European Respiratory Review最新文献

Background: Acute lower respiratory infections (ALRIs) are a significant health concern, particularly affecting children and older adults. Air pollution is a known risk factor. Despite numerous systematic reviews exploring this relationship, varying methodological quality hinders the derivation of reliable concentration-response functions essential for health risk assessment.

Methods: We critically appraised systematic reviews investigating the association between air pollution and ALRI incidence and mortality, evaluating both short-term and long-term effects across age groups. Comprehensive searches were conducted in PubMed and Embase (up to November 2024). Included systematic reviews were evaluated using AMSTAR2-EH (A MeaSurement Tool to Assess systematic Reviews-Environmental Health), assessing methodological quality specific to environmental epidemiology.

Results: Among 330 unique systematic reviews, 15 met inclusion criteria. Short-term systematic reviews did not meet methodological appraisal standards. Studies on other pollutants, like ozone (O₃) and sulfur dioxide (SO₂), lacked conclusive methodologically high-quality evidence. Long-term systematic reviews generally demonstrated methodological rigour, linking nitrogen dioxide (NO₂) exposure to ALRI incidence in children (relative risk 1.09, 95% CI 1.03-1.16) and ALRI mortality in adults (relative risk 1.06, 95% CI 1.02-1.10 and 1.08, 95% CI 1.04-1.12 for NO₂; relative risk 1.204, 95% CI 1.095-1.325 for particulate matter with a 50% cut-off aerodynamic diameter of 2.5 µm (PM_2.5)).

Conclusions: This overview systematically assessed systematic reviews using AMSTAR2-EH, highlighting methodological gaps, particularly in short-term studies, bias assessment and protocol registration. Overall, the evidence suggests a mild but significant association between short-term exposure to air pollutants and pneumonia incidence, and a stronger, more consistent association between long-term exposure and ALRI incidence and mortality, especially for NO₂ and PM_2.5. These findings can inform public health policies and environmental regulations aimed at reducing respiratory disease burden due to air pollution.

Background: Childhood bronchiectasis is an under-recognised and increasingly prevalent lung disease with a poorly understood pathogenesis. Traditional models focus on the damage in the large airways and the resultant microbial colonisation; however, the initiating events remain unclear.

Objective: We propose a unified, evidence-based model in which injury to the small airway epithelium leads to the formation of hyperconcentrated, stagnant mucus. This initiates a muco-inflammatory positive feedback loop that causes small airway wall thickening. The development of bronchiectasis in the large airways represents the final stage of this process.

Content: This review synthesises emerging clinical, histological and experimental data suggesting that small airway obstruction from hyperconcentrated mucus leads to localised hypoxia. In turn, hypoxic epithelial cells and stagnant mucus promote the release of alarmins, driving neutrophilic infiltration in the absence of infection. This process establishes a self-perpetuating muco-inflammatory loop characterised by excessive mucin production and immune dysregulation, which results in progressive thickening of the small airway walls through the formation of lymphoid follicles. Neutrophil recruitment into the major airways follows, marking the next step in the pathophysiology cascade. These events precede microbial colonisation and the characteristic radiological features of bronchiectasis.

Conclusion: By redefining hyperconcentrated mucus and small airway dysfunction as the initial events in the bronchiectasis cascade, our model offers novel mechanistic insight. Targeted interventions at various stages of this cascade are clearly needed. If validated, this model could shift therapeutic focus in paediatric bronchiectasis, from antibiotics toward muco-regulatory or anti-inflammatory agents, especially during the early, often asymptomatic stages of the disease.

