BMJ Open Respiratory Research最新文献

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.

Objective: Care guidelines for cystic fibrosis (CF) recommend annual screening for anxiety and depression using standardised measures, the Patient Health Questionnaire (PHQ-9) and the Generalised Anxiety Disorder Scale (GAD-7). Research in other chronic illness groups such as diabetes has demonstrated that illness-specific distress predicts daily functioning above and beyond depression alone. To address the need for a measure of illness-specific distress, we developed and validated the CF Stress Questionnaire (CFSQ), which could serve as a meaningful adjunct to mental health screening.

Methods: We developed a CF-specific measure of perceived stress with multiple phases of input from our patient population. We then conducted a multisite CFSQ validation study with 200 adults with CF across 3 geographically diverse CF centres, to examine the CFSQ's factor structure, internal consistency, convergent validity and test-retest reliability.

Results: Results of item and subscale-level analyses indicate that all but one subscale met the established internal consistency cut-off of >0.6. In terms of convergent validity, the CFSQ and its subscales were moderately to highly correlated with the PHQ-9 (r=0.73 for total score, p<0.05) and the GAD-7 (r=0.66 for total score, p<0.05) and moderately correlated with quality of life as measured by the Cystic Fibrosis Questionnaire Revised (CFQ-R) Social (r=-0.59 for total score, p<0.05) and Treatment Burden subscales (r=-0.63 for total score, p<0.05). Subscales of the CFSQ were moderately correlated with the CFQ-R Emotional or Physical Functioning subscales, and weakly correlated with forced expiratory volume in 1 s per cent predicted or body mass index.

Conclusions: The CFSQ is a valid and reliable measure in terms of internal consistency and convergent validity with existing measures of mental health and quality of life commonly used in CF care and research.

Background: Malignant pleural effusion (MPE) is common, affecting approximately 15% of patients with cancer. Over recent years, there have been significant changes in both the diagnostic and therapeutic strategies for the condition, and recent epidemiological studies have shown improvements in survival across most major cancer types. However, it is currently unclear whether there has been an increase in survival in patients with MPE.

Methods: Medical records of patients diagnosed with MPE between 2015 and 2023 at Oxford University Hospitals were retrospectively reviewed. Patients were split into groups of equal size based on the date of MPE diagnosis and Kaplan-Meier survival analyses were performed. Subgroup analyses were conducted in patients with MPE by causative cancer type, performance status at diagnosis and treatment with systemic anti-cancer therapy. Cox regression analyses were carried out using the individual year of MPE diagnosis as an included variable.

Results: 742 patients with MPE were included. There was no improvement in survival length in patients managed in more recent years. This was consistent across effusions secondary to any primary malignancy; effusion secondary to lung cancer, mesothelioma or breast cancer; in patients with better performance status; and in patients who received systemic anti-cancer therapy.

Conclusions: Despite recent changes in the management of MPE and improving survival trends in cancer overall, survival time following the development of MPE appears to have remained stagnant over the 8-year time period under study. This suggests that MPE should potentially be considered as a discrete clinical entity, necessitating investigation of oncological therapies specifically targeted to the pleural space.

Objective: To examine diagnostic testing patterns for symptoms associated with lung cancer in Australian general practice.

Design: Retrospective cohort study using a linked primary care database.

Setting: Victorian general practices enrolled in the University of Melbourne's primary care data repository, Patron.

Participants: Deidentified patients aged 40 years and over who presented with symptoms associated with lung cancer between 2008 and 2022.

Main outcome measures: The proportion of patients who underwent pathology, imaging or referral or who were prescribed medication; differences across sociodemographic variables and the proportion of patients diagnosed with lung cancer.

