title: 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). Δ Amil 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.
authors.affiliation: Dept of Cystic Fibrosis, Royal Brompton Hospital, London, SW3 6NP, UK. n.simmonds@imperial.ac.uk
authors.forename: N J
authors.initials: NJ
authors.lastname: Simmonds
authors.forename: L
authors.initials: L
authors.lastname: D'Souza
authors.forename: M
authors.initials: M
authors.lastname: Roughton
authors.forename: E W F W
authors.initials: EW
authors.lastname: Alton
authors.forename: J C
authors.initials: JC
authors.lastname: Davies
authors.forename: M E
authors.initials: ME
authors.lastname: Hodson
mesh_terms: D000293:Adolescent; D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics / Q000401:mortality* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D009154:Mutation; D009297:Nasal Mucosa / Q000503:physiopathology; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D017741:Survivors; D013542:Sweat / Q000737:chemistry / Q000502:physiology; D055815:Young Adult
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator