Rhinovirus type 16-induced exacerbation in asthma.

Asthma is characterized by episodic symptoms and variable airways obstruction accompanied with airway inflammation and airway remodelling. It appears that extracellular matrix (ECM) components within the airway smooth muscle (ASM) are altered in asthma and that ASM mass inversely correlates with lung function (FEV1). In addition, it has been observed that mast cell infiltration in ASM represents a typical aspect of inflammation in asthma, which is associated with airway hyperresponsiveness and impaired bronchodilation following a deep breath. Additionally, evidence has shown that dendritic cell (DC)-derived cytokines change the synthetic properties of ASM, suggesting that the distinct DC-phenotype in asthma might influence ASM phenotype.



Both inflammation and hyperresponsiveness are enhanced during an exacerbation. It has been observed that viral infection of the airways is a major factor causing these exacerbations. There is good evidence that this occurs by mechanisms related to epithelial and inflammatory cell pathways. Furthermore, the phenotype of the ASM layer is shown to be altered by viral infection, suggesting that smooth muscle and its direct environment are key determinants of the changes in airway function as observed during clinical episodes of both well- and poorly-controlled asthma. However, the precise mechanisms underlying this process are still poorly understood, resulting in the impediment of the development of adequate prophylaxis and treatment of exacerbations.

We hypothesize that the ASM phenotype of asthmatic patients:

1. Changes during an experimental, rhinovirus type 16 (RV16)-induced exacerbation;

2. Is associated with enhanced airway inflammation and hyperresponsiveness during an experimental, RV16-induced exacerbation.



Furthermore, we hypothesize that gene expression of the epithelial cells from the airway wall:

1. Changes in asthmatic patients during an experimental, RV16-induced exacerbation;

2. Changes differently between asthmatic and control-group subjects during an experimental, RV16-induced exacerbation.

Day -9: Screeningsvisit;

Day -1: Bronchoscopy pre-RV16 exposure;

Day 0: RV16 exposure;

Day 6: Bronchoscopy post-RV16 exposure;

Day 42: Follow-up visit.

Spirometry, bronchoprovocation with methacholine, allergy skin prick test, measurement of respiratory impedance using Forced Oscillation Technique, eNO measurement, bronchoscopy with brushes and biopsies, venapunction, once-only exposure to low-dose rhinovirus type 16 (10 TCID50).



All participants will be exposed to a low dose (10 TCID50) RV16, the common cold virus. This will take place once-only during visit 3 of the study. The RV16 inoculum will be diluted in sterile NaCl and a total volume of 0.75mL will be sprayed through one nostril using an atomizer.