Background: Chemokines are important mediators in immune cell recruitment, contributing to allergy development. However, extensive studies of chemokines in the circulation in relation to the presence and development of allergic diseases remain scarce. Our aim was to investigate associations of circulating allergy-related chemokines with development of asthma and sensitisation cross-sectionally and longitudinally in a population-based cohort. Methods: The chemokines CCL17, CCL22, CXCL10, CXCL11 and CCL18 were measured in plasma samples from children in the Manchester Asthma and Allergy Study. Samples were available from cord blood at birth (n=376), age 1 (n=195) and 8 years (n=334). Cross-sectional and longitudinal association analyses were performed in relation to asthma and allergic sensitisation, as well as allergic phenotype clusters previously derived using machine learning in the same study population. Results: In children with asthma and/or allergic sensitisation, CCL18 levels were consistently elevated at ages 1 and/or 8 years. In a longitudinal model including information on asthma from 4 time-points (ages 5, 8, 11 and 16 years), we observed a significant association between increasing CCL18 levels at age 1 and a higher risk of asthma from early school age to adolescence (OR=2.9, 95% CI 1.1-7.6, p=0.028). We observed similar associations in longitudinal models for allergic sensitisation. Asthma later in life was preceded by increased CXCL10 levels after birth, and decreased CXCL11 levels at birth. Conclusion: Elevated CCL18 levels throughout childhood precede the development of asthma and allergic sensitisation. The Th1-associated chemokines CXCL10 and CXCL11 also associated with development of both outcomes, with differential temporal effects.

Montelukast therapy in asthmatic children with and without food allergyUmit Murat Sahiner1*, Ebru Arik Yilmaz1*, Sara Fontanella2, Sadia Haider2, Ozge Soyer1, Adnan Custovic2, Omer Kalayci1, Cansin Sackesen1,3*Equal contribution1 Hacettepe University School of Medicine, Division of Pediatric Allergy, Ankara, Turkey2 National Heart and Lung Institute, Imperial College London, UK3 Koc University School of Medicine, Division of Pediatric Allergy, Istanbul TukeyRunning Title: Montelukast in asthma and food allergyFunding Source: The study drugs, placebos and laboratory kits were provided by Merck Sharpe and Dohme Company. The protocol was developed by the corresponding author Prof Cansin Sackesen and reviewed by Merck Sharpe and Dohme Company. However, there is no contribution of Merck Sharpe and Dohme Company to the results and discussion of the article.Conflicts of Interest: The authors declare no conflicts of interest in relation to this study.