European Respiratory Review最新文献

Introduction: Early chronic obstructive pulmonary disease (COPD) is considered to represent the initial phase of the disease. However, inconsistent terminology and lack of standardised definitions hinders research and clinical application. This systematic review examined clinical research on early COPD, analysed terms and definitions used, and evaluated predictors of disease progression. This serves as a platform to reach consensus and direct future research to target early disease states and improve patient outcomes.

Methods: Utilising a standardised protocol, we systematically screened all clinical studies on early COPD. Titles and abstracts were reviewed and compared against inclusion and exclusion criteria. Stage 1 assessed terminology and definitions and stage 2 evaluated predictors of progression. Two independent people reviewed studies at each stage. Study quality was appraised using a modified Downs and Black checklist.

Results: We identified 4871 articles, 1759 were screened after duplicate removal. The terms used included PRISm (preserved ratio impaired spirometry) (104 articles), GOLD 0 (Global Initiative for Chronic Obstructive Lung Disease stage 0) (63), early COPD (37), at-risk COPD (35) and pre-COPD (30). Definitions were heterogeneous and proposed early COPD definitions were not routinely used. Stage 2 included 43 full-text articles from cohort studies, of which 93% were of good quality. Predictors of progression included age (n=13 articles), smoking history (12), symptoms (12), exacerbations (one), lung function measures (20), computed tomography metrics (14), risk tools (three) and machine learning approaches (three).

Conclusion: We demonstrate an urgent need for consensus on clinically applicable definitions of the early disease course of COPD, prior to diagnosis. We highlight predictors of progression; these need validation to enable stratification of individuals early in their disease trajectory for targeted management to halt or modify progression.

The global rise in the older population poses novel challenges in healthcare systems. Ageing is associated with immunosenescence, a progressive decline and remodelling of the immune system, and with inflammageing, a chronic, low-grade inflammatory process. Both states are associated with increased susceptibility to infections and adverse outcomes, especially in the context of infections. In this review, we examine the molecular and cellular pathophysiological mechanisms of immunosenescence and inflammageing that predispose older adults to increased morbidity and mortality from respiratory viral infections. We also outline the clinical implications of the ageing immune system, along with the most up-to-date evidence on possible biomarkers, preventative measures and treatment options aimed at mitigating the effects of immunosenescence on the vulnerability of older adults in respiratory viral infections.

Prior to 2024, pulmonary hypertension (PH) associated with chronic lung diseases (group 3 in the classification of PH) was subclassified according to the type of ventilatory disorder (obstructive, restrictive lung disease or mixed patterns) and not according to the lung disease itself. In 2024, the 7th World Symposium on PH proposed a revised classification, describing associations with specific lung diseases, such as COPD, interstitial lung disease and combined pulmonary fibrosis and emphysema. This update highlights the distinct pathophysiological mechanisms, clinical manifestations, outcomes and management strategies across these subgroups. Of note, a nonparenchymal restrictive lung disease subgroup has been identified, which includes patients with hypoventilation syndromes (due to kyphoscoliosis, diaphragmatic diseases, obesity hypoventilation syndrome, central hypoventilation syndromes, etc.) or pneumonectomy. Paradoxically, despite being one of the earliest forms of PH described, PH associated with nonparenchymal restrictive lung diseases remains among the least studied subtypes. As with all causes of group 3 PH, the primary focus of management is to address the underlying condition whenever possible. There are few data on the efficacy, safety and tolerability of the treatments approved for pulmonary arterial hypertension in this specific population. This review aims to provide updates on this condition and its management, to highlight the mechanisms of PH in each nonparenchymal restrictive lung disease and to study the relevance of the new classification and the necessary avenues of research.

Lung transplant recipients face high rejection rates, causing significant disease burden and limiting long-term outcomes. Among immunological factors affecting lung allografts, anti-human leukocyte antigen (HLA) antibodies, particularly donor-specific anti-HLA antibodies (DSAs), are key mediators of antibody-mediated rejection. Yet, the biology, detection and interpretation of DSAs remain incompletely defined across the pre-, peri- and post-transplant continuum. HLAs are highly polymorphic immune recognition molecules, and donor-recipient mismatches drive alloimmune responses. HLA typing is used to assess genetic disparity, but low-resolution approaches risk misclassifying mismatches and DSAs, whereas high-resolution typing improves diagnostic accuracy yet is not universally implemented. Standard HLA antibody monitoring assays report median fluorescence intensity. However, median fluorescence intensity does not convey information on the affinity, avidity or functional capacity of these antibodies, and may be affected by technical factors such as bead saturation, the Hook effect or binding to denatured HLAs. Subclass profiling adds further complexity: IgG1 and IgG3 are potent complement activators, whereas IgG2 and IgG4 have weaker or regulatory roles and differ in clearance by apheresis. Functional assays, including C1q- or C3d-binding HLA antibody detection assays and emerging endothelial or natural killer-cell-based platforms, offer additional insights into antibody-binding, complement activation and cytotoxic potential, but are not routinely applied in current clinical practice.Prospective mechanistic studies are required to define the clinical benefit, cost-effectiveness and optimal integration of these advanced immunological tools into routine practice pre-, peri- and post-lung transplant.DSAs drive lung allograft injury, yet their detection and interpretation remain inconsistent. Implementation of high-resolution HLA typing and functional assays may improve risk assessment and guide future clinical practice.

Childhood interstitial lung disease (chILD) is a heterogeneous group of rare lung diseases that comprises more than 200 entities. The diagnostic process for chILD might require multiple investigations, which often include a combination of clinical assessments, imaging studies, genetic testing and invasive procedures. Given the prolonged diagnostic timeline, supportive treatments are typically initiated followed by more targeted therapies generally postponed until the underlying cause of the disease is identified. This systematic review aims to describe the current knowledge regarding different treatment strategies for chILD and critically appraise, compare and qualitatively summarise the current evidence on old and emerging therapies for chILD. Of the 5775 publications returned from the initial search, 100 studies met the inclusion criteria, of which 50% were reviews or task force reports from several scientific societies, 41% case reports or case series, 5% randomised controlled trials and 4% preclinical studies on emerging therapies. In order to provide a clearer description of the data analysed, we describe available therapeutic options for chILD in general, organised by treatment type, and then we report treatments categorised by specific pathology.

Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective modulator therapy associated with significant improvements in respiratory function and quality of life among people living with cystic fibrosis (CF). However, ETI has also been shown to result in significant weight gain and there is emerging interest regarding traditional cardiometabolic risk factors. This systematic review investigated the effects of ETI on cardiometabolic risk factors (obesity/overweight, body composition, glucose metabolism, lipids, blood pressure and bone parameters) in people living with CF. This review adhered with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO (CRD42025630118). The following databases were searched in December 2024 and June 2025: PubMed, Scopus, Web of Science and Embase. A total of 54 publications met inclusion criteria (including ETI treatment duration >4 months, >10 total participants, empirical studies) and underwent data extraction. Risk of bias was assessed using National Institutes of Health tools. Results were prepared in tabular format and narrative summary. There was notable heterogeneity in study design and results. In published studies to date, ETI initiation was generally followed by a decrease in glycated haemoglobin, but minimal change in other glycaemic or insulinaemic parameters. Some studies reported increased blood pressure, hypertension and overweight/obesity classification, and cholesterol levels. The observational design and short duration of most studies limit the ability to conclude direct effects of ETI, particularly in the long term. However, we conclude there is likely increased risk of certain traditional cardiometabolic risk factors in ageing people with CF, thus highlighting the importance of clinical surveillance and prompt intervention if needed.

The rising global prevalence of post-COVID-19 condition (PCC) underscores the substantial and ongoing burden faced by individuals following severe acute respiratory syndrome coronavirus 2 infection. The volume of emerging evidence regarding pulmonary-related PCC complications highlights the urgent need for current, evidence-informed guidelines to ensure timely assessment and effective treatment for those affected by PCC. Thus, the aim of this review was to synthesise existing research on the management and treatment of pulmonary complications in individuals with PCC. A rapid review of published and grey literature focused on pulmonary-related PCC complications was completed in November 2023 and updated in June 2025, in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. We identified 73 unique articles, including 12 guidance documents, 24 secondary studies (including 11 systematic reviews with meta-analyses, eight systematic reviews and three scoping reviews) and 37 primary research studies (13 randomised controlled trials) and narratively synthesised their findings. Guidance documents addressed workup and management for pulmonary-related PCC complications, recommending the use of pulmonary function testing with diffusing capacity and the importance of ruling out other conditions. Although evidence regarding the use of medical and pharmacological interventions for treatment of pulmonary-related PCC complications were limited and inconclusive, the current evidence base suggested potential effectiveness of a multidisciplinary rehabilitation approach for pulmonary-related PCC treatment, involving specialist consultations and tailored rehabilitation programmes. The heterogeneity in study quality and risk of bias warrants cautious interpretation of the findings. The current evidence and evolving healthcare landscape suggest the need for updated, evidence-informed clinical guidance.

Background: Physical inactivity is a common and potentially modifiable trait in individuals with chronic airways disease, yet disease-specific physical activity profiles and clinical determinants remain poorly defined.

Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines to characterise physical activity profiles across the spectrum of chronic airways disease. Studies reporting objectively measured physical activity in adults with COPD, asthma, noncystic fibrosis bronchiectasis, cystic fibrosis or primary ciliary dyskinesia were included. Primary outcomes were daily step count and time spent in moderate-to-vigorous physical activity (MVPA). Univariate and multivariate regression analysis was used to explore disease-specific determinants and associations with established clinical outcome measures.

Results: 236 studies (353 cohorts, n=25 278 with chronic airways disease) met the eligibility criteria. The mean daily step count was 5494 (95% CI 5152-5636) and MVPA was 48.2 min·day^-1 (95% CI 33.8-62.6), with the lowest levels observed in COPD. Physical activity levels were consistently lower than matched healthy controls. Disease-specific determinants of physical activity remained elusive; body mass index and percent predicted forced expiratory volume in 1 s (FEV₁) were significant in COPD and asthma. Step count associated positively with FEV₁ % pred and 6-min walk distance, and negatively with modified Medical Research Council scores.

Conclusion: Physical inactivity is highly prevalent across chronic airways diseases and is consistently associated with established clinical outcome measures. These findings highlight the clinical relevance of objective physical activity assessment and support its consideration within the treatable traits framework as part of routine disease evaluation and management.

Background: Paediatric noncystic fibrosis bronchiectasis (NCFB) is a chronic respiratory condition characterised by airway infection, chronic inflammation, mucociliary dysfunction and structural lung damage. Emerging evidence highlights the importance of the local immune response and microbial environment in driving disease progression.

Objectives: This systematic review aimed to summarise contemporary evidence on bronchoalveolar lavage (BAL)-derived cytokine levels, immune cell phenotypes and microbiota in paediatric NCFB, with a focus on their role in disease pathogenesis, phenotype classification and potential to inform targeted interventions.

Methods: The review followed PRISMA guidelines and was registered with PROSPERO (CRD42024520391). Six electronic databases were searched for studies investigating BAL cytokines, immune cells or microbiota in paediatric NCFB. Data extraction followed a pre-defined template and methodological quality was assessed using the RoB 2.0 and AXIS tools.

Results: 20 studies were included. Methodological and clinical heterogeneity precluded meta-analysis. Across studies, neutrophils consistently dominated the cellular profile, closely associated with pathogen detection, particularly Haemophilus influenzae and BAL-derived immunological biomarkers. Cytokine profiling demonstrated consistent elevations of pro-inflammatory mediators, notably interleukin-8, with variable associations to disease severity and pathogen-specific immune responses. Microbiota analyses, though limited, suggest that paediatric NCFB is not defined by a distinct microbial signature of the lower airways.

Conclusion: Current evidence supports a model in which neutrophilic inflammation, driven by dysregulated cytokine responses and potentially sustained by microbial dysbiosis, is central to the pathophysiology of paediatric NCFB. Key gaps remain regarding dysbiosis, adaptive immunity and the longitudinal trajectories of immune mediators. Addressing these may support biomarker development and targeted therapies.

Objective: This scoping review aims to map the available studies on single-breath pulmonary diffusing capacity for nitric oxide (D _LNO) in various clinical diseases and identify gaps for future research.

Methods: We followed the JBI methodology for scoping reviews. A systematic literature search was conducted in Embase, MEDLINE (EBSCOhost), PubMed, Scopus, Web of Science and the Cochrane Library to identify studies on D _LNO from 1983 to 2025. Two reviewers screened abstracts using Rayyan software and extracted data using standardised templates implemented into REDCap (Research Electronic Data Capture).

Results: We identified 1638 studies, of which 69 met the eligibility criteria. These studies represented respiratory (n=22), immunological/genetic/systemic (n=14), post-COVID-19 sequelae (n=13), cardiovascular (n=9), metabolic/endocrine/renal (n=6), environmental-related (n=3) and other (n=2) conditions. There was substantial heterogeneity in disease categories, sample sizes and reporting methods. Nearly half of the studies (49.3%) used convenience sampling, where participant selection processes are often poorly described; 62.3% included <50 participants. Only 18.8% reported a sample size calculation, and 10.1% registered or published a study protocol. Disparate findings within disease categories were often difficult to interpret; and small sample sizes limited generalisability. In some specific conditions, D _LNO showed sensitivity in detecting interstitial and fibrotic changes compared to conventional single-breath pulmonary diffusing capacity for carbon monoxide (D _LCO) while simultaneous D _LNO-D _LCO measurements permitted the detection of pulmonary vascular-haematological perturbations.

Conclusion: Single-breath D _LNO-D _LCO may provide additional pathophysiological insight by assessing the relative contributions from membrane and blood resistance of diffusion. Larger studies are required to clarify its interpretation across disease states.