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Indoor mould exposure, asthma and rhinitis: findings from systematic reviews and recent longitudinal studies

Denis Caillaud, Benedicte Leynaert, Marion Keirsbulck, Rachel Nadif on behalf of the mould ANSES working group
European Respiratory Review 2018 27: 170137; DOI: 10.1183/16000617.0137-2017
Denis Caillaud
1Pulmonary and Allergology Dept, CHU Clermont-Ferrand, Clermont Auvergne University, Clermont-Ferrand, France
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Benedicte Leynaert
2INSERM, UMR1152, Pathophysiology and Epidemiology of Respiratory Diseases. Epidemiology, Paris, France
3Univ Paris Diderot Paris 7, UMR 1152, Paris, France
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Marion Keirsbulck
4ANSES (French Agency for Food, Environmental and Occupational Health and Safety), Maisons-Alfort, France
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Rachel Nadif
5INSERM, U1168, VIMA: Ageing and Chronic Diseases, Epidemiological and Public Health Approaches, Villejuif, France
6Univ Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France
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    FIGURE 1

    Adjusted odds ratios (aOR) and 95% confidence intervals for asthma development and wheeze from the meta-analyses. CA: current asthma; E-DA: ever-diagnosed asthma; W: wheeze; A: asthma; MO: mould odour; VM: visible mould; D: dampness.

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  • TABLE 1

    Exposure to moulds using qualitative metrics and asthma occurrence in children (longitudinal studies)

    First author, location [ref.]Study designMould exposureMain outcomesResults
    Pekkanen, Finland [98]Cases n=121
    Controls n=242
    Home inspection
    Visible dampness and mould
    Children aged 1–7 years
    Doctor-diagnosed incident asthma
    Main living quarters
    Dampness: yes versus no
    OR 2.24 (1.25–4.01)
    Moulds: yes versus no
    OR 2.59 (1.15–5.85)
    Karvonen, Finland [99]Cohort
    n=396
    Home inspection
    Visible mould
    and humidity
    First 6 months of life
    Mother's questionnaire at 2, 12 and 18 monthsVisible mould: yes versus no
    Doctor-diagnosed wheezing
    Main living quarters
    aOR 3.92 (1.54–10)
    Child bedroom
    aOR 5.22 (1.48–18.35)
    Schroer, USA [100]Cohort (CCAPS)
    n=570
    Home inspection
    Visible mould
    Mould odour
    First year of life
    Parents’ ISAAC questionnaire
    Wheezing at 2 years
    Persistent wheezing at 1 and 2 years
    Visible mould: yes versus no
    Wheezing at 2 years
    aOR 2.12 (1.25–3.60)
    Persistent wheezing
    aOR 2.47 (1.27–4.80)
    Dales, Canada [101]Cohort
    n=330
    Home inspection
    Visible mould
    First year of life
    Acute and upper respiratory events
    Birth to 2 years
    Visible mould: yes versus no
    ns
    Larsson, Sweden [102]Cohort
    n=4779 children
    Self-reported visible dampness and mould
    Reported mould odour
    At birth
    Incident asthma
    at 6–8 years
    Parents’ questionnaire
    Mould odour:
    OR 2.99 (1.50–5.94)
    Hwang, Taiwan [103]1–7 years
    Cases n=188
    Controls n=376
    Self-reported mould or mould odour between birth and 1 yearReported doctor- diagnosed incident asthma 6 years laterVisible mould: yes versus no
    aOR 1.76 (1.18–2.62)
    Mould odour: yes versus no
    aOR 2.09 (1.30–3.37)
    Moulds + parent atopy
    aOR 5.10 (2.80–9.31)
    Odour + parent atopy
    aOR 4.11 (2.22–7.64)
    Hwang, Taiwan [21]1–7 years
    Cases n=188
    Controls n=376
    Self-reported mould or mould odour between birth and 1 yearReported doctor- diagnosed incident asthma 6 years later + polymorphisms of interleukin-4 promoterVisible mould: yes versus no
    CT versus TT polymorphism:
    OR 2.14 (1.05–4.34)
    Zhou, France [23]Cohort
    n=1765
    Self-reported humidity or moulds
    First year of life
    ISAAC questionnaire
    0–4, 4–8 and 8–12 months
    Humidity and diagnosed asthma + wheeze
    aOR 2.21 (1.04–4.71)
    Wheeze aOR 2.12 (1.30–3.46)
    Diagnosed life-time asthma
    aOR 2.19 (1.06–4.53)
    Wen, Taiwan [24]Cohort
    n=19 192
    Visible mould during pregnancy
    Health questionnaire at 0.5, 1.5, 3 and 5 years
    Ever doctor-diagnosed asthma in 5-year-old childrenVisible mould: yes versus no
    aOR 1.21 (1.01–1.46) Only in females
    Shorter, New Zealand [22]Nested incident cases n=150
    Controls n=300
    Bedroom wall (electrostatic dust cloth) for 4 weeks
    Visible mould and odour
    Children aged 1–7 years
    Incident wheezing
    Visible mould and mould odour in a dose-dependent manner
    Karvonen, Finland [25]Cohort
    n=398
    Home inspection
    Visible mould and humidity
    First 6 months of life
    Ever physician-diagnosed asthma
    ≤6 years
    Visible mould: yes versus no
    Living room
    aOR 7.51 (1.49–37.83)
    Child's bedroom
    aOR 4.82 (1.29–18.02)
    Allergic asthma
    aOR 9.08 (1.95–42.23)
    Thacher, Sweden [26]BAMSE cohort
    n=3798
    Any self-reported mould or dampness indicator (dampness damage, visible mould or mould odour) in infancy (2 months)Asthma ≤16 yearsAny indicator
    Asthma
    OR 1.31 (1.08–1.59)
    Nonallergic asthma
    aOR 1.80 (1.27–2.55)

