SUPPLEMENTARY FILES Air pollutants of the indoor environment … · 2013. 11. 21. · Litonjua et...

SUPPLEMENTARY FILES

Air pollutants of the indoor environment and respiratory health. Marion Hulina,b, Marzia Simonic, Giovanni Viegic,d, Isabella Annesi-Maesanoa,b

a INSERM, UMR 707, EPAR, Paris, F-75012 France b UPMC Univ Paris 06, UMR_S 707, EPAR, Paris, F-75012 France c Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Pisa, Italy d CNR Institute of Biomedicine and Molecular Immunology “A. Monroy”, Palermo, Italy

Table S1. Epidemiological evidence on the relationship between respiratory health and exposure to indoor moulds objectively assessed

Population Pollution assessment Main results

Strachan et al. 1990 [1]

Case-control on wheezing, Great-Britain

88 children (6-7 years old)

Total and specific mould levels: four air sampling (winter) in

living room and bedroom and in a third room (where visible moulds

was detected or in kitchen)

- Higher concentration of mycelia sterilia counts in the homes of wheezy children compared to the one of non-wheezy children

- No significant differences for all combined other mould species (Penicillium spp, Cladosporium spp, Sistotrema brinkmanii or white rot basidiomycetes)

Smedje et al. 1996 [2] Cross-sectional study at school (40

schools, Sweden 1,410 employees (16-64 years old)

MVOC concentration: one air sampling in classrooms, by pumps

- Positive associations between MVOC concentration (2-methyl-iso-borneol, 3-methyl furan, 2-heptatone, 1-octen-3-ol) and the risk of asthma

Smedje et al. 1997 [3] Cross-sectional study at school (11

schools), Sweden. 627 children (13-14 years old)

Total and specific mould levels: one dust sample from desks,

chairs and floor

- Positive associations between viable mould counts (increase of 1000 organism/m3) and the risk of current asthma

Garett et al., 1998 [4] Cross-sectional study at home,

Australia 148 children (7-14 years old)

Total airborne and specific fungal spore levels: one air sampling in

living room, bedroom and kitchen during 10h

- Positive association between Aspergillus concentration (increase of 10 CFU/m3) and the risk of atopy

- Positive associations between Aspergillus, Cladosporium and Penicillium concentrations (increase of 100 CFU/m3) and the risk allergic sensibilization to moulds

- Positive association between Penicillium concentration in winter (increase of 100 CFU/m3) and the risk of asthma

Elke et al., 1999 [5] Cross-sectional study at home,

Germany 132 children (5-7 years old)

MVOC concentration : one sampling period, in bedroom, by passive diffusion, during 4 weeks

- No association between MVOC concentration (high vs. low) and the risk of self-reported asthma, wheezing or allergies

Douwes et al. 2000 [6]

Case-control study on chronic respiratory symptoms (recent

wheezing, shortness of breath with wheezing, dry cough, and/or doctor-

diagnosed asthma ever in life), Netherlands


(1→3)-β-D-glucan concentration: one dust sample on living room,

bedroom floor and child’s mattress

- No differences of (1→3)-β-D-glucans concentration between children with or without respiratory symptoms

- Positive association between (1→3)-β-D-glucans concentrations and PEF variability among asthmatic and/or atopic children

Dharmage et al. 2001 [7]

Cross-sectional study at home, Australia

485 adults (20-44 years old)

Ergosterol concentration and total and specific moulds levels: one air sampling and dust sample in

- Positive association between ergosterol concentration (high vs. low, high= >7.6 µg/g) and the risk of allergic sensitization to moulds

bedroom - Negative association between the number of total moulds or specific to Penicillium or Cladosporium (high vs. low, high= >842, >146, >366 CFU/m3 respectively) and allergic sensitization to moulds

- Positive association between ergosterol concentration (high vs. low, high= >7.6 µg/g) and the risk of having “wheezing only”

- Positive between the number of total moulds or specific to Penicillium or Cladosporium (high vs. low, high= >842, >146, >366 CFU/m3 respectively) and the risk of having “BHR only”

- No association with current asthma

Jacob et al. 2002 [8] 2 case-control studies on asthma and/or

atopy, Germany 272 children (5-7 and 8-10 years old)

Total and specific fungal spore levels: one dust sample (winter) in

living room floor

- Positive associations between Cladosporium spore levels in winter (high vs. low, high= >35000 CFU/g), and Aspergillus (medium vs. low, medium= between LOD and >25000 CFU/g) with the risk of allergic sensitization

- No association with asthma or persistent wheezing

Smedje et al. 2001 [9]

Longitudinal study at school (39 schools), Sweden.

Cohort of 1,347 children (7-13 years old) followed during 4 years

Two sampling periods in classrooms, by active sampling,

during 4 hours, at start and end of the study

- No association between mould spore counts and the incidence of self-reported allergy and doctor-diagnosed asthma

- Among non atopic, positive association between total mould spore counts (increase of 10 units) and the incidence of doctor-diagnosed asthma

Gent et al. 2002 [10] Longitudinal study, United-States

Birth cohort of 819 children followed during 1 year

Total and specific mould counts: one air sampling in living room, during 1 mn, 2 to 4 months after

birth

- Positive associations between the number of Penicillium counts (high vs. low, high= >1000 CFU/m3) and the rate of wheezing and persistent cough

- No association with total or other specific mould levels

Belanger et al. 2003 [11]

Longitudinal study, United-States Birth cohort of 819 children followed

during 1 year

Total mould counts: one air sampling in living room and bedroom, during 1 mn, 2 to 4

months after birth

- Positive association between total mould counts (increase of 20 units) and the risk of wheezing among children of mothers with asthma

- No association with persistent cough

Jovanic et al. 2004 [12]

Case-control study on allergic diseases (lifetime: asthma, asthmatic-spastic or

obstructive bronchitis, hay fever, atopic eczema), Germany


Total mould counts: 4 air sampling and 1 dust sample in bedroom floor and the child’s

mattress

- No differences between cases and controls

Blanc et al. 2005 [13] Cross-sectional study, United-States 226 asthmatic or rhinitic adults

(1→3)-β-D-glucan concentration : dust samples from mattress,

kitchen and living room floors - No association with FEV1 (%) levels

Matheson et al. 2005 [14]

Longitudinal study, Australia Cohort of 360 adults (20-45 years old)

followed during 2 years

Ergosterol concentration: two air sampling in bedroom and dust samples in bedroom floor and

bed, at start and end of the study Total mould counts:

one dust sample in bedroom floor and bed, at start and end of the

study

- Positive associations between Cladosporium spore counts (double) and the risk of developing new asthma crises

- Positive association between total spore counts (double) and the risk of developing atopy

- Negative association between an increase in ergosterol concentration (double) and the remission of wheezing

- No association with self-reported asthma or wheezing

Douwes et al., 2006 [15]

Longitudinal study, Netherlands Birth cohort of 696 children followed

during 4 years

EPS-Pen/Asp et (1→3)-β-glucan concentrations: one dust sample on living room floor and

mattress, 3 months after birth

- Negative association between EPS-Pen/Asp concentration in living room (high vs. low, high= >8802.3 units/m2) and the risk of doctor-diagnosed asthma, persistent wheezing and atopy at 4 years. No modifying effect by atopy.

- No association with (1→3)-β-D-glucan concentration

Iossifova et al. 2006 [16]

Longitudinal study, United-States Birth cohort of 574 children followed

during 13 months in means

(1→3)-β-D-glucan concentration : one dust sample

from baby’s primary activity room floor, around 8 months after

birth

- Negative associations between (1→3)-β-D-glucan concentration (medium vs. low, medium= >134-900 µg/g) and the risk of recurrent wheezing, among both atopic and non atopic

- When considering high exposure (>900 µg/g), positive association between (1→3)-β-glucan and the risk of recurrent wheezing, among both atopic and non atopic concentration

- No association with atopy

Turyk et al. 2006 [17] Panel study, United-States 61 asthmatic children (6-13 year old)

Allergens : one dust sample from child’ mattress, living room and

bedroom floor

- Positive association between Penicillium concentration (high vs. low) in bedroom and asthma symptoms

- No association with total fungi concentration

Kim et al. 2007 [18] Cross-sectional study at school (8

schools), Sweden 1,014 children (5-14 years old)

Total mould counts: one air sampling in classrooms of 23

schools. MVOC concentration: one

sampling period (summer), by active sampling, during 4 hours

- Positive association between total mould counts (increase of 1 103/m3) and the risk of current wheezing

- Positive associations between MVOC concentration (high vs. low) and the risk of current wheezing (for 3-octanone), doctor-diagnosed asthma (MVOC, 2-heptanone, 2-Methyl-1-butanol) and nocturnal attacks of breathlessness

Zhao et al. 2008 [19] Cross-sectional study at school (10

schools), China 1,993 children (11-15 years old)

Ergosterol concentration: two dust samples in classrooms floor and

desks

- Negative association between ergosterol concentration (increase of 10 µg/g) and the risk of daytime attacks of breathlessness and history of atopy

- No association with cumulative incidence of asthma (ever and doctor-diagnosed), medication use, wheezing and nocturnal attacks of breathlessness

Bertelsen et al. 2010 [20]

Longitudinal study, Norway Birth cohort of 260 children, followed

during 10 years

(1→3)-β-D-glucan concentration : one dust sample on living room

floor, at the age of 2 years

- No association with the risk of asthma or atopy

MVOC = microbial volatile organic compounds; EPS-Asp/Pen = extracellular polysaccharides from Aspergillus and Penicillium, CFU = Colony Fungal Unit FEV1 = Forced expiratory volume in one second, AHR=airway hyperresponsiveness

Table S2. Epidemiological evidence on the relationship between respiratory health and exposure to indoor endotoxins objectively assessed



Cross-sectional study at school (11 schools), Sweden.


One dust sample from desks, chairs and floor

- No association between endotoxins concentration and current asthma


Case-control study on chronic respiratory symptoms (recent

wheezing, shortness of breath with wheezing, dry cough, and/or doctor-

diagnosed asthma ever in life), Netherlands


One dust sample on living room and bedroom floors and child’s

mattress

- Higher concentration in the mattress of children with cough then in the one of controls

- No association with PEF variability

Gereda et al. 2000 [21]

Cross-sectional study, United-States 61 wheezing children (9-24 months)

One dust sample from living-room floor and couch, kitchen

floor and participant’s bed

- Lower house-dust endotoxins concentrations in the homes of allergen-sensitized infants than in those of non-sensitized infants

Ghering et al. 2001 [22]

Longitudinal study, Germany Birth cohort of 1,884 children,

followed during 1 year

One dust sample from mother’s and children’s mattresses, 3

months after birth

- Positive association between endotoxins concentration in mother’s or children’s mattresses (High vs. low, high= >1973 EU/g) and the risk of cough with respiratory infection, bronchitis, or both in the first 6 months.

- Positive association between a high endotoxin concentration in mother’s mattresses (High vs. low: high= >4365 EU/g) and the risk of wheezing


Two cross-sectional studies, Germany

454 children (5-10 years)

One dust sample from living room floor

- Negative association between endotxins concentration and the risk of multiple sensitization and sensitization to Cladosporium herbarum.

- No association with the risk of asthma and wheezing

Litonjua et al. 2002 [24]

Longitudinal study, United-States Cohort of 226 siblings (81.3 EU/mg) and the risk of wheezing, especially in the year following samples, and the risk of repeated wheezing

Böttcher et al. 2003 [25]

Longitudinal study, Estonia and Sweden

Birth cohort of 219 children followed during 2 years

One dust sample, from a carpet and child’s mattress, between 3

and 12 months of age

- Negative association between endotoxin concentration in the carpet (increase of 10 EU/mg) and the development of atopy in Swedish children

Bolte et al. 2003 [26]

Longitudinal study, Germany Birth cohort of 1,942 children

One dust sample from mother’s and children’s mattresses, 3

- Positive association between endotoxin concentration in children’ mattress (high vs. low, high= >7752 EU/g) and the risk of

followed during 2 years months after birth repeated wheezing, independent of atopic status. - Positive association between endotoxin concentration and the risk

of repeated wheezing or allergic sensitization to inhalant allergens in infants with parental atopy

- No association with the incidence of physician-diagnosed asthma

Blanc et al. 2005 [13]

Cross-sectional study, United-States 226 asthmatic or rhinitic adults

Dust samples from mattress, kitchen and living room floors

- Association between endotoxin concentration (Medium vs. low, medium= >23 and 19.6 EU/mg) and the risk of wheezing (ever, past year and past month)

- Positive associations between a high concentration of endotoxin in the bedroom floor (>16.6 EU/mg) and the risk of asthma symptoms (past year) and wheezing (ever and past month)

- No significant association among children only - No significant interaction between endotoxin and respiratory

outcomes, but a higher risk among allergic subjects.

Tavernier et al. 2006 et 2005[29, 30]

Case-control study on asthma, Great-Britain


One dust sample, from living room carpet, child’s bedroom

floor or mattress

- Higher endotoxin concentration in the carpet of cases than the one of controls

- Positive association between endotoxin concentration in living-room carpet and asthma

Dales et al. 2006 [31]

Longitudinal study, Canada Birth cohort of 332 children


One air sampling, in bedroom and living room, during 5 to 7

days, before one year old

- Positive association between endotoxin concentration and the risk of illness episodes or the number of illness days (stuffy nose, cough, wheezing, and shortness of breath)


Longitudinal study, Netherlands Birth cohort of 696 children,


One dust sample from living room floor and child’s mattress, 3

months after birth

- Negative associations between endotoxin concentration (High vs. low, high= >142.2 EU/m2) and the risk of doctor-diagnosed asthma. No modifying effect by atopy.

- No association with wheezing or atopy

Iossifova et al. 2006 [16]

Longitudinal study, Unites-States Birth cohort of 574 children followed during 13 months

One dust sample from baby’s primary activity room floor, around 8 months after birth

- No association with the risk of recurrent wheezing or atopy

Perzanowski et al. 2006 [32]

Longitudinal study, Unites-States Birth cohort of 301 children

One dust sample, from bedroom floor, at the age of 12 or 36

- Positive association between an increase in endotoxin concentration and the risk of wheezing between 13 and 24 months

followed during 3 years months - No association with the risk of wheezing between 0 to 12 or 25 to 36 months

Celedon et al. 2007 [33]

Longitudinal study, United-States Birth cohort of 440 children,


One dust sample, from parents’ and child’s bed, child’bedroom,

living-room and kitchen floors, 2 to 3 months after birth

- Negative association between endotoxin concentration in living-room (medium vs. low, medium= 52.49 et 125.59 EU/mg) and the risk of atopy

- Positive associations between endotoxin concentration (high vs. low, high=>125.59 EU/mg) and the risk of persistent wheezing. No modifying effect by atopy.

- No association with the risk of asthma


Case-control study on wheezing, International


One dust sample on mattress or living-room floor

- Negative associations between endotoxin concentration (increase of one IQR=5.4) and the risk of ever asthma, in both atopic and non atopic subjects

- Negative associations between endotoxin load (increase of one IQR=4.2) and the risk of asthma ever, current wheezing and atopy

- Negative associations between endotoxin load and the risk of current wheezing only in atopic subjects

Rennie et al. 2008 [35]

Case-control study on asthma, Canada


One sample of dust, from activity room floor and child’s mattress - No association with the risk of asthma

Zhao et al. 2008 [19]

Cross-sectional study at school (10 schools)

1,993 children (11-15 years old)

LPS measurement: one dust sample on classroom floor and

desks

- Negative association between LPS levels (increase of 10nmol/sample) and daytime attacks of breathlessness but positive when adjustment on ergosterol and muramic acid concentrations

- Negative associations between LPS C10 concentration and wheezing, and LPS C10, C12, C14 and the risk of daytime attacks of breathlessness

- No association with wheezing, incidence of asthma and doctor-diagnosed asthma or history of atopy

Ryan et al. 2009 [36]

Longitudinal study, United-States Birth cohort of 624 children,


One dust sample from baby’s primary activity room floor, around 8 months after birth

