Relationship Between Sick Building Syndrome and Indoor Environmental Factors in Newly Built Japanese Dwellings

Int Arch Occup Environ Health (2009) 82:583–593
DOI 10.1007/s00420-009-0395-8
ORIGINAL ARTICLE

Relationship between sick building syndrome and indoor environmental factors in newly built Japanese dwellings

Makoto Takeda · Yasuaki Saijo · Motoyuki Yuasa · Ayako Kanazawa · Atsuko Araki · Reiko Kishi

Received: 13 December 2007 / Accepted: 18 January 2009 / Published online: 10 February 2009© Springer-Verlag 2009

AbstractObjectives Indoor air contaminants and dampness indwellings have become important environmental healthissues. The aim of this study is to clarify which factors arerelated to sick building syndrome (SBS) in newly builtdwellings at Hokkaido, Japan, through a comprehensiveevaluation of the indoor environment and validated sickbuilding symptom questionnaires.Methods The symptoms of 343 residents in 104 detachedhouses were surveyed by standardized questionnaires, andthe concentrations of formaldehyde, acetaldehyde, volatileorganic compounds (VOCs), airborne fungi, and dust miteallergen in their living rooms were measured. By summingthe presence or absence of the Wve dampness indicators(condensations, mold growth, moldy odor, high air humid-ity of the bathroom, water leakage), a dampness index wascalculated.Results SBS symptoms were found in 21.6% of surveyedindividuals. In a fully adjusted multivariate logistic regres-sion analysis, the dampness index [odds ratio (OR) = 1.50;95% conWdence interval (CI): 1.06–1.11], log formalde-hyde (OR = 23.79, 95% CI: 2.49–277.65), and log alpha-pinene (OR = 2.87, 95% CI: 1.36–6.03) had signiWcantlyhigher ORs for SBS symptoms. However, other VOCs,

airborne fungi, and dust mite allergen did not have signiW-cantly higher ORs.Conclusion Dampness, formaldehyde, and alpha-pinenewere signiWcantly related to SBS symptoms in newly builtdwellings. We should, therefore, take measures to reducethe chemicals and dampness in dwellings.

Keywords Sick building syndrome · Formaldehyde · Alpha-pinene · Mold · Airborne fungi · Mite allergen

Introduction

The airtightness of dwellings has been increasing recently,with the result that conditions similar to sick building syn-drome (SBS), which occurred in many countries in the1970s, have reemerged in newly built dwellings in Japansince the early 1990s. In Japan, the problem, called “sickhouse syndrome (SHS)”, and other indoor air problems ofdwellings have attracted broad interest (Torii 2002).

We have previously reported that condensation on win-dow panes/walls and mold growth were related to SBSsymptoms in newly built dwellings (Saijo et al. 2002; Saijoet al. 2004). Building dampness was also signiWcantly asso-ciated with airway infections in various types of dwellings(Bakke et al. 2007). In old multifamily dwellings, damp-ness and odor were signiWcantly related to asthma and SBSsymptoms (Engvall et al. 2001a, 2002). Dampness andmold were further signiWcantly associated with upper andlower respiratory symptoms in oYce buildings (Park et al.2004). Dampness at home has also been signiWcantlyrelated to allergy symptoms in preschool children (Bornehaget al. 2005).

Several mechanisms are assumed to account for thedampness eVect. Higher humidity in dwellings facilitates

M. Takeda · Y. Saijo · M. Yuasa · A. Kanazawa · A. Araki · R. Kishi (&)Department of Public Health Science, Graduated School of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo 060-8638, Japane-mail: [email protected]

Y. SaijoDepartment of Health Science, Asahikawa Medical College, Midorigaoka, E2-1-1-1, Asahikawa, Hokkaido 078-8510, Japan

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584 Int Arch Occup Environ Health (2009) 82:583–593

mold growth (Garrett et al. 1998b) and the proliferation ofdust mites (Garrett et al. 1998a; Hirsch et al. 1998; Emeniuset al. 2000; Bemt et al. 2006), both of which can aVect aresident’s health. Fungi can produce microbial volatileorganic compound (MVOC) (Elke et al. 1999; Kim et al.2007), endotoxin (Thorn and Rylander 1998; Park et al.2006), and (1–3)-beta-D-glucan (Beijer et al. 2002; Douwes2005) which may also inXuence a resident’s health. Struc-tural dampness which may be hidden may cause chemicaldegradation of building materials, leading to the formationand emission of 2-ethyl-1-hexanol from the alkaline degra-dation of di-(2-ethylhexyl) phthalate (DEHP) in poly-vinylchloride materials (Wieslander et al. 1999; Sakai et al.2006). The relationship of odor to SBS may be becausemoldy odor reXects exposure to MVOC and pungent odorreXects exposure to formaldehyde, ammonia and otherstrong chemicals (Engvall et al. 2002).

Indoor air quality has declined in part because of com-prehensive energy conservation campaigns and high energyprices which have motivated people to tighten their dwell-ings and reduce the rate of ventilation. As a consequence,air exchange in many homes is at a historically low level(Ole Fanger 2006). Furthermore, Japan includes snowyregions, like Hokkaido, whose dwellings seem to havegreater airtightness. Thus, the indoor environment of dwell-ings is important; yet, in Japanese dwellings, there havebeen few SBS studies which have evaluated comprehensiveindoor environments for the presence of aldehydes, VOCs,airborne fungi, dust mite allergen, etc.

The aim of this study is to clarify which factors arerelated to sick building symptoms in newly built dwellingsin Hokkaido, Japan through a comprehensive evaluation ofthe indoor environment and validated sick building symp-tom questionnaires.

Methods

Study population

During the period of 2003 through 2004, a questionnairesurvey of the indoor air quality and presence of SBS innewly built dwellings was performed in six regions ofJapan (Kish et al. submitted). In Sapporo city (Hokkaidoprefecture) in November 2003, the questionnaires were dis-tributed to the occupants of 1,240 dwellings, which were alldetached houses that had been newly built within 7 years intwo new residential areas. The dwellings were chosen froma list of building plan approval applications. The question-naires included queries about the building structure andcharacteristics, the residents’ habits in the home, and sub-jective symptoms. We asked, “Has any one in your dwell-ing experienced any symptoms such as tiredness, headache,

dermal and mucosal irritation, eczema, or allergic dis-eases?” We requested that the one resident with the mostsevere symptoms in the dwelling answer the questionnaireabout symptoms. The residents of 252 dwellings agreed toparticipate in the symptom questionnaire and have mea-surements of the concentrations of aldehydes, VOCs, airborne fungi, and house dust mite allergens performed intheir dwellings. We randomly selected 53 of 100 dwellingsin which at least one inhabitant complained of one or moresymptoms, and we also randomly selected 51 of 151 dwell-ings in which none of the inhabitants complained of symp-toms. The following year, we performed a comprehensiveindoor environment evaluation, and all residents of these104 dwellings completed the symptom questionnaire inSeptember through October of 2004. Average outdoor tem-perature and relative humidity in September 2004 were18.4°C and 68%, respectively, and in October 2004 theywere 12.5°C and 63%, respectively. During this timeperiod, windows are sometimes opened.

Questionnaire survey

We used two types of questionnaires: one for all residentsand the other for the head of the household or his/her part-ner. The questionnaire for all residents queried for informa-tion on personal characteristics and lifestyle, such as age,gender, current smoking, time spent in the dwelling, work-ing hours, stress level, etc. The questionnaire also containedquestions about the history of any previous treatment by aphysician for asthma or allergies. The questionnaire con-tained the symptoms query part of the Japanese version ofMM040EA, a validated questionnaire designed for epide-miologic assessment of SBS symptoms (Mizoue et al.2001). Symptoms surveyed for over the previous 3 monthsincluded the following: general symptoms (fatigue, feelingheavy-headed, headache, nausea/dizziness, diYculty con-centrating); eye symptoms (itching, burning or irritation ofthe eye); nasal symptoms (irritated, stuVy or runny nose);throat and respiratory symptoms (hoarse, dry throat,cough); and skin symptoms (dry or Xushed facial skin, scal-ing/itching of the scalp or ears, dry, itching or red-skinnedhands). For each symptom, the following answers werepossible: “Yes, often (every week);” “Yes, sometimes;”and “No, never.” An additional question concerning theattribution of a symptom to the home environment wasincluded in the questionnaire. SBS symptoms were scoredas positive if at least one sub-symptom was found to occuroften (every week)/sometimes and was thought to be attrib-uted to the home environment. In this paper, “generalsymptoms,” “eye symptoms,” “nasal symptoms,” “throatand respiratory symptoms,” and “skin symptoms” refer tothe above mentioned MM040 SBS symptoms. Further-more, “any symptom” was deWned as at least one positive

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Int Arch Occup Environ Health (2009) 82:583–593 585

SBS symptom. The questionnaire for children who couldnot read and/or write was answered by a parent.

The other questionnaire for the head of the household orhis/her partner contained questions about dwelling charac-teristics, such as renovation over the past 2 years, Xooringand wall materials in the living room, dampness (condensa-tion on window panes or walls, mold growth, moldy odor,slow drying of wet towels in the bathroom, water leakageduring past 5 years or since you have lived in the dwelling,if 5 years has not passed), pets in the dwelling, the presenceof a smoker in the dwelling, the use of room fragrance, andthe use of insect repellent. By summing the presence orabsence of the Wve dampness indicators, an overall damp-ness index (0–5) was calculated. Data on the structure andage of the dwelling were obtained from a previous surveydone in 2003.

Assessment of indoor environmental factors

Indoor air monitoring of aldehydes, acetone and VOCswere carried out in the living room of each dwelling. Airsamples were collected with a DSD-DNPH diVusion sam-pler (Supelco, Japan) for aldehydes and acetone, and aVOC-SD diVusion sampler (Supelco, Japan) for VOCs at100–150 cm above the Xoor for 24 h. Eleven aldehydes andacetone were quantiWed by HPLC and 27 VOCs were quan-tiWed by GC-MS, using a previously described method(Takigawa et al. 2004). The limit of quantiWcation of eachof the chemicals was 1.0 �g/m3. Total VOC (TVOC) wascalculated as the sum of all VOCs. To calculate TVOC,VOC values under the lower limits of quantiWcation wereconsidered to be half of the lower limit of quantiWcation.

Indoor airborne fungi were collected on dichloran 18%glycerol agar (DG-18) as cultural medium using a SAS airsampler (AINEX BIO-SAS, International Pbi, Italy) for a0.1 m3 air volume at a height of 150 cm above the Xoor inthe living room. The DG-18 medium was incubated at27°C, fungal colonies were counted and species were iden-tiWed morphologically at the Mitsubishi Chemical MedienceCorporation (Tokyo, Japan). The fungal levels wereexpressed as colony forming units per cubic meter of air(CFU/m3).

Dust samples on the Xoor of the living room were col-lected with a hand vacuum cleaner (HC-V15, National,Japan) equipped with a paper Wlter for 0.5 m2/min. Der p1and Der f1 levels of the dust samples were quantiWed byELISA at the LCD Allergic Center (Osaka, Japan); thelimit of quantiWcation of both mite allergens was 0.1 �g/g-Wne dust. Der 1 levels were calculated as the sum of quanti-Wed Der p1 and Der f1. To calculate Der 1, Der p1 and Derf1 values under the lower limit of quantiWcation were con-sidered to be half of the lower limit of quantiWcation.

The temperature and relative humidity in the living roomwere monitored by a Thermo Recorder TR-72U (T&D Cor-poration, Japan) for 24 h, and the average temperature andrelative humidity were calculated. Average indoor tempera-ture and relative humidity were 23.5°C and 56.1%, respec-tively.

Statistical analysis

Statistical analysis was performed by multiple logisticregression, and crude and adjusted odds ratios with 95%conWdence intervals (OR, 95% CI) were calculated. For allstatistical analyses, a 5% level of signiWcance was applied.To obtain adjusted ORs for SBS symptoms, we controlledfor age, gender, current smoking and time spent in thedwelling, which were introduced separately in the model.

To determine whether indoor environmental factors suchas aldehydes, VOCs, fungi and mite allergen were associ-ated with SBS symptoms, Mann–Whitney U tests wereconducted. Next, logarithmic values of aldehydes, VOCs,and fungi and mite allergens which were found to be sig-niWcantly associated with SBS symptom in the Mann–Whitney U tests were applied in the multiple logisticregression models. We controlled for age, gender, historyof allergy, current smoking, time spent in the dwelling andage of dwelling, and each selected variable was introducedseparately in the model. To transfer to their logarithmic val-ues, aldehyde and VOC values under the lower limits ofquantiWcation were considered as half of the lower limit ofquantiWcation, and 0 CFU/m3 for fungus was changed to0.5 CFU/m3.

Finally, the variables which were signiWcantly associ-ated with SBS symptoms in the previous logistic regressionanalyses and basic personal and building factors, such asage, gender, history of allergy, current smoking, time spentin the dwelling, age of the dwelling, dampness index, totalCFU and Der 1, were introduced in the multiple logisticregression model.

All analyses were conducted with SPSS software forWindows version 13.0 (SPSS Inc., Chicago, USA).

Results

Table 1 shows the characteristics of 104 dwellings. Most ofthe dwellings were wooden structures: 43.3% of those builtwithin 3 years and 56.7% of those built within the previous3–8 years.

Table 2 shows the characteristics of the study partici-pants. Among the 343 participants, the proportion offemales was 50.4%, 25.1% were under 10 years old, and11.1% were over 60 years old.

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Table 1 Characteristics of the dwellings

Number of dwellings (n = 104)

n %

Structure of dwelling

Wooden 102 98.1

Reinforced concrete or steel-reinforced concrete 1 1.0

Others 1 1.0

Age of dwelling

1– <2 18 17.3

2– <3 27 26.0

3– <4 18 17.3

4– <5 16 15.4

5– <6 19 18.3

6– <8 6 5.8

Renovation of dwelling over the past 2 years 3 2.9

Wooden Xooring 103 99.0

Wall materials at living room

Vinyl wallpaper 69 66.3

Cloth wallpaper 14 13.5

Plywood 7 6.7

Others 14 13.5

Dampness

Condensation on window panes or walls 50 48.1

Mold growth 69 66.3

Moldy odor 10 9.6

High air humidity in bathroom 18 17.3

Water leakage 14 13.5

Pet in dwelling 29 27.9

Presence of smoker in dwelling 39 37.5

Use of room fragrance 61 58.7

Use of insect repellent 43 41.3

Table 2 Characteristics of participants (n = 343)

Total (n = 343) Female (n = 173) Male (n = 170)

n % n % n %

Age

<10 86 25.1 42 24.3 44 25.9

10–19 36 10.5 16 9.2 20 11.8

20–29 18 5.2 7 4.0 11 6.5

30–39 87 25.4 50 28.9 37 21.8

40–49 47 13.7 20 11.6 27 15.9

50–59 31 9.0 20 11.6 11 6.5

¸60 38 11.1 18 10.4 20 11.8

History of allergy or asthma 186 54.2 113 65.3 73 42.4

Current smoking 57 16.6 13 7.5 44 25.9

Time spent in the dwelling (¸20 h) 78 22.7 60 34.7 18 10.6

Working hours (¸9 h) 95 27.7 26 15.0 69 40.6

Stressful 91 26.5 34 19.7 57 33.5

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Table 3 shows the prevalence of SBS symptoms in thissurvey. Throat and respiratory symptoms, nose symptoms,skin symptoms, eye symptoms, and general symptoms werefound in 13.1, 10.2, 6.4, 3.8, and 2.9% of participants,respectively. Any symptom (throat and respiratory, nose,skin, eye, and general symptom) was found in 21.6% ofparticipants. All symptoms, except for general symptoms,were found at a higher prevalence in females than in males.

Table 4 shows the crude and adjusted ORs of dampness andother variables. Dampness indicators, such as mold growth,moldy odor and water leakage, had signiWcantly higher ORsfor SBS symptoms. Time spent in the dwelling (¸20 h) alsohad a signiWcantly higher OR for SBS symptoms.

Table 5 shows aldehydes, VOCs, fungi and mite allergenlevels in relation to SBS symptoms. The detection rates ofaldehydes measured in this survey (except for threechemicals) were over 90%. Among VOCs, ethylbenzene,m,o,p-xylene, limonene, alpha-pinene, butyl acetate and

toluene had high detection rates in the dwellings. Formal-dehyde, acetone, benzaldehyde, iso-valeraldehyde, hexal-dehyde, crotonaldehyde, limonene, alpha-pinene, benzene,2-pentanone and TVOC had signiWcantly higher indoor airconcentrations in dwellings with SBS symptoms than inthose without.

Cladosporium, Penicillium, Alternaria, Eurotium,Aspergillus and Rhodotorula were the main organismsdetected in the dwellings. In terms of total CFU, Alternariaand Cladosporium had signiWcantly lower fungus levels indwellings with SBS symptoms than in those without. Onlyone fungal genus, Rhodotorula, had signiWcantly higherlevels in dwellings with SBS symptoms (interquartilerange; with SBS symptoms: 0–20, without SBS symptoms:0–10), although the overall detection rate of Rhodotorulawas low (28.8%).

The detection rate of Der 1 was 81.7%. Der p1 and Derf1 had signiWcantly higher levels in dwellings with SBS

Table 3 Prevalence of SBS symptoms in participants (n = 343)

Each symptom was scored as positive if at least one sub-symptom was found to occur often (every week)/sometimes and was thought to be attrib-uted to the home environment. Furthermore, “any symptom” was deWned as at least one positive SBS symptom

All (n = 343) Female (n = 173) Male (n = 170)

n % N % n %

Any symptoms 74 21.6 41 23.7 33 19.4

General 10 2.9 5 2.9 5 2.9

Eye 13 3.8 7 4.0 6 3.5

Nose 35 10.2 19 11.0 16 9.4

Throat and respiratory 45 13.1 29 16.8 16 9.4

Skin 22 6.4 16 9.2 6 3.5

Table 4 Odds ratios (OR) and their 95% conWdence intervals (95% CI) for SBS symptoms in relation to dampness, other dwelling characteristics and per-sonal characteristics

Unadjusted OR Adjusted ORa

OR 95% CI P-value OR 95% CI P-value

Dampness

Condensation on window panes or walls 0.96 0.57–1.60 n.s. 0.82 0.47–1.41 n.s.

Mold growth 2.08 1.10–3.93 0.022 1.83 0.94–3.57 n.s.

Moldy odor 2.55 1.17–5.52 0.021 2.83 1.27–6.31 0.011

High air humidity in bathroom 1.57 0.82–3.01 n.s. 1.62 0.83–3.15 n.s.

Water leakage 2.21 1.15–4.25 0.023 2.30 1.17–4.51 0.015

Pets in dwelling 0.48 0.25–0.91 0.022 0.48 0.25–0.92 0.026

Presence of smoker in dwelling 0.95 0.56–1.60 n.s. 0.73 0.40–1.32 n.s.

Use of room fragrance 0.90 0.53–1.51 n.s. 0.81 0.47–1.38 n.s.

Use of insect repellent 1.36 0.81–2.28 n.s. 1.34 0.79–2.28 n.s.

History of allergy or asthma 1.73 1.01–2.94 0.045 1.79 1.00–3.19 0.050

Current smoking 1.23 0.63–2.39 n.s. 0.63 0.30–1.29 n.s.

Time spent in the dwelling (¸20 h) 2.07 1.17–3.65 0.018 2.09 1.14–3.81 0.016

Working hours (¸9 h) 1.34 0.77–2.34 n.s. 1.64 0.87–3.12 n.s.

Stressful 1.32 0.75–2.32 n.s. 1.54 0.85–2.80 n.s.

a Each variable was introduced separately in the model and ad-justed for age, gender, current smoking and time spent in the dwelling

n.s.—Not signiWcant

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Table 5 SBS symptoms in rela-tion to chemicals, fungi and mite antigen

Detection rate (%) (104 dwellings)

Symptoms (n = 74) No symptom (n = 269)

Median Range (Min–max)

Median Range (Min–max)

P-valuea

Aldehydes and acetone (�g/m3)

Formaldehyde 100.0 70.1 22.1–202.8 63.2 22.1–202.8 0.001

Acetaldehyde 100.0 35.9 4.6–129.5 33.5 1.7–129.5 n.s.

Acetone 100.0 51.1 21.7–606.0 29.1 10.5–606.0 <0.001

Propionaldehyde 100.0 11.4 3.8–22.3 9.7 2.4–24.8 n.s.

Benzaldehyde 100.0 7.3 1.6–18.5 5.5 1.6–117.1 0.041

Iso-Valeraldehyde 100.0 5.8 1.4–16.6 4.6 1.4–104.6 0.037

Hexaldehyde 100.0 19.9 6.2–127.3 17.1 2.0–198.5 0.032

Crotonaldehyde 98.1 9.3 2.1–20.6 7.6 <1.0–20.6 0.001

Valeraldehyde 97.1 8.0 <1.0–39.2 7.3 <1.0–223.7 n.s.

n-Butyraldehyde 96.2 4.7 1.0–12.8 3.6 <1.0–16.6 n.s.

m,o,p-Tolualdehyde 69.2 2.1 <1.0–21.5 2.3 <1.0–21.5 n.s.

VOCs (�g/m3)

Ethylbenzene 100.0 4.6 1.8–15.1 4.5 1.1–21.8 n.s

m,o,p-Xylene 100.0 11.9 4.7–39.3 11.4 3.1–49.6 n.s.

Limonene 99.0 17.6 3.5–484.9 12.5 <1.0–267.6 <0.001

Alpha-Pinene 95.2 12.9 <1.0–302.5 6.9 <1.0–302.5 0.002

Butyl acetate 93.3 6.0 <1.0–61.4 4.9 <1.0–49.3 n.s.

Toluene 92.3 20.2 <1.0–139.8 16.3 <1.0–144.2 n.s.

n-Nonane 87.5 5.2 <1.0–34.6 4.4 <1.0–32.4 n.s.

Trimethylbenzene 85.6 5.1 <1.0–28.7 4.5 <1.0–24.8 n.s.

n-Octane 79.8 3.3 <1.0–19.9 3.6 <1.0–41.2 n.s.

n-Heptane 67.3 2.6 <1.0–35.3 2.3 <1.0–35.3 n.s.

Benzene 51.0 1.2 <1.0–8.5 <1.0 <1.0–9.2 0.047

2-Pentanone 43.3 1.3 <1.0–32.0 <1.0 <1.0–32.0 0.008

p-Dichlorobenzene 43.3 <1.0 <1.0–254.8 <1.0 <1.0–286.3 n.s.

n-Decane 35.6 <1.0 <1.0–56.2 <1.0 <1.0–23.5 n.s.

Ethyl acetate 26.0 <1.0 <1.0–87.7 <1.0 <1.0–87.7 n.s.

TVOC 100.0 181.6 45.2–775.7 127.6 35.5–547.6 <0.001

Fungi (CFU/m3)

Total CFU 98.1 200 0–2,520 320 0–2,520 0.004

Genera

Cladosporium 81.7 80 0–2,310 150 0–2,310 0.003

Penicillium 73.1 20 0–310 20 0–1,580 n.s.

Alternaria 50.0 0 0–80 10 0–100 0.003

Eurotium 38.5 0 0–60 0 0–310 n.s.

Aspergillus 33.7 0 0–950 0 0–950 n.s.

Rhodotorula 28.8 0 0–310 0 0–310 0.029

Candida 15.4 0 0–150 0 0–220 n.s.

Cryptococcus 14.4 0 0–70 0 0–70 n.s.

Aureobasidium 5.8 0 0–10 0 0–20 n.s.

Mite antigen (�g/g-Wne dust)

Der p1 22.1 <0.10 <0.10–40.40 <0.10 <0.10–40.40 0.019

Der f1 79.8 0.81 <0.10–19.20 0.32 <0.10–200.00 0.039

Der 1 81.7 1.14 <0.10–41.16 0.51 <0.10–200.00 n.s.

a Mann–Whitney U test

TVOC was calculated as sum of all VOCs

2,5-Dimetylaldehyde, Tetrachloroethylene, n-Undecane, Chloroform, 1,1,1-Trichloroethane, Styrene, n-Butanol, n-Hexane, 1,2-Dichloroethane, Chlorodibromomethane, 2,4-Dimetylpentane, Carbontetrachloride, 2-Butanone were omitted in this table, because the detection frequency of these compounds was below 25%

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symptoms than those without. There was also a greater ten-dency for symptoms at higher Der 1 levels (P < 0.1).

Table 6 shows the relationships between the SBS symp-toms and indoor environmental factors in the logisticregression analyses after adjustment for age, gender, his-tory of allergy, current smoking, time spent in the dwellingand age of the dwelling. Indoor chemical factors, such asformaldehyde, acetone, propionaldehyde, hexaldehyde,crotonaldehyde, m,o,p-xylene, limonene, alpha-pinene,benzene, 2-pentanone and TVOC, were signiWcantlyrelated to SBS symptoms.

As for indoor biological factors, only Rhodotorula wassigniWcantly related to SBS symptoms, and dust mite aller-gens were not related.

Finally, fully adjusted multivariate logistic regressionanalysis was performed. The variables introduced were asfollow: basic personal and building factors, such as age,gender, history of allergy, current smoking, time spent inthe dwelling, age of dwelling, dampness index, total CFU,Der 1, and those variables which were signiWcantly associ-ated with SBS symptoms in the previous logistic regressionanalyses. However, Cladosporium and Alternaria were notintroduced in the model, because total CFU, which is acomprehensive measure of fungi, was initially included inthe model and because their protective ORs were notbiologically plausible. In the fully adjusted model, thedampness index and formaldehyde, alpha-pinene and2-pentanone levels were found to be signiWcantly related toSBS symptoms (Table 7).