    aOR: adjusted odds ratio; CCAPS: Cincinnati Childhood Allergy and Air Pollution Study; ISAAC: International Study of Asthma and Allergies in Childhood; ns: nonsignificant; BAMSE: Barn/Child Allergy Milieu Stockholm Epidemiology.

    • TABLE 2

      Exposure to moulds and exacerbation of asthma in children (panel studies)

      First author, location [ref.]Study designMould exposureMain outcomesResults
      Hagmolen of Ten Have, the Netherlands [104]526 children with asthma (mean age 11 years)
      Follow-up: 2 weeks (2 visits)
      At baseline: positive response to a question on visible mould in the past 2 yearsDaily variability of peak flow
      Daily symptoms: wheezing, cough, BHR at follow-up
      No association between mould exposure and symptoms
      In exposed children: increased peak flow variability: +2.70% (95% CI 0.92–4.47, p=0.003), and higher BHR: aOR: 3.95 (1.82–8.57)
      Inal, Turkey [105]19 children with asthma or rhinitis, and monosensitised to mould (aged 4–13 years)
      Follow-up: 1 year
      Every month: indoor air:
      MAS-100 Eco 100 L·min−1
      Culture CFU·m−3: Cladosporium, Penicillium, Aspergillus, Alternaria and others (undefined or >1%)
      Daily variability of peak flow: morning and evening
      Daily symptoms (rhinitis and asthma scores)
      No association between mean exposure to mould (37.5 CFU·m−3) and daily variability of peak flow or symptoms
      Bundy, Western Massachusetts and Connecticut, USA [106]225 children with asthma (6–12 years old)
      Follow-up: 2 weeks
      At baseline: indoor air:
      Burkard 1 min 20 L·min−1
      Culture and classification:
      0 CFU·m−3, 1–499 CFU·m−3, 500–999 CFU·m−3, >1000 CFU·m−3, Cladosporium, Alternaria, Penicillium or Aspergillus
      Daily variability of peak flow: three series of measurements morning and evening performed by children
      Daily symptoms (wheezing, cough and nocturnal symptoms), drugs reported by the mother
      No association between mould exposure and symptoms
      Associations between Penicillium (0 versus detectable) and peak flow variability of >18.5% (75th percentile) aOR 2.39 (95% CI 1.19–4.81)
      Pongracic, the Inner-City Asthma Study: USA
      [107]
      469 children with mild to severe asthma and at least one positive SPT to mould (aged 5–11 years)
      Follow-up: 2 years
      At baseline and every 6 months: indoor air
      2 measurements Burkard 1 min 30.5 L·min−1, 1 m from floor, children's room
      Outdoor air
      Culture CFU·m−3: Cladosporium, Alternaria, Penicillium and Aspergillus
      Dust measurements on floor and bed
      Call report every 2 months:
      max number of days (in 2 weeks) with symptoms (wheezing, cough, chest tightness, awakening due to asthma or play activities stopped because of asthma)
      Number of unplanned visits to hospital or EV in the past 2 months
      Association between 10-fold increase in Penicillium level and increased number of days with symptoms: 1.19 days per 2 weeks, p<0.03
      Association between indoor mould and exacerbations and EV:
      aOR 1.22 (95% CI 1.05–1.43) and 1.13 (1.01–1.26)
      Association between Penicillium and EV:
      OR 1.15 (1.05–1.27) (all children), and 1.11 (1.03–1.20) in those SPT− for Penicillium
      Wu, USA [32]395 children with mild-to-moderate persistent asthma
      CAMP study
      (aged 5–12 years)
      Follow-up: 6 months and 3 years or before in case of moving
      At baseline and at the first follow-up (6 months):
      dust measurements on floor (main living room, bedrooms and kitchen) and on child's bed
      Vacuum cleaner equipped with a filter (Douglas ReadiVac model): 2 min for each zone of different surfaces
      Culture and classification: high mould dust exposure: >25 000 CFU·g−1 of house dust
      Severe asthma exacerbations
