Reviews and feature article
Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop

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Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.

Section snippets

Current definition and classification of childhood wheezing/asthma and allergic diseases

Birth cohort studies have been a highly productive source of knowledge about the characteristics of asthma phenotypes in childhood because of their unique longitudinal nature.

Studies in asthma have often used definitions developed by the International Study of Asthma and Allergies in Childhood (ISAAC)6 and partly adopted by the European birth cohort collaborations Global Allergy and Asthma European Network (GA2LEN)7 and MeDALL,8, 9 particularly physician-diagnosed asthma. In some studies,

The contribution of birth cohort studies to understanding risk and protective factors

Numerous environmental determinants have been assessed in birth cohorts: exposure to environmental tobacco smoke, ambient air pollution, and indoor factors, such as household chemicals, molds, and water damage. Environment plays a role during pregnancy and across the life cycle.33 Early animal exposure, such as keeping a dog, might be protective,34, 35, 36 but a meta-analysis37 showed no overall protection with pet exposure. Consistent protective associations were reported for growing up in a

The contribution of birth cohort studies to understand immune development

Immune responses at birth are related to risk factors for wheezing, asthma, lower respiratory tract infection, allergic sensitization, and atopic dermatitis in infancy. Even so, reconciling birth cohort findings is hindered by the complexity involved in immunologic predictors, their measurement, developmental changes, and uncertainties in outcomes definitions, such as wheezing and asthma phenotypes, and differences in methodology among investigators. Distinct immunologic patterns are associated

Contribution of birth cohort studies to understanding the effect of early lung function for later allergic diseases

Low lung function in early life is associated with low function in adulthood, an increased risk of wheeze in infancy and preschool children, and an increased risk of asthma in childhood.20, 21, 64, 65, 66 Male sex and maternal smoking during pregnancy increase the risks.

Reduced peak flow values have been found in preschool children exposed to high traffic-related air pollution, supporting findings in later childhood.67

The most predictive pulmonary function measurements are those that assess

Needs for harmonized birth cohorts

More than 130 birth cohorts with data on asthma and allergy have been initiated in the world over the past 30 years. The timing of the establishment of these cohorts is critical because they span the time period of a dramatic increase in these diseases. The information gathered is remarkable, but data are in isolated independent databases. Although the assessment methods of the studies vary, most cohorts were established and followed by using rigorous methodology, and data are usually available

Conclusions

Existing population-based birth cohorts have contributed to our knowledge of the development of asthma and atopy in many areas, such as (1) characterizing different wheezing phenotypes; (2) documenting the differing onset of aeroallergen reactivity; (3) describing the natural history of asthma and pulmonary functions; (4) noting the importance of early-life risk factors, such as lower lung function or prenatal and postnatal environmental tobacco smoke exposure, and the later development of

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    Supported by MeDALL (Mechanisms of the Development of Allergy, EU FP7 Grant agreement no. 261357). The workshop was supported in part by funds from the Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, and the Division of Lung Diseases, National Heart, Lung, and Blood Institute.

    Disclosure of potential conflict of interest: J. Bousquet is a member of scientific and advisory boards for Actelion, Almirall, Meda, Merck, Merck Sharp Dohme, Novartis, Sanofi-Aventis, Takeda, Teva, and Uriach; is on the Board of Directors of Stallergenes; has received payment for lectures from Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Meda, Merck, Merck Sharp Dohme, Novartis, OM Pharma, Sanofi-Aventis, Schering-Plough, Takeda, Teva, and Uriach; and has received travel support from Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Meda, Merck, Merck Sharp Dohme, Novartis, OM Pharma, Sanofi-Aventis, Schering-Plough, Takeda, Teva. and Uriach. J. E. Gern has received research support from the National Institutes of Health (NIH), Merck, AstraZeneca, and GlaxoSmithKline and has received personal fees from GlaxoSmithKline, Biota, Centocor, Boehringer, MedImmune, Theraclone, Merck, and Gilead. F. D. Martinez has received grants from the NIH and has received travel support from Abbott and Merck. C. C. Johnson has received research support from the National Institute of Allergy and Infectious Disease (NIAID) and has had consultant arrangements with McNeil. R. F. Lemanske, Jr, has received research support from the NIH/National Heart, Lung, and Blood Institute (NHLBI) and Pharmaxis; has received travel support from the NIH; has received fees for participation in review activities from the NIH; is Secretary/Treasurer of the American Academy of Allergy, Asthma & Immunology (AAAAI); has consultant arrangements with Merck, Sepracor, SA Boney and Associates, GlaxoSmithKline, the American Institute of Research, Genentech, Double Helix Development, and Boehringer Ingelheim; is employed by the University of Wisconsin School of Medicine and Public Health; has received payment for lectures from the Michigan Public Health Institute, Allegheny General Hospital, the American Academy of Pediatrics West Allegheny Health Systems, California Chapter 4, AAP, the Colorado Allergy Society, the Pennsylvania Allergy and Asthma Association, Harvard Pilgrim Health, the California Society of Allergy, the New York City Allergy Society, the World Allergy Organization, the American College of Chest Physicians, APAPARI, and the Western Society of Allergy, Asthma, and Immunology; has received payment for manuscript preparation from the AAAAI; has received royalties from Elsevier and UpToDate. P. N. Le Souëf has received research support from the National Health Medical Research Council of Australia. R. Tepper has received research support from the NIH. E. R. M. von Mutius is Associate Editor of the Journal of Allergy and Clinical Immunology; has consultant arrangements with GlaxoSmithKline, Novartis, Astellas Pharma Europe, and ALK-Abelló; and has received research support from Friesland Campina BV. S. H. Arshad has received research support from the NHLBI and Asthma UK. L. B. Bacharier has consultant arrangements with Aerocrine, GlaxoSmithKline, Genentech/Novartis, Merck, Schering, Cephalon, DBV Technologies, and Teva; has research support from the NHLBI/NIH, AsthmaNet, and VDAART Trial; has received payment for lectures from Aerocrine, AstraZeneca, Genentech/Novartis, GlaxoSmithKline, Merck, Schering-Plough, and Teva. A. Becker has received research support from the Canadian Institute of Health Research/AllergGen NCE, AstraZeneca, Merck Frosst, Novartis, and Pfizer; is a board member for Merck Frosst Canada and Novartis; receives payment for lectures from AstraZeneca, Merck Frosst, and Novartis; and has received payment for the development of educational presentations from Novartis and Pfizer. D. Bernstein has received research support from the National Institute of Environmental Health Sciences and the National Institute of Occupational Safety and Health; has consultant arrangements from Merck, Genentech, and Teva; and has received payment for lectures from Merck. M. D. Cabana has consultant arrangements with Mead Johnson and Abbott Nutrition and has received research support from Nestec and Wyeth Nutrition. M. Castro has received research support from the NIH, Asthmatx/Boston Scientific, Amgen, Ception/Cephalon/Teva, Genentech, MedImmune, Merck, Novartis, GlaxoSmithKline, Sanofi Aventis, Vectura, Next Bio, and KaloBios; has consultant arrangements with Asthmatx/Boston Scientific, Genentech, IPS Holaira, Pulmagen, and Sanofi-Aventis; has received payment for lectures from Merck, GlaxoSmithKline, Genentech, Asthmatx/Boston Scientific, and Boehringer Ingelheim; and has received royalties from Elsevier. P. J. Cooper is employed by the Liverpool School of Tropical Medicine and has received research support from the Wellcome Trust UK. D. R. Gold has received research support from and is employed by the NIH and the US Environmental Protection Agency. J. Henderson has received research support from the Medical Research Council UK and Wellcome Trust and has received travel support from the NIH. D. J. Jackson has received research support from the NHLBI and has consultant arrangements with GlaxoSmithKline and Genentech. T. Keil has received research support from the European Union and is employed by Charite Berlin. K. C. Lødrup Carlsen has received research support from RegionHealth Southeast, ThermoFisher Scientific, Furst Medical Laboratory, Regional Health Board East (Norway), Health and Rehabilitation (Norway), and the Norwegian Research Council and has received travel support from EU-FP7 MeDALL. W. J. Morgan has consultant arrangements with Genentech and the Cystic Fibrosis Foundation and is employed by the University of Arizona; has received research support from the Cystic Fibrosis Foundation, Mount Sinai Hospital/Research Institute, and the NHLBI; has received payment for lectures from the AAAAI and the American Thoracic Society; and has received royalties from Elsevier. D. R. Ownby has received research support from the National Institute of Allergy and Infectious Disease. M. R. Sears has consultant arrangements with AstraZeneca and Novartis and has received payment for lectures from AstraZeneca and Merck. A. Simpson has received research support from the Medical Research Council. R. Valenta has received research support from and has consultant arrangements with Biomay AG and ThermoFisher. S. T. Weiss has consultant arrangements with Novartis. R. Wood has consultant arrangements with the Asthma and Allergy Foundation of America, is employed by Johns Hopkins University, has received research support from the NIH, and has received royalties from UpToDate. A. L. Wright has received research support from the NIH. The rest of the authors declare that they have no relevant conflicts of interest.

    Deceased.

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