BMJ Open Respiratory Research最新文献

Background: The 2023 Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations advocate long-acting beta₂ agonist (LABA) and long-acting muscarinic antagonist (LAMA) combinations (LABA-LAMA) for the initial pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD) with multiple exacerbations. However, this choice, rather than combinations of LABA and inhaled corticosteroids (LABA-ICS), no longer recommended in GOLD, was based on randomised trials that excluded patients with multiple prior exacerbations.

Research question: What is the comparative effectiveness of initiating COPD treatment with LABA-ICS versus LABA-LAMA inhalers, particularly in patients with multiple COPD exacerbations, in a real-world clinical practice setting?

Study design and methods: We identified a cohort of patients with COPD, 40 years of age or older, from the United Kingdom's Clinical Practice Research Datalink. Treatment-naïve initiators of single-inhaler LABA-ICS or LABA-LAMA, with no prior asthma, LABA, LAMA or ICS use, were compared on the incidence of moderate or severe COPD exacerbation over 1 year, after adjustment by propensity score weighting.

Results: The study cohort included 20 750 initiators of LABA-ICS inhalers and 16 594 of LABA-LAMA. The overall adjusted HR of a first moderate or severe exacerbation with LABA-ICS relative to LABA-LAMA was 1.03 (95% CI 0.98 to 1.08). Among patients with two or more prior exacerbations, the HR of exacerbation with LABA-ICS versus LABA-LAMA was 0.89 (95% CI 0.81 to 0.97), while it was 1.07 (95% CI 1.00 to 1.15) among patients with no prior exacerbations. The HR was 0.92 (95% CI 0.86 to 0.99) among those with forced expiratory volume in 1 s (FEV₁)≥50% predicted.

Interpretation: In a real-world clinical practice setting of COPD treatment, initiating therapy with LABA-ICS inhalers may be more effective than LABA-LAMA inhalers among patients with multiple exacerbations, particularly those with FEV₁≥50% predicted, but less effective among those with no prior exacerbations and FEV₁<50% predicted. This study supports a targeted approach to initial therapy for COPD. .

Introduction: Despite the identification of multiple susceptibility loci by genome-wide association studies (GWAS), considerable chronic obstructive pulmonary disease (COPD) heritability remains unexplained.

Aim: To identify interaction networks of airway epithelial cell DNA methylation in COPD and further explore potential correlations with airway bacterial composition, as potentially collective regulators of biological pathways influencing COPD severity.

Methods: Using DNA isolated from bronchial airway brushings of 67 ever-smokers (>20 pack-years) from the SubPopulations and InteRmediate Outcomes Measures in COPD Study (SPIROMICS), we assessed proportion of DNA methylation (β) by epigenome-wide association study (EWAS) and examined associations of differentially methylated CpG probes (DMPs) with risk for moderate-to-severe COPD (N=34) versus absent or mild COPD (N=33). We tested co-methylation modules generated by Weighted Correlation Network Analyses (WGCNA) for associations with moderate-to-severe COPD and with bacterial genus-level relative abundances (16S rRNA sequencing).

Results: EWAS-identified nominally significant DMPs enriched for lung function GWAS loci. Eigengenes in six WGCNA modules were associated with moderate-to-severe COPD (false discovery rate <0.05). Four of those modules were enriched for forced expiratory volume in 1 s/forced vital capacity GWAS loci, and five overlapped with DMPs from EWAS. Overlapping CpG loci in three COPD-associated modules were adjacent to mucin genes; one had 10 genes highly ranked by connectivity with MUC5B, including important pathway genes: B3GNT6, DGKI and ITGA8. CpGs in an independent COPD-associated module showed the most correlations with Rothia, with directionality suggestive of negative associations with moderate-severe COPD.

Conclusions: Bronchial epithelial DNA methylation modules enriched for lung function GWAS loci associate with COPD severity in SPIROMICS. Potential module relationships to bronchial bacterial composition require further validation.

Background: High-flow nasal therapy (HFNT) is a widely used non-invasive respiratory support technique, but data on its clinical application remain limited. This study aimed to assess clinicians' self-reported practices, perceptions and barriers regarding HFNT use in acute and chronic respiratory failure.

Methods: A cross-sectional web-based survey was disseminated among members of the European Respiratory Society's respiratory intensive care, rehabilitation and chronic care, and allied respiratory professionals assemblies from September to November 2023. Descriptive analysis was performed, with results presented as frequencies and percentages.

Results: A total of 1176 clinicians from 104 countries participated, primarily pulmonologists (78.3%) and respiratory therapists (9.7%). HFNT was most commonly used for de novo acute respiratory failure (56.2%) and interstitial lung disease exacerbations (56.3%), with lower utilisation for chronic obstructive pulmonary disease with hypercapnia (47.4%) and trauma/atelectasis (41.5%). Despite guideline recommendations, 67% of respondents initiated HFNT only after conventional oxygen therapy failure. HFNT was also frequently used for symptom relief in palliative care, despite limited supporting evidence. Respiratory distress was the primary clinical trigger for HFNT initiation, while the ROX (Respiratory Rate-Oxygenation) index was rarely used to guide escalation of care (32%). Barriers to HFNT adoption included equipment costs (23%), lack of funding (22%) and limited clinician knowledge (18%). HFNT use increased during the COVID-19 pandemic (84%), but long-term application for chronic respiratory failure remained rare (16%).

Conclusions: This survey highlights significant variability in HFNT practices and a disconnect between guidelines and real-world implementation. Addressing financial and educational barriers may improve adherence to evidence-based recommendations.

Introduction: Effective management of chronic breathlessness requires understanding people's activity limitations. This study evaluated the extent to which chronic breathlessness limits people's self-reported everyday activities.

Methods: A web-based, cross-sectional survey (adults ≥18 years). Recruitment was through a marketing research company, stratified to the 2016 Australian Census for key demographics (age, sex, state/territory of residence, rurality). Self-reported measures included demographics, breathlessness limiting exertion (modified Medical Research Council (mMRC) breathlessness scale) and breathlessness impact (yes/no question; three most important activities affected). Impact was categorised as performing with difficulty/reduced/ceased.

Results: 7300 respondents were included (mean age 46.5 (SD 18.6); men 50.8%; mMRC ≥1 290.0%). 30.6% (648/2119) with mMRC ≥1 versus 2.6% (136/5181; p<0.001) with mMRC 0 reported activities affected; the proportions increased for each mMRC level.2342 activities were nominated with the most frequent being: high intensity sport, household chores and mobility. The order changed for mMRC 2 (household chores>high intensity sports>mobility) and mMRC 3-4 (mobility>household chores>high intensity sports). Breathlessness increased the likelihood of activities being reduced or ceased.In a logistic regression model exploring the WHO Disability Assessment Schedule, controlling for baseline factors, most affected domains were getting along (OR 2.5 (95% CI 1.5 to 4.2)), life activities (OR 1.8 (95% CI 1.2 to 2.7)) and participation (OR 6.4 (95% CI 4.2 to 9.9)).

Conclusion: Chronic breathlessness of every intensity above mMRC 0 affects people's ability to perform a range of everyday activities. The progressive loss of these activities is a key coping mechanism to avoid precipitating breathlessness and is mostly invisible to other people.

Background: Air pollution exacerbates chronic obstructive pulmonary disease (COPD), increasing hospitalisation and exacerbation rates. While inhaled therapy is a cornerstone of COPD management, pressurised metered-dose inhalers (pMDIs) significantly contribute to greenhouse gas (GHG) emissions. This study evaluates the interplay between air pollution exposure, inhaled therapy selection and COPD exacerbations to identify strategies that optimise clinical outcomes while reducing environmental impact.

Methods: A retrospective observational cohort study was conducted using COPD patient records (ICD-10: J44.0, J44.1, J44.8, J44.9) from the National Taiwan University Hospital Yunlin Branch (2016-2024). Patient visits, including outpatient, emergency and inpatient admissions, were analysed alongside air pollution data (PM_2.5, PM₁₀, NO₂, O₃, CO) from the Environmental Protection Administration. Regression models assessed the impact of inhaled therapies, short-acting β₂-agonists (SABAs), long-acting β₂-agonists (LABAs), long-acting muscarinic antagonists (LAMAs) and triple therapy (ICS/LABA/LAMA), on exacerbation rates and inhaler-associated carbon emissions.

Results: Higher PM_2.5 levels correlated with a 0.97% increase in COPD exacerbation rates (B=0.0291, p=0.0001). Triple therapy was significantly associated with reduced exacerbations (B=-0.0035, p=0.0003), whereas higher SABA use was associated with markers of poorer COPD control (B=7.145, p<0.001). The uptake of non-pMDIs, such as dry powder inhalers and soft mist inhalers, rose in 2020-2021 as hospitalisations declined. In 2022-2024, pMDI use and estimated emissions increased, while emergency room (ER) visits were unchanged and hospitalisations declined modestly. A 42% increase in non-pMDI prescriptions in 2020-2021 was associated with a decline in hospitalisations and emissions. However, a subsequent shift back to pMDIs in 2022-2024 coincided with an increase in exacerbations and increased carbon footprint.

Conclusion: In this single-centre retrospective study, higher ambient PM_2.5 was associated with higher COPD acute exacerbation (AE) rates, and greater use of triple therapy correlated with lower hospitalisations. Our inhaler carbon-footprint estimates quantify GHG differences between device types but were not linked to AE and should inform sustainability discussions rather than clinical effectiveness.

Introduction: Non-necrotising granulomas are the histological hallmark of sarcoidosis and chronic beryllium disease (CBD). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), transbronchial lung forceps biopsy (TBLB) and endobronchial biopsy (EBB) are often used as standard methods for obtaining suitable tissue. Transbronchial lung cryobiopsy (TBLC) is a novel biopsy technique well studied in different fibrosing lung diseases; however, data on its use in sarcoidosis are scarce. This study aimed to assess whether TBLC provides additional diagnostic value compared with standard diagnostic methods in detecting non-necrotising granulomas.

Methods: We retrospectively analysed 321 patients diagnosed with sarcoidosis or CBD between 2010 and 2020 in a single tertiary care centre. Patients who underwent intrathoracic biopsy were analysed to assess the diagnostic yield, factors influencing diagnostic success, as well as complications related to each technique.

Results: Intrathoracic biopsy procedures were performed on 264 patients (EBUS-TBNA n=215, EBB n=61, TBLB n=120 and TBLC n=66). The diagnostic yields for single methods ranged from 56.3% (EBB) to 63.6% (TBLC) (p=0.7643). Combination of EBUS-TBNA with TBLC increased the diagnostic yield to 91.7%. Notably, TBLC provided a superior diagnostic yield compared with TBB in cases without radiologically detected parenchymal involvement. Complication rates were numerically higher following TBLC compared with TBLB (16.7% vs 9.2%, p=0.1561).

Conclusions: The addition of TBLC significantly enhances the diagnostic yield in the workup of sarcoidosis and CBD, particularly in cases without radiologically detected parenchymal involvement. This underscores the added value of TBLC in improving diagnostic accuracy in challenging clinical scenarios.

Background: The Quit Smoking Lung Health Intervention Trials (QuLIT-1 and -2), and other studies, show that providing immediate smoking cessation support within lung cancer screening services substantially improves quit rates. However, in the QuLIT2 trial, only around half of those offered smoking cessation support actually accepted it. Understanding what underpins this and how to facilitate higher engagement would enhance the health impact of the Targeted Lung Health Check programme.

Method: We compared characteristics of participants in the intervention arm of the QuLIT-2 study who accepted or declined the offer of smoking cessation support and conducted thematic analysis of interviews with 15 smokers who had declined it.

Results: Of 152 study participants randomised to smoking cessation support (61.3±4.8 years, 42% female), 80 declined the offer and 15 dropped out after the initial session, leaving 57 'accepters'. Accepters were more likely to be female (53% vs 40% adjusted OR (AOR): 3.30, 95% CI 1.47 to 7.48), younger (AOR: 0.90 (0.80 to 0.98)) and were more likely to live in areas of medium or low deprivation (AOR: 5.30 (1.86 to 22.85)). Thematic analysis of the interviews revealed four main barriers to acceptance: (1) mental health as a barrier, (2) personal beliefs about quitting smoking, (3) perceived usefulness of the interventions offered and (4) past negative experiences of smoking cessation support.

Discussion: Cessation services embedded in lung screening programmes need to anticipate barriers such as mental health concerns, past unsuccessful quit attempts experiences and personal beliefs. Efforts should be made to design and offer equitable services that meet the needs of this population.

Trial registration number: ISRCTN12455871.

Objective: To describe the process of interpreting chest movement videos for respiratory rate (RR) assessment in children aged 0-59 months with suspected non-severe pneumonia by a video expert panel (VEP) and to evaluate the panel's performance.

Methods: Six physicians trained and standardised to RR assessment from recorded videos formed a VEP. The panel interpreted RR from recorded videos collected from health facilities in Bangladesh. The videos were distributed using a web-based system among the panel members. Each member was evaluated by assessing inter-reader agreement among the primary readers, each reader's agreement with the final panel reading and intrareader agreement using per cent agreement. Agreement was defined as the video being interpretable and the difference in RR count between two readers being ≤2 breaths per minute. The panel's performance was evaluated using Bland-Altman analysis against a panel of paediatricians who reviewed a randomly selected 10% subset of videos.

Results: Among the 605 videos, the VEP classified 89.9% (n=544) of them as interpretable with RR count difference ≤2 breaths per minute, 2.0% (n=12) as interpretable with RR count difference >2 breaths per minute and 8.1% (n=49) as uninterpretable. For the video interpretability, inter-reader agreement among primary readers ranged from 88% to 95%, each reader's agreement with the final panel was 90%-95%, and intrareader agreement was 98%-100%. For the RR measurement, five out of six VEP members demonstrated satisfactory inter-reader agreement (80%-83%), agreement with final panel reading (92%-97%) and intrareader agreement (92%-100%). One outlier reader showed lower agreement levels of 55%, 61% and 75%, respectively. The mean difference in RR counts between the VEP and paediatrician panel was -0.3 breaths per minute, and limits of agreement were -3.0-2.3 breaths per minute.

Conclusion: The performance of VEP was satisfactory for evaluating RR counting. The study provided valuable insights into the development and evaluation of the VEP as a potential reference standard.

Introduction: People living with chronic diseases can provide a unique perspective for research that often differs from that of healthcare professionals. This is particularly important in rare diseases like primary ciliary dyskinesia (PCD), with many knowledge gaps and limited research resources. We aimed to assess participation of patients and caregivers in PCD research and identify their research priorities in a mixed-method study.

Methods: We conducted in-depth, semistructured interviews with adults and adolescents with PCD, and caregivers of children with PCD. After verbatim transcription and thematic analysis, we developed an anonymous online survey, translated it into eight languages and circulated it widely in collaboration with PCD support groups worldwide and the European Lung Foundation.

Results: The findings from the interviews identified key areas to be explored further through the survey including: developing treatments for PCD and increasing knowledge about different topics such as mental health, fertility, upper airway problems, treatment burden and impact of environment and lifestyle. 399 participants completed the online survey from 29 countries with median age 41 (IQR 33-49), 74% were female. 180 participants (45%) had participated in research before. For the remaining, the main reason for no participation was not being informed about studies (65%). 172 (43%) preferred regular research updates during a study. The top three ranked research priorities were (1) finding a cure to restore ciliary function; (2) developing treatments to improve lung function and reduce infections and mucus production; (3) finding the best way to manage the disease using existing medication. Other priorities were: involving more doctors and people with PCD in research, raising awareness of the condition and increasing knowledge about mental health and fertility.

Conclusion: We found that people with PCD are motivated to participate in research when they are informed appropriately and invited. Their main research priorities relate to developing new treatments or improving the evidence base for existing treatments. Our findings will help the PCD research community to improve patient engagement in research and to draw common priorities together with the people who live with PCD and their families.

Background: Asthma remains a significant public health challenge worldwide, with high prevalence of uncontrolled cases in low- and middle-income countries. In Somaliland, evidence regarding the role of patient knowledge and attitude in asthma self-management is limited.

Objective: This study aimed to assess the influence of knowledge and attitude on asthma self-management and control among adult patients in Burao, Somaliland.

Methods: A facility-based cross-sectional study was conducted from May to June 2025 in four hospitals in Burao. A total of 363 adult asthma patients were selected using systematic random sampling. Data were collected through structured interviewer-administered questionnaires assessing sociodemographic, behavioural and clinical characteristics, asthma knowledge and attitude. Asthma control was evaluated using the asthma control test. Binary and multivariable logistic regression analyses were performed, and adjusted ORs (AORs) with 95% CIs were reported.

Results: Of the 363 participants, 209 (57.6%) had uncontrolled asthma. Patients with good knowledge were significantly less likely to have uncontrolled asthma compared with those with poor knowledge (AOR=0.60, 95% CI 0.37 to 0.97, p=0.036). Attitude did not show a significant association with asthma control (AOR=1.00, 95% CI 0.62 to 1.62, p=0.985). Regular medical follow-up reduced the odds of uncontrolled asthma by 59% (AOR=0.41, 95% CI 0.25 to 0.66, p<0.001). Asthma severity strongly predicted uncontrolled asthma, with moderate (AOR=11.30, 95% CI 5.31 to 24.03) and severe cases (AOR=7.34, 95% CI 2.42 to 22.30) showing much higher odds compared with mild cases.

Conclusion: Knowledge and regular medical follow-up are key determinants of asthma control, while disease severity substantially increases the risk of uncontrolled asthma. Interventions focusing on patient education, adherence to follow-up and tailored management for severe cases are essential to reduce the burden of uncontrolled asthma in Somaliland.