Non-specific interstitial pneumonia

Non-specific interstitial pneumonia (NSIP) is the second most common morphological and pathological pattern of the interstitial lung disease. NSIP has two main subtypes, cellular type which is less common but carries much better prognosis due to very good response to the treatments and the more common fibrotic type which has more dismal outcome. The most common features are relatively symmetric and bilateral ground glass opacities with associated fine reticulations and pulmonary volume loss resulting in traction bronchiectasis. Immediate subpleural sparing, when is present is considered very specific for NSIP. However, the diagnosis of NSIP still remains one of the biggest challenges for not only radiologists but also pulmonists and pathologists; studies showed correct diagnosis by chest radiologist varies between 65-85%. 

Epidemiology

It typically tends to present in middle-aged adults, 40-50 years of age ¹. It may be common in Caucasian-European populations ⁹. Overall prevalence is higher in women due to high association with collagen vascular diseases, but the prevalence of idiopathic NSIP is similar in both genders.

Clinical presentation

Symptoms are non-specific and include insidious onset of dyspneadyspnoea and dry cough with restrictive pattern of decreased lung function and reduced gas exchange capacity. 

Pathology

Temporal and spatial homogeneity in a specimen is a key feature. Historically NSIP is divided into three groups; however due to similar outcome groups II and III (mixed cellular and fibrotic and mostly fibrotic, respectively) are now both classified in fibrotic type:

• fibrotic non specific interstitial pneumonia: more common, interstitial thickening is more due to uniform dense or loose fibrosis and mild chronic inflammation, despite fibrotic changes lung structures still preserved 
• cellular non specific interstitial pneumonia: less common; interstitial thickening is mainly secondary to infiltration of inflammatory cells and Typetype II pneumocyte hyperplasia. Lung architecture is preserved ⁸

Important negative histological findings are the absence of acute lung injury including hyaline membranes, granulomas, organisms or viral inclusions, dominant airways disease or organising pneumonia, eosinophils and coarse fibrosis.

Associations

Primarily idiopathic but the morphological pattern can be seen in association with a number of conditions:

• connective tissue disorders
  • systemic lupus erythematosus
  • systemic sclerosis
  • Sjögren's syndrome
  • polymyositis ⁵
  • dermatomyositis ⁵
• other autoimmune diseases
  • rheumatoid arthritis
  • primary biliary cirrhosis
  • Hashimoto thyroiditis
  • anti synthetase syndrome
• drug induced lung disease: especially chemotherapy agents ⁴
• hypersensitivity lung disease
• slowly healing diffuse alveolar damage (DAD)
• relapsing organising pneumonia
• occupational exposure
• immunodeficiency (mainly HIV infection) ¹³
• graft versus host disease ¹³
• immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlap features with Rosai-Dorfman disease ¹³
• multicentric Castleman disease ¹³
• myelodysplastic syndrome ¹³

If there is no underlying cause, it is termed idiopathic NSIP; which is now considered a specific entity.

Smoking is not associated and it is not a protective factor either.

Radiographic features

Plain radiograph

Chest radiograph can be normal in early stages. There may be ill-defined or ground glass opacities with lower lobe distribution or consolidation in a patchy, reticulonodular or mixed pattern. A bilateral pulmonary infiltrative pattern with volume loss of lower lobes may be seen in those with advanced disease.

CT

Imaging features can overlap between cellular and fibrotic types as well as UIP in as high as 30% of patients.  Also temporal changes in the pattern of HRCT findings in subsequent studies shown in as high as 28% of cases resulted in change of provisional diagnosis from NSIP to UIP.

Involvement tends to be sub-pleural and generally symmetrical with apico-basilar gradient. Solely or predominantly upper lobe involvement or purely unilateral disease makes the diagnosis of NSIP less likely. 

Common manifestations include:

•  ground-glass opacities 
  • tends to be a dominant feature: can be symmetrically or diffusely distributed in all zones or display a basal predominance
  • immediate subpleural sparing ¹¹- a relatively specific sign
  • mostly bilateral and symmetrical (~86% ¹⁴) but can be bilateral and asymmetrical in (10%) and rarely unilateral (3%)
  • mostly subpleural in distribution (~68%) but can be random (21%), diffuse (8%),and rarely  central in distribution (3%) ¹⁴
• reticular opacities and irregular linear opacities (sometimes - minor subpleural reticulation) mainly with fibrotic NSIP ^6-7
• thickening of bronchovascular bundles: with fibrotic NSIP ⁶
• traction bronchiectasis: associated with fibrotic NSIP
• lung volume loss: particularly lower lobes
• in advanced disease
  • traction bronchiectasis
  • consolidation
  • microcystic honeycombing: relatively less common feature

The presence of following features, although they can be seen in NSIP, should make us think about other differentials:

• centrilobular nodules
• mosaic attenuation
• thin wall cysts

Treatment and prognosis

In general NSIP carries a much more favourable prognosis than a UIP type pattern with 90% 5 years survival rate for cellular and 45-90% 5 years survival in fibrotic subtype. Cellular NSIP shows even better response to corticosteroids and carries a substantially better prognosis than the fibrotic type. Correct and early diagnosis has significant impact on patients' outcome, because NSIP usually responds well to the corticosteroid therapy or cessation of inciting causes like drugs or organic allergens ¹².

History and etymology

It is thought to have been initially described by Katzenstein and Fiorelli in 1994 ¹⁴.

Differential diagnosis

The key differential is a usual interstitial pneumonitis (UIP) pattern: where there can be some overlap in imaging features ³. The features which favour the diagnosis of NSIP over UIP are symmetrical bilateral ground glass opacities with fine reticulations and sparing of the immediate subpleural space. Presence of macroscopic honeycombing is almost diagnostic for UIP.

Also it is important to carefully scrutinise the images, looking for findings such as joint or bony changes, esophageal dilatation, pleural and pericardial effusion, etc. cause as it has been mentioned earlier NSIP pattern is also associated with many other conditions.