Active clinical trials for "Asthma"

The purpose of this study is to confirm the safety profile for long term treatment and maximize doses and the control status on bronchial asthma in daily clinical usage

Research Problem Asthma is one of the most common chronic diseases in the world that affects approximately 300 million individuals worldwide. It is characterized by airway inflammation and bronchoconstriction leading to airflow obstruction, however, the triggering factors behind asthma development remains to be elucidated. Genetic risk factors have been suggested to play a central role in asthma development. Twin studies supported a strong genetic component to asthma, especially childhood asthma, with heritability estimates suggesting that 48-70% of asthma risk is attributed to genetic risk factors. Suggestive susceptibility genes have been identified in European and American populations but not yet in the Middle East including Saudi Arabia. Identified genes whether they are polymorphic variants of genes encoding known pathophysiological molecules or novel genes identified by linkage or genome-wide association studies (GWAS) are inconsistent in different populations thereby adding to the need to undertake genetic studies on different ethnic populations and in different countries. Here, the investigators hypothesize that polymorphic variation of novel susceptibility genes form a major risk factor for asthma development, response to treatment and progression in the Saudi population with strong diagnostic, prognostic and therapeutic implications. Research Significance Since the manifestation of complex inflammatory disorders with strong heritability is complex involving genetic and environmental interaction, each ethnically distinct population must be examined to know whether gene-disease association exists in that population. The objectives of this proposal are to discover novel asthma susceptibility genes in the Saudi population. A better understanding of the genetic mechanisms of asthma will enhance our knowledge of its pathophysiology. Asthmatic patients with distinct genotypes respond differently to asthma medications. Therefore, improvements in diagnostics and pharmacogenetics may be the first clinical developments of these extensive studies. This embraces the concept of asthma subphenotypes and stratified medicine where interventions are targeted at those individuals who will best benefit from them with minimal side effects. Physicians looking after asthmatic patients will be able to provide better medical service tailored to those patients, as well as to identify Saudi people at high risk for the development of asthma, especially the more severe forms of the disease. Research Objectives The main objective of our proposal is to identify known and novel asthma susceptibility genes in the Saudi population and to investigate their interaction with clinical, environmental, and inflammatory factors contributing to asthma pathophysiology. Research Methodology In this proposal, the investigators will investigate the genetic factors contributing to asthma susceptibility by determining in Saudi population, the presence of single nucleotide polymorphisms (SNPs) that have been previously reported from linkage and GWAS in other populations. Whole genome DNA will also be scanned for novel SNPs of selected "asthma genes" using microarrays. This will enable us to identify new SNPs that contribute to the risk of asthma specifically in the Saudi population. In addition, the investigators will cross-reference all genetic and immunological parameters with the corresponding clinical data in order to elucidate the impact of certain genes, or their products (e.g. cytokines), on the clinical manifestation of asthma.

To evaluate the effects of a new statewide program to enhance identification, referral and provision of care to rural families of Hispanic children with moderately severe to severe asthma. Specifically, to determine if comprehensive medical care (CMC) plus an educational self-management program for rural Hispanic children and their families had an impact on asthma morbidity, as well as on cost and family adaptation.

To investigate the genetics of asthma by reexamining a carefully characterized population of patients with asthma, and by studying their families.

Clinicians frequently observed that obese women referred for severe asthma do not respond to treatment. These patients, despite the presence of wheezing, often have normal expiratory flows and normal or "borderline" airway responsiveness. It is therefore possible that this mode of presentation reflect a pseudo-asthmatic state for which clinical definition and characteristics and optimal management remain to be determined. The aim of this study was to study the pulmonary physiological and airway inflammatory characteristics and response to treatment of obese women considered to have clinically severe asthma in order to demonstrate that some of these patients have a phenotype that is not that of asthma.

The CATO population is a very well documented population during two years. During this study patients were treated according to the CATO algorithm, after that patient were treated according to the Dutch national (GINA derived) guidelines up to 6 years of follow-up. The purpose of this prospective follow-up study is to understand the long-term effects of treatment. Therefore the measurements done at baseline (CATO part 1) are repeated after 6 years in this CATO-population (CATO follow-up).

The aim of the study is to evaluate the efficacy of ciclesonide in patients with persistent asthma over 3 months, especially in the cold season. Ciclesonide will be inhaled by a metered-dose inhaler. The study will provide further data on safety and tolerability of ciclesonide.

The purpose of this study is to study prospectively the early clinical and immunological events in children susceptible to rhinovirus induced early wheezing (i.e., recently found highest risk factor for recurrent wheezing/asthma) and the efficacy of systemic corticosteroid to modify these events. Up to 50% of children suffer from acute wheezing before school-age. The prevalence of childhood asthma is 5-7%. Although pediatric asthma is mainly allergic, the exacerbations are associated with respiratory viral infections in 95% of cases. The means to predict asthma from environmental factors have been limited mainly to sensitization to aeroallergens (3-fold risk), which start to develop usually at 2-3 years of age. VINKU 1-study (orig. VINKU-study) discovered simultaneously with two other groups, that early wheezing associated with rhinovirus, the "common cold" virus, is the strongest predictor of recurrent wheezing/asthma (up to 10-fold risky). Noteworthily, viral infections work as risk markers already during infancy, a lot earlier than the sensitization to aeroallergens. The investigators also found retrospectively that early wheezers affected by rhinovirus responded to 3 day course of oral prednisolone (inexpensive and widely available treatment): recurrent wheezing decreased by 50% during following 12 months and the difference appeared to continue. VINKU 5V-study is currently investigating the clinical history, prevalence of asthma and airway hyperreactivity of these same children at school-age. The mechanism of rhinovirus associated risk or why they respond to prednisolone are largely unknown. However, the susceptibility to rhinovirus infections is associated with atopy and therefore it is possible these children may have impaired anti-inflammatory (Treg) responses and more likely to wheeze with any pro-inflammatory response (Th1 or Th2). Moreover, they may not effectively clear viruses, because they can not limit rhinovirus to nose and it spreads to lower airways and causes wheezing. VINKU 2-study will prospectively investigate the immunological events in young first-time wheezers affected by rhinovirus, and prospectively study the clinical efficacy of systemic corticosteroid in them. Most likely these children will benefit from the drug in terms of less recurrent wheezing, the investigators will also explore immunological effects of the drug and their link to clinical efficacy. The results are expected to give basis for the prevention of asthma and for the development of new treatment strategies and they can be directly applied to clinical medicine.

Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases affecting millions of people worldwide. Inhaled corticosteroids (ICS) are by far the most effective treatment with a broad anti-inflammatory spectrum. Nevertheless, most COPD patients and a proportion of severe asthma patients are corticosteroid-resistant (CR) and to fail to respond to ICS even when higher doses are given. These corticosteroid-resistant patients suffer from persistent symptoms and repeated asthma exacerbations. It has been suggested that smoking and oxidative stress may induce corticosteroid-resistance. The reactive oxygen species (ROS) responsible for oxidative stress can be generated exogenously (air pollutants, cigarette smoke) and endogenously by metabolic reactions. After inhaling air pollutants or cigarette smoke, the bronchial epithelium is exposed. Preliminary data from our own lab suggest that smoking and oxidative stress may decrease epithelial cell-cell contact formation. This results not only in a decreased barrier function, but also in an increased production of pro-inflammatory mediators.

Cardiovascular disease is a major cause of morbidity and mortality worldwide. It is the second leading cause of death in Hong Kong. The disease burden is huge and effective control measures should target at prevention level. As the disease pathophysiology is linked to chronic low grade systemic inflammation, any therapeutics having the potential to reduce systemic inflammation should be vigorously explored. The use of long-term inhaled corticosteroid (ICS) treatment in recent 2 decades has become the cornerstone in the treatment of most patients with persistent asthma with reduction in its mortality and hospital utilization. The long term safety of ICS in adults is generally very high. Recent epidemiological studies utilizing large numbers of patients with asthma have shown that long term use of ICS is independently associated with a protective effect towards the development of myocardial infarction and cardiovascular mortality, with protective risk at 0.35 (95%CI 0.13-0.93). This effect is possibly mediated through the reduction of low grade systemic inflammation as reflected by plasma hs-CRP, from systemic absorption of the ICS. The purpose of this study is to explore the potential protective effect of ICS on cardiovascular morbidities and its underlying link with systemic inflammation in Chinese adults with asthma compared with matched controls from the general population.