Results: Between 33% and 53% of patients underwent no investigations. Among those investigated, blood tests were most common for fatigue (83%) and anorexia (69%), while X-rays were more commonly performed for chest infections (40%) and haemoptysis (38%). Two-thirds of patients with haemoptysis were investigated, but only 22% were referred for a chest CT scan. When medications were prescribed, antimicrobials were often used, particularly for chest infections (79%) and haemoptysis (67%), while beta-2 agonists were primarily prescribed for shortness of breath (46%). Ever-smokers exhibited only marginally higher odds of being investigated (OR 1.05). Patients with higher socioeconomic advantage were 1.39 times more likely to undergo investigation than those with the least advantage (p<0.001). Presenting multiple times increased the odds of testing. Overall, lung cancer was diagnosed in 0.15% of patients, with haemoptysis preceding the highest proportion of cases (23/727; 3.2%).

Conclusion: There is significant variation in diagnostic testing for lung cancer-related symptoms in Australian primary care. Future efforts should focus on optimising testing for high-risk symptoms, rationalising investigations for non-specific symptoms, implementing safety-netting for low-risk but not no-risk symptoms and addressing socioeconomic disparities in testing rates.

Background: Lung cancer with progressive bone metastases usually leads to skeletal-related events (SREs) and a reduced quality of life. Denosumab delays the onset of SREs and is associated with improved overall survival. However, other factors associated with overall survival in patients with lung cancer and bone metastases remain unclear. This study aimed to evaluate the survival benefit of denosumab use in patients with lung cancer and bone metastases and how other factors affect overall survival in these patients.

Methods: This retrospective cohort study included 622 patients with lung cancer treated at a southern Taiwan Medical Center between 2018 and 2022. The overall survival of patients with lung cancer and bone metastases treated with denosumab (n=90) was compared with that of patients who did not receive denosumab (n=212). Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the factors associated with the overall survival of these patients.

Results: Denosumab use was associated with improved overall survival among patients with lung cancer and bone metastases compared with untreated patients (HR 0.61, 95% CI 0.47 to 0.80, p<0.001, overall survival 455 days vs 172 days), particularly in patients who had received more than five cycles of treatment (HR 0.31, 95% CI 0.19 to 0.50, p<0.001). Systemic cancer treatments, such as tyrosine kinase inhibitors, chemotherapy and immunotherapy, were also associated with improved overall survival in these patients.

Conclusions: Denosumab usage, especially good compliance, for over five cycles in patients with lung cancer and bone metastases was associated with improved overall survival. Future studies should focus on strategies to improve adherence to denosumab treatment and maximise its clinical benefits.

Introduction: Evidence is growing for interventions beyond inhaled therapies in chronic obstructive pulmonary disease (COPD). Clinician attitudes and access to these therapies are crucial to informing COPD care pathways.

Aims: We sought to explore current attitudes, practices, future directions and challenges in the management of moderate to severe COPD among respiratory consultants in the Republic of Ireland (ROI).

Methods: A custom online survey was disseminated by email and text messaging to respiratory consultants in the ROI through the Irish Thoracic Society contact list.

Results: 37 responses were received (24.5% response rate), of which 36 were eligible for inclusion. Completion rate was 97.2% (n=35). Only 9 of 30 respondents (30%) reported sufficient access to pulmonary rehabilitation (PR), and 9 of 29 (31%) to a dedicated COPD multidisciplinary team (MDT). 10 of 29 respondents (34%) infrequently or never consider long-term non-invasive ventilation (LTNIV), despite 21 of 27 (78%) rating the quality of evidence for its benefit in reducing hospitalisations as moderate or high. 16 of 27 respondents (59%) infrequently or never consider lung volume reduction (LVR), despite 22 of 25 (88%) perceiving it to be moderately or highly beneficial towards improving quality of life. There was variable uncertainty regarding the evidence for biologics in COPD, with up to 11 of 24 respondents (46%) uncertain about Tezepelumab. Perceived challenges to integrating biologics into COPD care in the ROI included the absence of national drug reimbursement agreements, lack of dedicated COPD MDTs and administrative burden.

Conclusions: Our study highlights insufficient access to PR and COPD MDTs, variable attitudes towards LTNIV and LVR, and uncertainty around the role of biologics in COPD care. While the modest response rate may limit generalisability, our findings underscore the need to address infrastructural and systemic barriers to optimise care pathways for moderate to severe COPD in the ROI.

