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Internal Medicine

Nonspecific interstitial pneumonia (NSIP)

Chronic interstitial pneumonia with the homogeneous appearance of interstitial fibrosis and inflammation.

Chronic interstitial pneumonia with the homogeneous appearance of interstitial fibrosis and inflammation.

History:

In 1967, Liebow and carrington classified interstitial pneumonias into five subcategories by pathologic findings, usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), bronchiolits with interstitial pneumonia (BIP), lymphocytic interstitial pneumonia (LIP) and giant cell interstitial pneumonia (GIP). In 1986, Katzenstein identified acute interstitial pneumonia (AIP) as a new subcategory of fibroblasts is a main component in AIP, whereas the dense deposition of collagens is prominent in UPI. Katzenstein also indentified a sizable group of patients who cannot be subcategorized pathologically into one of above three entities of IPF and termed nonspecific interstitial pneumonia/fibrosis (NIP) in 1994.

Classification

Interstitial lung disease (ILD):

Interstitial lung disease (ILD), sometimes called diffused parenchymal diseases is a group of diseases characterized by a combination of chronic inflammation within the lung, consisting of an accumulation of chronic inflammatory cells (predominantly lymphocytes and macrophages) and increased levels of numerous pro-inflammatory cytokines, chemokines, and cell surface molecules; and varying degrees of lung fibrosis.

Idiopathic interstitial pneumonia (IIP):

Chronic, progressive fibrosing interstitial pneumonia characterized by idiopathic origin, occurrence primarily in older adults, exclusively pulmonary involvement and pattern of Usual Interstitial Pneumonia (UIP) proven by histopathology and/or radiology

American Thoracic Society/European Respiratory Society (ATS/ERS) 2002 consensus classification statement:

Histopathologic classification separating the IIPs into seven clinicopathologic entities (in order of relative frequency)
  • Idiopathic pulmonary fibrosis (IPF) (47-64%)
  • Nonspecific interstitial pneumonia (NSIP) (14-36%)
  • Respiratory bronchiolitis ILD(10-17%)
  • Cryptogenic organizing pneumonia (4-12%)
  • Acute interstitial pneumonia (AIP) (< 2%)
  • Lymphoid interstitial pneumonia (LIP) (< 2%)

Aetiology

Schematic classification of interstitial lung diseases according to aetiology. The finding of histological usual interstitial pneumonitis in a patient with an idiopathic interstitial pneumonia leads to the specific diagnosis of idiopathic pulmonary fibrosis. | NSIP = non-specific interstitial pneumonitis. | Mikolasch, T. A., Garthwaite, H. S., & Porter, J. C. (2017). Update in diagnosis and management of interstitial lung disease . Clinical medicine (London, England), 17(2), 146–153. https://doi.org/10.7861/clinmedicine.17-2-146

Secondary causes:

Nonspecific interstitial pneumonia (NSIP) can be idiopathic or associated with connective tissue disease, HIV infection, toxins, or numerous other causes. 
  • Connective tissue disease (CTD) (M/C): Systemic sclerosis, polymyositis/dermatomyositis, rheumatoid arthritis, and Sjogren syndrome.
  • Drug-induced: Amiodarone, methotrexate, nitrofurantoin, chemotherapeutic agents, and statin therapy
  • HIV infection 
  • Interstitial pneumonia with autoimmune features
  • Hypersensitivity pneumonitis
  • Others: Such as an IgG4-related systemic disease, familial interstitial pneumonia, and graft versus host disease

Pathophysiology

Epithelial injury, dysregulated repair, involvement of the immune system based in the presence of lymphocyte in the alveolar septae and bronchoalveolar lavage, and abnormal fibroblast/myofibroblast function leading to excess collagen deposition

Clinical features

  • Progressive dyspnea and cough (over weeks to months) (M/C symptom)
  • Fever
  • Weight loss 
  • Flu-like symptoms 

Connective tissue disease (CTD):

If connective tissue disease present, patient may have dry mouth, dry eyes, arthralgias, joint swelling, myalgias, dysphagia, skin changes, or other features

Clinical examination:

  • Fine crackles, especially at the bases 
  • Clubbing (10-35% cases) (non-specific finding)
  • Features of rheumatological disease:Skin changes, joint swelling

Diagnosis

Pulmonary function test (PFT):

Spirometric restrictive pattern on the PFTs with reduced TLC and DLCO

Chest X-ray:

  • Increased basilar markings and/or interstitial prominence bilaterally

High-resolution Computed Tomography (HRCT):

GOLD STANDARD
  • Increased reticular markings
  • Traction bronchiectasis
  • Volume loss
  • Ground glass opacification mainly in the lower zones
  • Honeycomb changes absent (common with UIP)

Surgical biopsy via VATS/thoracotomy:

Definitive diagnosis, though may not always be needed
  • Temporally homogeneous inflammatory and fibrosing interstitial process
  • Honeycombing of lung absent (UIP is characterised by temporally and spatially heterogenous lesions and honeycombing of lung)
A 47‐year‐old man with no past medical history presented with 4 months of cough, malaise and dyspnoea unresponsive to antibiotics. He had no history of tobacco abuse and no relevant exposure history. Physical exam was unremarkable and without rales. Spirometry demonstrated restriction with a total lung capacity of 70% predicted and diffusing capacity of the lung for carbon monoxide of 64% predicted. (a) A representative high‐resolution computed tomography image demonstrates lower lobe predominant peripheral ground‐glass opacities with areas of sub‐pleural sparing. (b) A representative image of the patient’s surgical lung biopsy, which was characteristic of cellular non‐specific interstitial pneumonia. The underlying alveolar architecture is preserved, and mononuclear cells have invaded the alveolar interstitium. The abnormalities demonstrate temporal uniformity. This sample also contains prominent fibromyxoid tissue. HE: 100×. | Belloli, E.A., Beckford, R., Hadley, R. and Flaherty, K.R. (2016), NSIP. Respirology, 21: 259-268. doi:10.1111/resp.12674

Differential diagnosis:

  • Other idiopathic interstitial pneumonia
  • Hypersensitivity pneumonitis
  • IgG-related systemic disease

Management

Treatment of NSIP depends on the cause and the severity of the disease:

Mild disease:

Mild symptoms and minimal impairment on their pulmonary functions tests.
  • Close follow up and observation

Moderate to severe disease:

Moderate to severe symptoms, with significant impairment on their pulmonary function tests as well as diffuse changes on HRCT chest scan
  • Systemic steroid therapy (prednisone)

Refractory disease:

Despite systemic steroid and immunosuppressive agents
  • Cyclophosphamide, rituximab, or calcineurin inhibitors
  • Lung transplantation (LAST OPTION)

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