title: Model-based stability assessment of ventilatory control in overweight adolescents with obstructive sleep apnea during NREM sleep.
abstract: Obstructive sleep apnea (OSA) involves the interplay of several different factors such as an unfavorable upper airway anatomy, deficiencies in pharyngeal muscle responsiveness, a low arousal threshold, and ventilatory control instability. Although the stability of ventilatory control has been extensively studied in adults, little is known about its characteristics in the pediatric population. In this study, we developed a novel experimental setup that allowed us to perturb the respiratory system during natural non-rapid eye movement (NREM) sleep conditions by manipulating the inspiratory pressure, provided by a bilevel pressure ventilator, to induce sighs after upper airway stabilization. Furthermore, we present a modeling framework that utilizes the noninvasively measured ventilatory responses to the induced sighs and spontaneous breathing data to obtain representations of the processes involved in the chemical regulation of respiration and extract their stability characteristics. After validation with simulated data, the modeling technique was applied to data collected experimentally from 11 OSA and 15 non-OSA overweight adolescents. Statistical analysis of the model-derived stability parameters revealed a significantly higher plant gain and lower controller gain in the OSA group (P = 0.046 and P = 0.007, respectively); however, no differences were found in loop gain (LG) and circulatory time delay between the groups. OSA severity and LG, within the 0.03-0.04-Hz frequency band, were significantly negatively associated (r = -0.434, P = 0.026). Contrary to what has been found in adults, our results suggest that in overweight adolescents, OSA is unlikely to be initiated through ventilatory instability resulting from elevated chemical loop gain.
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California; navaguer@usc.edu.
authors.forename: L
authors.initials: L
authors.lastname: Nava-Guerra
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California;
authors.forename: W H
authors.initials: WH
authors.lastname: Tran
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California;
authors.forename: P
authors.initials: P
authors.lastname: Chalacheva
authors.affiliation: Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: S
authors.initials: S
authors.lastname: Loloyan
authors.affiliation: Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: B
authors.initials: B
authors.lastname: Joshi
authors.affiliation: Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: T G
authors.initials: TG
authors.lastname: Keens
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California; Ming Hsieh Department of Electrical Engineering, University of Southern California, Los Angeles, California.
authors.forename: K S
authors.initials: KS
authors.lastname: Nayak
authors.affiliation: Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: S L
authors.initials: SL
authors.lastname: Davidson Ward
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California;
authors.forename: M C K
authors.initials: MC
authors.lastname: Khoo
mesh_terms: D000293:Adolescent; D000328:Adult; D001143:Arousal / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D050177:Overweight / Q000503:physiopathology*; D010609:Pharyngeal Muscles / Q000503:physiopathology; D010614:Pharynx / Q000503:physiopathology; D011312:Pressure; D012119:Respiration; D012890:Sleep / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D055815:Young Adult
keywords: mathematical modeling; obstructive sleep apnea; stability; ventilatory control