Impact of pulmonary exacerbations and lung function on generic health-related quality of life in patients with cystic fibrosis

Background: The analysis aimed to examine the impact of pulmonary exacerbations (PEs) and lung function on generic measures of HRQL in patients with cystic fibrosis (CF) using trial-based data. Methods: In a 48-week randomized, placebo-controlled study of ivacaftor in patients >= 12 years with CF and a G551D-CFTR mutation the relationship between PEs, PE-related hospitalizations and percent predicted forced expiratory volume in one second (ppFEV(1)) with EQ-5D measures (index and visual analog scale [VAS]) was examined in post-hoc analyses. Multivariate mixed-effects models were employed to describe the association of PEs, PE-related hospitalizations, and ppFEV(1) on EQ-5D measures. Results: One hundred sixty one patients (age: mean 25.5 [SD 9.5] years; baseline ppFEV(1): 63.6 [16.4]) contributed 1,214 observations (ppFEV(1): no lung dysfunction [n = 157], mild [n = 419], moderate [n = 572], severe [n = 66]). Problems were most frequently reported on pain/discomfort, anxiety/depression, and usual activities EQ-5D items. The mean (SE) EQ-5D index nominally decreased (worsened) with worsening severity of lung dysfunction (P = 0.070): 0.931 (0.023); mild: 0.923 (0.021); moderate: 0.904 (0.018); severe: 0.870 (0.020). 146 PEs were experienced by 72 patients, including 52 PEs (35.6 %) that required hospitalization. Mean EQ-5D index and VAS scores were lowest (worst) within 1 week (before or after PE start) for PEs requiring hospitalization. Pulmonary exacerbations, PE-related hospitalizations, and ppFEV1 were significant predictors of EQ-5D index and VAS. Conclusions: In a clinical study of patients with CF (>= 12 years of age and a G551D-CFTR mutation), PEs, primarily those requiring hospitalization, were associated with low EQ-5D index and VAS scores. The impact of ppFEV1 was relatively smaller. Reducing PEs, in particular those requiring hospitalization, would likely improve HRQL among these patients.