Study objectives: The association between genotype andphenotype in cystic fibrosis (CF) has been clearly established forpancreatic status, but not for lung disease.
Setting: A respiratory unit of ateaching hospital.
Patients: We studied 51 adult CFpatients for whom current data and genotype were available.Thirty-seven patients carried two severe mutations associated withpancreatic insufficiency phenotype (group S). Fourteen patients carriedat least one mild (and dominant) mutation associated with pancreaticsufficiency phenotype (group M).
Measurements: Wecompared the course of the disease between the two groups, looking fora genotype/phenotype association for lung disease.
Results: The mean age of the population was 30 years.Patients with two severe mutations presented more severe disease withearlier onset (1.7 years vs 7.9 years, p = 0.0001). They presentedwith a more severe respiratory impairment, with a lower meanFEV1 (29% of predictive value vs 58% of predictive value,p < 0.001); a higher Pseudomonas colonization rate (97% vs 57%,p < 0.01); a more frequent end-stage respiratory insufficiency,defined by a FEV1 < 30% (73% vs 29%,p < 0.05); and a more marked yearly decline of FEV1 (3%vs 1.4%, p < 0.001). By multivariate logistic regression analysis,carrying two severe mutations was the only independent predictor of aterminal respiratory insufficiency (relative risk, 6.75; 95%confidence interval, 1.79 to 26.50; p = 0.003).
Conclusion: This study suggests that pulmonary diseaseappears to be associated with the severity of CF transmembraneregulator mutations.