unknown

• Never Smokers: 69% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
• Former Smokers: 25% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
• Persistent Smokers: 6% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]

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Etiology

Infection

• Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus)
  • Epidemiology: NSIP is a frequently associated histology in ILD in AIDS patients

Rheumatologic Disease

• Polydermatomyositis (see Polydermatomyositis)
  • Epidemiology
    • NSIP is the Most Common Histologic Pattern Seen in Polydermatomyositis-Associated ILD
• Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
  • Epidemiology
    • Both Usual Interstitial Pneumonia (UIP) and NSIP are Seen in RA-Associated ILD
• Scleroderma (see Scleroderma)
  • Epidemiology
    • NSIP is the Most Common Histologic Pattern Seen in Scleroderma-Associated ILD
      • Other Less Common Histologic Patterns Include Usual Interstitial Pneumonia (UIP) and Centrilobular Fibrosis Patterns
• Sjogren’s Syndrome (see Sjogren’s Syndrome)
  • Epidemiology
    • NSIP is the Most Common Histologic Pattern Seen in Sjogren’s-Associated ILD
      • Other Less Common Histologic Patterns Include Lymphocytic Interstitial Pneumonia (LIP), Organizing Pneumonia, Usual Interstitial Pneumonia (UIP), Primary Pulmonary Lymphoma, and Diffuse Interstitial Amyloidosis
• Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
  • Epidemiology
    • XXX

Drug

• Amiodarone (see Amiodarone) (Radiographics, 2000)[MEDLINE]
• Carmustine (see Carmustine) (Radiographics, 2000)[MEDLINE]
• Chlorambucil (see Chlorambucil)
• Cyclophosphamide (Cytoxan) (see Cyclophosphamide)
• Flecainide (see Flecainide)
• HMG-CoA Reductase Inhibitors (Statins) (see HMG-CoA Reductase Inhibitors)
  • Simvastatin (Zocor) (see Simvastatin)
• Methotrexate (see Methotrexate)
• Nitrofurantoin (Macrodantin) (see Nitrofurantoin)

Other

• Hypersensitivity Pneumonitis (HP) (see Hypersensitivity Pneumonitis): NSIP may additionally be present in this condition
• Idiopathic Pulmonary Hemosiderosis (see Idiopathic Pulmonary Hemosiderosis)
• Organizing Pneumonia: NSIP may additionally be present in this condition
• Resolving Acute Respiratory Distress Syndrome (ARDS) (se Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]]): NSIP may additionally be present in this condition
• Resolving Pneumonia: NSIP may additionally be present in this condition

Idiopathic Non-Specific Interstitial Pneumonia (NSIP)

• Epidemiology
  • Many Patients Diagnosed with Idiopathic NSIP Meet the Case Definition for Undifferentiated Connective Tissue Disease (UCTD) by Laboratory and/or Clinical Features (Am J Respir Crit Care Med, 2007) [MEDLINE]: suggests that NSIP may be an autoimmune disease
• Laboratory or Clinical Features Suggestive of Undifferentiated Connective Tissue Disease (UCTD) (Am J Respir Crit Care Med, 2007) [MEDLINE]
  • Arthralgias (see Arthralgias)
  • Dysphagia (see Dysphagia)
  • Gastroesophageal Reflux Disease (GERD) (see Gastroesophageal Reflux Disease)
  • Raynaud’s Phenomenon (see Raynaud’s Phenomenon)
  • Sicca Symptoms
  • Positive Serologic Studies (Rheumatoid Factor, ANA, Antibodies Against SSA/SSB/RNP/Jo-1/SCL-70)

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Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas)

• Hypoxemia (see Hypoxemia)

Chest X-Ray (CXR) (see Chest X-Ray)

• Findings
  • Normal CXR: early in the course
  • Bilateral Reticular/Hazy Infiltrates: later in the course
    • Lower Lung-Predominance: however, an obvious apical-basilar gradient of infiltrates (as would be seen in IPF) is usually absent

High-Resolution Chest CT (HRCT) (see High-Resolution Chest Computed Tomography)

