To the Editors:
The recent study by Matricardi et al. 1 from the Multicentre Allergy Study (MAS) cohort provides useful confirmation of existing understanding about the origins of asthma. Thus, they highlight the early roots of much childhood wheeze and the good prognosis of not wheezing in early life. Their confirmation of the heterogeneity of childhood wheeze is also welcome and complements our similar work from the Isle of Wight Birth Cohort 2. They find common ground too with us on the importance of atopic family history and atopic sensitisation in predicting persistence of wheeze 3 in children with early-onset wheeze. However, we wish to discuss some of their main findings.
Matricardi et al. 1 restrict their discussion of predictive “risk scores” for outcome of early-life wheezing to the Tucson Index. We draw their attention to our own score, published 5 yrs ago in this journal 3. It comprises four factors: family history of asthma; recurrent chest infections in infancy; absence of nasal symptoms at age 2 yrs; and atopic sensitisation at age 4 yrs. When all four were present, there was a positive predictive value of 83.3 and a negative predictive value of 63.9 for predicting persistence of early-life wheezing up to the age of 10 yrs. That score is at least a starting point in developing a clinically relevant predictive tool. Testing it on a different population such as the MAS cohort would have been worthwhile and it is a pity that an opportunity to do that has been missed. Future collaboration between numerous research groups could provide meaningful answers to vexing questions such as “the outcome of early-life wheezing”.
The identification of risk factors for different wheezing phenotypes is important. When assessing risk factors in our cohort for development of early persistent childhood wheeze compared to never wheezing, we found somewhat different results to those of Matricardi et al. 1. Unlike them, we found that in addition to inherited atopy-related factors, environmental factors such as parental smoking, recurrent chest infections in infancy and lower social grouping were risk factors for development of that phenotype 4. It is surprising to see a lack of environmental influence in the MAS study findings. Study design may be important in that regard. Our sample was an unselected whole-population cohort, whereas the MAS cohort incorporated a subgroup deemed to be at high genetic risk of atopy. It is plausible that in the presence of overwhelming genetic predisposition for asthma and atopy such influences outweigh those of any environmental factor. Thus, the wider utility of their findings needs recognition. It is also worth noting that their “study subpopulation” was more likely to have nonsmoking parents and also to have been breastfed than the overall MAS cohort. These findings might explain the lack of environmental effects such as tobacco smoke and raise the possibility of unaccounted-for effects of social class, which might also have influenced results. Previously, we found in our cohort 5 that mothers of lower social class tended to smoke more and breastfeed less, all of which may have a complex influence on asthma risk.
The study of Matricardi et al. 1 addresses another taxing question: that of predicting which nonwheezers in early life will develop later wheeze. We previously 2 showed that such late-onset wheezers were a clinically significant group. Our findings 4 for risk factors for that phenotype showed a lack of association with environment that is consistent with those from the MAS cohort. Based on our findings for early persistent and late-onset wheeze, we proposed that while genetic predisposition towards developing asthma is crucial for wheezing phenotypes throughout childhood, environmental exposures in early life may facilitate earlier disease expression. Confirmation of such thinking is awaited but we recently highlighted 6 some of the intricate interactions of tobacco smoke and genetic polymorphism that might predispose to early persistent wheeze in our cohort. In the same issue of this journal as the study of Matricardi et al. 1, Bottema et al. 7 nicely demonstrated that the interplay of gene and environment is highly complex and intriguingly suggested that timing of environmental exposure may be paramount.
Matricardi et al. 1 serve a timely reminder of the diversity and complexity of childhood wheeze. However, the wider applicability of their findings remains to be seen and the role of environment in asthma pathogenesis merits further study. Indeed as expertise advances, the study of gene–environment relationships in wheeze and asthma development is entering an exciting new phase. As Sherlock Holmes 8 might say: “Come, Watson, come, the game is afoot!”
Statement of interest
None declared.
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