European Respiratory Review最新文献

Currently, the only known clinically relevant hereditary risk factor for emphysema is limited to mutations within the SERPINA1 gene, encoding alpha-1 antitrypsin. Although several additional rare high-impact variants have been proposed, their role in emphysema pathophysiology is unclear. This review discusses recent cases investigating novel candidate genes that may be Mendelian causes for emphysema development. We also explore potential methods to confirm the causal relation to COPD. Identifying potential new rare high-impact genetic variants may lead to novel therapeutic targets, thus improving the personalised treatment of COPD. Several gene mutations have been implicated in emphysema development, including SERPINA1, SERPINA3, PTPN6, TERT, TR, NAF1, BICD1, ELN, FBLN, FLNA and SFTPC Mutations of the SERPINA1 and PTPN6 genes are considered definitive causes of emphysema. Studies have ascertained rare variants in cutis laxa genes (ELN, FBLN and FLNA), which cause early-onset emphysema in infants and children via defective elastin synthesis. Telomerase pathway genes (TERT, TR, NAF1 and BICD1) have also been implicated in increased COPD risk along with another member of the serpin family (SERPINA3) and SFTPC These probable mutations for emphysema tend to present later in life. Due to being unconfirmed, they may involve a more complex gene interaction that requires further interrogation with next-generation sequencing and molecular methods, including CRISPR (clustered regularly interspaced short palindromic repeats) screening libraries, whole-exome sequencing or whole-genome sequencing. Although multiple novel mutations have been reported to cause emphysema, further validation is needed. Next-generation sequencing offers a promising method to understand early-onset emphysema and COPD pathogenesis.

Introduction: Streptococcus pneumoniae is a common cause of bacterial pneumonia, bacteraemia and meningitis in adults, especially among older adults and individuals with specific underlying medical conditions. The composition of the capsular polysaccharides distinguishes different pneumococcal serotypes and serves as the target for commercially available vaccines. The 20-valent pneumococcal conjugate vaccine (PCV20) was introduced in 2021, conferring protection to seven additional serotypes over PCV13 and five over PCV15, and, thus, providing increased coverage against common serotypes that cause invasive pneumococcal disease (IPD) and community-acquired pneumonia. The present narrative review summarises current recommendations for pneumococcal vaccination in different countries, focusing on adult and at-risk populations, safety, tolerability, and cost-effectiveness.

Methods: A comprehensive search of existing literature was conducted on PubMed, Scopus and government websites to gather relevant articles, studies and recommendations about PCV20. The information was summarised to provide an overview.

Results: The recommendations for adults over 65 years of age support the use of a single dose of PCV20, and a single booster of PCV20 for people who had previously received PCV13 or PPSV23. The administration of PCV20 is also recommended for those who have not completed the vaccine schedules for PCV13 or PPSV23. Several countries have recently included PCV20 in the vaccination of adults and children at higher risk of developing IPD.

Conclusion: The efficacy, safety and cost-effectiveness of PCV20 support its use in preventing invasive and noninvasive pneumococcal disease across age groups, including those with underlying health conditions.

Introduction: Low-dose computed tomography (LDCT) lung cancer screening (LCS) improves outcomes including mortality in clinical trials, but it is unclear whether this evidence is implemented effectively in real-world practice settings. This systematic review explored how knowledge translation (KT) strategies have been used to improve knowledge, decisional confidence and participation in LDCT LCS programmes.

Methods: Literature searches were performed for comparative studies incorporating KT strategies in relation to LDCT LCS. Articles included a KT intervention intended to facilitate knowledge, participation in screening, improve decisional confidence or increase screening uptake.

Results: 40 studies were selected for data extraction. Studies emanated from the USA (36), Canada (one), the UK (two) and Japan (one), published between 2014 and 2024. KT interventions reported included 41 implementation strategies targeting staff training, patient and provider education, shared decision-making tools, nurse clinics, navigators, forms, electronic reminders and triggers, data presentation modalities, materials targeting specific populations, and quality improvement tools. Meta-analysis identified significant increase in knowledge of risk (OR 2.87, 95% CI 1.29-6.38), LCS candidacy (OR 2.50, 95% CI 1.51-4.14), risk-benefit knowledge (OR 2.82, 95% CI 1.21-6.58), awareness of screening test (OR 11.91, 9.00-15.76) and increased LCS screening participation (OR 2.24, 95% CI 1.44-3.47) in response to KT strategies.

Conclusion: This systematic review identified multiple studies addressing the utilisation and effectiveness of implementation science strategies in KT interventions in the context of LCS. These included a broad range of implementation strategies and KT methodologies that were associated with increased LCS knowledge and participation. There is an urgent need to identify effective implementation strategies leading to enhanced knowledge and screening participation amongst at risk individuals in LDCT LCS programmes.

Introduction: Lung cancer screening (LCS) is an evolving field with variations in its implementation worldwide. National LCS programmes are limited and preliminary data from national implementation are scarce.

Aim: An up-to-date overview of the available literature about 12 LCS-related topics that were identified as priorities by a multidisciplinary task force (TF) panel and patient representatives as well as synthesis of published evidence to inform clinical practice and health decision-making about LCS implementation. In specific areas where the scientific evidence is limited or mixed, the limitations are discussed and best practices based on available evidence are concluded.

Materials and methods: A multidisciplinary TF expert panel collaborated with patient representatives, identified 12 areas of interest and incorporated patient priorities. A systematic literature search was conducted, followed by screening, review and synthesis of available evidence.

Results: There is a lack of national LCS programmes in most countries worldwide. LCS benefits and potential risks are well established. Low-dose computed tomography (LDCT) combined with smoking cessation should be offered as part of a LCS strategy to ensure optimal clinical outcomes. Age and smoking status cut-offs as well as other inclusion criteria vary and should be based on national epidemiological data. Available LCS risk predictor models and biomarkers require further clinical validation prior to implementation across the entire spectrum of LCS candidates. LCS frequency remains controversial with biennial LDCT being supported by current evidence. Technical standards, quality assurance and LCS management protocols are essential in LCS implementation.

Conclusions: LCS benefits override potential risks. There is slim evidence for specific cut-off values for inclusion criteria, the optimal duration of LCS programmes and the application of LCS biomarkers in clinical practice. Smoking cessation should be integrated within LCS programmes. Ongoing scientific activity in the area is expected to provide answers in the near future.

Background: The incidence and prevalence of disease caused by nontuberculous mycobacteria (NTM) are increasing globally, yet treatment regimens remain complex and often ineffective. Newer tetracyclines have shown promise as a potent therapeutic. In this systematic review, we assessed the evidence for the use of tetracyclines for the treatment of NTM disease, complemented by a narrative review of nonclinical data.

Methods: Medline (PubMed) and Web of Science were searched from inception to February 2024 for clinical studies that assessed the safety, tolerability or efficacy of tetracyclines for NTM disease. Search results were screened against pre-defined inclusion and exclusion criteria. Nonclinical data were identified using a targeted literature search and are presented in a narrative synthesis.

Results: A total of 89 citations were included, comprising 43 clinical studies (six prospective observational studies, 18 retrospective studies and 19 case series) and 46 nonclinical studies. Nonclinical studies demonstrated potent in vitro activity for tigecycline, omadacycline and eravacycline, particularly against rapidly growing mycobacteria (RGM). No randomised controlled trials (RCTs) were identified. Most clinical experience was for RGM (largely Mycobacterium abscessus) and supported the use of newer tetracyclines. Evidence for the treatment of slowly growing mycobacteria, particularly Mycobacterium avium complex, was more limited.

Conclusions: There remains a significant unmet need for effective, well-tolerated therapies for the treatment of NTM, especially those that improve quality of life. Although tetracyclines have not been evaluated in RCTs, clinical evidence suggests that tetracyclines may contribute to the efficacy of combination regimens used to treat NTM disease and further RCTs are warranted.

The case fatality of tuberculosis (TB) has progressively decreased since the use of antibiotics in anti-TB treatment, leaving 155 million TB survivors alive in 2020. Of the 122 million disability-adjusted life years (DALYs) due to TB in 2019, 58 million DALYs were attributed to the post-TB phase. TB causes massive lung structure damage, declined lung function and excessive inflammation, which persist even after microbiological cure and predispose to multiple lung diseases (e.g. COPD, chronic pulmonary aspergillosis, bronchiectasis and COVID-19). TB survivors also face a higher risk of cancers and cardiovascular diseases. These post-TB morbidities together with worse psychological and socioeconomic status lead to poor quality of life and a three- to four-fold higher mortality rate than the general population. Understanding the epidemiology of post-TB morbidities can help to set intervention and research priorities to lower public health burdens associated with post-TB morbidities. In this narrative review, we summarise what we know and do not know about the prevalence, risk factors and management of post-TB morbidities and their associated mortality. We identify the major post-TB morbidities based on current evidence. Delayed or incomplete TB treatment, residual lung structure damage and prolonged inflammation after TB treatment are important risk factors. Developing host-directed therapies to reduce lung structure damage, smoking cessation, implementing pulmonary rehabilitation to improve lung function and adopting well-tailored preventive strategies and screening protocols may improve the management of these post-TB morbidities and mortality and warrant future research.

This systematic review aims to summarise the impact of exercise training on peripheral muscle fatigability in people with COPD, addressing different assessment methods and exercise interventions (i.e. endurance, resistance and combined training).PubMed, CENTRAL, CINAHL and PEDro databases and trial registers were searched from inception to September 2024. We identified randomised and nonrandomised trials assessing pre-to-post-training changes in muscle fatigue resistance, assessed as a reduction in volitional or non-volitional measures of muscle strength or muscle total work output during standardised fatiguing protocols. The Cochrane Risk of Bias 2 (RoB 2) and Risk of Bias in Non-randomized Studies - of Interventions (ROBIN-I) tools were used for assessing risk of bias in randomised controlled trials and nonrandomised studies of interventions, respectively, and meta-analyses were performed.A total of 20 studies (574 participants from 14 randomised controlled trials and 217 from six nonrandomised studies of interventions) were included. Overall, combined endurance and resistance training appeared to improve muscle fatigue resistance. While results varied by study design, type of training and fatiguing protocols, similar improvements were observed in quadriceps fatigue resistance regardless of the assessment method. In contrast, no significant improvements were observed in the fatigue resistance of the arm muscles. However, the presence of moderate to high risk of bias in several included studies may have influenced the results.The findings of this systematic review suggest a positive effect of exercise training in improving muscle fatigue resistance, particularly in the leg muscles, in people with COPD. Future research should establish standardised protocols for assessing muscle fatigability and explore alternative tools to facilitate the clinical implementation of muscle fatigability outcomes into COPD rehabilitation.

Background: Chronic respiratory diseases, such COPD and asthma, increase the risk of atherosclerotic cardiovascular disease (ASCVD) through shared pathophysiological mechanisms and modifiable risk factors. There are a number of methods to assess ASCVD, and limited systematic information about how these may be applied to chronic respiratory diseases.

Objective: To systematically report existing methods of estimating ASCVD risk in chronic respiratory disease populations, highlighting strengths, limitations and clinical applicability.

Methods: A systematic search of MEDLINE, Embase, Scopus, and CINAHL was conducted up to June 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (www.crd.york.ac.uk/PROSPERO identifier CRD42024543335). An extended search was also performed. To assess search sensitivity, a random sample of 30 studies from the extended search were reviewed. Key international clinical guidelines were examined for recommended tools. Studies assessing ASCVD risk in chronic respiratory disease populations were included. A narrative synthesis was employed.

Results: 63 studies from 26 countries identified 68 ASCVD risk assessment tools and biomarkers in chronic respiratory disease. Imaging techniques such as coronary artery calcium scoring, and carotid intima-media thickness provide detailed anatomical information, but require equipment and expertise. Risk scores (Framingham Risk Score; Systematic Coronary Risk Evaluation) are practical, although they lack precision at the individual level. Biomarkers and functional tests provide holistic measurements yet are often resource-demanding. Arterial stiffness measurement directly assesses vascular pathology and requires specialist equipment.

Conclusion: Multiple ASCVD risk assessment methods exist for chronic respiratory diseases, highlighting the need to understand the strengths and weaknesses of tools for tailored solutions. Future studies should address validation, accessibility and improved personalised risk stratification.