Search

The prevalence of sleep-disordered breathing (SDB) is higher in older adults compared with younger individuals. The increased propensity for ventilatory control instability in older adults may contribute to the increased prevalence of central apneas. Reductions in the cerebral vascular response to CO(2) may exacerbate ventilatory overshoots and undershoots during sleep. Thus, we hypothesized that hypercapnia-induced cerebral vasodilation (HCVD) will be reduced in older compared with younger adults. In 11 older and 10 younger adults with SDB, blood flow velocity in the middle cerebral artery (MCAV) was measured using Doppler transcranial ultrasonography during multiple steady-state hyperoxic hypercapnic breathing trials while awake, interspersed with room air breathing. Changes in ventilation, MCAV, and mean arterial pressure (MAP) via finger plethysmography during the trials were compared with baseline eupneic values. For each hyperoxic hypercapnic trial, the change (Δ) in MCAV for a corresponding change in end-tidal CO(2) and the HCVD or the change in cerebral vascular conductance (MCAV divided by MAP) for a corresponding change in end-tidal CO(2) was determined. The hypercapnic ventilatory response was similar between the age groups, as was ΔMCAV/Δ [Formula: see text]. However, compared with young, older adults had a significantly smaller HCVD (1.3 ± 0.7 vs. 2.1 ± 0.6 units/mmHg, P = 0.004). Multivariable analyses demonstrated that age and nadir oxygen saturation during nocturnal polysomnography were significant predictors of HCVD. Thus, our data indicate that older age and SDB-related hypoxia are associated with diminished HCVD. We hypothesize that this impairment in vascular function may contribute to breathing instability during sleep in these individuals. NEW & NOTEWORTHY This study demonstrates, for the first time, in individuals with sleep-disordered breathing (SDB) that aging is associated with decreased hypercapnia-induced cerebral vasodilation (HCVD). In addition to advanced age, the magnitude of nocturnal oxygen desaturation due to SDB is an equal independent predictor of HCVD.

Sleep-disordered breathing (SDB) is highly prevalent in adults and leads to significant cardiovascular and neurologic sequelae. Intermittent hypoxia during sleep is a direct consequence of SDB. Administration of nocturnal supplemental oxygen (NSO) has been used as a therapeutic alternative to positive airway pressure (PAP) in SDB. NSO significantly improves oxygen saturation in OSA but is inferior to PAP in terms of reducing apnea severity and may prolong the duration of obstructive apneas. The effect of NSO on daytime sleepiness remains unclear, but NSO may improve physical function-related quality of life in OSA. Its effects on BP reduction remain inconclusive. The effects of NSO vs PAP in OSA with comorbid COPD (overlap syndrome) are unknown. NSO is effective in reducing central sleep apnea related to congestive heart failure; however, its impact on mortality and cardiovascular clinical outcomes are being investigated in an ongoing clinical trial. In conclusion, studies are inconclusive or limited regarding clinical outcomes with oxygen therapy compared with sham or PAP therapy in patients with OSA and overlap syndrome. Oxygen does mitigate central sleep apnea. This review examines the crucial knowledge gaps and suggests future research priorities to clarify the effects of optimal dose and duration of NSO, alone or in combination with PAP, on cardiovascular, sleep, and cognitive outcomes.

BackgroundEvaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). MethodsUsing previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. ResultsThe ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. ConclusionThis review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Introduction Cognitive impairment in older Veterans is an independent predictor of subsequent mortality and disability. Pilot data indicate that patients with OSA-COPD Overlap Syndrome (OVS) may have reduced sleep quality, cognitive function and quality of life (QoL). However, there are no prior systematic studies evaluating treatment paradigms in patients with OVS. Our ongoing clinical trial is investigating whether positive airway pressure (PAP) therapy alleviates sleep disturbances, sleepiness, and improves cognitive function and QoL in older adults with OVS. Methods The design is a prospective parallel group randomized controlled trial in Veterans 60 years and older, with moderate-to-severe OSA with concomitant COPD (OVS). 225 eligible participants will be randomized to two treatment groups (PAP and conservative care) in 2:1 ratio for a duration of 6 months. Participants on the conservative care arm are required to follow good sleep habits and sleep hygiene, and on the PAP arm, in addition, are required to be adherent to PAP treatment (CPAP or Bilevel PAP, as required). Sleep questionnaires are administered to evaluate sleepiness, sleep quality, and general and disease specific QoL. Cognitive function is evaluated using Trail Making Test Part A and B, Paced Auditory Serial Addition Test, Stroop Task, Digit Coding, Hopkins Verbal Learning Test-R, Weschler Abbreviated Scale Intelligence II, Weschler Memory Scale IV, and Psychomotor Vigilance Test, respectively. All tests are administered at baseline visit, 3 months, and 6 months. Results In year-2 of the study, we have screened 7878 Veterans, enrolled 137 participants, randomized 34 participants (31 males, 3 females; age: 70.7±6.6 years, BMI: 29.6±6.7 kg/m2, AHI: 47±22 events/hr, spirometry FEV1: 60.8±11.7% predicted, arterial blood gas (n=22) pCO2:41.2 ±3.6 mmHg, ESS: 1.9 ±2.4); 15 have completed the study per the protocol. Analysis of data will be completed at the end of the RCT. Conclusion Our research seeks to systematically study the effects of treating a novel target (OVS) to maximize daytime function and QoL, while also providing a framework for early treatment of mild cognitive impairment in vulnerable older Veterans. Support (if any) VHA RR&D Merit Award # 1I01RX003124-01

In 2017 the Veterans Administration (VA) and Department of Defense (DOD) launched development of clinical practice guidelines (CPGs) for the diagnosis and treatment of sleep disorders, with the goal of informing and improving patient care. The guideline development process followed GRADE methodology, considering studies and systematic reviews published over the 10-year period prior to guideline development. A total of 41 recommendations were made,18 related to the diagnosis and treatment of obstructive sleep apnea (OSA) and 23 regarding chronic insomnia disorder. In contrast to other published guidelines, the VA DoD CPGs provide a comprehensive approach to diagnosis and management of the two most common sleep disorders, including a discussion of the sequencing of diagnostic approaches and treatment options. Regarding OSA, strong recommendations were made for follow-up evaluation after non-diagnostic home sleep apnea tests, positive airway pressure therapy as first-line treatment, and the incorporation of supportive, educational and behavioral interventions for patients at high risk for PAP therapy non-adherence due to comorbid conditions. Strong recommendations were also made for the use of cognitive-behavioral therapy for insomnia and against the use of kava (an herbal supplement) in the treatment of chronic insomnia disorder. These guidelines, while intended to directly inform care within VA and DOD, are broadly relevant to the practice of sleep medicine. The majority of scientific evidence was based on studies of non-military, non-veteran populations. The CPG is a major milestone for the VA and DOD in recognizing the importance of evidence-based treatments for sleep disorders in military personnel and veterans. CITATION: Martin JL, Mysliwiec V, Chowdhuri S, Ulmer CS. The Veterans Administration and Department of Defense clinical practice guidelines for the diagnosis and management of sleep disorders: what does this mean for the practice of sleep medicine? J Clin Sleep Med. 2020;16(8):1377–1381.

Spinal cord injury (SCI) is an established risk factor for central sleep apnea. Acetazolamide (ACZ), a carbonic anhydrase inhibitor, has been shown to decrease the frequency of central apnea by inducing mild metabolic acidosis. We hypothesized that ACZ would decrease the propensity to develop hypocapnic central apnea and decrease the apneic threshold. We randomized 16 participants with sleep-disordered breathing (8 SCI and 8 able-bodied controls) to receive ACZ (500 mg twice a day for 3 days) or placebo with a 1-wk washout before crossing over to the other drug arm. Study nights included polysomnography and determination of the hypocapnic apneic threshold and CO2 reserve using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal Pco2 ([Formula: see text]) before and after. Steady-state plant gain, the response of end-tidal Pco2 to changes in ventilation, was calculated from [Formula: see text] and V̇e ratio during stable sleep. Controller gain, the response of ventilatory drive to changes in end-tidal Pco2, was defined as the ratio of change in V̇e between control and hypopnea to the ΔCO2 during stable non-rapid eye movement sleep. Treatment with ACZ for three days resulted in widening of the CO2 reserve (−4.0 ± 1.2 vs. −3.0 ± 0.7 mmHg for able-bodied, −3.4 ± 1.9 vs. −2.2 ± 2.2 mmHg for SCI, P < 0.0001), and a corresponding decrease in the hypocapnic apnea threshold (28.3 ± 5.2 vs. 37.1 ± 5.6 mmHg for able-bodied, 29.9 ± 5.4 vs. 34.8 ± 6.9 mmHg for SCI, P < 0.0001), respectively. ACZ significantly reduced plant gain when compared with placebo (4.1 ± 1.7 vs. 5.4 ± 1.8 mmHg/L min for able-bodied, 4.1 ± 2.0 vs. 5.1 ± 1.7 mmHg·L−1·min for SCI, P < 0.01). Acetazolamide decreased apnea-hypopnea index (28.8 ± 22.9 vs. 39.3 ± 24.1 events/h; P = 0.05), central apnea index (0.6 ± 1.5 vs. 6.3 ± 13.1 events/h; P = 0.05), and oxyhemoglobin desaturation index (7.5 ± 8.3 vs. 19.2 ± 15.2 events/h; P = 0.01) compared with placebo. Our results suggest that treatment with ACZ decreases susceptibility to hypocapnic central apnea due to decreased plant gain. Acetazolamide may attenuate central sleep apnea and improve nocturnal oxygen saturation, but its clinical utility requires further investigation in a larger sample of patients. NEW & NOTEWORTHY Tetraplegia is a risk factor for central sleep-disordered breathing (SDB) and is associated with narrow CO2 reserve (a marker of susceptibility to central apnea). Treatment with high-dose acetazolamide for 3 days decreased susceptibility to hypocapnic central apnea and reduced the frequency of central respiratory events during sleep. Acetazolamide may play a therapeutic role in alleviating central SDB in patients with cervical spinal cord injury, but larger clinical trials are needed.

Description In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. Methods In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.

Sleep-disordered breathing (SDB) is highly prevalent in heart failure (HF), and the coexistence of these two disease conditions increases mortality. The purpose of this review is to examine the mechanistic interactions and associations between SBD, specifically obstructive sleep apnea (OSA), obesity hypoventilation (OHS), left ventricular (LV) diastolic heart function, and pulmonary hypertension (PH), as factors that directly contribute to the development of HF. The mechanistic interactions may be thought of as direct and indirect effects. The direct effects are related to abnormalities caused by sleep-disordered breathing that induce LV remodeling. Recent studies support the notion that the severity of OSA and recurrent hypoxia enhance LV remodeling even after accounting for age, weight, and underlying cardiorespiratory comorbid conditions. Indirect effects are due to the mechanical alterations intrathoracic organs during sleep due to negative intrathoracic pressure, obesity, as well as multiple derangements causing activation of the sympathetic nervous system and endothelium. The review also delineates multiple mechanisms that eventually lead to pulmonary vascular remodeling and PH. The severity of daytime arterial oxygen levels and/or duration of nocturnal hypoxia, rather than the severity of SDB, seems to be the major determinants of PH in SBD, after adjusting for other cardiorespiratory diseases. Mechanisms by which hypercapnia contributes to PH and diastolic dysfunction need to be explored. Moreover, interactions between central sleep apnea and diastolic heart function are not well delineated. Further investigations are needed to elucidate any direct effect of hypercapnia on pulmonary pressures and potential cardiovascular consequences. There is limited evidence on the impact of PAP or oxygen therapy on these intermediary mechanisms of HF in SDB populations. The collection of evidence indicates that PAP may enhance diastolic function and reduce pulmonary artery pressure in OSA whereas studies in OHS populations are sparse and inconclusive. Thus, future research should delineate whether pathophysiology-based therapies can alleviate HF and HF related mortality in these SDB populations.

Obstructive sleep apnea (OSA) is common in older adults. However, there is controversy regarding the diagnosis, consequences, and treatment of OSA in this patient population. This review presents the current evidence pertaining to the pathogenesis, diagnosis, complications, and management of OSA in older adults. OSA is prevalent and underdiagnosed in the elderly. A growing body of evidence demonstrates that moderate to severe OSA in older adults is linked to neurocognitive decline and chronic vascular disease, including increased risk of incident heart failure and ischemic stroke. Positive airway pressure therapy remains the mainstay of treatment. Systematic investigations are needed to validate screening tools and diagnostic methods for OSA in elderly and to delineate the subpopulation of elderly in whom therapy is warranted. Targeted approach to diagnosis and treatment needs to be undertaken to avoid the deleterious consequences of sleep apnea in this vulnerable population.

Elderly adults demonstrate increased propensity for breathing instability during sleep compared with younger adults, and this may contribute to increased prevalence of sleep-disordered breathing (SDB) in this population. Hence, in older adults with SDB, we examined whether addition of supplemental oxygen (O(2)) will stabilize breathing during sleep and alleviate SDB. We hypothesized that exposure to supplemental O(2) during non-rapid eye movement (NREM) sleep will stabilize breathing and will alleviate SDB by reducing ventilatory chemoresponsiveness and by widening the carbon dioxide (CO(2)) reserve. We studied 10 older adults with mild-to-moderate SDB who were randomized to undergo noninvasive bilevel mechanical ventilation with exposure to room air or supplemental O(2) (Oxy) to determine the CO(2) reserve, apneic threshold (AT), and controller and plant gains. Supplemental O(2) was introduced during sleep to achieve a steady-state O(2) saturation ≥95% and fraction of inspired O(2) at 40%–50%. The CO(2) reserve increased significantly during Oxy versus room air (−4.2 ± 0.5 mmHg vs. −3.2 ± 0.5 mmHg, P = 0.03). Compared with room air, Oxy was associated with a significant decline in the controller gain (1.9 ± 0.4 L/min/mmHg vs. 2.5 ± 0.5 L/min/mmHg, P = 0.04), with reductions in the apnea-hypopnea index (11.8 ± 2.0/h vs. 24.4 ± 5.6/h, P = 0.006) and central apnea-hypopnea index (1.7 ± 0.6/h vs. 6.9 ± 3.9/h, P = 0.03). The AT and plant gain were unchanged. Thus, a reduced slope of CO(2) response resulted in an increased CO(2) reserve. In conclusion, supplemental O(2) reduced SDB in older adults during NREM sleep via reduction in chemoresponsiveness and central respiratory events. NEW & NOTEWORTHY This study demonstrates for the first time in elderly adults without heart disease that intervention with supplemental oxygen in the clinical range will ameliorate central apneas and hypopneas by decreasing the propensity to central apnea through decreased chemoreflex sensitivity, even in the absence of a reduction in the plant gain. Thus, the study provides physiological evidence for use of supplemental oxygen as therapy for mild-to-moderate SDB in this vulnerable population.

Opioid-induced sleep disordered breathing presents a therapeutic predicament with the increasing incidence of prescription opioid use for noncancer chronic pain in the United States. Central sleep apnea with a Biot or cluster breathing pattern is characteristic of polysomnography studies; however, long-term clinical outcomes and the impact of therapy remain unknown. Novel ampakine-based therapies are being investigated. Randomized controlled trials with therapies that target the underlying pathophysiologic mechanisms of opioid-induced sleep disordered breathing are required.

This guideline establishes clinical practice recommendations for the diagnosis of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Academy of Sleep Medicine (AASM) guidelines on the evaluation and treatment of sleep-disordered breathing in adults.The AASM commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use. In addition, the task force adopted foundational recommendations from prior guidelines as "good practice statements", that establish the basis for appropriate and effective diagnosis of OSA. The AASM Board of Directors approved the final recommendations.The following recommendations are intended as a guide for clinicians diagnosing OSA in adults. Under GRADE, a STRONG recommendation is one that clinicians should follow under most circumstances. A WEAK recommendation reflects a lower degree of certainty regarding the outcome and appropriateness of the patient-care strategy for all patients. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. Good Practice Statements: Diagnostic testing for OSA should be performed in conjunction with a comprehensive sleep evaluation and adequate follow-up. Polysomnography is the standard diagnostic test for the diagnosis of OSA in adult patients in whom there is a concern for OSA based on a comprehensive sleep evaluation.Recommendations: We recommend that clinical tools, questionnaires and prediction algorithms not be used to diagnose OSA in adults, in the absence of polysomnography or home sleep apnea testing. (STRONG). We recommend that polysomnography, or home sleep apnea testing with a technically adequate device, be used for the diagnosis of OSA in uncomplicated adult patients presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA. (STRONG). We recommend that if a single home sleep apnea test is negative, inconclusive, or technically inadequate, polysomnography be performed for the diagnosis of OSA. (STRONG). We recommend that polysomnography, rather than home sleep apnea testing, be used for the diagnosis of OSA in patients with significant cardiorespiratory disease, potential respiratory muscle weakness due to neuromuscular condition, awake hypoventilation or suspicion of sleep related hypoventilation, chronic opioid medication use, history of stroke or severe insomnia. (STRONG). We suggest that, if clinically appropriate, a split-night diagnostic protocol, rather than a full-night diagnostic protocol for polysomnography be used for the diagnosis of OSA. (WEAK). We suggest that when the initial polysomnogram is negative and clinical suspicion for OSA remains, a second polysomnogram be considered for the diagnosis of OSA. (WEAK).

Introduction Lung-to-finger circulation time (LFCT), the time taken for the circulation to reach the fingertips from the lungs, has been shown to correlate inversely with cardiac function (Hosokawa et al. 2015). LFCT can be measured on PSG as the time from the start of rebreathing after a central respiratory event to the nadir of the oxygen desaturation on the SpO2 signal. Patients with congestive heart failure (CHF) have been found to have increased LFCT, with even longer LFCT in patients with Cheyne-Stokes Respirations (CSR). We are reporting a case where LFCT increased throughout a single night by more than 40%. Report of Case A 66-year-old diabetic male with ischemic cardiomyopathy (LVEF 25%), CVA with residual L-sided paresthesias, CKD-IV and hypertension was diagnosed with severe CSA and OSA (AHI 31.5, CAI 13.9, OAI 0.0, MAI 0.2, hypopnea index of 17.4, minimum SpO2 of 80%; supine AHI 56.1). CSR was not mentioned on this diagnostic study. On his titration study, CPAP and BPAP failed to treat CSA, but ASV effectively treated his sleep-disordered breathing; however, he could not be started on ASV due to HFrEF. On a repeat titration after ICD implantation, CSR was prominent in the supine position, on both CPAP and BPAP S/T therapy. Cycle length progressively increased from 40 seconds at the beginning to 57 seconds at the end of the recording, an increase of 42% throughout the night. Circulation time also increased from 31 seconds to over 40 seconds. Scorable central respiratory events resolved but periodicity persisted. Conclusion To our knowledge, this is the first case of CSR with such progressive prolongation in cycle length during a single night. It again raises the question of the role of BPAP S/T in CSR with heart failure, and clarification of the potential use of supplemental oxygen in such situations.

INTRODUCTION: In this case series, five African American patients admitted with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection or coronavirus 2019 syndrome (COVID-19) manifested signs and symptoms of angioedema METHODS: All five patients were tested positive for COVID-19 Three of the five patients presented with shortness of breath requiring mechanical ventilation with subsequent prolonged and complicated hospital courses in the intensive care unit Each developed angioedema of their tongue and lips during their hospital stay without identifying a clear inciting factor The other two patients presented with angioedema to the emergency department and were discharged after a short observation period and evaluation by an ear, nose, throat (ENT) specialist None had prior known episodes of angioedema RESULTS: All five patients with COVID-19 and angioedema were of African American ethnicity and three of the five had severe sequelae, including prolonged ICU hospitalization for acute respiratory distress syndrome and acute renal failure CONCLUSIONS: To our knowledge, this is the first report of a possible association of angioedema with COVID-19 Clinicians may consider monitoring for angioedema in patients with COVID-19 either early or late in the disease course as it may impact the management of disease Angioedema (AE) is a potentially life-threatening condition that presents to the emergency department (ED) and frequently requires hospitalization and monitoring in the intensive care unit (ICU)1,2 AE has been has been classified as hereditary or acquired types3 and may be mediated via release of histamine, bradykinin or both This case series is the first report on the development of AE in patients with the severe acute respiratory syndrome-coronavirus-2 (SARSCoV- 2) or COVID-19 syndrome While COVID-19 presents with varying clinical symptomatology, some of which were recognized only recently4,5, the natural progression of the disease remains under investigation Awareness of the many clinical presentations of this novel coronavirus will allow early diagnosis, triage and management of COVID-19 and its complications

An update of the 2012 systematic review and meta-analyses were performed and a modified-GRADE approach was used to update the recommendation for the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea syndrome (CSAS) related to congestive heart failure (CHF). Meta-analyses demonstrated an improvement in LVEF and a normalization of AHI in all patients. Analyses also demonstrated an increased risk of cardiac mortality in patients with an LVEF of ≤ 45% and moderate or severe CSA predominant sleep-disordered breathing. These data support a Standard level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF > 45% or mild CHF-related CSAS. The application of these recommendations is limited to the target patient populations; the ultimate judgment regarding propriety of any specific care must be made by the clinician.

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.

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO2 reserve (−2.6 ± 0.4 vs. −4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min−1·mmHg−1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.

Sleep-disordered breathing (SDB) is highly prevalent in patients with spinal cord injury (SCI); the exact mechanism(s) or the predictors of disease are unknown. We hypothesized that patients with cervical SCI (C-SCI) are more susceptible to central apnea than patients with thoracic SCI (T-SCI) or able-bodied controls. Sixteen patients with chronic SCI, level T6 or above (8 C-SCI, 8 T-SCI; age 42.5 ± 15.5 years; body mass index 25.9 ± 4.9 kg/m2) and 16 matched controls were studied. The hypocapnic apneic threshold and CO2 reserve were determined using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal CO2 (PetCO2) before and after. Steady-state plant gain (PG) was calculated from PetCO2 and VE ratio during stable sleep. Controller gain (CG) was defined as the ratio of change in VE between control and hypopnea or apnea to the ΔPetCO2. Central SDB was more common in C-SCI than T-SCI (63% vs. 13%, respectively; P < 0.05). Mean CO2 reserve for all participants was narrower in C-SCI than in T-SCI or control group (−0.4 ± 2.9 vs.−2.9 ± 3.3 vs. −3.0 ± 1.2 l·min−1·mmHg−1, respectively; P < 0.05). PG was higher in C-SCI than in T-SCI or control groups (10.5 ± 2.4 vs. 5.9 ± 2.4 vs. 6.3 ± 1.6 mmHg·l−1·min−1, respectively; P < 0.05) and CG was not significantly different. The CO2 reserve was an independent predictor of apnea-hypopnea index. In conclusion, C-SCI had higher rates of central SDB, indicating that tetraplegia is a risk factor for central sleep apnea. Sleep-related hypoventilation may play a significant role in the mechanism of SDB in higher SCI levels.

Rationale: The association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) is complex, bidirectional, and may vary across groups. Understanding which cardiovascular risk factors vary in their relationship to OSA across population groups may improve knowledge of OSA-related CVD susceptibility. Objectives: To better understand the heterogeneity of associations, we assessed whether associations of OSA with cardiovascular risk factors vary by age, sex, and race/ethnicity. Methods: We performed cross-sectional analyses of 1,344 Multi-Ethnic Study of Atherosclerosis participants who underwent overnight full polysomnography, assays of fasting blood, and assessments of cardiovascular risk factors. Risk factors considered were blood pressure, glucose/lipid concentrations, white blood cell (WBC) total and subset counts, and cystatin C. The outcome was the apnea–hypopnea index (AHI). Linear regression analyses with tests for interactions were conducted. Results: The sample had a mean age of 68 ± 9 years. Forty-seven percent of the sample was male, and 32% had moderate or severe OSA (AHI, ≥15). Multivariable adjusted analysis showed significant associations between higher AHI with lower high-density lipoprotein cholesterol and higher diastolic blood pressure and neutrophil counts. Significant interactions with demographic factors were observed. Stronger associations were shown between AHI and higher total WBC count (P(int) = 0.006) and glucose concentrations (P(int) = 0.006) in younger (

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.

An update of the 2012 systematic review and meta-analyses were performed and a modified-GRADE approach was used to update the recommendation for the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea syndrome (CSAS) related to congestive heart failure (CHF). Meta-analyses demonstrated an improvement in LVEF and a normalization of AHI in all patients. Analyses also demonstrated an increased risk of cardiac mortality in patients with an LVEF of ≤ 45% and moderate or severe CSA predominant sleep-disordered breathing. These data support a Standard level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF45% or mild CHF-related CSAS. The application of these recommendations is limited to the target patient populations; the ultimate judgment regarding propriety of any specific care must be made by the clinician.

Control of ventilation occurs at different levels of the respiratory system through a negative feedback system that allows precise regulation of levels of arterial carbon dioxide and oxygen. Mechanisms for ventilatory instability leading to sleep-disordered breathing include changes in the genesis of respiratory rhythm and chemoresponsiveness to hypoxia and hypercapnia, cerebrovascular reactivity, abnormal chest wall and airway reflexes, and sleep state oscillations. One can potentially stabilize breathing during sleep and treat sleep-disordered breathing by identifying one or more of these pathophysiological mechanisms. This review describes the current concepts in ventilatory control that pertain to breathing instability during wakefulness and sleep, delineates potential avenues for alternative therapies to stabilize breathing during sleep, and proposes recommendations for future research.

We hypothesized that hypocapnia is responsible for increased expiratory resistance during NREM sleep. Hypocapnia was induced by hypoxic hyperventilation in 21 subjects (aged 29.4 ± 7.8 yrs, 10 women, BMI 24.4 ± 4.3 kg/m(2)). Isocapnic hypoxia was induced in 12 subjects of whom, 6 underwent hypocapnic hypoxia in the same night. Upper airway resistance (R(UA)) was measured at the linear pressure-flow relationship during inspiration and expiration. Inspiratory flow limitation (IFL) was defined as the dissociation in pressure-flow relationship. (1) Expiratory R(UA) increased during hypocapnic but not isocapnic hypoxia relative to control (11.0 ± 5.6 vs. 8.2 ± 3.6 cm H(2)O/L/s; p < 0.05, and 11.45.0 vs. 10.94.4 cm H(2)O/L/s; p = NS, respectively). (2) No gender difference was found in R(UA) (p = NS). (3) Increased expiratory R(UA) correlated with the IFL change during hypocapnic but not isocapnic hypoxia. (4) No changes were noted in inspiratory R(UA) or IFL. Expiratory R(UA) increased during hypocapnia and was associated with IFL, indicating upper airway narrowing. Gender does not influence the upper airway response to hypocapnic hypoxia.

Prazosin is recommended for treatment of Posttraumatic Stress Disorder (PTSD)-associated nightmares. Level A. Image Rehearsal Therapy (IRT) is recommended for treatment of nightmare disorder. Level A. Systematic Desensitization and Progressive Deep Muscle Relaxation training are suggested for treatment of idiopathic nightmares. Level B. Venlafaxine is not suggested for treatment of PTSD-associated nightmares. Level B. Clonidine may be considered for treatment of PTSD-associated nightmares. Level C. The following medications may be considered for treatment of PTSD-associated nightmares, but the data are low grade and sparse: trazodone, atypical antipsychotic medications, topiramate, low dose cortisol, fluvoxamine, triazolam and nitrazepam, phenelzine, gabapentin, cyproheptadine, and tricyclic antidepressants. Nefazodone is not recommended as first line therapy for nightmare disorder because of the increased risk of hepatotoxicity. Level C. The following behavioral therapies may be considered for treatment of PTSD-associated nightmares based on low-grade evidence: Exposure, Relaxation, and Rescripting Therapy (ERRT); Sleep Dynamic Therapy; Hypnosis; Eye-Movement Desensitization and Reprocessing (EMDR); and the Testimony Method. Level C. The following behavioral therapies may be considered for treatment of nightmare disorder based on low-grade evidence: Lucid Dreaming Therapy and Self-Exposure Therapy. Level C No recommendation is made regarding clonazepam and individual psychotherapy because of sparse data.

Summary of Recommendations: Modifying the sleep environment is recommended for the treatment of patients with RBD who have sleep-related injury. Level A Clonazepam is suggested for the treatment of RBD but should be used with caution in patients with dementia, gait disorders, or concomitant OSA. Its use should be monitored carefully over time as RBD appears to be a precursor to neurodegenerative disorders with dementia in some patients. Level B Clonazepam is suggested to decrease the occurrence of sleep-related injury caused by RBD in patients for whom pharmacologic therapy is deemed necessary. It should be used in caution in patients with dementia, gait disorders, or concomitant OSA, and its use should be monitored carefully over time. Level B Melatonin is suggested for the treatment of RBD with the advantage that there are few side effects. Level B Pramipexole may be considered to treat RBD, but efficacy studies have shown contradictory results. There is little evidence to support the use of paroxetine or L-DOPA to treat RBD, and some studies have suggested that these drugs may actually induce or exacerbate RBD. There are limited data regarding the efficacy of acetylcholinesterase inhibitors, but they may be considered to treat RBD in patients with a concomitant synucleinopathy. Level C The following medications may be considered for treatment of RBD, but evidence is very limited with only a few subjects having been studied for each medication: zopiclone, benzodiazepines other than clonazepam, Yi-Gan San, desipramine, clozapine, carbamazepine, and sodium oxybate. Level C

Rationale: There is increasing evidence of increased ventilatory instability in patients with obstructive sleep apnea (OSA), but previous investigations have not studied whether the hypocapnic apneic threshold is altered in this group. Objectives: To compare the apneic threshold, CO2 reserve, and controller gain between subjects with and without OSA matched for age, sex, and body mass index. Methods: Hypocapnia was induced via nasal mechanical ventilation for 3 minutes. Cessation of mechanical ventilation resulted in hypocapnic central hypopnea or apnea depending upon the magnitude of the hypocapnia. The apnea threshold (PetCO2–AT) was defined as the measured PetCO2 at which the apnea closest to the last hypopnea occurred. The CO2 reserve was defined as the change in PetCO2 between eupneic PetCO2 and PetCO2–AT. Controller gain was defined as the ratio of change in Ve between control and hypopnea or apnea to the ΔPetCO2. Measurements and Main Results: Eleven pairs of subjects were studied. There was no difference in the PetCO2–AT between the two groups. However, the CO2 reserve was smaller in the subjects with OSA (2.2 ± 0.6 mm Hg) compared with the control subjects (4.5 ± 1.4 mm Hg; P < 0.001). The controller gain was increased in the subjects with OSA (3.7 ± 1.3 L/min/mm Hg) compared with the control subjects (1.6 ± 0.5 L/min/mm Hg; P < 0.001). Controller gain decreased and CO2 reserve increased in seven subjects restudied after using continuous positive airway pressure for 1 month. Conclusions: Ventilatory instability is increased in subjects with OSA and is reversible with the use of continuous positive airway pressure.

UNLABELLED Episodic hypoxia (EH) is followed by increased ventilatory motor output in the recovery period indicative of long-term facilitation (LTF). We hypothesized that episodic hypoxia evokes LTF of genioglossus (GG) muscle activity in humans during non-rapid eye movement sleep (NREM) sleep. We studied 12 normal non-flow limited humans during stable NREM sleep. We induced 10 brief (3 min) episodes of isocapnic hypoxia followed by 5 min of room air. Measurements were obtained during control, hypoxia, and at 5, 10, 20, 30 and 40 min of recovery, respectively, for minute ventilation (V(I)), supraglottic pressure (P(SG)), upper airway resistance (R(UA)) and phasic GG electromyogram (EMG(GG)). In addition, sham studies were conducted on room air. During hypoxia there was a significant increase in phasic EMG(GG) (202.7+/-24.1% of control, p

A major burden of morbidity and mortality due to respiratory diseases can be directly related to the cardiovascular (CV) complications of these disorders. Evidence from cross-sectional and longitudinal studies link reduced lung function and cardiovascular diseases. However, the underlying pathogenic mechanisms are unclear. Hypoxia-induced increased sympathetic activity, blood viscosity, or inflammation, among other factors, may mediate the underlying pathogenesis. In addition, sleep-disordered breathing (SDB) has been implicated by association in multiple CV diseases including hypertension, ischemic heart disease, congestive heart failure, arrhythmias, and stroke. However, the exact contribution of SDB, including obstructive and central sleep apneas, to the development of cardiovascular diseases is not fully understood. In this context, the contribution of the new large, prospective, Jackson Heart Study could be significant in that it is designed to answer several of these questions, specifically in the African American population. This review examines the current evidence that links both reduced lung function and SDB to CV diseases.

Continuous positive airway pressure (CPAP) has become the treatment of choice for obstructive sleep apnea syndrome. Successful therapy with CPAP depends greatly on individual patient acceptance and compliance. Current indications for CPAP, including those for mild obstructive sleep apnea, will need to be revisited when results from the longitudinal follow-up of the Wisconsin Cohort and the Sleep Heart Health Study are made available.

The reason for increased sleep-disordered breathing with a predominance of central apneas in the elderly is unknown. We speculate that ventilatory control instability may provide a link between aging and the onset of unstable breathing during sleep. We sought to investigate potential underlying mechanisms in healthy, elderly adults during sleep. We hypothesized that there is 1) a decline in respiratory plasticity or long-term facilitation (LTF) of ventilation and/or 2) increased ventilatory chemosensitivity in older adults during non-, this should be hyphenated, non-rapid rapid eye movement (NREM) sleep. Fourteen elderly adults underwent 15, 1-min episodes of isocapnic hypoxia (EH), nadir O2saturation: 87.0 ± 0.8%. Measurements were obtained during control, hypoxia, and up to 20 min of recovery following the EH protocol, respectively, for minute ventilation (VI), timing, and inspiratory upper-airway resistances (RUA). The results showed the following. 1) Compared with baseline, there was a significant increase in VI(158 ± 11%, P < 0.05) during EH, but this was not accompanied by augmentation of VIduring the successive hypoxia trials nor in VIduring the recovery period (94.4 ± 3.5%, P = not significant), indicating an absence of LTF. There was no change in inspiratory RUAduring the trials. This is in contrast to our previous findings of respiratory plasticity in young adults during sleep. Sham studies did not show a change in any of the measured parameters. 2) We observed increased chemosensitivity with increased isocapnic hypoxic ventilatory response and hyperoxic suppression of VIin older vs. young adults during NREM sleep. Thus increased chemosensitivity, unconstrained by respiratory plasticity, may explain increased periodic breathing and central apneas in elderly adults during NREM sleep.

Objectives: A cohort of postmenopausal women complaining of chronic insomnia for over 6 months and free of hypnotic intake was recruited mostly from the community. Three hundred and ninety-four women were included. The following questions were addressed: How many presents sleep disordered breathing (SDB)? Which type of SDB (upper airway resistance syndrome [UARS] or obstructive sleep apnea syndrome [OSAS]) is the most frequent? Is there a specific upper airway anatomical abnormality in SDB patients predisposing to the syndrome? Population: Subjects were recruited in the community or referred by the Sleep Clinic and all had complaint of chronic poor sleep. Methodology: Questionnaires, visual analog scales, clinical interview, clinical evaluation with work-up, actigraphy, and ambulatory monitoring were used. Second step. Otolaryngologic evaluation, ambulatory sleep monitoring, and reading of results were used. Subjects negative for SDB at ambulatory monitoring had polysomnography (PSG) with pressure transducer/nasal cannula system and esophageal manometry measurements. Results: Population. Three hundred and ninety-four individuals responded to all entry criteria. Ambulatory monitoring identified 194 subjects with OSAS. Two hundred individuals were not recognized with SDB and were submitted to PSG. This further testing showed that 68 subjects had normal breathing, 62 had UARS, and 100 mild OSAS. Based on otolaryngological evaluation, subjects were classified based on the presence or absence of narrow upper airway, and the location of narrowing was assessed. Conclusion: A total of 326 postmenopausal women complaining of chronic insomnia had a SDB, usually with low apnea–hypopnea index (AHI). This total represents about 83% of the studied women. Questions of the role of SDB in the complaint of chronic insomnia are raised.

Objective: The question addressed here is: Can a discrete sleep disordered breathing (SDB) play a role in the insomnia complaint of postmenopausal chronic insomniacs? To respond to the query, two groups of individuals derived from a cohort of postmenopausal chronic insomniacs recruited mostly from the community were enlisted in a treatment protocol. These subjects were all individuals identified with normal breathing (n=68) and all those recognized with Upper Airway Resistance Syndrome (UARS) (n=62) pooled from a cohort of 349 postmenopausal insomniacs. Treatment protocol: The 62 UARS were allocated to either treatment of chronic insomnia by behavioral approaches or treatment of SDB. Based on ENTevaluation, health professionals in charge of patients selected either treatment with nasal CPAP or treatment of nasal turbinates. A stratification correction was performed to obtain a near equal number of both treatment modalities in each of the two subgroups. The 68 individuals with normal breathing were randomly allocated to immediate behavioral treatment of insomnia ordelaytreatment ofinsomnia. Thedelaytreatment receivedalistof 10 sleep hygiene recommendations by mail. Methodology: Questionnaires, visual analog scales (VAS), Epworth Sleepiness Scale (ESS), clinical interviews, clinical evaluation with otolaryngologic clinical assessment of a presence/absence of narrow upper airway and location of narrowing. Actigraphy and polysomnography (PSG) with pressure transducer/and nasal cannula system and esophageal manometry. Data analyses: All recording data were scored blind to patient’s condition. Results: Two subjects in the SBD-CPAP treated group (Group B) and two subjects in the delayed treatment group (Group D) dropped out. Total sleep time was improved compared to baseline in all groups, including the delayed treatment group. One group was significantly better (ANOVA, P=.05) with a more important d score compared to baseline, and this was the behaviorally treated non-SDB. Sleep latency was significantly decreased in the behaviorally treated group (with or without SBD), P=.05, compared to SBD-treated and delayed treatment groups. Sleep latency was, however, improved in all groups. VAS for ‘‘quality of sleep’’ was higher at 6 months in all the groups when compared to ‘‘baseline’’ values. VAS for ‘‘daytime fatigue’’ showed significant differences among the four groups (ANOVA, P=.01); the overall score at the end of treatment was significantly better in the SDB-treated group than the other three groups.SBDwastreatedeitherbyradiofrequencyonnasalturbinate orbynasalCPAP.CPAP-treatedpatientshadalowerVASscorethan nasal turbinate treatment, but the difference was only a trend. The d improvement (6-month baseline condition) in ‘‘daytime fatigue’’ of each subgroup was calculated and compared within and between groups. Despite the small number of subjects, the turbinate-treated subgroup was significantly different from Groups B, C and D (ANOVA, P=.05). When a similar comparison was made with the nasal CPAP group, there was only a nonsignificant trend when compared to Groups B, C and D. Conclusion: Abnormal breathing duringsleep significantly enhanced complaintsofdaytimefatigue in postmenopausal chronic insomniacs and this complaint improved with SDB treatment. This improvement is significantly better compared to SDB insomniacs treated with a behavioral regimen. Behavioral treatment, however, gave the best response in the nonSDBchronicinsomniagroupandimproved better longsleeplatency even in the SDB group. These results suggest the need to find an appropriate treatment for SBD even if mild and to recognize the role of SDB in relation to symptoms seen with chronic insomnia. D 2002 Elsevier Science Inc. All rights reserved.

Dr. Cranston and colleagues should be commended for the thorough job they did expanding upon the foundation of the article, “Best Practice Guide for the Treatment of Nightmare Disorder in Adults.”1 The authors have 3 criticisms of the article: (1) the methodology was used inconsistently at updated time points; (2) the article was missing references that were within the search criteria and therefore not reported; and (3) the search database used was insufficient. In the following sections, these concerns are addressed.