Influence of Obstructive Sleep Apnea (OSA) on Rostral Fluid Shift, and the Pathophysiology on Asthma

The presence of obstructive sleep apnea (OSA) in persons with asthma confers a heightened risk of overnight exacerbation of asthma, declined lung function, increased airway hyperresponsiveness, and greater need for asthma medications. Previous studies showed that overnight fluid shift from the legs into the neck and peripharyngeal tissues increases upper airway resistance and severity of OSA. Recent findings also indicated that in asthma, fluid shift into the thorax induced by lower body positive pressure (LBPP) while supine provokes an increase in small airway resistance. However, whether fluid redistribution links OSA with asthma remains unknown. This thesis aimed to investigate the role of fluid accumulation in the thorax in the pathophysiological link between OSA and asthma. The central hypothesis is that one mechanism by which OSA can predispose to small airway narrowing in asthma is by aggravating fluid accumulation in the thorax during sleep. We found that simulated obstructive apneas in awake participants increased thoracic fluid volume (TFV) by approximately 50 ml in both healthy and asthma groups. However, small airway narrowed only in the asthma group, indicating that increases in TFV resulting from negative intrathoracic pressure swings during simulated apneas, increase small airway narrowing in patients with asthma, but not in healthy controls (Chapter 3). We expanded this work into the overnight and clinical setting, and found that patients with asthma and co-existing OSA had a larger increase in TFV and greater small airway narrowing than asthma patients without OSA (Chapter 4). Moreover, we investigated whether asthma treatment with bronchodilators can prevent the airway narrowing that is attributable to rostral fluid shift. It was found that small airway narrowing would increase after application of LBPP, both with and without bronchodilator (Chapter 5). Finally, we developed a model of the respiratory system, to estimate elastance of the airway tissues and total respiratory system in patients with asthma in response to increase in TFV. Our modelling results showed that increases in TFV was associated with an increase in airway tissue elastance (Chapter 6). Taken together, these studies demonstrate that fluid accumulation in the thorax narrows the small airway in patients with asthma, and contributes to the pathophysiological link between OSA and asthma.

Department dc:contributor.department

Biomedical Engineering

Year dc:date.issued

2023

Author dc:creator

• Cao, Xiaoshu

Advisor dc:contributor.advisor

• Yadollahi, Azadeh A. Y.

• asthma
• obstructive sleep apnea
• rostral fluid shift
• small airway narrowing
• thoracic fluid accumulation

Statement dc:rights

• Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/128219

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/128219