BMJ Open Respiratory Research最新文献

Background: Reduced muscle strength and decreased muscle mass (sarcopenia) are known predictors of poor prognosis in chronic obstructive pulmonary disease (COPD). Isolated muscle weakness (dynapenia) or low muscle mass alone (presarcopenia) may also negatively impact outcomes. This study aims to compare the prognostic significance of dynapenia, presarcopenia and sarcopenia.

Methods: This prospective study enrolled patients with spirometry-confirmed COPD at a tertiary medical centre. Participants were categorised into dynapenia, presarcopenia and sarcopenia based on the presence of reduced handgrip strength (<28 kg for men, <18 kg for women) and/or decreased muscle mass (<7.0 kg/m² for men, <5.7 kg/m² for women). Physical performance was assessed using a 6 min walk test and Short Physical Performance Battery (SPPB).

Results: A total of 494 patients were enrolled, comprising 211, 59, 111 and 113 patients in the control, presarcopenia, dynapenia and sarcopenia groups, respectively. Both dynapenia and sarcopenia groups had shorter 6 min walk distances and more SPPB score ≤9 than the control group (348.7 m and 304.4 m vs 420 m, p<0.001; 30% and 44% vs 11%, p=0.036). Patients with presarcopenia and sarcopenia were prone to severe exercise-induced desaturation than the dynapenia and control group (26% and 30% vs 9% and 18%, p=0.001). The 2-year mortality was similar in the control, presarcopenia and dynapenia groups but considerably less than that in the sarcopenia group (6.2% vs 10.2% vs. 9.0% vs. 25.7%, p<0.05). Univariate and multivariate analysis showed that only sarcopenia was associated with an increased risk of mortality (HR: 4.93, 95% CI 2.56 to 9.50, p<0.001; HR: 2.07, 95% CI 1.02 to 4.21, p<0.05).

Conclusions: Aside from sarcopenia, both presarcopenia and dynapenia are not associated with an increased risk of mortality in COPD. However, patients with dynapenia experience significant functional deterioration, while those with presarcopenia present with more severe exercise-induced desaturation. Identifying each phenotype is crucial for the holistic management of COPD.

Rationale: Respiratory tract infections are transmitted in part by infectious aerosol. Developing a greater understanding of how clinical and demographic factors affect aerosol generation could help to identify airborne infection 'superspreaders'.

Objectives: To measure respiratory aerosol from a diverse clinical population, exploring the impact of demographics, physiological factors and disease status.

Methods: We recruited people with chronic lung disease, respiratory infection and healthy volunteers. We sampled aerosol from an enclosed circuit to exclude background non-respiratory aerosol, uniquely enabling bedside measurements of respiratory aerosol generation from an unwell population, while participants performed simple manoeuvres such as speaking and coughing.

Measurements and main results: Across 128 participants, we detected lower aerosol generation among patients with a lung disease during a forced expiratory manoeuvre. This is likely to be related to differences in forced exhalation rather than demographic or clinical status. We observed a 500-fold variation in peak aerosol production when coughing. There was an association between aerosol generation and higher body mass index during coughing, but not with other clinical or demographic factors, and most of the variation remained unexplained.

Conclusions: Our measurement of respiratory aerosol generation from patients with lung disease and infection is comparable with those published previously for healthy subjects. The amount of aerosol generation across the studied population was most closely linked with expiratory flow. While we observed variation in respiratory aerosol generation between participants in a clinical environment, there was no meaningful impact of demographics or respiratory disease on aerosol generation.

Background: Pleural infection remains a significant clinical challenge, requiring hospitalisation, intravenous antibiotics and early chest drain insertion. Medical thoracoscopy (MT), a minimally invasive procedure used electively in the UK for malignant effusions, has demonstrated good outcomes when applied to acute pleural infection in retrospective case series. However, it has not been evaluated as a first-line intervention in the UK in a randomised controlled trial (RCT).

Objectives: The Studying Pleuroscopy in Routine Pleural Infection Treatment (SPIRIT) trial assessed the feasibility of conducting a full-scale RCT comparing MT with chest drain insertion for acute pleural infection within UK National Health Service (NHS) hospitals.

Methods: SPIRIT was an open-label, randomised feasibility trial conducted across seven NHS centres between 2017 and 2019. Adults with suspected pleural infection were prescreened; eligible patients were randomised to either chest drain insertion (control) or MT (performed the same or following day) with 90-day follow-up. The primary outcome was feasibility, assessed through a composite of prescreen, screen and allocation failure rates. Secondary outcomes included inpatient-stay duration, mortality, radiological and microbiological outcomes, second-line interventions, patient-reported outcomes and adverse events.

Results: Of 193 patients prescreened, 181 (93.8%) were excluded due to at least one criterion. Key factors included lack of MT deliverability (49.2%), a not truly infected effusion (45.1%) and contraindications to drainage or study involvement (44.0%). Consequently, the primary feasibility endpoint was not met. All 12 eligible patients were randomised with no attrition. MT lasted 15 min longer than drain insertion, but chest drains remained in situ over 3 days longer (p=0.17) with a longer hospital stay (p=0.57). Radiological improvement, microbiological yield and symptom scores were similar. Adverse events occurred in one control and three MT patients.

Conclusion: A full-scale RCT is not likely to be feasible in an NHS setting on the proposed protocol. Targeted recruitment from centres equipped for emergency MT may enhance feasibility.

Trial registration number: ISRCTN98460319.

Background: Bacterial co-infections may occur in patients with influenza and respiratory syncytial virus (RSV), often leading to high unnecessary antibiotic exposure. Procalcitonin (PCT) may help reduce inappropriate antibiotic prescriptions in viral infections.

Methods: In this retrospective cohort study, data was analysed from 558 influenza A/B and 175 RSV patients (2017-2024). Patients were divided into PCT (antibiotic prescription guided by PCT levels) and control groups (antibiotic prescription based on clinical judgement). Outcomes included antibiotic use, defined daily dose (DDD), duration of antibiotic treatment (DOT) and secondary outcomes (readmissions, ICU admissions, mortality, mechanical ventilation).

Results: At admission, 139 (49.6%) of influenza patients in the control group and 148 (53.2%) in the PCT group received antibiotics (adjusted OR 1.20, 95% CI 0.79 to 1.83, p=0.325), indicating no significant difference compared with the control group. For RSV patients, 45 control patients (41.7%) and 33 PCT patients (49.3%) received antibiotics (adjusted OR 0.98, 95% CI 0.44 to 2.14, p=0.490), also showing no significant difference. For influenza, antibiotics were initiated in 175 control patients (62.7%) and 187 PCT patients (67.3%) (adjusted OR 1.25, 95% CI 0.81 to 1.92, p=0.313) during hospitalisation. For RSV, 62 control patients (57.4%) and 58 PCT patients (71.6%) received antibiotics (adjusted OR 1.30, 95% CI 0.60 to 2.89, p=0.498). No significant differences in DOT or DDD were observed for either group. PCT testing showed no significant impact on secondary outcomes.

Conclusion: In this retrospective design, PCT testing did not significantly reduce antibiotic use or dosage, suggesting limited utility for optimising antibiotic use in influenza and RSV infections.

Introduction: International organisations, scientists and the tuberculosis (TB) community have been advocating for a shorter, safer treatment for drug-susceptible (DS)-TB with equal or better efficacy than current regimens. A promising approach to achieve this is the combination of dose-optimised repurposed drugs.

Methods and analysis: The RML-TB trial is a phase IIb, randomised, non-inferiority, controlled, open-label, multicentre clinical trial. It compares an experimental regimen (optimised-dose rifampicin (R) at 30mg/kg/day, moxifloxacin 600mg/day and linezolid (L) 600 mg/day) with the standard fixed-dose combination regimen of R, isoniazid, pyrazinamide and ethambutol. In the experimental arm, L is administered at 600 mg two times per day for 2 weeks, then once daily for 6 weeks. The primary efficacy outcome is the proportion of patients with negative culture at 8 weeks. Sputum samples will be collected at screening visit, randomisation visit and 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks post randomisation. The primary safety outcome is the incidence of grade 3-4 adverse events or a change in treatment regimen within 8 weeks. Safety assessment will be done using the Common Terminology Criteria for Adverse Events classification version 5. Participants must be at least 18 years old, with smear-positive, DS pulmonary TB. Exclusion criteria include corrected QT interval (QTc) prolongation, HIV positive status, severely impaired blood counts or the use of QTc-prolonging drugs. The study will enrol 120 patients (60 per arm) over a 2.5-year period across 13 TB units in Spain.

Ethics and dissemination: The study was approved by the ethics committee from Vall d'Hebron University Hospital on the meeting held on 18 March 2022 and The Spanish Drug Agency. Patients will provide informed consent and can withdraw from the trial at any time without giving any reason. This decision will not affect their medical care. Data collection is minimal, and analysis will be blinded. Personal data will be restricted to principal investigators or authorised personnel. Results will be shared via the European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT) website and published in an open-source medical journal, guiding future TB clinical trials and treatment development.

Trial registration number: EUDRACT number: 2021-001626-22. CTIS: 2023-509075-17-00.

Background/objectives: Community-acquired pneumonia (CAP) imposes a significant health burden among low- and middle-income countries. The burden is exacerbated by antimicrobial resistance (AMR), often due to inappropriate antibiotic agent use and gaps in antimicrobial stewardship activities. This study aimed to explore physicians' perspectives on the diagnosis, treatment and prevention of CAP in Pakistan, with a focus on how international guidelines are interpreted and adapted to local clinical realities.

Methods: A qualitative study was conducted using semistructured interviews with 33 purposively selected physicians from various specialties, followed by a focus group discussion with 19 of them. Data were analysed through thematic analysis.

Results: Four cross-cutting themes were identified: (1) selective use of diagnostic agents based on severity and access; (2) pragmatic empiric prescribing influenced by resistance trends and antibiotic availability; (3) stewardship intentions constrained by delayed diagnostics and limited infrastructure and (4) underutilisation of preventive strategies including adult vaccinations due to cost and policy gaps. Physicians were aware of Infectious Diseases Society of America/American Thoracic Society guidelines but adapted them to local challenges and AMR concerns.

Conclusions: Most physicians were unaware of the exact prevalence of causative pathogens and their resistance patterns in Pakistan due to the unavailability of robust local data. Consequently, international guidelines were adapted to local challenges including resistance patterns, limited diagnostics and resource constraints. Physicians prioritised beta-lactam antibiotics use and restricted moxifloxacin and azithromycin to mitigate resistance propagation linked to multidrug-resistant tuberculosis and extensively drug-resistant typhoid. Efforts to improve antimicrobial utilisation for CAP in Pakistan need to address implementation barriers and focus on enhancing diagnostic access, vaccine coverage and funding for treatment optimisation.

Background: Asthma morbidity is high among young people, and studies have shown associations between asthma and school attendance and educational attainment. However, findings are unclear concerning associations between air pollution and these educational outcomes, and whether asthma might mediate any associations.

Objective: This review aimed to summarise, and find gaps in, the research on outdoor air pollution, asthma and educational outcomes. To our knowledge, this is the first review to consider the impact of air pollution or asthma, individually or in combination, on the school attendance and educational attainment of children and young people.

Design: This scoping review, using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews method, reports on searches for English language studies of air pollution, asthma and school attendance and educational attainment in eight databases with tabulation and synthesis of the extracted data.

Results: Association between air pollution and school absence was found to be weaker than for active asthma with this outcome. Uncontrolled asthma was associated with lower educational attainment, but findings on air pollution exposure were mixed. Two studies found associations for air pollution with poorer educational outcomes for young people with asthma. Long-term exposure to air pollution, and an increase in the frequency of peaks of air pollution, were associated with worse educational outcomes. Inequalities in access to healthcare and education were associated with uncontrolled asthma and lower educational outcomes. Only one study used linked health, environmental and educational data.

Conclusions: Linked administrative data will be important to enable longitudinal studies of exceptionally large populations to explore asthma exacerbation, baseline and spikes of air pollution and risk factors. Analyses should control for type of educational assessment and specific particulate exposure. Studies should examine temporal changes and a variety of geographical settings to identify even weak associations to inform approaches to address inequalities of public health and education.

Introduction: Pulmonary rehabilitation (PR) is an effective intervention for patients with chronic obstructive pulmonary disease (COPD) but impact typically only lasts 6-12 months. This paper presents results of an economic evaluation of a PR maintenance programme (Self-management Programme of Activity, Coping and Education (SPACE)) undertaken within a prospective assessor-blind randomised controlled trial.

Methods: Adults with COPD who had completed PR within the previous 4 weeks were randomised to SPACE or best usual care. Healthcare use, personal expenditure and societal costs were recorded at baseline, 6 and 12 months. SPACE costs included staff training, materials and delivery of group sessions. Health utility recorded (EQ-5D-5L) with analysis comparing differences in mean values at 6 and 12 months, over baseline utility scores. Observed changes compared with threshold for COPD clinical significance. Incremental cost-effectiveness ratios estimated from National Health Service and societal perspectives. Cost per quality-adjusted life-year (QALY) values compared with willingness-to-pay threshold (≤£30 000). Uncertainties in costs and outcomes incorporated into a sensitivity analysis. Missing values imputed using a Bayesian mixed model with confounders.

Results: 116 patients recruited between October 2019 and June 2022 (57 intervention and 59 control). No significant differences at baseline in age, body mass index, smoking, forced expiratory volume in 1 s and health utility (EQ-5D-5L). Mean healthcare costs in the SPACE group were £139.72 lower per patient over 12 months compared with usual care. At 12 months, the SPACE group retained higher (p=0.04) utility value 0.7609 (SE=0.0238) versus control patients 0.6738 (SE=0.0348). The recorded 0.1178 advantage in mean QALY values (p<0.05) is above the threshold (0.051) for COPD significance. Cost-effectiveness acceptability curves indicate a 97% chance of achieving £20 000 per QALY. Patient and societal costs increase this percentage.

Discussion: This study addresses an important gap in current evidence for non-pharmacological COPD interventions. The PR maintenance programme (SPACE) is shown to be highly cost-effective at 12 months. Future research should consider cost-effectiveness of telerehabilitation programmes, as well as tailored digital support beyond 12 months.

Background: Smoking cessation has proven to be the most effective non-pharmacological intervention to tackle poor outcomes in airway diseases. However, there is limited understanding of teachable/treatable moments (specific times when individuals may be particularly open to behavioural change) to support smoking cessation in patients with asthma or chronic obstructive pulmonary disease (COPD). Therefore, we aimed to investigate which health events could create treatable moments for nicotine dependence in these patients.

Methods: Patients aged ≥18 years, chronically using medication for obstructive lung diseases between 2017 and 2022 and currently smoking tobacco were identified in Belgian nationwide administrative health data. The impact of potential triggering events on evidence-based cessation attempts (reimbursed tobacco counselling or cessation medication) was investigated by multivariable Cox proportional hazard models. Additional analyses stratified by care setting where cessation was attempted (inpatient vs outpatient), restricted to a first attempt, incident triggering events only and stratified by hospital label (no label, asthma or COPD separately) were conducted.

Results: Among 94 788 chronic users of pulmonary medication (mean age 61.6 years, 49% female), 12 499 (13.2%) patients attempted smoking cessation. Severe exacerbations (adjusted HR (aHR) 1.82, 95% CI 1.73 to 1.90), use of antidepressants (aHR 1.70, 95% CI 1.64 to 1.76), smoking-related cancer (aHR 1.42, 95% CI 1.33 to 1.52), peripheral vascular disease (aHR 1.42, 95% CI 1.35 to 1.49), admission to critical care (aHR 1.42, 95% CI 1.35 to 1.49), spirometry testing (aHR 1.33, 95% CI 1.27 to 1.38), acute myocardial infarction (aHR 1.32, 95% CI 1.21 to 1.44) and stroke (aHR 1.28, 95% CI 1.18 to 1.38) were associated with a significantly increased likelihood of smoking cessation attempt by more than 25%. All additional analyses confirmed the main findings.

Conclusions: In this nationwide cohort study, we have identified significant treatable moments for smoking cessation beyond established triggering events (eg, stroke and acute myocardial infarction). Exacerbations and spirometry testing were associated with a significantly increased chance of a smoking cessation attempt.

Background: While simnotrelvir-ritonavir and nirmatrelvir-ritonavir, the oral antiviral agents targeting the 3C-like proteases, are widely used in China, robust data on their appropriate use remain limited in hospitalised patients. We therefore examined the appropriateness of simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in the inpatient setting.

Methods: A retrospective study was conducted to compare the potentially inappropriate use of simnotrelvir-ritonavir and nirmatrelvir-ritonavir in hospitalised patients between 1 July 2023 and 31 December 2023 in Beijing, China. Four factors are taken into consideration when defining and critiquing potentially inappropriate use: indications, dosage and timing of administration, contraindications and drug-drug interactions.

Results: We have identified 278 simnotrelvir-ritonavir and nirmatrelvir-ritonavir prescriptions in 226 hospitalised COVID-19 patients, of which 49.6% (138 prescriptions) satisfied all the criteria for appropriate use. Nirmatrelvir-ritonavir prescriptions were more likely to have potentially inappropriate indications (12.4% vs 3.2%, p=0.006) or dosage and timing of administration (13.1% vs 4.0%, p=0.009) than simnotrelvir-ritonavir prescriptions. Nirmatrelvir-ritonavir was prescribed to two patients in the presence of contraindications (severe renal impairment). No significant differences were identified in drug-drug interactions (DDIs) (p=0.657) and contraindicated DDIs (p=0.670) between simnotrelvir-ritonavir and nirmatrelvir-ritonavir. The most common contraindicated co-medication was estazolam, followed by quetiapine and clopidogrel.

Conclusions: About half of the patients use simnotrelvir-ritonavir and nirmatrelvir-ritonavir that might potentially be inappropriate. More extensive research is required to supplement the empirical evidence supporting COVID-19 therapeutics. Additionally, appropriate therapy requires collaboration with pharmacists and education on the appropriate use of COVID-19 therapeutics among physicians and patients.