BMJ Open Respiratory Research最新文献

Introduction: Targeted maximum likelihood estimation (TMLE) is a semiparametric doubly-robust estimator that integrates the SuperLearner in the estimation process, an ensemble method that allows us to model the exposure-outcome relationship combining multiple parametric and non-parametric methods.

Aim: We applied TMLE to assess the effect of maternal paracetamol use during the first trimester of pregnancy on child wheezing during the first 18 months of life, using data of the Italian NINFEA birth cohort.

Methods: We included three progressively larger sets of covariates for confounding adjustment. Set 1 included baseline socioeconomic and maternal characteristics, conditions and disorders. Set 2 additionally included maternal respiratory infections in the first pregnancy trimester. Set 3 added prepregnancy maternal mental health disorders.The effect was estimated with three TMLE implementations, differing in the methods used to model the exposure-outcome relationship: (1) parametric; (2) SuperLearner with parametric and semiparametric approaches and (3) SuperLearner with parametric, semiparametric and non-parametric approaches, and with hyperparameters tuning. We compared TMLE with multivariable regression, propensity score regression adjustment and inverse probability weighting.

Results: All methods provided similar results, suggesting a weak positive association that attenuated toward the null as progressively more covariates were adjusted for, from set 1 (TMLE 3: risk ratio, RR 1.15 (95% CI 1.03 to 1.29)) to set 3 (TMLE 3: RR 1.10 (95% CI 0.97 to 1.26), N=4099).

Conclusions: Such an association could be interpreted as a small positive effect or incomplete control for residual or unmeasured confounding, and its consistency across methods suggests it is unlikely to be driven by model misspecification.

Objective: Polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) is a glycopeptide transferase which is closely involved in the development and progression of cancer. This study aimed to investigate the effects of GALNT7 inhibition on non-small cell lung cancer (NSCLC) cell proliferation, apoptosis and invasiveness and to determine whether these effects are mediated by the protein kinase B (AKT) pathway.

Methods: Negative control small interfering RNA (siRNA) (si-NC) and siRNA targeting GALNT7 (si-GALNT7) were transfected into A549 and NCI-H1650 cells. Afterwards, the AKT activator '740 Y-P' was added to treat the cells with or without siRNA transfection.

Results: Cell proliferation was reduced after si-GALNT7 transfection compared with si-NC transfection at 24 hours, 48 hours and 72 hours in A549 cells, and at 48 hours and 72 hours in NCI-H1650 cells. Furthermore, the cell apoptosis rate was increased, but the cell invasive number was decreased after si-GALNT7 transfection compared with si-NC transfection in A549 cells and NCI-H1650 cells. Phosphorylated (p)-AKT/AKT expression was lower after si-GALNT7 transfection compared with si-NC transfection in A549 cells and NCI-H1650 cells. Worth noting, the effects of si-GALNT7 transfection on the above-mentioned cell proliferation, apoptosis and invasiveness were repressed by the addition of 740 Y-P in A549 cells and NCI-H1650 cells.

Conclusion: GALNT7 inhibition suppresses NSCLC cell proliferation and invasiveness while increasing apoptosis through inactivation of the AKT pathway.

Background: The burden of severe asthma due to asthma exacerbation is increasing. However, recent studies identifying exacerbation-related disease burden among patients with severe asthma in South Korea are lacking.

Objective: To evaluate the burden of asthma exacerbations in patients with severe asthma in South Korea.

Methods: A retrospective cohort study using National Health Insurance data from 2016 to 2019 was conducted. Patients with severe asthma were defined as satisfying the following criteria: (1) having been prescribed ≥1 inhaled corticosteroid-long-acting β-2 agonist and long-acting muscarinic antagonist with a diagnosis of asthma; (2) having experienced ≥4 asthma exacerbation events within 1 year, after meeting the first criterion. Exacerbation was defined as a corticosteroid burst. Healthcare utilisation, direct medical costs and case fatality rates related to asthma exacerbations were identified during the follow-up period.

Results: Outpatient visits accounted for 81.26% of all exacerbation events, followed by general ward hospitalisation (14.55%). The exacerbation-related costs were as follows: outpatient visit, $29.89; emergency room visit, $95.02; general ward hospitalisation, $1929.32; and intensive care unit admission, $7918.86. The case fatality rates were 2.65% for patients with asthma, 3.16% for patients who had exacerbations and 6.96% for patients who had exacerbations with hospitalisation.

Conclusion: This study is the first population-based cohort study observing exacerbation-related burdens in patients with severe asthma, using recent data and generating real-world evidence. The results of this study can be used as evidence for further research on the burden of asthma and to inform decision-making in healthcare policy.

Background: This study aims to evaluate the association of Life's Essential 8 (LE8) with chronic lower respiratory disease (CLRD)-specific mortality and impaired lung health outcomes.

Methods: This population-based cohort study used data from the National Health and Nutrition Examination Survey (NHANES, 2007-2018), including adults aged 20-79 years (n=10 135), with lung function measurements available for a subset (n=3188). Multivariable Cox proportional hazards and restricted cubic spline models were employed to assess the associations between LE8 scores and CLRD-specific mortality. Logistic and linear regression models evaluated the associations between LE8 scores and lung health. All models were adjusted for sociodemographic variables (age, sex, race/ethnicity, education, income-to-poverty ratio), cardiovascular disease, respiratory disease and smoking history. Sensitivity analyses were conducted to assess the stability of the results. The primary outcome was CLRD-specific mortality, and the secondary outcome was lung health.

Results: Over a median follow-up of 7.83 years, 50 CLRD-specific deaths were recorded. Higher LE8 scores were associated with reduced risks of CLRD-specific mortality (adjusted HR (aHR), 0.56 (0.40-0.79)), with a linear dose-response relationship observed (P for non-linear=0.574). Furthermore, each 10-point increase in total LE8 score was associated with impaired lung health, including lower odds of asthma (adjusted OR (aOR), 0.88 (0.83-0.93)), chronic bronchitis (aOR, 0.81 (0.74-0.88)), emphysema (aOR, 0.59 (0.52-0.65)), chronic obstructive pulmonary disease (aOR, 0.63 (0.45-0.89)) and lower relative risk of a restrictive spirometry pattern (adjusted relative risk ratio (aRRR), 0.66 (0.56-0.79)). Positive correlations were observed between total LE8 scores and lung function (p<0.001). The findings were robust in sensitivity analyses and consistent across key subgroups.

Conclusions: Higher LE8 scores were associated with reduced CLRD-specific mortality and improved lung health. Promoting LE8 adherence could significantly alleviate respiratory disease burdens and mortality.

Background: Birth weight (BW) Z-score is associated with outcomes in very preterm infants (VPIs). This study aimed to investigate the association between BW Z-score and the adverse outcomes in VPIs.

Methods: This retrospective cohort study included VPIs admitted to a tertiary neonatal intensive care unit between 1 January 2014 and 31 December 2023. Restricted cubic splines and multivariable logistic regression models were employed to assess associations between BW Z-score and primary outcomes. Infants were categorised based on the identified turning point of Z=-0.35 in the Z-score distribution, where the risk gradient changed most sharply. The primary outcome was bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age or discharge.

Results: Among 4632 included VPIs, a turning point at Z=-0.35 was identified. Compared with those with Z≥-0.35, VPIs with Z<-1 exhibited higher risks of primary outcomes (OR 3.10, 95% CI 2.53 to 3.79), while those with BW Z-score between -1 and -0.35 also showed increased risks (OR 1.81, 95% CI 1.52 to 2.15). Subgroup and sensitivity analyses further supported the robustness of these findings.

Conclusion: Compared with BW Z-score above -0.35, both substantially negative BW Z-score<-1 and moderate lower BW Z-score between -1 and -0.35 are associated with increased risk of BPD and mortality in VPIs. The findings underscore the importance of considering BW Z-score as a continuous variable in risk stratification and management of VPIs.

Background: Pulmonary rehabilitation (PR) is a highly effective intervention for people with chronic respiratory disease; however, it is not known how best to sustain its benefits. Clinical trials are needed to establish if participation in singing for lung health (SLH) groups following PR will improve health-related quality of life, healthcare utilisation and exercise capacity compared with usual care. A feasibility study would help to guide development of these trials.

Methods: In a multicentre, mixed-methods randomised controlled feasibility trial, PR participants at four sites were prescreened at baseline assessment. An SLH taster session was included routinely as part of the PR programmes. Eligible PR completers were invited to take part in the trial and randomised to usual care or a 12-week SLH course. Feasibility outcomes included recruitment rate, intervention compliance (at least 8/12 sessions) and health economic analysis. Interviews with participants and study personnel were undertaken and thematic analysis of the results was completed.

Results: Between October 2022 and November 2023, 1311 patients were assessed to start PR, 838 completed. Of those completing, 243 were ineligible to take part (predominantly due to vaccination status and excluded diagnoses for PR referral), and 531 declined. 64 people (33 female, mean (SD) age 69 (12), 41 ethnically white, 33 with chronic obstructive pulmonary disease, 16 with asthma, 9 with interstitial lung disease, 6 with bronchiectasis) were recruited, with 30 (93.8%) SLH and 29 (90.6%) controls completing the study. 20 (62.5%) of the SLH group completed at least 8/12 SLH sessions. There was enthusiasm for a definitive trial from participants, clinicians and singing group leaders' perspectives, based on positive experiences of trial involvement. Improvements to recruitment strategy, intervention structure, outcome measures and staffing were suggested.

Conclusions: A definitive randomised controlled trial of SLH post-PR appears feasible, with acceptable uptake and completion rates.

Trial registration number: ISRCTN11056049.

Introduction: Small-scale miners are known to experience high silica exposures, associated with high rates of silicosis and Tuberculosis (TB). TB has been shown to worsen underlying impairment of lung function in miners. We describe the spirometry outcomes, according to previous TB status, among a large cohort of small-scale miners attending a screening centre.

Methods: We collected cross-sectional spirometry and clinical data from consecutive miners and ex-miners, with negative Xpert TB results, attending a screening clinic in Northern Tanzania, between February 2018 and December 2020. Spirometry values assessed using the ATS/ERS 2019 quality criteria and compared with GLI 2022 global (GLIgl) reference values. We used multiple linear regression to model excess Forced Expiratory Volume in 1 s (FEV1) and Forced Vital Capacity (FVC) loss using an a priori interaction between duration of work and previous TB.

Results: Of 542 participants with spirometry results, 80 (15%) reported previous TB. At least moderate (z-score ≤-2.5) FEV1 reductions were present in 51% of participants with previous TB and 18% of those without previous TB. For FVC, respective values were 34% and 10%. A miner with TB and 10 years of work was modelled to have lost 1405 (95% CI 1134 to 1676) mls of FEV1 and 1342 (95% CI 1042 to 1641) mls of FVC compared with GLIgl reference values. For miners without previous TB, the corresponding excess FEV1 and FVC losses were 693 (95% CI 581 to 804) mls and 624 (95% CI 504 to 743) mls, respectively.

Discussion: Unmeasured silicosis may partially explain some of the observed effect of previous TB. However, this does not change our observation of a clinically significant burden of abnormal spirometry in a clinic-based population of small-scale miners. Reducing silica exposures and preventing TB are key to improving lung health in miners.

Introduction: Yoga is an emerging exercise choice for people with cystic fibrosis (CF), but evidence of its effect in this population is scarce, with a recent systematic review advocating for further research. Yoga Outcomes Get Assessed in CF (YOGA-CF) is a real-world multicentre randomised controlled trial (RCT) investigating a bespoke CF-specific online 12-week yoga intervention, vers usual care, to determine effectiveness for adults with CF.

