Microbial secondary metabolites in homes in association with moisture damage and asthma

We aimed to characterize the presence of microbial secondary metabolites in homes and their association with moisture damage, mold, and asthma development. Living room floor dust was analyzed by LC‐MS/MS for 333 secondary metabolites from 93 homes of 1‐year‐old children. Moisture damage was present in 15 living rooms. At 6 years, 8 children had active and 15 lifetime doctor‐diagnosed asthma. The median number of different metabolites per house was 17 (range 8–29) and median sum load 65 (4–865) ng/m². Overall 42 different metabolites were detected. The number of metabolites present tended to be higher in homes with mold odor or moisture damage. The higher sum loads and number of metabolites with loads over 10 ng/m² were associated with lower prevalence of active asthma at 6 years (aOR 0.06 (95% CI <0.001–0.96) and 0.05 (<0.001–0.56), respectively). None of the individual metabolites, which presence tended (P < 0.2) to be increased by moisture damage or mold, were associated with increased risk of asthma. Microbial secondary metabolites are ubiquitously present in home floor dust. Moisture damage and mold tend to increase their numbers and amount. There was no evidence indicating that the secondary metabolites determined would explain the association between moisture damage, mold, and the development of asthma.     

Modeling microbial growth in carpet dust exposed to diurnal variations in relative humidity using the “Time-of-Wetness” framework

Resuspension of microbes in floor dust and subsequent inhalation by human occupants is an important source of human microbial exposure. Microbes in carpet dust grow at elevated levels of relative humidity, but rates of this growth are not well established, especially under changing conditions. The goal of this study was to model fungal growth in carpet dust based on indoor diurnal variations in relative humidity utilizing the time-of-wetness framework. A chamber study was conducted on carpet and dust collected from 19 homes in Ohio, USA and exposed to varying moisture conditions of 50%, 85%, and 100% relative humidity. Fungal growth followed the two activation regime model, while bacterial growth could not be evaluated using the framework. Collection site was a stronger driver of species composition (P = 0.001, R² = 0.461) than moisture conditions (P = 0.001, R² = 0.021). Maximum moisture condition was associated with species composition within some individual sites (P = 0.001-0.02, R² = 0.1-0.33). Aspergillus, Penicillium, and Wallemia were common fungal genera found among samples at elevated moisture conditions. These findings can inform future studies of associations between dampness/mold in homes and health outcomes and allow for prediction of microbial growth in the indoor environment.     

Higher measured moisture in California homes with qualitative evidence of dampness

Relationships between measured moisture and qualitative dampness indicators (mold odor, visible mold, visible water damage, or peeling paint) were evaluated using data collected from California homes in a prospective birth cohort study when the infants were 6 or 12 months of age (737 home visits). For repeated visits, agreement between observation of the presence/absence of each qualitative indicator at both visits was high (71–87%, P < 0.0001). Among individual indicators, musty odor and visible mold were most strongly correlated with elevated moisture readings. Measured moisture differed significantly between repeated visits in opposite seasons (P < 0.0001), and dampness increased with the number of indicators in a home. Linear mixed‐effect models showed that 10‐unit increases in maximum measured moisture were associated with the presence of 0.5 additional dampness indicators (P < 0.001). Bedroom (BR) walls were damper than living room (LR) walls in the same homes (P < 0.0001), although both average and maximum readings were positively correlated across room type (r = 0.75 and 0.67, respectively, both P < 0.0001). Exterior walls were significantly damper than interior walls (P < 0.0001 in both LRs and BRs), but no differences were observed between maximum wall readings and measurements at either window corners or sites of suspected dampness.     

Influence of housing characteristics on bacterial and fungal communities in homes of asthmatic children

Variations in home characteristics, such as moisture and occupancy, affect indoor microbial ecology as well as human exposure to microorganisms. Our objective was to determine how indoor bacterial and fungal community structure and diversity are associated with the broader home environment and its occupants. Next‐generation DNA sequencing was used to describe fungal and bacterial communities in house dust sampled from 198 homes of asthmatic children in southern New England. Housing characteristics included number of people/children, level of urbanization, single/multifamily home, reported mold, reported water leaks, air conditioning (AC) use, and presence of pets. Both fungal and bacterial community structures were non‐random and demonstrated species segregation (C‐score, P < 0.00001). Increased microbial richness was associated with the presence of pets, water leaks, longer AC use, suburban (vs. urban) homes, and dust composition measures (P < 0.05). The most significant differences in community composition were observed for AC use and occupancy (people, children, and pets) characteristics. Occupant density measures were associated with beneficial bacterial taxa, including Lactobacillus johnsonii as measured by qPCR. A more complete knowledge of indoor microbial communities is useful for linking housing characteristics to human health outcomes. Microbial assemblies in house dust result, in part, from the building's physical and occupant characteristics.     

Dampness and mold in homes across China: Associations with rhinitis,ocular, throat and dermal symptoms,headache and fatigue among adults

We studied dampness and mold in China in relation to rhinitis, ocular, throat and dermal symptoms, headache and fatigue. A questionnaire study was performed in six cities including 36 541 randomized parents of young children. Seven self‐reported signs of dampness were evaluated. Multilevel logistic regression models were used to calculate odds ratios (ORs). Totally, 3.1% had weekly rhinitis, 2.8% eye, 4.1% throat and 4.8% skin symptoms, 3.0% headache and 13.9% fatigue. Overall, 6.3% of the homes had mold, 11.1% damp stains, 35.3% damp bed clothing, 12.8% water damage, 45.4% window pane condensation, 11.1% mold odor, and 37.5% humid air. All dampness signs were associated with symptoms (ORs from 1.2 to 4.6; P < 0.001), including rhinitis (ORs from 1.4 to 3.2; P < 0.001), and ORs increased by number of dampness signs. The strongest associations were for mold odor (ORs from 2.3 to 4.6) and humid air (ORs from 2.8 to 4.8). Associations were stronger among men and stronger in Beijing as compared to south China. In conclusion, dampness and mold are common in Chinese homes and associated with rhinitis and ocular, throat and dermal symptoms, headache and fatigue. Men can be more sensitive to dampness and health effects of dampness can be stronger in northern China.     

Onset and remission of rhinitis among students in relation to the home and school environment—A cohort study from Northern China

Few prospective studies exist on indoor and outdoor air pollution in relation to adolescent rhinitis. We studied associations between onset and remission of rhinitis among junior high school students in relation to the home and school environment. A 2‐year questionnaire cohort study was performed among 1325 students (11‐15 years) in eight schools in Taiyuan, Northern China. Climate and air pollution were measured by direct reading instruments and passive samplers inside and outside the schools at baseline. Associations were calculated by multilevel logistic regression. Two‐year onset of rhinitis and weekly rhinitis were 26.7% and 13.1%, respectively. RH (P < 0.001), CO₂ (P < 0.01) and PM₁₀ (P < 0.01) in the classrooms, PM₁₀ (P < 0.01) and NO₂ (P < 0.05) outside the schools, and redecoration (OR = 2.25) and dampness/indoor mold at home (OR = 2.04) were associated with onset of weekly rhinitis. RH (P < 0.05) and CO₂ (P < 0.05) in the classroom and dampness/indoor mold (OR = 0.67) and environmental tobacco smoke (ETS) at home (OR = 0.63) reduced remission of rhinitis. In conclusion, dampness/mold and chemical emissions from new materials at home can increase onset of rhinitis and ETS and dampness/mold can reduce the remission. PM₁₀, RH, CO₂, and NO₂ at school can increase the onset, and RH and CO₂ can reduce the remission of rhinitis.     

Students' school-level symptoms mediate the relationship between a school's observed moisture problems and students’ subjective perceptions of indoor air quality

Moisture damage can influence the subjective assessment of indoor air quality (subjective IAQ) in various ways. We studied whether the frequency of symptoms reported across students at school level mediates the relationship between observed mold and dampness in a school building and students’ subjective IAQ. To answer this research question, we tested a multilevel path model. The analyzed data were created by merging two nationwide data sets: (a) survey data from students, including information on subjective IAQ (N = 24,786 students); (b) data from schools, including information on mold and dampness in a school building (N = 222). After the background variables were adjusted, schools’ observed mold and dampness were directly and significantly related to poor subjective IAQ (standardized beta (β)= 0.22, P = .002). In addition, in schools with mold and dampness, students reported significantly more symptoms (β = 0.22, P = .023) than in schools without; the higher the prevalence of symptoms at school level, the worse the students’ subjective IAQ (β = 0.60, P < .001). This indirect path was significant (P = .023). In total, schools’ observed mold and dampness and student-reported symptoms explained 52% of the between-school variance in subjective IAQ.     

Building dampness and mold in European homes in relation to climate,building characteristics and socio‐economic status: The European Community Respiratory Health Survey ECRHS II

We studied dampness and mold in homes in relation to climate, building characteristics and socio‐economic status (SES) across Europe, for 7127 homes in 22 centers. A subsample of 3118 homes was inspected. Multilevel analysis was applied, including age, gender, center, SES, climate, and building factors. Self‐reported water damage (10%), damp spots (21%), and mold (16%) in past year were similar as observed data (19% dampness and 14% mold). Ambient temperature was associated with self‐reported water damage (OR=1.63 per 10°C; 95% CI 1.02‐2.63), damp spots (OR=2.95; 95% CI 1.98‐4.39), and mold (OR=2.28; 95% CI 1.04‐4.67). Precipitation was associated with water damage (OR=1.12 per 100 mm; 95% CI 1.02‐1.23) and damp spots (OR=1.11; 95% CI 1.02‐1.20). Ambient relative air humidity was not associated with indoor dampness and mold. Older buildings had more dampness and mold (P<.001). Manual workers reported less water damage (OR=0.69; 95% CI 0.53‐0.89) but more mold (OR=1.27; 95% CI 1.03‐1.55) as compared to managerial/professional workers. There were correlations between reported and observed data at center level (Spearman rho 0.61 for dampness and 0.73 for mold). In conclusion, high ambient temperature and precipitation and high building age can be risk factors for dampness and mold in homes in Europe.     

Indoor visible mold and mold odor are associated with new‐onset childhood wheeze in a dose‐dependent manner

Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case‐control study involving 150 children with new‐onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new‐onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new‐onset wheezing in a dose‐dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new‐onset wheezing. The association between mold and new‐onset wheeze was not modified by atopic status, suggesting a non‐allergic association.     

Stenotrophomonas,Mycobacterium, and Streptomyces in home dust and air: associations with moldiness and other home/family characteristics

Respiratory illnesses have been linked to children's exposures to water‐damaged homes. Therefore, understanding the microbiome in water‐damaged homes is critical to preventing these illnesses. Few studies have quantified bacterial contamination, especially specific species, in water‐damaged homes. We collected air and dust samples in twenty‐one low‐mold homes and twenty‐one high‐mold homes. The concentrations of three bacteria/genera, Stenotrophomonas maltophilia, Streptomyces sp., and Mycobacterium sp., were measured in air and dust samples using quantitative PCR (QPCR). The concentrations of the bacteria measured in the air samples were not associated with any specific home characteristic based on multiple regression models. However, higher concentrations of S. maltophilia in the dust samples were associated with water damage, that is, with higher floor surface moisture and higher concentrations of moisture‐related mold species. The concentrations of Streptomyces and Mycobacterium sp. had similar patterns and may be partially determined by human and animal occupants and outdoor sources of these bacteria.     

Building-related respiratory symptoms can be predicted with semi-quantitative indices of exposure to dampness and mold

Using a semi-quantitative mold exposure index, the National Institute for Occupational Safety and Health (NIOSH) investigated 13 college buildings to examine whether building-related respiratory symptoms among employees are associated with environmental exposure to mold and dampness in buildings. We collected data on upper and lower respiratory symptoms and their building-relatedness, and time spent in specific rooms with a self-administered questionnaires. Trained NIOSH industrial hygienists classified rooms for water stains, visible mold, mold odor, and moisture using semi-quantitative scales and then estimated individual exposure indices weighted by the time spent in specific rooms. The semi-quantitative exposure indices significantly predicted building-related respiratory symptoms, including wheeze [odds ratio (OR) = 2.3; 95% confidence interval (CI) = 1.1-4.5], chest tightness (OR = 2.2; 95% CI = 1.1-4.6), shortness of breath (OR = 2.7; 95% CI = 1.2-6.1), nasal (OR = 2.5; 95% CI = 1.3-4.7) and sinus (OR = 2.2; 95% CI = 1.2-4.1) symptoms, with exposure-response relationships. We found that conditions suggestive of indoor mold exposure at work were associated with building-related respiratory symptoms. Our findings suggest that observational semi-quantitative indices of exposure to dampness and mold can support action to prevent building-related respiratory diseases. PRACTICAL IMPLICATIONS: Current air sampling methods have major limitations in assessing exposure to mold and other biological agents that may prevent the demonstration of associations of bioaerosol exposure with health. Our study demonstrates that semi-quantitative dampness/mold exposure indices, based solely on visual and olfactory observation and weighted by time spent in specific rooms, can predict existence of excessive building-related respiratory symptoms and diseases. Relative extent of water stains, visible mold, mold odor, or moisture can be used to prioritize remediation to reduce potential risk of building-related respiratory diseases. From a public health perspective, these observational findings justify action to correct water leaks and repair water damage in order to prevent building-related respiratory diseases. This approach can also be a basis for developing practical building-diagnostic tools for water-incursion.     

Inflammatory potential in relation to the microbial content of settled dust samples collected from moisture‐damaged and reference schools: results of HITEA study

Aiming to identify factors causing the adverse health effects associated with moisture‐damaged indoor environments, we analyzed immunotoxicological potential of settled dust from moisture‐damaged and reference schools in relation to their microbiological composition. Mouse RAW264.7 macrophages were exposed to settled dust samples (n = 25) collected from moisture‐damaged and reference schools in Spain, the Netherlands, and Finland. After exposure, we analyzed production of inflammatory markers [nitric oxide (NO), tumor necrosis factor‐α (TNF‐)α, interleukin (IL)‐6, and macrophage inflammatory protein (MIP)2] as well as mitochondrial activity, viability, apoptosis, and cell cycle arrest. Furthermore, particle counts, concentration of selected microbial groups as well as chemical markers such as ergosterol, 3‐hydroxy fatty acids, muramic acid, endotoxins, and glucans were measured as markers of exposure. Dust from moisture‐damaged schools in Spain and the Netherlands induced stronger immunotoxicological responses compared to samples from reference schools; the responses to Finnish samples were generally lower with no difference between the schools. In multivariate analysis, IL‐6 and apoptosis responses were most strongly associated with moisture status of the school. The measured responses correlated with several microbial markers and numbers of particles, but the most important predictor of the immunotoxicological potential of settled dust was muramic acid concentration, a marker of Gram‐positive bacteria.     

Next‐generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development

Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture‐based microbial analysis. In the low‐income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years. The current analysis included 13 asthma cases and 28 controls. Next‐generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio (OR) 4.80 (95% confidence interval (CI) 1.04–22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk (OR 21.0, 95% CI 2.16–204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next‐generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community.     

Allergy and respiratory health effects of dampness and dampness‐related agents in schools and homes: a cross‐sectional study in Danish pupils

Little is known about the health effects of school‐related indoor dampness and microbial exposures. In this study, we investigated dampness and dampness‐related agents in both homes and schools and their association with allergy and respiratory health effects in 330 Danish pupils. Classroom dampness was identified based on technical inspection and bedroom dampness on parents' self‐report. Classroom and bedroom dust was analyzed for seven microbial components. Skin prick testing determined atopic sensitization. Lung function was expressed as z‐scores for forced expiratory volume in one‐second (zFEV₁), forced vital capacity (zFVC) and the ratio zFEV₁/zFVC using GLI‐2012 prediction equations. The parents reported children's allergies, airway symptoms, and doctor‐diagnosed asthma. High classroom dampness, but not bedroom dampness, was negatively associated with zFEV₁ (β‐coef. ?0.71; 95% CI ?1.17 to ?0.23) and zFVC (β‐coef. ?0.52; 95% CI ?0.98 to ?0.06) and positively with wheezing (OR 8.09; 95% CI 1.49 to 43.97). No consistent findings were found between any individual microbial components or combination of microbial components and health outcomes. Among other indoor risk factors, environmental tobacco smoke (ETS) decreased zFEV₁ (β‐coef. ?0.22; 95% CI ?0.42 to ?0.02) and zFEV₁/zFVCratio (β‐coef. ?0.26; 95% CI ?0.44 to ?0.07) and increased upper airway symptoms (OR 1.66; 95% CI 1.03–2.66). In conclusion, dampness in classrooms may have adverse respiratory health effects in pupils, but microbial agents responsible for this effect remain unknown.     

