BMJ Open Respiratory Research最新文献

Background: Lung cancer, a leading cause of cancer deaths, is influenced by smoking, air pollution and genetic factors. This study investigated the association between lung cancer polygenic risk score (PRS) and air pollution in lung adenocarcinoma (LUAD) cases in East Asia.

Methods: This Taiwanese case-control study included 57 257 participants, of whom 1059 were diagnosed with lung cancer and 857 had LUAD. Excluding individuals with missing PRS data, the final study group comprised 648 LUAD patients and 6480 age- and gender-matched controls. Logistic regression models were employed to assess the association between PRS and LUAD risk, and interaction effects between PRS and particulate matter (PM2.5/PM10) exposure were evaluated.

Results: PGS000070 demonstrated an OR of 2.796 (95% CI 2.236 to 3.497, p<0.001), while PGS000392 exhibited an OR of 1.938 (95% CI 1.559 to 2.409, p<0.001). Higher PM exposure increased LUAD risk among individuals in the highest quartile (Q4) of both PRSs compared with the lowest quartile (Q1). In the smoking subgroup, individuals in Q4 for PGS000070 showed significantly heightened LUAD risk when exposed to higher PM2.5 and PM10 levels, with ORs of 4.08 (p<0.0001) and 2.897 (p<0.0001), respectively. However, the interaction effect of PRS (PGS000070 and PGS000392) and PM exposure on LUAD risk was not statistically significant.

Conclusion: This hospital-based study indicated that LUAD patients had higher PRSs and greater exposure to PM. However, the interaction effect between PRS (PGS000070 and PGS000392) and PM exposure on LUAD risk was not statistically significant, suggesting these factors act independently. The accumulation of air pollution did not show a gradual increase in LUAD risk. Notably, the association between PRS and air pollution was more pronounced in the smoking subgroup for PGS000070 but not for PGS000392.

Background: Pulmonary hypertension (PH) associated with lung disease entails a poor prognosis. There is concern about the potential deleterious effect on gas exchange of drugs approved for pulmonary arterial hypertension (PAH) in patients with lung disease. We conducted a systematic review on the effects of drugs approved for PAH on arterial oxygenation in randomised clinical trials (RCTs) conducted in patients with PH associated with lung disease.

Methods: Five databases were searched until May 2025. We included RCTs with PAH therapies in patients with PH associated with lung disease that reported measurements of arterial oxygenation, either the partial pressure of arterial oxygen (PaO₂) or the arterial oxygen saturation (SpO₂). For analysis purposes, both measurements were merged into one single variable called 'overall oxygenation'. As secondary outcomes, we analysed the use of supplemental oxygen and the presence of adverse events related to oxygenation.

Results: Of the 393 reports returned by the initial search, nine articles, reporting 827 patients (64.6% male), were included. The overall oxygenation at the end of the trial in the intervention group (IG), treated with a PAH therapy, was similar to the control group (standard mean difference (SMD) -0.00; 95% CI -0.17 to 0.18; p=0.98). Similarly, the change in overall oxygenation postintervention in the IG was similar to the control group (SMD 0.01; 95% CI -0.22 to 0.24; p=0.91). Reported adverse events related to oxygenation were similar in the treatment and control arms.

Conclusion: There is currently no consistent evidence from RCTs to suggest a deleterious effect of PAH therapies on arterial oxygenation in patients with PH associated with lung disease.

Prospero registration number: CRD42022349299.

Background: Chronic obstructive pulmonary disease (COPD) patients are encouraged to manage exacerbations (acute exacerbation of COPD (AECOPD)) through self-management (SM) plans. Since only around half of AECOPD are bacterial, and sputum colour correlates with bacterial load, it may help guide antibiotic use. This pragmatic randomised controlled trial (RCT) assessed the safety and effectiveness of using a sputum colour chart in UK primary care.

Methods: The multicentre RCT, Colour COPD randomised COPD adults who had ≥2 AECOPD or ≥1 AECOPD hospital admission in the preceding year. The primary objective was to assess the non-inferiority of the Bronkotest sputum colour chart compared with usual care, with hospital admission for AECOPD at 12 months as the primary outcome. Secondary outcomes included second courses of treatment requirement and quality of life (CAT score). Nested substudies examined daily symptoms via e-diaries and sputum culture.

Results: 115 severe COPD patients (global obstructive lung disease(GOLD) D, 54% Medical Research Council (MRC) 4 or 5, CAT score 24) were randomised. A trend towards more hospital admissions (32% vs 16%, relative risk (RR) 1.95 (0.92-4.18)) and increased antibiotic use within 14 days (34% vs 18%, adjusted relative risk (aRR) 1.80 (0.85-3.79)) was seen in the colour chart group. From 38 sputum substudy patients, 57 samples were received (42 stable, 15 during AECOPD), with 30% containing potentially pathogenic bacterium (PPB). Purulent sputum was more frequent in bronchiectasis, independent of disease state (stable vs exacerbation) or PPB presence, suggesting sputum colour alone does not reliably guide antibiotic use.

Conclusion: Under-recruitment precluded definitive conclusions. However, sputum colour is unlikely to be a useful addition to COPD SM in primary care.

Trial registration number: The UK's Clinical Study Registry: ISRCTN14955629 (https://doi.org/10.1186/ISRCTN14955629; registration date: 11 Number 2020).

Background and objectives: The use of long-term oxygen therapy (LTOT) in idiopathic pulmonary fibrosis (IPF) is poorly studied. We assessed the proportion of patients with IPF receiving LTOT and compared the risk of death according to LTOT exposure.

Methods: Using the French national healthcare claims database, the use of LTOT and antifibrotics was studied in patients newly diagnosed with IPF from 1 January 2012 to 31 December 2019, followed until 31 December 2021. An adjusted Cox regression model was used to compare the risk of death by LTOT use, using exposure to antifibrotics and LTOT as time-dependent variables.

Results: Among 16 003 patients newly diagnosed with IPF, 4559 (28.5%) initiated LTOT during follow-up: median time to initiation was 273 days and median duration was 336 days. The proportion of patients initiating LTOT was 23.2% among those not receiving antifibrotics (78.5% of study population) and 42.0% in those treated by antifibrotics at inclusion (7.7%), with respective median time to LTOT initiation of 110 and 590 days, and respective median LTOT duration of 308 and 294 days. Patients exposed to LTOT had a significantly higher risk of death compared with those who were not (HR: 2.9 (95% CI: 2.8 to 3.0) among those without antifibrotics; 2.1 (95% CI 1.9 to 2.3) among those with concomitant antifibrotics).

Conclusions: The use of LTOT is limited among patients with IPF, even those receiving antifibrotics. The association between LTOT and mortality suggests that LTOT use is a marker of severity. Guidelines dissemination would help clinicians adopt appropriate LTOT management in patients with IPF and chronic respiratory failure.

Background and objective: High treatment quality, defined by mean adherence >4 hours per day, unintentional leaks <24 L/min and a residual Apnoea-Hypopnoea Index <5 events per hour, is associated with better outcomes. Adherence variance may reflect behaviour linked to better treatment quality. This study aimed to assess whether monthly adherence variance is associated with improved treatment quality in patients treated with non-invasive ventilation (NIV) for more than 4 months.

Methods: E-QualiNIV is a retrospective study evaluating treatment quality in 511 telemonitored patients with chronic respiratory failure, observed from 15 April to 31 October 2023. The study followed three steps: (1) hierarchical clustering based on individual adherence variance; (2) assessing whether monthly adherence variance in the preceding month predicted the proportion of alerts in the subsequent month and (3) evaluating treatment quality based on the number of months with low adherence variance.

Results: Cluster 1, consisting of patients with adherence variance below 3, had a significantly higher proportion (57.93%) of patients achieving high-quality treatment compared with other clusters (43.1% for cluster 2 and 46.4% for cluster 3) (p=0.035). Patients with a low adherence variance in the preceding month were more likely to achieve high-quality treatment in the following month (except for May, significant differences every month from p=0.04 to p<0.01). Those with 6 or more months of low adherence variance had a significantly higher probability of receiving high-quality treatment over the entire period (coefficient: 0.2649, p value: 0.0028) compared with those who did not (non-significant).

Conclusion: The E-QualiNIV study demonstrates that low adherence variance is associated with high-quality treatment and serves as a prognostic indicator of treatment stability and alert occurrence in the subsequent month.

Introduction: Chronic hypercapnic respiratory failure often necessitates non-invasive ventilation (NIV) at home. Our study aimed to assess the static and dynamic performance of six modern NIV home ventilators and one intensive care unit (ICU) ventilator and to identify performance clusters among the devices.

Methods: A two-compartment lung model was connected to seven NIV ventilators (Sefam Stan, Philips A40, Philips DreamStation, Resmed Lumis 150, Löwenstein PrismaVent 30C, Löwenstein PrismaVent 40 and BellaVista 1000) in pressure-support mode. Static and dynamic (triggering and pressurisation) performances were assessed through three distinct clinical phenotypes and four levels of unintentional leak. Clustering analysis was performed using K-means.

Results: For each of the seven ventilators, 144 conditions were tested, and a total of 3024 cycles were analysed. Static and dynamic performances were good to excellent across home ventilators, significantly higher than the ICU ventilator. Clustering analysis identified three performance clusters. Cluster 1 (Sefam Stan and Philips A40) showed significantly more precise accuracy of inspiratory pressure than Cluster 2 (Philips DreamStation, Resmed Lumis 150, Löwenstein PrismaVent 30C and Löwenstein PrismaVent 40) and Cluster 3 (BellaVista 1000): mean error=4.3%±5.1% versus 8.5%±6.7% versus 10.6%±14.7% respectively, p<0.001. For the triggering delay, Cluster 1 displayed shorter delays than Cluster 2 and Cluster 3 (41±5 ms vs 58±11 ms vs 67±13 ms, respectively, p<0.001). For the pressurisation delay, Cluster 1 displayed shorter delays than Cluster 2 and Cluster 3 (42±6 ms vs 64±14 ms vs 87±14 ms, respectively, p<0.001). For the pressure-time product at 300 ms, Cluster 1 displayed higher area under the curve for the first 300 ms than Cluster 2 and Cluster 3 (2.1±1.1 cmH₂O /s vs 1.6±0.8 cmH₂O/s vs 1.3±1.0 cmH₂O/s, respectively, p<0.001). Continuous unintentional leaks did not modify the pressurisation performances in Cluster 1 but altered them in Clusters 2 and 3.

Conclusion: The six NIV home ventilators demonstrated superior performance compared with the tested ICU ventilator. The ventilators of Cluster 1 were identified as top performers in clustering analysis and compensated for unintentional continuous leaks.

Introduction: A potential correlation between mechanical power (MP) and clinical outcomes in mechanically ventilated patients has been reported. Limited data exist regarding MP among patients admitted to surgical intensive care units (SICUs) who require mechanical ventilation (MV) support. The primary objective of this study was to determine MP in mechanically ventilated patients admitted to the SICU, and the secondary objective was to explore whether MP was associated with clinical outcomes.

Methods: This retrospective cohort study conducted at the SICU of the tertiary university-based hospital included 283 postoperative patients admitted to the SICU who required MV support for ≥12 hours. Ventilator parameters were recorded at MV initiation and 24 hours, and MP was subsequently computed. Cox regression analysis was employed to assess the association between MP and 90-day mortality.

Results: MP at MV initiation and 24 hours were median 11.9 (IQR 8.6-17.1) J/min and 11.9 (8.9-16.8) J/min, respectively. MP was significantly higher in non-survivors both at MV initiation and 24 hours (15.4 (12.5-21.2) J/min vs 11 (8.3-15.6) J/min, p<0.001 and 15.9 (10.6-20.2) J/min vs 10.9 (8.5-15.4) J/min, p=0.001, respectively). MP ≥12 J/min at MV initiation was associated with increased 90-day mortality (HR 2.21, 95% CI 1.09 to 4.48), particularly among patients with high acuity, those at a high risk of acute lung injury and those who did not receive lung protective ventilation. In patients with MP ≥12 J/min at MV initiation, a subsequent rise in MP of ≥5 J/min at 24 hours was correlated with accentuated 90-day mortality.

Conclusion: Among mechanically ventilated patients in the SICU, MP at the initiation and at 24 hours of MV support was approximately 12 J/min. An elevated MP was an independent predictor of elevated 90-day mortality, especially in cases with high illness acuity. Alterations in MP during MV support could impact the 90-day mortality in these individuals.

Background: Canada has one of the highest per capita greenhouse gas (GHG) emissions, with healthcare contributing ~5% of the total. Pressurised metered-dose inhalers (pMDIs) are significant contributors due to their use of hydrofluorocarbon propellants. While propellant-free dry powder inhalers (DPIs) and soft mist inhalers (SMIs) are available, their adoption remains limited. This population-based study evaluates inhaler dispensation trends in British Columbia (BC), Canada, projects future dispensation and emissions over the next decade, and explores mitigation strategies through pMDI substitution.

Methods: Historical inhaler dispensation data (2015-2022) from BC were analysed using negative binomial models to assess trends, project future usage and emissions (2023-2032) and evaluate four substitution scenarios replacing pMDIs with low-GHG alternatives or DPIs/SMIs. Emissions were estimated by inhaler type, sex, age and health region, with uncertainties addressed through Monte Carlo simulation for the projected values.

Results: An average of 2.1 million inhalers are dispensed annually in BC, with pMDIs comprising 64% of total inhaler use but contributing 98% of the ~30 000 tonnes of GHG emissions. There was regional variation and older populations contributed disproportionately, reflecting burden of disease. From 2015 to 2022 (excluding 2020 and 2021, the COVID-19 years), pMDI dispensations decreased by 1% annually while DPI/SMI dispensations increased by 5%. Projections show that, without intervention, emissions could rise to ~37 000 tonnes by 2032, varying by age group. All substitution scenarios, by replacing pMDIs with DPIs/SMIs, could reduce emissions by up to 42%.

Conclusion: High quality, guideline-directed diagnosis and management of respiratory disease is known to improve health and reduce emissions. Building on these benefits, our analysis shows that substituting pMDIs with lower-emission inhalers, when guided by policy and clinical decisions that prioritise patient safety and preference, can significantly reduce healthcare-related GHG emissions.

Introduction: Bronchiectasis exhibits substantial heterogeneity across geographic locations and includes a diverse range of aetiologies. Limited large-scale data are available for Southeast Asian countries.

Methods: This was a multicentre, retrospective, observational cohort study. Between January 2017 and June 2020, comprehensive clinical data were collected on enrolment, and 1-year follow-ups were conducted using an electronic case report form.

Results: A total of 2753 patients were enrolled. The mean age of the patients was 67 years. Forty-two per cent (1150/2753) of patients were male. The mean modified Reiff score was 5.0±3.3. The proportions of bacteria, tuberculosis and nontuberculous mycobacteria cultured from sputum within 1 year of follow-up were 46% (381/829), 1% (10/829) and 24% (202/829), respectively. The most prevalent bacterial isolate was Pseudomonas aeruginosa (22%), followed by Klebsiella pneumoniae (11%). Airflow obstruction was observed in 32% of patients, and 39% used inhaled bronchodilators. A substantial proportion (57%) of the patients were prescribed mucolytics. Seventeen per cent of the patients experienced severe exacerbations within a year. One-year all-cause mortality rate was 2% (52 of 2563 patients). Female patients demonstrated more severe imaging findings than male patients (modified Reiff score, 5.2 vs 4.6, p<0.001). However, they exhibited less obstructive lung function impairment (26% vs 40%, p<0.001), experienced fewer severe exacerbations (15% vs 20%, p=0.002) and had lower mortality rates (2% vs 5%, p<0.001). The risk of severe exacerbation and mortality increased significantly among patients older than 80 years.

Conclusion: Although female patients with bronchiectasis exhibited more severe imaging findings, their prognoses were better in Taiwan. Elderly patients older than 80 years had worse prognosis.

Objectives: To estimate the risk of subsequent exacerbations, in relation to history of exacerbations, in a cohort of older chronic obstructive pulmonary disease (COPD) patients in Canada.

Methods: Using provincial claims data from Ontario, Canada, patients with COPD aged≥65 years (identified between 2004 and 2018; followed up to 2020) were categorised into one of four mutually exclusive groups: no exacerbation; only one moderate; only one severe; or two or more exacerbations of any severity (moderate or severe) during the baseline period. The index date was the first documentation of a COPD diagnosis code; the subsequent 12 months served as the baseline period. Adjusted risks of subsequent exacerbations (any severity and severe exacerbation, separately) by the end of postbaseline year 1, 2 and 3 were estimated, accounting for differences in patient and disease characteristics and competing risk of death.

Results: A total of 591 686 patients were included. The majority (89.8%) had no exacerbation at baseline, 3.1% had one moderate exacerbation only, 3.6% had one severe exacerbation only and 3.6% had two or more exacerbations of any severity. Adjusted risks of a subsequent exacerbation of any severity by the end of year 3 were 28.6% (95% CI, 28.5% to 28.7%) with no baseline exacerbation; 56.6% (95% CI, 56.1% to 57.1%), one severe; 58.4% (95% CI, 58.0% to 58.8%), one moderate; and 77.5% (95% CI, 77.2% to 77.8%) two or more exacerbations. Adjusted risks of a subsequent severe exacerbation by the end of year 3 were 20.1% (95% CI, 20.0% to 20.2%) with no baseline exacerbation; 34.9% (95% CI, 34.5% to 35.4%), one moderate; 46.7% (95% CI, 46.2% to 47.2%), one severe; and 59.6% (95% CI, 59.3% to 60.0%) two or more exacerbations.

Conclusions: Having a history of a single severe or two or more exacerbations of any severity is associated with a higher risk of future exacerbations, with observed exacerbation rates and severity that are constant over time. Even one moderate exacerbation over a year is associated with poorer outcomes, compared with the absence of exacerbation, and moderate exacerbations should be managed accordingly.