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Atul Malhotra

Publications and source records attributed to Atul Malhotra.

At least 37 records · Page 2Linked to original sources
PubMed2005

High-frequency oscillatory ventilation: what large-animal studies have taught us!

BACKGROUND: Much of the information on the physiologic effects, mechanisms of gas exchange, and potential utility of high-frequency oscillation (HFO) has been acquired in animal studies. Specifically, large animal data have been useful in assessing adult application because large animals present many of the same concerns and challenges as adults. OBJECTIVE: To review the literature on HFO testing in large animal models, identifying contributions to the understanding of mechanisms of action and the physiology of HFO. RESULTS: Large animal studies have clarified the mechanisms of gas exchange during HFO, identified approaches to setting mean airway pressure based on lung mechanics, and identified a potentially better approach to applying partial liquid ventilation. CONCLUSION: The study of HFO in large animal models has been essential to our understanding of the optimal approach to applying HFO in human studies.

Animals↗
PubMed2005

Paradoxical responses to positive end-expiratory pressure in patients with airway obstruction during controlled ventilation.

OBJECTIVE: To reevaluate the clinical impact of external positive end-expiratory pressure (external-PEEP) application in patients with severe airway obstruction during controlled mechanical ventilation. The controversial occurrence of a paradoxic lung deflation promoted by PEEP was scrutinized. DESIGN: External-PEEP was applied stepwise (2 cm H(2)O, 5-min steps) from zero-PEEP to 150% of intrinsic-PEEP in patients already submitted to ventilatory settings minimizing overinflation. Two commonly used frequencies during permissive hypercapnia (6 and 9/min), combined with two different tidal volumes (VT: 6 and 9 mL/kg), were tested. SETTING: A hospital intensive care unit. PATIENTS: Eight patients were enrolled after confirmation of an obstructive lung disease (inspiratory resistance, >20 cm H(2)O/L per sec) and the presence of intrinsic-PEEP (> or =5 cm H(2)O) despite the use of very low minute ventilation. INTERVENTIONS: All patients were continuously monitored for intra-arterial blood gas values, cardiac output, lung mechanics, and lung volume with plethysmography. MEASUREMENTS AND MAIN RESULTS: Three different responses to external-PEEP were observed, which were independent of ventilatory settings. In the biphasic response, isovolume-expiratory flows and lung volumes remained constant during progressive PEEP steps until a threshold, beyond which overinflation ensued. In the classic overinflation response, any increment of external-PEEP caused a decrease in isovolume-expiratory flows, with evident overinflation. In the paradoxic response, a drop in functional residual capacity during external-PEEP application (when compared to zero-external-PEEP) was commonly accompanied by decreased plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The paradoxic response was observed in five of the eight patients (three with asthma and two with chronic obstructive pulmonary disease) during at least one ventilator pattern. CONCLUSIONS: External-PEEP application may relieve overinflation in selected patients with airway obstruction during controlled mechanical ventilation. No a priori information about disease, mechanics, or ventilatory settings was predictive of the response. An empirical PEEP trial investigating plateau pressure response in these patients appears to be a reasonable strategy with minimal side effects.

Adult↗
PubMed2005

Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy.

STUDY OBJECTIVES: To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]). DESIGN AND SETTING: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center. PARTICIPANTS: Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months. MEASUREMENTS AND RESULTS: The groups were similar demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/- 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment. CONCLUSIONS: Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.

Adult↗
PubMed2005

Interferon-gamma1b therapy in idiopathic pulmonary fibrosis: a metaanalysis.

CONTEXT: Despite the investigation of multiple therapeutic options, idiopathic pulmonary fibrosis (IPF) remains a devastating, progressively fatal disease. Much interest has focused on the use of interferon (IFN)-gamma1b therapy, but the efficacy of this treatment has not been proven. OBJECTIVE: To determine whether IFN treatment reduces mortality in patients with IPF. DESIGN: A meta-analysis of randomized controlled trials evaluating the use of IFN-gamma1b as treatment for IPF. MAIN OUTCOME MEASURE: Mortality in patients treated with IFN-gamma1b was compared to mortality in patients treated with control therapies. RESULTS: A total of three studies involving 390 patients was included in the analysis. IFN-gamma1b therapy was associated with reduced mortality (hazard ratio [HR], 0.418; 95% confidence interval [CI], 0.253 to 0.690; p = 0.0003). A comparison of mortality at different time points revealed that IFN-gamma1b therapy was associated with significantly reduced mortality at 1 year (0.0861; 95% CI, 0.0244 to 0.1478; p = 0.0063), 18 months (0.1682; 95% CI, 0.1065 to 0.2299; p < 0.0001), 650 days (0.1939; 95% CI, 0.1386 to 0.2492; p < 0.0001), and 2 years (0.2652; 95% CI, 0.1652 to 0.3652; p < 0.0001). CONCLUSION: When the results of multiple studies are combined in a meta-analysis, IFN-gamma1b therapy is associated with reduced mortality.

Humans↗
PubMed2005

The impact of anatomic manipulations on pharyngeal collapse: results from a computational model of the normal human upper airway.

Obstructive sleep apnea (OSA) is a common disease with important neurocognitive and cardiovascular sequelae. Existing therapies are unsatisfactory, leading investigators to seek alternative forms of anatomic manipulation to influence pharyngeal mechanics. We have developed a two-dimensional computational model of the normal human upper airway based on signal averaging of MRI. Using the finite element method, we can perform various anatomic perturbations on the structure in order to assess the impact of these manipulations on pharyngeal mechanics and collapse. By design, the normal sleeping upper airway model collapses at -13 cm H2O. This closing pressure becomes more negative (ie, less collapsible) when we perform mandibular advancement (-21 cm H2O), palatal resection (-18 cm H2O), or palatal stiffening (-17 cm H2O). Where clinical data are available in the literature, the results of our model correspond reasonably well. Furthermore, our model provides information regarding the site of obstruction and provides hypotheses for clinical studies that can be undertaken in the future (eg, combination therapies). We believe that, in the future, finite element modeling will provide a useful tool to help advance our understanding of OSA and its response to various therapies.

Airway Obstruction↗
PubMed2004

Assessment of automated scoring of polysomnographic recordings in a population with suspected sleep-disordered breathing.

STUDY OBJECTIVES: To assess the accuracy of an automated system (Morpheus I Sleep Scoring System) for analyzing and quantifying polysomnographic data from a population with sleep-disordered breathing. SETTING: Sleep laboratory affiliated with a tertiary care academic medical center. MEASUREMENTS AND RESULTS: 31 diagnostic polysomnograms were blindly analyzed prospectively with the investigational automated system and manually by 2 registered polysomnography technologists (M1 & M2) from the same laboratory. Sleep stages, arousals, periodic limb movements, and respiratory events (apneas and hypopneas) were scored by all 3. Agreement, Cohen kappa, and intraclass correlation coefficients were tabulated for each variable and compared between scoring pairs (A-M1, A-M2, M1-M2). The 26,876 epochs (224 hours of recording time) were analyzed. For sleep staging, agreement/kappa were A-M1: 78%/0.67, A-M2: 73%/0.61, and M1-M2: 82%/0.73. The mean respiratory disturbance indexes were M1: 20.6+/-23.0, M2: 22.5+/-24.5, and A: 23.7+/-23.4 events per hour of sleep. The respiratory disturbance index concordance between each scoring pair was excellent (intraclass correlation coefficients > or = 0.95 for all pairs), although there was disagreement in the classification of moderate sleep-disordered breathing (percentage of positive agreement: A-M1, 37.5% and A-M2, 44.4%) defined as a respiratory disturbance index between 15 and 30 events per hour of sleep. For respiratory-event detection, agreement/kappa were A-M1 and A-M2: 90%/0.66 and M1-M2: 95%/0.82. The agreement and kappa for limb movement detection were A-M1: 93%/0.68, A-M2: 92%/0.66, and M1-M2: 96%/0.77. The scoring of arousals was less reliable (agreement range: 76%-84%, kappa range: 0.28-0.57) for all pairs. CONCLUSIONS: Agreement between manual scorers in a population with moderate sleep-disordered breathing was close to the average pairwise agreement of 87% reported in the Sleep Heart Health Study. The automated classification of sleep stages was also close to this standard. The automated scoring system holds promise as a rapid method to score polysomnographic records, but expert verification of the automated scoring is required.

Adult↗
PubMed2004

Postural effects on pharyngeal protective reflex mechanisms.

STUDY OBJECTIVES: Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion. DESIGN: We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses. SETTING: Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital. SUBJECTS/PARTICIPANTS: 17 normal subjects. MEASUREMENTS AND RESULTS: We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum [%max] +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness. CONCLUSION: We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep.

Adult↗
PubMed2004

Ventilatory control and airway anatomy in obstructive sleep apnea.

Ventilatory instability may play an important role in the pathogenesis of obstructive sleep apnea. We hypothesized that the influence of ventilatory instability in this disorder would vary depending on the underlying collapsibility of the upper airway. To test this hypothesis, we correlated loop gain with apnea-hypopnea index during supine, nonrapid eye movement sleep in three groups of patients with obstructive sleep apnea based on pharyngeal closing pressure: negative pressure group (pharyngeal closing pressure less than -1 cm H(2)O), atmospheric pressure group (between -1 and +1 cm H(2)O), and positive pressure group (greater than +1 cm H(2)O). Loop gain was measured by sequentially increasing proportional assist ventilation until periodic breathing developed, which occurred in 24 of 25 subjects. Mean loop gain for all three groups was 0.37 +/- 0.11. A significant correlation was found between loop gain and apnea-hypopnea index in the atmospheric group only (r = 0.88, p = 0.0016). We conclude that loop gain has a substantial impact on apnea severity in certain patients with sleep apnea, particularly those with a pharyngeal closing pressure near atmospheric.

Adult↗
PubMed2004

Using a wrist-worn device based on peripheral arterial tonometry to diagnose obstructive sleep apnea: in-laboratory and ambulatory validation.

STUDY OBJECTIVES: To assess the accuracy of a wrist-worn device (Watch_PAT 100) to diagnose obstructive sleep apnea in the home. DESIGN: Participants completed 2 overnight diagnostic studies with the test device: 1 night in the laboratory with concurrent polysomnography and 1 night in the home with only the Watch_PAT. The order of the laboratory and home study nights was random. The frequency of respiratory events on the PSG was quantified using indexes based on 2 definitions of hypopnea: the respiratory disturbance index (RDI) using American Academy of Sleep Medicine Task Force criteria for clinical research, also referred to as the Chicago criteria (RDI.C), and the Medicare guidelines (RDI.M). The Watch_PAT RDI (PAT RDI) and oxygen desaturation index (PAT ODI) were then evaluated against the polysomnography RDI.C and RDI.M, respectively, for both Watch_PAT diagnostic nights, yielding IN-LAB and HOME-LAB comparisons. SETTING: Sleep laboratory affiliated with a tertiary-care academic medical center. PATIENTS: 30 patients referred with suspected OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The polysomnography and PAT measures were compared using the mean [2 SD] of the differences and the intra-class correlation coefficient (ICC). The receiver-operator characteristic curve was used to assess optimum sensitivity and specificity and calculate likelihood ratios. For the IN-LAB comparison, there was high concordance between RDI.C and PAT RDI (ICC = 0.88, mean difference 2.5 [18.9] events per hour); RDI.M and PAT ODI (ICC = 0.95, mean difference 1.4 [12.9] events per hour; and sleep time (ICC = 0.70, mean difference 7.0 [93.1] minutes) between the test device and PSG. For the HOME-LAB comparison, there was good concordance between RDI.C and PAT RDI (ICC = 0.72, mean difference 1.4 [30.1] events per hour) and RDI.M and PAT ODI (ICC = 0.80, mean difference 1.6 [26.4] events per hour) for the test device and PSG. Home studies were performed with no technical failures. CONCLUSIONS: In a population of patients suspected of having obstructive sleep apnea, the Watch_PAT can quantify an ODI that compares very well with Medicare criteria for defining respiratory events and an RDI that compares favorably with Chicago criteria for defining respiratory events. The device can be used with a low failure rate for single use in the lab and home for self-administered testing.

Adult↗
PubMed2004

The influence of gender and upper airway resistance on the ventilatory response to arousal in obstructive sleep apnoea in humans.

The termination of obstructive respiratory events is typically associated with arousal from sleep. The ventilatory response to arousal may be an important determinant of subsequent respiratory stability/instability and therefore may be involved in perpetuating obstructive respiratory events. In healthy subjects arousal is associated with brief hyperventilation followed by more prolonged hypoventilation on return to sleep. This study was designed to assess whether elevated sleeping upper airway resistance (R(UA)) alters the ventilatory response to arousal and subsequent breathing on return to sleep in patients with obstructive sleep apnoea (OSA). Inspired minute ventilation (V(I)), R(UA) and end-tidal CO(2) pressure (P(ET,CO(2))) were measured in 22 patients (11 men, 11 women) with OSA (mean +/-s.e.m., apnoea-hypopnoea index (AHI) 48.9 +/- 5.9 events h(-1)) during non-rapid eye movement (NREM) sleep with low R(UA) (2.8 +/- 0.3 cmH(2)O l(-1) s; optimal continuous positive airway pressure (CPAP) = 11.3 +/- 0.7 cmH(2)O) and with elevated R(UA) (17.6 +/- 2.8 cmH(2)O l(-1) s; sub-optimal CPAP = 8.4 +/- 0.8 cmH(2)O). A single observer, unaware of respiratory data, identified spontaneous and tone-induced arousals of 3-15 s duration preceded and followed by stable NREM sleep. V(I) was compared between CPAP levels before and after spontaneous arousal in 16 subjects with tone-induced arousals in both conditions. During stable NREM sleep at sub-optimal CPAP, P(ET,CO(2)) was mildly elevated (43.5 +/- 0.8 versus 42.5 +/- 0.8 Torr). However, baseline V(I) (7.8 +/- 0.3 versus 8.0 +/- 0.3 l min(-1)) was unchanged between CPAP conditions. For the first three breaths following arousal, V(I) was higher for sub-optimal than optimal CPAP (first breath: 11.2 +/- 0.9 versus 9.3 +/- 0.6 l min(-1)). The magnitude of hypoventilation on return to sleep was not affected by the level of CPAP and both obstructive and central respiratory events were rare following arousal. Similar results occurred after tone-induced arousals which led to larger responses than spontaneous arousals. V(I) for the first breath following arousal under optimal CPAP was greater in men than women (11.0 +/- 0.4 versus 7.6 +/- 0.6 l min(-1)). These results demonstrate that the ventilatory response to arousal is influenced by pre-arousal airway resistance and gender. Whether this contributes to the perpetuation of respiratory events and the pathogenesis of OSA is unclear.

Adult↗
PubMed2004

Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a meta-analysis.

STUDY OBJECTIVE: To compare the effectiveness of auto-titrating continuous positive airway pressure (APAP) versus conventional continuous positive airway pressure (CPAP) in reducing the apnea-hypopnea index (AHI), reducing the mean airway pressure, improving subjective sleepiness, and improving treatment adherence in patients with obstructive sleep apnea (OSA). DESIGN: Meta-analysis and metaregression of published randomized trials comparing APAP to CPAP. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: We identified 9 randomized trials studying a total of 282 patients. Compared to CPAP, there was no significant advantage of APAP in reducing AHI or sleepiness (pooled APAP-CPAP posttreatment AHI and Epworth Sleepiness Scale score = -0.20 events per hour, 95% confidence interval:[-0.74,0.35], and -0.56 [-1.4,0.3] respectively). The use of APAP reduced the mean applied pressure across the night by 2.2 cm water [1.9,2.5] compared to CPAP. Adherence with therapy was not substantially improved with APAP; pooled estimate of improvement was 0.20 hours per night ([-0.16,0.57], P = .28) using a random-effects model. CONCLUSIONS: Compared to standard CPAP, APAP is associated with a reduction in mean pressure. However, APAP and standard CPAP were similar in adherence and their ability to eliminate respiratory events and to improve subjective sleepiness. Given that APAP is more costly than standard CPAP, APAP should not be considered first-line chronic therapy in all patients with OSA. However, APAP may be useful in other situations (eg, home titrations, detection of mouth leak) or in certain subgroups of patients with OSA. Identifying circumstances in which APAP is a definite improvement over CPAP in terms of costs or effects should be the focus of future studies.

Humans↗
PubMed2004

Methods of monitoring shock.

Intensive monitoring is a crucial component of the management of shock. However, there is little consensus about optimal strategies for monitoring. Although the pulmonary artery catheter has been widely used, conflicting data exist about the utility of this device. A variety of other techniques have been developed in hopes of providing clinically useful information about myocardial function, intravascular volume, and indices of organ function. In addition, there is evolving evidence that targeting and monitoring certain physiological goals may be most important early in the course of shock. In this chapter, we examine many of the available monitoring techniques and the evidence supporting their use.

Journal Article↗
PubMed2004

The role of open-lung biopsy in ARDS.

STUDY OBJECTIVES: The role of open-lung biopsy in ARDS has been questioned due to potentially high morbidity and low diagnostic yield. The goals of this study were to better define the frequency of unexpected diagnoses made by open-lung biopsy, the frequency biopsy results lead to a change in clinical management, and the frequency of procedural complications. DESIGN: Case series. SETTING: A large tertiary referral center. PATIENTS: All individuals with available records undergoing open-lung biopsy between 1989 and 2000 for evaluation of ARDS based on the American-European Consensus Conference definition. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The mean age in this cohort of 57 patients was 53 years (SD, 18 years) with PaO(2)/fraction of inspired oxygen ratio of 145 mm Hg (SD, 61 mm Hg) at the time of biopsy. A pathologic diagnosis other than diffuse alveolar damage or fibroproliferation was found in 60% of patients. The most common alternative diagnoses were infection (n = 8), alveolar hemorrhage (n = 5), and bronchiolitis obliterans organizing pneumonia (n = 5). Alternative diagnoses were as frequent in immunocompetent as immunosuppressed hosts (60% vs 59%, respectively). Biopsy results led to a change in management in the majority of patients, with addition of specific therapy in 60% and withdrawal of unneeded therapy in 37%. Although the overall complication rate was 39%, major complications occurred in only 7% of cases. No deaths were attributable to the procedure. CONCLUSIONS: In selected patients with clinical ARDS, open-lung biopsy can be performed safely, often reveals an unsuspected diagnosis, and frequently leads to alterations in therapy.

Biopsy↗
PubMed2003

The influence of lung volume on pharyngeal mechanics, collapsibility, and genioglossus muscle activation during sleep.

STUDY OBJECTIVES: Previous studies in both awake and sleeping humans have demonstrated that lung-volume changes substantially affect upper-airway size and pharyngeal resistance and, thus, may influence pharyngeal patency. We sought to systematically investigate the isolated effects of lung-volume changes on pharyngeal collapsibility and mechanics and genioglossus muscle activation during stable non-rapid eye movement sleep. We hypothesized that lower lung volumes would lead to increased pharyngeal collapsibility, airflow resistance, and, in compensation, augmented genioglossus muscle activation. DESIGN: Nineteen normal individuals (age, 30.4 +/- 0.5 years; body mass index: 24.5 +/- 0.4 kg/m2) were studied during stable non-rapid eye movement sleep in a rigid head-out shell equipped with a variable positive/negative pressure attachment for manipulations of extrathoracic pressure and, thus, lung volume. SETTING: Sleep physiology laboratory. PARTICIPANTS: Normal healthy volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: We measured change in end-expiratory lung volume (EELV) (magnetometers), genioglossus electromyogram (GGEMG) (intramuscular electrodes), pharyngeal pressure, and collapsibility of the pharynx in response to a brief pulse of negative pressure (-8 to -15 cm H2O) under the following conditions: (1) baseline, (2) increased EELV (+1 liter), and (3) decreased EELV (-0.6 liter). Reduced lung volumes led to increased inspiratory airflow resistance (7.54 +/- 2.80 cm H2O x L(-1) x s(-1) vs 4.53 +/- 1.05 cm H2O x L(-1) x s(-1), mean +/- SEM, P = 0.02) and increased genioglossus muscle activation (GGEMG peak 14.6% +/- 1.5% of maximum vs 8.6% +/- 1.5% of maximum, maximum P = 0.001) compared to baseline. The pharynx was also more collapsible at low lung volumes (4.3 +/- 0.5 cm H2O vs 5.4 +/- 0.6 cm H2O, P = 0.04). CONCLUSIONS: We conclude that upper-airway muscles respond to changes in lung volumes but not adequately to prevent increased collapsibility. These results suggest that lung volume has an important influence on pharyngeal patency during non-rapid eye movement sleep in normal individuals.

Adult↗
PubMed2003

Control of upper airway muscle activity in younger versus older men during sleep onset.

Pharyngeal dilator muscles are clearly important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) are decreased at sleep onset, and that this decrement in muscle activity is greater in the apnoea patient than in healthy controls. We have also previously shown this decrement to be greater in older men when compared with younger ones. In order to explore the mechanisms responsible for this decrement in muscle activity nasal continuous positive airway pressure (CPAP) was applied to reduce negative pressure mediated muscle activation. We then investigated the effect of sleep onset (transition from predominantly alpha to predominantly theta EEG activity) on ventilation, upper airway muscle activation and upper airway resistance (UAR) in middle-aged and younger healthy men. We found that both GGEMG and TPEMG were reduced by the application of nasal CPAP during wakefulness, but that CPAP did not alter the decrement in activity in either muscle seen in the first two breaths following an alpha to theta transition. However, CPAP prevented both the rise in UAR at sleep onset that occurred on the control night, and the recruitment in GGEMG seen in the third to fifth breaths following the alpha to theta transition. Further, GGEMG was higher in the middle-aged men than in the younger men during wakefulness and was decreased more in the middle-aged men with the application of nasal CPAP. No differences were seen in TPEMG between the two age groups. These data suggest that the initial sleep onset reduction in upper airway muscle activity is due to loss of a 'wakefulness' stimulus, rather than to loss of responsiveness to negative pressure. In addition, it suggests that in older men, higher wakeful muscle activity is due to an anatomically more collapsible upper airway with more negative pressure driven muscle activation. Sleep onset per se does not appear to have a greater effect on upper airway muscle activity as one ages.

Adolescent↗
PubMed2003

Within-breath control of genioglossal muscle activation in humans: effect of sleep-wake state.

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnoea syndrome. Substantial data support the role of a local negative pressure reflex in modifying genioglossal activation across inspiration during wakefulness. Using a model of passive negative pressure ventilation, we have previously reported a tight relationship between varying intrapharyngeal negative pressures and genioglossal muscle activation (GGEMG) during wakefulness. In this study, we used this model to examine the slope of the relationship between epiglottic pressure (Pepi) and GGEMG, during stable NREM sleep and the transition from wakefulness to sleep. We found that there was a constant relationship between negative epiglottic pressure and GGEMG during both basal breathing (BB) and negative pressure ventilation (NPV) during wakefulness (slope GGEMG/Pepi 1.86+/-0.3 vs. 1.79+/-0.3 arbitrary units (a.u.) cmH2O(-1)). However, while this relationship remained stable during NREM sleep during BB, it was markedly reduced during NPV during sleep (2.27+/-0.4 vs. 0.58+/-0.1 a.u. cmH2O(-1)). This was associated with a markedly higher pharyngeal airflow resistance during sleep during NPV. At the transition from wakefulness to sleep there was also a greater reduction in peak GGEMG seen during NPV than during BB. These data suggest that while the negative pressure reflex is able to maintain GGEMG during passive NPV during wakefulness, this reflex is unable to do so during sleep. The loss of this protective mechanism during sleep suggests that an airway dependent upon such mechanisms (as in the patient with sleep apnoea) will be prone to collapse during sleep.

Adult↗