Pub Date : 2024-02-28Print Date: 2024-01-31DOI: 10.1183/16000617.0174-2023
Joshua L Robinson, Kathryn L Gatford, Danielle N Bailey, Andrea J Roff, Vicki L Clifton, Janna L Morrison, Michael J Stark
There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review.
在怀孕期间患有哮喘的妇女中,有 17%的人围产期不良预后的风险会增加。孕产妇哮喘与不良预后之间的关联机制尚不清楚,但它反映了遗传和产前接触孕产妇哮喘的共同影响。动物模型对于了解独立于遗传和合并症的潜在机制以及安全测试干预措施至关重要。本范围综述旨在探讨已发表的使用临床前孕产妇哮喘模型的研究的方法、表型、特征、结果和质量。我们使用先前验证过的检索字符串对 MEDLINE(PubMed)、Embase(Elsevier)和 Web of Science(科学网)进行了系统检索,涉及孕产妇哮喘和动物模型。两名审稿人分别独立筛选标题和摘要、全文,然后使用《动物研究:体内实验报告》(Animal Research:体内实验报告 (ARRIVE) 2.0 指南对每项研究进行提取和质量评估。在确定的 3618 项研究中,有 39 项符合提取条件。大多数研究以啮齿动物为对象(86%),所有研究均为过敏性哮喘模型。母体和后代的结果包括气道高反应性、气道阻力、炎症、肺免疫细胞、肺结构以及血清免疫球蛋白和细胞因子。报告最多的是实验设计(100%)、程序细节(97%)和原理(100%)。相反,少数研究报告了数据排除(21%)、盲法(18%)和不良事件(8%)。生理和发育时间的物种差异、使用与人类无关的过敏原以及缺乏可比较的结果测量可能会阻碍临床转化。未来探索母体哮喘模型的研究应遵守本综述中提出的最低核心结果集。
{"title":"Preclinical models of maternal asthma and progeny outcomes: a scoping review.","authors":"Joshua L Robinson, Kathryn L Gatford, Danielle N Bailey, Andrea J Roff, Vicki L Clifton, Janna L Morrison, Michael J Stark","doi":"10.1183/16000617.0174-2023","DOIUrl":"10.1183/16000617.0174-2023","url":null,"abstract":"<p><p>There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting of <i>In Vivo</i> Experiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-28Print Date: 2024-01-31DOI: 10.1183/16000617.0144-2023
Marielle C van de Veerdonk, Lize Roosma, Pia Trip, Deepa Gopalan, Anton Vonk Noordegraaf, Peter Dorfmüller, Esther J Nossent
Pulmonary hypertension (PH) is highly prevalent in patients with left heart disease (LHD) and negatively impacts prognosis. The most common causes of PH associated with LHD (PH-LHD) are left heart failure and valvular heart disease. In LHD, passive backward transmission of increased left-sided filling pressures leads to isolated post-capillary PH. Additional pulmonary vasoconstriction and remodelling lead to a higher vascular load and combined pre- and post-capillary PH. The increased afterload leads to right ventricular dysfunction and failure. Multimodality imaging of the heart plays a central role in the diagnostic work-up and follow-up of patients with PH-LHD. Echocardiography provides information about the estimated pulmonary artery pressure, morphology and function of the left and right side of the heart, and valvular abnormalities. Cardiac magnetic resonance imaging is the gold standard for volumetric measurements and provides myocardial tissue characterisation. Computed tomography of the thorax may show general features of PH and/or LHD and is helpful in excluding other PH causes. Histopathology reveals a spectrum of pre- and post-capillary vasculopathy, including intimal fibrosis, media smooth muscle cell hyperplasia, adventitial fibrosis and capillary congestion. In this paper, we provide an overview of clinical, imaging and histopathological findings in PH-LHD based on three clinical cases.
{"title":"Clinical-imaging-pathological correlation in pulmonary hypertension associated with left heart disease.","authors":"Marielle C van de Veerdonk, Lize Roosma, Pia Trip, Deepa Gopalan, Anton Vonk Noordegraaf, Peter Dorfmüller, Esther J Nossent","doi":"10.1183/16000617.0144-2023","DOIUrl":"10.1183/16000617.0144-2023","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is highly prevalent in patients with left heart disease (LHD) and negatively impacts prognosis. The most common causes of PH associated with LHD (PH-LHD) are left heart failure and valvular heart disease. In LHD, passive backward transmission of increased left-sided filling pressures leads to isolated post-capillary PH. Additional pulmonary vasoconstriction and remodelling lead to a higher vascular load and combined pre- and post-capillary PH. The increased afterload leads to right ventricular dysfunction and failure. Multimodality imaging of the heart plays a central role in the diagnostic work-up and follow-up of patients with PH-LHD. Echocardiography provides information about the estimated pulmonary artery pressure, morphology and function of the left and right side of the heart, and valvular abnormalities. Cardiac magnetic resonance imaging is the gold standard for volumetric measurements and provides myocardial tissue characterisation. Computed tomography of the thorax may show general features of PH and/or LHD and is helpful in excluding other PH causes. Histopathology reveals a spectrum of pre- and post-capillary vasculopathy, including intimal fibrosis, media smooth muscle cell hyperplasia, adventitial fibrosis and capillary congestion. In this paper, we provide an overview of clinical, imaging and histopathological findings in PH-LHD based on three clinical cases.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-28Print Date: 2024-01-31DOI: 10.1183/16000617.0220-2023
Michael J Holtzman, Yong Zhang, Kangyun Wu, Arthur G Romero
Respiratory viral infections are a major public health problem, with much of their morbidity and mortality due to post-viral lung diseases that progress and persist after the active infection is cleared. This paradigm is implicated in the most common forms of chronic lung disease, such as asthma and COPD, as well as other virus-linked diseases including progressive and long-term coronavirus disease 2019. Despite the impact of these diseases, there is a lack of small-molecule drugs available that can precisely modify this type of disease process. Here we will review current progress in understanding the pathogenesis of post-viral and related lung disease with characteristic remodelling phenotypes. We will also develop how this data leads to mitogen-activated protein kinase (MAPK) in general and MAPK13 in particular as key druggable targets in this pathway. We will also explore recent advances and predict the future breakthroughs in structure-based drug design that will provide new MAPK inhibitors as drug candidates for clinical applications. Each of these developments point to a more effective approach to treating the distinct epithelial and immune cell based mechanisms, which better account for the morbidity and mortality of post-viral and related types of lung disease. This progress is vital given the growing prevalence of respiratory viruses and other inhaled agents that trigger stereotyped progression to acute illness and chronic disease.
{"title":"Mitogen-activated protein kinase-guided drug discovery for post-viral and related types of lung disease.","authors":"Michael J Holtzman, Yong Zhang, Kangyun Wu, Arthur G Romero","doi":"10.1183/16000617.0220-2023","DOIUrl":"10.1183/16000617.0220-2023","url":null,"abstract":"<p><p>Respiratory viral infections are a major public health problem, with much of their morbidity and mortality due to post-viral lung diseases that progress and persist after the active infection is cleared. This paradigm is implicated in the most common forms of chronic lung disease, such as asthma and COPD, as well as other virus-linked diseases including progressive and long-term coronavirus disease 2019. Despite the impact of these diseases, there is a lack of small-molecule drugs available that can precisely modify this type of disease process. Here we will review current progress in understanding the pathogenesis of post-viral and related lung disease with characteristic remodelling phenotypes. We will also develop how this data leads to mitogen-activated protein kinase (MAPK) in general and MAPK13 in particular as key druggable targets in this pathway. We will also explore recent advances and predict the future breakthroughs in structure-based drug design that will provide new MAPK inhibitors as drug candidates for clinical applications. Each of these developments point to a more effective approach to treating the distinct epithelial and immune cell based mechanisms, which better account for the morbidity and mortality of post-viral and related types of lung disease. This progress is vital given the growing prevalence of respiratory viruses and other inhaled agents that trigger stereotyped progression to acute illness and chronic disease.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-14Print Date: 2024-01-31DOI: 10.1183/16000617.5284-2020
{"title":"\"Exercise intolerance in pulmonary arterial hypertension: insight into central and peripheral pathophysiological mechanisms.\" S. Malenfant, M. Lebret, É. Breton-Gagnon, <i>et al</i>. <i>Eur Respir Rev</i> 2021; 30: 200284.","authors":"","doi":"10.1183/16000617.5284-2020","DOIUrl":"10.1183/16000617.5284-2020","url":null,"abstract":"","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-14Print Date: 2024-01-31DOI: 10.1183/16000617.0145-2023
Shuoshuo Lv, Jie Yang, Jiayuh Lin, Xiaoying Huang, Haiyang Zhao, Chengguang Zhao, Lehe Yang
Lung cancer is the leading cause of cancer-related deaths worldwide, and ∼85% of lung cancers are classified as nonsmall cell lung cancer (NSCLC). These malignancies can proliferate indefinitely, in part due to dysregulation of the cell cycle and the resulting abnormal cell growth. The specific activation of cyclin-dependent kinases 4 and 6 (CDK4/6) is closely linked to tumour proliferation. Approximately 80% of human tumours exhibit abnormalities in the cyclin D-CDK4/6-INK4-RB pathway. Specifically, CDK4/6 inhibitors either as monotherapy or combination therapy have been investigated in pre-clinical and clinical studies for the treatment of NSCLC, and promising results have been achieved. This review article focuses on research regarding the use of CDK4/6 inhibitors in NSCLC, including the characteristics and mechanisms of action of approved drugs and progress of pre-clinical and clinical research.
{"title":"CDK4/6 inhibitors in lung cancer: current practice and future directions.","authors":"Shuoshuo Lv, Jie Yang, Jiayuh Lin, Xiaoying Huang, Haiyang Zhao, Chengguang Zhao, Lehe Yang","doi":"10.1183/16000617.0145-2023","DOIUrl":"10.1183/16000617.0145-2023","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related deaths worldwide, and ∼85% of lung cancers are classified as nonsmall cell lung cancer (NSCLC). These malignancies can proliferate indefinitely, in part due to dysregulation of the cell cycle and the resulting abnormal cell growth. The specific activation of cyclin-dependent kinases 4 and 6 (CDK4/6) is closely linked to tumour proliferation. Approximately 80% of human tumours exhibit abnormalities in the cyclin D-CDK4/6-INK4-RB pathway. Specifically, CDK4/6 inhibitors either as monotherapy or combination therapy have been investigated in pre-clinical and clinical studies for the treatment of NSCLC, and promising results have been achieved. This review article focuses on research regarding the use of CDK4/6 inhibitors in NSCLC, including the characteristics and mechanisms of action of approved drugs and progress of pre-clinical and clinical research.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-14Print Date: 2024-01-31DOI: 10.1183/16000617.0166-2023
Maria R Bonsignore, Emilia Mazzuca, Pierpaolo Baiamonte, Bernard Bouckaert, Wim Verbeke, Dirk A Pevernagie
Obstructive sleep apnoea (OSA) can occur in both rapid eye movement (REM) and non-REM sleep or be limited to REM sleep, when the upper airway is most prone to collapse due to REM sleep atonia. Respiratory events are usually longer and more desaturating in REM than in NREM sleep. The prevalence of REM OSA is higher in women than in men and REM OSA usually occurs in the context of mild-moderate OSA based on the apnoea-hypopnoea index calculated for the entire sleep study. Studies have highlighted some detrimental consequences of REM OSA; for example, its frequent association with systemic hypertension and a degree of excessive daytime sleepiness similar to that found in nonsleep-stage-dependent OSA. Moreover, REM OSA could increase cardiometabolic risk. Continuous positive airway pressure (CPAP) treatment aimed at preventing REM OSA should be longer than the 4 h usually considered as good compliance, since REM sleep occurs mostly during the second half of the night. Unfortunately, patients with REM OSA show poor adherence to CPAP. Alternative non-CPAP treatments might be a good choice for REM OSA, but data are lacking. This review summarises the available data on REM OSA and critically examines the weaknesses and strengths of existing literature.
阻塞性睡眠呼吸暂停(OSA)可发生在快速眼动睡眠(REM)和非快速眼动睡眠中,或仅限于快速眼动睡眠,因为快速眼动睡眠失张力最容易导致上气道塌陷。快速动眼期睡眠的呼吸时间通常比非快速动眼期睡眠更长、更不饱和。女性快速动眼期 OSA 的发病率高于男性,根据整个睡眠研究计算的呼吸暂停-低通气指数,快速动眼期 OSA 通常发生在轻度-中度 OSA 的情况下。研究强调了快速动眼期 OSA 的一些有害后果,例如,它经常与全身性高血压和白天过度嗜睡有关,其程度与非睡眠阶段依赖性 OSA 相似。此外,快速动眼期 OSA 还会增加心脏代谢风险。旨在预防快速动眼期 OSA 的持续气道正压(CPAP)治疗时间应长于通常被视为良好依从性的 4 小时,因为快速动眼期睡眠主要发生在后半夜。遗憾的是,快速动眼期 OSA 患者对 CPAP 的依从性很差。其他非 CPAP 治疗方法可能是治疗快速动眼期 OSA 的不错选择,但目前还缺乏相关数据。本综述总结了有关快速动眼期 OSA 的现有数据,并对现有文献的不足和优势进行了批判性研究。
{"title":"REM sleep obstructive sleep apnoea.","authors":"Maria R Bonsignore, Emilia Mazzuca, Pierpaolo Baiamonte, Bernard Bouckaert, Wim Verbeke, Dirk A Pevernagie","doi":"10.1183/16000617.0166-2023","DOIUrl":"10.1183/16000617.0166-2023","url":null,"abstract":"<p><p>Obstructive sleep apnoea (OSA) can occur in both rapid eye movement (REM) and non-REM sleep or be limited to REM sleep, when the upper airway is most prone to collapse due to REM sleep atonia. Respiratory events are usually longer and more desaturating in REM than in NREM sleep. The prevalence of REM OSA is higher in women than in men and REM OSA usually occurs in the context of mild-moderate OSA based on the apnoea-hypopnoea index calculated for the entire sleep study. Studies have highlighted some detrimental consequences of REM OSA; for example, its frequent association with systemic hypertension and a degree of excessive daytime sleepiness similar to that found in nonsleep-stage-dependent OSA. Moreover, REM OSA could increase cardiometabolic risk. Continuous positive airway pressure (CPAP) treatment aimed at preventing REM OSA should be longer than the 4 h usually considered as good compliance, since REM sleep occurs mostly during the second half of the night. Unfortunately, patients with REM OSA show poor adherence to CPAP. Alternative non-CPAP treatments might be a good choice for REM OSA, but data are lacking. This review summarises the available data on REM OSA and critically examines the weaknesses and strengths of existing literature.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-14Print Date: 2024-01-31DOI: 10.1183/16000617.0224-2023
Julia Krabbe, Katja Maria Steffens, Sarah Drießen, Thomas Kraus
Background: Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.
Research question: Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?
Study design and methods: A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.
Results: 52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.
Interpretation: This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.
背景:在肺纤维化中发现的重要分子通路也参与了癌症的发病过程,这表明肺纤维化和肺癌的发病过程存在共同的通路:研究问题:接触职业致癌物导致的肺纤维化是否是肺癌的独立风险因素?对 PubMed、Embase、Web of Science 和 Cochrane 数据库中 100 多个有关职业危害导致肺纤维化的检索词进行了全面检索。经过筛选和提取后,对证据质量和荟萃分析的资格标准进行了评估。采用随机效应模型进行荟萃分析:共确定了 52 项研究进行系统性审查。在调查尸检研究中矽肺的几率比(OR 1.47,95% CI 1.13-1.90)和矽肺患者肺癌死亡率的几率比(OR 3.21,95% CI 2.67-3.87)时,亚组的荟萃分析确定矽肺是肺癌的危险因素。只有将吸烟作为混杂因素进行调整的研究才发现肺癌风险显著增加(OR 1.58,95% CI 1.34-1.87)。然而,由于缺乏包括累积暴露的研究,因此无法纳入调整因素。在一项定性综述中,对于石棉沉滞症和矽肺作为肺癌独立风险因素的说法,无法得出明确的结论,部分原因是这些研究没有将累积暴露考虑在内:本系统综述证实了目前有关石棉沉滞症和矽肺病的知识,表明与没有纤维化的接触工人相比,接触石棉沉滞症和矽肺病的人患肺癌的风险更高。应对这些人进行肺癌监测,尤其是在存在石棉沉滞症或矽肺病的情况下。
{"title":"Lung cancer risk and occupational pulmonary fibrosis: systematic review and meta-analysis.","authors":"Julia Krabbe, Katja Maria Steffens, Sarah Drießen, Thomas Kraus","doi":"10.1183/16000617.0224-2023","DOIUrl":"10.1183/16000617.0224-2023","url":null,"abstract":"<p><strong>Background: </strong>Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.</p><p><strong>Research question: </strong>Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?</p><p><strong>Study design and methods: </strong>A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.</p><p><strong>Results: </strong>52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.</p><p><strong>Interpretation: </strong>This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-31DOI: 10.1183/16000617.0121-2023
Anastasia Polytarchou, Angeliki Moudaki, Eli Van de Perck, An Boudewyns, Athanasios G. Kaditis, Stijn Verhulst, Refika Ersu
The aim of this review is to summarise evidence that became available after publication of the 2017 European Respiratory Society statement on the diagnosis and management of obstructive sleep apnoea syndrome (OSAS) in 1- to 23-month-old children. The definition of OSAS in the first 2 years of life should probably differ from that applied in children older than 2 years. An obstructive apnoea–hypopnoea index >5 events·h–1 may be normal in neonates, as obstructive and central sleep apnoeas decline in frequency during infancy in otherwise healthy children and those with symptoms of upper airway obstruction. A combination of dynamic and fixed upper airway obstruction is commonly observed in this age group, and drug-induced sleep endoscopy may be useful in selecting the most appropriate surgical intervention. Adenotonsillectomy can improve nocturnal breathing in infants and young toddlers with OSAS, and isolated adenoidectomy can be efficacious particularly in children under 12 months of age. Laryngomalacia is a common cause of OSAS in young children and supraglottoplasty can provide improvement in children with moderate-to-severe upper airway obstruction. Children who are not candidates for surgery or have persistent OSAS post-operatively can be treated with positive airway pressure (PAP). High-flow nasal cannula may be offered to young children with persistent OSAS following surgery, as a bridge until definitive therapy or if they are PAP intolerant. In conclusion, management of OSAS in the first 2 years of life is unique and requires consideration of comorbidities and clinical presentation along with PSG results for treatment decisions, and a multidisciplinary approach to treatment with medical and otolaryngology teams.
本综述旨在总结2017年欧洲呼吸学会关于1至23个月大儿童阻塞性睡眠呼吸暂停综合征(OSAS)诊断和管理的声明发布后的证据。2岁前儿童OSAS的定义可能应不同于2岁以上儿童。阻塞性呼吸暂停–低通气指数>5 事件·h–1在新生儿中可能是正常的,因为在婴儿期,阻塞性和中枢性睡眠呼吸暂停在其他健康儿童和有上气道阻塞症状的儿童中出现的频率会下降。在这个年龄段的儿童中,经常可以观察到动态和固定的上气道阻塞,药物诱导的睡眠内窥镜检查可能有助于选择最合适的手术干预措施。腺样体切除术可改善患有 OSAS 的婴幼儿的夜间呼吸,孤立的腺样体切除术对 12 个月以下的儿童尤其有效。喉头水肿是导致幼儿 OSAS 的常见原因,喉上成形术可以改善中重度上气道阻塞的儿童的病情。不适合手术或术后持续存在 OSAS 的儿童可采用气道正压(PAP)治疗。对于术后出现持续性 OSAS 的幼儿,可以使用高流量鼻插管,作为最终治疗前的过渡,或者如果他们不耐受气道正压治疗。总之,出生后最初 2 年的 OSAS 的治疗是独特的,需要考虑合并症和临床表现以及 PSG 结果来做出治疗决定,并与医疗和耳鼻喉科团队一起采用多学科方法进行治疗。
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Pub Date : 2024-01-31DOI: 10.1183/16000617.0178-2023
Mariana Conceição, Michal Shteinberg, Pieter Goeminne, Josje Altenburg, James D Chalmers
Introduction: Pseudomonas aeruginosa is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known.
Methods: We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating P. aeruginosa eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for P. aeruginosa at 12 months after eradication treatment. Cystic fibrosis was excluded.
Results: Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month P. aeruginosa eradication rate of 40% (95% CI 34-45%; p<0.00001), with no significant heterogeneity (I2=0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41-55%) than systemic antibiotics alone (27%, 13-45%).
Conclusion: Eradication treatment in bronchiectasis results in eradication of P. aeruginosa from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone.
导言:铜绿假单胞菌是支气管扩张症中最常分离到的病原体,与恶化的预后有关。指南推荐进行根除治疗,但证据基础有限。临床实践中预期的根除成功率尚不清楚:根据流行病学观察性研究 Meta 分析指南,我们进行了系统回顾和荟萃分析。我们在PubMed、Embase、Cochrane系统综述数据库和Clinicaltrials.gov上搜索了有关支气管扩张患者使用抗生素(全身或吸入)根除铜绿假单胞菌的研究。主要结果为根除治疗后12个月铜绿假单胞菌阴性的患者比例。囊性纤维化除外:荟萃分析纳入了六项观察性研究,包括 289 名患者。我们的荟萃分析发现,12 个月的铜绿假单胞菌根除率为 40%(95% CI 34-45%;P2=0%)。与单独使用全身性抗生素(27%,13-45%)相比,联合使用全身性抗生素和吸入性抗生素治疗的根除率更高(48%,95% CI 41-55%):结论:支气管扩张症的根除治疗可使 40% 的病例在 12 个月内根除痰中的铜绿假单胞菌。与单独使用全身性抗生素相比,联合使用全身性抗生素和吸入性抗生素的根除率更高。
{"title":"Eradication treatment for <i>Pseudomonas aeruginosa</i> infection in adults with bronchiectasis: a systematic review and meta-analysis.","authors":"Mariana Conceição, Michal Shteinberg, Pieter Goeminne, Josje Altenburg, James D Chalmers","doi":"10.1183/16000617.0178-2023","DOIUrl":"10.1183/16000617.0178-2023","url":null,"abstract":"<p><strong>Introduction: </strong><i>Pseudomonas aeruginosa</i> is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating <i>P. aeruginosa</i> eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for <i>P. aeruginosa</i> at 12 months after eradication treatment. Cystic fibrosis was excluded.</p><p><strong>Results: </strong>Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month <i>P. aeruginosa</i> eradication rate of 40% (95% CI 34-45%; p<0.00001), with no significant heterogeneity (I<sup>2</sup>=0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41-55%) than systemic antibiotics alone (27%, 13-45%).</p><p><strong>Conclusion: </strong>Eradication treatment in bronchiectasis results in eradication of <i>P. aeruginosa</i> from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-31DOI: 10.1183/16000617.0194-2023
Zainab Ahmadi, Joar Björk, Hans Gilljam, Madhuri Gogineni, Torbjörn Gustafsson, Michael Runold, Thomas Ringbæk, Josefin Wahlberg, Lotta Wendel, Magnus Ekström