• Findings (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Craniocaudal Distribution
    • Lower Lobe Predominance: 92% of cases
    • Diffuse: 8% of cases
  • Axial Distribution
    • Diffuse: 47% of cases
    • Peripheral: 46% of cases
    • Central: 7% of cases
  • Reticulation: 87% of cases
  • Traction Bronchiectasis: 82% of cases
  • Lobar Volume Loss: 77% of cases
  • Ground-Glass Infiltrates: 44% of cases
  • Subpleural Sparing: 21% of cases
  • Consolidation: 13% of cases
  • Emphysema/Cysts: 12% of cases
  • Peribronchial Thickening: 7% of cases
  • Honeycombing: 5% of cases
  • Substantial Micronodules: 3% of cases
  • Absent/Inconspicuous Eosinophils
  • Absence of Granulomas
  • Absence of Hyaline Membranes

Clinical Data

• Radiology Study Using Thin-Section CT to Determine Features Which Differentiate Idiopathic Pulmonary Fibrosis (IPF), Nonspecific Interstitial Pneumonia (NSIP), and Chronic Hypersensitivity Pneumonitis (HP) (Radiology, 2008) [MEDLINE]
  • Radiographic Features Which Which Indicate the Diagnosis of NSIP Over the Diagnoses of IPF and Chronic HP
    • Relative Subpleural Sparing
    • Absence of Honeycombing
    • Absence of Lobular Areas with Decreased Attenuation
  • Radiographic Features Which Indicate the Diagnosis of Chronic HP Over the Diagnoses of IPF and NSIP
    • Lobular Areas with Decreased Attenuation and Vascularity
    • Centrilobular Nodules (see Bronchiolar Disorders)
    • Absence of Lower-Zone Predominance of Abnormalities
  • Radiographic Features Which Which Indicate the Diagnosis of IPF Over the Diagnoses of NSIP and Chronic HP
    • Basilar Predominance of Honeycombing
    • Absence of Relative Subpleural Sparing
    • Absence of Centrilobular Nodules

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)

• Patterns
  • Restrictive Pattern: 79% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Normal Pattern: 14% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Obstructive Pattern: 3% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Mixed Pattern: 3% of cases (Am J Respir Crit Care Med, 2008) [MEDLINE]

6-Minute Walk Test (6MWT) (see 6-Minute Walk Test)

• Useful to Follow Clinical Course

Bronchoscopy (see Bronchoscopy)

Bronchoalveolar Lavage (BAL)

• Cellular Differential: does not aid in the differentiation of NSIP from IPF
  • Lymphocytosis: may be >50%
  • Increased Alveolar Macrophages (>85%)
  • Neutrophilia (>3%)

Transbronchial Biopsy (TBB)

• xxx

Video-Assisted Thoracoscopic Surgery (VATS) with Lung Biopsy (see Video-Assisted Thoracoscopic Surgery)

• Pathology (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Uniform Temporal Appearance
  • NSIP Pattern
    • Cellular NISP (16% of Cases): mild to moderate interstitial chronic inflammatory infiltrate (mostly lymphocyte/plasma cells; neutrophils, eosinophils, and histiocytes are inconspicuous) with little fibrosis
    • Fibrotic NSIP (84% of Cases): interstitial thickening by uniform fibrosis of the same age usually preserving the alveolar architecture, with varying amounts of cellular inflammation
  • Interstitial Fibrosis with Enlarged Airspaces (Distinct from Honeycombing)
    • Absent: 13% of cases
    • <10%: 34% of cases
    • 10-50%: 36% of cases
    • >50%: 17% of cases
  • Interstitial Cellular Inflammation
    • Mild: 46% of cases
    • Moderate: 54% of cases
  • Organizing Pneumonia
    • Absent: 48% of cases
    • 0-9%: 49% of cases
    • 10-19%: 3% of cases
  • Vascular Medial Thickening: 64% of cases
  • Lymphoid Follicles: 57% of cases
  • Pleural Fibrosis: 55% of cases
  • Fibroblastic Foci: 21% of cases
  • Bronchiolar Metaplasia: 19% of cases
  • Bronchiolocentric Distribution of Inflammation/Fibrosis (as a Minor Finding): 13% of cases
  • Emphysema: 6% of cases

