Outcomes in families of middle aged probands with asthma and wheezy bronchitis
Childhood wheezing illness encompasses at least two overlapping clinical sydromes - atopic asthma and wheeze only in the presence of upper respiratory tract infection ("wheezy bronchitis"). Despite intense interest in the genetics of asthma and atopy the familial associations of childhood wheezing syndromes have been little studied. This study reports outcomes in a total of 506 individuals in 69 three generation families ascertained through well defined middle aged probands with childhood onset atopic asthma, wheezy bronchitis and neither symptoms nor atopy. Symptomatic outcomes in children of wheezy bronchitic probands were better than in children of asthmatic probands. Despite this lung function in male children of wheezy bronchitic probands was poorer than in either other group. Trends towards poorer lung function in parents and siblings of wheezy bronchitic probands suggest a heritable effect on lung function. Children of asymptomatic, non atopic probands had high levels of respiratory symptoms and specific atopic sensitisation implying recent environmental influences affecting a group at low genetic risk for asthma. Outcomes in probands siblings did not differ suggesting that familial effects in middle age are limited. Total serum IgE levels showed evidence of familial aggregation with segregation analysis indicating a recessive major gene effect. Specific atopic sensitisation was lower in families ascertained through non atopic probands except in children where levels of specific atopic sensitisation were uniformly high. There was no evidence for bias introduced by the spouses in the families studied. This study provides further evidence for differences in the aetiology of childhood wheezing syndromes and suggests that there may be heritable effects on symptoms and lung function associated with the wheezy bronchitis phenotype. The outcomes in children of asymptomatic non atopic probands point to the importance of environmental changes in the changing prevalence of asthma in this community over the last generation.