BACKGROUND:The fatality rate of pulmonary arterial hypertension (PAH) is high. This study aimed to determine the correlation between ACE2 and monocrotaline (MCT)-induced PAH in rats. METHODS:Rats were randomly divided into 4 groups: control group; MCT group; resorcinolnaphthalein (Rec) group; and Rec + A779 (Mas receptor antagonist) group. Rats in the control group received a single subcutaneous injection of normal saline on the 1st d, and an osmotic pump capsule combining normal saline subcutaneously since the 2nd d. The rats in the other 3 groups received a single subcutaneous injection of MCT on the 1st d. An osmotic minipumps containing normal saline, Rec, and Rec + A779 were implanted in rats in the MCT, Rec, and Rec + A779 groups, respectively. RESULTS:The PAH rat model was successfully constructed with MCT. ACE2 reduced the mPAP, right ventricular hypertrophy index, and pulmonary artery media in the PAH rats (p < 0.05). Rec activated ACE2 expression and significantly increased the Mas levels, phospho-Akt (P-Akt), and phospho-eNOS (P-eNOS) in lung tissues of PAH rats (p < 0.05). The mPAP, right ventricular hypertrophy index, and pulmonary artery media in the Rec + A779 group were significantly increased compared to the blank and Rec groups (p < 0.05). The Mas level, P-Akt, and P-eNOS in rat lung tissues were significantly decreased in the Rec + A779 group compared to the Rec group (p < 0.05). CONCLUSION:Rec upregulates ACE2 expression, and this elevated ACE2 expression may be associated with amelioration of MCT‑induced PAH in rats, likely through the downstream Akt/eNOS signaling pathway.
Background:No randomised controlled trials (RCTs) have compared inhaled corticosteroid (ICS)/formoterol reliever-based stepwise algorithms with short-acting β-agonist (SABA) reliever-based stepwise algorithms, titrated to levels of asthma control and exacerbations. Knowledge gaps remain in understanding ICS exposure over time, transitions between treatment steps, efficacy and participant satisfaction with different algorithm approaches. Objective:The aim of the study is to determine the exposure to ICS in adults and adolescents aged 16 to 75 years treated with a budesonide/formoterol reliever-based algorithm (Algorithm 1) compared to a salbutamol reliever-based algorithm (Algorithm 2) across the spectrum of asthma severity. Methods:This is an investigator-initiated, 52-week, single-site, open-label, parallel-groups, 2-arm RCT of 152 adults and adolescents with mild, moderate and moderate-severe asthma (ACTRN12624001488594). Participants will be randomly allocated in a 1:1 ratio to a budesonide/formoterol reliever-based or a salbutamol reliever-based algorithm. Global Initiative for Asthma (GINA) treatment step at enrolment according to the 2024 GINA Guidelines will be used to allocate participants to the corresponding steps of each algorithm. Treatment step transition will be in response to asthma exacerbations and level of asthma control. Those experiencing exacerbations or poorly controlled asthma will be stepped up, and those well controlled stepped down. The primary outcome is ICS exposure. Important secondary outcomes include composite systemic corticosteroid exposure, rates of asthma exacerbations, asthma control, T-helper 2 biomarkers, spirometry and participants' treatment perceptions and satisfaction. Conclusion:This is the first RCT to compare ICS/formoterol- and SABA-based reliever stepwise algorithmic approaches in asthma, with treatment adjusted according to asthma control and exacerbations.
Adopting race-neutral GLI 2022 reclassified 12.9% of Korean COPD patients from trial-eligible to ineligible mild disease, and these reclassified patients demonstrated significantly lower risks of exacerbations and mortality https://bit.ly/4cG1OZt.
Both moderate and severe exacerbations of COPD follow patient-specific, predictable patterns rather than occurring as random events of chance https://bit.ly/4d6TkMS.
Transitioning from selexipag to parenteral prostacyclin analogues yielded haemodynamic improvement. Outcomes are poor among those within this population who do not achieve a low-risk status after the transition. https://bit.ly/4sMY3aF.
Background:Breathlessness is a common symptom in long COVID (LC). Using hyperpolarised xenon magnetic resonance imaging (129Xe-MRI), we assessed whether this symptom could be attributed to abnormalities in the alveolar-capillary membrane not detected by standard investigations. We focused on never-hospitalised individuals without an identified cause for breathlessness. Methods:In this prospective, multicentre study, we compared 129Xe-MRI, lung function, exercise capacity and symptom questionnaires in LC patients with breathlessness (BLC) to those without breathlessness (NBLC) and healthy controls. Primary outcome was whether BLC demonstrated measurable impairments in gas exchange focusing on dissolved-phase 129Xe-MRI metrics: red blood cell to membrane ratio (RBC:M) and red blood cell to gas ratio (RBC:Gas). We also explored associations between symptoms and physiological measures. Results:Of 269 participants recruited, 196 were included in the analysis (109 BLC, 43 NBLC, 44 controls), with age and sex well matched across groups. BLC had a significantly longer interval from infection to MRI (median 632 days; p<0.001). No significant differences in global or regional RBC:M or RBC:Gas were observed across groups. BLC showed lower forced expiratory volume in 1 s, forced vital capacity, transfer factor of the lung for carbon monoxide (T L CO), and carbon monoxide transfer coefficient (K CO) z-scores compared to controls, though >90% of values remained within normal range. A subset of BLC participants with low T L CO (14 out of 109) showed reduced 129Xe-MRI metrics and higher breathlessness scores. Interpretation:Most nonhospitalised LC participants exhibited no detectable pulmonary abnormalities, including those with breathlessness. However, ∼13% of breathless individuals demonstrated minor reductions in T L CO and 129Xe-MRI gas exchange suggesting a potential pulmonary contribution for symptoms in this subgroup.
Beyond detecting obstruction and pathogens, bronchial lavage aids inflammatory phenotyping and risk stratification, especially in nonsputum, early-stage and TB-endemic cases where excluding active TB is crucial https://bit.ly/47AdhYS.
Pleural plaques are frequent in Iceland and independently associated with interstitial lung abnormalities, highlighting the persistent threat of asbestos-related disease and stressing the urgent need for continued monitoring https://bit.ly/4u4riGW.
Think bronchoscopy is just for samples? Think again. It impacts clinical management in >50% of bronchiectasis cases with a high safety profile: moving from expert opinion to data-driven care. https://bit.ly/3NYVAM3.
Background:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could result in pulmonary vascular injury, systemic inflammation, and endothelial dysfunction, which could increase future risk of pulmonary hypertension (PH) and related complications. Methods:We conducted a retrospective cohort study from the Montefiore Medical Center (Bronx, NY, USA) (1 March 2020 to 17 August 2024). Patients who had a COVID-19 PCR test were compared to those who did not have a positive COVID-19 PCR test on record. There were 15 721 hospitalised COVID-19 patients, 43 740 non-hospitalised COVID-19 patients, and 870 458 contemporary COVID-negative controls, and 634 892 historical (1 May 2016 to 31 December 2019) controls. The main analysis used propensity score matching for demographics, tobacco, substance use disorder, vaccination for SARS-CoV-2, and pre-existing comorbidities. New-onset PH and PH-related complications were assessed using Fine-Gray subdistribution hazard ratios (sHR). Sensitivity analyses included multivariable cause-specific Cox proportional hazard model, inverse probability weighting, and using matched historical cohort as controls. Long-term PH-related complications included heart failure, chronic kidney disease, and all-cause mortality compared to matched controls. Blood biomarkers during acute COVID-19 were analysed with respect to new-onset PH. Results:Compared to propensity-matched COVID-negative controls, COVID-19 hospitalised patients were (sHR) 1.41 (95% CI 1.27-1.57) times more likely to experience new-onset PH, and COVID-19 non-hospitalised patients were 1.42 (95% CI 1.25-1.61) times more likely to do so. Sensitivity analyses corroborated our main findings. Among those with new-onset PH, only hospitalised COVID-19 survivors had higher risks of subsequent heart failure (sHR 1.61, 95% CI 1.11-2.35), chronic kidney disease (2.18, 1.50-3.16), and all-cause mortality (1.81, 1.47-2.24) compared to matched controls. Abnormal troponin (sHR 1.61, 95% CI 1.05-2.48), brain natriuretic peptide (1.59, 1.20-2.11) and creatinine (1.24, 1.01-1.51) during acute COVID-19 were associated with outcomes, but not D-dimer, ferritin and haematological markers. Conclusions:SARS-CoV-2 infection is independently associated with elevated long-term risk of new-onset PH, whereas only hospitalised COVID-19 status is associated with higher risk of downstream PH-related complications. These findings underscore the importance of ongoing PH surveillance in COVID-19 survivors.
Introduction:Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has demonstrated efficacy in people with cystic fibrosis (pwCF) aged ≥6 years with ≥1 F508del allele in clinical trials. This registry-based cohort study aimed to describe real-world use and outcomes up to 36 months post-treatment initiation among pwCF aged ≥6 years treated with ELX/TEZ/IVA in France. Methods:Outcomes included per cent predicted forced expiratory volume in 1 s (ppFEV1), intravenous-treated pulmonary exacerbations (PEx), hospitalisations, nutrition, lung transplantation, mortality and, among pwCF ≥18 years, quality of life (CFQ-R). All results are presented by population (≥12 years and 6-11 years). In the ≥12 years cohort, a subgroup analysis of pwCF with advanced lung disease (ALD), defined as ppFEV1 <40% at baseline, is presented. Results:The study included 553 pwCF aged 6-11 years, with a mean±sd age of 8.8±1.9 years at baseline, ppFEV1 of 91.3±17.6% and mean follow-up of 8.9 months. In addition, 3313 pwCF aged ≥12 years were included, with a mean±sd age at baseline of 27.6±11.7 years, ppFEV1 of 65.4±24.8% and mean follow-up of 21.2 months. In the cohort aged 6-11 years, ppFEV1 improved by +9.6% (95% CI: 7.6-11.6) at 12 months and i.v.-treated PEx annual rate decreased from 0.15 (95% CI: 0.11-0.18) to 0.02 (0.00-0.04) after 0 to 12 months post-ELX/TEZ/IVA initiation. Among pwCF ≥12 years ppFEV1 improved post-ELX/TEZ/IVA initiation by +16.2% (95% CI: 15.6-16.8) at 24 months. i.v.-treated PEx annual rate decreased from 0.92 (95% CI: 0.88-0.95) during baseline to 0.14 (95% CI: 0.12-0.15) after 12 to 24 months post-ELX/TEZ/IVA initiation. Similar benefits to those in the ≥12 years population were observed in the ALD subgroup. Conclusion:This study confirms the longer term, transformational clinical benefit of ELX/TEZ/IVA in pwCF aged ≥6 years in a French population, demonstrating sustained improvements across multiple health outcomes, including in pwCF with ALD that were not part of the pivotal clinical trials.
Background:Fractional exhaled nitric oxide (F ENO) reflects type 2 airway inflammation, yet the prognostic utility of longitudinal F ENO changes in COPD remains unclear. We aim to explore whether 6-month F ENO variation patterns predict subsequent moderate-to-severe exacerbations in COPD patients receiving triple therapy. Methods:We prospectively evaluated COPD patients receiving triple inhaled therapy from 2023 to 2024. Four F ENO-related variables were used to derive F ENO variation phenotypes via K-means unsupervised clustering. Results:Three distinct F ENO-variation phenotypes were identified: a High F ENO-Persistently Elevated subtype (Cluster 1, 11.2%), a High F ENO-Declining subtype (Cluster 2, 20.3%) and a Low F ENO-Stable subtype (Cluster 3, 68.5%). During 6-12 months of follow-up, 75 patients (33.8%) experienced a moderate-to-severe exacerbation. Compared with Cluster 3, both Cluster 1 (OR 6.97, 95% CI 2.38-20.47) and Cluster 2 (OR 20.08, 95% CI 7.01-57.58) were independently associated with future exacerbations (p<0.001). The final prediction model incorporating F ENO variation phenotypes demonstrated excellent discrimination (AUC 0.889) and provided greater net clinical benefit than models using traditional clinical predictors alone (p=0.004). Subgroup analyses revealed consistent effect sizes across categories of age, prior-year exacerbations, baseline FEV1 % predicted, symptom burden, smoking status and proportion of days covered, supporting the robustness and internal consistency of the F ENO-variation phenotyping approach. Conclusion:Short-term longitudinal F ENO variation over 6 months was independently associated with future moderate-to-severe exacerbations in COPD patients receiving triple therapy, supporting risk stratification and hypothesis generation for future interventional studies rather than direct treatment guidance.
Background:Chronic airway dysbiosis plays an important role in the pathogenesis of cystic fibrosis (CF) lung disease and may serve as a therapeutic target. However, studies investigating the effects of direct therapeutic targeting of the airway microbiome are lacking. In this study, we therefore used βENaC-overexpressing (βENaC-Tg) mice and determined the evolution of abnormal lung microbiota and effects of re-balancing bacterial communities on chronic airway inflammation and mucus plugging in this model of CF lung disease. Methods:The development of the respiratory microbiome was determined by 16S rRNA gene sequencing and the effects of preventive intranasal instillation of endogenous probiotic bacteria on the lung phenotype were determined in βENaC-Tg mice and wild-type littermates. Results:Neonatal βENaC-Tg mice developed severe respiratory dysbiosis characterised by an increase in the relative abundance of Streptococcus and a decrease in Ligilactobacillus compared to wild-type littermates. Ligilactobacillus murinus SMH17 was identified as the dominant Ligilactobacillus species in the lungs of neonatal wild-type mice. Preventive treatment by intranasal instillation of L. murinus SMH17 was well tolerated and reduced age-specific markers of airway inflammation including inflammatory cell counts and proinflammatory cytokines in neonatal and juvenile βENaC-Tg mice. In addition, preventive treatment with L. murinus SMH17 reduced airway mucus plugging in βENaC-Tg mice by ∼40%. Conclusion:Preventive intrapulmonary application of the endogenous probiotic L. murinus SMH17 reduces airway inflammation and mucus plugging in mice with CF-like lung disease. These data support further elucidation of inhaled probiotics as a strategy to treat chronic airway dysbiosis in patients with CF.
Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of pulmonary embolism, leading to high pulmonary arterial pressures. Pulmonary endarterectomy (PEA) surgery is the gold standard treatment for CTEPH, significantly improving patient outcomes. Post-operative cardiac remodelling is an important consideration, highlighting the need to balance early exercise with potential impacts on cardiac recovery. The objective of the present study was to investigate the safety and feasibility of early exercise interventions following PEA surgery for CTEPH, and to review the existing literature on early exercise interventions post-PEA. Methods A systematic review was conducted using the AMED, CINAHL, Embase and MEDLINE databases. Search terms included “pulmonary endarterectomy”, “chronic thromboembolic pulmonary hypertension”, “exercise”, “exercise training”, “mobility” and “rehabilitation”. Studies were included if they involved adult patients with CTEPH who underwent PEA and participated in post-operative exercise interventions. Results The review identified studies with small, heterogeneous patient cohorts engaging in early post-operative exercise following PEA. Interventions included walking, cycling, dumbbell exercises and respiratory training. Safety measures, such as continuous monitoring of oxygen levels and heart rate, were implemented and no adverse events were reported. Improvements in exercise capacity and right heart measurements were observed, suggesting that early exercise is both safe and beneficial. Conclusion Early exercise interventions following PEA surgery appear safe and feasible, with potential benefits for exercise capacity and cardiac remodelling. Future research should include randomised controlled trials and qualitative studies to confirm these findings and assess impacts on patient quality of life.
Eosinophilic pleural effusion refers to a nonspecific entity that may occur secondary to a variety of aetiologies with most common causes being malignancy and pleural injury, while a considerable proportion of cases remain with no diagnosis https://bit.ly/42FxCcm.
Background A 5-domain composite Core Outcome Measures set for Severe Asthma (COMSA) has been introduced for evaluation of treatment response. Methods The COMSA evaluation strategy was tested in a real-world study of 78 patients with severe asthma with blood eosinophilia taking mepolizumab. Exacerbations, oral corticosteroid (OCS) use, forced expiratory volume in 1 s, Asthma Quality of Life Questionnaire score and Asthma Control Questionnaire-5 results were determined before treatment and 4, 12, 24 and 36 months thereafter. Responses were quantified as the sum of changes in domains using both the relative CONFiRM (CompOsite iNdexes For Response in asthMa) scale, where exacerbations and OCS use are given most weight, and Modified Equal Weight Score (MEWS), where each domain gives equal weight. Both scales use identical cut-offs for degree of change within domains. Results After 1 year, the MEWS scoring system classified 13% as non-responders, 28% as sufficient-responders, 40% as substantial-responders and 19% as super-responders. Using CONFiRM, the corresponding group stratification was 22%, 22%, 33% and 23%, respectively. Group assignments remained unchanged at 24 and 36 months, for 66% of patients in COMSA-MEWS and 68% in COMFiRM. Baseline exhaled nitric oxide was highest among the super-responders, whereas other type 2 markers were similar across the groups. Conclusion In this first real-world application, the COMSA stratification assigned patients into distinct, graded responder groups that may be used in clinical research and management of severe asthma. Although patient-reported symptoms are given greater weight in COMSA-MEWS, the two algorithms performed similarly.
Sex hormones may be treatable traits in asthma among women. Effects of hormone replacement therapy (HRT) on asthma exacerbations are mixed and likely vary by HRT-related factors and individual susceptibility, warranting further study. https://bit.ly/4cZXVzH.
A meta-analysis identifies NLRP2, Th2 signalling and ERVW-1 as key dysregulated pathways in asthma, highlighting novel targets while underscoring the need for phenotype-specific and single-cell insights https://bit.ly/4sOYUrz.
Modern long COVID rehabilitation must go beyond improving exercise capacity. It must serve as behavioural and physiological mediator enabling the "adaptive middle ground": a precise zone of symptom-titrated activity to navigate sustainable recovery. https://bit.ly/4nXML2v.
Background:The long-term effects of rehabilitation in individuals with long COVID remain unclear. This systematic review and meta-analysis evaluated the short- and long-term impacts of rehabilitation programmes on exercise capacity, health-related quality of life (HRQoL), pulmonary function, chronic dyspnoea, anxiety, depression and fatigue in people with long COVID. Methods:Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and the Cochrane Handbook for Systematic Reviews of Interventions, five databases were searched, with the final search updated in August 2025. Eligible studies included adults with long COVID who underwent rehabilitation interventions. Outcomes were synthesised using meta-analyses and narrative synthesis where appropriate. The risk of bias was assessed using appropriate tools for both randomised and nonrandomised studies. The review was prospectively registered on PROSPERO (CRD42024535365). Results:12 studies (n=1403 participants) published between 2020 and 2025 were included. In the short term, rehabilitation compared with usual care significantly increased exercise capacity (6-min walking test; mean difference (MD) 102.34 m; 95% CI 44.48-160.21 m; p<0.0001), reduced dyspnoea (modified Medical Research Council; MD -1.44; 95% CI -2.72- -0.16) and anxiety symptoms (hospital anxiety and depression scale-A; MD -1.64; 95% CI -3.02- -0.26; p=0.02). Studies showed wide variation in educational content and delivery. No significant long-term effects were observed in pooled quantitative analyses for HRQoL or dyspnoea; however, qualitative findings indicated sustained improvements in HRQoL in some longitudinal studies. Conclusion:Rehabilitation programmes yielded short-term benefits in exercise capacity, dyspnoea and anxiety. Evidence for long-term efficacy remains limited and inconsistent. Further high-quality, follow-up studies are needed to determine the durability of these effects in people with long COVID.
