Epidemiologic evidence suggests that high levels of salt consumption are associated with "spastic" disorders of smooth muscles, ie, essential hypertension and bronchial asthma. Experimentally, it has been shown that high intake of salt leads to increased bronchial hyperreactivity in asthmatics, ie, enhanced contractility of bronchial muscle to spasmogenic stimuli. On the basis of these observations, the following questions were asked: (1) Does salt loading worsen the clinical and functional findings in asthmatics? (2) Is it the sodium or the chloride in salt that is important?

Positive expiratory airway pressure seems to dilate narrowed or collapsed airways, but this may be accompanied by a maintained and harmful increase in resting lung volume in obstructive pulmonary disease.

To determine the value of theophylline in the maintenance therapy of patients with severe chronic obstructive pulmonary disease (COPD), we conducted a trial of theophylline therapy withdrawal in 38 clinically stable patients with severe COPD (FEV1 < 60 percent) predicted. Symptoms, lung function, blood gases, and 6-min walking distance were assessed on days 1 and 2. Quality of life and overall dyspnea were scored using four different clinical rating scales. Theophylline therapy was continued in 20 patients and replaced by placebo from day 3 on in the remainder; measurements were repeated on days 5 and 6. Withdrawal of theophylline therapy resulted in significant (p < 0.05) deterioration in lung function, exercise performance, and two indices of overall dyspnea, and a significant increase in scoring of symptoms and auscultation findings. Individual analysis revealed a clinically relevant deterioration in 72 percent of patients from whom theophylline therapy was withdrawn, while only 15 percent of patients receiving theophylline exhibited deterioration. No major side effects were observed. Our data show that about half of the patients with severe COPD can be considered as theophylline responders. The response of these patients to withdrawal of theophylline therapy suggests that the clinical effectiveness of this drug cannot be explained exclusively by bronchodilation. Due to the inherent difficulties in predicting response to theophylline, its effectiveness in patients with severe COPD should be determined individually, including assessment of exercise performance and ratings of dyspnea.

Selective beta 2-agonist aerosols may produce significant cardiovascular effects. In the present study we used Holter monitoring to compare the arrhythmogenic effects of inhaled terbutaline (TE), a beta 2-agonist, with that of ipratropium bromide (IB), a nonabsorbable cholinergic drug. Fourteen patients with concomitant obstructive lung disease, ischemic heart disease, and complaints of postinhalation palpitations were studied in a random, double-blind, cross-over fashion. Both drugs significantly improved vital capacity and FEV1. Heart rate and the frequency of premature beats were not significantly affected by the bronchodilators. We conclude that no clear connection between inhaled bronchodilators and arrhythmias could be demonstrated.

Propofol, a new intravenous sedative agent, was investigated in 41 asthmatic patients undergoing day-case (outpatient) fiberoptic bronchoscopy. The study design was a randomized comparison between propofol and midazolam, which is a well-established intravenous sedative agent. The age, weight, and American Society of Anesthesiologists physical status and lung function of the two groups were not significantly different. Mean (SD) induction dose of propofol was 104.7 (30.1) mg with a maintenance dose of 121.9 (38.5) mg. Corresponding values of midazolam were 9.3 (3.1) mg and 3.7 (2.3) mg. The required level of sedation was achieved significantly faster with propofol, mean (SD) 125.4 (39.8) s, compared with midazolam, 179.4 (55.2) s (p < 0.001). Significantly faster recovery was noted with propofol compared with midazolam in terms of time to recall name and date of birth 2.3 (1.7) min vs 6.3 (8.6) min, (p < 0.045). Alertness scored with the digital symbol substitution test (DSST) returned to prebronchoscopy values in the propofol group at 30 min, DSST score = 35.9 (18.2) vs 13.4 (9.1), in the midazolam group (p < .0001) and was still significantly higher at 90 min-39.4 (17.9) and 23.1 (13.8) (p < 0.01). We conclude that propofol is a useful sedating agent in fiberoptic bronchoscopy with similar efficacy to midazolam but with a faster onset of action and a more rapid recovery. These represent significant advantages for day-case procedures.

In small-cell lung cancer, the optimal combination of chemotherapy and radiotherapy is not clearly established. To assess the value of delayed thoracic radiotherapy, we performed a randomized clinical trial in 53 complete responder patients after eight courses of chemotherapy. Twenty-seven patients received a mean of 46.5 Gy-equivalent of radiotherapy and 26 patients received no treatment until relapse. No patient dropped out of the study. Median survival time from radiotherapy randomization was 316 days in the radiotherapy group and 496 days in the no radiotherapy group. No difference was observed in survival between the two groups (p = 0.66, log-rank test) perhaps because of the small sample size. In fact, this delayed thoracic radiotherapy seemed to worsen the outcome of complete responders with small-cell lung cancer and should be avoided.

Septic shock is frequently complicated by a syndrome of disseminated intravascular coagulation (DIC). Numerous uncontrolled clinical studies have reported that antithrombin III (ATIII) substitution might prevent DIC and death in septic shock.

To assess the cardiorespiratory effects of pressure-controlled ventilation (PCV) and pressure-controlled inverse ratio ventilation (PC-IRV), we compared pressure-controlled ventilation with an inspiratory-to-expiratory time ratio (I/E) of 1/2 (PCV) and of 2/1 (PC-IRV) to volume-controlled ventilation (VCV) with an I/E of 1/2 in 10 patients suffering from the adult respiratory distress syndrome. In all modes, the inspiratory oxygen fraction, tidal volume, respiratory rate, and total positive end-expiratory pressure (PEEPt = applied PEEP + intrinsic PEEP) were kept constant. Each ventilatory mode was applied for 1 h in a randomized order. No significant differences in PaO2 were observed among the three modes. The PaCO2 was lower (p < 0.05) in PC-IRV (39 +/- 4 mm Hg) than in PCV (43 +/- 5 mm Hg) and in VCV (45 +/- 5 mm Hg). The peak airway pressure was significantly lower in PC-IRV than in PCV (p < 0.05) and in PCV than in VCV (p < 0.05), but plateau pressure was not different in the 3 modes. The mean airway pressure (mPaw) was significantly higher (p < 0.05) in PC-IRV (21.4 +/- 0.7 cm H2O) than in PCV (17.1 +/- 0.7 cm H2O) and VCV (16.4 +/- 0.5 cm H2O). As a consequence of this increased mPaw, PC-IRV induced a decrease in cardiac index (CI) (3.3 +/- 0.2 vs 3.7 +/- 0.2 L/min/m2 in VCV; p < 0.05) and hence in oxygen delivery (DO2) (424 +/- 28 vs 469 +/- 38 ml/min/m2 in VCV; p < 0.05). Our results suggest that neither PCV nor PC-IRV bring any benefit over VCV in terms of arterial oxygenation. Moreover, the increase in mPaw induced by PC-IRV may be deleterious to the CI and DO2.

The effect of large doses of salbutamol (S) and ipratropium bromide (IB) were tested in a double-blind, randomized, crossover study. Nine patients with cystic fibrosis (CF), aged 12.8 +/- 2 years (mean +/- SE), were studied for 8 h on 2 separate days. Pulmonary function tests (PFTs) included spirometry (FEV1), lung volumes (FRC), and airway resistance (Raw) measured by body plethysmography. Heart rate (HR) and oxygen saturation (SaO2) were measured before each test. On 1 day patients received S 200 micrograms, S 400 micrograms, and IB 80 micrograms, by inhalation at 45-min interval (sequence A). On the other day, the sequence was IB 80 micrograms, S 200 micrograms, and S 400 micrograms (sequence B). The PFTs were obtained at baseline, 45 min after each inhalation, and 4 and 8 h after baseline measurements. Baseline PFTs (mean +/- SE) were not significantly different on the 2 study days (FEV1, 1.48 +/- 0.1 vs 1.42 +/- 0.1 L; FRC, 2.77 +/- 0.6 vs 2.87 +/- 0.6 L; Raw, 4.04 +/- 0.2 vs 4.00 +/- 0.3 cm H2O/L/s). The FEV1 and Raw improved from baseline after each inhalation, and at 4 and 8 h during both days (p < 0.05). Forty-five minutes after S 200 micrograms, plus S 400 micrograms, FEV1, FRC, and Raw were not significantly different compared with the values 45 min after IB 80 micrograms, plus S 200 micrograms (1.67 +/- 0.1 vs 1.63 +/- 0.1 L; 2.81 +/- 0.6 vs 2.65 +/- 0.5 L; and 2.98 +/- 0.2 vs 2.66 +/- 0.1 cm H2O/L/s, respectively). The PFTs were not significantly different after maximal doses of IB (80 micrograms) compared with S (600 micrograms). The HR and SaO2 were not significantly different from baseline throughout the study period. These results indicate that both single and sequential therapy have a similar acute bronchodilator effect provided that large doses are used. We speculate that adrenergic and muscarinic pathways are equally important in airflow obstruction in patients with CF.

Comparative studies of albuterol by wet nebulizer or metered dose inhaler have tested fixed doses of medications. We compared the dose-response relationship to albuterol by wet nebulization or metered dose inhaler in acute asthma.

Intravenous magnesium sulfate improves objective measures of expiratory flow in patients with acute severe exacerbations of asthma.

To characterize the short-term effects of grain dusts on pulmonary function, mucosal inflammation, and systemic responses, four women and three men inhaled nebulized corn and soybean dust extracts, endotoxin diluted with Hanks' balanced salt solution (HBSS), and HBSS. Subjects were volunteers recruited via newspaper advertisement and were required to be healthy, nonasthmatic, nonatopic never-smokers. The mean age was 26.9 years (range, 19 to 36 years). Using a randomized, double-blind, crossover design, each subject was challenged with each of the 4 substances with at least 10 days between challenges. Serial spirometry, peripheral blood leukocyte and differential cell counts, and 24-h postchallenge nasal lavages were performed. Extracts were produced by mixing 3 g of the corn or soybean dust with 30 ml HBSS followed by shaking for 60 min, centrifugation, then filter sterilization. The endotoxin solution was produced by mixing lyophilized Escherichia coli endotoxin (serotype 0111:B4) with HBSS to attain a final concentration of 7 mg/L, which was the same as the concentration of endotoxin in both grain dust solutions. The pH of all solutions and unmixed HBSS was adjusted to 5.8, which was the native pH of the soybean dust extract. Subjects were challenged with 0.08 ml/kg of each substance, resulting in a range of endotoxin doses of 30 to 60 micrograms, similar to that which a worker might inhale over the course of one workshift. The lowest mean percentage baseline FEV1 (+/- SD) after inhalation challenge was 99.2 +/- 2.1 for HBSS, and it was significantly lower for endotoxin (90.1 +/- 8.5, p = 0.03), corn dust extract (93.1 +/- 4.3, p = 0.02), and soybean dust extract (96.2 +/- 3.7, p = 0.03). In addition, a peripheral blood leukocytosis developed after exposure to all three endotoxin-containing solutions (p < 0.05), yet a lower peripheral blood lymphocyte count was found only after inhalation of corn dust extract (p = 0.02). Interestingly, this was associated with a higher nasal lavage lymphocyte count after inhalation of corn dust extract (p = 0.03). Neither the decrease in peripheral blood lymphocytes nor the increase in nasal lymphocytes were found after inhalation of soybean dust extract or endotoxin. Our results indicate that extracts of grain dusts have physiologic effects similar to endotoxin. However, in spite of the same endotoxin levels, the effects of corn dust extract appear to have different biologic activity than either soybean dust extract or endotoxin.

Ten of the 146 (7 percent) evaluable subjects developed PCP during the year study period, and there was no difference in the efficacy of the two regimens. Among patients receiving secondary prophylaxis, the attack rate of PCP at 1 year was 11 percent. This compares favorably with a 1-year attack rate of 19 percent in similar patients receiving standard dose (300 mg) prophylaxis and suggests, but does not prove, a dose-response effect. Concentrations of pentamidine in BAL fluid were not significantly different among the three lobes of the lung. Intrapulmonary pentamidine did not accumulate during the year of study. Aerosolized pentamidine was associated with a marginal but statistically significant increase in the residual volume, decreased flow rates, and increased airway reactivity.

The effect of intraoperative autotransfusion during coronary artery bypass grafting was studied in a randomized double-blind trial involving 38 patients. Nineteen patients had the collected RBCs washed and autotransfused (autotransfusion group), while the remaining patients had their washed cells discarded (control group). Postoperative hemoglobin and hematocrit values were similar. Exposure to banked blood was markedly decreased in the autotransfusion group compared with the control group. In addition, the mean volume of banked packed RBCs transfused per patient was significantly less in the autotransfusion group compared with the control group. Platelet utilization also was markedly decreased in the autotransfusion group. Cryoprecipitate and fresh frozen plasma utilization also was less in the autotransfusion group than in the control group, but this did not reach statistical significance. We conclude that the intraoperative use of autotransfusion decreases the volume of homologous blood products transfused, which results in reduced exposure of the patients to banked blood products.

In a multicenter, double-blind, group comparative trial, the efficacy of nedocromil sodium (nedocromil, 4 mg, four times daily [qid]), cromolyn sodium (2 mg, qid), and placebo was compared in patients receiving inhaled beta 2-agonists and inhaled corticosteroids for the treatment of chronic reversible obstructive airway disease. After a 2-week baseline period, 132 patients (8 centers) between the ages of 20 and 75 years entered a 4-week run-in period in which the dose of inhaled corticosteroid was reduced by 50 percent. During the run-in phase, deterioration of symptoms (total symptom score) by ten points qualified patients to enter the 6-week drug trial period. Patients in the nedocromil treatment group showed the most robust and consistent improvements over placebo and cromolyn sodium for all daily dairy variables. Statistically significant improvements over placebo were noted for both active treatment groups for daytime, nighttime, and total symptom score. Symptom scores for nedocromil were statistically significantly improved over both cromolyn sodium and placebo for both daytime and nighttime asthma. Patients treated with nedocromil also demonstrated a significant reduction in the use of nighttime as needed (prn) beta 2-agonists as compared with either the placebo- or cromolyn sodium-treated groups. Only nedocromil-treated patients demonstrated a statistically significant improvement in morning peak expiratory flow rate (PEFR) as compared with placebo. Both nedocromil and cromolyn sodium groups demonstrated statistically significant improvements in afternoon and evening PEFRs. Collectively, the improvements in nighttime symptoms, decreased bronchodilator use, and improved morning PEFR show that patients treated with nedocromil had improved nocturnal symptoms. Pulmonary function tests (FEV1, FVC, PEFR) demonstrated no statistically significant differences between the two active treatments, although trends favored nedocromil for both FEV1 and PEFR. Although symptoms improved in patients treated with cromolyn sodium, the level of symptom control was less than that achieved by nedocromil. As compared with baseline control (regular dose of inhaled steroids), patients treated with nedocromil plus the 50 percent reduced dosage of inhaled corticosteroid consistently demonstrated comparable or better symptom control. Although both active drugs reduced symptoms, nedocromil proved to be more effective than cromolyn sodium for treatment of reversible obstructive airway disease in patients normally well maintained on regimens of low to moderate doses of inhaled corticosteroids.

To evaluate the efficacy of the technique of selective decontamination of the digestive tract (SDD) in preventing secondary infections in patients with neurologic diseases requiring intensive care.

We wished to determine if magnesium infusion would improve respiratory muscle function in long-term ventilated patients even in the absence of hypomagnesemia.

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.