Dataset Information

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

ABSTRACT:

Background

People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls.

Methods

Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511).

Results

Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response.

Conclusion

Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists.

SUBMITTER: Moore LE

PROVIDER: S-EPMC10351735 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

Moore Linn E LE Brotto Andrew R AR Fuhr Desi P DP Rosychuk Rhonda J RJ Wong Eric E Bhutani Mohit M Stickland Michael K MK

PloS one 20230717 7

<h4>Background</h4>People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls.<h4>Methods</h4>Twenty-six people with asthma and 25 controls underwent t ...[more]

PMID: 37459335

Similar Datasets

Project description:ImportanceAsthma is one of the most burdensome chronic illnesses in the US. Despite widespread dissemination of evidence-based guidelines, more than half of the adults with asthma have uncontrolled symptoms.ObjectiveTo examine the efficacy of an online tool designed to improve asthma control.Design12-month single blind randomized controlled trial of the online tool (Intervention condition, IC) versus an active control tool (CC).SettingPatients enrolled in an insurance plan.ParticipantsParticipants were 408 adults (21-60 years of age) with persistent asthma.InterventionAt least once each month and before provider visits, participants in the IC answered questions online about their asthma symptoms, asthma medications and asthma care received from providers, such as an asthma management plan. The tool then provided tailored feedback to remind patients 1) to ask health care providers specific questions that may improve asthma control (e.g., additional controller medications) and 2) to consistently perform specific self-care behaviors (e.g., proper inhaler technique). Participants in the CC received similar questions and feedback, yet focused instead on preventive services unrelated to asthma control (e.g., cancer screening).Main outcome measuresThe main outcome measure was asthma control, as assessed by the 5-question Asthma Control Test (ACT). Secondary outcomes included quality of life, medication use and healthcare utilization (e.g., emergency department visits).ResultsAfter 12 months, 323 participants completed follow-up measures (79.2%). Participants in the IC reported a greater mean improvement in the ACT score than participants in the CC (2.3 vs. 1.2; p = 0.02) and 9 of 11 individual asthma control survey items showed non-significant improvements favoring the IC. No differences were observed in medication adherence, number of asthma controller medications or health care utilization.Conclusion and relevanceSimple and brief online patient reminders improved asthma control among insured patients. Although future studies are needed to understand the mechanism of the improvement, the magnitude of the effect on asthma control was similar to the addition of an additional controller medication. Given the widespread use of the Internet, simple tools such as this may be useful for improving the control of other chronic diseases as well.Trial registrationThis study is registered at clinicaltrials.gov, NCT00921401, "Improving the Quality of Asthma Care Using the Internet".

Project description:BackgroundThe anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate-to-severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.ObjectiveTo report safety and efficacy results from enrolled participants with available data from CLAVIER.MethodsWe performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm2 of basement membrane (cells/mm2 ). Pre-specified secondary and exploratory outcomes included change in IL-13-associated biomarkers and measures of airway remodelling.ResultsThere was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm2 in response to lebrikizumab (95% CI, -82.5%, 97.5%). As previously observed, FEV1 increased after lebrikizumab treatment. Moreover, subepithelial collagen thickness decreased 21.5% after lebrikizumab treatment (95% CI, -32.9%, -10.2%), and fractional exhaled nitric oxide, CCL26 and SERPINB2 mRNA expression in bronchial tissues also reduced. Lebrikizumab was well tolerated, with a safety profile consistent with other lebrikizumab asthma studies.Conclusions & clinical relevanceWe did not observe reduced tissue eosinophil numbers in association with lebrikizumab treatment. However, in pre-specified exploratory analyses, lebrikizumab treatment was associated with reduced degree of subepithelial fibrosis, a feature of airway remodelling, as well as improved lung function and reduced key pharmacodynamic biomarkers in bronchial tissues. These results reinforce the importance of IL-13 in airway pathobiology and suggest that neutralization of IL-13 may reduce asthmatic airway remodelling.Clinical trial registrationNCT02099656.

Project description:Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.

Project description:ContextAsymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.ObjectiveTo determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.Design, setting, and participantsThe Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.InterventionParticipating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157).Main outcome measuresThe primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.ResultsThe mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).ConclusionIn this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.Trial registrationclinicaltrials.gov Identifier: NCT00442013.

Dataset Information

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

Background

Methods

Results

Conclusion

Publications

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets