Respirology最新文献

Background and objective: β-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease and diffuse-type emphysema, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive analysis of lung function and mechanics of the adult β-ENaC-Tg model.

Methods: Adult β-ENaC-Tg and wild-type littermates underwent X-ray velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system (SCIREQ, Montreal, Canada).

Results: XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in β-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild types, β-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance, and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity.

Conclusion: This research highlights the utility of XV imaging in evaluating ventilation defects in the β-ENaC-Tg model and provides a comprehensive lung function analysis.

Background and objective: Proactive palliative interventions can improve symptom control and quality of life in individuals with chronic obstructive pulmonary disease (COPD); however, they are often underutilised. This study aimed to develop and validate a prediction model to identify women with COPD in their last year of life to facilitate timely palliative care referrals and interventions.

Methods: Data from 1236 women diagnosed with COPD from the 1921-1926 Australian Longitudinal Study on Women's Health cohort, linked to administrative health records, were analysed. We employed Lasso regression and multivariable logistic regression to select predictors. To assess the predictive performance of the model, we used the area under the receiver operating characteristic (AUROC) curve, calibration plot, and calibration metrics. The Youden index was used to establish the optimal cutoff point for risk classification. The clinical utility of the model was evaluated using decision curve analysis (DCA).

Results: The final model to predict 1-year all-cause mortality included six predictors: smoking status, body mass index, needing regular assistance with daily activities, number of supplied medications, duration of illness, and number of hospital admissions. The model performed well, with AUROC of 0.82 (95% CI: 0.80-0.85) and showed excellent calibration. Using a cutoff of 56.6% predicted risk, the model achieved a sensitivity of 72.3%, specificity of 77.7%, and accuracy of 75.0%. The DCA indicated that the model provided a greater net benefit for clinical decision-making.

Conclusion: Our prediction model for identifying women with COPD who may benefit from palliative care has shown robust predictive performance and can be easily applied, but requires external validation.

Background and objective: We determined the impact of genetic susceptibility and its interaction with smoking and air pollution on the risk of developing lung adenocarcinoma.

Methods: This retrospective case-control study utilised data from Taiwan Precision Medicine Initiative (TPMI) project conducted between June 2019 and November 2022. The study population consisted of lung adenocarcinoma patients and 1:4 age-, gender-, and index year-matched non-lung cancer controls. We analysed polygenic risk scores (PRS), smoking status, as well as PM_2.5 and PM₁₀ exposures.

Results: A total of 681 lung adenocarcinoma patients and 2724 non-lung cancer participants were included. PRS was significantly higher among lung adenocarcinoma patients than controls (p < 0.001). Overall, a higher PRS was associated with a higher risk of lung adenocarcinoma. A high PM_2.5 exposure was associated with a higher risk of lung adenocarcinoma (OR 1.88 [95% CI 1.12-3.14], p = 0.0163) among never-smokers with low genetic risk. Never-smokers with a higher genetic risk were associated with a higher OR for lung adenocarcinoma with the highest OR among Q4 participants with high PM_2.5 exposure (4.97 [95% CI 3.10-7.97], p < 0.001). There was no significant impact of PM_2.5 exposure among individuals with higher genetic risks. Similar phenomena were observed in the PM₁₀ analyses. There were no significant correlations of PRS with risk of lung adenocarcinoma among smokers.

Conclusion: PRS significantly predicted lung adenocarcinoma incident cases in a dose-dependent manner among never-smokers. The PRS effect was not noted in smokers. The results were consistent among participants exposed to different air pollution levels.

Background and objective: While short-term weight changes are known to influence obstructive sleep apnoea (OSA), the impact of body mass index (BMI) changes over the life course has been poorly documented. We examined the association between BMI trajectories from childhood to middle age and adult OSA, 10 years later.

Methods: Five BMI trajectories were previously identified in the population-based cohort Tasmanian Longitudinal Health Study (TAHS), using eight time-point BMI from age 5 to 43 years. The primary outcome was probable OSA at 53 years, defined using STOP-Bang questionnaire, with Berlin and OSA-50 questionnaires used to ensure consistency of findings. Clinically significant diagnosed OSA was defined as self-reported medical diagnosis or mild OSA with symptoms or moderate-to-severe OSA, using type-4 sleep studies. Associations were examined using multivariable logistic regression.

Results: Compared with the average BMI trajectory, the child average-increasing (aOR = 5.28, 95% CI 3.38-8.27) and persistently high trajectories (aOR = 3.73, 2.06-6.74) were associated with increased risk of probable OSA. These associations were consistent when using clinically significant diagnosed OSA (child average-increasing trajectory: aOR = 2.95, 1.30-6.72; high trajectory: aOR = 2.23, 0.82-6.09). Individuals belonging to the low trajectory were less likely than the average trajectory to have OSA. Notably, the child high-decreasing trajectory was not associated with OSA.

Conclusion: Physicians and the public should be aware of the potential risk of OSA in middle-aged adults when BMI is high or continuously increasing from childhood to mid-40s. Obese children who subsequently lose weight were not at higher risk of OSA in middle age-a novel and key finding.

Background and objective: Symptom-based questionnaires and handheld lung function devices are widely used for COPD case finding, but the optimal combination remains unclear. This study aimed to compare the diagnostic accuracy (DA) of various combinations of handheld lung function devices and questionnaires and develop a COPD case-finding strategy.

Methods: This cross-sectional, prospective, observational study enrolled participants aged ≥ 40 years with respiratory symptoms and ≥ 10 smoking pack-years. Participants completed three questionnaires (COPD diagnostic questionnaire [CDQ], lung function questionnaire; COPD Population Screener) and 2 handheld lung function devices (peak flow meter, microspirometer), followed by spirometry to confirm COPD (post-bronchodilation FEV₁/FVC < 0.7). DA is assessed using the area under the ROC curve (AUROC).

Results: Among 224 participants, COPD incidence was 29%. Individually, handheld devices showed significantly higher DA than questionnaires (AUROC 0.678-0.69 for questionnaires vs. 0.807 for peak expiratory flow rate [PEFR] and 0.888 for FEV₁/FEV₆; all pairwise p < 0.05). FEV₁/FEV₆-based combinations outperformed PEFR-based combinations (all n = 224; AUROC 0.897-0.903 vs. 0.810-0.818; p < 0.05). The CDQ and FEV₁/FEV₆ combination reached the highest DA (AUROC 0.903). FEV₁/FEV₆ < 0.76 was the optimal cutoff value. A two-staged strategy (sensitivity/specificity 0.82/0.84) was proposed: low-risk participants (CDQ ≤ 13) need no further testing; middle-risk (CDQ 14-26) should undergo FEV₁/FEV₆; and high-risk (CDQ ≥ 27) and middle-risk with FEV₁/FEV₆ < 0.76 require confirmatory spirometry. This approach would reduce misdiagnoses and save costs and time compared to FEV₁/FEV₆ alone.

Conclusion: FEV₁/FEV₆ and CDQ combination achieves the highest DA. A two-staged, risk-stratified strategy combining CDQ and FEV₁/FEV₆ can be accurate and cost-effective to detect at-risk, undiagnosed COPD subjects. External validation is required.

Background and objective: An imbalanced fat and muscle mass ratio might impact exacerbation of chronic obstructive pulmonary disease (COPD). We investigated the association of visceral fat-to-muscle ratio (VMR) with severe COPD exacerbation requiring hospitalisation.

Methods: This prospective cohort study in COPD patients was performed along with the Xinjiang Multi-Ethnic Cohort study between May 2018 and December 2023. Baseline VMR was calculated from visceral fat area and muscle mass measured by bioelectrical impedance analysis. Numbers of COPD exacerbation hospitalizations were monitored. Associations between various variables and exacerbation were assessed by logistics regression and Zero-inflated Poisson regression analyses.

Results: A total of 631 COPD patients were included, with 186 (29.48%) and 304 (48.18%) severe COPD exacerbation within 1 and 5 years, respectively. Compared with body mass index and other obesity indicators, VMR had stronger associations with severe exacerbation. A higher VMR was associated with increased risks of 1-year and 5-year exacerbation (odds ratio [OR] = 1.34 and 1.44, respectively). The subgroup female and overweight individuals showed a strong association (female OR = 1.89 and 1.99, overweight OR = 1.80 and 1.88, for 1 and 5-year exacerbation, respectively). The number of COPD exacerbation increased by 46% for each one-point VMR increase. These results remained unchanged in the sensitivity analyses after removing underweight patients or smoke influence, as well as in the competing risk analysis when considering other causes for death.

Conclusion: VMR was a risk factors of severe COPD exacerbation. Proactive assessment of VMR might be helpful to guide management of COPD patients.