Non-specific interstitial pneumonia

Last revised by Raymond Chieng on 16 Feb 2024

Non-specific interstitial pneumonia (NSIP) is the second most common morphological and pathological pattern of interstitial lung diseases. The recognition of this pattern has important implications for prognosis and treatment. Patients are typically younger compared to those with UIP pattern fibrosis and underlying connective tissue disease is common.

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

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

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. 

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. 

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.

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.

Imaging features can overlap between the cellular and fibrotic types of NSIP and with usual interstitial pneumonia (UIP) in as many as 30% of patients. Also, temporal changes in the pattern of HRCT findings in may occur in 28% of cases resulting in a change from NSIP to UIP pattern.

Symmetrical lower lobe distribution with peripheral predominance of ground-glass opacity and reticulation is typical. Sparing of the immediate subpleural lung is a helpful differentiating feature when present. Lower lobe volume loss and traction bronchiectasis spreading towards the hilum are typical.

Common manifestations include:

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

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

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

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.

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

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