Chronic obstructive pulmonary disease (COPD) is a severely disabling chronic lung disease characterized by persistent airway inflammation, which leads to limited expiratory airflow that deteriorates over time. Isorhamnetin (Iso) is one of the most important active components in the fruit of Hippophae rhamnoides L. and leaves of Ginkgo biloba L, which is widely used in many pulmonary disease studies because of its anti-inflammatory effects. Here, we investigated the pharmacological action of Iso in CS-induced airway inflammation and dissected the anti-inflammation mechanisms of Iso in COPD mice. A mouse model of COPD was established by exposure to cigarette smoke (CS) and intratracheal inhalation of lipopolysaccharide (LPS). Our results illustrated that Iso treatment significantly reduced leukocyte recruitment and excessive secretion of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation, normal T-cell expressed and secreted (RANTES) in BALF of CS-induced COPD mice in a dose-dependent manner. This improved airway collagen deposition and emphysema, and further alleviated the decline in lung functions and systemic symptoms of hypoxia and weight loss. Additionally, Iso treatment obviously improves the T lymphocyte dysregualtion in peripheral blood of COPD mice. Mechanistically, Iso may degrade Keap1 through ubiquitination of p62, thereby activating the nuclear factor erythroid 2-related factor (Nrf2) pathway to increase the expression of protective factors, such as heme oxygenase-1 (HO-1), superoxide dismutase (SOD) 1, and SOD2, in lungs of CS-exposed mice, which plays an anti-inflammatory role in COPD. In conclusion, our study indicates that Iso significantly alleviates the inflammatory response in CS-induced COPD mice mainly by affecting the Nrf2/Keap1 pathway. More importantly, Iso exhibited anti-inflammatory effects comparable with Dex in COPD and we did not observe discernible side effects of Iso. The high safety profile of Iso may make it a potential drug candidate for COPD.
Background: Balloon dilation is a primary treatment for nonmalignant tracheobronchial stenosis, but often requires multiple treatment sessions to maintain therapeutic efficacy. No guideline is available to suggest the appropriate maximum number of treatment sessions. This study aimed to investigate the relationship between the number of balloon dilation sessions and its long-term therapeutic effectiveness in Chinese patients with nonmalignant central airway stenosis. Methods: A total of 111 patients with nonmalignant central airway stenosis treated with flexible bronchoscopic balloon dilation from January 2005 to September 2012 were included. The cumulative long-term effective rate was compared between any two adjacent sessions of balloon dilation treatment by McNemar’s test. Multivariate Cox regression was performed to investigate the independent factors associated with long-term effectiveness. Results: The cumulative long-term effective rate was significantly increased between any two adjacent sessions before the 6th session of treatment (all p < 0.05) but was no longer significantly increased after the 6th session. The stenosis diameter was larger in the patients receiving ⩽6 treatment sessions than those receiving ⩾6 treatment sessions. Multivariate Cox regression showed that the treatment session was an independent factor associated with long-term effectiveness (hazard ratio = 0.65, 95% confidence interval: 0.57–0.76, p < 0.001). Conclusion: These results suggest that the maximum number of treatment sessions of balloon dilation may be six, and patients requiring more treatment sessions were more likely to have delayed long-term effectiveness.
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