Influence of simulated obstructive sleep apnea on thoracic fluid volume and airways resistance in healthy and asthmatic subjects

Xiaoshu Cao (1,2), Douglas T. Bradley (2,3), Shumit Saha (1,2),

Cristina O. Francisco (2), Azadeh Yadollahi (1,2)

1. Institute of Biomaterials & Biomedical Engineering, University of Toronto

2. University Health Network-Toronto Rehabilitation Institute

3. Department of Medicine, University of Toronto

Background:Obstructive sleep apnea (OSA) is common in asthmatics, with a significant overlap of 12-50%. OSA prevalence increases with increasing asthma severity, suggesting a pathophysiological link between the two. OSA is also a risk factor for frequent nocturnal asthma exacerbations. Overnight rostral fluid shift (fluid shift out of the legs into the neck and peripharyngeal tissues) has been found to increase upper airway resistance and severity of OSA. Recently, we have shown that in asthmatics while supine, fluid shifts from the legs into the thorax increases lower airways resistance (RLA). During an obstructive apnea, exaggerated negative pleural pressure is generated, which could draw blood into the thorax and further increase thoracic fluid volume (TFV). Therefore, we surmised that in asthmatics, generation of negative pleural pressure by co-existing OSA could draw fluid into the thorax and therefore exacerbate lower airways narrowing and increase RLA. We hypothesized that voluntarily generating negative pleural pressure by inspiratory efforts against an occluded upper airway will increase TFV and increase RLA to a greater extent in asthmatics than in healthy subjects.
Methods:Healthy subjects lied supine for 30 mins and were randomized to a control or intervention study arm with a 1-hour seated washout period between the arms. In the control arm, subjects breathed normally. In the intervention arm, subjects performed Mueller maneuvers (MM) by breathing against an occluded mouth and nose to simulate obstructive apneas. 25 MMs were performed for 15 seconds each at a pleural pressure of -40 cmH2O followed by 15 seconds of normal breathing. TFV and RLA were monitored continuously. Changes in TFV and RLA from 0 min to 30 min were calculated and compared between study arms using repeated measures ANOVA.
Results:In 9 healthy subjects and 2 asthmatics, MMs caused a significantly greater increase in TFV of 131ml than the control arm (P<0.0001). Airway resistance did not change significantly during MMs compared to control in 9 healthy subjects (0.5±0.3 vs -0.3±0.5 cmH2O/L.s, P = 0.16). However, airway resistance showed a trend toward increasing in 2 asthmatics during MMs compared to control (1.65 vs -1.05 cmH2O/L.s).
Conclusion:The result supports our hypothesis that generation of negative pleural pressure increases TFV and is associated with a trend toward an increase in airway resistance in asthmatics.