Arousal pattern following
central and obstructive breathing abnormalities in infants and children.
McNamara, Frances, Faiq
G. Issa, Colin E. Sullivan. J. Appl. Physiol. 81(6): 2651-2657, 1996
We analyzed the polysomnographic
records of 15 children and 20 infants with obstructive sleep apnea (OSA) to examine
the interaction between central and obstructive breathing abnormalities and arousal
from sleep. Each patient was matched for age with an infant or child who had no
OSA. We found that the majority of respiratory events in infants and children
were not terminated with arousal. In children, arousals terminated 39.3 +/- 7.2%
of respiratory events during quiet sleep and 37.8 +/- 7.2% of events during active
(REM) sleep. In infants, arousals terminated 7.9 +/- 1.0% of events during quiet
and 7.9 +/- 1.2% of events during active sleep. In both infants and children,
however, respiratory related arousals occurred more frequently following obstructive
apneas and hypopneas than central events. Spontaneous arousals occurred in all
patients with OSA during quiet and active sleep. The frequency of spontaneous
arousals was not different between children with OSA and their matched controls.
During active sleep, however, infants with OSA had significantly less spontaneous
arousals than control infants. We conclude that arousal is not an important mechanism
in the termination of respiratory events in infants and children and that EEG
criteria are not essential to determine the clinical severity of OSA in the pediatric
population.
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Gustatory stimulation
of the oropharynx fails to induce swallowing in the sleeping dog.
Issa FG
Gastroenterology. 107(3):650-6, 1994
BACKGROUND/AIMS: Very little
is known about the influence of sleep in initiation of swallowing in response
to gustatory stimulation of the oropharynx. The aim of the present study was to
examine the effect of sleep on swallowing. METHODS: Studies were performed in
a group of four dogs trained to sleep naturally in our laboratory. During nasal
breathing, tap water, 0.9% NaCl, 0.5 mol/L glucose, 0.5 mol/L NaHCO3, or acetic
acid (pH 5.2) were infused at 0.5 mL/s on the dorsum of the tongue using a special
feeding tube. The entire surface of the tongue was mapped for initiation of swallowing
in the awake and sleeping animal. RESULTS: Swallowing never occurred during non-rapid
eye movement and rapid eye movement sleep. Infusion of a solution either did not
cause any reaction, resulting in dribbling of the test fluid through the opening
between the jaws, or caused arousal that was occasionally followed by a swallow.
Arousal-swallow complex occurred most significantly after application of acid
and when the fluid was applied to the posterior tongue area. CONCLUSIONS: Wakefulness
is a prerequisite for swallowing.
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Control of ventilation
during continuous swallowing.
Issa FG, Porostocky
S.
American Journal of Respiratory & Critical Care Medicine. 150(5 Pt 1):1274-8,
1994
The upper airway performs
three distinct functions that must be coordinated to allow maximal operation of
each individual system. We tested the ventilatory response to progressive hypercapnia
in seven normal adults during continuous swallowing. Swallowing was induced by
oral infusion of water while the subject breathed through the nose. Infusion of
40 ml/min resulted in repetitive swallows (rate: 8.1 +/- 4.1 swallows/min, mean
+/- SD), but this did not cause a single incidence of coughing or aspiration.
Swallows interrupted inspiration and expiration and resulted in compensatory changes
in tidal volume and breathing frequency. Continuous drinking did not significantly
change the slope of the ventilatory response to hypercapnia. The test was repeated
in three subjects swallowing water infused at 60, 80, and 100 ml/min. The slope
of the response was also not significantly different from control in these tests.
We conclude that continuous swallowing does not override ventilatory control mechanisms
in human adults.
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Effect of sleep and sighing
on upper airway resistance in mongrel dogs.
Issa FG, Porostocky
S., Feroah T.
Journal of Applied Physiology 77(2):856-61, 1994
We investigated the effect
of sleep and sighing on supratracheal resistance in unrestrained mongrel dogs
breathing through the nose by comparing within-breath changes in upper airway
pressure-flow relationship in control, sigh, and five postsigh breaths recorded
during wakefulness and during non-rapid-eye-movement and rapid-eye-movement sleep.
A sigh breath was characterized by a high tidal volume and was typically followed
by an apnea of a variable duration. Sleep had little or no effect on supratracheal
resistance, measured at peak flow rates, during quiet breathing (awake 7.3 +/-
0.4, non-rapid eye movement 8.3 +/- 0.4, and rapid eye movement 6.8 +/- 0.4 cmH2O.l-1.s).
The resistance was identical in the early part of inspiration in control and sigh
breaths but increased during the augmented phase of sigh breaths. Resistance at
peak inspiratory flow was higher in sigh breaths than in control breaths in all
sleep states. The flow-pressure profile of postsigh breaths was identical to that
of control breaths in all sleep states. We conclude that upper airway resistance
is essentially unaffected by sleep state in the mongrel dog and that sighing increases
upper airway resistance regardless of sleep state.
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Effect of continuous swallowing
on respiration.
Issa FG, Porostocky
S.
Respiration Physiology. 95(2):181-93, 1994
We examined the effect of
continuous swallowing on breathing pattern and ventilation in 7 adult subjects.
Repetitive swallowing was induced by oral infusion of water at a variable rate
of 40, 60, 80 or 100 ml/min, while the subject breathed through the nose. The
number of swallows increased from a mean of 5.2 (+/- 2.7 SD) swallows/min during
the control period to 9.2 +/- 2.0 to 13.7 +/- 2.9 swallows/min during infusion
of 40 and 100 ml/min, respectively. The duration of interruption of breathing
was bolus volume-dependent, increasing from 0.55 +/- 0.09 sec with a mean bolus
volume of 4.6 +/- 1.4 ml to 0.87 +/- 0.23 sec with a bolus volume of 8.1 +/- 1.9
ml. The majority of swallows (73 +/- 12%) interrupted breathing during inspiration.
The mean tidal volume, inspiratory and expiratory times during swallowing periods
were higher than those recorded during the control period, but the mean level
of ventilation was not different from control, at all swallowing frequencies.
Repetitive swallowing did not result in a single incidence of aspiration or coughing.
We conclude that mechanisms integrating breathing and swallowing allow repetitive
swallowing to occur without compromising ventilation, and that these mechanisms
perfectly orchestrate between breathing and deglutition to prevent aspiration.
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Site of pharyngeal narrowing
predicts outcome of surgery for obstructive sleep apnea.
Launois SH. Feroah TR.
Campbell WN. Issa FG. Morrison D. Whitelaw WA. Isono S. Remmers JE.
American Review of Respiratory Disease. 147(1):182-9, 1993 Jan.
Uvulopalatopharyngoplasty
(UPPP), an operation that enlarges the pharyngeal airway at the level of the soft
palate, improves respiratory status during sleep in only 50% of patients with
obstructive sleep apnea (OSA). This poor outcome suggests that narrowing of the
pharyngeal airway at nonpalatal sites contributes to the obstructive process in
many patients with OSA. We have used a novel endoscopic method to identify regions
of the passive pharyngeal airway most susceptible to narrowing or complete closure.
In order to test the hypothesis that narrowing of the passive airway at the nasopharynx
predicts a favorable surgical outcome, we have preoperatively assessed the local
mechanics of the passive pharyngeal airway in 18 patients with OSA undergoing
UPPP. The patient population was prospectively divided into two groups: an exclusively
nasopharyngeal (ENP) group, consisting of patients exhibiting narrowing only in
the nasopharynx, and a not exclusively nasopharyngeal (NENP) group, consisting
of patients having at least one site of narrowing outside the nasopharynx. The
frequency of respiratory disturbances and arousals and the cumulative time in
apnea-hypopnea were significantly reduced after surgery for the ENP group, but
not for the NENP group. Improvement rate for the ENP group (86%) exceeded that
for the NENP group (18%) (p < 0.01). These differences became even greater
when selection criteria for the ENP group were made more restrictive (i.e., restricted
to the velopharynx) or more liberal (i.e., including secondary narrowing of the
oropharynx). Our results show that evaluation of passive pharyngeal mechanics
identifies patients with OSA likely to improve after UPPP.
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Effect of route of breathing
on the ventilatory and arousal responses to hypercapnia in awake and sleeping
dogs.
Issa FG, Bitner
S.
Journal of Physiology (London). 465:615-28, 1993
1. The influence of the upper
airway on the ventilatory and arousal responses to hypercapnia in wakefulness
and sleep was investigated using a chronic animal model.
2. Experiments were performed in five unrestrained dogs trained to sleep naturally
in the laboratory. The animal rebreathed through a chronic tracheostoma (thus
excluding the upper airway from the breathing circuit), or through the snout (intact
upper airway). Resistance to breathing and volume of dead space during quiet tracheal
breathing were matched to those in quiet nasal breathing during wakefulness and
sleep. CO2 rebreathing tests were performed during wakefulness, rapid eye movement
(REM) and non-REM (NREM) sleep, during nasal and tracheal breathing.
3. The ventilatory response to hypercapnia was significantly lower in nasal breathing
compared with tracheal breathing, in all behavioural states. This was due to a
smaller tidal volume and lower breathing frequency.
4. The ventilatory response to CO2 was lowest during REM sleep, irrespective of
route used for breathing.
5. Alveolar partial pressure of CO2 (PA,CO2) level at arousal was identical in
NREM nasal and tracheal rebreathing tests. Differences in PA,CO2 levels at arousal
between NREM and REM sleep were not significant in nasal tests and only marginally
different during tracheal breathing.
6. We conclude that nasal breathing influences the hypercapnic ventilatory response
in wakefulness and sleep, and that the presence of CO2 in the upper airway does
not affect arousal in NREM and REM sleep.
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Effect of sleep on changes
in breathing pattern accompanying sigh breaths.
Issa FG, Porostocky
S.
Respiration Physiology. 93(2):175-87, 1993
We studied the effect of
sleep on the characteristics of sigh breaths and the associated changes in breathing
pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an
intact upper airway. The sigh breath was characterized by its large tidal volume
(VT), long TI and TE in comparison with the control breath. The volume of the
sigh breath was larger in awake sighs than in those recorded during non-REM (NREM)
and REM sleep. The strength of Hering-Breuer reflex as determined by duration
of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during
wakefulness, NREM and REM sleep were associated with augmented activity of the
parasternal muscles during inspiration, and a persistent tonic abdominal muscle
activity during the expiratory period. Breathing pattern in the post-sigh period
was characterized by a smaller VT and longer TE in the first post-sigh breath
in all sleep states (compared with the control breath), but the pattern returned
to control level within the second or third post-sigh breath in both NREM and
REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal
breathing patterns in either wakefulness or sleep. We conclude that the respiratory
control mechanisms stabilizing breathing after a sigh in the awake dog are intact
in NREM and REM sleep.
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Digital
monitoring of sleep-disordered breathing using snoring sound and arterial oxygen
saturation.
Issa FG, Morrison
D, Hadjuk E, Iyer A, Feroah T, Remmers JE.
American Review of Respiratory Disease. 148(4 Pt 1):1023-9, 1993
A new portable digital recorder
(SNORESAT) that uses the sound of snoring and arterial oxygen saturation (SaO2)
to monitor breathing abnormalities during sleep was constructed and compared in
the laboratory with standard overnight polysomnography (PSG). The device digitally
records sound from a transducer applied to the chest and SaO2 from a commercially
available ear oximeter. A snore is identified when the moving time average of
the sound exceeds a threshold voltage level longer than 0.26 s. The stored data
are transferred to a personal computer for poststudy analysis. An analysis algorithm
identifies a respiratory disturbance event when a quiet period of 10 to 120 s
separates two snores and is associated with a fall in SaO2 exceeding 3%. The respiratory
disturbance index (RDI), mean apnea duration, mean lowest SaO2, and number of
desaturations > 3% are computed. A total of 129 referrals to the sleep apnea
outpatient clinic underwent simultaneous all-night recording of PSG and SNORESAT.
Using the computed RDI recorded by the SNORESAT, the sensitivity and specificity
of the monitor in detecting sleep apnea syndrome (SAS) ranged between 84 and 90%
and 95 and 98%, respectively, depending on the PSG value of RDI used to define
SAS (range, > or = 7 to > or = 20 events/h). Using a PSG value of RDI >
or = 10, or > or = 20 RD/h as the definition for SAS, the prevalence of SAS
in the referral population was 45 and 31%, respectively. Apositive diagnostic
value from SNORESAT decreased the post-test probability of OSA to 4 to 12%. We
conclude that laboratory testing of SNORESAT indicates that the device can estimate
the presence or absence of nocturnal breathing abnormalities with sufficient accuracy
to be clinically useful in SAS.
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Effect of clonidine in
obstructive sleep apnea.
Issa FG.
American Review of Respiratory Disease. 145(2 Pt 1):435-9, 1992
The current treatment of
choice for obstructive sleep apnea is continuous positive airway pressure. However,
not all patients tolerate this form of therapy. We evaluated the effect of clonidine
hydrochloride, an alpha 2-adrenergic agonist with REM-suppressant activity, in
eight male patients with obstructive sleep apnea. In each patient, sleep-stage
distribution and breathing pattern in two all-night sleep studies performed during
a 10-day course of clonidine were compared with those of two control and two placebo
nights. A dose of 0.2 mg of clonidine administered orally at bedtime totally suppressed
REM sleep in two patients. In the other six patients, the same dose decreased
percent time spent in REM sleep from a control of 13.4 +/- 1.0 to 8.6 +/- 1.4%
(mean +/- SEM, p less than 0.05). The latency to REM sleep increased in the latter
group from a control of 129 +/- 9 to 308 +/- 24 min (p less than 0.001). Clonidine
had no effect on the frequency and duration of non-REM breathing abnormalities.
Under clonidine, the level of nocturnal hypoxemia improved in six patients. This
was due to a total suppression of REM and the consequent lack of REM apneas in
two patients. In four patients, upper airway obstruction disappeared during period
of unsuppressed REM sleep, and SaO2 remained above 90% throughout this sleep stage.
Clonidine transformed the pattern of sleep-disordered breathing during unsuppressed
REM in the other two patients from that of repetitive obstructive hypopneas associated
with persistent hypoxemia to occlusive apneas and cyclical hypoxemia. These results
were observed consistently in all patients during both clonidine-sleep studies.
The data suggest that clonidine does not only alter mechanisms involved in the
initiation and maintenance of REM sleep but it also influences breathing pattern
during REM sleep.
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Identification of a subsurface
area in the ventral medulla sensitive to local changes in PCO2.
Issa FG. Remmers
JE.
Journal of Applied Physiology. 72(2):439-46, 1992
The exact location of the
central respiratory chemoreceptors sensitive to changes in PCO2 has not yet been
determined. To avoid the confounding effects of the cerebral circulation, we used
the in vitro brain stem-spinal cord of neonatal rats (1-5 days old) to identify
areas within 500 microns of the ventral surface of the medulla where changes in
PCO2 evoked a sudden increase in the rate of respiratory neural activity. The
preparation was superfused with mock cerebrospinal fluid (CSF) while maintained
at constant temperature (26 +/- 1 degrees C) and pH (7.34). Respiratory frequency
increased linearly with decreases in superfusate pH (r2 = 0.92, P less than 0.001),
indicating that the respiratory circuitry for the detection of CO2 and stimulation
of breathing was intact in this preparation. The search for central chemoreceptors
was performed with a specially designed micropipette that allowed microejection
of 2-10 nl of mock CSF equilibrated with different CO2-O2 gas mixtures. The pipette
was advanced in 50- to 100-microns steps by use of a microdrive to a maximum depth
of 500 microns from the surface of the ventral medulla. Depending on the location
of the micropipette, ejection of CO2-acidified mock CSF at depths of 100-350 microns
below the ventral surface of the medulla stimulated neural respiratory output.
Using this response as an indication of the location of central respiratory chemoreceptors,
we found that chemoreceptive elements were located in a column in the ventromedial
medulla extending from the hypoglossal rootlets caudally to an area 0.75 mm caudal
to VI nerve in the rostral medulla. At its caudal end, the column was 250 microns
wide and lay 0.50-0.75 mm from midline. Rostrally, it fanned laterally and lay
0.50-1.00 mm lateral to midline. In this column, ejection of CO2-enriched CSF
elicited an increase in respiratory neural output in 50-67% of the trials. We
conclude that chemoreception of CO2 occurs in part in an area located beneath
the surface of the ventral medulla.
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Restructuring of sleep
and reversal of REM-induced supraspinal hypotonia of respiratory muscles following
bilateral phrenicotomy.
Issa FG. Bitner
S. Neuroscience Letters. 139(2):231-3, 1992 May 25.
The long-term effect of diaphragm
paralysis on respiratory system function is still not clear. We monitored changes
in breathing pattern and the sleep/wake cycle in a dog before and after bilateral
phrenicotomy. The post-operative observation extended over 6 months. It was noted
that minute ventilation increased during wakefulness and non-REM sleep in the
initial 4-6 weeks (compared to pre-surgery period), but decreased during REM sleep,
mainly due to inhibition of chest wall and abdominal muscles. These episodes resulted
in hypoxemia and frequent arousals. Following this period, there was a restructuring
of REM sleep, increasing the frequency of REM sleep and reducing the duration
of each REM sleep episode. In addition, the enhanced activity of parasternal and
abdominal muscles was persistently seen during REM sleep. These changes in breathing
and sleep provided stable ventilation during sleep. We conclude that bilateral
phrenicotomy restructures breathing and alters sleep/wake cycle to prevent nocturnal
hypoxemia. The mechanisms underlying these changes may reflect plasticity in the
control of breathing and REM sleep.
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Respiratory failure and
sleep in neuromuscular disease.
Bye PT. Ellis ER. Issa
FG. Donnelly PM. Sullivan CE.
Thorax. 45(4):241-7, 1990
Sleep hypoxaemia in non-rapid
eye movement (non-REM) and rapid eye movement (REM) sleep was examined in 20 patients
with various neuromuscular disorders with reference to the relation between oxygen
desaturation during sleep and daytime lung and respiratory muscle function. All
the patients had all night sleep studies performed and maximum inspiratory and
expiratory mouth pressures (PI and Pemax), lung volumes, single breath transfer
coefficient for carbon monoxide (KCO), and daytime arterial oxygen (PaO2) and
carbon dioxide tensions (PaCO2) determined. Vital capacity in the erect and supine
posture was measured in 14 patients. Mean (SD) PI max at RV was low at 33 (19)
cm H2O (32% predicted). Mean PE max at TLC was also low at 53 (24) cm H2O (28%
predicted). Mean daytime PaO2 was 67 (16) mm Hg and PaCO2 52 (13) mm Hg (8.9 (2.1)
and 6.9 (1.7) kPa). The mean lowest arterial oxygen saturation (SaO2) was 83%
(12%) during non-REM and 60% (23%) during REM sleep. Detailed electromyographic
evidence in one patient with poliomyelitis showed that SaO2% during non-REM sleep
was maintained by accessory respiratory muscle activity. There was a direct relation
between the lowest SaO2 value during REM sleep and vital capacity, daytime PaO2,
PaCO2, and percentage fall in vital capacity from the erect to the supine position
(an index of diaphragm weakness). The simple measurement of vital capacity in
the erect and supine positions and arterial blood gas tensions when the patient
is awake provide a useful initial guide to the degree of respiratory failure occurring
during sleep in patients with neuromuscular disorders. A sleep study is required
to assess the extent of sleep induced respiratory failure accurately.
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Genioglossus and breathing
responses to airway occlusion: effect of sleep and route of occlusion.
Issa FG. Edwards
P. Szeto E. Lauff D. Sullivan C.
Journal of Applied Physiology. 64(2):543-9, 1988 Feb.
We examined the effect of
sleep state on the response of genioglossus muscle (EMGgg) activity to total airway
occlusion applied at 1) nasal (N) airway [and thus exposing the upper airway (UAW)
to pressure changes] and 2) tracheal (T) airway (thus excluding UAW from pressure
changes). A total of 233 tests were performed during wakefulness (W), 98 tests
in slow-wave sleep (SWS), and 72 tests in rapid-eye-movement (REM) sleep. Prolongation
of inspiratory time (TI) of the first occluded effort occurred in all tests irrespective
of behavioral state, with the greatest increase seen in awake N tests. Nasal tests
augmented EMGgg activity in the first occluded breath and produced a linear increase
in EMGgg during occlusion. The EMGgg activity at any given time during nasal occlusion
in SWS was less than that recorded during W tests. There was a marked reduction
in EMGgg response to N occlusion during REM sleep. The EMGgg activity during awake
T tests was significantly less than that of N tests at any given time during occlusion.
There was no relationship between the level of EMGgg activity and asphyxia in
T tests performed during SWS and REM sleep. Nasal tests decreased the force generated
by the inspiratory pump muscles and the central drive to breathing compared with
T tests. These results confirm the important role of the UAW in regulating breathing
pattern and indicate that both immediate and progressive load-compensating responses
during nasal occlusion are influenced by information arising from the UAW.
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Arousal responses to airway
occlusion in sleeping dogs: comparison of nasal and tracheal occlusions.
Issa FG. McNamara
SG. Sullivan CE.
Journal of Applied Physiology. 62(5):1832-6, 1987 May.
Previous studies have shown
that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is
greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep
(SWS). The aim of this study was to compare the arousal thresholds in SWS and
REM sleep in response to an upper airway pressure stimulus. We compared the waking
responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally
sleeping dogs. The dogs either breathed through a tracheal fistula or through
the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests
were performed in SWS and REM sleep. The mean time to arousal during N and T tests
was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal
occlusion was longer than that in N tests in only two of the four dogs. The total
number of tests inducing arousal within the first 15 s of SWS-nasal occlusion
tests was significantly more than that of T tests (N: 47%; T: 27%). There was
a marked depression of arousal within the initial 15 s of REM sleep in T tests
compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM
tests was less than that of SWS for both N and T tests. The early arousal in N
occlusion is in sharp contrast to the well-described depressed arousal responses
to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the
upper airway mechanoreceptors may play an important role in the induction of an
early arousal from nasal occlusion.
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The immediate effects
of nasal continuous positive airway pressure treatment on sleep pattern in patients
with obstructive sleep apnea syndrome.
Issa FG. Sullivan
CE.
Electroencephalography & Clinical Neurophysiology. 63(1):10-7, 1986 Jan.
We studied the immediate
effects of continuous positive airway pressure (CPAP) applied nasally on the pattern
of sleep in 12 patients, aged 30-58 years, with obstructive sleep apnea syndrome.
All patients demonstrated a moderate to severe syndrome on the control night;
apnea index ranged 28-83 apneas/h sleep. Nasal CPAP completely abolished all obstructive
apneas and allowed apnea-free breathing in all 12 patients. Nasal CPAP had a marked
effect on the sleep pattern. It significantly reduced stage I/II non-rapid eye
movement (NREM) sleep and markedly increased stage III/IV NREM and REM sleep on
the first treatment night. Stage I/II NREM sleep decreased from a control of 62.7
+/- 2.3% to 29.1 +/- 2.3% on the first treatment night. Stage III/IV NREM sleep
increased from a control of 6.7 +/- 1.6% to 31.5 +/- 1.6%. The rebound in this
sleep stage was especially marked in 3 patients aged 55-58 years. REM sleep increased
from a control of 18.4 +/- 2.0% to 30.6 +/- 2.0% on the first treatment night.
There was an increase in REM density. All patients were treated for another 2
nights and their sleep pattern analyzed on the third night. All sleep stages were
still significantly different to the control night. The possible mechanisms involved
are discussed.
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Reversal of central sleep
apnea using nasal CPAP.
Issa FG. Sullivan
CE.
Chest. 90(2):165-71, 1986 Aug.
Based on the theory that
obstructive (OSA) and central (CSA) sleep apneas share common pathophysiologic
mechanisms, we attempted to treat eight patients with predominantly CSA by continuous
positive airway pressure (CPAP). All patients exhibited repetitive episodes of
CSA and mixed sleep apneas (MSA) in the supine position with a mean duration of
23.7 +/- 0.7 s and 34.5 +/- 1.3 s, respectively. The pattern of apnea changed
when the subject lay in the lateral position. Five patients were observed to develop
OSA in the lateral position with a mean duration of 27.2 +/- 1.5 s, while the
other three patients snored continuously. High levels of CPAP (range 9.0 to 16.5
cm H2O) prevented all CSA and MSA and resulted in quiet breathing in all eight
patients. Intermediate levels of CPAP produced firstly MSA, then purely OSA and/or
continuous snoring. Low levels of nasal CPAP also prevented OSA and snoring occurring
in the lateral posture in all subjects (range 2.0 to 8.3 cm H2O). Three patients
are currently on home CPAP therapy for a range of four to 36 months. We conclude
that upper airway collapse in the supine posture has a key role in the induction
of CSA. We suggest that a reflex inhibition of respiration through activation
of supraglottic mucosal receptors during passive oropharyngeal airway closure
caused CSA in these patients.
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Influence of negative
pressure applied to the upper airway on the breathing pattern in unanesthetized
awake dogs.
McNamara SG. Issa FG.
Szeto E. Sullivan CE.
Respiration Physiology. 65(3):315-29, 1986 Sep.
We examined the influence
of changes in upper airway pressure on the breathing pattern in 5 unanesthetized
awake dogs. The dogs breathed through an endotracheal tube or through a comfortably
fitting fiberglass snout mask. With matched resistances and volume of the dead
space, the inspiratory duration, tidal volume, and minute ventilation were higher
during nasal breathing compared to tracheal breathing. Nasal and tracheal occlusion
produced prolongation of inspiration in the first occluded breathing attempt,
but the prolongation was more marked in nasal occlusion tests. Augmentation of
genioglossus muscle activity occurred on the first occluded breath in nasal but
not tracheal occlusion. In another series of experiments, negative pressure was
applied to the isolated upper airway while the dog breathed through a tracheostomy
tube. Negative pressure caused a prolongation of inspiratory duration which was
proportional to the level of the applied pressure. However, the prolongation of
inspiratory duration was significantly more marked when application of negative
pressure was timed simultaneously with tracheal occlusion. Our results demonstrate
that the upper airway has a powerful effect on the control of breathing, which
becomes more evident during tracheal occlusion.
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Upper airway dilating
forces during wakefulness and sleep in dogs.
Goh AS. Issa FG. Sullivan
CE.
Journal of Applied Physiology. 61(6):2148-55, 1986 Dec.
We measured the pressure
within an isolated segment of the upper airway in three dogs during wakefulness
(W), slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Measurements were
taken from a segment of the upper airway between the nares and midtrachea while
the dog breathed through a tracheostoma. These pressure changes represented the
sum of respiratory-related forces generated by all muscles of the upper airway.
The mean base-line level of upper airway pressure (Pua) was -0.5 +/- 0.03 cmH2O
during W, increased by a mean of 2.1 +/- 0.2 cmH2O during SWS, and was variable
during REM sleep. The mean inspiratory-related phasic change in Pua was -1.2 +/-
0.1 cmH2O during wakefulness. During SWS, this phasic change in Pua decreased
significantly to a mean of -0.9 +/- 0.1 cmH2O (P less than 0.05). During REM sleep,
the phasic activity was extremely variable with periods in which there were no
fluctuations in Pua and others with high swings in Pua. These data indicate that
in dogs the sum of forces which dilate the upper airway during W decreases during
SWS and REM sleep. The consistent coupling between inspiratory drive and upper
airway dilatation during wakefulness persists in SWS, but is frequently uncoupled
during REM sleep.
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Obstructive sleep apnea.
Sullivan CE. Issa FG.
Clinics in Chest Medicine. 6(4):633-50, 1985 Dec.
This chapter provides an
account of obstructive sleep apnea that is designed for clinicians. Current ideas
about the mechanism of upper airway obstruction are reviewed, and the clinical
features are discussed in a manner intended to facilitate the clinical assessment
of such patients. Various forms of treatment are reviewed, with major emphasis
given to the use of nasal positive airway pressure, a form of therapy developed
by the authors.
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Respiratory muscle activity
and thoracoabdominal motion during acute episodes of asthma during sleep.
Issa FG. Sullivan
CE.
American Review of Respiratory Disease. 132(5):999-1004, 1985 Nov.
To understand the mechanisms
of respiratory system compensation to internal loading during sleep, all-night
sleep studies were performed in 10 patients with chronic stable asthma. We used
noninvasive measurements to identify the onset of increased airway resistance
in sleep. In each sleep study, we recorded arterial oxygen saturation (SaO2) and
an array of electromyograms (diaphragm, external intercostal and sternomastoid)
as well as thoracoabdominal motion. Only 4 patients developed acute asthma during
sleep. A total of 6 such attacks were recorded. The attacks were detected by audible
wheeze, augmentation of diaphragm, external intercostal and sternomastoid activity,
associated with distinctive changes in thoracoabdominal motion. The duration of
these acute asthmatic attacks ranged between 20 and 140 min. One attack started
in stage I/II non-rapid-eye-movement (NREM) sleep, 3 in stage III/IV NREM sleep,
and 2 in rapid-eye-movement (REM) sleep. Acute asthma in NREM sleep resulted in
a paradoxical inward displacement of the abdomen during early inspiration. Attacks
occurring during REM sleep resulted in rib cage inward displacement during inspiration.
Attacks occurring during REM sleep resulted in rib cage inward displacement during
inspiration. Attacks occurring in both NREM and REM sleep did not result in a
significant fall in SaO2. We conclude that acute internal respiratory loading
during sleep can provoke different compensatory mechanisms in order to provide
adequate ventilation in adult asthmatics.
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Home treatment of obstructive
sleep apnoea with continuous positive airway pressure applied through a nose-mask.
Sullivan CE. Issa FG.
Berthon-Jones M. McCauley VB. Costas LJ.
Bulletin Europeen de Physiopathologie Respiratoire. 20(1):49-54, 1984 Jan-Feb.
Continuous positive airway
pressure (CPAP) applied through the nose completely prevented obstructive apnoea
during all night testing in 50 patients with severe obstructive apnoea. In early
1981, we began a home treatment trial of nasal CPAP. Patients were treated in
hospital for 3 to 5 nights, a period in which they were trained to fit the custom
made nose-mask used to provide nasal CPAP. Patients subsequently continued treatment
at home. Daytime somnolence resolved within days of starting therapy, and did
not recur while the nasal CPAP unit was used on a regular basis. At present, we
have 35 patients who have been on therapy for periods ranging between 3 and 30
months. Although each patient has displayed a reduction of severity of the underlying
sleep apnoea when tested without nasal CPAP, the majority continue to require
regular nightly nasal CPAP. In a few patients, treatment with nasal CPAP appeared
to help in weight control such that obstructive apnoea and snoring have resolved.
