Dataset Information

P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy.

ABSTRACT: The function of the P2X(7) nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied.To evaluate the association between P2X(7), asthma exacerbations, and incomplete symptom control in a more diverse population.A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X(7) pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently.A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting ?(2)-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2-6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1-9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV(1) reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase.P2X(7) pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy.

SUBMITTER: Denlinger LC

PROVIDER: S-EPMC3570642 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy.

Denlinger Loren C LC Manthei David M DM Seibold Max A MA Ahn Kwangmi K Bleecker Eugene E Boushey Homer A HA Calhoun William J WJ Castro Mario M Chinchili Vernon M VM Fahy John V JV Hawkins Greg A GA Icitovic Nicolina N Israel Elliot E Jarjour Nizar N NN King Tonya T Kraft Monica M Lazarus Stephen C SC Lehman Erik E Martin Richard J RJ Meyers Deborah A DA Peters Stephen P SP Sheerar Dagna D Shi Lei L Sutherland E Rand ER Szefler Stanley J SJ Wechsler Michael E ME Sorkness Christine A CA Lemanske Robert F RF

American journal of respiratory and critical care medicine 20121109 1

<h4>Rationale</h4>The function of the P2X(7) nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied.<h4>Objectives</h4>To evaluate the association between P2X(7), asthma exacerbations, and incomplete symptom control in a more diverse population.<h4>Methods</h4>A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Networ ...[more]

PMID: 23144325

Similar Datasets

Project description:BackgroundSmall airway dysfunction not only affects asthma control, but also has adverse effects on the psychological and/or social activities of asthma patients. However, few long-term observational studies have explored the complex relationship between small airway dysfunction and asthma control and health-related quality of life in patients with asthma exacerbations.MethodsThe study recruited 223 patients with exacerbations of asthma (i.e. those with at least one asthma attack over the past year) and 228 patients without exacerbations of asthma (i.e. those without asthma attacks over the past year). We evaluated SAD in patients with asthma exacerbations using impulse oscillometry method. At each evaluation time point within one year of follow-up, the attending physician conducts a case investigation of the patients. We analyzed the correlation between SAD and general characteristics (age, obesity, smoking history), type 2 inflammation (blood eosinophils, exhaled nitric oxide), FEV1, as well as asthma control (ACT) and health-related quality of life (mini-AQLQ) in patients with asthma exacerbations, and constructed a structural equation model to evaluate the causality of these clinical variables.ResultsThe SAD prevalence in patients with asthma exacerbation is as high as 75%. SAD is connected with poor asthma control and poor health-related quality of life. The structural equation model indicates that age, obesity, FeNO, and FEV1 are independent predictive factors of SAD. SAD is the main determinant factor of asthma control, which in turn affected health-related quality of life. FEV1 and age directly affect asthma control and affect health-related quality of life through asthma control. In addition, there is a bidirectional relationship between FEV1 and small airway dysfunction and between asthma control and health-related quality of life.ConclusionsSmall airways are involved from an early stage in asthma. Abnormal function of the small airways can significantly increase airway resistance in asthma patients, while worsening their clinical symptoms. In addition, aging is also a key risk factor for asthma control. Especially, small airway dysfunction links asthma control with health-related quality of life.

Project description:BackgroundAdjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART® Turbuhaler®) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4.MethodsThis is a post hoc analysis of the results of five large clinical trials (>12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined.ResultsAt each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting ?2-agonist (ICS/LABA) (plus short-acting ?2-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps.ConclusionsBUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.

Dataset Information

P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy.

Publications

P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets