The effects of noninvasive ventilators on COPD remain controversial because of their obscure mechanisms. A randomized crossover study, using iron lung and positive pressure nasal ventilation (BiPAP) each for 40 min, was performed in 11 stable patients with severe COPD. Throughout the study, we monitored surface EMGdi, EMGst, ECG, SaO2, ETCO2, and the movements of RC and AB. Afterwards the data were replayed to calculate VT, RR, PR, VT/TI, iEMG, and phase angle. No statistically significant improvement was found in view of the above parameters. However, the percentage of iEMGst change after 40-min BiPAP ventilation, compared with the baseline, was much more significant in patients with FEV1 below 0.55 L than those with FEV1 above 0.55 L (n = 4:7, delta iEMGst -62.93 percent +/- 23.27 percent vs 32.45 percent +/- 42.79 percent, p = 0.0056). delta iEMGst correlated significantly with FEV1 during BiPAP ventilation (p < 0.05, r = 0.59). We conclude that the iEMGst during short-term BiPAP ventilation correlates with the severity of the disease.

To evaluate the antihypertensive effects and tolerability of a sustained release preparation of nicardipine (NIC SR), a dihydropyridine calcium channel antagonist.

Community-acquired pneumonia is a major cause of death in third world countries. Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia. We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha (TNF-alpha) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy.

This study compared performance of three heat and moisture exchangers (HME) during short-term postoperative mechanical ventilation. Temperature and absolute humidity (AH) were measured at various points of the ventilatory circuit. There was no statistical difference between the groups, regarding ambient and body To, body weight, fraction of inspired oxygen, tidal volume, and respiratory rate. Only the hygroscopic HME (groups 2 and 3) provide adequate conditioning with regard to AH and To of the inspiratory gases. The performance of hydrophobic HME (group 1) was inferior and appears to be unsatisfactory. Indirect evaluation (variations of inspiratory gases and tracheal temperatures, AH of the expired gases) confirmed the superiority of the hygroscopic HME. These data suggest that humidification of inspiratory gases with a hygroscopic HME is a defensible practice during short-term postoperative mechanical ventilation. Performance of hydrophobic HME may be weak and can expose the patient to an unacceptable risk of endotracheal tube occlusion.

A cooperative, prospective randomized study to compare radiotherapy (50 Gy) or 2 courses of combination chemotherapy consisting of cisplatin (50 mg/m2) and vindesine (3 mg/m2) following curative resection was performed in 258 patients at 9 institutions between August 1985 and August 1987. In the two groups, no difference was present in the background factors such as sex, age, and the location and length of the tumor. Also, there was no difference of distribution of pT, pN, pM or p stage by the revised TNM classification of 1987. There was no significant difference in survival up to 5 years in the 2 groups. Concerning the side effects, the decrease in white blood cell and platelet counts was similar in the two groups, but elevation of blood urea nitrogen and creatinine concentrations was more marked in the group receiving chemotherapy than in the group with radiotherapy.

Inhaled furosemide prevents the obstructive response to several bronchoconstrictor stimuli in asthma. To verify whether this protective effect is also shared by other loop diuretics, we investigated the effect of inhaled piretanide on the bronchial obstructive response to ultrasonically nebulized distilled water (UNW) in ten patients with moderate, stable asthma. In a randomized, single-blind dose-response study, each subject performed an UNW test immediately after nebulization of different doses of piretanide between 12 and 48 mg or placebo. The effect of a single 40-mg dose of inhaled furosemide was also investigated in six subjects. Piretanide caused a significant, dose-dependent increase in UNW PD20 with respect to placebo, corresponding to 0.6 +/- 0.2 doubling doses (mean +/- SE) after 12 mg, 1.3 +/- 0.2 after 24 mg, and 2.0 +/- 0.2 after 48 mg, and had a remarkable diuretic effect; 40 mg of furosemide increased UNW PD20 by 2.3 +/- 0.3 doubling doses (p < 0.01), but showed only a modest diuretic activity. These data indicate that inhaled piretanide is as effective as furosemide in preventing UNW-induced asthma, and this effect is unrelated to their diuretic potency.

