Heterogeneity in Survival in Adult Patients With Cystic Fibrosis With FEV1 < 30% of Predicted in the United States

Abstract

Background: Lung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV₁ reaches < 30%. This study estimated transplant-free survival for patients with CF and an FEV₁ < 30% and identified predictors of death without LTx.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: FEV(1); cystic fibrosis; lung function; lung transplantation; survival.