Purpose
Although currently there are simplified methods to measure the pathophysiological traits that stimulate the occurrence and maintenance of obstructive sleep apnea–hypopnea (OSAH), they remain ...difficult to implement in routine practice. This pilot study aimed to find a simpler daytime approach to obtain a meaningful, similar pathophysiological phenotypic profile in patients with OSAH.
Methods
After obtaining diagnostic polygraphy from a group of consecutive patients with OSAH, we performed the dial-down CPAP technique during nocturnal polysomnography and used it as reference method. This allowed assessment of upper airway collapsibility, loop gain (LG), arousal threshold (AT), and upper airway muscle gain (UAG). We compared these results with a daytime protocol based on negative expiratory pressure (NEP) technique for evaluating upper airway collapsibility and UAG, on maximal voluntary apnea for LG, and on clinical predictors for AT.
Results
Of 15 patients studied, 13 patients with OSAH accurately completed the two procedures. There were strong (all
r
2
> 0.75) and significant (all
p
< 0.001) correlations for each phenotypic trait between the measurements obtained through the reference method and those achieved during wakefulness.
Conclusion
It is possible to phenotype patients with OSAH from a pathophysiological point of view while they are awake. Using this approach, cutoff values corresponding to those usually adopted using the reference method can be identified to detect abnormal traits, achieving profiles similar to those obtained through the dial-down CPAP technique.
OBJECTIVE:Treatment of obstructive sleep apnoea (OSA) has been shown to reduce blood pressure (BP). However, the effect size is modest and treatment of OSA is not recommended as the only treatment ...target when treating hypertension. Despite the limited effect of continuous positive airway pressure (CPAP) therapy on BP, it is likely that certain phenotypes of OSA patients respond better to CPAP than others. The aim of the present systematic review and meta-analysis was to identify potential predictors for BP response in patients with OSA undergoing CPAP treatment.(Figure is included in full-text article.)
DESIGN AND METHOD:A systematic search was conducted in three databases (MEDLINE, Embase and Web of Science) using terms exploring three domains (obstructive sleep apnoea, CPAP, clinical trial) based on the following inclusion criteriai) randomised controlled clinical trials published between January 1st 1960 to December 31st 2017 including a reasonable control group; iii) OSA diagnosis using polysomnography; iv) age >18 years; v) OSA severity of at least 5 AHI/h. The random effect model was fitted to estimate the pooled BP reductions calculated as the difference between the BP change (end-treatment minus baseline) in the CPAP and control group. Moreover, the original estimates have been stratified according to selected patient characteristics.
RESULTS:Out of 2445 articles, 59 RCTs were included (n = 7,329 subjects) comparing CPAP with control groups. CPAP was associated with a net reduction in systolic BP of −2.12 (95% CI −2.82 to −1.42) mmHg and in diastolic BP of −1.97 (95% CI −2.46 to −1.48) mmHg, favouring treatment of OSA using CPAP (both p-values < 0.001). The subgroup analysis showed that systolic BP reduction was greater in subjects younger than 60 years (−2.88 fro age 40–50, −2.78 for age 50–60 and −0.61 for age more than 60 years, p = 0.007) and in patients with controlled BP at baseline versus uncontrolled BP (−1.45 vs −4.14, p = 0.002) (Figure 1).
CONCLUSIONS:Younger patients (< 60 years) with uncontrolled blood pressure at baseline are more likely to experience significant BP reductions with CPAP therapy. Phenotypisation of specific cohorts of patients can guide clinicians to target OSA treatment and help to optimise patients’ cardiovascular risk.
Abstract
Background
Obstructive sleep apnoea (OSA) is characterised by the collapse of the upper airway during sleep, which determine intermittent hypoxia and sleep fragmentation leading to snoring, ...impaired cognitive function, excessive daytime sleepiness, and cardiovascular impairments. These disorders have a significant impact on the quality of life and health of both patient and partner, determining stress and frustration also to the couple relationship, and to the workplace. Although the gold standard of treatment for OSA is the use of continuous positive airway pressure (CPAP), many patients find it uncomfortable both for them and for their partners (difficulty in partner intimacy, fear of disturbing their partner's sleep) with consequent low adherence to treatment in about 50% of OSA patients.