Discussion

In this study of newly built dwellings in Hokkaido, on thenorthern island of Japan, dampness and several airbornechemicals were found to be signiWcantly related to SBS symp-toms, as determined by using a validated SBS questionnaire.

The dampness index was signiWcantly associated withSBS symptoms. In Swedish multi-resident houses, thedampness index, consisting of condensation on windows,high air humidity in the bathroom, moldy odor, and waterleakage, had a signiWcantly increased OR for SBS symp-toms (Engvall et al. 2001b). In the previous study on newdwellings in Japan, condensation on the windowpanes and/or walls and mold growth were observed in 41.7 and 15.6%of dwellings, respectively, and their ORs were signiWcantlyincreased for SBS symptoms (Saijo et al. 2004). The highercondensation and mold growth rates observed in the presentstudy may reXect the fact that the ages of the dwellings inthe present study are older than in our previous study, inwhich the dwellings were mainly <3 years old (98%). In thisstudy, condensation on the window panes and/or walls wasnot associated with SBS symptoms, even in the crude analy-

sis. We did not query about the degree of condensation, buta low degree of condensation may have a weaker inXuence.More than Wve cm of condensation on the window pane wasused in the Swedish study (Bornehag et al. 2005). Thus, weshould decide whether a more detailed deWnition of conden-sation on the window pane is required or not.

Table 6 Relationships between SBS symptoms and chemicals, fungiand mite allergens in the logistic regression model

Each variable was introduced separately in the model and adjusted forage, gender, history of allergy, current smoking, time spent in thedwelling and age of the dwellinga OR were calculated for a tenfold increase of the indoor air concen-trationb OR were calculated for a tenfold increase of the indoor air CFUc OR were calculated for a tenfold increase of the house dust miteantigen

OR 95% CI P-value

Aldehydes and acetonea

Formaldehyde 27.22 4.96–149.23 <0.001

Acetaldehyde 1.93 0.73–5.06 n.s.

Acetone 5.79 2.12–15.84 0.001

Benzaldehyde 1.78 0.74–4.28 n.s.

Iso-Valeraldehyde 1.73 0.72–4.15 n.s.

Hexaldehyde 1.99 0.93–4.30 n.s.

Crotonaldehyde 9.83 2.29–42.28 0.002

VOCsa

Ethylbenzene 2.59 0.82–8.20 n.s.

m,o,p-Xylene 3.49 1.01–12.06 0.048

Limonene 2.87 1.51–5.45 0.001

Alpha-Pinene 2.02 1.26–3.24 0.003

Toluene 0.73 0.46–1.16 n.s.

Benzene 1.67 0.86–3.26 n.s.

2-Pentanone 2.06 1.07–3.99 0.032

p-Dichlorobenzene 0.71 0.46–1.09 n.s.

TVOC 8.06 2.52–25.76 <0.001

Fungib

Total CFU 0.67 0.44–1.03 n.s.

Genera

Cladosporium 0.72 0.55–0.95 0.018

Penicillium 0.88 0.63–1.25 n.s.

Alternaria 0.59 0.40–0.87 0.007

Eurotium 0.66 0.43–1.01 n.s.

Aspergillus 1.31 0.86–1.98 n.s.

Rhodotorula 1.65 1.15–2.37 0.006

Candida 0.99 0.62–1.62 n.s.

Cryptococcus 1.49 0.84–2.66 n.s.

Aureobasidium 0.73 0.21–2.57 n.s.

Mite allergenc

Der p1 1.24 0.79–1.94 n.s.

Der f1 1.26 0.93–1.73 n.s.

Der 1 1.22 0.90–1.65 n.s.

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Median formaldehyde concentration in the dwellingswas 63.6 �g/m3 (Range; 22.1–202.8 �g/m3), and its detec-tion rate was 100%. In recent western reports, the geomet-ric mean (geometric standard deviation) formaldehydeconcentration was 24.3 (1.8) �g/m3 in living rooms of 61French dwellings (built over 50 years ago: 47%) (Clarisseet al. 2003), mean (standard deviation) formaldehyde con-centration was 35.7 (19.4) �g/m3 in the living rooms of 16French dwellings (building age: not described) (Marchandet al. 2006), and the geometric mean formaldehyde concen-tration was 33.2 �g/m3 (Range; 5.5–29.6 �g/m3) in 59Canadian dwellings (built within 18 years: 41.4%) (Gilbertet al. 2005). Formaldehyde concentrations in the presentstudy seem to be somewhat higher than those in recentwestern studies. Of 4,467 dwellings in the nationwide Japa-nese survey, formaldehyde concentrations in the Hokkaidoprefecture were the second highest among the 47 prefec-tures (Gilbert et al. 2005). We speculated that the higherairtightness in the northern dwellings produced the higherformaldehyde concentrations.

