Skip to main content

Advertisement

SpringerLink
Log in

Chronic lung disease in U.S. Veterans with rheumatoid arthritis and the impact on survival

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Assess the impact of chronic lung diseases (CLD) on survival in rheumatoid arthritis (RA). Among participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a prospective cohort of U.S. Veterans with RA, we identified CLD and cardiovascular disease (CVD) using administrative and registry data. Demographics, smoking status, RA characteristics including Disease Activity Score in 28 joints (DAS28), and disease-modifying anti-rheumatic drug (DMARD) use were obtained from registry data, which were linked to the National Death Index to obtain vital status. We evaluated associations of CLD with survival using the multivariable Cox regression models. Among a large (n = 2053), male-predominant (91%) RA cohort, 554 (27%) had CLD at enrollment. Mortality risk was increased 1.51-fold (95% CI 1.26–1.81) in RA patients with CLD after multivariable adjustment, a risk that was similar to that observed with CVD (HR CLD alone 1.46 [1.03–2.06]; CVD alone 1.62 [1.35–1.94]). Survival was significantly reduced in those with interstitial lung disease (ILD) as well as other forms of CLD. Mortality risk with methotrexate and biologic use was not different in those with CLD compared to those without (p interaction ≥ 0.15) using multiple exposure definitions and propensity score adjustment. Mortality risk is significantly increased in RA patients with CLD. This risk is attributable not only to ILD but also to other chronic lung conditions and does not appear to be substantially greater in those receiving methotrexate or biologic therapies. Comorbid lung disease should be targeted as a means of improving long-term outcomes in RA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. 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

    Article  Google Scholar 

  2. Shaw M, Collins BF, Ho LA, Raghu G (2015) Rheumatoid arthritis-associated lung disease. Eur Respir Rev 24(135):1–16

    Article  Google Scholar 

  3. 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

    Article  Google Scholar 

  4. Koduri G, Norton S, Young A, Cox N, Davies P, Devlin J, Dixey J, Gough A, Prouse P, Winfield J, Williams P, on behalf of ERAS (Early Rheumatoid Arthritis Study) (2010) Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort. Rheumatology 49(8):1483–1489

    Article  Google Scholar 

  5. England BR, Sayles H, Michaud K, Caplan L, Davis LA, Cannon GW, Sauer BC, Solow EB, Reimold AM, Kerr GS, Schwab P, Baker JF, Mikuls TR (2016) Cause-specific mortality in male US Veterans with rheumatoid arthritis. Arthritis Care Res (Hoboken) 68(1):36–45

    Article  Google Scholar 

  6. Sparks JA, Chang SC, Liao KP, Lu B, Fine AR, Solomon DH, Costenbader KH, Karlson EW (2016) Rheumatoid arthritis and mortality among women during 36 years of prospective follow-up: results from the Nurses’ Health Study. Arthritis Care Res (Hoboken) 68(6):753–762

    Article  Google Scholar 

  7. Nannini C, Medina-Velasquez YF, Achenbach SJ, Crowson CS, Ryu JH, Vassallo R, Gabriel SE, Matteson EL, Bongartz T (2013) Incidence and mortality of obstructive lung disease in rheumatoid arthritis: a population-based study. Arthritis Care Res (Hoboken) 65(8):1243–1250

    Article  Google Scholar 

  8. Swinson DR, Symmons D, Suresh U, Jones M, Booth J (1997) Decreased survival in patients with co-existent rheumatoid arthritis and bronchiectasis. Br J Rheumatol 36(6):689–691

    Article  CAS  Google Scholar 

  9. Tsuchiya Y, Takayanagi N, Sugiura H, Miyahara Y, Tokunaga D, Kawabata Y, Sugita Y (2011) Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome. Eur Respir J 37(6):1411–1417

    Article  CAS  Google Scholar 

  10. Puechal X, Genin E, Bienvenu T, Le Jeunne C, Dusser DJ (2014) Poor survival in rheumatoid arthritis associated with bronchiectasis: a family-based cohort study. PLoS One 9(10):e110066

    Article  Google Scholar 

  11. Kremer JM, Alarcón GS, Weinblatt ME, Kaymakcian MV, Macaluso M, Cannon GW, Palmer WR, Sundy JS, St. Clair EW, Alexander RW, Smith GJW, Axiotis CA (1997) Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis. A multicenter study with literature review. Arthritis Rheumatol 40(10):1829–1837

    Article  CAS  Google Scholar 

  12. Chikura B, Lane S, Dawson JK (2009) Clinical expression of leflunomide-induced pneumonitis. Rheumatology 48(9):1065–1068

    Article  CAS  Google Scholar 

  13. Khasnis AA, Calabrese LH. Tumor necrosis factor inhibitors and lung disease: a paradox of efficacy and risk. In: Seminars in arthritis and rheumatism. Elsevier. Abstract 40

  14. Lioté H, Lioté F, Séroussi B, Mayaud C, Cadranel J (2010) Rituximab-induced lung disease: a systematic literature review. Eur Respir J 35(3):681–687

    Article  Google Scholar 

  15. Weinblatt M, Combe B, Covucci A, Aranda R, Becker J, Keystone E (2006) Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study. Arthritis Rheumatol 54(9):2807–2816

    Article  CAS  Google Scholar 

  16. Suissa S, Hudson M, Ernst P (2006) Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. Arthritis Rheum 54(5):1435–1439

    Article  CAS  Google Scholar 

  17. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D (2012) Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis 71(9):1524–1529

    Article  Google Scholar 

  18. England BR, Thiele GM, Anderson DR, Mikuls TR (2018) Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ 361:k1036

    Article  Google Scholar 

  19. Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  CAS  Google Scholar 

  20. Mikuls TR, Reimold A, Kerr GS, Cannon GW (2015) Insights and implications of the VA Rheumatoid Arthritis Registry. Fed Pract 32:24–29

    Google Scholar 

  21. England BR, Sayles H, Mikuls TR, Johnson DS, Michaud K (2015) Validation of the rheumatic disease comorbidity index. Arthritis Care Res (Hoboken) 67(6):865–872

    Article  Google Scholar 

  22. Pincus T, Sokka T, Kautiainen H (2005) Further development of a physical function scale on a MDHAQ [corrected] for standard care of patients with rheumatic diseases. J Rheumatol 32(8):1432–1439

    PubMed  Google Scholar 

  23. van der Heijde DM, van’t Hof M, van Riel PL, van de Putte LB (1993) Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol 20(3):579–581

    PubMed  Google Scholar 

  24. Mikuls TR, Gould KA, Bynote KK et al (2010) Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione S-transferase in a cross-sectional study. Arthritis Res Ther 12(6):R213

    Article  Google Scholar 

  25. Miriovsky BJ, Michaud K, Thiele GM, O’Dell JR, Cannon GW, Kerr G, Richards JS, Johnson D, Caplan L, Reimold A, Hooker R, Mikuls TR (2010) Anti-CCP antibody and rheumatoid factor concentrations predict greater disease activity in men with rheumatoid arthritis. Ann Rheum Dis 69(7):1292–1297

    Article  Google Scholar 

  26. Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJL, Kvien TK, Dougados M, Radner H, Atzeni F, Primdahl J, Södergren A, Wallberg Jonsson S, van Rompay J, Zabalan C, Pedersen TR, Jacobsson L, de Vlam K, Gonzalez-Gay MA, Semb AG, Kitas GD, Smulders YM, Szekanecz Z, Sattar N, Symmons DPM, Nurmohamed MT (2017) EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis 76(1):17–28

    Article  CAS  Google Scholar 

  27. Sparks JA, Lin TC, Camargo CA Jr et al (2017) Rheumatoid arthritis and risk of chronic obstructive pulmonary disease or asthma among women: a marginal structural model analysis in the Nurses’ Health Study. Semin Arthritis Rheum

  28. McGuire K, Avina-Zubieta JA, Esdaile JM et al (2017) Risk of incident chronic obstructive pulmonary disease (COPD) in rheumatoid arthritis: a population based cohort study. Arthritis Care Res (Hoboken)

