Abstract
Background The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.
Methods We studied 49 334 participants from 14 population-based cohorts in different age-groups (≤10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as FEV1/FVC z-score <the lower limit of normal (LLN), whereas the restrictive as FEV1/FVC z-score ≥LLN, and FVC z-score <LLN.
Results The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio, aOR=2.55 [95% CI=2.14–3.04]), preterm birth (aOR=1.84 [1.27–2.66]), maternal smoking during pregnancy (aOR=1.16 [1.01–1.35]), and family history of asthma (aOR=1.44 [1.25–1.66]) were associated with a higher prevalence of obstructive, but not restrictive phenotype across ages (5–25 years). A higher current body mass index (BMI) was more often observed in those with the obstructive phenotype but less in those with the restrictive (aOR=1.05 [1.03–1.06] and aOR=0.81 [0.78–0.85], per kg/m2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24 [1.05–1.46]).
Conclusion Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
Footnotes
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Conflict of interest: Gang Wang has nothing to disclose.
Conflict of interest: Jenny Hallberg reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca AB, outside the submitted work.
Conflict of interest: Dimitrios Charalampopoulos has nothing to disclose.
Conflict of interest: Maribel Casas Sanahuja has nothing to disclose.
Conflict of interest: Robab Breyer-Kohansal has nothing to disclose.
Conflict of interest: Arnulf Langhammer has nothing to disclose.
Conflict of interest: Raquel Granell has nothing to disclose.
Conflict of interest: Judith M. Vonk has nothing to disclose.
Conflict of interest: Annemiek Mian reports that this study was funded by The Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No 733206, 2016; EUCAN-Connect grant agreement No 824989; ATHLETE, grant agreement No 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data, or writing of this report. Consulting fees received for being an opponent PhD defense committee at Copenhagen University, outside the submitted work.
Conflict of interest: Núria Olvera Ocaña reports funding for salary payment for the current manuscript from Centro de Investigación Biomédica en Red (CIBER) (Instituto de Salud Carlos III).
Conflict of interest: Lisbeth Mølgaard Laustsen has nothing to disclose.
Conflict of interest: Eva Rönmark has nothing to disclose.
Conflict of interest: Alicia Abellan has nothing to disclose.
Conflict of interest: Alvar Agusti has nothing to disclose.
Conflict of interest: Syed Hasan Arshad has nothing to disclose.
Conflict of interest: Anna Bergström has nothing to disclose.
Conflict of interest: H. Marike Boezen has nothing to disclose.
Conflict of interest: Marie-Kathrin Breyer has nothing to disclose.
Conflict of interest: Otto Burghuber has nothing to disclose.
Conflict of interest: Anneli Clea Bolund has nothing to disclose.
Conflict of interest: Adnan Custovic reports grants or contracts from Medical Research Council and Wellcome Trust, outside the submitted work. Personal consulting fees received from Philips and Stallergenes Greer, outside the submitted work. Speaker's fees from Thermo Fisher Scientific, Sanofi, Stallergenes Greer, AstraZeneca, and GSK, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Board of Director, WAO and BSACI council, outside the submitted work.
Conflict of interest: Graham Devereux has nothing to disclose.
Conflict of interest: Gavin Donaldson reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; AJRCCM (ATS) - Statistical Editor ARJCCM. FWO, EOS (Belgium) - Grant Reviewing, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for Novartis and Astra-Zeneca, outside the submitted work.
Conflict of interest: Liesbeth Duijts reports this study was funded by The Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No 733206, 2016; EUCAN-Connect grant agreement No 824989; ATHLETE, grant agreement No 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data, or writing of this report. Consulting fees for being an opponent PhD defense committee at Copenhagen University, outside the submitted work.
Conflict of interest: Ana Esplugues has nothing to disclose.
Conflict of interest: Maria Rosa Faner Canet reports during the planning of this work; I am supported by the Spanish National Health System Research Contrat Miguel Sevet (CP16/00039). Grants with Menarini, GSK,AZ outside this work. Consulting fees as well as payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, from GSK and Chiesi, outside the submitted work.
Conflict of interest: Ferran Ballester has nothing to disclose.
Conflict of interest: Judith Garcia-Aymerich has nothing to disclose.
Conflict of interest: Ulrike Gehring has nothing to disclose.
Conflict of interest: Sadia Haider has nothing to disclose.
Conflict of interest: Dr. Hartl reports grants from GSK, Böhringer, Menarini, Chiesi, Astra Zeneca, MSD, Novartis, Air Liquide, Vivisol, Pfizer, TEVA, personal fees from GSK, Böhringer, Menarini, Chiesi, Astra Zeneca, MSD, Novartis, Roche, Abbvie, TEVA, Takeda, outside the submitted work.
Conflict of interest: Helena Backman has nothing to disclose.
Conflict of interest: John W. Holloway has nothing to disclose.
Conflict of interest: Gerard H. Koppelman reports support for the current manuscript from Lung foundation of the Netherlands, payment made to institution. Grants or contracts paid to institution from H2020, Vertex, Ubbo Emmius Foundation, TEVA the Netherlands, and GSK, outside the submitted work. Consulting fees paid to institution from PURE IMS, and GSK, outside the submitted work. Unpaid member of the Board of the Stichting Astma Bestrijding, outside the submitted work.
Conflict of interest: Aitana Lertxundi has nothing to disclose.
Conflict of interest: Turid Lingaas Holmen has nothing to disclose.
Conflict of interest: Lesley Lowe has nothing to disclose.
Conflict of interest: Sara M. Mensink-Bout reports that this study was funded by The Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No 733206, 2016; EUCAN-Connect grant agreement No 824989; ATHLETE, grant agreement No 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data, or writing of this report. Consulting fees received for being an opponent PhD defense committee at Copenhagen University, outside the submitted work.
Conflict of interest: Clare Murray reports grants or contracts from Asthma UK, MRC, Moulton Charitable Foundation, NIHR, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline, Novartis, Astra Zeneca, ThermoFisher, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, outside the submitted work.
Conflict of interest: Graham Roberts has nothing to disclose.
Conflict of interest: Linnea Hedman has nothing to disclose.
Conflict of interest: Vivi Schlünssen has nothing to disclose.
Conflict of interest: Torben Sigsgaard has nothing to disclose.
Conflict of interest: Angela Simpson reports grant from UK Medical Research Council, outside the submitted work.
Conflict of interest: Jordi Sunyer has nothing to disclose.
Conflict of interest: Maties Torrent has nothing to disclose.
Conflict of interest: Stephen Turner has nothing to disclose.
Conflict of interest: Dr. van den Berge reports grants from GlaxoSmithKline, Astra Zeneca, Sanofi, Novartis, outside the submitted work.
Conflict of interest: Roel C. H. Vermeulen has nothing to disclose.
Conflict of interest: Sigrid Anna Aalberg Vikjord reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca and Boehringer Ingelheim, outside the submitted work.
Conflict of interest: Jadwiga A Wedzicha reports grants or contracts from GSK Astra Zeneca Boehringer, Chiesi, Novartis, and Greentech, outside the submitted work.
Conflict of interest: A.H. Maitland-van der Zee reports grants or contracts from Vertex, Boehringer Ingelheim, and Health Holland, outside the submitted work. Consulting fees paid to the institution received from Astra Zeneca and Boehringer Ingelheim, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from FIGON and EASYM, outside the submitted work.
Conflict of interest: Erik Melén has nothing to disclose.
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- Received July 28, 2021.
- Accepted August 24, 2021.
- Copyright ©The authors 2021
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