Respirology最新文献

Background and objective: Asthma-COPD overlap (ACO) is characterized by patients exhibiting features of both asthma and COPD. Currently, there is no specific treatment for ACO. This study aimed to investigate the therapeutic potential of targeting CD131, a shared receptor subunit for IL-3, IL-5 and GM-CSF, in ACO development and in preventing acute viral exacerbations.

Methods: A two-hit mouse model of ACO was established by house dust mite (HDM) allergen sensitization to model asthma, and elastase treatment to model emphysema. In a separate model, human rhinovirus 1b (RV1b) was used to induce an acute asthma exacerbation. A neutralizing antibody against CD131 was used to block CD131 in vivo signalling.

Results: Mice exposed to HDM and elastase developed cardinal features for asthma and COPD, including airway hyperreactivity (AHR) and emphysema. A mixed granulocytic inflammatory profile was identified in the lungs, including expansion of monocyte-derived macrophages, neutrophils and eosinophils. RT-qPCR analysis detected heightened gene expression of Mmp12, Il5 and Il13. Transcriptomic analysis further revealed pathway enrichment for type 2 inflammation and macrophage activation. Blockade of CD131 effectively reduced the lung inflammation and prevented the development of AHR, airway fibrosis and emphysema. Interestingly, pathway enrichment for Th1 response and interferon production detected in the model was not affected by the treatment. Consistently, CD131 antagonism prevented RV1b-induced asthma exacerbation without compromising RV1b clearance.

Conclusion: CD131 signalling coordinates multiple pathological pathways that drive airway inflammation and lung remodelling in ACO. Hence, CD131 antagonism represents a novel approach to combating the immunopathology in the complex ACO setting.

Background: Some individuals never achieve normal peak FEV₁ in early adulthood. It is unknown if this is due to airflow limitation and/or lung restriction.

Methods: To investigate this, we: (1) looked forward in 19,791 participants in the Dutch Lifelines general population cohort aged 25-35 years with 5-year follow-up; and (2) looked backwards in 2032 participants in the Swedish BAMSE birth cohort with spirometry at 24 years of age but also at 16 and/or 8 years.

Results: (1) In Lifelines 8.5% of participants had reduced FEV₁ at 25-35 years, 68% due to Preserved Ratio Impaired Spirometry ('PRISm') and 32% to airflow limitation ('low-limited'); besides, 3.8% participants with normal FEV₁ showed airflow-limitation ('normal-limited'). Low-limited and normal-limited, but not PRISm, reported higher smoking exposures and asthma diagnosis than normal (p < 0.05). At 5-year follow-up, 91.2% of participants remained in the same group, and FEV₁ decline was similar in normal and normal-limited participants, but statistically smaller (p < 0.05) in PRISm and low-limited; (2) these observations were largely reproduced in BAMSE at 24 years of age; and, (3) in BAMSE, low-limited or PRISm individuals were already identifiable at 8-16 years of age.

Conclusion: Low peak FEV₁ in early adulthood is most often due to PRISm and results in a significant burden of respiratory symptoms. Only low-limited and normal-limited, but not PRISm, associate with a doctor diagnosis of asthma, and FEV₁ decline was statistically different in PRISm indicating a need for differentiated clinical approaches. These spirometric abnormalities can be already identified in childhood and adolescence.

Background and objective: There is no strong evidence on the optimal duration of pulmonary rehabilitation (PR) programmes. The aim of the study was to determine whether an 8-week PR programme was equivalent to a 12-week PR programme in improving endurance exercise capacity in people with chronic obstructive pulmonary disease (COPD).

Methods: Participants with COPD were randomized to either an 8-week (8-wk Group) or 12-week (12-wk Group), twice weekly, supervised PR programme consisting of endurance and strength training and individualized self-management education. Between group comparisons were made at completion of each programme (i.e., week 8 or week 12), for both programmes at week 12, and at 6-12-month follow-up. The primary outcome was endurance exercise capacity measured by the endurance shuttle walk test (ESWT) with the minimally important difference of 186 s set as the equivalence limit.

Results: Sixty-six participants [mean (SD); age 69 (7) years, FEV₁ 48 (17) %predicted] were randomized (33 per group). Between-group comparisons demonstrated that the ESWT time was equivalent for the 12-wk Group compared to the 8-wk Group at programme completion [mean (95% CI)] [71 s (-61 to 203)], week 12 [70 s (-68 to 208)], and 6-12-month follow-up [93 s (-52 to 239)], though superiority of the 12-wk Group could not be ruled out at each time point.

Conclusion: Equivalence was shown between 8-and 12-week PR programmes for endurance exercise capacity, but superiority could not be ruled out for the 12-wk Group. Decisions about programme duration may depend on local waitlist times, healthcare budgets and patient preference.

Background and objective: Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours.

Methods: The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated.

Results: This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period.

Conclusion: Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs.