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Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study

Gang Wang, Jenny Hallberg, Dimitrios Charalampopoulos, Maribel Casas Sanahuja, Robab Breyer-Kohansal, Arnulf Langhammer, Raquel Granell, Judith M. Vonk, Annemiek Mian, Núria Olvera, Lisbeth Mølgaard Laustsen, Eva Rönmark, Alicia Abellan, Alvar Agusti, Syed Hasan Arshad, Anna Bergström, H. Marike Boezen, Marie-Kathrin Breyer, Otto Burghuber, Anneli Clea Bolund, Adnan Custovic, Graham Devereux, Gavin C. Donaldson, Liesbeth Duijts, Ana Esplugues, Rosa Faner, Ferran Ballester, Judith Garcia-Aymerich, Ulrike Gehring, Sadia Haider, Sylvia Hartl, Helena Backman, John W. Holloway, Gerard H. Koppelman, Aitana Lertxundi, Turid Lingaas Holmen, Lesley Lowe, Sara M. Mensink-Bout, Clare S. Murray, Graham Roberts, Linnea Hedman, Vivi Schlünssen, Torben Sigsgaard, Angela Simpson, Jordi Sunyer, Maties Torrent, Stephen Turner, Maarten Van den Berge, Roel C.H. Vermeulen, Sigrid Anna Aalberg Vikjord, Jadwiga A. Wedzicha, Anke H. Maitland van der Zee, Erik Melén on behalf of the CADSET Clinical Research Collaboration
ERJ Open Research 2021 7: 00457-2021; DOI: 10.1183/23120541.00457-2021
Gang Wang
1Dept of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Sichuan, China
2Dept of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
48Shared first authors
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Jenny Hallberg
2Dept of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
3Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden
48Shared first authors
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Dimitrios Charalampopoulos
4MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Maribel Casas Sanahuja
5ISGlobal, Barcelona, Spain
6Universitat Pompeu Fabra, Barcelona, Spain
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
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Robab Breyer-Kohansal
8Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
9Dept of Respiratory and Critical Care Medicine, Clinic Penzing, Vienna, Austria
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Arnulf Langhammer
10Dept of Public Health and Nursing, Faculty of Medicine and Health Sciences, HUNT Research Centre, Norwegian University of Science and Technology (NTNU), Levanger, Norway
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  • ORCID record for Arnulf Langhammer
Raquel Granell
4MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Judith M. Vonk
11Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
12University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, The Netherlands
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Annemiek Mian
13The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
14Division of Respiratory Medicine and Allergology, and Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Núria Olvera
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
15Institut d'investigacions biomediques August Pi I Sunyer, Barcelona, Spain
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Lisbeth Mølgaard Laustsen
16Dept of Public Health, Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
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Eva Rönmark
17Dept of Public Health and Clinical Medicine, Section for Sustainable Health, The OLIN Unit, Umeå University, Umeå, Sweden
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Alicia Abellan
5ISGlobal, Barcelona, Spain
6Universitat Pompeu Fabra, Barcelona, Spain
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
18Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain
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Alvar Agusti
15Institut d'investigacions biomediques August Pi I Sunyer, Barcelona, Spain
19Respiratory Institute, Hospital Clinic, Univ. Barcelona, Barcelona, Spain
20CIBERESP (ISCiii), Barcelona, Spain
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Syed Hasan Arshad
21David Hide Asthma and Allergy Research Centre, Newport, UK
22NIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK
23Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Anna Bergström
24Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
25Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden
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H. Marike Boezen
26Dept of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
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Marie-Kathrin Breyer
8Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
9Dept of Respiratory and Critical Care Medicine, Clinic Penzing, Vienna, Austria
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Otto Burghuber
8Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
27Faculty of Medicine, Sigmund Freud University, Vienna, Austria
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Anneli Clea Bolund
16Dept of Public Health, Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
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Adnan Custovic
28National Heart and Lung Institute, Imperial College London, London, UK
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Graham Devereux
29Liverpool School of Tropical Medicine, Liverpool, UK
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Gavin C. Donaldson
28National Heart and Lung Institute, Imperial College London, London, UK
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Liesbeth Duijts
13The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
14Division of Respiratory Medicine and Allergology, and Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
30Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Ana Esplugues
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
31Nursing Department, Faculty of Nursing and Chiropody, Universitat de València, Valencia, Spain
32Epidemiology and Environmental Health Joint Research Unit, FISABIO−Universitat Jaume I−Universitat de València, Valencia, Spain
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Rosa Faner
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
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Ferran Ballester
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
31Nursing Department, Faculty of Nursing and Chiropody, Universitat de València, Valencia, Spain
32Epidemiology and Environmental Health Joint Research Unit, FISABIO−Universitat Jaume I−Universitat de València, Valencia, Spain
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Judith Garcia-Aymerich
5ISGlobal, Barcelona, Spain
6Universitat Pompeu Fabra, Barcelona, Spain
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
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Ulrike Gehring
33Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
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Sadia Haider
28National Heart and Lung Institute, Imperial College London, London, UK
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Sylvia Hartl
8Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
9Dept of Respiratory and Critical Care Medicine, Clinic Penzing, Vienna, Austria
27Faculty of Medicine, Sigmund Freud University, Vienna, Austria
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Helena Backman
17Dept of Public Health and Clinical Medicine, Section for Sustainable Health, The OLIN Unit, Umeå University, Umeå, Sweden
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John W. Holloway
22NIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK
34Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
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Gerard H. Koppelman
12University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, The Netherlands
35Dept of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands
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Aitana Lertxundi
7Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
36Dept of Preventive Medicine and Public Health, Faculty of Medicine, University of the Basque Country (UPV/EHU), Leioa, Spain
37BIODONOSTIA Health Research Institute, Donostia-San Sebastian, Spain
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Turid Lingaas Holmen
38Dept of Public Health and General Practice, HUNT Research Center, NTNU, Levanger, Norway
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Lesley Lowe
39Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester Academic Health Science Centre, NIHR, Manchester, UK
40Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK
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Sara M. Mensink-Bout
13The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Clare S. Murray
39Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester Academic Health Science Centre, NIHR, Manchester, UK
40Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK
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Graham Roberts
21David Hide Asthma and Allergy Research Centre, Newport, UK
22NIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK
34Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
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Linnea Hedman
17Dept of Public Health and Clinical Medicine, Section for Sustainable Health, The OLIN Unit, Umeå University, Umeå, Sweden
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Vivi Schlünssen
16Dept of Public Health, Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
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Torben Sigsgaard
16Dept of Public Health, Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
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Angela Simpson
39Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester Academic Health Science Centre, NIHR, Manchester, UK
40Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK
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Jordi Sunyer
5ISGlobal, Barcelona, Spain
6Universitat Pompeu Fabra, Barcelona, Spain
41IMIM-Parc Salut Mar, Barcelona, Spain
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Maties Torrent
42ib-salut, Area de Salut de Menorca, Menorca, Spain
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Stephen Turner
43Royal Aberdeen Children's Hospital NHS Grampian, Aberdeen, UK
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Maarten Van den Berge
12University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, The Netherlands
44Dept of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Roel C.H. Vermeulen
33Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
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Sigrid Anna Aalberg Vikjord
10Dept of Public Health and Nursing, Faculty of Medicine and Health Sciences, HUNT Research Centre, Norwegian University of Science and Technology (NTNU), Levanger, Norway
45Dept of Medicine and Rehabilitation, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
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Jadwiga A. Wedzicha
28National Heart and Lung Institute, Imperial College London, London, UK
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Anke H. Maitland van der Zee
46Dept of Respiratory Medicine, Amsterdam University Medical Centers (UMC), University of Amsterdam
47Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands
49Shared last authors
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Erik Melén
2Dept of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
3Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden
49Shared last authors
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  • For correspondence: Erik.Melen@ki.se
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Figures

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  • FIGURE 1
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    FIGURE 1

    Prevalence of the a) obstructive and b) restrictive phenotypes from early childhood to young adulthood. The numbers above each bar represent the number of cases in the respective study. Cohorts linked by lines had the same mean age (in years).

  • FIGURE 2
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    FIGURE 2

    Prevalence of any wheezing in participants with obstructive or restrictive phenotypes, or normal lung function. The numbers above each bar represent the number of cases in the respective study. Cohorts linked by lines had the same mean age (in years).

  • FIGURE 3
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    FIGURE 3

    Meta-analysis results of association between asthma and obstructive phenotype in 5–25 years subgroup. TE: the estimated treatment effect; IV: inverse variance.

  • FIGURE 4
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    FIGURE 4

    Meta-analysis results of association between body mass index and restrictive phenotype in Model 2 in 5–25 years age group. TE: the estimated treatment effect; IV: inverse variance.

Tables

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  • TABLE 1

    Characteristics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio z-scores of each cohort included in the age groups

    CohortsNationsAge groupsnAge#FEV1FVCFEV1/FVC ratio
    GLI fit#Mean-centred¶GLI fit#Mean-centred¶GLI fit#Mean-centred¶
    ALSPAC+UK>5–1068048.7±0.30.04±1.00−0.09±1.02−0.06±1.02−0.02±1.040.15±1.02−0.10±1.07
    >15–20451915.5±0.3−0.68±1.29−0.04±1.26−1.02±1.290.04±1.250.61±1.16−0.14±1.21
    >20–25373124.5±0.8−0.52±1.010.06±1.00−0.37±1.020.13±0.98−0.27±0.94−0.1±0.98
    BAMSE+Sweden>5–1018328.3±0.50.47±0.94−0.06±0.940.59±0.90−0.00±0.91−0.27±0.87−0.07±0.89
    >15–20205216.7±0.40.06±0.92−0.11±0.940.16±0.92−0.01±0.92−0.19±0.93−0.15±0.96
    >20–25203222.5±0.5−0.23±0.85−0.03±0.86−0.12±0.850.07±0.85−0.20±0.88−0.15±0.90
    Generation R+Netherlands>5–1047389.8±0.30.19±0.93−0.04±0.930.21±0.890.02±0.92−0.08±0.90−0.01±0.96
    >10–15386913.6±0.4−0.15±1.01−0.06±0.93−0.09±0.980.04±0.99−0.13±0.920.00±1.02
    HUNT1Norway>10–15270514.1±0.6−0.23±1.11−0.02±1.11−0.19±1.100.01±1.10−0.07±1.03−0.05±1.03
    >15–20525617.1±1.3−0.12±1.04−0.03±1.04−0.09±1.010.02±1.01−0.08±0.98−0.08±0.98
    HUNT3Norway>10–15279214.1±0.60.01±1.03−0.01±1.030.10±1.050.04±1.05−0.15±1.02−0.22±1.02
    >15–20436316.9±1.20.09±0.99−0.04±0.990.19±1.010.03±1.01−0.19±0.98−0.09±0.97
    INMA+Spain1–57044.5±0.2−0.59±1.20−0.01±1.21−0.53±1.230.01±1.25−0.03±0.95−0.03±0.97
    >5–1012777.4±0.60.21±0.98−0.01±0.990.40±0.950.01±0.96−0.34±0.99−0.03±1.00
    >5–104769.3±0.9−0.02±1.07−0.03±1.050.17±1.04−0.00±1.01−0.21±0.98−0.06±0.95
    >10–1598811.2±0.6−0.20±1.00−0.01±1.03−0.06±1.030.02±1.04−0.25±0.95−0.04±1.01
    >10–1526614.6±0.20.04±0.94−0.04±0.95−0.04±0.98−0.02±0.950.13±0.87−0.03±0.90
    >15–2012017.7±0.3−0.34±0.92−0.03±0.89−0.32±0.980.07±0.94−0.04±0.99−0.15±1.02
    IoWUK>5–109809.9±0.30.37±0.97−0.04±0.990.16±0.880.02±0.880.33±0.96−0.09±1.01
    >15–2083617.8±0.60.30±0.92−0.15±0.990.14±0.850.01±0.930.22±1.07−0.21±1.11
    LEADAustria>5–104518.4±1.00.46±1.27−0.07±0.990.31±1.260.10±0.920.35±1.17−0.31±1.13
    >10–1552612.3±1.50.01±1.03−0.35±1.02−0.19±0.97−0.14±0.980.36±0.95−0.39±1.04
    >15–2054017.4±1.4−0.05±1.07−0.36±1.01−0.22±1.08−0.11±0.970.30±1.08−0.44±1.12
    >20–2570322.5±1.4−0.13±1.04−0.42±0.92−0.31±1.09−0.16±0.920.22±0.99−0.46±1.02
    LifelinesNetherlands>15–20255618.9±0.8−0.42±0.91−0.06±0.92−0.34±0.900.03±0.89−0.19±0.98−0.14±1.01
    >20–25502823.3±1.5−0.42±0.90−0.06±0.91−0.29±0.890.05±0.87−0.23±0.96−0.16±0.96
    MAAS+UK>5–107788.0±0.20.15±0.93−0.07±0.100.26±0.900.00±0.94−0.24±0.89−0.11±0.93
    >10–1577811.5±0.5−0.12±0.95−0.05±1.00−0.18±1.120.05±1.120.14±1.03−0.15±1.10
    >15–2056616.0±0.6−0.26±0.95−0.06±1.05−0.43±0.900.03±0.960.31±1.02−0.16±1.11
    >15–2050419.4±0.8−0.24±0.87−0.04±0.95−0.40±0.900.10±0.900.26±0.97−0.24±1.04
    OLINSweden>15–20147018.2±0.5−0.06±1.01−0.04±1.010.08±1.060.01±1.03−0.28±0.93−0.07±0.96
    PIAMA+Netherlands>5–1010588.1±0.30.54±0.88−0.05±0.910.29±0.880.00±0.900.42±1.06−0.09±1.09
    >10–15126712.7±0.4−0.56±0.84−0.04±0.86−0.37±0.85−0.01±0.86−0.37±0.87−0.04±0.89
    >15–2072016.4±0.2−0.19±0.86−0.07±0.880.02±0.86−0.00±0.82−0.40±0.92−0.10±0.94
    SEATON+UK1–54464.9±0.20.17±0.96−0.03±0.95−0.13±1.05−0.00±1.050.08±0.93−0.04±0.95
    >10–1543010.3±0.2−0.12±1.10−0.06±1.09−0.24±1.04−0.01±1.040.15±0.93−0.08±0.96
    >15–2053415.1±0.3−0.36±1.00−0.04±1.00−0.77±1.020.01±1.000.83±1.09−0.10±1.13
    SUSDenmark>15–20229418.9±1.3−0.29±0.90−0.01±0.90−0.33±0.880.05±0.880.01±1.00−0.09±1.00

    Data are expressed as mean±sd. GLI: Global Lung Function Initiative. #: based on the whole group of participants; ¶: based on non-asthmatic, asymptomatic lifelong nonsmokers; +: they are longitudinal cohorts with repeated measurement at different age.

    • TABLE 2

      Meta-analysis results of obstructive and restrictive phenotypes in Model 1# in different age groups

      VariablesAge groupsNumber of cohortsI2p-value for Q statisticOR (95% CI)
      Obstructive phenotype
       Preterm birth<10960.80.00891.82 (1.08–3.06)
      2.73 (1.67–4.46)
      1.61 (1.13–2.29)
      1.37 (0.88–2.12)
      1.84 (1.27–2.66)
      >10–15517.60.30
      >15–2086.70.38
      >20–2540.00.63
      5–251051.60.016
       Maternal smoking during  pregnancy<1090.00.611.11 (0.94–1.30)
      1.20 (0.90–1.59)
      1.43 (1.14–1.78)
      1.43 (1.07–1.93)
      1.16 (1.01–1.35)
      >10–1560.00.98
      >15–20109.10.36
      >20–2530.00.41
      5–25110.00.53
       Asthma family history<10926.90.201.34 (1.14–1.58)
      1.39 (1.01–1.93)
      1.46 (1.24–1.72)
      1.59 (1.22–2.07)
      1.44 (1.25–1.66)
      >10–1560.00.55
      >15–20110.00.52
      >20–25329.60.24
      5–25120.00.83
       BMI<10940.60.0971.06 (1.02–1.10)
      >10–15855.30.0221.04 (1.00–1.09)
      1.05 (1.04–1.07)
      1.03 (1.01–1.05)
      1.05 (1.03–1.06)
      >15–201217.70.27
      >20–2540.00.47
      5–251344.70.019
       Former smoker>10–1520.00.610.67 (0.45–1.01)
      0.83 (0.71–0.98)
      1.37 (1.04–1.82)
      0.93 (0.75–1.16)
      >15–201028.90.18
      >20–2540.00.63
      10–251141.30.048
       Current smoker>10–15251.00.150.88 (0.38–2.05)
      1.21 (1.01–1.44)
      1.34 (1.01–1.78)
      1.24 (1.05–1.46)
      >15–201135.50.11
      >20–2540.00.70
      10–251129.80.13
      Restrictive phenotype
       Preterm birth<1080.00.791.17 (0.78–1.75)
      1.46 (0.72–2.97)
      1.16 (0.72–1.87)
      0.88 (0.41–1.92)
      1.20 (0.84–1.70)
      >10–1550.00.92
      >15–2060.00.79
      >20–2530.00.87
      5–2590.00.98
       Maternal smoking during  pregnancy<1090.00.920.91 (0.73–1.14)
      1.16 (0.79–1.70)
      0.98 (0.61–1.58)
      0.84 (0.52–1.36)
      1.00 (0.82–1.22)
      >10–1560.00.95
      >15–20940.90.095
      >20–2540.00.73
      5–25110.00.66
       Asthma family history<1093.80.400.92 (0.74–1.15)
      0.91 (0.58–1.44)
      0.89 (0.71–1.12)
      0.97 (0.66–1.42)
      0.96 (0.79–1.16)
      >10–1560.00.97
      >15–201013.40.32
      >20–2540.00.64
      5–25120.00.84
       BMI<10969.30.0010.88 (0.80–0.96)
      0.80 (0.75–0.85)
      0.80 (0.75–0.85)
      0.84 (0.70–1.00)
      0.81 (0.78–0.85)
      >10–15851.60.035
      >15–201278.8<0.001
      >20–25492.6<0.001
      5–251375.1<0.001
       Former smoker>10–1520.00.350.65 (0.40–1.04)
      0.98 (0.79–1.21)
      0.57 (0.27–1.23)
      0.93 (0.76–1.12)
      >15–20925.30.24
      >20–25456.60.075
      10–251135.90.10
       Current smoker>10–15262.20.100.89 (0.27–2.97)
      0.80 (0.60–1.05)
      0.72 (0.48–1.06)
      0.85 (0.67–1.08)
      >15–201127.30.18
      >20–2540.00.54
      10–251119.60.23

      #: Model 1 was adjusted for asthma family history, maternal smoking during pregnancy, preterm birth, body mass index (BMI) and smoking status.

      • TABLE 3

        Meta-analysis results of obstructive and restrictive phenotypes in Model 2# in different age groups

        VariablesAge groupsNumber of cohortsI2p-value for Q statisticOR (95% CI)
        Obstructive phenotype
         Preterm birth<10853.10.0372.04 (1.24–3.34)
        2.83 (1.73–4.46)
        1.53 (1.06–2.22)
        1.49 (0.94–2.36)
        1.83 (1.31–2.57)
        >10–15621.00.28
        >15–2087.10.38
        >20–2540.00.47
        5–251040.10.06
         Maternal smoking during  pregnancy<1090.00.701.06 (0.89–1.28)
        1.28 (0.95–1.73)
        1.48 (1.20–1.82)
        1.23 (0.86–1.75)
        1.13 (0.97–1.33)
        >10–1560.00.97
        >15–201017.00.29
        >20–2530.00.79
        5–25110.00.58
         Asthma family history<10921.90.251.09 (0.90–1.32)
        1.17 (0.82–1.67)
        1.28 (1.07–1.52)
        1.33 (0.74–2.40)
        1.21 (1.04–1.41)
        >10–1560.00.63
        >15–20110.00.84
        >20–25369.60.037
        5–25120.00.67
         BMI<10953.70.0271.05 (1.00–1.11)
        1.06 (1.04–1.09)
        1.04 (1.03–1.06)
        1.04 (1.01–1.07)
        1.04 (1.03–1.06)
        >10–1580.00.50
        >15–201216.50.28
        >20–2540.00.88
        5–251334.40.071
         Former smoker>10–1520.00.720.67 (0.45–1.01)
        0.83 (0.70–0.97)
        1.55 (1.14–2.11)
        0.96 (0.76–1.22)
        0.89 (0.37–2.15)
        >15–201020.80.25
        >20–2540.00.59
        10–251147.00.023
         Current smoker>10–15254.10.14
        >15–201145.10.0521.18 (0.90–1.54)
        1.28 (0.92–1.79)
        1.18 (0.93–1.49)
        >20–2540.00.67
        10–251137.60.07
        Restrictive phenotype
         Preterm birth<1080.00.701.08 (0.68–1.73)
        1.80 (0.88–3.71)
        1.17 (0.72–1.92)
        0.76 (0.30–1.92)
        1.13 (0.77–1.68)
        >10–1550.00.85
        >15–2060.00.83
        >20–2530.00.95
        5–2590.00.97
         Maternal smoking during  pregnancy<1090.00.710.95 (0.75–1.22
        1.19 (0.78–1.79)
        0.98 (0.59–1.62
        1.01 (0.61–1.69)
        1.06 (0.86–1.32)
        >10–1560.00.98
        >15–20943.80.076
        >20–2540.00.99
        5–25110.00.59
         Asthma family history<1093.80.400.99 (0.77–1.27)
        0.89 (0.54–1.46)
        0.88 (0.69–1.12)
        0.99 (0.63–1.56)
        1.02 (0.83–1.25)
        >10–1550.00.88
        >15–201025.90.21
        >20–2540.00.61
        5–25120.00.84
         BMI<10975.0<0.0010.86 (0.77–0.95)
        0.79 (0.74–0.84)
        0.80 (0.75–0.85)
        0.84 (0.70–1.01)
        0.81 (0.77–0.85)
        >10–15850.80.039
        >15–201275.9<0.001
        >20–25492.2<0.001
        5–251376.9<0.001
         Former smoker>10–1520.00.350.64 (0.40–1.04)
        0.96 (0.77–1.20)
        0.69 (0.43–1.08)
        0.91 (0.75–1.11)
        >15–20940.30.12
        >20–25446.70.13
        10–251135.20.11
         Current smoker>10–15262.80.100.89 (0.26–3.07)
        0.74 (0.49–1.13)
        0.73 (0.47–1.15)
        0.87 (0.68–1.13)
        >15–201141.80.07
        >20–2540.00.56
        10–251119.20.24

