Surge of Sympathetic Activity during Hyperventilation at the End of Apnea for Patients with Obstructive Sleep Apnea.

Background and Objectives: The mechanisms connecting obstructive sleep apnea (OSA) and cardiovascular disease are multifactorial, involving intermittent hypoxia, hypercapnia, and sympathetic activation. The aim of this study was to explore the oscillations of sympathetic activity during the sleep apnea episodes throughout the entire night in patients with OSA. Materials and Methods: The participants received whole-night polysomnography (PSG), and electrocardiogram (EKG) data from the PSG were collected for heart rate variability (HRV) analysis. HRV measurements were conducted in the time and frequency domains. The root mean square of successive differences between normal heartbeats (RMSSD), which reflects parasympathetic activity, and the ratio of the absolute power of the low-frequency band (0.04-0.15 Hz) to the absolute power of the high-frequency band (0.015-0.4 Hz) (LF/HF ratio), which indicates sympathetic activity, were computed. Results: A total of 43 participants (35 men and 8 women) were included in the analysis. The mean age of the participants was 44.1 ± 11.3 years old, and the mean BMI was 28.6 ± 5.4 kg/m2. The sleep apnea episodes throughout the entire night in patients with OSA were selected randomly and occurred most frequently during the non-REM stages (39, 90.7%). The selected sleep apnea episodes typically exhibited multiple apneas, often interrupted by snoring respiration and followed by hyperventilation at the end of the episode (HE). Our findings indicate that the centers of the 5 min HRV window for the lowest and highest LF/HF ratios, at 111.8 ± 88.2 and 117.4 ± 88.6 min after sleep onset, respectively, showed a statistically significant difference (p < 0.001). Similarly, the ratios of the lowest and highest LF/HF, at 0.82 ± 0.56 and 3.53 ± 2.94, respectively, exhibited a statistically significant difference (p < 0.001). Conclusions: In the current study, the selected sleep apnea episodes throughout the entire night in patients with OSA occurred primarily during the non-REM stages. Additionally, we observed that sympathetic activity reached its peak in the window that includes hyperventilation at the end stage of apnea, potentially posing a cardiovascular risk. However, additional studies are needed to validate these results.

Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits?

Breath-holding preceded by either an overnight fast or hyperventilation has been shown to potentiate the risk of a hypoxic blackout. However, no study has explored the combined effects of fasting and hyperventilation on apneic performance and associated physiological responses. Nine nondivers (8 males) attended the laboratory on two separate occasions (≥48 h apart), both after a 12-h overnight fast. During each visit, a hyperoxic rebreathing trial was performed followed by three repeated maximal static apneas preceded by either normal breathing (NORM) or a 30-s hyperventilation (HYPER). Splenic volume, hematology, cardiovascular, and respiratory variables were monitored. There were no interprotocol differences at rest or during hyperoxic rebreathing for any variable (P ≥ 0.09). On nine occasions (8 in HYPER), the subjects reached our safety threshold (oxygen saturation 65%) and were asked to abort their apneas, with the preponderance of these incidents (6 of 9) occurring during the third repetition. Across the sequential attempts, longer apneas were recorded in HYPER [median(range), 220(123-324) s vs. 185(78-296) s, P ≤ 0.001], with involuntary breathing movements occurring later [134(65-234) s vs. 97(42-200) s, P ≤ 0.001] and end-apneic partial end-tidal pressures of oxygen (PETO2) being lower (P ≤ 0.02). During the final repetition, partial end-tidal pressure of carbon dioxide [(PETCO2), 6.53 ± 0.46 kPa vs. 6.01 ± 0.45 kPa, P = 0.005] was lower in HYPER. Over the serial attempts, preapneic tidal volume was gradually elevated [from apnea 1 to 3, by 0.26 ± 0.24 L (HYPER) and 0.28 ± 0.30 L (NORM), P ≤ 0.025], with a correlation noted with preapneic PETCO2 (r = -0.57, P < 0.001) and PETO2 (r = 0.76, P < 0.001), respectively. In a fasted state, preapnea hyperventilation compared with normal breathing leads to longer apneas but may increase the susceptibility to a hypoxic blackout.NEW & NOTEWORTHY This study shows that breath-holds (apneas) preceded by a 12-h overnight fast coupled with a 30-s hyperventilation as opposed to normal breathing may increase the likelihood of a hypoxic blackout through delaying the excitation of hypercapnic ventilatory sensory chemoreflexes. Evidently, this risk is exacerbated over a series of repeated maximal attempts, possibly due to a shift in preapneic gas tensions facilitated by an unintentional increase in tidal volume breathing.

Clinical and genetic characterization of 47 Chinese pediatric patients with Pitt-Hopkins syndrome: a retrospective study.

BACKGROUND: Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder that remains underdiagnosed and its clinical presentations and mutation profiles in a diverse population are yet to be evaluated. This retrospective study aims to investigate the clinical and genetic characteristics of Chinese patients with PTHS. METHODS: The clinical, biochemical, genetic, therapeutic, and follow-up data of 47 pediatric patients diagnosed with PTHS between 2018 and 2021 were retrospectively analyzed. RESULTS: The Chinese PTHS patients presented with specific facial features and exhibited global developmental delay of wide severity range. The locus heterogeneity of the TCF4 gene in the patients was highlighted, emphasizing the significance of genetic studies for accurate diagnosis, albeit no significant correlations between genotype and phenotype were observed in this cohort. The study also reports the outcomes of patients who underwent therapeutic interventions, such as ketogenic diets and biomedical interventions. CONCLUSIONS: The findings of this retrospective analysis expand the phenotypic and molecular spectra of PTHS patients. The study underscores the need for a long-term prospective follow-up study to assess potential therapeutic interventions.

Complex visceral hyperalgesia in an adolescent with Pitt-Hopkins syndrome.

An early-adolescent boy with a background of Pitt-Hopkins syndrome was transferred to a tertiary paediatric hospital with symptoms of a functional large bowel obstruction. He required extensive surgical intervention including a transverse colectomy, drainage of an abdominal abscess, laparotomy and adhesionolysis, and insertion of a gastrostomy and jejunostomy. He had significant ongoing issues with visceral hyperalgesia that was refractory to a wide range of pharmacological treatments and required admission to the intensive care unit on multiple occasions, and consultations with international experts in Pitt-Hopkins syndrome and pain specialists. An individualised pain plan was created and adjusted over time, with eventual good effect, and he was transferred back to his regional hospital and subsequently discharged home.

Impact of ambient temperature, diurnal temperature range on hyperventilation syndrome emergency admission: a time-series analysis in Beijing, China.

OBJECTIVES: To assess the association between ambient temperature and diurnal temperature range (DTR) on emergency admissions for hyperventilation syndrome (HVS). DESIGN: Distributed lag non-linear model design was used with a lag time to 5 days. SETTING: Emergency admission data used were from the Beijing Red Cross Emergency Centre (2017-2018). PARTICIPANTS AND EXPOSURE: Cases were those with emergency visits to the Beijing Emergency Center during the period 2017-2018 and who were given the primary outcome indicator defined as HVS according to the International Classification of Diseases, 10th edition code F45.303. Ambient temperature and DTR were used as exposure factors with adjustments for relative humidity, wind speed, precipitation, seasonality long-term trend and day of the week. MAIN OUTCOME MEASURE: We used the minimum emergency visits temperature as a reference to indicate the relative risk with 95% CI of exposure-response for the risk of HVS visits at different temperatures. RESULTS: A u-shape was described between ambient temperature and HVS visits, with a minimum risk at 12°C. Moderate heat (23°C) at lag (0-3) days, extreme heat at lag 0 days, had greatest relative risks on HVS visits, with 2.021 (95% CI 1.101 to 3.71) and 1.995 (95% CI 1.016 to 3.915), respectively. A stronger association between HVS visits and temperature was found in women and aged ≤44 years. Notably, the relationship between DTR and HVS visits appeared a reverse u-shaped. Low DTR (4°C) effect appeared at lag (0-1) days with 0.589 (95% CI 0.395 to 0.878), lasting until lag (0-3) days with 0.535 (95% CI 0.319 to 0.897) and was associated with a reduced risk of HVS visits in women and those aged ≤44 years. CONCLUSIONS: Ambient temperature and DTR were associated with HVS visits, appearing a differentiation in gender and age groups. Timely prevention strategies during high temperatures and control mild changes in temperature might reduce the risk of HVS.

Ultra-rapid, Free-breathing, Real-time Cardiac Cine MRI Using GRASP Amplified with View Sharing and KWIC Filtering.

Purpose To achieve ultra-high temporal resolution (approximately 20 msec) in free-breathing, real-time cardiac cine MRI using golden-angle radial sparse parallel (GRASP) reconstruction amplified with view sharing (VS) and k-space-weighted image contrast (KWIC) filtering. Materials and Methods Fourteen pediatric patients with congenital heart disease (mean age [SD], 9 years ± 2; 13 male) and 10 adult patients with arrhythmia (mean age, 62 years ± 8; nine male) who underwent both standard breath-hold cine and free-breathing real-time cine using GRASP were retrospectively identified. To achieve high temporal resolution, each time frame was reconstructed using six radial spokes, corresponding to acceleration factors ranging from 24 to 32. To compensate for loss in spatial resolution resulting from over-regularization in GRASP, VS and KWIC filtering were incorporated. The blur metric, visual image quality scores, and biventricular parameters were compared between clinical and real-time cine images. Results In pediatric patients, the incorporation of VS and KWIC into GRASP (ie, GRASP + VS + KWIC) produced significantly (P < .05) sharper x-y-t (blur metric: 0.36 ± 0.03, 0.41 ± 0.03, 0.48 ± 0.03, respectively) and x-y-f (blur metric: 0.28 ± 0.02, 0.31 ± 0.03, 0.37 ± 0.03, respectively) component images compared with GRASP + VS and conventional GRASP. Only the noise score differed significantly between GRASP + VS + KWIC and clinical cine; all visual scores were above the clinically acceptable (3.0) cutoff point. Biventricular volumetric parameters strongly correlated (R2 > 0.85) between clinical and real-time cine images reconstructed with GRASP + VS + KWIC and were in good agreement (relative error < 6% for all parameters). In adult patients, the visual scores of all categories were significantly lower (P < .05) for clinical cine compared with real-time cine with GRASP + VS + KWIC, except for noise (P = .08). Conclusion Incorporating VS and KWIC filtering into GRASP reconstruction enables ultra-high temporal resolution (approximately 20 msec) without significant loss in spatial resolution. Keywords: Cine, View Sharing, k-Space-weighted Image Contrast Filtering, Radial k-Space, Pediatrics, Arrhythmia, GRASP, Compressed Sensing, Real-Time, Free-Breathing Supplemental material is available for this article. © RSNA, 2024.

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

The acute influence of amateur boxing on dynamic cerebral autoregulation and cerebrovascular reactivity to carbon dioxide.

PURPOSE: The purpose of this study was to investigate the acute effect of head impacts, sustained over the course of three rounds of amateur boxing, on indices of cerebrovascular function. METHODS: Eighteen university amateur boxers (six female) completed three experimental trials in a randomised order; (1) three rounds of boxing (BOX), (2) an equivalent bout of pad boxing (where no blows to the head were sustained; PAD), and (3) a time-matched seated control trial (CON). Indices of cerebrovascular function were determined immediately before and 45 min after each trial. Specifically, dynamic cerebral autoregulation (dCA) was determined by considering the relationship between changes in cerebral blood velocity and mean arterial pressure during 5 min of squat-stand manoeuvres at 0.05 and 0.10 Hz. Cerebrovascular reactivity was determined using serial breath holding and hyperventilation attempts. RESULTS: Participants received an average of 40 ± 16 punches to the head during the BOX trial. Diastolic, mean and systolic dCA phase during squat stand manoeuvres at 0.05 Hz was lower after BOX compared to pre BOX (P ≤ 0.02, effect size (d) ≥ 0.74). No other alterations in dCA outcomes were observed at 0.05 or 0.10 Hz. The number of head impacts received during the BOX trial was associated with the change in systolic phase (r = 0.50, P = 0.03). No differences in cerebrovascular reactivity to breath holding or hyperventilation were observed. CONCLUSIONS: A typical bout of amateur boxing (i.e., three rounds) can subtly alter cerebral pressure-flow dynamics, and the magnitude of this change may be related to head impact exposure.

Pathogenic variants in SOX11 mimicking Pitt-Hopkins syndrome phenotype.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder characterised by severe intellectual disability (ID), distinctive facial features and autonomic nervous system dysfunction, caused by TCF4 haploinsufficiency. We clinically diagnosed with PTHS a 14 6/12 -year-old female, who had a normal status of TCF4. The pathogenic c.667del (p.Asp223MetfsTer45) variant in SOX11 was identified through whole exome sequencing (WES). SOX11 variants were initially reported to cause Coffin-Siris syndrome (CSS), characterised by growth restriction, moderate ID, coarse face, hypertrichosis and hypoplastic nails. However, recent studies have provided evidence that they give rise to a distinct neurodevelopmental disorder. To date, SOX11 variants are associated with a variable phenotype, which has been described to resemble CSS in some cases, but never PTHS. By reviewing both clinically and genetically 32 out of 82 subjects reported in the literature with SOX11 variants, for whom detailed information are provided, we found that 7/32 (22%) had a clinical presentation overlapping PTHS. Furthermore, we made a confirmation that overall SOX11 abnormalities feature a distinctive disorder characterised by severe ID, high incidence of microcephaly and low frequency of congenital malformations. Purpose of the present report is to enhance the role of clinical genetics in assessing the individual diagnosis after WES results.

Effects of caffeine on cerebral blood flow.

OBJECTIVE: The objective of the present study is to evaluate whether, after caffeine ingestion, there are variations in blood velocity of the middle cerebral arteries in clinically healthy young people as well as to evaluate whether this variation is dependent on the administered dose. METHODS: We used transcranial Doppler ultrasonography to record blood velocities of the middle cerebral arteries in three groups of 15 clinically healthy young adults each: no caffeine, a45 mg, and 120 mg of caffeine groups. Transcranial Doppler ultrasonography provided simultaneous bilateral velocity of the middle cerebral arteries measurements while participants performed functional tests (hyperventilation and hypoventilation orders) and three cognitive activities (test 1, short-term memory; test 2, solving a vocabulary problem; and test 3, solving a math problem) each in 31-s tests with 1-min rests between them. Participants were assessed before and 30 min after caffeine ingestion. RESULTS: There was a significant decrease in mean velocity, peak systolic velocity, end-diastolic velocity, and heart rate after high caffeine intake, except in hyperventilation, which was only observed in peak systolic velocity. With the intake of a lower dose, significant decreases were seen with hypoventilation and with test 1. In hyperventilation, there was only a significant decrease in end-diastolic velocity and heart rate; in test 2, it was found in mean velocity and peak systolic velocity; and in test 3, only in heart rate. CONCLUSION: With this study, we conclude that caffeine influences the cardiovascular system acutely, interfering with the velocity of the middle cerebral arteries, causing its decrease. We also conclude that this acute effect causes vasodilation of the cerebral arteries, more accentuated with higher doses of caffeine.

The reproducibility of breathing maneuvers as a vasoactive stimulus in the heart: an oxygenation-sensitive resonance imaging study.

BACKGROUND: Endothelial dysfunction and impaired oxygenation of the heart is a hallmark of several diseases, including coronary artery disease, hypertension, diabetes, and sleep apnea. Recent studies indicate that oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging combined with breathing maneuvers may allow for assessing coronary vascular responsiveness as a marker for coronary vascular function in various clinical settings. However, despite the use of OS-CMR in evaluating tissue oxygenation, the reproducibility of these standardized, combined breathing maneuvers as a vasoactive stimulus has yet to be systematically assessed or validated. In this study, we aimed to assess the reproducibility of vasoactive breathing maneuvers to assess vascular function in a population of healthy volunteers. METHODS: Eighteen healthy volunteers were recruited for the study. Inclusion criteria were an age over 18 years and absence of any evidence or knowledge of cardiovascular, neurological, or pulmonary disease. MRI was performed on a clinical 3 T MRI system (MAGNETOM Skyra, Siemens Healthineers, Erlangen, Germany). The OS-CMR acquisition was performed as previously described (1 min hyperventilation followed by a maximal, voluntary breath-hold). Standard statistical tests were performed as appropriate. RESULTS: Data from 18 healthy subjects was analyzed. The healthy volunteers had a mean age of 42 ± 15 years and a mean BMI of 25.4 ± 2.8 kg/m2, with an average heart rate of 72 ± 11 beats per minute, and ten of whom (56%) were female. There were no significant differences between global myocardial oxygenation (%[Formula: see text] SI) after hyperventilation (HV1: - 7.82 [Formula: see text] 5.2; HV2: - 7.89 [Formula: see text] 6.4, p = 0.9) or breath-hold (BH1: 5.34 [Formula: see text] 3.1; BH2: 6.0 [Formula: see text] 3.3, p = 0.5) between the repeated breathing maneuvers. The Bland-Altman analysis showed good agreement (bias: 0.074, SD of bias: 2.93). CONCLUSION: We conclude that in healthy individuals, the myocardial oxygenation response to a standardized breathing maneuver with hyperventilation and a voluntary breath-hold is consistent and highly reproducible. These results corroborate previous evidence for breathing-enhanced OS-CMR as a robust test for coronary vascular function.

Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy.

Vagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders. The most useful frequency band distinguishing responders and non-responders was the alpha frequency, and the most helpful time interval was hyperventilation and rest 4 (the end of EEG recording).

The ventilatory response to modified rebreathing is unchanged by hyperoxic severity: implications for the hyperoxic hyperventilation paradox.

Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs via an oxygen (O2)-specific mechanism or secondary to carbon dioxide (CO2) retention at the central chemoreceptors remains unclear. We measured the ventilatory response to hyperoxic CO2 rebreathing with O2 clamped at increasingly higher pressures. We hypothesized that the V̇e versus Pco2 relationship is fixed and independent of Po2. On four occasions, 20 participants (10 F; mean ± SD age: 24 ± 4 yr) performed three repetitions of modified rebreathing in four, randomized, isoxic-hyperoxic conditions: mild: Po2 = 150 mmHg; moderate: Po2 = 200 mmHg; high: Po2 = 300 mmHg; and extreme: Po2 ≈ 700 mmHg. Breath-by-breath V̇e, end-tidal CO2 ([Formula: see text]), and O2 ([Formula: see text]) were measured by pneumotach and gas analyzer. For each rebreathing trial, the [Formula: see text] at which V̇e rose was identified as the ventilatory recruitment threshold (VRT, mmHg), data before VRT provided baseline V̇e (V̇eBSL, L·min-1) and the slope of the response above VRT gave central chemoreflex sensitivity (V̇eS, L·min-1·mmHg-1). For each condition, VRT, V̇eBSL, and V̇eS from like-trials were averaged, and repeated measures ANOVA assessed between-condition differences. There were no effects of [Formula: see text] on V̇eBSL (mild: 7.4 ± 4.2 L·min-1; moderate: 6.9 ± 4.2 L·min-1; high: 6.5 ± 3.7 L·min-1; extreme: 7.5 ± 2.7 L·min-1; P = 0.24), VRT (mild: 42.8 ± 3.2 mmHg; moderate: 42.5 ± 2.7 mmHg; high: 42.3 ± 2.7 mmHg; extreme: 41.8 ± 2.7 mmHg; P = 0.07), or V̇eS (mild: 4.88 ± 2.6 L·min-1·mmHg-1; moderate: 4.76 ± 2.2 L·min-1·mmHg-1; high: 4.81 ± 2.3 L·min-1·mmHg-1; extreme: 4.39 ± 1.9 L·min-1·mmHg-1; P = 0.41). The V̇e-Pco2 relationship is unaltered across a range of mild to extreme Po2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.NEW & NOTEWORTHY Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs directly or indirectly through heightened central carbon dioxide pressure (Pco2) or via central chemoreflex sensitization is unclear. Participants who performed modified rebreathing at high oxygen pressures (Po2) of 150, 200, 300, and ≈700 mmHg exhibited no changes to their ventilatory responses to Pco2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.

