This meta-analysis extends previous work by focusing on atopy-controlled studies, which has been well established as a source of confounding in individual studies, and examining the relationship between SHS exposure and onset of childhood asthma. We have evaluated and adjusted for additional sources of heterogeneity among summary RR by meta-regression methods and observed consistent patterns of elevated RRs among studies. We observed a consistent, positive association between household SHS exposure and current, ever, and incident asthma. We also observed an elevated summary RR for incident asthma that was statistically significant among studies of schoolchildren with postnatal exposure to SHS. We did not find that restricting exposure to postnatal SHS was an important modifier of summary RRs for any of the asthma outcomes. Recent reports by Cook and Strachan (1999)
and the U.S. DHHS (2006)
have concluded that prenatal exposure to maternal smoking is not necessary to elicit an adverse effect. Our meta-regressions support this conclusion.
In our meta-regression of average household SHS exposure and ever asthma, covariate control accounted for much of the heterogeneity. The effect of not controlling for family history of atopy reduced the RR among ever asthma studies, and lack of control for both child and family history of atopy reduced the estimate of RR among incident asthma studies. These findings suggest that this confounding variable biases the estimate of RR toward the null.
Recent studies have identified elevated levels of endotoxin in cigarette smoke and SHS indoor spaces (Hasday et al. 1999
; Larsson et al. 2004
). It is plausible that elevated endotoxin exposure would cause elevated immunoglobulin E levels in families (including the child) exposed to SHS, and thus affect the likelihood of atopy and subsequent asthma. However, we were unable to analyze the relationship between exposed and unexposed family members and their atopy (and subsequent asthma) status separately because we did not have individual-level data.
We observed that summary RRs from studies that examined ever asthma among younger children were slightly higher than RRs from studies of exclusively older children. These findings are contrary to the findings from cohort studies but consistent with previous reviews (Cook and Strachan 1999
; Strachan and Cook 1998
Most of the cross-sectional studies assessed SHS exposure status by asking if household or parental sources currently smoked. One explanation of these findings is that RRs from cross-sectional studies of older children could be biased downward because assessment of current SHS exposure status may not reflect early-life exposure. For example, parental smoking habits may change once symptoms of allergy or asthma appear in their children. If this occurred among older asthmatics, then these children may be classified as nonexposed, which would result in a differential misclassification of exposure among cases. This source of bias is avoided in prospective cohort study designs.
When studies did not restrict subjects to nonsmoking children, summary RRs were higher, possibly due to bias upward from exposure among studies that overlooked this source of SHS exposure. It is also possible that study subjects who themselves are smokers are more likely to have been exposed to higher levels of household SHS (Wang et al. 1999
). Therefore, including smokers in the analysis would increase the RR of developing asthma among the study population. However, most studies did not assess whether asthma developed among study subjects before taking up a smoking habit of their own.
The RR for the average household SHS exposure effect on ever asthma appeared similar to the effect on current and incident asthma, according to our meta-regression analysis. The RR for prevalent asthma could be slightly lower because of bias downward if household exposure to SHS occurred up to the time of asthma diagnosis and then stopped. This would mean that asthmatics with past but not current household SHS might be misclassified as nonexposed.
Cook and Strachan (1999)
, Strachan and Cook (1998)
, and the U.S. DHHS (2006)
observed a stronger RR for incident asthma or wheezing illness among younger children compared with their findings among older children. These investigators suggested that the stronger relationship with younger children might be attributed to exacerbation of intercurrent infection among young children, resulting in transient wheeze that would tend to diminish with age and increasing airway caliber. This proposed mechanism would suggest that SHS may not be a sole primary cause of early childhood asthma; rather, it may be one of several required co-factors that when combined may lead to asthma development.
In our cohort study meta-regression, we also found that much of the observed heterogeneity was accounted for by the age category of children in the study. Most important, older children exposed to SHS were more likely than younger children to develop asthma. We found no evidence that RRs from studies using physician diagnosis to identify cases were systematically different than RRs from studies that did not identify cases in this way. The differences in our meta-analysis findings versus earlier studies are likely attributed to differences in approach and the inclusion of studies in our meta-analysis published after the previous meta-analyses. We looked more precisely at the relationship between SHS exposure and asthma as distinct from wheeze alone, and we restricted our analysis to studies that controlled for atopy history. Thus our meta-analysis examines a subtly different question than earlier meta-analyses (Cook and Strachan 1999
; Strachan and Cook 1998
), and takes advantage of the increased body of epidemiologic literature.
Because cohort studies classify subjects by exposure at the start of follow-up, it is less likely that exposure misclassification would occur and more likely that the child’s age is a reasonable surrogate measure of the length of time study subjects are exposed to household SHS. This positive relationship between a surrogate of duration of household SHS exposure and RR was also observed within individual studies (Neuspiel et al. 1989
; Wolf-Ostermann et al. 1995
). Hence, a finding that higher summary RRs occurred in studies of older children suggests that SHS exposure duration may also play a fundamental role in the development of asthma.
The positive relationship with age category identified in these studies suggests that the risk of developing asthma from a longer time of exposure to SHS increases in later childhood. The RRs among studies that examined incident asthma were more positively associated with SHS exposure than were studies of prevalent asthma. The elevated RRs for the association between household SHS and prevalent as well as incident asthma suggest that the association between SHS exposure and asthma is not caused by selection or misclassification biases.
A mechanistic theory consistent with our findings holds that the development of asthma can be causally associated with the chronic effects from exposure to SHS on bronchial hyperreactivity rather than the acute effects of SHS exposure on airway caliber (Halken et al. 1995
; U.S. EPA 1992
). Others have also recently drawn this conclusion [“postnatal exposure shows a causal link with the development of asthma in childhood” (Gilmour et al. 2006
); and “strong evidence also supports a causal role of environmental tobacco smoke in childhood asthma, especially in the induction of asthma, but also in the poor overall control of an established disease” Jaakkola and Jaakkola 2002
)]. The question of asthma incidence increasing with age and duration of exposure is important because if RR increases with age and duration of exposure, it becomes less likely that asthma from SHS exposure early in life is attributed solely to a transient vulnerability in early childhood that is less likely to result in enduring disease. It also means that public health interventions to stop childhood SHS exposure may have a positive benefit in preventing asthma induction beyond early childhood.