title: Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis.
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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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, restreposuar@uthscsa.edu.
authors.forename: José Félix
authors.initials: JF
authors.lastname: Restrepo
authors.forename: Inmaculada
authors.initials: I
authors.lastname: del Rincón
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Battafarano
authors.forename: Roy W
authors.initials: RW
authors.lastname: Haas
authors.forename: Merced
authors.initials: M
authors.lastname: Doria
authors.forename: Agustín
authors.initials: A
authors.lastname: Escalante
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D001799:Blood Sedimentation; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D017563:Lung Diseases, Interstitial / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000276:immunology; D012307:Risk Factors; D012907:Smoking / Q000276:immunology*; D013781:Texas
chemical_list: D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D008727:Methotrexate