European Respiratory Review最新文献

The management of asthma exacerbations is well established, including inhaled short-acting β₂-agonist administration, systemic corticosteroid therapy and supplemental oxygen. Severe asthma exacerbations (SAEs) nonresponsive to medical and O₂ therapy may require mechanical ventilation via endotracheal intubation (ETI), evaluation and admission to the intensive care unit (ICU). However, up to 35% of intubated and ventilated patients die due to conventional mechanical ventilation (CMV)-related life-threatening complications (i.e. barotrauma, circulatory collapse, cardiac arrhythmias, acute coronary syndrome, atelectasis and pneumonia). Among noninvasive respiratory therapies, the effectiveness of noninvasive ventilation (NIV) in preventing clinical deterioration and CMV in the earlier phases of SAE remains controversial. Limited tolerance to mechanical ventilation represents a drawback that can compromise treatment success. The high-flow nasal cannula (HFNC) is a widely applied respiratory supportive tool for the management of several patterns and types of acute respiratory failure, with patient acceptance being a key point favouring its application. Despite a potential pathophysiological rationale, clinical data on the feasibility and effectiveness of HFNC in SAEs are lacking. We conducted this concise narrative review to summarise the physiological and clinical benefits of HFNC compared to conventional oxygen therapy (COT) in adult patients with SAEs, focusing on outcomes such as dyspnoea, comfort, lung gas exchange, facilitation of inhaled therapy, hospitalisations, ETI and ICU admission. According to available data, there is no evidence of either superiority or inferiority of HFNC versus COT in SAEs. Further larger randomised control trials are required to define the role of HFNC in asthmatic attacks.

COPD is a heterogeneous, progressive inflammatory airway disease, with patients presenting with a wide variety of symptoms, comorbid conditions and underlying pathophysiology. Smoking is a major contributing factor to disease burden, alongside other environmental and patient-related risk factors. Airway inflammation is consistently present in COPD and is implicated in disease pathogenesis and progression. The airway epithelium functions as an active physiochemical barrier, protecting the lungs from pathogens and airborne environmental triggers, and as an immune organ that coordinates immunological activity in response to pollutant, bacterial, viral or allergen exposure. Inhalation of cigarette smoke and other airborne triggers can damage bronchial epithelial cells, leading to exaggerated inflammatory responses and airway remodelling. Airway inflammation in COPD, including neutrophilic and eosinophilic phenotypes, is mediated by the epithelium and epithelial cell-derived cytokines. Improving our understanding of epithelial-related inflammation in COPD is essential for the identification of novel biomarkers, stratification of patients, development of targeted therapeutics and creation of personalised treatment strategies. Here, we review the current understanding of the role of the airway epithelium in COPD pathogenesis, providing an overview of the pathological changes to the epithelium and the role of the epithelial-derived cytokines in driving different inflammatory phenotypes. We then consider biomarkers related to epithelial function in COPD and discuss how the epithelium might be targeted by novel COPD therapies.

A large proportion of patients (40-60%) with severe asthma present with persistent airway obstruction (PAO). Patients with severe eosinophilic asthma (SEA) and PAO appear to be an underrepresented group in clinical guidance, despite being associated with considerable healthcare and economic burden. High levels of eosinophils drive airway inflammation, obstruction and hyperresponsiveness, which are key characteristics of SEA and can increase the risk of PAO and subsequent irreversible worsening of lung function. Available clinical and real-world data must examine the effectiveness of biologic treatment targeting SEA in PAO to identify any data gaps that might help further define such patients and optimise their management. However, clinical trials of SEA frequently exclude the enrolment of patients with PAO. Eosinophils are activated and recruited to airways in response to different cytokines, particularly interleukin-5 (IL-5), produced via a complex molecular and cellular cascade. A few studies evaluating the effectiveness of benralizumab and mepolizumab were able to identify cohorts of patients with SEA and PAO who had a significant response to these IL-5/Rα-targeted biologics. PAO in patients with SEA represents a distinct clinical entity, one which could be referred to as "persistent eosinophilic airway obstruction". Patients with persistent eosinophilic airway obstruction are likely to be responsive to targeted biologic treatment, although additional clinical studies and real-world data are needed to further assess treatment efficacy and safety in this population and provide guidance to clinical practice.

Background: Barriers to delivery of pulmonary rehabilitation are not evenly distributed across people with chronic lung disease. The aim of this systematic review was to evaluate equity in pulmonary rehabilitation delivery and outcomes, in relation to the social determinants of health.

Methods: A systematic search of four online databases was undertaken. Two reviewers independently screened studies and extracted data. Social determinants of health were categorised according to the PROGRESS-Plus framework, and mapped to the Health Equity Implementation Framework. We reported the impact of PROGRESS-Plus factors on pulmonary rehabilitation access, uptake and completion, and outcomes of health-related quality of life and exercise capacity.

Results: 32 studies from 13 countries were included. Place of residence (rurality, travel distance) was consistently associated with poor access and uptake. Uptake was lower for Black people than White people (OR 0.87, 95% CI 0.81-0.95; two studies, n=1 128 623) and in those of low socioeconomic status (OR 0.63, 95% CI 0.55-0.73; two studies, n=1 134 811). Men were more likely to complete than women (OR 1.13, 95% CI 1.06-1.20; eight studies, n=20 509). People who were working were less likely to complete (OR 0.70, 95% CI 0.47-1.04; three studies, n=3292). There was no impact of PROGRESS-Plus features on improvements in health-related quality of life or exercise capacity with pulmonary rehabilitation.

Conclusions: There are inequities in delivery of pulmonary rehabilitation. Targeted efforts to improve pulmonary rehabilitation delivery in disadvantaged groups are required, to ensure that all people with chronic lung disease are able to realise its benefits.

Background: Pneumonia remains the predominant cause of childhood mortality and morbidity globally. While various imaging modalities have been employed for paediatric pneumonia diagnosis, the diagnostic accuracy remains inadequately characterised.

Objective: To systematically evaluate and compare the diagnostic accuracy of available imaging modalities for paediatric pneumonia through both diagnostic test accuracy (DTA) meta-analyses and network meta-analysis (NMA).

Methods: PubMed, Embase, Cochrane Library and Web of Science were searched up to March 2025. The risk of bias was graded using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Diagnostic accuracy measures were pooled using random-effects DTA meta-analyses, while relative diagnostic performance was compared through NMAs.

Results: 81 studies published in 22 countries since 2008 were included, with a total of 34 625 children. In most of the studies, there was an unclear risk of bias. When clinical examination served as reference test, lung ultrasound demonstrated high diagnostic accuracy with sensitivity of 0.91 and specificity of 0.93. NMAs showed superior overall diagnostic performance of computer-aided chest radiography compared to lung ultrasound across all indexes except specificity, where there was no difference in sensitivity or specificity between the two. Meta-regression identified study design and pneumonia type as significant modifiers of diagnostic sensitivity.

Conclusion: This comprehensive analysis provides robust evidence supporting the clinical utility of computer-aided chest radiography and lung ultrasound for paediatric pneumonia diagnosis. However, insufficient evidence precludes definitive conclusions regarding other computer-aided modalities. Future high-quality comparative studies are needed to validate these findings in diverse clinical settings and evaluate emerging imaging technologies.

Background: Molecular profiling has become essential in the management of nonsmall cell lung cancer (NSCLC). While endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a cornerstone in diagnosis, tissue scarcity may hinder comprehensive testing. Recent studies suggest that supernatant from EBUS-TBNA could serve as an alternative source for molecular analysis.

Methods: A systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO identifier CRD42024600046). Studies from 2000 to 2024 evaluating the feasibility, molecular concordance and turnaround time of EBUS-TBNA supernatant for molecular profiling in NSCLC were included. Outcomes included DNA yield, detection of actionable mutations and agreement with tissue-based results.

Results: Seven studies (n=506 patients) were included. Feasibility of molecular analysis using supernatant was high (87-100%). DNA yields varied across studies. In pooled analysis, storage temperature and preservation solution had no significant effect, while individual studies reported lower yields with high-speed centrifugation. Concordance with tissue samples ranged from 83% to 100%, with Cohen's κ 0.947 (95% CI 0.905-0.989), indicating an almost perfect agreement. Supernatant samples demonstrated faster turnaround times (reduction of 1-7.5 days).

Conclusions: EBUS-TBNA supernatant is a feasible and accurate source for molecular testing in NSCLC, with high concordance and shorter turnaround times. Standardisation of protocols is required before broader implementation in clinical practice.

Obstructive sleep apnoea (OSA) is a major public health concern, strongly linked to cardiovascular disease and cancer. Extracellular vesicles (EVs) have emerged as key mediators in intercellular communication, oxidative stress and inflammation, carrying molecules that can influence OSA pathophysiology. However, their role in OSA pathophysiology remains underexplored. This systematic review consolidates current research on EVs in OSA, focusing on their cargo, surface proteins and impact on oxidative stress, inflammation, cancer progression and cardiovascular dysfunction. Registered in the International Prospective Register of Systematic Reviews (ID CRD 42024537136), it explores the intricate links between OSA and EVs to uncover disease mechanisms and identify potential biomarkers. The search was conducted in PubMed/Medline and Web of Science databases to identify studies exploring OSA and EVs in clinical studies, animal studies and in vitro studies. Among the 600 unique studies screened, 27 met the inclusion criteria. These studies demonstrated that OSA-derived EVs influence key biological processes, such as endothelial dysfunction, inflammation and tumour cell proliferation. Transcriptomic and proteomic analyses revealed dysregulation of specific microRNAs and proteins in EVs from OSA patients in comparison with controls. Notably, EVs studies in clinical, animal and in vitro settings were shown to enhance cancer cell migration and endothelial dysfunction, underscoring their potential as biomarkers for OSA-related comorbidities. EVs hold great promise as minimally invasive, cost-effective biomarkers for understanding OSA mechanisms, diagnosis and prognosis. However, stricter characterisation and comprehensive profiling of their dynamics and cargo are essential to standardise methodologies and clarify their role in the disease.

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.