Analysis of nocturnal disturbed breathing in the elderly using desaturation index]

This study was conducted to examine the nocturnal ventilatory parameters and gas exchange in the elderly with nocturnal disturbed breathing. In order to facilitate analysis of ventilatory parameters with minimum manpower, we developed an unattended continuous nocturnal monitoring system for ventilation and arterial oxygen saturation. Using this system, nocturnal ventilatory parameters and gas exchange were investigated in our geriatric ward. We investigated 30 elderly subjects aged between 65 and 94 (mean age 77.8 +/- 6.5 years, male; female = 15:15). The subjects were free of severe cardiovascular and cerebrovascular disorders, and underwent 10 hours of continuous monitoring of ventilation and arterial oxygen saturation (SaO2). Number of significant desaturation (SDS; desaturation greater than 4% in SaO2 from the baseline value) and desaturation index (DI; sigma SDS(%) x duration (hour)) were calculated using the same system. The number of apnea episodes significantly correlated with DI and the number of SDS. DI also significantly correlated with lowest SaO2, while the number of SDS and the number of apneas were not found to be correlated with lowest SaO2. The number of SDS and the number of apnea episodes did not correlated with lowest SaO2. From the view point of gas exchange during the night, newly introduced DI is more comprehensive parameter when compared with the number of apneas or SDS. Subjects with a DI of over 0.5 were assigned to the group A (n = 8, mean age = 77.8) and the remaining subjects were assigned to group B (n = 22, mean age = 77.8). We compared the group A with the group B regarding nocturnal ventilatory parameters and SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep apnea syndrome and hypertension using desaturation index

To examine the roles of obstructive apnea (OA) and central apnea (CA) in oxygen desaturation on hypertension and sleep apnea syndrome (SAS), we performed a sleep study on 41 elderly subjects (mean age 69.5 +/- 6.8 years, male:female = 31:10). Nocturnal oxygen desaturation was documented with a pulse oximeter and apneas (OA and CA) were diagnosed on the basis of results of respiratory inductive plethysmography and oronasal flow. Significant desaturation (SDS, greater than 5% drop in SpO2 from baseline value) and desaturation index (DI; epsilon SDS (%) x duration (hour)) were calculated using the continuous nocturnal monitoring system with a pulse oximeter. We defined central type apnea above 50% as the central type group (n = 8, mean age 58.6 +/- 2.9, mean BMI 21.3 +/- 1.0, male:female = 7:1), and obstructive type and mixed type apnea above 50% as the obstructive type group (n = 21, mean age 70.0 +/- 3.2, mean BMI 25.3 +/- 1.0, male:female = 17:4). Other subjects were assigned to the control group (n = 12, mean age 64.3 +/- 2.3, mean BMI 23.8 +/- 1.2, male:female = 7:5). The DI (delta 5%) of the central type was 0.34 +/- 0.17, and that of the obstructive type was 1.78 +/- 0.7 showing a significant increase in the latter compared to the control group (p < 0.02). The DI (< 90%) of the central type was 0.14 +/- 0.07, and that of the obstructive type was 1.72 +/- 0.75, and that of the obstructive type was significantly greater than in the control group (p < 0.05) and central type (p < 0.05). There were 4 cases (33.3%) with hypertension in the control group and 4 cases (50.0%) with hypertension in the central type group, but there were 15 cases (71.4%) with hypertension in the obstructive type group. Hypertensive prevalence in the obstructive group was significantly more than in the control group (p < 0.05). No significant difference in body mass index or age were seen in the obstructive group and control group. There was a significant correlation between mean blood pressure and apnea index (AI). The AI of the hypertensive group was significantly higher than that of the normotensive group (p < 0.001). These results suggest that subjects with significant obstructive apneas may be at greater risk for hypertension than subjects with central apneas and that hypertension in the pathogenesis of SAS may be related to the severity of apneas rather than oxyhemoglobin desaturation.     

Hypercapnic and hypoxic ventilatory responses in parents and siblings of children with congenital central hypoventilation syndrome

Children with congenital central hypoventilation syndrome (CCHS) have abnormal ventilatory responses to metabolic stimuli. As there is a genetically determined component of chemoreceptor sensitivity, parents and siblings of children with CCHS may also have blunted ventilatory responses to hypercapnea and hypoxia. To test this, we studied hypercapnic ventilatory responses and hypoxic ventilatory responses in six mothers, four fathers, and five siblings (6 to 49 yr of age) of seven children with CCHS and compared them with 15 age- and sex-matched control subjects (5 to 47 yr of age). Pulmonary function tests were not different between relatives of children with CCHS and control subjects. To measure hypercapnic ventilatory responses, subjects rebreathed 5% CO2/95% O2 until PACO2 reached 60 to 70 mm Hg. To measure hypoxic ventilatory responses (L/min/% SaO2), subjects rebreathed 14% O2/7% CO2/balance N2 at mixed venous PCO2 until SaO2 fell to 75%. All tests were completed in less than 4 min. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory timing/total respiratory cycle timing) were calculated on a breath-by-breath basis. Hypercapnic ventilatory responses were 1.97 +/- 0.32 L/min/mm Hg PACO2 in children with CCHS relatives and 2.23 +/- 0.23 L/min/mm Hg PACO2 in control subjects. Hypoxic ventilatory responses were -1.99 +/- 0.37 L/min/% SaO2 in the relatives and -1.54 +/- 0.25 L/min/% SaO2 in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory and arousal responses to hypoxia in sleeping humans

We measured ventilatory and arousal responses to progressive eucapnic hypoxia during wakefulness, nonrapid-eye-movement (NREM) sleep, and rapid-eye-movement (REM) sleep using a progressive isocapnic rebreathing method. Nine healthy adults (4 female, 5 male) slept with a mask glued to the face with medical silicone rubber and breathed from a closed valveless biased flow circuit, including an in-line bag-in-box and a variable soda-lime absorber. Progressive hypoxia was induced by consumption of oxygen and by gradual replacement of circuit volume with nitrogen. Tidal volume was measured by electrical integration of the flow signal from a pneumotach on the box. Arterial hemoglobin oxygen saturation (SaO2) was measured with an ear oximeter and end-tidal CO2 tension (PetCO2) was measured continuously and kept constant by variable absorption. Sleep state was identified using standard criteria with 2 channels each of EEG, submental EMG, and EOG. There was marked variability in arousal level both in NREM and REM sleep, with subjects failing to awaken by 70% SaO2, our previously agreed safety limit, on 12 of 26 NREM tests, and 7 of 15 REM tests. During wakefulness, the mean slope +/- SEM of the ventilatory response to hypoxia was 0.68 +/- 0.07 L/min% SaO2 (n = 36, mean PetCO2 = 37.0 mmHg). In NREM sleep, this response decreased to a mean of 0.42 +/- 0.06 L/min/% SaO2 (n = 26, mean PetCO2 = 37.2 mmHg). In REM sleep, the average ventilatory response was further decreased to 0.33 +/- 0.06 L/min/% SaO2 (n = 15, mean PetCO2 = 37.8 mmHg). Analysis of variance showed a significant state-dependent effect on ventilatory response (p less than 0.01). The wake-NREM and wake-REM differences were significantly different (p less than 0.05), but the NREM-REM difference was not (p greater than 0.2). In REM sleep, breath-to-breath variability was marked, and in 2 cases, the response was not significantly different from zero. In all 3 states, the entire ventilatory response was due to increments in tidal volume. We conclude that (1) at normal alveolar CO2 tension, hypoxia is a poor arousal stimulus in humans, both in NREM and REM sleep, and (2) the eucapnic hypoxic response is reduced but present in NREM sleep and similarly reduced but not always present in REM sleep.     

Oxygen supplementation during exercise in cystic fibrosis

Fourteen female and 22 male patients with cystic fibrosis (CF), 8 to 29 yr of age, performed two progressive exercise tests to exhaustion on a cycle ergometer, breathing normoxic air (21% O2) for one test, and hyperoxic air (30% O2) for the other test. The order of gas administration was randomized. Minute ventilation (VE), oxygen uptake (VO2), end-tidal CO2 tension (PETCO2), work rate, oxyhemoglobin saturation (SAO2), and heart rate (HR) were measured throughout the tests. The SaO2 of 11 patients at peak exercise was 90% or less ("Low Sat" group). The SaO2 of 23 patients remained above 90% throughout the exercise ("High Sat" group). Hyperoxic air minimized desaturation during exercise in the Low Sat group to 2 +/- 2% compared to a decrease of 10 +/- 5% with normoxic air. The decrease in saturation was not significant for the High Sat group (1 +/- 1% for both 21% and 30% O2). Peak work rate and VO2 did not differ significantly between normoxic and hyperoxic conditions. However, VE and HR at peak exercise tended to be lower, and PETCO2 was higher during peak exercise with 30% O2 than 21% O2 for both groups. During submaximal exercise, O2 desaturation was diminished and HR was significantly lower with supplemental O2, specifically in the Low Sat group. VE was significantly lower for both groups during submaximal exercise with hyperoxic air. The results suggest that O2 supplementation minimizes O2 desaturation and enables patients with CF to exercise with reduced ventilatory and cardiovascular work.     

Episodes of hypoxemia during synchronized intermittent mandatory ventilation in ventilator-dependent very low birth weight infants

Distinct patterns of asynchrony, and episodes of hypoxemia, may occur in a spontaneously breathing preterm infant during conventional intermittent mandatory ventilation (IMV) on traditional time-cycled, pressure-limited ventilators. Synchronized IMV (SIMV) and assist/control ventilation are frequent modes of patient-triggered ventilation used with infant ventilators. The objective of this study was to use computerized pulse oximetry to quantify the occurrence of episodes of hypoxemia (oxygen desaturation) during SIMV vs. IMV, in preterm infants < or = 1,250 g who required mechanical ventilation at > or = 14 days of age. We performed a randomized, crossover study with each infant being randomized to IMV or SIMV (Infant Star ventilator) for initial testing for a 1-hr period. Patients were subsequently tested on the alternate modality after a stabilization period of 10 min at the same ventilator and fractional inspired oxygen concentration (FiO2) settings. Pulse oximetry data were obtained with a Nellcor N-200 monitor, a microcomputer, and a software program (SatMaster). An investigator blinded to the randomized assignment evaluated all measurements. Eighteen very low birth weight (VLBW) infants with a birth weight of 777 +/- 39 g (mean +/- SEM) and gestational age 25.1 +/- 0.3 weeks were studied. The average pulse oximeter oxygen saturation (SaO2) was higher on SIMV than IMV (P < 0.01). During SIMV, these infants had significantly fewer episodes of hypoxemia (duration of episodes of oxygen desaturation as a percentage of scorable recording time) to 86-90% SaO2 (P < 0.01), 81-85% SaO2 (P < 0.01), and 76-80% SaO2 (P < 0.05) when compared to IMV. There was also a significant decrease in percentage of time of desaturation to SaO2 < 90% (P = 0.002), < 85% SaO2 (P = 0.003), and < 80% SaO2 (P = 0.02) during SIMV vs. IMV. Our preliminary findings indicate that the use of SIMV in a population of VLBW ventilator-dependent infants (> or = 14 days of age) results in better oxygenation and decreased episodes of hypoxemia as compared to IMV.     

Comparison of oxygen desaturation during sleep and exercise in patients with cystic fibrosis

Patients with cystic fibrosis (CF) desaturate during sleep and during exercise but by different mechanisms. To determine the need for supplemental oxygen, many centers measure resting and exercise arterial oxygen saturation (SaO2). We examined the associations among resting, sleep, and exercise SaO2 to ascertain the validity of this approach. We studied 21 adult and adolescent CF patients, eight of whom were hypoxemic (SaO2 less than 95 percent; group A) and 13 of whom were nonhypoxemic (SaO2 greater than or equal to 95 percent; group B) by overnight oximetry and treadmill exercise testing. The whole group desaturated more during sleep than during exercise, the change in SaO2 being 10.59 +/- 8.35 vs 6.25 +/- 4.44 (p less than 0.002). Group B desaturated significantly more during sleep than during exercise, with a reduction in SaO2 of 7.9 +/- 3.3 vs 3.3 +/- 1.49 (p less than 0.05). Group A desaturated more during exercise than group B, with a reduction of 11 +/- 3.2 vs 3.3 +/- 1.5 (p less than 0.001). Despite a strong correlation between awake SaO2 and mean sleep SaO2 (r = 0.68; p less than 0.001), minimum sleep SaO2 (r = 0.55; p less than 0.01), and minimum exercise SaO2 (r = 0.92; p less than 0.001), there was no correlation between awake SaO2 and sleep-related desaturation or between exercise- and sleep-related desaturation. In conclusion, clinically significant oxygen desaturation during sleep may be missed unless specifically checked in CF patients, and awake and exercise SaO2 may not give an indication of the degree of sleep-related desaturation.     

Effect of sputum induction on spirometric measurements and arterial oxygen saturation in asthmatic patients, smokers, and healthy subjects.

BACKGROUND: Sputum production induced by inhalation of hypertonic saline solution has been proposed as a technique to collect secretions and inflammatory cells from the airways of subjects with bronchial asthma or with a history of smoking. The aim of this study was to determine the effect of a sputum induction procedure on spirometric results and arterial oxygen saturation (SaO(2)) in asthmatic patients, smokers, and healthy subjects. METHODS: We recruited 14 subjects suffering from asthma (11 men and 3 women; age range, 18 to 49 years), 14 subjects with a history of smoking (5 men and 9 women; age range, 23 to 64 years), and 9 healthy volunteers (7 men and 2 women; age range, 28 to 54 years). To obtain a sample of induced sputum, all subjects inhaled a mist of 3% hypertonic saline solution nebulized for 5 min and repeated the cycle no more than four times. Asthmatic patients were pretreated with 200 microg salbutamol (inhaled). During sputum induction, the transcutaneous SaO(2) was continuously measured and baseline, fall, and the differences between baseline and fall SaO(2) were recorded. Additionally, we measured the duration of mild desaturation (change in SaO(2), < 4%) and of marked desaturation (change in SaO(2), > 5%) in each subject. Finally, baseline FEV(1) and changes in FEV(1) as a percentage of baseline values were recorded in all subjects. RESULTS: We found that baseline and fall SaO(2) values for the three groups were similar. However, in each group a significant mean change in SaO(2) was evident during sputum production (asthmatic patients, 6.0%; smokers, 5.3%; healthy subjects, 6.0%). Moreover, the mean durations of mild desaturation were 7 min, 21 s in asthma patients; 8 min, 24 s in smokers; and 7 min, 16 s in healthy subjects. Similarly, the durations of marked desaturation were 1 min, 25 s in asthmatic patients, 1 min, 19 s in smokers, and 1 min, 21 s in healthy subjects. The mean (+/- SD) fall in FEV(1) was not statistically different among the three groups (asthmatic patients, 1.36 +/- 5.6%; smokers, 7.58 +/- 11.76%; and healthy subjects, 0.05 +/- 9.6%). However, one smoker did experience excessive bronchoconstriction (fall in FEV(1), > 20%). CONCLUSIONS: This study demonstrated a significant and comparable fall in SaO(2) during sputum induction by inhalation of hypertonic saline solution in asthmatic patients, smokers, and healthy subjects. The results suggest that subjects who are hypoxemic before sputum induction require SaO(2) monitoring during the procedure.     

Ethanol-induced depression of hypoxic drive and reversal by naloxone--a sex difference

The effects of ethanol ingestion and subsequent intravenously administered naloxone on the ventilatory response to hypercapnic hypoxia in 8 normal males and 8 normal females were examined. The responses of controls were lower in the females (-0.63 +/- 0.07 L/min/% SaO2) than the males (-1.11 +/- 0.18 L/min/% SaO2). Alcohol depressed the male response to a mean of -0.50 +/- 0.08 L/min/%SaO2 (p less than 0.01) but increased the mean female response to -0.87 +/- 0.11 L/min/%SaO2 (p less than 0.01). Naloxone reversed the ethanol-induced depression of the hypercapnic hypoxic response in males, but had no effect on the female response. In males there was a direct correlation between the magnitude of the initial hypoxic response and the extent of depression by ethanol; the higher the response the greater the depression. Females showed a significant direct correlation between the blood alcohol and the increase in hypercapnic hypoxic slope, whereas males showed a weaker inverse correlation to blood alcohol level. These results demonstrate that ethanol depresses male but not female hypoxic ventilatory responsiveness and suggest that this is mediated by opioid-like mechanisms. Because the alcohol-induced depression was seen in subjects with a high control hypoxic response, the male-female difference might simply reflect initially lower control responses in females. This suggests a qualitative difference in hypoxic ventilatory control mechanisms between sexes.     

The SaO2/t diagram as a useful means to express nocturnal hypoxemia

The computerization of SaO2 recording during polysomnographic monitoring allows the construction of a diagram expressing the percentage of TIB spent at different steps in saturation. We studied the value of this diagram in three groups of male patients: (1) nine healthy subjects (all volunteers); (2) 25 patients with COPD who had a mean daily SaO2 of 92.3 +/- 1.3 percent; and (3) 25 patients with SAS who had a mean daily SaO2 of 92.1 +/- 1.4 percent. The results show the existence of a discriminating quality in the diagram's morphology, the existence of strong correlations (p less than 0.01) between the percentage of TIB spent at SaO2 less than 85 percent, and the total duration of the desaturation dips.     

Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea

Patients with obstructive sleep apnea are considered to be at increased risk of sudden, presumably arrhythmia-related death during sleep. The present study was undertaken to determine the relationship between ventricular ectopy and the severity of oxyhemoglobin desaturation in these patients. Thirty-one male patients with obstructive sleep apnea (mean age, 55 +/- 11 years) underwent overnight polysomnography. Arterial oxyhemoglobin saturation (SaO2) was monitored by ear oximetry, and premature ventricular complexes (PVC) were detected using electrocardiographic leads CC5 and CM5. The data were recorded on electromagnetic tape for subsequent computer-assisted analysis to obtain PVC frequency as a function of decile levels of SaO2. Total sleep time averaged 333 +/- 75 minutes, the apnea index was 44 +/- 26 per hour, and the hypopnea index was 18 +/- 24 per hour. Premature ventricular complexes were observed in 23 (74 percent) of the subjects. By analysis of variance, no significant relationship was found between PVC frequency and decile levels of SaO2 for saturations greater than 60 percent; however, in the 16 subjects with SaO2 below 60 percent, a significant increase in PVC frequency was detected with decreasing SaO2 (p less than 0.01). Ventricular bigeminy was observed with SaO2 below 60 percent in three of these 16 subjects. From these results, we conclude that patients with obstructive sleep apnea are at relatively low risk of developing ventricular arrhythmias provided SaO2 remains greater than 60 percent, while those with SaO2 below 60 percent are at increased risk and should be managed accordingly.     

There is no relationship between chronic obstructive pulmonary disease and obstructive sleep apnea syndrome: a population study

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSAS) are common diseases. Some recent studies suggest an increased prevalence of COPD among subjects with OSAS. OBJECTIVES: The study objective was to evaluate whether there is an epidemiological relationship between COPD and OSAS in a random population sample. MATERIALS AND METHODS: The study population, 356 males (53%) and 320 females, mean age 56.6+/-8.2 years (range 41-72), was selected from a voting list for parliamentary election in Warsaw. The investigation included lung diseases and smoking history with polysomnography and spirometry. RESULTS: OSAS was diagnosed in 76 subjects (11.3%), 59 males (8.8%) and 17 females (2.5%), mean apnea/hypopnea index (AHI) was 25.3+/-16.1, mean overnight SaO2 92.1+/-3.3%, minimum SaO2 76.9+/-9.4%, and SaO2<90%=18.9+/-23.9% of total sleep time. COPD was diagnosed in 72 subjects (10.7%), 39 males and 33 females. Severity of airflow limitation was assessed according to European Respiratory Society (ERS) guidelines: mild in 70%, moderate in 22%, and severe in 8%. In 7 subjects (9.2% of OSAS population, 1% of total population) OSAS and COPD overlapped. Polysomnographic variables were compared between overlap (overlap syndrome, OS) and OSAS subjects. In the OS mean AHI was 19.0 versus 25.3 in OSAS (nonsignificant), mean SaO2 89.6 versus 92.3% in OSAS (p<0.005), and time spent in SaO2<90% was 25.4 versus 18.2% in OSAS (p=0.04). CONCLUSIONS: COPD in subjects with OSAS was as frequent as in the general population. In the OS group mean arterial blood saturation was lower and time spent in desaturation was longer than in OSAS. The presented data suggest a more severe course of sleep-disordered breathing in subjects with coexisting COPD.     

高原夜间血氧饱和度监测重叠综合征患者的临床价值

目的研究高原慢性阻塞性肺疾病（COPD）患者夜间动态血氧饱和度（SaO2）变化,评价不同SaO2指标对病情严重程度的临床价值及意义。方法用多导睡眠记录仪对单纯COPD组13例患者、重叠综合征12例患者进行夜间睡眠、呼吸及动态SaO2同步连续监测。结果COPD组的呼吸紊乱指数（AHI）为3．7±1．3,重叠综合征组为35．7±12．9,两组差异有显著性（P＜0．001）;两组患者的最低SaO2（ISaO2）、平均SaO2（MSaO2）、氧饱和度≤85％的时间占总监测时间的百分比（SIT85）、氧减饱和度指数（DI4）等措标比较,差异均有显著性（P＜0．001）,清醒时SaO2（HSaO2）的两组间差异无显著性（P＞0．05）、AHI与DI4直线相关（系数0．71,P＜0．05）,二者相关性较好。结论选用适当的DI4作指标,对初步筛选和准确判断COPD患者中的SAS具有重要的临床价值。     

Impact of plasma homocysteine and prothrombin G20210 A on primary antiphospholipid syndrome.

The prevalence of prothrombin (PT) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677 <-- T was assessed in 40 patients with primary antiphospholipid syndrome (APS) (14 male, 26 female; mean age, 37 +/- 14 years) and in 27 persistent carriers of antiphospholipid antibodies (aPL) (five male, 22 female; mean age, 40 +/- 16 years) without underlying diseases. Non-APS thrombotic patients (n = 100; 47 female, 53 male; mean age, 40 +/- 10 years) and healthy subjects (n = 100; 46 female, 54 male; mean age, 56 +/- 16 years) served as control groups. Plasma homocysteine (HC) (enzyme-linked immunosorbent assay) was measured in all aPL patients and in 51 subjects from the healthy control group (mean age, 38 +/- 16 years). Heterozygous prothrombin PT G20210A was more frequent in the thrombotic group without APS (18%) than in the control (4%), APS (12%) or aPL (11%) groups, whereas homozygous MTHFR C677 <-- T was equally distributed. After genotype sub-grouping, plasma HC was higher in APS patients with homozygous MTHFR C677 <-- T compared with non-homozygous APS patients (22 +/- 5.4 versus 11 +/- 1.3 micromol/l; P < 0.01) and with homozygous MTHFR C677 <-- T controls (22 +/- 5.4 versus 15 +/- 2.0 micromol/l). In the APS group, mean age at first event was lower in homozygous MTHFR C677 <-- T patients than in non-homozygous patients (26 +/- 7.5 versus 36 +/- 13 years; P = 0.008). In the same group, homozygous MTHFR C677 <-- T patients suffered an increased average number of events per person than non-homozygous patients (1.9 versus 1.3; P = 0.04). Heterozygous PT G20210A contributes little to the thrombotic tendency of primary APS whereas plasma HC may influence age at first event and number of events. Measurement of plasma HC in aPL subjects may identify patients at increased thrombotic risk requiring HC lowering.     

Oscillatory hyperventilation in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy

Thirty-one subjects with chronic congestive heart failure (CHF) were separated into 3 groups according to ventilatory patterns during graded exercise: Group 1--oscillators (n = 6); group 2-intermediate oscillators (n = 14); and group 3--nonoscillators (n = 11). Group 1 patients showed cyclic fluctuations in minute ventilation (change of 30 to 40 liters/min) and arterial PO2 (change of 38.0 +/- 4.1 mm Hg) and PCO2 (change of 11 +/- 2.8 mm Hg). The nadir in arterial PO2 occurred at times when wasted ventilatory effort was maximal. The amplitude of ventilatory oscillations in group 1 patients increased in the transition from rest to light exercise and damped with heavy exercise. There was no evidence of alveolar hypoventilation at the nadirs of minute ventilation; arterial PCO2 was always 40 mm Hg or less. Substantial hyperventilation (ventilatory equivalent for CO2 twice normal) occurred with maximal minute ventilation in group 1 patients. Oscillatory hyperventilation correlated with severity of CHF. Maximal oxygen uptake was significantly lower in group 1 (11.7 +/- 1.1 ml/kg/min) than group 3 (17.9 +/- 1.8 ml/kg/min) (p less than 0.05). Oscillatory hyperventilation during exercise may accompany severe CHF and compounds the inadequate delivery of oxygen by the failing heart.     

The breathing route dependence of ventilatory responses to hypercapnia and exercise is modulated by upper airway resistance

OBJECTIVE: The ventilatory response to hypercapnia is greater breathing orally than nasally. METHODOLOGY: We hypothesize that this is due to higher nasal resistance to airflow compared with oral resistance. Seven normal male subjects were studied during both progressive hyperoxic hypercapnia (HC) and exercise (EX) until ventilation exceeded 40 L/min. Under each condition, subjects breathed via the nose only or the mouth only. For each breathing route, ventilation and pathway resistance were calculated simultaneously at the highest common exercise workload (140 +/- 20 watt; mean +/- SE) or the same end-tidal CO2 level (8.0 +/- 0.5%). RESULTS: The ventilatory response breathing nasally was decreased by a similar amount for both EX and HC when compared with the oral route. The difference between nasal and oral ventilation was highly correlated with the difference between nasal resistance and oral resistance for both EX and HC (linear regression analysis; r = 0.91 for EX and r = 0.86 for HC; both P < 0.01). CONCLUSION: We conclude that the breathing route dependence of ventilatory responses to respiratory stimuli in normal subjects is independent of the method of stimulation and is substantially determined by the added resistance of nasal breathing.     

Ventilation and breathing pattern during sleep in Duchenne muscular dystrophy

Ventilatory data, including timing and partitioning of ventilation, were obtained from six subjects with advanced Duchenne muscular dystrophy, aged 16 to 22 years, during polysomnography on two consecutive nights; the subjects were randomized to breathing air or oxygen. Five of the six patients developed oxygen desaturation exceeding 5 percent during rapid eye movement (REM) sleep while breathing air. Minute ventilation on air (the mean of at least six consecutive minutes) was 6.9 +/- 0.7 (SEM) L min-1 but fell, owing to decreases in both tidal volume and frequency, to 4.9 +/- 0.3 L min-1 (p less than 0.05) in slow wave sleep and to 4.5 +/- 0.6 L min-1 (p less than 0.05) in REM sleep. Similar falls were seen on oxygen. The variability of all ventilatory data was significantly greater in REM than non-REM (NREM) sleep. The mean abdominal contribution to breathing was lower than predicted for wakefulness and all sleep stages, and two subjects showed paradoxical abdominal movement in NREM sleep; a correlation (p less than 0.05) existed between the NREM abdominal (diaphragmatic) contribution and the extent of oxygen desaturation subsequently seen in REM. We conclude that although awake minute ventilation is normal in Duchenne muscular dystrophy, hypoventilation occurs in all sleep stages, and those with diaphragmatic dysfunction are especially vulnerable to oxygen desaturation during REM sleep.     

Optimal continuous positive airway pressure in patients with obstructive sleep apnoea: role of craniofacial structure

Although nasal continuous positive airway pressure (CPAP) is effective in improving nocturnal obstructive apnoea, daytime sleepiness and well-being in patients with obstructive sleep apnoea syndrome (OSAS), not all patients tolerate this treatment. Since optimal CPAP titration is essential to maintain compliance, it is important to elucidate the factors that help to determine the optimal pressure. However, the determinants of the optimal CPAP level are controversial. The subjects comprised 27 Japanese male patients with OSAS who underwent standard polysomnography (PSG), pulmonary function tests, arterial blood gas analysis, cephalometry and CPAP titration. Twenty normal controls also underwent cephalometric analysis. The apnoea-hypopnoea index (AHI), mean oxygen saturation (mean SaO2) and the lowest SaO2 during sleep were found to be 54.7+/-22.6, 89.0+/-5.6%, and 69.7+/-9.0%, respectively by PSG. The mean optimal CPAP was 9.6+/-1.8 cmH2O. The cephalometric angles (SNA, SNB and NSBa) were similar to those found in the control subjects. but MP-H, and PNS-P were significantly longer than those in the control subjects as shown by cephalometry. The optimal CPAP was correlated with the mean SaO2 (P<0.0001), neck circumference (P<0.05) and three cephalometric variables (NSBa: P<0.01, MP-H: P<0.05, PNS-P: P<0.05). Multiple, step-wise, regression analysis showed that the mean SaO2 and NSBa were independent variables that best predicted the optimal CPAP. These variables accounted for 57.5% of the total variance (R2=0.575, P<0.001). Optimal CPAP was closely correlated with oxygen desaturation during sleep. However, the craniofacial structure had additional effects such as an independent factor in determining the optimal CPAP level.     

Effects of beta-blocker therapy on ventilatory responses to exercise in patients with heart failure

BACKGROUND: Ventilatory efficiency is the increase in ventilation relative to carbon dioxide production during exercise. Congestive heart failure (CHF) is associated with decreased ventilatory efficiency. beta-blockers improve hemodynamics, prolong survival, and improve functional class in patients with CHF, though peak exercise performance may not improve. We hypothesized beta-blockers increase ventilatory efficiency in patients with CHF. METHODS AND RESULTS: The study group comprised 614 subjects with left ventricular ejection fraction < or = 40% referred for cardiopulmonary exercise testing. Clinical and exercise data were reviewed and recorded. For comparison, subjects were divided into those treated with beta-blockers (n = 195) and those not treated (n = 419). Subjects on beta-blockers had lower minute ventilation (12 +/- 4 versus 14 +/- 4 L/min, P < .001) at rest, which remained lower during submaximal and maximal exercise, by 4 and 6 L/min, respectively (P = .001). Ventilatory efficiency was increased in subjects treated with beta-blockers at submaximal (32 +/- 6 versus 34 +/- 7, P = .002) and maximal (34 +/- 7 versus 37 +/- 10, P = .005) exercise. Differences between treatment subgroups remained significant by covariate analysis; beta-blockers were also independently associated with decreased minute ventilation by multiple regression. CONCLUSION: Beta-blockers may be associated with increased ventilatory efficiency in CHF patients, which may contribute to improved functional class and quality of life.     

Obstructive sleep apnea complicating negative-pressure ventilatory support in patients with chronic paralytic/restrictive ventilatory dysfunction

The purpose of this study was to determine the incidence and severity of obstructive events and oxyhemoglobin desaturation (dSaO2) in 37 patients with paralytic/restrictive ventilatory insufficiency during use of nocturnal ventilatory assistance provided by means of negative-pressure body ventilators (BVs). Thirteen of the 37 patients had mean oxyhemoglobin saturation (SaO2) less than 95 percent and a mean of ten or more episodes per hour when the dSaO2 was greater than or equal to 4 percent (4%dSaO2/h). In all, 26 of the 37 patients had evidence of significant multiple episodes of dSaO2 while asleep on BVs. Polysomnography performed on three of these patients substantiated the obstructive nature of the dSaO2. Twenty-two of the 37 patients who had a mean SaO2 of 90.6 +/- 7.2 percent and a mean of 17.7 +/- 16.1 4%dSaO2/h on BVs were switched to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP). Their mean SaO2 improved to 96.0 +/- 2.2 percent, and the 4%dSaO2/h decreased to 1.2 +/- 1.8 per hour. All symptoms similar to those of obstructive sleep apnea were relieved. We conclude that BV use is associated with significant dSaO2 in over 50 percent of patients. The dSaO2 is predominantly obstructive in nature but may be due to chronic underventilation in patients using less effective BVs. Patients with a mean SaO2 less than 95 percent or 10 or more 4%dSaO2/h may benefit from conversion to NV-PAP via the nose, the mouth, or an oral-nasal interface.