Rheumatoid lung disease

Kevin K Brown, Kevin K Brown

Abstract

Rheumatoid arthritis (RA) is a common, functionally disabling disease with genetic and environmental contributors. It occurs in approximately 1% of the population and adversely affects quality of life, functional status, and survival. Beyond its impact on the joints, pulmonary involvement occurs regularly and is responsible for a significant portion of the morbidity and mortality. Although pulmonary infection and/or drug toxicity are frequent complications, lung disease directly associated with the underlying RA is more common. The airways, vasculature, parenchyma, and pleura can all be involved, with variable amounts of pathologic inflammation and fibrosis. The true adverse clinical impact of the most important of these directly associated disorders, RA-associated interstitial lung disease (RA-ILD), has only recently begun to reveal itself. Our knowledge of the underlying pathobiology and the impact of our current immunomodulatory and biologic therapies on the lung disease are less than incomplete. However, what is clear is the importance of progressive lung fibrosis in shortening survival and impairing quality of life in RA as well as in other connective tissue diseases. The impact of historically available and newer biologic therapies in altering the outcome of RA-ILD is unknown; translational studies focused on the pathobiology and clinical studies focused on the treatment of RA-ILD are needed.

Figures

Figure 1.
Figure 1.
Survival in patients with rheumatoid arthritis (RA) and RA after first presentation of severe extraarticular disease manifestations (ExRA) compared with the expected survival from the general population. Reprinted by permission from Reference .
Figure 2.
Figure 2.
Comparison of the survival curves of all subject groups. CVD-NSIP = nonspecific interstitial pneumonia associated with collagen vascular disease; CVD-UIP = usual interstitial pneumonia associated with collagen vascular disease; I-NSIP = idiopathic nonspecific interstitial pneumonia; UIP = usual interstitial pneumonia. Reprinted by permission from Reference .
Figure 3.
Figure 3.
Comparison of the Kaplan-Meier survival curves between the subject groups and the UIP pattern associated with rheumatoid arthritis (RA-UIP). CVD-NSIP = nonspecific interstitial pneumonia associated with collagen vascular diseases; I-NSIP = idiopathic nonspecific interstitial pneumonia; IPF/UIP = idiopathic pulmonary fibrosis/usual interstitial pneumonia; non–RA-UIP = usual interstitial pneumonia in the patients with non–rheumatoid arthritis–collagen vascular diseases. The statistical significances between groups were as follows: RA-UIP versus non–RA-UIP, p = 0.015; RA-UIP versus CVD-NSIP, p = 0.043; RA-UIP versus I-NSIP, not significant; RA-UIP versus IPF/UIP, not significant. Reprinted by permission from Reference .
Figure 4.
Figure 4.
Cox model–based survival estimates for patients across three levels of FVC percentage change adjusted for usual interstitial pneumonia (UIP), onset of symptoms, female sex, and positive smoking history. Average patient profiles for UIP, onset of symptoms, sex, and smoking were used in the estimates. Dotted line, at least 10% increase in FVC; solid line, at least 10% decrease in FVC; dashed line, less than 10% increase or decrease in FVC; p = 0.01. Reprinted by permission from Reference .
Figure 5.
Figure 5.
Fibroblast foci appear to be isolated accumulations of matrix and myofibroblasts in usual interstitial pneumonia (left); however, when reconstructed in three dimensions, they appear to be physically connected and forming a reticulum. Reprinted by permission from Reference .

References

    1. Minaur NJ, Jacoby RK, Cosh JA, Taylor G, Rasker JJ. Outcome after 40 years with rheumatoid arthritis: a prospective study of function, disease activity, and mortality. J Rheumatol Suppl 2004;69:3–8.
    1. Gabriel SE, Crowson CS, Kremers HM, Doran MF, Turesson C, O'Fallon WM, Matteson EL. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum 2003;48:54–58.
    1. Sihvonen S, Korpela M, Laippala P, Mustonen J, Pasternack A. Death rates and causes of death in patients with rheumatoid arthritis: a population-based study. Scand J Rheumatol 2004;33:221–227.
    1. Update: direct and indirect costs of arthritis and other rheumatic conditions: United States, 1997. MMWR Morb Mortal Wkly Rep 2004;53:388–389.
    1. Turesson C, Matteson EL. Management of extra-articular disease manifestations in rheumatoid arthritis. Curr Opin Rheumatol 2004;16:206–211.
    1. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 2003;62:722–727.
    1. Turesson C, Jacobsson LT. Epidemiology of extra-articular manifestations in rheumatoid arthritis. Scand J Rheumatol 2004;33:65–72.
    1. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 2005;52:722–732.
    1. Suzuki A, Ohosone Y, Obana M, Mita S, Matsuoka Y, Irimajiri S, Fukuda J. Cause of death in 81 autopsied patients with rheumatoid arthritis. J Rheumatol 1994;21:33–36.
    1. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 2006;54:628–634.
    1. Winthrop KL. Serious infections with antirheumatic therapy: are biologicals worse? Ann Rheum Dis 2006;65:iii54–iii57.
    1. Zrour SH, Touzi M, Bejia I, Golli M, Rouatbi N, Sakly N, Younes M, Tabka Z, Bergaoui N. Correlations between high-resolution computed tomography of the chest and clinical function in patients with rheumatoid arthritis: prospective study in 75 patients. Joint Bone Spine 2005;72:41–47.
    1. Bilgici A, Ulusoy H, Kuru O, Celenk C, Unsal M, Danaci M. Pulmonary involvement in rheumatoid arthritis. Rheumatol Int 2005;25:429–435.
    1. Dawson JK, Fewins HE, Desmond J, Lynch MP, Graham DR. Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography and pulmonary function tests. Thorax 2001;56:622–627.
    1. Hakala M. Poor prognosis in patients with rheumatoid arthritis hospitalized for interstitial lung fibrosis. Chest 1988;93:114–118.
    1. Dawson JK, Graham DR, Desmond J, Fewins HE, Lynch MP. Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests. Rheumatology (Oxford) 2002;41:262–267.
    1. Kocheril SV, Appleton BE, Somers EC, Kazerooni EA, Flaherty KR, Martinez FJ, Gross BH, Crofford LJ. Comparison of disease progression and mortality of connective tissue disease-related interstitial lung disease and idiopathic interstitial pneumonia. Arthritis Rheum 2005;53:549–557.
    1. Vergnenegre A, Pugnere N, Antonini MT, Arnaud M, Melloni B, Treves R, Bonnaud F. Airway obstruction and rheumatoid arthritis. Eur Respir J 1997;10:1072–1078.
    1. Geddes DM, Webley M, Emerson PA. Airways obstruction in rheumatoid arthritis. Ann Rheum Dis 1979;38:222–225.
    1. Perez T, Remy-Jardin M, Cortet B. Airways involvement in rheumatoid arthritis: clinical, functional and HRCT findings. Am J Respir Crit Care Med 1998;157:1658–1665.
    1. Remy-Jardin M, Remy J, Cortet B, Mauri F, Delcambre B. Lung changes in rheumatoid arthritis: CT findings. Radiology 1994;193:375–382.
    1. Hayakawa H, Sato A, Imokawa S, Toyoshima M, Chida K, Iwata M. Bronchiolar disease in rheumatoid arthritis. Am J Respir Crit Care Med 1996;154:1531–1536.
    1. Shadick NA., Fanta CH, Weinblatt ME, O'Donnell W, Coblyn JS. Bronchiectasis: a late feature of severe rheumatoid arthritis. Medicine 1994;73:161–170.
    1. Radoux V, Menard HA, Begin R, Decary F, Koopman WJ. Airways disease in rheumatoid arthritis patients. Arthritis Rheum 1987;30:249–256.
    1. Schwarz MI, Lynch DA, Tuder R. Bronchiolitis obliterans: the lone manifestation of rheumatoid arthritis. Eur Respir J 1994;7:817–820.
    1. Homma S, Kawabata M, Kishi K, Tsuboi E, Narui K, Nakatani T, Uekusa T, Saiki S, Nakata K. Diffuse panbronchiolitis in rheumatoid arthritis. Eur Respir J 1998;12:444–452.
    1. Joseph J, Sahn SA. Connective tissue diseases and the pleura. Chest 1993;104:262–270.
    1. Helmers R, Galvin J, Hunninghake GW. Pulmonary manifestations associated with rheumatoid arthritis. Chest 1991;100:235–239.
    1. Morikawa J, Kitamura K, Habuchi Y, Tsujimura Y, Minamikawa T, Takamatsu T. Pulmonary hypertension in a patient with rheumatoid arthritis. Chest 1988;93:876–878.
