Respiratory and Allergic Health Effects of Dampness, Mold, and Dampness-related Agents

A Review of the Epidemiologic Evidence

Mark J. Mendell; Anna G. Mirer; Kerry Cheung; My Tong; Jeroen Douwes

Disclosures

Environ Health Perspect. 2011;119(6):748-756. 

In This Article

Results

IOM Review

The IOM review of epidemiologic evidence to 2003 on dampness-related health effects found no demonstrated causal associations (IOM 2004). Sufficient evidence of association was reported for four outcomes (upper respiratory tract symptoms, cough, wheeze, and asthma symptoms in sensitized persons, i.e., asthma exacerbation) for the two kinds of risk factor considered: exposure to damp indoor environments and presence of molds or other agents in damp indoor environments. Sufficient evidence of association was also reported between hypersensitivity pneumonitis in susceptible persons and mold or other agents in damp environments. The 45 studies included in the IOM review are summarized in Supplemental Material, Tables A1.1–A1.6 (doi:10.1289/ehp.1002410). Table 1 shows the numbers of studies included in the IOM review, by study design, for each type of health outcome.

New Primary Research

Our literature search identified 354 articles published by late 2009 that were not included in the IOM review. Table 1 categorizes 103 studies that met the inclusion criteria. Supplemental Material, Tables A2.1–A2.16 (doi:10.1289/ehp.1002410) summarize results of these studies by 16 health outcomes. Estimated strength of association was usually reported as ORs and 95% confidence intervals (CIs), but occasionally was reported as other ratio estimates such as relative risks (RRs) or incidence rate ratios (IRRs) or as linear regression coefficients or proportions.

Considering all current evidence, most published findings involved qualitative assessments of dampness or mold, including visible water damage, visible moisture, dampness, leaks, flooding, visible condensation on windows, visible mold or mildew, and moldy or musty odor. Fewer findings were available on quantitatively measured microbiologic factors, including specific or total culturable fungi or bacteria; microscopically enumerated, noncultured fungi or bacteria; ergosterol (a structural component of fungi, used as a marker for total fungal biomass); extracellular polysaccharides (produced by fungi and used as a marker for specific fungal groups); (1→3)-β-D-glucans (a cell wall compound with immunomodulating properties found in fungi but also in some bacteria and pollens); endotoxin or lipopolysaccharide (a cell-wall compound of Gram-negative bacteria with proinflammatory properties, associated with dampness but also with many other sources); and markers of endotoxin such as 3 hydroxyl fatty acids.

Meta-analyses

Three available quantitative meta-analyses combined multiple qualitative dampness or mold factors into a single set of dampness-related risk factors. Findings, summarized in Table 2, are described for specific outcomes below. Two meta-analyses using the same methods estimated summary ORs and 95% CIs for associations of dampness or mold in residences with respiratory effects: upper respiratory tract symptoms, cough, wheeze, asthma development, current asthma, and ever-diagnosed asthma (Fisk et al. 2007), and respiratory infections and bronchitis (Fisk et al. 2010). Antova et al. (2008) estimated summary ORs for dampness-related factors and ever-diagnosed asthma, bronchitis, allergic sensitization, hay fever, cough, and wheeze.

Results for Qualitative Dampness or Mold

We considered no health outcomes to have sufficient evidence to document a causal relationship with indoor dampness or mold.

We considered four health outcomes to have sufficient evidence for association with indoor dampness or mold that were already so classified in the IOM review: asthma exacerbation, cough, wheeze, and upper respiratory tract symptoms (Table 3).

For asthma exacerbation and dampness or mold, we consider current evidence sufficient to document association and strongly suggestive of causality. Among 31 currently available studies [see Supplemental Material, Tables A1.2 and A2.2 (doi:10.1289/ehp.1002410)], qualitative dampness-related factors were consistently associated with asthma exacerbation, with ORs consistently exceeding 1.0 in both adults [100% of findings in retrospective studies (ORs from 1.7 to 2.6) and 100% of findings in cross-sectional studies (ORs from 1.02 to 4.2)] and in children [100% of findings in intervention studies (protective associations, not reported as ORs), 100% of findings in prospective studies (ORs from 3.8 to 7.6), 100% of findings in retrospective studies (ORs from 1.5 to 4.9), and 95% of findings in cross-sectional studies (ORs from 1.0 to 7.6)]. Most notably, Kercsmar et al. (2006) conducted a controlled experimental intervention study on asthma exacerbation in houses of highly symptomatic asthmatic children. Comprehensive removal of dampness sources and visible mold caused dramatic reductions in asthma exacerbations. Acute care visits at 6–12 months after intervention were 90% fewer in those remediated versus controls (p = 0.003). This study (although of necessity unblinded), because of the implausibility of noncausal explanations for the findings and in conjunction with other available studies, strongly suggests a causal association between indoor dampness or mold and exacerbations in children with asthma.

