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A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings
Science of the Total Environment 407 (2009) 5223–5228
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Science of the Total Environment j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c i t o t e n v
A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings Tomoko Takigawa a,⁎, Bing-Ling Wang a, Noriko Sakano a, Da-Hong Wang a, Keiki Ogino a, Reiko Kishi b a b
Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Okayama, Japan Department of Public Health, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
a r t i c l e
i n f o
Article history: Received 2 March 2009 Received in revised form 27 May 2009 Accepted 23 June 2009 Available online 15 July 2009 Keywords: Sick building syndrome Aldehydes Volatile organic compounds Fungi Dust mite allergen
a b s t r a c t This study was performed to explore possible environmental risk factors, including indoor chemicals, mold, and dust mite allergens, which could cause sick building syndrome (SBS)-type symptoms in new houses. The study was conducted in 2004 and 2005 and the final study population consisted of 86 men and 84 women residing in Okayama, Japan. The indoor concentrations of indoor aldehydes, volatile organic compounds, airborne fungi, and dust mite allergens in their living rooms were measured and the longitudinal changes in two consecutive years were calculated. A standardized questionnaire was used concomitantly to gather information on frequency of SBS-type symptoms and lifestyle habits. About 10% of the subjects suffered from SBS in the both years. Crude analyses indicated tendencies for aldehyde levels to increase frequently and markedly in the newly diseased and ongoing SBS groups. Among the chemical factors and molds examined, increases in benzene and in Aspergillus contributed to the occurrence of SBS in the logistic regression model. Indoor chemicals were the main contributors to subjective symptoms associated with SBS. A preventive strategy designed to lower exposure to indoor chemicals may be able to counter the occurrence of SBS. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Sick building syndrome (SBS) is a constellation of health problems caused by indoor chemical and biological pollution, uncomfortable temperature and humidity, or other factors in office buildings, which has been acknowledged as a problem in Western countries since the 1970s (Godish, 1994; Skov et al., 1987; World Health Organization, 1983). Occupants suffer from a variety of nonspecific subjective symptoms, such as irritation of the eyes, nose, and throat, headache, and general fatigue (Burge et al., 1987; Finnegan et al., 1984; Lyles et al., 1991; Mendell and Smith, 1990). In Japan, some people living in newly-built or renovated residential buildings began to complain of various nonspecific subjective symptoms in the 1990s (Saijo et al., 2004). These symptoms are similar to SBS-related symptoms and have been called “sick house syndrome” (Ando, 2002; Seki et al., 2007; Torii, 2002). This concept has now been applied to similar situations in schools or cars (Schupp et al., 2005; Yoshino et al., 2004). SBS is difficult to define and no single cause has been identified. Many epidemiological studies have been performed, and a number of possible contributing factors have been reported, including airborne chemicals, microorganisms, physical condition, and psychosocial status (Bornehag et al., 2004; Marmot et al., 2006; Nakayama and ⁎ Corresponding author. Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Mailing address: 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Tel.: +81 86 235 7184; fax: +81 86 226 0715. E-mail address: [email protected] (T. Takigawa). 0048-9697/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.scitotenv.2009.06.023
Morimoto, 2007; Skov et al., 1989; Sunesson et al., 2006; Teeuw et al., 1994; Wolkoff and Kjaergaard, 2007). However, most of these studies had a cross-sectional design and there were differences among participants. Norback et al. (Norback et al., 1990) carried out a longitudinal research in occupational settings, primary schools, but they performed chemical measurements only in the 4th year. To exclude the time-invariant unobserved differences in individual characteristics, the present longitudinal study was performed to explore indoor aldehydes, VOCs, airborne fungi, house dust mite allergens, and other possible contributing factors. To our knowledge, there have been no longitudinal studies including both wide-ranging environmental measurements and questionnaire survey in many dwellings. 2. Materials and methods 2.1. Study population and selection of houses This study was conducted in Okayama Prefecture, located in the western part of Japan, between September and December in both 2004 and 2005. In 2003, a preliminary questionnaire survey was carried out on the indoor environment of newly built dwellings and SBS. Dwellings built within 5 years as of 2003 were chosen randomly from building plan approval applications, which are official data available for inspection. The occupants of 91 dwellings (247 residents) from among the respondents of 519 dwellings in the 2003 survey agreed to participate in the 2004 survey. Of the subjects in 2004, 185
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residents in 49 dwellings participated in the investigation in 2005. A final total of 170 people from 48 dwellings without missing data were included in the analyses. This epidemiological study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. All subjects gave their written informed consent. 2.2. Environmental monitoring of chemical substances Air samples were collected onto diffusive air samplers for aldehydes (DSD-DNPH; Sigma-Aldrich, Tokyo, Japan) and for VOCs (VOC-SD; Sigma-Aldrich) placed approximately 1.5 m above the floor for 24 h. To eliminate contamination effects, field blank samples were obtained simultaneously to subtract the blank results from the crude chemical concentrations. Temperature and relative humidity were also measured. Concentrations of 13 aldehydes (including one ketone, acetone) and 33 VOCs were quantified in the laboratory using the methods described in previously (Takigawa et al., 2004). Briefly, the derivatives in the DSD-DNPH samplers were eluted with acetonitrile before analysis by high-performance liquid chromatography equipped with a UV detector. The VOC-SD samplers were desorbed with carbon disulfide before analysis with a gas chromatograph/mass spectrometer. The analysis methods were standardized to make the results compatible between the two survey years. The list of chemicals included the major components of indoor chemicals detected in Japanese residences (Tanaka-Kagawa et al., 2005). Total VOC (TVOC) concentration was defined as the sum of concentrations of the target VOCs. If aldehydes and VOC concentrations were lower than the limits of quantification (1.0 μg/m3 for each substance), they were considered half the limit of quantification. 2.3. Environmental monitoring of microorganisms Airborne fungal spores were collected using an SAS air sampler (AINEX BIO-SAS, International PBI, Milano, Italy) for an air volume of for 0.1 m3 with dichloran 18% glycerol agar (DG-18) as culture medium. Samples were taken at a height of 1.5 m above the floor in the living room. After incubation, fungal colonies were counted and species were identified morphologically (Wang et al., 2008). The fungal concentrations were expressed as colony forming units per cubic meter of air (cfu/m3). Living room floor dust was collected by vacuuming 2 m2 of wooden floor or tatami (Japanese traditional rush mats), or 1 m2 of carpet. Dust samples were collected into paper bags using a hand vacuum cleaner (HC-V15; National, Osaka, Japan). Dust mite allergens were measured by ELISA for Der p1 and Der f1 and expressed in micrograms
Table 2 Indoor chemical concentrations in living rooms (n = 48). 2004 Formaldehyde Acetaldehyde Acetone Acrolein Propionaldehyde Crotonaldehyde n-Butyraldehyde Benzaldehyde iso-Valeraldehyde Valeraldehyde Tolualdehyde Hexaldehyde 2,5-Dimethylaldehyde Methylethylketone Ethyl acetate n-Hexane Chloroform 1,2-Dichloroethane 2,4-Dimethylpentane 1,1,1-Trichloroethane n-Butanol Benzene Carbon tetrachloride 1,2-Dichloropropane Trichloroethylene n-Heptane Methylisobutylketone Toluene Chlorodibromomethane Butyl acetate n-Octane Tetrachloroethylene Ethylbenzene m, p-Xylene Styrene n-Nonane o-Xylene α-Pinene 1,3,5-Trimethylbenzene n-Decane 1,2,4-Trimethylbenzene p-Dichlorobenzene 1,2,3-Trimethylbenzene Limonene n-Undecane TVOC
2005 25%
75%
Median
25%
75%
37.00 15.25 27.81 0.50 6.60 0.50 1.40 1.80 0.50 1.35 1.00 6.00 0.50 0.50 2.80 0.50 0.50 0.50 0.50 0.50 0.50 1.20 0.50 0.50 0.50 0.50 0.50 9.80 0.50 1.35 0.50 0.50 2.57 3.52 0.50 0.80 1.50 7.35 0.50 0.50 2.26 2.75 0.50 10.00 1.20 101.50
28.00 10.60 21.68 0.50 4.13 0.50 0.50 0.50 0.50 0.50 1.00 3.33 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 8.02 0.50 0.50 0.50 0.50 1.53 1.13 0.50 0.50 0.50 2.23 0.50 0.50 1.29 1.13 0.50 4.46 0.50 63.10
47.44 21.24 35.85 0.50 11.90 3.57 2.10 6.76 4.94 2.52 9.17 19.63 0.50 2.78 8.09 2.38 0.50 0.50 0.50 0.50 1.43 4.48 0.50 0.50 0.50 1.98 0.50 19.43 0.50 4.35 1.58 0.50 4.39 5.76 0.50 5.46 2.30 21.93 1.23 7.25 6.66 30.80 0.50 30.05 6.48 190.83
29.81 7.88 17.83 0.50 0.50 0.50 0.50 0.50 0.50 0.50 1.00 0.50 0.50 2.21 3.24 0.50 0.50 0.50 0.50 0.50 0.50 1.77 0.50 0.50 0.50 0.50 0.50 7.49 0.50 1.92 1.08 0.50 1.82 2.55 0.50 0.78 0.50 4.88 0.50 0.50 1.39 2.19 0.50 5.63 2.16 69.00
20.26 4.61 11.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 1.00 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 1.36 0.50 0.50 0.50 0.50 0.50 3.98 0.50 0.65 0.50 0.50 1.00 1.32 0.50 0.50 0.50 1.60 0.50 0.50 0.50 1.05 0.50 2.38 1.10 50.00
51.93 16.52 26.13 0.50 0.50 2.02 0.50 0.50 0.50 0.50 1.00 1.48 0.50 3.22 7.77 1.58 1.05 0.50 0.50 0.50 0.90 2.69 0.50 0.50 0.50 1.34 0.89 9.69 0.50 3.48 1.95 0.50 3.27 3.44 0.50 4.02 1.59 13.43 0.50 3.15 2.34 9.91 0.50 10.56 4.87 123.34
% Age at the first study b10 10–20 20–30 30–40 40–50 50–60 ≥60 Gender Male Female SBS Newly diseased Ongoing Recovered Symptom-free
26.5 7.1 9.4 25.9 11.8 12.9 6.5 50.6 49.4 8.8 3.5 7.6 80.0
0.30 b0.01 b0.01 0.32 b0.01 0.26 0.01 b0.01 b0.01 b0.01 b0.01 b0.01 0.03 0.29 0.84 0.48 0.59 0.05 0.66 0.32 0.90 0.76 1.00 1.00 0.18 0.63 0.42 b0.01 0.18 0.81 0.24 0.66 0.02 0.03 0.74 0.39 0.04 0.02 0.04 0.08 b0.01 0.01 0.98 0.01 0.74 0.01
Units: µg/m3; TVOC = total volatile organic compounds. ⁎Wilcoxon test.
Table 3 Concentrations of mold colonies and dust mite allergen levels in living rooms (n = 48). 2004
Table 1 Description of the subjects (n = 170).
P⁎
Median
Genus Alternaria Aspergillus Aureobasidium Candida Cladosporium Cryptococcus Eurotium Rhodotorula Strain Arthrinium sp. Penicillium sp. Fusarium sp. Total colonies Der p Der f Der 1
P*
2005
Median
25%
75%
Median
25%
75%
0 10 0 0 185 0 0 0
0 0 0 0 72.5 0 0 0
10 27.5 0 0 810 0 0 0
0 10 0 0 335 0 0 0
0 0 0 0 150 0 0 0
0 20 0 0 717.5 0 10 0
b 0.01 0.65 0.16 0.50 0.15 1.00 b 0.01 0.03
0 20 0 325 0.3 1.0 2.2
0 0 0 187.5 0.1 0.4 0.6
0 60 10 995 1.3 4.1 8.9
0 0 0 565 0.1 2.2 3.7
0 0 0 255 0.1 0.7 0.9
0 0 0 957.5 2.8 5.2 12.1
0.09 b 0.01 0.01 0.22 0.96 0.05 0.09
Units: cfu/m3 for mold colonies and µg/g fine dust for dust mite allergen levels. *Wilcoxon test.
T. Takigawa et al. / Science of the Total Environment 407 (2009) 5223–5228
per gram of fine dust (μg/g fine dust) (Wang et al., 2008). The limit of quantification for both mite allergens was 0.1 μg/g fine dust. Der 1 levels were calculated as the sum of quantified Der p1 and Der f1. To calculate Der 1, the values of Der p1 and Der f1 below the limits of quantification were assigned to half the limit of quantification. 2.4. Questionnaire study We distributed self-administered questionnaires based on the “questionnaire for national investigation for SBS and its potential risk factors in Japan” (Wang et al., 2007) to the participants when we visited their homes for environmental monitoring. The questions on subjective symptoms of SBS were derived from the Japanese version of MM040EA, a validated questionnaire designed for epidemiological assessment of SBS symptoms (Mizoue et al., 2001). Symptoms surveyed during the last 3 months, were as follows: optical symptoms (eye irritation), nasal symptoms (running or blocked nose, and sneezing), gular symptoms (hoarseness, dry throat, cough and wheezing), dermal symptoms (itching, dry, flushed, and erupted skin), and general symptoms (tired, feeling heavy-headed, headache,
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having nausea, dizzy, and having difficulty concentrating). For each symptom, the following responses were possible: always, sometimes, and never. Ongoing symptoms (“always”), were defined as occurring three or more times a week, and sporadic symptoms (“sometimes”) were defined as occurring once or twice a week. The respondents were also asked whether they attributed the symptom to their home environment. If subjects reported any ongoing or sporadic symptoms related to the home environment, they were designated positive for SBS symptoms. Those who complained about at least one positive symptom were classified as suffering from SBS. The questionnaire also included queries about age, gender, sufficiency of sleep, stress level at work, use of moth repellent, and history of allergic diseases. If the participants were too young or old to read or write, another family member answered the questionnaires on their behalf. 2.5. Statistical analysis Subjects were divided into four categories according to their status of SBS in the 2 years: newly diseased, ongoing, recovered, and symptom-free groups. Subjects who without an SBS symptom in
Table 4 Changesa in concentration of indoor chemicals in living rooms between ongoing or newly diseased groups and recovered or symptom-free groups (n = 170). Newly diseased or Ongoing Formaldehyde Acetaldehyde Acetone Acrolein Propionaldehyde Crotonaldehyde n-Butyraldehyde Benzaldehyde iso-Valeraldehyde Valeraldehyde Tolualdehyde Hexaldehyde 2,5-Dimethylaldehyde Methylethylketone Ethyl acetate n-Hexane Chloroform 1,2-Dichloroethane 2,4-Dimethylpentane 1,1,1-Trichloroethane n-Butanol Benzene Carbon Tetrachloride 1,2-Dichloropropane Trichloroethylene n-Heptane Methylisobutylketone Toluene Chlorodibromomethane Butyl acetate n-Octane Tetrachloroethylene Ethylbenzene m, p-Xylene Styrene n-Nonane o-Xylene α-Pinene 1,3,5-Trimethylbenzene n-Decane 1,2,4-Trimethylbenzene p-Dichlorobenzene 1,2,3-Trimethylbenzene Limonene n-Undecane TVOC
Recovered or Symptom-free
Mean
SD
25%
75%
Mean
SD
25%
75%
15.92 13.41 21.44 0.00 15.17 4.27 2.51 14.03 10.21 5.18 −8.62 15.31 2.16 −0.62 −0.83 0.87 1.14 −0.31 0.00 0.00 −0.23 1.27 0.00 0.00 0.00 0.72 −0.20 7.88 −2.56 1.95 −0.30 0.00 1.23 1.77 −0.15 1.71 0.80 3.70 0.20 0.83 2.08 −30.38 −0.40 12.98 −0.80 2.35
42.94 17.39 25.36 0.00 15.80 9.23 7.20 20.89 16.17 12.36 10.98 12.76 4.16 2.44 6.06 2.61 1.80 2.07 0.00 0.00 1.30 4.59 0.00 0.00 0.00 5.07 2.71 8.22 11.74 5.85 1.72 0.00 3.33 4.29 0.86 8.26 1.89 10.55 0.50 6.46 4.31 85.70 2.10 27.94 7.57 121.35
−8.01 1.29 −1.86 0.00 4.11 −1.32 0.00 0.37 0.00 0.04 −14.52 2.20 0.00 −2.05 −2.37 0.00 0.00 0.00 0.00 0.00 −0.27 −1.32 0.00 0.00 0.00 −0.30 0.00 1.76 0.00 −1.30 −1.73 0.00 0.10 0.41 0.00 0.00 −0.13 −1.30 0.00 0.00 −0.20 −3.61 0.00 −1.62 −4.03 −74.51
30.90 29.98 40.89 0.00 23.78 9.84 6.88 19.85 15.13 5.87 0.00 21.97 3.18 0.59 2.35 1.85 3.40 0.00 0.00 0.00 0.36 2.07 0.00 0.00 0.00 0.00 0.00 12.38 0.00 5.12 0.00 0.00 3.47 4.24 0.00 1.93 2.86 8.19 0.18 1.25 1.37 1.40 0.00 6.79 0.05 33.66
−2.34 5.96 2.67 0.04 9.11 2.16 0.67 7.45 5.12 3.48 −3.30 10.30 0.67 −0.04 −0.27 0.71 0.19 −0.15 −0.02 0.03 −0.06 −0.20 0.00 0.00 0.07 0.73 −0.32 8.03 −1.54 0.23 −0.10 0.00 0.52 1.17 0.64 1.56 0.66 4.62 0.59 1.93 2.51 10.37 0.15 11.15 1.01 44.17
27.09 10.86 51.79 0.46 9.18 7.94 6.71 15.40 11.97 9.09 7.72 11.78 2.46 2.54 7.30 3.41 1.19 1.32 0.14 0.16 1.19 6.42 0.00 0.00 0.36 5.38 1.83 11.77 9.36 4.13 3.61 0.22 3.44 5.37 6.09 10.03 3.19 13.79 3.05 9.41 5.48 25.80 2.89 29.58 13.39 108.02
−10.98 0.74 0.76 0.00 4.04 −1.33 0.00 0.00 0.00 0.00 −2.42 2.24 0.00 −1.72 −3.83 −0.56 0.00 0.00 0.00 0.00 0.00 −1.47 0.00 0.00 0.00 −0.82 0.00 0.94 0.00 −1.17 −1.54 0.00 −0.78 −1.16 0.00 −0.99 −0.07 −0.52 0.00 −0.83 −0.51 −0.68 0.00 −1.87 −3.46 −15.47
13.93 11.55 15.98 0.00 11.41 2.14 1.59 5.89 4.24 2.02 0.00 18.41 0.00 1.57 2.70 1.71 0.00 0.00 0.00 0.00 0.61 2.38 0.00 0.00 0.00 0.89 0.00 10.78 0.00 1.55 0.09 0.00 1.90 2.58 0.00 1.51 1.30 8.19 0.52 3.96 3.25 2.19 0.00 18.35 2.37 92.24
Units: µg/m3; SD = standard deviation, TVOC = total volatile organic compounds. ⁎t test; ⁎⁎Mann-Whitney test. a Changes were determined by subtracting the concentrations in 2004 from those in 2005.
P⁎
P⁎⁎
0.07 0.07 0.11 0.71 0.10 0.27 0.25 0.08 0.08 0.45 0.04 0.07 0.12 0.32 0.74 0.85 0.03 0.63 0.45 0.40 0.55 0.31 – – 0.37 0.99 0.80 0.96 0.65 0.21 0.81 0.97 0.37 0.63 0.55 0.95 0.84 0.77 0.57 0.61 0.73 0.04 0.41 0.79 0.55 0.10
0.02 0.14 0.03 0.71 0.15 0.10 0.29 0.05 0.02 0.14 b 0.01 0.14 0.02 0.32 0.67 0.39 0.04 0.46 0.45 0.40 0.78 0.63 – – 0.28 0.97 0.63 0.31 0.61 0.54 0.90 0.71 0.15 0.29 0.82 0.72 0.27 0.85 0.87 0.70 0.94 0.01 0.56 0.46 0.28 0.09
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Table 5 Changesa in mold colonies and dust mite allergen levels in living rooms between ongoing or newly diseased groups and recovered or symptom-free groups (n = 170). Newly diseased or ongoing Genus Alternaria Aspergillus Aureobasidium Candida Cladosporium Cryptococcus Eurotium Rhodotorula Strain Arthrinium sp. Penicillium sp. Fusarium sp. Total colonies Der p1 Der f1 Der 1
Recovered or symptom-free
Mean
SD
25%
75%
4.76 18.10 0.00 −13.81 305.71 0.48 −4.29 1.90
11.67 39.07 0.00 33.83 1203.72 2.18 9.78 6.80
0.00 −15.00 0.00 −5.00 −530.00 0.00 −5.00 0.00
0.95 58.10 8.10 305.71 −0.84 −2.57 −3.39
3.01 50.36 14.36 1321.68 4.81 9.88 9.39
0.00 15.00 0.00 −735.00 −0.12 −4.13 −6.58
Mean
SD
25%
10.00 60.00 0.00 0.00 900.00 0.00 0.00 0.00
5.17 4.16 0.87 −3.09 −124.23 −0.13 −8.66 2.68
9.91 39.11 4.18 18.38 604.88 2.32 15.97 27.23
0.00 −10.00 0.00 0.00 −510.00 0.00 −10.00 0.00
0.00 110.00 15.00 1100.00 0.43 2.73 2.78
2.42 84.30 6.78 −133.42 −0.58 −1.40 −1.96
10.76 352.10 19.70 737.92 9.08 8.62 12.08
0.00 0.00 0.00 −570.00 −0.18 −2.80 −5.95
P⁎
P⁎⁎
10.00 10.00 0.00 0.00 80.00 0.00 0.00 0.00
0.86 0.13 0.01 0.17 0.12 0.26 0.22 0.90
0.78 0.06 0.37 0.11 0.12 0.26 0.21 0.60
0.00 50.00 0.00 190.00 0.42 0.19 1.05
0.19 0.73 0.77 0.15 0.90 0.57 0.60
0.65 0.01 0.46 0.12 0.97 0.76 0.97
75%
Units: cfu/m3 for mold colonies and µg/g fine dust for mite allergen; SD = standard deviation. ⁎t test; ⁎⁎Mann-Whitney test. a Changes in mold colonies and mite allergen levels were determined by subtracting the concentrations in 2004 from those in 2005.
2004 in whom the symptom was observed in 2005 were defined as “newly diseased”, while subjects with the opposite findings were assigned to the “recovered” group. Subjects with SBS symptoms in both 2004 and 2005 were assigned to the “ongoing” group, while subjects with the opposite findings were assigned to the “symptomfree” group. Chemical and biological indoor pollutant concentrations in the living room were matched to each participant as environmental personal exposure factors. The changes in concentration of chemicals, fungi colonies, and dust mite allergens were determined by subtracting the concentration in 2004 from that in 2005. Wilcoxon test, t test, and Mann-Whitney test were used where appropriate. A linear-by-linear association test was used to examine a dose–response relationship between quartiles of concentration changes of environmental factors in the living rooms and newly diseased or ongoing SBS group subjects. A logistic regression analysis model was used to find the possible risk factors for SBS symptoms. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for SBS change in the two-year investigation. The SBS change between the 2 years, newly diseased or ongoing groups and recovered or symptom-free groups, was regarded as the dependent variable. The concentration changes of environmental factors were dichotomized into “≤ 0” and “N 0”, and entered into the model in a backward stepwise fashion as independent variables. The
probability value for inclusion was 0.05 and that for removal was 0.10. Other risk factors, including age, gender, sufficiency of sleep, stress level at work, use of moth repellent, and history of allergic diseases, which were from the baseline data of 2004, were also used in the model as adjusted variables. Two-tailed values of P b 0.05 were considered statistically significant. All analyses were performed with SPSS 13.0 for Windows (SPSS Inc., Chicago, IL). 3. Results Of the total number of eligible subjects, 170 people from 48 dwellings for whom no data were missing were included in the analysis. Table 1 shows the percentage distributions of age in the 2004 study, gender, and current status of SBS. The median age of participants included in the analysis was 34 (range 0–90) years. The average age of dwellings studied was 3.7 years with a range from 0.5 to 6.2 in 2004. The numbers of male and female participants were almost the same. About 11.1% (19 people) and 12.4% (21 people) of the subjects suffered from SBS in the first and second years, respectively. Actual chemical and biological contaminant concentrations were shown in Tables 2 and 3, respectively. Median concentration of formaldehyde was the highest among the determined chemicals, followed by acetone and acetaldehyde. Generally, the concentrations
Table 6 ORs (95% CIs) between each quartile of concentration changes of environmental factors in living rooms and newly diseased or ongoing SBS group. Chemicals Crude Formaldehyde iso-valeraldehyde 2,5-Dimethylaldehyde Aspergillus Penicillium sp. Adjusteda Formaldehyde iso-valeraldehyde 2,5-Dimethylaldehyde Aspergillus Penicillium sp.
Quartile
P⁎
1 (ref)
2
3
4
1 1 −c 1 1
0.70 (0.15–3.31) −b 1 0.17 (0.03–0.94) 1.68 (0.26–10.73)
0.77 (0.16–3.68) −b −c 1.12 (0.29–4.29) 4.37 (1.05–18.08)
3.17 (0.92–10.90) –b 3.11 (1.06–9.08) 1.93 (0.58–6.50) 4.70 (1.19–18.51)
1 1 −c 1 1
0.62 (0.13–3.03) −b 1 0.15 (0.02–0.96) 1.68 (0.25–11.27)
0.75 (0.15–3.73) −b −c 0.83 (0.19–3.68) 4.50 (1.03–19.57)
3.27 (0.88–12.05) –b 2.64 (0.85–8.22) 1.82 (0.51–6.53) 4.97 (1.18–20.84)
OR = odds ratio; CI = confidence interval; SBS = sick building syndrome. ⁎Linear-by-linear association. a Adjustments made for age, gender, sufficiency of sleep, stress at work, use of moth repellent, and history of allergic diseases. b The ORs is too high to be believable. c there is no newly diseased or ongoing subject.
0.03 0.04 0.03 0.03 0.01
T. Takigawa et al. / Science of the Total Environment 407 (2009) 5223–5228 Table 7 Effect of longitudinal changes of possible environmental factors for SBS symptoms. Adjusteda
Unadjusted Chloroform Benzene n-Nonane o-Xylene 1,2,4-Trimethylbenzene Aspergillus
OR
95%CI
P
OR
95%CI
P
4.41 5.01 ns ns 0.21 5.70
1.13–17.18 1.18–21.23 ns ns 0.06–0.80 1.47–22.07
0.03 0.03 ns ns 0.02 0.01
9.29 10.91 0.12 0.09 8.12 17.36
1.45–59.52 1.71–69.45 0.02–0.69 0.01–0.75 1.45–45.35 2.59–116.17
0.02 0.01 0.02 0.03 0.02 b0.01
SBS = sick building syndrome; OR = odds ratio; CI = confidence interval; ns = no significant difference. a Adjusted by age, gender, sufficiency of sleep, stress at work, use of moth repellent, and history of allergic diseases.
tended to decrease in 2005 among many chemicals. Cladosporium accounted for the majority of determined biological factors. Unlike the chemicals, an upward trend in the concentrations of Cladosporium and dust mite allergen was shown in the second year. No difference in the temperature and relative humidity was found between the first and second round sampling. Table 4 shows the changes in indoor chemical concentrations between the 2 years. Although only a few chemicals showed significant changes in concentration, most of the chemicals, especially aldehydes, tended to increase at high frequency and intensity among the newly diseased and ongoing SBS groups. Acetone showed the largest increase, followed by formaldehyde and hexaldehyde. With regard to VOCs, on the other hand, the concentrations fluctuated mildly and increased frequently in the recovered and symptom-free groups. As is shown in Table 5, there were few significant differences in the concentrations of biological factors, such as airborne mold and mite allergens on the floor. The total number of fungal colonies, however, increased markedly in the newly diseased and ongoing groups and decreased in the recovered and symptom-free groups, although these differences were not statistically significant. All of the mite allergen variables showed slightly greater tendencies to decrease in the newly diseased and ongoing groups. We examined a dose-response relationship between the concentration changes of environmental factors and newly diseased or ongoing SBS subjects (Table 6). Some chemicals and mold genius or strain showed such trends, especially for formaldehyde, Aspergillus, and Penicillium sp. In unadjusted and adjusted analyses, changes in SBS symptom status were associated with contaminant changes in risk factor concentrations (Table 7). VOCs mainly remained in the logistic regression model as possible risk factors for SBS, which was natural due to the large number of VOCs included in the analyses. Especially increments in the chemical factor, benzene, and the mold, Aspergillus, were associated with the occurrence of SBS. 4. Discussion In this study, residents in newly built homes allowed monitoring of indoor air contaminants and completed symptom questionnaires for 2 years. The results of crude analyses performed in this study indicated that SBS-type symptoms of inhabitants living in newly built houses have a tendency to be associated with increase of indoor chemical levels, especially aldehydes. Some environmental factors such as formaldehyde, Aspergillus, and Penicillium sp. showed a dose– response relationship with SBS symptoms. With adjustment for confounding factors, other chemicals such as benzene and chloroform or biological factors such as Aspergillus were shown to be possible risk factors for SBS symptoms. Of the indoor chemicals examined, acetone showed the largest increase in a year, followed by formaldehyde and hexaldehyde in the
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newly diseased and ongoing SBS group. These substances, ketone and aldehydes, were assumed to be emitted from building materials containing adhesive or antiseptic agents and air antiodorants or detergents (Vautz et al., 2006; Wang et al., 2007). It was suggested that more air exchange may reduce VOCs to a greater extent than formaldehyde (Kilburn, 2000), and our results supported this suggestion. Another study indicated that ventilation level was markedly responsible for variance of indoor formaldehyde concentration (Menzies et al., 1996). The increases in concentration may be partially due to low ventilation, although we did not monitor ventilation rate due to the lack of a convenient method for its measurement. Cladosporium and Penicillium sp. are fungi frequently found in Japanese dwellings (Nakayama and Morimoto, 2007; Takahashi, 1997) and in western buildings (Cooley et al., 1998). Cladosporium levels were increased in the newly diseased and ongoing SBS groups in the present study, although the difference was not statistically significant. The symptoms of some subjects may have been induced by the mold as fungal contamination in indoor environments was reported to produce SBS in occupants of buildings with indoor air quality problems (Cooley et al., 1998). There have been few studies of the association between longitudinal changes of mites, another biological factors, and SBS. Dust mite allergen was measured in the present study, but we found no apparent relationship with onset of SBS. Several factors as possible SBS risk factors were selected by the logistic regression model after adjusting for confounding factors. Increment of chemical substances such as benzene or chloroform showed strong and significant associations with the occurrence of SBS. Aspergillus and Cladosporium were reported to be associated with an increased risk of allergic sensitization (Jacob et al., 2002). The observations regarding increment of Aspergillus in our model as a risk factor for SBS were consistent with this finding. The strength of our survey included the repeated-measures design in the same seasons, which allowed us to negate the seasonal variations of measured or perceived indoor environment (Mizoue et al., 2004). Temperature and relative humidity measured in the 2 years also confirmed this with no significant difference. For our data to be interpreted properly, the limitations of this study must be addressed. A relatively small number of subjects were included in the longitudinal study, which introduced a biased selection of participants remaining for the survey, possibly characterized by having an interest in SBS or suffering from symptoms. In addition, not all chemical and biological factors in indoor air were determined in the present study. Some other unmeasured chemicals, so-called “stealth chemicals” may also cause subjective symptoms (Kostiainen, 1995). These chemicals, however, were detected at relatively few houses and the results were partially achieved by chance. We performed measurements only in the living room of each house. It was possible that there were concentration differences between the living room and other rooms, but the concentrations were considered to vary little between rooms in the same house (Park and Ikeda, 2004). The results of this study suggested that elevated levels of indoor chemicals increase the risk of SBS in newly built houses. The concentrations of chemical and biological factors vary over time; therefore, ongoing research should be conducted to explore the relationship between indoor environmental factors and subjective symptoms of residents in non-occupational settings. Acknowledgments This study is supported by a Health Science Research Grant for Research on Environmental Health from the Ministry of Health, Labour and Welfare of Japan. We are extremely grateful to the late professor Shohei Kira for his tremendous contributions. We are also indebted to Y. Yamasaki for her dedication in collecting data for the study.
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Contents lists available at ScienceDirect
Science of the Total Environment j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c i t o t e n v
A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings Tomoko Takigawa a,⁎, Bing-Ling Wang a, Noriko Sakano a, Da-Hong Wang a, Keiki Ogino a, Reiko Kishi b a b
Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Okayama, Japan Department of Public Health, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
a r t i c l e
i n f o
Article history: Received 2 March 2009 Received in revised form 27 May 2009 Accepted 23 June 2009 Available online 15 July 2009 Keywords: Sick building syndrome Aldehydes Volatile organic compounds Fungi Dust mite allergen
a b s t r a c t This study was performed to explore possible environmental risk factors, including indoor chemicals, mold, and dust mite allergens, which could cause sick building syndrome (SBS)-type symptoms in new houses. The study was conducted in 2004 and 2005 and the final study population consisted of 86 men and 84 women residing in Okayama, Japan. The indoor concentrations of indoor aldehydes, volatile organic compounds, airborne fungi, and dust mite allergens in their living rooms were measured and the longitudinal changes in two consecutive years were calculated. A standardized questionnaire was used concomitantly to gather information on frequency of SBS-type symptoms and lifestyle habits. About 10% of the subjects suffered from SBS in the both years. Crude analyses indicated tendencies for aldehyde levels to increase frequently and markedly in the newly diseased and ongoing SBS groups. Among the chemical factors and molds examined, increases in benzene and in Aspergillus contributed to the occurrence of SBS in the logistic regression model. Indoor chemicals were the main contributors to subjective symptoms associated with SBS. A preventive strategy designed to lower exposure to indoor chemicals may be able to counter the occurrence of SBS. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Sick building syndrome (SBS) is a constellation of health problems caused by indoor chemical and biological pollution, uncomfortable temperature and humidity, or other factors in office buildings, which has been acknowledged as a problem in Western countries since the 1970s (Godish, 1994; Skov et al., 1987; World Health Organization, 1983). Occupants suffer from a variety of nonspecific subjective symptoms, such as irritation of the eyes, nose, and throat, headache, and general fatigue (Burge et al., 1987; Finnegan et al., 1984; Lyles et al., 1991; Mendell and Smith, 1990). In Japan, some people living in newly-built or renovated residential buildings began to complain of various nonspecific subjective symptoms in the 1990s (Saijo et al., 2004). These symptoms are similar to SBS-related symptoms and have been called “sick house syndrome” (Ando, 2002; Seki et al., 2007; Torii, 2002). This concept has now been applied to similar situations in schools or cars (Schupp et al., 2005; Yoshino et al., 2004). SBS is difficult to define and no single cause has been identified. Many epidemiological studies have been performed, and a number of possible contributing factors have been reported, including airborne chemicals, microorganisms, physical condition, and psychosocial status (Bornehag et al., 2004; Marmot et al., 2006; Nakayama and ⁎ Corresponding author. Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Mailing address: 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Tel.: +81 86 235 7184; fax: +81 86 226 0715. E-mail address: [email protected] (T. Takigawa). 0048-9697/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.scitotenv.2009.06.023
Morimoto, 2007; Skov et al., 1989; Sunesson et al., 2006; Teeuw et al., 1994; Wolkoff and Kjaergaard, 2007). However, most of these studies had a cross-sectional design and there were differences among participants. Norback et al. (Norback et al., 1990) carried out a longitudinal research in occupational settings, primary schools, but they performed chemical measurements only in the 4th year. To exclude the time-invariant unobserved differences in individual characteristics, the present longitudinal study was performed to explore indoor aldehydes, VOCs, airborne fungi, house dust mite allergens, and other possible contributing factors. To our knowledge, there have been no longitudinal studies including both wide-ranging environmental measurements and questionnaire survey in many dwellings. 2. Materials and methods 2.1. Study population and selection of houses This study was conducted in Okayama Prefecture, located in the western part of Japan, between September and December in both 2004 and 2005. In 2003, a preliminary questionnaire survey was carried out on the indoor environment of newly built dwellings and SBS. Dwellings built within 5 years as of 2003 were chosen randomly from building plan approval applications, which are official data available for inspection. The occupants of 91 dwellings (247 residents) from among the respondents of 519 dwellings in the 2003 survey agreed to participate in the 2004 survey. Of the subjects in 2004, 185
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residents in 49 dwellings participated in the investigation in 2005. A final total of 170 people from 48 dwellings without missing data were included in the analyses. This epidemiological study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. All subjects gave their written informed consent. 2.2. Environmental monitoring of chemical substances Air samples were collected onto diffusive air samplers for aldehydes (DSD-DNPH; Sigma-Aldrich, Tokyo, Japan) and for VOCs (VOC-SD; Sigma-Aldrich) placed approximately 1.5 m above the floor for 24 h. To eliminate contamination effects, field blank samples were obtained simultaneously to subtract the blank results from the crude chemical concentrations. Temperature and relative humidity were also measured. Concentrations of 13 aldehydes (including one ketone, acetone) and 33 VOCs were quantified in the laboratory using the methods described in previously (Takigawa et al., 2004). Briefly, the derivatives in the DSD-DNPH samplers were eluted with acetonitrile before analysis by high-performance liquid chromatography equipped with a UV detector. The VOC-SD samplers were desorbed with carbon disulfide before analysis with a gas chromatograph/mass spectrometer. The analysis methods were standardized to make the results compatible between the two survey years. The list of chemicals included the major components of indoor chemicals detected in Japanese residences (Tanaka-Kagawa et al., 2005). Total VOC (TVOC) concentration was defined as the sum of concentrations of the target VOCs. If aldehydes and VOC concentrations were lower than the limits of quantification (1.0 μg/m3 for each substance), they were considered half the limit of quantification. 2.3. Environmental monitoring of microorganisms Airborne fungal spores were collected using an SAS air sampler (AINEX BIO-SAS, International PBI, Milano, Italy) for an air volume of for 0.1 m3 with dichloran 18% glycerol agar (DG-18) as culture medium. Samples were taken at a height of 1.5 m above the floor in the living room. After incubation, fungal colonies were counted and species were identified morphologically (Wang et al., 2008). The fungal concentrations were expressed as colony forming units per cubic meter of air (cfu/m3). Living room floor dust was collected by vacuuming 2 m2 of wooden floor or tatami (Japanese traditional rush mats), or 1 m2 of carpet. Dust samples were collected into paper bags using a hand vacuum cleaner (HC-V15; National, Osaka, Japan). Dust mite allergens were measured by ELISA for Der p1 and Der f1 and expressed in micrograms
