The incidence of idiopathic pulmonary fibrosis (IPF) is increasing every year; however, the potential biological mechanisms have not been completely clarified. The objective of this study is to reveal the etiologic effects of circulating metabolites on IPF.
Methods
This research evaluated the causal relationship between serum metabolites and IPF utilizing two-sample Mendelian randomization (MR) analysis. IVW served as the main method of analysis; concurrently, MR-Egger, weighted median, and MR-PRESSO acted as supplementary analyses. Sensitivity analyses were performed with Cochran's Q test, MR-Egger's intercept test, and leave-one-out method of analysis. All statistical analyses were accomplished in R software.
Results
Our results showed that 23 metabolites have a causal connection with IPF. Following sensitivity analysis, 2 robust and 12 potential causal association pairs were identified among the known metabolites. These 14 causal pairs concerned six metabolites.
Conclusion
This study presents a novel perspective on potential mechanisms involved in IPF with important significance for screening, prevention, and treatment.
{"title":"Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study","authors":"Yu Shi, Shuang Chen, Zhaokai Zhou, Mengke Huang, Yue Li, Xiaogang Jing","doi":"10.1111/crj.70087","DOIUrl":"https://doi.org/10.1111/crj.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The incidence of idiopathic pulmonary fibrosis (IPF) is increasing every year; however, the potential biological mechanisms have not been completely clarified. The objective of this study is to reveal the etiologic effects of circulating metabolites on IPF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This research evaluated the causal relationship between serum metabolites and IPF utilizing two-sample Mendelian randomization (MR) analysis. IVW served as the main method of analysis; concurrently, MR-Egger, weighted median, and MR-PRESSO acted as supplementary analyses. Sensitivity analyses were performed with Cochran's <i>Q</i> test, MR-Egger's intercept test, and leave-one-out method of analysis. All statistical analyses were accomplished in R software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that 23 metabolites have a causal connection with IPF. Following sensitivity analysis, 2 robust and 12 potential causal association pairs were identified among the known metabolites. These 14 causal pairs concerned six metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study presents a novel perspective on potential mechanisms involved in IPF with important significance for screening, prevention, and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. G. Pitsiou, “ Treatment Approaches for Pulmonary Hypertension in Colombia: A Call to Action,” Clinical Respiratory Journal19, no. 2 (2025), https://doi.org/10.1111/crj.70062.
In the References section, reference section 3 is outdated and should be updated to
3. Μ. Machado-Duque, Α. Gaviria-Mendoza, L. F. Valladales-Restrepo, et al., “Treatment Patterns of Patients With Pulmonary Hypertension: A Descriptive Study in Colombia,” Clinical Respiratory Journal 19, no. 2 (2025), https://doi.org/10.1111/crj.70063.
We apologize for this error.
G. G. Pitsiou，“哥伦比亚肺动脉高压的治疗方法：行动呼吁”，《临床呼吸杂志》第19期。2 (2025), https://doi.org/10.1111/crj.70062。在参考文献部分，参考文献部分3已经过时，应该更新为3。Μ。Machado-DuqueΑ。Gaviria-Mendoza， L. F. Valladales-Restrepo等，“肺动脉高压患者的治疗模式：哥伦比亚的一项描述性研究”，《临床呼吸杂志》第19期。2 (2025), https://doi.org/10.1111/crj.70063.We为这个错误道歉。
{"title":"Correction to “Treatment Approaches for Pulmonary Hypertension in Colombia: A Call to Action”","authors":"","doi":"10.1111/crj.70095","DOIUrl":"https://doi.org/10.1111/crj.70095","url":null,"abstract":"<p>\u0000 <span>G. G. Pitsiou</span>, “ <span>Treatment Approaches for Pulmonary Hypertension in Colombia: A Call to Action</span>,” <i>Clinical Respiratory Journal</i> <span>19</span>, no. <span>2</span> (<span>2025</span>), https://doi.org/10.1111/crj.70062.\u0000 </p><p>In the References section, reference section 3 is outdated and should be updated to</p><p>3. Μ. Machado-Duque, Α. Gaviria-Mendoza, L. F. Valladales-Restrepo, et al., “Treatment Patterns of Patients With Pulmonary Hypertension: A Descriptive Study in Colombia,” <i>Clinical Respiratory Journal</i> 19, no. 2 (2025), https://doi.org/10.1111/crj.70063.</p><p>We apologize for this error.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuberculosis (TB) is a globally prevalent chronic infectious disease. The World Health Organization estimates that mental illnesses will become the leading cause of global disease burden in 2030. The inability to detect and provide proper treatment for TB in mental illness patients is an epidemic prevention blind spot. The objective of this study was to retrospectively compare the incidence of TB between the general public and mental illness patients.
Methods
This study used data across Taiwan from 2002 to 2013. The National Health Insurance Research Database, Registry for Catastrophic Illness Patients, Tuberculosis Database, and Household Registration Records of Taiwan were analyzed. Propensity score matching was used to reduce basic characteristic differences between mental illness patients and the general public. The conditional Cox proportional hazards model and cumulative risk curve were used to compare their risk of developing TB.
Results
It was shown that TB incidence was 87 and 71 per 100 000 person-years in mental illness patients and the general public, respectively. The risk of developing TB in mental illness patients was 1.48 times (95% CI: 1.38–1.59) that of the general public.
Conclusion
Mental illness patients are a high-risk population for TB and should be listed as key subjects for TB prevention and control.
{"title":"Risk Assessment of Tuberculosis in Patients With Chronic Mental Illness and Related Factors: A Population-Based Cohort Study in Taiwan","authors":"Li-Chen Hung, Pei-Tseng Kung, Tung-Han Tsai, Wen-Chen Tsai, Kuang-Hua Huang","doi":"10.1111/crj.70088","DOIUrl":"https://doi.org/10.1111/crj.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Tuberculosis (TB) is a globally prevalent chronic infectious disease. The World Health Organization estimates that mental illnesses will become the leading cause of global disease burden in 2030. The inability to detect and provide proper treatment for TB in mental illness patients is an epidemic prevention blind spot. The objective of this study was to retrospectively compare the incidence of TB between the general public and mental illness patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used data across Taiwan from 2002 to 2013. The National Health Insurance Research Database, Registry for Catastrophic Illness Patients, Tuberculosis Database, and Household Registration Records of Taiwan were analyzed. Propensity score matching was used to reduce basic characteristic differences between mental illness patients and the general public. The conditional Cox proportional hazards model and cumulative risk curve were used to compare their risk of developing TB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was shown that TB incidence was 87 and 71 per 100 000 person-years in mental illness patients and the general public, respectively. The risk of developing TB in mental illness patients was 1.48 times (95% CI: 1.38–1.59) that of the general public.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Mental illness patients are a high-risk population for TB and should be listed as key subjects for TB prevention and control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pulmonary embolism (PE) is a common disease and a common cause of death. However, it is currently unclear which clinically common drugs can lead to PE.
Methods
We collected, organized, and analyzed reports from the first quarter of 2018 to the fourth quarter of 2022. We performed disproportionality analysis algorithms to calculate reporting odds ratio (ROR), which could quantify the signal values of different adverse events (AEs).
Results
We have screened a total of 3091 drugs, with AE containing “PE” and calculated the ROR signal values of the top 30 drugs reported and ranked them. TESTIM (ROR = 32.03[28.77–35.66]), BARICITINIB (ROR = 23.48[20.55–26.83]), and NUVARIANG (ROR = 19.89[17.13–23.10]) are the drugs with the strongest correlation with PE. In addition, among the 30 drugs with the strongest correlation with PE, most of which are Biologics & Immunomodulators. Therefore, when using these 30 drugs, it is necessary to be alert to the possible risk of PE.
Conclusion
In our study, we filtered 30 common drugs that could cause PE through the FAERS public database, which provides theoretical support for drug selection in the treatment of malignant tumors and IMID.
{"title":"An Exploratory Research to Evaluate the 30 Most Common Pulmonary Embolism Drugs in the Food and Drug Administration Adverse Event Reporting System","authors":"Hang Chen, Yiming Shen, Yinyu Mu, Shuguang Xu, Shimo Shen, Weiyu Shen, Zeyang Hu, Hongxiang Li, Keyue Qiu, Jiaheng Zhang, Zhe Chen, Guodong Xu","doi":"10.1111/crj.70054","DOIUrl":"https://doi.org/10.1111/crj.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>Pulmonary embolism (PE) is a common disease and a common cause of death. However, it is currently unclear which clinically common drugs can lead to PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected, organized, and analyzed reports from the first quarter of 2018 to the fourth quarter of 2022. We performed disproportionality analysis algorithms to calculate reporting odds ratio (ROR), which could quantify the signal values of different adverse events (AEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We have screened a total of 3091 drugs, with AE containing “PE” and calculated the ROR signal values of the top 30 drugs reported and ranked them. TESTIM (ROR = 32.03[28.77–35.66]), BARICITINIB (ROR = 23.48[20.55–26.83]), and NUVARIANG (ROR = 19.89[17.13–23.10]) are the drugs with the strongest correlation with PE. In addition, among the 30 drugs with the strongest correlation with PE, most of which are Biologics & Immunomodulators. Therefore, when using these 30 drugs, it is necessary to be alert to the possible risk of PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In our study, we filtered 30 common drugs that could cause PE through the FAERS public database, which provides theoretical support for drug selection in the treatment of malignant tumors and IMID.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Screening of lung nodules helps on early diagnosis of lung cancer, especially invasive pulmonary adenocarcinoma. Artificial intelligence (AI) has been applied in diagnosis of cancers. We used the AI-assisted lung nodule diagnostic system in the screening of lung nodules and lung cancer.
Case Presentation
A 66-year-old male complained of coughs and nodules in the right lung of 3-year duration. A ground-glass opacity was found in the right upper lung by routine computed tomography (CT). He had no family history of cancer, genetic diseases, or infectious diseases. AI-assisted analysis found four nodules, of which one was with the risk of malignancy of 88% (LungRads3), one was with the risk of malignancy of 15% (LungRads2), and the other two were smaller in size and considered benign. The patient underwent a thoracoscopic wedge resection of the right upper lung. The intraoperative frozen section pathology report confirmed invasive pulmonary adenocarcinoma, grade II, and primarily of alveolar and adherent types without metastasis.
Conclusion
In summary, AI-assisted lung nodule diagnostic system is effective in the screening of lung nodules and the differentiation between benign and malignant.
{"title":"Successful Application of Artificial Intelligence-Assisted Analysis of Invasive Pulmonary Adenocarcinoma Less Than 6 mm in Size: A Case Report and Literature Review","authors":"Lu Zhang, Dawei Yang, Xianwei Ye, Chunxue Bai","doi":"10.1111/crj.70073","DOIUrl":"https://doi.org/10.1111/crj.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Screening of lung nodules helps on early diagnosis of lung cancer, especially invasive pulmonary adenocarcinoma. Artificial intelligence (AI) has been applied in diagnosis of cancers. We used the AI-assisted lung nodule diagnostic system in the screening of lung nodules and lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 66-year-old male complained of coughs and nodules in the right lung of 3-year duration. A ground-glass opacity was found in the right upper lung by routine computed tomography (CT). He had no family history of cancer, genetic diseases, or infectious diseases. AI-assisted analysis found four nodules, of which one was with the risk of malignancy of 88% (LungRads3), one was with the risk of malignancy of 15% (LungRads2), and the other two were smaller in size and considered benign. The patient underwent a thoracoscopic wedge resection of the right upper lung. The intraoperative frozen section pathology report confirmed invasive pulmonary adenocarcinoma, grade II, and primarily of alveolar and adherent types without metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, AI-assisted lung nodule diagnostic system is effective in the screening of lung nodules and the differentiation between benign and malignant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiantian Cen, Zekai Cen, Xuan Chen, Zaichun Deng, Yiming Yu, Shanshan Wang, Hongying Ma
Background
The World Health Organization estimated that 65 million individuals have chronic obstructive pulmonary disease (COPD). However, large numbers remain undiagnosed. Anthropometric variables and lung function are closely related, such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). Therefore, it is essential to explore the relationship between anthropometric variables and lung function.
Methods
We recruited 7679 severe smokers. Severe smoking was defined as a smoking index ≥ 20 pack-years. Among these participants, there are 6214 severe smokers with mild, moderate, and moderately severe obstructive ventilation dysfunction and 1465 severe smokers with severe and very severe obstructive ventilation dysfunction. Otherwise, participants were divided into different groups according to questionnaires and sex.
Results
Lung function in the severe smoking community population was associated with anthropometric variables. The study results showed that BMI was negatively associated with the risk of severe and very severe obstructive ventilation dysfunction in a severe smoking community population with ventilatory dysfunction (OR 0.791, 95% CI 0.691–0.907, p = 0.001), the COPD Population Screener (COPD-PS) scores ≥ 5 group (OR 0.787, 95% CI 0.688–0.902, p = 0.001), the COPD Screening Questionnaire (COPD-SQ) scores ≥ 16 group (OR 0.791, 95% CI 0.689–0.908, p = 0.001), the COPD-PS scores ≥ 5 and COPD-SQ scores ≥ 16 group (OR 0.730, 95% CI 0.603–0.884, p = 0.001) and the male group (OR 0.813, 95% CI 0.708–0.933, p = 0.003). The study showed that WC was also associated with obstructive ventilation dysfunction.
Conclusion
Low BMI and WC were independent risk factors for severe and very severe obstructive ventilation dysfunction in the severe smoking community Chinese population with ventilatory dysfunction. Collecting COPD questionnaires may help manage lung function in the community population.
世界卫生组织估计，全球有6500万人患有慢性阻塞性肺疾病（COPD）。然而，仍有大量患者未得到诊断。身体质量指数（BMI）、腰围（WC）、腰高比（WHtR）等人体测量变量与肺功能密切相关。因此，有必要探讨人体测量变量与肺功能之间的关系。方法招募重度吸烟者7679人。重度吸烟定义为吸烟指数≥20包年。在这些参与者中，有6214名重度吸烟者伴有轻度、中度和中度阻塞性通气功能障碍，1465名重度吸烟者伴有重度和极重度阻塞性通气功能障碍。除此之外，参与者根据问卷和性别被分成不同的组。结果重度吸烟社区人群肺功能与人体测量变量相关。研究结果显示，在重度吸烟社区呼吸功能障碍人群中，BMI与重度和极重度阻塞性通气功能障碍的风险呈负相关（OR 0.791, 95% CI 0.691-0.907, p = 0.001）， COPD人群筛查（COPD- ps）评分≥5组（OR 0.787, 95% CI 0.688-0.902, p = 0.001）， COPD筛查问卷（COPD- sq）评分≥16组（OR 0.791, 95% CI 0.689-0.908, p = 0.001）， COPD人群评分≥16组（OR 0.791, 95% CI 0.689-0.908, p = 0.001）。COPD-PS评分≥5分、COPD-SQ评分≥16分组（OR 0.730, 95% CI 0.603 ~ 0.884, p = 0.001）和男性组（OR 0.813, 95% CI 0.708 ~ 0.933, p = 0.003）。研究表明，WC也与阻塞性通气功能障碍有关。结论低BMI和WC是中国重度吸烟人群重度和极重度阻塞性通气功能障碍的独立危险因素。收集COPD问卷可能有助于管理社区人群的肺功能。
{"title":"The Relationship Between Anthropometric Variables and Lung Function in a Severe Smoking Community Population With Ventilatory Dysfunction","authors":"Tiantian Cen, Zekai Cen, Xuan Chen, Zaichun Deng, Yiming Yu, Shanshan Wang, Hongying Ma","doi":"10.1111/crj.70076","DOIUrl":"https://doi.org/10.1111/crj.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The World Health Organization estimated that 65 million individuals have chronic obstructive pulmonary disease (COPD). However, large numbers remain undiagnosed. Anthropometric variables and lung function are closely related, such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). Therefore, it is essential to explore the relationship between anthropometric variables and lung function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 7679 severe smokers. Severe smoking was defined as a smoking index ≥ 20 pack-years. Among these participants, there are 6214 severe smokers with mild, moderate, and moderately severe obstructive ventilation dysfunction and 1465 severe smokers with severe and very severe obstructive ventilation dysfunction. Otherwise, participants were divided into different groups according to questionnaires and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lung function in the severe smoking community population was associated with anthropometric variables. The study results showed that BMI was negatively associated with the risk of severe and very severe obstructive ventilation dysfunction in a severe smoking community population with ventilatory dysfunction (OR 0.791, 95% CI 0.691–0.907, <i>p</i> = 0.001), the COPD Population Screener (COPD-PS) scores ≥ 5 group (OR 0.787, 95% CI 0.688–0.902, <i>p</i> = 0.001), the COPD Screening Questionnaire (COPD-SQ) scores ≥ 16 group (OR 0.791, 95% CI 0.689–0.908, <i>p</i> = 0.001), the COPD-PS scores ≥ 5 and COPD-SQ scores ≥ 16 group (OR 0.730, 95% CI 0.603–0.884, <i>p</i> = 0.001) and the male group (OR 0.813, 95% CI 0.708–0.933, <i>p</i> = 0.003). The study showed that WC was also associated with obstructive ventilation dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low BMI and WC were independent risk factors for severe and very severe obstructive ventilation dysfunction in the severe smoking community Chinese population with ventilatory dysfunction. Collecting COPD questionnaires may help manage lung function in the community population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant efficacy in patients with brain metastases (BMs) from EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable, and clinical data addressing key questions across treatment stages remain insufficient, limiting the formulation of precise treatment strategies.
Methods
This retrospective study analyzed 302 EGFR-mutant NSCLC patients with BMs treated at Shandong Cancer Hospital (2014–2022). Patients were divided into three cohorts: cohort A (first-/second-generation EGFR-TKIs without third-generation use), cohort B (first-/second-generation followed by third-generation EGFR-TKIs), and cohort C (first-line third-generation EGFR-TKIs). Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses across three treatment stages. Propensity score matching (PSM) adjusted for baseline imbalances.
Results
Third-generation EGFR-TKIs demonstrated superior progression-free survival (PFS) in first-line therapy compared to earlier-generation agents (median PFS1: 14.2 vs. 11.2 months; p = 0.0021), particularly for intracranial control (median iPFS1: 18.0 vs. 12.2 months; p = 0.0058). Patients with uncommon EGFR mutations had significantly shorter PFS on third-generation EGFR-TKIs than those with common mutations (4.4 vs. 12.9 months; p = 0.012). After resistance, combination therapy with immune checkpoint inhibitors (ICIs), antiangiogenics, and chemotherapy extended overall survival (OS) versus non-ICI regimens (median OS2: 17.3 vs. 10.4 months; p = 0.004).
Conclusions
Third-generation EGFR-TKIs are effective first-line options for BMs but show limited efficacy against uncommon mutations. Post-resistance regimens integrating ICIs, antiangiogenics, and chemotherapy may improve survival. Reassessment of genetic and PD-L1 status is critical for guiding sequential therapy.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在egfr突变的非小细胞肺癌（NSCLC）脑转移（BMs）患者中显示出显著疗效。然而，获得性耐药是不可避免的，跨治疗阶段解决关键问题的临床数据仍然不足，限制了精确治疗策略的制定。方法回顾性分析2014-2022年山东省肿瘤医院收治的302例egfr突变非小细胞肺癌脑转移患者。患者被分为三个队列：队列A（第一代/第二代未使用第三代EGFR-TKIs），队列B（第一代/第二代随后使用第三代EGFR-TKIs）和队列C（一线第三代EGFR-TKIs）。使用Kaplan-Meier和Cox回归分析评估三个治疗阶段的生存结果。倾向得分匹配（PSM）调整基线不平衡。与前代药物相比，第三代EGFR-TKIs在一线治疗中表现出更高的无进展生存期（PFS）(中位PFS1: 14.2个月vs 11.2个月；p = 0.0021)，特别是颅内控制(中位iPFS1: 18.0 vs. 12.2个月；p = 0.0058)。具有罕见EGFR突变的患者在第三代EGFR- tkis上的PFS明显短于具有常见突变的患者(4.4个月vs 12.9个月；p = 0.012)。耐药后，与非ici方案相比，免疫检查点抑制剂（ICIs）、抗血管生成药物和化疗联合治疗延长了总生存期（OS）(中位OS2: 17.3 vs 10.4个月；p = 0.004)。结论：第三代EGFR-TKIs是治疗脑转移的有效一线选择，但对罕见突变的疗效有限。耐药后的治疗方案整合了ICIs、抗血管生成药物和化疗，可以提高生存率。重新评估遗传和PD-L1状态对于指导序贯治疗至关重要。
{"title":"Survival Outcomes in EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Kaplan–Meier and Cox Regression Analyses Across Treatment Stages","authors":"Haoran Qi, Qiang Qiao, Xiaorong Sun, Ligang Xing","doi":"10.1111/crj.70085","DOIUrl":"https://doi.org/10.1111/crj.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant efficacy in patients with brain metastases (BMs) from EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable, and clinical data addressing key questions across treatment stages remain insufficient, limiting the formulation of precise treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study analyzed 302 EGFR-mutant NSCLC patients with BMs treated at Shandong Cancer Hospital (2014–2022). Patients were divided into three cohorts: cohort A (first-/second-generation EGFR-TKIs without third-generation use), cohort B (first-/second-generation followed by third-generation EGFR-TKIs), and cohort C (first-line third-generation EGFR-TKIs). Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses across three treatment stages. Propensity score matching (PSM) adjusted for baseline imbalances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Third-generation EGFR-TKIs demonstrated superior progression-free survival (PFS) in first-line therapy compared to earlier-generation agents (median PFS1: 14.2 vs. 11.2 months; <i>p</i> = 0.0021), particularly for intracranial control (median iPFS1: 18.0 vs. 12.2 months; <i>p</i> = 0.0058). Patients with uncommon EGFR mutations had significantly shorter PFS on third-generation EGFR-TKIs than those with common mutations (4.4 vs. 12.9 months; <i>p</i> = 0.012). After resistance, combination therapy with immune checkpoint inhibitors (ICIs), antiangiogenics, and chemotherapy extended overall survival (OS) versus non-ICI regimens (median OS2: 17.3 vs. 10.4 months; <i>p</i> = 0.004).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Third-generation EGFR-TKIs are effective first-line options for BMs but show limited efficacy against uncommon mutations. Post-resistance regimens integrating ICIs, antiangiogenics, and chemotherapy may improve survival. Reassessment of genetic and PD-L1 status is critical for guiding sequential therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wang Chun Kwok, Chung Ki Tsui, Sze Him Isaac Leung, Shuk Man Ngai, David Chi Leung Lam, Mary Sau Man Ip, James Chung Man Ho
Background
Inhaled corticosteroid (ICS) is a major pharmacotherapy for chronic obstructive pulmonary disease (COPD), which is associated with various adverse effects. Controversies exist in whether ICS use in COPD is associated with osteoporosis or fracture.
Objective
We performed a systematic review and meta-analysis to assess the risks of osteoporosis or fracture at different dosing levels of ICS. High-, medium- and low-dose ICS were defined according to the Global Initiative for Asthma (GINA) step definition.
Data sources
Cochrane, EMBASE, Ovid, PubMed and Web of Science were systematically searched until 8 December 2023.
Data extraction
Osteoporosis or fracture under ICS therapy was chosen as the primary efficacy outcome. Three reviewers were involved independently in the extraction process. The risk of bias of the included studies was evaluated by using different assessment tools.
Results
Twenty-one RCTs and eight observational studies were included. High-dose ICS was associated with increased risks of osteoporosis or fracture in RCTs with RR of 1.14 (95% CI = 1.03–1.28), observational studies with healthy controls 1.14 (95% CI = 1.05–1.24) and observational studies without healthy controls 1.10 (95% CI = 1.01–1.21). High-dose ICS was associated with increased risks in fracture in RCTs with RR of 1.12 (95% CI = 1.03–1.23), observational studies with health controls 1.15 (95% CI = 1.05–1.25) and observational studies without healthy controls 1.13 (95% CI = 1.03–1.24). Medium- and low-dose ICS were not associated with osteoporosis or fracture.
Conclusion
High-dose, but not medium- and low-dose, ICS use in COPD is associated with risks of osteoporosis or fractures.
背景：吸入皮质类固醇（ICS）是慢性阻塞性肺疾病（COPD）的主要药物治疗方法，但存在多种不良反应。对于慢性阻塞性肺病患者使用ICS是否与骨质疏松或骨折有关存在争议。目的：我们进行了一项系统回顾和荟萃分析，以评估不同剂量的ICS对骨质疏松或骨折的风险。根据全球哮喘倡议（GINA）分级定义高、中、低剂量ICS。系统检索数据来源为Cochrane、EMBASE、Ovid、PubMed和Web of Science，检索截止日期为2023年12月8日。选择ICS治疗下的骨质疏松或骨折作为主要疗效终点。三名审稿人独立参与了提取过程。采用不同的评估工具对纳入研究的偏倚风险进行评估。结果纳入21项随机对照试验和8项观察性研究。在随机对照试验中，高剂量ICS与骨质疏松或骨折风险增加相关，RR为1.14 (95% CI = 1.03-1.28)，健康对照观察性研究为1.14 (95% CI = 1.05-1.24)，无健康对照观察性研究为1.10 （95% CI = 1.01-1.21）。在随机对照试验中，高剂量ICS与骨折风险增加相关，RR为1.12 (95% CI = 1.03-1.23)，健康对照观察性研究为1.15 (95% CI = 1.05-1.25)，无健康对照观察性研究为1.13 （95% CI = 1.03-1.24）。中、低剂量ICS与骨质疏松或骨折无关。结论慢性阻塞性肺病患者使用高剂量而非中、低剂量ICS与骨质疏松或骨折风险相关。
