Asthma and lung development: Another piece in the jigsaw, but the full picture has yet to emerge

Abstract

longitudinal studies with repeated measures to adulthood. 1-3 These have been generally supportive of the concept that deviation of lung function variables from age-based norms are maintained (‘‘track’’) relative to normative trajectories from midchildhood onward. Naturally, this has generated a great deal of interest in the processes that influence the development of lung function in the formative early years. Asthma is associated with low lung function and might contribute to long-term airway development abnormalities through inflammation and remodeling, at least in patients with severe disease, 4 as well as sharing some features in common with chronic obstructive pulmonary disease. 5 Therefore it would appear to be a promising candidate for a role in determining lung function trajectory in early childhood. However, this is complicated by the difficulties of disaggregating the heterogeneous phenotypes of asthma and wheezing illnesses during the period of rapid lung development in the first 2 years after birth. Additionally, in those select cohort studies that have measured lung function soon after birth, it is clear that low lung function in infancy can precede the development of subsequent asthma in childhood. In this issue of the Journal, Lodrup Carlsen et al 6 report follow-up to adolescence of a group of childrenwhohadlungfunctionmeasuredasinfantsandwhohavehad their asthma status determined by using standardized instruments at age 10 and 16 years. 6 Their main finding was that an asthma phenotype defined on the basis of its comorbidity with eczema and rhinitis was associated with persistently low lung function from birth to age 16 years. However, despite the seeming importance of allergic diseases as components of the adverse asthma phenotype, there was no evidence to suggest that allergic sensitization influenced childhood lung function trajectories. The authors conclude that this evidence points to a process that has intrauterine origins, which are then manifest as a combination of pulmonary and immunologic developmental abnormalities, although without evidence of allergic sensitization occurring in the latter. This study was based on a subset of the Norwegian Environment and ChildAsthmapopulation-basedcohortstudyandusedastatistical approach that captured lung function trajectories of patients. The challenges of measuring lung function in infants has been a general limitation on the size of such population studies, including this one. Longitudinal measures were available for 329 participants, of whom 231 had no history of recurrent bronchial obstruction in early childhood or asthma later on. Therefore when asthma phenotypes were assigned, only 56 subjects had current asthma, and these were further subdivided into 4 groups, with inevitable limitations on the precision of estimates and statistical power to detect between-group differences. Another limitation is the definition of phenotypes at the outcome based on data at age 16 years, making comparison difficult with studies that defined asthma and allergy phenotypes prospectively from early childhood. This includes a number of studies that have defined asthma phenotypes on time-based criteria, 7,8 whichtheauthorsdismissasnoncontributorytotheunderstanding of lung development in childhood, despite clear and replicated differences in lung function outcomes in midchildhood associated with these phenotypes in large population samples. The authors’ own analyses of time-dependent phenotypes resulted in such small groups that it was unlikely any true differences in lung function outcomes would be revealed in this population. Despite the inherent technical challenges, a number of groups havesuccessfully developed cohorts with lung function measured in presymptomatic infants, although using different methods. These have provided fascinating insights into the association between lung function developmental variations and wheezing illnesses in young children. The Tucson Children’s Respiratory Study first drew attention to the association of transient early wheezing with low lung function soon after birth. 9 This is consis