Association between genetically determined pancreatic status and lung disease in adult cystic fibrosis patients.
OBJECTIVE
The association between genotype and phenotype in cystic fibrosis (CF) has been clearly established for pancreatic status, but not for lung disease.


METHODS
Retrospective study.


METHODS
A respiratory unit of a teaching hospital.


METHODS
We studied 51 adult CF patients for whom current data and genotype were available. Thirty-seven patients carried two severe mutations associated with pancreatic insufficiency phenotype (group S). Fourteen patients carried at least one mild (and dominant) mutation associated with pancreatic sufficiency phenotype (group M).


METHODS
We compared the course of the disease between the two groups, looking for a 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 with earlier onset (1.7 years vs 7.9 years, p = 0.0001). They presented with a more severe respiratory impairment, with a lower mean FEV(1) (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 FEV(1) < 30% (73% vs 29%, p < 0.05); and a more marked yearly decline of FEV(1) (3% vs 1.4%, p < 0.001). By multivariate logistic regression analysis, carrying two severe mutations was the only independent predictor of a terminal respiratory insufficiency (relative risk, 6.75; 95% confidence interval, 1.79 to 26.50; p = 0.003).


CONCLUSIONS
This study suggests that pulmonary disease appears to be associated with the severity of CF transmembrane regulator mutations.
Loubières
Yann
Y
Service de Pneumologie, Hôpital Foch, Suresnes, France.
Grenet
Dominique
D
Simon-Bouy
Brigitte
B
Medioni
Jacques
J
Landais
Paul
P
Férec
Claude
C
Stern
Marc
M
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000235:genetics; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000235:genetics; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000235:genetics; D011550:Pseudomonas aeruginosa; D012131:Respiratory Insufficiency / Q000175:diagnosis / Q000235:genetics*; D012306:Risk
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator