GENOTYPE-PHENOTYPE RELATIONSHIPS IN A COHORT OF ADULT CYSTIC-FIBROSISPATIENTS

In cystic fibrosis (CF), relationships between genotype and phenotype have been shown for pancreatic status but not for pulmonary disease. O ne hundred and ten adult CF patients were classified according to the expected effect of their mutations on cystic fibrosis transmembrane co nductance regulator (CFTR) protein: Group 1 (n=48) included Delta F508 homozygotes; Group 2 (n=261, patients with two ''severe'' mutations a nd no expected CFTR production; Group 3 (n=17), patients with expected partly functional CFTR corresponding to at least one ''mild'' mutatio n; Group 4 (n=19), patients with no mutation identified or only one id entified ''severe'' mutation. As compared to Groups 1 and 2: patients from Groups 3 and 4 had higher arterial oxygen tension (Pa,O-2) (9.5+/ -1.9 and 9.9+/-1.5 vs 8.8+/-1.5 and 8.3+/-1.7 kPa, respectively p<0.02 ); and a slower decline in their pulmonary function, estimated by the mean annual loss in forced vital capacity (FVC) (1.2+/-1.0 and 1.5+/-1 .1 vs 2.0+/-0.9 and 2.2+/-1.0%, respectively; p<0.01) and in forced ex piratory volume in one second (FEV1) (1.7+/-1.1 and 1.9+/-1.3 vs 2.6+/ -1.0 and 2.8+/-1.0%, respectively; p<0.005), They had fewer episodes o f colonization of the airways by Pseudomonas aeruginosa, and colonizat ion occurred at a more advanced age (median age 25 and 19 vs 15 and 17 yrs, respectively; p<0.01) and required fewer intravenous antibiotic courses (p<0.01), Pancreatic insufficiency was less frequent in Groups 3 (23%) and 4 (63%) than in Groups 1 (100%) and 2 (96%). This study s uggests that the phenotype of adult cystic fibrosis patients, includin g the severity of the lung disease, is related to the severity of the cystic fibrosis transmembrane conductance regulator mutations.