Frequency Of Apnea Research Articles

Comparison of oral caffeine and oral theophylline for apnea of prematurity: A randomized clinical trial

Background Caffeine and theophylline are methylxanthine compounds that have been widely used in the treatment of apnea of prematurity (AOP). Previous studies comparing the two agents have shown inconsistent results and have mostly used intravenous preparations. Objective To assess the effectiveness of oral administration of caffeine compared to oral theophylline as therapy for apnea of prematurity. Methods Fifty consecutively recruited premature neonates (gestational age 28-34 weeks, birth weight <2,500 g) with AOP who were able to tolerate at least 10 mL/kg of enteral feeding were randomized to receive either oral caffeine or oral theophylline for seven days. The main outcome was the daily frequency of apnea after treatment. Secondary outcomes were duration of oxygen or CPAP administration, duration of oxygen fraction (FiO2) taper to reach 21%, time to achievement of full feeding tolerance, length of hospital stay, and side effects. Results We randomized 25 subjects into each group. The distribution of baseline characteristics (gender, gestational age, mode of delivery, birth weight and length, age at onset of AOP, and initial frequency of AOP) was similar between both groups. The mean daily number of apnea episodes after treatment was significantly higher in the caffeine group compared to the theophylline group [3.16 (SD 1.31) vs. 2.28 (SD 1.40); P=0.031]. The caffeine group, compared to the theophylline group, also had a longer mean duration of oxygen or CPAP use [12.56 (SD 7.67) days vs. 8.40 (SD 6.41) days; P=0.030] and duration of FiO2 taper [5.76 (SD 2.68) vs. 4.08 (SD 2.54); P=0.035]. There were no significant differences in mean time to full feeding and mean length of hospital stay. There was no significant difference in the occurrence of side effects between the two groups. Conclusion In premature neonates with AOP, oral theophylline is slightly more effective than oral caffeine in reducing the frequency of apnea and is associated with a shorter duration of oxygen or CPAP use and duration to reach 21% FiO2.

Theophylline impact on weaning in oxygen-dependent infants followed in an outpatient Kangaroo Program.

Theophylline was an orally administered xanthine used for treatment of apnea of prematurity and Bronchopulmonary Dysplasia in ambulatory follow-up of Low-Birth-Weight infants (LBWI) with oxygen-dependency in the outpatient Kangaroo Mother Care Program (KMCP). Theophylline's main metabolic product is caffeine; therefore, it was an alternative due to the frequent lack of ambulatory oral caffeine in low and middle-income countries. To assess the effectiveness of oral theophylline in decreasing days with oxygen and to describe frequency of adverse related events. Quasi-experiment before and after withdrawal of theophylline given systematically to LBWI with ambulatory oxygen in two KMCPs. 729 patients were recruited; period 1: 319 infants when theophylline was given routinely and period 2: 410 infants when theophylline was no longer used. The theophylline cohort had less gestational age, less weight at birth, more days in Neonatal Intensive Care Unit, more days of oxygen-dependency at KMCP admission, and more frequencies of Intrauterine Growth Restriction and apneas. After adjusting with propensity score matching, multiple linear regression showed that nutrition was associated with days of oxygen-dependency, but theophylline treatment not. No differences were found in frequencies of readmissions up to 40 weeks, intraventricular hemorrhage or neurodevelopmental problems. Participants in period 2 had more tachycardia episodes. We did not find association between oral theophylline treatment and the reduction of days with ambulatory oxygen. For the current management of oxygen-dependency in LBW infants, the importance of nutrition based on exclusive breast feeding whenever possible, is the challenge.

Xylazine Exacerbates Fentanyl-Induced Respiratory Depression and Bradycardia.

Fatal opioid overdoses in the United States have nearly tripled during the past decade, with greater than 92% involving a synthetic opioid like fentanyl. Fentanyl potently activates the μ-opioid receptor to induce both analgesia and respiratory depression. The danger of illicit fentanyl has recently been exacerbated by adulteration with xylazine, an α2-adrenergic receptor agonist typically used as a veterinary anesthetic. In 2023, over a 1,000% increase in xylazine-positive overdoses was reported in some regions of the U.S. Xylazine has been shown to potentiate the lethality of fentanyl in mice, yet a mechanistic underpinning for this effect has not been defined. Herein, we evaluate fentanyl, xylazine, and their combination in whole-body plethysmography (to measure respiration) and pulse oximetry (to measure blood oxygen saturation and heart rate) in male and female CD-1 mice. We show that xylazine decreases breathing rate more than fentanyl by increasing the expiration time. In contrast, fentanyl primarily reduces breathing by inhibiting inspiration, and xylazine exacerbates these effects. Fentanyl but not xylazine decreased blood oxygen saturation, and when combined, xylazine did not change the maximum level of fentanyl-induced hypoxia. Xylazine also reduced heart rate more than fentanyl. Finally, loss in blood oxygen saturation correlated with the frequency of fentanyl-induced apneas, but not breathing rate. Together, these findings provide insight into how the addition of xylazine to illicit fentanyl may increase the risk of overdose.

Effect of positive allosteric modulation and orthosteric agonism of dopamine D2-like receptors on respiration in mouse models of Rett syndrome

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the methyl-CPG-binding protein 2 (Mecp2) gene. Frequent apneas and irregular breathing are prevalent in RTT, and also occur in rodent models of the disorder, including Mecp2Bird and Mecp2R168X mice. Sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT (Abdala et al., 2014). Targeting the 5HT1a receptor alone also improves respiration in RTT mice (Levitt et al., 2013). However, the contribution of D2-like receptors in correcting these respiratory disturbances remains untested. PAOPA, a dopamine D2-like receptor positive allosteric modulator, and quinpirole, a dopamine D2-like receptor orthosteric agonist, were used in conjunction with whole-body plethysmography to evaluate whether activation of D2-like receptors is sufficient to improve breathing disturbances in female heterozygous Mecp2Bird/+ and Mecp2R168X/+ mice. PAOPA did not significantly change apnea incidence or irregularity score in RTT mice. PAOPA also had no effect on the ventilatory response to hypercapnia (7 % CO2). In contrast, quinpirole reduced apnea incidence and irregularity scores and improved the hypercapnic ventilatory response in Mecp2R168X/+ and Mecp2Bird/+ mice, while also reducing respiratory rate. These results suggest that D2-like receptors could contribute to the positive effects of sarizotan in the correction of respiratory abnormalities in Rett syndrome. However, positive allosteric modulation of D2-like receptors alone was not sufficient to evoke these effects.

Predictive value of serum MED1 and PGC-1α for bronchopulmonary dysplasia in preterm infants

ObjectiveThis study aimed to predict the bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age(GA) < 32 weeks utilizing clinical data, serum mediator complex subunit 1 (MED1), and serum peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α).MethodsThis prospective observational study enrolled 70 preterm infants with GA < 32 weeks. The infants were categorized into two groups: non-BPD group(N = 35) and BPD group(N = 35), including 25 cases with mild BPD and 10 patients with moderate/severe subgroups. We performed multifactorial regression analysis to investigate the postnatal risk factors for BPD. Furthermore, we compared serum levels of biomarkers, including MED1 and PGC-1α, among infants with and without BPD at postnatal days 1, 7, 14, 28, and PMA 36 weeks. A logistic regression model was constructed to predict BPD’s likelihood using clinical risk factors and serum biomarkers.ResultsSerum levels of MED1 on the first postnatal day, PGC-1α on the 1st, 7th, and 28th days, and PMA at 36 weeks were significantly lower in the BPD group than in the non-BPD group (P < 0.05). Furthermore, the predictive model for BPD was created by combing serum levels of MED1 and PGC-1α on postnatal day 1 along with clinical risk factors such as frequent apnea, mechanical ventilation time > 7 d, and time to reach total enteral nutrition. Our predictive model had a high predictive accuracy(C statistics of 0.989) .ConclusionMED1and PGC-1α could potentially serve as valuable biomarkers, combined with clinical factors, to aid clinicians in the early diagnosis of BPD.

Ageing-related modification of sleep and breathing in orexin-knockout narcoleptic mice.