Background: The prognostic value of respiratory symptom profiles for predicting exacerbation risk and lung function decline remains unclear in mild-to-moderate chronic obstructive pulmonary disease (COPD).

Research question: Are respiratory symptom profiles associated with both exacerbation risk and lung function decline in mild-to-moderate COPD?

Study design and methods: This was a posthoc analysis of data from participants with mild-to-moderate COPD from the SubPopulations and InteRmediate Outcome Measures in COPD Study. Respiratory symptom profiles were identified through latent class analysis. Outcomes included exacerbation rates evaluated by zero-inflated negative binomial regressions, time-to-first exacerbation evaluated by Cox regression and longitudinal forced expiratory volume in 1 second (FEV₁) decline evaluated by linear mixed-effects models.

Results: Among the 954 participants with mild-to-moderate COPD, five distinct respiratory symptom profiles were identified. Compared with the 'minimal respiratory' profile, the 'productive cough' profile was associated with a higher rate of any respiratory exacerbations (relative ratio [RR] 1.84; 95% confidence interval [CI] 1.29 to 2.64) and severe respiratory exacerbations (RR 2.05; 95% CI 1.12 to 3.74). Similarly, the 'Wheeze' profile was associated with higher rates of any (RR 1.55; 95% CI 1.12 to 2.15) and severe exacerbations (RR 1.73; 95% CI 1.00 to 2.98). The 'nearly all respiratory symptoms' profile was associated with a higher rate of exacerbations (any exacerbation: RR 2.12; 95% CI 1.56 to 2.89; severe exacerbations: RR 2.07; 1.23 to 3.47) and an accelerated annual FEV₁ decline (-15.41 mL/year; 95% CI -30.33 to -0.51 mL/year). The 'dry cough' profile exhibited the lowest FEV₁ trajectory despite a non-significant annual decline.

Interpretation: Respiratory symptom profiles identifies distinct prognostic outcomes in mild-to-moderate COPD. The productive cough is associated with increased exacerbation risk, while the dry cough is associated with a lower lung function trajectory.

Trial registration number: NCT0196934.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by repeated exposure to inhaled antigens, leading to small airway and parenchymal inflammation. Diagnosis is based on a detailed clinical history, chest imaging and invasive tests such as bronchoalveolar lavage. Distinguishing HP from other ILDs is challenging. Respiratory oscillometry, a novel pulmonary function test (PFT), is highly sensitive to small airway abnormalities. Oscillometry measurement of reactance is strongly correlated with gender-age-physiology score, a prognostic tool used to predict mortality and disease severity in idiopathic pulmonary fibrosis (IPF).

Objective: To determine if oscillometry and standard PFT patterns are different in HP and IPF.

Methods: 39 HP (79.5% with fibrotic HP) were enrolled from October 2022 to December 2023 for oscillometry before clinically-indicated standard PFTs and compared with 39 age-matched and sex-matched patients with IPF who also had same day oscillometry and standard PFTs. The main oscillometry metrics of interest were R5-19 (the difference in resistance from 5 to 19 Hz, a metric of small airway function and ventilatory inhomogeneity that increases with worsening respiratory mechanics), X5 (reactance at 5 Hz) which primarily reflects respiratory elastance and AX (area of reactance), a summative measure of the respiratory system stiffness across a range of frequencies, that behaves similarly but in opposite direction to X5.

Results: Patients with HP exhibited higher residual volume/total lung capacity (RV/TLC), lower per cent predicted (%) forced expiratory volume in 1 s (FEV₁) and % predicted forced vital capacity (FVC) than IPF (p<0.05) while FEV₁/FVC and %TLC were similar. Oscillometry showed higher R5-19 in HP. RV/TLC ratio correlated with AX (r²=0.72), X5 (r²=0.66) and R5-19 (r²=0.64).

Conclusion: Gas trapping (RV/TLC>0.40) is a feature of HP not observed in IPF. The strong correlations of RV/TLC with AX, X5 and R5-19 suggest that oscillometry can provide non-invasive markers of small airway obstruction in HP that can differentiate it from IPF.