Large variability in definitions of sleep apnea indices used in clinical studies.

STUDY OBJECTIVES: We explored the variability of sleep apnea indices and definitions of obstructive sleep apnea in clinical studies of continuous positive airway pressure. METHODS: In a systematic review of the long-term clinical effects of continuous positive airway pressure, we noted variability across studies in how sleep apnea was defined. We, thus, sought to quantify the heterogeneity. RESULTS: Across 57 comparative studies of long-term clinical outcomes of continuous positive airway pressure, only 40% fully and explicitly reported their definitions of apnea and hypopnea. Most studies defined apnea as 100% airflow cessation, but a minority used 90% or even down to 75% thresholds. Almost half of the studies defined hypopnea as ≥ 50% airflow cessation, but the majority used 30% or even 25% thresholds. Similarly, about half of the studies used a 4% desaturation threshold to define oxygen desaturation and about half used a 3% threshold, with 2 studies using both thresholds for different purposes. Randomized trials were no more consistent or better-reported than observational studies. Studies that cited published criteria generally reported definitions that were different from the cited criteria. CONCLUSIONS: The criteria used to define sleep apnea indices (apnea, hypopnea, and oxygen desaturation) were highly variable, even among studies stating that definitions were based on the same standard criteria. It was often difficult to discern the actual criteria used. The great variability across studies and lack of transparency about their sleep study methods hampers the interpretability and utility of the studies and calls into question whether studies are generalizable from one setting to another. CITATION: Balk EM, Adam GP, D'Ambrosio CM. Large variability in definitions of sleep apnea indices used in clinical studies. J Clin Sleep Med. 2024;20(3):461-468.

Long-term effects on clinical event, mental health, and related outcomes of CPAP for obstructive sleep apnea: a systematic review.

STUDY OBJECTIVES: We performed a systematic review of long-term health outcomes of continuous positive airway pressure (CPAP) use in adults with obstructive sleep apnea. METHODS: We updated prior systematic reviews with searches in multiple databases through January 3, 2023. We included randomized controlled trials (RCTs) and adjusted nonrandomized comparative studies that reported prespecified long-term (mostly > 1 year) health outcomes. We assessed risk of bias, conducted meta-analyses, and evaluated strength of evidence. RESULTS: We found 38 eligible studies (16 trials, 22 observational). All conclusions were of low strength of evidence given study and data limitations. RCTs found no evidence of effect of CPAP on mortality (summary effect size [ES] 0.89; 95% confidence interval [CI] 0.66, 1.21); inclusion of adjusted nonrandomized comparative studies yields an association with reduced risk of death (ES 0.57; 95% CI 0.44, 0.73). RCTs found no evidence of effects of CPAP for cardiovascular death (ES 0.99; 95% CI 0.64, 1.53), stroke (ES 0.99; 95% CI 0.73, 1.35), myocardial infarction (ES 1.05; 95% CI 0.78, 1.41), incident atrial fibrillation (ES 0.89; 95% CI 0.48, 1.63), or composite cardiovascular outcomes (all statistically nonsignificant). RCTs found no evidence of effects for incident diabetes (ES 1.02; 95% CI 0.69, 1.51) or accidents (all nonsignificant) and no clinically significant effects on depressive symptoms, anxiety symptoms, or cognitive function. CONCLUSIONS: Whether CPAP use for obstructive sleep apnea affects long-term health outcomes remains largely unanswered. RCTs and nonrandomized comparative studies are inconsistent regarding the effect of CPAP on mortality. Current studies are underpowered, with relatively short duration follow-up and methodological limitations. CITATION: Balk EM, Adam GP, Cao W, Bhuma MR, D'Ambrosio C, Trikalinos TA. Long-term effects on clinical event, mental health, and related outcomes of CPAP for obstructive sleep apnea: a systematic review. J Clin Sleep Med. 2024;20(6):895-909.

Obstructive sleep apnea in infants.

Obstructive sleep apnea in infants has a distinctive pathophysiology, natural history, and treatment compared with that of older children and adults. Infants have both anatomical and physiological predispositions toward airway obstruction and gas exchange abnormalities; including a superiorly placed larynx, increased chest wall compliance, ventilation-perfusion mismatching, and ventilatory control instability. Congenital abnormalities of the airway, such as laryngomalacia, hemangiomas, pyriform aperture stenosis, choanal atresia, and laryngeal webs, may also have adverse effects on airway patency. Additional exacerbating factors predisposing infants toward airway collapse include neck flexion, airway secretions, gastroesophageal reflux, and sleep deprivation. Obstructive sleep apnea in infants has been associated with failure to thrive, behavioral deficits, and sudden infant death. The proper interpretation of infant polysomnography requires an understanding of normative data related to gestation and postconceptual age for apnea, arousal, and oxygenation. Direct visualization of the upper airway is an important diagnostic modality in infants with obstructive apnea. Treatment options for infant obstructive sleep apnea are predicated on the underlying etiology, including supraglottoplasty for severe laryngomalacia, mandibular distraction for micrognathia, tonsillectomy and/or adenoidectomy, choanal atresia repair, and/or treatment of gastroesophageal reflux.

Catathrenia in children: clinical presentation, polysomnographic features, natural history, and response to therapy.

STUDY OBJECTIVES: To determine the clinical presentation, polysomnographic appearance, and the response to therapy of catathrenia in children. METHODS: A retrospective analysis was performed in children referred or evaluated at the Boston Children's Hospital Sleep Center between 1998 and 2021 who were documented to have catathrenia either as a chief complaint or an incidental finding. RESULTS: Catathrenia was identified in 21 children. The age of onset by parent report was 6.4 ± 4.4 years (range: birth-14 years), but the diagnosis was at 8.3 ± 3.8 years (range: 1.5-14 years). Catathrenia was the chief complaint for 24% of patients and was incidentally identified in 76% referred for breathing concerns. Bruxism was observed in 62% of patients. Catathrenia events most often occur following an electrocortical arousal (79%) and are most common in the second half of the night (73%). Catathrenia was observed exclusively in rapid eye movement (REM) sleep (16%), exclusively in non-REM sleep (32%), and in both sleep states (52%). Treatment of obstructive sleep apnea resulted in resolution or improvement in the obstructive sleep apnea in all patients, but the catathrenia persisted at a reduced level. CONCLUSIONS: Most catathrenia in children is diagnosed incidentally during evaluation for sleep-disordered breathing, although the groaning often started many years earlier. Catathrenia events decreased considerably after treatment of obstructive sleep apnea, but persisted in all patients. Catathrenia was also observed in children without signs or symptoms of sleep-disordered breathing, indicating that these are distinct conditions. The majority of children with catathrenia had no sleepiness or behavioral concerns. CITATION: Katz ES, D'Ambrosio C. Catathrenia in children: clinical presentation, polysomnographic features, natural history, and response to therapy. J Clin Sleep Med. 2023;19(8):1505-1511.

Sex and Gender in Lung Diseases and Sleep Disorders: A State-of-the-Art Review: Part 2.

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder.

Sex and Gender in Lung Disease and Sleep Disorders: A State-of-the-Art Review.

The terms sex and gender often are used interchangeably, but have specific meaning when it comes to their effects on lung disease. Ample evidence is now available that sex and gender affect the incidence, susceptibility, presentation, diagnosis, and severity of many lung diseases. Some conditions are more prevalent in women, such as asthma. Other conditions are seen almost exclusively in women, like lymphangioleiomyomatosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as higher number of exacerbations experienced by women with COPD and greater cardiovascular morbidity in women with sleep-disordered breathing. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors often are not addressed adequately in clinical trials. Various aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for women. This article is a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of lung diseases. Pathobiological mechanisms explaining sex differences in these diseases are beyond the scope of this article. We review the literature and focus on recent guidelines about using sex and gender in research. We also review sex and gender differences in lung diseases.

Sex Differences in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) for many years has been thought to be a disease of men, but research performed more recently has revealed women are at significant risk for OSA as well as the morbidity associated with leaving it untreated. There are estimates that up to 90% of women with severe sleep apnea are not being diagnosed and that if diagnosed, they are less likely to be treated. This article will explore the sex differences in OSA, specifically addressing areas of prevalence, phenotypes, diagnostic criteria, and treatment.

Sleep and Delirium in Adults Who Are Critically Ill: A Contemporary Review.

Sleep is important to health and well-being, and studies in healthy adults have demonstrated that sleep deprivation impacts respiratory, immune, and cognitive function. Historically, because of the nature of critical illness, sleep has not been considered a priority for patient care in the ICU. More recently, research has demonstrated that sleep is markedly abnormal in patients who are critically ill. In addition, there is often disruption of circadian rhythms. Delirium is a syndrome of acute alteration in mental status that occurs in the setting of contributing factors such as serious illness, medication, and drug or alcohol intoxication or withdrawal. Delirium is a frequent occurrence in critical illness, and research has demonstrated several adverse outcomes associated with delirium including persistent cognitive impairment and increased mortality. Sleep deprivation and delirium share many common symptoms. The similarity in symptoms between sleep disruption and delirium have prompted experts to draw links between the two and question both the relationship and its direction. In addition, the inclusion of sleep disturbance to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition in its constellation of symptoms used in diagnosing delirium has increased awareness of the link between sleep and delirium. This paper will review the literature on sleep in critical illness and the potential mechanisms and pathways that may connect sleep and delirium.

Nocturnal noninvasive ventilation.

Nocturnal noninvasive ventilation (NNV), the provision of ventilatory assistance via a noninvasive interface mainly during sleep, has assumed an important role in the management of chronic hypoventilatory syndromes. This review focuses on recent developments related to the use of NNV to treat various forms of chronic respiratory failure or insufficiency. In the past, NNV has been used mainly to treat respiratory insufficiency in patients with neuromuscular disease (NMD) or chest wall deformity; it should be instituted when these patients have orthopnea or daytime symptoms associated with nocturnal hypoventilation. An emerging application is to treat obesity-hypoventilation syndrome, particularly in continuous positive airway pressure (CPAP) failures. Additionally, it has a role in managing some patients with obstructive sleep apnea who are hypoventilating or find the lower expiratory pressure with bilevel positive pressure ventilators more tolerable than with CPAP alone. NNV to treat severe, stable COPD remains controversial, although a subgroup of patients with hypercapnea and sleep-disordered breathing (SDB) seems most likely to respond favorably. NNV to treat central SDB in patients with congestive heart failure continues to be investigated. Recent findings from a Canadian CPAP trial were disappointing, but preliminary results on a novel adaptive NNV mode are promising.

Sleep and mechanical ventilation.

Critically ill patients have severe sleep disruption and typically encounter loss of circadian sleep pattern, steep fragmentation, increasing proportions of transitional stages of sleep, and loss of slow wave and rapid eye movement sleep. Mechanical ventilation is associated with these same sleep abnormalities, but what is attributable to the intensive care unit environment versus mechanical ventilation itself may be difficult to discern. Recent studies have shown that the ventilator mode and inappropriate settings can contribute to sleep fragmentation, and it is important to avoid overventilation that can induce central apneas when using spontaneous breathing modes. Noninvasive ventilation in the acute setting seems to be associated with the same sleep abnormalities as invasive ventilation. Long-term noninvasive positive pressure ventilation assists ventilation nocturnally and improves for patients with chronic respiratory failure caused by restrictive thoracic disorders.

COPD Advanced Patient Management.

COPD is the third leading cause of death in the United States, with current rates of both morbidity and mortality persisting and contributing significantly to long-term disability. More than 11 million Americans are diagnosed with COPD, with an additional 13 million people estimated to be living with undiagnosed disease. For patients diagnosed with COPD, the turning point will be hospitalization. It is important, therefore, that new treatment techniques that manage the signs and symptoms of the COPD and impact the prevalence and severity of exacerbations, hospital admissions, quality of life, and activities of daily living, and innovative clinical management strategies that optimize hospital discharge planning, all show promise in improving outcomes for patients with COPD. In particular, readmissions following COPD hospitalization are associated with high morbidity, mortality, and costs of care, and therefore hospital readmissions are receiving close scrutiny as an opportunity to improve patient care. To this end, programs to assess the presence and severity of dyspnea, and secretion burden and clearance, through implementation of a telemedicine program, use of noninvasive ventilation or supplemental oxygen, and development of a comprehensive self-management program have all been found to be variously effective as elements of a posthospitalization treatment plan. In this series of multi-media presentations and roundtable discussions published in CHEST (available at http://journal.cme.chestnet.org/copd-advanced-patient), leading international faculties discuss some of these specific interventions in detail to provide clinicians with possible solutions to the challenges of managing their patients with advanced COPD.

Noninvasive ventilation in the older patient who has acute respiratory failure.

Older patients are at significantly increased risk of acute respiratory failure from multiple causes. Noninvasive positive pressure ventilation has been shown to dramatically improve care of patients with acute respiratory failure. Patient selection is important in all patients being treated with noninvasive positive pressure ventilation but is especially important in older patients. Delirium, confusion, and dementia can lead to difficulty for patients in tolerating this procedure and lead to a worsening respiratory status. The presence of a do-not-intubate order does not necessarily preclude the use of noninvasive positive pressure ventilation, and some patients may derive significant benefit from its use. Overall, noninvasive positive pressure ventilation is a reasonable and justifiable option in the treatment of acute respiratory failure in older patients.

Effect of sleep on patient/ventilator asynchrony in patients undergoing chronic non-invasive mechanical ventilation.

BACKGROUND: Patients who require home non-invasive ventilation (NIV) during sleep normally have the ventilation settings adjusted empirically during daytime wakefulness. However, patient-ventilator asynchrony may occur during sleep. To detect the incidence of ineffective efforts (IE) during the sleep compared to wakefulness, we studied 48 patients already enrolled in a long-term home NIV programme. METHODS: We evaluated arterial blood gases, breathing pattern during spontaneous breathing (SB) and ventilation during wakefulness. In addition, we assessed the breathing pattern and oxygen gas exchange during night-time NIV. RESULTS: Daytime NIV significantly improved blood gases compared to SB (PaO2 NIV 10.2 +/- 1.95 kPa vs PaO2 SB 8 +/- 1.37, p < 0.001; PaCO2 NIV 5.75 +/- 1.08 kPa, vs PaCO2 SB 6.5 +/- 1.25, p < 0.001). The IE index was higher during sleep compared to wakefulness (48 +/- 39.5 events/h versus 0 +/- 0). The IE index was correlated with the time spent with SaO2 < 90% (r = 0.39, p < 0.01), but not with ventilator parameters, underlying disease, ventilation mode or type of mask. Eight patients had an IE index >100 events/h; these patients had a faster respiratory rate, required a higher level of inspiratory assistance and had poor gas exchange during sleep. CONCLUSIONS: We conclude that IE to breath are common during nocturnal NIV and that they may be associated with desaturations even in patients who are considered compliant and effectively treated.

Recommended Amount of Sleep for Pediatric Populations: A Consensus Statement of the American Academy of Sleep Medicine.

ABSTRACT: Sleep is essential for optimal health in children and adolescents. Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method. The recommendations are summarized here. A manuscript detailing the conference proceedings and the evidence supporting these recommendations will be published in the Journal of Clinical Sleep Medicine.

Consensus Statement of the American Academy of Sleep Medicine on the Recommended Amount of Sleep for Healthy Children: Methodology and Discussion.

ABSTRACT: Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method. After review of 864 published articles, the following sleep durations are recommended: Infants 4 months to 12 months should sleep 12 to 16 hours per 24 hours (including naps) on a regular basis to promote optimal health. Children 1 to 2 years of age should sleep 11 to 14 hours per 24 hours (including naps) on a regular basis to promote optimal health. Children 3 to 5 years of age should sleep 10 to 13 hours per 24 hours (including naps) on a regular basis to promote optimal health. Children 6 to 12 years of age should sleep 9 to 12 hours per 24 hours on a regular basis to promote optimal health. Teenagers 13 to 18 years of age should sleep 8 to 10 hours per 24 hours on a regular basis to promote optimal health. Sleeping the number of recommended hours on a regular basis is associated with better health outcomes including: improved attention, behavior, learning, memory, emotional regulation, quality of life, and mental and physical health. Regularly sleeping fewer than the number of recommended hours is associated with attention, behavior, and learning problems. Insufficient sleep also increases the risk of accidents, injuries, hypertension, obesity, diabetes, and depression. Insufficient sleep in teenagers is associated with increased risk of self-harm, suicidal thoughts, and suicide attempts. COMMENTARY: A commentary on this article apears in this issue on page 1439.

Sleep, breathing, and menopause: the effect of fluctuating estrogen and progesterone on sleep and breathing in women.

BACKGROUND: Sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), is more common in men than in women. However, menopause increases the risk for development of OSA. Administration of estrogen and progesterone to postmenopausal women with OSA decreases apnea and hypopnea during sleep. OBJECTIVE: Because beneficial changes can be observed soon after administration of a short course of hormones, we hypothesized that suppression of these hormones would rapidly result in the development of SDB. METHODS: Production of sex hormones was suppressed with daily administration of leuprolide acetate (LA), a gonadotropin-releasing hormone analogue, for 5 weeks in women who were participating in a study on pharmacologically induced menopause and physiology. The subjects underwent polysomnographic evaluation at baseline and after 5 weeks of LA administration. RESULTS: In the 12 healthy women aged 18 to 34 years who participated in the study, sleep architecture and respiration were normal at baseline. After LA administration, the subjects stopped their menses, and their plasma concentrations of l7beta-estradiol (preadministration, mean [SD] 33.9 [9.0] pg/mL; post administration, 10.2 [3.4] pg/mL) and progesterone (preadministration, 0.48 [0.05] ng/mL; post administration, 0.40 [0.06] ng/mL) reached menopausal levels. Sex hormone deficiency was associated with climacteric vasomotor symptoms such as hot flashes and sweating. Sleep latencies and architecture did not change significantly with LA administration. The participants subjectively noticed some increased snoring that was not confirmed by polysomnogram. Specifically, there was no change in arousal index and no evidence for sleep fragmentation to suggest the presence of increased upper-airway resistance during sleep. The apnea-hypopnea index, 0.07 (0.02) to 0.22 (0.11) events per hour of sleep, did not change with sex hormone deficiency. CONCLUSIONS: In this study, sex hormone deficiency in young women resulted in climacteric symptoms and cessation of menses, and was not associated with sleep fragmentation or clinically significant SDB.

Telemedicine in the intensive care unit: state of the art.

Critical care medicine is at a crossroads in which limited numbers of staff care for increasing numbers of patients as the population ages and use of ICUs increases. Also at this time health care spending must be curbed. The high-intensity intensivist staffing model has been linked to improved mortality, complications, and costs. Tele-ICU uses technology to implement this high-intensity staffing model in areas that are relatively underserved. When implemented correctly and in the right populations this technology has improved outcomes. Future studies regarding implementation, organization, staffing, and innovation are needed to determine the optimal use of this critical care professional enhanced technology.

Restless leg syndrome in pregnancy.

Restless leg syndrome, more recently renamed Willis-Ekbom disease, is a condition that disrupts sleep and occurs more frequently in the pregnant population. We present a 39-year-old woman with restless legs syndrome in the third trimester and discuss the epidemiology, pathophysiology and therapeutic options in the pregnant population while highlighting the challenges posed by the lack of safety data of approved drugs.