Frequency Of Apnea Research Articles

The effect of sensory stimulation on apnea of prematurity

ObjectivesThe study aims to assess the effect of sensory stimulation on apnoea among premature newborns. MethodsThirty preterm newborns that were diagnosed with apnoea of prematurity, had a gestational age between 32 and 34 weeks, had low birth weight, and were appropriate for gestational age from 1200 to 2000 g were included in this prospective randomized study. Subjects were divided into two equivalent groups: a control group that received the standard care including nasal oxygen (one litre per minute) and caffeine citrate, and a study group that received the same care plus sensory stimulation (tactile, proprioceptive, and kinaesthetic). Participants’ heart rate, oxygen saturation, and apnoea frequency were measured by the neonatal intensive care unit team using a pulse-oximeter. The sensory stimulation sessions were 10 min, 3 times per day, totalling 30 min over a 7 day period. ResultsThere was a significant decrease in heart rate within both groups after receiving treatment from before treatment (p < 0.05), with no significant differences between the two groups. Furthermore, there was no significant difference in oxygen saturation within the groups after treatment compared with the levels before treatment, with no significant differences between the two groups (p > 0.05). Before treatment, there was a non-significant difference in the apnoea rate between both groups (p = 0.464), whereas there was a significant decrease in the apnoea rate of the study group after treatment compared with the control group (p = 0.031). ConclusionSensory stimulation applied with standard respiratory care can decrease the frequency of apnoea of prematurity.

Reduced Plasma Estradiol Levels are Associated with Sleep Apnea in Depressed Peri- and Post-Menopausal Women.

ObjectiveThis study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods.MethodsA total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea–hypopnea index (AHI)≥5) (OSA vs non-OSA). The correlation between estradiol levels and apnea–hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone.ResultsAmong the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p<0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875–0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826–0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012–1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389–4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136–2.353, p = 0.008) are correlated with OSA.ConclusionThe ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.

Sensory stimulation for apnoea mitigation in preterm infants.

Apnoea, a pause in respiration, is ubiquitous in preterm infants andare often associated with physiological instability, which may lead to longer-term adverse neurodevelopmental consequences. Despite current therapies aimed at reducing the apnoea burden, preterm infants continue to exhibit apnoeic events throughout their hospital admission. Bedside staff are frequently required to manually intervene with different forms of stimuli, with the aim of re-establishing respiratory cadence and minimizing the physiological impact of each apnoeic event. Such a reactive approach makes apnoea and its associated adverse consequences inevitable and places a heavy reliance on human intervention. Different approaches to improving apnoea management in preterm infants have been investigated, including the use of various sensory stimuli. Despite studies reporting sensory stimuli of various forms to have potential in reducing apnoea frequency, non-invasive intermittent positive pressure ventilation is the only automated stimulus currently used in the clinical setting for infants with persistent apnoeic events. We find that the development of automated closed-looped sensory stimulation systems for apnoea mitigation in preterm infants receiving non-invasive respiratory support is warranted, including the possibility of stimulation being applied preventatively, and in a multi-modal form. IMPACT: This review examines the effects of various forms of sensory stimulation on apnoea mitigation in preterm infants, namely localized tactile, generalized kinesthetic, airway pressure, auditory, and olfactory stimulations. Amongst the 31 studies reviewed, each form of sensory stimulation showed some positive effects, although the findings were not definitive and comparative studies were lacking. We find that the development of automated closed-loop sensory stimulation systems for apnoea mitigation is warranted, including the possibility of stimulation being applied preventatively, and in a multi-modal form.

Effect of different maintenance doses of caffeine citrate on ventilator weaning in very preterm infants with respiratory distress syndrome: a prospective randomized controlled trial.

To study the effect of different maintenance doses of caffeine citrate on the success rate of ventilator weaning in very preterm infants (gestational age of ≤32 weeks) with respiratory distress syndrome (RDS). A total of 162 preterm infants with RDS who were admitted to the hospital from January 2016 to December 2018 were enrolled in this prospective trial. These infants had a gestational age of ≤32 weeks and required invasive mechanical ventilation. They were randomly divided into a high-dose caffeine group and a low-dose caffeine group, with 81 infants in each group. Within 6 hours after birth, both groups were given caffeine at a dose of 20 mg/kg. After 24 hours, the high- and low-dose caffeine groups were given caffeine at a maintenance dose of 10 mg/kg and 5 mg/kg, respectively. The two groups were compared in terms of re-intubation rate within 48 hours after ventilator weaning, durations of ventilation and oxygen therapy, enteral feeding, weight gain, and the incidence rates of complications and adverse reactions during hospitalization. The high-dose caffeine group had a significantly lower re-intubation rate within 48 hours after ventilator weaning than the low-dose caffeine group (P<0.05), with frequent apnea as the main reason for failed ventilator weaning in both groups. The high-dose caffeine group had significantly shorter durations of mechanical ventilation and oxygen therapy than the low-dose caffeine group (P<0.05). There were no significant differences between the two groups in the time to total enteral feeding, average daily weight gain, body weight at discharge, and the incidence rates of complications (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intracranial hemorrhage) and adverse reactions (tachycardia, hypertension, and feeding intolerance) (P>0.05). A high maintenance dose of caffeine can safely and effectively reduce the incidence rate of apnea after ventilator weaning and the failure rate of ventilator weaning in RDS preterm infants with a gestational age of ≤32 weeks, and therefore, it holds promise for clinical application.

The frequency of obstructive sleep apnea in patients with primary Sjogren's syndrome.

IntroductionThere is a lack of information about the frequency of obstructive sleep apnea (OSA) in primary Sjogren’s syndrome (pSS). Using all-night polysomnography (PSG), this study aimed to investigate the frequency of OSA in pSS and the factors affecting the frequency of OSA in this condition. MethodsConsecutive patients with pSS who presented to the Collagen Tissue Diseases follow-up polyclinic of the Department of Chest Diseases between 1 April 2019 and 31 December, 2020, were included in the study. Demographic characteristics, chronic diseases, smoking history in pack-years, anthropometric data, Epworth Sleepiness Scale score, pulmonary function test parameters, current thorax computed tomography findings, and PSG data were recorded. The control group was created by the retrospective screening of patients admitted to the sleep polyclinic and who underwent PSG but did not have pSS.ResultsOSA was detected in 37 (84%) of 44 patients with pSS who underwent PSG. Of 37 patients with OSA, 25 (68%) had moderate or severe OSA. Snoring and witnessed apneas, REM%, snoring index, and maximum apnea and maximum hypopnea duration were statistically significantly lower in the pSS group compared with the control group (p < 0.001, p = 0.003, p = 0.025, p = 0.001, p = 0.028, and p = 0.035, respectively).ConclusionThe frequency of OSA in patients with pSS was 84%, with a decrease in REM%. Although a correlation between symptoms suggesting OSA and the presence of radiological lung involvement, spirometry, and DLCO values with OSA could not be demonstrated, physicians are recommended to be attentive for the presence of OSA in all patients with pSS and to investigate OSA using PSG.

Association of Sleep-Related Hypoxia With Risk of COVID-19 Hospitalizations and Mortality in a Large Integrated Health System

The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.

Increased CaMKII-dependent pro-arrhythmic activity in a novel mouse model of obstructive sleep apnoea

