Vigorous respiratory therapy can prevent the development of postoperative pulmonary complications which occur with increased frequency after upper abdominal surgery. Obesity poses an additional risk factor. To study the effects of postoperative chest percussion with postural drainage (CPT), 53 consecutive patients undergoing Roux-en-Y gastric stapling procedures for treatment of morbid obesity were randomized to two groups. Both received identical postoperative respiratory care, except the study group received additional CPT. It was concluded that the addition of CPT to patients without prior chronic lung disease undergoing upper abdominal surgery caused patient discomfort, increased hospital cost, and failed to affect the incidence of postoperative pulmonary complications.

A metered-dose aerosol formulation of terbutaline sulfate (Brethaire), 0.400 mg four times daily, was compared with an identical formulation of isoproterenol sulfate, 0.150 mg four times daily, in a parallel, double-blind, clinical study completed by 40 adult patients with asthma. All patients had been stabilized on theophylline (serum levels of 10 to 20 micrograms/ml). The effectiveness of isoproterenol peaked between 5 and 15 minutes after administration. The effectiveness of terbutaline peaked between 5 and 120 minutes after administration. In each of five visits spaced over a three-month period, patients receiving terbutaline showed a longer duration of bronchodilatory effect than those receiving isoproterenol, with the greatest difference occurring at 60 and 120 minutes after drug administration.

The efficacy of a new antiarrhythmic agent, lorcainide, was compared with that of quinidine gluconate in a fixed-dose, randomized, crossover trial. Of 26 previously untreated patients with frequent ventricular ectopic beats documented by 24-hour ambulatory monitoring, 17 completed four weeks of therapy with quinidine and 12 with lorcainide. Of 22 patients receiving both drugs, early termination of therapy due to side effects occurred in ten (45 percent) patients receiving lorcainide and five (23 percent) receiving quinidine. Lorcainide (100 mg twice daily or three times daily, dependent on body weight) effectively suppressed ventricular arrhythmias in seven of 12 (58 percent) patients completing four weeks of therapy, and suppression by quinidine gluconate (324 mg three times daily) occurred in five of 12 (59 percent) patients. We conclude that in a dose of 100 mg twice or three times daily, lorcainide is as effective as quinidine gluconate, 324 mg three times daily, for the suppression of chronic ventricular arrhythmias. However, the high incidence of adverse reactions experienced with lorcainide make it an unacceptable agent for first-line antiarrhythmic therapy.

We compared the efficacy of corticosteroid therapy initiated as an alternate-day regimen to that of a four-times-daily regimen in patients with stable chronic obstructive pulmonary disease. In this double-blind study, 44 patients with moderate to severe COPD (mean FEV1 740 +/- 310 ml) were hospitalized and randomly allocated to receive methylprednisolone, 8 mg qid, 64 mg qod, or placebo for a ten-day period. The mean FEV1 and FVC improved significantly to a comparable degree in both steroid-treated groups, but not in the placebo-treated group. Eight of the 29 steroid-treated patients (28 percent) had improved FEV1 of more than 25 percent compared with only one of the 15 placebo-treated patients. Those in the qod group also had notable improvement in SaO2. Although the correlation between the improvement after the administration of nebulized bronchodilators and that after corticosteroid therapy was significant, some patients had more than a 25 percent improvement in their FEV1 with corticosteroids, but less than a 10 percent improvement after nebulized bronchodilators. We conclude that a substantial proportion of all patients with stable COPD will have a greater than 25 percent improvement in their flow rates with corticosteroid administration. Since the response to a qod regimen is comparable to that of a qid regimen, and since the qod regimen is associated with fewer side effects, we recommend that a qod regimen be tried initially.

Twenty-eight patients with advanced emphysema and/or chronic bronchitis and severe airflow obstruction were randomly assigned to receive either bitolterol or isoproterenol aerosol delivered by a metered dose device which was administered three times daily. Randomization resulted in similar patients with like degrees of airflow obstruction and responsiveness to a test dose of inhaled bronchodilator. Significantly greater improvement in airflow was achieved by administration of bitolterol compared to isoproterenol. Pharmacologic responses continued after 90 days of daily dosing. Both drugs were well tolerated and side effects included mild degrees of tachycardia for both drugs. Two patients assigned to isoproterenol stopped therapy during the study due to side effects. This study indicates that bitolterol is more effective than isoproterenol in degree and duration of bronchodilatation in patients with advanced chronic obstructive pulmonary disease.

Autopsy findings and a morphometric study of the lungs were compared in 18 subjects receiving nocturnal oxygen and 15 receiving continuous oxygen in the National Heart, Lung, and Blood Institute Nocturnal Oxygen Therapy Trial (about half of those who died). The emphysema score, average interalveolar wall distance, central airway lesions, peripheral airway lesions, and the ratio of weights of left ventricle plus septum to right ventricle were similar in the two groups. The causes of death in the two groups were also similar. This evidence supports the hypothesis that the improved prognosis observed with continuous oxygen therapy nocturnal oxygen therapy in patients with severe chronic airflow obstruction and hypoxemia was due to treatment. There was a trend for there to be more interstitial fibrosis and type 2 alveolar epithelial cell hyperplasia in those treated with nocturnal oxygen; in the hands of one observer, the type 2 cell hyperplasia was significant.

Lorcainide, a new type I antiarrhythmic agent, was compared to quinidine in respect to antiarrhythmic efficacy and clinical safety. Thirteen subjects completed an open, randomized, crossover study with analysis of 24-hour ambulatory ECG monitoring and drug blood levels. The QRS and Q-T intervals increased with both lorcainide and quinidine. The mean reduction in total ventricular premature beats (VPBs) with quinidine was 16 percent compared to 68 percent with lorcainide (p less than .05). With lorcainide eight of 13 subjects had a significant (greater than 82 percent) reduction in VPBs compared to only three of 13 subjects taking quinidine (p less than .05). This same relationship was observed when mean VPB/1,000 heartbeats was analyzed. Ventricular tachycardia was no longer present in five of nine subjects taking lorcainide and in two of nine taking quinidine. No relationship could be established between drug level and arrhythmia suppression in this small population. Some CNS effects were reported in both groups, but no significant hematologic, chemical, or urinary adverse effects were seen with either drug. Thus, lorcainide compares favorably to quinidine in regard to arrhythmia suppression, but was limited in its clinical utility by CNS side effects.

The Memorial Sloan-Kettering lung cancer screening program was begun in 1974 to evaluate sputum cytology as a supplement to the annual chest x-ray examination for early detection and diagnosis. The 10,040 adult, male cigarette smokers who enrolled were randomly assigned to receive annual chest x-ray examinations only or a dual screen with annual chest x-ray examination and four monthly sputum cytology evaluation. Over 40 percent of the 288 who developed lung cancer were diagnosed in stage I, and their survival was 76 percent at five years; overall survival was 35 percent. Nearly one third of the lung cancers detected on first examination on the dual screen, and 14 percent of those on subsequent examinations were found by cytologic examination. The same number of cancers developed in the x-ray screen only group, and were diagnosed at a later date. Despite the delay, survival and mortality were the same, suggesting that the squamous carcinomas detected by cytologic examination alone are very slow growing and tend to remain localized until detectable by x-ray examination.

Twenty-one patients with stable chronic obstructive pulmonary disease (mean FEV1 = 0.98 L) and high-normal serum theophylline levels (15-20 micrograms/ml) were evaluated in a randomized, double-blind fashion for additional bronchodilator response to aerosolized normal saline, atropine, or metaproterenol. Patients were classified as responders (R; n = 9) or nonresponders (NR; n = 12) to inhaled isoproterenol when they were taking no medications. Atropine and metaproterenol caused a significant additional increase in FEV1 for R (p less than .05), whereas only atropine resulted in a significant increase for NR (p less than .05). For R, the increase due to atropine was significantly greater compared to metaproterenol (p less than .05). We conclude that inhaled atropine (an anticholinergic drug) may be preferable to inhaled metaproterenol (a beta-adrenergic agonist) when additional bronchodilation is needed in patients with chronic obstructive pulmonary disease and high-normal serum theophylline levels.

The effectiveness of inhaled fenoterol doses of 0.4 mg and 0.8 mg in preventing exercise-induced asthma was investigated in 12 patients. Exercise-induced asthma was prevented by both doses for two hours after administration, but the effect of neither dose was significantly different from that of placebo four hours after. There was no statistically significant difference between the effects of the two fenoterol doses; and only a few patients were protected for more than two hours by the higher dose.

Manual chest wall vibration is one physiotherapeutic technique frequently employed in the management of respiratory disease. A clinical study was undertaken to examine the effects of manual chest wall vibrations on pulmonary function and arterial oxygen saturation in patients with chronic bronchitis. Twelve patients participated in a three-day experimental design where the factors of three different days and three different treatments were randomized and balanced. On one day, deep-breathing exercises were given; on another, deep-breathing exercises with vibrations; and on the remaining day, no treatment was given. Lung volumes were measured before and after each maneuver, and arterial oxygen saturation was monitored continuously. There was a significant decrease in the expiratory reserve volume (ERV) immediately following the deep-breathing exercises alone, which remained constant after the 15-minute rest period (p = 0.032). The remaining outcome parameters do not appear to be significantly affected. Chest wall vibrations do not decrease the ERV in patients with chronic bronchitis.

We compared the effects of inhaled glycopyrrolate (G), 1.3 mg, and atropine (A), 2.6 mg, and placebo on FEV1 and specific conductance (sGaw) before and after exercise in six men with exercise-induced asthma. Subjects exercised with cold air (-2 degrees C) 30 and 120 minutes after each aerosol treatment. Spirometry was performed and sGaw determined before aerosol treatment (baseline) and before and after exercise. Decreased airway tone was noted before exercising with A and G but not with placebo. The decreases in FEV1 and sGaw resulting from exercise were not significantly different among the three treatment groups at either exercise session. Postexercise FEV1 and sGaw were significantly higher after A and G compared to P. Dry mouth, flushing, and resting tachycardia were prominent with group A. Symptoms in G did not differ from those in P. This study suggests that A and G do not prevent bronchoconstriction induced by exercise and cold air but improve postexercise pulmonary function by achieving preexercise bronchodilation. Systemic side effects were minimal with G compared to A.

Thirty patients undergoing elective cholecystectomy were randomly assigned to two groups. Fifteen patients received postoperative intermittent positive pressure breathing (IPPB) for four days together with physiotherapy while the other 15 had the same postoperative care but without IPPB. Vital capacity (VC), functional residual capacity (FRC) and PO2 were measured preoperatively and on days 0, 1, 3, and 5 postoperatively. The incidence of postoperative pulmonary complications utilizing chest x-ray films, sputum analysis, temperature, and clinical assessment was determined. Both groups had significant deterioration in pulmonary function but did not differ except for a greater depression in VC in the IPPB group (p less than .05). In patients receiving postoperative physiotherapy, the addition of IPPB did not usually result in improved pulmonary function.

We evaluated 12 patients with stable chronic airflow obstruction (CAO) and no clinical evidence of left ventricular disease to determine the effects of oral digoxin on exercise capacity (VO2 max) and on right ventricular pump function during exercise. In this randomized, double blind, placebo controlled, cross-over study, patients performed exercise tests and underwent measurement of ejection fractions after two weeks of therapy with oral digoxin (0.25 mg/day) and after two weeks of placebo. Incremental upright exercise testing to a symptom-limited maximum was performed on a cycle ergometer. Right and left ventricular ejection fractions (RVEF, LVEF) were obtained in the supine position at rest and at approximately 75 percent of the maximum workload by gated equilibrium radionuclide angiography. All patients had abnormal right ventricular function, manifested either by a low resting RVEF (less than 45 percent) or a subnormal response to exercise (less than 5 percent increase). The small increases in RVEF with digoxin (mean +/- SE) at rest (44 +/- 5 vs 41 +/- 4 percent) and during exercise (46 +/- 4 vs 44 +/- 3 percent) did not achieve statistical significance. With digoxin, small increases in exercise duration (10.0 +/- 1.5 vs 9.0 +/- 1.4 min), maximum workload achieved (48 +/- 6 vs 42 +/- 5 W), VO2 max (0.85 +/- 0.06 vs 0.81 +/- 0.06 L/min), and oxygen-pulse (O2-P) (6.6 +/- 0.5 vs 6.3 +/- 0.4 ml/beat) occurred. Only the increase in O2-P was significant (p less than 0.05). From this study we conclude that digoxin does not significantly improve exercise capacity in severe chronic airflow obstruction with impaired right ventricular function, nor does it improve RVEF either at rest or during supine submaximal exercise.

To assess whether verapamil taken orally twice daily (bd) was as effective as four times daily (qd) in patients with angina a placebo controlled double blind crossover trial was conducted in 12 patients. Each patient was randomized to verapamil, 160 mg bd, 80 mg qd, or corresponding placebo, each for three weeks. Patients were assessed subjectively and by treadmill exercise test. On both verapamil regimens, patients had less angina with delayed onset of ST segment depression during exercise compared to placebo, without any differences between the two regimens. On bd verapamil, patients could increase their exercise capacity as much as on qd without any increase in adverse effects. Angina threshold during exercise was increased by both regimens with a slightly higher threshold on qd verapamil compared to bd. Therefore, administration of verapamil twice daily is effective in patients with stable angina pectoris, with a similar efficacy to taking verapamil four times daily without any increase in adverse effects.

Controversy exists concerning possible tachyphylaxis of the acute bronchodilating effect of albuterol, especially with regard to the duration of its acute bronchodilating action. We evaluated 140 patients with bronchial asthma in a prospective double-blind controlled study of possible tachyphylaxis to albuterol aerosol as compared to isoproterenol aerosol. We demonstrated statistically significant tachyphylaxis with regard to duration of acute bronchodilating effect. We believe that this tachyphylaxis is not clinically significant because there was no tachyphylaxis with regard to peak bronchodilating effect and because the duration of bronchodilating effect remains significantly greater, both quantitatively and statistically, when compared to isoproterenol aerosol. Moreover, it appeared that most of the tachyphylaxis was present at four weeks of therapy. There was a small increment of tachyphylaxis after eight weeks of therapy, but no further increase in tachyphylaxis was demonstrated after 13 weeks of inhaled albuterol therapy. We therefore feel that clinically significant tachyphylaxis to inhaled albuterol aerosol must be quite unusual and that chronic therapy with inhaled albuterol aerosol is probably both safe and efficacious for bronchospastic disorders.

Nine men who were habitual snorers were studied during a control and a treatment night (in random order) to assess the effect of nasal continuous positive airway pressure (CPAP) on snoring, sleep-disordered breathing, and nocturnal oxygen desaturation. Four subjects had symptoms suggestive of the sleep apnea syndrome, but the other five were asymptomatic. Polysomnography and recordings of snores were obtained on both nights. On the treatment night, the subjects wore a customized infant anesthesia mask over their noses, and CPAP was applied and adjusted upward from 4 cm H2O to a level that obliterated snoring. Nasal CPAP (range 4 to 13 cm H2O) reduced the mean number of snores per night from 1,015 per subject to 23 per subject (p less than 0.01). Mean numbers of episodes of apnea, hypopnea, and desaturation were also significantly reduced. Analysis of sleep structure showed no significant differences in sleep period time, total sleep time, or the percentages of stages 3 and 4 sleep. The percentage of stages 1 and 2 was significantly greater on control nights, and the percentage of REM sleep was greater on treatment nights. On the control nights, snoring was common in stages 3 and 4 and least common during REM sleep.

At rest and during exercise, noninvasive studies of cardiopulmonary physiology in patients with chronic obstructive pulmonary disease (COPD) were carried out to determine the objective benefits of commonly used oral bronchodilator drugs in 15 stable patients without cardiovascular disease or reversible obstruction of airflow. Theophylline, terbutaline, a combination of theophylline and terbutaline, and placebo were given for ten days each in a randomly sequenced double-blind protocol for outpatients. Spirometric values, the ratio of physiologic dead space to tidal volume (VDp/VT), and the alveolar-arterial oxygen pressure difference (P[A-a]O2) were studied at rest on each regimen. During steady-state exercise the changes in VDp/VT and P(A-a)O2, as well as the ventilatory equivalent for oxygen and oxygen pulse, were measured. When compared with placebo, no significant change was noted in the previously mentioned measurements with any regimen, with the exception of a small improvement in the forced expiratory volume in one second, which was significant for all regimens. These findings suggest that commonly used oral bronchodilator drugs in usual doses may have small effects on airflow even in "irreversible" COPD but that the objective effect of these agents on gas exchange during rest and exercise is not significant.