Asthma and lower airway diseaseThe chitinase-like protein YKL-40: A possible biomarker of inflammation and airway remodeling in severe pediatric asthma
Section snippets
Methods
In this cross-sectional, explorative case-control study, children aged 6 to 18 years with problematic severe asthma were compared with age-matched peers with controlled asthma. These 2 conditions were defined in accordance with guidelines established by the Global Initiative for Asthma,17 which takes into account the severity of the underlying disease, as indicated by the need for treatment and degree of symptom control achieved.18 Inclusion criteria are presented in Table I. Written informed
Results
Clinical characteristics of the included patients are presented in Table II. Children with therapy-resistant asthma (n = 34) received higher doses of inhaled corticosteroids, had inferior asthma control (P < .001), more airflow obstruction (P = .03), increased bronchial hyperresponsiveness (P = .01), and increased numbers of blood eosinophils (P = .04) and neutrophils (P = .03) compared to children with controlled asthma (n = 39). There were no differences between these 2 groups of children
Discussion
In this cohort of well-characterized school-aged children with asthma, we demonstrate associations between YKL-40 levels, clinical characteristics, and disease severity. We show for the first time that serum YKL-40 level is increased in children with severe, therapy-resistant asthma compared with healthy children. Furthermore, serum levels of YKL-40 significantly correlate with asthma control, airway remodeling measured as bronchial wall thickening by HRCT, and blood neutrophils in children
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2021, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Clusters IV to VI were overrepresented with genes that influenced attributes related to Epiintegrity. For example, clusters V and VI were enriched for genes implicated in airway remodeling (eg, OSM57 and CHI3L158-61) and epithelial barrier (eg, FLG62,63), respectively. In contrast, clusters I to III were overrepresented with inflammation-related genes (Fig 7, B).
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2019, Seminars in ImmunologyCitation Excerpt :The airway transcriptome analysis showed activation of non-type-2 inflammatory pathways [174]. However, YKL-40 expression positively correlates to neutrophilic and IL-17-driven inflammation in asthmatic patients, suggesting CLPs may also be important for non-Th2 asthma phenotypes that are often strongly associated with innate immune responses. [175] Lai et al. has demonstrated that patients with elevated levels of YKL-40 had significantly greater corticosteroid use than patients with lower levels, which suggests that high levels of serum YKL-40 may be refractory to current asthma treatments.
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This study was supported by the Freemason Child House Foundation in Stockholm, the Konsul Th. C. Bergh's Foundation, the Swedish Asthma and Allergy Association's Research Foundation, the Centre for Allergy Research at Karolinska Institutet, the Pediatric Research Foundation of Astrid Lindgren Children's Hospital, the Swedish Heart-Lung Foundation, Karolinska Institutet, the Bernard Osher Initiative for Research on Severe Asthma, Stockholm County Council Research Funds, and VINNOVA, Swedish Governmental Agency for Innovation Systems.
Disclosure of potential conflict of interest: B. Dahlén is a Board member for Actelion DMC; has received one or more grants from or has one or more grants pending with the Swedish Heart-Lung Foundation, the Swedish MRC, and the Swedish Asthma and Allergy Foundation; and has received one or more payments for lecturing from or is on the speakers' bureau for Novartis and for Meda. S. E. Dahlén has been supported by one or more grants from the Swedish MRC, the Swedish Heart-Lung Foundation, and the Stockholm County Council Research Funds; has consultancy arrangements with GSK & AZ Respiratory; and has received one or more payments for lecturing from or is on the speakers' bureau for Nigaard Pharmaceuticals. J. R. Konradsen has received grants from the Freemason Child House Foundation in Stockholm, the Konsul Th. C. Bergh's Foundation, the Swedish Asthma and Allergy Association's Research Foundation, the Centre for Allergy Research at Karolinska Institutet, the Pediatric Research Foundation of Astrid Lindgren Children's Hospital, and the Swedish Heart-Lung Foundation; and has received payment for lecturing from Novartis and Thermo Fisher Scientific. K. C. Lödrup Carlsen has received one or more public grants, has received or has one or more grants pending with the Kloster Foundation, and has received one or more payments for lecturing from or is on the speakers' bureau for GSK. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.