Cystic fibrosis and survival to 40 years: A study of cystic fibrosis transmembrane conductance regulator function

Abstract

Significant survival heterogeneity exists in cystic fibrosis. Our aim was to determine whether residual function of the cystic fibrosis transmembrane conductance regulator (CFTR) is present in long-term survivors with severe mutations. Nasal potential difference (PD) and sweat chloride were measured in 34 long-term survivors (aged ≥40 yrs) and compared with young patients (18-23 yrs) with severe (n=30) and mild (n=31) lung disease. Baseline PD was not significantly different across the three groups (long-term survivors, -42.8 (range -71.0- -20.5) mV; young/mild, -40.5 (-58.8- -19.5) mV; young/severe,-46.3 (-74.0- -20.0) mV). Response to amiloride (ΔAmil) was significantly different across the three groups (p=0.01); long-term survivors had values (27.8 (range 8.5-46) mV) which were not different to either young group, but the young/severe group had significantly higher values (29.5 (11-47) mV) than those in the young/mild group (22.0 (7-39) mV; p<0.01). Baseline PD and ΔAmil were associated with forced expiratory volume in 1 s (FEV1) (co-efficient (95% CI) -0.13 (-0.23- -0.03); p=0.009 and -0.12 (-0.20- -0.04); p=0.003, respectively). Sweat chloride was lowest (p <0.05) in the young/severe group (93.5 (74-111) mmol·L-1 versus 98.8 (76.5-116.0) mmol·L-1; long-term survivors; and 99.5 (80.0-113.5) mmol·L-1; young/mild). ΔAmil is associated with FEV1 but our findings indicate that long-term survival cannot be explained by residual CFTR function when measurements are taken in later life. Copyright©ERS 2011.