Dataset Information

The complex relationship between inflammation and lung function in severe asthma.

ABSTRACT: Asthma is a common respiratory disease affecting ?300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness (AHR) remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we used the T-helper (T(H))-17 cells adoptive transfer mouse model of asthma to induce pulmonary inflammation, which was lessened by tumor necrosis factor (TNF)-? neutralization or neutrophil depletion. Although decreased airspace inflammation following TNF? neutralization and neutrophil depletion rescued lung compliance, neither intervention improved AHR to methacholine, and tissue inflammation remained elevated when compared with control. Further, sputum samples were collected and analyzed from 41 severe asthmatics. In severe asthmatics with elevated levels of sputum neutrophils, but low levels of eosinophils, increased inflammatory markers did not correlate with worsened lung function. This subset of asthmatics also had significantly higher levels of T(H)17-related cytokines in their sputum compared with severe asthmatics with other inflammatory phenotypes. Overall, this work suggests that lung compliance may be linked with cellular inflammation in the airspace, whereas T-cell-driven AHR may be associated with tissue inflammation and other pulmonary factors.

SUBMITTER: Manni ML

PROVIDER: S-EPMC4138304 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The complex relationship between inflammation and lung function in severe asthma.

Manni M L ML Trudeau J B JB Scheller E V EV Mandalapu S S Elloso M M MM Kolls J K JK Wenzel S E SE Alcorn J F JF

Mucosal immunology 20140219 5

Asthma is a common respiratory disease affecting ∼300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness (AHR) remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we used the T-helper (T(H))-17 cells adoptive transfer mouse model o ...[more]

PMID: 24549277

Similar Datasets

Project description:Background:Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200?mg or 300?mg every 2?weeks reduced exacerbations and improved forced expiratory volume in 1?s (FEV1) and quality of life over 52?weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods:Patients were randomised to 52?weeks of subcutaneous dupilumab 200?mg every 2 weeks, 300?mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ?150?eosinophils·µL-1, ?300?eosinophils·µL-1, ?25?ppb fractional exhaled nitric oxide (F eNO), and both ?150?eosinophils·µL-1 and ?25?ppb F eNO, at baseline. Results:Dupilumab treatment (200?mg and 300?mg every 2?weeks) resulted in significant improvements versus placebo after 52?weeks in pre-bronchodilator FEV1 (0.20 and 0.13?L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13?L, respectively), forced vital capacity (FVC) (0.20 and 0.14?L, respectively), forced expiratory flow (0.19 and 0.13?L·s-1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4-52) was significant (0.04?L·year-1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or F eNO levels for most outcomes. Conclusions:Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

Dataset Information

The complex relationship between inflammation and lung function in severe asthma.

Publications

The complex relationship between inflammation and lung function in severe asthma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets