[Exercise capacity in children with mild sleep-disordered breathing]. / Capacité physique de l'enfant présentant un syndrome d'apnée du sommeil léger.

INTRODUCTION: While the association between sleep-disordered breathing (SDB) and low physical activity has been reported in children, little information is available on the impact of SDB on exercise capacity. The aim of this study was to assess exercise capacity in children with SDB in order to estimate the relevance of exercise training intervention. METHODS: Twelve young patients with suspected SDB matched with 11 presumably healthy subjects of same age range (aged 13±0.5yr) were investigated. Both groups underwent physical activity assessment, full night polysomnography, incremental and all-out exercise tests. RESULTS: The respiratory disturbance index was higher in the patient group (4.6±4.7 vs 0.8±0.6; P=0.02). Children with SDB had lower VO2max (32.0±9.9 vs 42.3±5.7mL.kg-1.min-1, P=0.007) and lower peak power (8.6±3.4 vs 11.8±1.9W.kg-1, P=0.009). A significant correlation between VO2max and weekly physical activity only was found in the SDB group (P=0.005). CONCLUSION: Mild SDB may be associated with impairment of both aerobic and anaerobic exercise capacity in children, related to poor physical activity. Exercise training could bring clinical benefit in this population.

Lung mechanics and breathing pattern during wakefulness and sleep in children with enlarged tonsils.

Thirteen children (mean age, 45 months) with nocturnal symptoms of upper airway obstruction, the result of enlarged tonsils, were tested during wakefulness (W) and sleep (S) induced by chloral hydrate (less than or equal to 50 mg/kg). During W, lung mechanics, blood gas, breathing pattern, and airflows during tidal breathing were in the normal range. During S, total lung resistance increased significantly, and dynamic lung compliance and transcutaneous PO2 decreased significantly. During S, the tidal volume (VT) and the mean inspiratory flow, normalized for body weight (BW), decreased whereas the ratio of the inspiratory time (TI) over the total duration of the respiratory cycle (TTOT) rose, indicating a longer contraction time of the respiratory muscles. The time to reach peak inspiratory flow, measured as a percentage of TI (dTI/TI), increased in seven children, with no change in the ratio of the expiratory flow over the inspiratory flow, both measured at 50% of VT (EF50/IF50). In three other patients dTI/TI decreased with an increase in EF50/IF50. We conclude that in children with enlarged tonsils, S modified lung mechanics, gas exchange, and the inspiratory components of the breathing pattern and airflow.

Trigeminal airstream stimulation. Maturation-related cardiac and respiratory responses during REM sleep in human infants.

Thirty-three premature and full-term infants (PCA, 31.5 to 50 weeks) who were free from neurologic and cardiopulmonary disease at the time of testing underwent a standardized TAS test during polygraphically controlled REM sleep. The R-R interval and the TTOT were measured before and during TAS. The R-R interval and TTOT changes during TAS were compared to the preceding 60-second mean R-R interval and TTOT in each infant and expressed as a percentage of mean control values (ie, % RR and % TTOT). During TAS, there was a significant negative correlation between cardiac and respiratory responses and postconceptional age (p less than 0.001 and p less than 0.0001, respectively). Prolongation of both the R-R interval and the TTOT elicited by TAS was significantly blunted by maturation.

Radionuclide evaluation of cardiac function during sleep in children with bronchopulmonary dysplasia.

The influence of sleep on cardiac function in severe bronchopulmonary dysplasia was assessed in five children 1.5 to 5 years of age. Left and right ventricular ejection fractions (LVEF and RVEF) were investigated by equilibrium radionuclide ventriculography in five children undergoing polygraphic monitoring during the different states of alertness: wakefulness, nonrapid eye movement sleep, and rapid eye movement sleep. Intraobserver and interobserver LVEF and RVEF measurement reproducibility was high. During quiet, supine wakefulness, LVEF was normal, but RVEF was low. During sleep, a decrease in both LVEF and RVEF, expressed as a percentage of the awake value, was marked in the two children with the most nocturnal desaturation and longest duration of paradoxic rib cage motion during inspiration. It is concluded that radionuclide ventriculography can be easily performed during sleep in children and can provide useful information regarding right ventricular function during sleep in children with severe bronchopulmonary dysplasia.

Respiration during sleep in children with COPD.

Seventeen children (mean age, nine years) with chronic obstructive pulmonary disease (COPD) were studied during sleep. Electroencephalography, electrooculography, and electromyography were all recorded. Airflow was measured by nasal and oral thermistors, and abdominal and thoracic anteroposterior diameters by magnetometers. Transcutaneous partial pressure of O2 (tcPO2) and of CO2 (tcPCO2) were monitored. The average total sleep time was 283 min +/- 36 (1 SD). Breathing pauses (BP) five seconds or longer were measured. The mean time of BP expressed as a percentage of TST was 1.3 percent +/- 0.8 (1 SD). The BP occurred most frequently during REM sleep. Forty-six percent of BP were obstructive (OBP). The percentage of OBP was significantly related to the degree of lung resistance during wakefulness. Periodic breathing was observed with a mean frequency of 2.2 times per night (range: 0 to 7). Episodes with paradoxic inward rib cage motion were seen one to 29 times (mean 6.6). Drops in tcPCO2 greater than 5 mm Hg occurred one to eight times and 67 percent were observed during REM sleep. Compared to tcPCO2 during W the mean maximal decrease in tcPCO2 was 14 mm Hg (range 8 to 29). tcPCO2 rose with a mean maximal of 9.1 mm Hg (range 6 to 13). It was concluded that children with COPD had worsened gas exchange during sleep.

Chemoreceptor and vagal influences on thyroarytenoid muscle activity in awake lambs during hypoxia.

This study was designed to identify the various controllers of thyroarytenoid (TA) activity in lambs during resting breathing, hypocapnic hypoxia, and isocapnic hypoxia. The TA muscle is known as the major adductor of the laryngeal aperture. We assumed that both the chemoreceptors and vagal nerves would interact to inhibit TA activity during hypoxia and to favor the occurrence of hyperpnea as a defense against hypoxia. We recorded TA activity directly in 11 awake lambs, aged 11 to 22 days, and studied them in three groups: four normals, four carotid body denervated, and three vagotomized. To test the contribution of the chemoreceptors to TA activity, we used pure O2 tests (Dejours' test) to silence the effects of the peripheral arterial chemoreceptors on the larynx during resting breathing and during the course of two hypoxia tests (the first: hypocapnic hypoxia; the second: isocapnic hypoxia). Our results confirmed 1) that both the peripheral arterial chemoreceptors and the vagal nerves inhibit the TA activity of 15-day-old lambs, during both resting and hypocapnic hypoxia conditions, and 2) that their effects override the hypocapnic effects that would otherwise recruit the TA muscle and close the glottis during hypocapnic hypoxia. We also found that vagotomy, or the pure O2 test, causes major recruitment of TA activity. These findings confirm that 15-day-old lambs are capable of using sustained hyperventilation as a means of fighting hypoxia, and that, because of the control of both the vagus nerves and the chemoreceptors, the laryngeal dynamic is able to keep the glottis aperture actively open, thereby favoring the hyperpnea.

Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs.

The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO(2) rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.

Thyroarytenoid muscle activity during hypocapnic central apneas in awake nonsedated lambs.

In this study, we examined whether the glottis is open or closed during central apnea and the effect of arterial PO2 (PaO2) on this control. We hyperventilated nine 11- to 30-day-old awake nonsedated lambs via a tracheostomy for 1 min to induce central apnea. Four gas mixtures (8, 15, 21, and 30% O2) were used. At the end of the hyperventilation period, the lambs were allowed to breathe spontaneously through intact upper airways. Using a pneumotachograph attached to a face mask, we measured airflow, and we continuously recorded electromyographic (EMG) activity of the thyroarytenoid (TA), the main glottic adductor muscle. We also studied the lateral cricoarytenoid muscle (LCA, laryngeal adductor), the posterior cricoarytenoid muscle (PCA, laryngeal abductor), the cricothyroid muscle (CT), and the diaphragm. We found that hyperventilation consistently induced hypocapnic central apnea in all nine lambs in hyperoxic conditions [30% inspiratory fraction of O2 (FIO2)], in eight of nine lambs in normoxia or mild hypoxia (15 and 21% FIO2), and in four of seven lambs in hypoxia (8% FIO2). During baseline room air breathing, there was no glottic adductor muscle expiratory EMG activity or expiratory airflow braking. Continuous TA EMG activity began early during hyperventilation and continued throughout the central apnea, regardless of PaO2. The first subsequent breathing efforts were marked by expiratory flow braking and expiratory activity of the TA. The LCA and the TA demonstrated the same EMG activity pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal maturation of peripheral chemoreceptor ventilatory response to O2 and CO2 in newborn lambs.

Although studies on lambs have shown that carotid body sensitivity to O2 is reset postnatally, it is still unknown whether O2 and CO2 peripheral chemoreflexes undergo parallel postnatal maturation. The present study was designed to analyze maturation of O2 and CO2 peripheral chemoreflexes in 10 lambs at < 24 h and at 12 days of age. We measured the ventilatory (VE) response to three tidal breaths of pure N2 or 13% CO2 in air. Overall, the N2 peripheral chemoreflex increased significantly with maturation [VE/end-tidal O2 (ml.min-1.kg-1.Torr-1) = 2.94 +/- 0.91 at < 24 h vs. 5.13 +/- 0.59 at 12 days, P < 0.05], whereas the CO2 peripheral chemoreflex did not change (VE/end-tidal CO2 = 7.04 +/- 0.98 at < 24 h vs. 7.75 +/- 1.07 at 12 days, not significant). We conclude that the CO2 peripheral chemoreflex does not change in awake lambs within the time frame studied, in contrast to a marked postnatal maturation of the O2 peripheral chemoreflex. The different time courses of O2 and CO2 peripheral chemoreflex maturation support the concept that carotid body sensitivities to O2 and CO2 do not depend on the same basic mechanisms.

Periodic breathing induced on demand in awake newborn lamb.

Spontaneous periodic breathing, although a common feature in fullterm and preterm human infants, is scarce in other newborn mammals. The aim of this study was to induce periodic breathing in lambs. Four 10-day-old and two <48-h-old awake lambs were instrumented with jugular catheters connected to an extracorporeal membrane lung aimed at controlling arterial PCO2 (PaCO2). Arterial PO2 (PaO2) was set and maintained at the desired level by changing inspired O2 fraction and providing O2 through a small catheter into the "apneic" lung. At a critical PaO2/PaCO2 combination, the four 10-day-old lambs exhibited periodic breathing that could be initiated, terminated, and reinitiated on demand. In the 2-day-old lambs with low chemoreceptor gain, periodic breathing was hardly seen, regardless of the trials done to find the critical PO2/PCO2 combination. We conclude that periodic breathing can be induced in lambs and depends on critical PaO2/PaCO2 combinations and maturity of the chemoreceptors.

Vagal afferents and active upper airway closure during pulmonary edema in lambs.

The present study was undertaken to gain further insight into the mechanisms responsible for the sustained active expiratory upper airway closure previously observed during high-permeability pulmonary edema in lambs. The experiments were conducted in nonsedated lambs, in which airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activity were recorded. We first studied the consequences of hemodynamic pulmonary edema (induced by impeding pulmonary venous return) on upper airway dynamics in five lambs; under this condition, a sustained expiratory upper airway closure consistently appeared. We then tested whether expiratory upper airway closure was related to vagal afferent activity from bronchopulmonary receptors. Five bivagotomized lambs underwent high-permeability pulmonary edema: no sustained expiratory upper airway closure was observed. Finally, we studied whether a sustained decrease in lung volume induced a sustained expiratory upper airway closure. Five lambs underwent a 250-ml pleural infusion: no sustained expiratory upper airway closure was observed. We conclude that 1) the sustained expiratory upper airway closure observed during pulmonary edema in nonsedated lambs is related to stimulation of vagal afferents by an increase in lung water and 2) a decrease in lung volume does not seem to be the causal factor.

Vagal and chemoreceptor influences on abdominal muscle activity in awake lambs during hypoxia.

The ventilatory response to hypoxia is a complex phenomenon involving several control mechanisms. We designed this study to examine the dynamic control of abdominal muscle expiratory electromyogram (EMG) activity during room-air breathing and hypoxia and then to analyze the relative contribution of the chemoreceptors and vagal afferents. We studied 12 11- to 22-day-old awake nonsedated lambs, six intact and six vagotomized. To assess the dynamic influence of peripheral chemoreceptors on abdominal muscle expiratory activity, we performed transient testing of peripheral chemoreceptor function (pure O2 and N2 inhalation, KCN injection). To assess the influence of central chemoreceptor afferents, we compared results obtained during hypocapnic and isocapnic 15-min hypoxic runs (fractional concentration of inspired O2 0.08) in each lamb. We also compared results obtained in intact and vagotomized lambs so that the importance of vagal afferents could be assessed. We consistently observed abdominal muscle expiratory EMG activity in each lamb, whether intact or vagotomized, during baseline room air breathing; further recruitment was observed during hypoxia. We also consistently observed abdominal muscle expiratory recruitment during hypocapnic hypoxia in each lamb, although it was significantly less marked than during isocapnic hypoxia. Our transient testing of peripheral chemoreceptor function showed, furthermore, that peripheral chemoreceptor afferents dynamically modulate abdominal muscle expiratory activity. Thus, during hypoxia in 11- to 22-day-old awake nonsedated lambs, increased afferent information from peripheral chemoreceptors forcefully enhances abdominal muscle expiratory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroarytenoid muscle activity during hypoxia in awake lambs.

It is generally accepted that hypoxia in early life results in active laryngeal braking of expiratory airflow via the recruitment of glottic adductor muscles. We examined the electromyogram expiratory activity of the thyroarytenoid muscle in seven 11- to 18-day-old awake nonsedated lambs exposed to an inspired O2 fraction of 0.08 for 18 min. The lambs breathed through a face mask and a pneumotachograph. During baseline prehypoxic breathing, the thyroarytenoid muscle was largely inactive in each awake lamb. Unexpectedly, no recruitment of the thyroarytenoid muscle was recorded during hypoxia in any of the seven lambs; simultaneous examination of the flow-volume curves revealed an absence of expiratory airflow braking. Also unexpectedly, marked expiratory activity of the thyroarytenoid muscle was recorded, with each expiration occurring within less than 10 s after the return to room air. The resulting delay of expiration was apparent in the flow-volume loops. Thus, in awake 11- to 18-day-old lambs, 1) active expiratory glottic adduction is absent during hypoxia and 2) a return from hypoxia to room air results in prolonged expiration as well as active glottic adduction that controls end-expiratory lung volume.

Laryngeal and abdominal muscle electrical activity during periodic breathing in nonsedated lambs.

We recently reported that glottic closure was present throughout central apneas in awake lambs. The present study tested whether glottic closure was also observed during periodic breathing (PB). We attempted to induce PB in 21 nonsedated lambs on return from hypocapnic hypoxia to room air. Airflow and thyroarytenoid (a laryngeal constrictor, n = 16), cricothyroid (a laryngeal dilator, n = 10), and abdominal (n = 9) muscle electrical activity (EMG) were monitored continuously. PB was observed in 16 lambs, with apneic phases in 8 lambs. Thyroarytenoid muscle EMG was observed at the nadir of PB, either throughout apnea or with prolonged expiration during the lowest respiratory efforts. Phasic inspiratory cricothyroid muscle EMG and phasic expiratory abdominal EMG disappeared at the nadir of PB. Active glottic closure at the nadir of PB, without abdominal muscle contraction, could be a beneficial mechanism, preserving alveolar gas stores for continuing gas exchange during the apneic/hypopneic phase of PB. However, consequences of active glottic closure on ventilatory instability, either enhancing or reducing, are unknown.

Coordination between glottic adductor muscle and diaphragm EMG activity in fetal lambs in utero.

It has previously been reported that active glottic adduction is present during prolonged apneas but absent during periods of breathing movements in fetal lambs in utero. The present study was aimed at examining the precise coordination between fetal breathing movements [diaphragm electromyographic (EMG) activity (Di EMG)] and glottic adduction [thyroarytenoid muscle EMG activity (TA EMG)]. Electrodes for electroencephalogram, eye movements, TA EMG, and Di EMG and an arterial catheter were surgically implanted in fetal lambs 123-142 days postconception. Polygraphic recordings were performed without sedation while the ewe breathed room air (n = 11) or various gas mixtures (hypoxia, n = 5; hyperoxia, n = 4; hypercapnia, n = 5; hypercapnia+hyperoxia, n = 5). Tonic TA EMG was observed throughout >90% of apneas (>6 s) in both non-rapid-eye-movement and rapid-eye-movement sleep, and when Di EMG frequency decreased in rapid-eye-movement sleep. In all but two fetuses, TA EMG was immediately inhibited when Di EMG appeared. Altering blood gases did not modify these results. In conclusion, Di EMG and TA EMG are well coordinated in late gestation in fetal lambs, except in a few cases. These findings may have consequences for understanding the pathogenesis of mixed/obstructive apneas of prematurity.

Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs.

Newborn mammals exhibit an active expiratory upper airway closure during the first hours of extrauterine life. We have recently shown that permeability pulmonary edema led to active expiratory glottic closure in awake newborn lambs while hypoxia (inspired O2 fraction 8%; 15 min) did not. In the present study, we tested the hypothesis that expiratory glottic closure was accompanied by an increase in pharyngeal constrictor muscle expiratory electromyographic (EMG) activity. We studied seven awake nonsedated lambs aged 8-20 days. Airflow (facial mask + pneumotachograph), blood gases (arterial catheter), and EMG activity of both the thyroarytenoid muscle (a glottic adductor) and the inferior pharyngeal constrictor muscle were recorded before and after intravenous injection of halothane (0.05 ml/kg) to induce a permeability pulmonary edema. A central apnea (duration 15 s to 5 min) with continuous thyroarytenoid and inferior pharyngeal constrictor activity was observed within seconds after halothane injection. One lamb died despite rescuing maneuvers. An expiratory phasic thyroarytenoid and inferior pharyngeal constrictor muscle activity with simultaneous zero airflow gradually took place and, by 30 min after halothane injection, was present at each expiration in the six remaining lambs. Expiratory glottic and pharyngeal constrictor muscle EMG activity was subsequently present during the whole study period (1.5-5 h), even after correction of the initial hypoxia. Permeability lung edema was present at postmortem examination in all seven lambs. We conclude that a permeability pulmonary edema induced by intravenous halothane in non-sedated lambs enhances both glottic and pharyngeal constrictor muscle expiratory EMG. We hypothesize that expiratory contraction of the inferior pharyngeal constrictor muscle could participate in the active expiratory upper airway closure; this, in turn, might improve alveolocapillary gas exchange by increasing the end-expiratory lung volume.

Effects of capsaicin pretreatment on expiratory laryngeal closure during pulmonary edema in lambs.

The present study, performed in nonsedated, conscious lambs, consisted of two parts. In the first part, we 1) examined for the first time whether a respiratory response to pulmonary C-fiber stimulation could be elicited in nonsedated newborns and 2) determined whether this response could be abolished by capsaicin pretreatment. Then, by using capsaicin-desensitized lambs, we studied whether pulmonary C fibers were involved in the sustained, active expiratory upper airway closure previously observed during pulmonary edema. Airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activities were recorded. In the first set of experiments, a 5-10 microg/kg capsaicin bolus intravenous injection in seven intact lambs consistently led to a typical pulmonary chemoreflex, showing that C fibers are functionally mature in newborn lambs. In the second series of experiments, eight lambs pretreated with 25-50 mg/kg subcutaneous capsaicin did not exhibit any respiratory response to 10-50 microg/kg intravenous capsaicin injection, implicating C fibers in the response. Finally, in the above capsaicin-desensitized lambs, we observed that halothane-induced high-permeability pulmonary edema did not cause the typical response of sustained expiratory upper airway closure seen in the intact lamb. We conclude that functionally mature C fibers are present and responsible for a pulmonary chemoreflex in response to capsaicin intravenous injection in nonsedated lambs. Capsaicin pretreatment abolishes this reflex. Furthermore, the sustained expiratory upper airway closure observed during halothane-induced pulmonary edema in intact nonsedated lambs appears to be related to a reflex involving stimulation of pulmonary C fibers.

Abdominal muscle activity during CO2 rebreathing in sleeping neonates.

Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.

Apnea threshold and breathing rhythmicity in newborn lambs.

This study was designed to determine the effect of the removal of chemical stimuli on breathing rhythmicity in awake newborn lambs; it was also designed to define the chemical threshold below which breathing would stop [arterial PCO2 (PaCO2) apnea threshold]. We used a technique of graded extracorporeal CO2 removal with apneic oxygenation in three groups of animals according to age and carotid body (CB) integrity: < 2 days, CB intact (n = 5); 12 days, CB intact (n = 7); and 12 days, CB denervated (CBD; n = 5). In all animals, whatever their age and CB status, suppression of the chemical drive resulted in sustained apnea. The study, performed at four constant levels of oxygenation (hyperoxia, normoxia, moderate hypoxia, and severe hypoxia), allowed precise determination of the PaCO2 apnea threshold. We found that this PaCO2 apnea threshold depended on the degree of postnatal maturation (it was higher in the younger lambs), the level of arterial oxygenation (it was lowered by hypoxia), and CB status (it was higher in CBD animals). Moreover, we found that the 12-day-old CBD lambs breathe at a level of PaCO2 set close to the point of apnea.(ABSTRACT TRUNCATED AT 250 WORDS)