Methods and analysis: A multicentre RCT of adults with CF across the UK. Participants are randomised to usual care or a 12-week online bespoke yoga programme with an expectation of two classes completed weekly. Assessments of lung function, 1 min sit-to-stand, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and other trial questionnaires are completed preintervention and postintervention (0 and 12 weeks) and after 12 weeks of follow-up (week 24). The primary outcome is the difference in respiratory-related quality of life measured using the CFQ-R before and after yoga/control. Sample size was calculated based on detecting a minimally clinically important difference of 4 for the CFQ-R respiratory domain, with power of 80% and 5% significance level (total target, n=314).

Ethics and dissemination: Ethics approval gained from the South Yorkshire and Humber Research Ethics Committee (REC) (reference: 23/YH/0270, project ID 303898). Dissemination to involve direct participant feedback and lay webinar, scientific conference presentation and publication in a peer-reviewed journal.

Trial registration number: NCT06120465.

Background: Chronic obstructive pulmonary disease (COPD) incurs significant mortality worldwide. Less is known about the burden in the last decade across Europe. We report trends and variations in mortality for patients with COPD across 27 European countries from 2011 to 2021.

Methods: COPD mortality was extracted from the EUROSTAT database, using the International Classification of Diseases 10 codes J43 and J44 for each country. Age-standardised and sex-standardised mortality rates (SMR) were calculated and joinpoint regression identified average annual percentage change (AAPC) in deaths from 2011 to 2021. Global Burden of Disease tobacco prevalence data were used to try and best contextualise the mortality.

Results: The overall SMR in Europe for this period was 32.1 (95% CI 32.0 to 32.1) per 100 000 person-years, with substantial geographical heterogeneity. There was a fivefold difference in mortality rates between the countries with the greatest versus the least deaths. Although there was an apparent 3% (95% CI -4.4% to -1.6%) decrease in average annual deaths from 2011 to 2021 across Europe, there was no significant change in deaths from 2011 to 2018, prior to the UK leaving the dataset (a noticeably high outlier in SMR) and the COVID-19 pandemic. A 2% reduction (95% CI -2.6% to -1.2%) in annual mortality rate was noted in males from 2011 to 2018, while females increased (AAPC 1.3% (95% CI 0.1% to 2.6)%) in the same time frame.

Conclusion: The plateau in COPD-related deaths across Europe from 2011 to 2018 demands focus. Geographical variation in mortality suggests under-reporting in some countries, which may underestimate the true burden.

Background: UK General Internal Medicine (GIM) registrars are traditionally expected to be able to perform pleural procedures out-of-hours (OOH) if required. Pleural exposure for GIM registrars has declined, with procedures increasingly performed by specialists in-hours. Pleural procedures can cause significant harm. We explored the role of the GIM registrar in performing OOH pleural procedures, with particular focus on competence and confidence.

Methods: An anonymous survey was distributed to GIM registrars and respiratory consultants across the UK.

Results: Responses were received from 391 non-respiratory GIM registrars and 93 respiratory consultants. 37% of registrars reported being 'signed-off' as independent in chest drain insertion for pneumothorax. 69% had not done a pleural procedure for at least a year. Regarding perceived confidence for OOH chest drain insertion for pneumothorax, 42% reported no confidence to perform the procedure even if directly supervised, with only 11% feeling confident to proceed unsupervised. Consultants rated the pleural competence of an average non-respiratory GIM registrar; only 4% felt they could perform the procedure unsupervised. Common themes in the free text included anxiety surrounding pleural procedures, patient safety concerns, insufficient available training opportunities to maintain competency and differing opinions on the evolving role of the medical registrar and who should be expected to perform OOH pleural procedures.

Conclusions: The majority of UK GIM registrars are neither confident nor perceived by trainers as competent to independently perform OOH chest drain insertion. This has implications for patient safety and service delivery, informing broader discussions regarding GIM training, curriculum and the need to establish local OOH pleural pathways.