Bronchial epithelium in children: a key player in asthma.
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ABSTRACT:
SUBMITTER: Carsin A
PROVIDER: S-EPMC9487245 | biostudies-literature | 2016 Jun
REPOSITORIES: biostudies-literature
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Bronchial epithelium in children: a key player in asthma.
Carsin Ania A Mazenq Julie J Ilstad Alexandra A Dubus Jean-Christophe JC Chanez Pascal P Gras Delphine D
European respiratory review : an official journal of the European Respiratory Society 20160601 140
Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on childre ...[more]
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Project description:Background: Uncontrolled asthma (BA) can be complicated by cardiac conduction disturbances and arrhythmias. It is typical mainly for adult asthmatics patients. In asthmatics children the effect of bronchoconstriction on cardiac conduction, including the supraventricular component of the ECG, is currently under discussion. The objective of the research is to analyze ECG parameters of the atrial complex and atrioventricular conduction and to assess their relationship with spirometric indicators in children with BA. Methods: Hundred three patients with BA from the age of 6–17 years were examined. The spirometric parameters were evaluated, including the Tiffeneau index (TI): FEV1/FVC (%), according to the level of which the patient groups were distinguished. Group 1 (G1): with TI more than 85%, (n = 15); Group 2 (G2): with TI from 85 to 75%, (n = 40); Group 3 (G3): with TI <75%, (n = 48). The ECG parameters that characterize supraventricular conduction, including the PQ interval (sec) and the sPQ segment (sec), were analyzed. We had calculated relative PQ (rPQ) by the formula rPQ=PQ/PQmed, where PQ is the patient's PQ, PQmed are the median PQ values of healthy children of age selected. Results: The duration of the PQ in groups G1 and G2 was 0.13 (0.11; 0.14) s; and 0.13 (0.12; 0.14) s, respectively, which is statistically significantly less than in patients of groups G3–0.14 (0.13; 0.15] s, p = 0.01. The duration of the sPQ segment in children of groups G1 and G2 was also generally shorter than in patients of groups G3, and amounted, respectively, to 0.05 (0.04; 0.06) s, 0.04 (0.04; 0.05) s, and 0.06 (0.04; 0.07) s, p = 0.02. The rPQ increased progressively as TI decreased and amounted in G1 to 92.9 (85.7; 106.3) %, in G2 100.0 (92.9; 103.0) %, and in G3 104 (100.0; 107.7) %, p = 0.009. A statistically significant negative correlation between IT and PQ–r = ?0.23, p = 0.02; with sPQ–r = ?0.20, p = 0.045; and with rPQ–r = ?0.25, p = 0.01 was revealed. Conclusion: A decrease in TI in asthmatics children is associated with a prolongation of the PQ. This may indicate a slowdown in supraventricular conduction in patients with uncontrolled asthma and, thus, be considered as a risk for the formation of subsequent supraventricular arrhythmias.
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Project description:BackgroundBoth anti-viral and anti-inflammatory bronchial effects are warranted to treat viral infections in asthma. We sought to investigate if imiquimod, a TLR7 agonist, exhibits such dual actions in ex vivo cultured human bronchial epithelial cells (HBECs), targets for SARS-CoV-2 infectivity.ObjectiveTo investigate bronchial epithelial effects of imiquimod of potential importance for anti-viral treatment in asthmatic patients.MethodsEffects of imiquimod alone were examined in HBECs from healthy (N=4) and asthmatic (N=18) donors. Mimicking SARS-CoV-2 infection, HBECs were stimulated with poly(I:C), a dsRNA analogue, or SARS-CoV-2 spike-protein 1 (SP1; receptor binding) with and without imiquimod treatment. Expression of SARS-CoV-2 receptor (ACE2), pro-inflammatory and anti-viral cytokines were analyzed by RT-qPCR, multiplex ELISA, western blot, and Nanostring and proteomic analyses.ResultsImiquimod reduced ACE2 expression at baseline and after poly(I:C) stimulation. Imiquimod also reduced poly(I:C)-induced pro-inflammatory cytokines including IL-1β, IL-6, IL-8, and IL-33. Furthermore, imiquimod increased IFN-β expression, an effect potentiated in presence of poly(I:C) or SP1. Multiplex mRNA analysis verified enrichment in type-I IFN signaling concomitant with suppression of cytokine signaling pathways induced by imiquimod in presence of poly(I:C). Exploratory proteomic analyses revealed potentially protective effects of imiquimod on infections.ConclusionImiquimod triggers viral resistance mechanisms in HBECs by decreasing ACE2 and increasing IFN-β expression. Additionally, imiquimod improves viral infection tolerance by reducing viral stimulus-induced epithelial cytokines involved in severe COVID-19 infection. Our imiquimod data highlight feasibility of producing pluripotent drugs potentially suited for anti-viral treatment in asthmatic subjects.
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