For these reasons, efforts to develop drug therapies for the treatment of OSA have been ongoing for at least 20 years. Recently, we conducted a randomized controlled trial (RCT) in Italy to test the combination of reboxetine (a noradrenergic agent) and oxybutynin (an antimuscarinic) for OSA treatment with promising results. The aim of this study is to understand how OSA drug therapy has influenced couples' life.
Methods
The study was conducted from February to March 2020 by the research nurse who participated during the trial. We interviewed 11 patients participating in the pharmacological RCT and 7 partners. The data analysis was conducted in order to collect the subjects' answers in categories, and to identify a core category as the central element for the explanation of the process.
Results
Interviews permitted to extrapolate 6 main categories and the relative subcategories for patients: 1) OSA: unconscious danger; 2) OSA and couple life (subcategories: sleepiness and nervousness, lack of sleep); 3) transitory situations; 4) drug therapy and couple (subcategories:change in intimacy and sleep quality); 5) motivation to help others (subcategories: therapy recommended for everyone; intention to continue); 6) partner awareness helps in adherence to therapy (subcategories: partner as caregiver, presence and proximity, partner support). While for partners, 7 main categories and the relative subcategories emerged: 1) apprehension and concern for the partner; 2) repercussions on daily life (subcategorie: discomfort); 3) OSA and the couple's lives; 4) drug therapy and couple; 5) support during therapy (subcategorie: before therapy, during therapy); 6) changes during drug therapy; 7) recommended therapy (subcategories: helping others, partner support). “The OSA is our problem” was the core category of the study that linked the categories together.
Conclusions
Drug therapy is well embraced by both patients and partners as it allows the couple to recover intimacy during sleep and in daily life. The results of this study provide useful information on the need to involve the partner in order to promote adherence to therapy.
Funding Acknowledgement
Type of funding sources: None.
for the ADVENT-HF Investigators Rationale: Adaptive servo-ventilation (ASV) is a positive airway pressure (PAP) device designed to treat sleep-disordered breathing (SDB) in patients with heart ...failure (HF). The purpose of this study was to evaluate ASV adherence in HF patients with CSA and OSA enrolled in the "Effect of Adaptive-servo Ventilation on Survival and Cardiovascular Hospital Admissions in Patients with HF and Sleep Apnea" (ADVENT-HF) trial, to determine the short and long-term predictors of ASV adherence.
Rationale: In patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF), hyperpnea during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is associated with ...a reduction in stroke volume (SV). Methods: HFrEF patients underwent polysomnography (PSG) and continuous noninvasive beat-by-beat measurements of arterial blood pressure (BP), heart rate (HR), SV, cardiac output (CO) and total peripheral resistance (TPR) using digital photoplethysmography.
Blazars are a sub-class of quasars with Doppler boosted jets oriented close to the line of sight, and thus efficient probes of supermassive black hole growth and their environment, especially at high ...redshifts. Here we report on Very Long Baseline Interferometry observations of a blazar J0906 + 6930 at z = 5.47, which enabled the detection of polarised emission and measurement of jet proper motion at parsec scales. The observations suggest a less powerful jet compared with the general blazar population, including lower proper motion and bulk Lorentz factor. This coupled with a previously inferred high accretion rate indicate a transition from an accretion radiative power to a jet mechanical power based transfer of energy and momentum to the surrounding gas. While alternative scenarios could not be fully ruled out, our results indicate a possibly nascent jet embedded in and interacting with a dense medium resulting in a jet bending.
Cardiac disease is associated with deleterious emission of mitochondrial reactive oxygen species (mito-ROS), as well as enhanced oxidation and activity of the sarcoplasmic reticulum (SR) Ca
2+
...release channel, the ryanodine receptor (RyR2). The transfer of Ca
2+
from the SR via RyR2 to mitochondria is thought to play a key role in matching increased metabolic demand during stress. In this study, we investigated whether augmented RyR2 activity results in self-imposed exacerbation of SR Ca
2+
leak, via altered SR-mitochondrial Ca
2+
transfer and elevated mito-ROS emission. Fluorescent indicators and spatially restricted genetic ROS probes revealed that both pharmacologically and genetically enhanced RyR2 activity, in ventricular myocytes from rats and catecholaminergic polymorphic ventricular tachycardia (CPVT) mice, respectively, resulted in increased ROS emission under β-adrenergic stimulation. Expression of mitochondrial Ca
2+
probe mtRCamp1h revealed diminished net mitochondrial Ca
2+
with enhanced SR Ca
2+
leak, accompanied by depolarization of the mitochondrial matrix. While this may serve as a protective mechanism to prevent mitochondrial Ca
2+
overload, protection is not complete and enhanced mito-ROS emission resulted in oxidation of RyR2, further amplifying proarrhythmic SR Ca
2+
release. Importantly, the effects of augmented RyR2 activity could be attenuated by mitochondrial ROS scavenging, and experiments with dominant-negative paralogs of the mitochondrial Ca
2+
uniporter (MCU) supported the hypothesis that SR-mitochondria Ca
2+
transfer is essential for the increase in mito-ROS. We conclude that in a process whereby leak begets leak, augmented RyR2 activity modulates mitochondrial Ca
2+
handling, promoting mito-ROS emission and driving further channel activity in a proarrhythmic feedback cycle in the diseased heart.
Context.
The properties, distribution, and evolution of inhomogeneities on the surface of active stars, such as dark spots and bright faculae, significantly influence the determination of the ...parameters of an orbiting exoplanet. The chromatic effect they have on transmission spectroscopy, for example, could affect the analysis of data from future space missions such as
James Webb
Space Telescope and Ariel.
Aims.
To quantify and mitigate the effects of those surface phenomena, we developed a modelling approach to derive the surface distribution and properties of active regions by modelling simultaneous multi-wavelength time-series observables.
Methods.
We present an upgraded version of the
StarSim
code, now featuring the capability to solve the inverse problem and derive the properties of the stars and their active regions by modelling time-series data. As a test case, we analyse ~600 days of
BV RI
multiband photometry from the 0.8-m
Joan Oró
(TJO) and 1.2-m STELLA telescopes of the K2 V exoplanet host star WASP-52. From the results, we further simulated the chromatic contribution of surface phenomena on the observables of its transiting planet.
Results.
Using
StarSim
we are able to determine the relevant activity parameters of WASP-52 and reconstruct the time-evolving longitudinal map of active regions. The star shows a heterogeneous surface composed of dark spots with a mean temperature of 575 ± 150 K lower than the photospheric value, with filling factors ranging from 3 to 14%. We used the results to study the chromatic effects on the depths of exoplanet transits obtained at different epochs and corresponding to different stellar spot distributions. In the case of WASP-52, which has peak-to-peak photometric variations of ~7% in the visible, the residual effects of dark spots on the measured transit depth of its giant planet, after applying the calculated corrections, are about 10
−4
at 550 nm and 3 × 10
−5
at 6
μ
m.
Conclusions.
We demonstrate that by using contemporaneous ground-based multiband photometry of an active star, it is possible to reconstruct the parameters and distribution of active regions over time, thus making it feasible to quantify the chromatic effects on the planetary radii measured with transit spectroscopy and mitigate them by about an order of magnitude.
Ultra-hot Jupiters are highly irradiated gas giants with equilibrium temperatures typically higher than 2000 K. Atmospheric studies of these planets have shown that their transmission spectra are ...rich in metal lines, with some of these metals being ionised due to the extreme temperatures. Here, we use two transit observations of WASP-76b obtained with the CARMENES spectrograph to study the atmosphere of this planet using high-resolution transmission spectroscopy. Taking advantage of the two channels and the coverage of the red and near-infrared wavelength ranges by CARMENES, we focus our analysis on the study of the Ca
II
infrared triplet (IRT) at 8500 Å and the He
I
triplet at 10 830 Å. We present the discovery of the Ca
II
IRT at 7
σ
in the atmosphere of WASP-76b using the cross-correlation technique, which is consistent with previous detections of the Ca
II
H&K lines in the same planet, and with the atmospheric studies of other ultra-hot Jupiters reported to date. The low mass density of the planet, and our calculations of the XUV (X-ray and EUV) irradiation received by the exoplanet, show that this planet is a potential candidate to have a He
I
evaporating envelope and, therefore, we performed further investigations focussed on this aspect. The transmission spectrum around the He
I
triplet shows a broad and red-shifted absorption signal in both transit observations. However, due to the strong telluric contamination around the He
I
lines and the relatively low signal-to-noise ratio of the observations, we are not able to unambiguously conclude if the absorption is due to the presence of helium in the atmosphere of WASP-76b, and we consider the result to be only an upper limit. Finally, we revisit the transmission spectrum around other lines such as Na
I
, Li
I
, H
α
, and K
I
. The upper limits reported here for these lines are consistent with previous studies.
PDF