- Positive associations between endotoxin concentration associated with high exposure to traffic-related particles and the risk of persistent wheezing and predictive index of asthma, in the whole and non atopic population

Bertelsen et al. 2010 [20]

Longitudinal study, Norway Birth cohort of 260 children,


One dust sample on living room floor, at the age of 2 years

- No association between endotoxin and the risk of atopy or asthma

LPS = lipopolysaccharides, EU = Endotoxin unit, IQR = Interquartile range, FEV1 = Forced expiratory volume in one second, PEF = peak expiratory flow

Table S3. Epidemiological evidence on the relationship between respiratory health and exposure to indoor nitrogen dioxide objectively assessed


Melia et al. 1982 [37]

Cross-sectional study, England 179 children (5-6 years old)

One sampling period (winter) in bedroom and the living room, by passive diffusion, during

14 weeks

- Positive association (p45 µg/m3) and the risk of having one or more asthmatic or bronchitic symptoms

Berwick et al. 1989 [38]

Longitudinal study, United-States Cohort of 121 children (30 µg/m3) and the risk of having lower respiratory symptoms among children under the age of 7.

Neas et al. 1991 [39]

Longitudinal study, United-States Cohort of 1,567 children (7-11 years old)

followed during 18 months

Two sampling periods (summer, winter), in kitchen, the activity room and the bedroom, by passive diffusion, during one week

- Positive association between NO2 concentration (increase of 27 µg/m3) and the incidence of lower respiratory symptoms. - No association with asthma and lower respiratory symptoms taken independently (shortness of breath, chronic wheezing, chronic cough, chronic phlegm and bronchitis) - Positive association between NO2 concentration (increase of 27 µg/m3) and FEV1/FVC levels

Samet et al. 1993 [40]

Longitudinal study, United-States Birth cohort study of 1,205 children followed

during 18 months

Several sampling periods in bedroom, by passive diffusion

- No association between NO2 concentration and the incidence of lower respiraotry symptoms

Pilotto et al. 1997 [41]

Longitudinal study at school (8 schools), Australia


At school : 9 sampling periods (every two weeks) in classrooms, by passive diffusion, 6h, and sampling every hours during 2 weeks At home: 4 sampling periods during evenings for children exposed to gas appliances

- Positive dose-reponse trends between mean NO2 concentration and mean rates for cough with phlegm - No association with dry cough or wheezing


Cross-sectional study at school (11 schools), Sweden


One sampling period (spring) by passive diffusion, during 6 to 7 days

- No association with current asthma

Garrett et al. 1998 [42]

Cross-sectional study at home, Australia 148 children (7-14 years old).

4 sampling periods (summer, winter) in bedroom, the living room and the kitchen, by

passive diffusion, during 4 days

- Positive association between NO2 concentration in the bedroom (high vs. low, high= >20 µg/m3) in summer and respiratory symptom score (cough, shortness of breath,

waking due to shortness of breath, wheezing, asthma attacks, chest tightness, cough in the morning, and chest tightness in the morning.) - No association with atopy, asthma ou respiratory symptoms taken independently or lung function change

Shima et al. 2000 [43]

Longitudinal study, Japan Cohort of 842 children (9-10 years old)

Two sampling period (summer, winter) in living room, by passive diffusion, during 24 hours

- Positive associations between NO2 concentration (increase of 18 µg/m3) and the risk of doctor-diagnosed of asthma, bronchitis or self-reported wheezing among girls - No association with history of allergic diseases or incidence of wheezing or asthma.

Smith et al., 2000 [44]

Panel study, Australia 125 asthmatics (all ages)

3 sampling periods, by passive badges, at home, during one week

- Positive association between daily NO2 concentration and the report of chest tightness, breathlessness on exertion and night and daytime asthma attacks the same day or the day after. - No association with wheezing, cough or breathlessness

Emenius et al. 2003 [45]

Nested case-control study on recurrent wheezing, Sweden


One sampling period (winter), in living room, by passive diffusion, during 4 weeks

- No association between NO2 concentration and the risk of recurrent wheezing in the first two years - Positive association between NO2 concentration (high vs. low) and exposure to tobacco smoke and the risk of recurrent wheezing (significant interaction)

Venn et al., 2003 [46]

Case-control study on wheezing, Great-Britain 416 children (9 à 11 years old)

One sampling period (winter) in kitchen, by passive diffusion, during 4 weeks

- No association between NO2 concentration and wheezing, or with respiratory symptoms among cases

Simoni et al. 2004 [47]

Two cross-sectional studies, Italy 1,090 adults (>15 years old)

Two sampling periods (summer, winter) in living room, by passive diffusion, during one week. Evaluation of exposure (exposure time*concentration)

- No association between NO2 exposure and bronchitic and/or asthmatic symptoms (sputum from the chest, shortness of breath, attack of shortness of breath, wheezings) without fever and without acute respiratory illnesses

Sunyer et al. 2004 [48]

Longitudinal study, Spain. Birth cohort of 1,611 children followed

during 1 year

One sampling period, in living room, by passive diffusion, during 2 weeks, 3 months after birth

- No association with cumulative rates of lower respiratory tract infections

Van Strien et al. 2004 [49]

Longitudinal study, United-States Birth cohort of 768 children with asthmatic

siblings, followed during one year

One sampling period, in living room, by passive diffusion, during 2 weeks, 2 to 4 months after birth

- Positive associations between NO2 concentration (high vs. low, high= >31.3 µg/m3) and the number of days of wheezing or shortness of breath - No association with cough


