Pub Date : 2025-01-30DOI: 10.1016/j.pupt.2025.102344
Wei Du , Yuqing Ouyang , Xiaofan Feng , Chunyan Yu, Haoke Zhang, Siqi Chen, Zixuan Liu, Bo Wang, Xueying Li, Zihe Liu, Weimin Deng
Metabolic reprogramming in tumor cells plays a crucial role in promoting cell proliferation and metastasis, and is currently recognized as a significant marker of tumor progression. Interleukin-10 receptor subunit alpha (IL-10RA), a member of the type II cytokine receptor family, is predominantly expressed on macrophages and T cells and plays a crucial role in regulating immune cell metabolism and immune response. However, its role in the energy metabolic pathways of tumor cells remains unclear. In this study, we found increased expression of IL-10RA in human non-small cell lung cancer (NSCLC), and a correlation between increased IL-10RA expression and tumor stage, tumor size, and short overall survival of patients with NSCLC. IL-10RA overexpression significantly promoted the proliferation of NSCLC cell lines and enhanced glycolysis and fatty acid oxidation (FAO), thereby boosting energy production. Correspondingly, the downregulation of IL-10RA inhibited proliferation, glycolysis, and FAO in NSCLC cell lines. Bioinformatic analyses indicated that IL-10RA upregulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. STAT3 inhibitor effectively blocked the increase in FAO levels and cell proliferation induced by IL-10RA overexpression. These findings suggest that IL-10RA accelerates NSCLC cell proliferation by increasing FAO levels via the STAT3 pathway, highlighting IL-10RA as a potential therapeutic target for NSCLC.
{"title":"IL-10RA promotes lung cancer cell proliferation by increasing fatty acid oxidation via STAT3 signaling pathway","authors":"Wei Du , Yuqing Ouyang , Xiaofan Feng , Chunyan Yu, Haoke Zhang, Siqi Chen, Zixuan Liu, Bo Wang, Xueying Li, Zihe Liu, Weimin Deng","doi":"10.1016/j.pupt.2025.102344","DOIUrl":"10.1016/j.pupt.2025.102344","url":null,"abstract":"<div><div>Metabolic reprogramming in tumor cells plays a crucial role in promoting cell proliferation and metastasis, and is currently recognized as a significant marker of tumor progression. Interleukin-10 receptor subunit alpha (IL-10RA), a member of the type II cytokine receptor family, is predominantly expressed on macrophages and T cells and plays a crucial role in regulating immune cell metabolism and immune response. However, its role in the energy metabolic pathways of tumor cells remains unclear. In this study, we found increased expression of IL-10RA in human non-small cell lung cancer (NSCLC), and a correlation between increased IL-10RA expression and tumor stage, tumor size, and short overall survival of patients with NSCLC. IL-10RA overexpression significantly promoted the proliferation of NSCLC cell lines and enhanced glycolysis and fatty acid oxidation (FAO), thereby boosting energy production. Correspondingly, the downregulation of IL-10RA inhibited proliferation, glycolysis, and FAO in NSCLC cell lines. Bioinformatic analyses indicated that IL-10RA upregulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. STAT3 inhibitor effectively blocked the increase in FAO levels and cell proliferation induced by IL-10RA overexpression. These findings suggest that IL-10RA accelerates NSCLC cell proliferation by increasing FAO levels via the STAT3 pathway, highlighting IL-10RA as a potential therapeutic target for NSCLC.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102344"},"PeriodicalIF":3.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-19DOI: 10.1016/j.pupt.2024.102343
Elena Pistocchini, Alicia Maria Carrillo Heredero, Melissa Mazan, Laurent Couetil, Simone Bertini, Luigino Calzetta
{"title":"Corrigendum to \"Clinical efficacy of inhaled corticosteroids in equine asthma: A meta-analysis and number needed to treat\" [Pulm. Pharmacol. Therapeut. (88), March 2025, 102342].","authors":"Elena Pistocchini, Alicia Maria Carrillo Heredero, Melissa Mazan, Laurent Couetil, Simone Bertini, Luigino Calzetta","doi":"10.1016/j.pupt.2024.102343","DOIUrl":"https://doi.org/10.1016/j.pupt.2024.102343","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":" ","pages":"102343"},"PeriodicalIF":3.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1016/j.pupt.2024.102342
Elena Pistocchini , Alicia Maria Carrillo Heredero , Melissa Mazan , Laurent Couetil , Simone Bertini , Luigino Calzetta
Equine asthma, a prevalent chronic inflammatory condition affecting the equine population, significantly compromises the performance and quality of life in affected horses. Inhaled corticosteroids (ICS) are often the first-line pharmacological intervention due to their potent anti-inflammatory properties. This meta-analysis investigates the clinical efficacy of ICS in treating equine asthma, emphasizing the number needed to treat (NNT) and the likelihood of achieving a clinical response. A comprehensive literature search identified relevant studies comparing ICS with placebo (PCB) controlled treatments. Data were synthesized from four clinical trials involving 252 asthmatic horses. Results indicate an overall NNT of 3.2 (95 % CI 2.3–4.7), meaning that approximately three horses must be treated with ICS for one to achieve a significant clinical response. Additionally, the relative risk of achieving clinical improvement with ICS versus PCB was 1.73 (95 % CI 1.47–2.02), demonstrating a marked increase in therapeutic effectiveness. Subgroup analysis revealed an NNT of 3.0 for severe cases, underscoring the efficacy of ICS across different severity levels. Despite potential biases noted in some studies, sensitivity analyses confirmed the robustness of these findings. The GRADE assessment rated the quality of evidence as high. These results highlight the therapeutic value of ICS in managing equine asthma, providing evidence-based recommendations for their clinical use. Future research should explore long-term outcomes and potential synergistic effects of ICS combined with other treatments to enhance clinical efficacy in managing equine asthma.
马哮喘是一种影响马群的普遍慢性炎症性疾病，严重影响马的表现和生活质量。吸入皮质类固醇（ICS）通常是第一线的药物干预，由于其有效的抗炎特性。本荟萃分析调查了ICS治疗马哮喘的临床疗效，强调了治疗所需的数量（NNT）和实现临床反应的可能性。综合文献检索确定了比较ICS与安慰剂（PCB）对照治疗的相关研究。数据来自252匹哮喘马的四项临床试验。结果显示总体NNT为3.2 (95% CI 2.3 - 4.7)，这意味着大约三匹马必须接受ICS治疗才能获得显著的临床反应。此外，ICS与PCB实现临床改善的相对风险为1.73 (95% CI 1.47-2.02)，表明治疗效果显着提高。亚组分析显示，重症病例的NNT为3.0，强调了ICS在不同严重程度上的疗效。尽管在一些研究中指出了潜在的偏差，但敏感性分析证实了这些发现的稳健性。GRADE评估将证据质量评为高。这些结果突出了ICS在治疗马哮喘方面的治疗价值，为其临床应用提供了循证建议。未来的研究应探索ICS联合其他治疗方法的长期疗效和潜在的协同效应，以提高治疗马哮喘的临床疗效。
{"title":"Clinical efficacy of inhaled corticosteroids in equine asthma: A meta-analysis and number needed to treat","authors":"Elena Pistocchini , Alicia Maria Carrillo Heredero , Melissa Mazan , Laurent Couetil , Simone Bertini , Luigino Calzetta","doi":"10.1016/j.pupt.2024.102342","DOIUrl":"10.1016/j.pupt.2024.102342","url":null,"abstract":"<div><div>Equine asthma, a prevalent chronic inflammatory condition affecting the equine population, significantly compromises the performance and quality of life in affected horses. Inhaled corticosteroids (ICS) are often the first-line pharmacological intervention due to their potent anti-inflammatory properties. This meta-analysis investigates the clinical efficacy of ICS in treating equine asthma, emphasizing the number needed to treat (NNT) and the likelihood of achieving a clinical response. A comprehensive literature search identified relevant studies comparing ICS with placebo (PCB) controlled treatments. Data were synthesized from four clinical trials involving 252 asthmatic horses. Results indicate an overall NNT of 3.2 (95 % CI 2.3–4.7), meaning that approximately three horses must be treated with ICS for one to achieve a significant clinical response. Additionally, the relative risk of achieving clinical improvement with ICS versus PCB was 1.73 (95 % CI 1.47–2.02), demonstrating a marked increase in therapeutic effectiveness. Subgroup analysis revealed an NNT of 3.0 for severe cases, underscoring the efficacy of ICS across different severity levels. Despite potential biases noted in some studies, sensitivity analyses confirmed the robustness of these findings. The GRADE assessment rated the quality of evidence as high. These results highlight the therapeutic value of ICS in managing equine asthma, providing evidence-based recommendations for their clinical use. Future research should explore long-term outcomes and potential synergistic effects of ICS combined with other treatments to enhance clinical efficacy in managing equine asthma.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"88 ","pages":"Article 102342"},"PeriodicalIF":3.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pupt.2024.102334
Enping Li , Jianliang Huang , Jiale Huang , Fuying Zhang , Chengyou Li , Mingkai Xia , Zhuo Li , Bo Peng , Ying Liu , Jinan Ma , Mingsheng Lei
Radiation-induced lung injury is a significant complication of thoracic malignant tumor radiotherapy, yet effective treatments remain scarce. Aldehyde dehydrogenase 2 (ALDH2) possesses antioxidant and anti-inflammatory properties, but its specific role in radiation-induced lung injury is not well understood. This study aimed to investigate the impact of ALDH2 on radiation-induced lung injury and elucidate the underlying mechanisms. Through analysis of radiation-induced lung injury datasets, intervention with ALDH2 agonists and inhibitors in an in vivo radiation-induced lung injury model, and establishment of an in vitro radiation-induced lung injury model using A549 stable cells with varying ALDH2 expressions, we discovered that ALDH2 expression is reduced in radiation-induced lung injury. Enrichment analysis suggested that ALDH2 may mitigate radiation-induced lung injury by modulating oxidative stress and inflammation levels. Additionally, single-cell data analysis reveals that ALDH2 is primarily localized in myeloid macrophages within the lungs, with its expression also being reduced in lung cancer patients. Subsequent examination of mouse pathological sections, reactive oxygen species (ROS), and inflammatory factor levels confirmed that ALDH2 can lessen radiation-induced lung injury by suppressing ROS and inflammatory factors. Both in vivo and in vitro Western blot analysis further validated that ALDH2 can attenuate epithelial-mesenchymal transition and inhibit the TGF-β1/Smad pathway. Therefore, ALDH2 shows promise in reducing radiation-induced lung injury by inhibiting ROS and TGF-mediated epithelial-mesenchymal transition, making it a potential target for the treatment of radiation-induced lung injury.
{"title":"ALDH2 attenuates radiation-induced lung injury by inhibiting ROS and epithelial-mesenchymal transition mediated by the TGF-β1/Smad pathway","authors":"Enping Li , Jianliang Huang , Jiale Huang , Fuying Zhang , Chengyou Li , Mingkai Xia , Zhuo Li , Bo Peng , Ying Liu , Jinan Ma , Mingsheng Lei","doi":"10.1016/j.pupt.2024.102334","DOIUrl":"10.1016/j.pupt.2024.102334","url":null,"abstract":"<div><div>Radiation-induced lung injury is a significant complication of thoracic malignant tumor radiotherapy, yet effective treatments remain scarce. Aldehyde dehydrogenase 2 (ALDH2) possesses antioxidant and anti-inflammatory properties, but its specific role in radiation-induced lung injury is not well understood. This study aimed to investigate the impact of ALDH2 on radiation-induced lung injury and elucidate the underlying mechanisms. Through analysis of radiation-induced lung injury datasets, intervention with ALDH2 agonists and inhibitors in an in vivo radiation-induced lung injury model, and establishment of an in vitro radiation-induced lung injury model using A549 stable cells with varying ALDH2 expressions, we discovered that ALDH2 expression is reduced in radiation-induced lung injury. Enrichment analysis suggested that ALDH2 may mitigate radiation-induced lung injury by modulating oxidative stress and inflammation levels. Additionally, single-cell data analysis reveals that ALDH2 is primarily localized in myeloid macrophages within the lungs, with its expression also being reduced in lung cancer patients. Subsequent examination of mouse pathological sections, reactive oxygen species (ROS), and inflammatory factor levels confirmed that ALDH2 can lessen radiation-induced lung injury by suppressing ROS and inflammatory factors. Both in vivo and in vitro Western blot analysis further validated that ALDH2 can attenuate epithelial-mesenchymal transition and inhibit the TGF-β1/Smad pathway. Therefore, ALDH2 shows promise in reducing radiation-induced lung injury by inhibiting ROS and TGF-mediated epithelial-mesenchymal transition, making it a potential target for the treatment of radiation-induced lung injury.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102334"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pupt.2024.102333
D. Bagnasco , I. Ansotegui , I. Baiardini , A. Benfante , J.A. Bernstein , A. Bikov , B. Bondi , L.P. Boulet , C. Panaitescu , G.W. Canonica , H. Chong-Neto , L. Dubuske , R. El-Owaidy , M. Ferraris , M. Filipovic , F.J. Gonzalez-Barcala , G. Guidos Fogelbach , J.C. Ivancevich , E. Jusufovic , K. Kowal , F. Braido
Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma.
