Work-Related Sleep Disorders: Causes and Impacts.

Insufficient sleep syndrome, shift work disorder, and obstructive sleep apnea (OSA) not only significantly impact the health of affected individuals, but also pose a threat to public safety. This article describes the clinical manifestations and impact of these sleep disorders, particularly as they pertain to workers' health and those with safety-sensitive positions. Sleep deprivation, circadian rhythm disruptions, and excessive daytime sleepiness-hallmarks of insufficient sleep, shift work disorder, and OSA, respectively-all lead to a series of cognitive deficits and impaired concentration that affect workers in a wide variety of fields. We describe the health consequences of these disorders along with treatment strategies, with a focus on current regulatory standards and the under-recognition of OSA in commercial drivers. Given its large scale, there is a need for improved guidelines and regulations for the screening, diagnosis, treatment, and long-term follow-up of OSA in commercial motor vehicle drivers. Increased recognition of the ways in which these sleep disorders impact workers will pave the way for significant improvements in occupational health and safety.

The distribution of acquired peripheral nerve injuries associated with severe COVID-19 implicate a mechanism of entrapment neuropathy: a multicenter case series and clinical feasibility study of a wearable, wireless pressure sensor.

We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

The COVID-19 pandemic and sleep medicine: a look back and a look ahead.

The coronavirus disease 2019 (COVID-19) pandemic is a reminder that global infectious disease outbreaks are not new and they have the potential to cause catastrophic morbidity and mortality, disrupt health care delivery, demand critical decision making in the absence of scientific certainty, interrupt trainee education, inflict economic damage, and cause a spike in demand for health care services that exceeds societal capacity. In this article, we look back at how the sleep medicine community adapted to challenges imposed by the COVID-19 pandemic. To mitigate viral transmission perhaps the single most effective and efficient adaptation was the rapid adoption of telemedicine. Many additional strategies were taken up virtually overnight, including more home sleep apnea testing, reconsideration of potential risks of positive airway pressure therapy, a reduction or cessation of laboratory services, and deployment of workers to provide frontline care to infected patients. During some periods, critical shortages in essential personal protective equipment, respiratory assist devices, and even oxygen added to logistical challenges, which were exacerbated by persistent financial threats and insufficient staffing. Through ongoing innovation, resiliency, and adaptability, breakthroughs were made in assigning staff responsibilities and designing workflows, using clinical spaces, obtaining legislative support, and achieving professional society collaboration and guidance so that the missions of providing health care, teaching, and academic pursuits could continue. Here we summarize what we have learned through these critical months and highlight key adaptations that deserve to be embraced as we move forward. CITATION: Khosla S, Beam E, Berneking M, et al. The COVID-19 pandemic and sleep medicine: a look back and a look ahead. J Clin Sleep Med. 2022;18(8):2045-2050.

Diaphragm and Phrenic Nerve Ultrasound in COVID-19 Patients and Beyond: Imaging Technique, Findings, and Clinical Applications.

The diaphragm, the principle muscle of inspiration, is an under-recognized contributor to respiratory disease. Dysfunction of the diaphragm can occur secondary to lung disease, prolonged ventilation, phrenic nerve injury, neuromuscular disease, and central nervous system pathology. In light of the global pandemic of coronavirus disease 2019 (COVID-19), there has been growing interest in the utility of ultrasound for evaluation of respiratory symptoms including lung and diaphragm sonography. Diaphragm ultrasound can be utilized to diagnose diaphragm dysfunction, assess severity of dysfunction, and monitor disease progression. This article reviews diaphragm and phrenic nerve ultrasound and describes clinical applications in the context of COVID-19.

Optimal NIV Medicare Access Promotion: Patients With Thoracic Restrictive Disorders: A Technical Expert Panel Report From the American College of Chest Physicians, the American Association for Respiratory Care, the American Academy of Sleep Medicine, and the American Thoracic Society.

The existing coverage criteria for noninvasive ventilation (NIV) do not recognize the benefits of early initiation of NIV for those with thoracic restrictive disorders and do not address the unique needs for daytime support as the patients progress to ventilator dependence. This document summarizes the work of the thoracic restrictive disorder Technical Expert Panel working group. The most pressing current coverage barriers identified were: (1) delays in implementing NIV treatment; (2) lack of coverage for many nonprogressive neuromuscular diseases; and (3) lack of clear policy indications for home mechanical ventilation (HMV) support in thoracic restrictive disorders. To best address these issues, we make the following key recommendations: (1) given the need to encourage early initiation of NIV with bilevel positive airway pressure devices, we recommend that symptoms be considered as a reason to initiate therapy even at mildly reduced FVCs; (2) broaden CO2 measurements to include surrogates such as transcutaneous, end-tidal, or venous blood gas; (3) expand the diagnostic category to include phrenic nerve injuries and disorders of central drive; (4) allow a bilevel positive airway pressure device to be advanced to an HMV when the vital capacity is < 30% or to address severe daytime respiratory symptoms; and (5) provide additional HMV when the patient is ventilator dependent with use > 18 h per day. Adoption of these proposed recommendations would result in the right device, at the right time, for the right type of patients with thoracic restrictive disorders.

Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 21 consecutive severe post-COVID-19 survivors admitted to an inpatient rehabilitation hospital, 16 (76%) of them had at least one sonographic abnormality of diaphragm muscle structure or function. This corresponded to a significant reduction in diaphragm muscle contractility as represented by thickening ratio (muscle thickness at maximal inspiration/end-expiration) for the post-COVID-19 compared to non-COVID-19 cohorts. These findings may shed new light on neuromuscular respiratory dysfunction as a contributor to prolonged functional impairments after hospitalization for post-COVID-19.

Extubating to Noninvasive Ventilation: Noninvasive Ventilation from Intensive Care Unit to Home.

Weaning to noninvasive ventilation in intensive care unit and bridging the patients to home with respiratory support is evolving as the technology of noninvasive ventilation is improving. In patients with chronic obstructive pulmonary disease exacerbation, timing of initiation of noninvasive ventilation is the key, as persistently hypercapnic patients show benefits. High-intensity pressure support seems to do better in comparison to low-intensity pressure support. In patients with obesity and hypercapnia, obesity hypoventilation cannot be ruled out especially in an inpatient setting, and it is crucial that these patients are discharged with noninvasive ventilation.

TECPR2 mutation-associated respiratory dysregulation: more than central apnea.

None: Children with rare genetic diseases that cause respiratory dysregulation are at particularly high mortality risk due to development of respiratory failure. The tectonin ß-propeller-containing protein 2 (TECPR2) mutations are proposed to cause autophagy defect affecting axonal integrity and development of progressive neurodegenerative and neuromuscular disease. Published TECPR2 mutation cases have described a high prevalence of respiratory failure. We review respiratory pathology in previously published cases and a new case of a 5-year-old girl with previously undescribed TECPR2 mutation demonstrating progressive central apnea due to respiratory cycle dysregulation. This is the first TECPR2 mutation case to demonstrate an ataxic (Biot's) breathing pattern with consistently inconsistent inspiratory and expiratory times and with relatively intact chemoreception during sleep. Therefore, we propose that the central apnea index alone may not be the appropriate marker for mortality risk. Rather, the morbidity and mortality associated with TECPR2 mutations are multisystem in nature and this burden complicates the ultimate needs for ventilation support and prognosis.

Sleep disordered breathing in Marfan syndrome: Value of standard screening questionnaires.

BACKGROUND: A high prevalence of sleep disordered breathing (SDB) has been reported in persons with Marfan syndrome (MFS), a single gene disorder of connective tissue resulting in premature death from aortic rupture. The burden of SDB and accompanying hemodynamic stress could warrant broad screening in this population. Our goal was to assess the utility of traditional SDB screening tools in our sample of persons with MFS. METHODS: Participants were recruited during an annual Marfan Foundation meeting and Marfan status confirmed using the Ghent criteria. Screening questionnaires were administered and SDB assessed by home sleep testing. We assessed accuracy of screening tools using receiver-operating characteristic curve analyses. RESULTS: The prevalence of moderate-severe SDB was 32% in our sample of 31 MFS participants. The Stop-Bang questionnaire had the highest positive predictive value (PPV) of 60% and the highest negative predictive value (NPV) of 100% using the high- and moderate-risk cut-offs, respectively, and the Berlin questionnaire had a PPV of 50% and an NPV of 92.3% at the high-risk cut-off. When those with mild SDB were included, the Stop-Bang and the Sleep Apnea Clinical Score (SACS) questionnaires demonstrated useful screening accuracies with PPVs of 94.7% and 92.9%, and NPVs of 63.6% and 47.1%, respectively, at the moderate-risk cut-offs. CONCLUSION: A survey of SDB in a sample of persons with MFS reveals not only a high burden of SDB but also that conventional screening instruments have utility if adapted appropriately. Future studies should validate the utility of these screening tools given concerns that SDB may contribute to progression of aortic pathology in MFS.

Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease.

The role of noninvasive positive pressure ventilation (NIV) in severe chronic obstructive pulmonary disease (COPD) has been controversial. Over the past two decades, data primarily obtained from Europe have begun to define the clinical characteristics of patients likely to respond, the role of high-intensity NIV, and the potential best timing of initiating therapy. These approaches, however, have not been validated in the context of the U.S. healthcare delivery system. Use of NIV in severe COPD in the United States is limited by the practicalities of doing in-hospital titrations as well as a complex system of reimbursement. These systematic complexities, coupled with a still-emerging clinical trial database regarding the most effective means to deliver NIV, have led to persistent uncertainty regarding when in stable severe COPD treatment with NIV is actually appropriate. In this review, we propose an assessment algorithm and treatment plan that can be used in clinical practice in the United States, but we acknowledge that the absence of pivotal clinical trials largely precludes a robust evidence-based approach to this potentially valuable therapy.

Automatic EPAP intelligent volume-assured pressure support is effective in patients with chronic respiratory failure: A randomized trial.

BACKGROUND AND OBJECTIVE: Patients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm. METHODS: This prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of >5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order. RESULTS: A total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P < 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP. CONCLUSION: A single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure. CLINICAL TRIAL REGISTRATION: NCT02683772 at clinicaltrials.gov.

Respiratory dysfunction following initiation of mirabegron: A case report.

BACKGROUND: Mirabegron, a ß3 adrenergic receptor agonist, is FDA approved for treatment of overactive bladder. Approved in 2012 in the US, there have been no reports of any effects of mirabegron on pulmonary function. CASE PRESENTATION: We report the case of a 65 year old male with a history of Parkinson's disease, OSA, and aspiration pneumonia presenting with subacute worsening dyspnea and found to have worsening restrictive ventilatory defect with a pattern consistent with neuromuscular weakness. After recalling that initiation of mirabegron correlated with onset of his worsening symptoms, the patient decided to perform a trial period off the drug. He subsequently reported prompt improvement in his respiratory symptoms, which was confirmed objectively by pulmonary function tests. In this case, mirabegron was temporally associated with subacute worsening of the patient's pulmonary restrictive physiology, with subsequent resolution after discontinuation of the medication. CONCLUSIONS: The mechanism of this adverse effect is unknown, but we speculate that this effect may be potentially mediated by the effect of ß3 adrenergic receptor agonism on skeletal muscle, in this case in a patient with pre-existing neuromuscular disease. Careful assessment of patients who develop shortness of breath while on mirabegron should include an assessment for restrictive lung disease secondary neuromuscular dysfunction. Additional study is needed of the effects of ß3 agonism on skeletal muscle.

Respiratory Management of the Patient With Duchenne Muscular Dystrophy.

In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the Centers for Disease Control and Prevention, was published in Lancet Neurology, and in 2018, these guidelines were updated. Since the publication of the first set of guidelines, survival of individuals with Duchenne muscular dystrophy has increased. With contemporary medical management, survival often extends into the fourth decade of life and beyond. Effective transition of respiratory care from pediatric to adult medicine is vital to optimize patient safety, prognosis, and quality of life. With genetic and other emerging drug therapies in development, standardization of care is necessary to accurately assess treatment effects in clinical trials. This revision of respiratory recommendations preserves a fundamental strength of the original guidelines: namely, reliance on a limited number of respiratory tests to guide patient assessment and management. A progressive therapeutic strategy is presented that includes lung volume recruitment, assisted coughing, and assisted ventilation (initially nocturnally, with the subsequent addition of daytime ventilation for progressive respiratory failure). This revision also stresses the need for serial monitoring of respiratory muscle strength to characterize an individual's respiratory phenotype of severity as well as provide baseline assessments for clinical trials. Clinical controversies and emerging areas are included.

Sleep disorders in traumatic brain injury.

BACKGROUND: Sleep disorders play a significant role in the care of those with Traumatic Brain Injury (TBI). OBJECTIVE: To provide a literature review on the interaction of sleep and circadian processes on those with TBI. METHODS: A literature review was conducted on PubMed using the following key words and their combination: "Sleep Apnea", "Traumatic Brain Injury", "Circadian", "Parasomnia", "Insomnia", "Hypersomnia", "Narcolepsy", and "Restless Legs". We review the spectrum of traumatic brain injury associated sleep disorders and discuss clinical approaches to diagnosis and treatment. RESULTS: Disordered sleep and wakefulness after TBI is common. Sleep disruption contributes to morbidity, such as the development of neurocognitive and neurobehavioral deficits, and prolongs the recovery phase after injury. Early recognition and correction of these problems may limit the secondary effects of traumatic brain injury and improve neuro recovery/patient outcomes. CONCLUSIONS: A more focused approach to sleep health is appropriate when caring for those with TBI.

Phase Relationship between DLMO and Sleep Onset and the Risk of Metabolic Disease among Normal Weight and Overweight/Obese Adults.

Circadian misalignment is hypothesized to contribute to increased diabetes and obesity among shift workers and individuals with late sleep timing. Accordingly, the goal of our study was to identify-among normal and overweight/obese adults-associations between circadian timing (dim light melatonin onset; DLMO) and circadian misalignment (the interval between DLMO and sleep onset) with metabolic disease risk. This was a secondary analysis of data from a larger study. Participants ages 18 to 50 years without depression, diabetes, or shift work, with sleep duration 6.5 h or more, completed the following evaluations: 7 days of wrist actigraphy, circadian timing assessment (DLMO), and a fasting blood draw to measure glucose and insulin and calculate the Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR). Data were analyzed using correlation and regression analyses controlling for age, sex, DLMO, and sleep duration. Analyses were conducted for the entire sample ( n = 54) and stratified by normal weight ( n = 36) and overweight/obese groups ( n = 18). Mean age was 26.4 years (SD = 7.1 years). Average sleep duration was 436.2 min (SD = 55.1 min), DLMO was 2250h (SD = 01:31), and interval between DLMO and sleep onset was 2 h 18 min (SD = 53 min). Average BMI was 24.3 kg/m2 (SD = 4.5 kg/m2). Circadian timing and interval between DLMO and sleep onset were not associated with glucose, insulin, or HOMA-IR in the main analyses. Among overweight/obese participants, a shorter interval between DLMO and sleep onset was associated with higher insulin ( B[SE] = -5.12 [2.24], p = 0.04) and HOMA-IR ( B[SE] = -1.32 [0.57], p = 0.04). Results of our multivariable model indicated that among overweight/obese participants, insulin was 5.1 pmol/L higher and HOMA was 1.3 µU/mL higher for every hour closer that sleep onset was to DLMO. The strengths of this study include the use of objective measures of circadian timing, but results should be considered hypothesis generating due to the small sample size and use of subgroup analyses.

Respiratory Pattern and Tidal Volumes Differ for Pressure Support and Volume-assured Pressure Support in Amyotrophic Lateral Sclerosis.

RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease resulting in respiratory failure and death. Use of noninvasive ventilation (NIV) improves survival. However, use of volume-assured pressure support (VAPS) has not been extensively studied in ALS. OBJECTIVES: To explore the clinical usefulness of a detailed evaluation of device-recorded NIV data in the management of chronic respiratory failure in ALS, and to determine whether there are differences in efficacy between patients using VAPS or PS. METHODS: We performed a retrospective chart review of 271 patients with ALS using either PS or VAPS, along with an evaluation of device-recorded data to explore differences in attainment of goal tidal volumes (Vt) and ratio of respiratory rate to tidal volume (f/Vt), in addition to triggering and cycling ability. RESULTS: Two hundred and fifteen patients were using PS, while 56 were using VAPS. There were no significant differences in demographic data, symptoms, pulmonary function, or patient compliance. Compared with VAPS, achieved Vt was significantly lower for PS while f/Vt was significantly higher. Percent spontaneous triggering was relatively preserved in both cohorts, whereas percent spontaneous cycling was considerably decreased in both. Furthermore, there was no association found between spontaneous triggering or cycling, and pulmonary function, indicating the presence of low spontaneous breath cycling or triggering ability is difficult to predict. CONCLUSIONS: Examination of device data for exhaled tidal volumes and f/Vt may be of use in evaluating efficacy of NIV in ALS. VAPS provides more reliable goal Vt than does PS, and is associated with decreased f/Vt. Spontaneous cycling is decreased in ALS despite preservation of triggering ability. Although a set backup rate may address decreased triggering, perhaps more importantly, setting a sufficient fixed inspiratory time would address the issue of decreased cycling.

The Impact of High-Frequency Chest Wall Oscillation on Healthcare Use in Patients with Neuromuscular Diseases.

RATIONALE: People with neuromuscular disease frequently have difficulty clearing pulmonary secretions, which leads to pneumonia and respiratory failure. High-frequency chest wall oscillation (HFCWO) is one intervention used to facilitate secretion clearance. OBJECTIVES: The objective of this study was to determine if HFCWO therapy leads to improved outcomes as measured by lower healthcare use for patients who have a chronic neuromuscular disease. METHODS: We performed a cohort study comparing healthcare claims before and after initiation of HFCWO. Data were obtained from two large databases of commercial insurance claims. Study subjects were commercial insurance members with an International Classification of Diseases, Ninth Revision, code for a neuromuscular disease and a claim for HFCWO between 2007 and 2011. The study included both children and adults. MEASUREMENTS AND MAIN RESULTS: There were 426 patients in this study. Their mean age was 29.9 ± 22 years. Total medical costs per member per month decreased by $1,949 (18.6%) after initiation of HFCWO (P = 0.002). Inpatient admission costs decreased by $2,392 (41.7%) (P = 0.001), and pneumonia costs decreased by $514 (18.1%) (P = 0.015). To account for the possibilities of misclassification based on diagnosis and bias due to loss to follow-up, we compared outcomes between those lost to follow-up and those not, and we found similar results. CONCLUSIONS: Total medical costs, hospitalizations, and pneumonia claims were less after than before initiation of HFCWO in a broad group of patients with neuromuscular disease. Subject to the limitations that administrative data did not capture how HFCWO was used and that HFCWO may be a marker of generally better care, our findings lend support to the routine use of this intervention in the care of patients with neuromuscular diseases.

The role of noninvasive ventilation in the management and mitigation of exacerbations and hospital admissions/readmissions for the patient with moderate to severe COPD (multimedia activity).

As seen in this CME online activity (available at http://journal.cme.chestnet.org/home-niv-copd), COPD is a common and debilitating disease and is currently the third leading cause of death in the United States. The role of noninvasive ventilation (NIV) in the management of severe, hypercapnic COPD has been controversial. However, it was concluded that current data would support the following recommendations. Patients with COPD with a waking Paco2 > 50 to 52 mm Hg, an overnight Paco2 > 55 mm Hg, or both who are symptomatic and compliant with other therapies should be eligible for NIV. In addition, multiple previous hospital admissions for COPD exacerbation, requiring noninvasive/invasive mechanical ventilation, strongly suggest a need for chronic NIV. Patients with COPD with a BMI > 30 kg/m2 respond particularly well to this therapy. When the decision is made to start NIV, this treatment is probably best initiated during a short hospitalization, although this can be accomplished in the clinic, home, or sleep laboratory if well-trained clinicians are available. Newer modes of NIV such as volume-assured pressure support, particularly with autotitrating expiratory positive airway pressure (EPAP), may create the opportunity for home NIV initiation easier for less experienced physicians. Regardless of the mode selected, inspiratory pressures must be in the 20 to 25 cm H2O range to meaningfully increase tidal volume, reduce work of breathing, and, importantly, reduce waking arterial Paco2. EPAP is currently set at 4 to 5 cm H2O, although future technologies may allow this to be individualized to maximally reduce auto-positive end expiratory pressure. The NIV device should have a backup rate although it is controversial as to whether this should be set at a high (18-20 breaths/min) vs a low (8-10 breaths/min) rate. The proper use of NIV in appropriately chosen patients with COPD can improve quality of life and increase survival. Ongoing studies are assessing if the frequency of future hospitalizations can be reduced with NIV. Thus, NIV should be strongly considered in any patients with COPD meeting the criteria described here.