Comparison of Airway Remodeling Mediators Following Experimental Human Rhinovirus Infection in Subjects With Mild to Moderate Asthma and Healthy, Non-asthmatic Control Subjects
Human rhinovirus is also called the common cold virus because it causes at least half of all of the common colds experienced each year. In patients with asthma, getting a rhinovirus infection can cause worsening of asthma symptoms. Although these symptoms are well known, researchers do not fully understand how the virus worsens these asthma symptoms, nor do they really know whether virus infection causes longer term structural changes (often referred to as airway remodeling) in the airways. This study plans to address and answer these questions. Doing so will provide the researchers with a better understanding of how to treat the worsening of asthma that are caused by human rhinovirus infections. The epithelial cell is the cell that lines the surface of your airways from your nose down to your lungs, and is also the cell type that gets infected by rhinovirus. At present, it is thought that the virus causes symptoms by changing epithelial cell biology in a way that causes airway inflammation. Some of these inflammatory molecules are also thought to cause scarring (remodeling) of the airways, which over time, may lead to a loss of lung function. In order to examine how the virus causes inflammation, many earlier studies have used experimental infection with the virus and have measured various markers of inflammation. The purpose of this study is to compare the levels of inflammatory and remodeling products in the airways of study participants with mild to moderate asthma and healthy, non-asthmatic subjects after infection with rhinovirus (the common cold virus).
• Male or female volunteers with intermittent or persistent mild to moderate allergic asthma, as defined by GINA guidelines.
• Between ≥18 and ≤ 65 years of age
• Objective evidence of variable airflow limitation (≥12% and at least 200mL post-bronchodilator reversibility from baseline) and airway hyperresponsiveness (PC20 methacholine \<16mg/mL) at screening or within past 5 years
• Spirometry at baseline shows FEV1 ≥ 60% of predicted; FEV1/FVC ≥ 0.40
• Atopic, as evidenced by positive skin prick tests to ≥1 common aero-allergen, where positive is defined by a wheal of ≥2 mm greater than the negative control
• Not be exposed to sensitizing seasonal allergens for at least 4 weeks before visit 2
• Asthma symptoms controlled by either inhaled beta 2-agonists alone, or by low or moderate dose (≤800 μg of budesonide or equivalent per day) inhaled corticosteroid (ICS) administered either as monotherapy or in a fixed-dose combination with a long-acting beta 2-agonist (LABA)
• Be a non-smoker for ≥1 year and have a lifetime ≤ 10 pack-year smoking history of smoking
• In good general health (other than asthma) without clinically significant medical history of other comorbidities, and a BMI of ≤ 35 kg/m2.
⁃ Healthy, Non-asthmatic Cohort
• Male or female volunteers in good general health, without clinically significant medical history and a BMI of ≤ 35 kg/m2
• Between ≥18 and ≤ 65 years of age
• Non-asthmatic, as defined by history and normal spirometry (FEV1 ≥80% predicted; FEV1/FVC ≥ 0.75)
• Normal airway responsiveness (PC20 methacholine not detected at, or less than, 16 mg/mL)
• Non-atopic, as determined by skin prick tests to common aero-allergens, where a positive test is defined as a wheal of ≥2 mm greater than the negative control.
• Be a non-smoker for ≥1 year and have a lifetime ≤ 10 pack-year smoking history of smoking
• Willing to participate in study and be able to provide written consent prior to starting the study.