Airway epithelium and asthma Virus exposure, airway inflammation and metabolism

Asthma is a respiratory chronic inflammatory disease with well-established symptoms, but the pathophysiological mechanisms remain largely unexplored. In this thesis, we aim to analyse and clarify responses of asthmatic airway epithelial cells.
In chapter 2, we showed that bronchial epithelium from mild asthma patients in response to in vivo RV16 challenge, display a marked interferon-induced response that correlates with increased airway inflammation. In chapter 3, we showed temporal responses of nasal epithelial cells from moderate asthma patients to RV16. Exposure to a fixed dose of rhinovirus in vivo, enabled efficient viral replication in all individuals, but the increment of the interferon response, irrespective of RV16 load, determined viral clearance and nasal symptoms.
In chapter 4, we reported that hyperresponsive production of pro-inflammatory cytokines in bronchial epithelial cells from most asthma patients is due to a defective translational control. This enhanced production neutrophilic mediators by bronchial epithelium links to neutrophilic inflammation in the bronchial lumen of asthma patients. In chapter 5, we described the intrinsic translational defect in epithelium, is imprinted in subsequent samplings. Moreover, there is further enhanced production of neutrophilic mediators post-RV16 exposure.
In chapter 6, we presented data to show an altered expression of metabolic genes in bronchial epithelium and that decreases with increasing disease severity (mild to severe). Strikingly, these metabolic changes can be reversed by bronchial thermoplasty treatment. Taken together, the work described in this thesis has given us more insights in the contribution of airway epithelium to asthma pathogenesis with some potential leads for intervention.