Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion.
BACKGROUND
In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma.


OBJECTIVE
Using 15-year follow-up data from the Copenhagen City Heart Study, we now further explore this relationship.


METHODS
As part of 3 surveys in 1976 to 1978, 1981 to 1983, and 1991 to 1994, we measured pulmonary function and asked all participants about asthma and pulmonary risk factors.


RESULTS
There was no difference in annual decline in lung function between DeltaF508 heterozygotes and noncarriers overall; however, among individuals with familial asthma, the annual declines in FEV(1) and forced vital capacity (FVC) were 49 and 36 mL in DeltaF508 heterozygotes versus 24 and 17 mL in noncarriers (P =.01 and P =.12, respectively). Cross-sectionally based on triple measurements, FEV(1) and FVC in individuals aged 20 to 70 years were lower in heterozygous participants versus noncarriers (P =.02 and P =.004, respectively). The average reduction of FEV(1) and FVC in DeltaF508 heterozygotes versus noncarriers was 70 mL (P =.06) and 136 mL (P =.008). Finally, 10% of carriers reported asthma versus 7% of noncarriers (P =.02), resulting in an odds ratio of 2.0 (1.3-3.2) for asthma in DeltaF508 heterozygotes.


CONCLUSIONS
Cystic fibrosis DeltaF508 heterozygotes may be overrepresented among individuals with asthma and may have poorer lung function than noncarriers. Furthermore, DeltaF508 heterozygosity in context with familial predisposition to asthma may be associated with a greater annual FEV(1) decline.
Dahl
M
M
Department of Clinical Biochemistry, Glostrup, Herlev, and Copenhagen University Hospital, Copenhagen, Denmark.
Nordestgaard
B G
BG
Lange
P
P
Tybjaerg-Hansen
A
A
D000328:Adult; D000368:Aged; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics; D003062:Codon / Q000235:genetics*; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012129:Respiratory Function Tests; D012307:Risk Factors; D017384:Sequence Deletion; D012907:Smoking / Q000453:epidemiology; D014797:Vital Capacity
C505032:CFTR protein, human; D003062:Codon; D019005:Cystic Fibrosis Transmembrane Conductance Regulator