Other Testing

• Anti-Nuclear Antibody (ANA) (see Anti-Nuclear Antibody, [[Anti-Nuclear Antibody]])
  • ANA is Positive in 43% of Cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
• Serum Rheumatoid Factor (RF) (see Serum Rheumatoid Factor, [[Serum Rheumatoid Factor]])
  • RF is Positive in 23% of Cases (Am J Respir Crit Care Med, 2008) [MEDLINE]
• Anti-Jo-1 (see xxxx, [[xxxx]])
  • Jo-1 is Positive in 0% of Cases (Am J Respir Crit Care Med, 2008) [MEDLINE]

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Clinical Manifestations

Pulmonary Manifestations

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)

• Clinical
  • Cough (see Cough)
  • Subacute or Insidious Onset of Dyspnea (see Dyspnea, [[Dyspnea]]): symptoms may be present for up to 8 mo prior to diagnosis

Rheumatologic Manifestations

Various Rheumatologic Clinical and Laboratory Features

• Epidemiology
  • Many Patients Diagnosed with Idiopathic NSIP Meet the Case Definition for Undifferentiated Connective Tissue Disease (UCTD) by Laboratory and/or Clinical Features (Am J Respir Crit Care Med, 2007) [MEDLINE]: suggests that NSIP may be an autoimmune disease
• Laboratory or Clinical Features Suggestive of Undifferentiated Connective Tissue Disease (UCTD) (Am J Respir Crit Care Med, 2007) [MEDLINE]
  • Arthralgias
  • Dysphagia
  • GERD
  • Raynaud’s Phenomenon
  • Sicca Symptoms
  • Positive Serologic Studies (Rheumatoid Factor, ANA, Antibodies Against SSA/SSB/RNP/Jo-1/SCL-70)

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Treatment

Corticosteroids (see Corticosteroids)

• Good Response: complete recovery is possible

Azathioprine (Imuran) (see Azathioprine)

• Addition of Azathioprine to Corticosteroids May Be More Effective in NSIP Over Corticosteroids Alone

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Prognosis

Survival Rate (Am J Respir Crit Care Med, 2008) [MEDLINE]

• 5-Year Survival: 82.#%
• 10-Year Survival: 73.2%

Other Survival Data

• 17-Year Mortality Rate: 11%
  • Survival Rate of NSIP is Significantly Better than that of IPF: even when controlling for age, gender, smoking history, and physiologic variables
• Cellular Pattern of NSIP Has the Best Prognosis
• Patients with NSIP Pattern in One Lobe and UIP Pattern in Another Lobe: these patients have a prognosis similar to that of IPF (with UIP)

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References

• Nonspecific interstitial pneumonia and the other idiopathic interstitial pneumonias: classification and diagnostic criteria. Am J Surg Pathol. 2000 Jan;24(1):1-3 [MEDLINE]
• Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000;20(5):1245 [MEDLINE]
• Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease? Am J Respir Crit Care Med. 2007;176(7):691 [MEDLINE]
• Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1338-47. doi: 10.1164/rccm.200611-1685OC. Epub 2008 Apr 3 [MEDLINE]
• Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology. 2008;246(1):288-297 [MEDLINE]
• HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era. Am J Respir Crit Care Med. 2011 Feb 1;183(3):388-95. doi: 10.1164/rccm.201006-0836OC. Epub 2010 Sep 17 [MEDLINE]
• Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection. Semin Respir Crit Care Med. 2016 Apr;37(2):289-302. doi: 10.1055/s-0036-1572560. Epub 2016 Mar 14 [MEDLINE]
• The impact of HAART on the respiratory complications of HIV infection: longitudinal trends in the MACS and WIHS cohorts. PLoS One. 2013;8(3):e58812. doi: 10.1371/journal.pone.0058812. Epub 2013 Mar 12 [MEDLINE]