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Atul Malhotra

Publications and source records attributed to Atul Malhotra.

53 records · Page 3Linked to original sources
PubMed2003

Anatomic and physiologic predictors of apnea severity in morbidly obese subjects.

STUDY OBJECTIVES: While obesity is the most common risk factor for the development of obstructive sleep apnea, the correlation between measures of obesity and apnea severity is only moderate. We thus attempted to identify anatomic and physiologic predictors of apnea severity. DESIGN: We combined a careful assessment of upper airway anatomy, upper airway physiology, and ventilatory control in a group of obese individuals to identify predictors of apnea severity. SETTING: Tertiary care academic medical center. PATIENTS: 14 morbidly obese subjects being evaluated for weight-reduction surgery. INTERVENTIONS: N/A MEASUREMENT AND RESULTS: We found no relationship between obesity (weight or body mass index) and apnea severity (respiratory disturbance index, RDI). However, those with severe apnea (RDI > 30) were found to have higher peak genioglossus EMG (GGEMG) (23.5 +/- 1.9 vs. 14.1 +/- 3.7 %max, p = 0.05) and greater airway collapsibility during pulses of negative pressure (7.6 +/- 0.9 vs. 4.4 -/+/-0.7 cmH2O, p =0.02). Airway collapsibility was significantly associated with RDI (r = 0.62, p < 0.01) as was peak GGEMG (r = 0.55, p < 0.05). Of the anatomic variables airway shape (A-P/lateral ratio) and volume change of the pharyngeal airway between total lung capacity and residual volume were different between those with and without severe apnea. Both correlated with RDI (A-P/lateral ratio: r = 0.70, p < 0.01 and volume change: r = 0.77, p < 0.01). CONCLUSIONS: We believe these findings suggest that specific anatomic and physiologic properties of the airway interact with obesity to predispose to the development of airway collapse during sleep.

Adult↗
PubMed2003

Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis.

BACKGROUND: Although continuous positive airway pressure (CPAP) has become the standard of care in the treatment of obstructive sleep apnea (OSA), 2 systematic reviews have questioned its utility. Since the publication of these reviews, several randomized controlled trials have been reported. We, therefore, performed a meta-analysis to assess the effect of CPAP on subjective and objective sleepiness. METHODS: We conducted a thorough literature search to identify all published randomized controlled trials of CPAP in patients with OSA. Meta-analyses were performed using a random-effects model. Statistical heterogeneity was assessed using the Q statistic. RESULTS: Twelve trials of CPAP in patients with OSA meeting our inclusion criteria were found. The Epworth Sleepiness Scale score was reported in 11 studies (706 patients). A meta-analysis found that CPAP reduced the Epworth Sleepiness Scale score an average of 2.94 points more than placebo (P<.001). The heterogeneity (Q10 = 57.7, P<.001) between studies could not be explained by differences in sex composition, mean age, mean body mass index, or country of study. Trials recruiting subjects with severe OSA plus sleepiness (mean apnea-hypopnea index, > or =30 events per hour; and mean Epworth Sleepiness Scale score, > or =11) had a greater decrease in the Epworth Sleepiness Scale score than the other studies (4.75 vs 1.10; P<.001). Objective measures of sleepiness were reported in 8 trials (482 subjects). Continuous positive airway pressure increased sleep onset latency by 0.93 minute (P =.04) more than placebo. CONCLUSIONS: Continuous positive airway pressure therapy significantly improves subjective and objective measures of sleepiness in patients with OSA across a diverse range of populations. Patients with more severe apnea and sleepiness seem to benefit the most.

Female↗
PubMed2003

A prospective study of sleep duration and coronary heart disease in women.

BACKGROUND: Long-term sleep deprivation is common in today's society. Recent experiments have demonstrated that short-term sleep deprivation in healthy subjects results in adverse physiologic changes, including a decreased glucose tolerance and an increased blood pressure. However, the long-term health consequences of long-term sleep deprivation are unclear. The objective of this study was to determine whether decreased sleep duration (from self-reports) is associated with an increased risk of coronary events. METHODS: We studied a cohort of 71 617 US female health professionals (aged 45-65 years), without reported coronary heart disease (CHD) at baseline, who were enrolled in the Nurses' Health Study. Subjects were mailed a questionnaire in 1986 asking about daily sleep duration. Subjects were followed up until June 30, 1996, for the occurrence of CHD-related events. We assessed the relationship between self-reported sleep duration and incident CHD. RESULTS: A total of 934 coronary events were documented (271 fatal and 663 nonfatal) during the 10 years of follow up. Age-adjusted relative risks (95% confidence intervals) of CHD (with 8 hours of daily sleep being considered the reference group) for individuals reporting 5 or fewer, 6, and 7 hours of sleep were 1.82 (1.34-2.41), 1.30 (1.08-1.57), and 1.06 (0.89-1.26), respectively. The relative risk (95% confidence interval) for 9 or more hours of sleep was 1.57 (1.18-2.11). After adjusting for various potential confounders, including snoring, body mass index, and smoking, the relative risks of CHD (95% confidence intervals) for individuals reporting 5 or fewer, 6, and 7 hours of sleep were 1.45 (1.10-1.92), 1.18 (0.98-1.42), and 1.09 (0.91-1.30), respectively. The relative risk (95% confidence interval) for 9 or more hours of sleep was 1.38 (1.03-1.86). CONCLUSION: Short and long self-reported sleep durations are independently associated with a modestly increased risk of coronary events.

Adult↗
PubMed2003

Awake negative pressure reflex response of the genioglossus in OSA patients and normal subjects.

We hypothesized that the response of the genioglossus to negative pressure during wakefulness should be intact in obstructive sleep apnea (OSA) patients despite published evidence showing impairment of the response of palatal muscles (Mortimore IL and Douglas NJ. Am J Respir Crit Care Med 156: 867-873, 1997). Thus the response of the genioglossus to brief nasal negative pressure applications (NPAs) in early inspiration was compared between OSA patients and an age-matched group of normal subjects at two study sites (n = 11 per group in Long Beach, n = 14 per group in Boston). Subjects were studied in the sitting (Long Beach) or supine (Boston) posture, and the genioglossus electromyogram (EMGgg) was measured with an intraoral surface electrode (Long Beach) or intramuscular electrode (Boston). The response of the EMGgg was expressed as the percent change from baseline where the baseline EMGgg was the value at the onset of the NPA. In Long Beach, the EMGgg response was significantly higher in the OSA patients at a lower suction pressure of approximately 10 cmH(2)O (75.2 +/- 8.4 vs. 37.4 +/- 4.0% increase; P < 0.001) but not at a higher suction pressure of approximately 20 cmH(2)O. In Boston, the response in the OSA patients was also greater (107.2 +/- 25.9 vs. 46.3 +/- 8.3%; P < 0.05) at a suction pressure of approximately 13 cmH(2)O. We conclude that the response of the genioglossus to NPA during wakefulness is not impaired in OSA patients compared with normal subjects and is greater at low suction pressures.

Adult↗
PubMed2003

Interactions between hypoglycemia and sleep architecture in children with type 1 diabetes mellitus.

OBJECTIVES: To assess the interactions between nocturnal hypoglycemia and sleep in children with type 1 diabetes mellitus (DM). STUDY DESIGN: Children with DM (n = 15) and 15 matched control children underwent full night polysomnographic recordings. Blood glucose levels were measured in the diabetic children by means of the MiniMed Continuous Glucose Monitoring System. Six of the diabetic children were also studied by peripheral arterial tonometry (an indirect indicator of sympathetic responses). RESULTS: Five children with DM (33%) had profound nocturnal hypoglycemia, which was associated with increased sleep efficiency, increased slow wave sleep, and increased Delta power in spectral analysis of the electroencephalogram. Hypoglycemic episodes were not associated with sympathetic activation. Rapid decline in glucose levels (>25 mg/dL/hour) but not the absolute degree of hypoglycemia were associated with awakenings from sleep. CONCLUSIONS: We conclude that sleep may inhibit sympathetic and arousal response to hypoglycemia. Rapid changes in glucose levels, independent of absolute glucose levels, may result in awakening from sleep. Continuous measurement of glucose levels during sleep may add important features in the treatment of children with DM.

Adolescent↗
PubMed2002

The male predisposition to pharyngeal collapse: importance of airway length.

Obstructive sleep apnea is an important disorder because of both its prevalence and its cardiovascular and neurocognitive sequelae. Despite the fact that male sex is a major risk factor for this disorder, the mechanisms underlying this predisposition are unclear. To understand the pathophysiologic basis of the male predisposition for pharyngeal collapse, we performed a detailed analysis of the anatomic and physiologic features of the upper airway in a cohort of normal and near-normal subjects (equal number of men and women). Although no important physiologic (genioglossal electromyogram, airflow resistance) differences were observed between sexes, a number of anatomic differences were apparent. The pharyngeal airway length was substantially longer in men compared with women. There was also an increased cross-sectional area of the soft palate and an increased airway volume in men compared with women. Using signal-averaged anatomic data from male and female subjects, we developed representative male and female finite element airway models. This model demonstrated the male airway to be substantially more collapsible than the female airway, solely on the basis of anatomic differences. This study suggests that the male predisposition to pharyngeal collapse is anatomically based, primarily as the result of an increased length of vulnerable airway as well as increased soft palate size.

Adult↗
PubMed2002

Respiratory system loop gain in normal men and women measured with proportional-assist ventilation.

We hypothesized that increased chemical control instability (CCI) in men could partially explain the male predominance in obstructive sleep apnea (OSA). CCI was assessed by sequentially increasing respiratory control system loop gain (LG) with proportional-assist ventilation (PAV) in 10 men (age 24-48 yr) and 9 women (age 22-36 yr) until periodic breathing or awakening occurred. Women were studied in both the follicular and luteal phases of the menstrual cycle. The amount by which PAV amplified LG was quantified from the tidal volume amplification factor [(VtAF) assisted tidal volume/unassisted tidal volume]. LG was calculated as the inverse of the VtAF occurring at the assist level immediately preceding the emergence of periodic breathing (when LG x VtAF = 1). Only 1 of 10 men and 2 of 9 women developed periodic breathing with PAV. The rest were resistant to periodic breathing despite moderately high levels of PAV amplification. We conclude that LG is low in the majority of normal men and women and that higher volume amplification factors are needed to determine whether gender differences exist in this low range.

Adult↗
PubMed2002

Obstructive sleep apnoea.

Obstructive sleep apnoea is a disease of increasing importance because of its neurocognitive and cardiovascular sequelae. Abnormalities in the anatomy of the pharynx, the physiology of the upper airway muscle dilator, and the stability of ventilatory control are important causes of repetitive pharyngeal collapse during sleep. Obstructive sleep apnoea can be diagnosed on the basis of characteristic history (snoring, daytime sleepiness) and physical examination (increased neck circumference), but overnight polysomnography is needed to confirm presence of the disorder. Repetitive pharyngeal collapse causes recurrent arousals from sleep, leading to sleepiness and increased risk of motor vehicle and occupational accidents. The surges in hypoxaemia, hypercapnia, and catecholamine associated with this disorder have now been implicated in development of hypertension, but the association between obstructive sleep apnoea and myocardial infarction, stroke, and congestive heart failure is not proven. Continuous positive airway pressure, the treatment of choice for obstructive sleep apnoea, reduces sleepiness and improves hypertension.

Female↗
PubMed2002

Genioglossus muscle responsiveness to chemical and mechanical stimuli during non-rapid eye movement sleep.

Previous studies have suggested that during non-rapid eye movement (NREM) sleep, neither large short-duration resistive loads nor sustained normoxic hypercapnia alone leads to increased genioglossus muscle activation. However, in normal individuals during stable NREM sleep, genioglossus activity rises above baseline as PCO2 rises and airway resistance increases. We therefore hypothesized that combinations of chemical (PCO2, PO2) and mechanical stimuli during NREM sleep would lead to increased genioglossal activation. We studied 15 normal subjects (9 males, 6 females) during stable NREM sleep, measuring genioglossus electromyogram, epiglottic/choanal pressure, and airflow under six conditions: (1) baseline, (2) inspiratory resistive loading (-5 to -15 cm H2O/ L/second), (3) increased PCO2 (5-10 mm Hg above baseline), (4) combined resistive loading and increased PCO2, (5 ) hypoxia (SaO2 80-85%), and (6 ) combined hypoxia/inspiratory resistive loading. Only the combined condition of hypercapnia and resistive loading led to significantly increased genioglossal activation, 3.91 +/- 0.77% to 9.64 +/- 1.96% of maximum. These data suggest that the genioglossus muscle is less responsive to either chemical stimuli (hypercapnia, hypoxia) or inspiratory resistive loading alone during NREM sleep at the degrees tested. When hypercapnia is combined with resistive loading, the muscle does respond. However, the possibility that higher levels of PCO2 or greater resistive loading alone could activate the muscle cannot be excluded.

Adult↗
PubMed2002

Pharyngeal pressure and flow effects on genioglossus activation in normal subjects.

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnea syndrome. Substantial data support the role of local mechanisms in mediating pharyngeal dilator muscle activation in normal humans during wakefulness. Using a recently reported iron lung ventilation model, we sought to determine the stimuli modulating genioglossus activity, dissociating the influences of pharyngeal negative pressure, from inspiratory airflow, resistance, and CO(2). To achieve this aim, we used two gas densities at several levels of end-tidal CO(2) and a number of intrapharyngeal negative pressures. The correlations between genioglossus electromyography (GGEMG) and epiglottic pressure across a breath remained robust under all conditions (R values range from 0.71 +/- 0.07 to 0.83 +/- 0.05). In addition, there was no significant change in the slope of this relationship despite variable gas density or CO(2) levels. Although flow also showed strong correlations with genioglossus activity, there was a significant change in the slope of the GGEMG/flow relationship with altered gas density. For the group averages across conditions (between breath analysis), the correlation with GGEMG was robust for negative pressure (R(2) = 0.98) and less strong for other variables such as flow and resistance. These data suggest that independent of central pattern generator activity, intrapharyngeal negative pressure itself modulates genioglossus activity both within breaths and between breaths.

Adult↗
PubMed2002

Angiogenic growth factors in the pathophysiology of a murine model of acute lung injury.

Capillary leakage and alveolar edema are hallmarks of acute lung injury (ALI). Neutrophils and serum macromolecules enter alveoli, promoting inflammation. Vascular endothelial growth factor (VEGF) causes plasma leakage in extrapulmonary vessels. Angiopoietin (Ang)-1 and -4 stabilize vessels, attenuating capillary leakage. We hypothesized that VEGF and Ang-1 and -4 modulate vessel leakage in the lung, contributing to the pathogenesis of ALI. We examined a murine model of lipopolysaccharide (LPS)-induced ALI. C57BL/6 and 129/J mice were studied at baseline and 24, 48, and 96 h after single or multiple doses of aerosolized LPS. Both strains exhibited time- and dose-dependent increases in inflammation and a deterioration of lung mechanics. Bronchoalveolar lavage (BAL) protein levels increased significantly, suggesting capillary leakage. Increased BAL neutrophil and total protein content correlated with time-dependent increased tissue VEGF and decreased Ang-1 and -4 levels, with peak VEGF and minimum Ang-1 and -4 expression after 96 h of LPS challenge. These data suggest that changes in the balance between VEGF and Ang-1 and -4 after LPS exposure may modulate neutrophil influx, protein leakage, and alveolar flooding during early ALI.

Acute Disease↗
PubMed2002

Severe hypersomnolence after pituitary/hypothalamic surgery in adolescents: clinical characteristics and potential mechanisms.

OBJECTIVES: After resection of hypothalamic/pituitary tumors, children are at risk for development of hormonal deficiencies, obesity, and hypersomnolence. However, the prevalence and pathophysiology of these complications are unclear. The purpose of this study was to assess the prevalence and severity of hypersomnolence in children after resection of pituitary tumors and to study the potential factors that contribute to this sleepiness if present. We further hypothesized that decrements in orexin levels may contribute to the sleepiness. METHODS: Six children who underwent hypothalamic/pituitary surgery were identified. Five of these patients and 5 matched control subjects underwent overnight polysomnography followed by a multiple sleep latency test. Children who had a primary sleep disorder (eg, obstructive sleep apnea) underwent treatment and were restudied subsequently (n = 2). Blood levels of pituitary hormones were measured. Blood and cerebrospinal fluid (CSF) were drawn from 4 patients and 3 control subjects to measure orexin levels. RESULTS: Endocrine control was appropriate in all children. Although patients had longer sleep duration but similar sleep efficiency than control subjects, relatively severe daytime somnolence was present (mean sleep latency: 10.3 +/- 5.3 minutes vs 26.2 +/- 1.1 minute in control subjects). Sleepiness did not correlate with body mass index or age. Furthermore, serum and CSF orexin levels did not differ between patients and control subjects. CONCLUSIONS: Severe daytime sleepiness is frequent among children who undergo pituitary/hypothalamic surgery and does not seem to result from inappropriate cortisol or thyroxine replacement, disturbed nocturnal sleep, or low levels of orexin in the serum or CSF. We therefore speculate that other, unidentified neurohormonal mechanisms may mediate the excessive sleepiness of these patients.

Adolescent↗
PubMed2000

Post-traumatic stress disorder and sleep-what a nightmare!

According to DSM IV criteria, sleep disturbances are incorporated in the definition of post-traumatic stress disorder (PTSD). These include the re-experiencing symptoms (nightmares, criteria B) and a hyperarousal state (difficulty initiating and maintaining sleep, criteria D). PTSD patients commonly complain of sleep disturbances. Moreover, insomnia, restless sleep and trauma-related dreams might be the primary complaint of some patients. However, although subjective sleep disturbances are considered characteristic of PTSD, sleep laboratory studies have provided inconsistent evidence of objective sleep disorders. A variety of sleep architectures and sleep patterns has been reported in PTSD. However, only a few studies have controlled for comorbidities. Thus, uncertainty exists to what extent the sustained complaints of sleep disturbances in chronic PTSD are specifically related to the impact of exposure to traumatic stress, or rather are a consequence of comorbid disorders. Specific changes in REM sleep suggest a pathophysiologic role of REM sleep abnormality in PTSD (e.g. anxiety dreams, increased REM density, exaggerated startle response, decreased dream recall and elevated awakening thresholds from REM sleep). However, again, studies have failed to show consistent changes in percentage of REM sleep or in REM latency. There might be a coexistence of pressure to REM along with inhibitory forces of REM that result in high variability of REM parameters across patients. Alternatively, changes in REM sleep might reflect the effect of comorbid psychiatric disorders that results in inconsistent findings between patients. The current review tries to address these issues based on recent studies carried out in this field.

Journal Article↗