Nasal CPAP is a safe, fully effective therapy for obstructive apnoea, and can
be used indefinitely by the patient at home.
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Upper airway closing pressures
in obstructive sleep apnea.
Issa FG. Sullivan
CE.
Journal of Applied Physiology: Respiratory, Environmental & Exercise Physiology.
57(2):520-7, 1984 Aug.
We studied 18 patients with
obstructive sleep apnea (OSA). Each subject slept while breathing through the
nose with a specially designed valveless breathing circuit. Low levels of continuous
positive airway pressure (CPAP) applied through the nose (2.5-15.0 cmH2O) prevented
OSA and allowed long periods of stable stage III/IV sleep and rapid-eye-movement
(REM) sleep. Externally applied complete nasal occlusion while the upper airway
was patent resulted in upper airway closure during inspiration which was identified
by a sudden deviation of nasal pressure from tracheal or esophageal pressure.
The level of upper airway closing pressure (UACP) did not change throughout the
occlusion test, suggesting that upper airway dilator muscles do not respond to
asphyxia during sleep. The upper airway was more collapsible during stage I/II
non-rapid-eye-movement (NREM) and REM sleep compared with stage III/IV NREM sleep.
The pooled mean UACP was 3.1 +/- 0.4 cmH2O in stage I/II NREM, 4.2 +/- 0.2 cmH2O
in stage III/IV NREM, and 2.4 +/- 0.2 cmH2O in REM sleep. Nasal occlusion at successively
higher levels of CPAP did not alter the level of UACP in stage I/II NREM and REM
sleep but resulted in the upper airway becoming more stable in stage III/IV NREM
sleep, suggesting a reflex which augments the tone of upper airway dilator muscles.
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Upper airway closing pressures
in snorers.
Issa FG. Sullivan
CE.
Journal of Applied Physiology: Respiratory, Environmental & Exercise Physiology.
57(2):528-35, 1984 Aug.
We studied 14 subjects who
were selected to represent the broad range of severity of snoring: group A, four
subjects who gave a history of snoring only when provoked by nasal obstruction
or alcohol intake; group B, six subjects who typically snored for long periods
each night; and group C, four subjects who snored heavily all night and who typically
experienced a few episodes of obstructive apnea (mean apnea index 4 apneas/h).
Low levels of nasal continuous positive airway pressure (CPAP) (range, 2.0-6.0
cmH2O; mean, 4.0 cmH2O) prevented snoring. Nasal occlusion caused upper airway
closure during inspiratory efforts in all 14 subjects. There was a relationship
between the clinical severity of snoring and the upper airway closing pressure
(UACP). Upper airway closure occurred at greater suction pressures in group A
than in group C but there was overlap between the three categories. The upper
airway was consistently more collapsible in rapid-eye-movement sleep than in non-rapid-eye-movement
sleep. There was little evidence of breath-by-breath improvement of upper airway
stability during sustained asphyxia, the UACP remaining constant despite marked
increases in drive to the diaphragm. In five subjects UACP was measured following
alcohol intake. Alcohol reduced upper airway stability in all subjects in a dose-dependent
manner.
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Studies of oxygenation
during sleep in patients with interstitial lung disease.
Bye PT. Issa F.
Berthon-Jones M. Sullivan CE.
American Review of Respiratory Disease. 129(1):27-32, 1984 Jan.
The pattern of change in
arterial oxyhemoglobin saturation (SaO2%) during sleep was characterized in 13
patients with interstitial lung disease (ILD), 12 of whom had restrictive ventilatory
impairment. Four patients snored during sleep. During the studies, 9 patients
had unequivocal rapid eye movement (REM) sleep episodes. The total duration of
each patient's REM episodes averaged 49 min (range, 26 to 93 min), which was 22
+/- 7% (1SD) of the total sleep duration. Seven of these 9 patients were nonsnorers
but had definite falls in SaO2% during REM sleep (mean fall in SaO2%, 8 +/- 3%),
and in 6 of them the falls in SaO2% were transient, with a mean duration of 28
+/- 12 s and a total duration of 6.4 +/- 3.9 min or 16 +/- 12% of the total REM
sleep duration. The other nonsnorer showed sustained desaturation (SaO2, 80 to
85%) for his entire REM sleep period of 26 min. In the nonsnoring patients, the
falls in SaO2% during REM sleep (8 +/- 3%) were usually greater than those occurring
during awake exercise (6 +/- 7%). Two snorers had unexpected sleep apnea syndrome
(minimal SaO2% during NREM sleep, 83 and 77%, respectively; minimal SaO2% during
REM sleep, 58 and 67%, respectively). The other snorers had greater than 10% falls
in SaO2% during NREM sleep. The breathing frequency in NREM sleep in patients
with ILD (mean, 23 +/- 5 breaths/min) was persistently above the normal range
(mean, 15 +/- 0.4 breaths/min). The possibility of sleep hypoxemia should be considered
in the management of patients with ILD.