Cerebral uptake of microvesicles occurs in normocapnic but not hypocapnic passive hyperthermia in young healthy male adults.

Passive hyperthermia causes cerebral hypoperfusion primarily from heat-induced respiratory alkalosis. However, despite the cerebral hypoperfusion, it is possible that the mild alkalosis might help to attenuate cerebral inflammation. In this study, the cerebral exchange of extracellular vesicles (microvesicles), which are known to elicit pro-inflammatory responses when released in conditions of stress, were examined in hyperthermia with and without respiratory alkalosis. Ten healthy male adults were heated passively, using a warm water-perfused suit, up to core temperature + 2°C. Blood samples were taken from the radial artery and internal jugular bulb. Microvesicle concentrations were determined in platelet-poor plasma via cells expressing CD62E (activated endothelial cells), CD31+ /CD42b- (apoptotic endothelial cells), CD14 (monocytes) and CD45 (pan-leucocytes). Cerebral blood flow was measured via duplex ultrasound of the internal carotid and vertebral arteries to determine cerebral exchange kinetics. From baseline to poikilocapnic (alkalotic) hyperthermia, there was no change in microvesicle concentration from any cell origin measured (P-values all >0.05). However, when blood CO2 tension was normalized to baseline levels in hyperthermia, there was a marked increase in cerebral uptake of microvesicles expressing CD62E (P = 0.028), CD31+ /CD42b- (P = 0.003) and CD14 (P = 0.031) compared with baseline, corresponding to large increases in arterial but not jugular venous concentrations. In a subset of seven participants who underwent hypercapnia and hypocapnia in the absence of heating, there was no change in microvesicle concentrations or cerebral exchange, suggesting that hyperthermia potentiated the CO2 /pH-mediated cerebral uptake of microvesicles. These data provide insight into a potential beneficial role of respiratory alkalosis in heat stress. KEY POINTS: The hyperthermia-induced hyperventilatory response is observed in most humans, despite causing potentially harmful reductions in cerebral blood flow. We tested the hypothesis that the respiratory-induced alkalosis is associated with lower circulating microvesicle concentrations, specifically in the brain, despite the reductions in blood flow. At core temperature + 2°C with respiratory alkalosis, microvesicles derived from endothelial cells, monocytes and leucocytes were at concentrations similar to baseline in the arterial and cerebral venous circulation, with no changes in cross-brain microvesicle kinetics. However, when core temperature was increased by 2°C with CO2 /pH normalized to resting levels, there was a marked cerebral uptake of microvesicles derived from endothelial cells and monocytes. The CO2 /pH-mediated alteration in cerebral microvesicle uptake occurred only in hyperthermia. These new findings suggest that the heat-induced hyperventilatory response might serve a beneficial role by preventing potentially inflammatory microvesicle uptake in the brain.

Hyperventilation and Seizures: Not a New Sense: A Literature Review.

Hyperventilation and seizures have a long association in the clinical literature and were known to have a relationship long before the electroencephalogram (EEG) was used to record changes in brain activity. As the use of EEG recording progressed, hyperventilation was the first activation method used to assist with diagnosis of epilepsy. Along with slowing of brain activity, hyperventilation can activate epileptiform spiking activity in patients with epilepsy. Currently, hyperventilation is used in standard practice to assist with the diagnosis of epilepsy during EEG recording. Hyperventilation activates epileptiform spiking activity more often than seizures but can trigger clinical seizures in up to 50% of patients with generalized epilepsy. It is more likely to trigger events in children with absence seizures than adults, and it acts as a trigger in patients with focal epilepsy far less often. However, while some clinicians suggest that its diagnostic value is limited, especially in adults with focal epilepsies, others suggest that it is simple, safe, and an important diagnostic tool, even in these patients. This review presents the history of hyperventilation and seizures, its use in the clinical practice, and possible mechanisms involved.

Physiological association of the breakpoint with the duration of hyperventilation.

OBJECTIVES: To determine the relationship of body mass index (BMI) with breath-holding time (BHT) as well as that of BHT with the duration of hyperventilation (DOH) in young healthy adults. METHODS: An observational study was performed at Shalamar Medical and Dental College, Lahore, Pakistan, between May 2021 and June 2022. Healthy first-year Bachelor of Medicine, Bachelor of Surgery students aged 18-22 years, with a normal BMI were included. Spirometric measurements were taken through a spirometer pod connected to a pneumotachometer (model: Power Lab 26T). Body mass index was calculated as the weight (kg) to height (m2) ratio. Pearson correlation, linear regression, and t tests were applied using SPSS. RESULTS: A total of 101 subjects participated, comprising of 44 men and 57 women. A weak negative association was found between BMI and BHT in all subjects (r= -0.08, p=0.34), in men (r= -0.24, p=0.11), and in women (r= -0.092, p=0.497). Furthermore, a strong association was observed between BHT and DOH in all subjects (r=0.64, p=0.000), in men (r=0.604, p=0.000), and in women (r=0.518, p=0.000). Moreover, a nonsignificant weak inverse linear regression was found between the BMI and BHT of all subjects (ß= -0.087, p=0.38), of men (ß= -0.241, p=0.11), and of women (ß= -0.092, p=0.49). Lastly, a significantly strong positive regression was observed between the BHT and DOH of all subjects (ß=0.637, p=0.000), of men (ß=0.604, p=0.000), and of women (ß=0.518, p=0.000). CONCLUSION: No association was found between BMI and BHT. A strong positive association was observed between BHT and DOH in all healthy young people.

Association between the presence of an advanced airway and ventilation rate during pediatric CPR: A report from the Videography in Pediatric Resuscitation (VIPER) collaborative.

OBJECTIVE: To determine the association between presence of an advanced airway during pediatric cardiopulmonary resuscitation (CPR) and ventilation rates. METHODS: Prospective observational study, January 2017 to June 2020. Patients ≤18 years receiving CC for ≥2 minutes were enrolled. Ventilation rate and type of airway (advanced airway (AA), either endotracheal tube (ETT) or supraglottic airway (SGA); or natural airway (NA)) were collected from video review and analyzed in 'CPR segments' (periods of CPR by individual providers). Ventilation rate (breaths per minute, bpm) was calculated for each segment; hyperventilation was defined as >12 bpm according to 2015 American Heart Association guidelines. Univariate analysis between airway type was done by χ2 testing. Multivariate regression was used to determine the association between the presence of AA with hyperventilation while controlling for within-patient covariance. RESULTS: 779 CPR segments from 94 CPR event were analyzed. The mean ventilation rate per CPR segment across all events was 22 bpm (±16 bpm)). Mean ventilation rates were higher with AA, either ETT (24 ± 17 bpm) or SGA (34 ± 19 bpm), than with NA (17 ± 14, p < 0.001). Hyperventilation occurred more often with AA in place (ETT: 68%; SGA: 96%; NA: 43%; p < 0.001). The presence of AA was independently associated with hyperventilation (AOR 9.3, 95% CI 4.3-20.1). CONCLUSIONS: During pediatric CPR, hyperventilation occurs more often with an AA in place than during CPR with NA. Future research should focus on respiratory physiology during pediatric CPR to determine optimal ventilation rate(s) during pediatric cardiac arrest.

