Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea

Bradley A. Edwards, Danny J. Eckert, David G.P. McSharry, Scott A. Sands, Amar Desai, Geoffrey B. Kehlmann, Jessie P. Bakker, Pedro R. Genta, Robert L. Owens, David P. White, Andrew Wellman, Atul Malhotra

Research output: Contribution to journalArticlepeer-review

218 Citations (Scopus)


Rationale: A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements. Objectives: To determine the physiologic determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH. Methods: Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter to measure the ArTH (nadir epiglottic pressure before arousal). The ArTH was measured from up to 20 non-REM and REM respiratory events selected randomly. Multiple linear regression was used to determine the independent predictors of the ArTH. Logistic regression was used to develop a clinical scoring system. Measurements and Main Results: Nadir oxygen saturation as measured by pulse oximetry, apnea-hypopnea index, and the fraction of events that were hypopneas (Fhypopneas) were independent predictors of the ArTH (r2 = 0.59; P < 0.001). Using this information, we used receiver operating characteristic analysis and logistic regression to develop a clinical score to predict a low ArTH, which allocated a score of 1 to each criterion that was satisfied: (apnea-hypopnea index, <30 events per hour) 1 (nadir oxygen saturation as measured by pulse oximetry >82.5%) 1 (Fhypopneas >58.3%). A score of 2 or above correctly predicted a low arousal threshold in 84.1% of participants with a sensitivity of 80.4% and a specificity of 88.0%, a finding that was confirmed using leave-one-out cross-validation analysis. Conclusions: Our results demonstrate that individuals with a low ArTH can be identified from standard, clinically available variables. This finding could facilitate larger interventional studies targeting the ArTH.

Original languageEnglish
Pages (from-to)1293-1300
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number11
Publication statusPublished - 1 Dec 2014


  • Sleep apnea
  • respiratory-induced arousals
  • Arousal threshold
  • phenotype traits
  • Lung
  • Phenotype traits
  • Respiratory-induced arousals


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