Nonspecific Interstitial Pneumonia

ABSTRACT

Nonspecific interstitial pneumonia (NSIP) describes a histopathologic pattern that can be seen in patients with immunodeficiency, drug or environmental exposures, and connective tissue diseases. The clinical diagnosis of NSIP, however, should be reserved for idiopathic cases in which no causative factor is identified. Patients typically present with cough, dyspnea, restrictive pulmonary physiology with decreased gas transfer, and ground-glass infiltrates on high-resolution computed tomography (HRCT). Response to immunosuppressive therapy is often successful; however, patients with progressive disease are at increased risk of subsequent mortality and should be considered for alternative treatment strategies such as lung transplantation.

KEYWORDS

Nonspecific interstitial pneumonia - pulmonary fibrosis

REFERENCES

• 1 Suffredini A F, Ognibene F P, Lack E E et al.. Nonspecific interstitial pneumonitis: a common cause of pulmonary disease in the acquired immunodeficiency syndrome.  Ann Intern Med. 1987;  107 7-13
• 2 Simmons J T, Suffredini A F, Lack E E et al.. Nonspecific interstitial pneumonitis in patients with AIDS: radiologic features.  AJR Am J Roentgenol. 1987;  149 265-268
• 3 Sattler F, Nichols L, Hirano L et al.. Nonspecific interstitial pneumonitis mimicking Pneumocystis carinii pneumonia.  Am J Respir Crit Care Med. 1997;  156(3 Pt 1) 912-917
• 4 Travis W D, Fox C H, Devaney K O et al.. Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.  Hum Pathol. 1992;  23 529-541
• 5 Griffiths M H, Miller R F, Semple S J. Interstitial pneumonitis in patients infected with the human immunodeficiency virus.  Thorax. 1995;  50 1141-1146
• 6 Bojko T, Notterman D A, Greenwald B M, De Bruin W J, Magid M S, Godwin T. Acute hypoxemic respiratory failure in children following bone marrow transplantation: an outcome and pathologic study.  Crit Care Med. 1995;  23 755-759
• 7 Katzenstein A, Fiorelli R. Nonspecific interstitial pneumonia/fibrosis: histologic features and clinical significance.  Am J Surg Pathol. 1994;  18 136-147
• 8 Cottin V, Donsbeck A-V, Revel D, Loire R, Cordier J-F. Nonspecific interstitial pneumonia: individualization of a clinicopathologic entity in a series of 12 patients.  Am J Respir Crit Care Med. 1998;  158 1286-1293
• 9 Fujita J, Yamadori I, Suemitsu I et al.. Clinical features of non-specific interstitial pneumonia.  Respir Med. 1999;  93 113-118
• 10 Douglas W W, Tazelaar H D, Hartman T E et al.. Polymyositis-dermatomyositis-associated interstitial lung disease.  Am J Respir Crit Care Med. 2001;  164 1182-1185
• 11 Miki H, Mio T, Nagai S et al.. Fibroblast contractility: usual interstitial pneumonia and nonspecific interstitial pneumonia.  Am J Respir Crit Care Med. 2000;  162 2259-2264
• 12 Bouros D, Wells A, Nicholson A et al.. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome.  Am J Respir Crit Care Med. 2002;  165 1581-1586
• 13 Kim D S, Yoo B, Lee J S et al.. The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia.  Sarcoidosis Vasc Diffuse Lung Dis. 2002;  19 121-127
• 14 Yamadori I, Fujita J, Bandoh S et al.. Nonspecific interstitial pneumonia as pulmonary involvement of primary Sjö gren's syndrome.  Rheumatol Int. 2002;  22 89-92
• 15 Yoshinouchi T, Ohtsuki Y, Fujita J et al.. Nonspecific interstitial pneumonia pattern as pulmonary involvement of rheumatoid arthritis.  Rheumatol Int. 2005;  26 121-125
• 16 Vourlekis J S, Schwarz M I, Cool C D, Tuder R M, King T E, Brown K K. Nonspecific interstitial pneumonitis as the sole histologic expression of hypersensitivity pneumonitis.  Am J Med. 2002;  112 490-493
• 17 Pesenti S, Lauque D, Daste G, Boulay V, Pujazon M C, Carles P. Diffuse infiltrative lung disease associated with flecainide: report of two cases.  Respiration. 2002;  69 182-185
• 18 Lantuejoul S, Brambilla E, Brambilla C, Devouassoux G. Statin-induced fibrotic nonspecific interstitial pneumonia.  Eur Respir J. 2002;  19 577-580
• 19 American Thoracic Society, and . American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the Idiopathic Interstitial Pneumonias.  Am J Respir Crit Care Med. 2002;  165 277-304
• 20 Bjoraker J, Ryu J, Edwin M et al.. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 1998;  157 199-203
• 21 Flaherty K, Toews G, Travis W et al.. Clinical significance of histological classification of idiopathic interstitial pneumonia.  Eur Respir J. 2002;  19 275-283
• 22 Riha R, Duhig E, Clarke B, Steele R, Slaughter R, Zimmerman P. Survival of patients with biopsy-proven usual interstitial pneumonia and nonspecific interstitial pneumonia.  Eur Respir J. 2002;  19 1114-1118
