Symptoms, lung function, and β 2-adrenoceptor polymorphisms in a birth cohort followed for 10 years

Abstract

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta-2 adrenoceptor (β 2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of β 2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV 1 (P=0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V′maxFRC was reduced in those possessing Gln 27 or Arg 16 alleles, but there was no effect of β 2AR polymorphisms on FEV 1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness. © 2004 Wiley-Liss, Inc.