ERJ Open Research最新文献

Background: Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with an increased body mass index and an increased risk of cardiovascular disease and metabolic disorders. However, the strength and consistency of these associations across populations remain unclear. This systematic review and meta-analysis aimed to quantify the relationship between PRISm and key cardiometabolic comorbidities, including diabetes mellitus, hypertension, hypercholesterolaemia, ischaemic heart disease and heart failure.

Methods: A systematic search of PubMed, Embase and Web of Science was conducted to identify observational studies comparing the prevalence of cardiometabolic comorbidities in PRISm and normal spirometry populations. Meta-analyses were performed for conditions reported in three or more studies, and heterogeneity was assessed using the I² statistic. Sensitivity and influence analyses were conducted to ensure the robustness of findings.

Results: A total of 18 studies were included, comprising over 500 000 participants. Meta-analysis showed significant associations between PRISm and diabetes (OR 2.08, 95% CI 1.78-2.42), hypertension (OR 1.78, 95% CI 1.55-2.03), ischaemic heart disease (OR 2.05, 95% CI 1.59-2.64), heart failure (OR 2.82, 95% CI 1.40-5.67) and hypercholesterolaemia (OR 1.46, 95% CI 1.16-1.85). PRISm populations also exhibited a higher body mass index (mean difference 1.49 kg·m^-2, 95% CI 0.92-2.05 kg·m^-2).

Conclusion: PRISm is strongly associated with cardiometabolic disease, reinforcing its role as a systemic condition rather than a purely pulmonary abnormality. These findings highlight the need for integrated screening and management strategies for PRISm patients to address their broader multimorbid risk profile.

Background: There is growing interest in identifying novel, non-invasive biomarkers reflecting endogenous inflammatory processes in asthma. This study aimed to evaluate the presence of volatile organic compounds (VOCs) in exhaled breath from patients with clinically controlled asthma and assess how tobacco exposure influences their expression.

Methods: Exhaled breath samples from 120 clinically controlled asthma patients and 89 healthy controls were collected using BioVOC breath samplers. Samples were analysed by gas chromatography-mass spectrometry, assessing five previously characterised VOCs: hexanal, heptanal, nonanal, propanoic acid and nonanoic acid.

Results: Compared to healthy controls, asthma patients exhibited a lower frequency of propanoic acid exhalation (25.0% versus 53.9%; p<0.001) and higher frequencies of nonanoic acid (30.8% versus 15.7%; p=0.019). These differences persisted after adjusting for smoking status. Stratified analysis revealed reduced propanoic acid exhalation in both smoking and non-smoking asthma subgroups compared to their respective controls (21.0% versus 55.6% and 29.3% versus 51.4%, respectively; p<0.001). Additionally, asthma current and former smokers had significantly increased detection of nonanoic acid compared to controls (33.9% versus 11.1%; p=0.0359). Multivariate analysis identified propanoic acid as a protective factor against asthma (OR 0.2 (95% CI 0.1-0.4); p<0.001), whereas nonanoic acid significantly increased asthma risk (OR 4.5 (95% CI 1.8-12.6); p=0.003).

Conclusions: Exhaled propanoic and nonanoic acids may serve as complementary non-invasive biomarkers for monitoring controlled asthma, independently of tobacco exposure. VOC analysis has promising potential to improve asthma management, therapeutic monitoring and patient stratification.

Introduction: Comorbid cardiovascular disease has been reported extensively in community COPD populations, but to a lesser degree in acute hospital settings. Shared risk factors and acute infection both increase acute coronary syndrome (ACS) risk. Our objective is to assess a cohort of adults hospitalised for an acute lower respiratory tract infection (aLRTI) to determine whether COPD status is an independent risk factor for ACS.

Methods: A prospective observational cohort study of adults aged ≥40 years (n=8496) with community-acquired aLRTI (Bristol, UK) was conducted between 27 July 2020 and 28 November 2022. Cases included physician diagnosis of COPD; controls were aLRTI without COPD. Outcomes included physician-diagnosed ACS occurring within 30 days of admission. Logistic regression models were adjusted for shared cardiovascular risk factors and aLRTI severity.

Results: 30-day ACS events in patients hospitalised with aLRTI with COPD were 7.59% (190 out of 2502), versus without COPD 6.96% (417 out of 5994) (p=0.3094). Across both groups ACS incidence was 95.1 events per 100 inpatient years. There was no association between COPD and 30-day ACS risk, when adjusting for shared cardiovascular risk factors (OR 1.14, 95% CI 0.93-1.39). However, a diagnosis of COPD increased ACS risk in those without pneumonia versus controls (OR 1.38, 95% CI 1.02-1.87). Markers of infection were associated with increased risk of ACS in both groups (white cell count >10×10⁹ cells·L^-1 OR 1.31, 95% CI 1.10-1.56). Pneumonia was associated with the highest risk of ACS (OR 1.49, 95% CI 1.19-1.87 (no COPD); OR 1.46, 95% CI 1.11-1.92 (with COPD)).

Conclusions: In this large, real-world cohort of hospitalised adults with aLRTI, 30-day ACS event rates were high at ∼7-13%. A diagnosis of COPD even in the absence of pneumonia increases ACS risk versus our control group without COPD. Markers of infection severity appear to be key drivers of ACS in this population. This highlights the importance of both COPD and infection severity on risk of ACS following hospitalisation with aLRTI.

Background: COPD is often managed with triple therapy (long-acting β₂-agonist, long-acting anticholinergic and inhaled corticosteroid). However, some patients experience COPD exacerbations and persistent symptoms, indicating poor disease control. This study aimed to describe the characteristics of uncontrolled COPD patients and assess clinical burden by comparing overall survival and exacerbation frequency between uncontrolled and controlled COPD patients, and between uncontrolled COPD patients and the general population.

Methods: This retrospective study included patients >40 years old, treated with triple therapy for ≥90 consecutive days in 2015, from the French National Health Data System. Patients were followed for up to 5 years. COPD patients were classified as uncontrolled (one or more severe, or two moderate exacerbations within 12 months before inclusion) or controlled. A random sample from the general population was included. Propensity score matching (1:2 for uncontrolled versus general population, 1:1 for uncontrolled versus controlled) was used. Overall survival was estimated using the Kaplan-Meier method; exacerbation risks were assessed using the Kalbfleisch and Prentice method.

Results: Of 186 963 COPD patients on triple therapy, 21.3% (n=39 847) had uncontrolled COPD. Uncontrolled patients had a shorter overall survival and higher mortality risk compared with controlled patients (hazard ratio (HR) 1.21, 95% CI 1.18-1.23) and the general population (HR 2.51, 95% CI 2.45-2.57). Median time to first exacerbation was 0.39 years for uncontrolled versus 1.80 years for controlled patients.

Discussion: This study demonstrates the high clinical burden of uncontrolled COPD, defined by persistent exacerbations and characterised by reduced survival and frequent exacerbations despite triple therapy.

Hybrid modalities of pulmonary rehabilitation (PR) have the potential to address some of the existing barriers associated with conventional centre-based PR. These models can be used to complement, and not only replace, centre-based PR. https://bit.ly/4nFtySE.

The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed dramatically over the past two decades, with improved prognosis owing to the availability of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and approved medications. Recently, treatment strategies combining these options have been determined by a multidisciplinary team according to localisation, characteristics, haemodynamics and comorbidities. This review summarises recent advances in hybrid therapy, combining PEA and BPA as a treatment approach for CTEPH, and discusses future perspectives.

Background: Short-acting β₂-agonist (SABA) rescue therapy can relieve COPD symptoms. We assessed post-randomisation treatment effects on exacerbations and health-related quality of life in ETHOS by rescue SABA use.

Methods: In ETHOS (NCT02465567), symptomatic people with COPD and an exacerbation history were randomly assigned 1:1:1:1 to budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) (320/14.4/10 or 160/14.4/10 μg), glycopyrronium/formoterol fumarate dihydrate (GFF) (14.4/10 μg) or budesonide/formoterol fumarate dihydrate (BFF) (320/10 μg). Post hoc analyses assessed exacerbation rates by baseline and post-randomisation SABA use (>4 versus ≤4 inhalations·day^-1), St George's Respiratory Questionnaire change from baseline by post-randomisation SABA use (>4 versus ≤4 inhalations·day^-1), and post-randomisation SABA use surrounding (30 days before, day of onset, 30 days after) the first exacerbation.