      Hospitalisations or urgent care visits during the 4 years of follow-up (report every 4 months)
      Polymorphisms (SNPs) in chitinase genes
      24% (n=95) had high mould dust exposure
      Number of urgent care visits increased with high mould dust exposure in children with genetic polymorphisms (rs2486953, rs4950936 and rs1417149) in the CHIT1 gene
      Gent, Western Massachusetts and Connecticut, USA [108]1233 school-aged children with asthma (aged 5–10 years)
      Follow-up: 1 month
      At baseline: indoor air:
      Burkard 1 min 20 L·min−1, culture: CFU·m−3
      Dust measurements on floor and furniture in the main living room
      Blood allergens: mould, mites, cat, dog (µg·g−1) and cockroaches (U·g−1)
      Daily symptoms (wheezing, cough), drugs and severity (five levels)
      Allergic sensitisation: allergens and IgE
      In sensitised children: associations between Penicillium and risk of wheezing: aOR 2.12 (95% CI 1.12–4.04), cough: 2.01 (1.05–3.85) and asthma severity score: 1.99 (1.06–3.72)
      Vicendese, Melbourne, Australia [33]Nested incident case–control study within the MAPCAH study: 44 children (aged 2–17 years)
      Follow-up: September 2009 to December 2011
      Air fungi in the child's bedroom: two-stage Andersen Sampler for 1 min, flow rate: 28 L·min−1
      Total fungi, Cladosporium, Penicillium/Aspergillus and Alternaria, CFU per 28 L of air
      Standardised questionnaires from the ISAAC and NZ Otago studies
      Incident asthma readmissions
      Association between every doubling concentration of CFU of airborne Cladosporium (per 28 L of air) in the bedroom and asthma readmission:
      aOR 1.68 (95% CI 1.04–2.72)
      Dannemiller, Western Massachusetts and Connecticut, USA [34]n=196, subgroup of the 1233 school-aged children with asthma (aged 5–10 years)
      Follow-up: 1 month
      At baseline: indoor air: Burkard 1 min 20 L·min−1, culture: CFU·m−3
      Dust measurements on floor and furniture in the main living room
      Total fungi concentration dichotomised at the median (high and low exposure)
      Daily symptoms (wheezing, cough), and medication use
      Asthma severity (five levels) expressed as mild (reference, 0 or 1) or severe (3 or 4), level 2 not included in the analyses
      Total and specific IgE
      Association between high fungal concentration and asthma severity in all children:
      aOR 2.02 (95% CI 1.14–3.56) and in nonatopic children:
      aOR 2.40 (95% CI 1.06–5.44), but not in atopic children:
      1.69 (0.77–3.75)
      Casas, HITEA project: Spain, the Netherlands, Finland
      [35]
      419 children (aged 6–12 years) from 25 schools: 106 children from 8 schools in Spain, 150 children from 11 schools in the Netherlands, 163 children from 6 schools in Finland
      Follow-up: 1 year
      School with or without (reference) moisture damage: number, extent, severity and location of dampness, and moisture damage observations recorded during inspectionsThree symptom diaries: a 2-week diary starting before the summer school holiday (May–July 2009), a 3-week diary starting at the end of the summer holiday (August–October 2009) and a 2-week diary during winter and spring (January–May 2010)
      16 symptoms in the past 24 h: wheeze, shortness of breath, dry cough during day or at night, phlegm, woken up… and severity (no symptom, slight, moderate or severe)
      Holiday and weekends were associated with lower scores
      Results were heterogeneous across the three countries
      In Spain, all adjusted IRRs <1 for summer holiday (ref. school day) in schools with moisture damage: lower respiratory symptoms IRR 0.61 (95% CI 0.46–0.81), upper respiratory or allergy symptoms 0.78 (95% CI 0.63–0.93), other symptoms 0.64 (95% CI 0.49–0.83)
      Similar results in Finland for summer holiday and weekend
      All random-effect combined IRRs <1

      HITEA: Health Effects of Indoor Pollutants: Integrating Microbial, Toxicological and Epidemiological Approaches; BHR: bronchial hyperresponsiveness; aOR: adjusted odds ratio; EV: emergency visit; SPT: skin prick test; SNP: single nucleotide polymorphism; Ig: immunoglobulin; MAPCAH: Melbourne Air Pollen Children and Adolescent Health; ISAAC: International Study of Asthma and Allergies in Childhood; IRR: incidence rate ratio.

      • TABLE 3

        Longitudinal studies on occupational asthma related to working in mouldy buildings

        First author, location [ref.]Study designMould exposureMain outcomesResults
        Park, USA [46]Nested study
        Cases n=49
        Controls n=152
        Employees working in a water-damaged building
        Floor and chair dust
        TCF
        HF
        Endotoxins
        Pet allergens
        POAPOA (for increasing IQR)
        and chair dust
        Single environmental variable
         aOR (95% CI)
        TCF 1.67 (1.07–2.60)
        HF 1.85 (1.19–2.89)
        Multiple environmental variables:
        HF 1.79 (1.12–2.85)
        Karvala, FIOH: Finland
        [42]
        Patients assessed between 1995 and 2004 for suspicion of mould-induced OA
        n=258
        Retrospective work exposure:
        building damage report and microbial analyses
        SIC with mould extracts, especially A. fumigatus, C. cladosporioides and A. kiliense
        Three OA groups: probable, possible, unlikely
        Mould duration exposure usually >5 years
        Sensitisation to moulds:
        probable: 20.4%
        possible: 10.7%
        unlikely: 4.4%
        Among 133 probable OA (SIC+):
        A. fumigatus: 85
        C. cladosporioides: 26
        A. kiliense: 19
        Karvala, FIOH: Finland [43]Longitudinal study over 3–12 years
        n=483
        Exposure:
        building damage report and microbial analyses
        Doctor-diagnosed incident asthma among patients
        with ALS related to damp workplaces, but without asthma at baseline
        Doctor-diagnosed incident asthma
        No more exposition (ref.)
        Same remediated
        OR 2 (95% CI 0.7–5.4)
        Persistent exposure:
        OR 4.6 (95% CI 1.8–11.6)
        Park, USA [47]Employees working in a damp building. Baseline
        n=131 BR-RS without asthma
        n=361 without BR-RS and asthma at baseline
        Floor dust:
        TCF
        Ergosterol
        Endotoxins
        BR-AS developmentBR-AS development: aOR (95% CI)
        BR-RS 1.00 (ref.)
        BR-RS+ 2.24 (1.34–3.72)
        Baseline TCF
        1st tertile 1 (ref.)
        2nd tertile 3.59 (1.46–8.83)
        3rd tertile: 4.92 (1.90–12.72)
        Karvala, FIOH: Finland [44]Longitudinal study over 3–12 years
        n=1267
        Exposure: building damage report and microbial analysesQuality of life
        SF12 physical and mental component scores
        Four baseline groups
        n=127 OA
        n=453 WEA
        n=483 ALS
        n=204 URS
        SF12, physical component score
        Mean±sd
        URS 69.7±28.9
        ALS 62.9±29.7
        WEA 54.7±30.6
        OA 45.4±29.1
        p <0.001
        Karvala, FIOH: Finland
        [45]
        Longitudinal study over 7–8 years
        n=1098
        Exposure: building damage report and microbial analysesSelf-rated work ability
        0: low <scale<10: best
        Early withdrawal from work owing to disability Four baseline groups
        n=127 OA
        n=453 WEA
        n=483 ALS
        n=204 URS
        Low self-rated work ability (scale <8)
        %, aOR (95% CI)
        URS 34%, 1.0
        ALS 40%, 1.2 (0.8–1.7)
        WEA 50%, 1.8 (1.2–2.8)
        OA 57%, 2.6 (1.4–4.7)
        Early withdrawal from work
        %, aOR (95% CI)
        URS 7%, 1.0
        ALS 13%, 1.6 (0.8–3.1)
        WEA 13%, 1.6 (0.8–3.1)
        OA 33%, 5.7 (2.8–11.9)

