European Respiratory Journal最新文献

Background: Exercise pulmonary hypertension (PH) was defined by a mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope >3 mmHg·min·L^-1 between rest and exercise in the 2022 European Society of Cardiology/European Respiratory Society PH guidelines. However, large, multicentre studies on the prognostic relevance of exercise haemodynamics and its added value to resting haemodynamics are missing.

Patients and methods: The PEX-NET (Pulmonary Haemodynamics during Exercise Network) registry enrolled patients who underwent clinically indicated right heart catheterisations both at rest and ergometer exercise from 23 PH centres worldwide. In this retrospective analysis we included subjects with resting mPAP <25 mmHg and complete haemodynamic data at rest and exercise in the same body position. Mixed effects Cox proportional hazard models with random effect centre were applied to identify independent markers of prognosis among the haemodynamic parameters.

Results: We included 764 patients (64% females; median (interquartile range) age 59 (46-69) years and mPAP 17 (14-20) mmHg). Median (range) observation time was 6.8 (0.1-15.9) years and 87 patients (11%) died during follow-up. After adjustment for age, sex, haemoglobin level and resting haemodynamics, CO (hazard ratio (HR) 0.85, 95% CI 0.77-0.93; p=0.001) and transpulmonary gradient (HR 1.04, 95% CI 1.00-1.08; p=0.044) at peak exercise and the mPAP/CO slope (HR 1.12, 95% CI 1.06-1.18; p<0.001) were the only independent predictors of prognosis. Patients with a mPAP/CO slope >3 mmHg·min·L^-1 had significantly worse survival compared to those with a mPAP/CO slope ≤3 mmHg·min·L^-1 (HR 2.04, 95% CI 1.16-3.58; p=0.013).

Conclusion: The mPAP/CO slope is a robust and independent predictor of prognosis in patients with normal or mildly elevated resting PAP that provides prognostic information beyond resting haemodynamics and appears suitable to define exercise PH.

Introduction: Outpatient management of pulmonary embolism (PE) remains controversial in patients with cancer due to their higher risks of mortality, recurrent venous thromboembolism (VTE) and bleeding complications. This systematic review and meta-analysis aimed to evaluate the safety and feasibility of outpatient management of cancer-associated PE.

Methods: We searched MEDLINE, Embase, Cochrane Central, and Scopus databases from inception to May 30, 2024, for studies on outpatient management of cancer-associated PE. Eligible studies included randomized controlled trials, cohort studies, and case-control studies with ≥10 patients. The primary outcome was 30-day-all-cause mortality; secondary outcomes included VTE-related mortality, major bleeding and recurrent VTE at 30 days. Meta-analysis was performed using random effects models, and heterogeneity was assessed with the I² statistic.

Results: Nineteen studies (13 full-article, 6 abstract-only) with a total of 1589 patients managed as outpatients were identified. Criteria for outpatient management of cancer-associated PE were reported in 14 studies. The pooled 30-day all-cause mortality rate was 1.74% (95% CI: 0.99-3.03; I²=0%, 691 patients, 6 full-article). The 30-day major bleeding pooled rate was 2.71% (95% CI: 1.51-4.83; I²=0%; 406 patients, 6 full-article), and the 30-day recurrent VTE pooled rate was 1.26% (95% CI: 0.53-3.00; I²=0%; 396 patients, 5 full-article).

Conclusion: Selected patients with cancer-associated PE managed as outpatients appear to have low short-term rates of mortality, major bleeding and recurrent VTE suggesting this may be a safe strategy. Further research with larger, prospective studies is needed to confirm these findings and refine risk stratification protocols.

Background: The number of young people who use electronic cigarettes (e-cigarettes) is rising. It remains unclear whether e-cigarettes use impairs lung function. We aimed to compare ventilation distribution between young adults exposed to e-cigarettes with an unexposed group.

Methods: Study participants included otherwise healthy young adults (18 to 24 years) who self-reported e-cigarette use, and participates who had no history of e-cigarette, tobacco or cannabis exposure. Exposure to e-cigarettes was defined using three measures 1) ever exposed, 2) daily use, and 3) puff frequency, which includes: none (unexposed), low (1-2 puffs/hour), moderate (3-4 puffs/hour) and heavy (5+ puffs/hour). Ventilation distribution was measured using the multiple breath washout test and reported as lung clearance index (LCI).

Results: A total of 93 participants were recruited, 38 unexposed and 41 exposed participants had LCI measures. The exposed group consisted predominately of participants who used flavoured e-liquids (94.5%) that contained nicotine (93.5%). The magnitude and direction of the difference in LCI across the exposure definitions was similar. Compared with the unexposed group, in the unadjusted models LCI was higher in those with any e-cigarette use (mean difference 0.16 units; 95% CI 0.004; 0.31), daily users (mean difference 0.11; 95% CI 0.06; 0.28) and heavy users (mean difference 0.22; 95% CI 0.03; 0.41).

Conclusion: This preliminary work suggests that LCI may be a useful biomarker to measure the effects of e-cigarette use on ventilation distribution and to track early functional impairment of the small airways.

Background: We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biologics for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life (QoL).

Methods: International expert healthcare professionals (HCPs) and patients with severe asthma were invited to: 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA; 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of HCPs evaluated CONFiRM's external validity.

Results: Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroids use were rated as most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between HCPs and patients, although patients assigned greater importance to QoL. The CONFiRM score quantified response to a biological from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (AUC≥0.92) and a substantial (AUC≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult respectively (p<0.0001)).

Conclusions: We have developed novel patient-centred paediatric and adult CONFiRMs which include QoL measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.

Background: Several major risk factors for chronic obstructive pulmonary disease (COPD), such as population aging, smoking rates, and air pollution levels are rapidly changing, causing inevitable changes in the population burden of COPD. We determined the excess direct costs of COPD and their trend from 2001 to 2020.

Methods: Using administrative health data from British Columbia, Canada, we created a retrospective matched cohort of physician-diagnosed COPD patients and non-COPD individuals. Excess direct medical costs (2020 $CAD) were estimated by analysing hospital records, outpatient services, medications, and community-care services. Comorbidity classes were assessed using the International Classification of Diseases codes. Excess COPD costs were estimated as the adjusted difference in direct medical costs between COPD and non-COPD cohorts.

Results: There were 208 554 and 404 703 individuals in the COPD and non-COPD cohorts, respectively (47.8% female; mean baseline age 69.1 and 68.2 years, respectively). Direct medical costs for COPD were $9224 per patient-year (/PY), compared to $3396/PY for non-COPD, giving rise to excess costs of $5828/PY (95% confidence interval [CI] 5759-5897). Excess costs increased by 48% over the study period. Excess costs due to comorbidities were $3588/PY (95% CI 3554-3622), with cardiovascular-related conditions alone exceeding the costs attributed to COPD ($1375/PY versus $904/PY).

Conclusion: Despite multifaceted prevention and management initiatives, COPD-related economic burden is increasing, with the majority of costs due to comorbid conditions. Rising per-patient costs, combined with the flat or increasing prevalence of COPD in many jurisdictions, indicates a significant increase in COPD burden.

Background: Concerted efforts aim to reduce the burden of 6 months of anti-tuberculous treatment for tuberculosis (TB). Treatment cessation at 8 weeks is effective for most but incurs increased risk of disease relapse. We tested the hypothesis that blood RNA signatures or C-reactive protein (CRP) measurements discriminate 8-week sputum culture status, as a prerequisite for a biomarker to stratify risk of relapse following treatment cessation at this time-point.

Methods: We identified blood RNA signatures of TB disease or cure by systematic review. We evaluated these signatures and CRP measurements in a pulmonary TB cohort, pre-treatment, at 2 and 8 weeks of treatment, and sustained cure after treatment completion. We tested biomarker discrimination of 8-week sputum culture status using area under the receiver operating characteristic curve (AUROC) analysis and, secondarily, assessed correlation of biomarker scores with time to culture positivity at 8 weeks of treatment.

Results: 12 blood RNA signatures were reproduced in the dataset from 44 individuals with sputum culture-positive pulmonary TB. These normalised over time from TB treatment initiation. 11 out of 44 cases with blood RNA, CRP and sputum culture results were sputum culture-positive at 8 weeks of treatment. None of the contemporary blood RNA signatures discriminated sputum culture status at this time-point or correlated with bacterial load. CRP achieved modest discrimination with AUROC 0.69 (95% CI 0.52-0.87).

Conclusions: Selected TB blood RNA signatures and CRP do not provide biomarkers of microbiological clearance to support TB treatment cessation at 8 weeks. Resolution of blood transcriptional host responses in sputum culture-positive individuals suggests Mycobacterium tuberculosis may colonise the respiratory tract without triggering a detectable immune response.

Arousal Threshold Modifies the Effect of CPAP on Executive Function Among Individuals with Obstructive Sleep Apnea.

Background: Obstructive Sleep Apnea (OSA) is associated with neurocognitive dysfunction. However, randomized trials evaluating the effects of continuous positive airway pressure (CPAP) on neurocognition in those without dementia do not show a benefit. We thus aimed to assess whether arousal threshold (ArTH) modifies the effect of CPAP on neurocognitive function.

Methods: We performed a secondary analysis of a randomized, sham-controlled trial, Apnea Positive Pressure Long-term Efficacy Study. ArTH was estimated from polysomnography using a translatable method (Sands et al., SLEEP 2018). Neurocognitive outcomes included the Sustained Working Memory Test-Overall-Mid-Day score (SWMT-OMD, executive function, primary outcome), with the Pathfinder Number Test - total time (attention) and Buschke Selective Reminding Test - sum recall (learning and memory) as secondary outcomes. Generalized linear modeling assessed whether the effect of CPAP was modified by baseline ArTH (treatment-by-ArTH interaction). 833 participants with OSA, [apnea-hypopnea index (AHI) ≥10 events/h], available ArTH, and outcomes were analyzed (CPAP n=437, Sham n=396).

Results: For executive function, the effect of CPAP treatment was modified by ArTH (p-interaction=0.042). Specifically, for every 1 sd increase in ArTH, the SWMT-OMD score improved by 0.10 95% CI (0.01, 0.18) in active compared to sham CPAP at 6 months; At ArTH 1 sd above the mean SWMT-OMD improvements were nearly three times that in those with average ArTH (0.139 [0.018, 0.261] versus 0.053 [-0.034, 0.140] respectively. No effect modification was observed for attention (p=0.311) or learning and memory (p=0.744).

Conclusion: In OSA, a higher ArTH is associated with greater improvements in executive function following CPAP therapy.