Short apneas and periodic breathing in preterm infants in the neonatal intensive care unit-Effects of sleep position, sleep state, and age.

This observational study investigated the effects of sleep position and sleep state on short apneas and periodic breathing in hospitalized preterm infants longitudinally, in relation to postmenstrual age. Preterm infants (25-31 weeks gestation, n = 29) were studied fortnightly after birth until discharge, in prone and supine positions, and in quiet sleep and active sleep. The percentage of time spent in each sleep state (percentage of time in quiet sleep and percentage of time in active sleep), percentage of total sleep time spent in short apneas and periodic breathing, respectively, the percentage of falls from baseline in heart rate, arterial oxygen saturation and cerebral tissue oxygenation index during short apneas and periodic breathing, and the associated percentage of total sleep time with systemic (arterial oxygen saturation < 90%) and cerebral hypoxia (cerebral tissue oxygenation index < 55%) were analysed using a linear mixed model. Results showed that the prone position decreased (improved) the percentage of falls from baseline in arterial oxygen saturation during both short apneas and periodic breathing, decreased the proportion of infants with periodic breathing and the periodic breathing-associated percentage of total sleep time with cerebral hypoxia. The percentage of time in quiet sleep was higher in the prone position. Quiet sleep decreased the percentage of total sleep time spent in short apneas, the short apneas-associated percentage of falls from baseline in heart rate, arterial oxygen saturation, and proportion of infants with systemic hypoxia. Quiet sleep also decreased the proportion of infants with periodic breathing and percentage of total sleep time with cerebral hypoxia. The effects of sleep position and sleep state were not related to postmenstrual age. In summary, when sleep state is controlled for, the prone sleeping position has some benefits during both short apneas and periodic breathing. Quiet sleep improves cardiorespiratory stability and is increased in the prone position at the expense of active sleep, which is critical for brain maturation. This evidence should be considered in positioning preterm infants.

Central and mixed apneas in children with obstructive sleep apnea: effect of adenotonsillectomy.

PURPOSE: Investigate the effect of adenotonsillectomy on mixed apnea index (MAI) and central apnea index (CAI) in children with moderate-to-severe obstructive sleep apnea syndrome (OSAS). METHODS: Observational retrospective analysis of polysomnographic data in children diagnosed with moderate-to-severe OSAS and without comorbidity, submitted to adenotonsillectomy. RESULTS: Data were available for 80 children, 55 boys and 25 girls, with a median age of 3.6 years (2.1-5.9). Before surgery AHI was 14.1 (11.0-18.4) per hour, with a median preoperative OAI of 7.1 (4.1-10.6), MAI of 1.2 (0.6-1.6) and CAI of 1.0 (0.4-2.0). Adenotonsillectomy caused significant improvements in MAI, from 1.2 (0.6-1.6) to 0.5 (0.1-0.8) (p < 0.001) and CAI from 1.0 (0.4-2.0) to 0.5 (0.1-0.9) (p < 0.001). This represents a normalization of MAI in 91.7% and CAI in 75.6% of children that had an abnormal value prior surgery. CONCLUSION: Non obstructive apneas are common in children with OSAS. Adenotonsillectomy caused significant decrease not only in OAI, but also in MAI and CAI in children with moderate-to-severe OSAS.

Effects of sacubitril-valsartan on central and obstructive apneas in heart failure patients with reduced ejection fraction.

OBJECTIVE: This study aimed to evaluate the effect of sacubitril-valsartan (SV) on central apneas (CA) and obstructive apneas (OA) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In patients with HFrEF, SV initiation was titrated to the highest tolerable dosage. Patients were evaluated with portable apnea monitoring, echocardiography, and cardiopulmonary exercise testing at baseline and 3 months later. RESULTS: Of a total of 18 patients, 9 (50%) had OA, 7 (39%) had CA, and 2 (11%) had normal breathing. SV therapy was related to a reduction in NT-pro BNP and an improvement in LV function after 3 months. Portable apnea monitoring revealed a significant decrease of the respiratory event index (REI) after treatment with SV (20 ± 23 events/h to 7 ± 7 events/h, p = 0.003). When subgrouping according to type of apneas, REI, and time spent below 90% saturation (T90) decreased in patients with CA and OA (all p < 0.05). CONCLUSION: In this prospective study, SV treatment for 3 months in patients with CA and OA is associated with a significant decrease in REI.

Increased spleen volume provoked by temperate head-out-of-water immersion.

This study tested the hypotheses that 1) spleen volume increases during head-out-of-water immersion (HOWI) and returns to pre-HOWI values postdiuresis, and 2) the magnitude of apnea-induced spleen contraction increases when preapnea spleen volume is elevated. Spleen volume was measured before and after a set of five apneas in 12 healthy adults (28 ± 5 yr, 3 females) before, during (at 30 and 150 min), and 20 min after temperate temperature (36 ± 1°C) HOWI. At each time point, spleen length, width, and thickness were measured via ultrasound, and spleen volume was calculated using the Pilström equation. Compared with pre-HOWI (276 ± 88 mL), spleen volume was elevated at 30 (353 ± 94 mL, P < 0.01) and 150 (322 ± 87 mL, P < 0.01) min of HOWI but returned to pre-HOWI volume at post-HOWI (281 ± 90 mL, P = 0.58). Spleen volume decreased from pre- to postapnea bouts at each time point (P < 0.01). The magnitude of reduction in spleen volume from pre- to postapneas was elevated at 30 min of HOWI (-69 ± 24 mL) compared with pre-HOWI (-52 ± 20 mL, P = 0.04) but did not differ from pre-HOWI at 150 min of HOWI (-54 ± 16 mL, P = 0.99) and post-HOWI (-50 ± 18 mL, P = 0.87). Thus, spleen volume is increased throughout 180 min of HOWI, and whereas apnea-induced spleen contraction is augmented after 30 min of HOWI, the magnitude of spleen contraction is unaffected by HOWI thereafter.

Speckle tracking echocardiography in heart failure development and progression in patients with apneas.

Obstructive (OA) and central apneas (CA) are highly prevalent breathing disorders that have a negative impact on cardiac structure and function; while OA promote the development of progressive cardiac alterations that can eventually lead to heart failure (HF), CA are more prevalent once HF ensues. Therefore, the early identification of the deleterious effects of apneas on cardiac function, and the possibility to detect an initial cardiac dysfunction in patients with apneas become relevant. Speckle tracking echocardiography (STE) imaging has become increasingly recognized as a method for the early detection of diastolic and systolic dysfunction, by the evaluation of left atrial and left and right ventricular global longitudinal strain, respectively. A growing body of evidence is available on the alterations of STE in OA, while very little is known with regard to CA. In this review, we discuss the current knowledge and gap of evidence concerning apnea-related STE alterations in the development and progression of HF.

EEF1A2 pathogenic variant presenting in an infant with failure to thrive and frequent apneas requiring respiratory support.

EEF1A2 is a gene whose protein product, eukaryotic translation elongation factor 1 alpha 2 (eEF1A2), plays an important role in neurodevelopment. Reports of individuals with pathogenic variants in EEF1A2 are rare, with less than 40 individuals reported world-wide, however a common feature is the association of the variant with developmental and epileptic encephalopathy. Thus far, there have been limited reports of other organ systems or body functions affected by variants in this gene. Here, we present a case of a child with EEF1A2-related disorder who presented at 3 months of age with hypotonia, microcephaly, failure to thrive, and respiratory insufficiency with central apneas requiring respiratory support. Our case highlights the notion that the respiratory system may be highly implicated in EEF1A2-related disorder, allowing for better phenotypic characterization of the disorder.

Craniofacial reconstructions in children with craniosynostosis.

BACKGROUND: Craniosynostosis is a rare congenital disease of the skull. They arise when one or more cranial sutures ossify prematurely. This causes an obstruction to normal brain growth and leads to specific deformations of the skull, which may result in intracranial hypertension and cognitive delay. MATERIALS AND METHODS: We have retrospectively analysed all children treated at the Unit of paediatric neurosurgery of the University Medical Centre Ljubljana between June 2015 and September 2020. The following items have been recorded: affected suture, underlying syndromic condition, hydrocephalus, Chiari malformation, raised intracranial pressure, age at surgery, surgical technique, need for multiple operations and surgical complications. RESULTS: During the study period, 71 children have been treated for craniosynostosis. The median postoperative follow-up was 31 months. There were: 54.9% sagittal, 25.3% metopic, 14.0% unicoronal, 1.4% bicoronal and 1.4% unilateral lambdoid craniosynostosis. Multiple sutures were affected in 2.8% cases. 7.0% of the cases were syndromic. Overall, 74 surgical procedures have been performed: frontoorbital advancement represented 40.5% of them; biparietal remodelling 32.4%: total cranial vault remodelling 22.9%; posterior distraction 2.7%; posterior expansion 1.3%. Median age at surgery was 12.8 months. CONCLUSIONS: The treatment of craniosynostosis is surgical and requires a multidisciplinary approach, with expertise in plastic and reconstructive surgery, maxillofacial surgery and neurosurgery. The aim of surgical treatment is to release the constrictive and deformative effect that the synostosis has on skull growth. This requires a remodelling of the neurocranium and, if necessary, of the viscerocranium. Beyond aesthetic purposes, the primary aim of surgical treatment is to permit a normal development of the brain.

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome.

STUDY OBJECTIVES: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. METHODS: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. RESULTS: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.

Cardiorespiratory Events in Infants Born Preterm during the Transitional Period.

OBJECTIVE: To investigate the features of cardiorespiratory events in infants born preterm during the transitional period, and to evaluate whether different neonatal characteristics may correlate with event type, duration, and severity. STUDY DESIGN: Infants with gestational age (GA) <32 weeks and/or birth weight <1500 g were enrolled in this observational prospective study. Heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded continuously over the first 72 hours. Cardiorespiratory events of ≥10 seconds were clustered into isolated desaturation (SpO2 <85%), isolated bradycardia (HR <100 bpm or <70% of baseline), or combined desaturation/bradycardia and classified as mild, moderate, or severe. The daily incidences of isolated desaturation, isolated bradycardia, and combined desaturation and bradycardia were analyzed. The effects of relevant clinical variables on cardiorespiratory event type and severity were assessed using generalized estimating equations. RESULTS: Among the 1050 events analyzed, isolated desaturations were the most frequent (n = 625) and isolated bradycardias the least common (n = 171). The number of cardiorespiratory events increased significantly from day 1 to day 2 (P = .028). One in 5 events had severe characteristics; event severity was highest for combined desaturation and bradycardia (P < .001). Compared with other event types, the incidence of combined desaturation and bradycardia was inversely correlated with GA (P = .029) and was higher with the use of continuous positive airway pressure (P = .002). The presence of a hemodynamically significant patent ductus arteriosus was associated with the occurrence of isolated desaturations (P = .001) and with a longer duration of cardiorespiratory events (P = .003). CONCLUSIONS: Cardiorespiratory events during transition exhibit distinct types, duration, and severity. Neonatal characteristics are associated with the clinical features of these events, indicating that a tailored clinical approach may reduce the hypoxic burden in preterm infants aged 0-72 hours.

A New Wearable System for Home Sleep Apnea Testing, Screening, and Classification.

We propose an unobtrusive, wearable, and wireless system for the pre-screening and follow-up in the domestic environment of specific sleep-related breathing disorders. This group of diseases manifests with episodes of apnea and hypopnea of central or obstructive origin, and it can be disabling, with several drawbacks that interfere in the daily patient life. The gold standard for their diagnosis and grading is polysomnography, which is a time-consuming, scarcely available test with many wired electrodes disseminated on the body, requiring hospitalization and long waiting times. It is limited by the night-by-night variability of sleep disorders, while inevitably causing sleep alteration and fragmentation itself. For these reasons, only a small percentage of patients achieve a definitive diagnosis and are followed-up. Our device integrates photoplethysmography, an accelerometer, a microcontroller, and a bluetooth transmission unit. It acquires data during the whole night and transmits to a PC for off-line processing. It is positioned on the nasal septum and detects apnea episodes using the modulation of the photoplethysmography signal during the breath. In those time intervals where the photoplethysmography is detecting an apnea, the accelerometer discriminates obstructive from central type thanks to its excellent sensitivity to thoraco-abdominal movements. Tests were performed on a hospitalized patient wearing our integrated system and the type III home sleep apnea testing recommended by The American Academy of Sleep Medicine. Results are encouraging: sensitivity and precision around 90% were achieved in detecting more than 500 apnea episodes. Least thoraco-abdominal movements and body position were successfully classified in lying down control subjects, paving the way toward apnea type classification.

Complex sleep apnea after full-night and split-night polysomnography: the Greek experience.

PURPOSE: Treatment-emergent central sleep apnea (TE-CSA) is defined as the emergence or persistence of central respiratory events during the initiation of positive airway pressure (PAP) without a back-up rate in obstructive sleep apnea (OSA) patients and after significant resolution of obstructive events. Previous studies have estimated a prevalence from 0.56 to 20.3%. The aim of this study was to establish the prevalence of TE-CSA in a Greek adult population. METHODS: One thousand fifty nine patients with newly diagnosed OSA, who were referred to the Sleep Disorders Center of Evangelismos Hospital of Athens over an 18-month period, were included in this study. A split-night polysomnography (PSG), or two formal overnight PSGs (diagnostic and continuous PAP (CPAP) titration study), were performed. RESULTS: Patients with OSA were divided in two groups; the first group included 277 patients, who underwent two separate studies (diagnostic and CPAP titration study), and the second group 782 patients, who underwent split-night studies. The prevalence of TE-CSA in the first group was 2.53% (7 patients), and in the second group was 5.63% (44 patients). CONCLUSIONS: The prevalence of TE-CSA in Greece was lower compared to most previous reported studies. The significant variation in the prevalence of TE-CSA between different centers throughout the world is mainly associated with the used diagnostic criteria as well as methodological and technical aspects.

Pulse transit time as a tool to characterize obstructive and central apneas in children.

PURPOSE: The characterization of apneas during polysomnography (PSG) as obstructive or central is a key element of a sleep study. Pulse transit time (PTT) has demonstrated its potential as a noninvasive surrogate marker for inspiratory efforts. The aim of the study was to assess the ability of PTT to classify apneas as central or obstructive, as compared to respiratory inductance plethysmography (RIP) in children. METHODS: Overnight PSG with simultaneous PTT recording was performed on 11 consecutive children (mean age 8.9 years, range 1-18.2 years). The same observer scored the apneas using two blinded configurations: (1) the RIP scoring used the nasal pressure, thermistors, thoracic and abdominal movements, and pulse oximetry signals: (2) the PTT scoring used PTT in combination with all the other signals without the thoracic and abdominal movements. RESULTS: One hundred fourteen apneas out of a total of 520 respiratory events were analyzed. With RIP, 58 (51%) apneas were scored as obstructive and 56 (49%) as central. Using PTT, 77 (68%) of the apneas were scored as obstructive and 37 (32%) as central. When using PTT, 30 apneas scored as central by RIP were scored as obstructive. PTT was highly sensitive (81%) but poorly specific (46%) in scoring 58 apneas as obstructive. PTT was less sensitive (46%) but highly specific (81%) to score 56 apneas as central. CONCLUSION: PTT may be used as an additional tool to RIP to improve the scoring of apneas as obstructive or central in children. The high percentage of artifact is a limitation of PTT.

Effects of ion channel noise on neural circuits: an application to the respiratory pattern generator to investigate breathing variability.