Narcolepsy type-1 (NT1) is a lifelong sleep disease, characterised by impairment of the orexinergic system, with a typical onset during adolescence and young adulthood. Since the wake-sleep cycle physiologically changes with ageing, this study aims to compare sleep patterns between orexin-knockout (KO) and wild type (WT) control mice at different ages. Four groups of age-matched female KO and WT mice (16 weeks of age: 8 KO-YO and 9 WT-YO mice; 87 weeks of age: 13 KO-OLD and 12 WT-OLD mice) were implanted with electrodes for discriminating wakefulness, rapid-eye-movement sleep (REMS), and non-REMS (NREMS). Mice were recorded for 48 h in their home cages and for 7 more hours into a plethysmographic chamber to characterise their sleep-breathing pattern. Regardless of orexin deficiency, OLD mice spent less time awake and had fragmentation of this behavioural state showing more bouts of shorter length than YO mice. OLD mice also had more NREMS bouts and less frequent NREMS apneas than YO mice. Regardless of age, KO mice showed cataplexy-like episodes and shorter REMS latency than WT controls and had a faster breathing rate and an increased minute ventilation during REMS. KO mice also had more wakefulness, NREMS and REMS bouts, and a shorter mean length of wakefulness bouts than WT controls. Our experiment indicated that the lack of orexins as well as ageing importantly modulate the sleep and breathing phenotype in mice. The narcoleptic phenotype caused by orexin deficiency in female mice was substantially preserved with ageing.

Targeted TGF-βR2 Knockdown in the Retrotrapezoid Nucleus Mitigates Respiratory Dysfunction and Cognitive Decline in a Mouse Model of Cerebral Amyloid Angiopathy with and without Stroke.

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO2 sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-β) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke. Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-β2R2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-βR2 and GFAP expressions in the RTN. CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-βR2 knockdown in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-βR2 knockdown similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-βR2 and GFAP expressions in the RTN following knockdown. Our findings demonstrate that increased TGF-β signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-βR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models.

Obstructive sleep apnea and acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Acute decompensated heart failure is a condition with a high frequency of hospitalizations and mortality. Screening and treatment for obstructive sleep apnea can be helpful in these patients. Purpose To determine the frequency of obstructive sleep apnea in patients with acute decompensated heart failure. To add CPAP home therapy to standard medical treatment for heart failure. To follow patients for 1 year. Methods We conducted a single-centre, prospective cohort study form 150 consecutive patients hospitalized for exacerbation heart failure in the cardiology department. 81 patients meet inclusion criteria – Apnea-Hypopnea index (AHI) &amp;gt; 5, Epworth Sleepiness Scale (ESS) &amp;gt; 8, NYHA class II/III and NTproBNP&amp;gt;900 pg/ml. Patients with OSA were offered to purchase a CPAP device for the home. They were divided into two groups with CPAP and no-CPAP. All patients receiving optimal medical treatment. The follow-up period was 1 year. At the end of the period, patients underwent a physical examination, an echocardiography, and ESS. In the non-CPAP group, 29 patients were followed up and 13 patients dropped out due to mortality. In the CPAP group, 16 patients were followed up, with 1 dropped out. Sleep apnea screening was performed with ApneaLinkTM. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and the E/e‘m ratio. Results From 81 with sleep apnea 72.8% (n=59) has obstructive sleep apnea (OSA) and 27.2% (n=22) has central sleep apnea (CSA). Of the 59 patients with OSA, 17 patients (28.8%) purchased a device and continued therapy at home, while 42 patients (71.2%)on optimal drug therapy without CPAP. There is a statistically significant difference in BMI in the group with CPAP compared to the no-CPAP group at the beginning and at the end of the follow-up (CPAP group at the start 36.47±7.3 vs. the end 33.3±5.7, p=0.001 and no-CPAP group at the start 36.35±7.34 vs. the end 35.74±7.46 , p=0.356). A similar relationship is found in systolic blood pressure(SBP) and diastolic blood pressure(DBP). SBP in CPAP group at start 136.2±6.2 mmHg vs. end 123.1±5.9 mmHg; р&amp;lt;0.001. relative to no-CPAP group – start 131.2±9.8 mmHg vs. end 131.3±7.7 mmHg; р=0.965. DBP in CPAP group at start 85.9±6.7 mmHg vs. end 77.3±5.3 mmHg; р&amp;lt;0.001 and no-CPAP group start 82.1±7.4 mmHg vs. end 81.7±5.7 mmHg, р=0.644. There is a significant change in LVEF between the two groups at the beginning and at the end of the follow-up (in CPAP group at start 47.5±8.7, vs. at end 50.07±7.5; р=0.005, between no-CPAP at start 52.5±6.9 vs. at end 52.2±7.1; р=0.389). The CPAP group had a median survival of 11.7 months vs. 10.1 months in no CPAP group(Log Rank (Mental-Cox) p=0.044 ). Conclusion Obstructive sleep apnea is a common comorbidity in patients with acute decompensated heart failure. The addition of CPAP therapy in these patients improved BMI, SBP, DBP and increases LVEF. All this improves the prognosis for these patients.

Acute stress augments obstructive apneas and related O2-desaturations in urethane-anesthetised rats via disruption of cholinergic modulation

Obstructive sleep apnea (OSA) is a multifactorial respiratory disorder affecting nearly 1 billon of adults worldwide. Anomalies in respiratory control during sleep contribute to airway obstructions and recurrent desaturations; however, the origins of the problem are not well known. Stress disrupts brain function and increases the risk of OSA co-morbidities, including hypertension and obesity. Because, hypothalamic structures regulating the stress response also project to medullary areas regulating cardiorespiratory function and airway motor control, we hypothesised that exposure to a single stress session is suffcient to induce cardiorespiratory disturbances associated with OSA. Experiments were performed in urethane-anesthetised rats; this approach allows sleep-like brain state alternations with significant reductions in upper airway (genioglossus; GG), but not diaphragmatic (DIA), muscle tone during the transition from NREM-like to REM-like states. Adult male rats were either subjected to a 90 min session of immobilisation stress (n = 21) or handled briefly by the experimenter (n = 18). 24h later, rats were anesthetised (urethane, 1.6 g/kg; i.v.) and instrumented to monitor DIA and GG EMG. O2 saturation was measured by pulse oximetry (S pO2). Blood pressure was measured by an arterial catheter. Rats were placed in a supine position and respiratory airflow was measure by a temperature probe near the nares. Obstructive apneas were identified by the absence of airflow in the presence of DIA activity with a S pO2 drop greater than 3%. Stress did not affect distribution of sleep-like states or the state-related changes in phasic GG activity. However, stress augmented the incidence of obstructive apneas (0.5 vs 2.2 events/h; p = 0.05) and doubled the severity of desaturations associated with apneas (-6% vs -12% drop; p = 0.03). Pre-treatment with atropine (0.5 mg/kg) reduced obstructive apneas (drug effect: p = 0.04). Atropine blocked apnea-related O2 desaturations in stressed but not controls (apnea x stress x atropine: p = 0.04). Atropine treatment augmented GG activity; this effect was greater in NREM-like state, especially in stressed rats (atropine x state x stress: p = 0.05). We conclude that, in urethane anesthetised rats, stress disrupts cardiorespiratory control in ways that favor significant obstructive apneas. Disruption of cholinergic modulation of GG activity and cardiovascular function likely contributes to this process. These data point to an important factor in the onset of OSA. While the frequency of apneas was modest we propose that recurrent exposure to stressors or more significant events will worsen the condition over time. Supported by the Canadian Institutes of Health Research and the Foundation of the Québec Heart &amp; Lung Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Does ovariectomy exacerbate the cardiorespiratory and metabolic consequences of moderate intermittent hypoxia in female rats?

Intermittent hypoxia (IH) is a major consequence of sleep apnea (SA). IH causes respiratory dysfunction and contributes to numerous co-morbidities of SA including hypertension and obesity. The fact that menopause increases the prevalence of SA and related diseases in women indicates the importance of loss of ovarian function in the pathophysiology. Here, we determined whether experimental loss of ovarian function (ovariectomy; OVX) exacerbates the cardiorespiratory and metabolic consequences of IH. We explored neuroendocrine changes by assessing hormones known to be involved in energy balance, respiratory control, and stress responses (leptin, ACTH and corticosterone). We subjected adult (8 weeks) Sprague Dawley female rats to bilateral OVX (n = 13) or sham operation (n = 14). Rats were housed in pairs, and after two weeks of recovery, animals were exposed to room air (control; n = 16) or to a 7-day moderate IH protocol (n = 11). Within their cage, rats intermittently received a nitrogen-enriched hypoxic mixture, followed by room air for reoxygenation. Each bout of hypoxia lasted 30 seconds (nadir FIO2 = 0.10) and was followed by 5-minutes of reoxygenation (10 cycles/h, for 8hrs between 10h-18h). Apnea frequency, acute responses to hypoxia (FIO2 = 0.12; 120 sec) and hypercapnia (FICO2 = 0.05; 10 min) were measured by whole-body plethysmography. Blood pressure was assessed by the tail cuff method, and body weight was followed throughout the protocol. Plasma corticosterone and leptin were measured by multiplex assays. OVX increased apneic events, whereas IH reduced them; with the highest frequency observed in OVX females maintained in normoxia. Ventilatory responses (hypoxia and CO2) and blood pressure were not affected by IH or OVX. Over the course of the protocol, OVX increased weight gain whereas IH induced weight loss. OVX (but not IH) increased ACTH and corticosterone. IH (but not OVX) reduced leptin. Correlation matrix analysis showed that weight gain was the best predictor of apnea frequency (r = 0.759; p = 0.03). We conclude that loss of ovarian function and related weight gain have the greatest impact on respiratory function during sleep. Additionally, OVX-related activation of the stress pathways may contribute to this process. These results fail to demonstrate a role for OVX in exacerbating the cardiorespiratory and metabolic consequences of IH. Lack of weight gain following IH likely contributes to this finding. This study is supported by operating grants from the Canadian Institutes of Health Research (RK and VJ). NJM is supported by a Sentinel North Partnered Research Chair in Sleep Pharmacometabolism and a Canada Research Chair in Metabolism and Sleep Neurobiology. MG received a doctoral scholarship from the Fonds de Recherche du Québec — Santé (FRQS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea.

Apnea behavior in early- and late-stage mouse models of Parkinson's disease: Cineradiographic analysis of spontaneous breathing, acute stress, and swallowing

This study aimed to evaluate the timing and frequency of spontaneous apneas during breathing and swallowing by using cineradiography on mouse models of early/initial or late/advanced Parkinson’s disease (PD). C57BL/6 J mice received either 6-OHDA or vehicle injections into their right striatum, followed by respiratory movement recordings during spontaneous breathing and swallowing, and a stress challenge, two weeks later. Experimental group animals showed a significantly lower respiratory rate (158.66 ± 32.88 breaths/minute in late PD, 173.16 ± 25.19 in early PD versus 185.27 ± 25.36 in controls; p<0.001) and a significantly higher frequency of apneas (median 1 apnea/minute in both groups versus 0 in controls; p<0.001). Other changes included reduced food intake and the absence of swallow apneas in experimental mice. 6-OHDA-induced nigrostriatal degeneration in mice disrupted respiratory control, swallowing, stress responsiveness, and feeding behaviors, potentially hindering airway protection and elevating the risk of aspiration.

High frequency of Obstructive Sleep Apnea in consecutive patients with primary hyperaldosteronism: preliminary results

High frequency of Obstructive Sleep Apnea in consecutive patients with primary hyperaldosteronism: preliminary results

A Giant Frontoethmoidal Sinus Osteoma Presenting With Frequent Sleep Apnea Attacks: A Case Report

Background: Paranasal sinus osteomas are benign, slow-growing tumors that are typically asymptomatic. However, in rare cases, these tumors can grow to a giant size and extend into neighboring structures such as the brain, orbit, or nasal cavity, leading to clinical symptoms. These symptoms may include chronic headaches, rhinorrhea, neurological deficits, and visual impairment. Case presentation: Here, we present the case of a 27-year-old male patient who presented to our hospital with chronic headaches and frequent sleep apnea. Upon rhinoscopic examination, mucosal polyposis was observed. Further evaluation through computed tomography revealed a giant fibroosseous tumor in the frontal sinus, which exhibited aggressive extension into the brain parenchyma. Contrast-enhanced magnetic resonance imaging confirmed the presence of a giant tumor with an 8 cm diameter, exerting a mass effect on the underlying brain tissue. To address this complex case, the patient underwent a combined transcranial and transnasal surgical approach. Following the surgery, the patient experienced significant improvement in his symptoms. Conclusions: This report highlights a rare case of sleep apnea secondary to a giant frontoethmoidal osteoma with intracranial extension. The presence of frontal sinus osteomas can lead to serious clinical consequences. Timely diagnosis and intervention are crucial to prevent intracranial extension and mitigate potential complications associated with these lesions.

Frequency of Obstructive Sleep Apnea in Patients With Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis and Its Association With Clinical Findings.

This study was designed to assess obstructive sleep apnea (OSA) in adult patients with cystic fibrosis (CF) and non-CF bronchiectasis (BE) and to relate it with clinical characteristics. Thirty-five CF (27 years) and 35 non-CF (24 years) BE patients were included. Demographic characteristics, medications, comorbidities, BMI, dyspnea scales, pulmonary functions, sputum cultures, exacerbations, and hospitalizations were recorded. The Epworth Sleepiness Scale (ESS) questionnaire was filled and polysomnography was performed for each patient. ESS scores did not show any significant difference between CF and non-CF BE patients. Thirty-seven (53%) of all patients had OSA. There was no significant difference in OSA risk between CF and non-CF BE patients (54% vs 51%, respectively). Male gender was found to be a risk factor for OSA (68% of males vs 41%of females, respectively, p:0.026). Total sleep time, sleep efficiency, sleep latency, time spent awake after falling asleep, oxygen desaturation index, apnea-hypopnea-index (AHI), AHI in the supine position, and rapid eye movementphase did not show any significant difference between CF and non-CF patients. CF patients had significantly lower mean oxygen saturation (p:0.001) and lowest oxygen saturation (p:0.0024) levels and higher heart rate (p:0.02) compared to non-CF BE patients. Multiple logistic regression analysis of all patients revealed male gender and disease duration as risk factors for OSA (p:0.023 and p:0.041 respectively). It is remarkable that more than half of the patients in both CF and non-CF bronchiectasis groups had OSA. Male gender and disease duration were found as risk factors for OSA.

Exploring the role of the Kölliker-Fuse nucleus in breathing variability by mathematical modelling.

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

Sleep bruxism and associated physiological events in children with obstructive sleep apnea: a polysomnographic study.

The aim of this study was to evaluate the physiological events associated with sleep bruxism (Sleep Bruxism [SB]; presence of mandibular movement activity) and the control window (4 minutes prior to SB event, where no mandibular movement activity was detected) in a polysomnography study in children with mild sleep apnea. Polysomnography data from children aged 4 to 9 years old diagnosed with mild sleep apnea were analyzed by 2 trained examiners. The mandibular movement activity (bruxism event; SB) was classified into phasic and tonic. The control window was selected 4 minutes prior to the SB event. All physiological events were recorded in both bruxism and control windows, including sleep phase (N1, N2, N3, and rapid eye movement), arousal, leg movements, tachycardia, bradycardia, oxygen desaturation, and number of obstructive and central sleep apnea events. The moment in which those phenomena occurred when associated with SB was also analyzed (before/after). Data were analyzed using 95% confidence intervals (α = 5%). A total of 661 mandibular movements were analyzed and classified as tonic (n = 372) or phasic (n = 289). The mean apnea-hypopnea index was 1.99 (SD = 1.27) events/h. The frequency of leg movements, microarousal, and tachycardia was increased in SB events when compared with the control window (P < .05). There was an increase in bradycardia frequency in the control window when compared with SB (in both tonic and phasic events). The frequency of obstructive and central apnea during SB was lower when compared with the other physiological phenomena. There is a difference in the physiological parameters evaluated in children with mild sleep apnea when comparing the 2 windows (SB and control). Sleep bruxism is associated with other physiological phenomena, such as leg movements, tachycardia, and microarousal. The use of a control window (where no mandibular activity was detected) was representative since it did not show activation of the sympathetic nervous system. Bonacina CF, Soster LMSFA, Bueno C, etal. Sleep bruxism and associated physiological events in children with obstructive sleep apnea: a polysomnographic study. J Clin Sleep Med. 2024;20(4):565-573.

Cumulative brain desaturation: Time to consider brain derived parameters to measure daytime sleepiness in obstructive sleep apnea

Objective/Background: The change in cerebral hemodynamics induced by sleep apneas and hypopneas may contribute to the daytime sleepiness in patients with obstructive sleep apnea (OSA). However, previous studies failed to discovery their relationship. We propose and test a new parameter, the cumulative brain oxygen desaturation, which may contribute to OSA patient's daytime sleepiness. Patients/methods22 patients with severe OSA (apnea-hypopnea index (AHI) at diagnosis [mean ± standard deviation, std.]: 52.1 ± 21.6/h, median: 45.1/h, interquartile range: 34.4–60.2/h) were monitored by polysomnography during routine continuous positive airway pressure titration. The reductions of brain tissue oxygen saturation (StO2) in all respiratory events at baseline sleep were measured by frequency-domain near-infrared spectroscopy (NIRS). The cumulative brain desaturation was calculated as AHI times the mean StO2 desaturation (i.e., AHI×ΔStO2‾). Similarly, cumulative peripheral desaturation was also calculated, i.e., AHI×ΔSpO2‾ where ΔSpO2‾ was the mean reduction of peripheral arterial oxygen saturation (SpO2). The correlations between Epworth sleepiness scale (ESS) and AHI, ΔStO2‾, AHI×ΔStO2‾, and AHI×ΔSpO2‾ were tested, respectively. Linear regression was applied to predict ESS using AHI×ΔStO2‾ and AHI×ΔSpO2‾, with age and BMI as covariates. ResultsESS significantly correlates to the cumulative brain desaturation (Pearson's correlation coefficient: 0.68, p = 0.00056), not the other parameters. Regression analysis only finds significant association between ESS and the cumulative cerebral desaturation (p = 0.00195) but not the cumulative peripheral desaturation (p = 0.71). ConclusionsThe cumulative brain oxygen desaturation, which comprehensively combines total sleep time, the frequency of apnea and hypopnea events, and the severity of cerebral oxygen desaturation, is a new indicator for daytime sleepiness in severe OSA.

Sleep apnoea syndrome prevalence in chronic kidney disease and end-stage kidney disease patients: a systematic review and meta-analysis.

Several studies have examined the frequency of sleep apnoea (SA) in patients with chronic kidney disease (CKD), reporting different prevalence rates. Our systematic review and meta-analysis aimed to define the clinical penetrance of SA in CKD and end-stage kidney disease (ESKD) patients. Ovid-MEDLINE and PubMed databases were explored up to 5 June 2023 to identify studies providing SA prevalence in CKD and ESKD patients assessed by different diagnostic methods, either sleep questionnaires or respiration monitoring equipment [such as polysomnography (PSG), type III portable monitors or other diagnostic tools]. Single-study data were pooled using the random-effects model. The Chi2 and Cochrane-I2 tests were used to assess the presence of heterogeneity, which was explored performing sensitivity and/or subgroup analyses. A cumulative analysis from 32 single-study data revealed a prevalence of SA of 57% [95% confidence interval (CI) 42%-71%] in the CKD population, whereas a prevalence of 49% (95% CI 47%-52%) was found pooling data from 91 studies in ESKD individuals. The prevalence of SA using instrumental sleep monitoring devices, including classical PSG and type III portable sleep monitors, was 62% (95% CI 52%-72%) and 56% (95% CI 42%-69%) in CKD and ESKD populations, respectively. Sleep questionnaires revealed a prevalence of 33% (95% CI 16%-49%) and 39% (95% CI 30%-49%). SA is commonly seen in both non-dialysis CKD and ESKD patients. Sleep-related questionnaires underestimated the presence of SA in this population. This emphasizes the need to use objective diagnostic tools to identify such a syndrome in kidney disease.

A Review of Novel Oximetry Parameters for the Prediction of Cardiovascular Disease in Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is a sleep disorder with repetitive collapse of the upper airway during sleep, which leads to intermittent hypoxic events overnight, adverse neurocognitive, metabolic complications, and ultimately an increased risk of cardiovascular disease (CVD). The standard diagnostic parameter for OSA, apnoea-hypopnoea index (AHI), is inadequate to predict CVD morbidity and mortality, because it focuses only on the frequency of apnoea and hypopnoea events, and fails to reveal other physiological information for the prediction of CVD events. Novel parameters have been introduced to compensate for the deficiencies of AHI. However, the calculation methods and criteria for these parameters are unclear, hindering their use in cross-study analysis and studies. This review aims to discuss novel parameters for predicting CVD events from oximetry signals and to summarise the corresponding computational methods.