Introduction and main sub-projects

Preschool wheeze affects half of all preschool children below 6 years and is considered a risk factor for later asthma development since more than one third of all preschool wheezers later develop asthma in school age.

Risk factors associated with preschool wheeze developing into school-age asthma include eczema, allergic sensitization (presence of Immunoglobulin E antibodies), heredity for asthma and allergies, mode of delivery, wheezing onset, prematurity, vitamin D and environmental factors. Despite the many proposed risk factors, it is not possible to reliably predict which preschool wheezers will develop school-age asthma.

GEWAC is a prospective case-cohort study in which 156 children with an episode of acute wheeze (cases) were recruited from the Pediatric Emergency Department or after admission to the Pediatric Emergency Ward at Astrid Lindgren’s Children’s Hospital between October 2008 and September 2012. During the same time of inclusion of cases, 102 age-matched healthy controls were recruited. The cases have been assessed at inclusion, at a first revisit 3 months later (3 months follow-up), annually from the emergency visit until 7 years of age as well as at 11 years. The controls have been evaluated at inclusion, at 7 and at 11 years of age.

The overall aim is to study risk factors for and prediction of persistent asthma in children suffering from pre-school wheeze.

Figure 1. Flowchart of the GEWAC study. †Study I: 113 cases included who attended the 7-year follow-up, of these 100 attended the first revisit and 97 at the first annual follow-up. 54 healthy controls attended the 7-year follow-up and are included in study I. ‡Study II: 107 cases included who attended the 11-year follow-up, of these 100 attended the first revisit, 80 attended the 5-year follow-up and 92 attended the 7-year follow-up. §Study III: 145 cases with available plasma at inclusion and 113 cases with available plasma at the first revisit, along with 101 healthy controls with available plasma at inclusion are included in study III. ¶Study IV: 72 cases with available sera at inclusion (n = 7) or first revisit (n = 65) and at the 7-year follow-up along with 43 healthy controls with available sera at inclusion. ††2 cases were excluded after inclusion due to prematurity and pseudo-croup.

Main sub-projects

• Risk factors and risk assessment for persistent asthma among children suffering from preschool wheeze
• Clinical features of the wheezing episode
• Microbiological etiology of the wheezing episode including Rhinovirus, Respiratory Syncytial virus.
• Allergic sensitization and biomarkers of allergy, including molecular allergy diagnostics.
• Inflammation and inflammatory biomarkers
• Heredity and genetic risk factors
• Vitamin D levels

Investigators and study personnel

Jon Konradsen, Associate professor, PI for clinical investigations
Cilla Söderhäll, Associate professor, PI for molecular investigations
Idun Holmdahl
Anastasia Filiou
Katharina Stenberg
Sofia Luning

Responsible university or institution

Karolinska Institutet.

Collaborators

Marianne van Hage
Magnus Borres
Anna Asarnoj
Anna James
Sci-Life lab Karolinska Institutet
Thermo Fisher Scientific

Funders

Karolinska Institutet, Region Stockholm, The Swedish Research Council, the Swedish Heart‐Lung foundation, Konsul Th C Bergh foundation, the Freemason Child House Foundation in Stockholm, the Centre for Allergy Research at Karolinska Institutet, the Samaritan Foundation, Sigurd and Elsa Goljes Memorial Fund, Crown princess Lovisas association for Childcare, Axel Tielmans Memorial Fund, the Stockholm County Council, the Cancer‐and Allergy Foundation, The Swedish Asthma and Allergy Association’s Research Foundation, the Hesselman Foundation, and King Gustaf V 80th Birthday Foundation. 

How to collaborate with GEWAC

Please contact:

Jon Konradsen, jon.konradsen@ki.se
Cilla Söderhäll, cilla.soderhall@ki.se

Key publications

Holmdahl I, Filiou A, Stenberg Hammar K, et al. Early Life Wheeze and Risk Factors for Asthma-A Revisit at Age 7 in the GEWAC-Cohort. Children (Basel). 2021;8(6).

Chakraborty S, Hammar KS, Filiou AE, et al. Longitudinal eosinophil-derived neurotoxin measurements and asthma development in preschool wheezers. Clin Exp Allergy. 2022;52(11):1338-42.

Filiou A, Holmdahl I, Asarnoj A, et al. Development of Sensitization to Multiple Allergen Molecules from Preschool to School Age Is Related to Asthma. Int Arch Allergy Immunol. 2022;183(6):628-39.

Filiou A, Hoyer A, Holmdahl I, et al. Vitamin D receptor genetic variant associated with asthma in Swedish school-children. Clin Exp Allergy. 2023;53(10):1045-9.

Holmdahl I, Chakraborty S, Hoyer A, et al. Inflammatory related plasma proteins involved in acute preschool wheeze. Clin Transl Allergy. 2023;13(11):e12308.

Holmdahl I, Luning S, Gerdin SW, et al. Rhinovirus-induced wheeze was associated with asthma development in predisposed children. Acta Paediatr. 2024;113(6):1376-84.

Stenberg Hammar K, Hedlin G, Konradsen JR, et al. Subnormal levels of vitamin D are associated with acute wheeze in young children. Acta Paediatr. 2014;103(8):856-61.

Stenberg-Hammar K, Niespodziana K, Soderhall C, et al. Rhinovirus-specific antibody responses in preschool children with acute wheeze reflect severity of respiratory symptoms. Allergy. 2016;71(12):1728-35.

James A, Stenberg Hammar K, Reinius L, et al. A longitudinal assessment of circulating YKL-40 levels in preschool children with wheeze. Pediatr Allergy Immunol. 2017;28(1):79-85.

Stenberg Hammar K, Niespodziana K, van Hage M, et al. Reduced CDHR3 expression in children wheezing with rhinovirus. Pediatr Allergy Immunol. 2018;29(2):200-6.

Katayama S, Stenberg Hammar K, Krjutskov K, et al. Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication. Eur Respir J. 2020;55(1).

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