Abstract Background Obstructive sleep apnoea (OSA) is frequently associated with atrial arrhythmias, but detailed mechanisms remain elusive. Most recently, we found an increased CaMKII-dependent pro-arrhythmic activity in patients with sleep apnoea. Since patients suffer from various confounding comorbidities, we have developed a novel mouse model of OSA by tongue enlargement. Purpose We tested if mice with OSA exhibit increased atrial CaMKII-dependent pro-arrhythmic activity. Methods Polytetrafluorethylene (PTFE) was injected into the tongue of 12 wild-type (WT) and 10 CaMKII knock-out (CKO) mice. 9 WT and 9 CKO mice were used as control without PTFE injection. Inspiratory flow limitations and apnoeas were monitored during murine sleep phases by whole-body plethysmography (Buxco). After eight weeks, isolated atrial cardiomyocytes were incubated with the Ca-sensitive dye FURA-2 AM for 15 min. Regular Ca transients were elicited by electrical field stimulation (1 Hz, 20 V for 4 ms) using epifluorescence microscopy. Pro-arrhythmic non-stimulated events were defined as deviations from diastolic Ca baseline between two stimulated Ca transients. Results Sonographic measurements revealed a significant increase in mean tongue diameter from (in mm) 3.7±0.1 to 5.1±0.1 after PTFE injection (n=23, p&amp;lt;0.0001). There was a significant correlation between magnitude of tongue diameter and frequency of apnoeas in OSA mice (p=0.046, r2=0.19, Fig. 1A). Interestingly, we observed a significantly increased frequency of pro-arrhythmic events of (in s–1) 0.06±0.01 in WT OSA mice compared to 0.02±0.01 in WT control mice (p=0.047, Fig. 1B). Similar results were observed at higher stimulation frequencies (2 and 4 Hz). There was a significant correlation of pro-arrhythmic events with inspiratory flow limitations (p=0.03, r2=0.24, Fig. 1C) and with the frequency of apnoeas by strong trend (p=0.06, r2=0.18). In contrast, no increase in atrial pro-arrhythmic events was observed in CKO mice after PTFE injection (for CKO mice after PTFE vs. CKO mice without PTFE, 0.03±0.01 s–1 vs. 0.03±0.01 s–1, p=0.89, Fig. 1B). Accordingly, the correlations between pro-arrhythmic events and both inspiratory flow limitations (p=0.36, r2=0.05, Fig. 1C) and apnoeas (p=0.82, r2=0.004) were completely abolished in CKO mice. Conclusion In a novel mouse model of obstructive sleep apnoea, atrial pro-arrhythmic activity was increased in a CaMKII-dependent fashion, which may have therapeutic implications. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Benedikt Schaner / Mr., this work is supported by a research grant of the German Cardiac Society (DGK); Stefan Wagner / Professor, was funded by DFG grants Figure 1

The Frequency of Obstructive Sleep Apnea in Asthmatic Patients, and Impact of OSA on Asthma Control

Abstract Background Obstructive sleep apnea (OSA) and asthma are common inflammatory respiratory diseases of childhood. The similarities between and the parallel rise of both diseases raise the question of whether OSA is indeed more common in asthmatic children. Objectives The present study is cross section study conducted on fifty children with bronchial asthma the aim of study was to evaluate the frequency of obstructive sleep apnea in asthmatic patients, and impact of OSA on asthma control. Patients and Methods The present work is a Cross-sectional study conducted on fifty Children (27 females and 23 males) aging 5 to 18 years diagnosed as bronchial asthma following up in pulmonology clinic or admitted to pulmonology department in Pediatric Hospital- Ain Shams University. Patients were excluded from presence of any other chronic chest diseases, any congenital malformation in upper respiratory, any genetic disease or inborn error of metabolism, morbid obesity and other medical co morbidities that might interfere with sleep quality. All patients were subjected to full history taking, meticulous general and local chest examination, pulmonary function tests and exposed questionnaire: Asthma control questionnaire (ACQ) and OSA-18 quality of life questionnaire. Children were positive OSA with OSA-18 quality of life questionnaire referred to sleep study. Results 54 % of cases were females and 46% were males. There mean age=10.1, mean of OSA score =75.6. 20% diagnosed OSA according to questionnaire. OSA score increased in patients with history of PICU and hospital admission. OSA score was highly correlated with severity and degree of control of bronchial asthma. 10% of children were positive OSA with OSA-18 quality of life questionnaire suggestive have obstructive sleep apnea according to polysomnogram. Conclusion OSA has a direct and significant impact on asthma severity and control. Asthma and OSA are common disorders, and the concomitant presence of both conditions can be detrimental. Due to the bidirectional association of both conditions, we as clinicians should be aware of it.

Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome

Rationale: Congenital central hypoventilation syndrome (CCHS) is characterized by life-threatening sleep hypoventilation and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation, with patients requiring lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome. Objectives: To determine if Phox2b27Ala/+ mice, which present the main symptoms of CCHS and die within hours after birth, also express obstructive apneas, and to investigate potential underlying mechanisms. Methods: Apneas were classified as central, obstructive, or mixed by using a novel system combining pneumotachography and laser detection of abdominal movement immediately after birth. Several respiratory nuclei involved in airway patency were examined by immunohistochemistry and electrophysiology in brainstem-spinal cord preparations. Measurements and Main Results: The median (interquartile range) of obstructive apnea frequency was 2.3 (1.5-3.3)/min in Phox2b27Ala/+ pups versus 0.6 (0.4-1.0)/min in wild types (P < 0.0001). Obstructive apnea duration was 2.7 seconds (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7 seconds (1.1-1.9) in wild types (P < 0.0001). Central and mixed apneas presented similar significant differences. In Phox2b27Ala/+ preparations, the hypoglossal nucleus had fewer (P < 0.05) and smaller (P < 0.01) neurons, compared with wild-type preparations. Importantly, coordination of phrenic and hypoglossal motor activities was disrupted, as evidenced by the longer and variable delay of hypoglossal activity with respect to phrenic activity onset (P < 0.001). Conclusions: The Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also to obstructive and mixed apneas, likely because of hypoglossal dysgenesis. These results thus demand attention toward obstructive events in infants with CCHS.

Cardiorespiratory Events Following the Second Routine Immunization in Preterm Infants: Risk Assessment and Monitoring Recommendations.

Due to frequent cardiorespiratory events (CREs) in response to the first routine immunization (rIM), current guidelines recommend readmitting and monitoring extremely preterm infants after the second rIM, though evidence on CREs in response to the second rIM is weak. In a prospective observational study, preterm infants with an increase in CREs after the first rIM were monitored for CREs before and after the second rIM. Seventy-one infants with a median gestational age of 26.4 weeks and a median weight of 820 g at birth were investigated at a median postnatal age of 94 days. All but seven infants showed an increase in CREs after the second rIM. The frequency of hypoxemias (p < 0.0001), apneas (p = 0.0003) and cardiorespiratory events requiring tactile stimulation (CRE-ts) (p = 0.0034) increased significantly. The 25 infants (35%) presenting with CRE-ts were significantly more likely to have been continuously hospitalized since birth (p = 0.001) and to receive analeptic therapy at the first rIM (p = 0.002) or some kind of respiratory support at the first (p = 0.005) and second rIM (p < 0.0001). At a postmenstruational age of 43.5 weeks, CRE-ts ceased. Our data support the recommendation to monitor infants who fulfil the above-mentioned criteria during the second rIM up to a postmenstruational age of 44 weeks.

Association Between Sleep Apnea and Valvular Heart Diseases.

Background: Although sleep respiratory disorders are known as a relevant source of cardiovascular risk, there is a substantial lack of trials aimed to evaluate the eventual occurrence of associations between sleep apnea (SA) and valvular heart diseases (VHD).Methods: We recruited 411 patients referring to our sleep disorder unit, among which 371 had SA. Ninety-three subjects with SA also suffered from VHD. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient. Patient subgroups were comparatively evaluated through cross-sectional analysis.Results: A statistically significant increase in the prevalence of VHD was detected in relation to high apnea hypopnea index (AHI) values (p = 0.011). Obstructive sleep apnea occurrence was higher in SA patients without VHD (p < 0.0001). Conversely, central and mixed sleep apneas were more frequent among SA patients with VHD (p = 0.0003 and p = 0.002, respectively). We observed a direct correlation between AHI and BMI values (p < 0.0001), as well as between AHI and serum uric acid levels (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), and indexed left ventricular end-diastolic volume (p < 0.015), respectively. BMI and VHD resulted to be the main predictors of AHI values (p < 0.0001).Conclusions: Our study suggests that a significant association can occur between SA and VHD. It is clinically relevant that when compared to SA patients without VHD, higher frequencies of central and mixed apneas were found in subjects with SA and VHD. Moreover, after elevated BMI, VHD represented the second predictor of AHI values.

Push versus gravity for intermittent bolus gavage tube feeding of preterm and low birth weight infants.

Many small, sick, and preterm infants are unable to co-ordinate sucking, swallowing, and breathing, and therefore require gavage feeding. In gavage feeding, milk feeds are delivered through a tube passed via the nose or the mouth into the stomach. Intermittent bolus milk feeds may be administered by a syringe to gently push milk into the infant's stomach (push feed). Alternatively, milk can be poured into a syringe attached to the tube and allowed to drip in by gravity (gravity feed). To determine whether use of push feeding compared with gravity feeding results in more rapid establishment of full gavage feeds without increasing adverse events among preterm or low birth weight infants, or both, who require intermittent bolus tube feeding. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We included RCTs and quasi-RCTs comparing push versus gravity intermittent gavage tube feeding in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 grams) infants, or both. We assessed the methods of trials regarding blinding of randomisation and outcome measurement. We evaluated treatment effects with a fixed-effect model using risk ratio (RR), relative risk reduction, risk difference (RD), and number needed to treat for an additional beneficial outcome (NNTB) for categorical data; and using mean, standard deviation, and mean difference (MD) for continuous data. We analysed outcomes measured as count data, for example, frequency of apnoea, bradycardia, and episodes of pulse oximeter oxygen (SpO₂) desaturation, by comparing rates of events and the rate ratio. We evaluated heterogeneity to help determine the suitability of pooling results. We used the GRADE approach to assess the certainty of evidence. One small cross-over trial (31 infants) met the criteria for inclusion in this review. The certainty of evidence for all outcomes was very low due to imprecision of estimates, wide confidence intervals, and unclear risk of bias. The primary outcome - time taken to establish full gavage feeding (days) and feeding intolerance (number of episodes per day) - was not reported in the included study. The evidence is very uncertain about the effects of push versus gravity intermittent gavage tube feeding on all other outcomes. Investigators reported respiratory rate (breaths per minute) at completion of feeding (MD 0.58, 95% confidence interval (CI) -5.97 to 7.13; 1 study, 31 participants; very low-certainty evidence); respiratory rate (breaths per minute) 10 to 30 minutes after completion of feeding (MD 3.1, 95% CI -3.43 to 9.63; 1 study, 31 participants; very low-certainty evidence); heart rate (beats per minute) at completion of feeding (MD 2.6, 95% CI -9.71 to 4.51; 1 study, 31 participants; very low-certainty evidence); and heart rate (beats per minute) 10 to 30 minutes after completion of feeding (MD 2.4, 95% CI -9.16 to 4.36; 1 study, 31 participants; very low-certainty evidence). We are very uncertain of the effects of push versus gravity intermittent gavage feeding on respiratory rate during and after feeding. We do not have sufficient evidence to determine the effects of intermittent bolus gavage feeding for preterm and low birth weight infants. The single small study of 31 infants comparing effects of push versus gravity bolus gavage feeding did not report the primary outcome identified in this review. Thus, evidence is insufficient to show whether use of push compared with gravity gavage feeding results in more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight infants who receive intermittent bolus gavage feeding. In addition, the included study was too small to measure potential adverse events that can occur during gavage tube feeding, for example, episodes of oxygen desaturation, apnoea, or bradycardia.

Thyroid hormones during the perinatal period are necessary to respiratory network development of newborn rats

Thyroid hormones (THs) are essential for foetal brain development. Because the gestating mother is the main source of THs to the foetus, maternal hypothyroidism and/or premature birth compromise neurological outcomes in the offspring. Respiratory instability and recurrent apneas due to immaturity of the respiratory control network are major causes of morbidity in infants. Inadequate TH supply may be sufficient to delay perinatal maturation of the respiratory control system; however, this hypothesis remains untested. To address this issue, maternal hypothyroidism was induced by adding methimazole (MMI; 0.02% w/v) to the drinking water of pregnant dams from conception to postpartum day 4 (P4). The effect of TH supplementation on respiratory function was tested by injecting levothyroxine (L-T4) in newborns at P1. Respiratory function was assessed by plethysmography (in vivo) and recording of phrenic output from medullary preparations (in vitro). By comparison with controls, TH deficiency increased the frequency of apneas and decreased basal ventilation in vivo and prevented the age-dependent increase in phrenic burst frequency normally observed in vitro. The effects of TH deficiency on GABAergic modulation of respiratory activity were measured by bath application of muscimol (GABAA agonist) or bicuculline (GABAA antagonist). The phrenic burst frequency responses to GABAergic agents were consistently greater in preparations from TH deficient pups. L-T4 supplementation reversed part of the respiratory anomalies related to MMI treatment in vitro. We conclude that TH deficiency during the perinatal period is sufficient to delay maturation of the respiratory control network development. Excessive GABAergic inhibition may contribute to this effect.

