TY - JOUR
T1 - Polysomnographic endotyping to select patients with obstructive sleep apnea for oral appliances
AU - Bamagoos, Ahmad A.
AU - Cistulli, Peter A.
AU - Sutherland, Kate
AU - Madronio, Melanie
AU - Eckert, Danny J.
AU - Hess, Lauren
AU - Edwards, Bradley A.
AU - Wellman, Andrew
AU - Sands, Scott A.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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 endotypebased subgroup of patients expected to show superior efficacy. Methods: In 93 patients (baseline apnea-hypopnea index [AHI], >20 events/h), we examined whether polysomnography-estimated OSA traits (pharyngeal: Collapsibility and muscle compensation; nonpharyngeal: Loop gain, arousal threshold, and ventilatory response to arousal) were associated with oral appliance efficacy (percentage reduction in AHI from baseline) and could predict responses to treatment. Multivariable regression (with interactions) defined endotype-based subgroups of "predicted" responders and nonresponders (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 nonpharyngeal traits (lower loop gain, higher arousal threshold, and lower response to arousal), moderate (nonmild, nonsevere) pharyngeal collapsibility, and weaker muscle compensation (overall R2 = 0.30; adjusted R2 = 0.19; P = 0.003). Predicted responders (n = 54), compared with predicted nonresponders (n = 39), exhibited a greater reduction in AHI from baseline (mean [95% confidence interval], 73% [66-79] vs. 51% [38-61]; P,0.0001) and a lower treatment AHI (8 [6-11] vs. 16 [12-20] events/h; 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 endotype-based subgroup of patients that is highly responsive to oral appliance therapy. Prospective validation is warranted.
AB - 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 endotypebased subgroup of patients expected to show superior efficacy. Methods: In 93 patients (baseline apnea-hypopnea index [AHI], >20 events/h), we examined whether polysomnography-estimated OSA traits (pharyngeal: Collapsibility and muscle compensation; nonpharyngeal: Loop gain, arousal threshold, and ventilatory response to arousal) were associated with oral appliance efficacy (percentage reduction in AHI from baseline) and could predict responses to treatment. Multivariable regression (with interactions) defined endotype-based subgroups of "predicted" responders and nonresponders (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 nonpharyngeal traits (lower loop gain, higher arousal threshold, and lower response to arousal), moderate (nonmild, nonsevere) pharyngeal collapsibility, and weaker muscle compensation (overall R2 = 0.30; adjusted R2 = 0.19; P = 0.003). Predicted responders (n = 54), compared with predicted nonresponders (n = 39), exhibited a greater reduction in AHI from baseline (mean [95% confidence interval], 73% [66-79] vs. 51% [38-61]; P,0.0001) and a lower treatment AHI (8 [6-11] vs. 16 [12-20] events/h; 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 endotype-based subgroup of patients that is highly responsive to oral appliance therapy. Prospective validation is warranted.
KW - Mandibular advancement splints
KW - Phenotype
KW - Precision medicine
KW - Sleep-disordered breathing
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85073418408&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/nhmrc/1116942
U2 - 10.1513/AnnalsATS.201903-190OC
DO - 10.1513/AnnalsATS.201903-190OC
M3 - Article
C2 - 31394914
AN - SCOPUS:85073418408
SN - 2325-6621
VL - 16
SP - 1422
EP - 1431
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 11
ER -