Biomedical subjects

C W Zwillich

Publications and source records attributed to C W Zwillich.

At least 55 records · Page 3Linked to original sources

PubMed1987

Relationship of respiratory drives to dyspnea and exercise performance in chronic obstructive pulmonary disease.

Frequently, patients with COPD with similar spirometric impairment have marked differences in dyspnea and exercise limitation. As the classic "blue bloater" with attenuated respiratory drive is described as being less dyspneic than his "pink puffer" counterpart, we wondered whether the variability in dyspnea and exercise tolerance in a group of patients with COPD with relatively similar degrees of air-flow obstruction might be partly explained by the variability in resting respiratory drives (unstimulated P0.1 and hypoxic and hypercapnic P0.1 responses). Therefore, we measured unstimulated mouth occlusion pressure (P0.1), hypoxic response (-delta P0.1/delta SaO2), hypercapnic response (delta P0.1/delta PCO2), 6-min walk distance, VO2max, steady-state exercise VE/VO2, exercise SaO2, and dyspnea using an oxygen cost diagram in 15 subjects with severe COPD (mean FEV1% 35.2 +/- 1.9 SEM). No correlations between spirometric impairment and either dyspnea or exercise performance were seen. Unstimulated P0.1 correlated inversely with spirometric impairment but did not correlate with dyspnea, VO2max or 6-min walk distance. Both hypoxic and hypercapnic responses were significantly correlated with greater exercise ventilation (VE/VO2), less exercise O2 desaturation, and a greater VO2max, but not with dyspnea or 6-min walk distance. The results of this study do not support the concept that depressed respiratory drives are associated with less dyspnea or greater exercise capability in COPD.

Adult↗

PubMed1987

Effects of oral narcotics on sleep-disordered breathing in healthy adults.

Alcohol and benzodiazepines may increase sleep-disordered breathing by decreasing activity of pharyngeal dilating muscles, favoring the development of obstructive apneas and hypopneas. Narcotics cause greater depression of wakeful respiration than the previously mentioned drugs; however, the influence of narcotics on the upper airway and breathing during sleep has not been studied. We, therefore, examined, in 12 healthy adults, the effects of oral hydromorphone hydrochloride (2 and 4 mg) on breathing during sleep and on a variety of awake respiratory variables (minute ventilation, gas exchange, and chemoresponsiveness). In addition, awake pharyngeal inspiratory airflow resistance was determined before and after narcotic administration to assess the drug's influence on patency of the upper airway. Following both doses, minute ventilation decreased, and carbon dioxide pressure increased. The 4-mg dose of hydromorphone hydrochloride also produced a significant decrement in the hypoxic ventilatory response, whereas hypercapnic responsiveness and pharyngeal resistance did not change following either dose of the drug. Despite the respiratory depression during wakefulness described previously, no significant change was observed in any measure of sleep-disordered breathing after either dose of narcotic. We conclude that in healthy individuals without suspected sleep apnea, oral hydromorphone in standard dosages does not significantly increase sleep-disordered breathing. This result may be due to a lack of selective depression of upper-airway muscular function by the doses of narcotic used.

Adult↗

PubMed1986

Effect of inspiratory nasal loading on pharyngeal resistance.

Nasal obstruction has been shown to increase the number of apneas during sleep in normal subjects and in some may actually cause the sleep apnea syndrome. We postulated that the pharynx may act as a Starling resistor, where increases in negative inspiratory pressure result in elevated resistance across a collapsible pharyngeal segment. To test this theory in normal subjects we studied 10 men and 10 women during wakefulness. Pharyngeal resistance (the resistance across the airway segment between the choanae and the epiglottis) was determined in the normal state and with three inspiratory loads added externally. Flow was measured using a pneumotachometer and a sealed face mask; epiglottic pressure by a latex balloon placed just above the epiglottis and choanal pressure by anterior rhinometry. Pharyngeal resistance (measured at 300 ml/s) could thus be determined. Base-line inspiratory pharnygeal resistance was 1.6 +/- 0.2 cmH2O . l-1 . s. This increased to 2.3 +/- 0.3, 2.8 +/- 0.4, and 2.9 +/- 0.4 cmH2O . l-1 . s, respectively, with the addition of 1.3, 2.7, and 6.7 cmH2O . l-1 . s inspiratory load. The resistance at each level of load was significantly different from the base-line resistance determination (P less than 0.05) but not different from each other. We conclude that added nasal resistive loads during inspiration cause an increase in pharyngeal resistance during wakefulness but that this resistance does not increase further with additional increments of load.

Adult↗

PubMed1986

Influence of testosterone on breathing during sleep.

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.

Arousal↗

PubMed1986

Breathing route during sleep.

Nasal obstruction has been associated with apneic episodes during sleep. However, the normal distribution of nasal and oral air flow while asleep has not been investigated. To determine the normal route of ventilation during sleep, we studied 7 healthy men and 7 healthy women using a sealed face mask that mechanically separated nasal and oral air flow. Standard sleep staging techniques were employed. The subjects slept 297 +/- 29 (SEM) min, with a mean of 197 +/- 15 min of ventilation recorded. Ventilation was decreased during sleep as has been previously demonstrated. However, during sleep, we found that men breathed a greater percentage of total ventilation through the mouth (29.0 +/- 8.2%) than did women (5.0 +/- 1.0%, p less than 0.02). The same trend applied during wakefulness but did not reach significance (p = 0.06). Although none was symptomatic, 4 subjects, all men, had more than 3 apneas per hour. These 4 men had a greater percentage of mouth ventilation (37.3 +/- 19.0%) than did the other 10 subjects with few or no apneas (8.1 +/- 2.7%, p less than 0.02). It was also noted that increasing age in men was associated with an increasing percentage of mouth ventilation (r = 0.83 p less than 0.03) but this relationship was not observed in women. We conclude that mouth breathing may be associated with apneas during sleep and that breathing through the mouth occurs commonly in men, particularly in those who are older. This suggests that nasal breathing may be important in the maintenance of ventilatory rhythmicity during sleep.

Adult↗

PubMed1986

Breathing during sleep in stable asthmatic subjects. Influence of inhaled bronchodilators.

The bronchoconstriction of asthma displays a circadian rhythm with exacerbations often occurring in the early morning hours. Gas exchange abnormalities during sleep in patients with severe asthma have been documented; however, the influence of sleep on gas exchange in the asthmatic with few or no daytime or nocturnal symptoms is poorly understood. To determine if abnormalities in oxygenation might occur during sleep, we studied 12 stable adult asthmatic patients with reversible airflow obstruction during sleep on three consecutive nights, with night 1 being for acclimatization. On test nights 2 and 3, the subjects received, in random double-blind fashion, either inhaled fenoterol or its placebo. Spirometry was performed before and after bronchodilator treatment and on the next morning. The mean FEV1 was 63 percent predicted before treatment. There was significant (p less than 0.05) improvement in FEV1 on fenoterol night after treatment which was also present the next morning. Mean prefenoterol FEV1 was 2.04 +/- .15 (SEM) and increased to 2.61 +/- .17 after the bronchodilator. The mean morning FEV1 was 2.27 +/- .20. Mean preplacebo FEV1 was 2.07 +/- .12 and did not change significantly with placebo bronchodilator. Sleep analysis demonstrated no significant differences in total sleep time or duration of oxyhemoglobin desaturation between nights. The incidence of sleep disordered breathing was very low (0.14 apneas/hour). The frequency of apneas and hypopneas did not change significantly with treatment. Two of the 12 subjects experienced an asthma attack on placebo night which did not recur following active bronchodilator administration. We conclude that stable asthmatic patients with few nocturnal complaints have a low frequency of disordered breathing and desaturation events during sleep.

Adolescent↗

PubMed1986

Transient oxygen desaturation following radiographic contrast medium administration.

To determine if angiography results in arterial oxygen desaturation, we prospectively studied 40 clinically stable patients undergoing arterial angiography. Arterial oxygen saturation (Sao2) was monitored before, during, and for at least three minutes after contrast medium injection. The mean (+/- SEM) Sao2 was 94.2% +/- 0.39% before injection and fell to 92.6% +/- 0.66% following injection. Eleven patients (28%) demonstrated a decrease in Sao2 of more than 3%, with six (15%) having a postinjection Sao2 of less than 90%. To determine if the vascular route of injected contrast medium influenced the subsequent level of oxygenation, we similarly evaluated the Sao2 of 20 consecutive patients undergoing venous angiography. The Sao2 was 94.2% +/- 0.33% before contrast medium injection and fell to 92.5% +/- 0.78% following injection. Six patients (30%) experienced a fall in Sao2 of more than 3%, with four (20%) having a postinjection Sao2 of less than 90%. We conclude that arterial oxygen desaturation occurs frequently in patients undergoing angiography.

Adult↗

PubMed1985

Medical therapy of obstructive sleep apnea.

Guidelines for the medical therapy of obstructive sleep apnea are difficult to define precisely. While some elegant investigations have been completed, most study populations have been small. Also, the long-term effects of most forms of therapy are not known. Some patients will respond to a given form of therapy or combination of therapies while others will not. In most instances the responders cannot be recognized prior to the institution of therapy and a cycle of trial and error ensues. One of the best nonsurgical approaches appears to be weight loss, albeit unsuccessful in most cases. Almost all experts would agree, however, that in nonemergent situations weight loss should be strongly suggested. Nasal CPAP appears to be the single most promising device. Protriptyline may have a role, although in our opinion its true efficacy remains to be determined. Oxygen will probably serve more an adjunctive role in therapy, and medroxyprogesterone appears to be beneficial only in the treatment of the obesity-hypoventilation syndrome. A reasonable approach to the medical treatment of the obstructive sleep apnea patient should include, first, by history, physical examination, and appropriate laboratory testing, elimination of anatomically correctable, pharmacologic, or endocrinologic causes of OSA. If apnea length, degree of desaturation, cardiac arrhythmias, or levels of hypersomnolence are so severe as to be potentially life threatening, immediate tracheostomy is suggested. In specialized centers, nasal CPAP would be used. In less severely affected patients, medical management, as discussed above, should begin. We believe that in view of the lack of controlled trials demonstrating which form of therapy is best, the clinician must recommend therapy on the basis of local clinical experience and patient acceptance. Of fundamental importance is the need for serial reevaluation so that the impact of therapeutic failure can be minimized.

Almitrine↗

PubMed1985

Cheyne-Stokes breathing during sleep in patients with left ventricular heart failure.

Fifteen patients with left ventricular heart failure (LVF) without known breathing disorders during sleep had full-night recordings of sleep and breathing to study the incidence and impact of the apnea of Cheyne-Stokes breathing. This group showed a marked degree of sleep-related breathing abnormalities, 40% demonstrating Cheyne-Stokes breathing with five or more central apneas per hour of sleep. Cheyne-Stokes breathing during sleep in patients with LVF predicted an increased short-term mortality rate. All six patients with LVF and Cheyne-Stokes breathing with more than five apneas per hour of sleep were dead within six months, while only three of nine patients without recurrent apnea died within six months, a significant difference (P less than .05) even in this small group. Among seven patients with LVF studied with the polysomnogram, there were statistically significant differences between the Cheyne-Stokes and non-apnea groups in total sleep time, awakening per hour, and the number of arterial desaturations. Although sleep disturbances have been anecdotally described in patients with LVF, no previous investigation has determined the incidence and impact of Cheyne-Stokes breathing during sleep in LVF. Our findings that Cheyne-Stokes breathing predicts an adverse short-term mortality rate confirm the clinical impression that Cheyne-Stokes breathing is a poor prognostic sign in LVF.

Adult↗

PubMed1985

Pharyngeal resistance in normal humans: influence of gender, age, and obesity.

Investigation into the etiology of obstructive sleep apnea is beginning to focus increasing attention on upper airway anatomy and physiology (patency and resistance). Before conclusions concerning upper airway resistance in these patients can be made, the normal range of supraglottic and, more specifically, pharyngeal resistance needs to be better defined. We measured supraglottic and pharyngeal resistances during nasal breathing in a normal population of 35 men and women. Our technique measured epiglottic pressure with a balloon-tipped catheter, choanal pressure using anterior rhinometry, and flow with a sealed face mask and pneumotachograph. Resistance was measured at a flow rate of 300 ml/s during inspiration. Men had a mean pharyngeal resistance (choanae to epiglottis) of 4.6 +/- 0.8 (SE) cmH2O X l-1 X s, whereas women demonstrated a significantly (P less than 0.01) lower value, 2.3 +/- 0.3 cmH2O X l-1 X s. Supraglottic resistance was also higher in men (P = 0.01). Age (r = 0.73, P less than 0.01) correlated closely with pharyngeal resistance in men, but no such correlations could be found in women. These results may have implications in the epidemiology of obstructive sleep apnea.

Adult↗

PubMed1985

Metabolic rate and breathing during sleep.

Recent investigation suggests that both ventilation (VE) and the chemical sensitivity of the respiratory control system correlate closely with measures of metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)]. However, these associations have not been carefully investigated during sleep, and what little information is available suggests a deterioration of the relationships. As a result we measured VE, ventilatory pattern, VO2, and VCO2 during sleep in 21 normal subjects (11 males and 10 females) between the ages of 21 and 77 yr. When compared with values for awake subjects, expired ventilation decreased 8.2 +/- 2.3% (SE) during sleep and was associated with a 8.5 +/- 1.6% decrement in VO2 and a 12.3 +/- 1.7% reduction in VCO2, all P less than 0.01. The decrease in ventilation was a product primarily of a significant decrease in tidal volume with little change in frequency. None of these findings were dependent on sleep stage with results in rapid-eye-movement (REM) and non-rapid-eye-movement sleep being similar. Through all sleep stages ventilation remained tightly correlated with VO2 and VCO2 both within a given individual and between subjects. Although respiratory rhythmicity was somewhat variable during REM sleep, minute ventilation continued to correlate with VO2 and VCO2. None of the parameters described above were influenced by age or gender, with male and female subjects demonstrating similar findings. Ten of the subjects demonstrated at least occasional apneas. These individuals, however, were not found to differ from those without apnea in any other measure of ventilation or metabolic rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Influence of testosterone on ventilation and chemosensitivity in male subjects.

There is increasing evidence that men have higher ventilatory responses to chemical stimuli than age-matched women and that certain disorders of respiratory rhythmicity, particularly sleep apnea, occur more commonly in men. Accordingly, we studied the influence of the male hormone, testosterone, on the control of breathing. Twelve hypogonadal males were studied at least 30 (mean +/- SE: 69.7 +/- 8.9) days after discontinuing testosterone replacement and again following hormone administration. In each subject plasma testosterone concentration, metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)], minute ventilation (VE), and chemosensitivity [hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses] were determined on and off hormone replacement. With testosterone administration VO2 increased from 248 +/- 15 to 276 +/- 18 ml/min (P less than 0.05), with VCO2 showing a similar but nonsignificant trend. This was associated with an increase in VE from 8.41 +/- 0.78 to 9.91 +/- 0.75 l/min (P less than 0.05) but no change in PCO2. The HVR, expressed as A, increased 44% with hormone replacement from a value of 122 +/- 23 to 176 +/- 28 (P less than 0.01), whereas the HCVR was minimally affected by testosterone administration. These findings may in part explain the previously described differences between male and female subjects in hypoxic sensitivity.

Adult↗

PubMed1985

The effects of nasal anesthesia on breathing during sleep.

Inability to breathe through the nose is an increasingly recognized cause of disordered breathing during sleep. To test the hypothesis that this respiratory dysrhythmia could result from loss of neuronal input to respiration from receptors located in the nose, we anesthetized the nasal passages of 10 normal men during sleep. Each subject spent 4 consecutive nights in the sleep laboratory while sleep stages, breathing patterns, respiratory effort, and arterial oxygen saturation were monitored. Night 1 was for acclimatization with Nights 3 and 4 being randomized to nasal spraying with either 4% lidocaine or placebo. On the lidocaine and placebo nights (Nights 3 and 4) the nasal passages were also sprayed with a decongestant to prevent increased nasal air-flow resistance resulting from mucosal swelling. To control for the possible effects of this decongestant, an additional night (Night 2) was included during which the nasal passages were sprayed with room air. Parallel studies conducted during wakefulness demonstrated low nasal resistance during the lidocaine-decongestant regimen. Because of the short duration of anesthesia with lidocaine, spraying was done at lights out and 2.5 and 5 h later. On the placebo night (decongestant plus saline) there were 6.4 +/- 1.8 (SEM) disordered breathing events (apneas plus hypopneas) per subject, whereas with lidocaine (plus decongestant) this increased fourfold to 25.8 +/- 7.8 events per subject (p less than 0.05). The majority of the disordered breathing events were apneas and were fairly evenly distributed between central and obstructive events. The magnitude of these changes is similar to that previously reported with complete nasal obstruction. These results suggest that nasal receptors sensitive to air flow may be important in maintaining breathing rhythmicity during sleep.

Adult↗

PubMed1985

Moderate alcohol ingestion increases upper airway resistance in normal subjects.

Apnea during sleep has been associated with both increased pharyngeal resistance and nasal obstruction. Alcohol can worsen obstructive sleep apnea, but its influence on pharyngeal resistance and nasal patency has not been evaluated. Accordingly, we determined the effects of alcohol on pharyngeal and nasal resistances in 11 normal awake subjects on 2 separate days. Baseline pharyngeal resistance prior to placebo and alcohol was not significantly different. After placebo, pharyngeal resistance did not change significantly. However, after alcohol, pharyngeal resistance increased from 1.9 +/- 0.5 (SEM) to 3.3 +/- 0.8 cm H2O/L/s at 45 min (p less than 0.05) and returned to near baseline level by 90 min. Baseline nasal resistance varied considerably within subjects on the 2 days, but the mean values for baseline nasal resistance on alcohol and placebo days were not significantly different. Nasal resistance did not change after placebo, but after alcohol, nasal resistance increased from 2.4 +/- 0.9 at baseline to 3.7 +/- 0.8 at 45 min (NS) and to 4.3 +/- 1.2 cm H2O/L/s at 90 min (p less than 0.05). We conclude that a decrease in pharyngeal airway size and an increase in nasal resistance may account for alcohol's ability to worsen obstructive sleep apnea.

Adult↗

PubMed1985

The effect of positional changes on oxygenation in patients with pleural effusions.

In unilateral parenchymal pulmonary disease, arterial oxygenation decreases when the patient is positioned such that the abnormal lung is dependent; however, few studies have evaluated the effect of the body position on oxygenation in patients with unilateral or asymmetric pleural effusions. To our knowledge, no previous study has evaluated the possible transient effects of changing position on the level of arterial oxygen saturation (SaO2) in such patients. Accordingly, we studied ten normoxic patients spontaneously breathing room air, who had asymmetric pleural effusions as documented by chest x-ray film and physical examination. We monitored pulse, respiratory rate, and blood pressure every five minutes and SaO2 by ear oximetry continuously while patients were in the following positions: sitting; supine; and left and right lateral decubitus. The mean SaO2 was 95 percent and 94.3 percent in the sitting and supine positions, respectively. Mean SaO2 fell to 93.4 percent when the patients were positioned so that the side with the largest pleural effusion was dependent. When the side with the pleural effusion was down, the mean SaO2 was significantly lower than in either the sitting position or with the side with the pleural effusion up. We could find no significant relationship between the size of the pleural effusion and the amount of arterial oxygen desaturation. We conclude that there is a decrease in SaO2 in normoxic patients when the side with the larger pleural effusion is dependent; however, this decreased SaO2 does not appear to be clinically significant in patients with normal SaO2.

Aged↗

PubMed1985

The effect of drugs on breathing during sleep.

We hope that the reader is impressed with the relatively limited amount of information available about the effects of drugs on breathing during sleep in both normal subjects and patients with sleep-disordered breathing. Although more reports are appearing, well-controlled evaluations remain limited in number. We believe that this information gap will quickly close because it is now increasingly appreciated that either spontaneous or drug-induced breathing abnormalities measured during wakefulness may be strikingly magnified during sleep. Therefore, this area of investigation is exciting. Finally, we hope the reader shares our view that, to date, drug therapy for sleep apnea has limited efficacy.

Almitrine↗

PubMed1985

Sleep and respiration: a postscript.

The recent advances in our understanding of breathing in sleep include an evolution in the selection and surgical therapy of patients with the sleep apnea syndrome. Recent work suggests that shorter polysomnographic studies may be adequate for diagnostic purposes in many sleep apnea patients. It is now clear that central apnea may occur, paradoxically, in patients with either very blunted chemical drives to breathe or increased drives to breathe.

Acetazolamide↗

PubMed1984

Obstructive sleep apnea in hypothyroidism.

To determine the incidence and frequency of sleep apnea in persons with hypothyroidism, 11 consecutive patients with newly diagnosed disease were studied before and during thyroid hormone replacement therapy. Nine patients had episodes of apnea, with the number of episodes per hour of sleep ranging from 17 to 176 (mean, 71.8). Six of the nine patients were obese and had 99.5 episodes per hour compared with 16.3 episodes per hour in the 3 nonobese patients (p less than 0.02). After 3 to 12 months of thyroxine replacement therapy, mean apnea frequency decreased from 71.8 +/- 18.0 (SE) to 12.7 +/- 6.1 episodes per hour, without reduction in body weight. There were fewer changes in sleep stage per hour during treatment (22.1 +/- 4.9) than pretreatment (57.6 +/- 14.5). Carbon dioxide response tests done under non-loaded and flow-resistive loaded conditions before and during thyroxine replacement therapy showed increases in the loaded respiratory effort and ventilation during thyroxine treatment. Sleep apnea episodes are common in persons with untreated hypothyroidism, even with normal lung function. Thyroxine replacement therapy decreases apnea frequency, even without change in body weight.

Adult↗