Immediate Physiological Responses to Inspiratory Flow Limited Events in Mild Obstructive Sleep Apnea.

Rationale: Inspiratory flow limitation (IFL), characterized by flattening of individual breaths on the airflow/time tracing, is a noninvasive indicator of elevated upper airway resistance. An IFL "event" in isolation has not been defined, nor has the ability to reproducibly identify event occurrence been tested. IFL events and their association with immediate physiological responses-as well as the impact of characteristics such as age, sex, sleep stage, sleepiness, and event duration on their association with such outcomes-have not been studied. Symptomatic patients with a normal to mildly abnormal apnea-hypopnea index who have predominant IFL on their polysomnography may benefit from treatment. Objectives: To test the reproducibility of identifying IFL events and their termination and to determine the frequency of the immediate physiological response to their occurrence, including desaturation, electroencephalography (EEG) arousal, and increased heart rate (HR). Methods: Fifty-eight patients with obstructive sleep apnea (OSA) underwent full diagnostic polysomnography. IFL events and their termination were identified manually using predefined rules from the unscored nasal cannula flow channel alone and were evaluated for responses such as EEG arousal, oxygen desaturation of ⩾3%, and HR increase. Results: Interscorer reliability was acceptable, with an average percent agreement for occurrence of 82% ± 3%. Of all IFL events, 24% (regardless of the definition) were not associated with an EEG arousal, an increase in HR, or O2 desaturation. Of all IFL events scored, 25% caused O2 desaturation, 40% were associated with an EEG arousal, and 55% were associated with an increase in HR; 67% caused either an EEG arousal and/or an increase in HR. Responses were observed to occur either in isolation or in combination. IFL events that terminated with at least two non-IFL breaths, one of which had a 200% increase in amplitude, were significantly associated with O2 desaturation, EEG arousal, and increase in HR compared with events that ended in one non-IFL breath. IFL events that had a >50% reduction in flow amplitude compared with baseline were significantly associated with O2 desaturation compared with events that had a 30% reduction or less. Conclusions: Most IFL events resulted in immediate physiological responses, and no single consequence reliably occurred after every event. We propose a framework that can incorporate the scoring of IFL events into assessing the diagnosis and severity of OSA and suggest that no single consequence be used to define IFL as a respiratory event. The relationship of IFL events to OSA outcomes remains to be tested.

Pitolisant to Treat Excessive Daytime Sleepiness and Cataplexy in Adults with Narcolepsy: Rationale and Clinical Utility.

Narcolepsy is a sleep disorder marked by chronic, debilitating excessive daytime sleepiness and can be associated with cataplexy, sleep paralysis and sleep-related hallucinations. Pharmacological therapy for narcolepsy primarily aims to increase wakefulness and reduce cataplexy attacks. Pitolisant is a first-in-class agent utilizing histamine to improve wakefulness by acting as an antagonist/inverse agonist of the presynaptic histamine 3 receptor. This review summarizes the clinical efficacy, safety and tolerability of pitolisant in treating the symptoms of narcolepsy. Randomized and observational studies demonstrate pitolisant to be effective in treating both hypersomnolence and cataplexy while generally being well tolerated at prescribed doses. The most common adverse reactions include headache, insomnia and nausea.