Abstract
BackgroundBronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes.MethodsEndobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining.ResultsIn all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034).In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes.ConclusionsBronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.
Highlights
Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma
Bronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium
Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes
Summary
Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. Bronchial thermoplasty is a non-pharmacological treatment for severe asthma It is based on selective heating of the airways using a bronchoscope-inserted catheter that ends in 4 electrodes and generates a temperature of 65 °C for 10 s [2]. Integrated in vitro and in silico modelling suggested that the reduction in airway smooth muscle cells (ASMC) after bronchial thermoplasty cannot be fully explained by acute heating and it could not confer the great improvement in asthma control [5]. Tο this end, it was suggested that the heat energy that is produced during bronchial thermoplasty can alter airway structural components other than ASMC that are involved in airway narrowing and bronchial reactivity such as neuroendocrine epithelial cells and nerve endings [6]. Histological analysis of endobronchial biopsies is an important tool to ascertain the constitution of the epithelial and mesenchymal bronchial compartments that may reflect underlying inflammatory processes (endotypes) which translate in diverse clinical presentations (phenotypes) [7, 8]
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