        FIOH: Finnish Institute of Occupational Health; TCF: total culturable fungi; HF: hydrophilic fungi; POA: post-occupancy asthma; IQR: interquartile range; aOR: adjusted odds ratio; OA: occupational asthma; SIC: specific inhalation challenge; A. fumigatus: Aspergillus fumigatus; C. cladosporioides: Cladosporium cladosporioides; A. kiliense: Acremonium kiliense; ALS: asthma-like symptoms; BR: building-related; RS: rhinosinusitis; AS: asthma symptoms, WEA: work-exacerbated asthma; URS: upper respiratory symptoms; SF12: 12-item short form survey.

        • TABLE 4

          Mould exposure and rhinitis: findings from meta-analyses, longitudinal studies and birth cohorts

          First author [ref.]Study designMould exposureMain outcomes#Results
          Fisk [15]Meta-analysis
          13 cross-sectional + longitudinal studies
          Children and adults
          Dampness and/or mouldUpper respiratory tract symptomsOR 1.70 (95% CI 1.44–2.00)
          Antova [5]Pooled analysis of seven cross-sectional studies as part of the PATY study
          Children aged 6–12 years
          Visible mouldHay feverOR 1.35 (95% CI 1.18–1.53)
          p-value from test for between-country heterogeneity p=0.20
          Tischer [7]Meta-analysis
          11 cross-sectional + longitudinal studies
          Children
          Visible mouldAllergic rhinitis or hay feverOR 1.39 (95% CI 1.28–1.51)
          Tischer [8]Pooled analysis of six birth cohorts as part of the ENRIECO initiativeEarly exposure to mouldAllergic rhinitisIn early school age (6–8 years)
          aOR 1.12 (95% CI 1.02–1.23)
          In childhood (3–10 years)
          aOR 1.18 (95% CI 1.09–1.28)
          No significant heterogeneity between the cohorts
          Jaakkola [48]Cross-sectional, case–control and cohort studies in children or adults
          (31 studies overall)
          Water damage, dampness, visible mould and mould odourAllergic rhinitisEE (95% CI)
          Dampness:
          (6 studies) mild heterogeneity
          1.50 (1.38–1.62)
          All EEs >1; 6/6 EEs significant
          Visible mould:
          (12 studies) no heterogeneity
          1.51 (1.39–1.64)
          All EEs >1; 6/12 EEs significant
          Mould odour:
          (3 studies) strong heterogeneity
          1.87 (0.95–3.68)
          All EEs >1; 2/3 EEs significant
          Biagini, USA [109]Birth cohort (CCAPS) with at least one parent with positive SPT
          n=495 infants with SPT at the age of 1 year
          Visible mould during home visitURTI (sinus or ear infection and antibiotic use) reported in diary
          Allergic rhinitis = rhinitis symptoms + at least one positive SPT
          Visible mould:
          aOR (95% CI) for URTI (versus ref.= no visible mould)
          Low 1.5 (1.01–2.3)
          High 5.1 (2.2–12.0)
          aOR (95% CI) for allergic rhinitis
          Low 1.2 (0.6–2.5)
          High 3.2 (0.7–14.8)
          Osborne, USA [110]Birth cohort (CCAPS) with at least one parent with positive SPT
          n=144 children aged 1–3 years
          Long-term air sampling and total fungal spore enumeration in the 8 months around clinical examinationSPT to two food allergens and 15 aeroallergens
          Questionnaire for parents on rhinitis (sneezing, runny or stuffy nose, when you did not have a cold?)
          Positive associations between rhinitis and: total concentration (p=0.10), Ganoderma (p=0.06), basidiospores (p=0.01)
          Negative associations between rhinitis and: Alternaria (p=0.10)
          Positive associations between positive SPT and Alternaria (p=0.01), Penicillium/Aspergillus type (p=0.01)
          Negative associations between positive SPT and Ganoderma (p=0.10), basidiospores (p=0.09) and Cladosporium (p=0.04)
          Inal, Turkey [105]19 children aged 4–13 years with asthma or rhinitis, and monosensitised to mould
          Follow-up 1 year
