Al Ahmari, M; (2013) Non-Invasive Respiratory Support is a Pro-inflammatory Stimulus to the Upper and Lower Airways. Doctoral thesis , UCL (University College London).

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Abstract

Non-invasive respiratory support (NIV) is associated with a high prevalence of local side- effects which may be associated with induction of upper airway inflammation. This thesis examines the effect of NIV on the upper and lower airway by examining bronchial epithelial cell cultures, healthy subjects, obstructive sleep apnoea (OSA), and chronic obstructive pulmonary disease (COPD) patients. The rationale for this thesis is based on reports suggesting that continuous positive airway pressure (CPAP) may induce early upper airway inflammation, and discusses the relationship between upper and lower airways in COPD. To examine the addressed rationale we used both an in vitro and in vivo approach. In vitro, we examined the release of the inflammatory cytokines from a human bronchial epithelial cell line over time-intervals using CPAP therapy. In vivo studies investigated whether induction of nasal inflammation was associated with the development of systemic inflammation, nasal symptoms, and changes in nasal mucociliary clearance after a short period of CPAP therapy. Results were investigated further in OSA by investigating whether induction of nasal inflammation was associated with the development of systemic inflammation, nasal symptoms, airway obstruction, and impaired adherence to CPAP therapy and quality of sleepiness over a six months follow-up period. Additional pilot data obtained involved a comparison of local and systemic inflammatory indices in COPD patients using and not using NIV. The key finding was that CPAP is pro-inflammatory. The in vitro data showed that CPAP resulted in the release of inflammatory mediators from cultured human bronchial epithelial cells, in a time-and-pressure-dependent manner. Meanwhile, in vivo data from healthy control subjects showed CPAP was associated with dose (pressure) response changes in nasal and systemic inflammatory markers, reduced nasal function, and the development of nasal symptoms. The development of nasal symptoms was associated with the degree of functional impairment and nasal inflammatory response. These in vitro and in vivo results were novel in reporting the effects of CPAP in this way, providing new data on the mechanisms of CPAP intolerance in the crucial, early phase of therapy. Furthermore, the long-term CPAP study with OSA resulted in nasal inflammation, reduction in nasal mucociliary function, and significant other adverse effects. However, sleep quality and the perceived benefits of therapy improved over time, despite the presence of side-effects. These results have important implications for clinical practice, since it demonstrates a relationship between nasal symptoms, mucociliary clearance, inflammation and compliance in patients with OSA initiating and continuing CPAP therapy. Further investigation of strategies to combat the initial side-effects and nasal inflammation associated with this treatment modality might target the epithelial lining of the nose in an attempt to address the origin of the inflammatory response. In addition, educational and support strategies to improve patients‟ tolerance of side effects may further increase compliance with nasal CPAP treatment for OSA patients.

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