{"title":"Dose of Inhaled Corticosteroid in Chronic Obstructive Pulmonary Disease and Risks of Osteoporosis or Fracture—A Systematic Review and Meta-Analysis","authors":"Wang Chun Kwok, Chung Ki Tsui, Sze Him Isaac Leung, Shuk Man Ngai, David Chi Leung Lam, Mary Sau Man Ip, James Chung Man Ho","doi":"10.1111/crj.70086","DOIUrl":"https://doi.org/10.1111/crj.70086","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inhaled corticosteroid (ICS) is a major pharmacotherapy for chronic obstructive pulmonary disease (COPD), which is associated with various adverse effects. Controversies exist in whether ICS use in COPD is associated with osteoporosis or fracture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We performed a systematic review and meta-analysis to assess the risks of osteoporosis or fracture at different dosing levels of ICS. High-, medium- and low-dose ICS were defined according to the Global Initiative for Asthma (GINA) step definition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Data sources</h3>\u0000 \u0000 <p>Cochrane, EMBASE, Ovid, PubMed and Web of Science were systematically searched until 8 December 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Data extraction</h3>\u0000 \u0000 <p>Osteoporosis or fracture under ICS therapy was chosen as the primary efficacy outcome. Three reviewers were involved independently in the extraction process. The risk of bias of the included studies was evaluated by using different assessment tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one RCTs and eight observational studies were included. High-dose ICS was associated with increased risks of osteoporosis or fracture in RCTs with RR of 1.14 (95% CI = 1.03–1.28), observational studies with healthy controls 1.14 (95% CI = 1.05–1.24) and observational studies without healthy controls 1.10 (95% CI = 1.01–1.21). High-dose ICS was associated with increased risks in fracture in RCTs with RR of 1.12 (95% CI = 1.03–1.23), observational studies with health controls 1.15 (95% CI = 1.05–1.25) and observational studies without healthy controls 1.13 (95% CI = 1.03–1.24). Medium- and low-dose ICS were not associated with osteoporosis or fracture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>High-dose, but not medium- and low-dose, ICS use in COPD is associated with risks of osteoporosis or fractures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to explore the diagnostic and predictive value of lncRNA HOXA-AS2 for acute respiratory distress syndrome (ARDS) and 28-day mortality in sepsis patients.
Methods
The levels of HOXA-AS2 in sepsis and ARDS patients were detected by real-time quantitative reverse transcription PCR (RT-qPCR). The receiver operating curve (ROC) curve was used to evaluate the diagnostic value of HOXA-AS2 for sepsis and ARDS. The K-M curve was used to evaluate the effect of HOXA-AS2 on the prognosis. Logistic regression analysis and COX regression analysis were used to explore the risk factors influencing ARDS and death. Additionally, an ARDS cell model was constructed to explore the effects of HOXA-AS2 on cell viability, inflammation, and endothelial glycocalyx.
Results
HOXA-AS2 decreased in sepsis patients who developed ARDS and died. This molecule can not only serve as a diagnostic marker for sepsis but also act as a risk factor to predict the risk of ARDS and death within 28 days in patients with sepsis. Sepsis patients with low levels of HOXA-AS2 are more prone to ARDS and death. In cells attacked by lipopolysaccharide (LPS), overexpression of HOXA-AS2 inhibited apoptosis, inflammation, and the degradation of endothelial glycocalyx.
Conclusion
In sepsis patients, HOXA-AS2 has the potential to serve as a predictive marker for ARDS and 28-day mortality. This molecule may delay the progression of ARDS by inhibiting inflammation and the degradation of the endothelial glycocalyx.
{"title":"LncRNA HOXA-AS2 Can Predict the Risk of Acute Respiratory Distress Syndrome and 28-Day Mortality in Patients With Sepsis","authors":"Youhong Quan, Song Gao","doi":"10.1111/crj.70082","DOIUrl":"https://doi.org/10.1111/crj.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the diagnostic and predictive value of lncRNA HOXA-AS2 for acute respiratory distress syndrome (ARDS) and 28-day mortality in sepsis patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The levels of HOXA-AS2 in sepsis and ARDS patients were detected by real-time quantitative reverse transcription PCR (RT-qPCR). The receiver operating curve (ROC) curve was used to evaluate the diagnostic value of HOXA-AS2 for sepsis and ARDS. The K-M curve was used to evaluate the effect of HOXA-AS2 on the prognosis. Logistic regression analysis and COX regression analysis were used to explore the risk factors influencing ARDS and death. Additionally, an ARDS cell model was constructed to explore the effects of HOXA-AS2 on cell viability, inflammation, and endothelial glycocalyx.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HOXA-AS2 decreased in sepsis patients who developed ARDS and died. This molecule can not only serve as a diagnostic marker for sepsis but also act as a risk factor to predict the risk of ARDS and death within 28 days in patients with sepsis. Sepsis patients with low levels of HOXA-AS2 are more prone to ARDS and death. In cells attacked by lipopolysaccharide (LPS), overexpression of HOXA-AS2 inhibited apoptosis, inflammation, and the degradation of endothelial glycocalyx.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In sepsis patients, HOXA-AS2 has the potential to serve as a predictive marker for ARDS and 28-day mortality. This molecule may delay the progression of ARDS by inhibiting inflammation and the degradation of the endothelial glycocalyx.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G protein-coupled receptors (GPCRs), the largest family of cell-surface molecules involve in various signal transduction, have recently been recognized as important drivers of cancer. However, few studies have reported on the potential of GPCRs as therapeutic targets or biomarkers in lung adenocarcinoma (LUAD).
Methods
The expression profiles and clinical data of LUAD in the GSE30219 and GSE18842 datasets of the Cancer Genome Atlas were analyzed. LUAD-associated module genes were screened utilizing weighted gene co-expression network analysis (WGCNA). Prognostic signature genes were identified by univariate Cox survival analysis, LASSO regression, and multivariate Cox regression analyses. The immune status was evaluated and drug sensitivity was determined, conducting in vitro experiments for validation.
Results
Patients with LUAD exhibited lower GPCR score than the controls, and 38 dysregulated GPCRs were identified by screening with differential analysis and WGCNA module genes. An optimal prognostic signature was identified, including OR51E1, LGR4, ADRB1, ADGRD1, and ADGRE3. The model established based on these five genes harbored moderate predictive performance for the survival of patients with LUAD. The risk score was negatively correlated with the infiltrating levels of multiple immune cells, including M2 macrophages, myeloid dendritic cells, and neutrophils, but positively correlated with fewer immune cells, such as Th1/Th2 CD4 + T cell. ADGRE3 and OR51E1 expression was positively correlated with drug sensitivity, including to cisplatin, ribociclib, and pevonedistat. Silencing OR51E1 inhibited the malignant cytological behaviors of LUAD cells.
Conclusion
GPCRs demonstrated prognostic potential in LUAD, with five genes identified as potential therapeutic targets and prognostic biomarkers for LUAD.
{"title":"Therapeutic and Prognostic Potential of G Protein-Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments","authors":"Feiyan Yang, Jianye Yang, Guobiao Yang, Ya Zhang","doi":"10.1111/crj.70080","DOIUrl":"https://doi.org/10.1111/crj.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>G protein-coupled receptors (GPCRs), the largest family of cell-surface molecules involve in various signal transduction, have recently been recognized as important drivers of cancer. However, few studies have reported on the potential of GPCRs as therapeutic targets or biomarkers in lung adenocarcinoma (LUAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression profiles and clinical data of LUAD in the GSE30219 and GSE18842 datasets of the Cancer Genome Atlas were analyzed. LUAD-associated module genes were screened utilizing weighted gene co-expression network analysis (WGCNA). Prognostic signature genes were identified by univariate Cox survival analysis, LASSO regression, and multivariate Cox regression analyses. The immune status was evaluated and drug sensitivity was determined, conducting in vitro experiments for validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with LUAD exhibited lower GPCR score than the controls, and 38 dysregulated GPCRs were identified by screening with differential analysis and WGCNA module genes. An optimal prognostic signature was identified, including OR51E1, LGR4, ADRB1, ADGRD1, and ADGRE3. The model established based on these five genes harbored moderate predictive performance for the survival of patients with LUAD. The risk score was negatively correlated with the infiltrating levels of multiple immune cells, including M2 macrophages, myeloid dendritic cells, and neutrophils, but positively correlated with fewer immune cells, such as Th1/Th2 CD4 + T cell. ADGRE3 and OR51E1 expression was positively correlated with drug sensitivity, including to cisplatin, ribociclib, and pevonedistat. Silencing OR51E1 inhibited the malignant cytological behaviors of LUAD cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GPCRs demonstrated prognostic potential in LUAD, with five genes identified as potential therapeutic targets and prognostic biomarkers for LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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