          Monthly sampling of indoor airDaily symptom score of rhinitis in diaryNo association between exposure to mould (total or Cladosporium, Alternaria, Penicillium or Aspergillus concentration CFU·m−3) and daily symptom score
          Jaakkola, Finland [111]Population-based prospective cohort
          n=1863 children aged 1–7 years, free of allergic rhinitis at baseline in 1991
          (n=246 incident cases)
          Visible mould, wet spots, water damage and indicator of “any” exposureDevelopment of allergic rhinitis (incident cases) (history of or current physician-diagnosed allergic rhinitis during the 6-year follow-up period)OR for allergic rhinitis incidence (compared to ref=no exposure)
          Visible mould at baseline 1.06 (0.51–2.21);
          at follow-up 1.98 (1.32–2.99)
          Mould odour at baseline 0.94 (0.36–2.45);
          at follow-up 1.45 (0.89–2.37)
          Any exposure at baseline 1.55 (1.10–2.18);
          at follow-up 1.62 (1.21–2.18);
          at baseline and follow-up 1.96 (1.29–2.98)
          Behbod, USA [28]Prospective birth cohort
          408 children with family history of allergic disease or asthma followed-up to age 13 years
          Parental report of home dampness and culturable fungi in bedroom air and dust, and in outdoor air when children were aged 2–3 months Indoor air: Burkard DG18: 1 min 45 L·min−1 Culture: identification of fungal genusSymptoms/disease onset from birth to age 13 years
          For rhinitis: parental report of physician-diagnosed hay fever and nasal symptoms (runny nose)
          Mould sensitisation status tested at ages 7 and 13 years (in n=285)
          HR (95% CI) for rhinitis onset
          Home dampness 1.11 (0.73–1.68)
          Dust (bedroom floor)
          Alternaria 0.79 (0.51–1.22)
          Cladosporium 0.91 (0.77–1.08)
          Aspergillus 1.39 (1.11–1.74)
          Penicillium 1.04 (0.89–1.21)
          Yeasts 1.06 (0.92–1.22)
          Nonsporulating fungi 1.05 (0.88–1.25)
          Measures in indoor air: no significant association observed
          Thacher, Sweden [26]Birth cohort (BAMSE)
          n=3798 children with follow-up data at age 16 years
          Parental report when the child was 2 months, of mould odour ever in the home, visible mould in the home in the past year or moisture damage in the homeRhinitis: eye or nose symptoms following exposure to allergens in the past 12 months and/or a doctor's diagnosis of allergic rhinitis (+/- positive Phadiatop test) at age 16 yearsOR (95% CI) for rhinitis at age 16 years
          Visible mould 1.28 (1.04–1.58)
          Mould odour 1.29 (1.03–1.62)
          Any mould or dampness indicator for nonallergic rhinitis 1.41 (1.03–1.93);
          allergic rhinitis 0.88 (0.74–1.05)

          PATY: Pollution and the Young; ENRIECO: Environmental Health Risks in European Birth Cohorts; aOR: adjusted odds ratio; EE: effect estimate; CCAPS: Cincinnati Childhood Allergy and Air Pollution Study; SPT: skin prick test; URTI: upper respiratory tract infection; BAMSE: Barn/Child Allergy Milieu Stockholm Epidemiology. #: other outcomes are considered in the articles cited.

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          Indoor mould exposure, asthma and rhinitis: findings from systematic reviews and recent longitudinal studies
          Denis Caillaud, Benedicte Leynaert, Marion Keirsbulck, Rachel Nadif
          European Respiratory Review Jun 2018, 27 (148) 170137; DOI: 10.1183/16000617.0137-2017

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          Indoor mould exposure, asthma and rhinitis: findings from systematic reviews and recent longitudinal studies
          Denis Caillaud, Benedicte Leynaert, Marion Keirsbulck, Rachel Nadif
          European Respiratory Review Jun 2018, 27 (148) 170137; DOI: 10.1183/16000617.0137-2017
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