Strengths, weaknesses, opportunities and threats of using AI-enabled technology in sleep medicine: a commentary.

Over the past few years, artificial intelligence (AI) has emerged as a powerful tool used to efficiently automate several tasks across multiple domains. Sleep medicine is perfectly positioned to leverage this tool due to the wealth of physiological signals obtained through sleep studies or sleep tracking devices and abundance of accessible clinical data through electronic medical records. However, caution must be applied when utilizing AI, due to intrinsic challenges associated with novel technology. The Artificial Intelligence in Sleep Medicine committee of the American Academy of Sleep Medicine (AASM) reviews advancements in AI within the sleep medicine field. In this article, the Artificial Intelligence in Sleep Medicine committee members provide a commentary on the scope of AI technology in sleep medicine. The commentary identifies three pivotal areas in sleep medicine which can benefit from AI technologies: clinical care, lifestyle management and population health management. This article provides a detailed analysis of the strengths, weaknesses, opportunities, and threats associated with using AI enabled technologies in each pivotal area. Finally, the article broadly reviews barriers and challenges associated with using AI enabled technologies and offers possible solutions.

Dysregulated 24 h melatonin secretion associated with intrinsically photosensitive retinal ganglion cell function in diabetic retinopathy: a cross-sectional study.

AIMS/HYPOTHESIS: The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function. METHODS: Participants with type 2 diabetes, with diabetic retinopathy (n=14) and without diabetic retinopathy (n=9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR). Habitual sleep duration, efficiency and variability were assessed by actigraphy. RESULTS: Participants with diabetic retinopathy compared to participants without diabetic retinopathy had smaller PIPR (p=0.007), lower 24 h serum melatonin output (p=0.042) and greater day-to-day sleep variability (p=0.012). By contrast, 24 h cortisol profiles, sleep duration and efficiency were similar in both groups. Six individuals with diabetic retinopathy had no detectable dim-light melatonin onset. PIPR correlated with 24 h mean melatonin levels (r=0.555, p=0.007). CONCLUSIONS/INTERPRETATION: ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy.

Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes.

Sleep irregularity and variability have been shown to be detrimental to cardiometabolic health. The present pilot study explored if higher day-to-day sleep irregularity and variability were associated with systemic inflammation, as assessed by high-sensitivity C-reactive protein, in type 2 diabetes. Thirty-five patients with type 2 diabetes (mean age 54.3 years, 54.3% female) who were not shift-workers participated. The presence of diabetic retinopathy was determined. The standard deviation of sleep duration and sleep midpoint across all recorded nights were used to quantify sleep variability and regularity, respectively, assessed by 14-day actigraphy. The presence and severity of sleep apnea were assessed using an overnight home monitor. Low-density lipoprotein, haemoglobin A1C and high-sensitivity C-reactive protein were collected. Multiple regression analysis using natural-log-transformed values was performed to establish an independent association between sleep variability and high-sensitivity C-reactive protein. Twenty-two (62.9%) patients had diabetic retinopathy. The median (interquartile range) of high-sensitivity C-reactive protein was 2.4 (1.4, 4.6) mg L-1 . Higher sleep variability was significantly associated with higher high-sensitivity C-reactive protein (r = 0.342, p = 0.044), as was haemoglobin A1C (r = 0.431, p = 0.010) and low-density lipoprotein (r = 0.379, p = 0.025), but not sleep regularity, sleep apnea severity or diabetic retinopathy. Multiple regression analysis showed that higher sleep variability (B = 0.907, p = 0.038) and higher HbA1c (B = 1.519, p = 0.035), but not low-density lipoprotein, contributed to higher high-sensitivity C-reactive protein. In conclusion, higher sleep variability in patients with type 2 diabetes who were not shift-workers was independently associated with higher systemic inflammation, conferring increased cardiovascular risk. Whether sleep interventions to reduce sleep variability can reduce systemic inflammation and improve cardiometabolic health should be investigated.

Race and Socioeconomic Status: Interlinked Drivers of Sleep Health Disparities.

The effect of race and socioeconomic status on sleep disorders has significant effects on the availability of healthcare and health outcomes. This paper examines how race and SES contribute to sleep health disparities, emphasizing the importance of understanding their impact on sleep disorders and treatment particularly in minority populations and veterans.

Defining the impact of continuous positive airway pressure therapy on diastolic function in adults with moderate-to-severe obstructive sleep apnea.

Although studies have shown that continuous positive airway pressure (CPAP) therapy to treat obstructive sleep apnea improves left ventricular diastolic function, modifiers of improvement are unknown. We explored race and pre-treatment 24-h non-dipping blood pressure status as modifiers of improved diastolic function. Participants (N = 220) with obstructive sleep apnea (apnea-hypopnea index ≥15 events/h) and hypertension were recruited to a cohort study that examined effects of 3-month CPAP therapy on 24-h blood pressure. Those who completed echocardiogram at baseline and follow-up were included in this analysis. Diastolic function parameters (E, A, e', E/A, E/e') were assessed. Race was categorised to African American versus others. Participants were categorised as nocturnal dippers (night-time blood pressure decrease by ≥10%) versus non-dippers. We compared changes in parameters of diastolic function by race and nocturnal dipping status. A total of 92 participants were included. They were men (86%), African American (67.4%), and current smoker (29.5%). Mean apnea-hypopnea index was 32.9 events/h. Mean CPAP usage was 3.15 h/day. After 3 months of CPAP treatment, there were significant improvements in measures of diastolic function: a median (interquartile range [IQR]) increase in E velocity by 4.00 (-5.75 to 13.75) cm/s, an increase in e' by 2.00 (0-4.00) cm/s, and a decrease in the E/e' ratio by 1.74 (-4.27 to 0.00) at follow-up (p < 0.05). These changes did not differ by race or nocturnal dipping status. Improvements in diastolic function after CPAP therapy did not differ by race or nocturnal dipping status. Further studies are needed to understand predictors of CPAP effects on diastolic function.

Therapy for insomnia with chronic obstructive pulmonary disease: a randomized trial of components.

STUDY OBJECTIVES: To determine efficacy and mechanisms of cognitive behavioral therapy for insomnia (CBT-I) and chronic obstructive pulmonary disease (COPD) education (COPD-ED) on clinical outcomes in adults with concurrent COPD and insomnia. METHODS: We conducted a 2 × 2 factorial study to test the impact of CBT-I and COPD-ED delivered alone or in combination on severity of insomnia and fatigue, sleep, and dyspnea. Participants were randomized to 1 of 4 groups-group 1: CBT-I + attention control (AC; health videos, n = 27); group 2: COPD-ED + AC, n = 28; group 3: CBT-I + COPD-ED, n = 27; and group 4, AC only, n = 27. Participants received six 75-minute weekly sessions. Dependent variables included insomnia severity, sleep by actigraphy, fatigue, and dyspnea measured at baseline, immediately postintervention, and at 3 months postintervention. Presumed mediators of intervention effects included beliefs and attitudes about sleep, self-efficacy for sleep and COPD, and emotional function. RESULTS: COPD patients (percent predicted forced expiratory volume in 1 second [FEV1pp] 67% ± 24% [mean ± standard deviation]), aged 65 ± 8 years, with insomnia participated in the study. Insomnia and sleep improved more in patients who received CBT-I than in those who did not, an effect that was sustained at 3 months postintervention and mediated by beliefs and attitudes about sleep. CBT-I was associated with clinically important improvements in fatigue and dyspnea. When CBT-I and COPD-ED were concurrently administered, effects on insomnia, fatigue, and dyspnea were attenuated. CONCLUSIONS: CBT-I produced significant and sustained decreases in insomnia improved sleep and clinically important improvement in fatigue, and dyspnea. The combination of CBT-I and COPD-ED reduced CBT-I's effectiveness. Further research is needed to understand the mechanisms associated with effects of insomnia therapy on multiple symptoms in COPD. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Behavioral Therapy for Insomnia Co-existing with COPD; URL: https://clinicaltrials.gov/ct2/show/NCT01973647; Identifier: NCT01973647. CITATION: Kapella M, Steffen A, Prasad B, et al. Therapy for insomnia with chronic obstructive pulmonary disease: a randomized trial of components. J Clin Sleep Med. 2022;18(12):2763-2774.

Deep Learning Analyses of Brain MRI to Identify Sustained Attention Deficit in Treated Obstructive Sleep Apnea: A Pilot Study.

Purpose: Persistent sustained attention deficit (SAD) after continuous positive airway pressure (CPAP) treatment is a source of quality of life and occupational impairment in obstructive sleep apnea (OSA). However, persistent SAD is difficult to predict in patients initiated on CPAP treatment. We performed secondary analyses of brain magnetic resonance (MR) images in treated OSA participants, using deep learning, to predict SAD. Methods: 26 middle-aged men with CPAP use of more than 6 hours daily and MR imaging were included. SAD was defined by psychomotor vigilance task lapses of more than 2. 17 participants had SAD and 9 were without SAD. A Convolutional Neural Network (CNN) model was used for classifying the MR images into +SAD and -SAD categories. Results: The CNN model achieved an accuracy of 97.02±0.80% in classifying MR images into +SAD and -SAD categories. Assuming a threshold of 90% probability for the MR image being correctly classified, the model provided a participant-level accuracy of 99.11±0.55% and a stable image level accuracy of 97.45±0.63%. Conclusion: Deep learning methods, such as the proposed CNN model, can accurately predict persistent SAD based on MR images. Further replication of these findings will allow early initiation of adjunctive pharmacologic treatment in high-risk patients, along with CPAP, to improve quality of life and occupational fitness. Future augmentation of this approach with explainable artificial intelligence methods may elucidate the neuroanatomical areas underlying persistent SAD to provide mechanistic insights and novel therapeutic targets.

Socioeconomic status impacts blood pressure response to positive airway pressure treatment.

STUDY OBJECTIVES: Positive airway pressure (PAP) treatment of obstructive sleep apnea reduces blood pressure (BP). Retrospective data suggest that African Americans (AA), a group at high-risk for hypertensive organ dysfunction, may have a greater BP response to PAP therapy than European Americans (EA). We examined the difference in 24-hour BP response to 3 months of PAP treatment between AA and EA. METHODS: Participants (n = 259, 161 AA and 98 EA) with apnea-hypopnea index ≥ 15 events/h from 2 prospective cohorts were included. t-Tests and multiple linear regression were used to examine BP outcomes in AA vs EA, adjusting for PAP adherence, socioeconomic status, and baseline characteristics. RESULTS: Participants were middle aged (mean ± SD, 53.8 ± 9.3 years), 86% (227) men, apnea-hypopnea index 35.6 ± 19.2 events/h, and PAP adherence of 3.36 ± 2.24 h/day. The reductions in 24-hour systolic and diastolic BP (mm Hg) were not different in AA vs EA (systolic = -1.13 ± 12.1 vs -0.61 ± 12.8, P = .80 and diastolic = -0.74 ± 7.9 vs -0.80 ± 7.4, P = .96), and race was not a predictor of 24-hour systolic or diastolic BP reduction (P = .75 and 0.54). Socioeconomic status and PAP adherence demonstrated a significant interaction; low socioeconomic status was associated with an increase in 24-hour systolic BP (ß = 19.3, P = .03) in the absence of PAP use but a greater reduction in 24-hour systolic BP with higher PAP adherence (ß = -3.96, P = .03). CONCLUSIONS: Twenty-four hour BP response to PAP treatment is similar in AA and EA. Adherence to PAP treatment is more effective in improving 24-hour systolic BP in those with low SES. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Race and CPAP Effectiveness (RACE); URL: https://clinicaltrials.gov/ct2/show/NCT01960465; Identifier: NCT01960465 and Registry: ClinicalTrials.gov; Name: The Effects of Treating Obese and Lean Patients with Sleep Apnea (PISA); URL: https://clinicaltrials.gov/ct2/show/NCT01578031; Identifier: NCT01578031. CITATION: Imayama I, Gupta A, Yen PS, et al. Socioeconomic status impacts blood pressure response to positive airway pressure treatment. J Clin Sleep Med. 2022;18(5):1287-1295.

Racial Differences in Functional and Sleep Outcomes with Positive Airway Pressure Treatment.

It is unclear if the response to positive airway pressure (PAP) treatment is different between African American (AA) and European Americans (EA). We examined whether race modifies the effects of PAP on sleep and daytime function. We assessed Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire, Psychomotor Vigilance Task and actigraphy in 185 participants with moderate-to-severe obstructive sleep apnea before and 3-4 months after PAP treatment. The participants were middle-aged (mean, 55.1 years), 83.8% men and 60.5% AA. Linear regression models were used to examine the effect of race on outcomes. The AA had smaller reductions in ESS (mean change (95% confidence interval, CI) AA, -2.30 [-3.35, -1.25] vs. EA, -4.16 [-5.48, -2.84] and frequency of awakenings (AA, -0.73 [-4.92, 3.47] vs. EA, -9.35 [-15.20, -3.51]). A race × PAP usage interaction term was added to the model to examine if the change in outcomes per 1 h increase in PAP usage differed by race. AA exhibited greater improvement in wake after sleep onset (ß (95% CI) AA, -8.89 [-16.40, -1.37] vs. EA, 2.49 [-4.15, 9.12]) and frequency of awakening (ß (95% CI) AA, -2.59 [-4.44, -0.75] vs. EA, 1.71 [-1.08, 4.50]). The results indicate the importance of race in evaluating outcomes following PAP treatment.

Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea.

STUDY OBJECTIVES: To explore the association of continuous positive airway pressure (CPAP) adherence with clinical outcomes in patients with type 2 diabetes and obstructive sleep apnea in a real-world setting. METHODS: This was a retrospective study of patients with type 2 diabetes diagnosed with obstructive sleep apnea between 2010 and 2017. CPAP adherence (usage for ≥ 4 h/night for ≥ 70% of nights) was determined from the first CPAP report following the polysomnography. Data including estimated glomerular filtration rate, hemoglobin A1c, systolic and diastolic blood pressure, lipid panel, and incident cardiovascular/peripheral vascular/cerebrovascular events were extracted from medical records. Mixed-effects linear regression modeling of longitudinal repeated measures within patients was utilized for continuous outcomes, and logistic regression modeling was used for binary outcomes. Models were controlled for age, sex, body mass index, medications, and baseline levels of outcomes. RESULTS: Of the 1,295 patients, 260 (20.7%) were CPAP adherent, 318 (24.5%) were CPAP nonadherent, and 717 (55.3%) had insufficient data. The follow-up period was, on average, 2.5 (1.7) years. Compared to those who were CPAP nonadherent, those who were adherent had a significantly lower systolic blood pressure (ß = -1.95 mm Hg, P = .001) and diastolic blood pressure (ß = -2.33 mm Hg, P < .0001). Among the patients who were CPAP adherent, a 17% greater CPAP adherence was associated with a 2 mm Hg lower systolic blood pressure. Lipids, hemoglobin A1c, estimated glomerular filtration rate, and incident cardiovascular/peripheral vascular/cerebrovascular events were not different between the 2 groups. CONCLUSIONS: Achieving CPAP adherence in patients with type 2 diabetes and obstructive sleep apnea was associated with significantly lower blood pressure. Greater CPAP use within patients who were adherent was associated with lower systolic blood pressure. CITATION: Sheth U, Monson RS, Prasad B, et al. Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea. J Clin Sleep Med. 2021;17(8):1563-1569.

The need for specificity in quantifying neurocirculatory vs. respiratory effects of eucapnic hypoxia and transient hyperoxia.

KEY POINTS: The carotid chemoreceptor mediates the ventilatory and muscle sympathetic nerve activity (MSNA) responses to hypoxia and contributes to tonic sympathetic and respiratory drives. It is often presumed that both excitatory and inhibitory tests of chemoreflex function show congruence in the end-organ responses. Ventilatory and neurocirculatory (MSNA, blood pressure and heart rate) responses to chemoreflex inhibition elicited by transient hyperoxia and to chemoreflex excitation produced by steady-state eucapnic hypoxia were measured in a cohort of 82 middle-aged individuals. Ventilatory and MSNA responsiveness to hyperoxia and hypoxia were not significantly correlated within individuals. It was concluded that ventilatory responses to hypoxia and hyperoxia do not predict MSNA responses and it is recommended that tests using the specific outcome of interest, i.e. MSNA or ventilation, are required. Transient hyperoxia is recommended as a sensitive and reliable means of quantifying tonic chemoreceptor-driven levels of sympathetic nervous system activity and respiratory drive. ABSTRACT: Hypersensitivity of the carotid chemoreceptor leading to sympathetic nervous system activation and ventilatory instability has been implicated in the pathogenesis and consequences of several common clinical conditions. A variety of treatment approaches aimed at lessening chemoreceptor-driven sympathetic overactivity are now under investigation; thus, the ability to quantify this outcome variable with specificity and precision is crucial. Accordingly, we measured ventilatory and neurocirculatory responses to chemoreflex inhibition elicited by transient hyperoxia and chemoreflex excitation produced by exposure to graded, steady-state eucapnic hypoxia in middle-aged men and women (n = 82) with continuous positive airway pressure-treated obstructive sleep apnoea. Progressive, eucapnic hypoxia produced robust and highly variable increases in ventilation (+83 ± 59%) and muscle sympathetic nerve activity (MSNA) burst frequency (+55 ± 31%), whereas transient hyperoxia caused marked reductions in these variables (-35 ± 14% and -42 ± 16%, respectively). Coefficients of variation for ventilatory and MSNA burst frequency responses, indicating test-retest reproducibility, were respectively 9% and 24% for hyperoxia and 35% and 28% for hypoxia. Based on statistical measures of rank correlation or even comparisons across quartiles of corresponding ventilatory and MSNA responses, we found that the magnitudes of ventilatory inhibition with hyperoxia or excitation with eucapnic hypoxia were not correlated with corresponding MSNA responses within individuals. We conclude that, in conscious, behaving humans, ventilatory sensitivities to progressive, steady-state, eucapnic hypoxia and transient hyperoxia do not predict MSNA responsiveness. Our findings also support the use of transient hyperoxia as a reliable, sensitive, measure of the carotid chemoreceptor contribution to tonic sympathetic nervous system activity and respiratory drive.

Deep learning applied to polysomnography to predict blood pressure in obstructive sleep apnea and obesity hypoventilation: a proof-of-concept study.

STUDY OBJECTIVES: Nocturnal blood pressure (BP) profile shows characteristic abnormalities in OSA, namely acute postapnea BP surges and nondipping BP. These abnormal BP profiles provide prognostic clues indicating increased cardiovascular disease risk. We developed a deep neural network model to perform computerized analysis of polysomnography data and predict nocturnal BP profile. METHODS: We analyzed concurrently performed polysomnography and noninvasive beat-to-beat BP measurement with a deep neural network model to predict nocturnal BP profiles from polysomnography data in 13 patients with severe OSA. RESULTS: A good correlation was noted between measured and predicted postapnea systolic and diastolic BP (Pearson r ≥ .75). Moreover, Bland-Altman analyses showed good agreement between the 2 values. Continuous systolic and diastolic BP prediction by the deep neural network model was also well correlated with measured BP values (Pearson r ≥ .83). CONCLUSIONS: We developed a deep neural network model to predict nocturnal BP profile from clinical polysomnography signals and provide a potential prognostic tool in OSA. Validation of the model in larger samples and examination of its utility in predicting CVD risk in future studies is warranted.

Comparing VA and Community-Based Care: Trends in Sleep Studies Following the Veterans Choice Act.

BACKGROUND: To address concerns about access to care, the Veterans Access, Choice, and Accountability Act of 2014 was enacted to make care available in the community when Veterans Health Administration (VA) care was unavailable or not timely. This paper examined VA referrals for diagnostic sleep studies from federal fiscal year (FY) 2015-2018. DESIGN: Sleep studies completed between FY2015 and 2018 for Veterans tested within VA facilities (VAF) or referred to VA community care (VACC) providers were identified using VA administrative data files. Sleep studies were divided into laboratory and home studies. KEY RESULTS: The number of sleep studies conducted increased over time; the proportion of home studies increased in VAF (32 to 47%). Veterans were more likely to be referred for a sleep study to VACC if they lived in a rural or highly rural area (ORs = 1.47 and 1.55, respectively), and had public or public and private insurance (ORs = 2.01 and 1.35), and were less likely to be referred to VACC if they were age 65+ (OR = 0.72) and were in the highest utilization risk based on Nosos score (OR = 0.78). Regression analysis of sleep study type revealed that lab studies were much more likely for VACC referrals (OR = 3.16), for persons living in rural areas (OR = 1.21), with higher comorbidity scores (OR = 1.28) and for ages 44-54, 55 to 64, and 65+ (ORs = 1.12, 1.28, 1.45, respectively) compared to younger Veterans. Veterans with some or full VA copayments (ORs = 0.91 and 0.86, respectively), and overweight Veterans (OR = 0.94) were less likely to have lab studies. CONCLUSIONS: The number of sleep studies performed on Veterans increased from 2015 to 2018. Access to sleep studies improved through a combination of providing care through the Veteran Choice Program, predominantly used by rural Veterans, and increased use of home sleep studies by VA.

Obstructive Sleep Apnea Is Associated with Newly Diagnosed Gestational Diabetes Mellitus.