Cross-sectional study, United-States 226 asthmatic or rhinitic adults

One sampling period, in kitchen, by passive diffusion, during 1 week - No association with FEV1 levels

Belanger et al. 2006 [50]

Longitudinal study, United-States Cohort of 768 asthmatic siblings (100 µg/m3) and the risk of frequent respiratory symptoms (cough, wheezing, or shortness of breath) in non atopic children - No association with the risk of PEF40 years)

Three air sampling in three sites in kitchen, by active sampling, during 5 minutes - No association with COPD

Osman et al. 2007 [56]

Cross-sectional study, Scotland 148 adults with COPD

One sampling period (winter), in living room, by passive diffusion, during 1 week

- No association with respiratory symptom score

Hansel et al. 2008 [57]

Longitudinal study, United-States 150 asthmatic children (2-6 years old)

3 sampling period every 3 months, in bedroom, by passive diffusion, during 72h.

- Positive association between NO2 concentration (increase of 36 µg/m3) and frequency of limited speech due to wheezing, coughing without a cold, and nocturnal awakenings due to cough, wheezing, and shortness of breath or chest tightness and while running. - No association with wheezing, and shortness of breath or chest tightness during the daytime, and having to slow activity due to asthma, wheezing, chest tightness or cough - Higher association between NO2 concentration and nocturnal symptoms in atopic children than among non atopic ones (significant interaction)

Zhao et al. 2008 [58]

Cross-sectional study at school (10 schools), China

1,993 children (11-15 years old)

One sampling period,in classrooms, by passive diffusion, during one week

- Positive association between NO2 concentration (increase of 10 µg/m3) and the risk of nocturnal attacks of breathlessness - No association with cumulative asthma, wheezing or whistling in the chest, daytime attacks of breathlessness or furry pet or pollen allergy

Raaschou-Nielsen et al. 2010 [59]

Longitudinal study, Denmark. Birth cohort of 378 children from asthmatic

mothers followed during 18 months

Up to 3 measurement in bedroom during the first 18 months of life, by passive diffusion,

during 10 weeks

- No association with the risk of symptom-day or the number of symptom-days of wheezing

NO2= nitrogen dioxide, FEV1=Forced expiratory volume in one second, FVC=Force vital capacity, COPD= chronic obstructive pulmonary disease

Table S4. Epidemiological evidence on the relationship between respiratory health and exposure to indoor particles objectively assessed


Neas et al. 1994 [60]

Longitudinal study, United-States

Cohort of 1,237 children (7-11 years) followed during 3 years

2 consecutive 1-week sampling periods (winter, summer) in the activity room, by impactor.

- Positive association between PM2.5 concentration (increase of 30 µg/m3) and the cumulative incidence of respiratory symptoms (shortness of breath, persistent wheezing, chronic cough, chronic phlegm or bronchitis) among the 9-10 years old children - Positive associations between an increase of PM2.5 concentration (increase of 30 µg/m3) and the cumulative incidence of bronchitis and lower respiratory symptoms among boys - No association with asthma, shortness of breath, persistent wheezing, chronic cough or chronic phlegm


Longitudinal study at school (39 schools), Sweden.

Cohort of 1,347 children (7-13 years old) followed during 4

years

Two sampling periods (at start and end of the follow-up) in classrooms, by direct

reading, twice in each classroom during 15 mn

- Positive association between respirable particles concentration (increase of 10 µg/m3) and the incidence of self-reported allergy to pet - No association with the incidence of self-reported allergy to pollen or asthma diagnosis, even after stratification for a history of allergy.

Delfino et al. 2004 [61]

Panel study, United-States 19 asthmatic children (9-17

years)

One sampling period in the living room, by pumps, during 24h

- Negative association between PM2.5 concentration (increase of one IQR) and a change in FEV1 levels (%)


Two cross-sectional studies, Italy

1,090 adults (>15 years)

Two sampling periods (summer, winter) in the living room, by pumps, during 2 consecutive 48-h. Evaluation of exposure (exposure time*concentration)

- Positive association between PM2.5 concentration (high vs. low) and bronchitic and/or asthmatic symptoms (sputum from the chest, shortness of breath, attack of shortness of breath, wheezings) without fever and without acute respiratory illnesses - Positive associations between a PM2.5 concentration (high vs. low) and PEF maximum amplitude (%) and diurnal variation (%).

Koenig et al. 2005 [62]

Panel study, United-States 19 asthmatic children (6-13

years)

Estimation of exposure based on particles

measurement at home, by impactor

- Negative association between indoor-generated PM2.5 concentration (increase of 10 µg/m3) and FEV1 and FVC levels among children not using inhaled corticosteroid

Tavernier et al, 2006 [29]

Case-control study on asthma, Great-Britain 200 children (4-

17 years old)

Two sampling periods in the bedroom and the living

room, by impactor


Trenga et al. 2006 [63]

Panel study, United-States 57 adults (56-89 years) , 17

children with asthma

5 to 10 sampling periods in home over a period of 3 years, by impactor, during

- Negative association between PM2.5 concentration (increase of 10 µg/m3) and a change in FEV1 levels in adults. No association with a change in PEF levels. - Negative association between PM2.5 concentration (increase of 10 µg/m3)

24h and a change in FEV1 and PEF, and MMEF levels in children not taking inflammatory medication.

Diette et al. 2007 [53]

Nested case-control study on asthma, United-States


One sampling period of 72 h, in the bedroom, by impactor + PM gravimetric analysis


Liu et al. 2007 [55] 2 cross-sectional studies, China 194 women (>40 years)

Three air sampling in three sites in the kitchen, by

active sampling, during 5 minutes

- No association with the risk of COPD

Osman et al. 2007 [56]

Cross-sectional study, Scotland 148 adults with COPD

One sampling period (winter), in the living room, by direct reading, during 12

to 18 hours

- Positive associations between PM2.5 concentration and respiratory symptom score

Ma et al. 2008 [64] Panel study at hospital, Japan 19 severe asthmatic children

(8-15 years)

Seven sampling periods, at hospital, by direct

measurement, during 24h

- Negative associations between PM2.5 concentration (increase of 10 µg/m3) and change in PEF levels in the morning and the evening. - Positive association between PM2.5 concentration (increase of 10 µg/m3) and the prevalence of wheezing in the morning or the evening

McCormack et al. 2009 [65]

Longitudinal study, United-States

Cohort of 150 asthmatic children (2-6 years)

Three sampling periods every 3 months, in the bedroom, by impactor,

during 3 days

- Positive associations between PM2.5-10 concentration (increase of 10 µg/m3) and the incidence rate of cough, wheezing or chest tightness, nocturnal symptoms, wheezing that limited speaking ability and rescue medication use. - Positive associations between PM2.5 concentration (increase of 10 µg/m3) and the incidence rate of asthma symptoms that need to slow down or stop activities, symptoms with exercise, nocturnal symptoms, wheezing that limited speaking ability and rescue medication use.

De Hartog et al. 2010 [66]

Cross-sectional study, Europe 135 subjects with asthma or

COPD (>35 years)

One sampling period, by impactor and direct

measurement, during 24h - No association between PM2.5 concentration and change in lung function


Longitudinal study, Denmark. Birth cohort of 378 children

from asthmatic mothers followed during 18 months

Up to 3 measurement in the bedroom during the first 18 months of life, by cyclone

and pumps, for 1 week

- No association between PM2.5 concentration and the risk of symptom-day or number of symptom-days of wheezing


Cross-sectional study at school (21 schools), Europe

654 children (10 years)

One sampling period in classrooms, by direct

measurement, for 1 to 2 h

- No association between PM2.5 concentration (high vs. low, high:>50 µg/m3 or an increase of 10 µg/m3) and the prevalence of wheezing or dry cough at night.

PM2.5=particulate matter with an aerodynamic diameter

Table S5. Epidemiological evidence on the relationship between respiratory health and exposure to indoor formaldehyde objectively assessed


Krzyzanowski et al. 1990 [68]

Cross-sectional study, United States

298 children (5 - 15 years) + 613 adults (>15 years)

Two sampling periods, in kitchen, living room and each subject’s bedroom, by passive diffusion,

during one week

- Higher prevalence of doctor-diagnosed asthma and bronchitis in children living in homes with high level of pollution (>75µg/m3)

- Decreased in the levels of PEF as formaldehyde concentration increased

- No association with respiratory symptoms (chronic cough, wheezing, chronic phlegm, attacks of shortness of breath) or in adults

Norbäck et al. 1995 [69]

Case-control study on respiratory symptoms (asthma

attacks, nocturnal breathlessness, current use of asthma medication), Sweden.

88 adults (20-45 years)

One sampling period in bedroom and living room, by active sampling, during 2 hours

- Positive association between formaldehyde concentration (increase of 10 µg/m3) and the risk of nocturnal breathlessness

- No significant association between formaldehyde concentration and bronchial hyperresponsiveness, variability in PEF and change in FEV1

Smedje et al. 1997 [3] Cross-sectional study at school

(11 schools) , Sweden 627 children (13-14 years)

One sampling period (summer) in classrooms, by active sampling,

during 4 hours

- Positive association between formaldehyde concentration (increase of 10 µg/m3) and the risk of current asthma

Garett et al. 1999 [70] Cross-sectional study, Australia 148 children (7-14 years).

4 sampling periods (summer, winter) in bedroom, living room

and kitchen, by passive diffusion, during 4 days

- Higher number of positive skin prick test in relation with higher formaldehyde concentration ( >50 µg/m3)

- No association with current asthma - Positive association between formaldehyde concentration

(High vs. low, high=>50 µg/m3) and respiratory symptom score (cough, cough in the morning, waking due to shortness of breath, wheezing/whistling, asthma attacks, chest tightness, chest tightness in the morning) in children suffering from respiratory symptoms


Longitudinal study at school (39 schools), Sweden


2 sampling periods (at start and end of the follow-up) in

classrooms, by active sampling, during 4 hours

- No association with the incidence of self-reported allergy - In non allergic children, positive association between

formaldehyde concentration (increase of 10 µg/m3) and the incidence of doctor-diagnosed asthma

Rumchev et al. 2002 [71]

Case-control study on asthma, Australia

192 children (6 months-3 years).

2 sampling periods (summer, winter) in living room and

bedroom, by passive diffusion, during 8 hours

- Positive association between formaldehyde concentration (increase of 10 µg/m3, and high vs. low, high= >60 µg/m3) and the risk of doctor-diagnosed asthma

Venn et al., 2003 [46] Case-control study on current

wheezing, Great-Britain 416 children (9- 11 years)

Onse sampling period (winter) in bedroom, by passive diffusion,

during 3 days

- No association with current wheezing - Among cases, positive association between formaldehyde

concentration (high vs. low, high=>32 µg/m3) and the risk of nocturnal symptoms


Cross-sectional study, United-States

226 asthmatic or rhinitic adults

One sampling period, in kitchen, by passive diffusion, during 1

week - No association with change in FEV1

Mi et al. 2006 [51] Cross-sectional study at school

(10 schools), China 1,414 children (13-14 years).

One sampling period in 30 classroom, by active sampling,

during 4hours

- No association with respiratory symptoms (wheezing, attack of breathlessness, asthma attacks, asthma medication), current asthma and self-reported allergy to furry pet or pollen

Tavernier et al, 2006 [29] Case-control study on asthma,

Great-Britain 200 children (4-17 years)

Two sampling period one week apart, in bedroom and living

room, by active sampling - No differences between cases and controls

Kim et al. 2007 [18] Cross-sectional study at school

(8 schools), Sweden 1,014 children (5-14 years)

One sampling period (summer) in 3 classrooms of each school, by active sampling, during 6 hours

- No association with current wheezing, doctor-diagnosed asthma or attacks of breathlessness

Zhao et al. 2008 [58] Cross-sectional study at school

(10 schools), China 1,993 children (11-15 years)

One sampling period in classrooms, by passive diffusion,

during 7 days

- Positive association between formaldehyde concentration (increase of 10 µg/m3) and the risk nocturnal attacks of breathlessness and current wheezing

- No association with ever asthma, daytime attacks of breathlessness or self-reported allergy to furry pets or pollens


Longitudinal study, Danemark. Birth cohort of 378 children

from asthmatic mothers followed during 18 months

Up to 3 measurement in bedroom during the first 18 months of life, by passive diffusion, during 10

weeks

- No association with the risk of symptom-day or the number of symptom-days of wheezing

FEV1=Forced expiratory volume in one second, PEF= peak expiratory flow

Table S6. Epidemiological evidence on the relationship between respiratory health and exposure to indoor VOCs objectively assessed


Norbäck et al. 1995 [69]

Case-control study on respiratory symptoms (asthma attacks, nocturnal breathlessness, current use of asthma

medication), Sweden. 88 adults (20-45 years)

One sampling period in bedroom and living room, by active sampling, during 2 hours

- Positive associations between toluene, C8-aromatics, terpene and TVOC concentrations (10 fold increase) and nocturnal attacks of breathlessness

- No association with wheezing, daytime attacks of breathlessness or tightness in the chest

- Positive association between limonene concentration (10 fold increase) and bronchial hyper-reactivity

- Positive association between α-pinene and δ-karen concentration (10 fold increase) and PEF variability


Cross-sectional study at school (11 schools), Sweden


One sampling period (summer) in classrooms, by active sampling, during 7

days

- Positive association between TVOC concentration (increase of 10 µg/m3) and current asthma

Diez et al. 2000 [72]

Longitudinal study, Germany Birth cohort of 266 children with risk of allergy, followed during one year

One sampling period, in bedroom, by passive diffusion, 4 weeks after birth - No association with the risk of wheezing


Longitudinal study at school (39 schools), Sweden


2 sampling periods (at start and end of the follow-up) in classrooms, by active

sampling, during 4 hours

- No association with the incidence of self-reported allergy or doctor-diagnosed asthma

Venn et al., 2003 [46]

Case-control study on current wheezing, Great-Britain

416 children (9 to 11 years old)

One sampling period (winter) in bedroom, by passive diffusion, during 4 weeks

- No association with the risk of wheezing or respiratory symptoms among cases

Lehmann et al. 2001 [73]

Cross-sectional study, Germany 120 children (3 years)

One sampling period, in bedroom, by passive diffusion, during 4 weeks - No association with allergic sensitization to aeroallergens

Rumchev et al. 2004 [74]

Case-control study on asthma, Australia

192 children (6 months- 3 years).

2 sampling periods (summer/winter) in living room and bedroom, by passive

diffusion, during 8 hours

- Positive association between benzene, toluene, ethylbenzene, m,p-xylene, 1.2-dichlorobenzene, 1.4-dichlorobenzene and TVOC concentrations (increase of 10µg/m3) and the risk of doctor-diagnosed asthma

Tavernier et al, 2006 [29]

Case-control study on asthma, Great-Britain

200 children (4- 17 years)

Two sampling period one week apart, in bedroom and living room, by active

sampling - No differences between cases and controls

TVOC= Total volatile organic compounds, PEF= peak expiratory flow

Table S7. Epidemiological evidence on the relationship between respiratory health and exposure to indoor pollutants objectively assessed in rural areas: farming environment in children


Braun-Fahrländer et al. 2002 [75]

Cross-sectional study, Austria, Germany and Switzerland 812 children (6-13 years)

Endotoxin concentration: one dust sample in mattress

- Negative associations between endotoxin load (high vs. low) and atopic sensitization, atopic asthma and atopic wheezing

Van Strien et al. 2004 [76]

Cross-sectional study, Austria, Germany and Switzerland 553 children (6-13 years)

Muramic acid concentration: one dust sample in mattress

- Negative association between muramic acid concentration (increase of 108 ng/mg) and the risk of wheezing

- No association with atopy or asthma

Schram-Bijkerk et al. 2005 [77]

Case-control study on atopic wheezing, Europe


Endotoxin, fungal β(1,3)-glucans and fungal EPS concentrations: One dust

sample form living room floor and mattress

- Negative association between endotoxin and EPS concentrations (increase f a factor 4 and 3 respectively) and the risk of atopic wheezing

- No association with glucan concentration - No association when mutually adjusted for all pollutant

Schram-Bijkerk et al. 2006 [78]

Cross-sectional study, Europe 402 children (5-13 years)

Mite allergens concentration: one dust sample in mattress

- Positive association between mite allergen concentration (medium vs. low) and the risk of allergic sensitization

EPS= extracellular polysaccharides

Table S8. Epidemiological evidence on the relationship between respiratory health and exposure to indoor pollutants objectively assessed in rural areas: farming environment in adults


Preller et al. 1995 [79]

Cross-sectional study, the Netherlands

194 pig farmers selected toward chronic respiratory symptoms

Endotoxin concentration and dust quantity: 2 personal inhalable dust sampling

(winter/summer), during one work shift, during 8 hours in mean. Evaluation of exposure

- In asymptomatic farmers (without chronic respiratory symptoms), negative association between endotoxin exposure and FVC and FEV1 levels.

- No association with dust concentration

Post et al. 1998 [80]


140 workers of grain processing and animal feed industry

Endotoxin concentration and dust quantity: 2 personal dust sampling during specific

task, in 8 facilities, during 8 hours. Evaluation of exposure

- Negative association between dust exposure (high vs. low) and FEV1 and MMEF levels.

- Negative association with endotoxin concentration (high vs. low) and FEV1 levels

- No association with FVC and MMEF values.

Volgezang et al. 1998 [81]

Longitudinal study, The Netherlands

171 pig farmers selected toward chronic respiratory symptoms

Endotoxin concentration and dust quantity: 2 personal inhalable dust sampling

(winter/summer), during one work shift, during 8 hours in mean. Evaluation of exposure

- Association between long-term average endotoxin exposure and FEV1 and FVC decline

- Association between long-term average exposure to dust and FVC decline

Eduard et al. 2001 [82]

Cross-sectional study, Norway 290 farmers

Fungal spores, Endotoxins, β(1->3) glucans, EPS Pen/Asp concentrations: three

personal dust sampling during specific tasks, with an upper limit of 1 hour.

Evaluation of exposure

- Positive associations between fungal spores concentration (high vs. low, high= 0.5-17*106/m3) and the risk of cough.

- No associations with chest tightness or wheezing. - No association with dust quantity

Monso et al. 2004 [83]

Cross-sectional study, Europe 105 animal farmers

Endotoxin concentration and dust quantity: personal dust sampling during daily work in

buildings

- Positive association between total dust concentration (high vs. low, high= >17ppm) and the risk of COPD

- No association with endotoxin concentration

Kirychuk et al. 2006 [84]

Cross-sectional study, Canada 111 poultry farmers Endotoxin: personal dust sampling

- Positive association between endotoxin concentration (high vs. low, high= >6.38 ln[EU/mg]) and the risk of chronic phlegm

- No association with lung function or other respiratory symptoms (cough, wheezing or shortness of breath)


Cross-sectional study, Norway 1,614 farmers

Fungal spores, endotoxin concentrations and dust quantity: personal dust sampling,

in a random sample of farms, during 12 specific tasks.

Evaluation of exposure for all farms.

- Positive association between fungal spores exposure (high vs. low, high= >3.5 106/m3) and the risk of asthma in non-atopic farmers

- Negative association between fungal spores exposure (high vs low, high= >3.5 106/m3) and the risk of asthma in non-atopic farmers

- Positive association between total dust exposure (high vs. low, high= >2.7 mg/m3) and the risk of asthma in non-atopic farmers

- No association with exposure to endotoxin

Portengen et al. 2005 [86]


194 pig famers

Endotoxin concentration: two dust samples (summer/winter)


- Positive association between endotoxin exposure and the risk of AHR in sensitized farmers

- Negative association between endotoxin exposure and atopic sensitization to common allergens

- No association with respiratory symptoms and FEV1 level

Smit et al. 2008 [87]


877 famers and agricultural industry workers

Endotoxin concentration: 249 full-shift personal airborne endotoxin, by pumps.


- Positive associations between endotoxin exposure (increase of one IQR) and cough symptoms (daily cough, daily cough with phlegm, woken due to cough), shortness of breath, wheezing.

- Associations in allergic and non allergic farmers


Cross-sectional study, Norway 4,735 farmers

Fungal spores, Endotoxins, β(1->3) glucans, EPS Pen/Asp concentrations: three

personal dust sampling during specific tasks, with an upper limit of 1 hour.


- Positive associations between exposure (10-fold increase) to fungal spores and actinomycete spores and the risk of chronic bronchitis and COPD

- Positive associations between exposure to EPS Asp/Pen antigens (10-fold increase) and the risk of chronic bronchitis and FEV1 level

- Positive association between dust exposure (10-fold increase) and the risk of COPD in atopic farmers

- Positive association between dust exposure (10-fold increase) and the risk of chronic bronchitis in non atopic farmers

Smit et al. 2010 [89]


427 farmers and agricultural industry workers

Endotoxin concentration: 249 full-shift personal airborne endotoxin, by pumps.


- Positive associations between endotoxin exposure (increase of one IQR) and the risk of wheezing and BHR

- Negative associations between endoxin exposure (increase of one IQR) and the risk of allergic sensitization, especially to grass pollen

COPD= chronic obstructive pulmonary diseases, BHR= bronchial hyperresponsivness, AHR= airway hyperresponsivness, FEV1=Forced expiratory volume in one second, FVC=Force vital capacity, MMEF= maximum midexpiratory flow, EU= endotoxin unit, IQR= interquartile range

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