        #: Model 2 was adjusted for asthma family history, maternal smoking during pregnancy, preterm birth, body mass index (BMI) and smoking status, as well as for current asthma.

        Supplementary Materials

        • Figures
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        • Supplementary Material

          Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

          Supplementary material 00457-2021.SUPPLEMENT

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        Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study
        Gang Wang, Jenny Hallberg, Dimitrios Charalampopoulos, Maribel Casas Sanahuja, Robab Breyer-Kohansal, Arnulf Langhammer, Raquel Granell, Judith M. Vonk, Annemiek Mian, Núria Olvera, Lisbeth Mølgaard Laustsen, Eva Rönmark, Alicia Abellan, Alvar Agusti, Syed Hasan Arshad, Anna Bergström, H. Marike Boezen, Marie-Kathrin Breyer, Otto Burghuber, Anneli Clea Bolund, Adnan Custovic, Graham Devereux, Gavin C. Donaldson, Liesbeth Duijts, Ana Esplugues, Rosa Faner, Ferran Ballester, Judith Garcia-Aymerich, Ulrike Gehring, Sadia Haider, Sylvia Hartl, Helena Backman, John W. Holloway, Gerard H. Koppelman, Aitana Lertxundi, Turid Lingaas Holmen, Lesley Lowe, Sara M. Mensink-Bout, Clare S. Murray, Graham Roberts, Linnea Hedman, Vivi Schlünssen, Torben Sigsgaard, Angela Simpson, Jordi Sunyer, Maties Torrent, Stephen Turner, Maarten Van den Berge, Roel C.H. Vermeulen, Sigrid Anna Aalberg Vikjord, Jadwiga A. Wedzicha, Anke H. Maitland van der Zee, Erik Melén
        ERJ Open Research Oct 2021, 7 (4) 00457-2021; DOI: 10.1183/23120541.00457-2021

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        Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study
        Gang Wang, Jenny Hallberg, Dimitrios Charalampopoulos, Maribel Casas Sanahuja, Robab Breyer-Kohansal, Arnulf Langhammer, Raquel Granell, Judith M. Vonk, Annemiek Mian, Núria Olvera, Lisbeth Mølgaard Laustsen, Eva Rönmark, Alicia Abellan, Alvar Agusti, Syed Hasan Arshad, Anna Bergström, H. Marike Boezen, Marie-Kathrin Breyer, Otto Burghuber, Anneli Clea Bolund, Adnan Custovic, Graham Devereux, Gavin C. Donaldson, Liesbeth Duijts, Ana Esplugues, Rosa Faner, Ferran Ballester, Judith Garcia-Aymerich, Ulrike Gehring, Sadia Haider, Sylvia Hartl, Helena Backman, John W. Holloway, Gerard H. Koppelman, Aitana Lertxundi, Turid Lingaas Holmen, Lesley Lowe, Sara M. Mensink-Bout, Clare S. Murray, Graham Roberts, Linnea Hedman, Vivi Schlünssen, Torben Sigsgaard, Angela Simpson, Jordi Sunyer, Maties Torrent, Stephen Turner, Maarten Van den Berge, Roel C.H. Vermeulen, Sigrid Anna Aalberg Vikjord, Jadwiga A. Wedzicha, Anke H. Maitland van der Zee, Erik Melén
        ERJ Open Research Oct 2021, 7 (4) 00457-2021; DOI: 10.1183/23120541.00457-2021
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