Sleep health and quality of life in the Detroit Research on Cancer Survivors cohort.

PURPOSE: Sleep disturbances represent a modifiable target to improve quality of life and longer-term outcomes in cancer survivors. However, the association between sleep health and overall quality of life in African American cancer survivors has been poorly assessed, a population at increased risk for morbidity and mortality. METHODS: Seven hundred and eighteen Detroit Research on Cancer Survivors (ROCS) cohort participants completed a supplemental sleep survey at the time of enrollment, which included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Insomnia Severity Index (ISI). Linear and logistic regression was used to evaluate the association between sleep and mental health, while block regression models were used to estimate the contribution of clustered factors to Health-Related Quality of Life (HRQOL). RESULTS: Nearly 60% of the cohort reported symptoms indicative of poor sleep quality on the PSQI, 15% reported excessive daytime sleepiness on the ESS, and 12% reported moderate to severe insomnia on the ISI. Survivors with elevated ISI scores reported FACT-G scores that were 17 points lower than those without symptoms of insomnia (95% CI: - 13.1, - 21.2). Poor sleep health accounted for the largest proportion of variability in FACT-G scores (R2 = 0.27) and change in R2 value (0.18) when compared to comorbidities, health behaviors, cancer-related factors, and demographics. CONCLUSIONS: Overall sleep health was significantly associated with poorer HRQOL and variability in FACT-G scores. Additional studies investigating a causal relationship between sleep and HRQOL are needed to determine whether sleep quality could affect disparities in cancer outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Addressing sleep quality in cancer survivors may improve long-term health and HRQOL.

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.

Intensive support does not improve positive-airway pressure use in spinal cord injury/disease: a randomized clinical trial.

STUDY OBJECTIVE: Treatment of sleep-disordered breathing (SDB) with positive airway pressure (PAP) therapy has unique clinical challenges in individuals living with spinal cord injuries and diseases (spinal cord injury [SCI]/D). Interventions focused on increasing PAP use have not been studied in this population. We aimed to evaluate the benefits of a program to increase PAP use among Veterans with SCI/D and SDB. METHODS: Randomized controlled trial comparing a behavioral Intervention (n = 32) and educational control (n = 31), both including one face-to-face and five telephone sessions over 3 months. The intervention included education about SDB and PAP, goal setting, troubleshooting, and motivational enhancement. The control arm included non-directive sleep education only. RESULTS: Primary outcomes were objective PAP use (nights ≥4 hours used within 90 days) and sleep quality (Pittsburgh Sleep Quality Index [PSQI] at 3 months). These did not differ between intervention and control (main outcome timepoint; mean difference 3.5 [-9.0, 15.9] nights/week for PAP use; p = .578; -1.1 [-2.8, 0.6] points for PSQI; p = .219). Secondary outcomes included fatigue, depression, function, and quality of life. Only fatigue improved significantly more in the intervention versus the control group (p = .025). Across groups, more PAP use was associated with larger improvements in sleep quality, insomnia, sleepiness, fatigue, and depression at some time points. CONCLUSIONS: PAP use in Veterans with SCI/D and SDB is low, and a 3-month supportive/behavioral program did not show significant benefit compared to education alone. Overall, more PAP use was associated with improved symptoms suggesting more intensive support, such as in-home assistance, may be required to increase PAP use in these patients. CLINICAL TRIALS INFORMATION: Title: "Treatment of Sleep Disordered Breathing in Patients with SCI." Registration number: NCT02830074. Website: https://clinicaltrials.gov/study/NCT02830074?cond=Sleep%20Apnea&term=badr&rank=5.

Medication-Induced Central Sleep Apnea: A Unifying Concept.

Medication-induced central sleep apnea (CSA) is one of the 8 categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioids medications including sodium oxybate, baclofen, valproic acid, gabapentin and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.

Feasibility of oropharyngeal and respiratory muscle training in individuals with OSA and spinal cord injury or disease: A pilot study.

OBJECTIVES: To examine the feasibility of individuals with spinal cord injury or disease (SCI/D) to perform combined oropharyngeal and respiratory muscle training (RMT) and determine its impact on their respiratory function. METHODS: A prospective study at a single Veterans Affairs (VA) Medical Center. Inclusion criteria included: 1) Veterans with chronic SCI/D (>6 months postinjury and American Spinal Injury Association (ASIA) classification A-D) and 2) evidence of OSA by apnea-hypopnea index (AHI ≥5 events/h). Eligible participants were randomly assigned to either an experimental (exercise) group that involved performing daily inspiratory, expiratory (using POWERbreathe and Expiratory Muscle Strength Trainer 150 devices, respectively), and tongue strengthening exercises or a control (sham) group that involved using a sham device, for a 3-month period. Spirometry, maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), polysomnography, and sleep questionnaires were assessed at baseline and at 3 months. RESULTS: Twenty-four individuals were randomized (12 participants in each arm). A total of eight (67%) participants completed the exercise arm, and ten (83%) participants completed the sham arm. MIP was significantly increased (p < 0.05) in the exercise group compared with the baseline. CONCLUSIONS: Combined oropharyngeal and RMT are feasible for individuals with SCI/D. Future studies are needed to determine the clinical efficacy of these respiratory muscle exercises.

The Clinical Relevance of Autonomic Dysfunction, Cerebral Hemodynamics, and Sleep Interactions in Individuals Living With SCI.

A myriad of physiological impairments is seen in individuals after a spinal cord injury (SCI). These include altered autonomic function, cerebral hemodynamics, and sleep. These physiological systems are interconnected and likely insidiously interact leading to secondary complications. These impairments negatively influence quality of life. A comprehensive review of these systems, and their interplay, may improve clinical treatment and the rehabilitation plan of individuals living with SCI. Thus, these physiological measures should receive more clinical consideration. This special communication introduces the under investigated autonomic dysfunction, cerebral hemodynamics, and sleep disorders in people with SCI to stakeholders involved in SCI rehabilitation. We also discuss the linkage between autonomic dysfunction, cerebral hemodynamics, and sleep disorders and some secondary outcomes are discussed. Recent evidence is synthesized to make clinical recommendations on the assessment and potential management of important autonomic, cerebral hemodynamics, and sleep-related dysfunction in people with SCI. Finally, a few recommendations for clinicians and researchers are provided.

Respiratory disorders and their association with clinical outcomes in COVID-19: a narrative review of current literature.

BACKGROUND AND OBJECTIVE: The coronavirus disease 2019, also known as COVID-19, has caused significant worldwide morbidity and mortality. Given the direct effect of severe acute respiratory syndrome virus-2 (SARS-CoV-2) on the respiratory system, it is important that clinicians who manage chronic respiratory conditions are familiar with the pathophysiology and impact of COVID-19 on pre-existing respiratory disease. METHODS: Literature review relating to COVID-19 and respiratory disorders from PubMed and Google Scholar was conducted, with aim to encompass all publications relating to the most commonly encountered respiratory diseases in clinical practice, namely chronic obstructive lung disease (COPD), asthma, interstitial lung disease (ILD), obstructive sleep apnea (OSA), as well as obesity given it's known effect on both gas exchange and mechanistic aspects of respiration. The publications were analyzed for relevance to clinical implications and pathophysiologic mechanisms. Additional manual literature review was conducted based on citations from large review articles and society guidelines/statement papers. KEY CONTENT AND FINDINGS: Certain respiratory disorders such as COPD, ILD, OSA, and obesity carry higher burden of morbidity and mortality associated with COVID-19. Surprisingly, and in contrast to previously studied viral epidemics, asthma does not carry increased associated risk of contracting the virus or worse clinical outcomes. CONCLUSIONS: A thorough understanding of the mechanisms responsible for control of breathing and the effect of COVID-19 on pulmonary pathophysiology will allow clinicians who manage chronic respiratory disease to effectively predict associated clinical outcomes as well as improve management strategies.

Racial differences in upper airway collapsibility and loop gain in young adult males.

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.

Insomnia severity predicts depression, anxiety, and posttraumatic stress disorder in veterans with spinal cord injury or disease: a cross-sectional observational study.

STUDY OBJECTIVES: To assess the association of insomnia symptoms and psychiatric symptoms in patients with spinal cord injury or disease (SCI/D). METHODS: In this cross-sectional observational study, veterans with SCI/D (n = 72; mean = 59.85 ± 10.4 years; 92% male) completed baseline measures, including the Insomnia Severity Index (ISI) during the baseline phase of a clinical trial on treatment of sleep disorders in veterans with SCI/D. Depression severity was measured by the Patient Health Questionnaire (PHQ-9; sleep items excluded), anxiety severity was measured by the Generalized Anxiety Disorder screener (GAD-7), and probable posttraumatic stress disorder (PTSD) was measured by the Primary Care PTSD screener. Blocked regression was used to evaluate the impact of insomnia symptoms (ISI) on mental health measures after accounting for demographics and level of spinal cord injury/disease. RESULTS: On average, participants scored in the mild range for depression (PHQ-9 = 7.4 ± 5.9) and anxiety severity (GAD-7 = 6.1 ± 6.1). In total, 36.1% (n = 26) screened positive for probable PTSD. ISI explained 19% of the variance in PHQ-9 and 20% of the variance in GAD-7 (P < .001) over and above demographics and SCI/D level of injury/disease. Odds of probable PTSD were increased 1.22-fold for each 1 unit increase in ISI (P = .001) after accounting for demographics and level of injury/disease. CONCLUSIONS: In veterans with SCI/D, insomnia severity was linked to depression and anxiety symptom severity and risk of PTSD. Study results warrant further research to evaluate the impact of insomnia treatment on depression, anxiety, and PTSD in patients with SCI/D. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment of Sleep-disordered Breathing in Patients With SCI; URL: https://clinicaltrials.gov/ct2/show/NCT02830074; Identifier: NCT02830074. CITATION: Kelly MR, Zeineddine S, Mitchell MN, et al. Insomnia severity predicts depression, anxiety, and posttraumatic stress disorder in veterans with spinal cord injury or disease: a cross-sectional observational study. J Clin Sleep Med. 2023;19(4):695-701.

Identifying gaps in clinical evaluation and treatment of sleep-disordered breathing in women veterans.

PURPOSE: Sleep-disordered breathing (SDB) is a common sleep disorder in veterans; however, limited research exists in women veterans. We sought to estimate patterns of care in terms of evaluation, diagnosis, and treatment among women veterans with factors associated with elevated SDB risk. METHODS: Within one VA healthcare system, women identified through electronic health record data as having one or more factors (e.g., age >50 years, hypertension) associated with SDB, completed telephone screening in preparation for an SDB treatment study and answered questions about prior care related to SDB diagnosis and treatment. RESULTS: Of 319 women, 111 (35%) reported having completed a diagnostic sleep study in the past, of whom 48 (43%) were diagnosed with SDB. Women who completed a diagnostic study were more likely to have hypertension or obesity. Those who were diagnosed with SDB based on the sleep study were more likely to have hypertension, diabetes, or be ≥50 years old. Of the 40 women who received treatment, 37 (93%) received positive airway pressure therapy. Only 9 (24%) had used positive airway pressure therapy in the prior week. Few women received other treatments such as oral appliances or surgery. CONCLUSIONS: Findings support the need for increased attention to identification and management of SDB in women veterans, especially those with conditions associated with elevated SDB risk.

Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea.

PURPOSE: Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnotic zolpidem on the frequency of respiratory-related arousals and central apnea in patients with moderate-to-severe SDB. We hypothesized that zolpidem decreases the severity of SDB by decreasing the frequency of respiratory-related arousals. METHODS: Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5 mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO2 reserve and the respiratory arousal threshold, were also compared. RESULTS: Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO2 reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86 mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmH2O, P = 0.41). CONCLUSION: Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO2 reserve or increase the arousal threshold. TRIAL REGISTRATION: Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).

Central sleep apnea: pathophysiologic classification.

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.

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.

Central sleep apnea.

Central apnea syndrome is a disorder with protean manifestations and concomitant conditions. It can occur as a distinct clinical entity or as part of another clinical syndrome. The pathogenesis of central sleep apnea (CSA) varies depending on the clinical condition. Sleep-related withdrawal of the ventilatory drive to breathe is the common denominator among all cases of central apnea, whereas hypocapnia is the final common pathway leading to apnea in the majority of central apnea. Medical conditions most closely associated with CSA include heart failure, stroke, spinal cord injury, and opioid use, among others. Nocturnal polysomnography is the standard diagnostic method, including measurement of sleep and respiration. The latter includes detection of flow, measurement of oxyhemoglobin saturation and detection of respiratory effort. Management strategy incorporates clinical presentation, associated conditions, and the polysomnographic findings in an individualized manner. The pathophysiologic heterogeneity may explain the protean clinical manifestations and the lack of a single effective therapy for all patients. While research has enhanced our understanding of the pathogenesis of central apnea, treatment options are extrapolated from treatment of obstructive sleep apnea. Co-morbid conditions and concomitant obstructive sleep apnea influence therapeutic approach significantly. Therapeutic options include positive pressure therapy, pharmacologic therapy, and supplemental Oxygen. Continuous positive airway pressure (CPAP) is the initial standard of care, although the utility of other modes of positive pressure therapy, as well as pharmacotherapy and device-based therapies, are currently being investigated.

Daily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male Patients with Obstructive Sleep Apnea and Hypertension.

Rationale: Daily exposure to mild intermittent hypoxia (MIH) may elicit beneficial cardiovascular outcomes. Objectives: To determine the effect of 15 days of MIH and in-home continuous positive airway pressure treatment on blood pressure in participants with obstructive sleep apnea and hypertension. Methods: We administered MIH during wakefulness 5 days/week for 3 weeks. The protocol consisted of twelve 2-minute bouts of hypoxia interspersed with 2 minutes of normoxia. End-tidal carbon dioxide was maintained 2 mm Hg above baseline values throughout the protocol. Control participants were exposed to a sham protocol (i.e., compressed air). All participants were treated with continuous positive airway pressure over the 3-week period. Results are mean ± SD. Measurements and Main Results: Sixteen male participants completed the study (experimental n = 10; control n = 6). Systolic blood pressure at rest during wakefulness over 24 hours was reduced after 15 days of MIH (142.9 ± 8.6 vs. 132.0 ± 10.7 mm Hg; P < 0.001), but not following the sham protocol (149.9 ± 8.6 vs. 149.7 ± 10.8 mm Hg; P = 0.915). Thus, the reduction in blood pressure from baseline was greater in the experimental group compared with control (-10.91 ± 4.1 vs. -0.17 ± 3.6 mm Hg; P = 0.003). Modifications in blood pressure were accompanied by increased parasympathetic and reduced sympathetic activity in the experimental group, as estimated by blood pressure and heart rate variability analysis. No detrimental neurocognitive and metabolic outcomes were evident following MIH. Conclusions: MIH elicits beneficial cardiovascular and autonomic outcomes in males with OSA and concurrent hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT03736382).