For cough, most studies found positive associations with dampness or mold. In adults, 94% of ORs in cross-sectional studies exceeded 1.0 (range, 0.8–4.0). In children, 85% of ORs in prospective or retrospective studies exceeded 1.0 (range, 0.5–2.1), and 94% of cross-sectional ORs exceeded 1.0 (range, 0.2–5.7).

For wheeze, most studies found positive associations with dampness or mold. In adults, 100% of retrospective ORs exceeded 1.0 (range, 1.5–2.8), and 91% of cross-sectional ORs exceeded 1.0 (range, 0.4–5.8). In children, 95% of prospective or retrospective ORs exceeded 1.0 (range, 0.7–6.2), and 92% of cross-sectional ORs exceeded 1.0 (range, 0.5–8.7).

For upper respiratory tract symptoms, most studies found positive associations with dampness or mold. In adults, 81% of cross-sectional ORs exceeded 1.0 (range, 0.4–4.4). In children, 88% of prospective or retrospective ORs exceeded 1.0 (range, 1.0–1.8), and 95% of cross-sectional ORs exceeded 1.0 (range, 0.4–5.9).

We classified eight health outcomes as having sufficient evidence for association with indoor dampness or mold that were not so classified or not evaluated in the IOM review: asthma development, current asthma, asthma ever, dyspnea, respiratory infections, bronchitis, allergic rhinitis, and eczema (Table 3).

Asthma development is a health outcome of special public health importance. Five studies included in the IOM report [of the eight listed there for asthma development; see Supplemental Material, Table A1.1 (doi:10.1289/ehp.1002410)] explicitly examined associations between dampness or mold and asthma development (Jaakkola et al. 2002; Nafstad et al. 1998; Oie et al. 1999; Thorn et al. 2001; Yang et al. 1998). Eight new studies were identified (Supplemental Material, Table A2.1) (Cox-Ganser et al. 2009; Gunnbjornsdottir et al. 2006; Hyvarinen et al. 2006; Iossifova et al. 2009; Jaakkola et al. 2005; Matheson et al. 2005; Park et al. 2008; Pekkanen et al. 2007). Among all currently available studies (five studies in Supplemental Material, Table A1.1; all studies in Supplemental Material, Table A2.1), 78% of findings exceeded 1.0. In retrospective case–control studies of adults, 60% of ORs exceeded 1.0 (range, 0.8–2.2). Among children, 80% of prospective or retrospective/case–control ORs exceeded 1.0 (range, 0.6 to 4.1). The three studies in infants (Iossifova et al. 2009; Nafstad et al. 1998; Oie et al. 1999) reported ORs all exceeding 1.0 (range, 1.7–7.1); however, as asthma cannot be reliably assessed in infants, these findings should be interpreted with caution. Infant studies were excluded from the meta-analysis of Fisk et al. (2007), which reported a summary OR (95% CI) of 1.3 (0.9–2.1) for asthma development and dampness factors. One of the strongest reported studies, by Pekkanen et al. (2007), showed in an incident case–control study of asthma cases that dampness or mold in the main living area of houses was related in a dose–response fashion to asthma development in infants and children. Multivariate-adjusted ORs (95% CIs) for asthma incidence, for baseline and two increasing levels of maximum severity of moisture damage (assessed by civil engineers), were 1.0, 2.8 (1.4–5.4), and 4.0 (1.6–10.2). This well-designed study provides the strongest evidence (e.g., incident case–control, large and statistically significant effects, dose–response relation, unbiased exposure assessment), within a body of generally consistent other findings, that dampness-related exposures may cause asthma development in infants and children.

For dyspnea, considered in the IOM report to have limited or suggestive evidence of association with dampness, the number of available studies for adults and children has increased from 4 to 16, all cross-sectional except 1 controlled intervention study. The intervention study found significant improvements in perceived breathing after mold removal, fungicide application, and ventilation increase (Burr et al. 2007). Among the 14 other available studies of dampness or mold [Supplemental Material, Tables A1.3 and A2.5 (doi:10.1289/ehp.1002410)], measures of association for dampness or mold with dyspnea were predominantly (84%) > 1.0, with ORs ranging from 0.7 to 9.4 in adults and from 0.4 to 2.3 in children.

We included findings on current asthma when defined as either asthma diagnosis in prior 12 months, asthma diagnosis ever plus asthmatic symptoms in prior 12 months, or recent prescription of asthma medication. Current asthma, not specifically evaluated in the IOM review, was consistently associated in available studies [Supplemental Material, Table A2.4 (doi:10.1289/ehp.1002410)] with dampness or mold. In these cross-sectional studies of adults, children, or both, almost all ORs (94%) exceeded 1.0 (ranging from 0.3 to 13.0). Fisk et al. (2007) reported, as a summary effect estimate, an OR (95% CI) of 1.6 (1.3–1.9) for current asthma and qualitative dampness factors.

Ever-diagnosis with asthma [Supplemental Material, Table A2.3 (doi:10.1289/ehp.1002410)] was associated consistently with dampness or mold (91% of ORs; range, 0.6–2.6) in both adults and children. Most studies were cross-sectional and in children. All studies in adults and the single prospective study in children found completely consistent positive associations. Both available meta-analyses found increased summary ORs for ever-asthma diagnosis and residential dampness or mold, with ORs (95% CIs) of 1.37 (1.23–1.53) for children and adults in Fisk et al. (2007) and 1.35 (1.20–1.51) for children in Antova et al. (2008).

Studies on respiratory infections showed consistent associations between dampness or mold and respiratory infections [Supplemental Material, Table A2.11 (doi:10.1289/ehp.1002410)], including common colds, and with or without inclusion of otitis media. One cross-sectional study in adults found an elevated OR (3.1); two prospective studies of children found consistently elevated ORs (range, 1.34–5.10); and five cross-sectional studies in children found mostly (70%) elevated ORs (range, 0.65–1.85). The few findings on otitis media, in three studies in children, included ORs ranging from 1.0 to 1.37 for dampness or mold. The meta-analysis by Fisk et al. (2010) reported summary ORs and 95% CIs for various categories of respiratory infections (Table 2): for respiratory infections overall, in adults, and in children: 1.44 (1.31–1.59), 1.49 (1.14–1.95), and 1.48 (1.33–1.65), respectively, and for respiratory infections excluding nonspecific upper respiratory infections: 1.50 (1.32–1.70).

Dampness or mold was associated consistently with bronchitis [Supplemental Material, Table A2.7 (doi:10.1289/ehp.1002410)], with 96% of ORs > 1.0. Most studies were in children; the two prospective studies in children found generally increased ORs up to 3.8. Both available meta-analyses found positive associations between bronchitis and residential dampness or mold, with ORs (95% CIs) of 1.45 (1.32–1.59) for children and adults in Fisk et al. (2010) and 1.38 (1.38–1.47) for children in Antova et al. (2008).

Dampness or mold was associated consistently with allergic rhinitis (92% of findings, all in children), with ORs ranging from 0.7 to 3.5 [Supplemental Material, Table A2.14 (doi:10.1289/ehp.1002410)]. We included only allergic rhinitis outcomes defined as either medically diagnosed allergic rhinitis or the combination of rhinitis symptoms with documented atopy. The strongest single study (prospective) found dose–response increases in allergic rhinitis associated with visible mold, with ORs to 3.2 (Biagini et al. 2006).

Dampness or mold was associated consistently with eczema [Supplemental Material, Table A2.12 (doi:10.1289/ehp.1002410)], with 89% of ORs > 1.0 (range 0.2 to 2.9). The strongest study, a prospective study in children, found consistently increased ORs up to 2.9 for prenatal mold exposure to infants with no parental atopic history.

Other outcomes evaluated here but not in the prior IOM report include common cold, allergy/atopy, and altered lung function (Table 1). Common cold [Supplemental Material, Table A2.11 (doi:10.1289/ehp.1002410)] was positively associated with dampness or mold in 71% of reported findings. However, the methodologically strongest single study, a prospective study in children, found only 4 of 9 estimates elevated, with ORs ranging from 0.6 to 1.8. Therefore, we consider this association only suggestive.

Increase in allergy/atopy (excluding allergic rhinitis and eczema) [Supplemental Material, Table A2.13 (doi:10.1289/ehp.1002410)] in association with dampness or mold was found in 77% of reported assessments in the available studies; ORs ranged from 0.6 to 2.4. Findings in the strongest studies, two prospective studies in children, were overall somewhat inconsistent, as were the other studies. This association is made more plausible by the increased summary ORs in the meta-analysis by Antova et al. (2008) for sensitivity to inhaled antigens and for hay fever, as well as by the consistent association found in this review between dampness or mold and both allergic rhinitis and eczema. However, the overall evidence linking allergy/atopy and dampness or mold was inconsistent enough that we currently consider it only (strongly) suggestive.

The evidence associating altered lung function with dampness or mold [Supplemental Material, Table A2.8 (doi:10.1289/ehp.1002410)] was considered too inconsistent to draw conclusions. No eligible epidemiologic studies were found on hypersensitivity pneumonitis and dampness or mold (but see "Discussion" regarding overall evidence).

Results for Measured Microbiologic Factors

Findings on health risks associated with quantitatively assessed microbiologic factors were sparse across specific health outcomes and 53 specific types of microbial measurements. Suggestive associations (as defined in "Methods" for conclusions about quantitatively assessed microbiologic factors: requiring at least 80% consistency of estimates either ≤ 1.0 or > 1.0, among at least five estimates available from three or more studies) were not seen for measurements in air but were apparent for some measurements in dust (Table 4). Higher concentrations of ergosterol in dust were associated with increases in current asthma. Higher concentrations of endotoxin in dust were associated with increases in wheeze. For (1→3)-β-D-glucan in dust, although medium concentrations were associated with increases in wheeze, the highest concentrations were associated with decreases in wheeze. We consider these associations with quantitative microbiologic assessments to be only suggestive. Other microbial measurements used in reviewed studies [listed in Supplemental Material, Table A3.1 (doi:10.1289/ehp.1002410)] had inadequate or insufficient evidence to determine whether associations with specific health effects exist.

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