TY - JOUR

T1 - Neonatal airway immune profiles and asthma and allergy endpoints in childhood

AU - Chawes, Bo L.

AU - Wolsk, Helene M.

AU - Carlsson, Christian J.

AU - Rasmussen, Morten A.

AU - Følsgaard, Nilofar

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Brix, Susanne

AU - Schoos, Ann-Marie M.

AU - Bisgaard, Hans

N1 - Funding information: COPSAC is funded by private and public research funds all listed on www.copsac.com: The Lundbeck Foundation (grant no R16-A1694); The Danish Ministry of Health (903516); Danish Council for Strategic Research (0603-00280B); and The Capital Region Research Foundation have provided core support for COPSAC. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 946228). No pharmaceutical company was involved in the study. The funding agencies did not have any role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, or approval of the manuscript.

PY - 2021

Y1 - 2021

N2 - Background: The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood. Methods: We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition. Results: A neonatal airway immune profile particularly characterized by enhanced IL-1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1β and CXCL8, showed trend of association with development of early asthma endpoints. Conclusions: Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.

AB - Background: The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood. Methods: We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition. Results: A neonatal airway immune profile particularly characterized by enhanced IL-1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1β and CXCL8, showed trend of association with development of early asthma endpoints. Conclusions: Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.

KW - allergy

KW - asthma

KW - chemokines

KW - children

KW - cytokines

U2 - 10.1111/all.14862

DO - 10.1111/all.14862

M3 - Journal article

C2 - 33864271

AN - SCOPUS:85104964057

VL - 76

SP - 3713

EP - 3722

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 12

ER -