Treatment and prognosis of nonspecific interstitial pneumonia
- Kevin R Flaherty, MD, MS
Kevin R Flaherty, MD, MS
- Section Editor — Interstitial Lung Disease
- Associate Professor of Medicine
- University of Michigan Health System
Nonspecific interstitial pneumonia (NSIP) can be idiopathic or can be seen in association with connective tissue disease, HIV infection, a variety of drugs, and hypersensitivity pneumonitis. When idiopathic, NSIP is considered one of the idiopathic interstitial pneumonias (IIPs), which also include usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), acute interstitial pneumonia (AIP), and cryptogenic organizing pneumonia (COP) (table 1) . Idiopathic NSIP can present alone or in combination with one of the other IIPs.
The treatment and prognosis of NSIP will be reviewed here. The clinical manifestations, evaluation, and diagnosis of NSIP and the diagnosis and management of the other IIPs are discussed separately. (See "Causes, clinical manifestations, evaluation, and diagnosis of nonspecific interstitial pneumonia" and "Idiopathic interstitial pneumonias: Clinical manifestations and pathology" and "Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis" and "Treatment of idiopathic pulmonary fibrosis" and "Respiratory bronchiolitis-associated interstitial lung disease" and "Cryptogenic organizing pneumonia" and "Acute interstitial pneumonia (Hamman-Rich syndrome)".)
OVERVIEW OF TREATMENT
The treatment of NSIP depends on the cause, disease severity, and rate of progression. While the discussion in the sections that follow will emphasize the treatment for idiopathic NSIP, much of the support for treatment selections is based on experience in connective tissue associated NSIP.
●Drug or inhalational exposure – For patients with NSIP associated with a drug or inhalational exposure, the first step is to remove the inciting exposure. This alone may be adequate treatment. (See "Causes, clinical manifestations, evaluation, and diagnosis of nonspecific interstitial pneumonia", section on 'Definition and causes'.)
●Connective tissue disease – For patients with NSIP complicating a known connective tissue disease (eg, polymyositis/dermatomyositis, rheumatoid arthritis, systemic sclerosis), specific therapies for those diseases may guide treatment of the NSIP. (See "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis" and "Overview of lung disease associated with rheumatoid arthritis" and "Interstitial lung disease associated with Sjögren's syndrome: Clinical manifestations, evaluation, and diagnosis" and "Overview of pulmonary complications of systemic sclerosis (scleroderma)" and "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis".)
- Travis WD, Costabel U, Hansell DM, 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.
- Sattler F, Nichols L, Hirano L, et al. Nonspecific interstitial pneumonitis mimicking Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 1997; 156:912.
- Duggal L, Puri V, Vasdev N. Non-specific interstitial pneumonia in an HIV positive patient. J Assoc Physicians India 2005; 53:564.
- George MP, Singh V, Gladwin MT. Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection. Semin Respir Crit Care Med 2016; 37:289.
- Nagai S, Kitaichi M, Itoh H, et al. Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP. Eur Respir J 1998; 12:1010.
- Belloli EA, Beckford R, Hadley R, Flaherty KR. Idiopathic non-specific interstitial pneumonia. Respirology 2016; 21:259.
- Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 Suppl 5:v1.
- Daniil ZD, Gilchrist FC, Nicholson AG, 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.
- Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance. Am J Surg Pathol 1994; 18:136.
- Cottin V, Donsbeck AV, Revel D, et al. Nonspecific interstitial pneumonia. Individualization of a clinicopathologic entity in a series of 12 patients. Am J Respir Crit Care Med 1998; 158:1286.
- Fujita J, Yamadori I, Suemitsu I, et al. Clinical features of non-specific interstitial pneumonia. Respir Med 1999; 93:113.
- 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.
- Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 2000; 24:19.
- Flaherty KR, Toews GB, Travis WD, et al. Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J 2002; 19:275.
- Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 157:199.
- Nicholson AG, Colby TV, du Bois RM, et al. 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.
- Kondoh Y, Taniguchi H, Yokoi T, et al. Cyclophosphamide and low-dose prednisolone in idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia. Eur Respir J 2005; 25:528.
