Tuberc Respir Dis.  2019 Oct;82(4):277-284. 10.4046/trd.2018.0092.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 3. Idiopathic Nonspecific Interstitial Pneumonia

• Lee J
• Kim YH
• Kang JY
• Jegal Y
• Park SY
• on behalf of Korean Interstitial Lung Diseases Study Group

• KMID: 2459051
• DOI: http://doi.org/10.4046/trd.2018.0092

Abstract

Idiopathic nonspecific interstitial pneumonia (NSIP) is one of the varieties of idiopathic interstitial pneumonias. Diagnosis of idiopathic NSIP can be done via multidisciplinary approach in which the clinical, radiologic, and pathologic findings were discussed together and exclude other causes. Clinical manifestations include subacute or chronic dyspnea and cough that last an average of 6 months, most of which occur in non-smoking, middle-aged women. The common findings in thoracic high-resolution computed tomography in NSIP are bilateral reticular opacities, traction bronchiectasis, reduced volume of the lobes, and ground-glass opacity in the lower lungs. These lesions can involve diffuse bilateral lungs or subpleural area. Unlike usual interstitial pneumonia, honeycombing is sparse or absent. Pathology shows diffuse interstitial inflammation and fibrosis which are temporally homogeneous, namely NSIP pattern. Idiopathic NSIP is usually treated with steroid only or combination with immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. Prognosis of idiopathic NSIP is better than idiopathic pulmonary fibrosis. Many studies have reported a 5-year survival rate of more than 70%.

Keyword

Lung Diseases, Interstitial; Idiopathic Interstitial Pneumonias; Guideline

MeSH Terms

Azathioprine
Bronchiectasis
Cough
Cyclophosphamide
Cyclosporine
Diagnosis*
Dyspnea
Female
Fibrosis
Humans
Idiopathic Interstitial Pneumonias
Idiopathic Pulmonary Fibrosis
Immunosuppressive Agents
Inflammation
Lung
Lung Diseases, Interstitial*
Pathology
Prognosis
Survival Rate
Traction
Azathioprine
Cyclophosphamide
Cyclosporine
Immunosuppressive Agents

Figure

• 

  Figure 1 High-resolution computed tomography (HRCT) of nonspecific interstitial pneumonia. (A) HRCT axial images (lung window setting) show ill-defined ground glass opacities in periphery of the both lower lobes. (B) HRCT axial images (lung window setting) at level of both lower lobes demonstrate reticulation, ill-defined ground glass opacities, and traction bronchiectasis along bronchovascular bundles or along subpleural lungs.

• 

  Figure 2 Pathologic findings of nonspecific interstitial pneumonia (NSIP) pattern. (A) Lung architecture is preserved with uniform appearance (×20). (B) Cellular NSIP shows uniform thickening of alveolar septa with cellular infiltration (×200). (C) Fibrotic NSIP shows uniform thickening of alveolar septa by collagen (×200).

Reference

1. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013; 188:733–748. PMID: 24032382.

2. Travis WD, Hunninghake G, King TE Jr, Lynch DA, Colby TV, Galvin JR, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med. 2008; 177:1338–1347. PMID: 18388353.

3. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis: histologic features and clinical significance. Am J Surg Pathol. 1994; 18:136–147. PMID: 8291652.

4. American Thoracic Society. European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002; 165:277–304. PMID: 11790668.

5. Flaherty KR, Martinez FJ. Nonspecific interstitial pneumonia. Semin Respir Crit Care Med. 2006; 27:652–658. PMID: 17195141.

6. Hyldgaard C, Hilberg O, Muller A, Bendstrup E. A cohort study of interstitial lung diseases in central Denmark. Respir Med. 2014; 108:793–799. PMID: 24636811.

7. Scientific Committee of the Korean Academy of Tuberculosis and Respiratory Diseases. 2008 National survey of idiopathic interstitial pneumonia in Korea. Tuberc Respir Dis. 2009; 66:141–151.

8. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018; 198:e44–e68. PMID: 30168753.

9. Romagnoli M, Nannini C, Piciucchi S, Girelli F, Gurioli C, Casoni G, et al. Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders? Eur Respir J. 2011; 38:384–391. PMID: 21273390.

10. Fujita J, Ohtsuki Y, Yoshinouchi T, Yamadori I, Bandoh S, Tokuda M, et al. Idiopathic non-specific interstitial pneumonia: as an “autoimmune interstitial pneumonia”. Respir Med. 2005; 99:234–240. PMID: 15715192.

11. Kinder BW, Collard HR, Koth L, Daikh DI, Wolters PJ, Elicker B, et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease? Am J Respir Crit Care Med. 2007; 176:691–697. PMID: 17556720.

12. Kim DS, Yoo B, Lee JS, Kim EK, Lim CM, Lee SD, et al. The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2002; 19:121–127. PMID: 12108451.

13. Collins B, Raghu G. Interstitial pneumonia with autoimmune features: the new consensus-based definition for this cohort of patients should be broadened. Eur Respir J. 2016; 47:1293–1295. PMID: 27037322.

14. Silva CI, Muller NL, Hansell DM, Lee KS, Nicholson AG, Wells AU. Nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis: changes in pattern and distribution of disease over time. Radiology. 2008; 247:251–259. PMID: 18270375.

15. Hartman TE, Swensen SJ, Hansell DM, Colby TV, Myers JL, Tazelaar HD, et al. Nonspecific interstitial pneumonia: variable appearance at high-resolution chest CT. Radiology. 2000; 217:701–705. PMID: 11110931.

