The Role of Surface Tension of Upper Airway Lining Liquid and Breathing Route in Sleep Disordered Breathing

This thesis examines the relationship between surface tension in the upper airway liquid, breathing route, and sleep disordered breathing. Upper airway surface tension values were examined in both healthy subjects and in those with obstructive sleep apnoea. To determine whether the enforced oral breathing route induced sleep disordered breathing via surface tension mediated mechanisms, healthy subjects were given exogenous surfactant with enforced oral route of breathing during sleep. The relationship between uncontrolled route of breathing and surface tension was then examined in subjects with severe obstructive sleep apnoea. Finally, exogenous surfactant and normal saline were administered to subjects to determine the presence of any therapeutic effect on obstructive sleep apnoea. The studies in this thesis i) described a range of surface tensions in healthy subjects, and in those with OSA, ii) investigated the role of breathing route on upper airway surface tension and OSA severity, and iii) investigated the role of exogenous surfactant as a therapeutic agent in both oral breathing induced sleep disordered breathing (in healthy subjects) and in subjects with mild to moderate obstructive sleep apnoea

The Effects of Exogenous Phospholipids on Airway Function in Asthmatics

The studies described in this thesis examined whether application of lecithin to the oropharyngeal mucosa in asthmatics protected against bronchoconstiction and cough induced by airway challenge with inhaled mannitol powder. An initial study was conducted with 24 physician diagnosed adult asthmatics to determine the safety, convenience and suitability of mannitol airway challenge. Mannitol airway challenge was found to be a safe and convenient type of airway challenge in asthmatics, but marked interindividual variation in the degree of bronchoconstriction evoked by mannitol airway challenge was evident which confirmed previous reports. Twelve suitable adult asthmatics (6 men and 6 women) who showed a fall in the forced expiratory volume in one second (FEV₁) of ≥ 10% after mannitol airway challenge successfully completed the second study. This entailed airway challenges with equivalent doses of inhaled mannitol on two separate days after gargling with water or an aqueous suspension of soy lecithin in random order. Soy lecithin was used because of its high phospholipid content (1,680 mg of phosphatidylcholine, 960 mg of phosphatidylinositol). Prechallenge lung function values were reproducible over the two experimental test days. The results suggest that oropharyngeal application of phospholipids can protect asthmatics against mannitol airway challenge in addition to improving baseline lung function, and that these effects may be sustained for at least an hour. The mechanisms for this protective effect have not been elucidated but it is plausible that attenuated reflex bronchoconstriction and cough resulting from the masking and desensitizing of oropharyngeal neural receptors by adhering phospholipids was responsible. Thus, the findings of this study provide new evidence suggesting that oropharyngeal afferent pathways may be involved in the reflex regulation of airway function and cough during asthmatic exacerbations. The findings also suggest that orpharyngeal phospholipids may have therapeutic potential in the clinical management of asthma by providing the airways with sustained protection against factors that commonly provoke worsening asthmatic symptoms such as inhaling cold dry air and exercise, as well as alleviating upper airway irritation and cough in other common disorders such as viral respiratory tract infections. These findings and the implications arising from them warrant further investigation