Studies on respiratory muscle resting by negative pressure ventilation (NPV) in patients with stable COPD have given conflicting results. Probable explanations lie in criteria of patients' selection, method of NPV application, and lack of supervision of respiratory muscle rest. Thirteen hypercapnic patients with COPD were, therefore, randomly assigned to either a NPV group or a control group. The NPV was applied by an airtight jacket (pneumosuit), 5 h a day, 5 consecutive days a week for 4 weeks. Both NPV group and control group performed in-hospital pulmonary rehabilitation program for a 4-week period. Arterial blood gases, spirometry, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), breathing pattern, and electromyogram (EMG) of the diaphragm and parasternal intercostal muscles were measured on the preintervention day, and at the end of the second and fourth weeks of treatment (days 13 and 27, respectively). The short-term effect of NPV on EMG suppression was also checked throughout the ventilatory sessions in three different days (1, 12, and 26, respectively). A 6-min walking test (WT) and level of dyspnea by a modified Borg scale were evaluated on the preintervention and the last days. Negative pressure ventilation resulted in a significant reduction in EMG activity of both diaphragm and parasternal muscles, associated with significant increase in MIP, tidal volume, and ventilation, and increase in PaO2 and decrease in PaCO2. A significant relationship between change in MIP and change in PaCO2 was observed (r = 0.72, p < 0.01). Improve-ment in 6-min WT and dyspnea sensation was also observed, both being the sole changes in the control group. These data seem to indicate a beneficial role of respiratory muscle rest in improving respiratory function. Adequate supervision by personnel familiar with the equipment is likely to contribute to successful treatment.

In patients at risk for sepsis after cardiac surgery, the efficacy of intravenous immunoglobulin (Ig) treatment was compared with a historical control population, equivalent in patient characteristics and disease severity. Using APACHE II scores, especially in the high-risk group (IgG), we could discriminate between low-risk patients (score < 19; mortality 1 percent) and the small groups at risk (score 19 to 23) and high risk (score > or = 24) with a significantly higher mortality (14 percent and 76 percent, respectively) [corrected]. Subsequently, among 1,341 consecutive patients we prospectively identified and treated (IgG n = 41 IgGMA: n = 25) these at-risk groups. In contrast to controls (risk: n = 21; high-risk; n = 21), we found a marked fall in APACHE II scores, especially in the high-risk group (IgG, n = 26: p < 0.05; IgGMA, n = 13: p = 0.08) [corrected]. In this group, Ig therapy produced higher (p < 0.05) response rates (score decrease 7 within 4 days: IgG: 54 percent, IgGMA: 62 percent; controls: 19 percent) and reduced mortality (IgG: 46 percent, IgGMA: 46 percent; controls: 76 percent), statistically significant (p < 0.05) for Ig treatment overall. Thus, early Ig treatment improves disease severity and may improve prognosis in prospectively score-identified high-risk postcardiac surgical patients.

This study examines the effects of respiratory muscle feedback and breathing retraining (BRT) on lung function in patients with cystic fibrosis (CF). Twenty-six patients with CF were matched for age and severity of disease. Standard respiratory spirometry was performed on all subjects before and after biofeedback training. Thirteen experimental subjects underwent eight sessions of pneumographic or strain-gauge feedback from the abdominal muscles and electromyogram feedback from accessory respiratory muscles to assist in learning diaphragmatic and pursed-lips breathing maneuvers. Control subjects received biofeedback-assisted (hand warming) relaxation training. Results revealed a significant improvement in FEV1 and mean forced expiratory flow during the middle half of forced vital capacity (FVC) for the biofeedback group, while the control group showed no change. A similar trend was noted for FVC. These data suggest that respiratory muscle feedback and BRT may improve lung function in patients with CF.

To compare aerosol delivery to the lungs in ventilated patients from two devices with holding chamber and two devices without holding chamber.

To determine the effects of intravenous N-acetylcysteine (NAC) on the development of severe adult respiratory distress syndrome (ARDS) and mortality rate in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score.

In an attempt to restore functional surfactant to the lungs of patients with the adult respiratory distress syndrome (ARDS), we have treated six patients within the first 2 days of the onset of ARDS with a single dose of hydrophobic components of porcine surfactant. Surfactant (4 g in 50 ml) delivered via a bronchoscope in aliquots to each of the lobar bronchi was well tolerated and caused a modest transient improvement in gas exchange. No significant changes in chest radiograph or lung compliance were detected. Analysis of bronchoalveolar lavage (BAL) fluid showed no change in albumin, alpha-1-proteinase inhibitor specific activity, or cell count. Bronchoalveolar lavage phospholipid concentrations were elevated 3 h after surfactant administration relative to preadministration levels and fell by 24 h. In addition, in two patients we found reduced inhibition of surfactant function in BAL after surfactant replacement. These observations suggest a role for surfactant replacement in the treatment of patients with ARDS and support the need for continuing investigation.

