A survey of four inhaled beta-agonist agents was evaluated as a means of selecting the optimum agent for chronic therapy in patients with stable COPD. Eighteen patients completed as protocol of prebronchodilator and postbronchodilator spirometry utilizing albuterol, metaproterenol, pirbuterol, and terbutaline daily in random order. Subsequently, each patient received treatment with either the greatest or least response-invoking agent for four weeks, followed by a second interval with the opposite agent. At the end of each interval, the results of repeat spirometry, arterial blood gas determinations, 12-min walks, dyspnea questionnaires, and self-monitored peak expiratory flow rates were recorded. Use of the greatest response-invoking agent resulted in significantly larger prebronchodilator and postbronchodilator FEV1 and FVC. No other study factor was significantly different. Acute bronchodilator surveys may have a role in medication selection in view of the improvement in spirometric volumes.

Our objective was to compare the differential effects of age and drug type on bronchodilator response.

Survival rates for persons receiving intensive care for Pneumocystis carinii pneumonia have improved. However, the utility of prolonged intensive care for patients who do not show initial improvement remains unclear. We assessed survival in a nested cohort study of patients receiving intensive care while participating in a randomized trial of early adjunctive corticosteroids for Pneumocystis pneumonia. Twenty-eight of 251 (11 percent) participants were admitted to an intensive care unit. Fourteen (50 percent) of these were discharged alive from the intensive care unit and 11 (39 percent) were discharged alive from the hospital. Survivors and nonsurvivors were similar demographically and with respect to treatment received but differed in the mean days of intensive care received (4.5 vs 8.6 [p = 0.02]). The conditional probability surviving to hospital discharge after intensive care dropped steadily from 39 percent at intensive care unit admission to 17 percent after one week and to 0 percent after two weeks.

The optimal antibiotic dosage in serious chest infections is not established and commonly used regimens may well be excessive. We have compared the efficacy of a low dose of cefotaxime (2 g every 12 h) with a more usual dose (2 g every 8 h) in a prospective, randomized study of the treatment of chest infections in the seriously ill. Fifty intensive care unit patients received either regimen for five days. The two groups appeared demographically comparable. Clinical resolution occurred in 86 percent, no change occurred in 4 percent, and deterioration occurred in 10 percent. Microbiologic clearance occurred in 52 percent of those in whom a pathogen was isolated (46 percent of patients). There was no significant difference in clinical or microbiologic response between the two regimens. It is concluded that cefotaxime in a dose of 2 g twice daily is effective in the treatment of serious chest infections.

We compared the bronchodilator effects and systemic tolerability of 12, 24 and 48 micrograms formoterol DP capsules with 12 micrograms formoterol MDI and placebo in 30 patients with reversible obstructive airway disease. Pulmonary function tests were done and pulse rate and blood pressure were recorded. We observed significant differences between all active substances vs placebo regarding peak effect, duration of effect and AUC value. No significant difference was observed between either 12 or 24 micrograms formoterol DP and 12 micrograms from MDI in all mentioned parameters. With 48 micrograms DP, increased peak effect, AUC and duration of effect were noted. Heart rate Holter monitoring showed a slightly more pronounced effect with 48 micrograms. We conclude that 12 to 24 micrograms formoterol DP capsules are equivalent to 12 micrograms of formoterol MDI regarding efficacy and tolerability, while 48 micrograms formoterol DP capsules cause more profound effects in bronchodilation and on the heart rate.

Astemizole, administered for seven days to asthmatic subjects, had an effect of bronchoconstriction induced by inhaled histamine for a mean period of 42 days. This study evaluates whether a single dose of astemizole would have the same effect.

A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.

To determine the effects of a 6-month exercise training program on left ventricular (LV) function and remodeling, 49 consecutive patients (pts) with first Q anterior myocardial infarction (51 +/- 8 years), in I-II NYHA class, were studied 4 to 8 weeks after the acute episode and 6 months later by 2D-ECHO and upright bicycle ergometric test. At entry, pts were randomly allocated to physical training (T = 25pts) or control (C = 24pts). Global endocardial surface area (ESA), LV volumes and EF, extent of abnormal wall motion (%WMA), of regional dilatation (%REG DIL), and the shape distortion (DIST) index were analyzed. After 6 months, a significant increase in work capacity (4,589 +/- 1,417 to 5,379 +/- 1,485 KPM/min, p less than 0.03) and in lactic anaerobic threshold (45 +/- 13 to 63 +/- 15 W, p less than 0.01) was observed only in T. Initial ESA, EDV, EF, %WMA, %REG DIL, and DIST index were similar and they did not change after 6 months in both groups. However, pts with less than 40%EF had greater (p less than 0.0001) EDV and %WMA with marked DIST index at entry and showed further (p less than 0.01) deterioration after 6 months both in C and in T (EDV, ml/m2: 68 +/- 12 to 77 +/- 18 in C, 71 +/- 12 to 74 +/- 18 in T; %REG DIL: 39 +/- 20 to 49 +/- 24 in C, 32 +/- 12 to 35 +/- 23 in T; DIST index: 0.16 +/- 0.07 to 0.21 +/- 0.09 in C, 0.2 +/- 0.07 to 0.22 +/- 0.1 in T). These variables did not change in pts with greater than 40%EF. Thus, from these preliminary data, pts with less than 40%EF at entry are prone to further global and regional LV deterioration. Physical training does not seem to increase this spontaneous deterioration.

To investigate the effects of physical training on neurovegetative profile of patients with previous anterior myocardial infarction (MI), we studied 38 patients out of the EAMI study at 4 to 6 weeks after anterior MI (test 1), who were then assigned randomly to a training group (n = 22) or to a control group (n = 16) and studied again 6 months later (test 2). Neurovegetative function was assessed by analyzing the heart rate variability (HRV) of 24 h, from ambulatory ECG recording, both in time domain, as standard deviation of sinus rhythm RR intervals (sdRR) and percentage of differences greater than 50 ms for successive sinus rhythm R-R intervals (pNN50), and in frequency domain, as low frequency (LF) and high frequency (HF) components of RR variability power spectrum. At test 1, HRV was almost in normal range or slightly decreased in few subjects. HRV increased on average at test 2: sdRR augmented significantly (p less than 0.05) without significant differences between training group and control group; mean LF/HF ratio increased slightly (p less than 0.05) at test 2. This might suggest a shift of neurovegetative balance toward a sympathetic rule, but the difference is too small and the patient population limited to reach firm conclusions. Analysis of 24-h dynamics of HRV in single patients showed different patterns and different adaptations during the time course of 6 months after anterior MI.

Signs of sympathetic hyperactivity and low parasympathetic activity have been found during the acute and recovery phases of myocardial infarction and have been associated with an increased risk of cardiac mortality. Beneficial effects of physical training have been recently reported in post-myocardial infarction patients. We tested the hypothesis that physical training would be effective in improving the autonomic balance by studying 22 patients with a first and recent myocardial infarction who were randomly assigned to enter or not enter a 4-week in-hospital physical training program. Spectral indices of heart rate variability were analyzed at rest and during 70 degrees head-up tilt before and after the index training, not training period. As expected, physical training induced a significant increase in exercise duration (13.7 +/- 0.8 vs 17.1 +/- 0.1 min, p less than 0.001) and in the anaerobic threshold (9.5 +/- 0.7 vs 12.0 +/- 1.0 min, p less than 0.02) in trained patients, while no changes were observed in the untrained group. At entry, in both groups, spectral profile of heart rate variability was characterized by a predominant LF component and a smaller HF component with no further modification after head-up tilt. After 4 weeks, in resting conditions, no significant changes in spectral components were observed in both trained and untrained patients. After physical training, head-up tilt produced significant modifications in spectral profile with an increase in the LF component (84 +/- 3 vs 69 +/- 5 nu, p less than 0.01) and a decrease in the HF component (7 +/- 1 vs 19 +/- 4 nu, p less than 0.05) in trained patients, while no changes were observed in the untrained patients. Our data suggest that in postmyocardial infarction patients, 4 weeks of physical training may induce an improvement in the autonomic balance with a restoration toward normal in the reflex activity of the system.