With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians. The questionnaire has been distributed through Interasma social media between June and September 2023.
Besides a descriptive analysis, to assess the responses gathered from the questionnaire, Spearman's non-parametric statistical method was employed.
Totally, three hundred fourteen questionnaires were completed. Clinicians' attitudes and behaviours toward timing and methodologies adopted in prescribing ITT, were analysed. 35.7 % specialists consider ITT as a relevant therapeutic option, 61.8 % that is second option after reaching high dose of ICS-LABA and 89.2 % agreed that optimization of inhaled therapy should be attempted before the use of biological drugs. Persistent flow limitation and high reversibility are considered predictive factors of response.
Specialists consider ITT a resource in asthma management. Although its efficacy in decreasing exacerbation rate and improving lung function were well known, the survey revealed persistent uncertainties among clinicians in positioning it highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice.
GINA 报告建议，长效毒蕈碱拮抗剂（LAMA）与吸入皮质类固醇（ICS）加长效β-2 受体激动剂（LABA）联合使用，作为第 4 步治疗的进一步选择和第 5 步治疗的首选。尽管吸入三联疗法（ITT）的疗效和安全性得到了一致的证明，但仍未在哮喘患者中得到广泛应用。为了探索哮喘专科医生的信念和行为，Interasma 科学网络（INESnet）专家小组制定了一项特别调查，随后在国际医生小组中进行了两轮德尔菲调查。调查问卷已于 2023 年 6 月至 9 月间通过 Interasma 社交媒体发布。除了描述性分析外，还采用了斯皮尔曼非参数统计方法来评估从问卷中收集到的答复。总共完成了 34 份问卷。调查分析了临床医生对开具 ITT 处方的时间和方法的态度和行为。35.7%的专家认为 ITT 是一种相关的治疗选择，61.8%的专家认为 ITT 是在使用大剂量 ICS-LABA 后的第二种选择，89.2%的专家同意在使用生物药物前应尝试优化吸入疗法。持续性血流受限和高可逆性被认为是预测反应的因素。专家认为 ITT 是哮喘治疗的一种资源。虽然 ITT 在降低哮喘加重率和改善肺功能方面的疗效众所周知，但调查显示临床医生对 ITT 的定位一直存在不确定性，这突出表明有必要采取进一步措施，将研究成果有效融入日常临床实践中。
{"title":"Triple inhaled therapy in asthma: Beliefs, behaviours and doubts","authors":"D. Bagnasco , I. Ansotegui , I. Baiardini , A. Benfante , J.A. Bernstein , A. Bikov , B. Bondi , L.P. Boulet , C. Panaitescu , G.W. Canonica , H. Chong-Neto , L. Dubuske , R. El-Owaidy , M. Ferraris , M. Filipovic , F.J. Gonzalez-Barcala , G. Guidos Fogelbach , J.C. Ivancevich , E. Jusufovic , K. Kowal , F. Braido","doi":"10.1016/j.pupt.2024.102333","DOIUrl":"10.1016/j.pupt.2024.102333","url":null,"abstract":"<div><div>Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma.</div><div>With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians. The questionnaire has been distributed through Interasma social media between June and September 2023.</div><div>Besides a descriptive analysis, to assess the responses gathered from the questionnaire, Spearman's non-parametric statistical method was employed.</div><div>Totally, three hundred fourteen questionnaires were completed. Clinicians' attitudes and behaviours toward timing and methodologies adopted in prescribing ITT, were analysed. 35.7 % specialists consider ITT as a relevant therapeutic option, 61.8 % that is second option after reaching high dose of ICS-LABA and 89.2 % agreed that optimization of inhaled therapy should be attempted before the use of biological drugs. Persistent flow limitation and high reversibility are considered predictive factors of response.</div><div>Specialists consider ITT a resource in asthma management. Although its efficacy in decreasing exacerbation rate and improving lung function were well known, the survey revealed persistent uncertainties among clinicians in positioning it highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102333"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1016/j.pupt.2024.102332
Hyun Woo Lee , Jung-Kyu Lee , Youlim Kim , June Hong Ahn , Chang Youl Lee , Yong Bum Park , Hyoung Kyu Yoon , Ji Ye Jung , Kwang Ha Yoo , Deog Kyeom Kim
Background
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation. This study investigates the prevalence and clinical significance of pre-bronchodilator (PREO) and post-bronchodilator (POSTO) airflow obstruction in COPD.
Methods
This retrospective cohort study analyzed data from 3252 COPD patients aged ≥40 years, registered from January 2012 to December 2019 at 54 medical centers in South Korea. Patients were categorized into three groups: PREO & post-bronchodilator non-obstruction (POSTN), pre-bronchodilator non-obstruction (PREN) & POSTO, and PREO & POSTO. The primary outcome was moderate-to-severe exacerbation over 3 years. Secondary outcomes included GOLD group progression and rapid FEV₁ decline.
Results
The majority of patients (96.2 %) were in the PREO & POSTO group, with smaller proportions in the PREO & POSTN (2.8 %) and PREN & POSTO (1.0 %) groups. During the 3-year observation, 21.6 % of patients experienced moderate-to-severe exacerbations, 6.2 % exhibited GOLD group progression, and 20.0 % showed rapid FEV₁ decline. The PREO & POSTO group had a higher risk of exacerbations compared to the PREO & POSTN group (odds ratio = 8.33 [95 % CI = 1.53–45.4], P-value = 0.014), but this was not statistically significant in multivariable analysis. Post-bronchodilator spirometry patterns did not significantly impact GOLD group progression or FEV₁ decline.
Conclusion
PREO & POSTO was common among COPD patients, while isolated PREO & POSTN was rare, supportingpre-bronchodilator spirometry as a screening tool. Although patients with PREO & POSTO showed higher exacerbation risks in univariable analysis, statistical significance disappeared after adjustment. GOLD group progression or FEV₁ decline did not significantly differ by post-bronchodilator spirometry patterns.
背景：慢性阻塞性肺疾病（COPD）是一种以持续气流受限为特征的进行性呼吸系统疾病。本研究探讨了慢性阻塞性肺疾病患者支气管扩张剂前（PREO）和支气管扩张剂后（POSTO）气流阻塞的患病率和临床意义：这项回顾性队列研究分析了2012年1月至2019年12月期间在韩国54家医疗中心登记的3252名年龄≥40岁的慢性阻塞性肺病患者的数据。患者被分为三组：PREO 和支气管扩张剂后无阻塞（POSTN）组、支气管扩张剂前无阻塞（PREN）和 POSTO 组以及 PREO 和 POSTO 组。主要结果是 3 年内中度至重度病情加重。次要结果包括 GOLD 组进展和 FEV₁ 快速下降：大多数患者（96.2%）属于 PREO & POSTO 组，PREO & POSTN 组（2.8%）和 PREN & POSTO 组（1.0%）所占比例较小。在 3 年的观察期间，21.6% 的患者出现中度至重度病情加重，6.2% 的患者出现 GOLD 组进展，20.0% 的患者出现 FEV₁ 快速下降。与 PREO & POSTN 组相比，PEO & POSTO 组的病情加重风险更高（几率比=8.33 [95% CI=1.53-45.4]，P 值=0.014），但在多变量分析中并无统计学意义。支气管扩张剂后肺活量测量模式对 GOLD 组的进展或 FEV₁ 下降没有显著影响：PREO和POSTO在慢性阻塞性肺病患者中很常见，而孤立的PREO和POSTN则很少见，这支持将支气管扩张前肺活量测定作为一种筛查工具。虽然在单变量分析中，PEO & POSTO 患者的病情恶化风险较高，但经过调整后，统计学意义消失了。GOLD组的进展或FEV₁的下降在支气管舒张术后肺活量测量模式上没有显著差异。
{"title":"Prevalence and clinical significance of pre- and post-bronchodilator airflow obstruction in COPD patients","authors":"Hyun Woo Lee , Jung-Kyu Lee , Youlim Kim , June Hong Ahn , Chang Youl Lee , Yong Bum Park , Hyoung Kyu Yoon , Ji Ye Jung , Kwang Ha Yoo , Deog Kyeom Kim","doi":"10.1016/j.pupt.2024.102332","DOIUrl":"10.1016/j.pupt.2024.102332","url":null,"abstract":"<div><h3>Background</h3><div>Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation. This study investigates the prevalence and clinical significance of pre-bronchodilator (PREO) and post-bronchodilator (POSTO) airflow obstruction in COPD.</div></div><div><h3>Methods</h3><div>This retrospective cohort study analyzed data from 3252 COPD patients aged ≥40 years, registered from January 2012 to December 2019 at 54 medical centers in South Korea. Patients were categorized into three groups: PREO & post-bronchodilator non-obstruction (POSTN), pre-bronchodilator non-obstruction (PREN) & POSTO, and PREO & POSTO. The primary outcome was moderate-to-severe exacerbation over 3 years. Secondary outcomes included GOLD group progression and rapid FEV₁ decline.</div></div><div><h3>Results</h3><div>The majority of patients (96.2 %) were in the PREO & POSTO group, with smaller proportions in the PREO & POSTN (2.8 %) and PREN & POSTO (1.0 %) groups. During the 3-year observation, 21.6 % of patients experienced moderate-to-severe exacerbations, 6.2 % exhibited GOLD group progression, and 20.0 % showed rapid FEV₁ decline. The PREO & POSTO group had a higher risk of exacerbations compared to the PREO & POSTN group (odds ratio = 8.33 [95 % CI = 1.53–45.4], <u>P-value = 0.014</u>), but this was not statistically significant in multivariable analysis. Post-bronchodilator spirometry patterns did not significantly impact GOLD group progression or FEV₁ decline.</div></div><div><h3>Conclusion</h3><div><u>PREO & POSTO was common among COPD patients, while isolated PREO & POSTN was rare,</u> supporting<u>pre-bronchodilator spirometry as a screening tool.</u> Although patients with PREO & POSTO showed higher exacerbation risks <u>in univariable analysis, statistical significance disappeared</u> after adjustment. GOLD group progression or FEV₁ decline did not significantly differ by post-bronchodilator spirometry patterns.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102332"},"PeriodicalIF":3.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.pupt.2024.102331
Maria Gabriella Matera , Luigino Calzetta , Barbara Rinaldi , Carmela Belardo , Francesco Facciolo , Filippo Tommaso Gallina , Clive P. Page , Mario Cazzola , Paola Rogliani
Asthma management often includes inhaled corticosteroids (ICSs), with additional controllers like long-acting muscarinic antagonists (LAMAs) for severe cases. The primary goal of this study was to investigate the pharmacological interaction between various concentrations of fluticasone furoate (FF) and umeclidinium (UME) in isolated human airways to determine the nature of their interaction, whether synergistic or additive. Medium bronchi and small airways obtained from patients undergoing lobectomy were passively sensitized to mimic asthmatic conditions. The effects of FF and UME, alone and in combination, on airway relaxation were evaluated using histamine-induced contraction and electrical field stimulation. Pharmacological interactions were analyzed using the Bliss Independence theory. Results indicated that FF induced a partial, concentration-dependent relaxation of sensitized airways, while UME induced a larger relaxation in medium bronchi but a weaker effect in small airways. The combination of FF and UME resulted in significantly greater relaxation than either drug alone, demonstrating synergism at high concentrations in medium bronchi but only additive effects in small airways. This study suggests that higher doses of FF might be necessary in a fixed dose combination to achieve optimal synergistic bronchodilation with UME. Future research should focus on clinical trials to confirm these findings and explore the molecular mechanisms underlying these interactions, potentially improving personalized asthma therapy.
{"title":"Interaction between fluticasone furoate and umeclidinium in passively sensitized isolated human airways","authors":"Maria Gabriella Matera , Luigino Calzetta , Barbara Rinaldi , Carmela Belardo , Francesco Facciolo , Filippo Tommaso Gallina , Clive P. Page , Mario Cazzola , Paola Rogliani","doi":"10.1016/j.pupt.2024.102331","DOIUrl":"10.1016/j.pupt.2024.102331","url":null,"abstract":"<div><div>Asthma management often includes inhaled corticosteroids (ICSs), with additional controllers like long-acting muscarinic antagonists (LAMAs) for severe cases. The primary goal of this study was to investigate the pharmacological interaction between various concentrations of fluticasone furoate (FF) and umeclidinium (UME) in isolated human airways to determine the nature of their interaction, whether synergistic or additive. Medium bronchi and small airways obtained from patients undergoing lobectomy were passively sensitized to mimic asthmatic conditions. The effects of FF and UME, alone and in combination, on airway relaxation were evaluated using histamine-induced contraction and electrical field stimulation. Pharmacological interactions were analyzed using the Bliss Independence theory. Results indicated that FF induced a partial, concentration-dependent relaxation of sensitized airways, while UME induced a larger relaxation in medium bronchi but a weaker effect in small airways. The combination of FF and UME resulted in significantly greater relaxation than either drug alone, demonstrating synergism at high concentrations in medium bronchi but only additive effects in small airways. This study suggests that higher doses of FF might be necessary in a fixed dose combination to achieve optimal synergistic bronchodilation with UME. Future research should focus on clinical trials to confirm these findings and explore the molecular mechanisms underlying these interactions, potentially improving personalized asthma therapy.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102331"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.pupt.2024.102330
Anders Kjellberg , Allan Zhao , Anna Lussier , Adrian Hassler , Sarah Al-Ezerjawi , Emil Boström , Sergiu-Bogdan Catrina , Peter Bergman , Kenny Alexandra Rodriguez-Wallberg , Peter Lindholm
Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.
In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.
Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO2/FiO2 was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).
We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls.
Trial registration
NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).
{"title":"Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial","authors":"Anders Kjellberg , Allan Zhao , Anna Lussier , Adrian Hassler , Sarah Al-Ezerjawi , Emil Boström , Sergiu-Bogdan Catrina , Peter Bergman , Kenny Alexandra Rodriguez-Wallberg , Peter Lindholm","doi":"10.1016/j.pupt.2024.102330","DOIUrl":"10.1016/j.pupt.2024.102330","url":null,"abstract":"<div><div>Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.</div><div>In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.</div><div>Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO<sub>2</sub>/FiO<sub>2</sub> was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).</div><div>We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls.</div></div><div><h3>Trial registration</h3><div>NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102330"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1016/j.pupt.2024.102329
Honglei Shi , Zehu Chen , Qianqian Lei , Donghai Ma , Meizhu Chen , Jing Liu
Background
To evaluate the benefits of omalizumab treatment in patients through real-world follow-up and assess the impact of omalizumab treatment on airway remodeling using chest CT.
Methods
This is a single-center prospective, observational study included Chinese patients with refractory asthma who received omalizumab treatment from May 2021 to December 2022. We collected real-world clinical data, including their hospitalization information, pulmonary function, FENO, laboratory assessment, ACT scores, chest CT at baseline and every follow-up month. A comparison was made between the pre-treatment and post-treatment laboratory indicators, pulmonary function, airway parameters, and mucous plug scores under chest CT.
Results
This study included a total of 61 patients with refractory asthma treated with omalizumab. The study found that: ①regardless of whether the treatment lasted for a full four months or not, it significantly improved patient asthma control scores and reduced hospitalization costs and length of stay (p < 0.05). ②After four months of treatment, pulmonary ventilation function examination revealed significant improvements (p < 0.05) in MEF75, MEF50, MEF75/25, PEF, and FEV1/FVC. ③After four months of omalizumab treatment, the ratio of wall thickness and outer radius (T/D) and wall area percentage (WA%) of the bronchial wall decreased significantly (p < 0.05). ④After medication, the expression of airway mucous plugs decreased.
Conclusions
Omalizumab treatment can reduce airway wall thickness, decrease the percentage of airway wall area, and the expression of airway mucous plugs, thereby improving airflow limitation. Utilizing chest CT provides a novel and intuitive assessment of the efficacy of omalizumab treatment.
Trial registration
This study was registered in Chinese Clinical Trial Registry, the number is ChiCTR2100046343.
{"title":"Chest CT assess the impact of omalizumab treatment on airway remodeling in refractory asthma","authors":"Honglei Shi , Zehu Chen , Qianqian Lei , Donghai Ma , Meizhu Chen , Jing Liu","doi":"10.1016/j.pupt.2024.102329","DOIUrl":"10.1016/j.pupt.2024.102329","url":null,"abstract":"<div><h3>Background</h3><div>To evaluate the benefits of omalizumab treatment in patients through real-world follow-up and assess the impact of omalizumab treatment on airway remodeling using chest CT.</div></div><div><h3>Methods</h3><div>This is a single-center prospective, observational study included Chinese patients with refractory asthma who received omalizumab treatment from May 2021 to December 2022. We collected real-world clinical data, including their hospitalization information, pulmonary function, FENO, laboratory assessment, ACT scores, chest CT at baseline and every follow-up month. A comparison was made between the pre-treatment and post-treatment laboratory indicators, pulmonary function, airway parameters, and mucous plug scores under chest CT.</div></div><div><h3>Results</h3><div>This study included a total of 61 patients with refractory asthma treated with omalizumab. The study found that: ①regardless of whether the treatment lasted for a full four months or not, it significantly improved patient asthma control scores and reduced hospitalization costs and length of stay (p < 0.05). ②After four months of treatment, pulmonary ventilation function examination revealed significant improvements (p < 0.05) in MEF75, MEF50, MEF75/25, PEF, and FEV1/FVC. ③After four months of omalizumab treatment, the ratio of wall thickness and outer radius (T/D) and wall area percentage (WA%) of the bronchial wall decreased significantly (p < 0.05). ④After medication, the expression of airway mucous plugs decreased.</div></div><div><h3>Conclusions</h3><div>Omalizumab treatment can reduce airway wall thickness, decrease the percentage of airway wall area, and the expression of airway mucous plugs, thereby improving airflow limitation. Utilizing chest CT provides a novel and intuitive assessment of the efficacy of omalizumab treatment.</div></div><div><h3>Trial registration</h3><div>This study was registered in Chinese Clinical Trial Registry, the number is ChiCTR2100046343.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102329"},"PeriodicalIF":3.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1016/j.pupt.2024.102328
E. Fragoso , R. Boaventura , L. Almeida , A. Amorim , F. Gamboa , A.S. Santos , F. Gonçalves , C.M. Cruz , A. Carreiro , A.S. Gonçalves , V. Teixeira , P. Azevedo
Background
Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.
Methods
Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.
Results
132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the F508del variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV1 was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV1 was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m2 (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was −44.5 mmol/L (95 % CI: −49.8, −39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = −0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.
Conclusions
ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.
{"title":"Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience","authors":"E. Fragoso , R. Boaventura , L. Almeida , A. Amorim , F. Gamboa , A.S. Santos , F. Gonçalves , C.M. Cruz , A. Carreiro , A.S. Gonçalves , V. Teixeira , P. Azevedo","doi":"10.1016/j.pupt.2024.102328","DOIUrl":"10.1016/j.pupt.2024.102328","url":null,"abstract":"<div><h3>Background</h3><p>Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 <em>F508del-CFTR</em> allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.</p></div><div><h3>Methods</h3><p>Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.</p></div><div><h3>Results</h3><p>132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the <em>F508del</em> variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV<sub>1</sub> was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV<sub>1</sub> was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m<sup>2</sup> (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was −44.5 mmol/L (95 % CI: −49.8, −39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = −0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.</p></div><div><h3>Conclusions</h3><p>ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102328"},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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