Non-specific interstitial pneumonia

Non-specific interstitial pneumonia (NSIP) is the second most common morphological and pathological pattern of interstitial lung diseases after UIP. NSIP is commonly associated with connective tissue disease (CTD) and the underlying diagnosis and management are best decided by a multidisciplinary team.

Epidemiology

Non-specific interstitial pneumonia typically tends to present in middle-aged adults 40-50 years of age ¹. It may be more common in the White-European population ⁹. The overall prevalence is higher in women due to an association with collagen vascular disease, but the prevalence of idiopathic NSIP is similar in both genders.

Associations

NSIP is associated with a number of conditions:

• connective tissue disorders

  • systemic lupus erythematosus (SLE)

  • scleroderma

  • Sjögren syndrome

  • polymyositis ⁵

  • dermatomyositis ⁵

• other autoimmune diseases

  • rheumatoid arthritis

  • primary biliary cirrhosis (see interstitial lung disease associated with primary biliary cholangitis)

  • Hashimoto thyroiditis

  • antisynthetase syndrome

• drug-induced lung disease: especially chemotherapy agents ⁴

  • thalidomide ¹⁶

• hypersensitivity lung disease

• slowly healing diffuse alveolar damage (DAD)

• relapsing organizing pneumonia

• occupational exposure

• immunodeficiency (mainly HIV infection) ¹³

• graft versus host disease (GVHD) ¹³

• immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlapping 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 distinct entity.

Smoking is neither protective nor a risk factor for NSIP. 

Clinical presentation

The symptoms of non-specific interstitial pneumonia include insidious onset of dyspnea and dry cough with a restrictive pattern of decreased lung function and reduced gas exchange capacity. 

Pathology

Temporal and spatial homogeneity in a specimen is an essential feature. Historically, non-specific interstitial pneumonia was divided into three groups; however, due to similar outcomes, groups II and III (mixed cellular and fibrotic and mostly fibrotic, respectively) are now both classified as fibrotic type:

• fibrotic non-specific interstitial pneumonia

  • more common

  • interstitial thickening is due to uniform dense or loose fibrosis and mild chronic inflammation

  • despite fibrotic changes, lung structures are still preserved

• cellular non-specific interstitial pneumonia

  • ​less common

  • interstitial thickening is mainly due to infiltration of inflammatory cells and type II pneumocyte hyperplasia

  • lung architecture is preserved ⁸

  • better response to treatment and better prognosis

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

Radiographic features

Plain radiograph

A chest radiograph can be normal in the 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

Fibrotic NSIP maximally and symmetrically affects the peribronchovascular interstitium of both lower lobes causing irregular bronchiectasis extending towards the hilum accompanied by lower lobe contraction. Relative subpleural sparing is a useful distinguishing feature when present. Ground-glass opacity may indicate cellular NSIP or fine fibrosis beyond the resolution of CT. Ground-glass opacity may also coexist with reticulation ¹⁸.

The NSIP pattern often evolves into a UIP pattern over time. Evaluation of prior CT scans is essential to correct categorization ¹⁸.

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 is a relatively specific sign

  • mostly bilateral and symmetrical (~86% ¹⁴) but can be bilateral and asymmetrical (10%) or, rarely, unilateral (3%)

  • mostly peripheral in distribution (~68%) but can be random (21%), diffuse (8%) or, rarely, central in distribution (3%) ¹⁴

• reticular opacities and irregular linear opacities (sometimes, minor subpleural reticulation), mainly in fibrotic NSIP ^6,7

• thickening of bronchovascular bundles: in fibrotic NSIP ⁶

• traction bronchiectasis: associated with fibrotic NSIP

• lung volume loss: particularly lower lobes with traction bronchiectasis extending from the periphery to the hilum

• in advanced disease:

  • traction bronchiectasis

  • consolidation

  • microcystic honeycombing: a relatively less common feature

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

• centrilobular nodules

• mosaic attenuation

• thin-walled cysts

Treatment and prognosis

In general, non-specific interstitial pneumonia (NSIP) carries a much more favorable prognosis than a usual interstitial pneumonia (UIP) pattern, with a 90% 5-year survival rate for the cellular subtype and a ~60% (range 45-90%) 5-year survival for the fibrotic subtype. Cellular NSIP shows a better response to corticosteroids and carries a substantially better prognosis than the fibrotic type. Correct and early diagnosis has a significant impact on patient outcomes because NSIP usually responds well to corticosteroid therapy or cessation of inciting causes, e.g. drugs or organic allergens ¹². Mycophenolate mofetil has also been shown to improve lung function ¹⁵. 

History and etymology

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

Differential diagnosis

The key differential is the usual interstitial pneumonia (UIP) pattern, with which there can be some overlap in imaging features ³. The features that favor the diagnosis of NSIP over UIP are symmetrical bilateral ground-glass opacities with fine reticulations and sparing of the immediate subpleural space. The presence of macrocystic honeycombing is practically diagnostic for UIP.

Practical points

Examination of prior scans is essential to correct categorization of the CT pattern.

CTD-ILD may display features which suggest the diagnosis including esophageal dilatation, serositis, joint erosions or muscle atrophy.