To investigate the additive effect of oral theophylline on combined inhaled anticholinergic agent and beta 2-agonist therapy, 12 patients with stable COPD (64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial of oral theophylline for a 4-week period (400 mg for 2 weeks, followed by 600 mg for 2 weeks). All of the patients continued to inhale both salbutamol, 200 micrograms, and ipratropium bromide, 40 micrograms, using a metered-dose inhaler four times a day. Spirometry was assessed before, and 15 and 60 min after the inhalation of bronchodilators at 2-week intervals. Even after the inhalation of salbutamol and ipratropium, theophylline significantly improved FEV1 and daily peak expiratory flow rate compared with the placebo. No significant improvement in the daily symptom scores for cough, sputum, wheezing, or shortness of breath was observed throughout the different phases of treatment. This study shows that the additive bronchodilating effect of theophylline, when used in combination with salbutamol, 200 micrograms, and ipratropium, 40 micrograms, is significant but small in stable COPD. The addition of theophylline did not significantly improve the patient's symptoms. Oral theophylline, when used in combination with an inhaled anticholinergic agent and an inhaled beta 2-agonist, may be of limited value in the treatment of stable COPD.

The effects of exercise on asthmatic airway caliber are well recognized. Only a few studies, however, evaluated the effects of prior exercise on asthmatic airway reactivity. Eight asthmatic children (ages 10 to 16 years; mean, 12) performed histamine inhalation tests on three occasions assigned in random order: (1) control; (2) 40 to 60 min after exercise (6 min ergometer cycling) done while breathing cold dry (CD) air (temperature = -13 degrees C, relative humidity = 0 percent); and (3) 40 to 60 min after exercise done while breathing warm humid (WH) air (temperature = 33 degrees C, relative humidity = 100 percent). While there was a marked exercise-induced bronchoconstriction (EIB) in the CD test with a postexercise fall in FEV1 of 39.2 +/- 8 percent (mean +/- SEM), there was no EIB in the WH test (4.6 +/- 2 percent). There was no difference, however, in the geometric mean histamine concentration required to produce a 20 percent fall in FEV1 (PC20) among the CD, WH, and control tests (0.52 mg/ml, 0.60 mg/ml, and 0.55 mg/ml, respectively). Airway reactivity in asthmatic children is not influenced by a prior exercise challenge, independent of the conditions of the inspired air during the exercise. Moreover, exercise per se, regardless of development of EIB, does not change the reactivity.

This study looked at the effects of posture on the morning/evening expiratory flows and airway responsiveness to methacholine. Fourteen nonsmoking subjects with stable asthma (eight men, six women) were included in the study. Subjects were randomly allocated to spend 4 h in the supine or seated position on separate days, in the morning from 8 to 12 AM and in the evening from 8 to 12 PM. The FEV1 was measured hourly in the assigned position. Before and after each 4-h period, a methacholine inhalation test was done in the sitting position. In the morning study, baseline FEV1 measurements on the supine and seated days were not different. There was no significant difference between the baseline and postsession FEV1 on both days (baseline and postsession FEV1 percent predicted +/- SEM; seated: 83.6 +/- 2.9, 83.8 +/- 3.3; supine: 85.8 +/- 2.8, 85.4 +/- 3.7; n = 13). delta FEV1 (baseline/postsession) was not different between the two sessions. In the evening study, baseline FEV1 measurements on the supine and seated days were similar. FEV1 decreased after both sessions, although this difference reached statistical significance only in the supine position (baseline and postsession FEV1 percent predicted +/- SEM; seated: 90.0 +/- 4.1, 84.9 +/- 4.1, p = 0.08; supine: 90.7 +/- 3.1, 82.9 +/- 4.5, p = 0.02; n = 8). delta FEV1 (baseline/postsession) was not different between the two evening sessions. In the morning, after the seated position, PC20 methacholine was unchanged (mean PC20 [mg/ml]: beginning = 1.00, end = 1.02) while after the supine position it was slightly reduced from a mean of 0.97 to 0.73 mg/ml. This last reduction was mainly observed in the most hyperresponsive subjects and its magnitude was significantly correlated with baseline PC20 (r = 0.637, p = 0.024). The increase in methacholine response (delta PC20) after the supine session was significantly higher than after the seated session. In the evening study, there was a slight reduction in PC20 after both sessions, but this was only significant after the supine position (mean PC20 baseline and postsession [mg/ml]: seated: 0.63, 0.47, p = 0.08; supine: 0.62, 0.44, p = 0.04). No difference was found between delta PC20 of the two sessions. We conclude that the supine position does not have persistent effects on FEV1, but it may increase airway responsiveness in the most hyperreactive subjects.

The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1. Secondary outcomes are the development of respiratory and nonrespiratory morbidity and mortality. After screening 73,694 cigarette smokers, aged 35 to 60 years, 5,887 participants were randomized into three equal groups: usual care, smoking intervention with daily use of a metered-dose inhaler with ipratropium bromide, and smoking intervention with inhalation of placebo. Eligible participants had a ratio of FEV1 to forced vital capacity (FVC) of 70 percent or less, were free of known life-limiting conditions, expressed willingness to enter the intervention program if so randomized, and gave written informed consent prior to entry into the trial. Spirometry, methacholine challenge, and questionnaires were strictly standardized within and across centers. The purpose of this report is to describe the characteristics of randomized participants at the time of entry into the study. For both sexes, three measures of lung function--average cross-sectional FEV1/FVC ratio, FEV1, and FEV1 percentage of predicted normal--showed slight downward trends for each successively older 5-year age cohort. The increase in FEV1 after isoproterenol was 15 percent or more in only 2.4 percent of men and 2.8 percent of women. A positive response to methacholine (defined as a fall in FEV1 of > 20 percent from baseline at concentrations up to 25 mg/ml) occurred in 63 percent of men and 87 percent of women. The cross-sectional prevalences of cough, phlegm, wheeze on most days or nights, and shortness of breath were 49 percent, 43 percent, 32 percent, and 43 percent, respectively. Respiratory symptoms were reported by a higher proportion of participants in the younger age groups than in the older age groups. Participants who reported cough, phlegm, and/or wheeze averaged lower FEV1 percent predicted and higher probability of positive response to methacholine than participants who did not. Shortness of breath appeared to be significantly associated with lower lung function and higher reactivity in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

To compare the ability of dopamine and norepinephrine to reverse hemodynamic and metabolic abnormalities of human hyperdynamic septic shock.

Bacterial extracts can act as immune stimulants and in some instances have been used, rather empirically, to prevent recurrent infections in the nonimmunocompromised host. Some agents are administered via oral route with the goal to increase airways immune defenses. In animal models and in normal humans, gut-associated lymphoid tissue (GALT) stimulation is able to induce a generalized response by the whole mucosal-associated lymphoid tissue (MALT). The aim of this placebo-controlled, double-blind, parallel-group study was to evaluate whether the stimulation of the GALT through oral administration of a polyvalent bacterial extract (BE) could lead to significant immune modifications either systemically or locally in the respiratory tract in patients suffering from chronic bronchitis. We selected 20 subjects (5 nonsmokers, 6 smokers, and 9 ex-smokers) for at least 3 years. According to a balanced-block randomization method, ten patients received active treatment and ten received placebo. Either drug or placebo was to be taken as one capsule daily the first 10 days of 3 consecutive months. Each capsule of the active product contained 7 mg of a BE obtained from eight different bacterial strains. On entry (T0) and 90 days after beginning of treatment (T90), all patients underwent bronchoalveolar lavage (BAL) and peripheral blood withdrawal to assay BAL fluids and serum samples for immune parameters. The BAL recoveries, cellularity, cell differentials, and lymphocyte subsets (CD19, CD3, CD4, CD8) did not show significant differences. IgG/albumin and IgA/albumin values were not significantly different, but IgA/albumin was significantly increased in the treatment (T0 = 0.14, 0.01 to 0.27, median and range, T90 = 0.15, 0.08 to 0.45, p = 0.028) vs the placebo group when data from current smokers were excluded. Functional tests on alveolar macrophages (AM) (leading front stimulated motility and superoxide anion-O2(-)-release) showed a significant increase of random migration (T0 = 10.6, 7.0 to 23.6, T90 = 13.4, 8.1 to 28.8 microns, p = 0.02) and of stimulated motility after FMLP 10(-7) M (T0 = 13.2, 8.3 to 46.4, T90 = 18.3, 8.4 to 49.6 microns, p = 0.04), a significant increase of O2- release in basal conditions (T0 = 6.0, 1.7 to 30.5 nM/10(6) AM/10', T90 = 11.1, 5.5 to 24.5, p = 0.05) and after stimulation with opsonized zymosan (T0 = 17.7, 4.7 to 35.2, T90 = 22.1, 13.8 to 53.3, p = 0.009) in the treatment group only. Data were not significantly different in the placebo group between T0 and T90. No modifications in systemic immunity were ever observed.(ABSTRACT TRUNCATED AT 400 WORDS)

To elucidate the effect of oxitropium bromide (OTB), an anticholinergic drug, on dyspnea and gas exchange during exercise in patients with chronic obstructive pulmonary disease (COPD), we performed the cycle exercise test on 19 patients with COPD (mean age, 72.0 +/- 1.9 years; mean FEV1, 1.28 +/- 0.07 L) before and after inhalation of OTB, 300 micrograms, or placebo, 300 micrograms, in randomized fashion. Spirometry was performed immediately before and 30 min after inhalation of either OTB or placebo. Dyspnea during exercise was evaluated using the Borg scale (BS) and the slope of the regression between BS and oxygen uptake (VO2) during exercise (Borg scale slope: BSS). Arterial oxygen saturation (SaO2) was continuously monitored by pulse oximeter during and after exercise. We also measured the recovery time, which was defined as the time to recover decreases in SaO2 after exercise. After OTB, spirometric indices were improved (delta FEV1 16.8 +/- 0.9 percent) and maximal VO2 during exercise increased significantly (from 986 +/- 46 ml/min to 1,156 +/- 55 ml/min, p < 0.01), but not after placebo. The maximal scores of BS and the BSS were significantly decreased after OTB, but not after placebo. Although the SaO2 at rest and during exercise did not differ with or without either OTB or placebo, the recovery time after OTB (77.3 +/- 6.8 s) was significantly shorter than that before administration (98.4 +/- 14.6 s) (p < 0.01). We conclude that the inhaled OTB produces small but significant improvement both in dyspnea during exercise and in exercise performance in stable COPD and may contribute to improve the quality of life in some patients with COPD. However, gas exchange during exercise of COPD patients is little affected by OTB.

We examined the effect of pyridostigmine (PY) at a dose of 30 mg orally three times a day on nonspecific bronchial hyperreactivity in ten normal nonsmokers (NNS), ten smokers (SM), and ten mild asthmatics (AS). We conducted a double-blind, placebo-controlled, crossover trial, randomly assigning subjects to receive either placebo (PL) or PY before undergoing bronchoprovocation challenge with eucapnic voluntary hyperventilation (EVH) using dry gas. Compliance with PY was confirmed by measuring red blood cell acetylcholinesterase (Achase) levels during both days of testing. While taking PL, the mean (+/- SEM) falls in FVC and FEV1 after the bronchoprovocation were as follows: NNS, 1.0 percent (+/- 0.6) FVC and 4.3 percent (+/- 1.0) FEV1; SM, 2.4 percent (+/- 1.1) FVC and 2.7 percent (+/- 1.3) FEV1; AS, 5.3 percent (+/- 2.3) FVC and 11.5 percent (+/- 2.8) FEV1. The mean decreases in FVC and FEV1 while taking PY were as follows: NNS, 1.8 percent (+/- 0.7) FVC and 4.3 percent (+/- 0.8) FEV1; SM, 3.8 percent (+/- 1.4) FVC and 5.2 percent (+/- 1.6) FEV1; AS, 4.4 percent (+/- 1.3) FVC and 11.8 percent (+/- 2.8) FEV1. Within each category, using a paired t test to compare the results on each day of testing, no statistically significant differences were noted. Pyridostigmine at the tested dose has no significant effect on nonspecific bronchial hyperreactivity in normal NNS, SM, or AS.