Possible Preventative/Rehabilitative Role of Gliflozins in OSA and T2DM. A Systematic Literature Review-Based Hypothesis

Obstructive sleep apnoea (OSA) is characterized by frequent apnoea episodes during sleep due to upper airway obstruction. The present review summarizes current knowledge on inter-relationships between OSA and type 2 diabetes mellitus (T2DM) and suggests the former as a possible target for sodium-glucose co-transporter-2 inhibitors (SGLT-2i). Based on pathophysiological mechanisms underlying OSA onset and renal SGLT-2 effects, we suggest that SGLT-2i indications might expand beyond current ones, including glucose, lipids, uric acid, blood pressure, and body weight control as well as chronic heart failure and kidney disease prevention.

The Frequency of Obstructive Sleep Apnea in Patients with Non-cystic Fibrosis Bronchiectasis.

Interruption or reduction in airflow and desaturation is a theoretically expected result in bronchiectasis accompanied by excessive secretions in the airways, bronchial wall thickening, and destruction of the wall structure. The same mechanism of interruption or reduction in airflow and desaturation is valid for obstructive sleep apnea (OSA). However, data on the association of bronchiectasis with OSA are scarce. We aimed to investigate the frequency of OSA and related parameters in patients with non-cystic fibrosis bronchiectasis (NCFB). All 43 consecutive patients who presented to the outpatient clinic for bronchiectasis follow-up between January 1, 2018 and January 1, 2019 were included. The polysomnography (PSG) data of the 43 patients were reviewed. Groups of patients with and without OSA, as detected using PSG, were compared in terms of clinical, demographic, and polysomnographic parameters. The mean age of the 43 patients was 50 ± 15 years; 28 (65.2%) were female. OSA was detected in 24 (55.8%) of 43 patients, of whom 14 (32.6%) had mild, 5 (11.6%) had moderate, and 5 (11.6%) had severe OSA. Three (7.0%) patients were REM-dependent and 7 (16.3%) were position-dependent. When evaluated using logistic regression analysis, REM percentage (16.8% vs. 11.8%, P = .03) and presence of witnessed apnea (33.3% vs. 15.7%, P = .01) were observed to be significantly higher in the patients with OSA. The age factor was found at the significance limit (P = .05). The frequency of OSA in patients with NCFB is 55.8%. Investigating OSA using PSG is important in patients with NCFB, especially at advanced ages.

Olfactory Stimulation of Preterm Infants with Breast Milk.

Maintaining stable physiological responses may be important for the growth and development of preterm infants. The purpose of our study was to evaluate the effects of olfactory stimulation with maternal breast milk on the occurrence of abnormal physiological responses in preterm infants. With a non-equivalent control group pretest-posttest design, 13 preterm infants in the experimental group and 18 preterm infants in the control group completed the intervention. The intervention was implemented three times a day for 5 days in a row with 2 hours of administration per intervention. The frequency of abnormal physiological responses was assessed over 6 days (one day before intervention administration and 5 days during intervention administration). With repeated-measures analysis of variance, the experimental group showed a significantly lower frequency of apnea than the control group (p = .021). Olfactory stimulation with maternal breast milk may be an effective nursing intervention for reducing apnea episodes in preterm infants.

