1 (1) Dampness in Buildings and Health report from an ongoing epidemiological investigation in Sweden Linda Hägerhed Engman, PhD student, SP Swedish National Testing and Research Institute Carl-Gustaf Bornehag, PhD SP Swedish National Testing and Research Institute Technical University of Denmark Public Health Sciences, Karlstad University, Sweden KEYWORDS: epidemiology, asthma, allergy, dampness, home, ventilation SUMMARY: With the aim to identify health relevant exposures in buildings an epidemiological study Dampness in Buildings and Health (DBH) started in the year 2000 in Sweden. The health focus of the study is on asthma and allergic symptoms among small children and their parents. The first step of the study was an epidemiological cross-sectional questionnaire study on housing and health on pre-school children in the county of Värmland in Sweden, (March-April 2000). Self reported moisture related problems in the building were strongly associated to asthma, allergic symptoms, and airway infections among children and adults. Other factors associated with symptoms among the children were allergic heredity, smoking in family, male sex, urban living, short breast-feeding, pet keeping, day-care attendance, non-farming life and some food habits. The second step of the study was a nested case-control study including 198 children with symptoms and 202 healthy controls. A detailed clinical examination by physicians in parallel with extensive inspections and measurements in the subjects homes were conducted during October 2001-April The influence of selection bias has been studied, and questionnaires on self reported symptoms and building characteristics have been validated. Identified risk factors for allergic symptoms are e.g. inspector observed mouldy odour, a low ventilation rate, endotoxin, penicillium and phthalates in dust. In the third phase, a 5-year follow up study will be carried out during The same questionnaire as used in DBHphase I will be distributed to the children/parents that responded on the first questionnaire in Finally, controlled experimental studies in climate chamber with in vitro and in vivo tests with findings from DBHphase 1,II and III are planned to be conducted during Introduction The prevalence of asthma and allergy in children and young people has increased during the last past decades (Aberg, 1989; Beasley et al., 2003; Ellwood et al., 2005). Numerous risk factors for allergic disease have been identified such as heredity, urban living, exposure to tobacco smoke, premature birth, low birth weight and living in a home with mould and moisture problems. Two multidisciplinary reviews on moisture related problems and associations to health effects concluded that dampness was a consistent risk factor for several health effects such as asthma and other allergic symptoms, sick building syndrome (SBS) and airway infections (Bornehag et al., 2001; Bornehag et al., 2004; Etzel, 2003). Different types of reported moisture problems like visible mould, damp stains, detached or discoloured flooring materials, flooding, condensation on windows and bad odour were associated to these health effects. However, the health relevant exposure substances responsible for the health effects are still unknown but both chemicals from degraded ma-
2 (2) terials and microbiological exposures are suspected to play a role. Referring to the reviews, there is a strong need for more factual multidisciplinary studies. 2. Method In order to identify health relevant exposures in buildings with moisture related problems a multidisciplinary epidemiological study Dampness in Buildings and Health started in the year Since children have a higher incidence of allergies than adults and their dominant environment is the home, the focus of the study has been on preschool children. The study is divided into three phases where results and findings from a previous step will be taken into account when planning the next phase, figure 1. Phase 1 consisted of an epidemiological cross sectional questionnaire study on housing and health on pre-school children in the county of Värmland in Sweden (March 2000). A nested case control study of 400 children, 198 children with symptoms and 202 healthy controls, including detailed examinations by physicians in parallel with inspections and measurements within the subjects home (October 2001-April 2002) constituted the second phase. In a third phase, a follow up questionnaire will be sent to the cohort from the first phase and in a further studies, experimental investigations of findings from the DBH will be tested in climate chamber DBH-phase I Cross-Sectional Study March 2000 Questionnaire n= children (1-6 y) (79 %) DBH-phase III Cross-Sectional Study Follow-up April 2005 Questionnaire n= 7557 children (6-11y) DBH-phase II Case-Control Study October 2001-April 2002 Exposure measurements Clinical examinations n=400 children/390 dwellings Experimental studies Experimental studies Climate chamber studies In vitro test, Intervention studies Figure 1. Design of the DBH study 2.1 Statistical methods Statistical analyses were performed with Statistical Package for Social Science (SPSS). Associations between exposure and outcome have been estimated in logistic regression models and odds ratio (OR) was calculated including 95 % confidence interval. 3. Results Up to the present date, the first and the second phase of the DBH study is finished and the third phase and the experimental studies in climate chambers has just previously started. 3.1 Results from DBH phase I A questionnaire was distributed to the parents of all children aged 1-6 years (n=14 077) in the county of Värmland in Sweden, response rate 79 %. The questionnaire included 84 questions on health symptoms, building characteristics including dampness related problems and life-style factors Background factors and health Risk factors for reported asthma and allergic symptoms among the children were smoking parents, allergic symptoms in the family, male sex, urban living, short breastfeeding, living in a multi family house and day care attendance
3 (3) (Berner and Bornehag, 2004; Bornehag et al., 2004; Forsman, 2001; Hägerhed-Engman et al., 2005). Adjustments for background factors have been made in subsequent statistical analyses Self reported dampness and building characteristics Visible mould and/or damp spots (discoloured spots) were reported from 1.3 % of the single-family houses and 1.6 % of the multi family houses. Signs of a moisture problem in the floor (detached, discoloured plastic floor covering, blackened parquet or flooding last year) was reported in 6.5 % and 13.9 %, condensation on the inside of window pane in the child s bedroom 12.5 and 16.9 % respectively. Perceptions of bad indoor air quality was more reported from the multi family houses; stuffy air 22.3 and 42.8 %, mouldy odour 3.9 and 5.8 % and dry air 17.3 and 33.7 % respectively. Older buildings, use of natural ventilation, living in a rented flat or house and a former renovation due to mould and moisture problems were associated with increased complaints on bad indoor air quality and higher frequency of visible dampness indicators. (Hägerhed-Engman et al., 2005; Hägerhed et al., 2002) Self-reported dampness and health Self reported dampness was a consistent risk factor for asthma and allergic symptoms (OR ) (Bornehag et al., 2004; Bornehag et al., 2002). Furthermore, self reported dampness at home increased the risk for sick building syndrome symptoms among the parents (Bornehag et al., 2003) The healthy pet-keeping effect The lowest prevalence of symptoms was found among children with a furred pet at home. However, the highest prevalence was found among those families who had a pet at the time of birth but not at the time of the questionnaire. This shows that pet keeping in the population partly is explained by avoidance behaviour, i.e. those having pets are those who can stand them a healthy pet keeping effect. This implies that a strong selection bias must be taken into account when investigating associations between pet keeping and allergies (Bornehag et al., 2003) Farming life Several recent studies, including the DBH study have shown that children living on a farm with animals report less allergic symptoms than other children. It has been suggested that the protecting factor is the exposure to animals, however, our study have shown numerous of other environmental differences between these children growing up at farms compare to other. Life style factors like smoking, day care attendance, family size, antibiotic treatment and pet keeping differed. Furthermore, farmers lived in older houses, single family houses, less PVC, less concrete slab on ground, more natural ventilation and they complained less regarding indoor air quality than others (Bornehag et al., 2002; Engström, 2001) Day care attendance and health Several studies, including the DBH study, have shown that day care attendance increase the prevalence of airway infections, otitis media, asthma and rhinitis (hay-fever). Regarding to the hygiene hypothesis some studies have found a protective effect of early day care attendance and less allergy later in life. This was not supported in the DBH-study for the oldest children in our study (5-6 years of age) (Hägerhed-Engman et al., 2005). The long-term effects will possibly be studied in the follow up questionnaire (DBH-phase III). 3.2 Results from DBH phase II The second phase of the DBH study was a nested case control study with 198 symptomatic children (at least two symptoms of asthma, rhinitis or eczema last year). Further inclusion criteria were: not moved and no renovation due to mould and moisture. A medical examination of the children included a routine control, blood sample (Phadiatop, RAST), exhaled breath condensate (CB) and nasal lavage (NAL) for analyses of inflammation markers (IL-1, IL-8, ph) and antibodies (IgE). Within the same week an ocular inspection for signs of moisture damage and mouldy odour were performed in the children s home (n=390, 10 siblings) together with measurements of temperature and relative humidity indoors and outdoors, air change rate, air- and dust samples.
4 (4) Selection bias in the case control study A systematic difference between characteristics of selected and non-selected individuals selection bias may be introduced if participants chose themselves for a study. For identifying potential selection bias information on the family, health and building characteristics from the baseline questionnaire (DBH phase I) were compared between participating and non-participating families in the nested case control study. The results showed that families were more inclined to participate if the child was reported to have more symptoms, if they had avoided pet keeping, if they belonged to a higher social group and if the parents were non-smoking (Bornehag et al., 2004) Validation of self reported symptoms Physicians diagnosis of the 400 children agreed well with the case control status as reported in the questionnaire, the sensitivity was 94 % and the specificity was 83 %. All children with obvious asthma were found among the cases while two children with rhinitis and eight children with eczema were found among the controls. It was concluded that the selection with multiple self reported symptoms well predicted clinically verified asthma, allergic rhinitis and atopic eczema (Hasselgren et al., 2005) Validation of self reported home characteristics The concurrence between inspectors observations and the parents questionnaire reports were measured by their kappa value. Cohen s kappa measures the percentage of data values in the main diagonal of the 2x2 table or nxn table and then convert these values for the amount of agreement. The questionnaire was considered to be reliable on technical parameters such as type of house, location and type of foundation. It was a high concurrence between questionnaire and inspections on wooden flooring but not for PVC and linoleum since these flooring materials often were mixed up. The agreement on type of ventilation system between questionnaire reports and inspectors observations was moderate to good (kappa= ) for single-family houses but poor for multi family houses (kappa=0-0.29). The agreement expressed in kappa-value and positive proportional agreement was very low for inspectors reports on visible signs of dampness and perception on of mouldy odour compare to parents reports in the questionnaire. Conversely, the value of negative proportional agreement were high (P neg = ) which implies that the questionnaire was better for predicting non-problem dwellings than detecting problems of mouldy odour and visible indications of dampness in the way that professional inspectors define it (Hägerhed-Engman et al., 2005; Hägerhed et al., 2003) Inspectors observation of mouldy odour and visible signs of moisture problem Six engineers performed an ocular inspection and odour assessment in the 390 dwellings together with the measurements and sample taking described below. The observations were graded depending on their severity; 0, 1, 2 or 3 where 0 corresponded to no visible indication of a moisture problem / no mouldy odour and 3 was noted for a distinct and strong mouldy smell or grave moisture damage. Following frequencies are base on grade 2 and 3. The inspectors found visible mould spots on indoor surfaces in the children's bedroom in only four houses (1.0 %), all with natural ventilation. Damp stains were more frequently observed in the bedrooms (11.3 %) and more common in older houses (p trend =0.002). Indications of a moisture problem in the floor (blackened parquet or PVC-flooring with bubbles) were observed in 3.0 % of the buildings and more often in houses from the sixties and seventies however the difference was not significant. A mouldy odour was significantly more often detected in houses from the seventies (31.1 %) compared with older buildings (17.8 %, p=0.010) and newer buildings (9.3 %, p=0.002) (Hägerhed-Engman et al., 2005) Observed moisture problems, mouldy odour and children s health Visible mould, indications of a moisture problem in the floor and a general mouldy odour in the rooms were somewhat more frequently observed in the homes of the cases (1.5 %, 4.0 % and 20.7 %) compared to controls (0.5 %, 2.0 % and 20.3 %), but the difference was not significant. However, the inspectors' report of a mouldy odour along the skirting board was associated with case status compared with controls (AOR 1.66 (95% CI: )), with asthma (AOR 1.39 (95% CI: )), with rhinitis (AOR 2.32 (95% CI: )), and with eczema compared with controls (AOR 1.88 (95% CI: )). There was also a significant dose response relationship between a
