Invited commentary: is indoor mold exposure a risk factor for asthma?

A remarkably consistent association between home dampness and respiratory symptoms and asthma has been observed in a large number of studies conducted across many geographic regions (1–10). In a recent review of 61 studies, it was concluded that dampness was a significant risk factor for airway effects such as cough, wheeze, and asthma, with odds ratios ranging from 1.4 to 2.2 (8). Positive associations have been shown in infants (4, 5), children (1, 2, 10), and adults (6, 7, 9), and some evidence for doseresponse relations has also been demonstrated (11). Although it has been concluded that the evidence for a causal association between dampness and respiratory morbidity is strong (3, 8), this evidence is based mainly on crosssectional studies and prevalence case-control studies; few prospective studies have been conducted (12). Therefore, it is not clear whether indoor dampness causes or only exacerbates preexisting respiratory conditions such as asthma. Interestingly, a recent large European multicenter study in adults showed not only a significant homogenous association across centers between self-reported mold exposure and asthma symptoms but also a higher prevalence of asthma in centers with high self-reported indoor mold exposures (9); this suggests that dampness/moldiness may potentially be involved in the primary causation of asthma. It is not clear whether molds are merely markers of dampness or are causally related to the symptoms associated with dampness (12, 13). Assessment of exposure to molds in most studies has invariably been done by questionnaire, and it is unknown to what extent questionnaire reports of mold growth correlate with exposure to relevant mold components. The studies that have included objective measurements of mold exposure have generally involved culturing spores from indoor air (14) or from settled dust (15); only a few of these studies showed a positive association between measured exposure and asthma or asthma-like symptoms (see reviews by Verhoeff and Burge (13) and Garrett et al. (14)). Perhaps more importantly, very few longitudinal studies have been performed that have included exposure measurements. Thus, the study by Belanger et al. in this issue of the Journal (16) is one of the first to address the issue of mold exposure and asthma development in a birth cohort study. Belanger et al. measured a number of indoor exposures early in life, including mold exposure, both by questionnaire and by measuring total airborne culturable spores, and studied the association with wheeze and cough at 12 months of age. Interestingly, the strongest association was found for mold exposure, whether it was assessed by questionnaire (odds ratios = 1.55–2.27; p < 0.05) or by measured exposure (per 20 colonies, odds ratios = 1.10– 1.23; p < 0.05 only in children whose mothers had asthma), whereas no associations or only minor associations were found for indoor allergen levels. Mold effects were most pronounced among infants whose mothers had asthma, which suggests potential differences in susceptibility to these exposures for children with and without asthmatic mothers. In a previous article, Gent et al. (17) showed in the same infants that high levels of measured Penicillium were significantly associated with both wheeze (relative risk = 2.15; p < 0.05) and persistent cough (relative risk = 2.06; p < 0.05). No associations were observed for other mold species. These results thus suggest that early mold exposure may increase the risk of asthma (with perhaps a larger risk for children of asthmatic mothers). However, these findings should be interpreted with caution because of the poor predictability of early wheeze and cough in asthma development (18). In addition, infants were selected on the basis of having an older asthmatic sibling; therefore, it is not clear whether results can be extrapolated to a “normal,” low(er)risk population. Finally, although the associations with reported exposure were “confirmed” by measured mold exposure, it is debatable whether a one-time measurement of airborne culturable mold spores qualifies as a valid measure of chronic exposure (see below).