We compared two modes of aerosol bronchodilator delivery in 34 patients hospitalized with obstructive airways diseases. The standard mode, therapist-administered up-draft nebulization (UDN), is labor-intensive and therefore relatively costly. The alternative mode, self-administration by a metered dose inhaler (MDI), is less costly, but its efficacy over an entire hospitalization has heretofore not been established. Patients were enrolled after transfer to the pulmonary ward from the emergency room or intensive care units (ICU). We then randomized them to receive metaproterenol q4h either via MDI or UDN. Daily spirometry revealed that MDI and UDN were associated with equivalent bronchodilation initially and equivalent improvement at discharge. The duration of hospitalization for the two groups was also the same. Thus, the two delivery methods were equally effective. We could not attribute this equivalence to pretreatment intergroup differences or to differences in concomitant therapy with steroids, theophylline, other bronchodilators, or antibiotics. Routine use of MDI rather than UDN in all non-ICU adult patients would save $253,487 per year at our institution alone.

The short-term effects of intravenously administered diltiazem on pulmonary and systemic hemodynamics were evaluated in patients with hypoxic pulmonary hypertension. Twelve patients were randomly assigned to two groups in a double-blind fashion. One group (eight patients) received diltiazem, and the other group (four patients) received a placebo. Three increasing doses of diltiazem (0.2, 0.3, and 0.4 mg/kg of body weight) were injected into each patient, followed each time by an infusion (2 micrograms/kg/min, 3 micrograms/kg/min, and 4 micrograms/kg/min). The effects of the drug were also compared with those of oxygen, and the combined effect of high oxygen and diltiazem was tested. The mean plasma concentrations of diltiazem were, successively, 64 +/- 4, 158 +/- 19, and 267 +/- 40 ng/ml with the three increasing doses. There was no significant effect of diltiazem on the pulmonary vascular resistance even when given with oxygen. Diltiazem was well tolerated even at high doses. The arterial oxygen pressure, systemic oxygen supply, and oxygen consumption were unchanged. We conclude that diltiazem does not seem to decrease acutely hypoxic pulmonary vasoconstriction in patients with chronic hypoxia; however, diltiazem may be given safely to these patients for other indications, such as angina pectoris.

Energy expenditure was studied in ten patients with chronic obstructive pulmonary disease (COPD) and weight loss, and in five malnourished patients without clinical evidence of COPD (control group) prior to and after a two-week refeeding regimen. Patients received 5 percent dextrose solution (plus electrolytes) for 36 hours to establish standard baseline conditions and were then randomly assigned to either a carbohydrate-based (CB; 53 percent of calories) or fat-based (FB; 55 percent of calories) diet for the first week. The alternate diet was given the following week. Total calorie intake was set at 70 percent above the energy expenditure measured prior to institution of nutritional support. During energy repletion, energy expenditure was greater than predicted (116 percent) in patients with COPD and less than predicted (90 percent) in the control patients. Thermic effect of nutrients during administration of either regimen was significantly greater (p less than .05) in patients with COPD than in those without COPD during both diets. The difference between the two groups was enhanced during the CB regimen. These observations suggest that malnourished patients with COPD have an elevated resting energy expenditure, and an enhanced thermic response to nutrients as compared to malnourished patients without COPD. Increased diet-induced thermogenesis may contribute to weight loss in patients with COPD, in addition to factors previously described such as decreased caloric intake and increased resting energy expenditure.

We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm-5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects.

Glycopyrrolate, a quaternary ammonium anticholinergic compound is a potentially useful bronchodilator. To determine the efficacy, optimal dose, and duration of action of inhaled glycopyrrolate, we gave the drug to 11 asthmatic patients. Each subject received placebo or glycopyrrolate (100, 200, 600, or 1,200 micrograms) by inhalation in a double-blind, randomized, crossover design. Measurements included FEV1, FVC, heart rate, and blood pressure before administration of the drug and periodically for 12 hours. For eight hours following all doses of glycopyrrolate, both FEV1 and FVC (both as percent of predicted) were significantly greater for drug than for placebo. Glycopyrrolate may be a useful long-acting drug for the treatment of asthma.

We have previously shown that one night of sleep deprivation results in significant deterioration of spirometric performance and ventilatory responsiveness to inhaled carbon dioxide in normal people. Since even a small decrease in pulmonary function may be clinically important in patients with chronic limitation of airflow, we undertook the present study to assess the effects of sleep loss on breathing in patients with chronic obstructive pulmonary disease (COPD). Criteria for inclusion in this study were a ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) of less than 60 percent, no hospital admission for pulmonary disease within two weeks of testing, stable (less than 30 percent variation) in tests of pulmonary function on two occasions within three months of testing, and no history of asthma. We studied 15 men (mean age, 57 +/- 3 years) on two consecutive mornings. Patients were studied with and without sleep deprivation in a randomized fashion. Patients were hospitalized for the study so that sleep deprivation, medications, smoking, and diet could be monitored and enforced. We found small but statistically significant falls in FEV1 (1.06 +/- 0.11 to 1.00 +/- 0.09 L; p less than 0.05) and in FVC (2.56 +/- 0.20 to 2.43 +/- 0.17 L; p less than 0.05) following sleep deprivation. Changes of similar magnitude which were not statistically significant occurred in maximal voluntary ventilation (MVV) and response to carbon dioxide. The arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions were not affected. Maximal expiratory pressure at the mouth increased slightly, but there was a fall in maximal inspiratory pressure (MIP) at the mouth. We conclude that sleep loss is associated with small but significant falls in FEV1 and FVC, as well as changes of similar magnitude in MVV, minute ventilation, and MIP in patients with severe COPD. Although the sleep loss which frequently accompanies exacerbations of COPD may be a slight additional stress of pulmonary reserve, a single night's loss of sleep in the patient with stable chronic airflow obstruction does not have major clinical consequences.

Twenty-four patients (five women) aged 53-72 yr with both ischemic heart disease and asthma or chronic bronchitis receiving oral beta 2-agonists also received additional bronchodilating therapy with theophylline (600 mg daily), enprofylline (600 mg daily) or placebo. The study was double-blind, randomized, triple-crossover with each regimen given for two weeks. Holter monitoring was used during 48 consecutive hours in each period. Compared with placebo, addition of theophylline and enprofylline were associated with an increased mean hourly heart rate of 6 bpm (p less than 0.001). A small, but statistically significant (p less than 0.05) increase in mean hourly frequency of premature ventricular beats (PVBs) occurred with enprofylline as compared with placebo. However, in only two patients with enprofylline (and one patient with theophylline) the increase in PVBs was such that a clinically relevant proarrhythmic effect seems possible. Furthermore, ventricular tachycardia was not more frequently observed with any xanthine than with placebo. Thus, combined oral bronchodilator therapy is not contraindicated in patients with obstructive lung disease and concomitant ischemic heart disease. Holter monitoring is recommended to assess the individual patient's response to such therapy.

To evaluate the efficacy of a mild anxiolytic, alprazolam, in relieving dyspnea, we conducted a randomized, placebo-controlled double-blind study on patients with chronic obstructive lung disease. Twenty-four patients had alprazolam (0.5 mg bid) or placebo administered for one week, followed by placebo for one week, then either placebo or alprazolam for the third week. Assessment tests were performed at the outset, end of the first and second weeks, and finally end of the third week. The parameters measured were: pulmonary function, exercise testing on a bicycle ergometer, and the distance covered in a 12 minute walk. Subjective sensations of dyspnea at rest and during guarded exercise, as well as subjective feelings of calmness or anxiety were also recorded. There was no difference in mechanical lung function, but the PO2 tended to decrease and PCO2 to increase after alprazolam administration. The maximum exercise level attained and the distance covered in the 12 minute walk was unchanged. The subjective perception of dyspnea was the same before and after alprazolam, at rest and during exercise. We conclude that alprazolam is not effective in relieving exercise dyspnea in patients with obstructive lung disease.

Benign thymic hyperplasia (BTH) is a known feature of hyperthyroidism, but is infrequently appreciated by clinicians. In most cases thymic enlargement is minimal; however, it may occasionally present as an appreciable anterior mediastinal mass. While surgical resection is a common approach to such a mass, recognition of the benign nature of BTH and its regression following treatment of hyperthyroidism would prevent a major surgical procedure. We present three cases of BTH associated with hyperthyroidism and describe our approach to this syndrome.

Pulmonary dysfunction commonly follows open heart surgery. To evaluate the effects of positive end-expiratory pressure (PEEP) upon the course and severity of impaired oxygen transfer and roentgenographic evidence of atelectasis after coronary artery bypass grafting (CABG), we randomly assigned 44 patients to positive pressure ventilation and 0, 5, or 10 cm H2O PEEP. Study groups did not differ with respect to preoperative P(A-a)O2 or time on cardiopulmonary bypass. We observed a significant reduction of P(A-a)O2 during positive pressure ventilation with 10 cm H2O PEEP and FIO2 = 0.6 (182 +/- 6 vs 135 +/- 7 mm Hg, p less than .005). Following extubation, P(A-a)O2 measurements of the three groups did not differ when compared 24, 48, 72, 96, or 120 hours after surgery. Roentgenographic atelectasis scores did not differ on the fifth postoperative day. Five days after CABG, P(A-a)O2 exceeded preoperative P(A-a)O2 (29 +/- 1 vs 18 +/- 1 mm Hg, p less than .001), although the roentgenographic distances from hemidiaphragm to lung apex were unchanged (21.2 +/- 0.9 vs 22.0 +/- 0.9 cm). We conclude that routine PEEP improves pulmonary oxygen transfer but, once discontinued, PEEP offers no sustained beneficial effect upon impaired oxygen transfer or roentgenographic evidence of atelectasis following CABG.

We randomized patients with severe hypertension in the Medical Intensive Care Unit to a treatment regimen of oral nifedipine or intravenous nitroprusside. Patients treated with nifedipine achieved a sustained reduction in diastolic blood pressure to less than or equal to 120 mm Hg in an average of less than five hours. Patients treated with nitroprusside achieved a similar reduction in 14 hours (p less than 0.05). Treatment with nifedipine was less expensive and required less time in the ICU than treatment with nitroprusside and was accompanied by no associated increase in morbidity or mortality. Oral nifedipine can be used as an alternative to intravenous nitroprusside in severe uncomplicated hypertension.

Although the mechanisms of nocturnal asthma are still uncertain, increased vagal cholinergic tone may be contributory factor. To examine this hypothesis, we have studied the effect of an anticholinergic drug, oxitropium bromide, on the early morning fall in peak expiratory flow (PEF) in patients with nocturnal asthma. Eighteen patients (aged 18 to 76 years; seven men) with documented nocturnal asthma were studied in a double-blind randomized cross-over study in which they received either oxitropium bromide (200 micrograms or 400 micrograms) or placebo in a single dose at night for two-week periods. With placebo the mean (+/- SE) fall in PEF (expressed as percentage of evening PEF) was 17.3 +/- 2.0 percent, which was significantly reduced to 10.3 +/- 3.3 percent after oxitropium (400 micrograms) (p less than 0.05; ANOVA). Closer analysis revealed that nine of the 18 patients had responded in a dose-dependent manner, with the mean percentage decreases with placebo, 200 micrograms, and 400 micrograms of oxitropium being 19.1 +/- 3.2, 11.5 +/- 4.4, and 5.0 +/- 4.5 percent, respectively (p less than 0.01 between each treatment). The remaining patients were unaffected by therapy. There were no differences between "responders" and "non-responders" in terms of age, atopic status, duration of asthma, severity of asthma, or bronchodilator response to albuterol (salbutamol). There were no differences in nocturnal symptoms between periods of treatment, and no side effects were recorded. We conclude that anticholinergic drugs may protect against nocturnal asthma in some patients, indicating the involvement of vagal cholinergic mechanisms.

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.

While nasal mucosal stimulation in animals has been reported to produce central apneas and while nasal packing in humans is known to produce sleep-disordered breathing, it is controversial whether intranasal obstruction in humans produces predominantly central or obstructive apnea. To answer this question, we studied eight normal men by having them sleep in random order with their nose open or occluded with petrolatum gauze. Esophageal pressure was measured to detect respiratory effort, and standard techniques were used to monitor and score the stages of sleep. Intranasal occlusion increased both the number of apneas plus hypopneas per hour of sleep and the minutes of obstructive events per hour of sleep (p less than 0.05). The minutes of central events per hour of sleep also increased significantly but not to the degree that occurred with obstructive events. Nasal obstruction produced no immediate changes in pulmonary function. The subject with the highest resistance measured through the mouth with the pulse flow method had the most apneas following nasal occlusion. We conclude that intranasal obstruction produces predominantly obstructive apneas and hypopneas during sleep.

Eighteen COPD patients enrolled in a comprehensive, multidisciplinary pulmonary rehabilitation program were randomly assigned to perform either: 1) walking, or 2) ventilatory muscle exercise training (VMT) using a prototype, portable device for isocapnic hyperventilation training. Both groups performed exercise training at home. Twelve patients completed the study and follow-up evaluation (five VMT, seven walkers). Pulmonary function did not change in either group. For the VMT patients, there were modest increases in ventilatory muscle endurance and exercise performance. VO2max and VEmax increased significantly. For the walkers, only walking endurance time increased significantly. These results indicate that isocapnic hyperventilation exercise training can be performed successfully by COPD patients in an unsupervised home setting and can lead to improvement in both ventilatory muscle endurance and exercise performance. Walking exercise training did not improve ventilatory muscle endurance.

Pursed lips breathing (PLB) training is often used in the management of patients with chronic obstructive lung disease (COLD). Previous clinical studies have demonstrated that PLB improves arterial oxygen saturation (SaO2) and CO2 removal as well as relieving dyspnea. Twelve hypoxemic subjects with stable COLD were randomly assigned to either the pursed lips (P) or control group consisting of general relaxation (R). The SaO2 was monitored via ear oximetry, and respiratory rate and tidal volume were monitored using a strain gage transducer and the minute volume was calculated. The PLB was taught by an experienced instructor using the ear oximeter as a monitoring display with a goal toward increasing SaO2. The subject was taught general relaxation (Rlx) with the aid of pleasant music. We compared PLB and Rlx treatments using an A-B-A crossover study design. In both groups, PLB significantly improved SaO2 over baseline (p less than 0.001) whereas Rlx did not. We conclude that patients can learn to increase their SaO2 by PLB using ear oximetry adjunctively.

Several calcium antagonists, each with significantly different chemical structures, have demonstrated variable attenuation of exercise-induced asthma. Quantitative comparisons have been hampered by differences in the intensity of challenge and the severity of the underlying disease between groups of patients. In 12 asthmatic adults with relatively severe exercise-induced asthma, we compared the effect of a new calcium antagonist, PY 108-068, in doses of 75 mg and 150 mg with nifedipine (30 mg) and placebo on resting flow rates and flow rates after exercise. Over a three-week period, each patient completed a four-day, randomized, double-blind Latin-square study. After receiving one of four oral drugs, spirometry was repeated every 30 minutes for two hours, followed by a six-minute treadmill exercise test breathing dry air. The exercise tests were well matched for work rate, ventilation, heart rate, and oxygen uptake. Spirometry was then repeated seven times over the next 30 minutes after exercise. Though both 150 mg of PY 108-068 and nifedipine were associated with mild bronchodilation before exercise, only the latter was significant (p less than 0.05). Exercise-induced asthma (expressed as maximal percent fall in the forced expiratory volume in one second from before baseline) was significantly attenuated only by 150 mg of PY 108-068 compared to placebo (24 +/- 13 vs 40 +/- 16; p less than 0.05). Headache, which occurred in six subjects after nifedipine, five after 150 mg of PY 108-068, one after 75 mg of PY 108-068, and none after placebo, was subjectively more severe after nifedipine. We conclude that in these patients, there was a tendency for mild bronchodilation before exercise with both 150 mg of PY 108-068 and nifedipine, but only the 150-mg dose provided significant protection against exercise-induced asthma two hours after the drug.

We evaluated the efficacy of the esophageal airway (EA) by prospectively randomizing 175 prehospital cardiopulmonary arrest patients to receive either an esophageal gastric tube airway (EGTA) or an endotracheal tube (ET). If attempts with the initial airway failed, the alternate airway was attempted. The cost of training paramedics in EA use was considerably less than the ET ($80 vs $1,000). Survival to the emergency room, to hospitalization and to discharge in ET and EGTA groups were 64.4 percent, 25.6 percent, 11.1 percent, and 54.1 percent, 27.1 percent, 12.9 percent, respectively--differences not statistically significant. The incidence of neurologic residual (ET 50 percent, EGTA 36.4 percent) and congestive heart failure (ET 40 percent, EGTA 45.5 percent) in surviving ET and EGTA patients did not differ (NS). An additional 125 consecutive patients with only the opportunity to receive an EA were also evaluated and did not differ in mortality, neurologic residual, or congestive heart failure from ET patients. We conclude that the EA is a satisfactory alternative to the ET for short-term prehospital use in cardiopulmonary arrest patients.

Seventy-three patients who underwent thoracic surgery were randomly selected for intraoperative intercostal nerve block using phenol (32 block and 41 control subjects). The patients were divided into three groups: pneumonectomies, lobectomies and explorative thoracotomies and evaluated by pain level, respiratory function parameters (VT, IRV, ERV, VC) and blood-gas analysis, both six and 24 hrs after surgery. The patients who had intraoperative nerve block using phenol enjoyed a more comfortable postoperative period. In particular, respiratory parameters were statistically better.