5 (5) higher severity of mouldy odour along the skirting board and case status (p=0.013), rhinitis (p=0.002) and eczema (p=0.003) and near significance for asthma (p=0.054). An inverse dose response association were found between observations of damp/discoloured stains and eczema (p=0.022). This indicates that visible signs of moisture problem appear not to be a health relevant sign of dampness as it is in many other studies in other climates. The results show that an inspection should be focused on detecting moisture damage inside the construction, at least in Scandinavia (Hägerhed-Engman et al., 2005) Ventilation rate in the homes The air change rate of the 390 homes were measured during one week with a passive tracer gas method (Stymne et al., 2002). The study shows that the ventilation rates in the Swedish houses are low. About 80 % of the single-family houses and 60 % of the multi family houses did not fulfil the minimum requirements in the Swedish building code (0.5 ach). Cases had significantly lower ventilation rates than controls and a dose response relationship was indicated in single-family houses. When adjusting the analyses for other building factors like type of ventilation system, construction period, type of foundation and numbers of floors in the building, the estimated risk for symptoms was somewhat reduced. This indicates that other building factors co-varying with ventilation rate are of importance for allergic symptoms among children (Bornehag et al., 2003; Bornehag et al., 2004) Dust samples Dust samples were collected with a vacuum cleaner onto filters in the 390 homes; on the floor in the living room and in the child s room (on the floor, above the floor and in the bed). Two foliated boxes were sited in the living room and child s bedroom for one to three months for settled dust Endotoxin Preliminary results show that Endotoxin (LPS) were highly correlated to pet keeping. Analyses are ongoing Mould The prevalence of moulds in the 390 dust samples were: Alternaria tenuis grp (60 %), Aspergillus versicolor (9 %), Cladosporium sphaerospermum (4 %), Penicillium chrysogenum (2 %), Penicillium (Total) (85 %), Phoma sp. (13 %), Stachybotrys chartarum (3 %), Trichoderma viride and harzianum (35 %), Ulocladium oudemansii (24 %) and Yeasts (52 %). Stachybotrys chartarum, which can be found in moistened constructions of gypsum boards, is almost absent in this study. Preliminary results show that mould spores (penicillium) in indoor dust are associated with case status as well as selected diseases (asthma, rhinitis and eczema). These findings and others have to be tested in epidemiological studies with longitudinal design as well as in experimental studies Glucan The levels of glucan in the dust were Mean (SE) 28.8 (4,8) and 39,9 (9,4) µg/g dust in the bedrooms and the living rooms, respectively. Analyses of glucan are in progress Phthalates Phthalates are more or less ubiquitous and are often used as plasticizers in a wide range of products; adhesives, vinyle tiles, PVC, cosmetic products, solvents, artificial leather etc. A significant higher median concentration of BBzP (nbutyl benzyl phthalate) in dust was found among cases. BBzP was mainly associated to rhinitis (p=0.007) and eczema (p=0.003) while DEHP (di(2-ethylhexyl) phthalate) was associated with asthma (p=0.016). This study indicates that phthalates within the range that is normally found in indoor environments may be a risk for allergic symptoms in children (Bornehag et al., 2005; Bornehag et al., 2004) VOC Gas chromatography-uv spectrometry (GC-UV) was used for analyses of VOC on dust (Nilsson et al., 2004). Analyses are ongoing Allergen, Ergosterol Analyses are ongoing.
6 (6) Air samples (mvoc, svoc, spores) Spores and bacteria were collected on two different agars in three rooms indoors and outdoors. mvoc were sampled on Tenax in the child s room and svoc were passively collected in the child s room for one month in a sub sample. Analyses are ongoing. 3.3 DBH phase III In April 2005, a follow up questionnaire will be distributed to the original cohort of children from the first step of the DBH study, children who five years later are between 6 and 11 years old, n=7557. The aim of the follow up study is to estimate the incidence of allergic symptoms and to identify potential risk factors in the home for such symptoms. 3.4 Experimental studies in climate chambers Experimental studies in climate chambers have recently started where findings from the DBH study are tested in in vivo and in vitro studies at the Technical University of Denmark and Aarhus University. 4. Co-operative institutions DBH-phase 1 was conducted by the Swedish National Testing and Research Institute in Borås, Karlstad University, International Centre for Indoor Environment and Energy at Technical University of Denmark, Sahlgrenska University Hospital in Gothenburg and Aarhus University in Denmark. DBH-phase 2 was organized into different subprojects from the medical and technical investigations: Medical: Examinations by physicians, County Council of Värmland. Analyses of clinical samples (blood, NAL, CB), Aarhus University Technical: Inspections, measurements of ventilation, temperature, relative humidity, taking samples of dust and air; Swedish National Testing and Research Institute. Analyses of endotoxin (LPS), mold, glucan in dust; Aarhus University, University of Iowa, Danish Technological Institute. Analyses of allergen in dust; University of Linköping. Analyses of phthalates on dust; Swedish National Testing and Research Institute. Analyses of VOC on dust; University of Linköping. Analyses of settled dust; National Institute of Occupational Health, Denmark. Analyses of mvoc in the air; NILU Norway. Analyses on svoc in air; Stockholm University. Analyses of spores in the air; Mycoteam Norway. 