Airway immune mediator levels during asthma‐like symptoms in young children and their possible role in response to azithromycin. Issue 6 (20th November 2020)

• Record Type: Journal Article
• Authors: Carlsson, Christian J.; Rasmussen, Morten A.; Pedersen, Susanne B.; Wang, Ni; Stokholm, Jakob; Chawes, Bo L.; Bønnelykke, Klaus; Bisgaard, Hans
• Is Part Of: Allergy. Volume 76:Issue 6(2021)
• Page Start: 1754
• Page End: 1764
• Publication Date: 2020-11-20
• Subjects: allergy and immunology -- asthma -- chemokines -- cytokines -- pediatrics; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.14651
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: Asthma‐like symptoms in young children are orchestrated by the local airway immune response, but current knowledge largely relies on in vitro airway models. Azithromycin has been shown to reduce the duration of episodes with asthma‐like symptoms, but efficacy may depend on the individual child's immune response. Objectives: To investigate in vivo upper airway immune mediator levels during episodes with asthma‐like symptoms in young children and their ability to predict the clinical response to azithromycin treatment. Methods: A total of 535 children aged 0‐3 years from the Copenhagen Prospective Studies of Asthma in Childhood‐2010 mother‐child cohort were examined for immune mediator levels in samples of nasal epithelial lining fluid during episodes with asthma‐like symptoms as well as in the asymptomatic state. In a sub‐study, children with recurrent asthma‐like symptoms were randomized to either a 3‐day course of oral azithromycin (10 mg/kg; n = 32) or placebo (n = 38). In the current study, we compared the pretreatment immune mediator levels with the clinical response to treatment with azithromycin in an exploratory post hoc analysis. Results: The immune mediator concentrations during vs outside episodes were significantly upregulated for IFN‐ɣ (ratio 1.73), TNF‐α (ratio 2.05), IL‐1β (ratio 1.45), IL‐10 (ratio 1.97), while CCL22 (ratio 0.65) was downregulated. Low levels of TNF‐α and IL‐10 and high levels of CCL22 predicted better treatment response to azithromycin ( P ‐values < .05). Conclusion: Upper airway immune mediator levels were altered during episodes of asthma‐like symptoms, and levels of TNF‐α, CCL22, and IL‐10 may predict the response to azithromycin treatment. Abstract : IFN‐ɣ, TNF‐α, IL‐1β and IL‐10 were upregulated in the upper airway mucosa whereas CCL22 was relatively downregulated during episodes of asthma‐like symptoms compared to asymptomatic periods in young children. The immune mediator profile is consistent with neutrophilic inflammation as the primary acute disease process during such episodes. TNF‐α, IL‐10 and CCL22 predicted treatment effect of azithromycin for episodes of asthma‐like symptoms, with improved responses in episodes where the child was unable to mount a sufficient response of TNF‐α and IL‐10 while having a relatively increased expression of CCL22 (ie mediator levels opposite to what was typically observed during episodes of asthma‐like symptoms). Abbreviations: CCL22, C‐C motif chemokine 22; IFN‐?, interferon gamma; IL‐10, interleukin 10; RCT, randomized controlled trial; TNF‐a, tumor necrosis factor alpha.