The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Aug 2013
The chitinase-like protein YKL-40: a possible biomarker of inflammation and airway remodeling in severe pediatric asthma.
Problematic severe childhood asthma includes a subgroup of patients who are resistant to therapy. The specific mechanisms involved are unknown, and novel biomarkers are required to facilitate treatment and diagnosis of therapy-resistant asthma. The chitinase-like protein YKL-40 has been related to asthma and airway remodeling. ⋯ YKL-40 levels are increased in children with severe, therapy-resistant asthma compared to healthy children, and also compared to children with controlled asthma following correction for genotype.
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J. Allergy Clin. Immunol. · Aug 2013
Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.
Thymic stromal lymphopoietin (TSLP) pathway blockade is a potential strategy for asthma treatment because the main activities of TSLP are activation of myeloid dendritic cells (mDCs) and modulation of cytokine production by mast cells. TSLP-activated mDCs prime the differentiation of naive T cells into inflammatory TH2 cells. ⋯ These results demonstrate promising efficacy for TSLPR blockade in an allergic lung inflammation model in which TSLP activation of mDCs might play a key role.
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Some patients with adult-onset asthma have severe disease, whereas others have mild transient disease. It is currently unknown whether patients with severe adult-onset asthma represent a distinct clinical phenotype. ⋯ The majority of patients with severe adult-onset asthma are nonatopic and have persistent eosinophilic airway inflammation. This suggests that severe adult-onset asthma has a distinct underlying mechanism compared with milder disease.
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J. Allergy Clin. Immunol. · Aug 2013
Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids.
Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. ⋯ Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.
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J. Allergy Clin. Immunol. · Aug 2013
Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion.
TH17 cells are proposed to play a role in the pathology of asthma, including steroid-resistant (SR) disease. We previously identified a steroid-enhancing function of vitamin D in patients with SR asthma in restoring the impaired response to steroids for production of the anti-inflammatory cytokine IL-10. ⋯ Patients with severe asthma exhibit increased levels of TH17 cytokines, which are not inhibited by steroids. 1,25(OH)2D3 inhibits TH17 cytokine production in all patients studied, irrespective of their clinical responsiveness to steroids, identifying novel steroid-enhancing properties of vitamin D in asthmatic patients.