Neural activity generally displays irregular firing patterns even in circuits with apparently regular outputs, such as motor pattern generators, in which the output frequency fluctuates randomly around a mean value. This "circuit noise" is inherited from the random firing of single neurons, which emerges from stochastic ion channel gating (channel noise), spontaneous neurotransmitter release, and its diffusion and binding to synaptic receptors. Here we demonstrate how to expand conductance-based network models that are originally deterministic to include realistic, physiological noise, focusing on stochastic ion channel gating. We illustrate this procedure with a well-established conductance-based model of the respiratory pattern generator, which allows us to investigate how channel noise affects neural dynamics at the circuit level and, in particular, to understand the relationship between the respiratory pattern and its breath-to-breath variability. We show that as the channel number increases, the duration of inspiration and expiration varies, and so does the coefficient of variation of the breath-to-breath interval, which attains a minimum when the mean duration of expiration slightly exceeds that of inspiration. For small channel numbers, the variability of the expiratory phase dominates over that of the inspiratory phase, and vice versa for large channel numbers. Among the four different cell types in the respiratory pattern generator, pacemaker cells exhibit the highest sensitivity to channel noise. The model shows that suppressing input from the pons leads to longer inspiratory phases, a reduction in breathing frequency, and larger breath-to-breath variability, whereas enhanced input from the raphe nucleus increases breathing frequency without changing its pattern. NEW & NOTEWORTHY: A major source of noise in neuronal circuits is the "flickering" of ion currents passing through the neurons' membranes (channel noise), which cannot be suppressed experimentally. Computational simulations are therefore the best way to investigate the effects of this physiological noise by manipulating its level at will. We investigate the role of noise in the respiratory pattern generator and show that endogenous, breath-to-breath variability is tightly linked to the respiratory pattern.

CDKL5 deficiency entails sleep apneas in mice.

A recently discovered neurodevelopmental disorder caused by the mutation of the cyclin-dependent kinase-like 5 gene (CDKL5) entails complex autistic-like behaviours similar to Rett syndrome, but its impact upon physiological functions remains largely unexplored. Sleep-disordered breathing is common and potentially life-threatening in patients with Rett syndrome; however, evidence is limited in children with CDKL5 disorder, and is lacking altogether in adults. The aim of this study was to test whether the breathing pattern during sleep differs between adult Cdkl5 knockout (Cdkl5-KO) and wild-type (WT) mice. Using whole-body plethysmography, sleep and breathing were recorded non-invasively for 8 h during the light period. Sleep apneas occurred more frequently in Cdkl5-KO than in WT mice. A receiver operating characteristic (ROC) analysis discriminated Cdkl5-KO significantly from WT mice based on sleep apnea occurrence. These data demonstrate that sleep apneas are a core feature of CDKL5 disorder and a respiratory biomarker of CDKL5 deficiency in mice, and suggest that sleep-disordered breathing should be evaluated routinely in CDKL5 patients.

[STOP-BANG, a useful and easy tool for the screening of obstructive sleep apnea]. / STOP-BANG, una herramienta útil y sencilla para el cribado del síndrome de apneas hipopneas obstructivas del sueño.

The STO-BANG questionnaire, S standing for snore, T tired, O observed apneas, P pressure (arterial hypertension), B BMI (body mass index > 35 kg/ m2), A age (> 50 years old), N neck circumference (> 40 cm), G gender (male); is a simple tool that enables the detection of patients with obstructive sleep apnea syndrome (OSA). If the patient adds 3 or more points, it is considered to have a high probability of having this disease. Our goal was to evaluate the capacity of the STOP-BANG questionnaire and to compare it with the ability of a sleep trained pulmonologist in determining the probability of OSA. A retrospective analysis of 327 patients suspected of having this condition was performed. One hundred and seventy-one were males (52.3%), 49.8 years old (37.9-61.7), BMI 38.7 kg/m2 (32.5-46), neck circumference 44 cm (41-47.5), 311 snorers (95.1%), 232 with daytime sleepiness or usual tiredness (70.9%), 206 with observed apneas (63%), 169 with arterial hypertension (51.7%), normal polysomnography 42 (12.9%), mild 65 (19.9%), moderate 59 (18%), severe 161 (49.2%). The STOP-BANG's sensibility and specificity, taking as a cut-off point a respiratory disturbance index (RDI) > or = to 15, was 99.1% and 14.0% respectively, area under curve (AUC) 0.755 (0.704-0.800), the values for the PR actioner's ability were 89.1% and 58.9% respectively, AUC 0.550 (0.542-0.638). The STOP-BANG questionnaire is easy to implement as a screening tool.

Observational study of hypertension and snoring in Northeastern Italy (Limana Hypertension Study).

OBJECTIVE: To evaluate through an observational study on volunteers some important cardiovascular disease risk factors such as hypertension and snoring in a population from Limana, a town of a subalpine zone of northeastern Italy. DESIGN: Limana residents were informed by post and at a public meeting and then attended an outpatient clinic set up by the town of Limana for clinical history, measurement of blood pressure, weight and height. PATIENTS: Of 202 subjects (94 men and 108 women), 92.6% of whom were residents of Limana, having a mean age of 59.7 years, which was significantly higher than the mean (44.7 years), took part in the study. RESULTS: Only 32.3% of study subjects with hypertension had normal blood pressure values while 38.6% of the subjects without hypertension treatment, were hypertensive. We found no significant association between hypertension and smoking and there were significant associations between hypertension and age and hypertension and snoring. CONCLUSIONS: Given the limitations of an observational study based on volunteer participation, nevertheless, our study presents some interesting results: (1) a low number of subjects with hypertension whose blood pressure is well controlled; (2) a significant number of "normal" subjects with high values of blood pressure; (3) no significant relationship between hypertension and smoking; (4) a significant relationship between subjects who snored and were hypertensive.

Sleep disturbance: a forgotten syndrome in patients with Chiari I malformation.

INTRODUCTION: Chiari type I malformation (CM-I) is characterised by caudal ectopia of the cerebellar tonsils through the foramen magnum. This is associated with brain stem, high spinal cord, and cranial nerve compression phenomena. The most frequent symptoms are occipital headaches and dizziness. Less well-known symptoms are sleep disorders and nocturnal respiratory abnormalities. SOURCES: MEDLINE and information from patients evaluated at the Neurosurgery and Clinical Neurophysiology Departments at Hospital Universitario Vall d'Hebron. DEVELOPMENT: Review article based on data obtained from MEDLINE articles since 1966, using combinations of the following keywords: «Chiari malformation¼ or «Arnold-Chiari malformation¼ and «sleep apnea¼ or «sleep disorders¼. CONCLUSIONS: CM-I patients show a higher prevalence of sleep disorders than that observed in the general population. Some studies report a 50% prevalence of sleep apnea-hypopnea syndrome (SAHS), probably associated with sudden death in some cases. These results support analysing sleep respiratory parameters in theses patients. Identifying SAHS symptoms may help optimise treatment, thereby improving quality of life and prognosis.

Clinical and prognostic significance of central and obstructive apneas in patients with transthyretin cardiac amyloidosis.

AIMS: Central (CA) and obstructive apneas (OA) are highly prevalent in patients with chronic heart failure (HF) and transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized HF etiology. This study aimed to investigate the prevalence and impact of CA and OA in patients with ATTR-CA. METHODS: Consecutive patients with ATTR-CA underwent a 24-hour ambulatory cardiorespiratory monitoring to evaluate the prevalence and severity of breathing disorders. The severity of these disorders was quantified using the apnea-hypopnea index (AHI). Accordingly, patients were categorized as having normal breathing (NB, AHI <5 events/hour), obstructive apnea (OA, AHI ≥5 events/hour with >50% being obstructive), or central apnea (CA, AHI >5 events/hour with ≥50% being central). The primary endpoint at follow-up was all-cause mortality. RESULTS: Out of 142 patients enrolled (n=142, aged 77±7 years, 91% males, 96% wild-type ATTR-CA), considering the 24 hours, 20% had NB (39% at daytime, 8% at nighttime), while 35% had CA (45% at daytime, 39% at nighttime) and 45% had OA (25% at daytime, 54% at nighttime). After a median 2.3 (1.4-3.3) years follow-up, 24-hour, daytime, and nighttime AHI were higher in non-survivors vs. survivors (all p<0.05), independently of the prevalent apnea type (p=0.64). At multivariable regression analysis (adjusted for the possible clinical, echocardiographic, and biohumoral confounders), nighttime AHI ≥30 events/hour (hazard ratio 2.37 [95%CI 1.07-5.23], p=0.033) and hs-troponin T (hazard ratio 2.43 [95%CI 1.42-4.17], p=0.001) were predictors of mortality. CONCLUSION: CA and OA are highly prevalent both at daytime and nighttime in patients with ATTR-CA and are associated with higher mortality.

This study investigated the prevalence and prognostic significance of central (CA) and obstructive apneas (OA) in 142 patients with transthyretin cardiac amyloidosis (ATTR-CA). Both CA and OA were highly prevalent during the whole 24-hour period, with only 20% classified as having normal breathing (meant as an apnea-hypopnea-index <5 events/hour during the 24-hour). OA were more frequent than CA, particularly during the night, while the prevalence of CA increased with worsening left ventricular systolic and diastolic dysfunction. At follow-up, 24-hour, daytime, and nighttime AHI were higher in non-survivors vs. survivors, independently of the prevalent apnea type and, at multivariable regression analysis (adjusted for the possible clinical, echocardiographic, and biohumoral confounders), nighttime AHI ≥30 events/hour was an independent predictor of mortality.

Pharmacological interventions for pediatric obstructive sleep apnea (OSA): Network meta-analysis.

IMPORTANCE: Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of different pharmacologic interventions for the treatment of OSA in children is still lacking. OBJECTIVE: This study aims to conduct a comprehensive systematic review and network meta-analysis of pharmacological interventions for the management of obstructive sleep apnea in pediatric population. DATA SOURCES: PubMed, Web of Science, Embase, The Cochrane Library, and CNKI were searched from 1950 to November 2022 for pediatric OSA. STUDY SELECTION: Multiple reviewers included Randomized controlled trials (RCTs) concerning drugs on OSA in children. DATA EXTRACTION AND SYNTHESIS: Multiple observers followed the guidance of the PRISMA NMA statement for data extraction and evaluation. Bayesian network meta-analyses(fixed-effect model) were performed to compare the weighted mean difference (WMD), logarithmic odds ratios (log OR), and the surface under the cumulative ranking curves (SUCRA) of the included pharmacological interventions. Our protocol was registered in PROSPERO website (CRD42022377839). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes were improvements in the apnea/hypopnea index (AHI), while secondary outcomes included adverse events and the lowest arterial oxygen saturation (SaO2). RESULTS: 17 RCTs with a total of 1367 children with OSA aged 2-14 years that met the inclusion criteria were eventually included in our systematic review and network meta-analysis. Ten drugs were finally included in the study. The results revealed that Mometasone + Montelukast (WMD-4.74[95%CrIs -7.50 to -2.11], Budesonide (-3.45[-6.86 to -0.15], and Montelukast(-3.41[-5.45 to -1.39] exhibited significantly superior therapeutic effects compared to the placebo concerning apnea hypopnea index (AHI) value with 95%CrIs excluding no effect. Moreover, Mometasone + Montelukast achieved exceptionally high SUCRA values for both AHI (85.0 %) and SaO2 (91.0 %). CONCLUSIONS AND RELEVANCE: The combination of mometasone furoate nasal spray and oral montelukast sodium exhibits the highest probability of being the most effective intervention. Further research is needed to investigate the long-term efficacy and safety profiles of these interventions in pediatric patients with OSA.

Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVE: Summarize the evidence on drug therapies for obstructive sleep apnea. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. RESULTS: 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. CONCLUSION: The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO REGISTRATION NUMBER: CRD42022362639.