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Arousal and breathing
responses to airway occlusion in healthy sleeping adults.
Issa FG. Sullivan
CE.
Journal of Applied Physiology: Respiratory, Environmental & Exercise Physiology.
55(4):1113-9, 1983 Oct.
The arousal and breathing
responses to total airway occlusion during sleep were measured in 12 normal subjects
(7 males and 5 females) aged 25-36 yr. Subjects slept while breathing through
a specially designed nosemask, which was glued to the nose with medical-grade
silicon rubber. The lips were sealed together with a thin layer of Silastic. The
nosemask was attached to a wide-bore (20 mm ID) rigid tube to allow a constant-bias
flow of room air from a blower. Total airway occlusion was achieved by simultaneously
inflating two rubber balloons fixed in the inspiratory and expiratory pipes. A
total of 39 tests were done in stage III/IV nonrapid-eye movement (NREM) sleep
in 11 subjects and 10 tests in rapid-eye-movement (REM) sleep in 5 subjects. The
duration of total occlusion tolerated before arousal from NREM sleep varied widely
(range 0.9-67.0 s) with a mean duration of 20.4 +/- 2.3 (SE) s. The breathing
response to occlusion in NREM sleep was characterised by a breath-by-breath progressive
increase in suction pressure achieved by an increase in the rate of inspiratory
pressure generation during inspiration. In contrast, during REM sleep, arousal
invariably occurred after a short duration of airway occlusion (mean duration
6.2 +/- 1.2 s, maximum duration 11.8 s), and the occlusion induced a rapid shallow
breathing pattern. Our results indicate that total nasal occlusion during sleep
causes arousal with the response during REM sleep being more predictable and with
a generally shorter latency than that in NREM sleep.
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Remission of severe obesity-hypoventilation
syndrome after short-term treatment during sleep with nasal continuous positive
airway pressure.
Sullivan CE. Berthon-Jones
M. Issa FG.
American Review of Respiratory Disease. 128(1):177-81, 1983 Jul.
Two patients with the Pickwickian
syndrome and with life-threatening sleep hypoxemia were treated with continuous
positive airway pressure (CPAP) applied through the nares only during sleep periods.
Each patient presented with severe daytime somnolence, disturbed sleep, nocturnal
confusion, and daytime awake cardiorespiratory failure (PaCO2, 63 and 55 mmHg).
Both patients demonstrated grossly abnormal breathing during sleep with severe
sleep hypoxemia, the arterial oxyhemoglobin saturation (SaO2%) falling repetitively
to levels below 50%. One patient had a hypoxemic convulsion during the initial
sleep evaluation. Low levels (3.5 and 8.0 cm H2O) of continuous positive airway
pressure, when applied via a comfortable nose mask, prevented occlusive apnea
and obstructive hypopnea during sleep in both patients and maintained steady levels
of arterial oxyhemoglobin saturation. There was rapid recovery of mental function
and loss of cardiorespiratory failure within 3 days of treatment. After short-term
treatment with nocturnal CPAP therapy (23 days and 35 days) both patients were
able to sleep, unaided, without sleep-induced upper airway occlusion with arterial
oxyhemoglobin levels sustained above 80%. We conclude that nasal CPAP therapy
during sleep is an effective noninvasive therapy for patients with the Pickwickian
syndrome, and may lead to a stable remission of the underlying severe disordered
breathing in sleep.
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Alcohol, snoring and sleep
apnea.
Issa FG. Sullivan
CE.
Journal of Neurology, Neurosurgery & Psychiatry. 45(4):353-9, 1982 Apr.
We studied the effect of
alcohol ingestion on sleep-induced breathing abnormalities and arterial oxyhaemoglobin
saturation in seven patients with a range of sleep-induced upper airway occlusion.
The characteristics of each patient's sleep-induced breathing abnormality was
established on one or more control all-night studies, and then a further all-night
study was done immediately following alcohol ingestion. Alcohol increased the
duration and frequency of the occlusive episodes in five patients with obstructive
sleep apnoea, and resulted in a marked increase in the degree of hypoxaemia in
the first hour of sleep. In two patients with benign chronic snoring, alcohol
induced frank obstructive sleep apnoea during the first hour of sleep. We suggest
that the increased tendency to develop obstructive apnoea after alcohol is the
result of alcohol-induced oropharyngeal muscle hypotonia, while the increased
duration of obstructive apnea is the result of alcohol-induced depression of arousal
mechanisms.
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Reversal of obstructive
sleep apnoea by continuous positive airway pressure applied through the nares.
Sullivan CE. Issa FG.
Berthon-Jones M. Eves L. Lancet. 1(8225):862-5, 1981 Apr 18.
Five patients with severe
obstructive sleep apnoea were treated with continuous positive airway pressure
(CPAP) applied via a comfortable nose mask through the nares. Low levels of pressure
(range 4.5-10 cm H2O) completely prevented upper airway occlusion during sleep
in each patient and allowed an entire night of uninterrupted sleep. Continuous
positive airway pressure applied in this manner provides a pneumatic splint for
the nasopharyngeal airway and is a safe, simple treatment for the obstructive
sleep apnoea syndrome.
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