• 23 Travis W, Matsui K, Moss J, Ferrans V. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns.  Am J Surg Pathol. 2000;  24 19-33
• 24 Nagai S, Kitaichi M, Itoh H, Nishimura K, Izumi T, Colby T V. Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP.  Eur Respir J. 1998;  12 1010-1019
• 25 Coultas D, Zumualt R, Black W, Sobonya R. The epidemiology of interstitial lung diseases.  Am J Respir Crit Care Med. 1994;  150 967-972
• 26 Iwai K, Mori T, Yamada N, Yamaguchi M, Hosoda Y. Idiopathic pulmonary fibrosis: epidemiologic approaches to occupational exposure.  Am J Respir Crit Care Med. 1994;  150 670-675
• 27 Scott J, Johnston I, Britton J. What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust.  BMJ. 1990;  301 1015-1017
• 28 Flaherty K R, King Jr T E, Raghu G et al.. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis?.  Am J Respir Crit Care Med. 2004;  170 904-910
• 29 Flaherty K, Thwaite E, Kazerooni E et al.. Radiological versus histological diagnosis in UIP and NSIP: survival implications.  Thorax. 2003;  58 143-148
• 30 Hartman T, Swensen S, Hansell D et al.. Nonspecific interstitial pneumonia: variable appearance at high-resolution chest CT.  Radiology. 2000;  217 701-705
• 31 MacDonald S, Rubens M, Hansell D et al.. Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparative appearances at and diagnostic accuracy of thin-section CT.  Radiology. 2001;  221 600-605
• 32 Aziz Z A, Wells A U, Hansell D M et al.. HRCT diagnosis of diffuse parenchymal lung disease: inter-observer variation.  Thorax. 2004;  59 506-511
• 33 Park C, Jeon J, Park S et al.. Nonspecific interstitial pneumonia/fibrosis: clinical manifestations, histologic and radiologic features.  Korean J Intern Med. 1996;  11 122-132
• 34 Daniil Z, Gilchrist F, Nicholson A et al.. A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis.  Am J Respir Crit Care Med. 1999;  160 899-905
• 35 Nicholson A, Colby T, DuBois R, Hansell D, Wells A. 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
• 36 Takehara H, Tada S, Kataoka M et al.. Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia.  Acta Med Okayama. 2001;  55 205-211
• 37 Ishii H, Mukae H, Kadota J et al.. Increased levels of interleukin-18 in bronchoalveolar lavage fluid of patients with idiopathic nonspecific interstitial pneumonia.  Respiration. 2005;  72 39-45
• 38 Jegal Y, Kim D S, Shim T S 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
• 39 Kakugawa T, Mukae H, Hayashi T et al.. Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia.  Respir Res. 2005;  6 57-68
• 40 Veeraraghavan S, Latsi P, Wells A et al.. BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.  Eur Respir J. 2003;  22 239-244
• 41 Nagai S, Handa T, Tabuena R, Kitaichi M, Izumi T. Nonspecific interstitial pneumonia: a real clinical entity?.  Clin Chest Med. 2004;  25) 705-715 , vi
• 42 Park J, Lee K, Kim J et al.. Nonspecific interstitial pneumonia with fibrosis: radiographic and CT findings in seven patients.  Radiology. 1995;  195 645-648
• 43 Kim T, Lee K, Chung M et al.. Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings.  AJR Am J Roentgenol. 1998;  171 1645-1650
• 44 Kim E, Lee K, Chung M, Kwon O, Kim T, Hwang J. Nonspecific interstitial pneumonia with fibrosis: serial high-resolution CT findings with functional correlation.  AJR Am J Roentgenol. 1999;  173 1734-1739
• 45 Johkoh T, Muller N, Cartier Y et al.. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients.  Radiology. 1999;  211 555-560
• 46 Akira M, Inoue G, Yamamoto S, Sakatani M. Non-specific interstitial pneumonia: findings on sequential CT scans of nine patients.  Thorax. 2000;  55 854-859
• 47 Nishiyama O, Kondoh Y, Taniguchi H et al.. Serial high resolution CT findings in nonspecific interstitial pneumonia/fibrosis.  J Comput Assist Tomogr. 2000;  24 41-46
• 48 Johkoh T, Muller N, Colby T et al.. Nonspecific interstitial pneumonia: correlation between thin-section CT findings and pathologic subgroups in 55 patients.  Radiology. 2002;  225 199-204
• 49 Kim E A, Lee K S, Johkoh T et al.. Interstitial lung diseases associated with collagen vascular diseases: radiologic and histopathologic findings.  Radiographics. 2002;  22 S151-S165
• 50 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 1096-1103
• 51 Lynch D A, Travis W D, Muller N L et al.. Idiopathic interstitial pneumonias: CT features.  Radiology. 2005;  236 10-21
• 52 Hunninghake G, Lynch D, Galvin J et al.. Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia.  Chest. 2003;  124 1215-1223
• 53 Nicholson A G, Addis B J, Bharucha H et al.. Inter-observer variation between pathologists in diffuse parenchymal lung disease.  Thorax. 2004;  59 500-505
• 54 Lettieri C J, Veerappan G R, Parker J M et al.. Discordance between general and pulmonary pathologists in the diagnosis of interstitial lung disease.  Respir Med. 2005;  99 1425-1430
• 55 Flaherty K, Travis W, Colby T et al.. Histologic variability in usual and nonspecific Interstitial pneumonias.  Am J Respir Crit Care Med. 2001;  164 1722-1727
• 56 Monaghan H, Wells A U, Colby T V, du Bois R M, Hansell D M, Nicholson A G. Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias.  Chest. 2004;  125 522-526
• 57 Katzenstein A L, Zisman D A, Litzky L A, Nguyen B T, Kotloff R M. Usual interstitial pneumonia: histologic study of biopsy and explant specimens.  Am J Surg Pathol. 2002;  26 1567-1577
• 58 Terasaki Y, Fukuda Y, Ishizaki M, Yamanaka N. Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in mice.  Am J Respir Cell Mol Biol. 2000;  23 168-174
• 59 Suga M, Iyonaga K, Okamoto T et al.. Characteristic elevation of matrix metalloprotinase activity in idiopathic interstitial pneumonias.  Am J Respir Crit Care Med. 2000;  162 1949-1956
• 60 Thomas A Q, Lane K, Phillips III J et al.. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred.  Am J Respir Crit Care Med. 2002;  165 1322-1328
• 61 Brasch F, Griese M, Tredano M et al.. Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene.  Eur Respir J. 2004;  24 30-39
• 62 Nogee L M, Dunbar III A E, Wert S E, Askin F, Hamvas A, Whitsett J A. A mutation in the surfactant protein C gene associated with familial interstitial lung disease.  N Engl J Med. 2001;  344 573-579
• 63 Stevens P A, Pettenazzo A, Brasch F et al.. Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene.  Pediatr Res. 2005;  57 89-98
• 64 Chibbar R, Shih F, Baga M et al.. Nonspecific interstitial pneumonia and usual interstitial pneumonia with mutation in surfactant protein C in familial pulmonary fibrosis.  Mod Pathol. 2004;  17 973-980
• 65 Steele M P, Speer M C, Loyd J E et al.. Clinical and pathologic features of familial interstitial pneumonia.  Am J Respir Crit Care Med. 2005;  172 1146-1152
• 66 Eitzman D T, McCoy R D, Zheng X et al.. Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene.  J Clin Invest. 1996;  97 232-237
• 67 Kubo H, Nakayama K, Yanai M et al.. Anticoagulant therapy for idiopathic pulmonary fibrosis.  Chest. 2005;  128 1475-1482
• 68 Kim K K, Flaherty K R, Long Q et al.. A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia.  Mol Med. 2003;  9 52-56
• 69 Jakubzick C, Choi E S, Kunkel S L et al.. Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia.  J Clin Pathol. 2004;  57 477-486
• 70 Keogh K A, Limper A H. Characterization of lymphocyte populations in nonspecific interstitial pneumonia.  Respir Res. 2005;  6 137-143
• 71 Choi E S, Jakubzick C, Carpenter K J et al.. Enhanced monocyte chemoattractant protein-3/CC chemokine ligand-7 in usual interstitial pneumonia.  Am J Respir Crit Care Med. 2004;  170 508-515
• 72 Park C, Chung S, Ki S et al.. Increased levels of interleukin-6 are associated with lymphocytosis in bronchoalveolar lavage fluids of idiopathic nonspecific interstitial pneumonia.  Am J Respir Crit Care Med. 2000;  162 1162-1168
• 73 Selman M, King Jr T, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.  Ann Intern Med. 2001;  134 136-151
• 74 Wen F Q, Skold C M, Liu X D et al.. Glucocorticoids and TGF-beta1 synergize in augmenting fibroblast mediated contraction of collagen gels.  Inflammation. 2001;  25 109-117
• 75 Keerthisingam C B, Jenkins R G, Harrison N K et al.. Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor-beta in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice.  Am J Pathol. 2001;  158 1411-1422
• 76 Flaherty K, Mumford J, Murray S et al.. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia.  Am J Respir Crit Care Med. 2003;  168 543-548
• 77 Latsi P I, du Bois R M, Nicholson A G et al.. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends.  Am J Respir Crit Care Med. 2003;  168 531-537
• 78 Shimizu S, Yoshinouchi T, Ohtsuki Y et al.. The appearance of S-100 protein-positive dendritic cells and the distribution of lymphocyte subsets in idiopathic nonspecific interstitial pneumonia.  Respir Med. 2002;  96 770-776
• 79 Kondoh Y, Taniguchi H, Yokoi T et al.. Cyclophosphamide and low-dose prednisone in idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia.  Eur Respir J. 2005;  25 528-533