Results: Across treatments, higher moderate/severe exacerbation rates were observed for participants with higher (range: 1.62-2.51) versus lower (range: 1.14-1.51) SABA use at baseline or post-randomisation. Post-randomisation SABA use increased in the 30 days preceding, and decreased in the 30 days following, an exacerbation. Evidence of BGF benefit versus dual therapies in reducing moderate/severe exacerbation rates were seen regardless of SABA use level at baseline or post-randomisation, with greater BGF benefit observed versus GFF with higher SABA use (rate ratios (95% CI): high baseline SABA, 0.62 (0.53-0.72); high post-randomisation SABA, 0.64 (0.54-0.76)).

Conclusion: These results suggest increased SABA use is associated with an impending exacerbation. Further, BGF reduces exacerbation rates regardless of SABA use, with greater benefit in those with higher SABA use.

Background: The incremental shuttle walk test (ISWT) may be a valuable tool for measuring exercise tolerance in patients after a hospital admission with COVID-19. However, the safety, physiological response and repeatability of the ISWT are unknown in this cohort. The present study aimed to explore the properties of this test using the Post-Hospital COVID-19 (PHOSP-COVID) study.

Methods: Participants performed two ISWTs, with a 30-min rest between tests, at 5 and 12 months post-hospital discharge for COVID-19. Heart rate and fingertip peripheral oxygen saturation were recorded pre- and post-test. Reasons for test termination were noted.

Results: 1593 individuals (median (interquartile range) age 58 (50-66) years and body mass index 31.2 (27.6-35.8) kg·m^{- 2}; 967 (60.7%) males) performed an ISWT; two tests were performed by 1034 and 390 participants at the 5- and 12-month visit, respectively. At 5 months post-discharge, six patients (0.4%) had an adverse event and the most common reason contributing to test termination was breathlessness (826 (54.2%) participants). 336/1470 (22.9%) participants experienced exertional desaturation. Distance walked was greater in the second ISWT compared to the first ISWT at 5 and 12 months post-discharge (mean±sd difference: 5 months: 19±94 m; 12 months: 11±80 m; p<0.05), with an intraclass correlation coefficient estimate of 0.96 (95% CI 0.95-0.97) at 5 months and 0.97 (95% CI 0.96-0.97) at 12 months.

Conclusions: The ISWT appeared to be safe in this large cohort, supporting use of this field walking test for this population in clinical and research settings. A familiarisation test is recommended, with further study needed to determine the number of familiarisation tests required to achieve acceptable within-day repeatability.

Diaphragm fatigue does not affect IC manoeuvres across exercise in healthy males, likely due to compensation by other inspiratory muscles. Future work should examine its impact on IC in people with compromised respiratory muscle function. https://bit.ly/4433O9M.

Introduction: Functional analysis of microbiome with microbial-derived metabolites (MDMs) has emerged as key for several inflammatory and cardiovascular diseases. However, the data on the relationship of pulmonary embolism (PE) to microbiome are scarce. This study aimed to compare MDM levels between acute PE patients and healthy controls, and to investigate their associations with predisposing factors (i.e. unprovoked, provoked and cancer-associated thrombosis).

Methods: We collected serum samples from a multicentric cohort, including 96 patients with acute PE at hospital admission and 30 healthy controls. Serum concentrations of MDMs and inflammation/coagulation-related markers were quantified by liquid chromatography-mass spectrometry and flow cytometry, respectively.

Results: Compared with healthy controls, patients with acute PE showed significantly higher serum levels of trimethylamine N-oxide (TMAO) (11.5 μM versus 6.7 μM; p=0.02) and acetate (48.3 μM versus 33.0 μM; p=0.04); and lower levels of propionate (3.8 μM versus 5.3 μM; p=0.007), butyrate (4.03 µM versus 7.68 µM; p=0.009), isobutyrate (5.0 μM versus 7.32 μM; p=0.002) and valerate (0.4 μM versus 0.63 μM; p<0.001). Valerate showed the best discrimination between PE and controls (area under the receiver operating characteristic curve 0.758, 95% CI 0.66-0.86). In the multinomial analysis, higher values of TMAO and acetate were associated with a higher probability of unprovoked PE. MDM levels exhibited different correlation with inflammation-related markers highlighting TGF-β1, CCL2 and CXCL10.

Conclusion: These findings reveal imbalances in the serological concentrations of MDMs in patients with acute PE and highlight the potential role of the microbiome and its functional metabolites as novel predisposing risk factors for PE.