- Nanki N, Fujita J, Yamaji Y, et al. Nonspecific interstitial pneumonia/fibrosis completely recovered by adding cyclophosphamide to corticosteroids. Intern Med 2002; 41:867.
- Park IN, Jegal Y, Kim DS, et al. Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia. Eur Respir J 2009; 33:68.
- Lee JY, Jin SM, Lee BJ, et al. Treatment response and long term follow-up results of nonspecific interstitial pneumonia. J Korean Med Sci 2012; 27:661.
- Flaherty KR, Toews GB, Lynch JP 3rd, et al. Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival. Am J Med 2001; 110:278.
- Douglas WW, Tazelaar HD, Hartman TE, et al. Polymyositis-dermatomyositis-associated interstitial lung disease. Am J Respir Crit Care Med 2001; 164:1182.
- Homma S, Sakamoto S, Kawabata M, et al. Cyclosporin treatment in steroid-resistant and acutely exacerbated interstitial pneumonia. Intern Med 2005; 44:1144.
- Bakker JA, Drent M, Bierau J. Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease. Curr Opin Pulm Med 2007; 13:458.
- Ginzler E, Diamond H, Kaplan D, et al. Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum 1978; 21:37.
- Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183:96.
- Chartrand S, Swigris JJ, Stanchev L, et al. Clinical features and natural history of interstitial pneumonia with autoimmune features: A single center experience. Respir Med 2016; 119:150.
- Zhang Y, Zheng Y. Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases. Rheumatol Int 2014; 34:1765.
- Arend SM, Kroon FP, van't Wout JW. Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993. An analysis of 78 cases. Arch Intern Med 1995; 155:2436.
- Corte TJ, Ellis R, Renzoni EA, et al. Use of intravenous cyclophosphamide in known or suspected, advanced non-specific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis 2009; 26:132.
- Chartrand S, Swigris JJ, Peykova L, Fischer A. Rituximab for the treatment of connective tissue disease-associated interstitial lung disease. Sarcoidosis Vasc Diffuse Lung Dis 2016; 32:296.
- Sharp C, McCabe M, Dodds N, et al. Rituximab in autoimmune connective tissue disease-associated interstitial lung disease. Rheumatology (Oxford) 2016; 55:1318.
- Fitzgerald DB, Moloney F, Twomey M, et al. Efficacy and Safety of Rituximab in Connective Tissue Disease related Interstitial Lung Disease. Sarcoidosis Vasc Diffuse Lung Dis 2015; 32:215.
- Kurita T, Yasuda S, Amengual O, Atsumi T. The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis/dermatomyositis. Lupus 2015; 24:3.
- Kurita T, Yasuda S, Oba K, et al. The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis. Rheumatology (Oxford) 2015; 54:39.
- Lama VN, Flaherty KR, Toews GB, et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003; 168:1084.
- du Bois RM, Weycker D, Albera C, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med 2011; 184:1382.
- Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015; 34:1.
- Yusen RD, Edwards LB, Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart-Lung Transplant Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant 2016; 35:1170.
- Travis WD, Hunninghake G, King TE Jr, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med 2008; 177:1338.
- 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.
- Nunes H, Schubel K, Piver D, et al. Nonspecific interstitial pneumonia: survival is influenced by the underlying cause. Eur Respir J 2015; 45:746.
- Latsi PI, du Bois RM, Nicholson AG, et al. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med 2003; 168:531.
- Jegal Y, Kim DS, Shim TS, et al. Physiology is a stronger predictor of survival than pathology in fibrotic interstitial pneumonia. Am J Respir Crit Care Med 2005; 171:639.
- Flaherty KR, Mumford JA, Murray S, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003; 168:543.
- OVERVIEW OF TREATMENT
- Supportive care
- OBSERVATION FOR MILD STABLE DISEASE
- INITIAL THERAPY FOR MODERATE TO SEVERE DISEASE
- Pulse methylprednisolone
- Additional immunosuppressive drugs
- - Azathioprine
- - Mycophenolate mofetil
- REFRACTORY DISEASE
- Calcineurin inhibitors
- ONGOING MONITORING
- LUNG TRANSPLANTATION
- SUMMARY AND RECOMMENDATIONS