In the fully adjusted analysis, the formaldehyde concen-tration was signiWcantly associated with SBS symptoms.Similar to the World Health Organization air quality guide-lines for Europe, the formaldehyde guideline value forJapan provided by the Japanese Ministry of Health, Labour

and Welfare is 100 �g/m3, and the concentrations in 10dwellings exceeded this guideline value. Among 88 Swed-ish adult subjects, the formaldehyde concentrationexceeded the guideline value for dwellings (100 �g/m3) inone building, and asthmatic symptoms were signiWcantlyrelated to the formaldehyde concentrations (Norback et al.1995). Several studies have reported a relationship betweenchildhood asthma and formaldehyde (Garrett et al. 1999;Smedje and Norback 2001), and one study reported thatchildren exposed to formaldehyde levels of 60 �g/m3 ormore are at an increased risk of having asthma (Rumchevet al. 2002). In one experimental study, a mean formalde-hyde concentration of 92.2 60 �g/m3 exposure enhancedbronchial responsiveness to mite allergens in mite-sensi-tized subjects with asthma (Casset et al. 2006).

In our previous study, the formaldehyde concentrationwas not related to SBS symptoms (Saijo et al. 2004).Because the concentrations in the previous study (mean56.0 ppb: range 6.5–146.9 ppb) were not so diVerent fromthis study, higher VOC concentrations in the previous studyhad a higher impact on the SBS symptoms which may havelessened the eVect of the formaldehyde. Furthermore, sea-sonal diVerences (previous study: summer; present study:late summer to autumn) may inXuence the diVerence inresults. It has been reported that higher room temperatureand photochemical oxidants potentially inXuenced the for-mation of indoor formic acid from formaldehyde, and for-mic acid has a mucosal irritation eVect (Sekine et al. 2001).Because such metabolized chemicals possibly inXuenceSBS symptoms (van Thriel et al. 2006), further studies areneeded to clarify these eVects in the dwellings.

Acetone had no signiWcant association in multivariateanalysis. With respect to odor detection thresholds (0.5–11,600 ppm), a wide range of values are reported, but irrita-tion of eyes, nose and/or throat were reported at concentrationsranging from a few hundreds ppm (250–1,000 ppm) to afew thousands ppm (2,500–8,000 ppm) and to several tenthousands ppm (32,000–130,000 ppm) (Arts et al. 2006).And there has been no report of signiWcant association ofacetone on SBS symptoms.

With respect to VOCs in this study, the identiWcation ratesof ethylbenzene, m,o,p-Xylene, limonene, alpha-pinene,butyl acetate, and toluene were relatively high. Xylene andalpha-pinene were mainly detected in Finnish residentialbuildings whose constructed age was 12–15 months(Jarnstrom et al. 2006). Xylene, limonene, alpha-pinene, andtoluene were the main VOCs detected in German dwellings(Schlink et al. 2004). Thus, the main VOCs detected in thisstudy were thought to be similar to those in European dwell-ings. In the fully adjusted model, only alpha-pinene was sig-niWcantly associated with SBS symptoms. This studyinvolved mainly wooden houses, and wooden building mate-rials are known to emit alpha-pinene (Sato et al. 2003).

Table 7 Relationships between the SBS symptoms and indoorenvironmental factors in the multiple logistic regression model

All cited variables, age, gender, history of allergy, current smoking,time spent in the dwelling and age of dwelling were included in themodela Dampness index includes “condensation on window pane or walls”,“mold growth”, “moldy odor”, “high air humidity in bathroom”, “wa-ter leakage”, and OR was calculated for one increase of these damp-ness itemsb OR were calculated for a tenfold increase of the indoor air concen-trationc OR were calculated for a tenfold increase of the indoor air CFUd OR were calculated for a tenfold increase of the house dust mite anti-gen

OR 95% CI P-value

Dampness indexa 1.50 1.06–2.11 0.022

Formaldehydeb 23.79 2.49–227.65 0.006

Acetoneb 0.96 0.23–4.02 n.s.

Crotonaldehydeb 3.46 0.48–24.72 n.s.

m,o,p-Xyleneb 1.95 0.29–12.92 n.s.

Limoneneb 1.30 0.49–3.46 n.s.

Alpha-Pineneb 2.87 1.36–6.03 0.006

2-Pentanoneb 2.98 1.32–6.75 0.009

TVOCb 0.79 0.08–8.18 n.s.

Total CFUc 0.41 0.25–0.70 0.001

Rhodotorulac 1.35 0.84–2.18 n.s.

Der 1d 1.21 0.83–1.76 n.s.

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In our previous study, toluene, butyl acetate, ethylben-zene, alpha-pinene, p-dichlorobenzene, nonanal, xylene,and TVOC were signiWcantly related to SBS symptoms(Saijo et al. 2004). The initial levels of VOCs in the newhomes decreased dramatically and were close to the meanvalues for the older homes after 1 year. However, formalde-hyde and alpha-pinene did not follow the trend for VOCs,particularly in the wooden framed houses. Formaldehydeand alpha-pinene related to wooden materials will need alonger Xushing period than other compounds in new homes(Park and Ikeda 2006). As previously mentioned, the age ofthe dwellings in the present study was older than that of ourprevious study where the dwelling age was <3 years (98%).Indeed, the mean toluene level in the previous study washigher (325.5 �g/m3). Thus, building age diVerences possi-bly caused the diVerent eVect of VOCs.

Oxidation reactions of alpha-pinene can occur naturally,and the metabolites have an irritant eVect (WolkoV et al.2006). Our previous study revealed that alpha-pinene had asigniWcantly higher odds ratio for throat and respiratorysymptoms and any symptoms (Saijo et al. 2004). However,there have been no other reports of signiWcant eVects ofalpha-pinene on SBS symptoms. The metabolites of theoxidation of limonene can also have an irritation eVect(Nojgaard et al. 2005), but limonene had no signiWcanteVect in the multivariate analysis. Therefore, further studiesare needed to clarify alpha-pinene and limonene metaboliteexposure and their inXuence on SBS symptoms.

2-Pentanone was signiWcantly associated with SBS symp-toms, but the exposure levels were rather low. Unknownexposures or chance may be confounding the result.

Many of the fungal genera that we recovered (Cladospo-rium, Penicillium, Alternaria) were similar to those foundcommonly in other studies of residential environments(Takahashi 1997; Chew et al. 2003; Hargreaves et al. 2003;Lee and Jo 2006). After adjustment for age, gender, historyof allergy, current smoking, time spent in the dwelling andage of the dwelling, Rhodotorula had a signiWcantly higherOR for SBS symptoms; however, the signiWcance disap-peared in the fully adjusted model. Airborne fungi levelshave a large seasonal variation (Takahashi 1997) as well astemporal and spatial variability (Douwes and Pearce 2003).This variability can cause potential misclassiWcation of fun-gal exposure in epidemiological studies. Furthermore, deadmolds or mold components are not detected, even thoughthey may have toxic/allergenic properties (Douwes andPearce 2003). These variations and unevaluated fungal fac-tors may be the cause of the signiWcantly lower OR of totalCFU in this study. As a way to control these variations,fungi and endotoxin measurements in dust may be morerepresentative of long term exposure (Chew et al. 2003).

Mite allergens levels were not related to SBS symptoms.The Third International Workshop on Dust Mite Allergens

and Asthma, under the auspices of the International Associ-ation of Allergology and Clinical Immunology and theWorld Health Organization, reported that exposure to 2 �g/g-dust Der 1 allergen is considered to increase the risk ofsensitization (Platts-Mills et al. 1997). The median Der 1value of this study was 0.58 �g/g-dust, and more than halfof dwellings’ Der 1 values were lower than 2 �g/g-dust.Thus, lower mite allergen exposure levels may attenuate thehealth eVect. Moreover, in a German study, the medianDer1 value of carpets was 0.41 �g/g-dust (max 96 �g/g-dust) while that of mattresses was 2.16 �g/g-dust (max278.9 �g/g-dust) (Hirsch et al. 1998). Therefore, exposurefrom bedding should be further investigated.

The present study has several limitations. Based on theprevious questionnaire survey, we selected participantsfrom 53 dwelling that had reported symptoms and 51dwelling that had not reported symptoms. At the time ofchemical, mite and dampness exposures measurements, weasked again about symptoms to elucidate the relationshipsbetween the exposures and the symptoms which weresimultaneous with the exposures. Because this was a cross-sectional study, causal relationships between variablescould not be determined. Moreover, previous health prob-lems may alter lifestyle habits, such as cleaning frequency,ventilation time, etc., which would dilute the eVects ofexposure. In Table 4, pets at home had signiWcantly lowerodds ratio. However, this must be a reverse cause–eVectrelationship, because residents who have pet allergies areprone to avoid owning pets. Furthermore, because the par-ticipants were limited to those who were interested in expo-sure measurements, they had a higher prevalence of theSBS symptoms compared to the general population. Secondwe evaluated only the living rooms of the dwellings forcontaminants. Japanese houses are not so large, and mostresidents seemed to stay in the living room for many hours,except for sleeping time; therefore, we considered that theexposure levels of residents in the living room representedthe overall exposure levels in the dwellings (Sakaguchi andAkabayashi 2003). However, as previously mentioned, themite allergen levels of bedding may be a better exposureindicator. Third, seasonal variation could not be evaluatedin this study. In particular, the seasonal variation of air-borne fungi levels may aVect the results. Fourth, socio-eco-nomic status was not measured. However, since all thehouseholds had their own newly built detached house, itwas considered that the participants had socio-economicstatuses and belonged to the middle class. Fifth, we did notmeasure carbon dioxide levels even though it can causeSBS symptoms, because carbon dioxide problems do notoccur in Japanese dwellings (Norback and Nordstrom2008).

In conclusion, dampness, formaldehyde, and alpha-pinene were signiWcantly related to SBS symptoms in

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newly built dwellings. We should take measures to reducethe chemicals and dampness in dwellings. Further studiesare needed to clarify seasonal variations in the eVects ofcontaminants, metabolites of chemicals, and bedding miteallergen eVects.

Acknowledgment This study was supported by a grant-in-aid fromthe Ministry of Health, Labour and Welfare, Health and LabourSciences Research Grant, Japan (Research on Health Services:H15-Ganyobou-093). We would like to express grate gratitude toMs. K. Yamashita for her cooperation.

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Relationship Between Sick Building Syndrome and Indoor Environmental Factors in Newly Built Japanese Dwellings