We hypothesized that continuous, automatic turning utilizing a patient-friendly, low air loss surface would reduce the incidence of early ICU pneumonia in selected groups of critically ill medical patients.

Compare unsupported (UAEx) vs supported (SAEx) arm exercise in training of patients with severe chronic airflow obstruction (CAO).

Continuous irrigation-suction catheter (Irri-cath) is a double-lumen device that allows for simultaneous saline solution infusion and aspiration. This system may theoretically be more effective than conventional dry intermittent suction due to its vortex principle. To test this hypothesis, we performed 200 suction maneuvers in 20 ventilated patients. Identically shaped catheters were used in a randomized sequence. For the same individual, we used equal instilled saline solution volume (40 ml), vacuum pressure (-180 cm H2O), and ventilatory parameters. Effectiveness of suction was determined by measuring the total aspirated volume, the dry lyophilized weight of secretion, the corrected dry weight (dry weight-weight of instilled salt), and protein concentration. No difference in heart rate, respiratory frequency, O2 saturation, systemic blood pressure, peak inspiratory pressure, or patient discomfort was found when the two modalities were compared; however, the total volume of secretions collected, the dry weight, the corrected dry weight, and the protein concentration were significantly higher with continuous irrigation suction catheter when compared with the conventional method (p < 0.05). The suction time was shorter with the Irri-cath (p < 0.05). We conclude that the Irri-Cath is more effective than conventional intermittent suction catheter in clearing bronchial secretions in patients on mechanical ventilation.

The purpose of this study was to determine if a computer-directed weaning system could wean patients with complex medical problems from mechanical ventilation and appropriately respond to signs of respiratory failure more effectively than traditional physician-directed weaning methods. In a prospective, randomized, controlled study, we tested the system in 15 patients who had required prolonged mechanical ventilation and met predetermined weaning tests. Patients were randomly assigned to one of two groups: (1) automatic, computer-directed weaning or (2) physician-controlled weaning. The computer-directed system decreased or increased the synchronized intermittent mandatory ventilation rate and pressure support (PS) based on predetermined limits of patient respiratory rate (RR) and tidal volume (TV). Pulse oximeter oxygen saturation was monitored, and alarms were triggered by an oxygen saturation of < 90 percent. In the physician control group, weaning progressed with SIMV rate and PS reduction, as judged appropriate by the physician. Nine patients were assigned to the computer group; six patients were assigned to the control group. The average patient age was 64.8 +/- 14.9 years for the computer group, 65.2 +/- 22.7 years for the control group. The average time on mechanical ventilation prior to weaning was 13.4 +/- 7.8 days for the computer group and 14.5 +/- 11.1 days for the control group. Seven of the nine computer group patients weaned within 48 h of the study, with an average time to wean of 18.7 +/- 5.9 h. All seven were breathing spontaneously 48 h after weaning. Two of the six control group patients weaned within 48 h of the study, with an average time of 25.6 +/- 5.6 h. Both patients who weaned were placed back on mechanical ventilation within 30 h. The number of arterial blood gas samples drawn during the study was 1.4 +/- 0.7 for the computer group, 7.2 +/- 4.3 for the control group. The number of minutes per hour outside acceptable limits of RR > 30, RR < 8, or TV < 5 ml/kg was 3.2 +/- 2.8 min for the computer group and 6.6 +/- 4.1 min for the control group. The study suggests that use of the computer-directed weaning system results in fewer arterial blood gas samples, shorter weaning times, and less time spent outside acceptable RR and TV parameters.

The purpose of this study was to assess the validity of the 20-m shuttle test with 1-min stages (20-MST) to estimate maximal oxygen uptake (VO2 max) and its ability to register cardiorespiratory modifications over the course of an individualized aerobic training program for mild to moderately asthmatic children acclimatized to moderate altitude.