BMJ Open Respiratory Research最新文献

Background: Re-expansion pulmonary oedema (RPO) is a serious and potentially life-threatening complication following rapid drainage of pleural effusion or pneumothorax. However, the incidence and risk factors for RPO following medical thoracoscopy (MT) remains unknown.

Methods: We performed a retrospective cohort study of patients who underwent MT between January 2017 and December 2024. All procedures were performed with a semirigid thoracoscope under conscious sedation.

Results: A total of 362 patients were included in the study. Approximately half (52.8%) of patients had pleural effusions occupying >50% of the hemithorax on preprocedural chest radiographs. Malignant pleural effusion and tuberculous pleuritis accounted for 85.1% (n=308) and 8.6% (n=31) of the final diagnoses, respectively. Six (1.7%) patients developed clinical RPO with hypoxia requiring oxygen supplementation, of whom three required invasive mechanical ventilation, and one patient required non-invasive ventilation. Compared with patients without RPO, those who developed clinical RPO were younger in age (median 55 (IQR: 35-64) vs 69 (IQR: 60-75) years, p=0.031), had a higher proportion of effusions occupying >50% hemithorax (100% (6/6) vs 52.0% (185/356), p=0.031) and greater pleural fluid drainage volumes during MT (median 2795 (IQR:1425-4050) vs 1375 (IQR:1000-1831) mL, p=0.009). Radiological RPO occurred in 20 patients (6.1%). On univariable and multivariable analysis, younger age (<60 years), larger volume of pleural fluid drained and expandable lung following pleural fluid drainage were associated with the development of radiological RPO. There were no deaths related to MT or RPO in our study.

Conclusion: RPO is a clinically significant complication of MT, with younger age and large-volume effusions being possible risk factors. Physicians performing MT should exercise vigilance for RPO to facilitate early recognition and prompt management.

Aim: To evaluate the association between the presence or absence of comorbid mental health disorders and the risk of asthma exacerbations in adults with prevalent asthma.

Methods: This was a cohort study of adults in England with prevalent asthma and mental health disorders (depression, anxiety, bipolar disorder and schizophrenia) between 2017 and 2019 using primary care electronic healthcare records.Adult asthma patients with mental health disorders (exposed) were matched by age, sex, ethnicity and general practice to asthma patients without a mental health disorder (unexposed) in a 1:1 ratio. The primary outcome was an exacerbation of asthma documented in primary care records. Poisson regression was used to estimate adjusted incidence rate ratios (IRR).

Results: 873 482 adults with asthma were followed up for a total of 1 580 157 years.Mean age was 49 years; 66% were female, and 78% were white. Adults with asthma and any mental health disorder had an asthma exacerbation incidence rate of 56 per 1000 person years compared with 34 per 1000 person years for those without a mental health disorder.Adults with asthma and any mental health disorder had an adjusted IRR of 1.46 (95% CI 1.44 to 1.48) compared with matched controls. The highest IRR was in those with depression (IRR 1.34, 95% CI 1.32 to 1.37), followed by those with anxiety (IRR 1.20, 95% CI 1.18 to 1.22). There were no significant differences in patients with bipolar disorder or schizophrenia compared with matched controls (IRR 1.00, 95%CI 0.93 to 1.07; and 1.03, 95% CI 0.95 to 1.11, respectively).

Conclusion: This study shows a significant increased risk of asthma exacerbations in asthma patients with depression or anxiety compared with those with asthma without comorbid mental health disorders.

Introduction: Despite a severely degraded quality of life in the advanced stages, chronic obstructive pulmonary disease (COPD) patients rarely discuss end-of-life issues and have little access to palliative care. After knowing this fact, some organisations recommend advance care planning integrated into the respiratory rehabilitation. Considering the important role played by physiotherapists in this rehabilitation, the aim of this study is to understand the professional practices of physiotherapists regarding this planning during rehabilitation and the factors influencing these practices.

Methods: The research consisted of a qualitative study with physiotherapists practising in France and conducting respiratory rehabilitation with COPD patients. Semi-structured interviews were conducted, followed by a thematic analysis.

Results: This study shows that discussions relating to the end of life are very frequent during respiratory rehabilitation. This high prevalence appears to be influenced both by the context in which respiratory rehabilitation is completed and by the trusting relationship established between the physiotherapist and their patients. Nevertheless, these discussions are merely a draft of advance care planning, which is a broader concept. It appears that a lack of knowledge about advance care planning itself, combined with insufficient training in palliative care among professionals, as well as a lack of rigour in therapeutic education, hinders the implementation of advance care planning.

Conclusion: In spite of the limited training in palliative care and sometimes the imprecise therapeutic education, physiotherapists appear to play an important role in addressing end-of-life issues during respiratory rehabilitation. However, physiotherapists are not the only professionals who should raise these topics. This is especially important in the French healthcare system, where fewer than half of COPD patients have access to rehabilitation with a physiotherapist.

Background: Pulmonary rehabilitation (PR) improves physical status and symptoms in patients with long COVID, but access to specialised hospital-based centres is challenging. This trial studied the effect of primary care PR on functional exercise capacity and symptoms in patients with long COVID.

Methods: In this pragmatic randomised controlled trial (PuRe-COVID), patients with long COVID were randomised to a 12-week stepwise PR programme in primary care, or to a control group without PR. The primary end point was change in 6 min walk distance (6MWD) from baseline to 12 weeks. Additional outcomes, measured at 6, 12, 24 and 36 weeks, included patient-reported outcomes, physical activity, maximal inspiratory (MIP) and expiratory pressures and hand grip strength.

Results: In total, 76 patients were randomised (PR/control group (n=39/37); mean age 49±13 years). The change in 6MWD at 12 weeks was estimated to be +39 m in the PR group compared with the control group (95% CI (18 to 59), p<0.001). Furthermore, a decrease in Checklist Individual Strength (CIS)-fatigue was found for the PR group (-6 points; 95% CI (-10 to -2), p=0.011). At 12 weeks, patients in the intervention group were more likely to have a clinically significant improvement in 6MWD (OR 5.7, 95% CI (2.0 to 16.1), p=0.001), CIS-fatigue (OR 3.8, 95% CI (1.2 to 12.0), p=0.020), MIP (OR 3.7, 95% CI (1.05 to 12.7), p=0.036) and modified Medical Research Council dyspnoea score (OR 5.2, 95% CI (1.6 to 16.4), p=0.003).

Conclusions: Primary care stepwise individual PR may improve functional exercise capacity, fatigue and dyspnoea in patients with long COVID. It therefore may be a promising treatment option in primary care for patients with long COVID experiencing fatigue and/or respiratory symptoms.

Trial registration number: NCT05244044.

Background: Asthma is the most common non-communicable disease among children, with increasing prevalence. The current standard of care in high-income countries in adults and adolescents includes the use of combination inhaled corticosteroids (ICSs) with rapid-onset long-acting ß₂ agonists (LABA) for all severities of asthma. The primary objective of this trial is to assess the efficacy of a budesonide/formoterol inhaler used 'both as required, and regularly' to reduce asthma exacerbations compared with the standard of care for asthma in children and adolescents.

Methods: Children and adolescents aged 6-18 years with a diagnosis of asthma with at least one asthma exacerbation in the previous 12 months will be randomised to receive either budesonide/formoterol inhaler or the standard of care, which includes ICS and short-acting ß₂ agonist (SABA). The primary outcome will be the number of severe asthma exacerbations over 1-year follow-up period. Secondary objectives will include evaluating the quality of life, lung function and health economic outcomes.

Discussion: The current standard of care in South Africa recommends use of separate ICSs and SABA inhalers for asthma management in children with no recommendation for ICS/LABA in children under the age of 12 years for non-severe asthma. Budesonide/formoterol has transformed asthma treatment in high-income countries for use 'as needed' as anti-inflammatory reliever and for maintenance and reliever in adolescence, 12-18 years and adults. This strategy has been shown to reduce asthma exacerbations and hospitalisations. This trial will bridge the gap for the efficacy of budesonide/formoterol in children <12 years of age and address the economic arguments and safety of this approach for implementation in the lower to middle income countries. If this trial demonstrates positive results in the study population, it could provide strong scientific evidence and policy relevance to be adopted by policymakers for clinical implementation.

