DELTA-F508 HETEROZYGOSITY IN CYSTIC-FIBROSIS AND SUSCEPTIBILITY TO ASTHMA

Background Cystic fibrosis is a recessive disorder mainly characterise d by lung disease. We tested the hypothesis that individuals heterozyg ous for the common cystic fibrosis Delta F508 mutation are at risk of obstructive pulmonary disease. Methods We studied a cross-sectional sa mple from the general population of Copenhagen, Denmark, aged 20 years and older, We did spirometry to measure forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), and did genotyping on blood samples of 9141 individuals. We asked all participants whether they h ad asthma, and asked for information on smoking and other factors that could have contributed to obstructive pulmonary disease. Findings We identified 250 carriers of the Delta F508 mutation (2.7% [95% CI 2.5-3 .1]). 9% of carriers reported having asthma compared with 6% of non-ca rriers (p=0.04). The odds ratio for asthma in participants heterozygou s for Delta F508 mutation was 2.0 (1.2-3.5, p=0.02). Furthermore, amon g individuals with airway obstruction, the percentage predicted FEV1 a nd FVC were significantly lower in participants heterozygous for Delta F508 than in non-carriers (49 vs 58%, p=0.004; and 70 vs 82%, p<0.001 , respectively), mainly due to an effect in those with self-reported a sthma. Interpretation Cystic fibrosis Delta F508 heterozygosity may be over-represented among people with asthma and seems to be associated with decreased pulmonary function in people with airway obstruction wh o also have asthma.