Table 2.

Recommendations for Future Research

1. Develop clinical tests that detect and classify the physiological mechanisms for breathing instability during sleep and wakefulness

2. Determine the genetic basis of individual susceptibility to sleep-disordered breathing in adults and children

3. Systematically evaluate pharmacologic agents that stabilize breathing during NREM sleep to delineate their effects on chemoresponsiveness, CVR to carbon dioxide, upper airway tone, and EEG arousal.

4. Clarify the role of chronic intermittent hypoxia and LTF: is LTF beneficial or harmful for patients with sleep apnea?

5. Based on findings from Nos. 1-3, develop therapies that specifically target chemoresponsiveness and other pathophysiological mechanisms

6. Perform clinical trials to study the physiological effects of sex hormones, ampakines, antioxidants, orexin antagonists, and other agents on breathing stability in individuals with high loop gain

7. Perform prospective randomized placebo-controlled clinical trials using supplemental oxygen or ACZ alone or in combination with other therapies in patients with CHF with CSA

8. Perform prospective randomized clinical trials of ampakine alone or in combination with other interventions in patients with CSA due to opioid use

ACZ = acetazolamide; CHF = congestive heart failure; CSA = central sleep apnea; CVR = cerebrovascular responsiveness; LTF = long-term facilitation; NREM = non-rapid eye movement.