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[This corrects the article DOI: 10.1183/23120541.01257-2025.].
[This corrects the article DOI: 10.1183/23120541.00970-2025.].
[This corrects the article DOI: 10.1183/23120541.01000-2025.].
[This corrects the article DOI: 10.1183/23120541.01022-2025.].
Small peripheral pulmonary lesions are nowadays preferably diagnosed by navigation bronchoscopy, yet reported diagnostic yields vary across different techniques. Shape-sensing robotic-assisted bronchoscopy (ssRAB), now also available in Europe, combines real-time shape sensing with an actively steerable catheter, potentially improving diagnostic yield. We aimed to compare ssRAB combined with cone-beam computed tomography (CBCT) imaging (ssRAB+CBCT) against our current standard, CBCT-based navigation bronchoscopy (CBCT-NB) alone. We conducted a single-centre, propensity score-matched analysis comparing patients undergoing ssRAB+CBCT with patients undergoing CBCT-NB for the diagnosis of small peripheral pulmonary lesions. Matching was performed on known lesion characteristics influencing yield. Primary outcome was strict diagnostic yield. Secondary outcomes included diagnostic accuracy at follow-up, safety and procedure-related metrics. A total of 131 patients with 183 biopsied lesions were included in the ssRAB+CBCT arm. Median lesion size was 12 mm (interquartile range 8-18 mm). Propensity score matching with lesions from our reference CBCT-NB cohort was successful in 150 out of 183 lesions. The diagnostic yield at the lesion level was 73% for the ssRAB+CBCT arm and 70% for the CBCT-NB arm; the mean difference of 3.3% (95% CI -6.9-13.5%) was not statistically significant (p=0.521). The diagnostic yield at the patient level for the ssRAB+CBCT arm was 82%. ssRAB+CBCT has a diagnostic yield similar to that of our highly optimised CBCT-NB programme, and was below the study's powering assumption of a 15% increase in diagnostic yield. There was a suggestion of benefit in small nodules with a negative bronchus sign. The unique features of ssRAB mean that it holds promise, but larger studies are warranted to clarify its position and optimal case selection, compared with other navigation bronchoscopy technologies, its clinical impact and its cost-effectiveness.
Bronchiectasis research has advanced significantly through international and national registries, such as the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry, revealing crucial insights into the disease's heterogeneous nature. These efforts underscore the importance of precise patient phenotyping and the identification of underlying causes to improve management and outcomes in bronchiectasis. The prospective, non-interventional PROGNOSIS registry has collected data from over 1500 computed tomography-confirmed adult bronchiectasis patients across 38 German sites, excluding those with cystic fibrosis or lung transplants. Aligned with the EMBARC registry, it ensures comprehensive clinical data collection. Statistical analyses of baseline and follow-up data aims to assess disease progression and patient outcomes. Key outcomes include a reduction in median (interquartile range (IQR)) exacerbations (2 (1-4) to 1 (1-3); p<0.001) and hospitalisations (1 (1-2) to 1 (1-1); p<0.001), demonstrating an improvement in managing the disease during patients' participation in the registry. Lung function (median (IQR) forced expiratory volume in 1 s % pred 73% (51-90%) to 73% (52-92%); p=0.6) remained stable over time, contradicting the expected decline in such chronic lung conditions. There was a significant decrease in active smokers (4.4% to 3.6%; p<0.001), and improvements were seen in sputum quantity and quality. There was an increase in the detection of pathogens, particularly Pseudomonas aeruginosa (32% to 36%; p<0.001). Notable shifts in the underlying causes of bronchiectasis were observed over the registry period, including a decrease in idiopathic cases (35% to 28%; p<0.001) and an increase in cases with a proven aetiology. The PROGNOSIS registry highlights the critical role of comprehensive management in bronchiectasis, emphasising infection control and treatment adherence. It underscores the need for personalised treatment by identifying the underlying aetiology and reinforces the ongoing importance of research in improving patient care and quality of life.
Gait speed, a key component of exercise capacity, has been underutilised in COPD, despite its prognostic potential. We aimed to evaluate the association between gait speed and clinical outcomes in COPD using 3-year longitudinal data from the Korean COPD Subgroup Study cohort. Poor gait speed (<1.0 m·s-1) was defined by usual pace during the 6-min walk test per Asian Working Group for Sarcopenia 2019 criteria. Lung function, symptoms, acute exacerbations (AEs) and mortality were compared between gait speed groups. Analyses included propensity score-matching, quartile classification, subgroup analyses and longitudinal trajectory modelling using random coefficient models. Among 2063 participants, poor gait speed (n=831, 40.3%) was associated with older age, higher symptom burden and more previous AEs despite similar lung function. This group showed higher AE risk and frequency than the normal-speed group: adjusted odds ratios 1.37-1.45 for moderate and 1.64-1.65 for severe AEs; adjusted incidence rate ratios 1.24-1.36 for moderate and 1.63-1.86 for severe AEs. The 3-year mortality was significantly higher in the poor-gait-speed group (adjusted hazard ratio 2.30, 95% CI 1.42-3.73). Longitudinally, the poor-gait-speed group demonstrated persistently worse COPD Assessment Test (CAT) and St George's Respiratory Questionnaire for COPD scores at baseline, with modest CAT worsening over time (+0.44 point/year, p=0.01), while lung function decline was similar. Gait speed provides a simple, integrative marker that independently predicts exacerbation risk, mortality and symptom progression in COPD.
Bronchiectasis is a complex disease with geographical variability in its presentation and management. Despite the growing contribution of international registries, real-world data on the Italian bronchiectasis population remain limited. The objective of the present study was to describe the demographic, clinical, microbiological, functional and treatment characteristics of Italian patients with bronchiectasis and to compare them with those of patients from other Southern European countries. This was a secondary analysis of adults from 18 Italian centres included in the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry, with comparisons made to patients in Spain, Greece, Portugal, Turkey, Israel and Malta (Southern European countries). Demographics, comorbidities, exacerbation history, spirometry, microbiology and treatment patterns were evaluated. Among 1657 Italian patients, the majority were female (70.5%) with a median age of 65 years, with high rates of idiopathic bronchiectasis (55.4%) and preserved lung function. Compared with other Southern European countries (n=2638), Italian patients had lower disease severity (median Bronchiectasis Severity Index: 6 versus 7; p<0.001), less frequent isolation of Pseudomonas aeruginosa, and lower prevalence of daily sputum production and purulence, despite identical quality of life (median Quality of Life Questionnaire-Bronchiectasis Respiratory Symptom Score: 70.4 in both groups). Treatment patterns differed, with lower use of inhaled antibiotics (1.1% versus 13.1%) and macrolides (6.0% versus 14.3%), but more widespread use of airway clearance (48.4% versus 35.9%) among patients from Italy versus other Southern European countries. These findings may reflect earlier referral, diagnostic preferences or structural differences in care delivery in Italy compared with other Southern European countries. This work lays the foundation for tailored national strategies and future longitudinal studies. The largest bronchiectasis cohort ever studied in Italy reveals unique clinical traits and highlights key differences from other Southern European countries, and provides real-world data to shape better care models and guide future research.
Acute exacerbations of COPD without respiratory acidosis lack reliable and practical physiological markers to monitor treatment response or predict clinical deterioration. In this prospective observational study, 51 hospitalised acute exacerbations of COPD (AECOPD) patients without respiratory acidosis underwent diaphragm ultrasound and surface electromyography within 48 h of admission and at discharge. Associations between study parameters and dyspnoea (Borg scores and modified Medical Research Council scales) were assessed, and their predictive value for clinical outcomes (progression to noninvasive ventilation or in-hospital death, and 30-day readmission). An increase in diaphragm excursion during maximal inspiration associated weakly, yet significantly, with improvements in Borg scores (rs=-0.365, p=0.011). A higher diaphragmatic excursion tidal breathing/maximal inspiration ratio at admission was associated with in-hospital deterioration (OR per 0.1-unit increase 1.59, 95% CI 1.05 to 2.41; p=0.029) and exploratory analysis suggested discriminative value of the excursion-to-surface electromyography (sEMG) ratio (0.941, 95% CI 0.855 to 1.000; p=0.013), although interpretation is limited by few events. Higher Borg scores (OR 2.19, 95% CI 1.22 to 3.94; p=0.009) and lower thickening fraction (area under the receiver operating characteristic curve 0.807, 95% CI 0.687 to 0.927; p=0.004) at discharge were independently associated with 30-day readmission. Bedside ultrasound and sEMG provide potential physiological markers associated with clinical deterioration in non-acidotic AECOPD patients. These exploratory findings suggest a role in identifying at-risk patients and guiding personalised care. Validation in larger cohorts with more events is needed. Furthermore, we found that short-term readmission risk may be predicted by a simple bedside question: "How breathless do you feel right now?"
Pulmonary hypertension (PH) is a progressive and multifactorial disease marked by elevated pulmonary arterial pressure and right ventricular (RV) dysfunction. Among its subtypes, pulmonary arterial hypertension (PAH) is characterised by profound vascular remodelling, inflammation and fibrosis. Despite therapeutic advances targeting the endothelin, nitric oxide, prostacyclin, and, more recently, the activin signalling pathway via sotatercept, outcomes in PAH remain suboptimal, particularly in patients with cardiovascular comorbidities. This has prompted growing interest in novel metabolic-based interventions, such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs). GLP-1RAs, initially developed for type 2 diabetes and obesity, exhibit pleiotropic properties including vasodilation, anti-inflammatory, antifibrotic and endothelial-protective effects. In experimental models of PAH GLP-1RAs administration attenuates the severity of PH. Additional studies highlight their ability to protect against lung fibrosis and preserve endothelial function. Indirect enhancement of GLP-1 signalling through dipeptidyl peptidase-4 (DPP-4) inhibition similarly improves pulmonary haemodynamics and mitigates fibrosis and inflammation, underscoring the relevance of this pathway. Although no clinical trials have specifically evaluated GLP-1RAs in PH, observational studies in patients with heart failure with preserved ejection fraction suggest potential cardiopulmonary benefits. GLP-1RAs emerge as promising candidates bridging metabolic, vascular and cardiac domains in PH, warranting rigorous clinical validation. These findings support further translational research and randomised clinical trials to evaluate GLP-1RAs as a disease-modifying therapy in PAH.
The organisation and implementation of long-term home noninvasive ventilation treatment for COPD patients across Europe is complex and heterogeneous. Further research and experience sharing is required to optimise and align the patient pathway. https://bit.ly/3M3r566.
The e-Lung weighted reticulovascular score (WRVS) is an automated computed tomography biomarker that quantifies interstitial lung disease (ILD) severity and is associated with prognosis in patients with idiopathic pulmonary fibrosis (IPF). The aims of the present study were to evaluate WRVS as a prognostic factor in patients with non-IPF ILD. The test cohort comprised patients from the Open Source Imaging Consortium and the validation cohort, patients recruited to the prospective German CoWorker ILD registry. Associations between baseline and serial WRVS with future forced vital capacity (FVC) decline and survival were tested. Median survival was 7.1 and 6.1 years in the test (n=302) and validation (n=378) cohorts, respectively. Baseline WRVS was associated with mortality in test (hazard ratio (HR) 1.11, 95% CI 1.08-1.14; p<0.001, C-index 0.75) and validation (HR 1.12, 95% CI 1.09-1.15; p<0.001, C-index 0.72) cohorts. A threshold WRVS of ≥15% was associated with mortality in both cohorts (HR 4.77, 95% CI 3.11-7.31; p<0.001, C-index 0.71, and HR 3.49, 95% CI 2.48-4.91; p<0.001, C-index 0.63 for test and validation cohorts, respectively). After adjustment for FVC, age and sex, baseline WRVS was associated with future FVC decline or death in test (OR 1.13, 95% CI 1.06-1.21; p<0.001, C-index 0.72) and validation (OR 1.18, 95% CI 1.11-1.25; p<0.001, C-index 0.72) cohorts. A rise in WRVS of 3% on serial computed tomography was associated with mortality in both test (HR 5.69, 95% CI 2.77-11.70; p<0.001, C-index 0.75) and validation cohorts (HR 1.99, 95% CI 1.09-3.65; p=0.026, C-index 0.57). In patients with non-IPF ILD, the e-Lung WRVS biomarker is associated with mortality and FVC decline when applied to baseline high-resolution computed tomography scans replicating previous studies in IPF. Patients with an increase in WRVS of 3% on serial computed tomography scans have significantly increased risk of mortality.
Isolated small airways obstruction (SAO) is common, a precursor of COPD and associated with increased cardiovascular disease (CVD) mortality. Whether isolated SAO predicts CVD incidence is unknown. Using longitudinal data on 139 568 UK Biobank participants (median age 58 years), we calculated CVD incidence in those with, versus without, isolated SAO defined as forced expiratory volume in 3 s (FEV3)/forced expiratory volume in 6 s (FEV6) <lower limit of normal (LLN) with a normal forced expiratory volume in 1 s (FEV1)/FEV6 ratio. A second analysis was performed where isolated SAO was defined as forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) <LLN with a normal FEV1/FEV6 ratio. Using mixed effects quasi-Poisson regression models, we assessed the association between isolated SAO and CVD, investigating differences in association by sex and smoking status. At baseline, 10 480 participants (7.5%) had isolated SAO. During follow-up (median 9.2 years), CVD was diagnosed in 30 763 (22%) participants, more commonly among those with isolated SAO at baseline (risk ratio 1.05 (95% CI 1.01-1.09)). This association was not significant in males (risk ratio 1.03 (95% CI 0.98-1.08)) nor in never-smokers (risk ratio 1.02 (95% CI 0.97-1.09)). The risk of CVD was increased when isolated SAO was defined using FEF25-75%. Adults with isolated SAO have a modest increased risk of developing CVD. However, this association is potentially driven by smoking. Further research should explore underlying mechanisms for this increased risk and how best this can be mitigated.
COPD remains a leading cause of global morbidity and mortality, with acute exacerbations driving disease progression and healthcare utilisation. Artificial intelligence (AI) offers new opportunities to predict exacerbation risk by integrating multimodal data such as electronic health records (EHRs), spirometry and wearable sensor inputs. This systematic review, conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251165476), evaluated AI-based models developed for COPD exacerbation prediction using combined data modalities. Comprehensive searches of PubMed, Embase and Google Scholar identified 859 records, of which five studies published between 2021 and 2025 met inclusion criteria. Study designs ranged from prospective monitoring cohorts to EHR-based and hybrid datasets. Models applied diverse approaches including random forests, gradient boosting, convolutional neural networks and ensemble learning frameworks. Reported discriminative performance was moderate to high, with area under the curve values between 0.73 and 0.92 and accuracies up to 0.92. Most of these performance metrics were derived from internal validation, with limited external testing, which restricts assumptions about generalisability. Sensitivity reached 0.94 in wearable-driven models, while only one study reported formal calibration assessment. Despite encouraging performance, methodological heterogeneity, limited external validation and incomplete reporting of preprocessing and explainability methods restrict clinical translation. Current evidence supports the potential of multimodal AI to enhance early detection of COPD exacerbations, but future research must prioritise transparent reporting, external validation and integration into real-world care pathways.
Optimisation of underlying chronic respiratory disease (CRD) is a necessary first step to addressing breathlessness. We aimed to develop and evaluate a disease-agnostic education package and mnemonic to support primary care providers to recognise breathlessness and facilitate optimisation of underlying CRD. A blended education package comprising one live webinar, three self-paced online courses, two podcasts and five case studies was developed by a working group of general practitioners (GPs), respiratory clinicians and researchers and adapted into a practical mnemonic (the BREATHE clinical approach). Content was validated against a systematic state-of-the-art review of international and national guidelines. Semi-structured interviews with GPs, general practice nurses and a practice manager were conducted to evaluate the educational content and design. Interviews were transcribed and analysed thematically with inductive coding. Seven disease-agnostic recommendations were developed and validated against 33 clinical practice documents: Breathlessness (measure severity); Respiratory illness (confirm diagnosis); Extra illnesses (consider other causes of breathlessness); Adherence (check medication use and technique); Tobacco (discuss smoking cessation); Help (consider referral to specialist services); Exercise (consider pulmonary rehabilitation). 13 interviews were conducted (eight GPs; four nurses; one practice manager); this showed the BREATHE educational package and clinical approach to be acceptable. Time constraints were frequently cited as a barrier to education engagement, with flexible education preferred. Respondents described the BREATHE clinical approach as a comprehensive tool that would enable clinicians to "remember the specifics", while highlighting the need for multiple consultations to address all elements of care. The BREATHE clinical approach and education package were favourably received as useful tools to support primary care providers to optimise treatment for people with CRD.
Frailty often coexists in patients with COPD regardless of disease severity and may serve as a treatable trait. We hypothesised that factors associated with frailty may differ by COPD severity. This study aimed to comprehensively explore related factors including symptoms, physical activity, dietary behaviour, serum biomarkers and computed tomography (CT) parameters. This cross-sectional analysis of a multicentre prospective cohort study included patients with COPD aged ≥50 years with a smoking history ≥10 pack-years. Frailty was assessed using the Kihon checklist. Data were collected using questionnaires on symptoms, physical activity and dietary behaviour, as well as blood tests and CT parameters. Associations between frailty and clinical variables were assessed using multivariable linear and logistic regressions in all patients and within the COPD severity subgroups. Among 225 patients, 45 (20%) were diagnosed with frailty. These patients were older, more likely to have cardiovascular disease (CVD) and had a higher neutrophil-to-lymphocyte ratio. Stratified by COPD severity, age, forced expiratory volume in 1 s (FEV1) and calorie intake did not differ by frailty status, whereas patients with frailty exhibited more severe symptoms. In multivariable analysis, frailty was associated with social factors (living alone, unemployment), comorbidities (CVD, gastro-oesophageal reflux disease) and CT airway parameters (wall area percentage (WA%)), but not emphysema, independent of FEV1. Furthermore, living alone was linked to frailty in mild COPD. Social factors, comorbidities and WA% were associated with frailty in patients with COPD. Social factors were more relevant in patients with mild COPD.
The World Health Organization recommends screening and providing preventive treatment of tuberculosis in high-risk groups. We compared the performance of the latest versions of two widely used interferon (IFN)-γ release assays (IGRAs), the QuantiFERON-TB Gold Plus chemiluminescent assay (QFT-Plus CLIA) and the semi-automated T-SPOT.TB assay, and assessed the potential benefit of a dual-testing strategy in immunosuppressed patients and/or candidates for biological therapy. From September 2022 to December 2023, we included 3748 immunosuppressed patients. IGRAs were performed according to manufacturers' instructions. Agreement was evaluated using Cohen's kappa (κ), and subgroup analyses were stratified by age and underlying disease. At least one IGRA was positive in 13.4% of patients (12.0% QFT-Plus CLIA; 9.9% T-SPOT.TB). Indeterminate results were infrequent (1.8% QFT-Plus CLIA; 2.6% T-SPOT.TB). Overall agreement was high (93.0%; κ=0.67), but lower among IGRA-positive cases (63.9%; κ=0.62). Discrepancies occurred in 7.0% of patients, most frequently in children (0-14 years: 15.4%), older adults (≥75 years: 13.8%), individuals living with HIV (38%), rheumatoid arthritis/Sjögren's syndrome (12.4%) and other chronic inflammatory diseases, transplant recipients or immunodeficiencies (11.9%). Among IGRA-positive cases (n=502), most discordant results corresponded to QFT-Plus CLIA-positive/T-SPOT.TB-negative patterns (131 of 181; 72.4%). In immunosuppressed patients, dual IGRA testing enhances diagnostic sensitivity and can strengthen clinical decision-making. Concordant results increase diagnostic certainty, whereas discordant findings gain interpretative value when contextualised by disease group and assay-specific behaviour IGRA.
The molecular determinants for lung graft-versus-host disease-associated bronchiolitis obliterans syndrome (BOS) are poorly understood, and biomarkers in children following haematopoietic stem cell transplant do not exist. To address this gap, we analysed plasma samples from 21 paediatric stem cell transplant recipients prior to and at diagnosis of BOS. Participants included three cohorts: seven with BOS; seven sex-, age- and timepoint-matched with severe graft-versus-host disease alone; and seven sex-, age- and timepoint-matched transplant recipients without BOS or other graft-versus-host disease. Our proteomic approach evaluated the expression of 190-12 588 protein isoforms, depending on statistical stringency, and distinguished the three cohorts of paediatric patients prior to and at the time of BOS diagnosis. Differences included proteins that regulate chromatin modification, acute phase signalling, complement, fibrosis, hypoxia, serine protease inhibition, vitamin transport, glucocorticoid receptor transactivation and blood coagulation pathways. A subset of newly discovered proteins was cross-platform validated by ELISA in a larger cohort of paediatric patients 14 (n=107), 30 (n=108), 60 (n=108) and 100 (n=134) days post-transplant. Pathways analysis highlighted potential therapeutics including azithromycin, statins, pazopanib and cediranib. Our strategy offers a potential for early diagnosis and the identification of interventions for paediatric stem cell transplant-associated graft-versus-host disease and BOS.
COPD is a systemic disorder associated with cognitive impairment and affective dysfunction. However, the underlying neurobiological mechanisms remain unclear. This study examines brain reorganisation in patients with COPD and investigates potential neural mediators of cognitive and affective deficits. We enrolled 51 COPD patients and 50 age- and sex-matched healthy controls. All participants underwent high-resolution structural magnetic resonance imaging (MRI) and resting-state functional MRI. Comprehensive neuropsychological assessments for cognitive function (Montreal Cognitive Assessment (MoCA)) and affective symptoms (Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI)) were conducted. Voxel-wise analyses compared grey matter volume, fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity strength between groups. Mediation analysis was performed to explore causal pathways linking COPD, brain alterations and cognitive-affective dysfunction. COPD patients exhibited significant cognitive deficits (lower MoCA scores) compared with healthy controls, and greater affective symptom burden (higher BDI and STAI scores). Neuroimaging revealed no grey matter volume differences, but distinct functional abnormalities: increased fALFF in bilateral lingual gyri and decreased fALFF in the right inferior orbitofrontal and left middle occipital regions, alongside enhanced long-range functional connectivity strength in the right frontal and fusiform areas (cluster-level p<0.05, family-wise error-corrected). Functional connectivity between bilateral lingual gyri was strengthened in those with COPD and correlated with anxiety symptoms. Critically, mediation analysis demonstrated that increased fALFF in the left lingual gyrus and enhanced interhemispheric connectivity in the lingual region mediated COPD-related cognitive decline, suggesting compensatory mechanisms. COPD is associated with functional brain reorganisation, particularly in cognitive and emotional regions, without overt structural changes. The lingual gyrus emerges as a key compensatory hub, where heightened activity and connectivity may mediate cognitive impairment. These findings illuminate neuroprotective pathways in COPD and propose the lingual gyrus as a potential target for interventions aimed at preserving cognitive function.
Acute slow deep breathing reduces muscle sympathetic nerve activity and improves the efficiency of breathing in pulmonary hypertension https://bit.ly/3MtwkfK.