title: Poor survival in rheumatoid arthritis associated with bronchiectasis: a family-based cohort study.
abstract: BACKGROUND
  Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear.
  
  
  METHODS
  We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations.
  
  
  RESULTS
  During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5-48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1-81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1-113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4-37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10(-5)).
  
  
  CONCLUSIONS
  DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.
authors.affiliation: National Referral Center for Rare Systemic Autoimmune Diseases, Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France; INSERM U1016, CNRS UMR 8104, Institut Cochin, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Puéchal
authors.affiliation: INSERM UMR-1078, Centre Hospitalier Universitaire, Brest, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Génin
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
authors.affiliation: National Referral Center for Rare Systemic Autoimmune Diseases, Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Le Jeunne
authors.affiliation: Department of Respiratory Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dusser
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000401:mortality*; D001987:Bronchiectasis / Q000150:complications* / Q000401:mortality*; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011336:Probability; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome