Asthma prevalence has been rising over the past 20 years. 1 This trend is apparent worldwide and is especially clear among developed countries. 2 The most common chronic disease of childhood, asthma places a substantial burden on the individual, the family, and society. Reversible airway obstruction due to airway inflammation—the hallmark of asthma—is probably initiated by immune system effects (selective maturation of T-lymphocyte subtypes and allergic sensitization) occurring for most asthmatics very early in life. 3 While asthma development is thought to require a genetic susceptibility, environmental factors are likely critical, and almost certainly play the primary role for the increasing incidence. Supporting this perspective, the International Study of Asthma and Allergy in Childhood (ISAAC), using standardized case ascertainment, has demonstrated an extraordinarily high degree of between-country geographic variation in asthma prevalence. 4,5 A wide variety of environmental factors has been the source of study or speculation, including prenatal exposures, perinatal factors, breast-feeding and nutritional factors, childhood infections (or their absence), specific allergens, and indoor and outdoor air pollutants. 6–11
Although a body of research is developing regarding the role of air pollutant exposures on severity, exacerbations, or prevalence of asthma, 12–15 there is relatively little research on asthma initiation. For that reason, the study by Ponsonby and colleagues in this issue should attract considerable attention. 16 Their study creates a cohort of children with prospective data from infancy by linking a cross-sectional survey for asthma occurrence at age 7 with an infant cohort originally assembled to study sudden infant death syndrome (SIDS). This clever approach provides the opportunity to examine associations with asthma for some important risk factors, including certain indoor air pollutants. Notably, their results point toward the possible role of exposure to indoor combustion products on asthma initiation.
Ponsonby and colleagues provide some provocative insights into these questions by virtue of their cohort design, but our confidence in their conclusions suffers from the limitations inherent in the combination of two studies. Because of its initial focus, the infant data collection reflected the goals of the original SIDS study; and questions targeting asthma risk factors were limited. Apparently there were no biological or environmental samples collected on the original cohort. Assuming a dose-response effect of environmental tobacco smoke (ETS) on asthma onset, the cotinine validation study from a separate cohort of infants points to a different exposure pattern than the one suggested by the asthma onset pattern in the original cohort—the lowest cumulative incidence occurred in smoking homes where infant ETS exposures were limited rather than in nonsmoking homes. The available ETS, indoor gas combustion, and ventilation predictors are suggestive of an effect of combustion dose, but the results are not consistent. Exposure misclassification is one likely candidate for these inconsistent results. Another possible explanation is bias due to the interplay between exposure-related selection in the original SIDS cohort and the potential for response-related selection in the cross-sectional asthma survey. 17 Importantly, the identified associations only account for a small attributable fraction in this population. Looking beyond these concerns, we believe this study provides good justification for investing in a much more targeted asthma study beginning in infancy.
Most air pollution epidemiology studies of asthma health effects are opportunistic studies of public use datasets (eg, ecologic time-series studies of short-term ambient air pollutant effects on morbidity outcomes), relatively inexpensive observational studies such as asthma panel studies, or large cross-sectional studies. While these studies have been successful in identifying influences of criteria air pollutants on lung function changes or worsening of asthma symptoms, they have two substantial drawbacks. They do not provide insight into the increase in asthma incidence, and they have been unable to separate the relative contributions of the myriad putative environmental risk factors. The ability to separate indoor from ambient source pollutant exposures would be a particularly important contribution.
We believe it is time to study the role of air pollutants on asthma onset with a prospective birth cohort design. Despite the expense of this approach, we think that a comprehensive study of asthma initiation risk factors with an emphasis on pollutant exposures would be the most productive. Because indoor and ambient source exposures tend to be independent, 18 a well-designed cohort study has some hope of separating the effects of indoor from ambient combustion sources. Although indoor source exposures will vary across individuals in a community, it will be necessary to draw the cohort from multiple communities with diverse ambient air pollutant levels to address the effects of ambient source pollutants on asthma onset. By having a focus on air pollutants, the cohort study could include appropriate cumulative exposure monitoring (eg, passive air pollution monitors) that has the potential to give reasonable direct exposure measurements (as opposed to reliance on questionnaire data where the underlying exposures need to be inferred). A prospective cohort study will also be able to obtain good measurements of other suspected genetic and environmental risk factors.
Discriminating indoor from ambient source exposures poses a substantial challenge to the design and conduct of an affordable prospective study of air pollutant effects. Nevertheless, to make sound decisions on environmental controls for the primary prevention of asthma, this research is necessary.
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