Rationale: Sleep-disordered breathing (SDB) is associated with increased risk of adverse pregnancy outcomes, including gestational diabetes mellitus (GDM). GDM is a significant cause of maternal and infant morbidities. Assessing these risk factors concurrently may facilitate both the identification of women at GDM risk and the initiation of GDM prevention strategies.Objectives: To investigate whether SDB events, including SDB in rapid eye movement (REM) sleep and other sleep parameters, are associated with increased risk of GDM and to evaluate the performance of the models investigating associations between breathing and sleep parameters and GDM risk.Methods: In this case-control study, 46 women with newly diagnosed GDM and 46 healthy control subjects, who were individually matched for age, gestational age, body mass index, race, and parity, completed overnight polysomnographic studies and sleep questionnaires after being screened for GDM during the late-second to mid-third trimesters. Conditional logistic regression analysis was used to identify models investigating associations between risk factors and GDM risk. The Bayesian information criterion (BIC) was employed to compare models; the model with the lowest BIC is preferred.Results: Obstructive sleep apnea (OSA; defined as an apnea-hypopnea index [AHI] >5 events/h) was present in 22% of subjects with GDM and 9% of control subjects (P < 0.001). Women with OSA had a higher GDM risk (odds ratio [OR], 4.71; 95% confidence interval [CI], 1.05-21.04). In individual models, GDM risk was also significantly higher among women with higher overall AHI (events/h OR, 1.81; 95% CI, 1.01-3.27), higher AHI in REM (events/h OR, 2.09; 95% CI, 1.02-4.31), higher oxygen desaturation index greater than or equal to 4% (ODI4; events/h OR, 2.21; 95% CI, 1.03-4.73), and higher Sleep Apnea Symptom Score (OR, 2.72; 95% CI, 1.11-6.69). The percentage of non-REM sleep was significantly associated with decreased risk of GDM (percentage of non-REM sleep OR, 0.88; 95% CI, 0.78-0.99). The BIC supports the conclusion that there is a strong association between AHI in REM and GDM risk compared with the other significant models.Conclusions: SDB events, including REM-related OSA, are linked to increased GDM risk. GDM risk is also influenced by intercorrelated sleep variables.

ATS Core Curriculum 2020. Adult Sleep Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3-4-year recurring cycle of topics. These topics will be presented at the 2020 Virtual Conference. Below is the adult sleep medicine core that includes topics pertinent to sleep-disordered breathing and insomnia.

Asthma and Obstructive Sleep Apnea Overlap: What Has the Evidence Taught Us?

Obstructive sleep apnea (OSA) and asthma are highly prevalent chronic respiratory disorders. Beyond their frequent coexistence arising from their high prevalence and shared risk factors, these disorders feature a reciprocal interaction whereby each disease impacts the severity of the other. Emerging evidence implicates airway and systemic inflammation, neuroimmune interactions, and effects of asthma-controlling medications (corticosteroids) as factors that predispose patients with asthma to OSA. Conversely, undiagnosed or inadequately treated OSA adversely affects asthma control, partly via effects of intermittent hypoxia on airway inflammation and tissue remodeling. In this article, we review multiple lines of recently published evidence supporting this interaction. We provide a set of recommendations for clinicians involved in the care of adults with asthma, and identify critical gaps in our knowledge about this overlap.

Circulating plasma exosomes in obstructive sleep apnoea and reverse dipping blood pressure.

BACKGROUND: Obstructive sleep apnoea (OSA) increases the risk of an abnormal nondipping 24 h blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal microRNA (miRNA) expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP), an extreme form of nondipping, to understand the mechanisms underlying nondipping blood pressure in OSA. METHODS: 46 patients (15 RDBP versus 31 NDBP) matched for OSA severity (respiratory event index 32.6±22.5 versus 32.2±18.1 events·h-1; p=0.9), age (54.8±12.9 versus 49±9.9 years; p=0.09) and body mass index (36.2±6.6 versus 34.4±6.8 kg·m-2; p=0.4) were included. Plasma exosomes were characterised by flow cytometry and functional in vitro reporter assays were conducted on cultured endothelial cells. Exosome miRNA cargo was profiled with microarrays followed by bioinformatics analyses. RESULTS: Exosomes from RDBP patients increased the permeability of endothelial cell tight junctions and adhesion molecule expression. Principal component analyses of miRNA array data showed strict separation and identification of the two groups. A restricted and validated signature of exosomal miRNAs was identified in the RDBP versus NDBP group. Their predicted target genes involved phosphatidylinositol 3-kinase-Akt (p=0.004), Ras (p=3.42E-05), Wnt (p=0.003) and hypoxia inducible factor-1 signalling (p=0.04), inflammatory mediator regulation of transient receptor potential channels (p=0.01), and several cancer-related pathways. CONCLUSIONS: Patients with RDBP have altered miRNA cargoes in circulating exosomes that invoke in vitro endothelial dysfunction. A selected number of circulating exosomal miRNAs play an important role in abnormal circadian regulation of blood pressure and may provide prognostic biomarkers of CVD risk in OSA.