The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States.

STUDY OBJECTIVES: The aims of this study were to characterize obstructive sleep apnea (OSA) care pathways among commercially insured individuals in the United States and to investigate between-groups differences in population, care delivery, and economic aspects. METHODS: We identified adults with OSA using a large, national administrative claims database (January 1, 2016-February 28, 2020). Inclusion criteria included a diagnostic sleep test on or within ≤ 12 months of OSA diagnosis (index date) and 12 months of continuous enrollment before and after the index date. Exclusion criteria included prior OSA treatment or central sleep apnea. OSA care pathways were identified using sleep testing health care procedural health care common procedure coding system/current procedural terminology codes then selected for analysis if they were experienced by ≥ 3% of the population and assessed for baseline demographic/clinical characteristics that were also used for model adjustment. Primary outcome was positive airway pressure initiation rate; secondary outcomes were time from first sleep test to initiation of positive airway pressure, sleep test costs, and health care resource utilization. Associations between pathway type and time to treatment initiation were assessed using generalized linear models. RESULTS: Of 86,827 adults with OSA, 92.1% received care in 1 of 5 care pathways that met criteria: home sleep apnea testing (HSAT; 30.8%), polysomnography (PSG; 23.6%), PSG-Titration (19.8%), Split-night (14.8%), and HSAT-Titration (3.2%). Pathways had significantly different demographic and clinical characteristics. HSAT-Titration had the highest positive airway pressure initiation rate (84.6%) and PSG the lowest (34.4%). After adjustments, time to treatment initiation was significantly associated with pathway (P < .0001); Split-night had shortest duration (median, 28 days), followed by HSAT (36), PSG (37), PSG-Titration (58), and HSAT-Titration (75). HSAT had the lowest sleep test costs and health care resource utilization. CONCLUSIONS: Distinct OSA care pathways exist and are associated with differences in population, care delivery, and economic aspects. CITATION: Wickwire EM, Zhang X, Munson SH, et al. The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States. J Clin Sleep Med. 2024;20(4):505-514.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

Treatment of Adult Obstructive Sleep Apnea with Positive Airway Pressure: An American Academy of Sleep Medicine Clinical Practice Guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for positive airway pressure (PAP) treatment of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Academy of Sleep Medicine (AASM) guidelines in the evaluation and treatment of sleep-disordered breathing in adults. METHODS: The AASM commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of clinically significant benefits and harms, patient values and preferences, and resource use. In addition, the task force adopted recommendations from prior guidelines as "good practice statements" that establish the basis for appropriate and effective treatment of OSA. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENTS: The following good practice statements are based on expert consensus, and their implementation is necessary for appropriate and effective management of patients with OSA treated with positive airway pressure: (1) Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing. (2) Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA. RECOMMENDATIONS: The following recommendations are intended as a guide for clinicians using PAP to treat OSA in adults. A STRONG (ie, "We recommend…") recommendation is one that clinicians should follow under most circumstances. A CONDITIONAL recommendation (ie, "We suggest…") reflects a lower degree of certainty regarding the outcome and appropriateness of the patient-care strategy for all patients. The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources. (1) We recommend that clinicians use PAP, compared to no therapy, to treat OSA in adults with excessive sleepiness. (STRONG) (2) We suggest that clinicians use PAP, compared to no therapy, to treat OSA in adults with impaired sleep-related quality of life. (CONDITIONAL) (3) We suggest that clinicians use PAP, compared to no therapy, to treat OSA in adults with comorbid hypertension. (CONDITIONAL) (4) We recommend that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities. (STRONG) (5) We recommend that clinicians use either CPAP or APAP for ongoing treatment of OSA in adults. (STRONG) (6) We suggest that clinicians use CPAP or APAP over BPAP in the routine treatment of OSA in adults. (CONDITIONAL) (7) We recommend that educational interventions be given with initiation of PAP therapy in adults with OSA. (STRONG) (8) We suggest that behavioral and/or troubleshooting interventions be given during the initial period of PAP therapy in adults with OSA. (CONDITIONAL) (9) We suggest that clinicians use telemonitoring-guided interventions during the initial period of PAP therapy in adults with OSA. (CONDITIONAL).

Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity.

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h(-1), diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp ) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104-0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196-0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.

Leptin and the control of pharyngeal patency during sleep in severe obesity.

RATIONALE: Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep. METHODS: An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions. RESULTS: Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth. CONCLUSION: Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

Association between systemic inflammation and obstructive sleep apnea in men with or at risk for HIV infection.

BACKGROUND: We sought to determine whether markers of systemic inflammation are associated with the presence of moderate/severe obstructive sleep apnea (OSA) and whether this association differs based on HIV and HIV treatment status. METHODS: HIV-uninfected men (HIV-; n=60), HIV-infected men receiving HAART (HIV+/HAART; n=58) and HIV-infected men not receiving HAART (HIV+/no HAART; n=41) underwent polysomnograpy and measurement of plasma levels of tumour necrosis factor (TNF)-α, soluble TNF-α receptors I and II (sTNFRI and sTNFRII) and interleukin (IL)-6. The relationship between moderate/severe OSA (respiratory disturbance index ≥15 apnea/hypopnea events/h) and inflammatory markers was assessed with multivariable regression models. RESULTS: Compared with the HIV- men, HIV+/HAART men and HIV+/no HAART men had higher levels of TNF-α, sTNFRI and sTNFRII, independent of age, race, smoking status, obstructive lung disease (OLD) and body mass index (BMI). Moderate/severe OSA was present in 48% of the sample (HIV- 57%; HIV+/HAART 41%; HIV+/no HAART 44%). Among the HIV+/no HAART men, but not in the other groups, TNF-α, sTNFRII and IL-6 levels were higher in those with moderate/severe OSA compared to men with no/mild OSA after adjustment for age, race, smoking status, OLD and BMI. Within this group, the association of high TNF-α concentrations with moderate/severe OSA was also independent of CD4(+) T-cell count and plasma HIV RNA concentration. CONCLUSIONS: Compared with HIV+/HAART men and HIV- men, markers of systemic inflammation were higher in HIV+/no HAART men. In these men, TNF-α was significantly related to OSA, independent of HIV-related covariates.

Sleep apnea determines soluble TNF-α receptor 2 response to massive weight loss.

BACKGROUND: The effects of surgical weight loss (WL) on inflammatory biomarkers associated with sleep apnea remain unknown. We sought to determine if any biomarkers can predict amelioration of sleep apnea achieved by bariatric surgery. We hypothesized that surgical WL would substantially reduce severity of sleep apnea and levels of proinflammatory cytokines. METHODS: Twenty-three morbidly obese adults underwent anthropometric measurements, polysomnography, and serum biomarker profiling prior to and 1 year following bariatric surgery. We examined the effect of WL and amelioration of sleep apnea on metabolic and inflammatory markers. RESULTS: Surgical WL resulted in significant decreases in BMI (16.7 ± 5.97 kg/m(2)/median 365 days), apnea-hypopnea index (AHI), CRP, IL-6, sTNFαR1, sTNFαR2, and leptin levels, while ghrelin, adiponectin, and soluble leptin receptor concentrations increased significantly. Utilizing an AHI cutoff of 15 events/h, we found significantly elevated levels of baseline sTNFαR2 and greater post-WL sTNFαR2 decreases in subjects with baseline AHI ≥15 events/h compared to those with AHI <15 events/h despite no significant differences in baseline BMI, age, and ΔBMI. In a multivariable linear regression model adjusting for sex, age, impaired glucose metabolism, ΔBMI, and follow-up period, the post-WL decreases in AHI were an independent predictor of the decreases in sTNFαR2 and altogether accounted for 46% of the variance of ΔsTNFαR2 (P = 0.011) in the entire cohort. CONCLUSIONS: Of all the biomarkers, the decrease in sTNFαR2 was independently determined by the amelioration of sleep apnea achieved by bariatric surgery. The results suggest that sTNFαR2 may be a specific sleep apnea biomarker across a wide range of body weight.

Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults.

BACKGROUND: Obstructive sleep apnea (OSA) is a common chronic disorder that often requires lifelong care. Available practice parameters provide evidence-based recommendations for addressing aspects of care. OBJECTIVE: This guideline is designed to assist primary care providers as well as sleep medicine specialists, surgeons, and dentists who care for patients with OSA by providing a comprehensive strategy for the evaluation, management and long-term care of adult patients with OSA. METHODS: The Adult OSA Task Force of the American Academy of Sleep Medicine (AASM) was assembled to produce a clinical guideline from a review of existing practice parameters and available literature. All existing evidence-based AASM practice parameters relevant to the evaluation and management of OSA in adults were incorporated into this guideline. For areas not covered by the practice parameters, the task force performed a literature review and made consensus recommendations using a modified nominal group technique. RECOMMENDATIONS: Questions regarding OSA should be incorporated into routine health evaluations. Suspicion of OSA should trigger a comprehensive sleep evaluation. The diagnostic strategy includes a sleep-oriented history and physical examination, objective testing, and education of the patient. The presence or absence and severity of OSA must be determined before initiating treatment in order to identify those patients at risk of developing the complications of sleep apnea, guide selection of appropriate treatment, and to provide a baseline to establish the effectiveness of subsequent treatment. Once the diagnosis is established, the patient should be included in deciding an appropriate treatment strategy that may include positive airway pressure devices, oral appliances, behavioral treatments, surgery, and/or adjunctive treatments. OSA should be approached as a chronic disease requiring long-term, multidisciplinary management. For each treatment option, appropriate outcome measures and long-term follow-up are described.

Effect of a high-flow open nasal cannula system on obstructive sleep apnea in children.

OBJECTIVE: Obstructive sleep apnea syndrome in children is associated with significant morbidity. Continuous positive airway pressure (CPAP) treats obstructive apnea in children, but is impeded by low adherence. We, therefore, sought to assess the effect of warm humidified air delivered through an open nasal cannula (treatment with nasal insufflation [TNI]) on obstructive sleep apnea in children with and without adenotonsillectomy. METHODS: Twelve participants (age: 10 +/- 1 years; BMI: 35 +/- 14 kg/m(2)), with obstructive apnea-hypopnea syndrome ranging from mild to severe (2-36 events per hour) were administered 20 L/min of air through a nasal cannula. Standard sleep architecture, sleep-disordered breathing, and arousal indexes were assessed at baseline, on TNI, and on CPAP. Additional measures of the percentage of time with inspiratory flow limitation, respiratory rate, and inspiratory duty cycle were assessed at baseline and on TNI. RESULTS: TNI reduced the amount of inspiratory flow limitation, which led to a decrease in respiratory rate and inspiratory duty cycle. TNI improved oxygen stores and decreased arousals, which decreased the occurrence of obstructive apnea from 11 +/- 3 to 5 +/- 2 events per hour (P < .01). In the majority of children, the reduction in the apnea-hypopnea index on TNI was comparable to that on CPAP. CONCLUSIONS: TNI offers an alternative to therapy to CPAP in children with mild-to-severe sleep apnea. Additional studies will be needed to determine the efficacy of this novel form of therapy.

Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity.

RATIONALE: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. OBJECTIVES: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. METHODS: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n = 20) were obtained during bariatric surgery. MEASUREMENTS AND MAIN RESULTS: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 +/- 29 events/hour and the median oxygen desaturation during apneic events was 4.6 +/- 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. CONCLUSIONS: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.

Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase.

Obstructive sleep apnea leads to chronic intermittent hypoxia (CIH) and is associated with atherosclerosis. We have previously shown that C57BL/6J mice exposed to CIH and a high-cholesterol diet develop dyslipidemia, atherosclerosis of the aorta, and upregulation of a hepatic enzyme of lipoprotein secretion, stearoyl coenzyme A desaturase 1 (SCD-1). We hypothesized that (1) SCD-1 deficiency will prevent dyslipidemia and atherosclerosis during CIH; and (2) human OSA is associated with dyslipidemia and upregulation of hepatic SCD. C57BL/6J mice were exposed to CIH or normoxia for 10 weeks while being treated with either SCD-1 or control antisense oligonucleotides. Obese human subjects underwent sleep study and bariatric surgery with intraoperative liver biopsy. In mice, hypoxia increased hepatic SCD-1 and plasma very-low-density lipoprotein cholesterol levels and induced atherosclerosis lesions in the ascending aorta (the cross-section area of 156514+/-57408 microm(2)), and descending aorta (7.0+/-1.2% of the total aortic surface). In mice exposed to CIH and treated with SCD-1 antisense oligonucleotides, dyslipidemia and atherosclerosis in the ascending aorta were abolished, whereas lesions in the descending aorta showed 56% reduction. None of the mice exposed to normoxia developed atherosclerosis. In human subjects, hepatic SCD mRNA levels correlated with the degree of nocturnal hypoxemia (r=0.68, P=0.001). Patients exhibiting oxyhemoglobin desaturations at night showed higher plasma triglyceride and low-density lipoprotein cholesterol levels, compared to subjects without hypoxemia. In conclusion, CIH is associated with dyslipidemia and overexpression of hepatic SCD in both humans and mice alike; SCD-1 deficiency attenuates CIH-induced dyslipidemia and atherosclerosis in mice.