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Sleep-disordered breathing, ranging from habitual snoring to severe obstructive sleep apnea, is a prevalent public health issue. Despite rising interest in sleep and awareness of sleep disorders, sleep research and diagnostic practices still rely on outdated metrics and laborious methods reducing the diagnostic capacity and preventing timely diagnosis and treatment. Consequently, a significant portion of individuals affected by sleep-disordered breathing remain undiagnosed or are misdiagnosed. Taking advantage of state-of-the-art scientific, technological, and computational advances could be an effective way to optimize the diagnostic and treatment pathways. We discuss state-of-the-art multidisciplinary research, review the shortcomings in the current practices of SDB diagnosis and management in adult populations, and provide possible future directions. We critically review the opportunities for modern data analysis methods and machine learning to combine multimodal information, provide a perspective on the pitfalls of big data analysis, and discuss approaches for developing analysis strategies that overcome current limitations. We argue that large-scale and multidisciplinary collaborative efforts based on clinical, scientific, and technical knowledge and rigorous clinical validation and implementation of the outcomes in practice are needed to move the research of sleep-disordered breathing forward, thus increasing the quality of diagnostics and treatment. [ABSTRACT FROM AUTHOR]

Summary: Current forms of mechanical treatment in obstructive sleep apnea (OSA) are generally effective in eliminating sleep and breathing disorders. However, they do have drawbacks, such as incomplete tolerability and non-compliance. Several attempts have been made to identify pharmacological treatments for OSA, but no drug has consistently reduced the severity of the condition by more than 50%. OSA, in most cases, is a condition characterized by considerable comorbidity, including hypertension, obesity, metabolic derangement and hormonal dysfunction. Daytime sleepiness and cognitive dysfunction represent common, but not consistent, findings in people with this nocturnal sleep and breathing disorder. Hence, future pharmacological treatments for OSA may need to take aspects other than the nocturnal breathing events alone into consideration. Drug research into OSA has been hampered by the lack of useful experimental systems and animal models for drug screening. In addition, the phenotypic characterization of OSA seems to be incomplete, and this limits the possibility of using stringent criteria for patient selection in drug studies. Finally, the criteria for defining the severity of OSA and disease impact seem to be insufficient for adequate definition of efficacy end points in clinical trials. This review will list some potential shortcomings and possibilities of pharmacological treatment in OSA, and discuss some of the already attempted modes of treatment. [Copyright &y& Elsevier]

Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO 2), and percentage of time with SpO 2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO 2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO 2 , minimum SpO 2 , and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88–1.54], −0.16 [-0.20 to −0.11], −0.51 [-0.64 to −0.37], 1.76 [1.48–2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01–1.08], p = 0.013). We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA. • Bicarbonate level is associated with nocturnal hypoxia in obstructive sleep apnea. • Higher bicarbonate level increases risk of uncontrolled hypertension in sleep apnea. • Measure of bicarbonate is useful for sleep apnea endotyping and tailored treatment. [ABSTRACT FROM AUTHOR]

Objectives: This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d.Methods: In two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open-label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy.Results: After 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was -0.84%, compared with 0.54% for placebo, in participants with OSA; and -0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was -1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg, -1.2%; 300 mg, -2.5%). Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of -2.2% and -1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss ≥5% relative to baseline was 25.7% overall and increased in a dose-dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among subgroups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss ≥5%, respectively. No weight-related treatment-emergent adverse events were serious.Conclusions: Solriamfetol treatment was associated with decreases in body weight in a dose-related manner. [ABSTRACT FROM AUTHOR]

• An investigational NTHi vaccine was tested for the first time in adults with COPD. • The vaccine had acceptable safety and reactogenicity. • Vaccine-elicited antibody concentrations were higher than baseline 1 year post-dose 2. Loss of airway microbial diversity is associated with non-typeable Haemophilus influenzae (NTHi) infection and increased risk of exacerbation in chronic obstructive pulmonary disease (COPD). We assessed the safety and immunogenicity of an investigational vaccine containing NTHi antigens, recombinant protein D (PD) and combined protein E and Pilin A (PE-PilA), and AS01 adjuvant in adults with moderate/severe COPD and prior exacerbations. In this phase 2, observer-blind, controlled trial (NCT02075541), 145 COPD patients aged 40–80 years randomly (1:1) received two doses of NTHi vaccine or placebo 60 days apart, on top of standard care. Reactogenicity in the 7-day post-vaccination period was higher following NTHi vaccine than placebo. Most solicited adverse events (AEs) were mild/moderate. At least one unsolicited AE was reported during the 30-day post-vaccination period by 54.8% of NTHi vaccine and 51.4% of placebo recipients. One serious AE (placebo group) was assessed by the investigator as vaccine-related. Anti-PD, anti-PE and anti-PilA geometric mean antibody concentrations increased up to 30 days after each NTHi vaccine dose, waned thereafter, but remained higher than baseline (non-overlapping confidence intervals) up to 13 months post-dose 2. The frequency of specific CD4+ T cells increased following two doses of NTHi vaccine and remained higher than baseline. Exploratory analysis showed a statistically non-significant lower yearly rate of moderate/severe exacerbations in the NTHi vaccine group than following placebo (1.49 versus 1.73) in the one-year period post-dose 2, with estimated vaccine efficacy of 13.3% (95% confidence interval −24.2 to 39.5; p = 0.44). The NTHi vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in adults with COPD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Atrial fibrillation is one of the most common arrhythmias in clinical practice and it is often diagnosed after a complication occurs. The study aimed to evaluate the predictive value of atrial natriuretic peptide (ANP) for atrial fibrillation in a male population-based study. Methods and results: This study is a part of the “Study of Men Born in 1913 and 1923”, a longitudinal prospective cohort study of men, living in the city of Gothenburg in Sweden. A population-based sample of 528 men was investigated in 1988 when they were aged 65years (n =134) and 75years (n =394), and they were followed up for 16years. Blood samples were collected from all 528 men at baseline and plasma ANP levels were analyzed by radioimmunoassay. Hazard ratios were estimated by competing-risk regression analysis. One hundred five participants were excluded because of a prior diagnosis of atrial fibrillation, congestive heart failure, severe hypertension, or severe chronic renal insufficiency. Of the remaining 423 participants, 90 men were diagnosed with atrial fibrillation over the 16-year follow-up. In multivariable analysis, men in the two highest quartiles of ANP levels had a significantly higher risk for atrial fibrillation compared with men in the lowest ANP quartile. The adjusted ratio was 3.14 (95% CI 1.59–6.20) for the third ANP quartile and 3.36 (95% CI 1.72–6.54) for the highest quartile of ANP level. Conclusions: In this population-based longitudinal study, we found that elevated ANP levels at baseline predicted atrial fibrillation during a follow-up time of 16years. [Copyright &y& Elsevier]

Abstract: Objectives: Sleep disturbances can impair alertness and neurocognitive performance and increase the risk of falling asleep at the wheel. We investigated the prevalence of sleep disorders among public transport operators (PTOs) and assessed the interventional effects on hypersomnolence and neurocognitive function in those diagnosed with obstructive sleep apnea (OSA). Methods: Overnight polygraphy and questionnaire data from 101 volunteers (72 males, median age 48 range [22–64] years, 87 PTOs) employed at the Gothenburg Public Transportation Company were assessed. Treatment was offered in cases with newly detected OSA. Daytime sleep episodes and neurocognitive function were assessed before and after intervention. Results: At baseline, symptoms of daytime hypersomnolence, insomnia, restless legs syndrome as well as objectively assessed OSA (apnea hypopnea index (AHI, determined by polygraphic recording)=17[5–46]n/h) were highly present in 26, 24, 10 and 22%, respectively. A history of work related traffic accident was more prevalent in patients with OSA (59%) compared to those without (37%, p <0.08). In the intervention group (n =12) OSA treatment reduced AHI by −23 [−81 to −5]n/h (p =0.002), determined by polysomnography. Reduction of OSA was associated with a significant reduction of subjective sleepiness and blood pressure. Measures of daytime sleep propensity (microsleep episodes from 9 [0–20.5] to 0 [0–12.5], p <0.01) and missed responses during performance tests were greatly reduced, indices of sustained attention improved. Conclusions: PTOs had a high prevalence of sleep disorders, particularly OSA, which demonstrated a higher prevalence of work related accidents. Elimination of OSA led to significant subjective and objective improvements in daytime function. Our findings argue for greater awareness of sleep disorders and associated impacts on daytime function in public transport drivers. [Copyright &y& Elsevier]

Abstract: Objective: To assess the daytime consequences in outpatients suffering from different insomnia symptoms in primary care practice. Methods: An international cross-sectional survey was conducted in 5293 outpatients complaining of sleep disturbances in primary care practice. A sleep questionnaire addressing daytime consequences, insomnia symptoms, socio-demographic characteristics, and other sleep variables was administered by 647 physicians in 10 countries. Results: Overall, 20–33% of subjects reported “severe” daytime impairments associated with sleep disturbances. Approximately 45% of patients complaining of sleep disturbances in primary care practice suffered from a combination of insomnia symptoms. Patients suffering from all insomnia symptoms reported the most severe daytime functioning impairments compared with patients suffering from initiation or maintenance insomnia only. Conversely, the majority of patients suffering from non-restorative sleep reported little daytime functioning impairments compared to the patients suffering from other combinations of insomnia symptoms. The strongest risk factor associated with “severe” daytime functioning impairments was sleep quality perception. Conclusions: Primary insomnia disturbs subjective daytime functioning. A report of combined insomnia symptoms reflected the most damaging insomnia subtype and had a negative impact on a wide range of daytime functioning consequences. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To describe the characteristics of insomnia in primary care physicians’ (PCPs’) practices in 10 countries and to understand how the difficulty of maintaining sleep (DMS) was or was not associated with other insomnia symptoms such as difficulty initiating sleep (DIS), early morning awakenings (EMA) or nonrestorative sleep (NRS) in PCPs patients with insomnia. Methods: International, noninterventional, cross-sectional, observational survey conducted in a primary care setting in subjects complaining of sleep disturbances in 10 countries. A questionnaire based on DSM-IV and ICSD criteria was administered. Results: Thirteen thousand one hundred twenty-four subjects were enrolled by 647 physicians; 5293 of them (32.6%) had insomnia and were surveyed. The population was predominantly female (63.9%) with a mean age of 47.8±15.3years; 39.9% of these patients have already been treated for sleep difficulties. Combination of all types of insomnia symptoms (DIS+DMS+EMA+NRS) was the most frequently reported combination (38.6% of the subjects), while the percentage of subjects presenting with only one type of insomnia symptom (DIS, DMS, EMA or NRS) was very low: 3%, 1.8%, 0.9% and 1.4% respectively. DMS was on average the most commonly reported insomnia symptom (80.2%). Multiple logistic regression showed that DMS, EMA and NRS symptoms were significantly linked with each other and also to other insomnia criteria (sleep satisfaction, sleep quality, sleep duration, number of hours of sleep, frequency of insomnia symptoms, wake up rested / unrested and non restorative sleep). Conclusions: Patients visiting PCPs with insomnia are likely to present with severe and poly-symptomatic insomnia. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral α-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients. Methods: A double-blind, crossover study comparing equipotent dosages of DO (4mg/day for 2weeks with 8mg/day for an additional 2weeks) and EN (10mg/day and 20mg/day, respectively) was undertaken in 16 male OSA patients (age 55±7years, body mass index 30.1±3.8kg/m2) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed. Results: There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129±13 vs. 119±23mm Hg, P =0.02; diastolic BP 81±12 vs. 74±14mm Hg, P =0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P <0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P <0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P =0.002). Conclusion: Digital vasoconstrictions associated with apneic events are α-receptor mediated. DO compared to EN has a proportionally poor effect on nocturnal BP control in OSA patients, which may be due to the enhanced sympathetic nervous system activity characteristic of this condition. [Copyright &y& Elsevier]

Premenstrual dysphoria is characterized by symptoms such as irritability and depressed mood, present during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Subjects with premenstrual dysphoria have previously been reported to display enhanced respiratory variability, and to experience anxiety when exposed to panicogens, such as CO2. In the present study, the possible influence of the estrus cycle and estrus cycle-related aggression on respiratory variability was investigated in female rats of the Wistar strain. The rats were subdivided into two groups: those displaying estrus cycle-related aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the estrus cycle. This model has been developed to serve as an animal model of premenstrual irritability. The former group was found to display higher tidal volume variability in diestrus, as compared to the non-aggressive rats. There was no effect of estrus cycle phase on respiratory variability. These results are well in line with the clinical observation that women with premenstrual dysphoria display higher respiratory variability than controls, and the notion that respiratory variability is a parameter of interest in this context. In our opinion, they also strengthen the concept of this animal model as a model of premenstrual irritability. [Copyright &y& Elsevier]