Lowering surface tension (gamma) of upper airway lining liquid (UAL) reduces upper airway opening (anesthetized humans) and closing (anesthetized rabbits) pressures. We now hypothesize that in sleeping obstructive sleep apnea hypopnea syndrome (OSAHS) patients lowering gamma of UAL will enhance upper airway stability and decrease the severity of sleep-disordered breathing. Nine OSAHS patients [respiratory disturbance index (RDI): 49 +/- 8 (SE) events/h, diagnostic night] participated in a two-part, one-night, polysomnography study. In the first part, upper airway closing pressures (during non-rapid eye movement sleep, Pcrit) were measured and samples of UAL (awake) were obtained before and after 2.5 ml of surfactant (Exosurf, Glaxo Smith Kline) was instilled into the posterior pharynx. The gamma of UAL was determined with the use of the "pull-off" force technique. In the second part, subjects received a second application of 2.5 ml of surfactant and then slept the remainder of the night (205 +/- 30 min). Instillation of surfactant decreased the gamma of UAL from 60.9 +/- 3.1 mN/m (control) to 45.2 +/- 2.5 mN/m (surfactant group) (n = 9, P < 0.001). Pcrit decreased from 1.19 +/- 1.14 cmH2O (control) to -0.56 +/- 1.15 cmH2O (surfactant group) (n = 7, P < 0.02). Compared with the second half of diagnostic night, surfactant decreased RDI from 51 +/- 8 to 35 +/- 8 events/h (n = 9, P < 0.03). The fall in RDI (deltaRDI) correlated with the fall in gamma of UAL (deltagamma) (deltaRDI = 1.8 x deltagamma, r = 0.68, P = 0.04). Hypopneas decreased approximately 50% from 42 +/- 8 to 20 +/- 5 events/h (n = 9, P < 0.03, paired t-test). The gamma of UAL measured the next morning remained low at 49.5 +/- 2.7 mN/m (n = 9, P < 0.001, ANOVA, compared with control). In conclusion, instillation of surfactant reduced the gamma of UAL in OSAHS patients and decreased Pcrit and the occurrence of hypopneas. Therapeutic manipulation of gamma of UAL may be beneficial in reducing the severity of sleep-disordered breathing in OSAHS patients.
Rationale: Oral appliance therapy is efficacious in many patients with obstructive sleep apnea (OSA) but prediction of treatment outcome is challenging. Small, detailed physiological studies have identified key OSA endotypic traits (pharyngeal collapsibility and loop gain) as determinants of greater oral appliance efficacy. Objectives: We used a clinically-applicable method to estimate OSA traits from routine polysomnography and identify an endotype-based subgroup of patients expected to show superior efficacy. Methods: In 93 patients (baseline apnea-hypopnea index [AHI] ≥20 events/hr), we examined whether polysomnography-estimated OSA traits (pharyngeal: collapsibility and muscle compensation; non-pharyngeal: loop gain, arousal threshold and ventilatory response to arousal) were associated with oral appliance efficacy (percent reduction in AHI from baseline) and could predict responses to treatment. Multivariable regression (with interactions) defined endotype-based subgroups of "predicted" responders and non-responders (based on 50% reduction in AHI). Treatment efficacy was compared between the predicted subgroups (with cross-validation). Results: Greater oral appliance efficacy was associated with favorable non-pharyngeal traits (lower loop gain, higher arousal threshold and lower response to arousal), moderate (non-mild, non-severe) pharyngeal collapsibility and weaker muscle compensation (overall R 2 =0.30, adjusted R 2 =0.19, p=0.003). Predicted responders (N=54), compared with predicted nonresponders (N=39), exhibited a greater reduction in AHI from baseline (73[66-79] vs. 51[38-61]%, mean[95%CI], p<0.0001) and a lower treatment AHI (8[6-11] vs. 16[12-20]events/hr, p=0.002). Differences persisted after adjusting for clinical covariates (including baseline AHI, body mass index, and neck circumference). Conclusions: Quantifying OSA traits using clinical polysomnography can identify an endotypebased subgroup of patients that is highly responsive to oral appliance therapy. Prospective validation is warranted.
Patients with OSAHS have normal salivary flow rate but an increased gamma of UAL. In both healthy subjects and OSAHS patients, nasal breathing during sleep was associated with an overnight fall in the gamma of UAL.
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