Maintenance of wakefulness test in obstructive sleep apnea syndrome.

The usefulness of a 40-min per trial version of the maintenance of wakefulness test was assessed in 322 patients with obstructive sleep apnea. This test is a variant of the multiple sleep latency test in which patients are asked to remain awake in a quiet darkened room, and then monitored for electroencephalographic sleep onset. The four trials of the test are each stopped after 40 min. The mean sleep latency for all patients was 26.0 +/- 11.8 (SD) min. In a group of 24 patients who underwent treatment with nasal continuous positive airway pressure, the mean sleep latency increased from 18.0 +/- 12.3 to 31.9 +/- 10.4. The strongest nocturnal correlates of the MWT sleep latency were respiratory arousal index (r = -.35), mean oxygen saturation (r = .30), and weight/height ratio (r = -.25). These correlations were comparable to other studies using the MSLT. There were strong intercorrelations among the variables. In the more severe groups, measures of hypoxemia were more strongly correlated with MWT sleep latency. A two-factor analysis of variance using respiratory arousal index and several measures of oxyhemoglobin saturation indicated that both arousals from sleep and degree of hypoxemia contribute interactively to daytime dysfunction in patients with sleep apnea. The MWT appears useful in evaluating disability from daytime sleepiness.

Safety and possible efficacy of fiberoptic bronchoscopy with lavage in the management of refractory asthma with mucous impaction.

Mucous impaction may be suspected in asthmatic exacerbation when, despite aggressive medical management, patients continue to produce sputum containing mucous plugs and exhibit prominent rhonchi and/or wheezes on chest auscultation. Spirometric measurements in this setting corroborate lack of improvement and reveal significant impairment in indices that may reflect small airways function (FEF25-75). We hypothesized that clearance of inspissated secretions by fiberoptic bronchoscopy with lavage (FOBwL) may promote or hasten the clinical improvement of such patients. Fifty-one therapeutic FOBwL were accomplished in 19 patients during 20 episodes of stabilized yet refractory asthma with mucous impaction. No significant complications were encountered. After FOBwL, spirometric measurements of FEV1, FEF25-75, and FVC increased significantly (P less than .01, paired t test), and correlated with relief of dyspnea and mobilization of secretions with cough. FOBwL can be safely performed in stabilized, refractory asthma, and with apparent efficacy. Further investigation is needed to document the therapeutic utility of FOBwL in refractory asthma.

Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.

A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.

Effect of triazolam on sleep and arterial oxygen saturation in patients with chronic obstructive pulmonary disease.

We compared the effects of a placebo with 0.125 and 0.25 mg of triazolam (Halcion) on sleep quality, oximetry, and respiratory events during sleep in ten stable outpatients with chronic obstructive pulmonary disease. The subjects had a forced expiratory volume in 1 s ranging from 17% to 76% of the predicted value (mean +/- SD, 38.1% +/- 19%) and a waking arterial oxygen pressure from 46 to 84 mm Hg (mean +/- SD, 67 +/- 12 mm Hg). Polysomnography was done on three nights within a two-week period after the patients received on a "blinded" basis either placebo or 0.125 or 0.25 mg of triazolam. Triazolam produced improvements in total sleep duration, time spent in stage 2 nonrapid eye movement (NREM) sleep, and subjective of sleep quality. For most patients, there was a nighttime drop in arterial oxygen percentage of saturation (SaO2) in the placebo condition, but triazolam did not cause a significant worsening, of the mean SaO2, minimum SaO2, or the number of apneic and hypopneic events. Across all experimental conditions, we documented little desaturation during wakefulness (mean low, 87.2% +/- 10.2%), more during NREM sleep (mean low, 83.2% +/- 12.6%), and most desaturation in REM sleep (mean low, 80.1% +/- 15.7%). We conclude that single-night use of triazolam improved the quality and duration of sleep in patients with chronic obstructive pulmonary disease. In patients without severe waking hypoxemia and without carbon dioxide retention, triazolam did not increase either nocturnal hypoxemia or respiratory events during sleep.

Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam.

Clonazepam (1 mg h.s.) and temazepam (30 mg h.s.) were studied in 10 patients diagnosed as having insomnia with nocturnal myoclonus. Each subject underwent two nocturnal polysomnographic recordings while drug-free, two during treatment with clonazepam, and two during treatment with temazepam. Treatment sessions were 7 days long, and recordings were done on nights 6 and 7 of the treatment sessions. A 14-day washout period separated the treatment sessions. The order of drugs used in the first and second treatment sessions was randomized. Objective and subjective sleep laboratory data showed that both drugs improved the sleep of patients with insomnia in association with nocturnal myoclonus. Neither drug significantly reduced the number of nocturnal myoclonic events. Sleep changes were consistent with those produced by sedative benzodiazepines in general. Thus, the data support clinical reports that clonazepam, a benzodiazepine marketed for the indication of seizure, is useful in improving sleep disturbances associated with nocturnal myoclonus. Temazepam, a benzodiazepine marketed for the indication of insomnia, was found to be a suitable alternative to clonazepam in the treatment of insomnia associated with nocturnal myoclonus. The present data and other studies suggest the need for a model that explains why leg movements and sleep disturbances may wax and wane independently.

Treatment of narcolepsy: objective studies on methylphenidate, pemoline, and protriptyline.

Methylphenidate, pemoline, and protriptyline were studied for their treatment efficacy in narcolepsy. A low, intermediate, and high dose level of each drug was studied for 1 week. For methylphenidate the doses were 10, 30, or 60 mg/day; for pemoline, 18.75, 56.25, or 112.5 mg/day; and for protriptyline 10, 30, or 60 mg/day. The order of dose levels was random from subject to subject and the daily dose was divided into thirds and taken in identically appearing capsules morning, noon, and afternoon. Subjects were 6 narcoleptic patients studied on methylphenidate (5 women and 1 man; mean age 54.5 + 11.7 years), 7 narcoleptic patients studied on pemoline (5 women and 2 men; mean age 43.0 + 7.1 years), and 4 narcoleptic patients studied on protriptyline (2 women and 2 men; mean age 42.5 + 16.9 years). Testing consisted of day-long sessions occurring at the end of each dose level and involving a clinical status questionnaire as well as maintenance of wakefulness, Wilkinson addition, and Digit-Symbol Substitution tests. Results were compared with 9 control subjects with no sleep disorder (5 women and 4 men; mean age 39.2 + 8.4 years) who were given placebo that was purported to be a "stimulant drug" and tested in a similar manner. Results demonstrated profound differences in ability to stay awake and perform between narcoleptic patients and controls. Data also suggested that methylphenidate significantly improves ability to stay awake. Pemoline seems to improve ability to perform. Protriptyline does not significantly alter ability to stay awake or to perform.

Acute effects of oxygen treatment upon information processing in hypoxemic COPD patients.

The present study investigated the effects of oxygen therapy upon human information processing for hypoxemic COPD patients. Each of ten patients was admitted to a general clinical research center for a two-day period. In a randomly counter-balanced factorial design, patients breathed either room air or enriched oxygen for either six hours or 20 minutes prior to testing. The tests evaluated speed of information processing, ability to detect correct sequence of tones, and serial memory. In addition, patients were evaluated on critical flicker fusion and story recall. The results suggested that acute oxygen therapy does not reverse information processing deficits observed in hypoxemic COPD patients.

Hemodynamic response to oxygen therapy in chronic obstructive pulmonary disease.

At six centers, 203 patients with stabilized hypoxemic chronic obstructive pulmonary disease were evaluated hemodynamically during a continuous or 12-hour oxygen therapy program. Neither oxygen therapy program resulted in correction or near-correction of the baseline hemodynamic abnormalities. The continuous oxygen therapy group did show improvement in pulmonary vascular resistance, pulmonary arterial pressure, and stroke volume index. The improvement in pulmonary vascular resistance was associated with improved cardiac function, as evidenced by an increase in baseline and exercise stroke volume index. The nocturnal oxygen therapy group showed stable hemodynamic variables. For both groups, changes in mean pulmonary artery pressure during the first 6 months were associated with subsequent survival after adjustment for association with the baseline mean pulmonary artery pressure. Continuous oxygen therapy can improve the hemodynamic abnormalities of patients with hypoxic chronic obstructive pulmonary disease. The hemodynamic response to this treatment is predictive of survival.

The effect of short-term oxygen supplementation on oxygen hemoglobin affinity in patients with chronic obstructive pulmonary disease.

In 12 hypoxemic patients with chronic obstructive pulmonary disease, the partial pressure of oxygen at which hemoglobin is 50% saturated (P50) and levels of 2,3-diphosphoglycerate (2,3-DPG) were determined under 3 study conditions: (1) while breathing room air, (2) during oxygen supplementation for 72 h sufficient to increase PaO2 above 70 mmHg, and (3) at 72 h after the period of oxygen supplementation. The data showed that in the control period in hypoxemic (PaO2, 52 +/- 6 mmHg), mildly hypercapnic (PaCO2, 47 +/- 6 mmHg) patients with a borderline elevation of pH (7.42 +/- 0.03), there was an increase in P50 (28.6 +/- 1.6 versus a normal value of 26.5 +/- 1; p less than 0.005), and a concomitant increase in 2,3-DPG (19.02 +/- 1.77 mg/g Hb versus a normal value of 13.52 +/- 1.27; p less than 0.005). Nine patients received oxygen for 24 h, and 5 received oxygen for 72 h. In these 5 patients, oxygen supplementation resulted in a shift in P50 to a normal value of 26.7 +/- 1.8 (this value was different from the patients' level while breathing room air and not different from that of the normoxemic control subjects) and a decrease in 2,3-DPG toward but not to a normal value (16.34 +/- 1.92; p less than 0.01). This shift in P50 to the left could be related to the decrease in 2,3-DPG. Accordingly, in patients with COPD who are treated with supplemental oxygen, the net effect on oxygen transport would be a function of the changes produced in PaO2 versus those in hemoglobin-oxygen affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Deciding who should receive outpatient oxygen therapy.

Comprehensive treatment of advanced chronic airway obstruction includes consideration of outpatient oxygen therapy. A physician's decision as to whether a patient should receive this form of therapy rests on the clinical and investigative information that defines the benefits and problems.

Neuropsychologic findings in hypoxemic chronic obstructive pulmonary disease.

As part of a six-center clinical trial of the effectiveness of continuous v nocturnal oxygen in the management of hypoxemic chronic obstructive pulmonary disease (COPD), we performed detailed neuropsychologic assessments of these patients prior to their beginning treatment. The 203 patients (age, 65 years; Pao2, 51 mm Hg; forced expiratory volume in 1 s, 0.74 L) performed significantly worse than controls on virtually all neuropsychologic tests. Moderate to severe test impairment suggestive of cerebral dysfunction was found in 42% of the patients, as compared with 14% of controls. Higher cognitive functions (abstracting ability, complex perceptual-motor integration) were most severely affected, although half the patients also showed decrements in motor speed, strength, and coordination. Low-order significant inverse correlations were found between neuropsychologic impairment and Pao2, resting arterial oxygen saturation and hemoglobin levels and maximum work. It is concluded that cerebral disturbance is common in hypoxemic COPD and may be related in part to decreased availability of oxygen to the brain.

Life quality of patients with chronic obstructive pulmonary disease.

Two hundred three patients with hypoxemic chronic obstructive pulmonary disease (COPD) and 73 healthy control subjects matched for age, sex, race, and neighborhood of residence were administered three self-report inventories concerned with the following four dimensions of life quality: emotional functioning, social-role functioning, activities of daily living, and recreational pastimes. An additional inventory was administered to a spouse or another close relative of each patient. The life quality of patients with COPD was found to be impaired relative to healthy subjects on all dimensions. Depression was the preponderant emotional disturbance reported; difficulties with home management and reduction in social interaction were the primary social-role deficits. Ambulation, mobility, sleep and rest, and a variety of recreational pastimes were also severely affected. Life quality exhibited moderate but significant relationships to neuropsychological, pulmonary, and cardiac functioning and to exercise capability. Age and socioeconomic status were found to be possible moderators of the relationship of COPD to life quality. A model to integrate these findings is proposed. Implications for the management of COPD and for the evaluation of medical treatments of chronic disabling conditions are described.

Selection of patients with chronic obstructive pulmonary disease for long-term oxygen therapy.

The Nocturnal Oxygen Therapy Trial, a study of oxygen therapy in patients with chronic obstructive pulmonary disease, has combined the experience of six centers concerning the selection of patients for oxygen treatment. Forty-five percent of hypoxic patients initially selected for the study improved enough during the one month of outpatient observation to allow suspension of plans to treat them with oxygen. Therefore, long-term oxygen therapy plans should only be made without a month of careful observation. Resting PaO2 values less than 40 mm Hg suggest instability or that chronic obstructive pulmonary disease is not the only cause of the hypoxemia. Nasal prong oxygen flow of 1 to 3 L/min reversed hypoxemia in 95% of stable patients with chronic obstructive pulmonary disease.