16. Bna C, Zompatori M, Poletti V, Spaggiari E, Chetta A, Calabro E, et al. Differential diagnosis between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) assessed by high-resolution computed tomography (HRCT). Radiol Med. 2005; 109:472–487. PMID: 15973221.

17. Ryu YJ, Chung MP, Han J, Kim TS, Lee KS, Chun EM, et al. Bronchoalveolar lavage in fibrotic idiopathic interstitial pneumonias. Respir Med. 2007; 101:655–660. PMID: 16919929.

18. Veeraraghavan S, Latsi PI, Wells AU, Pantelidis P, Nicholson AG, Colby TV, et al. BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia. Eur Respir J. 2003; 22:239–244. PMID: 12952254.

19. Leslie KO. Historical perspective: a pathologic approach to the classification of idiopathic interstitial pneumonias. Chest. 2005; 128(5 Suppl 1):513S–519S. PMID: 16304241.

20. Nicholson AG, Colby TV, du Bois RM, Hansell DM, Wells AU. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med. 2000; 162:2213–2217. PMID: 11112140.

21. Kligerman SJ, Groshong S, Brown KK, Lynch DA. Nonspecific interstitial pneumonia: radiologic, clinical, and pathologic considerations. Radiographics. 2009; 29:73–87. PMID: 19168837.

22. Wells AU, Kokosi M, Karagiannis K. Treatment strategies for idiopathic interstitial pneumonias. Curr Opin Pulm Med. 2014; 20:442–448. PMID: 25032814.

23. Park IN, Jegal Y, Kim DS, Do KH, Yoo B, Shim TS, et al. Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia. Eur Respir J. 2009; 33:68–76. PMID: 18829672.

24. Kim YJ, Park JW, Kyung SY, Lee SP, Chung MP, Kim YH, et al. Clinical characteristics of idiopathic pulmonary fibrosis patients with diabetes mellitus: the national survey in Korea from 2003 to 2007. J Korean Med Sci. 2012; 27:756–760. PMID: 22787370.

25. Watanabe K, Higuchi K, Ninomiya K, Ohshima T, Aritomi T, Kawabata Y, et al. Steroid treatment based on the findings of transbronchial biopsy in idiopathic interstitial pneumonia. Eur Respir J. 2002; 20:1213–1219. PMID: 12449176.

26. Tomassetti S, Ryu JH, Piciucchi S, Chilosi M, Poletti V. Nonspecific interstitial pneumonia: what is the optimal approach to management? Semin Respir Crit Care Med. 2016; 37:378–394. PMID: 27231862.

27. Flaherty KR, Toews GB, Travis WD, Colby TV, Kazerooni EA, Gross BH, et al. Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J. 2002; 19:275–283. PMID: 11866008.

28. Nanki N, Fujita J, Yamaji Y, Maeda H, Kurose T, Kaji M, et al. Nonspecific interstitial pneumonia/fibrosis completely recovered by adding cyclophosphamide to corticosteroids. Intern Med. 2002; 41:867–870. PMID: 12413012.

29. Xu W, Xiao Y, Liu H, Qin M, Zheng W, Shi J. Nonspecific interstitial pneumonia: clinical associations and outcomes. BMC Pulm Med. 2014; 14:175. PMID: 25380997.

30. Kinder BW. Nonspecific interstitial pneumonia. Clin Chest Med. 2012; 33:111–121. PMID: 22365250.

31. Kondoh Y, Taniguchi H, Yokoi T, Nishiyama O, Ohishi T, Kato T, et al. Cyclophosphamide and low-dose prednisolone in idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia. Eur Respir J. 2005; 25:528–533. PMID: 15738299.

32. Corte TJ, Ellis R, Renzoni EA, Hansell DM, Nicholson AG, du Bois RM, et al. Use of intravenous cyclophosphamide in known or suspected, advanced non-specific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2009; 26:132–138. PMID: 20560293.

33. Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, et al. Rituximab in severe, treatment-refractory interstitial lung disease. Respirology. 2014; 19:353–359. PMID: 24286447.

34. Poletti V, Romagnoli M, Piciucchi S, Chilosi M. Current status of idiopathic nonspecific interstitial pneumonia. Semin Respir Crit Care Med. 2012; 33:440–449. PMID: 23001799.

35. Latsi PI, du Bois RM, Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A, et al. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med. 2003; 168:531–537. PMID: 12791580.

36. Jegal Y, Kim DS, Shim TS, Lim CM, Lee SD, Koh Y, et al. Physiology is a stronger predictor of survival than pathology in fibrotic interstitial pneumonia. Am J Respir Crit Care Med. 2005; 171:639–644. PMID: 15640368.

37. Belloli EA, Beckford R, Hadley R, Flaherty KR. Idiopathic non-specific interstitial pneumonia. Respirology. 2016; 21:259–268. PMID: 26564810.

38. Troy L, Corte TJ. Management of the idiopathic interstitial pneumonias. Aust Prescr. 2012; 35:202–206.

39. Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998; 157:199–203. PMID: 9445300.

40. Park IN, Kim DS, Shim TS, Lim CM, Lee SD, Koh Y, et al. Acute exacerbation of interstitial pneumonia other than idiopathic pulmonary fibrosis. Chest. 2007; 132:214–220. PMID: 17400667.

41. Sato T, Fujita J, Yamadori I, Ohtsuki Y, Yoshinouchi T, Bandoh S, et al. Non-specific interstitial pneumonia; as the first clinical presentation of various collagen vascular disorders. Rheumatol Int. 2006; 26:551–555. PMID: 16283322.

42. Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015; 46:976–987. PMID: 26160873.