title: Heterogeneity in Survival in Adult Patients With Cystic Fibrosis With FEV1< 30% of Predicted in the United States.
abstract: Lung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV1reaches < 30%. This study estimated transplant-free survival for patients with CF and an FEV1< 30% and identified predictors of death without LTx.
  
  
  
  We conducted a retrospective cohort study using the CF Foundation Patient Registry from January 1, 2003 to December 31, 2013. Adult patients (≥ 18 years) with FEV1< 30% prior to LTx were included. We performed Kaplan-Meier survival estimates censored at LTx. Multivariable Cox proportional hazard regression identified predictors of mortality.
  
  
  
  There were 3,340 patients with an FEV1< 30%. Death without LTx occurred in 1,250 patients (37.4%); 951 patients (28.5%) underwent LTx; 918 patients (27.5%) remained alive without LTx at the end of follow-up; and 221 patients (6.6%) were lost to follow-up. Median transplant-free survival after FEV1< 30% was 6.6 years (95% CI, 5.9-7.0). Adjusted predictors of death without LTx included supplemental oxygen use (hazard ratio [HR], 2.1; 95% CI, 1.7-2.6), Burkholderia cepacia infection (HR, 1.8; 95% CI, 1.3-2.6), BMI ≤ 18 (HR, 1.6; 95% CI, 1.3-1.9), female sex (HR, 1.6; 95% CI, 1.2-2.0), CF-related diabetes in patients receiving insulin (HR, 1.4; 95% CI, 1.2-1.8), and ≥ one exacerbation per year (HR, 1.7; 95% CI, 1.3-2.2 vs. 0 exacerbations).
  
  
  
  Median survival was > 6.5 years for patients with CF and an FEV1< 30%, exceeding prior survival estimates. There was substantial heterogeneity in survival, with some patients with CF dying soon after reaching this lung function threshold and others living for many years. For this reason, we conclude that FEV1< 30% remains an important marker of disease severity for patients with CF. Patients with a supplemental oxygen requirement or frequent exacerbations should have prompt referral because of their increased risk of death.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA. Electronic address: ramoskj@uw.edu.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Ramos
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Quon
authors.affiliation: Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, WA; Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA.
authors.forename: Erika D
authors.initials: ED
authors.lastname: Lease
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA.
authors.forename: Moira L
authors.initials: ML
authors.lastname: Aitken
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA; Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Goss
mesh_terms: D000328:Adult; D019121:Burkholderia Infections / Q000453:epidemiology; D016956:Burkholderia cepacia; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008168:Lung / Q000503:physiopathology*; D016040:Lung Transplantation; D008297:Male; D010102:Oxygen Inhalation Therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D011552:Pseudomonas Infections / Q000453:epidemiology; D012189:Retrospective Studies; D012737:Sex Factors; D015996:Survival Rate; D014481:United States; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: FEV(1); cystic fibrosis; lung function; lung transplantation; survival