Abstract
Rationale We previously demonstrated increased expression of programmed cell death 5 (PDCD5) in asthmatic patients and ovalbumin-induced allergic asthma. International guidelines (GINA 2019) have included the use of tiotropium bromide for chronic treatment of the most severe and frequently exacerbated asthma in patients ≥6 years old, who do not have good response to inhaled corticosteroids. Objective To explore the role of tiotropium and its effect on PDCD5 level in a mouse model of chronic asthma. Methods We divided 12 female mice into 2 groups: untreated asthma (n = 6) and tiotropium-treated asthma (n = 6). The impact of tiotropium was assessed by histology of lung tissue and morphometry. Pulmonary function was tested by using pressure sensors. The number of cells in bronchoalveolar lavage fluid (BALF) was detected. Levels of PDCD5, active caspase-3, and muscarinic acetylcholine receptors M2 (ChRM2) and M3 (ChRM3) were examined. Results Tiotropium treatment significantly reduced airway inflammation and remodeling in asthmatic mice and intensified the lung function. PDCD5 level was reduced with tiotropium (p < 0.05). Moreover, active caspase-3 level was decreased with tiotropium (p < 0.001), and ChRM3 level was increased. Conclusions Tiotropium treatment may alleviate the pathological changes with asthma by regulating apoptosis.
Highlights
Allergic asthma is a major health concern worldwide, with chronic inflammatory disorder of the airways and airway remodeling
Periodic acid-Schiff staining (PAS) and Masson’s trichrome staining (Masson) kits were from Shanghai Yuanye Bio-Technology. e home-made mouse anti-programmed cell death 5 (PDCD5) monoclonal antibody and the PDCD5 ELISA kit were gifts from Prof
Tiotropium treatment enhanced peak inspiratory flow (PIF) from 2.26 ± 0.03 L/s in the untreated asthma group to 2.29 ± 0.01 L/s in the tiotropium-treated asthma group and peak expiratory flow (PEF) from 4.66 ± 0.04 L/ s to 4.80 ± 0.12 L/s (p < 0.05). e intra-airway pressure (IP) slope decreased from 96.02 ± 3.69 mmHg/s in untreated asthmatic mice to 74.90 ± 4.90 mmHg/s in tiotropium-treated asthmatic mice (p < 0.001) (Table 1)
Summary
Allergic asthma is a major health concern worldwide, with chronic inflammatory disorder of the airways and airway remodeling. Airway remodeling can lead to irreversible airflow limitation and accelerate lung function decline [1]. Despite advances in the pathogenesis and therapeutics for asthma, for some patients, the disease remains uncontrolled without good response to inhaled corticosteroids. Novel treatment strategies need to be explored. Tiotropium bromide (tiotropium), a selective long-acting, muscarinic acetylcholine receptor (mAChR) antagonist, is important for treating chronic obstructive pulmonary disease (COPD). Anticholinergic drugs relax airway smooth muscle by blocking mAChRs in the airway and are considered an alternative bronchodilator therapeutic option for asthma. Clinical evidence revealed that tiotropium can reduce severe asthma relapse [2].
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