Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is associated with significant morbidity and is a critical cause of mortality in patients with RA.
Our aim was to evaluate predictive and prognostic factors for RA-ILD and to describe the therapeutic management of the condition from a large China cohort.
This was a retrospective cohort study. We collected data of 1121 RA patients who underwent chest HRCT from 2008 to 2017. Patients without ILD at RA diagnosis were included in the analysis. The development and evolution of ILD in RA patients were followed up. Determinants of ILD development and progression were identified through multivariable logistic analysis. Cox hazards analysis was used to determine significant variables associated with survival.
A total of 923 patients without ILD at RA diagnosis were identified and enrolled. Among them, 278 cases (30.12%) were diagnosed as ILD during follow-up. Logistic regression analysis showed that advanced age (> 60 years old) at RA onset (OR: 1.485), male (OR: 1.882), short duration of RA (0~5 years) (OR: 2.099), RF positive (OR: 1.728), elevated lactate dehydrogenase (LDH) (OR: 3.032), and no medication (OR: 1.833) were closely correlated to the development of RA-ILD. No correlation was found between ILD development and traditional DMARDs such as methotrexate and leflunomide. According to the follow-up data, 83 RA-ILD patients were identified as interstitial lung disease (ILD) progression, and 102 participants were stable. Logistic regression modeling demonstrated that DLCO% < 45% (OR: 3.025) and UIP possible pattern on HRCT (OR: 3.476) were independent risk factors for the ILD progression. No correlation was found between ILD progression and traditional DMARDs such as methotrexate and leflunomide. A total of 53 RA-ILD deaths occurred during follow-up. Cox hazards analysis revealed that advanced age (> 60 years old) at RA-ILD diagnosis (HR: 3.181) and extensive lung involvement on HRCT (HR: 2.401) were associated with worse survival. Treatment with cyclophosphamide (HR: 0.210) was associated with better survival.
Advanced age, male, short duration of RA, RF positive, elevated LDH, and no medication are closely correlated with RA-ILD. No correlation was found between traditional DMARDs and ILD development. DLCO% < 45% and UIP possible pattern are predictive factors for ILD progression. No correlation was found between traditional DMARDs and ILD progression. Advanced age and extensive lung involvement on HRCT independently predict mortality; cyclophosphamide treatment helps to improve the prognosis of RA-ILD.
• We designed this study to investigate the predictive and prognostic factors for RA-ILD and to explore the potential role of DMARDs in the evolution of RA-ILD from the development to progression and death.
• Patients without ILD at RA diagnosis were enrolled and followed up retrospectively.
• Our results showed that no correlation was found between traditional DMARDs and the development and progression of ILD, and regular treatment may improve the development of RA-ILD.
• Our results revealed that clinical variables appeared predictive implications for the diagnosis of ILD and physiological and radiological variables appeared predictive implications for the prognosis of ILD, which can provide reference to rheumatologists and help to improve poor prognosis of RA-ILD.
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Solomon JJ, Fischer A (2014) Rheumatoid arthritis interstitial lung disease: time to take notice. Respirology 19(4):463–464
Suda T (2015) Up-to-Date Information on rheumatoid arthritis-associated interstitial lung disease. Clin Med Insights Circ Respir Pulm Med 9(Suppl 1):155–162
Bongartz T, Nannini C, Medina-Velasquez YF, Achenbach SJ, Crowson CS, Ryu JH, Vassallo R, Gabriel SE, Matteson EL (2010) Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. Arthritis Rheum 62(6):1583–1591
Olson AL, Swigris JJ, Sprunger DB, Fischer A, Fernandez-Perez ER, Solomon J, Murphy J, Cohen M, Raghu G, Brown KK (2011) Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med 183(3):372–378
Kelly C, Hamilton J (2007) What kills patients with rheumatoid arthritis?. Rheumatology (Oxford) 46(2):183–184
Lake F, Proudman S (2014) Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir Crit Care Med 35(2):222–238
Alarcon GS, Kremer JM, Macaluso M et al (1997) Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med 127(5):356–364
Conway R, Low C, Coughlan RJ, O'Donnell MJ, Carey JJ (2016) Leflunomide use and risk of lung disease in rheumatoid arthritis: a systematic literature review and metaanalysis of randomized controlled trials. J Rheumatol 43(5):855–860
Villeneuve E, Nam J, Emery P (2010) 2010 ACR-EULAR classification criteria for rheumatoid arthritis. Rev Bras Reumatol 50(5):481–483
Arnett FC, Edworthy SM, Bloch DA, McShane D, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324
Bizzaro N, Bartoloni E, Morozzi G, Manganelli S, Riccieri V, Sabatini P, Filippini M, Tampoia M, Afeltra A, Sebastiani G, Alpini C, Bini V, Bistoni O, Alunno A, Gerli R, Forum Interdisciplinare per la Ricerca nelle Malattie Autoimmuni (FIRMA Group) (2013) Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study. Arthritis Res Ther 15(1):R16
Md YM, Kabia A, Darby M et al (2017) Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years' experience at a single centre. Rheumatology (Oxford) 56(8):1348–1357