Prevalence and Characteristics of Insomnia Problems Among Adults in Central Istria

Aim: We sought to examine the frequency and characteristics of insomnia among adults in central Istria, as well as to analyse sociodemographic characteristics and explore whether there is an association between symptoms of insomnia and sociodemographic parameters. Methods: This research included 685 participants that visited family medicine offices (FMOs) in Central Istria from September till December 2016. Mean age of the sample was 52.73 ± 17.93 years. Participants were randomly selected and interviewed and all gave their informed consent. Participants with sleep disturbances and insomnia lasting one year prior to study enrolment were assessed using the questionnaire designed for the study; along with gathering of sociodemographic data. Results: More than half of the participants had insomnia, 30% of them each night or several times a week, mostly older participants and women. Regardless of the frequency of insomnia symptoms, all participants reported great impairment in all areas of daytime functioning. The most frequent incidence of insomnia was associated with more frequent sleep apnoea and less frequent bruxism. Frequent night awakenings and restless legs syndrome were not related to a greater incidence of insomnia. Conclusion: Insomnia is a common problem among patients treated in primary care. Family physicians are therefore in an ideal position to identify, evaluate and treat insomnia. The high prevalence of insomnia highlights the need for a more adequate recognition and treatment of this psychiatric illness.

Evaluation of sleep-disordered breathing and its relationship with respiratory parameters in children with mucopolysaccharidosis Type IVA and VI.

The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r= -0.594, p= .009; r= -0.636, p= .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.

Effect of Positive Allosteric Modulation of Dopamine D2 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 respiratory disturbances are prevalent in Rett syndrome, and also occur in rodent models of the disorder, including Mecp2Bird and Mecp2R168X mice. Prior research has demonstrated that sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT. However, the contribution of D2 receptors in correcting these respiratory disturbances remains untested. Given that D2 receptors inhibit expiratory neurons in the parabrachial complex and the caudal ventral respiratory group, we hypothesized that compounds targeting the D2 receptor would correct apnea and irregular breathing in mouse models of RTT by enhancing dopamine responses in expiratory neurons. PAOPA, the dopamine D2 receptor positive allosteric modulator, and quinpirole, a dopamine D2 receptor agonist, were used in conjunction with whole-body plethysmography to evaluate whether activation of D2 receptors is sufficient to restore a normal respiratory phenotype in Mecp2Bird and Mecp2R168X mice. There were no significant differences in apnea incidence or irregularity score between saline and PAOPA treated RTT mice. PAOPA also had no effect on the ventilatory response to hypercapnia (7 % CO2). These results suggest that dopamine D2 receptor activity may not be an ideal candidate in the correction of respiratory abnormalities in Rett syndrome.

Cerebral erythropoietin promotes sex dependent prevention of disrupted neural control of respiration induced by neonatal stress

Stress experienced during a critical period of development is a major cause of adult disease (Kivimäki and Steptoe, 2018; Nelson and Gabard-Durnam, 2020; Shonkoff, 2016; Shonkoff et al., 2009); it has persistent and sex-specific effects on health and the brain is a major target. One neural system of considerable interest is the neural system regulating breathing. Pathology in this homeostatic control system underlies important clinical disorders such as sleep disordered breathing (SDB). Adult rodents previously subjected to early life stress in the form neonatal maternal separation (NMS) show key features of SDB, including a greater incidence of apneas during sleep and a significant sexual dimorphism. Erythropoietin (EPO) is a potent neuroprotective factor secreted by neurons and astrocytes that prevents stress-related neurological insults. Because treatment options for SDB are limited, we tested the hypothesis that over expression of neural EPO alleviates NMS-related respiratory control dysfunction in adult mice. To test this hypothesis, we used a transgenic animal model that selectively overexpress EPO in the brain (Tg21). Mouse pups were raised under standard conditions or subjected to NMS (3h/day; postnatal days 3 to 12). At adulthood, the apnea index and reflexive responses to O2 (hypoxia) and CO2 (hypercapnia) were measured using whole body plethysmography; corticosterone levels were measured by ELISA assay. In wild type, NMS augmented apnea frequency in males (not females). This effect of NMS was not observed in Tg21 mice. NMS also caused a sex-specific increase in basal corticosterone (males only). EPO overexpression reduced this effect. We conclude that overexpression of neural EPO prevents the deleterious impacts of NMS on the development of the stress neuraxis and respiratory control.