The clinical utility of the Breathing Pattern Assessment Tool (BPAT) to identify dysfunctional breathing (DB) in individuals living with postural orthostatic tachycardia syndrome (POTS).

BACKGROUND: Dysfunctional breathing (DB) resulting in inappropriate breathlessness is common in individuals living with postural orthostatic tachycardia syndrome (POTS). DB in POTS is complex, multifactorial, and not routinely assessed clinically outside of specialist centres. To date DB in POTS has been identified and diagnosed predominately via cardiopulmonary exercise testing (CPEX), hyperventilation provocation testing and/or specialist respiratory physiotherapy assessment. The Breathing Pattern Assessment Tool (BPAT) is a clinically validated diagnostic tool for DB in Asthma. There are, however, no published data regarding the use of the BPAT in POTS. The aim of this study was therefore to assess the potential clinic utility of the BPAT in the diagnosis of DB in individuals with POTS. METHODS: A retrospective observational cohort study of individuals with POTS referred to respiratory physiotherapy for formal assessment of DB. DB was determined by specialist respiratory physiotherapist assessment which included physical assessment of chest wall movement/breathing pattern. The BPAT and Nijgmegen questionnaire were also completed. Receiver operating characteristics (ROC) analysis was used to compare the physiotherapy assessment based diagnosis of DB to the BPAT score. RESULTS: Seventy-seven individuals with POTS [mean (sd) age 32 (11) years, 71 (92 %) female] were assessed by a specialist respiratory physiotherapist, with 65 (84 %) being diagnosed with DB. Using the established BPAT cut off of four or more, receiver operating characteristics (ROC) analysis indicated a sensitivity of 87 % and specificity of 75 % for diagnosing DB in individuals with POTS with an area under the curve (AUC) of 0.901 (95 % CI 0.803-0.999), demonstrating excellent discriminatory ability. CONCLUSION: BPAT has high sensitivity and moderate specificity for identifying DB in individuals living with POTS.

Home-based pulmonary rehabilitation for adults with severe asthma exposed to psychosocial chronic stressors.

OBJECTIVE: To evaluate the effects of a home-based pulmonary rehabilitation (PR) programme on hyperventilation symptoms, anxiety and depressive symptoms, general fatigue, health-related quality of life (HRQoL) and exercise capacity in adults with severe asthma who have been exposed to psychosocial chronic stressors. METHODS: Data on 111 non-selected consecutive adults with severe asthma who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) was retrospectively analysed. Chronic stressors included physical, sexual and psychological violence and/or a traumatic experience related to an intensive care unit stay. Hyperventilation symptoms (Nijmegen questionnaire), Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, COPD Assessment Test, Six-Minute Stepper Test and Timed-Up and Go test were assessed at baseline and after PR. RESULTS: At baseline, participants who have been exposed to chronic stressors (n = 48, 43.2%) were younger, more often female, more often treated for anxiety and depressive disorders, and had a higher score for anxiety symptoms, hyperventilation symptoms and a poorer HRQoL, compared to those who had not been exposed to chronic stressors (p < 0.05). All the study assessments were statistically improved after PR for both groups (p < 0.001). Anxiety and depressive symptoms, fatigue and health-related quality of life questionnaires were also clinically improved based on the minimal clinically important difference. CONCLUSION: A large proportion of adults with severe asthma, mainly women, have been exposed to chronic stressors at the time of starting a PR programme, resulting in higher anxiety symptoms and hyperventilation symptoms. However, it did not prevent these individuals from benefiting from PR.