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Respiratory epidemiology
Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL
  1. Cynthia Hohmann1,
  2. Theresa Keller1,
  3. Ulrike Gehring2,
  4. Alet Wijga3,
  5. Marie Standl4,
  6. Inger Kull5,6,
  7. Anna Bergstrom7,8,
  8. Irina Lehmann9,10,
  9. Andrea von Berg11,
  10. Joachim Heinrich4,12,
  11. Susanne Lau13,
  12. Ulrich Wahn13,
  13. Dieter Maier14,
  14. Josep Anto15,16,
  15. Jean Bousquet17,18,
  16. Henriette Smit19,
  17. Thomas Keil1,20 and
  18. Stephanie Roll1
  1. 1Institute for Social Medicine, Epidemiology and Health Economics, Charité Universitätsmedizin Berlin, Berlin, Germany
  2. 2Department of Pulmonology, University Medical Centre Groningen Thoraxcentre, Groningen, The Netherlands
  3. 3National Institute for Public Health and the Environment, Bilthoven, The Netherlands
  4. 4Institute of Epidemiology, Helmholtz Zentrum Munchen Deutsches Forschungszentrum fur Umwelt und Gesundheit, Neuherberg, Germany
  5. 5Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden
  6. 6Sachs’ Children’s Hospital, Stockholm, Sweden
  7. 7Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  8. 8Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
  9. 9Molecular Epidemiology Unit, Charité Universitätsmedizin Berlin, Berlin, Germany
  10. 10Berlin Institute of Health, Berlin, Germany
  11. 11Research Institute, Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany
  12. 12Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians University Munich, Munchen, Germany
  13. 13Department of Paediatric Pneumology, Immunology and Intensive Care Unit, Charité Universitätsmedizin Berlin, Berlin, Germany
  14. 14Biomax Informatics, Munich, Germany
  15. 15Universitat Pompeu Fabra, Barcelona, Spain
  16. 16ISGlobal, Barcelona, Spain
  17. 17University Hospital Centre Montpellier, Montpellier, France
  18. 18UVSQ, UMR-S 1168, Université de Versailles, Saint-Quentin-en-Yvelines, France
  19. 19Utrecht University, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
  20. 20Institute for Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany
  1. Correspondence to Cynthia Hohmann; cynthia.hohmann{at}gmail.com

Abstract

Introduction To understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences.

Methods We used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex–puberty interaction terms and conducted a one-stage individual participant data meta-analysis.

Results Girls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases.

Discussion We found an incidence ‘sex shift’ in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.

  • sex shift
  • allergy
  • asthma
  • rhinitis
  • respiratory multimorbidity
  • incidence
  • MeDALL
  • puberty

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjresp-2019-000460

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    Footnotes

    • Contributors CH wrote the initial draft under the supervision of SR and TKei. TKel developed the statistical analysis plan and conducted the initial analyses. TKel, CH, UG, AW and HS augmented the statistical analyses plan, and TKel conducted and interpreted the statistical analyses with supervision of SR. CH, TKei, JA and JB coordinated the development of common standardised questionnaires and standard operational procedures, coordinated the follow-up assessment of the MeDALL birth cohorts, and participated in the development of the initial statistical analysis plan. MS, AvB (GINIplus), JH, IL (LISA), UG, AW, HS (PIAMA), AB, IK (BAMSE), SL, TKei and UW (MAS) coordinated the local follow-up assessments and provided the data on the harmonised follow-up and the birth cohort data. They, along with DM, participated in the planning of the common database and in the preparation of harmonised data sets for central storage and analyses. DM built the common database. DM was responsible for the correct and safe storage of the data in the common database and the data distribution to different research teams. All authors read the different versions of the manuscript, revised them and provided comments, participated in the revision of the final manuscript, and approved the final version.

    • Funding This study was funded by MeDALL, a joint project conducted within the European Union under the Health Cooperation Work Programme of the 7th Framework Programme (grant agreement no 261357). The BAMSE study was supported by the Swedish Research Council, Swedish Heart and Lung Foundation, Swedish Research Council for Working Life and Social Welfare, Swedish Asthma and Allergy Association Research Foundation, Swedish Research Council Formas, Stockholm County Council (ALF), and the European Commission’s Seventh Framework 29 Programme MeDALL under grant agreement no 261357. The GINIplus study was supported by the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum Munich (former GSF) (observational arm), by respective budgets of the five study centres (Helmholtz Zentrum Munich (former GSF), Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich, IUF - Leibniz Research-Institute for Environmental Medicine at the University of Düsseldorf) and by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the GINIplus study was supported by the Commission of the European Communities, the 7th Framework Programme: MeDALL project, as well as by the companies Mead Johnson and Nestlé. The LISA study was supported by grants from the Federal Ministry for Education, Science, Research and Technology, and in addition by Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Environmental Research - UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, by the respective budgets of the involved partners (Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Environmental Research - UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf) and by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the 7th Framework Programme: MeDALL project. The PIAMA study was supported by the Netherlands Organization for Health Research and Development; the Netherlands Organization for Scientific Research; the Netherlands Asthma Fund (grant 4.1.14.001); the Netherlands Ministry of Spatial Planning, Housing, and the Environment; and the Netherlands Ministry of Health, Welfare and Sport. The MAS study was funded by the German Federal Ministry of Education and Research (BMBF; reference numbers 07015633, 07 ALE 27, 01EE9405/5, 01EE9406) and the German Research Foundation (DFG; reference number KE 1462/2-1).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval Ethical approval was obtained from the local ethics committees for each study.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement No data are available.