Effect of Tiotropium Bromide on Airway Inflammation and Programmed Cell Death 5 in a Mouse Model of Ovalbumin-Induced Allergic Asthma
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Abstract:
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.To explore the role of tiotropium and its effect on PDCD5 level in a mouse model of chronic asthma.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.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.Tiotropium treatment may alleviate the pathological changes with asthma by regulating apoptosis.Keywords:
Tiotropium bromide
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目的:观察吸入噻托嗅铵在稳定期慢性阻塞性肺病(COPD)的临床疗效.方法:将我院2009年1月-2010年12月就诊的确诊稳定期COPD患者60例,随机分为治疗组和对照组.对照组给予常规综合治疗,治疗组在此基础上给予吸入噻托嗅铵.结果:与治疗前相比,噻托溴铵组病人第1 s用力呼气容积(FEV1)和用力肺活量(FVC)均显著增加(P<0.05);治疗1年时,噻托溴铵组病人FEv1谷值明显上升(P<0...
Tiotropium bromide
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Objective To observe the levels of Th17 associated inflammatory factor IL-17 and Treg associated inflammatory factor IL-10 in serum and bronchoalveolar lavage fluid (BALF) of bronchial asthma mice, and to explore the mechanism of Jian'erle Granule (JG) for preventing and treating asth- ma. Methods Totally 40 Balb/c mice were divided into 4 groups according to random digit table, i.e., the normal control group, the asthma group, the post-excitation asthma group, the JG +asthma group, 10 in each group. Asthma model was established by 1% ovalbumin (OVA) (grade V) solution sensitization and excitation after intraperitoneal injection of antigen suspension in all groups except the normal control group. JG (0. 36 g/mL) was administrated to mice in the JG +asthma group after modeling. Equal volume of normal saline was administrated to mice in the rest 3 groups. All medication lasted for 14 successive days. After medication mice in the JG +asthma group and the asthma group were excited with 1% OVA (grade I) again for 40 min by atomization inhalation. Lung inflammation was examined by HE staining. Levels of IL-10 and IL-17 in BALF and serum were measured by ELISA. Results Bronchial structure in lung tissue was normal in mice of the normal control group, with no inflammatory infiltration seen. Mucosal epithelial cells of bronchial wall were injured in the asthma group and the post-excitation asthma group, with inflammatory infiltration seen. Inflammation around bronchus and blood vessels was obviously attenuated in the JG+asthma group. Compared with the normal control group,the IL-17 level in serum and BALF significantly increased, IL-10 level significantly decreased in the asthma group (P <0.01). Compared with the asthma group, IL-17 level in serum and BALF increased and IL-10 level in serum and BALF decreased in the post-excitation asthma group (P <0.01). Compared with the asthma group, the IL-17 level in serum and BALF significantly decreased, IL-10 level significantly increased in the JG +asth- ma group (P <0. 01). Compared with the post-excitation.asthma group,the IL-17 level in serun and BALF significantly decreased and IL-10 level in serum and BALF significantly increased in the JG + asthma group (P <0. 01). Conclusion The mechanism for JG preventing and treating asthma might be correla- ted with regulating Th17/Treg cytokine balance in serum and BALF.
Intraperitoneal injection
Cellular infiltration
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Intraperitoneal injection
Aerosolization
Infiltration (HVAC)
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Background: Wheezing in infants and children is a common problem presented to primary care offices.Approximately 25 to 30 percent of infants will have at least one episode of wheezing.By three years of age, an episode of wheezing will have occurred in 40 percent of children, and by six years of age, almost one half of children will have at least one episode of wheezing.Most infants and children with recurrent wheezing have asthma, but other causes should be considered in the differential diagnosis.The most common diagnoses in children with persistent wheezing are asthma, allergies, gastroesophageal reflux, infections, foreign body aspiration and bronchopulmonary dysplasia.Objective: the present study was designed to evaluate the clinical role of different types of bronchoscope and bronchoalveolar lavage in diagnosis of undefined persistent wheezy chest among the age group from 6 months to 14 years, at Al-Azhar University Hospitals in Cairo.Patients and Methods: This a prospective study was conducted on 50 children complaining from different respiratory problems who had enrolled consecutively from the Outpatient Clinic and the Inpatient Pediatric Department of Al-Azhar Faculty of Medicine University Hospitals (AL-Hussein and Bab-Elshareya), from January 2017 to December 2018.Patients ages ranged between 6 months and 14 years.Results: as regard distribution of patients according to post bronchoscopy diagnosis, the study showed that foreign body inhalation n16 (32%), Chronic aspiration n9 (18%), tracheobronchomalacia n2 (4%), bronchial mass n1 (2%), streptococcus pneumonia n7 (14%), hemophilus influenza n2 (4%), staphylococcus aureus n3 (6%) and pseudomonas aeuroginosa n2 (4%), candida albicans n1 (2%), Mycobacterium TB n1 (2%).Conclusion: It could be concluded that if radiography is normal and the child continues to wheeze, bronchoscopy should be the next step, the bronchoscope is a valuable tool in the diagnosis and treatment of airway disorders in children.It has a good safety profile with rarely reported life threatening or long-standing complications.
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Methacholine
Allergic Inflammation
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Inflammatory effects in the rat lung have been investigated, non-invasively by MRI, at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (LPS) challenges. Six hours after challenge with OA, a strong, even inflammatory signal was present around the periphery of the lung in a region corresponding to the pleura. Histological analysis confirmed the presence of marked edema associated with the pleural cavity of OA-treated animals. Lower levels of pleural edema were observed in MRI and histological evaluation of LPS-treated animals and no abnormality was observed in actively sensitized and naïve, saline-treated groups. Diffuse edematous signals were detected in the lung 3 and 6 h after challenge with OA or LPS; the signal volumes were larger at both time points following OA instillation. Bronchoalveolar lavage (BAL) fluid analysis performed 6 h after challenge revealed increased levels of protein and greater cellular activation in OA- than in LPS-treated animals. Furthermore, increased levels of peribronchial edema were found by histology 6 h after OA. BAL fluid and histological assessments demonstrated that the inflammatory signals were due to edema and not mucus as no significant changes in BAL mucin concentrations or differences in goblet cells were identified between OA or LPS challenge and their respective vehicle groups. Our data show that MRI is able to detect, non-invasively, inflammatory signals in both the lung and the pleura in spontaneously breathing animals, highlighting its potential to study the consequences of pulmonary insults on both sites.
Histology
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