Abstract: Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea-hypopnea index [AHI] 48.6 +/- 5.2/h, mean +/- SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 +/- 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 microg/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 +/- 1.2 mm Hg before CPAP versus 13.9 +/- 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 +/- 19.6 versus 186.4 +/- 12.3 dyn. s. cm(-)(5), p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (DeltaPpa/DeltaSa(O(2)) 10.0 +/- 1.6 mm Hg before versus 6.3 +/- 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa (O(2)). We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.

Abstract: STUDY OBJECTIVE: We compared the validity of a new portable polysomnographic recorder against a laboratory-based polysomnographic system from the same manufacturer. DESIGN AND PATIENTS: Simultaneous, full polysomnographic recordings from the portable device (PSGP) and the laboratory-based system (PSGL) were obtained using separate sets of sensors on 20 patients referred for investigation of sleep apnea. SETTING: After initial optimization of signals, the portable device was left unattended in 10 of the patients (to simulate home studies), while in the other 10 the signals were reviewed on a laptop computer screen and adjustments to electrode or sensor placement made as needed during the studies. Recordings were manually scored by a technologist blinded to the origin of the data. MEASUREMENTS AND RESULTS: The quality of signals was comparable between the PSGP and PSGL studies, apart from a slight decrease in respiratory signal quality during PSGP studies that led to reduced confidence in respiratory event scoring. SaO2 signal loss was also greater in unattended PSGP. There was good agreement between PSGP and PSGL for sleep variables and the apnea-hypopnea index (r=0.99). The periodic limb movement index was slightly lower during unattended PSGP. Blinded physician assessment of the records led to a recommendation for repeat studies due to poor signal quality in one (10%) attended and one (10%) unattended portable recording. There was no significant discordance between PSGP and PSGL in the final diagnostic formulations. CONCLUSION: Portable polysomnography is a viable alternative to laboratory-based polysomnography and may be improved further by better sensor attachment.

Abstract: It is controversial whether obstructive sleep apnea (OSA) causes pulmonary hypertension (PH) in the absence of hypoxemic lung disease. To investigate this further we measured awake pulmonary hemodynamics, pulmonary gas exchange, and small airways function in 32 patients with OSA (apnea- hypopnea index, mean +/- SE, 46.2 +/- 3. 9/h) who had normal screening lung function. Pulmonary artery pressure (Ppa) and cardiac output were measured by Doppler echocardiography at three levels of inspired oxygen (FIO2 0.50, 0.21, and 0.11) and during incremental increases in pulmonary blood flow (10, 20, and 30 microgram/kg/min dobutamine infusions) while breathing 50% oxygen. Eleven patients had PH (mean Ppa >/= 20 mm Hg, Group I). They did not differ from patients without PH (Group II) in lung function, severity of sleep-disordered breathing, age, or body mass. Compared with Group II, Group I patients had increased small airways closure during tidal breathing (FRC-closing capacity: Group I, -0.16 +/- 0.11; Group II, 0.27 +/- 0.09 L; p < 0.05), more ventilation-perfusion inequality (AaPO2: 23.8 +/- 2.8; 19.8 +/- 1.4 mm Hg; p = 0.08), a greater pulmonary artery pressor response to hypoxia (DeltaPpa FIO2, 0.50 to 0.11: 16.4 +/- 1.93; 6.4 +/- 0.77 mm Hg; p < 0.05) and a marked rise in Ppa during increased pulmonary blood flow. We conclude that PH may develop in some patients with OSA without lung disease and that it is associated with small airways closure during tidal breathing and heightened pulmonary pressor responses to hypoxia and during increased pulmonary blood flow. Such changes are consistent with remodeling of the pulmonary vascular bed in affected patients with OSA, seemingly unrelated to severity of sleep-disordered breathing.

Abstract: Sleep disordered breathing is common in patients with tetraplegia. Nocturnal arterial hypoxemia and sleep fragmentation due to sleep apnoea may be associated with cognitive dysfunction. We therefore studied the influence of sleep disordered breathing on neuropsychological function in 37 representative tetraplegic patients (mean age 34 +/- 9.7 years). Thirty percent (11 of 37 patients) had clinically significant sleep disordered breathing, defined as apnoea plus hypopnoea index (AHI) greater than 15 per hour of sleep. Most apnoeas were obstructive in type. Seven patients (19%) desaturated to < 80% during the night. Neuropsychological variables were significantly correlated with measures of sleep hypoxia, but not with the AHI and the frequency of sleep arousals. The neuropsychological functions most affected by nocturnal desaturation were: verbal attention and concentration, immediate and short-term memory, cognitive flexibility, internal scanning and working memory. There appeared to be a weak association between the presence of severe sleep hypoxia and visual perception, attention and concentration but no association was found between sleep variables and depression scores. We concluded that sleep disordered breathing is common in patients with tetraplegia and may be accompanied with significant oxygen desaturation. The latter impairs daytime cognitive function in these patients, particularly attention, concentration, memory and learning skills. Cognitive disturbances resulting from sleep apnoea might adversely affect rehabilitation in patients with tetraplegia.

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Abstract: Changes in sleep posture have been shown to improve obstructive sleep apnea (OSA). To investigate the mechanisms by which this occurs we assessed upper airway stability in eight patients with severe OSA in three postures (supine, elevated to 30 degrees, and lateral). We used a specially adapted nasal continuous positive airway pressure (nCPAP) mask to measure upper airway closing pressure (UACP) and upper airway opening pressure (UAOP) during non-REM sleep. Statistical comparisons were made between postures using ANOVA for repeated measures. Elevation resulted in a less collapsible airway compared with both the supine and lateral positions (mean UACP: 30 degrees elevation -4.0 +/- 3.2 compared with supine 0.3 +/- 2.4 cm H2O, p < 0.05 and; lateral -1.1 +/- 2.2 cm H2O, p < 0.05). Supine UACP and lateral UACP were not significantly different. Elevation or lateral positioning produced a 50% reduction in mean UAOP (supine 10.4 +/- 3.5 cm H2O compared with 30 degrees elevation 5.3 +/- 2.1, p < 0.05; and lateral 5.5 +/- 2.1 cm H2O, p < 0.05). We conclude that in severely affected OSA patients upper body elevation, and to a lesser extent lateral positioning, significantly improve upper airway stability during sleep, and may allow therapeutic levels of nCPAP to be substantially reduced.

Abstract: Sleep-related respiratory disturbances are more common in men than in premenopausal women. This might, in part, be due to different susceptibilities to the respiratory depressant effects of hypoxia. Therefore, we compared ventilation during 10 min of baseline room-air breathing and 20-min sustained isocapnic hypoxia (fractional inspired O2 = 11%, arterial saturation of O2 approximately 80%) followed by 10 min of breathing 100% O2 in 10 normal men and in 10 women in the follicular phase of the menstrual cycle. Control measurements were made during two transitions from room air (10 min) to 100% O2 (10 min) and averaged. Inspired minute ventilation (VI) after 2 min of hypoxia was the same in men and women [131 +/- 6.1% baseline for men, 136 +/- 7.7% baseline for women; not significant (NS)] and declined to the same level after 20 min (115 +/- 5.0% baseline for men, 116 +/- 6.6% baseline for women; NS) associated with a similar decline in inspiratory time and tidal volume. Breathing frequency did not change. VI decreased transiently during subsequent 100% O2 breathing in both men and women, associated with reduced frequency and duty cycle and increased expiratory time. The fall in VI was significantly greater than that observed during control hyperoxia experiments in men but not in women. We conclude that ventilatory responses to sustained isocapnic hypoxia do not differ between awake healthy men and women in the follicular phase of their menstrual cycle. However, after termination of isocapnic hypoxia, men appear to depress their ventilation to a greater degree than women.

Abstract: STUDY OBJECTIVES AND PATIENTS: Pulmonary hypertension (PH) is common in COPD and may predict mortality in this disorder. We have compared the pulmonary vasodilator effects, dose-response characteristics, and tolerability of two calcium channel blockers, amlodipine and extended-release (ER) felodipine, in 10 patients (seven men, age 68+/-4.8 [SD] years) with clinically stable COPD and PH. DESIGN: Drugs were given in equal single daily oral doses (2.5, 5, and 10 mg), increasing weekly for 3 weeks, in a randomized investigator-blinded crossover manner with a 1-week wash-out period between the two treatments. MEASUREMENTS: Doppler measurements of pulmonary hemodynamics were made on the seventh day of treatment at each drug dose. Lung function, arterial blood gases, and adverse events were also monitored weekly. RESULTS: A dose-dependent decline of pulmonary artery pressure (PAP) was observed with each drug. A dose of 2.5 mg produced a significant decrease in PAP compared with baseline (20% amlodipine, 17% felodipine ER). Additional decreases in PAP were observed at 5 mg and 10 mg that were similar for both drugs, but did not reach statistical significance compared with 2.5 mg. There was a dose-related decrease in pulmonary vascular resistance and increase in oxygen delivery with amlodipine and felodipine ER. Lung function and blood gas values were stable throughout. Side effects (headache and ankle edema) were less frequent during amlodipine treatment (p<0.05). CONCLUSIONS: Both amlodipine and felodipine ER, given as a single daily oral dose of > or = 2.5 mg, are effective pulmonary vasodilators in COPD patients with PH. Their dose-response characteristics are similar, but amlodipine treatment was associated with fewer side effects.

Abstract: The gamma aminobutyric acid (GABA)-B agonist, baclofen, is a centrally-acting, anti-spasmodic agent and muscle relaxant used in spinal cord lesions, multiple sclerosis and other neurological disorders. In a previous pilot study of quadriplegic patients, 75% of whom were treated with baclofen, we found a high prevalence of sleep-disordered breathing. Because of the depressant effects of GABA on the central nervous system, we hypothesized that baclofen might aggravate sleep-disordered breathing in susceptible individuals by depressing central ventilatory drive, increasing upper airway obstruction and/or increasing the arousal threshold to apnoea. We therefore conducted a double-blind, placebo-controlled, cross-over study of baclofen 25 mg, administered before sleep in 10 snorers with mild sleep-disordered breathing (respiratory disturbance index < 30 events per sleep hour). Each subject underwent two standard polysomnographic assessments, one week apart. Total sleep time was significantly prolonged by baclofen (placebo 356 +/- 9.9 SEM min; baclofen 386 +/- 9.9 min). Both nonrapid eye movement(REM) and REM sleep duration were increased (nonREM: placebo 295 +/- 6.8 min; baclofen 311 +/- 8.9 min; REM: placebo 61 +/- 7.5 min; baclofen 76 +/- 9.0 min). Time spent awake after sleep onset was reduced after baclofen (placebo 71 +/- 10.3 min; baclofen 51 +/- 9.7 min). There was a slight reduction in mean overnight oxygen saturation (placebo 95.2 +/- 0.5%; baclofen 94.4 +/- 0.7%). The frequency of apnoeas plus hypopnoeas (respiratory disturbance index (RDI)) did not change significantly (placebo 9 +/- 1.8 events.h-1; baclofen 13 +/- 3.4 events.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: BACKGROUND--This study was undertaken to establish the prevalence of, and the factors contributing towards, sleep disordered breathing in patients with quadriplegia. METHODS--Forty representative quadriplegic patients (time since injury > 6 months, injury level C8 and above, Frankel category A, B, or C; mean (SE) age 35.0 (1.7) years) had home sleep studies in which EEG, EOG, submental EMG, body movement, nasal airflow, respiratory effort, and pulse oximetry (SpO2) were measured. Patients reporting post traumatic amnesia of > 24 hours, drug or alcohol abuse or other major medical illness were excluded from the study. A questionnaire on medications and sleep was administered and supine blood pressure, awake SpO2, spirometric values, height, and neck circumference were measured. RESULTS--A pattern of sustained hypoventilation was not observed in any of the patients. Sleep apnoeas and hypopnoeas were, however, common. Eleven patients (27.5%) had a respiratory disturbance index (RDI, apnoeas plus hypopnoeas per hour of sleep) of > or = 15, with nadir SpO2 ranging from 49% to 95%. Twelve of the 40 (30%) had an apnoea index (AI) of > or = 5 and, of these, nine (75%) had predominantly obstructive apnoeas-that is, > 80% of apnoeas were obstructive or mixed. This represents a prevalence of sleep disordered breathing more than twice that observed in normal populations. For the study population RDI correlated with systolic and diastolic blood pressure and neck circumference. RDI was higher in patients who slept supine compared with those in other postures. Daytime sleepiness was a common complaint in the study population and sleep architecture was considerably disturbed with decreased REM sleep and increased stage 1 non-REM sleep. CONCLUSIONS--Sleep disordered breathing is common in quadriplegic patients and sleep disturbance is significant. The predominant type of apnoea is obstructive. As with non-quadriplegic patients with sleep apnoea, sleep disordered breathing in quadriplegics is associated with increased neck circumference and the supine sleep posture.