View clinical trials related to Rhinovirus Infection in Asthma.
Filter by:The aim of this study is to investigate the mechanisms of interplay between allergy (IgE and Th2 mediated inflammation) and virus infection in the development of asthma, as well as the risk and severity of acute exacerbations of asthma. Understanding these mechanisms should identify new approaches for novel therapies for the prevention of asthma development and for prevention/treatment of asthma exacerbations. Such treatment has potential to have a major impact on patient quality of life and to result in enormous reductions in health care costs. A human model will be used to identify dysregulated genes/proteins and determine relationships with disease outcomes. This study will compare lower airway responses between asthmatic and healthy control subjects undergoing rhinovirus (RV) experimental infection (subjects will be infected with rhinovirus as part of the study). This will have the dual advantage of investigating mechanisms in the most natural model possible, as well as developing a better model for testing novel therapeutic approaches. The investigators will analyse the samples from both subject groups, to determine their relevance to the human disease. Any genes/proteins shown to be dysregulated and related to disease outcomes in the human model will be very strong candidates for immediate translation into human intervention studies. Up to 12 asthmatic and/or healthy subjects will be recruited for a preliminary pilot study. These subjects will be ineligible to enter the main study due to the presence of neutralizing antibody to RV16 (~50% of subjects otherwise suitable for the study). These subjects will meet all other inclusion/exclusion criteria for the main study. The 12 participants will undergo tests including a single bronchoscopy, nasal sampling and blood tests allowing for optimisation of all sample processing techniques. They will not be infected with RV-16. In the main study the investigators will aim to study up to 15 healthy volunteers and 15 volunteers with moderate asthma (all on inhaled steroid treatment). Subjects will undergo a single baseline bronchoscopy 2 weeks prior to inoculation with the RV16 virus. Following infection with the virus participants will be required to attend for regular sample collection including 2 further bronchoscopies post-infection. Patients will be followed until convalescence 6 weeks post infection.
We, the investigators, hypothesise that there are distinct gene profiles in rhinovirus-induced acute exacerbations of asthma. We further hypothesise that these changes in gene expression involve both known mediators of the asthma phenotype as well as other molecules not previously associated with asthma. The primary objective of this study is to use gene array analysis to determine differentially expressed genes in bronchial epithelial cells and alveolar macrophages from normal and asthmatic subjects before and during rhinovirus infection in vivo. A secondary objective is to determine whether any altered expressions are related to symptom severity, virus load, lung function or airway inflammation in vivo. We plan to recruit 45 subjects: 15 healthy volunteers, 15 asthmatics naïve to inhaled corticosteroid therapy, and 15 asthmatics on inhaled corticosteroids who will undergo two bronchoscopies, one prior to infection with rhinovirus and the second 4 days post inoculation. Bronchial brushings, biopsies and bronchoalveolar lavage (BAL) will be performed. RNA will be extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and purified by passage through RNeasy columns (Qiagen, Valencia, CA). Exon 1.0ST array chips (Affymetrix, Santa Clara, CA) will be used to analyse changes in gene expression. These are the most powerful genome expression tools available with 1.4 million probe sets and over 5.5 million features per array. Genes found to be significantly upregulated will be confirmed by quantitative RT-PCR. Using a novel method of collecting undiluted bronchial epithelial lining fluid (bronchosorption) large numbers of proteins will be measured with a MesoScale Discovery multiplexed array system (MesoScale Discovery, Gaithersburg, Md) allowing further confirmation of the gene array results as well as providing in vivo evidence of dysregulated protein production in asthmatics. Gene expression and protein levels will be correlated with viral load, symptom scores, lung function and airway inflammation in vivo. This study represents the first comprehensive evaluation of changes in bronchial epithelial gene expression during rhinovirus infection in vivo and therefore has the potential to provide significant insights into the host response in asthma and identify potential novel targets for further evaluation.