Inflammation-induced loss of CFTR-expressing airway ionocytes in non-eosinophilic asthma.

Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non-eosinophilic asthma. Non-eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non-eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non-eosinophilic asthma. Patient-derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air-liquid interface. Single cell RNA-sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma. We identified that hBECs from patients with non-eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR-expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic-dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma-like inflammatory cytokine mixture led to a reduction in ionocytes. Inflammation-induced loss of CFTR-expressing ionocytes in airway cells from non-eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target.

被引量：- 发表：1970

Coronary artery calcification detected on low-dose computed tomography in high-risk participants of an Australian lung cancer screening program: A prospective observational study.

被引量：- 发表：1970

World Lung Day 2024-Clean air and healthy lungs for all.

被引量：- 发表：1970

Addressing tuberculosis and mental health amidst the Sudan conflict.

被引量：- 发表：1970

Effect of pulmonary rehabilitation duration on exercise capacity and health-related quality of life in people with chronic obstructive pulmonary disease (PuRe Duration Trial): A randomized controlled equivalence trial.

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). 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. 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. 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.

被引量：- 发表：1970