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Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis

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Abstract

Objective

The objective of this study is to examine the clinical, genetic, and environmental factors associated with interstitial lung disease (ILD) in rheumatoid arthritis (RA).

Method

We recruited patients with RA from rheumatology practices at the time of a scheduled visit. Each patient participated in a comprehensive assessment that included ascertainment of age, sex, joint tenderness and swelling, subcutaneous nodules, disease severity, use of methotrexate and prednisone, smoking status, rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP),erythrocyte sedimentation rate (ESR), the 28-joint Disease Activity Score (DAS28), and the presence of the HLA–DRB1 shared epitope (SE). As part of a thorough quantification of comorbidity, we identify all comorbid conditions, including ILD. We examined variables associated with ILD using logistic regression. We tested interaction terms between SE and other covariates.

Results

We studied 779 RA patients, among whom, ILD was recognized clinically in 69 (8.8 %). Variables significantly associated with ILD in a multivariable analysis included male sex, RA duration, the ESR, the DAS28, anti-CCP, and RF. There was a significant interaction between the HLA–DRB1 SE and smoking, ILD being associated with smoking only in the presence of SE. The association between ILD and anti-CCP, RF, and the ESR displayed a biological gradient, higher titers being more strongly associated with ILD.

Conclusion

Anti-CCP antibodies and the RF may be pathogenically related to ILD. The association between ILD and smoking is dependent on the HLA–DRB1 SE, which may reflect gene–environment interaction.

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Funding

NIH Grant Numbers: K23-HL-004481, R01-HL-085742, R01-HD-037151, and UL1-RR-025767.

Conflict of interest

We confirm that this manuscript has not been submitted elsewhere and that no portion of the data has been or will be published in proceeding or transactions of meetings or symposium volumes. All authors meet the criteria for authorship and accept responsibility for the scientific content of the manuscript. We declare that we have no conflict of interest. No financial or commercial interest.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA

    José Félix Restrepo, Inmaculada del Rincón, Roy W. Haas, Merced Doria & Agustín Escalante

  2. San Antonio Military Medical Center (SAMMC), San Antonio, TX, USA

    Daniel F. Battafarano

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  1. José Félix Restrepo
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  2. Inmaculada del Rincón
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  3. Daniel F. Battafarano
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  5. Merced Doria
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  6. Agustín Escalante
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Correspondence to José Félix Restrepo.

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Restrepo, J.F., del Rincón, I., Battafarano, D.F. et al. Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis. Clin Rheumatol 34, 1529–1536 (2015). https://doi.org/10.1007/s10067-015-3025-8

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  • DOI: https://doi.org/10.1007/s10067-015-3025-8

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