BMJ Open Respiratory Research最新文献

Introduction: As China is scaling up tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) in its national programmes, the objective of this study was to evaluate the feasibility and performance of 6-month regimen of isoniazid monotherapy (6H) in terms of preventive therapy acceptance, adherence, effectiveness and outcomes in minority areas with a high burden of tuberculosis (TB) and HIV/AIDS.

Method: A prospective observational cohort study was initiated among 461 PLHIV in Butuo County after ruling out active TB (ATB) and followed up for up to 3 years to collect incidence events in real-world settings. TB incidence and protective rates were calculated. The risk factors related to acceptance and adherence were identified using a logistic regression model.

Results: Of the 688 PLHIV screened for TB, 115 (16.72 %) had ATB. Among the 461 participants eligible for 6H, 392 (85.03%) initiated 6H, and 277 (70.67%) completed the therapy. In total, 15 were identified as having ATB during follow-up. The incidence of ATB in the complete group was 0.62/100 person years (95% CI 0.20 to 1.45) as compared with the incomplete group 2.96/100 person years (95% CI 1.36 to 5.63) (p=0.005), and the protective rate of 6H was 79.05%. The protection rate between the complete and incomplete and refusal groups was 69.31%. In total, 142 (36.22%) patients experienced adverse drug reactions during isoniazid preventive therapy. The logistic regression model revealed several factors associated with 6H acceptance: first CD4⁺ T lymphocyte count was between 200 and 350 cells/mm³ (adjusted OR (aOR)=0.30, 95% CI 0.10 to 0.92) or>500 cells/mm³ (aOR=0.25, 95% CI 0.08 to 0.77). Factors associated with 6H adherence: 36-45 years old (aOR=2.76, 95% CI 1.49 to 5.10), middle school education (aOR=0.26, 95% CI 0.08 to 0.79) and history of prior TB (aOR=0.09, 95% CI 0.05 to 0.20).

Conclusion: 6H can reduce the incidence of ATB in minority areas with high burdens of TB and HIV/AIDS. Periodic counselling of patients on adherence and retraining of the TPT staff are essential. Health monitoring and education for specific populations improve TPT acceptance and adherence.

Introduction: We assessed the impact of recruitment criteria on lung cancer detection in a future Danish screening programme with low-dose CT.

Methods: We combined data from two Danish population-based health examination surveys with eligibility criteria from seven randomised controlled trials on lung cancer screening. Incident lung cancers were identified by linkage with the National Pathology Data Bank (Patobank). For an average of 4.4 years of follow-up, we calculated sensitivity, specificity, efficient frontier and number needed to screen (NNS) for lung cancer detection.

Results: When applying the different eligibility criteria to the 48 171 persons invited to the two surveys, the number of lung cancer cases identified in the target groups varied from 46 to 68. The National Lung Screening Trial (NLST) criteria had the highest sensitivity of 62.6% (95% CI 52.7 to 71.8) and the Dutch-Belgian NEderlands-Leuvens Screening ONderzoek (NELSON) criteria had the highest specificity 81.6% (95% CI 81.0 to 82.1). Sensitivity was higher for men than for women (NLST criteria 71.7% (95% CI 57.7 to 83.2) and 53.7% (95% CI 39.6 to 67.4), respectively). The NLST criteria identified the target population obtaining the lowest NNS with 46.3. The application of the NLST criteria showed that the higher the sensitivity, the lower the number of false-negative cases and, thus, the lower the NNS.

Conclusions: This study highlights the impact of the definition of the at-risk population on lung cancer screening efficacy. We found lower sensitivity among women regardless of screening criteria used. This should be carefully addressed in a possible screening programme.

Rationale: Preterm infants diagnosed with bronchopulmonary dysplasia (BPD) are thought to have fewer and larger alveoli than their term peers, but it is unclear to what degree this persists later in life.

Objectives: To investigate to what degree the distal airspaces are enlarged in adolescents born preterm and to evaluate the new Airspace Dimension Assessment (AiDA) method in investigating this group.

Methods: We investigated 41 adolescents between 15 and 17 years of age, of whom 25 were born very preterm (a gestational age <31 weeks, with a mean of 26 weeks) and 16 were term-born controls. Of the preterms, 17 were diagnosed with BPD. The AiDA method was used to measure the average distal airspace radius (r_AiDA) in the lungs. In addition, lung function was evaluated by spirometry, impulse oscillometry and diffusing capacity of carbon monoxide (D_LCO).

Measurements and main results: We observed a mean r_AiDA of 295±53 µm for the preterm group compared with 231±12 µm for the control group (p<0.0001). The adolescents diagnosed with BPD had a mean r_AiDA of 313±54 µm. There was a strong negative correlation between gestational age and distal airspace radius (p<0.0001). The BPD group had a decreased FEV₁ (forced expiratory volume in 1 s, z-score: -1.28±1.37, p=0.012) and D_LCO (z-score: -0.92±1.01, p=0.013) compared with the controls, but all other lung function variables showed normal values.

Conclusions: Our results suggest that the enlarged airspaces seen in preterm infants likely remain in adolescence. Distal airspace radius as measured by AiDA was the lung function variable that showed the most significant difference between preterm and term-born adolescents.

Background and objective: The 2014 Hazelwood coal mine fire exposed residents in nearby Morwell to high concentrations of particulate matter <2.5 µm (PM_2.5) for approximately 6 weeks. This analysis aimed to evaluate the long-term impact on respiratory health.

Methods: Adults from Morwell and the unexposed town of Sale completed validated respiratory questionnaires and performed spirometry, gas transfer and oscillometry 3.5-4 years (round 1) and 7.3-7.8 years (round 2) after the fire. Individual PM_2.5 exposure levels were estimated using chemical transport models mapped onto participant-reported time-location data. Mixed-effects regression models were fitted to analyse associations between PM_2.5 exposure and outcomes, controlling for key confounders.

Results: From 519 (346 exposed) round 1 participants, 329 (217 exposed) participated in round 2. Spirometry and gas transfer in round 2 were mostly lower compared with round 1, excepting forced vital capacity (FVC) (increased) and forced expiratory volume in 1 second (minimal change). The effect of mine fire-related PM_2.5 exposure changed from a negative effect in round 1 to no effect in round 2 for both pre-bronchodilator (p=0.005) and post-bronchodilator FVC (p=0.032). PM_2.5 was not associated with gas transfer in either round. For post-bronchodilator reactance and area under the curve, a negative impact of PM_2.5 in round 1 showed signs of recovery in round 2 (both p<0.001).

Conclusion: In this novel study evaluating long-term respiratory outcomes after medium-duration high concentration PM_2.5 exposure, the attenuated associations between exposure and respiratory function may indicate some recovery in lung function. With increased frequency and severity of landscape fires observed globally, these results inform public health policies and planning.

Background: Metered dose inhalers (MDIs) are important devices for delivering inhaled medications; however, they have an outsized carbon footprint due to their propellant gas. Many short-acting beta-agonist inhalers contain HFA-134a which has a global warming potential >1000 fold higher than carbon dioxide. We aimed to determine the practices around MDI use and disposal within Australia's major lung function testing laboratories and identify the actions that most influence the carbon footprint of bronchodilator responsiveness (BDR) testing.

Methods: Australia's 45 accredited lung function laboratories were invited to participate in an online survey asking about their volume of BDR testing, as well as practices around MDI use such as the number of actuations per BDR test, reuse of MDIs between patients and disposal method. We calculated MDI-associated carbon dioxide equivalent (CO2e) emissions by combining previously published estimates.

Results: 39 laboratories completed the survey. Most laboratories used 4 actuations of salbutamol per BDR test for both adults (27/34, 79.4%) and children (17/20, 85%), but this ranged from 2 to 12. Only three (7.7%) laboratories did not routinely reuse MDIs between patients; however, they all sent their used MDIs for high-temperature incineration. Based on different combinations of observed MDI practices in Australia, we identified a potential sixfold difference in CO2e per 100 BDR tests, from as low as 23.3 kg CO2e up to 166 kg CO2e.

Conclusions: We identified three key practices to reduce the carbon footprint of BDR testing: disposing of MDIs via high-temperature incineration, reducing the number of actuations per BDR test and reusing MDIs between patients.

Introduction: Acute lower respiratory infections (ALRIs) are a major contributor to the global infectious disease burden and a common cause of hospitalisation for children under 2 years. We compared clinical severity in children hospitalised with respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus (hMPV) and influenza virus (IFV).

Methods: We used a probabilistically linked population cohort born in Western Australia between 2010 and 2020 and hospitalised before the age of 2 years. Outcomes compared included length of hospital stay (LOS), admission to intensive care unit (ICU), need for respiratory support (RS), complex hospital course (RS, death, ICU admission or LOS >75th percentile), 7-day and 30-day mortality, hospital-in-the-home care, 30-day all-cause and ALRI-specific readmissions and emergency department presentations 14 days prior to hospitalisation. Logistic regression was used for binary outcomes, and negative binomial regression was used for discrete count variables. Incidence rates, time to RS and time to readmissions were calculated using survival analysis techniques.

Results: The final cohort included 210 997 hospitalised children under 24 months of age for a total of 315 769 admissions. Infants hospitalised before 6 months had the highest rates for all virus-specific hospitalisations, particularly RSV hospitalisations (50.4 per 1000 child-years (95% CI 48.7 to 52.1)). Infants <6 months had higher odds of an ICU admission (adjusted OR (aOR) 2.39, 95% CI 1.36 to 4.19) and RS (aOR 4.68, 95% CI 2.95 to 7.44) and a complex hospital course (aOR 2.69, 95% CI 2.13 to 3.42) with RSV and four times higher hazards of requiring RS earlier (adjusted HR (aHR) 4.06, 95% CI 2.59 to 6.36). An ALRI-coded 30-day readmission was recorded in 10%-24% of virus-specific hospitalisations.

Discussion: Young infants have a more severe and complex hospital course with RSV hospitalisation compared with hospitalisation with other respiratory viruses and should be prioritised for prevention measures such as the single-dose monoclonal antibody, nirsevimab.

Introduction: Biologics provide significant benefits in asthma, reducing exacerbations and symptoms. Some biologics have shown promising results in small subgroups of patients with chronic obstructive pulmonary disease (COPD) and frequent exacerbations. Nevertheless, real-life data on the size of the COPD target population remain scarce.

Methods: We analysed the characteristics of COPD and coexisting asthma and COPD patients included in the prospective multicentre, French COhort of BRonchial obstruction and Asthma, between 2008 and 2023 and evaluated the number of patients who could correspond to the inclusion criteria of randomised controlled trials evaluating various biologics targeting interleukin 33 (IL-33) (-receptor), IL-5 (-receptor), IL-4Rα or TSLP, in routine clinical practice.

Results: Among 434 COPD patients, only 21.7% met inclusion criteria for at least one biologic. Among patients with asthma, 54 (3.5%) had coexisting features of COPD in terms of age, smoking status and airflow obstruction and met inclusion criteria for at least one biologic. Notably, these patients were predominantly female, with worse lung function. Globally, the target chronic airway diseases population of the eagerly awaited biologics remains limited to a small part (ie, 1.3%-8%, depending on the biologic).

Conclusion: In a real-life COPD and asthma population (including asthmatic patients with features of COPD), the proportion of patients satisfying selection criteria applied in randomised controlled trials assessing the efficacy of biologics remains limited to less than 10% of the whole population.

Introduction: The management of a chronic and frequent pathology, such as obstructive sleep apnoea (OSA), requires personalised programmes that implement new technology-based tools to improve the comprehensive treatment of the patient to reduce the morbidity associated with this disease. This study will evaluate the effectiveness of an eHealth tool in managing the pathophysiological consequences of OSA and how they impact the quality of life after 3 months of intervention among adults.

Methods and analysis: This is a mixed-method sequential exploratory study protocol. Participants will be≥18 years with a new diagnosis of moderate OSA and diagnosed with hypertension. The qualitative phase will consist of personal semistructured interviews. The quantitative phase will be a triple-blind randomised controlled trial. The experimental group (n=135) will receive an eHealth intervention using an electronic wrist device and a mobile application that will offer specific healthcare recommendations, physical activity indications and hygienic and dietary advice. These recommendations will be based on the information obtained in the qualitative phase. Those in the control group (n=135) will receive the usual educational materials from the sleep unit. The primary outcome will be blood pressure changes at 3 months. Secondary outcomes are subjective sleep quality, sleep apnoea-related parameters, daytime sleepiness, physical activity, empowerment and motivation for change, quality of life, anthropometry, cost-benefit and adherence.

Ethics and dissemination: Ethical approval for the study has been obtained from the Hospital Universitari Arnau de Vilanova (CEIC-2511). Results will be published in a peer-reviewed journal.

Trial registration number: ClinicalTrials.gov Identifier: NCT05380726.

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder with a high degree of interindividual variability. Gastrointestinal dysfunction is common in patients with COPD and has been proposed to influence the clinical progression of the disease. Using the presence of bile acid(s) (BA) in bronchoalveolar lavage (BAL) fluid as a marker of gastric aspiration, we evaluated the relationships between BAs, clinical outcomes and bacterial lung colonisation.

Methods: We used BAL specimens from a cohort of patients with COPD and healthy controls. BAs were profiled and quantified in BAL supernatants using mass spectrometry. Microbial DNA was extracted from BAL pellets and quantified using quantitative PCR. We profiled the BAL microbiota using an amplicon sequencing approach targeting the V3-V4 region of the 16S rRNA gene.

Results: Detection of BAs in BAL was more likely at the earliest clinical stages of COPD and was independent of the degree of airway obstruction. BAL specimens with BAs demonstrated higher bacterial biomass and lower diversity. Likewise, the odds of recovering bacterial cultures from BAL were higher if BAs were also detected. Detection of BAs in BAL was not associated with either inflammatory markers or clinical outcomes. We also observed different bacterial community types in BAL, which were associated with different clinical groups, levels of inflammatory markers and the degree of airway obstruction.

Conclusion: Detection of BAs in BAL was associated with alterations in the airway bacterial communities. Further studies are needed to evaluate whether BAs in BAL can be used to stratify patients and predict disease progression trajectories.

Background: Limited data exist on the reliability, efficacy and safety of ultrasound-guided transbronchial cryobiopsy for suspicious mediastinal and hilar lesions. This study shares findings from implementing this method and compares the results with those of the standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Methods: Patients undergoing diagnostic bronchoscopy for mediastinal or hilar lesions in four Swiss centres were included. The study aims to assess the diagnostic yield and safety of EBUS-guided cryobiopsy compared with EBUS-TBNA. Tunnelling to the target lesion was performed using an electric needle knife (70.8%), a 19 G- (12.4%) or a 22 G needle (16.8%). Cryobiopsies were obtained with a freezing time of 4-7 s (18.2% with a 1.7 mm probe) or 6-10 s (81.8% with a 1.1 mm probe).

Results: Altogether, 137 patients were enrolled with a median follow-up of 89 days. The overall diagnostic yield was 56.2% for EBUS-TBNA and 91.2% for cryobiopsies (p<0.001). Cryobiopsies increased the diagnostic yield for benign disorders (+28.5%), uncommon tumours (+5.9%) and other metastatic cancer (+0.6%), but not for lung cancer (+0%). For lung cancer (n=27), immunohistochemistry was obtainable in 40.7% of EBUS-TBNA (median of 3 probes [IQR 3 to 3]), significantly lower than cryobiopsy's 88.9% yield (median of 4 probes [IQR 3 to 5]) (p<0.001). Adverse events were found in 23.4% of participants; 10.2% had mild to moderate bleeding, 0.7% had pneumonia, and 0.7% (one) of patients had pneumothorax following pneumomediastinum. No deaths or mediastinum infections were observed.

Conclusion: Cryobiopsy of mediastinal and hilar lesions improves the diagnostic yield compared with EBUS-TBNA while maintaining a favourable safety profile.