© 2004 American Thoracic Society
Fungal Exposure and Lower Respiratory Illness in ChildrenTo the Editor:The limitation of data concerning clinically relevant exposures to agents, including fungi, in the indoor environment has been identified as an important problem by scientists studying building-related illness (1, 2). Despite the attempts to objectively characterize fungal exposure, the recent study of lower respiratory illness (LRI) among children by Stark and colleagues (3) appears to have important limitations in exposure assessment. The method of defining fungal exposure used in that study places emphasis on specific fungal types, but does not allow for any characterization of the total fungal count in the areas being evaluated. As described in the study by Stark and colleagues (3), a home could have a "high fungal level" when persons in other homes could easily be exposed to greater concentrations of total fungi. For example, a home with an airborne Aspergillus level of 100 cfu/m3 but no other fungi would be considered to have a "high fungal level," whereas a home with an Aspergillus level of 37 cfu/m3, Cladosporium of 177 cfu/m3, and Penicillium of 130 cfu/m3 (mean airborne concentrations from the study, yet totaling 240 cfu/m3) would not be "high" because none of those concentrations exceed the 90th percentile. Given the uncertainties concerning mechanisms of illness related to fungi, misclassification bias would be an important consideration for this type of exposure assessment. We agree with the authors that another important limitation of their exposure assessment involves fungal samples being taken only once at the beginning of the survey, whereas information on the outcome measures were collected every 2 months for a year. It remains unclear whether there is any clinical relevance of measures of fungal exposure taken up to 12 months before LRI (or any other health effect). In the article by Stark and colleagues (3), there appears not to have been any assessment of exposure to environmental tobacco smoke (ETS), whether at home or in daycare settings. Because ETS is known to be associated with increased morbidity in children (4), some assessment of ETS among the study participants would be important. Finally, the authors draw conclusions concerning the relationship of measured fungal concentrations in houses with the presence or absence of water damage or visible mold in those houses. The methods of assessment of water damage/visible mold are not described, but the assessment appears to be based on parental self-report. We question the usefulness of such occupant self-report and suggest that an objective assessment of the indoor environment for moisture (perhaps using a moisture meter) would be more appropriate. In summary, problems with assessment of exposure to fungi in the indoor environment, such as those pointed out above, are certainly not unique to the study in question. However, it is important to point out these limitations because they call into question the ability of the authors to draw conclusions concerning (1) appropriate types of evaluation techniques for indoor environments (the need for fungal sampling) and (2) the relationship of illness to exposure to fungi in the indoor environment.
National Institute for Occupational Safety and Health Centers for Disease Control and Prevention Cincinnati, Ohio FOOTNOTES Conflict of Interest Statement: D.B.T. and E.H.P. have no declared conflict of interest. REFERENCES
From the Authors: There is no consensus on a correct manner of characterizing potential fungal exposure in the home. Each method of estimating exposure through fungal measurement has significant limitations that would generally result in an underestimate of health effects by attenuating associations (1) (bias to the null). Because our starting point was examining the prospective associations between lower respiratory illness (LRI) and the presence of home levels of individual taxa that were relatively high for the cohort (>90th percentile for the cohort), it was sensible to follow these analyses by testing the a priori hypothesis that having a relatively high level of any one of the taxa might increase the risk for LRI. Drs. Trout and Page present an equally valid but different hypothesis: that even if one does not have a relatively "high" level of any one taxon, having an absolutely high total fungal count in the home may be associated with health effects. By examining "total" fungal counts exclusively, one would place emphasis only on the most abundant taxa—taxa that grow well on the plate or are abundant in ambient air or in the carpet/floor coverings. For example, homes with relatively high dust Alternaria levels (90th percentile, 8,333 cfu/g) but low yeasts (90th percentile, 58,000 cfu/g) would not be considered to have high fungal levels. We tested the alternative hypothesis that being in the 90th percentile of total fungi (for the taxa presented in the article [2]) predicted LRI, and found that being in homes with greater than 90th percentile for total airborne fungi predicted marginally higher risk for LRI (relative risk = 1.46; 95% confidence interval: 1.00–2.15), but being in homes with greater than 90th percentile for total dust-borne fungi did not. This suggests that in our cohort, having relatively high levels of known taxa, many of which have documented irritant or allergenic properties, is more predictive of infant LRI than having absolutely higher total levels of fungi, regardless of taxon composition. An additional limitation of using total culturable fungi is that many fungi that could be involved in exposure may be intrinsically unculturable, and thus are not included in the total count, constituting a significant confounder for total counts, but not for counts of specific culturable taxa. As we stated (2), we were limited in that air and dust samples were taken only once in the first 2 to 3 months of each child's life and may not represent integrated exposure over the entire first year of life. However, it is a reasonable hypothesis that exposure to fungi in the first few months of life may influence the immune system or the propensity to respiratory symptoms, or both, over the first year of life. Moreover, it is possible that dust fungi represent, perhaps more than air fungi, the fungal characteristics of the home over longer periods. We did consider the potential independent or confounding effects of environmental tobacco smoke (ETS) (2). Only 7% of children were exposed to ETS at home and 6% in daycare settings. Thus, whereas other studies with higher smoking rates have found reproducible significant effects of ETS on LRI in infancy, we did not. In univariate analyses, smoking in daycare settings was marginally (p = 0.12) associated with LRI; but in our final models, the association was less significant and did not change the magnitude or precision of the estimate of the effect of fungi on risk for LRI. Moisture meters and point measurements of relative humidity are not gold standards for evaluating home dampness (3, 4). With their acknowledged limitations, questions regarding home dampness are a well established and accepted tool used to evaluate the reproducible associations between dampness and LRI in infancy (4). The combination of exposures that home dampness represents is not fully understood. Dampness likely represents other exposures in addition to fungi, and may represent conditions leading to fungal exposure not detected through culturable fungal methods (5). In cross-sectional studies, parents who have children with symptoms may tend to be biased toward answering positively to home dampness questions, but our study was longitudinal and less prone to this bias. In summary, although we recognize the limitations of all studies of associations of home fungal levels with LRI, we believe that it is unlikely that the associations that we found between fungi and LRI risk are caused by bias or unmeasured confounders. Confidence in these findings will come if they are reproducible in other studies (4), and more work is needed to develop feasible methods of improving the characterization of early childhood fungal exposure in large-scale birth cohort studies.
a Channing Laboratory, Brigham and Women's Hospital Harvard Medical School Boston, Massachusetts FOOTNOTES Conflict of Interest Statement: D.G. and P.C.S. have no declared conflict of interest. H.A.B. consults for the Sharper Image, which markets an air cleaner designed to address exposure to fungal spores and other airborne contaminants, and receives approximately $6000 per month for these services. REFERENCES
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