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King te Jr, Kondoh Y, Myers J, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann HJ, ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten C, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, ATS/ERS Task Force (2005) Standardisation of spirometry. Eur Respir J 26(2):319–338
Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, Corte TJ, Sander CR, Ratoff J, Devaraj A, Bozovic G, Denton CP, Black CM, du Bois RM, Wells AU (2008) Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 177(11):1248–1254
Dawson JK, Fewins HE, Desmond J, Lynch MP, Graham DR (2002) Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis. Ann Rheum Dis 61(6):517–521
Travis WD, Costabel U, Hansell DM, King te Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D, ATS/ERS Committee on Idiopathic Interstitial Pneumonias (2013) 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 188(6):733–748
Gruden JF (2016) CT in idiopathic pulmonary fibrosis: diagnosis and beyond. AJR Am J Roentgenol 206(3):495–507
Travis WD, Matsui K, Moss J, Ferrans VJ (2000) 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 24(1):19–33
Bellia M, Cannizzaro F, Scichilone N, Riili M, Triolo G, Midiri M, Lagalla R (2009) HRCT and scleroderma: semiquantitative evaluation of lung damage and functional abnormalities. Radiol Med 114(2):190–203
Goldin JG, Lynch DA, Strollo DC, Suh RD, Schraufnagel DE, Clements PJ, Elashoff RM, Furst DE, Vasunilashorn S, McNitt-Gray M, Brown MS, Roth MD, Tashkin DP, Scleroderma Lung Study Research Group (2008) High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest 134(2):358–367
Karazincir S, Akoglu S, Guler H et al (2009) The evaluation of early pulmonary involvement with high resolution computerized tomography in asymptomatic and non-smoker patients with rheumatoid arthritis. Tuberk Toraks 57(1):14–21
Mori S, Cho I, Koga Y, Sugimoto M (2008) Comparison of pulmonary abnormalities on high-resolution computed tomography in patients with early versus longstanding rheumatoid arthritis. J Rheumatol 35(8):1513–1521
Doyle TJ, Dellaripa PF, Batra K, Frits ML, Iannaccone CK, Hatabu H, Nishino M, Weinblatt ME, Ascherman DP, Washko GR, Hunninghake GM, Choi AMK, Shadick NA, Rosas IO (2014) Functional impact of a spectrum of interstitial lung abnormalities in rheumatoid arthritis. Chest 146(1):41–50
Zhang Y, Li H, Wu N, Dong X, Zheng Y (2017) Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol 36(4):817–823
Demoruelle MK, Solomon JJ, Fischer A et al (2014) The lung may play a role in the pathogenesis of rheumatoid arthritis. Int J Clin Rheumtol 9(3):295–309
Kusume K (1991) Lung injury in idiopathic pulmonary fibrosis and measurement of immunoreactive neutrophil elastase and alpha 1-protease inhibitor in blood. Nihon Kyobu Shikkan Gakkai Zasshi 29(10):1254–1260
Dong X, Zhou J, Guo X, Li Y, Xu Y, Fu Q, Lu Y, Zheng Y (2018) A retrospective analysis of distinguishing features of chest HRCT and clinical manifestation in primary Sjogren's syndrome-related interstitial lung disease in a Chinese population. Clin Rheumatol 37(11):2981–2988
Picchianti DA, Markovic M, Argento G et al (2017) Therapeutic management of patients with rheumatoid arthritis and associated interstitial lung disease: case report and literature review. Ther Adv Respir Dis 11(1):64–72
Fu Q, Wang L, Li L, Li Y, Liu R, Zheng Y (2019) Risk factors for progression and prognosis of rheumatoid arthritis-associated interstitial lung disease: single center study with a large sample of Chinese population. Clin Rheumatol 38(4):1109–1116
Kelly CA, Saravanan V, Nisar M, Arthanari S, Woodhead FA, Price-Forbes AN, Dawson J, Sathi N, Ahmad Y, Koduri G, Young A, British Rheumatoid Interstitial Lung (BRILL) Network (2014) Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study. Rheumatology (Oxford) 53(9):1676–1682
Solomon JJ, Chung JH, Cosgrove GP, Demoruelle MK, Fernandez-Perez ER, Fischer A, Frankel SK, Hobbs SB, Huie TJ, Ketzer J, Mannina A, Olson AL, Russell G, Tsuchiya Y, Yunt ZX, Zelarney PT, Brown KK, Swigris JJ (2016) Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J 47(2):588–596
Li L, Gao S, Fu Q et al (2019) A preliminary study of lung abnormalities on HRCT in patients of rheumatoid arthritis-associated interstitial lung disease with progressive fibrosis. Clin Rheumatol
Sathi N, Urwin T, Desmond S, Dawson JK (2011) Patients with limited rheumatoid arthritis-related interstitial lung disease have a better prognosis than those with extensive disease. Rheumatology (Oxford) 50(3):620
Assayag D, Lubin M, Lee JS, King TE, Collard HR, Ryerson CJ (2014) Predictors of mortality in rheumatoid arthritis-related interstitial lung disease. Respirology 19(4):493–500
Kim EJ, Collard HR, King TJ (2009) Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern. Chest 136(5):1397–1405
Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Scleroderma Lung Study Research Group (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354(25):2655–2666
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Li, L., Liu, R., Zhang, Y. et al. A retrospective study on the predictive implications of clinical characteristics and therapeutic management in patients with rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol (2019). https://doi.org/10.1007/s10067-019-04846-1
- Clinical characteristics
- Interstitial lung disease
- Rheumatoid arthritis
- Therapeutic management