Residential culturable fungi, (1‐3, 1‐6)‐β‐d‐glucan,and ergosterol concentrations in dust are not associated with asthma,rhinitis, or eczema diagnoses in children

Qualitative reporting of home indoor moisture problems predicts respiratory diseases. However, causal agents underlying such qualitative markers remain unknown. In the homes of 198 multiple allergic case children and 202 controls in Sweden, we cultivated culturable fungi by directly plating dust, and quantified (1‐3, 1‐6)‐β‐d ‐glucan and ergosterol in dust samples from the child's bedroom. We examined the relationship between these fungal agents and degree of parent or inspector‐reported home indoor dampness, and microbiological laboratory's mold index. We also compared the concentrations of these agents between multiple allergic cases and healthy controls, as well as IgE‐sensitization among cases. The concentrations of culturable fungal agents were comparable between houses with parent and inspector‐reported mold issues and those without. There were no differences in concentrations of the individual or the total summed culturable fungi, (1‐3, 1‐6)‐β‐d ‐glucan, and ergosterol between the controls and the multiple allergic case children, or individual diagnosis of asthma, rhinitis, or eczema. Culturable fungi, (1‐3, 1‐6)‐β‐d ‐glucan, and ergosterol in dust were not associated with qualitative markers of indoor dampness or mold or indoor humidity. Furthermore, these agents in dust samples were not associated with any health outcomes in the children.     

Moisture damage in home associates with systemic inflammation in children

This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6 years. Subclinical inflammation at the age of 6 years was assessed by measuring the circulating levels of C‐reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)‐1β and IL‐6 and tumor necrosis factor (TNF)‐α were measured in unstimulated, and in phorbol 12‐myristate 13‐acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)‐stimulated whole blood. Major moisture damage in the child's main living areas (living room, kitchen, or child's bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.     

Early age exposure to moisture damage and systemic inflammation at the age of 6 years

Cross‐sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C‐reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1‐beta (IL‐1β), IL‐6, and tumor necrosis factor alpha (TNF‐α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12‐myristate 13‐acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251‐270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS‐stimulated production of TNF‐α and minor moisture damage was inversely associated with PI‐stimulated IL‐1β. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life.     

Effect of moisture‐damage intervention on the immunotoxic potential and microbial content of airborne particles and on occupants' upper airway inflammatory responses

This intervention study evaluated the effect of moisture‐damage repairs on the exposure and on the upper airway inflammatory responses of the occupants. The airborne microbial exposure was followed by quantitative PCR analyses of 13 microbial species in repeated long‐term indoor air samples before (N = 26) and after (N = 28) repairs of the school building. Airborne particulate matter was collected similarly from the same premises (before N = 25, after N = 34) for determination of nitric oxide (NO), tumor necrosis factor α (TNFα), and interleukin‐6 (IL‐6), measured in the cell culture medium of mouse macrophages. NO, TNFα, IL‐6, and IL‐4 were also analyzed in the nasal lavage (NAL) samples of the occupants (N = 13) to characterize their upper airway inflammatory responses during the exposure and after its cessation. After the repairs, concentrations of the measured airborne microbes decreased, the difference being significant for six of 13 species. After renovation, airborne particulate matter also caused significantly lower production of IL‐6 and TNF‐α in mouse macrophages than the material collected before the renovation. The concentration of IL‐4 in the NAL samples was significantly lower after the renovation. These results show that the inflammatory potential of the airborne material decreases after intensive repair of the moisture damage.     

Development of a method to relate the moisture content of a building material to its water activity

Subjective indicators of building dampness consistently have been linked to health, but they are, at best, semi‐quantitative, and objective and quantitative assessments of dampness are also needed to study dampness‐related health effects. Investigators can readily and non‐destructively measure the “moisture content” (MC) of building materials with hand‐held moisture meters. However, MC does not indicate the amount of the water in a material that is available to microorganisms for growth, that is, the “water activity” (A_w). Unfortunately, A_w has not been readily measurable in the field and is not relatable to MC unless previously determined experimentally, because for the same moisture meter reading, A_w can differ across materials as well as during moisture adsorption vs desorption. To determine the A_ws that correspond to MC levels, stable air relative humidities were generated in a glove box above saturated, aqueous salt solutions, and the A_w of gypsum board and the relative humidity of the chamber air were tracked until they reached equilibrium. Strong correlations were observed between meter readings and gravimetrically determined MC (r=.91‐1.00), among readings with three moisture meters (r=.87‐.98), and between meter readings and gypsum board A_w (r=.77‐.99).