Patients with COPD feel better and are able to sustain a given level of activity longer after a program of exercise training, but the underlying physiologic mechanisms have not been completely elucidated. Since the physical performance of patients with COPD is limited mainly by pathophysiologic derangements of the ventilatory system, the exercise performance can be ameliorated by increasing the level of ventilation that they can sustain or by reducing the ventilatory requirement for a given level of activity. Almost all studies have yielded negative results in patients with COPD in terms of exercise training having the ability to improve VEmax. The only way to reduce the ventilatory requirement is to reduce CO2 output. Lower levels of lactate result in less nonmetabolic CO2 produced by bicarbonate buffering and this is the likely mechanism responsible for a lower ventilatory requirement for work rates above the pretraining anaerobic threshold. We specifically wished to determine whether a program of intensity, frequency, and duration known capable of producing a physiologic training effect in healthy subjects would do so in patients with COPD. Further, we sought to determine whether exercise training at a work rate associated with lactic acidosis is more effective in inducing a training effect in patients with COPD than a work rate not associated with lactic acidosis. Nineteen patients with COPD were selected and performed an incremental test as well as 2 square wave tests at a low and a high work rate. Identical tests were performed after an 8-week program of cycle ergometer training either for 45 min/day at a high work rate or for a proportionally longer time at a low work rate. For the high work rate training group, identical work rates engendered less lactate (4.5 vs 7.2 mEq/L) and less VE (48 vs 55 L/min) after training; the low work rate training group had significantly less lactate and VE decrease (p less than 0.01). Further, in the first group, there was an increase in exercise tolerance averaging 71% in the high constant work rate test. There was a good correlation (r = 0.73, p less than 0.005) between the decrease in blood lactate and the decrease in ventilation. The major findings of this study are that patients with COPD who experience lactic acidosis during exercise can achieve physiologic training responses from a program of endurance training and that training work rates engendering high levels of blood lactate are more effective than work rates eliciting low lactate levels.

A new program of rehabilitation is less demanding on cardiac output than standard programs. Twenty-five patients with chronic heart failure (ejection fraction [EF]: 0.26 +/- 0.10) were randomized into 2 groups: a control group with 13 patients and a rehabilitation group of 12 patients. In the control group, 2 did not complete the study (cancer, cardiac transplantation). For the 11 others, the different parameters studied were comparable at day 0 with group R and did not significantly change over 3 months outside of a spontaneous improvement in endurance performance by 22%. In the rehabilitation group (40 sessions over 90 days; specialized equipment) there were no incidents. Tolerance was excellent (heart rate during sessions less than 115 bpm) and all functional parameters improved. Training did not modify the isotopic ejection fraction. The quality of life score increased respectively by 52% (p less than 0.0001 in comparison with the control group) and by 63% (p less than 0.0001); 80% of the patients requested that training be prolonged. The functional improvement obtained by purely peripheral effect had no adverse effect on the heart.

The reduction in morbidity and mortality associated with thrombolytic therapy in patients with acute myocardial infarction was initially attributed to early restoration of arterial patency, salvage of ischemic myocardium, and preservation of left ventricular function. Recombinant tissue plasminogen activator (rt-PA) was initially the favored thrombolytic agent because of selected studies showing superior early patency rates. Interestingly, averaged results of studies using conventional dosing regimens show 90-min patency rates for streptokinase, rt-PA, and anisoylated plasminogen streptokinase activator complex (APSAC) to be 53%, 68%, and 72%, respectively, suggesting that previous claims exaggerated differences in early patency. More recently, it was found that administering the full 100-mg dose of rt-PA within 90 min increased 90-min patency rates to approximately 85% and that infusing rt-PA plus urokinase or streptokinase halved reocclusion rates. These results again suggest the unrealized potential of rt-PA to offer a unique clinical benefit. However, three important recent trials have challenged the concept that early patency conveys a survival benefit by showing no difference in mortality in patients treated with different thrombolytic agents. Other trials have shown survival benefit in patients in whom patency of the infarct artery was achieved in a time frame beyond that in which myocardial salvage could be expected. The "open-artery hypothesis" suggests that survival may be more dependent on improved left ventricular remodeling and healing, increased electrical stability, and better myocardial perfusion than on infarct size reduction. In an attempt to determine whether 90-min patency or 24-h patency is more predictive of survival, the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial will randomize approximately 40,000 patients to (1) streptokinase and subcutaneous heparin; (2) streptokinase and intravenous heparin; (3) front-loaded, weight-adjusted rt-PA and intravenous heparin; or (4) the combination of streptokinase and rt-PA and intravenous heparin.

Twenty-one subjects with known bronchial hyperreactivity were prospectively randomized in double-blind fashion to receive one of two angiotensin-converting enzyme inhibitors (ACE-I), enalapril or spirapril, for three weeks. Spirometry and methacholine provocation were performed prior to, during, and following ACE-I usage. Three of 21 subjects developed a nonproductive cough. However, only one subject wheezed slightly. Spirometry and bronchial reactivity (PD20) were unchanged throughout the study.

In order to investigate the role of hypoxia on the cyclic oscillation of transmural pulmonary artery pressure (PAP) in obstructive sleep apnea, oxygen was administered during one half of the night to six patients affected by obstructive sleep apnea syndrome during a nocturnal polysomnographic study. In each patient, transmural PAP measurements were performed on 15 randomly selected apneas recorded while breathing room air, and on 15 during O2 administration. During O2 administration in all patients, apneas were associated with a higher oxyhemoglobin saturation (SaO2), a smaller SaO2 swing, and a higher transcutaneous PCO2. The mean highest level of transmural PAP in the apneic episodes, commonly reached at their end, was significantly lower than while breathing room air in only two patients; however, due to a decrease in the mean lowest PAP level (at the beginning of apneas), the extent of the PAP increase within apneas did not differ between air and O2 breathing; these patients showed the smallest increase in transcutaneous PCO2 in our sample. End-apneic transmural PAP during O2 administration was significantly higher in one subject (for systolic values) and was not significantly different in the remaining three subjects. The extent of the increase in transmural PAP within apneas was greater in one patient; it was smaller in another one, but only for the diastolic values; and it did not differ significantly with respect to the value observed while breathing room air in all of the other subjects. The results suggest that hypoxia in obstructive apneas, at least in some patients, may lead to a steady increase in PAP, detectable both at the beginning and at the end of the episodes; conversely, the increase in PAP within apneas does not seem to be influenced by the simultaneous decrease in SaO2.

To determine whether formoterol, a new beta 2 agonist with experimentally documented long duration, is clinically more effective than salbutamol in the maintenance treatment of chronic asthma.

Twelve patients with documented obstructive sleep apnea were enrolled in a double-blind placebo controlled crossover trial of oral theophylline, (Uniphyllin) 800 mg, taken at night for four weeks. Overnight polysomnography, using standard techniques, was performed at the end of each treatment period. The total number of apneas (A) and hypopneas (H) decreased significantly while receiving theophylline compared to placebo, from 398 (69), mean (SEM), to 283 (72), p less than 0.01. Sleep quality was, however, significantly worse while receiving theophylline. Obstructive A and H were very much decreased with theophylline (p less than .001), and even when the data were adjusted for the more disturbed sleep with theophylline, this decrease remained significant; the obstructive A and H index fell from 49 (8.7) on placebo to 40 (9) while receiving theophylline, p = 0.02. There was no difference in the numbers of central or mixed A and H, and mean A and H duration was unchanged on the two study nights. Oxygen desaturations greater than 4 percent were less with theophylline treatment (p = 0.02), but mean overnight SaO2 was unchanged. We conclude that theophylline may be beneficial in patients with OSA, but part of the improvement is due to a deterioration in sleep quality.

Acetazolamide treatment ameliorates the symptoms of AMS; however, the mechanism by which this occurs is unclear. To examine the effects of acetazolamide on oxygenation, CO2 responsiveness and ventilatory pattern during acute exposure to HA, we studied two groups of subjects at SL and following rapid (less than 8 h) transport to HA. Acetazolamide or placebo tablets were given to groups 1 and 2, respectively, in a double-blind manner after baseline SL measurements; treatment was continued during HA exposure. There was no difference in the ventilatory pattern at HA, between the two groups. While the Ve achieved in response to CO2 at HA vs SL was much greater in each group the percent change from baseline at HA versus that at SL was not significantly different. The beneficial effects of acetazolamide in AMS are associated with a higher level of ventilation at HA and better oxygenation: CO2 chemosensitivity is not affected by acetazolamide at HA.

To assess the efficacy and safety of nedocromil sodium metered dose aerosol as an adjunct to sustained-released theophylline therapy in adult theophylline-dependent asthma patients and to examine the ability of nedocromil sodium to substitute for theophylline.

We undertook this study to characterize the postthoracotomy compartmental displacement and respiratory mechanical changes occurring during and after the performance of the incentive spirometry maneuver. We also evaluated the effect of recumbency angle on compartmental recruitment. Sixteen patients were randomized to perform incentive spirometry either at 30 degrees or 60 degrees recumbency angle. They were studied using respiratory inductance plethysmography to measure tidal volume, respiratory frequency, inspiratory time, rib cage motion/tidal volume ratio, inspiratory duty cycle, and inspiratory flow. Patients were studied before surgery and on postoperative days 1 and 3. Statistical analysis was accomplished using multiple measures ANOVA with post-hoc Student's t-tests when appropriate. Preoperative incentive spirometry augmented VT by increasing both VT/TI and TI. Postoperatively, the incentive recruitment of VT was reduced, a result of a decrease in TI and TI/TTOT; VT/TI was unchanged. There was postoperative decrease of AB and AB/VT during incentive spirometry, greatest in the 60 degrees group. Our results characterize the nature of the respiratory recruitment afforded by incentive spirometry, before and after thoracotomy. We also found evidence of postthoracotomy diaphragmatic derecruitment during incentive spirometry exacerbated by a high recumbency angle.