COPD is associated with significant morbidity including substantial daytime fatigue exertional intolerance and ventilatory impairment, which hits is a nadir in the morning. Although COPD related impairments in ventilation are considered to play a role for sleep disturbances, the mechanisms of how COPD specific alterations in ventilation affects sleep, particularly in patients without sleep apnea, remain unclear. We hypothesize that in patients with COPD sleep attenuates compensatory mechanisms needed to defend ventilation leading to periods of dynamic hyperinflation and hypoventilation resulting in sleep disturbances. In the current proposal, we use a novel diagnostic flow-sensor for quantifying ventilation during sleep to detect specific mechanisms accountable for ventilatory decompensation during sleep and to determine the prevalence of COPD related sleep disordered breathing episodes in a community recruited cohort of individuals with COPD. While long-term oxygen treatment significantly improved mortality, studies examining the effects of nocturnal oxygen administration in patients with borderline hypoxia on clinical outcomes and sleep quality in COPD have been inconclusive. Our preliminary data demonstrate that oxygen administration during sleep reduces neuromuscular drive to the upper airway and aggravates ventilatory decompensation in patients with COPD. Thus, although oxygen may help to relieve daytime symptoms, nocturnal use of oxygen may in fact be harmful in patients with COPD as it exaggerates impairments in ventilation during sleep. In contrast, the PI recently established that nasal insufflation of room air (NI) effectively stabilizes breathing during sleep in patients with inspiratory flow limitation. Moreover, we now demonstrate that, in contrast to nocturnal oxygen, this novel approach can lower hypercapnia by mitigating the mechanisms accountable for ventilatory failure during sleep. The current proposal will extend our knowledge of the pathophysiologic mechanisms for the development of sleep disordered breathing in patients with COPD. It will also change current paradigms for diagnosing and treating COPD patients. This shift will be built through: (1) the establishment of a high prevalence of COPD specific sleep disordered breathing episodes independent of obstructive sleep apnea (OSA) (SA1),(2) the determination of the underlying mechanisms for dynamic hyperinflation and hypoventilation during sleep in COPD (SA2), and (3) the demonstration that NI improves sleep and breathing better than supplemental oxygen in COPD (SA3).

Public Health Relevance

We hypothesize that in patients with COPD sleep attenuates compensatory mechanisms necessary to defend expiratory airflow limitation leading to periods of dynamic hyperinflation, hypoventilation and sleep disturbances. Moreover, we demonstrate that nocturnal use of oxygen exaggerates these impairments in ventilation during sleep, while nasal insufflation of room air (NI) can mitigate these effects. We determine the underlying mechanisms for dynamic hyperinflation and hypoventilation during sleep in COPD, and demonstrate that NI improves sleep and breathing better than supplemental oxygen in COPD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL105546-03
Application #
8494076
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Twery, Michael
Project Start
2011-07-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$390,320
Indirect Cost
$152,320
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kirkness, Jason P (2014) Hypopnea: 'rule of thumb' or ruler and plumb? Sleep Breath 18:683-5
Mundel, Toby; Feng, Sheng; Tatkov, Stanislav et al. (2013) Mechanisms of nasal high flow on ventilation during wakefulness and sleep. J Appl Physiol (1985) 114:1058-65
Nilius, Georg; Franke, Karl-Josef; Domanski, Ulrike et al. (2013) Effects of nasal insufflation on arterial gas exchange and breathing pattern in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure. Adv Exp Med Biol 755:27-34