The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines.

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.

An Official American Thoracic Society Research Statement: Impact of Mild Obstructive Sleep Apnea in Adults.

BACKGROUND: Mild obstructive sleep apnea (OSA) is a highly prevalent disorder in adults; however, whether mild OSA has significant neurocognitive and cardiovascular complications is uncertain. OBJECTIVES: The specific goals of this Research Statement are to appraise the evidence regarding whether long-term adverse neurocognitive and cardiovascular outcomes are attributable to mild OSA in adults, evaluate whether or not treatment of mild OSA is effective at preventing or reducing these adverse neurocognitive and cardiovascular outcomes, delineate the key research gaps, and provide direction for future research agendas. METHODS: Literature searches from multiple reference databases were performed using medical subject headings and text words for OSA in adults as well as by hand searches. Pragmatic systematic reviews of the relevant body of evidence were performed. RESULTS: Studies were incongruent in their definitions of "mild" OSA. Data were inconsistent regarding the relationship between mild OSA and daytime sleepiness. However, treatment of mild OSA may improve sleepiness in patients who are sleepy at baseline and improve quality of life. There is limited or inconsistent evidence pertaining to the impact of therapy of mild OSA on neurocognition, mood, vehicle accidents, cardiovascular events, stroke, and arrhythmias. CONCLUSIONS: There is evidence that treatment of mild OSA in individuals who demonstrate subjective sleepiness may be beneficial. Treatment may also improve quality of life. Future research agendas should focus on clarifying the effect of mild OSA and impact of effective treatment on other neurocognitive and cardiovascular endpoints as detailed in the document.

Prevalence of central sleep apnea among veterans and response rate to continuous positive airway pressure therapy.

Study Objectives: Sleep-disordered breathing (SDB) is common in the Veteran population. In this retrospective study, we investigated the prevalence of comorbid central and obstructive SDB and the response rate to PAP among Veterans. Methods: Veterans were screened from a single VA medical center who had polysomnography (PSG) study from 2017 to 2021 to ascertain the presence, severity, and type of SDB by measuring the apnea-hypopnea index (AHI) and central apnea index (CAI). Patients were excluded if they did not have complete studies (diagnostic and PAP titration studies). The inclusion criteria for these analyses were central sleep apnea (CSA) defined as AHI ≥ 10 events/hour and CAI ≥ 5 events/hour. Diagnostic "CSA only" was defined as AHI ≥ 10 events/hour and CAI ≥ 50% of AHI. "OSA only" was defined if AHI ≥ 10 events/hour and CAI < 5 events/hour. Comorbid central and obstructive sleep apnea (COSA) was defined if AHI ≥ 10 events/hour and CAI > 5 events/hour but < 50% of AHI. The responsiveness to PAP therapy was determined based on the CAI < 5 events/hour on the titration study. Results: A total of 90 patients met the inclusion criteria and from those 64 Veterans were found to have COSA (71%), 18 (20%) were CSA only, and 8 (9%) were OSA only. A total of 22 (24.4%) Veterans diagnosed with CSA or COSA were responsive to PAP therapy. Sixty days after treatment initiation, both responsive and nonresponsive groups had significant decreases in AHI and CAI (p < 0.05). Conclusions: Comorbid central and obstructive SDB is common among Veterans. The response to PAP therapy is suboptimal but improves over time.

International Consensus Statement on Obstructive Sleep Apnea.

BACKGROUND: Evaluation 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). METHODS: Using 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. RESULTS: The 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. CONCLUSION: This 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.

Tetraplegia is associated with increased hypoxic ventilatory response during nonrapid eye movement sleep.

People with cervical spinal cord injury (SCI) are likely to experience chronic intermittent hypoxia while sleeping. The physiological effects of intermittent hypoxia on the respiratory system during spontaneous sleep in individuals with chronic cervical SCI are unknown. We hypothesized that individuals with cervical SCI would demonstrate higher short- and long-term ventilatory responses to acute intermittent hypoxia (AIH) exposure than individuals with thoracic SCI during sleep. Twenty participants (10 with cervical SCI [9 male] and 10 with thoracic SCI [6 male]) underwent an AIH and sham protocol during sleep. During the AIH protocol, each participant experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2 ) and 40% carbon dioxide (CO2 ) to achieve an oxygen saturation of less than 90%. This was followed by two breaths of 100% oxygen (O2 ). Measurements were collected before, during, and 40 min after the AIH protocol to obtain ventilatory data. During the sham protocol, participants breathed room air for the same amount of time that elapsed during the AIH protocol and at approximately the same time of night. Hypoxic ventilatory response (HVR) during the AIH protocol was significantly higher in participants with cervical SCI than those with thoracic SCI. There was no significant difference in minute ventilation (V.E. ), tidal volume (V.T. ), or respiratory frequency (f) during the recovery period after AIH in cervical SCI compared to thoracic SCI groups. Individuals with cervical SCI demonstrated a significant short-term increase in HVR compared to thoracic SCI. However, there was no evidence of ventilatory long-term facilitation following AIH in either group.

Increased propensity for central apnea in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure.

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 (Pet(CO2)-AT) was defined as the measured Pet(CO2) at which the apnea closest to the last hypopnea occurred. The CO2 reserve was defined as the change in Pet(CO2) between eupneic Pet(CO2) and Pet(CO2)-AT. Controller gain was defined as the ratio of change in Ve between control and hypopnea or apnea to the DeltaPet(CO2). MEASUREMENTS AND MAIN RESULTS: Eleven pairs of subjects were studied. There was no difference in the Pet(CO2)-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.

Oxygen Therapy in Sleep-Disordered Breathing.

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.

Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults.

BACKGROUND: Practice parameters for the treatment of obstructive sleep apnea syndrome (OSAS) in adults by surgical modification of the upper airway were first published in 1996 by the American Academy of Sleep Medicine (formerly ASDA). The following practice parameters update the previous practice parameters. These recommendations were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. METHODS: A systematic review of the literature was performed, and the GRADE system was used to assess the quality of evidence. The findings from this evaluation are provided in the accompanying review paper, and the subsequent recommendations have been developed from this review. The following procedures have been included: tracheostomy, maxillo-mandibular advancement (MMA), laser assisted uvulopalatoplasty (LAUP), uvulopalatopharyngoplasty (UPPP), radiofrequency ablation (RFA), and palatal implants. RECOMMENDATIONS: The presence and severity of obstructive sleep apnea must be determined before initiating surgical therapy (Standard). The patient should be advised about potential surgical success rates and complications, the availability of alternative treatment options such as nasal positive airway pressure and oral appliances, and the levels of effectiveness and success rates of these alternative treatments (Standard). The desired outcomes of treatment include resolution of the clinical signs and symptoms of obstructive sleep apnea and the normalization of sleep quality, the apnea-hypopnea index, and oxyhemoglobin saturation levels (Standard). Tracheostomy has been shown to be an effective single intervention to treat obstructive sleep apnea. This operation should be considered only when other options do not exist, have failed, are refused, or when this operation is deemed necessary by clinical urgency (Option). MMA is indicated for surgical treatment of severe OSA in patients who cannot tolerate or who are unwilling to adhere to positive airway pressure therapy, or in whom oral appliances, which are more often appropriate in mild and moderate OSA patients, have been considered and found ineffective or undesirable (Option). UPPP as a sole procedure, with or without tonsillectomy, does not reliably normalize the AHI when treating moderate to severe obstructive sleep apnea syndrome. Therefore, patients with severe OSA should initially be offered positive airway pressure therapy, while those with moderate OSA should initially be offered either PAP therapy or oral appliances (Option). Use of multi-level or stepwise surgery (MLS), as a combined procedure or as stepwise multiple operations, is acceptable in patients with narrowing of multiple sites in the upper airway, particularly if they have failed UPPP as a sole treatment (Option). LAUP is not routinely recommended as a treatment for obstructive sleep apnea syndrome (Standard). RFA can be considered as a treatment in patients with mild to moderate obstructive sleep apnea who cannot tolerate or who are unwilling to adhere to positive airway pressure therapy, or in whom oral appliances have been considered and found ineffective or undesirable (Option). Palatal implants may be effective in some patients with mild obstructive sleep apnea who cannot tolerate or who are unwilling to adhere to positive airway pressure therapy, or in whom oral appliances have been considered and found ineffective or undesirable (Option). Postoperatively, after an appropriate period of healing, patients should undergo follow-up evaluation including an objective measure of the presence and severity of sleep-disordered breathing and oxygen saturation, as well as clinical assessment for residual symptoms. Additionally, patients should be followed over time to detect the recurrence of disease (Standard). CONCLUSIONS: While there has been significant progress made in surgical techniques for the treatment of OSA, there is a lack of rigorous data evaluating surgical modifications of the upper airway. Systematic and methodical investigations are needed to improve the quality of evidence, assess additional outcome measures, determine which populations are most likely to benefit from a particular procedure or procedures, and optimize perioperative care.

Central sleep apnoea.

Central sleep apnoea (CSA) is characterized by the cessation of breathing during sleep due to absent ventilatory drive and may be associated with symptoms of insomnia, excessive daytime sleepiness or frequent arousals. Central apnoeas occur through two pathophysiologic patterns, either post- hyperventilation or post-hypoventilation. The prevalence of CSA is dependent on the population being studied, the predominant risk factors being elderly age group and co-morbid conditions.Data regarding the racial distribution of this disorder are very limited. CSA may be a clinical marker of underlying medical disorders, including cardiac or neurological disease, with resultant significant morbidity and mortality. Given that the underlying pathogenesis remains poorly understood, therapeutic options are currently limited to empiric treatment with PAP devices and rudimentary attempts at pharmacologic therapy with respiratory stimulant drugs and/or oxygen/carbon dioxide gas supplementation as well as treating the underlying cause. The long-term impact of CSA on health and mortality needs further clarification. Future research should be aimed at elucidating the physiologic determinants and consequences of central breathing instability in populations of different age groups, gender and racial descent, as a prerequisite to the development of novel therapeutic interventions in the different populations.

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?

None: 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.

Effect of acetazolamide on susceptibility to central sleep apnea in chronic spinal cord injury.

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 (PETCO2) before and after. Steady-state plant gain, the response of end-tidal Pco2 to changes in ventilation, was calculated from PETCO2 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.

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep.

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<0.01) and in V (I) (123.0+/-3.3% of control, p<0.05); however, only phasic EMG(GG) demonstrated a significant persistent increase throughout the recovery. (198.9+/-30.9%, 203.6+/-29.9% and 205.4+/-26.4% of control, at 5, 10, and 20 min of recovery, respectively, p<0.01). In multivariate regression analysis, age and phasic EMG(GG) activity during hypoxia were significant predictors of EMG(GG) at recovery 20 min. No significant changes in any of the measured parameters were noted during sham studies. CONCLUSION: (1) EH elicits LTF of GG in normal non-flow limited humans during NREM sleep, without concomitant ventilatory or mechanical LTF. (2) GG activity during the recovery period correlates with the magnitude of GG activation during hypoxia, and inversely with age.

Apnea in Older Adults.

Sleep-disordered breathing (SDB) is a highly prevalent chronic disease in older adults. A growing body of evidence demonstrates that SDB in older adults is linked to many adverse cardiovascular, neurocognitive, and metabolic sequelae. However, several unanswered questions remain regarding the diagnosis, consequences, and treatment of SDB in older adults. This review presents the current evidence pertaining to the management of SDB in older adults and identifies crucial gaps in knowledge that need further investigation.

Aging is associated with increased propensity for central apnea during NREM sleep.

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.

Correlates and consequences of central sleep apnea in a national sample of US veterans.

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.

Cardiovascular complications of respiratory diseases.

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 for the treatment of sleep apnea.

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.

Sleep Disordered Breathing Caused by Chronic Opioid Use: Diverse Manifestations and Their Management.

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.

Control of Ventilation in Health and Disease.

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.