ERJ Open Research最新文献

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.

Resting P _aO2 >9.30 kPa is the best predictor of a pass on a hypoxic challenge test (HCT), suggesting that decisions about the need for a HCT, and therefore the ability to fly without supplemental oxygen, can be made from a blood gas reading in ILD https://bit.ly/40Db0bH.

This first study evaluating a miniaturised videoendoscopy probe (Iriscope) for real-time exploration of GGOs allowed direct visualisation of GGOs with high Sp and PPV, and could identify a tumoral aspect in 50% of cases when the r-EBUS was negative https://bit.ly/45rFaBV.

[This corrects the article DOI: 10.1183/23120541.00950-2023.].

Background: Animal-derived components in cell culture, such as fetal bovine serum and extracellular matrix proteins, pose ethical concerns and contribute to variability in experimental outcomes. This study explores the use of animal-free cell culture media and substrates to support the growth and differentiation of primary human bronchial epithelial cells, as well as their infection by respiratory syncytial virus (RSV).

Methods: We evaluated the performance of jellyfish collagen 0 and recombinant extracellular matrix proteins as alternatives to traditional mammalian substrates. Additionally, we assessed the use of animal-free medium and human serum (HS) in viral propagation using HEp2 cells.

Results: The use of animal-free medium, matrix proteins and HS can support primary epithelial cell growth and differentiation with high levels of ciliation and barrier integrity. RSV propagation in animal-free medium produced an increase in viral titres, indicating the potential of these systems for antiviral research.

Conclusion: Transitioning to include more animal-free medium and substrates for primary cell culture and viral propagation will help improve the ethical standing of research and offer more human-relevant models for studying viral diseases in the future.

Background: The impact of applying different lung function reference equations and interpretation methods in fibrotic interstitial lung disease (ILD) is poorly understood. We aimed to evaluate disease severity classification, trajectories and prognostic significance of percent-predicted and z-scores of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (D _LCO) using the Global Lung Function Initiative (GLI) reference equations in patients with fibrotic ILD, compared to registry-recorded values.

Methods: Serial lung function measurements of 5026 patients from three prospective registries were used to calculate percent-predicted and z-scores using 2012- and 2023-GLI FVC reference equations and 2017-GLI D _LCO reference equations, which were compared with registry-recorded values. Differences for baseline and longitudinal assessments, classification for lung function impairment severity and progression, and association with transplant-free survival and performance of the ILD-Gender-Age-Physiology model with external validation were assessed.

Results: Baseline FVC and D _LCO percent-predicted values were consistently higher using the 2012- and 2023-GLI FVC and 2017-GLI D _LCO reference equations compared to registry-recorded values. The agreements for all percent-predicted reference equations were good for lung function severity classification (unweighted κ for FVC 0.69-0.76, D _LCO 0.70), but only moderate for the counterpart z-scores (FVC 0.41-0.50, D _LCO 0.45). The largest 1-year declines were observed using the 2023-GLI FVC reference equations and the 2017-GLI D _LCO reference equations. Lower baseline GLI and registry-recorded FVC and D _LCO values were associated with worse transplant-free survival and had similar performance for risk stratification, except for a lack of association of baseline 2023-GLI FVC percent-predicted and z-scores for adjusted analyses in the non-White cohort.

Conclusions: Use of different lung function reference equations and interpretation methods may impact disease severity classification and longitudinal trajectory in patients with fibrotic ILD, although prognostic significance is similar, except for 2023-GLI FVC in non-White patients.