    1. Walters MN, Ojeda VJ. Pleuropulmonary necrobiotic rheumatoid nodules. A review and clinicopathological study of six patients. Med J Aust 1986;144:648–651.
    1. Ziff M. The rheumatoid nodule. Arthritis Rheum 1990;33:761–767.
    1. Anaya JM, Diethelm L, Ortiz L, Gutierrez M, Citera G, Welsh RA, Espinoza LR. Pulmonary involvement in rheumatoid arthritis. Semin Arthritis Rheum 1995;24:242–254.
    1. Caplan A. Certain unusual radiographic appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax 1953;8:19–37.
    1. Biederer J, Schnabel A, Muhle C, Gross WL, Heller M, Reuter M. Correlation between HRCT findings, pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritis. Eur Radiol 2004;14:272–280.
    1. Lee HK, Kim DS, Yoo B, Seo JB, Rho JY, Colby TV, Kitaichi M. Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease. Chest 2005;127:2019–2027.
    1. Yousem SA, Colby TV, Carrington CB. Lung biopsy in rheumatoid arthritis. Am Rev Respir Dis 1985;131:770–777.
    1. Weyand CM, Schmidt D, Wagner U, Goronzy JJ. The influence of sex on the phenotype of rheumatoid arthritis. Arthritis Rheum 1998;41:817–822.
    1. Gabbay E, Tarala R, Will R, Carroll G, Adler B, Cameron D, Lake FR. Interstitial lung disease in recent onset rheumatoid arthritis. Am J Respir Crit Care Med 1997;156:528–535.
    1. Vessey MP, Villard-Mackintosh L, Yeates D. Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception 1987;35:457–464.
    1. Albano SA, Santana-Sahagun E, Weisman MH. Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 2001;31:146–159.
    1. Harrison BJ. Influence of cigarette smoking on disease outcome in rheumatoid arthritis. Curr Opin Rheumatol 2002;14:246–252.
    1. Saag KG, Kolluri S, Koehnke RK, Georgou TA, Rachow JW, Hunninghake GW, Schwartz DA. Rheumatoid arthritis lung disease. Determinants of radiographic and physiologic abnormalities. Arthritis Rheum 1996;39:1711–1719.
    1. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, Ronnelid J, Harris HE, Ulfgren AK, Rantapaa-Dahlqvist S, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006;54:38–46.
    1. McDonagh J, Greaves M, Wright AR, Heycock C, Owen JP, Kelly C. High resolution computed tomography of the lungs in patients with rheumatoid arthritis and interstitial lung disease. Br J Rheumatol 1994;33:118–122.
    1. Ayhan-Ardic FF, Oken O, Yorgancioglu ZR, Ustun N, Gokharman FD. Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis and ankylosing spondylitis without respiratory symptoms. Clin Rheumatol 2006;25:213–218.
    1. Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004;50:380–386.
    1. Manfredsdottir VF, Vikingsdottir T, Jonsson T, Geirsson AJ, Kjartansson O, Heimisdottir M, Sigurdardottir SL, Valdimarsson H, Vikingsson A. The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis. Rheumatology (Oxford) 2006;45:734–740.
    1. Masdottir B, Jonsson T, Manfredsdottir V, Vikingsson A, Brekkan A, Valdimarsson H. Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology (Oxford) 2000;39:1202–1205.
    1. Sakaida H. IgG rheumatoid factor in rheumatoid arthritis with interstitial lung disease [Japanese]. Ryumachi 1995;35:671–677.
    1. Luukkainen R, Saltyshev M, Pakkasela R, Nordqvist E, Huhtala H, Hakala M. Relationship of rheumatoid factor to lung diffusion capacity in smoking and non-smoking patients with rheumatoid arthritis. Scand J Rheumatol 1995;24:119–120.
    1. American Thoracic Society; European Respiratory Society. 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.
    1. Hubbard R, Venn A. The impact of coexisting connective tissue disease on survival in patients with fibrosing alveolitis. Rheumatology (Oxford) 2002;41:676–679.
    1. Park JH, Kim DS, Park IN, Jang SJ, Kitaichi M, Nicholson AG, Colby TV. Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes. Am J Respir Crit Care Med 2007;175:705–711.
    1. Hakala M, Paakko P, Huhti E, Tarkka M, Sutinen S. Open lung biopsy of patients with rheumatoid arthritis. Clin Rheumatol 1990;9:452–460.
    1. Akira M, Sakatani M, Hara H. Thin-section CT findings in rheumatoid arthritis-associated lung disease: CT patterns and their courses. J Comput Assist Tomogr 1999;23:941–948.
    1. Hunninghake GW, Lynch DA, Galvin JR, Gross BH, Muller N, Schwartz DA, King TE Jr, Lynch JP III, Hegele R, Waldron J, et al. Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia. Chest 2003;124:1215–1223.
    1. Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch IJ, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;28:28.
    1. Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2003;168:538–542.
    1. Kawabata H, Nagai S, Hayashi M, Nakamura H, Nagao T, Shigematsu M, Kitaichi M, Izumi T. Significance of lung shrinkage on CXR as a prognostic factor in patients with idiopathic pulmonary fibrosis. Respirology 2003;8:351–358.
    1. Lynch DA, David Godwin J, Safrin S, Starko KM, Hormel P, Brown KK, Raghu G, King TE Jr, Bradford WZ, Schwartz DA, et al. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 2005;172:488–493.
    1. Martinez F, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 2005;142:963–967.
    1. Latsi PI, Du Bois RM, Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A, Veeraraghavan S, Hansell DM, Wells AU. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med 2003;5:5.
    1. Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, Aziz N, Kaminski N, Zlotnik A. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. Am J Respir Crit Care Med 2006;173:188–198.
    1. Vourlekis JS, Schwarz MI, Cherniack RM, Curran-Everett D, Cool CD, Tuder RM, King TE Jr, Brown KK. The effect of pulmonary fibrosis on survival in patients with hypersensitivity pneumonitis. Am J Med 2004;116:662–668.
    1. Flaherty KR, Colby TV, Travis WD, Toews GB, Mumford J, Murray S, Thannickal VJ, Kazerooni EA, Gross BH, Lynch JP III, et al. Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease. Am J Respir Crit Care Med 2003;167:1410–1415.
    1. Cool CD, Groshong SD, Rai PR, Henson PM, Stewart JS, Brown KK. Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum. Am J Respir Crit Care Med 2006;174:654–658.
    1. Collard HR, Cool CD, Leslie KO, Curran-Everett D, Groshong S, Brown KK. Organizing pneumonia and lymphoplasmacytic inflammation predict treatment response in idiopathic pulmonary fibrosis. Histopathology 2007;50:258–265.
    1. Collard HR, Ryu JH, Douglas WW, Schwarz MI, Curran-Everett D, King TE Jr, Brown KK. Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest 2004;125:2169–2174.
    1. Lateef O, Shakoor N, Balk RA. Methotrexate pulmonary toxicity. Expert Opin Drug Saf 2005;4:723–730.
    1. Khadadah ME, Jayakrishnan B, Al-Gorair S, Al-Mutairi M, Al-Maradni N, Onadeko B, Malaviya AN. Effect of methotrexate on pulmonary function in patients with rheumatoid arthritis–a prospective study. Rheumatol Int 2002;22:204–207.
    1. Beyeler C, Jordi B, Gerber NJ, Im Hof V. Pulmonary function in rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study. Br J Rheumatol 1996;35:446–452.
    1. De Rycke L, Verhelst X, Kruithof E, Van den Bosch F, Hoffman IE, Veys EM, De Keyser F. Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis. Ann Rheum Dis 2005;64:299–302.
    1. Vassallo R, Matteson E, Thomas CF Jr. Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor necrosis factor-alpha inhibition. Chest 2002;122:1093–1096.
    1. Peno-Green L, Lluberas G, Kingsley T, Brantley S. Lung injury linked to etanercept therapy. Chest 2002;122:1858–1860.
    1. Miyagawa Y, Nagata N, Nakanishi Y, Aizawa H, Satake M, Hayashi S, Yagawa Y. A case of steroid-responsive organizing pneumonia in a patient with rheumatoid arthritis showing migratory infiltration and normal glucose levels in pleural effusions. Br J Rheumatol 1993;32:829–831.
    1. Kondoh Y, Taki F, Ando M, Ikuta N, Matsumoto K, Tanaka H, Suzuki K, Suzuki R, Yamaki K, Takagi K, et al. A case of bronchiolitis obliterans organizing pneumonia in a patient with rheumatoid arthritis who responded to corticosteroid and immunosuppressant therapy [in Japanese].Nihon Kyobu Shikkan Gakkai Zasshi 1992;30:1165–1170.
    1. Chang HK, Park W, Ryu DS. Successful treatment of progressive rheumatoid interstitial lung disease with cyclosporine: a case report. J Korean Med Sci 2002;17:270–273.
    1. Puttick MP, Klinkhoff AV, Chalmers A, Ostrow DN. Treatment of progressive rheumatoid interstitial lung disease with cyclosporine. J Rheumatol 1995;22:2163–2165.
    1. Ogawa D, Hashimoto H, Wada J, Ueno A, Yamasaki Y, Yamamura M, Makino H. Successful use of cyclosporin A for the treatment of acute interstitial pneumonitis associated with rheumatoid arthritis. Rheumatology (Oxford) 2000;39:1422–1424.
    1. Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC. Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum 2006;54:723–732.
    1. Higashida J, Wun T, Schmidt S, Naguwa SM, Tuscano JM. Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment. J Rheumatol 2005;32:2109–2115.
    1. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572–2581.
    1. Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 2005;353:1114–1123.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner