Indoor mould exposure, asthma and rhinitis: findings from systematic reviews and recent longitudinal studies

Exposure to moulds using qualitative metrics and asthma occurrence in children (longitudinal studies)

The publications selected addressed the relationship between dampness, visible mould, mould odour and respiratory health. They include two types of studies: birth cohort studies in children with several years of follow-up and studies involving incident asthma [4] (table 1).

We found six newly published studies not referenced in the previous reviews. In the first, incident asthma in older children was associated with reported visible mould and mould odour. This relationship was stronger in children carrying the CT genotype of the interleukin-4 promoter than in those carrying the TT genotype [21]. In the second study, observations of visible mould in New Zealand were strongly associated with new-onset wheezing, in children aged 1–7 years [22]. In the third, parent-reported dampness or moulds were associated with various asthma phenotypes, especially wheeze at 12 months [23]. In the fourth study [24], performed in 19 192 mother–child pairs representative of the population of Taiwan, exposure to visible mould on the walls during pregnancy was independently associated with an increased risk of asthma diagnosed at the age of 5 years in females. In the fifth study, performed in Finland, exposures at an early age to moisture damage and mould in the child's main living room were associated with physician-diagnosed ever-asthma during the first 6 years [25]. In the last study, any self-reported mould or dampness indicator in infancy (2 months) was associated with asthma up to 7 years of age [26].

These studies confirm the review performed by Quansah et al. [9], whose findings showed the causal relationship between fungi, mainly in living rooms, and the occurrence of respiratory symptoms, especially asthma. The relationship was progressively stronger with visible mould and mould odour and more marked in children one of whose parents was atopic.

Exposure to moulds using quantitative measured mould species or components and asthma occurrence in children (longitudinal studies)

Analysis of epidemiological data shows that a large variety of methods were used for assessing mould exposure and indicators: mould components from indoor air or settled dust such as (1, 3)-β-D-glucans, extracellular polysaccharides and ergosterol, as previously reported in reviews and meta-analyses. The most recent publications studied the relationship between fungal exposures measured by culture-based methods and molecular techniques and asthma occurrence in children (table E1).

Two fungal culture studies using data from the Boston birth cohort showed that wheezing at 1 year of age was associated with Alternaria and Cladosporium in dust [27] and asthma at the age of 13 years with airborne Alternaria [28]. The study by Rosenbaum et al. [29] indicated that Penicillium measured in the air at 3 months was associated with wheezing at 1 year. In contrast, the Boston birth cohort identified a protective effect of yeasts measured in bedroom dust samples taken at the age of 3 months on wheezing at 1 year, and on the development of asthma at 13 years.

In studies using molecular techniques, the risk of asthma was associated with a high ERMI score [19]. In a small case–control study, low fungal diversity was associated with increased risk of asthma development at the age of 7 years, but no significant associations were found with fungal levels [30]. In the LISA German birth cohort [31], exposure to higher fungal diversity in the living room in infancy, assessed using terminal restriction fragment length polymorphism, was associated with reduced risk of developing sensitisation at 6 years and ever-wheezing until the age of 10 years. However, these associations were no more significant in the longitudinal analyses considering the impact of several follow-ups and their correlation with each other. In a case–control incident asthma study performed in 1–7-year-old children in New Zealand, measurements of qPCR microbial levels in the bedroom children using electrostatic dust cloths were not associated with new-onset wheezing, in contrast to observations of visible mould [22].

In conclusion, given the small number of longitudinal studies, and their conflicting and inconclusive results, there is currently insufficient evidence to determine whether an association exists between quantitatively measured mould species or components and the occurrence of asthma.

Exposure to moulds and exacerbations of asthma in children (panel studies)

We found nine studies (table 2), six being already referenced in the recent reviews by Kanchongkittiphon et al. [16], Sharpe et al. [17], Vesper and Wymer [18], and Pei Zam et al. [20]. Five out of the six panel studies investigated the evolution of asthma symptoms or changes in peak expiratory flow in asthmatic children exposed to mould for periods ranging from 2 weeks to 3 years. In these studies, an association, albeit modest, was consistently found between mould exposure in asthmatic children, in particular exposure to Penicillium, and an increased variability in peak expiratory flow rate, a higher asthma severity score, or an increase in the number of days with symptoms or in the unplanned hospital visits. Interestingly, in unadjusted analyses in children of unspecified atopic status, Wu et al. [32] found that high levels of total culturable fungi in dust were associated with an increased number of urgent care visits only in those with genetic polymorphisms that caused reduced enzymatic breakdown of chitin, an important fungal protein. This study provides biological plausibility for nonallergic mechanisms for exacerbation of asthma in relation to fungal exposures. Overall, these results, from studies performed in children with variable level of severity at baseline, show an increase in asthma activity associated with mould exposure, irrespective of the children's allergic sensitisation to moulds.

Although of small sample size, the first recent study showed an association between indoor Cladosporium levels in the child's bedroom and readmissions for asthma [33]. The second one showed that high fungal concentrations in the main living area in which the child spent the most time was associated with asthma severity [34]. After stratification according to atopy, the same association was found significant in nonatopic children. Interestingly, compared to mild asthma, the fungal communities in house dust from atopic children with severe asthma had low compositional variation, whereas no differences were found between homes of nonatopic children with severe compared to mild asthma. Lastly, among 419 children from 25 schools in three European countries, Casas et al. [35] found that children with respiratory conditions report fewer symptoms and/or less severe respiratory symptoms during weekends and summer holidays compared with school days, the association being clearer among those attending schools with moisture damage problems.

In summary, all these studies provide strong evidence for associations between indoor mould exposure and exacerbation of asthma in children, with arguments for causality.

Exposure to moulds using qualitative metrics and asthma in adults (longitudinal studies)

To date, few longitudinal studies have investigated the relationships between mould exposure and respiratory health in adults. These studies were either not included in previous reviews or their findings were grouped together with those in children despite the fact that asthma development in adults may result from different risk factors than in children (table E2).

We only identified four longitudinal studies published after 2006. Owing to the scarcity of studies in adults, we decided to include one report that collected data on mould exposure, although only home dampness was included in the longitudinal analyses. Two studies were performed in northern Europe, and two studies were carried out as part of the European Community Respiratory Health Survey (ECRHS).

In a population-based incident case–control study in Finland, Jaakkola et al. [36] investigated the independent and joint effects of indoor exposure to mould and interior surface material and incident asthma. No independent association was observed for exposure to mould at home or at work. However, combined exposure to mould and wall-to-wall carpet in the workplace was associated with a significant increased risk of incident asthma.

In the general population, the analysis of data on dampness retrospectively collected as part of the Respiratory Health in Northern Europe (RHINE) follow-up showed that subjects living in damp homes had a higher risk to develop respiratory symptoms, compared to those living in dry homes [37]. Conversely, the remission of respiratory symptoms was less common in damp homes. As regards asthma, no significant association was observed despite the large sample size and relatively high number of new-onset asthma cases. Questions specifically focusing on mould exposure were only asked at follow-up. The cross-sectional analysis of these data showed a significant relationship between asthma and the presence of visible mould.

Analyses of the ECRHS population-based study of young adults considered “dampness” and “mould” scores calculated as the number of positive answers to the presence of “mould or mildew on any surface inside the home” ever and in the past 12 months both at baseline and follow-up (9 years after baseline) [38, 39]. In addition, 3118 homes were inspected at follow-up for the presence of dampness and mould. Dampness and mould were common at baseline and follow-up (∼10% of the sample reported water damage and ∼16% reported visible mould in the past 12 months). It is noteworthy that the dampness score and the mould score showed relatively poor agreement. No significant relationship was found between reported or observed mould exposure and lung function decline [38]. However, other aspects of building dampness (such as water leakage or damp spots) were associated with accelerated lung function decline, but only in females. The reasons why a stronger effect was observed in females are unclear. A greater susceptibility or a longer exposure time in the dwelling for females is speculated. Another study of the same cohort was focused on the risk of asthma onset in subjects without asthma or respiratory symptoms at baseline [39]. There was an excess risk of new asthma onset in subjects reporting mould indoor in the past 12 months at baseline, although no significant relationship was found when considering specifically mould (ever) in the bedroom or in the living room at baseline. A dose–response effect was observed when the score combining exposure at baseline and follow-up was used. No significant interaction by sex was observed, apart for mould exposure in the living room which showed a significant effect only in females. Some heterogeneity was observed between centres. Therefore, this study is one of the first to show a significant relationship between mould exposure in the dwelling and subsequent asthma onset, and to report a dose–response effect. However, the score used for the dose–response relationship combined data from baseline and follow-up.

To summarise the four longitudinal studies identified in our literature review: one study showed an effect of the combined exposure to wall-to-wall carpets and to mould at work, but found no significant effect of visible mould or mould odour at home [36]; one study showed an excess incidence and less frequent remission of respiratory symptoms in individuals living in damp homes, but no significant association with asthma [37]; one study [39] reported a significant relationship between mould exposure in the dwelling and subsequent asthma onset; and the final study showed a significant relationship between lung function decline and various aspects of building dampness, but not with mould exposure when considered specifically [38].

In conclusion, given the small number of longitudinal studies with a particular focus on mould exposure, and the lack of consistent findings, there is limited evidence on the effect of mould exposure on asthma onset in adults from the general population. Further studies are clearly warranted.

Longitudinal studies on occupational asthma related to working in mouldy buildings

Studies on respiratory health in adults working in damp buildings provide additional evidence for the existence of associations between mould exposure and the incidence and morbidity of asthma in adults (table 3).

In Finland, Jaakkola et al. [40] had already shown that the risk of incident asthma was related to the presence of visible mould and/or mould odour in the workplace. In a later study a relationship was demonstrated between incident asthma and the combined presence of mould problems and wall-to-wall carpet in the workplace [36]. In this country, indoor moulds from water-damaged buildings have become the most important causative agents of occupational asthma since 2001 [41]. In compliance with compensation policy, most cases referred to the Finnish Institute of Occupational Health are confirmed objectively by specific inhalation challenge tests with mould extracts.

In a first study (table 3), Karvala et al. [42] followed 136 patients with “probable” occupational asthma. After 6 months of follow-up, 42% were no longer working, while none of the 13 still exposed reported improvement of symptoms. In a second study [43], 483 patients with asthma-like symptoms related to damp workplaces, but without objective evidence of asthma at inclusion, were followed-up for 3–12 years. The risk of developing asthma was 4.6 times higher in patients still exposed. Additional studies of workers with mould-induced asthma further evidenced impaired quality of life, work disability and a high rate of work withdrawal [44, 45]. In a study of US employees in a water-damaged office, Park et al. [46] showed a significant association between asthma with post-occupancy onset and the levels of exposure to mould, especially hydrophilic fungi. In another study [47], the same authors found a dramatic increase in the risk of developing building-related asthma symptoms (OR 7.4, 95% CI 2.8–19.9) in individuals with a high level of both fungal exposure and building-related rhinosinusitis at inclusion. Of note, only the initial mould exposure, but not subsequent exposures, was a significant predictor of building-related asthma symptoms, which suggests that it might be more relevant to understand the historical exposure to dampness rather than focusing on recent exposure. The authors proposed that building-related rhinosinusitis should be considered as a warning for increased risk of developing asthma symptoms and prompt identification of mould problems and timely effective remediation.

In conclusion, these prospective studies provide sufficient evidence of an association between indoor mould exposure at work and the development of asthma, but insufficient evidence for a causal relationship, with further prospective studies in other countries being needed.

Recent reviews, meta-analyses and longitudinal studies on rhinitis

Several meta-analyses have covered the relationships between mould or dampness exposure and rhinitis (table 4). In 2007, combining data from 13 cross-sectional and longitudinal studies, Fisk et al. [15] showed a significant relationship between exposure to mould and/or dampness and upper respiratory tract symptoms, with no evidence of publication bias. In the Pollution and the Young (PATY) consortium [5], consisting of seven cross-sectional studies in children from different areas, visible mould was associated with an increased risk of hay fever.

In their review, Mendell et al. [6] concluded that there was sufficient evidence for the existence of an association between home dampness or mould exposure and risk of upper respiratory tract symptoms and allergic rhinitis, but insufficient evidence of a causal relationship, because of insufficient evidence with regards to causal microbial exposure or dose–response relationships to define “safe” levels of exposure.

Tischer et al. [7] performed a systematic review in children, considering more specific criteria for mould exposure and giving more weight to longitudinal studies. However, their meta-analysis included both cross-sectional and longitudinal studies. They concluded that exposure to visible mould was associated with an increased risk of allergic rhinitis in children, and that the results were consistent with the evaluation of causation according to Hill's criteria. However, the authors also reported findings showing a tendency towards a lower risk of allergic health outcomes in children exposed to mould-derived components [7]. In addition, they found some suggestion of moderate publication bias.

In another study, pooling data from six European birth cohorts, Tischer et al. [8] showed that exposure to visible mould and/or dampness during the first 2 years of life was associated with an increased risk of allergic rhinitis later in childhood. It is the largest longitudinal study to show relationships between exposure to dampness and the development of allergic rhinitis. However, its focus was not specifically on mould exposure.

A more recent meta-analysis by Jaakkola et al. [48] included findings published up to August 2012. The authors considered various criteria to define mould exposure. For allergic rhinitis, the highest effect estimate was obtained when the exposure concerned mould odour. A significant and relatively homogeneous association was observed with visible mould. However, most of the studies were cross-sectional. Because the risks of rhinitis and allergic rhinitis were similarly increased, the authors suggested that other mechanisms than allergic ones could also play a role.

Few longitudinal studies have focused on mould exposure (table 4), and only two were not referenced in the systematic reviews. In the Boston birth cohort [28], children with higher levels of Aspergillus in bedroom floor dust in infancy were more likely to develop rhinitis, but no association was observed for total fungi. In the BAMSE (Barn/Child Allergy Milieu Stockholm Epidemiology) cohort, visible mould and mould odour in infancy were associated with an increased risk of rhinitis up to the age of 16 years [26]. It is noteworthy that exposure to any mould or dampness indicator during infancy was associated with a significant increased risk of nonallergic rhinitis and with a nonsignificant decreased risk of allergic rhinitis at age 16 years.

To summarise, systematic reviews and meta-analyses published since 2006 on the relationships between mould exposure and allergic rhinitis provide sufficient evidence of an association, with an odds-ratio generally >1.35 (table 4). However, most of the studies that specifically focused on exposure to mould are cross-sectional studies, while the longitudinal studies considered “exposure to mould and/or dampness”. Conversely, some studies have suggested there is a possible decreased risk of allergic rhinitis in individuals exposed to mould-derived components. Moreover, the few longitudinal studies to date do not provide consistent evidence. Further longitudinal studies are needed to specifically study the associations between mould exposure and allergic rhinitis, nonallergic rhinitis and rhinitis severity to yield conclusive evidence of the differential effect of the various fungal components related to home dampness.