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Air pollution and IgE sensitization in 4 European birth cohorts—the MeDALL project - 04/02/21

Doi : 10.1016/j.jaci.2020.08.030 
Erik Melén, MD, PhD a, b, Marie Standl, PhD c, Ulrike Gehring, PhD d, Hicran Altug, PhD e, Josep Maria Antó, MD, PhD f, g, h, i, Dietrich Berdel, MD j, Anna Bergström, PhD k, Jean Bousquet, MD, PhD l, m, Joachim Heinrich, PhD c, n, o, Gerard H. Koppelman, MD, PhD p, q, Inger Kull, PhD a, b, Christian Lupinek, MD r, Iana Markevych, PhD c, n, s, Tamara Schikowski, PhD e, Elisabeth Thiering, PhD c, t, Rudolf Valenta, MD r, u, v, w, Marianne van Hage, MD, PhD x, Andrea von Berg, MD j, Judith M. Vonk, PhD q, y, Magnus Wickman, MD, PhD z, Alet Wijga, PhD aa, Olena Gruzieva, MD, PhD k, bb,
a Department of Clinical Sciences and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden 
b Sachs Children’s Hospital, Stockholm, Sweden 
c Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany 
d Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands 
e IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany 
f ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain 
g Universitat Pompeu Fabra, Barcelona, Spain 
h CIBER Epidemiología y Salud Pública, Madrid, Spain 
i Hospital de Mar Medical Research Institute, Barcelona, Spain 
j Research Institute, Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany 
k Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 
l MACVIA-France, Contre les Maladies Chroniques pour un Vieillissement Actif en France European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier, France 
m INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, France 
n Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany 
o Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia 
p University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, Groningen, The Netherlands 
q University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands 
r Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria 
s Institute of Psychology, Jagielonian University, Cracow, Poland 
t Division of Metabolic and Nutritional Medicine, Dr von Hauner Children’s Hospital, University Hospital, LMU of Munich, Munich, Germany 
u Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia 
v National Research Center–Institute of Immunology FMBA of Russia, Moscow, Russia 
w Karl Landsteiner University of Health Sciences, Krems, Austria 
x Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden 
y Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 
z Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden 
aa National Institute for Public Health and the Environment, Bilthoven, The Netherlands 
bb Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden 

Corresponding author: Olena Gruzieva, MD, PhD, Karolinska Institutet, Institute of Environmental Medicine, Nobels väg 13, Box 210, SE-17177, Stockholm, Sweden.Karolinska InstitutetInstitute of Environmental MedicineNobels väg 13Box 210StockholmSE-17177Sweden

Abstract

Background

Whether long-term exposure air to pollution has effects on allergic sensitization is controversial.

Objective

Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years.

Methods

A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021).

Results

Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-μg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-μg/m3 increase in exposure).

Conclusion

Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.

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Key words : Allergy, allergen, air pollution, children, cohort, IgE, sensitization, meta-analysis

Abbreviations used : BAMSE, ESCAPE, Fel d 1, GINIplus, ISAC, ISU-E, LISA, LUR, MeDALL, NO2, NOx, OR, Phl p 1, PIAMA, PM2.5, PM10, PM2.5 absorbance, PMcoarse


Plan


 The research leading to these results has received funding from the European Community’s Seventh Framework Program under grant agreement numbers: 211250 (European Study of Cohorts for Air Pollution Effects [ESCAPE]), and 261357 (Mechanisms of the Development of ALLergy [MeDALL]). Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) was supported by The Swedish Research Council, The Swedish Heart-Lung Foundation, Region Stockholm (ALF project, and database maintenance), the Strategic Research Programme in Epidemiology at Karolinska Institutet, the Swedish Research Council Formas and the Swedish Environment Protection Agency, the Swedish Asthma and Allergy Research Foundation, the Cancer and Allergy Foundation. E.M. is supported by a grant from the European Research Council (grant agreement 757919, TRIBAL). O.G. is supported by the Swedish Research Council for Health, Working Life and Welfare (FORTE 2017-01146). R.V. is supported the by Austrian Science Fund (grant F4605) and is a recipient of a Megagrant of the Government of the Russian Federation (grant 14.W03.31.0024). The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study was supported by project grants from The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; The Netherlands Asthma Fund; The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport. U.G. was supported by a Grant of The Netherlands Organization for Scientific Research. The German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) study was mainly supported for the first 3 years of the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum Munich (formerly GSF) (observational arm). The 4-year, 6-year, 10-year, and 15-year follow-up examinations of the GINIplus study were covered from the respective budgets of the 5 study centers (Helmholtz Zentrum Munich [formerly GSF], Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich), and from year 6 onward it was also supported with funding from from IUF-Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf and by a grant from the Federal Ministry for Environment (IUF Düsseldorf [grant FKZ 20462296]). Furthermore, the 15-year follow-up examination of the GINIplus study was supported by the Commission of the European Communities, the Seventh Framework Program MeDALL project, and by the companies Mead Johnson and Nestlé. The Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA) study was mainly supported by grants from the Federal Ministry for Education, Science, Research and Technology and also from Helmholtz Zentrum Munich (formerly GSF), the Helmholtz Centre for Environmental Research-UFZ, Leipzig, the Research Institute at Marien-Hospital Wesel, Pediatric Practice, and Bad Honnef for the first 2 years. The 4-year, 6-year, 10-year, and 15-year follow-up examinations of the LISA study were covered from the respective budgets of the involved partners (Helmholtz Zentrum Munich [formerly GSF], the Helmholtz Centre for Environmental Research-UFZ, Leipzig, the Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, and IUF–Leibniz-Research Institute for Environmental Medicine at the University of Düsseldorf) and also by a grant from the Federal Ministry for Environment (IUF Düsseldorf [grant FKZ 20462296]). Furthermore, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the Seventh Framework Program: MeDALL project. I.M. is supported by a grant from the NeuroSmog: Determining the Impact of Air Pollution on the Developing Brain (grant POIR.04.04.00-1763/18-00) which is implemented as part of the TEAM-NET programme of the Foundation for Polish Science and cofinanced with funding from European Union resources obtained from the European Regional Development Fund under the Smart Growth Operational Programme.
 Disclosure of potential conflict of interest: R. V. reports that he has received research funding from Viravaxx, Vienna, Austria, and serves as a consultant for the company. M. v-H. serves as consultant for Biomay, Vienna, Austria.


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Vol 147 - N° 2

P. 713-722 - février 2021 Retour au numéro
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