Non-specific interstitial pneumonia
Non-specific interstitial pneumonia (NSIP) is the second most common morphological and pathological pattern of interstitial lung diseases. NSIP has two main subtypes:
- fibrotic type: most common, having a more dismal outcome
- cellular type: less common, but carries a much better prognosis due to a very good response to the treatments
On imaging, 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 present is considered very specific for NSIP.
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.
Symptoms are non-specific and 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 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 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 due to infiltration of inflammatory cells and type 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 organizing pneumonia, eosinophils and coarse fibrosis.
Primarily idiopathic but the morphological pattern can be seen in association with a number of conditions:
- connective tissue disorders
- other autoimmune diseases
- drug-induced lung disease: especially chemotherapy agents 4
- 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 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 distinct entity.
Smoking is not associated, and it is not a protective factor either.
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 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 the change of provisional diagnosis from NSIP to UIP.
Involvement tends to be subpleural and generally symmetrical with an 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
The presence of the following features, although they can be seen in NSIP, should make us think about other differentials:
Treatment and prognosis
In general, NSIP carries a much more favourable prognosis than a UIP-type pattern with 90% 5-year survival rate for cellular and ~60% (range 45-90%) 5-year survival in the fibrotic subtype. Cellular NSIP shows an even better response to corticosteroids and carries a substantially better prognosis than the fibrotic type. Correct and early diagnosis has a 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. Mycophenolate mofetil (MMF) has also shown to improve lung function 15.
History and etymology
It is thought to have been initially described by Katzenstein and Fiorelli in 1994 14.
The key differential is a usual interstitial pneumonitis (UIP) pattern, with which there can be some overlap in imaging features 3. The features which 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 macroscopic honeycombing is almost 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 it has been mentioned earlier NSIP pattern is also associated with many other conditions
- 1. Mueller-mang C, Grosse C, Schmid K et-al. What every radiologist should know about idiopathic interstitial pneumonias. Radiographics. 27 (3): 595-615. doi:10.1148/rg.273065130 - Pubmed citation
- 2. Simmons JT, Suffredini AF, Lack EE et-al. Nonspecific interstitial pneumonitis in patients with AIDS: radiologic features. AJR Am J Roentgenol. 1987;149 (2): 265-8. AJR Am J Roentgenol (abstract) - Pubmed citation
- 3. Sverzellati N, Wells AU, Tomassetti S et-al. Biopsy-proved idiopathic pulmonary fibrosis: spectrum of nondiagnostic thin-section CT diagnoses. Radiology. 2010;254 (3): 957-64. doi:10.1148/radiol.0990898 - Pubmed citation
- 4. Rossi SE, Erasmus JJ, Mcadams HP et-al. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 20 (5): 1245-59. Radiographics (full text) - Pubmed citation
- 5. Arakawa H, Yamada H, Kurihara Y et-al. Nonspecific interstitial pneumonia associated with polymyositis and dermatomyositis: serial high-resolution CT findings and functional correlation. Chest. 2003;123 (4): 1096-103. doi:10.1378/chest.123.4.1096 - Pubmed citation
- 6. Kim TS, Lee KS, Chung MP et-al. Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings. AJR Am J Roentgenol. 1998;171 (6): 1645-50. AJR Am J Roentgenol (abstract) - Pubmed citation
- 7. Park JS, Lee KS, Kim JS et-al. Nonspecific interstitial pneumonia with fibrosis: radiographic and CT findings in seven patients. Radiology. 1995;195 (3): 645-8. Radiology (abstract) - Pubmed citation
- 8. Lynch DA. Nonspecific interstitial pneumonia: evolving concepts. Radiology. 2001;221 (3): 583-4. doi:10.1148/radiol.2213011510 - Pubmed citation
- 9. Kim DS, Collard HR, King TE. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006;3 (4): 285-92. doi:10.1513/pats.200601-005TK - Free text at pubmed - Pubmed citation
- 10. Elliot TL, Lynch DA, Newell JD et-al. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr. 2005;29 (3): 339-45. Pubmed citation
- 11. Silva CI, Müller NL, Hansell DM et-al. Nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis: changes in pattern and distribution of disease over time. Radiology. 2008;247 (1): 251-9. doi:10.1148/radiol.2471070369 - Pubmed citation
- 12. Kligerman SJ, Groshong S, Brown KK et-al. Nonspecific interstitial pneumonia: radiologic, clinical, and pathologic considerations. Radiographics. 2009;29 (1): 73-87. doi:10.1148/rg.291085096 - Pubmed citation
- 13. Poletti V, Romagnoli M, Piciucchi S et-al. Current status of idiopathic nonspecific interstitial pneumonia. Semin Respir Crit Care Med. 2012;33 (05): 440-9. doi:10.1055/s-0032-1325155 - Pubmed citation
- 14. Hartman TE, Swensen SJ, Hansell DM et-al. Nonspecific interstitial pneumonia: variable appearance at high-resolution chest CT. Radiology. 2000;217 (3): 701-5. doi:10.1148/radiology.217.3.r00nv31701 - Pubmed citation
- 15. Fischer A, Brown KK, Du Bois RM, Frankel SK, Cosgrove GP, Fernandez-Perez ER, Huie TJ, Krishnamoorthy M, Meehan RT, Olson AL, Solomon JJ, Swigris JJ. Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. The Journal of rheumatology. 40 (5): 640-6. doi:10.3899/jrheum.121043 - Pubmed