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

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Int Arch Occup Environ Health (2009) 82:583593

DOI 10.1007/s00420-009-0395-8

O R I G I N A L A R T I CL E

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

Abstract
Objectives Indoor air contaminants and dampness in
dwellings have become important environmental health
issues. The aim of this study is to clarify which factors are
related to sick building syndrome (SBS) in newly built
dwellings at Hokkaido, Japan, through a comprehensive
evaluation of the indoor environment and validated sick
building symptom questionnaires.
Methods The symptoms of 343 residents in 104 detached
houses were surveyed by standardized questionnaires, and
the concentrations of formaldehyde, acetaldehyde, volatile
organic compounds (VOCs), airborne fungi, and dust mite
allergen in their living rooms were measured. By summing
the presence or absence of the Wve dampness indicators
(condensations, mold growth, moldy odor, high air humidity of the bathroom, water leakage), a dampness index was
calculated.
Results SBS symptoms were found in 21.6% of surveyed
individuals. In a fully adjusted multivariate logistic regression analysis, the dampness index [odds ratio (OR) = 1.50;
95% conWdence interval (CI): 1.061.11], log formaldehyde (OR = 23.79, 95% CI: 2.49277.65), and log alphapinene (OR = 2.87, 95% CI: 1.366.03) had signiWcantly
higher ORs for SBS symptoms. However, other VOCs,

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, Japan
e-mail: rkishi@med.hokudai.ac.jp
Y. Saijo
Department of Health Science, Asahikawa Medical College,
Midorigaoka, E2-1-1-1, Asahikawa, Hokkaido 078-8510, Japan

airborne fungi, and dust mite allergen did not have signiWcantly higher ORs.
Conclusion Dampness, formaldehyde, and alpha-pinene
were signiWcantly related to SBS symptoms in newly built
dwellings. We should, therefore, take measures to reduce
the 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 syndrome (SBS), which occurred in many countries in the
1970s, have reemerged in newly built dwellings in Japan
since the early 1990s. In Japan, the problem, called sick
house syndrome (SHS), and other indoor air problems of
dwellings have attracted broad interest (Torii 2002).
We have previously reported that condensation on window panes/walls and mold growth were related to SBS
symptoms in newly built dwellings (Saijo et al. 2002; Saijo
et al. 2004). Building dampness was also signiWcantly associated with airway infections in various types of dwellings
(Bakke et al. 2007). In old multifamily dwellings, dampness and odor were signiWcantly related to asthma and SBS
symptoms (Engvall et al. 2001a, 2002). Dampness and
mold were further signiWcantly associated with upper and
lower respiratory symptoms in oYce buildings (Park et al.
2004). Dampness at home has also been signiWcantly
related to allergy symptoms in preschool children (Bornehag
et al. 2005).
Several mechanisms are assumed to account for the
dampness eVect. Higher humidity in dwellings facilitates

123

584

mold growth (Garrett et al. 1998b) and the proliferation of


dust mites (Garrett et al. 1998a; Hirsch et al. 1998; Emenius
et al. 2000; Bemt et al. 2006), both of which can aVect a
residents health. Fungi can produce microbial volatile
organic compound (MVOC) (Elke et al. 1999; Kim et al.
2007), endotoxin (Thorn and Rylander 1998; Park et al.
2006), and (13)-beta-D-glucan (Beijer et al. 2002; Douwes
2005) which may also inXuence a residents health. Structural dampness which may be hidden may cause chemical
degradation of building materials, leading to the formation
and emission of 2-ethyl-1-hexanol from the alkaline degradation of di-(2-ethylhexyl) phthalate (DEHP) in poly-vinyl
chloride materials (Wieslander et al. 1999; Sakai et al.
2006). The relationship of odor to SBS may be because
moldy odor reXects exposure to MVOC and pungent odor
reXects exposure to formaldehyde, ammonia and other
strong chemicals (Engvall et al. 2002).
Indoor air quality has declined in part because of comprehensive energy conservation campaigns and high energy
prices which have motivated people to tighten their dwellings 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 snowy
regions, like Hokkaido, whose dwellings seem to have
greater airtightness. Thus, the indoor environment of dwellings is important; yet, in Japanese dwellings, there have
been few SBS studies which have evaluated comprehensive
indoor environments for the presence of aldehydes, VOCs,
airborne fungi, dust mite allergen, etc.
The aim of this study is to clarify which factors are
related to sick building symptoms in newly built dwellings
in Hokkaido, Japan through a comprehensive evaluation of
the indoor environment and validated sick building symptom questionnaires.

Methods
Study population
During the period of 2003 through 2004, a questionnaire
survey of the indoor air quality and presence of SBS in
newly built dwellings was performed in six regions of
Japan (Kish et al. submitted). In Sapporo city (Hokkaido
prefecture) in November 2003, the questionnaires were distributed to the occupants of 1,240 dwellings, which were all
detached houses that had been newly built within 7 years in
two new residential areas. The dwellings were chosen from
a list of building plan approval applications. The questionnaires included queries about the building structure and
characteristics, the residents habits in the home, and subjective symptoms. We asked, Has any one in your dwelling experienced any symptoms such as tiredness, headache,

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Int Arch Occup Environ Health (2009) 82:583593

dermal and mucosal irritation, eczema, or allergic diseases? We requested that the one resident with the most
severe symptoms in the dwelling answer the questionnaire
about symptoms. The residents of 252 dwellings agreed to
participate in the symptom questionnaire and have measurements of the concentrations of aldehydes, VOCs, air
borne fungi, and house dust mite allergens performed in
their dwellings. We randomly selected 53 of 100 dwellings
in which at least one inhabitant complained of one or more
symptoms, and we also randomly selected 51 of 151 dwellings in which none of the inhabitants complained of symptoms. The following year, we performed a comprehensive
indoor environment evaluation, and all residents of these
104 dwellings completed the symptom questionnaire in
September through October of 2004. Average outdoor temperature and relative humidity in September 2004 were
18.4C and 68%, respectively, and in October 2004 they
were 12.5C and 63%, respectively. During this time
period, windows are sometimes opened.
Questionnaire survey
We used two types of questionnaires: one for all residents
and the other for the head of the household or his/her partner. The questionnaire for all residents queried for information on personal characteristics and lifestyle, such as age,
gender, current smoking, time spent in the dwelling, working hours, stress level, etc. The questionnaire also contained
questions about the history of any previous treatment by a
physician for asthma or allergies. The questionnaire contained the symptoms query part of the Japanese version of
MM040EA, a validated questionnaire designed for epidemiologic assessment of SBS symptoms (Mizoue et al.
2001). Symptoms surveyed for over the previous 3 months
included the following: general symptoms (fatigue, feeling
heavy-headed, headache, nausea/dizziness, diYculty concentrating); eye symptoms (itching, burning or irritation of
the eye); nasal symptoms (irritated, stuVy or runny nose);
throat and respiratory symptoms (hoarse, dry throat,
cough); and skin symptoms (dry or Xushed facial skin, scaling/itching of the scalp or ears, dry, itching or red-skinned
hands). For each symptom, the following answers were
possible: Yes, often (every week); Yes, sometimes;
and No, never. An additional question concerning the
attribution of a symptom to the home environment was
included in the questionnaire. SBS symptoms were scored
as positive if at least one sub-symptom was found to occur
often (every week)/sometimes and was thought to be attributed to the home environment. In this paper, general
symptoms, eye symptoms, nasal symptoms, throat
and respiratory symptoms, and skin symptoms refer to
the above mentioned MM040 SBS symptoms. Furthermore, any symptom was deWned as at least one positive

Int Arch Occup Environ Health (2009) 82:583593

SBS symptom. The questionnaire for children who could


not read and/or write was answered by a parent.
The other questionnaire for the head of the household or
his/her partner contained questions about dwelling characteristics, such as renovation over the past 2 years, Xooring
and wall materials in the living room, dampness (condensation on window panes or walls, mold growth, moldy odor,
slow drying of wet towels in the bathroom, water leakage
during past 5 years or since you have lived in the dwelling,
if 5 years has not passed), pets in the dwelling, the presence
of a smoker in the dwelling, the use of room fragrance, and
the use of insect repellent. By summing the presence or
absence of the Wve dampness indicators, an overall dampness index (05) was calculated. Data on the structure and
age of the dwelling were obtained from a previous survey
done in 2003.
Assessment of indoor environmental factors
Indoor air monitoring of aldehydes, acetone and VOCs
were carried out in the living room of each dwelling. Air
samples were collected with a DSD-DNPH diVusion sampler (Supelco, Japan) for aldehydes and acetone, and a
VOC-SD diVusion sampler (Supelco, Japan) for VOCs at
100150 cm above the Xoor for 24 h. Eleven aldehydes and
acetone were quantiWed by HPLC and 27 VOCs were quantiWed by GC-MS, using a previously described method
(Takigawa et al. 2004). The limit of quantiWcation of each
of the chemicals was 1.0 g/m3. Total VOC (TVOC) was
calculated as the sum of all VOCs. To calculate TVOC,
VOC values under the lower limits of quantiWcation were
considered 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 air
sampler (AINEX BIO-SAS, International Pbi, Italy) for a
0.1 m3 air volume at a height of 150 cm above the Xoor in
the living room. The DG-18 medium was incubated at
27C, fungal colonies were counted and species were identiWed morphologically at the Mitsubishi Chemical Medience
Corporation (Tokyo, Japan). The fungal levels were
expressed as colony forming units per cubic meter of air
(CFU/m3).
Dust samples on the Xoor of the living room were collected with a hand vacuum cleaner (HC-V15, National,
Japan) equipped with a paper Wlter for 0.5 m2/min. Der p1
and Der f1 levels of the dust samples were quantiWed by
ELISA at the LCD Allergic Center (Osaka, Japan); the
limit of quantiWcation of both mite allergens was 0.1 g/gWne dust. Der 1 levels were calculated as the sum of quantiWed Der p1 and Der f1. To calculate Der 1, Der p1 and Der
f1 values under the lower limit of quantiWcation were considered to be half of the lower limit of quantiWcation.

585

The temperature and relative humidity in the living room


were monitored by a Thermo Recorder TR-72U (T&D Corporation, Japan) for 24 h, and the average temperature and
relative humidity were calculated. Average indoor temperature and relative humidity were 23.5C and 56.1%, respectively.
Statistical analysis
Statistical analysis was performed by multiple logistic
regression, and crude and adjusted odds ratios with 95%
conWdence intervals (OR, 95% CI) were calculated. For all
statistical analyses, a 5% level of signiWcance was applied.
To obtain adjusted ORs for SBS symptoms, we controlled
for age, gender, current smoking and time spent in the
dwelling, which were introduced separately in the model.
To determine whether indoor environmental factors such
as aldehydes, VOCs, fungi and mite allergen were associated with SBS symptoms, MannWhitney U tests were
conducted. Next, logarithmic values of aldehydes, VOCs,
and fungi and mite allergens which were found to be signiWcantly associated with SBS symptom in the Mann
Whitney U tests were applied in the multiple logistic
regression models. We controlled for age, gender, history
of allergy, current smoking, time spent in the dwelling and
age of dwelling, and each selected variable was introduced
separately in the model. To transfer to their logarithmic values, aldehyde and VOC values under the lower limits of
quantiWcation were considered as half of the lower limit of
quantiWcation, and 0 CFU/m3 for fungus was changed to
0.5 CFU/m3.
Finally, the variables which were signiWcantly associated with SBS symptoms in the previous logistic regression
analyses and basic personal and building factors, such as
age, gender, history of allergy, current smoking, time spent
in the dwelling, age of the dwelling, dampness index, total
CFU and Der 1, were introduced in the multiple logistic
regression model.
All analyses were conducted with SPSS software for
Windows version 13.0 (SPSS Inc., Chicago, USA).

Results
Table 1 shows the characteristics of 104 dwellings. Most of
the dwellings were wooden structures: 43.3% of those built
within 3 years and 56.7% of those built within the previous
38 years.
Table 2 shows the characteristics of the study participants. Among the 343 participants, the proportion of
females was 50.4%, 25.1% were under 10 years old, and
11.1% were over 60 years old.

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Int Arch Occup Environ Health (2009) 82:583593

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

1.0

Others

1.0

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

5.8

Age of dwelling

Renovation of dwelling over the past 2 years

2.9

103

99.0

Vinyl wallpaper

69

66.3

Cloth wallpaper

14

13.5

Wooden Xooring
Wall materials at living room

Plywood

6.7

14

13.5

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

Others
Dampness

Table 2 Characteristics of
participants (n = 343)

Total (n = 343)

Female (n = 173)

Male (n = 170)

Age
<10

86

25.1

42

24.3

44

25.9

1019

36

10.5

16

9.2

20

11.8

2029

18

5.2

4.0

11

6.5

3039

87

25.4

50

28.9

37

21.8

4049

47

13.7

20

11.6

27

15.9

5059

31

9.0

20

11.6

11

6.5

60

38

11.1

18

10.4

20

11.8

186

54.2

113

65.3

73

42.4

57

16.6

13

7.5

44

25.9

History of allergy or asthma


Current smoking

123

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

Int Arch Occup Environ Health (2009) 82:583593

587

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


All (n = 343)

Female (n = 173)

Male (n = 170)

Any symptoms

74

21.6

41

23.7

33

19.4

General

10

2.9

2.9

2.9

Eye

13

3.8

4.0

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

3.5

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 attributed to the home environment. Furthermore, any symptom was deWned as at least one positive SBS symptom

Table 4 Odds ratios (OR) and


their 95% conWdence intervals
(95% CI) for SBS symptoms in
relation to dampness, other
dwelling characteristics and personal characteristics

Each variable was introduced


separately in the model and adjusted for age, gender, current
smoking and time spent in the
dwelling
n.s.Not signiWcant

Adjusted ORa

Unadjusted OR
OR

95% CI

P-value

OR

95% CI

P-value

Condensation on window panes or walls

0.96

0.571.60

n.s.

0.82

0.471.41

n.s.

Mold growth

2.08

1.103.93

0.022

1.83

0.943.57

n.s.

Moldy odor

2.55

1.175.52

0.021

2.83

1.276.31

0.011

High air humidity in bathroom

1.57

0.823.01

n.s.

1.62

0.833.15

n.s.

Dampness

Water leakage

2.21

1.154.25

0.023

2.30

1.174.51

0.015

Pets in dwelling

0.48

0.250.91

0.022

0.48

0.250.92

0.026

Presence of smoker in dwelling

0.95

0.561.60

n.s.

0.73

0.401.32

n.s.

Use of room fragrance

0.90

0.531.51

n.s.

0.81

0.471.38

n.s.

Use of insect repellent

1.36

0.812.28

n.s.

1.34

0.792.28

n.s.

History of allergy or asthma

1.73

1.012.94

0.045

1.79

1.003.19

0.050

Current smoking

1.23

0.632.39

n.s.

0.63

0.301.29

n.s.

Time spent in the dwelling (20 h)

2.07

1.173.65

0.018

2.09

1.143.81

0.016

Working hours (9 h)

1.34

0.772.34

n.s.

1.64

0.873.12

n.s.

Stressful

1.32

0.752.32

n.s.

1.54

0.852.80

n.s.

Table 3 shows the prevalence of SBS symptoms in this


survey. Throat and respiratory symptoms, nose symptoms,
skin symptoms, eye symptoms, and general symptoms were
found 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% of
participants. 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 and
other variables. Dampness indicators, such as mold growth,
moldy odor and water leakage, had signiWcantly higher ORs
for SBS symptoms. Time spent in the dwelling (20 h) also
had a signiWcantly higher OR for SBS symptoms.
Table 5 shows aldehydes, VOCs, fungi and mite allergen
levels in relation to SBS symptoms. The detection rates of
aldehydes measured in this survey (except for three
chemicals) were over 90%. Among VOCs, ethylbenzene,
m,o,p-xylene, limonene, alpha-pinene, butyl acetate and

toluene had high detection rates in the dwellings. Formaldehyde, acetone, benzaldehyde, iso-valeraldehyde, hexaldehyde, crotonaldehyde, limonene, alpha-pinene, benzene,
2-pentanone and TVOC had signiWcantly higher indoor air
concentrations in dwellings with SBS symptoms than in
those without.
Cladosporium, Penicillium, Alternaria, Eurotium,
Aspergillus and Rhodotorula were the main organisms
detected in the dwellings. In terms of total CFU, Alternaria
and Cladosporium had signiWcantly lower fungus levels in
dwellings with SBS symptoms than in those without. Only
one fungal genus, Rhodotorula, had signiWcantly higher
levels in dwellings with SBS symptoms (interquartile
range; with SBS symptoms: 020, without SBS symptoms:
010), although the overall detection rate of Rhodotorula
was low (28.8%).
The detection rate of Der 1 was 81.7%. Der p1 and Der
f1 had signiWcantly higher levels in dwellings with SBS

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588

Int Arch Occup Environ Health (2009) 82:583593

Table 5 SBS symptoms in relation to chemicals, fungi and mite


antigen

Detection rate (%)


(104 dwellings)

Symptoms (n = 74)

No symptom (n = 269)

Median Range
(Minmax)

Median

Range
(Minmax)

P-valuea

63.2

22.1202.8

0.001

Aldehydes and acetone (g/m3)


Formaldehyde

100.0

70.1

22.1202.8

Acetaldehyde

100.0

35.9

4.6129.5

33.5

1.7129.5

n.s.

Acetone

100.0

51.1

21.7606.0

29.1

10.5606.0

<0.001

Propionaldehyde

100.0

11.4

3.822.3

9.7

2.424.8

n.s.

Benzaldehyde

100.0

7.3

1.618.5

5.5

1.6117.1

0.041

Iso-Valeraldehyde

100.0

5.8

1.416.6

4.6

1.4104.6

0.037

Hexaldehyde

0.032

100.0

19.9

6.2127.3

17.1

2.0198.5

Crotonaldehyde

98.1

9.3

2.120.6

7.6

<1.020.6

0.001

Valeraldehyde

97.1

8.0

<1.039.2

7.3

<1.0223.7

n.s.

n-Butyraldehyde

96.2

4.7

1.012.8

3.6

<1.016.6

n.s.

m,o,p-Tolualdehyde

69.2

2.1

<1.021.5

2.3

<1.021.5

n.s.
n.s

VOCs (g/m )
Ethylbenzene

100.0

4.6

1.815.1

4.5

1.121.8

m,o,p-Xylene

100.0

11.9

4.739.3

11.4

3.149.6

n.s.

Limonene

99.0

17.6

3.5484.9

12.5

<1.0267.6

<0.001

Alpha-Pinene

95.2

12.9

<1.0302.5

6.9

<1.0302.5

0.002

Butyl acetate

93.3

6.0

<1.061.4

4.9

<1.049.3

n.s.

Toluene

92.3

20.2

<1.0139.8

16.3

<1.0144.2

n.s.

n-Nonane

87.5

5.2

<1.034.6

4.4

<1.032.4

n.s.

Trimethylbenzene

85.6

5.1

<1.028.7

4.5

<1.024.8

n.s.

n-Octane

79.8

3.3

<1.019.9

3.6

<1.041.2

n.s.

n-Heptane

67.3

2.6

<1.035.3

2.3

<1.035.3

n.s.

Benzene

51.0

1.2

<1.08.5

<1.0

<1.09.2

0.047

2-Pentanone

43.3

1.3

<1.032.0

<1.0

<1.032.0

0.008

p-Dichlorobenzene

43.3

<1.0

<1.0254.8

<1.0

<1.0286.3

n.s.

n-Decane

35.6

<1.0

<1.056.2

<1.0

<1.023.5

n.s.

Ethyl acetate

26.0

<1.0

<1.087.7

<1.0

<1.087.7

n.s.

100.0

181.6

45.2775.7

127.6

35.5547.6

<0.001

98.1

200

02,520

320

02,520

0.004

Cladosporium

81.7

80

02,310

150

02,310

0.003

Penicillium

73.1

20

0310

20

01,580

n.s.

Alternaria

50.0

080

10

0100

0.003

Eurotium

38.5

060

0310

n.s.

Aspergillus

33.7

0950

0950

n.s.

Rhodotorula

28.8

0310

0310

0.029

Candida

15.4

0150

0220

n.s.

Cryptococcus

14.4

070

070

n.s.

5.8

010

020

n.s.

TVOC
Fungi (CFU/m3)
Total CFU
Genera
a

MannWhitney 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%

123

Aureobasidium

Mite antigen (g/g-Wne dust)


Der p1

22.1

<0.10

<0.1040.40

<0.10

<0.1040.40

0.019

Der f1

79.8

0.81

<0.1019.20

0.32

<0.10200.00

0.039

Der 1

81.7

1.14

<0.1041.16

0.51

<0.10200.00

n.s.

Int Arch Occup Environ Health (2009) 82:583593

symptoms than those without. There was also a greater tendency for symptoms at higher Der 1 levels (P < 0.1).
Table 6 shows the relationships between the SBS symptoms and indoor environmental factors in the logistic
regression analyses after adjustment for age, gender, history of allergy, current smoking, time spent in the dwelling
and age of the dwelling. Indoor chemical factors, such as
formaldehyde, acetone, propionaldehyde, hexaldehyde,
crotonaldehyde, m,o,p-xylene, limonene, alpha-pinene,
benzene, 2-pentanone and TVOC, were signiWcantly
related to SBS symptoms.
As for indoor biological factors, only Rhodotorula was
signiWcantly related to SBS symptoms, and dust mite allergens were not related.
Finally, fully adjusted multivariate logistic regression
analysis was performed. The variables introduced were as
follow: basic personal and building factors, such as age,
gender, history of allergy, current smoking, time spent in
the dwelling, age of dwelling, dampness index, total CFU,
Der 1, and those variables which were signiWcantly associated with SBS symptoms in the previous logistic regression
analyses. However, Cladosporium and Alternaria were not
introduced in the model, because total CFU, which is a
comprehensive measure of fungi, was initially included in
the model and because their protective ORs were not
biologically plausible. In the fully adjusted model, the
dampness index and formaldehyde, alpha-pinene and
2-pentanone levels were found to be signiWcantly related to
SBS symptoms (Table 7).

Discussion
In this study of newly built dwellings in Hokkaido, on the
northern island of Japan, dampness and several airborne
chemicals were found to be signiWcantly related to SBS symptoms, as determined by using a validated SBS questionnaire.
The dampness index was signiWcantly associated with
SBS symptoms. In Swedish multi-resident houses, the
dampness index, consisting of condensation on windows,
high air humidity in the bathroom, moldy odor, and water
leakage, had a signiWcantly increased OR for SBS symptoms (Engvall et al. 2001b). In the previous study on new
dwellings 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 signiWcantly
increased for SBS symptoms (Saijo et al. 2004). The higher
condensation and mold growth rates observed in the present
study may reXect the fact that the ages of the dwellings in
the present study are older than in our previous study, in
which the dwellings were mainly <3 years old (98%). In this
study, condensation on the window panes and/or walls was
not associated with SBS symptoms, even in the crude analy-

589
Table 6 Relationships between SBS symptoms and chemicals, fungi
and mite allergens in the logistic regression model
OR

95% CI

P-value

Formaldehyde

27.22

4.96149.23

<0.001

Acetaldehyde

1.93

0.735.06

n.s.

Acetone

5.79

2.1215.84

0.001

Benzaldehyde

1.78

0.744.28

n.s.

Iso-Valeraldehyde

1.73

0.724.15

n.s.

Aldehydes and acetonea

Hexaldehyde

1.99

0.934.30

n.s.

Crotonaldehyde

9.83

2.2942.28

0.002

Ethylbenzene

2.59

0.828.20

n.s.

m,o,p-Xylene

3.49

1.0112.06

0.048

Limonene

2.87

1.515.45

0.001

Alpha-Pinene

2.02

1.263.24

0.003

VOCs

Toluene

0.73

0.461.16

n.s.

Benzene

1.67

0.863.26

n.s.

2-Pentanone

2.06

1.073.99

0.032

p-Dichlorobenzene

0.71

0.461.09

n.s.

TVOC

8.06

2.5225.76

<0.001

0.67

0.441.03

n.s.

Cladosporium

0.72

0.550.95

0.018

Penicillium

0.88

0.631.25

n.s.

Alternaria

0.59

0.400.87

0.007

Eurotium

0.66

0.431.01

n.s.

Aspergillus

1.31

0.861.98

n.s.

Rhodotorula

1.65

1.152.37

0.006

Candida

0.99

0.621.62

n.s.

Cryptococcus

1.49

0.842.66

n.s.

Aureobasidium

0.73

0.212.57

n.s.

1.24

0.791.94

n.s.

Der f1

1.26

0.931.73

n.s.

Der 1

1.22

0.901.65

n.s.

Fungi

Total CFU
Genera

Mite allergenc
Der p1

Each variable was introduced separately in the model and adjusted for
age, gender, history of allergy, current smoking, time spent in the
dwelling and age of the dwelling
a
OR were calculated for a tenfold increase of the indoor air concentration
b
OR were calculated for a tenfold increase of the indoor air CFU
c
OR were calculated for a tenfold increase of the house dust mite
antigen

sis. We did not query about the degree of condensation, but


a low degree of condensation may have a weaker inXuence.
More than Wve cm of condensation on the window pane was
used in the Swedish study (Bornehag et al. 2005). Thus, we
should decide whether a more detailed deWnition of condensation on the window pane is required or not.

123

590

Int Arch Occup Environ Health (2009) 82:583593

Table 7 Relationships between the SBS symptoms and indoor


environmental factors in the multiple logistic regression model
OR
Dampness indexa
Formaldehydeb

1.50
23.79

95% CI

P-value

1.062.11

0.022

2.49227.65

0.006

Acetoneb

0.96

0.234.02

n.s.

Crotonaldehydeb

3.46

0.4824.72

n.s.

m,o,p-Xyleneb

1.95

0.2912.92

n.s.

Limoneneb

1.30

0.493.46

n.s.

Alpha-Pineneb

2.87

1.366.03

0.006

2-Pentanoneb

2.98

1.326.75

0.009

0.79

0.088.18

n.s.

Total CFUc

0.41

0.250.70

0.001

Rhodotorulac

1.35

0.842.18

n.s.

Der 1d

1.21

0.831.76

n.s.

TVOC

All cited variables, age, gender, history of allergy, current smoking,


time spent in the dwelling and age of dwelling were included in the
model
a
Dampness index includes condensation on window pane or walls,
mold growth, moldy odor, high air humidity in bathroom, water leakage, and OR was calculated for one increase of these dampness items
b
OR were calculated for a tenfold increase of the indoor air concentration
c
OR were calculated for a tenfold increase of the indoor air CFU
d
OR were calculated for a tenfold increase of the house dust mite antigen

Median formaldehyde concentration in the dwellings


was 63.6 g/m3 (Range; 22.1202.8 g/m3), and its detection rate was 100%. In recent western reports, the geometric mean (geometric standard deviation) formaldehyde
concentration was 24.3 (1.8) g/m3 in living rooms of 61
French dwellings (built over 50 years ago: 47%) (Clarisse
et al. 2003), mean (standard deviation) formaldehyde concentration was 35.7 (19.4) g/m3 in the living rooms of 16
French dwellings (building age: not described) (Marchand
et al. 2006), and the geometric mean formaldehyde concentration was 33.2 g/m3 (Range; 5.529.6 g/m3) in 59
Canadian dwellings (built within 18 years: 41.4%) (Gilbert
et al. 2005). Formaldehyde concentrations in the present
study seem to be somewhat higher than those in recent
western studies. Of 4,467 dwellings in the nationwide Japanese survey, formaldehyde concentrations in the Hokkaido
prefecture were the second highest among the 47 prefectures (Gilbert et al. 2005). We speculated that the higher
airtightness in the northern dwellings produced the higher
formaldehyde concentrations.
In the fully adjusted analysis, the formaldehyde concentration was signiWcantly associated with SBS symptoms.
Similar to the World Health Organization air quality guidelines for Europe, the formaldehyde guideline value for
Japan provided by the Japanese Ministry of Health, Labour

123

and Welfare is 100 g/m3, and the concentrations in 10


dwellings exceeded this guideline value. Among 88 Swedish adult subjects, the formaldehyde concentration
exceeded the guideline value for dwellings (100 g/m3) in
one building, and asthmatic symptoms were signiWcantly
related to the formaldehyde concentrations (Norback et al.
1995). Several studies have reported a relationship between
childhood asthma and formaldehyde (Garrett et al. 1999;
Smedje and Norback 2001), and one study reported that
children exposed to formaldehyde levels of 60 g/m3 or
more are at an increased risk of having asthma (Rumchev
et al. 2002). In one experimental study, a mean formaldehyde concentration of 92.2 60 g/m3 exposure enhanced
bronchial responsiveness to mite allergens in mite-sensitized subjects with asthma (Casset et al. 2006).
In our previous study, the formaldehyde concentration
was not related to SBS symptoms (Saijo et al. 2004).
Because the concentrations in the previous study (mean
56.0 ppb: range 6.5146.9 ppb) were not so diVerent from
this study, higher VOC concentrations in the previous study
had a higher impact on the SBS symptoms which may have
lessened the eVect of the formaldehyde. Furthermore, seasonal diVerences (previous study: summer; present study:
late summer to autumn) may inXuence the diVerence in
results. It has been reported that higher room temperature
and photochemical oxidants potentially inXuenced the formation of indoor formic acid from formaldehyde, and formic acid has a mucosal irritation eVect (Sekine et al. 2001).
Because such metabolized chemicals possibly inXuence
SBS symptoms (van Thriel et al. 2006), further studies are
needed to clarify these eVects in the dwellings.
Acetone had no signiWcant association in multivariate
analysis. With respect to odor detection thresholds (0.5
11,600 ppm), a wide range of values are reported, but irritation of eyes, nose and/or throat were reported at concentrations
ranging from a few hundreds ppm (2501,000 ppm) to a
few thousands ppm (2,5008,000 ppm) and to several ten
thousands ppm (32,000130,000 ppm) (Arts et al. 2006).
And there has been no report of signiWcant association of
acetone on SBS symptoms.
With respect to VOCs in this study, the identiWcation rates
of ethylbenzene, m,o,p-Xylene, limonene, alpha-pinene,
butyl acetate, and toluene were relatively high. Xylene and
alpha-pinene were mainly detected in Finnish residential
buildings whose constructed age was 1215 months
(Jarnstrom et al. 2006). Xylene, limonene, alpha-pinene, and
toluene were the main VOCs detected in German dwellings
(Schlink et al. 2004). Thus, the main VOCs detected in this
study were thought to be similar to those in European dwellings. In the fully adjusted model, only alpha-pinene was signiWcantly associated with SBS symptoms. This study
involved mainly wooden houses, and wooden building materials are known to emit alpha-pinene (Sato et al. 2003).

Int Arch Occup Environ Health (2009) 82:583593

In our previous study, toluene, butyl acetate, ethylbenzene, 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 new
homes decreased dramatically and were close to the mean
values for the older homes after 1 year. However, formaldehyde and alpha-pinene did not follow the trend for VOCs,
particularly in the wooden framed houses. Formaldehyde
and alpha-pinene related to wooden materials will need a
longer Xushing period than other compounds in new homes
(Park and Ikeda 2006). As previously mentioned, the age of
the dwellings in the present study was older than that of our
previous study where the dwelling age was <3 years (98%).
Indeed, the mean toluene level in the previous study was
higher (325.5 g/m3). Thus, building age diVerences possibly 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 a
signiWcantly higher odds ratio for throat and respiratory
symptoms and any symptoms (Saijo et al. 2004). However,
there have been no other reports of signiWcant eVects of
alpha-pinene on SBS symptoms. The metabolites of the
oxidation of limonene can also have an irritation eVect
(Nojgaard et al. 2005), but limonene had no signiWcant
eVect in the multivariate analysis. Therefore, further studies
are needed to clarify alpha-pinene and limonene metabolite
exposure and their inXuence on SBS symptoms.
2-Pentanone was signiWcantly associated with SBS symptoms, but the exposure levels were rather low. Unknown
exposures or chance may be confounding the result.
Many of the fungal genera that we recovered (Cladosporium, Penicillium, Alternaria) were similar to those found
commonly 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, history
of allergy, current smoking, time spent in the dwelling and
age of the dwelling, Rhodotorula had a signiWcantly higher
OR for SBS symptoms; however, the signiWcance disappeared in the fully adjusted model. Airborne fungi levels
have a large seasonal variation (Takahashi 1997) as well as
temporal and spatial variability (Douwes and Pearce 2003).
This variability can cause potential misclassiWcation of fungal exposure in epidemiological studies. Furthermore, dead
molds or mold components are not detected, even though
they may have toxic/allergenic properties (Douwes and
Pearce 2003). These variations and unevaluated fungal factors may be the cause of the signiWcantly lower OR of total
CFU in this study. As a way to control these variations,
fungi and endotoxin measurements in dust may be more
representative 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

591

and Asthma, under the auspices of the International Association of Allergology and Clinical Immunology and the
World Health Organization, reported that exposure to 2 g/gdust Der 1 allergen is considered to increase the risk of
sensitization (Platts-Mills et al. 1997). The median Der 1
value of this study was 0.58 g/g-dust, and more than half
of dwellings Der 1 values were lower than 2 g/g-dust.
Thus, lower mite allergen exposure levels may attenuate the
health eVect. Moreover, in a German study, the median
Der1 value of carpets was 0.41 g/g-dust (max 96 g/gdust) while that of mattresses was 2.16 g/g-dust (max
278.9 g/g-dust) (Hirsch et al. 1998). Therefore, exposure
from bedding should be further investigated.
The present study has several limitations. Based on the
previous questionnaire survey, we selected participants
from 53 dwelling that had reported symptoms and 51
dwelling that had not reported symptoms. At the time of
chemical, mite and dampness exposures measurements, we
asked again about symptoms to elucidate the relationships
between the exposures and the symptoms which were
simultaneous with the exposures. Because this was a crosssectional study, causal relationships between variables
could not be determined. Moreover, previous health problems may alter lifestyle habits, such as cleaning frequency,
ventilation time, etc., which would dilute the eVects of
exposure. In Table 4, pets at home had signiWcantly lower
odds ratio. However, this must be a reverse causeeVect
relationship, because residents who have pet allergies are
prone to avoid owning pets. Furthermore, because the participants were limited to those who were interested in exposure measurements, they had a higher prevalence of the
SBS symptoms compared to the general population. Second
we evaluated only the living rooms of the dwellings for
contaminants. Japanese houses are not so large, and most
residents seemed to stay in the living room for many hours,
except for sleeping time; therefore, we considered that the
exposure levels of residents in the living room represented
the overall exposure levels in the dwellings (Sakaguchi and
Akabayashi 2003). However, as previously mentioned, the
mite allergen levels of bedding may be a better exposure
indicator. Third, seasonal variation could not be evaluated
in this study. In particular, the seasonal variation of airborne fungi levels may aVect the results. Fourth, socio-economic status was not measured. However, since all the
households had their own newly built detached house, it
was considered that the participants had socio-economic
statuses and belonged to the middle class. Fifth, we did not
measure carbon dioxide levels even though it can cause
SBS symptoms, because carbon dioxide problems do not
occur in Japanese dwellings (Norback and Nordstrom
2008).
In conclusion, dampness, formaldehyde, and alphapinene were signiWcantly related to SBS symptoms in

123

592

newly built dwellings. We should take measures to reduce


the chemicals and dampness in dwellings. Further studies
are needed to clarify seasonal variations in the eVects of
contaminants, metabolites of chemicals, and bedding mite
allergen eVects.
Acknowledgment This study was supported by a grant-in-aid from
the Ministry of Health, Labour and Welfare, Health and Labour
Sciences Research Grant, Japan (Research on Health Services:
H15-Ganyobou-093). We would like to express grate gratitude to
Ms. K. Yamashita for her cooperation.

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