5. Acknowledgements The study has been supported by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas), Swedish Asthma and Allergy Association s Research Foundation, the Swedish Foundation for Health Care Sciences and Allergy Research, European Council of Plasticizers and Intermediates, and County Council of Värmland, Sweden. Furthermore, involved institutions have got local funding for different sub-projects. 6. Nomenclature OR AOR CI SE Odds ratio. Probability of a certain effect (disease) between groups with different exposure. An odds ratio of 1 means that there is no association between exposure and disease. Odds ratio greater than 1 mean the exposure is associated with the disease. Adjusted odds ratio. Calculated in multiple logistic regression analyses. Adjustments are made for potential confounders such as heredity, sex, smoking etc, i.e. factors that can co-vary both with the exposure and the effect. Confidence Interval. OR and AOR are given with its confidence interval. The 95 % confidence interval is ± 1.96 SE (Standard error). CI gives an idea of the precision of the estimate. Standard error. The standard error of a rate is a measure of the sampling variability of the rate.
7 (7) p-value A p-value lower than 0.05 means a statistically significant association corresponding to a 95 % confidence interval. p-trend A Chi-square test called linear by linear association calculate the p-value (95 % CI) for a trend in a NxN-table. Kappa (κ) 7. References Cohen s kappa is a measure of agreement between two binary variables that measure the same thing. Kappa of 1 implies perfect agreement; negative kappa means that the agreement is lower than by chance. Often used interpretations of the score of kappa; poor agreement < 0.20, fair agreement , moderate agreement , good agreement and very good agreement (Chapman and Hall, 1991). Aberg, N. (1989) Asthma and allergic rhinitis in Swedish conscripts. Clin Exp Allergy, 19(1): Beasley, R., Ellwood, P. and Asher, I. (2003) International patterns of the prevalence of pediatric asthma the ISAAC program. Pediatr Clin North Am, 50(3): Berner, A. and Bornehag, C. (2004) Breastfeeding less than three months increases the risk for airway and rhinitis symptoms in children. Proceeding of The Annual Meeting of the American Academy of Allergy, Asthma and Immunology 2004, San Francisco, California, USA. Bornehag, C.G., Blomquist, G., Gyntelberg, F., Jarvholm, B., Malmberg, P., Nordvall, L., Nielsen, A., Pershagen, G. and Sundell, J. (2001) Dampness in buildings and health. Nordic interdisciplinary review of the scientific evidence on associations between exposure to "dampness" in buildings and health effects (NORDDAMP). Indoor Air, 11(2): Bornehag, C.G., Sundell, J., Hägerhed, L. and Bengtsson, M. (2002) Differences in possible risk factors for allergic diseases between children living on farms and other children. Proceeding of 9th International Conference on Indoor Air Quality and Climate 2002, Monterey, California, USA. Bornehag, C.G., Sundell, J., Hägerhed, L. and Janson, S. (2002) Dampness in Buildings and Health. Dampness at home as a risk factor for symptoms among Swedish children (DBH-Step 1). Proceeding of 9th International Conference on Indoor Air Quality and Climate 2002, Monterey, California, USA. Vol. III, Bornehag, C.G., Sundell, J., Hagerhed, L. and Janson, S. (2003) Pet-keeping in early childhood and airway, nose and skin symptoms later in life. Allergy, 58(9): Bornehag, C.G., Sundell, J. and Hägerhed, L. (2003) Dampness in dwelling and sick building syndrome among adults: a cross sectional study of 8918 Swedish homes. Proceeding of 7th International Conference on Healthy Buildings 2003, Singapore. Bornehag, C.G., Sundell, J. and Hägerhed, L. (2003) Ventilation rate in 400 homes and its impact on asthma and allergy among children in Sweden, A case control study. Proceeding of Cold Climate HVAC 2003, Trondheim, Norway. Bornehag, C.G., Sundell, J., Bonini, S., Custovic, A., Malmberg, P., Skerfving, S., Sigsgaard, T. and Verhoeff, A. (2004) Dampness in buildings as a risk factor for health effects, EUROEXPO: a multidisciplinary review of the literature ( ) on dampness and mite exposure in buildings and health effects. Indoor Air, 14(4): Bornehag, C.G., Sundell, J., Hägerhed-Engman, L., Sigsgaard, T., Janson, S. and Åberg, N. (2004) Dampness at home and its association with airway, nose and skin symptoms among preschool children in Sweden: a cross sectional study. Indoor Air, in press. Bornehag, C.G., Sundell, J., Sigsgaard, T. and Hagerhed-Engman, L. (2004) Association between ventilation rates in 390 Swedish homes and allergic symptoms in children: a nested case control study. Indoor Air, in press.