Table 2 Indoor chemical concentrations in living rooms (n = 48). 2004 Formaldehyde Acetaldehyde Acetone Acrolein Propionaldehyde Crotonaldehyde n-Butyraldehyde Benzaldehyde iso-Valeraldehyde Valeraldehyde Tolualdehyde Hexaldehyde 2,5-Dimethylaldehyde Methylethylketone Ethyl acetate n-Hexane Chloroform 1,2-Dichloroethane 2,4-Dimethylpentane 1,1,1-Trichloroethane n-Butanol Benzene Carbon tetrachloride 1,2-Dichloropropane Trichloroethylene n-Heptane Methylisobutylketone Toluene Chlorodibromomethane Butyl acetate n-Octane Tetrachloroethylene Ethylbenzene m, p-Xylene Styrene n-Nonane o-Xylene α-Pinene 1,3,5-Trimethylbenzene n-Decane 1,2,4-Trimethylbenzene p-Dichlorobenzene 1,2,3-Trimethylbenzene Limonene n-Undecane TVOC
2005 25%
75%
Median
25%
75%
37.00 15.25 27.81 0.50 6.60 0.50 1.40 1.80 0.50 1.35 1.00 6.00 0.50 0.50 2.80 0.50 0.50 0.50 0.50 0.50 0.50 1.20 0.50 0.50 0.50 0.50 0.50 9.80 0.50 1.35 0.50 0.50 2.57 3.52 0.50 0.80 1.50 7.35 0.50 0.50 2.26 2.75 0.50 10.00 1.20 101.50
28.00 10.60 21.68 0.50 4.13 0.50 0.50 0.50 0.50 0.50 1.00 3.33 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 8.02 0.50 0.50 0.50 0.50 1.53 1.13 0.50 0.50 0.50 2.23 0.50 0.50 1.29 1.13 0.50 4.46 0.50 63.10
47.44 21.24 35.85 0.50 11.90 3.57 2.10 6.76 4.94 2.52 9.17 19.63 0.50 2.78 8.09 2.38 0.50 0.50 0.50 0.50 1.43 4.48 0.50 0.50 0.50 1.98 0.50 19.43 0.50 4.35 1.58 0.50 4.39 5.76 0.50 5.46 2.30 21.93 1.23 7.25 6.66 30.80 0.50 30.05 6.48 190.83
29.81 7.88 17.83 0.50 0.50 0.50 0.50 0.50 0.50 0.50 1.00 0.50 0.50 2.21 3.24 0.50 0.50 0.50 0.50 0.50 0.50 1.77 0.50 0.50 0.50 0.50 0.50 7.49 0.50 1.92 1.08 0.50 1.82 2.55 0.50 0.78 0.50 4.88 0.50 0.50 1.39 2.19 0.50 5.63 2.16 69.00
20.26 4.61 11.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 1.00 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 1.36 0.50 0.50 0.50 0.50 0.50 3.98 0.50 0.65 0.50 0.50 1.00 1.32 0.50 0.50 0.50 1.60 0.50 0.50 0.50 1.05 0.50 2.38 1.10 50.00
51.93 16.52 26.13 0.50 0.50 2.02 0.50 0.50 0.50 0.50 1.00 1.48 0.50 3.22 7.77 1.58 1.05 0.50 0.50 0.50 0.90 2.69 0.50 0.50 0.50 1.34 0.89 9.69 0.50 3.48 1.95 0.50 3.27 3.44 0.50 4.02 1.59 13.43 0.50 3.15 2.34 9.91 0.50 10.56 4.87 123.34
% Age at the first study b10 10–20 20–30 30–40 40–50 50–60 ≥60 Gender Male Female SBS Newly diseased Ongoing Recovered Symptom-free
26.5 7.1 9.4 25.9 11.8 12.9 6.5 50.6 49.4 8.8 3.5 7.6 80.0
0.30 b0.01 b0.01 0.32 b0.01 0.26 0.01 b0.01 b0.01 b0.01 b0.01 b0.01 0.03 0.29 0.84 0.48 0.59 0.05 0.66 0.32 0.90 0.76 1.00 1.00 0.18 0.63 0.42 b0.01 0.18 0.81 0.24 0.66 0.02 0.03 0.74 0.39 0.04 0.02 0.04 0.08 b0.01 0.01 0.98 0.01 0.74 0.01
Units: µg/m3; TVOC = total volatile organic compounds. ⁎Wilcoxon test.
Table 3 Concentrations of mold colonies and dust mite allergen levels in living rooms (n = 48). 2004
Table 1 Description of the subjects (n = 170).
P⁎
Median
Genus Alternaria Aspergillus Aureobasidium Candida Cladosporium Cryptococcus Eurotium Rhodotorula Strain Arthrinium sp. Penicillium sp. Fusarium sp. Total colonies Der p Der f Der 1
P*
2005
Median
25%
75%
Median
25%
75%
0 10 0 0 185 0 0 0
0 0 0 0 72.5 0 0 0
10 27.5 0 0 810 0 0 0
0 10 0 0 335 0 0 0
0 0 0 0 150 0 0 0
0 20 0 0 717.5 0 10 0
b 0.01 0.65 0.16 0.50 0.15 1.00 b 0.01 0.03
0 20 0 325 0.3 1.0 2.2
0 0 0 187.5 0.1 0.4 0.6
0 60 10 995 1.3 4.1 8.9
0 0 0 565 0.1 2.2 3.7
0 0 0 255 0.1 0.7 0.9
0 0 0 957.5 2.8 5.2 12.1
0.09 b 0.01 0.01 0.22 0.96 0.05 0.09
Units: cfu/m3 for mold colonies and µg/g fine dust for dust mite allergen levels. *Wilcoxon test.
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per gram of fine dust (μg/g fine dust) (Wang et al., 2008). The limit of quantification for both mite allergens was 0.1 μg/g fine dust. Der 1 levels were calculated as the sum of quantified Der p1 and Der f1. To calculate Der 1, the values of Der p1 and Der f1 below the limits of quantification were assigned to half the limit of quantification. 2.4. Questionnaire study We distributed self-administered questionnaires based on the “questionnaire for national investigation for SBS and its potential risk factors in Japan” (Wang et al., 2007) to the participants when we visited their homes for environmental monitoring. The questions on subjective symptoms of SBS were derived from the Japanese version of MM040EA, a validated questionnaire designed for epidemiological assessment of SBS symptoms (Mizoue et al., 2001). Symptoms surveyed during the last 3 months, were as follows: optical symptoms (eye irritation), nasal symptoms (running or blocked nose, and sneezing), gular symptoms (hoarseness, dry throat, cough and wheezing), dermal symptoms (itching, dry, flushed, and erupted skin), and general symptoms (tired, feeling heavy-headed, headache,
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having nausea, dizzy, and having difficulty concentrating). For each symptom, the following responses were possible: always, sometimes, and never. Ongoing symptoms (“always”), were defined as occurring three or more times a week, and sporadic symptoms (“sometimes”) were defined as occurring once or twice a week. The respondents were also asked whether they attributed the symptom to their home environment. If subjects reported any ongoing or sporadic symptoms related to the home environment, they were designated positive for SBS symptoms. Those who complained about at least one positive symptom were classified as suffering from SBS. The questionnaire also included queries about age, gender, sufficiency of sleep, stress level at work, use of moth repellent, and history of allergic diseases. If the participants were too young or old to read or write, another family member answered the questionnaires on their behalf. 2.5. Statistical analysis Subjects were divided into four categories according to their status of SBS in the 2 years: newly diseased, ongoing, recovered, and symptom-free groups. Subjects who without an SBS symptom in
Table 4 Changesa in concentration of indoor chemicals in living rooms between ongoing or newly diseased groups and recovered or symptom-free groups (n = 170). Newly diseased or Ongoing Formaldehyde Acetaldehyde Acetone Acrolein Propionaldehyde Crotonaldehyde n-Butyraldehyde Benzaldehyde iso-Valeraldehyde Valeraldehyde Tolualdehyde Hexaldehyde 2,5-Dimethylaldehyde Methylethylketone Ethyl acetate n-Hexane Chloroform 1,2-Dichloroethane 2,4-Dimethylpentane 1,1,1-Trichloroethane n-Butanol Benzene Carbon Tetrachloride 1,2-Dichloropropane Trichloroethylene n-Heptane Methylisobutylketone Toluene Chlorodibromomethane Butyl acetate n-Octane Tetrachloroethylene Ethylbenzene m, p-Xylene Styrene n-Nonane o-Xylene α-Pinene 1,3,5-Trimethylbenzene n-Decane 1,2,4-Trimethylbenzene p-Dichlorobenzene 1,2,3-Trimethylbenzene Limonene n-Undecane TVOC
Recovered or Symptom-free
Mean
SD
25%
75%
Mean
SD
25%
75%
15.92 13.41 21.44 0.00 15.17 4.27 2.51 14.03 10.21 5.18 −8.62 15.31 2.16 −0.62 −0.83 0.87 1.14 −0.31 0.00 0.00 −0.23 1.27 0.00 0.00 0.00 0.72 −0.20 7.88 −2.56 1.95 −0.30 0.00 1.23 1.77 −0.15 1.71 0.80 3.70 0.20 0.83 2.08 −30.38 −0.40 12.98 −0.80 2.35
42.94 17.39 25.36 0.00 15.80 9.23 7.20 20.89 16.17 12.36 10.98 12.76 4.16 2.44 6.06 2.61 1.80 2.07 0.00 0.00 1.30 4.59 0.00 0.00 0.00 5.07 2.71 8.22 11.74 5.85 1.72 0.00 3.33 4.29 0.86 8.26 1.89 10.55 0.50 6.46 4.31 85.70 2.10 27.94 7.57 121.35
−8.01 1.29 −1.86 0.00 4.11 −1.32 0.00 0.37 0.00 0.04 −14.52 2.20 0.00 −2.05 −2.37 0.00 0.00 0.00 0.00 0.00 −0.27 −1.32 0.00 0.00 0.00 −0.30 0.00 1.76 0.00 −1.30 −1.73 0.00 0.10 0.41 0.00 0.00 −0.13 −1.30 0.00 0.00 −0.20 −3.61 0.00 −1.62 −4.03 −74.51
30.90 29.98 40.89 0.00 23.78 9.84 6.88 19.85 15.13 5.87 0.00 21.97 3.18 0.59 2.35 1.85 3.40 0.00 0.00 0.00 0.36 2.07 0.00 0.00 0.00 0.00 0.00 12.38 0.00 5.12 0.00 0.00 3.47 4.24 0.00 1.93 2.86 8.19 0.18 1.25 1.37 1.40 0.00 6.79 0.05 33.66
−2.34 5.96 2.67 0.04 9.11 2.16 0.67 7.45 5.12 3.48 −3.30 10.30 0.67 −0.04 −0.27 0.71 0.19 −0.15 −0.02 0.03 −0.06 −0.20 0.00 0.00 0.07 0.73 −0.32 8.03 −1.54 0.23 −0.10 0.00 0.52 1.17 0.64 1.56 0.66 4.62 0.59 1.93 2.51 10.37 0.15 11.15 1.01 44.17
27.09 10.86 51.79 0.46 9.18 7.94 6.71 15.40 11.97 9.09 7.72 11.78 2.46 2.54 7.30 3.41 1.19 1.32 0.14 0.16 1.19 6.42 0.00 0.00 0.36 5.38 1.83 11.77 9.36 4.13 3.61 0.22 3.44 5.37 6.09 10.03 3.19 13.79 3.05 9.41 5.48 25.80 2.89 29.58 13.39 108.02
−10.98 0.74 0.76 0.00 4.04 −1.33 0.00 0.00 0.00 0.00 −2.42 2.24 0.00 −1.72 −3.83 −0.56 0.00 0.00 0.00 0.00 0.00 −1.47 0.00 0.00 0.00 −0.82 0.00 0.94 0.00 −1.17 −1.54 0.00 −0.78 −1.16 0.00 −0.99 −0.07 −0.52 0.00 −0.83 −0.51 −0.68 0.00 −1.87 −3.46 −15.47
13.93 11.55 15.98 0.00 11.41 2.14 1.59 5.89 4.24 2.02 0.00 18.41 0.00 1.57 2.70 1.71 0.00 0.00 0.00 0.00 0.61 2.38 0.00 0.00 0.00 0.89 0.00 10.78 0.00 1.55 0.09 0.00 1.90 2.58 0.00 1.51 1.30 8.19 0.52 3.96 3.25 2.19 0.00 18.35 2.37 92.24
Units: µg/m3; SD = standard deviation, TVOC = total volatile organic compounds. ⁎t test; ⁎⁎Mann-Whitney test. a Changes were determined by subtracting the concentrations in 2004 from those in 2005.
P⁎
P⁎⁎
0.07 0.07 0.11 0.71 0.10 0.27 0.25 0.08 0.08 0.45 0.04 0.07 0.12 0.32 0.74 0.85 0.03 0.63 0.45 0.40 0.55 0.31 – – 0.37 0.99 0.80 0.96 0.65 0.21 0.81 0.97 0.37 0.63 0.55 0.95 0.84 0.77 0.57 0.61 0.73 0.04 0.41 0.79 0.55 0.10
0.02 0.14 0.03 0.71 0.15 0.10 0.29 0.05 0.02 0.14 b 0.01 0.14 0.02 0.32 0.67 0.39 0.04 0.46 0.45 0.40 0.78 0.63 – – 0.28 0.97 0.63 0.31 0.61 0.54 0.90 0.71 0.15 0.29 0.82 0.72 0.27 0.85 0.87 0.70 0.94 0.01 0.56 0.46 0.28 0.09
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Table 5 Changesa in mold colonies and dust mite allergen levels in living rooms between ongoing or newly diseased groups and recovered or symptom-free groups (n = 170). Newly diseased or ongoing Genus Alternaria Aspergillus Aureobasidium Candida Cladosporium Cryptococcus Eurotium Rhodotorula Strain Arthrinium sp. Penicillium sp. Fusarium sp. Total colonies Der p1 Der f1 Der 1
Recovered or symptom-free
Mean
SD
25%
75%
4.76 18.10 0.00 −13.81 305.71 0.48 −4.29 1.90
11.67 39.07 0.00 33.83 1203.72 2.18 9.78 6.80
0.00 −15.00 0.00 −5.00 −530.00 0.00 −5.00 0.00
0.95 58.10 8.10 305.71 −0.84 −2.57 −3.39
3.01 50.36 14.36 1321.68 4.81 9.88 9.39
0.00 15.00 0.00 −735.00 −0.12 −4.13 −6.58
Mean
SD
25%
10.00 60.00 0.00 0.00 900.00 0.00 0.00 0.00
5.17 4.16 0.87 −3.09 −124.23 −0.13 −8.66 2.68
9.91 39.11 4.18 18.38 604.88 2.32 15.97 27.23
0.00 −10.00 0.00 0.00 −510.00 0.00 −10.00 0.00
0.00 110.00 15.00 1100.00 0.43 2.73 2.78
2.42 84.30 6.78 −133.42 −0.58 −1.40 −1.96
10.76 352.10 19.70 737.92 9.08 8.62 12.08
0.00 0.00 0.00 −570.00 −0.18 −2.80 −5.95
P⁎
P⁎⁎
10.00 10.00 0.00 0.00 80.00 0.00 0.00 0.00
0.86 0.13 0.01 0.17 0.12 0.26 0.22 0.90
0.78 0.06 0.37 0.11 0.12 0.26 0.21 0.60
0.00 50.00 0.00 190.00 0.42 0.19 1.05
0.19 0.73 0.77 0.15 0.90 0.57 0.60
0.65 0.01 0.46 0.12 0.97 0.76 0.97
75%
Units: cfu/m3 for mold colonies and µg/g fine dust for mite allergen; SD = standard deviation. ⁎t test; ⁎⁎Mann-Whitney test. a Changes in mold colonies and mite allergen levels were determined by subtracting the concentrations in 2004 from those in 2005.
2004 in whom the symptom was observed in 2005 were defined as “newly diseased”, while subjects with the opposite findings were assigned to the “recovered” group. Subjects with SBS symptoms in both 2004 and 2005 were assigned to the “ongoing” group, while subjects with the opposite findings were assigned to the “symptomfree” group. Chemical and biological indoor pollutant concentrations in the living room were matched to each participant as environmental personal exposure factors. The changes in concentration of chemicals, fungi colonies, and dust mite allergens were determined by subtracting the concentration in 2004 from that in 2005. Wilcoxon test, t test, and Mann-Whitney test were used where appropriate. A linear-by-linear association test was used to examine a dose–response relationship between quartiles of concentration changes of environmental factors in the living rooms and newly diseased or ongoing SBS group subjects. A logistic regression analysis model was used to find the possible risk factors for SBS symptoms. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for SBS change in the two-year investigation. The SBS change between the 2 years, newly diseased or ongoing groups and recovered or symptom-free groups, was regarded as the dependent variable. The concentration changes of environmental factors were dichotomized into “≤ 0” and “N 0”, and entered into the model in a backward stepwise fashion as independent variables. The
probability value for inclusion was 0.05 and that for removal was 0.10. Other risk factors, including age, gender, sufficiency of sleep, stress level at work, use of moth repellent, and history of allergic diseases, which were from the baseline data of 2004, were also used in the model as adjusted variables. Two-tailed values of P b 0.05 were considered statistically significant. All analyses were performed with SPSS 13.0 for Windows (SPSS Inc., Chicago, IL). 3. Results Of the total number of eligible subjects, 170 people from 48 dwellings for whom no data were missing were included in the analysis. Table 1 shows the percentage distributions of age in the 2004 study, gender, and current status of SBS. The median age of participants included in the analysis was 34 (range 0–90) years. The average age of dwellings studied was 3.7 years with a range from 0.5 to 6.2 in 2004. The numbers of male and female participants were almost the same. About 11.1% (19 people) and 12.4% (21 people) of the subjects suffered from SBS in the first and second years, respectively. Actual chemical and biological contaminant concentrations were shown in Tables 2 and 3, respectively. Median concentration of formaldehyde was the highest among the determined chemicals, followed by acetone and acetaldehyde. Generally, the concentrations
Table 6 ORs (95% CIs) between each quartile of concentration changes of environmental factors in living rooms and newly diseased or ongoing SBS group. Chemicals Crude Formaldehyde iso-valeraldehyde 2,5-Dimethylaldehyde Aspergillus Penicillium sp. Adjusteda Formaldehyde iso-valeraldehyde 2,5-Dimethylaldehyde Aspergillus Penicillium sp.
Quartile
P⁎
1 (ref)
2
3
4
1 1 −c 1 1
0.70 (0.15–3.31) −b 1 0.17 (0.03–0.94) 1.68 (0.26–10.73)
0.77 (0.16–3.68) −b −c 1.12 (0.29–4.29) 4.37 (1.05–18.08)
3.17 (0.92–10.90) –b 3.11 (1.06–9.08) 1.93 (0.58–6.50) 4.70 (1.19–18.51)
1 1 −c 1 1
0.62 (0.13–3.03) −b 1 0.15 (0.02–0.96) 1.68 (0.25–11.27)
0.75 (0.15–3.73) −b −c 0.83 (0.19–3.68) 4.50 (1.03–19.57)
3.27 (0.88–12.05) –b 2.64 (0.85–8.22) 1.82 (0.51–6.53) 4.97 (1.18–20.84)
OR = odds ratio; CI = confidence interval; SBS = sick building syndrome. ⁎Linear-by-linear association. a Adjustments made for age, gender, sufficiency of sleep, stress at work, use of moth repellent, and history of allergic diseases. b The ORs is too high to be believable. c there is no newly diseased or ongoing subject.
0.03 0.04 0.03 0.03 0.01
T. Takigawa et al. / Science of the Total Environment 407 (2009) 5223–5228 Table 7 Effect of longitudinal changes of possible environmental factors for SBS symptoms. Adjusteda
Unadjusted Chloroform Benzene n-Nonane o-Xylene 1,2,4-Trimethylbenzene Aspergillus
OR
95%CI
P
OR
95%CI
P
4.41 5.01 ns ns 0.21 5.70
1.13–17.18 1.18–21.23 ns ns 0.06–0.80 1.47–22.07
0.03 0.03 ns ns 0.02 0.01
9.29 10.91 0.12 0.09 8.12 17.36
1.45–59.52 1.71–69.45 0.02–0.69 0.01–0.75 1.45–45.35 2.59–116.17
0.02 0.01 0.02 0.03 0.02 b0.01
SBS = sick building syndrome; OR = odds ratio; CI = confidence interval; ns = no significant difference. a Adjusted by age, gender, sufficiency of sleep, stress at work, use of moth repellent, and history of allergic diseases.
tended to decrease in 2005 among many chemicals. Cladosporium accounted for the majority of determined biological factors. Unlike the chemicals, an upward trend in the concentrations of Cladosporium and dust mite allergen was shown in the second year. No difference in the temperature and relative humidity was found between the first and second round sampling. Table 4 shows the changes in indoor chemical concentrations between the 2 years. Although only a few chemicals showed significant changes in concentration, most of the chemicals, especially aldehydes, tended to increase at high frequency and intensity among the newly diseased and ongoing SBS groups. Acetone showed the largest increase, followed by formaldehyde and hexaldehyde. With regard to VOCs, on the other hand, the concentrations fluctuated mildly and increased frequently in the recovered and symptom-free groups. As is shown in Table 5, there were few significant differences in the concentrations of biological factors, such as airborne mold and mite allergens on the floor. The total number of fungal colonies, however, increased markedly in the newly diseased and ongoing groups and decreased in the recovered and symptom-free groups, although these differences were not statistically significant. All of the mite allergen variables showed slightly greater tendencies to decrease in the newly diseased and ongoing groups. We examined a dose-response relationship between the concentration changes of environmental factors and newly diseased or ongoing SBS subjects (Table 6). Some chemicals and mold genius or strain showed such trends, especially for formaldehyde, Aspergillus, and Penicillium sp. In unadjusted and adjusted analyses, changes in SBS symptom status were associated with contaminant changes in risk factor concentrations (Table 7). VOCs mainly remained in the logistic regression model as possible risk factors for SBS, which was natural due to the large number of VOCs included in the analyses. Especially increments in the chemical factor, benzene, and the mold, Aspergillus, were associated with the occurrence of SBS. 4. Discussion In this study, residents in newly built homes allowed monitoring of indoor air contaminants and completed symptom questionnaires for 2 years. The results of crude analyses performed in this study indicated that SBS-type symptoms of inhabitants living in newly built houses have a tendency to be associated with increase of indoor chemical levels, especially aldehydes. Some environmental factors such as formaldehyde, Aspergillus, and Penicillium sp. showed a dose– response relationship with SBS symptoms. With adjustment for confounding factors, other chemicals such as benzene and chloroform or biological factors such as Aspergillus were shown to be possible risk factors for SBS symptoms. Of the indoor chemicals examined, acetone showed the largest increase in a year, followed by formaldehyde and hexaldehyde in the
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newly diseased and ongoing SBS group. These substances, ketone and aldehydes, were assumed to be emitted from building materials containing adhesive or antiseptic agents and air antiodorants or detergents (Vautz et al., 2006; Wang et al., 2007). It was suggested that more air exchange may reduce VOCs to a greater extent than formaldehyde (Kilburn, 2000), and our results supported this suggestion. Another study indicated that ventilation level was markedly responsible for variance of indoor formaldehyde concentration (Menzies et al., 1996). The increases in concentration may be partially due to low ventilation, although we did not monitor ventilation rate due to the lack of a convenient method for its measurement. Cladosporium and Penicillium sp. are fungi frequently found in Japanese dwellings (Nakayama and Morimoto, 2007; Takahashi, 1997) and in western buildings (Cooley et al., 1998). Cladosporium levels were increased in the newly diseased and ongoing SBS groups in the present study, although the difference was not statistically significant. The symptoms of some subjects may have been induced by the mold as fungal contamination in indoor environments was reported to produce SBS in occupants of buildings with indoor air quality problems (Cooley et al., 1998). There have been few studies of the association between longitudinal changes of mites, another biological factors, and SBS. Dust mite allergen was measured in the present study, but we found no apparent relationship with onset of SBS. Several factors as possible SBS risk factors were selected by the logistic regression model after adjusting for confounding factors. Increment of chemical substances such as benzene or chloroform showed strong and significant associations with the occurrence of SBS. Aspergillus and Cladosporium were reported to be associated with an increased risk of allergic sensitization (Jacob et al., 2002). The observations regarding increment of Aspergillus in our model as a risk factor for SBS were consistent with this finding. The strength of our survey included the repeated-measures design in the same seasons, which allowed us to negate the seasonal variations of measured or perceived indoor environment (Mizoue et al., 2004). Temperature and relative humidity measured in the 2 years also confirmed this with no significant difference. For our data to be interpreted properly, the limitations of this study must be addressed. A relatively small number of subjects were included in the longitudinal study, which introduced a biased selection of participants remaining for the survey, possibly characterized by having an interest in SBS or suffering from symptoms. In addition, not all chemical and biological factors in indoor air were determined in the present study. Some other unmeasured chemicals, so-called “stealth chemicals” may also cause subjective symptoms (Kostiainen, 1995). These chemicals, however, were detected at relatively few houses and the results were partially achieved by chance. We performed measurements only in the living room of each house. It was possible that there were concentration differences between the living room and other rooms, but the concentrations were considered to vary little between rooms in the same house (Park and Ikeda, 2004). The results of this study suggested that elevated levels of indoor chemicals increase the risk of SBS in newly built houses. The concentrations of chemical and biological factors vary over time; therefore, ongoing research should be conducted to explore the relationship between indoor environmental factors and subjective symptoms of residents in non-occupational settings. Acknowledgments This study is supported by a Health Science Research Grant for Research on Environmental Health from the Ministry of Health, Labour and Welfare of Japan. We are extremely grateful to the late professor Shohei Kira for his tremendous contributions. We are also indebted to Y. Yamasaki for her dedication in collecting data for the study.
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