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Background High loop gain (unstable ventilatory control) is an important—but difficult to measure—contributor to obstructive sleep apnea (OSA) pathogenesis, predicting OSA sequelae and/or treatment response. Our objective was to develop and validate a clinical prediction tool of loop gain. Methods A retrospective cohort of consecutive adults with OSA (apnea–hypopnea index, AHI > 5/hour) based on in-laboratory polysomnography 01/2017–12/2018 was randomly split into a training and test-set (3:1-ratio). Using a customized algorithm (“reference standard”) loop gain was quantified from raw polysomnography signals on a continuous scale and additionally dichotomized (high > 0.7). Candidate predictors included general patient characteristics and routine polysomnography data. The model was developed (training-set) using linear regression with backward selection (tenfold cross-validated mean square errors); the predicted loop gain of the final linear regression model was used to predict loop gain class. More complex, alternative models including lasso regression or random forests were considered but did not meet pre-specified superiority-criteria. Final model performance was validated on the test-set. Results The total cohort included 1055 patients (33% high loop gain). Based on the final model, higher AHI (beta = 0.0016; P < .001) and lower hypopnea-percentage (beta = −0.0019; P < .001) predicted higher loop gain values. The predicted loop gain showed moderate-to-high correlation with the reference loop gain (r = 0.48; 95% CI 0.38–0.57) and moderate discrimination of patients with high versus low loop gain (area under the curve = 0.73; 95% CI 0.67–0.80). Conclusion To our knowledge this is the first prediction model of loop gain based on readily-available clinical data, which may facilitate retrospective analyses of existing datasets, better patient selection for clinical trials and eventually clinical practice.

Obstructive and central sleep apnea affects ~1 billion people globally and may lead to serious cardiovascular and neurocognitive consequences, but treatment options are limited. High loop gain (ventilatory instability) is a major pathophysiological mechanism underlying both types of sleep apnea and can be lowered pharmacologically with acetazolamide, thereby improving sleep apnea severity. However, individual responses vary and are strongly correlated with the loop gain reduction achieved by acetazolamide. To aid with patient selection for long‐term trials and clinical care, our goal was to understand better the factors that determine the change in loop gain following acetazolamide in human subjects with sleep apnea. Thus, we (i) performed several meta‐analyses to clarify how acetazolamide affects ventilatory control and loop gain (including its primary components controller/plant gain), and based on these results, we (ii) performed physiological model simulations to assess how different baseline conditions affect the change in loop gain. Our results suggest that (i) acetazolamide primarily causes a left shift of the chemosensitivity line thus lowering plant gain without substantially affecting controller gain; and (ii) higher controller gain, higher paCO2 at eupneic ventilation, and lower CO2 production at baseline result in a more pronounced loop gain reduction with acetazolamide. In summary, the combination of mechanistic meta‐analyses with model simulations provides a unified framework of acetazolamide’s effects on ventilatory control and revealed physiological predictors of response, which are consistent with empirical observations of acetazolamide's effects in different sleep apnea subgroups. Prospective studies are needed to validate these predictors and assess their value for patient selection. (a) Based on mechanistic meta‐analyses in patients with sleep apnea, acetazolamide primarily causes a left‐shift of the chemosensitivity line thus lowering plant gain without substantially affecting controller gain; the net effect is a relative reduction in overall loop gain similar to the reduction in plant gain. (b) Based on model simulations, a higher controller gain, higher paCO2 at eupneic ventilation, and lower CO2 production at baseline each result in a more pronounced loop gain reduction with acetazolamide, and thus may predict response to acetazolamide.

Study Objectives: Scleroderma is associated with abnormal skin thickening, interstitial lung disease, pulmonary hypertension, and abnormalities of the upper airway. These changes can cause cardiopulmonary complications, potentially including sleep-disordered breathing. The objective of this study is to examine the risk of sleep-disordered breathing in patients with scleroderma. Methods: We retrospectively identified patients with documented scleroderma. We abstracted data from their electronic health records, including findings from antibody tests, serial pulmonary function tests, transthoracic echocardiography, high-resolution computed tomography, and overnight forehead oximetry. Results: We identified 171 patients with scleroderma. Mean age at the time of initial consult was 56.5 years (range, 18–96 years), and 150 (86.7%) were women. Scleroderma was categorized as limited disease for 108 (62.4%), diffuse disease for 59 (34.1%), and mixed connective tissue disease for 6 (3.5%). Fifty-four patients (31.2%) had abnormal overnight forehead oximetry results, defined as an oxygen desaturation index greater than 5 or a baseline mean arterial oxygen saturation level less than 90%. Conclusions: Cardiopulmonary complications are common in patients with scleroderma, one of which may be sleep-disordered breathing. In our cohort, approximately one-third of individuals with scleroderma had evidence of sleep-disordered breathing. Moreover, the rate of sleep-disordered breathing in our population of scleroderma patients was twice the rate of pulmonary hypertension and was approximately the same as the rate of interstitial lung disease. Future prospective studies are needed to further assess the role of sleep-disordered breathing in scleroderma clinical outcomes. Citation: Nokes BT, Raza HA, Cartin-Ceba R, Lyng PJ, Krahn LE, Wesselius L, Jokerst CE, Umar SB, Griffing WL, Neville MR, Malhotra A, Parish JM. Individuals with scleroderma may have increased risk of sleep-disordered breathing. J Clin Sleep Med . 2019;15(11):1665–1669.

There is a need for alternatives to positive airway pressure for the treatment of obstructive sleep apnea and snoring. Improving upper airway dilator function might alleviate upper airway obstruction. We hypothesized that transoral neuromuscular stimulation would reduce upper airway collapse in concert with improvement in genioglossal muscle function. Subjects with simple snoring and mild OSA (AHI < 15/h on screening) underwent in‐laboratory polysomnography with concurrent genioglossal electromyography (EMGgg) before and after 4–6 weeks of twice‐daily transoral neuromuscular stimulation. Twenty patients completed the study: Sixteen males, mean ± SD age 40 ± 13 years, and BMI 26.3 ± 3.8 kg/m2. Although there was no change in non‐rapid eye movement EMGgg phasic (p = 0.66) or tonic activity (p = 0.83), and no decrease in snoring or flow limitation, treatment was associated with improvements in tongue endurance, sleep quality, and sleep efficiency. In this protocol, transoral neurostimulation did not result in changes in genioglossal activity or upper airway collapse, but other beneficial effects were noted suggesting a need for additional mechanistic investigation. Daytime transoral neuromuscular stimulation is a novel treatment for mild obstructive sleep apnea and snoring. We sought to evaluate the mechanism by which this method of sleep apnea improves disease severity. There was no change in neural drive to genioglossus, but there was an improvement in tongue endurance.

Study Objectives: Obstructive sleep apnea (OSA) is a common chronic medical condition that results in impaired daytime functioning. While the link between OSA and cardiovascular disease is important, there has been increasing recognition of the impact of OSA on daytime functioning and experience. Better insight into illness perceptions can help better understand how to initiate and maintain treatment. Methods: Data from 2 OSA clinical trials were examined. The baseline respiratory event index was obtained from diagnostic sleep testing. The Brief Illness Perception Questionnaire assesses the cognitive and emotional representation of illness and was administered at baseline along with the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Results: A total of 523 patients diagnosed with OSA were studied. The sample had a mean age of 51.1 ± 16.6, mean respiratory event index of 28.6 ± 17.9 events/h, and mean body mass index of 32.8 ± 15.5 kg/m 2 . The mean Brief Illness Perception Questionnaire total score at baseline was 43.3 ± 11.3. Brief Illness Perception Questionnaire scores were significantly correlated with sleepiness and sleep quality but not with respiratory event index. Relative to other common chronic conditions with major comorbidities, Brief Illness Perception Questionnaire scores for patients with OSA were higher on consequences, identity, concern, and emotional representation dimensions. Conclusions: The study shows that veterans with OSA report elevated illness perceptions across several dimensions at levels as high, or higher, than other common chronic conditions. Implications for clinical practice are that it is important to ask patients about their understanding of illness across several dimensions to appreciate better patient needs and preferences. Citation: Zamora T, Nokes B, Malhotra A, Stepnowsky C. Obstructive sleep apnea illness perception relative to other common chronic conditions. J Clin Sleep Med . 2025;21(2):229–235.

Introduction Mild obstructive sleep apnea (OSA) is increasingly common in the VA. The first-line therapies are medical devices worn each night while asleep to control or manage OSA. These devices are burdensome for our patients with mild OSA. Stronger oral musculature can help reduce mild OSA. A new transoral Neuromuscular Electrical Stimulation (NMES) device was recently approved by the US FDA called eXciteOSA (Signifier Medical Technologies, Needham, MA). The eXciteOSA device provides gentle, low-frequency electrical stimulation intraorally to the tongue muscle and is efficacious for mild OSA. Methods A retrospective review of the data of the 71 patients prescribed the eXciteOSA device at the VA San Diego was analyzed. The device is prescribed for use over two phases: (1) one 20-minute session per day over 42 consecutive days and then (2) one 20-minute session on two days out of each week. Respiratory therapists performed 1-2 phone call visits to assess symptoms and address device concerns. Results 68 of the 71 patients used the device for at least one 20-minute session over the first 42 days. Three patients (4.2%) did not use the device. Adherence was 60% for all 71 patients and 63% for the 68 patients who used it at least once. This means that, on average, our Veteran patients completed one 20-minute session on 25 of the first 42 days. Conclusion Recent non-Veteran data showed an adherence rate of ~80% (percentage of days with one completed 20-minute session over the first 42 days). Our analysis found an adherence rate of ~60%, suggesting significant room for improvement in eXciteOSA device use in Veterans. Future adherence studies should look at methods to improve device use over the first 42 days. In addition, more research may be needed to understand better what amount of use is efficacious on an individual basis. Some patients may obtain an adequate response with fewer sessions, while others may need more. It is unknown which endotypes of OSA most benefit from NMES, but further research is ongoing. Support (if any) VA RR&D D2651-R and the Sleep Medicine Section of the VA San Diego Healthcare System supported this project.

Nokes B, Raza H, Malhotra A. Pulmonary hypertension and obstructive sleep apnea. J Clin Sleep Med. 2020;16(4):649.

Introduction The Veterans Health Administration (VA) is one of the largest integrated healthcare systems in the United States. Key risk factors for obstructive sleep apnea (OSA) include aging, weight, and male gender, all of which are highly prevalent in the VA population and help to explain the higher rates of OSA in the VA. The Pulmonary Sleep Program at the VA San Diego Healthcare System (VASDHS) started a patient database over twenty years ago for its home sleep apnea testing (HSAT) program. An analysis of ten years of diagnostic HSAT data was reported on over 12,500 patients in 2014. This analysis focuses on an update on the last four years and a comparison to 2014. Methods A retrospective review of the local clinical database of HSAT diagnostic testing was conducted. The database contained 8,928 sleep studies from 2018 to 2022. Invalid studies were removed. Only initial diagnostic studies were included. Results Of the 8,928 diagnostic studies, 2,564 tested negative for OSA (28.7%). Of the 6,364 positive cases, 43.3% were mild, 28.8% were moderate, and 27.9% were severe. The percentages of each OSA severity level were stable across these years (mild: 42%-45%; moderate: 27%-32%; and severe: 26%-29%). The mean AHI did not significantly change from 2018 (24.1+/-20.6) to 2022 (25.1+/-21.2) (overall mean 24.4+/-20.3; range: 5-140). Conclusion Based on this extensive retrospective review of diagnostic testing at a single, high-volume HSAT program, it appears that OSA severity levels have stabilized over these past five years, with the highest percentage of mild OSA cases (~43%) followed by moderate (~29%) and severe (~28%). Our facility saw a significant decrease in severe cases (60% to 30%) and increase in mild OSA (7% to 35%) from 2004 to 2013. Today, over 4 out of every 10 new OSA diagnoses are mild, which has significant treatment implications given that adherence to the two primary medical device options is suboptimal. Identifying patient-centered treatment options for these patients is a priority. Support (if any) VA RR&D D2651-R and the Sleep Medicine Section of the VA San Diego Healthcare System supported this project.