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Relationship Between Sick Building Syndrome and Indoor Environmental Factors in Newly Built Japanese Dwellings
Relationship Between Sick Building Syndrome and Indoor Environmental Factors in Newly Built Japanese Dwellings
Relationship Between Sick Building Syndrome and Indoor Environmental Factors in Newly Built Japanese Dwellings
DOI 10.1007/s00420-009-0395-8
O R I G I N A L A R T I CL E
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,
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
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,
123
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
585
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.
123
586
Structure of dwelling
Wooden
102
98.1
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
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
50
48.1
Mold growth
69
66.3
Moldy odor
10
9.6
18
17.3
Water leakage
14
13.5
Pet in dwelling
29
27.9
39
37.5
61
58.7
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
123
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
587
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
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
Adjusted ORa
Unadjusted OR
OR
95% CI
P-value
OR
95% CI
P-value
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
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
0.95
0.561.60
n.s.
0.73
0.401.32
n.s.
0.90
0.531.51
n.s.
0.81
0.471.38
n.s.
1.36
0.812.28
n.s.
1.34
0.792.28
n.s.
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.
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.
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
123
588
Symptoms (n = 74)
No symptom (n = 269)
Median Range
(Minmax)
Median
Range
(Minmax)
P-valuea
63.2
22.1202.8
0.001
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
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.
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.
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
123
590
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
123
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
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