  29. Mannino DM, Buist AS, Petty TL, Enright PL, Redd SC (2003) Lung function and mortality in the United States: data from the first National Health and Nutrition Examination Survey follow-up study. Thorax 58(5):388–393

    Article  CAS  Google Scholar 

  30. Myasoedova E, Gabriel SE, Matteson EL, Davis JM 3rd, Therneau TM, Crowson CS (2017) Decreased cardiovascular mortality in patients with incident rheumatoid arthritis (RA) in recent years: dawn of a new era in cardiovascular disease in RA? J Rheumatol 44(6):732–739

    Article  Google Scholar 

  31. Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, Kraft J, Lynde C, Pope J, Gulliver W, Keeling S, Dutz J, Bessette L, Bissonnette R, Haraoui B (2015) The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis 74(3):480–489

    Article  CAS  Google Scholar 

  32. Saravanan V, Kelly CA (2004) Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis. Rheumatology (Oxford) 43(2):143–147

    Article  CAS  Google Scholar 

  33. 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

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Center of Excellence for Suicide Prevention, Joint Department of Veterans Affairs (VA) and Department of Defense (DoD) Suicide Data Repository-National Death Index (NDI).

Funding

Dr. England is supported by UNMC Internal Medicine Scientist Development Award, UNMC Physician-Scientist Training Program, and UNMC Mentored Scholars Program. Dr. Mikuls is supported by a VA Merit Award (CX000896) and grants from the National Institutes of Health: National Institute of General Medical Sciences (U54GM115458), National Institute on Alcohol Abuse and Alcoholism (R25AA020818), and National Institute of Arthritis and Musculoskeletal and Skin Diseases (2P50AR60772). Dr. Poole is supported by the National Institute of Environmental Health Sciences (R01ES019325). Dr. Caplan is supported by VA Merit Award IIR 14-048-3. Dr. Baker is supported by a VA Career Development Award from Clinical Science Research and Development (IK2 CX000955). Dr. Cannon is supported by Specialty Care Center of Innovation, Veterans Health Administration, Department of Veterans Affairs.

Author information

Authors and Affiliations

  1. VA Nebraska-Western IA Health Care System, Omaha, NE, USA

    Bryant R. England, Geoffrey M. Thiele & Ted R. Mikuls

  2. Division of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, 986270 Nebraska Med Center, Omaha, Nebraska, United States

    Bryant R. England, Harlan Sayles, Kaleb Michaud, Geoffrey M. Thiele & Ted R. Mikuls

  3. Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA

    Harlan Sayles

  4. National Data Bank for Rheumatic Diseases, Wichita, KS, USA

    Kaleb Michaud

  5. Department of Internal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, NE, USA

    Jill A. Poole

  6. Denver VA and University of Colorado, Denver, CO, USA

    Liron Caplan

  7. VA Salt Lake City and University of Utah, Salt Lake City, UT, USA

    Brian C. Sauer & Grant W. Cannon

  8. Dallas VA and University of Texas Southwestern, Dallas, TX, USA

    Andreas Reimold

  9. Washington DC VAMC, Georgetown and Howard University, Washington, DC, USA

    Gail S. Kerr

  10. Corporal Michael J. Crescenz VA and University of Pennsylvania, Philadelphia, PA, USA

    Joshua F. Baker

Authors
  1. Bryant R. England
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harlan Sayles
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kaleb Michaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Geoffrey M. Thiele
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jill A. Poole
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liron Caplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brian C. Sauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Grant W. Cannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andreas Reimold
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gail S. Kerr
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Joshua F. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ted R. Mikuls
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bryant R. England.

Ethics declarations

Disclosures

None.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs.

Electronic supplementary material

ESM 1

(DOCX 17 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

England, B.R., Sayles, H., Michaud, K. et al. Chronic lung disease in U.S. Veterans with rheumatoid arthritis and the impact on survival. Clin Rheumatol 37, 2907–2915 (2018). https://doi.org/10.1007/s10067-018-4314-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4314-9

Keywords

Search

Navigation