Trial registration number: This study has been registered and approved by the South African Health Regulatory Authority 20231016, on 14 December 2023, KwaZulu Natal Health Research Committee KZ_202304_008 on 11 January 2024, University of KwaZulu Natal Biomedical Research Ethics Committee BREC/0000/5663/2023 on 6 February 2024, South African Clinical Trials Register DOH-27-032024-4778 on 14 March 2024, ClinicalTrial.gov NCT06429475 on 20 May 2024 and Pan African Clinical Trial Registry on 27 February 2025; the unique identification number for the registry is PACTR202502547023775.

Background: Acute exacerbations profoundly influence asthma prognosis, yet large-scale data linking baseline blood eosinophil counts to both short-term and long-term exacerbation risk remain limited. We therefore examined this association in one of the largest nationwide cohorts.

Methods: Using Taiwan's asthma pay-for-performance database linked to nationwide claims, we conducted a retrospective cohort study of adults with asthma (2015-2020). Baseline peak eosinophil counts defined two groups: high (≥300 cells/µL) and low (<300 cells/µL). Propensity-score matching (1:1) yielded two balanced subcohorts. Multivariable Cox models estimated adjusted HRs (aHRs) for moderate (outpatient, steroid-treated) and severe (Emergency Department visit or hospitalisation) exacerbations within 1 year and over the entire follow-up, controlling for age, sex, Charlson comorbidity score and propensity score.

Results: Among 407 725 and 961 268 asthma patients in the high and low eosinophil groups, respectively, matched subgroups of 50 360 patients each were analysed. The high eosinophil group had higher rates of severe acute exacerbations (SAEs) within 1 year (14.67 vs 10.950 per 100 person-years) with an adjusted HR of 1.392. Similar trends were observed for moderate acute exacerbations (AEs) (HR 1.548) and all AEs (HR 1.373) within 1 year. These associations persisted after adjustment for age, gender, Charlson comorbidity score and propensity score.

Conclusions: In this first nationwide, propensity-matched cohort exceeding 100 000 adults, elevated blood eosinophil counts independently predicted both short-term and long-term moderate-to-severe asthma exacerbations across all age and sex strata. Peak eosinophil measurement thus offers a practical biomarker for early identification of high-risk patients who may benefit from intensified anti-eosinophilic or inhaled corticosteroid/long-acting beta agonist-based strategies.

Aim: This study aims to evaluate the effectiveness of combined artificial intelligence (AI)-based tools for early patient identification, risk stratification and tracking in increasing the follow-up rate of incidentally detected lung nodules, potentially leading to earlier diagnoses of lung cancer, particularly non-small cell lung cancer (NSCLC).

Patients and methods: We conducted a retrospective cohort study involving all patients who underwent CT scans at an academic medical centre over an 8-month period. Real-world practice was compared with modelling of a hypothetical intervention with AI tools. This study was complemented by a multi-reader multi-case analysis to enhance the robustness of our findings.

Results: The implementation of AI tools significantly increased the rates of guideline-concordant follow-up for detected nodules, rising from 34% without the tool to 94% with the AI intervention (p<0.0001, McNemar's test). Furthermore, the median time to diagnosis of NSCLC was reduced from 129 days to 25 days (p<0.001, Wilcoxon signed-rank test).

Conclusion: These findings provide compelling evidence that AI tools can enhance the follow-up rates for patients with incidentally detected lung nodules and expedite the diagnosis of lung cancer. The integration of AI in clinical practice may significantly improve patient outcomes in lung cancer detection and management.

Rationale: COVID-19 pandemic had a significant impact on patients with chronic respiratory diseases (CRD) and was associated with an increased risk of severe outcomes. However, long-term burden of COVID-19 and the dynamics on healthcare utilisation of patients with CRD remain largely unknown.

Objective: The objective was to evaluate outcomes and healthcare utilisation trajectories 1 year after hospitalisation for COVID-19 in patients with CRD.

Methods: Data were extracted from the French National Health Database (SNDS). All adults with CRD who had a first hospitalisation for symptomatic COVID-19 and discharged alive between March 2020 and January 2021 were included. Postdischarge care trajectories, including any hospitalisations and ambulatory care recorded in the SNDS, over a 1-year period, were analysed using state sequence analysis. Healthcare utilisation patterns between the year prior to and the year following hospitalisation were then compared, and a multinomial logistic regression analysis was performed to identify baseline CRD category associated with trajectory clusters.

Results: Among the 40 066 patients with CRD discharged alive, chronic obstructive pulmonary disease was the main CRD followed by asthma, sleep apnoea and interstitial lung disease. Overall, 6913 (17.3%) died at 1 year. Proportion of days alive spent at home without any care decreased from 91.1% to 64.4%. Five distinct clusters of healthcare trajectories were identified: 'home' (52%) with a slight increase in healthcare utilisation, 'home with care' (22%) with a high healthcare utilisation, 'extended hospitalisation' (9.4%) in long-term care or acute care, 'early death' (11%) and 'late death' (5.1%). Asthma was more often associated with the 'home' trajectory, while other CRD categories were more often associated with other clusters.

Conclusion: Patients with CRD hospitalised for COVID-19 had heterogeneous 1-year trajectories, characterised by increased healthcare utilisation and risk of death. Asthma was the only CRD category not associated with excess mortality or high healthcare consumption.

Introduction: There is an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygotes for the alpha-1 antitrypsin (AAT) Z allele (PI*MZ), but there is significant variation in outcomes. Matrix metalloproteinases (MMPs) contribute to worse airway disease and emphysema. Given that the AAT protein is an antiprotease, we hypothesised that MMPs play a modifying role among AAT-deficient individuals.

Methods: We studied PI*MZ (n=39) and PI*ZZ (n=27) individuals from the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study cohort. MMP (MMP3, MMP9, MMP10, MMP12 and MMP15) gene expression was assessed in bronchoalveolar lavage cells and peripheral blood mononuclear cells. Plasma protein MMP (MMP3, MMP9, MMP10 and MMP12) expression was assessed using SomaScan and BAL MMP15 protein using ELISA. MMP values were log-transformed, and linear regression analyses were used to assess lung function, patient-reported outcomes and CT emphysema adjusted for age, body mass index, sex and duration of smoking.

Results: Alveolar MMP3 and MMP15 were uniquely associated with worse lung function, patient-reported outcomes and emphysema among PI*MZ individuals. MMP10 was associated with less disease severity among PI*MZ individuals.

Discussion: Our study shows that alveolar MMP3 and MMP15 may uniquely contribute to disease among PI*MZ individuals, raising the possibility that they could serve as biomarkers or therapeutic targets in this highly prevalent COPD phenotype. Furthermore, we show that MMP10 may serve a protective effect. In aggregate, these data support further studies of the MMP pathway among lung-affected PI*MZ individuals, as they may serve as biomarkers or pharmacological targets in future studies.

Background: Ferroptotic cell death is a highly regulated process characterised by the iron-dependent accumulation of lipid peroxides on cell membranes. However, the role of ferroptosis-related genes (FRGs) in severe influenza is not well characterised.

Methods: Influenza-related gene expression data and FRG lists were, respectively, downloaded from the gene expression omnibus and ferroptosis database. Differentially expressed FRGs (DE-FRGs) were then identified by comparing samples from patients with and without severe influenza, respectively, defined by patients who did and did not require mechanical ventilation. Enrichment analyses of these DE-FRGs were performed, and hub genes were subsequently identified, enabling the establishment of hub gene-drug interaction and competing endogenous RNA (ceRNA) networks.

Results: In total, these analyses revealed 171 DE-FRGs from patients with and without severe influenza. Least absolute shrinkage and selection operator and support vector machine-recursive feature elimination algorithms were used to identify eight hub genes from this dataset (ALOX12, MUC1, stearoyl-CoA desaturase, DECR1, EZH2, toll-like receptor 4 (TLR4), RICTOR and GSTM1), all of which exhibited good diagnostic utility for severe influenza. Functional enrichment analyses indicated that these genes may influence influenza pathogenesis through the regulation of immune and inflammatory responses. Single-sample gene set enrichment analysis approaches indicated that the expression levels for these hub DE-FRGs were negatively correlated with lymphocyte activity, whereas they were positively correlated with inflammatory cell activity. Predictive analyses additionally enabled the identification of 71 drugs targeting five of these genes, while ceRNA network diagrams highlighted the complex regulatory relationships among these genes.

Conclusion: The eight hub FRGs established in this study may play an important role in shaping the pathogenesis of severe influenza in individuals and may offer value as biomarkers that can guide the personalised prevention and treatment of this severe form of disease.