Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort

Methods

Results

The 3798 children included in our study population did not differ from the complete cohort (N = 4089) with regard to the distribution of risk factors (Table S1). At baseline, 299 (9.1%) of children were exposed to mold odor, 325 (8.6%) to visible mold, 758 (23.5%) to dampness damage, and 967 (30.4%) to any mold or dampness indicator. The overlap between mold odor, visible mold, and dampness damage is presented in Fig. S1. Dampness damage was the most prevalent mold or dampness indicator, and coincided with both visible mold and mold odor.

Exposure to any mold or dampness was more prevalent among children exposed to maternal smoking during pregnancy, parental smoking during infancy, parental allergic disease, shorter duration of breastfeeding, younger mothers, lower socioeconomic status, pet ownership, having older siblings, and homes constructed 1975 and earlier (Table 1).

At 16 years of age, 199 (6.4%) of children had asthma, 785 (25.4%) had rhinitis, and 1162 (45.9%) were sensitized to any food or aeroallergen.

In longitudinal analyses up to 16 years of age, exposure to mold odor, visible mold, and dampness damage as an infant were all associated with an overall increased risk of prevalent asthma (Fig. 1). Increased risks for prevalent rhinitis through 16 years of age were also observed among children exposed to mold odor (OR 1.29; 95% CI 1.03–1.62) and visible mold (OR 1.28; 95% CI 1.04–1.58), but not for dampness damage. No apparent associations were observed between any mold or dampness indicator and IgE sensitization to airborne or food allergens. Following adjustment for mold and dampness indicators during the follow‐up, our findings remained relatively unchanged (Fig. S2).

In exposure–response analyses, we observed a significant trend for increased odds of asthma with increasing exposure score (P _trend = 0.002) (Table 2). Children exposed to all three indicators of mold or dampness had an overall increased odds of asthma up to 16 years of age (OR 1.73; 95% CI 1.10–2.74) compared with those unexposed to mold or dampness. A positive trend was also suggested for rhinitis (P _trend = 0.14), but not for aeroallergen or food allergen sensitization.

The association between any mold or dampness indicator with allergic and nonallergic phenotypes of asthma and rhinitis is summarized in Table 3. Among children exposed to any mold or dampness indicator during infancy, increased risks were observed for nonallergic asthma (OR 1.80; 95% CI 1.27–2.55) and nonallergic rhinitis (OR 1.41; 95% CI 1.03–1.93), but no associations were observed for allergic asthma or rhinitis. Similar patterns were observed when exposure to mold odor, visible mold, and dampness damage was analyzed separately (data not shown).

In analyses of clinical phenotypes of asthma, children exposed to any mold or dampness indicator during infancy had an increased odds of persistent asthma (OR 1.73; 95% CI 1.20–2.50), but not early‐transient or late‐onset asthma (Fig. 2). The association between asthma clinical phenotypes with mold odor, visible mold, and dampness damage provided a similar picture for persistent asthma. Exposure to dampness damage was associated with late‐onset asthma (OR 1.41; 95% CI 1.02–1.95).

Comparable odds ratios for asthma were observed across strata of building construction periods (Tables 4 and S2). For rhinitis, somewhat higher odds ratios were suggested among children living in buildings constructed after 1975. However, there were no significant interactions between any mold or dampness indicator and year of construction for either asthma or rhinitis (data not shown).

In addition, exposure to any mold or dampness indicator was associated with comparable odds ratios for asthma among children with (OR 1.49; 95% CI 1.10–2.02) and without (OR 1.21; 95% CI 0.93–1.57) parental allergic disease (Table S3). In an interaction model, no statistical significant interaction was suggested (P = 0.35). Likewise, no differences between strata or significant interaction was observed for rhinitis (P = 0.94).

In a sensitivity analysis of movers (n = 3135) and nonmovers (n = 663), children exposed to visible mold during infancy and moved had increased risks for asthma (OR 1.49; 95% CI 1.14–1.96) and rhinitis (OR 1.41; 95% CI 1.13–1.77) that was not observed in nonmovers (Table S4). Analogous results were seen for mold odor, while an increased risk of asthma was suggested for both movers and nonmovers among children exposed to dampness damage or any indicator.

Discussion

In this prospective birth cohort study, we found that exposure to mold or dampness indicators during infancy increased the odds of asthma through adolescence. An increase in the number of mold and dampness indicators was associated with a greater risk of asthma. Similarly, infants exposed to mold odor or visible mold had an increased risk of rhinitis. These associations remained following adjustment for mold and dampness indicators throughout follow‐up. In analyses of allergic phenotypes, the association was confined to nonallergic asthma and rhinitis. No association was observed between mold and dampness indicators and IgE sensitization to aero‐ or food allergens. Looking at clinical phenotypes, exposure to mold or dampness was associated with persistent asthma, but not with early‐transient or late‐onset asthma.

Our results are in line with other studies reporting associations between early mold or dampness exposures and asthma in young children 3, 8, 10, 23. In addition, we demonstrated that exposure to mold or dampness indicators in early infancy was associated with an increased risk of asthma up to 16 years of age. Few prospective studies have been able to examine this association beyond 10 years of age, and a German birth cohort showed no association between exposure to mold in early in life and asthma up to 20 years of age 15.

Our findings for rhinitis are also consistent with recent studies of infants, children, and adults, which found increased risks related to mold or dampness exposure in the home 8, 23, 24. Likewise, a systematic review concluded that the highest risk of rhinitis was among those exposed to mold odor and visible mold 11.

Previous studies of allergic and nonallergic phenotypes of asthma and rhinitis have shown conflicting results 9, 25, 26, but our data support the findings that the association is confined to nonallergic asthma and rhinitis 9. In addition, the lack of association between mold and dampness indicators and IgE sensitization in our study is in line with some 6, 8, 10 but not all previous studies 27, 28, 29, 30.

Our study is unique in that we were able to assess clinical phenotypes of asthma and track the onset and persistence of asthma. We show that early exposure contributes to persistent asthma symptoms through adolescence, but not to early‐transient asthma. Rhinitis is rather uncommon before school age 31, 32; therefore, we chose not explore clinical phenotypes of rhinitis in the present study.

Our finding that early‐life exposure to mold or dampness may play a role for development of asthma and rhinitis is analogous to corresponding associations for other environmental exposures such as air pollution or secondhand tobacco smoke 18, 33, 34. These findings lend support to the hypothesis that early‐life exposures contribute to health outcomes later in life.

Early‐life exposure to molds could cause recurrent irritation and immune activation in the respiratory tract, inducing prolonged inflammation, prompting the genesis of inflammatory‐related diseases, like asthma and rhinitis 10, 23. Certain fungal species are associated with inflammatory processes, and molds may contain substances which have inflammatory effects such as β‐1‐3‐glucans in the cell wall structure, microbial volatile organic compounds (mVOCs), extracellular polysaccharides, and mycotoxins 3, 6, 8, 35. Our results indicate that exposure to any mold or dampness indicator primarily increases the risk of nonallergic asthma and rhinitis, which may speak in favor of irritative rather than allergic inflammatory changes in the airways. Evidence from a case–control study suggests that nonallergic asthmatics have higher nasal and bronchial epithelia sensitivity to nonallergic factors like strong smells, air pollution, cold air, and respiratory viruses, compared with allergic asthmatics 36. Supporting our findings, two mouse models identified fungal glucans [(1→3)‐β‐d‐glucans] and toxic metabolites to influence nonallergic inflammatory respiratory effects, such as increased concentrations of leukocytes and pro‐inflammatory cytokines in bronchoalveolar lavage fluid 37, 38.

Somewhat higher risks of rhinitis were suggested among children living in homes built after 1975 compared with children living in homes constructed prior to 1961. This is in line with a previous study in Swedish adults that indicated higher risks of current rhinitis among those living in homes constructed from 1976 to 1985 39. Buildings constructed from 1976 to 1985 were influenced by energy saving constraints due to the rapid rise in oil prices in 1974, and utilized novel building materials and techniques 40. Furthermore, in Sweden from 1977 to 1983 a self‐leveling mortar containing the protein casein was utilized, but has since shown to emit certain chemicals such as ammonia and sulfhydryl compounds when exposed to dampness 39.

In analyses stratified on moving status, visible mold or mold odor was associated with an increased risk of asthma and rhinitis among children who had ever moved, but not among the nonmovers. One could speculate that among families that moved, some may have done so due to a suspected or apparent mold problem. However, as 83% of the cohort moved during follow‐up, the numbers are low among nonmovers, and no reasons for moving were queried, so these results cannot be ruled out as spurious findings.

The prospective design, large number of participants, high retention rate, and repeated assessments of allergic disease at six different time points are significant strengths of our study. The longitudinal design allowed us to investigate the temporal sequence between early‐life exposure and health outcomes up to adolescence, and to study the timing of onset and persistence of these allergic diseases.

Several limitations to our study should be acknowledged. Exposure to mold and dampness were ascertained by parental questionnaires, and some exposure misclassification is probable. Questionnaire‐based data are subjective and lack sensitivity and specificity. For example, perceived mold odor in the home may in fact be from chloroanisoles, which are produced by microbes that methylate chlorophenols in wood preservatives in moist conditions, but which do not necessarily indicate major problems with dampness and molds as the odor thresholds of some common chloroanisoles are extremely low 41. Home inspection is a more standardized way of assessing exposure, but it is not often feasible to perform with a large number of participants and homes, and interinspector variation is common 5, 42. In the BAMSE birth cohort, a subset of 540 children's homes were inspected between the child's age of 1 and 2 years for dampness and mold indicators. The overall agreement between the parental reported and inspector noted signs of mold and dampness was rather weak, but increased odds of recurrent wheezing in infancy were observed for both exposures 43. Parents and inspectors reported at different times, so remediation of dampness or mold problems could have occurred prior to the inspector's visit. In this subset of our cohort, families with parental allergic disease more often reported problems with mold or dampness, and also had a tendency toward higher measured values of indoor humidity 43. In the present analyses, risk estimates for asthma and rhinitis were elevated both among children with and without parental allergic disease. Outcome misclassification can be a concern when analyzing data collected by questionnaires, but the definitions of asthma and rhinitis used in this study were modified based on the validated ISAAC questionnaire 44 and have been used in prior publications 18, 31.

In conclusion, our findings indicate that exposure to mold or dampness during infancy increases the risk of asthma and rhinitis through 16 years of age, particularly for disease without IgE sensitization. Early exposure to mold or dampness may be particularly associated with persistent asthma up to adolescence.

Author contributions

JDT, OG, GP, EM, JCL, IK, and AB contributed to the design and planning of this study, participated in the interpretation of the findings, and critically revised the manuscript. JDT performed the data analyses and drafted the initial manuscript. All authors approved the final manuscript as submitted.

Funding

The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Research Council for Working Life and Social Welfare, The Swedish Asthma and Allergy Association Research Foundation, The Swedish Research Council Formas, Stockholm County Council, and the European Commission's Seventh Framework 29 Program MeDALL under grant agreement No. 261357. Thermo Fisher Scientific kindly provided the reagents for IgE analyses. None of the funding sources had a role in the study design, conduct, analysis, or reporting.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supporting information

Thacher JD, Gruzieva O, Pershagen G, Melén E, Lorentzen JC, Kull I, Bergström A. Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort. Allergy 2017; 72:967–974.