Quantifying ventilation by X-ray velocimetry in healthy adults.

RATIONALE: X-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means. OBJECTIVES: To assess agreement between XV-analysis of fluoroscopic lung images and pitot tube flowmeter measures of ventilation. METHODS: XV- and pitot tube-derived ventilatory parameters were compared during tidal breathing and with bilevel-assisted breathing. Levels of agreement were assessed using the Bland-Altman analysis. Mixed models were used to characterize the association between XV- and pitot tube-derived values and optimize XV-derived values for higher ventilatory volumes. MEASUREMENTS AND MAIN RESULTS: Twenty-four healthy volunteers were assessed during tidal breathing and 11 were reassessed with increased minute ventilation with bilevel-assisted breathing. No clinically significant differences were observed between the two methods for respiratory rate (average Δ: 0.58; 95% limits of agreement: -1.55, 2.71) or duty cycle (average Δ: 0.02; 95% limits of agreement: 0.01, 0.03). Tidal volumes and flow rates measured using XV were lower than those measured using the pitot tube flowmeter, particularly at the higher volume ranges with bilevel-assisted breathing. Under these conditions, a mixed-model based adjustment was applied to the XV-derived values of tidal volume and flow rate to obtain closer agreement with the pitot tube-derived values. CONCLUSION: Radiographically obtained measures of ventilation with XV demonstrate a high degree of correlation with parameters of ventilation. If the accuracy of XV were also confirmed for assessing the regional distribution of ventilation, it would provide information that goes beyond the scope of conventional pulmonary function tests or static radiographic assessments.

Association of x-ray velocimetry (XV) ventilation analysis compared to spirometry.

Introduction: X-ray Velocimetry (XV) ventilation analysis is a 4-dimensional imaging-based method for quantifying regional ventilation, aiding in the assessment of lung function. We examined the performance characteristics of XV ventilation analysis by examining correlation to spirometry and measurement repeatability. Methods: XV analysis was assessed in 27 patients receiving thoracic radiotherapy for non-lung cancer malignancies. Measurements were obtained pre-treatment and at 4 and 12-months post-treatment. XV metrics such as ventilation defect percent (VDP) and regional ventilation heterogeneity (VH) were compared to spirometry at each time point, using correlation analysis. Repeatability was assessed between multiple runs of the analysis algorithm, as well as between multiple breaths in the same patient. Change in VH and VDP in a case series over 12 months was used to determine effect size and estimate sample sizes for future studies. Results: VDP and VH were found to significantly correlate with FEV1 and FEV1/FVC (range: -0.36 to -0.57; p < 0.05). Repeatability tests demonstrated that VDP and VH had less than 2% variability within runs and less than 8% change in metrics between breaths. Three cases were used to illustrate the advantage of XV over spirometry, where XV indicated a change in lung function that was either undetectable or delayed in detection by spirometry. Case A demonstrated an improvement in XV metrics over time despite stable spirometric values. Case B demonstrated a decline in XV metrics as early as 4-months, although spirometric values did not change until 12-months. Case C demonstrated a decline in XV metrics at 12 months post-treatment while spirometric values remained normal throughout the study. Based on the effect sizes in each case, sample sizes ranging from 10 to 38 patients would provide 90% power for future studies aiming to detect similar changes. Conclusions: The performance and safety of XV analysis make it ideal for both clinical and research applications across most lung indications. Our results support continued research and provide a basis for powering future studies using XV as an endpoint to examine lung health and determine therapeutic efficacy.

Sleep disordered breathing in Marfan syndrome: Value of standard screening questionnaires.

BACKGROUND: A high prevalence of sleep disordered breathing (SDB) has been reported in persons with Marfan syndrome (MFS), a single gene disorder of connective tissue resulting in premature death from aortic rupture. The burden of SDB and accompanying hemodynamic stress could warrant broad screening in this population. Our goal was to assess the utility of traditional SDB screening tools in our sample of persons with MFS. METHODS: Participants were recruited during an annual Marfan Foundation meeting and Marfan status confirmed using the Ghent criteria. Screening questionnaires were administered and SDB assessed by home sleep testing. We assessed accuracy of screening tools using receiver-operating characteristic curve analyses. RESULTS: The prevalence of moderate-severe SDB was 32% in our sample of 31 MFS participants. The Stop-Bang questionnaire had the highest positive predictive value (PPV) of 60% and the highest negative predictive value (NPV) of 100% using the high- and moderate-risk cut-offs, respectively, and the Berlin questionnaire had a PPV of 50% and an NPV of 92.3% at the high-risk cut-off. When those with mild SDB were included, the Stop-Bang and the Sleep Apnea Clinical Score (SACS) questionnaires demonstrated useful screening accuracies with PPVs of 94.7% and 92.9%, and NPVs of 63.6% and 47.1%, respectively, at the moderate-risk cut-offs. CONCLUSION: A survey of SDB in a sample of persons with MFS reveals not only a high burden of SDB but also that conventional screening instruments have utility if adapted appropriately. Future studies should validate the utility of these screening tools given concerns that SDB may contribute to progression of aortic pathology in MFS.

The Efficacy of Low-Level Continuous Positive Airway Pressure for the Treatment of Snoring.

STUDY OBJECTIVES: To assess effects of low-level continuous positive airway pressure (CPAP) on snoring in habitual snorers without obstructive sleep apnea (OSA). METHODS: A multicenter prospective in-laboratory reversal crossover intervention trial was conducted between September 2013 and August 2014. Habitual snorers were included if they snored (inspiratory sound pressure level ≥ 40 dBA) for ≥ 30% all sleep breaths on a baseline sleep study (Night 1), and if significant OSA and daytime somnolence were absent. Included participants then underwent a CPAP titration study at 2, 4, or 6 cm H2O (Night 2) to examine snoring responses to step-increases in nasal pressure, a treatment night at optimal pressure (Night 3), followed by baseline night (Night 4). At each pressure, snoring intensity was measured on each breath. Snoring frequency was quantified as a percentage of sleep breaths at thresholds of 40, 45, 50, and 55 dBA. Sleep architecture and OSA severity were characterized using standard measurements. RESULTS: On baseline sleep studies, participants demonstrated snoring at ≥ 40 dBA on 53 ± 3% and ≥ 45 dBA on 35 ± 4% of breaths. Snoring frequency decreased progressively as nasal pressure increased from 0 to 4 cm H2O at each threshold, and plateaued thereafter. CPAP decreased snoring frequency by 67% and 85% at 40 and 45 dBA, respectively. Intervention did not alter sleep architecture and sleep apnea decreased minimally. CONCLUSIONS: Low-level CPAP below the range required to treat OSA diminished nocturnal snoring, and produced uniform reduction in nightly noise production below the World Health Organization's limit of 45 dBA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT01949584.

Nasal high-flow therapy reduces work of breathing compared with oxygen during sleep in COPD and smoking controls: a prospective observational study.

Patients with chronic obstructive pulmonary disease (COPD) endure excessive resistive and elastic loads leading to chronic respiratory failure. Oxygen supplementation corrects hypoxemia but is not expected to reduce mechanical loads. Nasal high-flow (NHF) therapy supports breathing by reducing dead space, but it is unclear how it affects mechanical loads of patients with COPD. The objective of this study was to compare the effects of low-flow oxygen and NHF therapy on ventilation and work of breathing (WOB) in patients with COPD and controls during sleep. Patients with COPD (n = 12) and controls (n = 6) were recruited and submitted to polysomnography to measure sleep parameters and ventilation in response to administration of oxygen and NHF. A subset of six patients also had an esophageal catheter inserted for the purpose of measuring WOB. Patients with COPD had similar minute ventilation (V̇e) but lower tidal volumes than matched controls. With oxygen, [Formula: see text]was increased and V̇e was reduced in both controls and patients with COPD, but there was an increase in transcutaneous CO2 levels. NHF produced a greater reduction in V̇e and was associated with a reduction in CO2 levels. Although NHF halved WOB, oxygen produced only a minor reduction in this parameter. We conclude that oxygen produced little change in WOB, which was associated with CO2 elevations. On the other hand, NHF produced a large reduction in V̇e and WOB with a concomitant decrease in CO2 levels. Our data indicate that NHF improves alveolar ventilation during sleep compared with oxygen and room air in patients with COPD and therefore can decrease their cost of breathing. NEW & NOTEWORTHY: Nasal high-flow (NHF) therapy can support ventilation in patients with chronic obstructive pulmonary disease during sleep by decreasing the work of breathing and improving CO2 levels. On the other hand, oxygen supplementation corrects hypoxemia, but it produces only a minimal reduction in work of breathing and is associated with increased CO2 levels. Therefore, NHF can be a useful method to assist ventilation in patients with increased respiratory mechanical loads.

Utilizing inspiratory airflows during standard polysomnography to assess pharyngeal function in children during sleep.

OBJECTIVES: Obstructive sleep apnea (OSA) is the result of pharyngeal obstruction that occurs predominantly during REM in children. Pathophysiologic mechanisms responsible for upper airway obstruction, however, are poorly understood. Thus, we sought to characterize upper airway obstruction in apneic compared to snoring children during sleep. We hypothesized that apneic compared to snoring children would exhibit an increased prevalence and severity of upper airway obstruction, that would be greater in REM compared to non-REM, and would improve following adenotonsillectomy. STUDY DESIGN: Apneic children were assessed with routine polysomnography before and after adenotonsillectomy, and compared to snoring children matched for gender, age, and BMI z-score. In addition to traditional scoring metrics, the following were used to characterize upper airway obstruction: maximal inspiratory airflow (%VI max) and percent of time with inspiratory flow-limited breathing (%IFL). RESULTS: OSA compared to snoring children had similar degrees of upper airway obstruction in non-REM; however, during REM, children with sleep apnea exhibited a higher %IFL (98 ± 2% vs.73 ± 8%, P < 0.01) and lower %VI max (56 ± 6 vs.93 ± 10%, P < 0.01). In children with OSA, CO2 levels were elevated during both wake and sleep. Following adenotonsillectomy, upper airway obstruction improved during REM manifest by decreased %IFL (98 ± 2 to 63 ± 9%, P = 0.04), increased %VI max (56 ± 6 to 95 ± 5%, P = 0.01) and decreased CO2 levels. CONCLUSIONS: Differences in the prevalence and severity upper airway obstruction suggest impaired compensatory responses during REM in children with OSA, which improved following adenotonsillectomy.

The effect of increased lung volume in chronic obstructive pulmonary disease on upper airway obstruction during sleep.

Patients with chronic obstructive pulmonary disease (COPD) exhibit increases in lung volume due to expiratory airflow limitation. Increases in lung volumes may affect upper airway patency and compensatory responses to inspiratory flow limitation (IFL) during sleep. We hypothesized that COPD patients have less collapsible airways inversely proportional to their lung volumes, and that the presence of expiratory airflow limitation limits duty cycle responses to defend ventilation in the presence of IFL. We enrolled 18 COPD patients and 18 controls, matched by age, body mass index, sex, and obstructive sleep apnea disease severity. Sleep studies, including quantitative assessment of airflow at various nasal pressure levels, were conducted to determine upper airway mechanical properties [passive critical closing pressure (Pcrit)] and for quantifying respiratory timing responses to experimentally induced IFL. COPD patients had lower passive Pcrit than their matched controls (COPD: -2.8 ± 0.9 cmH2O; controls: -0.5 ± 0.5 cmH2O, P = 0.03), and there was an inverse relationship of subject's functional residual capacity and passive Pcrit (-1.7 cmH2O/l increase in functional residual capacity, r(2) = 0.27, P = 0.002). In response to IFL, inspiratory duty cycle increased more (P = 0.03) in COPD patients (0.40 to 0.54) than in controls (0.41 to 0.51) and led to a marked reduction in expiratory time from 2.5 to 1.5 s (P < 0.01). COPD patients have a less collapsible airway and a greater, not reduced, compensatory timing response during upper airway obstruction. While these timing responses may reduce hypoventilation, it may also increase the risk for developing dynamic hyperinflation due to a marked reduction in expiratory time.

Nasal insufflation treatment adherence in obstructive sleep apnea.

BACKGROUND: Nasal insufflation (NI) is a novel treatment method that has been introduced for improving respiration during sleep. NI's warmed and humidified nasal airflow provides ventilatory assistance delivered as a rapidly dispersed pressure head, with minimal side wall pressures, that may affect treatment tolerability. The aim of the current study was to investigate objective and subjective adherence rates for NI therapy in mild to moderate obstructive sleep apnea (OSA). METHODS: Ten patients (three men and seven women; age, 51.3 ± 9.6 years; BMI, 32.2 ± 7.7 kg/m2 [mean ± sd]) with recently diagnosed mild to moderate OSA (10.9 ± 5.8 events/h) were investigated. A crossover design was used to compare adherence to NI and continuous positive airway pressure (CPAP) therapy using a range of objective and subjective measurements. Objective (sleep efficiency (%) and arousal indices (arousal/h)) and subjective evaluations of sleep quality were carried out each night in the laboratory. During in-home treatment, adherence for both therapies was assessed objectively (time on therapy) and subjectively (self-reported sleep diary). RESULTS: Objectively derived adherence values were comparable for CPAP and NI, with both treatment devices sharing similar usage per night (3.5 ± 2.5 vs. 3.6 ± 1.6 h/night; respectively) and the number of nights with at least 4 h of treatment (5.5 ± 4.3 vs. 6.8 ± 3.3 nights/trial, respectively). Self-reported adherence was significantly higher than objectively assessed adherence (p < 0.03). CONCLUSIONS: This study showed similar adherence to NI and CPAP over a short period of usage. A randomized clinical trial is now essential for determining the comparative effectiveness of NI therapy in relation to treatment with CPAP.

Sleep and respiratory physiology in adults.

Respiration during sleep is determined by metabolic demand; respiratory drive is determined by a central respiratory generator. Changes in pharyngeal dilator muscle tone resulting in increased upper airway resistance and collapsibility contribute to hypoventilation. Relative hypotonia of respiratory muscles, body posture changes, and altered ventilatory control result in additional physiologic changes contributing to hypoventilation. This article reviews mechanisms of central control of respiration and normal upper and lower airway physiology. Understanding sleep-related changes in respiratory physiology will help in developing new therapies to prevent hypoventilation in susceptible populations.

Leptin and the control of pharyngeal patency during sleep in severe obesity.

RATIONALE: Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep. METHODS: An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions. RESULTS: Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth. CONCLUSION: Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

A Remote-Controlled Airbag Device Can Improve Upper Airway Collapsibility by Producing Head Elevation With Jaw Closure in Normal Subjects Under Propofol Anesthesia.

Continuous maintenance of an appropriate position of the mandible and head purely by manual manipulation is difficult, although the maneuver can restore airway patency during sleep and anesthesia. The aim of this paper was to examine the effect of head elevation with jaw closure using a remote-controlled airbag device, such as the airbag system, on passive upper airway collapsibility during propofol anesthesia. Seven male subjects were studied. Propofol infusion was used for anesthesia induction and maintenance, with a target blood propofol concentration of 1.5-2 [Formula: see text]g/ml. Nasal mask pressure ([Formula: see text]) was intermittently reduced to evaluate upper airway collapsibility (passive [Formula: see text]) and upstream resistance ([Formula: see text]) at three different head and jaw positions, jaw opening position in the supine position, jaw opening position in the sniffing position with 6-cm head elevation, and jaw closure at a 6-cm height sniffing position. The 6-cm height sniffing position with jaw closure was achieved by an airbag device that was attached to the subject's head-like headgear. Patient demographics, [Formula: see text] and [Formula: see text] in each condition were compared using one-way ANOVA with a post hoc Tukey test. [Formula: see text] was considered significant. We also confirmed the effects of our airbag device on improvement of upper airway collapsibility in three obstructive sleep apnea patients in a clinical study. The combination of 6-cm head elevation with jaw closure using the air-inflatable robotic airbag system decreased upper airway collapsibility ([Formula: see text]-cm H[Formula: see text]O) compared with the baseline position ([Formula: see text]-cm H[Formula: see text]O, [Formula: see text]). In the clinical study, there was improvement of upper airway obstruction in sleep apnea patients, including decreased apnea and hypopnea duration and increased the lowest level of oxygen saturation. We demonstrated that establishment of head elevation with jaw closure achieved by a remote-controlled airbag device using an inflatable airbag system can produce substantial decreases in upper airway collapsibility and maintain upper airway patency during propofol anesthesia and sleep.

Approach for streamlining measurement of complex physiological phenotypes of upper airway collapsibility.

UNLABELLED: The critical closing pressure (PCRIT), a quantitative assessment of upper airway collapsibility, is derived from pressure flow relationship during sleep. The analytic generation of the pressure flow relationships are non-standardized due to various regression models (linear, spline, median), breath characteristics (flow limited, non-flow limited) or known covariates (sleep stage, body position). We propose a GUI based PCRIT Analysis Software (PAS) to streamline PCRIT analysis and validate its reliability and accuracy compared to current analysis procedures. METHODS: Seventeen subjects underwent a physiology sleep study in which the PCRIT was determined during NREM sleep. Data analysis was performed independently using three paradigms: (1) PAS (Igor Pro; median regression), (2) non-graphic statistics application (SAS; spline regression), and (3) manual spreadsheet calculations (Excel; linear regression). The reliability and accuracy of the PAS was examined through the agreement between each approach using Bland-Altman plots of the mean difference and within-individual variation using intra-class correlation (ICC). RESULTS: There was no difference in the group mean values for PCRIT using the PAS (-1.7 ± 0.7 cm H2O) compared to spline regression (-1.6 ± 0.7 cm H2O; p=0.69) or linear regression (-2.1 ± 0.7 cm H2O; p=0.92). The Bland-Altman analysis did not demonstrate a systematic bias between the PAS and either approach. There was a mean difference of 0.39 ± 0.2 cm H2O between the PAS and linear regression approaches, with upper and lower limits of agreement of 1.81 and -1.02 cm H2O, respectively. The PAS and spline analyses demonstrated an even smaller mean difference of -0.10 ± 0.1cm H2O, with upper and lower limits of 0.90 and -1.08 cm H2O, respectively. CONCLUSION: PAS preserves the reliability and accuracy of the original PCRIT analysis methods while vastly improving their efficiency through graphic user interface and automation of analytic processes. Providing a standardized platform for physiologic data processing offers the ability to implement quality assurance and control procedures for multicenter studies as well as cost saving by improving the efficiency of complex repetitive tasks.

Effects of nasal insufflation on arterial gas exchange and breathing pattern in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure.

High flow nasal insufflations (NI) can improve gas exchange and alleviate dyspnea in patients with acute respiratory failure. In the present study we investigated the effects of high flow nasal insufflations in COPD patients with chronic hypercapnic respiratory failure (HRF). Seventeen patients with severe COPD and HRF were recruited. We delivered a mixture of 20 L/min room air and 2 L/min O(2) through a nasal cannula either into both nostrils (NI) or into one nostril (Partial NI). Respiratory pattern and PaCO(2) responses under NI were compared with low flow oxygen of 2 L/min. High flow nasal insufflations led to a systematic reduction in respiratory rate from 19.8 ± 4.2 at baseline to 18.0 ± 4.7 during NI (p < 0.008) and 18.1 ± 5.2 breaths/min during Partial NI (P < 0.03). The mean group inspiratory duty cycle (T(I)/T(T)) and mean group PaCO(2) remained constant between all experimental conditions. Individual responses to NI were heterogeneous: six patients demonstrated marked reductions in respiratory rate (>20% fall from baseline), another group (n = 6) demonstrated no change in respiratory rate but marked reductions in arterial carbon dioxide of more than 8 mmHg. In conclusion, high flow (20 L/min) nasal insufflations of warm and humidified air during wakefulness for 45 min reduced respiratory rate without deterioration of hypercapnia. Our data indicate that high flow NI improved efficiency of breathing and may be used as an adjunct to low flow oxygen for preventing hypercapnic respiratory failure in severely ill COPD patients.

Effects of leptin and obesity on the upper airway function.

Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob(-)/ob(-) mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P(N)) to determine the passive expiratory critical pressure (P(CRIT)) and active responses to reductions in P(N), including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the P(N) threshold at which IFL developed, maximum inspiratory airflow (Vi(max)), and genioglossus electromyographic (EMG(GG)) activity. Elevations in body weight were associated with progressive elevations in P(CRIT) (0.1 ± 0.02 cmH(2)O/g), independent of mouse strain. P(CRIT) was also elevated in ob(-)/ob(-) compared with BL6 mice (1.6 ± 0.1 cmH(2)O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P(N) threshold and lower VI(max). Very obese ob(-)/ob(-) mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and P(N) threshold (from -0.8 ± 1.1 to -5.6 ± 0.8 cmH(2)O) and increase in VI(max) (from 354.1 ± 25.3 to 659.0 ± 71.8 µl/s). Nevertheless, passive P(CRIT) in leptin-treated mice did not differ significantly from that seen in nontreated ob(-)/ob(-) mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.

Compensatory responses to upper airway obstruction in obese apneic men and women.

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ∼20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.