Long-term health outcomes for patients with obstructive sleep apnea: placing the Agency for Healthcare Research and Quality report in context-a multisociety commentary.

This multisociety commentary critically examines the Agency for Healthcare Research and Quality (AHRQ) final report and systematic review on long-term health outcomes in obstructive sleep apnea. The AHRQ report was commissioned by the Centers for Medicare & Medicaid Services and particularly focused on the long-term patient-centered outcomes of continuous positive airway pressure, the variability of sleep-disordered breathing metrics, and the validity of these metrics as surrogate outcomes. This commentary raises concerns regarding the AHRQ report conclusions and their potential implications for policy decisions. A major concern expressed in this commentary is that the AHRQ report inadequately acknowledges the benefits of continuous positive airway pressure for several established, long-term clinically important outcomes including excessive sleepiness, motor vehicle accidents, and blood pressure. While acknowledging the limited evidence for the long-term benefits of continuous positive airway pressure treatment, especially cardiovascular outcomes, as summarized by the AHRQ report, this commentary reviews the limitations of recent randomized controlled trials and nonrandomized controlled studies and the challenges of conducting future randomized controlled trials. A research agenda to address these challenges is proposed including study designs that may include both high quality randomized controlled trials and nonrandomized controlled studies. This commentary concludes by highlighting implications for the safety and quality of life for the millions of people living with obstructive sleep apnea if the AHRQ report alone was used by payers to limit coverage for the treatment of obstructive sleep apnea while not considering the totality of available evidence. CITATION: Patil SP, Billings ME, Bourjeily G, et al. Long-term health outcomes for patients with obstructive sleep apnea: placing the Agency for Healthcare Research and Quality report in context-a multisociety commentary. J Clin Sleep Med. 2024;20(1):135-149.

Home Sleep Apnea Testing for the Diagnosis of Obstructive Sleep Apnea.

A 50-year-old patient with epilepsy, hypertension, loud snoring, recent 50-lb weight gain, and abrupt awakenings with a feeling of breathlessness but no headaches or excessive daytime sleepiness presented with concerns. What would you do next?

Examining the feasibility of adult quality-of-life measurement for obstructive sleep apnea in clinical settings: what is the path forward for sleep centers?

Quality of life (QoL) is one of the outcomes that can be measured as a component of the required standards for sleep facility accreditation by the American Academy of Sleep Medicine. Utilization of a psychometrically robust QoL instrument is recommended; however, clinicians face a challenge balancing psychometric properties with questionnaire completion and scoring characteristics. This article provides an overview of common QoL instruments as a reference for clinicians when selecting a QoL tool for use in the clinical setting for adult patients with obstructive sleep apnea. CITATION: Colvin L, Collop N, Lorenz R, Morgenthaler T, Weaver TE. Examining the feasibility of adult quality-of-life measurement for obstructive sleep apnea in clinical settings: what is the path forward for sleep centers? J Clin Sleep Med. 2023;19(6):1145-1155.

Sphinganine is associated with 24-h MAP in the non-sleepy with OSA.

INTRODUCTION: Excessive daytime sleepiness is a debilitating symptom of obstructive sleep apnea (OSA) linked to cardiovascular disease, and metabolomic mechanisms underlying this relationship remain unknown. We examine whether metabolites from inflammatory and oxidative stress-related pathways that were identified in our prior work could be involved in connecting the two phenomena. METHODS: This study included 57 sleepy (Epworth Sleepiness Scale (ESS) ≥ 10) and 37 non-sleepy (ESS < 10) participants newly diagnosed and untreated for OSA that completed an overnight in-lab or at home sleep study who were recruited from the Emory Mechanisms of Sleepiness Symptoms Study (EMOSS). Differences in fasting blood samples of metabolites were explored in participants with sleepiness versus those without and multiple linear regression models were utilized to examine the association between metabolites and mean arterial pressure (MAP). RESULTS: The 24-h MAP was higher in sleepy 92.8 mmHg (8.4) as compared to non-sleepy 88.8 mmHg (8.1) individuals (P = 0.03). Although targeted metabolites were not significantly associated with MAP, when we stratified by sleepiness group, we found that sphinganine is significantly associated with MAP (Estimate = 8.7, SE = 3.7, P = 0.045) in non-sleepy patients when controlling for age, BMI, smoking status, and apnea-hypopnea index (AHI). CONCLUSION: This is the first study to evaluate the relationship of inflammation and oxidative stress related metabolites in sleepy versus non-sleepy participants with newly diagnosed OSA and their association with 24-h MAP. Our study suggests that Sphinganine is associated with 24 hour MAP in the non-sleepy participants with OSA.

Optimal NIV Medicare Access Promotion: Patients With OSA: 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.

This document summarizes the work of the CPAP and bilevel PAP therapy for OSA Technical Expert Panel working group. For positive airway pressure (PAP) therapy, the most pressing current coverage barriers identified were: an insufficient symptom list describing all potential symptoms in patients with mild OSA; the 4 h per night of PAP usage requirement to keep the device; the additional sleep studies requirement to re-qualify for PAP or supplemental oxygen; and the inability to use telehealth visits for follow-up visits. Critical evidence supports changes to current policies and includes: symptom list inadequate to cover all scenarios based on updated clinical practice guidelines; published evidence that 2 h per night of PAP use can result in benefit to quality of life and other metrics; the costs of another sleep study not justified for all nonadherent patients or for supplemental oxygen due to other types of assessment currently available; and the remarkable success and acceptance of telehealth visits. To achieve optimal access for patients on PAP therapy, we make the following key suggestions: removing symptom criteria for mild OSA; reduce continued coverage criteria to > 2 h per night; eliminate the need for a sleep study to re-qualify if nonadherent or for new Centers for Medicare & Medicaid Services beneficiaries already on and adherent to PAP therapy; allow telehealth visits for documenting benefit and adherence; and allow PAP reports and domiciliary oximetry to qualify for supplemental oxygen with PAP if needed. This paper shares our best vision for bringing the right device to the right patient at the right time.

Nocturnal Asthma.

Nocturnal asthma has unique pathophysiological mechanisms, comorbid diseases, and intervention. Even though the treatments for asthma have been highly developed, there are a high number of patients with asthma whose symptoms are not well controlled, particularly those with nocturnal asthma in which symptoms occur during the night and interfere with sleep. Moreover, nocturnal asthma also causes poor sleep quality, impairs quality of life, and deteriorates daytime cognitive performance. Overall, the prevalence of nocturnal asthma is estimated to be between 44-61% of patients with asthma. Pathophysiological mechanisms of nocturnal asthma included circadian rhythmicity and diurnal variation of inflammatory process, beta 2-adrenergic receptor polymorphism, and polluted environments. Furthermore, co-morbid conditions, such as obstructive sleep apnea and gastroesophageal reflux disease, may contribute to nocturnal asthma. In addition to optimal medical treatment, management of co-morbid conditions should be considered. Utilization of continuous positive airway pressure (CPAP) has been shown to significantly improve nocturnal symptoms in patients with co-existing obstructive sleep apnea as supported by numerous studies, but improvement of pulmonary function is still controversial. In addition, several studies also demonstrate that use of proton-pump inhibitors may assist those patients with gastroesophageal reflux disease resulting in an increase of peak expiration flow rate and/or FEV1.

Metrics of sleep apnea severity: beyond the apnea-hypopnea index.

Obstructive sleep apnea (OSA) is thought to affect almost 1 billion people worldwide. OSA has well established cardiovascular and neurocognitive sequelae, although the optimal metric to assess its severity and/or potential response to therapy remains unclear. The apnea-hypopnea index (AHI) is well established; thus, we review its history and predictive value in various different clinical contexts. Although the AHI is often criticized for its limitations, it remains the best studied metric of OSA severity, albeit imperfect. We further review the potential value of alternative metrics including hypoxic burden, arousal intensity, odds ratio product, and cardiopulmonary coupling. We conclude with possible future directions to capture clinically meaningful OSA endophenotypes including the use of genetics, blood biomarkers, machine/deep learning and wearable technologies. Further research in OSA should be directed towards providing diagnostic and prognostic information to make the OSA diagnosis more accessible and to improving prognostic information regarding OSA consequences, in order to guide patient care and to help in the design of future clinical trials.

Randomized Controlled Trial of a Novel Communication Device Assessed During Noninvasive Ventilation Therapy.

BACKGROUND: Noninvasive ventilation (NIV), a form of positive airway pressure (PAP) therapy, is the standard of care for various forms of acute respiratory failure (ARF). Communication impairment is a side effect of NIV, impedes patient care, contributes to distress and intolerance, and potentially increases intubation rates. This study aimed to evaluate communication impairment during CPAP therapy and demonstrate communication device improvement with a standardized protocol. RESEARCH QUESTION: How does an oronasal mask affect communication intelligibility? How does use of an NIV communication device change this communication intelligibility? STUDY DESIGN AND METHODS: A single-center randomized controlled trial (36 outpatients with OSA on CPAP therapy) assessed exposure to CPAP 10 cm H2O and PAP communication devices (SPEAX, Ataia Medical). Communication impairment was evaluated by reading selected words and sentences for partners to record and were tabulated as %words correct. Each outpatient-partner pair performed three assessments: (1) baseline (conversing normally), (2) mask baseline (conversing with PAP), and (3) randomized to functioning device (conversing with PAP and device) or sham device. After each stage, both outpatients and partners completed Likert surveys regarding perceived intelligibility and comfort. RESULTS: While conversing with PAP, word and sentence intelligibility decreased relatively by 52% (87% vs 41%) and relatively by 57% (94% vs 40%), respectively, compared with normal conversation. Word and sentence intelligibility in the intervention arm increased relatively by 75% (35% vs 61%; P < .001) and by 126% (33% vs 76%; P < .001) higher than the control arm, respectively. The device improved outpatient-perceived PAP comfort relatively by 233% (15% vs 50%, P = .042) and partner-perceived comfort by relatively 245% (20% vs 69%, P = .0074). INTERPRETATION: Use of this PAP communication device significantly improves both intelligibility and comfort. This is one of the first studies quantifying communication impairment during PAP delivery. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03795753; URL: www.clinicaltrials.gov.

A network meta-analysis of different positive airway pressure interventions in obesity hypoventilation syndrome.

Continuous positive airway pressure (CPAP) and different types of non-invasive ventilation (NIV) have been studied in obesity hypoventilation syndrome such as bi-level PAP with back-up rate (BPAP-BUR), BPAP without BUR, and the new hybrid devices that target a pre-set volume by adjustment of pressure support (VT-PS). Although several studies have compared one PAP intervention with the other, none has compared all four in a head-to-head design, which formed the basis of this network meta-analysis. PubMed and Web of Science were searched for potentially includable randomised active comparator trials. Changes in partial pressure of carbon dioxide (PaCO2 ) and Epworth Sleepiness Score (ESS) were the primary outcomes of interest. Network meta-analysis was done in R program using the 'frequentist' framework. A total of seven trials were included. Only VT-PS and BPAP-BUR showed statistically significant reductions in PaCO2 compared to control, with no significant inter-PAP differences except for the comparison between VT-PS and CPAP. Only VT-PS showed a statistically significant improvement in ESS as compared to control, with no other significant inter-PAP differences. P-score ranking (based on effect size and standard errors) and Hasse diagram ranked VT-PS and BPAP as superior to other PAPs for both primary outcomes. There were no significant differences between the different PAP interventions for hospital or emergency department admissions. The results of this network meta-analysis suggest superiority of VT-PS and BPAP over other PAP interventions at least for daytime hypercapnia and subjective daytime somnolence.

Daytime sleepiness predicts inflammation and ambulatory blood pressure in sleep apnoea.

INTRODUCTION: Sleepiness in obstructive sleep apnoea is associated with cardiovascular risk; however, the biological mechanisms are not known. This study explored whether those with subjective sleepiness have increased plasma tumour necrosis factor-related protein 1 (C1qTNF1), a novel adipose-derived hormone (adipokine), and 24-h ambulatory blood pressure (ABP) compared to those without sleepiness in newly diagnosed, treatment-naïve participants with obstructive sleep apnoea. METHODS: Overall, 94 participants were included in the analysis. Participants completed the Epworth Sleepiness Scale (ESS), 24-h ABP was monitored, and plasma C1qTNF1 was measured. Sleepy participants were defined as ESS≥10 and nonsleepy as ESS<10. Multiple linear regression was used to explore differences in C1qTNF1, and 24-h mean arterial pressure (MAP) between sleepy and nonsleepy participants, adjusting for age, sex, body mass index, apnoea-hypopnoea index, and smoking status. RESULTS: C1qTNF1 was significantly higher in sleepy participants (n=57) compared to nonsleepy participants (n=37) (ß=0.41 NPX, 95% CI 0.02, 0.80; p=0.04). The 24-h MAP was significantly higher in sleepy participants compared to nonsleepy participants (ß=4.06 mmHg, 95% CI 0.36, 7.77; p=0.03). CONCLUSIONS: Our findings show that sleepiness is associated with inflammation and higher 24-h MAP in sleep apnoea.

Improving the performance of peripheral arterial tonometry-based testing for the diagnosis of obstructive sleep apnea.

Outside sleep laboratory settings, peripheral arterial tonometry (PAT, eg, WatchPat) represents a validated modality for diagnosing obstructive sleep apnea (OSA). We have shown before that the accuracy of home sleep apnea testing by WatchPat 200 devices in diagnosing OSA is suboptimal (50%-70%). In order to improve its diagnostic performance, we built several models that predict the main functional parameter of polysomnography (PSG), Apnea Hypopnea Index (AHI). Participants were recruited in our Sleep Center and underwent concurrent in-laboratory PSG and PAT recordings. Statistical models were then developed to predict AHI by using robust functional parameters from PAT-based testing, in concert with available demographic and anthropometric data, and their performance was confirmed in a random validation subgroup of the cohort. Five hundred synchronous PSG and WatchPat sets were analyzed. Mean diagnostic accuracy of PAT was improved to 67%, 81% and 85% in mild, moderate-severe or no OSA, respectively, by several models that included participants' age, gender, neck circumference, body mass index and the number of 4% desaturations/hour. WatchPat had an overall accuracy of 85.7% and a positive predictive value of 87.3% in diagnosing OSA (by predicted AHI above 5). In this large cohort of patients with high pretest probability of OSA, we built several models based on 4% oxygen desaturations, neck circumference, body mass index and several other variables. These simple models can be used at the point-of-care, in order to improve the diagnostic accuracy of the PAT-based testing, thus ameliorating the high rates of misclassification for OSA presence or disease severity.

Consequences and Solutions for the Impact of Communication Impairment on Noninvasive Ventilation Therapy for Acute Respiratory Failure: A Focused Review.

OBJECTIVES: With over 2 million cases of acute respiratory failure in the United States per year, noninvasive ventilation has become a leading treatment modality, often supplanting invasive mechanical ventilation as the initial treatment of choice. Most acute respiratory failure patients use a full face (oronasal) mask with noninvasive ventilation, which is known to impair communication, but its popularity and benefit has led many providers to accept the communication impairment. Medical staff periodically remove masks to communicate with patients, but patients are often limited to short utterances and risk lung derecruitment upon removal of positive pressure. These problems can lead to noninvasive ventilation failure, which is often linked to worse outcomes than first initiating invasive mechanical ventilation and can lead to increased hospitalization costs. DATA SOURCES: We searched MEDLINE and Google Scholar for "speech," "communication," "impairment," "failure," "complications," "NIPPV," "NIV," and "noninvasive ventilation." STUDY SELECTION: We included articles with patients in acute respiratory failure. We excluded articles for patients using noninvasive ventilation therapy for obstructive sleep apnea. DATA SYNTHESIS: Communication impairment has been associated with increasing noninvasive ventilation anxiety (odds ratio, 1.25). Of patients using noninvasive ventilation, 48% require early discontinuation, 22% refuse noninvasive ventilation, and 9% are ultimately intubated. Improvements to communication have been shown to reduce fear and anxiety in invasive mechanical ventilation patients. Analogous communication problems exist with effective solutions in other fields, such as fighter pilot masks, that can be easily implemented to enhance noninvasive ventilation patient care, increase adherence to noninvasive ventilation treatment, and improve patient outcomes. CONCLUSIONS: Communication impairment is an underappreciated cause of noninvasive ventilation complications and failure and requires further characterization. Analogous solutions-such as throat microphones and mask-based microphones-that can be easily implemented show potential as cost-effective methods to reduce noninvasive ventilation failure.

Performance of peripheral arterial tonometry-based testing for the diagnosis of obstructive sleep apnea in a large sleep clinic cohort.

STUDY OBJECTIVES: Peripheral arterial tonometry (PAT)-based technology represents a validated portable monitoring modality for the diagnosis of OSA. We assessed the diagnostic accuracy of PAT-based technology in a large point-of-care cohort of patients studied with concurrent polysomnography (PSG). METHODS: During study enrollment, all participants suspected to have OSA and tested by in-laboratory PSG underwent concurrent PAT device recordings. RESULTS: Five hundred concomitant PSG and WatchPat tests were analyzed. Median (interquartile range) PSG AHI was 18 (8-37) events/h and PAT AHI3% was 25 (12-46) events/h. Average bias was + 4 events/h. Diagnostic concordance was found in 42%, 41%, and 83% of mild, moderate, and severe OSA, respectively (accuracy = 53%). Among patients with PAT diagnoses of moderate or severe OSA, 5% did not have OSA and 19% had mild OSA; in those with mild OSA, PSG showed moderate or severe disease in 20% and no OSA in 30% of patients (accuracy = 69%). On average, using a 3% desaturation threshold, WatchPat overestimated disease prevalence and severity (mean + 4 events/h) and the 4% threshold underestimated disease prevalence and severity by -6 events/h. CONCLUSIONS: Although there was an overall tendency to overestimate the severity of OSA, a significant percentage of patients had clinically relevant misclassifications. As such, we recommend that patients without OSA or with mild disease assessed by PAT undergo repeat in-laboratory PSG. Optimized clinical pathways are urgently needed to minimize therapeutic decisions instituted in the presence of diagnostic uncertainty.

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.