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Study Objectives Previous studies reported that the apnea–hypopnea index was similar in young adult Black and White participants. However, whether this similarity reflects an analogous combination of apneas and hypopneas is unknown. Likewise, the physiological mechanisms underlying this similarity has not been explored. Methods 60 Black and 48 White males completed the study. After matching for age and body mass index, 41 participants remained in each group. All participants completed a sleep study. Subsequently, standard sleep indices along with loop gain and the arousal threshold were determined. In addition, airway collapsibility (24 of 60 and 14 of 48 participants) and the hypoxic ventilatory response during wakefulness (30 of 60 and 25 of 48 participants) was measured. Results The apnea–hypopnea index was similar in Blacks and Whites (p = .140). However, the index was comprised of more apneas (p = .014) and fewer hypopneas (p = .025) in Black males. These modifications were coupled to a reduced loop gain (p = .0002) and a more collapsible airway (p = .030). These differences were independent of whether or not the groups were matched. For a given hypoxic response, loop gain was reduced in Black compared to White males (p = .023). Conclusions Despite a similar apnea–hypopnea index, more apneas and fewer hypopneas were evident in young adult Black compared to White males. The physiological mechanisms that contribute to these events were also different between groups. Addressing these differences may be important when considering novel therapeutic approaches to eliminate apnea in Black and White participants.

Introduction Clinical guidelines recommend avoiding benzodiazepines and z-drugs (BZRAs) in older adults due to an increased risk of adverse outcomes (e.g., falls) in this population. Efforts to reduce BZRA use among older adults are growing, yet long-term BZRA deprescribing among patients with insomnia is challenging. We examined whether clinical conditions commonly comorbid with insomnia (i.e., depression, pain, nightmares, and anxiety) are barriers to BZRA deprescribing. Methods In an ongoing multi-site trial comparing two BZRA deprescribing programs (both include cognitive behavioral treatments for insomnia), participants aged >=55 years with chronic BZRA use for insomnia (N=165, mean age 68.7, sd 7.9) completed baseline Patient Health Questionnaire-9 (PHQ9), Brief Pain Inventory (BPI), Disturbing Dreams and Nightmare Severity Index (DDNSI), and Generalized Anxiety Disorder-7 (GAD-7). Deprescribing outcomes (discontinuation, dose, and frequency of use over 7-days) were assessed 1 week and 6 months after completing the deprescribing program. Using logistic and linear regression models, we assessed whether depression, pain severity, nightmare severity, and anxiety were predictors of BZRA deprescribing outcomes, controlling for site, gender, and age. Results Among participants assessed 1 week (n=133) and 6 months (n=106) after intervention, 77% and 66% discontinued their BZRA use, respectively. Worse PHQ-9 was associated with reduced odds of discontinuation (OR 0.88, 95% CI 0.79-0.99, p=.027) at 6 months, but not frequency of use or dose at follow up. Pain severity predicted more frequent use (b=0.26, p=.02) and higher dose (b=0.94, p=.016) but not discontinuation at 6 months. DDNSI (p values >=.068) and GAD-7 (p values >= 0.15) were not significant predictors of discontinuation, frequency, or dose at follow-up. Conclusion More severe depression at baseline is a predictor of BZRA deprescribing failure long-term. Pain is also a barrier to BZRA reduction efforts. Programs aimed at reducing and discontinuing BZRAs used for insomnia should consider interventions that not only address underlying insomnia, but also depression and pain. Support (if any) NIA R01AG057929; VA IIR 17-234

Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. In some conditions, such as heart failure, central apneic events are due to transient inhibition of ventilatory motor output during sleep, owing to the overlapping influences of sleep and hypocapnia. Specifically, the sleep state is associated with removal of wakefulness drive to breathe; thus, rendering ventilatory motor output dependent on the metabolic ventilatory control system, principally PaCO2. Accordingly, central apnea occurs when PaCO2 is reduced below the “apneic threshold”. Our understanding of the pathophysiology of central sleep apnea has evolved appreciably over the past decade; accordingly, in disorders such as heart failure, central apnea is viewed as a form of breathing instability, manifesting as recurrent cycles of apnea/hypopnea, alternating with hyperpnea. In other words, ventilatory control operates as a negative—feedback closed-loop system to maintain homeostasis of blood gas tensions within a relatively narrow physiologic range, principally PaCO2. Therefore, many authors have adopted the engineering concept of “loop gain” (LG) as a measure of ventilatory instability and susceptibility to central apnea. Increased LG promotes breathing instabilities in a number of medical disorders. In some other conditions, such as with use of opioids, central apnea occurs due to inhibition of rhythm generation within the brainstem. This review will address the pathogenesis, pathophysiologic classification, and the multitude of clinical conditions that are associated with central apnea, and highlight areas of uncertainty.

Introduction Despite increasing evidence that sleep disordered breathing (SDB) is common in women veterans, little is known of how to screen for SDB in this population. Some evidence suggests there are sex-related differences in SDB presentation, where women may be more likely to present with fatigue or depression, compared to men who may present with daytime sleepiness. The goal of this study was to evaluate whether commonly used measures predict SDB in women veterans. Methods Women veterans (N=179) without treated SDB, but with 1 or more SDB risk factors (identified from electronic medical records) completed baseline assessment as part of an ongoing controlled trial of treatment for SDB. Measures included: age, body mass index (BMI), Epworth Sleepiness Scale (ESS), Flinders Fatigue Scale (FSS), Insomnia Severity Index (ISI), Patient-Health Questionnaire 9-item (PHQ-9), STOP-BANG score, and apnea-hypopnea index (AHI via WatchPAT home sleep apnea testing). Descriptive statistics and bivariate correlations testing the relationship between AHI and other measures were performed. Results Mean age was 49.8 [±13.8] years and BMI 29.6 [±6.0] kg/m2. Mean ESS was 8.1, FFS 13.9, ISI 14.0, PHQ-9 7.1, and STOP-BANG score 2.7. Mean AHI was 15.4 [±13.2], where higher AHI correlated with higher BMI (r=0.3, p Conclusion These findings support the use of the STOP-BANG score to predict SDB severity in women veterans with risk factors for SDB. Age and BMI may be particularly important predictors of SDB in this population. Sleepiness, depression, insomnia, and fatigue questionnaires were not related to SDB severity. Further work is needed to understand the role of patient-reported symptoms in those at-risk for SDB and to inform guidelines for the recognition of SDB in this important and understudied population. Support (If Any) VA HSR&D IIR 16-244 and RCS 20-191; NIH/NHLBI K24 HL143055, HRS&D COIN; VAGLAHS GRECC.

Introduction Benzodiazepine receptor agonists (BZAs) are often prescribed for insomnia in older adults. Polypharmacy increases risk of adverse events in this population in general, particularly when medications within the same class are prescribed. During an ongoing hypnotic deprescribing trial, we explored use of more than one BZA (multi-BZA use) and self-reported sleep quality among older adults. Methods Telephone surveys were performed for recruitment to an ongoing BZA deprescribing trial. Participants aged ≥ 55 years who were prescribed at least one BZA (i.e., alprazolam, clonazepam, lorazepam, temazepam, or zolpidem) from a Department of Veterans Affairs pharmacy in Southern California were asked about their use of each BZA over the past 3 months for sleep (yes/no). Multi-BZA use was defined as using > 1 different BZA over the past 3 months. Self-reported sleep items included duration of sleep problems (12 months), sleep quality (very or fairly good, fairly or very bad), and sleep efficiency (mean total sleep time over time in bed). Analyses compared sleep variables between multi-BZA and non-multi-BZA users (Fisher’s Exact or t-tests). Results Among participants (N=359), 152 (42.3%) reported using zolpidem, 41 (11.4%) lorazepam, 39 (10.9%) alprazolam, 31 (8.6%) clonazepam, and 29 (8.1%) temazepam during the past 3 months. 35 (9.8%) participants reported taking more than one of these drugs. 93.9% reported their sleep problems were present for ≥3 months. 68.3% of participants reported their sleep was fairly/very bad, and mean sleep efficiency was 67.9 (SD 18.5). There were no significant differences between multi-BZA versus non-multi-BZA users in duration of sleep complaints (Fisher’s Exact=1.0; p=.842), sleep quality (Fisher’s Exact=0.70; p=0.56) or sleep efficiency (p=0.91). Conclusion We found 1 in 10 older adults prescribed a BZA for sleep reported multi-BZA use over the past 3 months. Multi-BZA use was unrelated to duration of sleep complaints, sleep quality or sleep efficiency. Whether the use was simultaneous or staggered, these findings are concerning, given the elimination half-life of most of the BZAs and that polypharmacy, especially within medication class, may increase risk of adverse events (e.g., falls). Further research is needed to explore factors contributing to multi-BZA use. Support (If Any) NIA R01AG057929, VA IIR 17-234

Introduction In our recent national survey study, 13% of women Veterans reported a diagnosis of Sleep Disordered Breathing (SDB), of whom 65% used positive airway pressure (PAP) treatment. We also found many women Veterans at high risk for SDB were undiagnosed (43%). The current study builds upon this survey research to identify rates of evaluation, diagnosis, treatment, and treatment adherence among women Veterans with risk factors for SDB. Methods We analyzed telephone screening data from an ongoing SDB treatment adherence intervention study for women Veterans in Los Angeles county. A total of 173 women Veterans, identified by retrospective chart review as having at least one risk factor for SDB (i.e. high blood pressure, diabetes, obesity, depression, or > 50 years old), completed the screener. Screening questions included 1) previous diagnostic testing for SDB, 2) SDB diagnosis 3) SDB treatment type, and 4) past week SDB treatment use. Descriptive statistics regarding evaluation and treatment of SDB are reported. Results In total, 31% of respondents endorsed having previously completed diagnostic testing, of whom, 54% reported an SDB diagnosis. Of those with diagnosed SDB, 82.8% were prescribed treatment (PAP [72.4%], oral appliance [6.9%], surgery [3.5%]), and 17.2% did not report being prescribed any SDB treatment. Of the 21 (72.4%) women Veterans diagnosed with SDB that were prescribed PAP, only 33% reported using treatment in the past week. Of the 2 women Veterans (6.9%) prescribed an oral appliance, 0% reported past week use. Conclusion Less than 1/3 of women Veterans with at least one risk factor for SDB had previously been evaluated for SDB; however, over 1/2 of women Veterans who were evaluated tested positive for SDB. Additionally, most women Veterans had not used PAP or oral appliance therapy in the past week. Greater clinical attention is needed to identify, evaluate, and diagnose SDB in women Veterans. Moreover, further research is needed to evaluate and inform interventions to address SDB treatment adherence barriers in women Veterans. Support (if any) VA HSR&D IIR 16–244 and RCS 20–191; NIH/NHLBI K24 HL143055, VAGLAHS GRECC and VA Office of Academic Affiliations.

Introduction Fatigue is a core symptom of Multiple Sclerosis (MS) and impairs function and quality of life. Studies show that sleep-disordered breathing (SDB) is also common in persons with MS and may exacerbate fatigue. Within a larger study of patients with spinal cord injuries and disorders, we evaluated the relationships among sleep-disordered breathing severity, sleep quality, and functional outcomes in patients with MS. Our objective was to examine the impact of SDB severity and sleep quality on the severity of fatigue and functional impairment in this population. Methods Twenty-five subjects (average age=57(11), min=35, max=79; 80% male; average AHI=27(20) min=3, max=70; and 67% with AHI > 15) 24 completed in-laboratory polysomnography (PSG) to measure apnea-hypopnea index (AHI) and sleep efficiency (SE) and questionnaires about sleep and function: Insomnia Severity Index (ISI), Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Flinders Fatigue Scale (FFS), PHQ-9 depression scale (excluding sleep item), Brief Pain Inventory (BPI) and World Health Organization Quality of Life (WHOQOL). Relationships between sleep measures (AHI and SE from PSG, ISI and PSQI) and daytime function (ESS, FFS, PHQ-9, BPI and WHOQOL) were assessed by bivariate correlation. Results At the baseline visit, we assessed participant’s daytime sleepiness, fatigue, sleep quality, and depression. The mean scores on questionnaires: ESS was 8.0(5.6), ISI was 11.5(6.7), PSQI was 9.3(4.4), FFS was 17.3(8.7), BPI severity was 3.4 (3.13), BPI interference was 3.5 (3.5), PHQ-9 was 7.3(5.8). There were significant relationships between ISI and FFS (r=0.78, p Conclusion In veterans with MS, insomnia symptom severity was associated with daytime fatigue and decreased quality of life (QOL). Insomnia may represent a modifiable cause of daytime fatigue in patients with MS. Recognition and management of insomnia may improve outcomes in this population. Further research should evaluate whether insomnia interventions may benefit daytime fatigue and improve QOL. Support (if any) VA Rehabilitation Research and Development Service, (RX002116; PI Badr); VA HSR&D RCS20-191 and NIH/NHLBI K24 HL143055 (PI Martin).

Introduction Sleep disordered breathing (SDB) is underdiagnosed in older women, despite a significant increase in SDB prevalence post-menopause. Few studies have assessed the diagnostic accuracy of SDB screening questionnaires in older women, particularly older Women Veterans (WV). WV have higher rates of SDB compared to non-Veteran women and are particularly vulnerable to sleep disorders in general. We examined the diagnostic accuracy of the STOP questionnaire compared to home sleep apnea testing (HSAT) that includes sleep time estimation (i.e., WatchPAT) in older WV. Methods Cross-sectional baseline data obtained from chart review were combined from two behavioral sleep intervention studies targeting WV with sleep difficulties (i.e., insomnia symptoms) or SDB risk factors (e.g., hypertension, obesity). A total of 136 older WV (50-91y; age=60.0±7.8y) completed the STOP questionnaire (yes/no: snoring, tiredness, observed breathing pauses, and high blood pressure [BP]) and had an apnea-hypopnea index (AHI) available from their baseline HSAT (WatchPAT). Sensitivity, specificity, and positive and negative likelihood ratios (+LR/-LR) were calculated to characterize the diagnostic accuracy of STOP≥2 for AHI≥5 (mild SDB) or AHI≥15 (moderate SDB). Results 70.6% (n=96) of participants endorsed a STOP≥2, 83.8% (n=114) demonstrated an AHI≥5 and 46.3% (n=63) demonstrated an AHI≥15. For AHI≥5, sensitivity was 73.7% (95% CI=64.6,81.5%), specificity was 45.5% (95% CI=24.4,67.8%), +LR was 1.35 (95% CI=0.91, 2.01), and -LR was 0.58 (95% CI=0.33,1.00). For AHI≥15, sensitivity was 76.2% (95% CI=63.8,86%), specificity was 34.2% (95% CI=23.5,46.3%), +LR was 1.16 (95% CI=0.93,1.44), and -LR was 0.70 (95% CI=0.30,1.20). Conclusion The likelihood ratios for STOP≥2 limited the utility of the STOP vs. an HSAT system with sleep scoring in determining AHI. While the STOP correctly identified 3/4 of older WV with SDB on WatchPAT, it correctly identified Support (if any) VA HSR&D IIR-13–058, IIR 16–244 and RCS 20–191; NIH/NHLBI K24 HL143055, VAGLAHS GRECC, VA Office of Academic Affiliations, and AASM Foundation.

Introduction Sleep-disordered breathing (SDB) is highly prevalent among patients with spinal cord injury or disease (SCI/D). In-laboratory polysomnography (PSG) is difficult for these patients due to functional limitations and the physical construction of most sleep laboratories. Our objective was to evaluate the concordance between simulated HSAT and PSG in identifying SDB severity and subtypes of respiratory events in this patient population. Methods Within a larger study, 33 Veterans with SCI/D completed one night of in-laboratory PSG. Limited-channel HSAT was simulated by extracting 5 channels from PSG signals to include nasal pressure, thermistor, thoracic and abdominal belts, and oxygen saturation. Results Mean age of patients was 59.8 ± 10.9 years; 87.9% were male, and the average BMI was 28.1 ± 6.3. The mean Apnea-Hypopnea Index (AHI) from PSG was 35.5 ± 22.7. The mean Respiratory Event Index (REI) based on simulated HSAT was 22.5 ± 18.6. Thirty-one patients (93.9%) had SDB defined as AHI ≥5/hour. Simulated limited-channel HSAT accurately identified 32 out of 33 patients (96.96%). When SDB was further classified into mild (AHI 5-15 events/hr), moderate (AHI 15-30 events/hr), and severe (AHI>30/hr), simulated HSAT consistently underestimated the severity of underlying SDB. Spearman correlation between estimating AHI (PSG-HSAT) and subtypes of respiratory events was primarily accounted for by the difference in the number of hypopneas (r=0.72, -0.021 and -0.001 for hypopneas, obstructive and central apneas, respectively). Conclusion Our findings support the diagnostic utility of HSAT in SCI/D patients with SDB; however, HSAT underestimation of SDB may lead to difficulties in optimizing therapy. The misclassification of SDB severity is mainly driven by the number of hypopneas. Classification of hypopneas as obstrcutive or central may shed further light on the nature of this difference. Further research on the usability of HSAT devices in this patient population is needed. Support VA Rehabilitation Research and Development Service (RX002116; PI Badr and RX002885; PI Sankari) and NIH/NHLBI (K24HL143055; PI: Martin)

Introduction Sleep apnea (SA) is the most commonly diagnosed sleep disorder among patients in the US Veterans Administration (VA). The dramatic rise in women receiving VA care makes it essential to understand the presentation and treatment of SA in women Veterans. We performed a nationwide survey about sleep among US women Veterans and compared characteristics of respondents with and without a self-reported history of SA diagnosis and treatment. Methods A survey was mailed to a random sample of 4000 women VA healthcare users. The survey included demographics, Insomnia Severity Index (ISI), Patient Health Questionnaire-4 (PHQ-4 depression/anxiety), Primary Care-Post-Traumatic Stress Disorder (PC-PTSD), RLS symptom presence, SA symptoms (snore loudly, observed breathing pauses), diagnosis of SA, and use of PAP therapy (APAP, BPAP, CPAP). We compared women with and without SA, and (among those with SA) women who did and did not use PAP, using Chi-square and t-tests. Results 1,498 completed surveys were returned (mean age 51.6 years, range 18-105 years, 62% non-Hispanic White). 200 respondents (13.4%) reported diagnosed SA. Women with SA were older (p Conclusion One in 7 women who receive VA care report diagnosed SA. Women with SA had more mental health symptoms and comorbid sleep problems. Most reported using PAP therapy, although the amount of use is unknown. Those with SA symptoms were more likely to use PAP. Future work is needed to understand barriers to diagnosis and treatment of SA among women Veterans. Support Funding: VA Quality Enhancement Research Initiative RRP12-189 (Martin); NIH/NHLBI K24 HL143055 (Martin).

Introduction Sleep disordered breathing (SDB) is common among individuals with spinal cord injuries or diseases (SCI/D), many of whom are military Veterans, and physical limitations make use of positive airway pressure (PAP) therapy challenging. This study sought to test the effects of an educational and behavioral intervention to improve PAP adherence among Veterans with SCI/D over the first 3 months of use. Methods 63 Veterans (mean age=60.7(10.2) years; 92% male) with SCI/D (33 SCI, 30 SCD; 25 cervical involvement; 38 thoracic and below) and SDB (23 with AHI 5-15; 40 with AHI≥15) who received PAP treatment (CPAP or BPAP) were randomly assigned to receive a comprehensive 3-month intervention (INT) or an equal attention control (EAC). INT and EAC both included 1 face-to-face session (week 1) and 5 additional telephone sessions (weeks 2, 3, 4, 8 and 12). Main outcome measures were PAP use over the first 3 months: nights of use, nights of use ≥4 hours, and mean hours of use per night. Repeated measures ANCOVA models were used to test the differences between INT and EAC over the first 3 months of treatment. Results Number of nights with ≥4 hours of use in months 1-3 was 9, 7, and 6 nights in the INT and 8, 5 and 4 nights in the EAC (p’s≥.37), respectively. There were no significant differences between INT and EAC for number of nights with any use (p’s≥.24), or mean hours of use per night (p’s≥.30). All 3 PAP use variables declined over time in both groups. Conclusion Sustained use of PAP therapy was difficult to achieve among those with SCI/D, and a 6-session behavioral intervention did not lead to significant improvements in use. Even when relatively high levels of initial use are achieved, this is difficult to sustain over time. Future studies should explore whether SCI/D patients experience significant symptom relief with PAP, and if so, whether home-based interventions or more intensive face-to-face PAP adherence programs will be effective. Support VA Rehabilitation Research and Development Service, Merit Review (1RX002116; PI: Badr); NIH/NHLBI K24 HL143055 (Martin).

The prevalence and consequences of central sleep apnea (CSA) in adults are not well described. By utilizing the large Veterans Health Administration (VHA) national administrative databases, we sought to determine the incidence, clinical correlates, and impact of CSA on healthcare utilization in Veterans. Analysis of a retrospective cohort of patients with sleep disorders was performed from outpatient visits and inpatient admissions from fiscal years 2006 through 2012. The CSA group, defined by International Classification of Diseases-9, was compared with a comparison group. The number of newly diagnosed CSA cases increased fivefold during this timeframe; however, the prevalence was highly variable depending on the VHA site. The important predictors of CSA were male gender (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.94–2.76, p < 0.0001), heart failure (HF) (OR = 1.78, 95% CI: 1.64–1.92, p < 0.0001), atrial fibrillation (OR = 1.83, 95% CI: 1.69–2.00, p < 0.0001), pulmonary hypertension (OR = 1.38, 95% CI:1.19–1.59, p < 0.0001), stroke (OR = 1.65, 95% CI: 1.50–1.82, p < 0.0001), and chronic prescription opioid use (OR = 1.99, 95% CI: 1.87–2.13, p < 0.0001). Veterans with CSA were at an increased risk for hospital admissions related to cardiovascular disorders compared with the comparison group (incidence rate ratio [IRR] = 1.50, 95% CI: 1.16–1.95, p = 0.002). Additionally, the effect of prior HF on future admissions was greater in the CSA group (IRR: 4.78, 95% CI: 3.87–5.91, p < 0.0001) compared with the comparison group (IRR = 3.32, 95% CI: 3.18–3.47, p < 0.0001). Thus, CSA in veterans is associated with cardiovascular disorders, chronic prescription opioid use, and increased admissions related to the comorbid cardiovascular disorders. Furthermore, there is a need for standardization of diagnostics methods across the VHA to accurately diagnose CSA in high-risk populations.

STUDY OBJECTIVES: Sleep quality is poor among patients with chronic obstructive pulmonary disease (COPD), and studies show that sleep disturbance is associated with low overall quality of life in this population. We evaluated the impact of patient-reported sleep quality and sleep apnea risk on disease-specific and overall quality of life within patients with COPD enrolled in the SPIROMICS study, after accounting for demographics and COPD disease severity. METHODS: Baseline data from 1341 participants [892 mild/moderate COPD (FEV(1) ≥ 50% predicted); 449 severe COPD (FEV(1) < 50%)] were used to perform three nested (blocks) regression models to predict quality of life (Short Form-12 mental and physical components and St. George’s Respiratory Questionnaire). Dependent measures used for the nested regressions included the following: Block1: demographics and smoking history; Block 2: disease severity (forced expiratory volume 1 s; 6 min walk test); Block 3: risk for obstructive sleep apnea (OSA; Berlin questionnaire); and Block 4: sleep quality (Pittsburgh Sleep Quality Index [PSQI]). RESULTS: Over half of participants with COPD reported poor sleep quality (Mean PSQI 6.4 ± 3.9; 50% with high risk score on the Berlin questionnaire). In all three nested regression models, sleep quality (Block 4) was a significant predictor of poor quality of life, over and above variables included in blocks 1–3. CONCLUSIONS: Poor sleep quality represents a potentially modifiable risk factor for poor quality of life in patients with COPD, over and above demographics and smoking history, disease severity, and risk for OSA. Improving sleep quality may be an important target for clinical interventions. CLINICAL TRIAL: SPIROMICS CLINICAL TRIAL URL: http://www2.cscc.unc.edu/spiromics/ CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01969344

RATIONALE: Current scoring criteria of non-apneic events (ie, hypopnea) require the presence of oxyhemoglobin desaturation and/or arousal. However, other sleep study parameters may help to identify abnormal respiratory events (REs) and assist in making more accurate diagnosis. OBJECTIVES: To investigate whether non-apneic REs without desaturation or cortical arousal are associated with respiratory and cardiac consequences. METHODS: Thirteen participants with sleep disturbances (snoring and/or excessive day time sleepiness), were screened using attended in laboratory polysomnography (PSG) while monitoring pressure and airflow via a nasal mask with an attached pneumotach. To separate the contribution of the upper airway resistance (R(UA)) and total pulmonary resistance (R(L)), supraglottic and esophageal pressures were measured using Millar pressure catheters. R(L) and R(UA) were calculated during baseline and hypopneas. R(L) was defined as the resistive pressure divided by the maximal flow during inspiration and expiration. Hypopnea was defined 30% decrease in flow with 3% desaturation and/or cortical arousal. REs was defined as 30% decrease in the flow without desaturation and/or cortical arousal. In eight subjects continuous positive airway pressure (CPAP) was titrated to optimal pressure. R-R interval (RRI) was defined as consecutive beat-to-beat intervals on single lead electrocardiograph (ECG) during baseline, RE/hypopnea and on optimal CPAP. RESULTS: REs associated with increased expiratory R(UA) (14.6 ± 11.3 vs. 7.5 ± 4.5 cmH(2)O L(−1) s(−1); p < .05), and increased expiratory R(L) relative to baseline (29.2 ± 14.6 vs. 20.9 ± 11.0 and 23.7 ± 12.1 vs. 14.3 ± 5.6 cmH(2)O L(−1) s(−1) during inspiration and expiration, respectively; p < .05). RRI decreased significantly following RE and hypopnea relative to baseline (804.8 ± 33.1 vs. 806.4 ± 36.3 vs. 934.3 ± 45.8 ms; p < .05). Optimal CPAP decreased expiratory R(UA) (4.0 ± 2.5 vs. 7.5 ± 4.5 cmH(2)O L(−1) s(−1); p < .05), decreased inspiratory R(L) (12.6 ± 14.1 vs. 7.5 ± 4.5 cmH(2)O L(−1) s(−1); p < .05), and allowed RRI to return to baseline (p < .05). RRI dips index was an independent predictor of sleep-disordered breathing (SDB) when non-apneic REs were accounted for in symptomatic patients (p < .05). CONCLUSIONS: Non-apneic REs without cortical arousal or desaturation are associated with significant respiratory and heart rate changes. Optimal CPAP and the reduction of resistive load are associated with the normalization of heart rate indicating potential clinical benefit.

STUDY OBJECTIVES Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. DESIGN Randomization to oral finasteride vs. sham, single-center study. SETTING Sleep research laboratory. PARTICIPANTS Fourteen healthy young males without sleep apnea. INTERVENTION Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. MEASUREMENTS AND RESULTS The apnea threshold (AT) was defined as the end-tidal CO₂(P(ET)CO₂) that demarcated the central apnea closest to the eupneic P(ET)CO₂. The CO₂ reserve was defined as the difference in P(ET)CO₂ between eupnea and AT. The apneic threshold and CO₂ reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO₂ reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. CONCLUSIONS Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations.