Project description:Rhinovirus (RV) is ubiquitous and typically causes only minor upper respiratory symptoms. However, especially in children and adolescent asthmatics, RV is responsible for most exacerbations. This ability of RV to drive exacerbations typically requires the concomitant presence of exposure to a bystander allergen. Susceptibility to RV-mediated exacerbations is also related to the genetic background of the host, which contributes to greater infectivity, more severe infections, altered immune responses, and to greater inflammation and loss of asthma control. Given these responses, there are several treatments available or being developed that should improve the control of exacerbations related to RV infection.
Project description:ObjectiveMost exacerbations are mild to moderate, and antibiotic treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is recommended for patients with severe exacerbations or severe underlying chronic obstructive pulmonary disease (COPD). Therefore, we aimed to investigate the patient factors that are associated with the prescription of antibiotics for inappropriate indication in AECOPD.Material and methodsThis study was an observational cross-sectional study conducted in an outpatient clinic. The patients diagnosed with AECOPD and prescribed an antibiotic by a pulmonary physician were enrolled in the study. These prescriptions were documented by the pharmacist who asked the patient about the three cardinal symptoms. Appropriate and inappropriate prescription groups were defined by the types of exacerbations, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD report.ResultsThere were 138 patients, predominantly male (83%), with a mean age of 64 (±9) years. A total of 64% of the prescriptions were appropriate; however, there were 50 (36%) patients with inappropriate antibiotic prescription according to the mentioned criteria. When we compared the patient factors between the appropriate and inappropriate antibiotic prescriptions, there was no statistically significant difference in terms of age, Forced expiratory volume in first second % (FEV1%) predicted, FEV1 ml, forced vital capacity (FVC) ml, FEV1/FVC, and amount (packs/year) of smoking (p>0.05 for all parameters). FVC% was statistically significantly lower in the appropriate antibiotic prescription group compared with that in the inappropriate antibiotic prescription group (p=0.049).ConclusionThis study shows that most pulmonary physicians have a tendency to prescribe antibiotics for AECOPD according to the defined GOLD criteria. However, some of the physicians also prefer to prescribe antibiotics self-directedly, irrespective of the GOLD criteria. A physician-based questionnaire can be completed for future studies to define the underlying reasons for antibiotic prescription demands for cases of mild AECOPD.
Project description:To investigate mechanisms underlying frequent asthma exacerbation, we profiled the nasal transcriptome of both frequent and non-frequent asthma exacerbators.
Project description:INTRODUCTION:Effective home management of childhood asthma by caregivers requires education along with a written asthma action plan (AAP), which should outline clear instructions for treatment during exacerbations. However, a large number of asthma exacerbations continue to be managed in the emergency department (ED) and in hospitals, particularly in Canada. The objective of this study was to assess caregiver management of acute asthma at home following the 2015 Global Initiative for Asthma (GINA) guidelines and to identify factors that may be associated with deviations from these guidelines. METHODS:122 caregivers of children, aged 3-17 years, with physician diagnosed asthma, completed a paper-based questionnaire. Correct caregiver management (defined according to the GINA guidelines) of acute asthma as well as their use of an AAP were assessed. RESULTS:Out of all caregivers, 74.6% incorrectly treated their child's asthma exacerbation in a home setting. Among those who used an AAP, we observed significantly more ED visits (0.9 ± 1.2 versus 0.5 ± 0.9, p = 0.04) and hospitalizations (0.2 ± 0.4 versus 0.0 ± 0.0, p = 0.02) when compared to non-AAP users in the past 1 year. CONCLUSIONS:Caregivers of children with asthma in Canada may still lack skills for proper home management of asthma exacerbations. We found a higher number of ED visits and hospitalizations in those using an AAP compared to those who did not use an AAP. These data suggest that current AAPs may not be sufficient for home asthma management.
Project description:Global patterns of gene expression was profiled in nasal lavage samples obtained from asthmatic children during an acute Picornavirus-induced exacerbation and 7-14 days later. Gene coexpression network analysis and prior knowledge was employed to reconstruct the wiring diagram of the underlying gene networks. The study design consisted of paired samples obtained during the acute exacerbation and 7-14 days later from 16 asthmatic children.
Project description:The prevalence of asthma has increased worldwide. Asthma exacerbations triggered by upper respiratory tract viral infections remain a major clinical problem and account for hospital admissions and time lost from work. Virus-induced asthma exacerbations cause airway inflammation, resulting in worsening asthma and deterioration in the patients' quality of life, which may require systemic corticosteroid therapy. Despite recent advances in understanding the cellular and molecular mechanisms underlying asthma exacerbations, current therapeutic modalities are inadequate for complete prevention and treatment of these episodes. The pathological role of cellular senescence, especially that involving the silent information regulator 2 homolog sirtuin (SIRT) protein family, has recently been demonstrated in stable and exacerbated chronic respiratory disease states. This review discusses the role of SIRT1 in the pathogenesis of bronchial asthma. It also discusses the role of SIRT1 in inflammatory cells that play an important role in virus-induced asthma exacerbations. Recent studies have hypothesized that SIRT1 is one of major contributors to cellular senescence. SIRT1 levels decrease in Th2 and non-Th2-related airway inflammation, indicating the role of SIRT1 in several endotypes and phenotypes of asthma. Moreover, several models have demonstrated relationships between viral infection and SIRT1. Therefore, targeting SIRT1 is a novel strategy that may be effective for treating virus-induced asthma exacerbations in the future.
Project description:Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)