Since their market introduction in 2007, electronic cigarettes (e-cigarettes) have rapidly gained popularity, often marketed as a safer alternative to traditional smoking. Their appeal, especially among adolescents, is heightened by the wide variety of available flavours. However, both acute and chronic exposure to e-cigarettes has been linked to adverse health effects, including oxidative stress, inflammation and airway barrier dysfunction. While several cell culture and animal studies have explored the effects of e-cigarette exposure on the respiratory tract, comprehensive comparisons of the cellular and physiological outcomes across in vitro, in vivo and human studies remain limited. In this review, we evaluate in vitro and in vivo models of e-cigarette exposure, alongside human studies examining the respiratory outcomes of e-cigarette use. Common in vitro models, such as human bronchial epithelial cells and primary lung fibroblasts, have been exposed to e-cigarettes, with assessments including cell viability and cytokine release. Similarly, in vivo models using mice or rats exposed to e-cigarette aerosols or extracts have revealed effects ranging from inflammation to lung tissue damage. Additionally, we review human studies that track biomarker changes to directly assess the impact of e-cigarette smoke on participants' respiratory health. By integrating findings from diverse approaches, we aim to provide greater insight on the impact of e-cigarettes on lung health that will guide future research in selecting the most appropriate models for studying airway damage. Ultimately, this synthesis of research will contribute to advancing the scientific dialogue on e-cigarette use and its implications for respiratory health.

Introduction: Interstitial lung diseases (ILDs) are complex, requiring multifaceted care for optimal management of patients' symptoms and health outcomes. This systematic review evaluated the content coverage of currently available clinical guidance documents ILD.

Methods: A systematic search was performed to identify clinical guidance documents published between 2011 and March 2025 in the Embase, Ovid Medline and Trip databases. Document characteristics, quality and contents covered were independently assessed by two reviewers.

Results: A total of 79 ILD clinical guidance documents were identified, with clinical practice guidelines (n=50) having superior quality based on the Institute of Medicine standards. The content of most documents (84%) focused on ILD aetiology, with connective tissue disease (44%) being the most discussed. Only 46% of documents covered pulmonary manifestations, which often encompassed pulmonary hypertension (30%) and hypoxaemia (28%). Extrapulmonary morbidities were covered in 28% of documents, with gastro-oesophageal reflux disease (23%) and obstructive sleep apnoea (10%) being commonly presented. Behavioural and lifestyle factors were covered in 34% of documents, with most addressing physical inactivity (30%). Additionally, 51% of documents covered overall diagnostic approach for ILD, 35% lung transplantation, 22% acute exacerbations and 19% palliative care.

Conclusion: Despite growing awareness of ILD, most clinical guidance documents have limited coverage for domains of patient care outside of diagnosis and pharmacotherapies. Future clinical guidance documents on ILD should address the content gaps to deliver comprehensive care for patients with ILD, with engagement of different stakeholders from various regions.

Background: Recurrence-, progression-, disease- and event-free survival are often selected as the primary end-points for trials assessing peri-operative systemic therapy for nonsmall cell lung cancer (NSCLC). As overall survival (OS) has increased, these surrogates, which we hereafter collectively term "recurrence-/progression-free survivals (RPFS)", have become more attractive end-points.

Methods: This systematic review, without meta-analysis, was conducted in accordance with the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (UMIN000052558). Electronic databases were searched on 11 October 2023. English-language articles presenting a randomised controlled trial assessing neoadjuvant and/or adjuvant systemic therapy for NSCLC were included. The main outcome was the weighted Spearman's rank correlation coefficient (r) between the hazard ratios (HRs) of OS (HRos) and RPFS (HRrpfs). The weight assigned to each study was determined using the inverse variance of the log HRos. Pathological subtype and driver mutations were not questioned.

Results: We identified 31 trials with a total of 15 776 patients. The weighted correlation coefficient was 0.86 based on the raw data from the 31 trials. After reciprocal duplication, the weighted correlation coefficient was 0.91 (p<0.001 for unweighted r). Subgroup analyses showed the correlation was 0.98 for trials with immune checkpoint inhibitors but was 0.54 for molecular targeted therapy CONCLUSIONS: We hope that our data will justify the use of the HRs of recurrence-, progression-, disease- and event-free survival as primary end-points in peri-operative immune checkpoint inhibitor regimens for NSCLC.

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.