8 (8) Bornehag, C.G., Sundell, J., Sigsgaard, T. and Janson, S. (2004) Potential self-selection bias in a nested case control study on indoor environmental factors and their association to asthma and allergy among pre-school children. Scand J Publ Health, in press. Bornehag, C.G., Sundell, J., Weschler, C.J., Sigsgaard, T., Lundgren, B., Hasselgren, M. and Hagerhed-Engman, L. (2004) The Association between Asthma and Allergic Symptoms in Children and Phthalates in House Dust: A Nested Case-Control Study. Environ Health Perspect, 112(14): Bornehag, C.G., Sundell, J., Lundgren, B., Weschler, C.J., Sigsgaard, T. and Hagerhed-Engman, L. (2005) Phthalates in indoor dust and their association with building characteristics. Environ Health Perspect, submitted. Chapman, M.D. and Hall, (1991) Practical Statistics for Medical Research. Ellwood, P., Asher, M.I., Beasley, R., Clayton, T.O. and Stewart, A.W. (2005) The international study of asthma and allergies in childhood (ISAAC): phase three rationale and methods. Int J Tuberc Lung Dis, 9(1): Engström, M. (2001) Differencies in possible risk-factors for allergic diseases between children living on farms and other children., Karlstad University, Sweden. Etzel, R.A. (2003) How environmental exposures influence the development and exacerbation of asthma. Pediatrics, 112(1 Pt 2): Forsman, G. (2001) Differences in prevalence of allergic symptoms and airway infections between different day care centers in Karlstad, Sweden. Karlstad University, Sweden. Hasselgren, M., Hederos, C.A., Bornehag, C., Anderson, S., Janson, S., Åberg, N. and Sigsgaard, T. (2005) Clinical validation of self-reported airway, nose an skim in pre-school children. A nested case-control study, DBHphase II. In manuscript. Hägerhed-Engman, L., Bornehag CG and Sundell, J. (2005) Building characteristics and its associations to moisture related problems in Swedish dwellings. A cross sectional questionnaire study. In manuscript. Hägerhed-Engman, L., Bornehag, C.G. and Sundell, J. (2005) How valid are questionnaire data on building characteristics and signs of dampness? DBH-step2. In manuscript. Hägerhed-Engman, L., Åberg, N. and Bornehag, C. (2005) Day care attendance increase the risk for infections and other asthmatic and allergic symptoms, DBH phase 1. In manuscript. Hägerhed, L., Bornehag, C.G. and Sundell, J. (2002) Dampness in buildings and health (DBH). Building characteristics as predictors for "dampness" in Swedish dwellings. Proceeding of 9th International Conference on Indoor Air Quality and Climate 2002, Monterey, California, USA. Vol: V, Hägerhed, L., Bornehag, C. and Sundell, J. (2003) Validation of Questionnaire Data With Inspections on Dampness Indications in 390 Swedish Dwellings- DBH Step 2. Proceeding of 7th International Conference on Healthy Buildings 2003, Singapore. Nilsson, A., Lagesson, V., Tagesson, C., Bornehag, C.G. and Sundell, J. (2004) Chemical analyses of volatile compounds in indoor dust using gas chromatography-uv spectrometry. Atmospheric Environment, submitted. Stymne, H., Sandberg, M. and Boman, C. (2002) Tracer gas techniques for measurement of ventilation in multi-zone buildings - a review. Proceeding of 9th International Conference on Indoor Air Quality and Climate 2002, Monterey, California, USA.