Severe asthma often requires high-dose corticosteroid therapy. However, steroid therapy is fraught with many side effects. There are conflicting reports in the literature regarding the role of methotrexate in reducing the steroid requirements of these patients. This study examined the role of low-dose methotrexate in the management of steroid-dependent asthma. Eleven subjects with stable steroid-dependent asthma were enrolled in a placebo-controlled double-blind crossover trial. Patients received methotrexate, 15 mg/wk, or placebo each for two 12-week periods. There was significant improvement of pulmonary function and reduction of prednisone requirement in both placebo and methotrexate treatment periods. However, methotrexate was not superior to placebo. Only 3 of 11 patients responded to methotrexate. Although low-dose methotrexate therapy may have a role in a small select group of steroid-dependent asthmatics, it provided no additional benefit overall.

Previously, we have shown rapid and complete dispersion of tetracycline hydrochloride in the pleural space following chest tube instillation. To assess the clinical relevance of this observation, we randomized patients with symptomatic pleural effusions to rotation (R) (n = 19) and nonrotation (NR) (n = 21) groups following administration of tetracycline hydrochloride, 20 mg/kg (n = 30); 300 mg of minocycline hydrochloride (n = 6); and 500 mg of doxycycline hydrochloride (n = 4) through a chest tube. Patients in the R group were maneuvered through six positions for the 2 h that the chest tube remained clamped. The NR patients remained supine for 2 h. Rotation and nonrotation groups were similar in demographics, source of pleural effusion, symptoms, and serum and pleural fluid analyses (all p = NS). A chest radiograph was scored based on pleural fluid recurrence throughout survival or up to 12 months. Survival, duration of chest tube instillation, and success of pleurodesis assessed by radiographic pleural fluid reaccumulation (73.7 vs 61.9 percent; R vs NR) were similar (p = NS). Rotational maneuvers appear to offer no benefit to the success of pleural symphysis after intrapleural instillation of tetracycline class agents.

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.

Oxitropium bromide is a novel anticholinergic bronchodilator agent. The purpose of this study was to compare the bronchodilating and cardiovascular effects of oxitropium (0.2 mg), fenoterol (0.4 mg), combined oxitropium and fenoterol (0.2 mg and 0.4 mg, respectively) over a 10-h test period. Fourteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 0.95 +/- 0.38L) were studied in a randomized, double-blind, placebo-controlled trial. Combined oxitropium and fenoterol produced significantly greater improvements in FEV1 over a time span of 15 min to 10 h and in the area under the time-FEV1 curve (AUC) than either oxitropium or fenoterol alone. The effects of oxitropium on both FEV1 and AUC values were similar to those of fenoterol. Oxitropium resulted in a greater increase in FEV1 than the placebo even after 10 h. In contrast; fenoterol produced a significant improvement in the FEV1 for only 15 min to 4 h. Oxitropium showed no adverse cardiovascular effects, whereas fenoterol was associated with an increased heart rate at 15 min and 1 h after the administration. We conclude that oxitropium bromide is an effective and safe bronchodilator for even elderly patients with COPD.

To determine whether inhaled furosemide can modify the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with both atopic and nonatopic asthma, a single-blind, randomized, placebo-controlled study was undertaken. The UNDW inhalation challenge was performed in 21 asthmatic children (atopic, 14; nonatopic, 7; mean +/- SEM age, 11.5 +/- 0.5 years), who had a fall in FEV1 of at least 20 percent after distilled water inhalation. On separate days, these subjects underwent UNDW challenge test after inhalation of furosemide (10 mg/body square meters) or placebo (saline solution). Inhaled furosemide exerted a protective effect against bronchoconstriction induced by UNDW in children with both atopic and nonatopic asthma (p < 0.01, p < 0.05, respectively). These results indicate that the protective action of furosemide against UNDW-induced bronchoconstriction may be independent of its direct inhibitory effect on airway mast cell activation.

To demonstrate the utility of a new blood-conserving arterial line system in reducing blood loss associated with blood drawing in the critical care setting.

To evaluate the efficacy of amrinone for facilitating weaning from cardiopulmonary bypass (CPB).

Gastroesophageal reflux (GER) is a common cause of chronic cough. Moreover, chronic cough can be the sole presenting manifestation of GER disease (GERD). It has been suggested recently that GER most often causes chronic cough by stimulating the distal esophagus. To gain further diagnostic and pathophysiologic knowledge, we prospectively evaluated a group of patients with chronic cough likely to be due to GER with extensive gastrointestinal and respiratory studies and then observed their response to antireflux therapy.

Clarithromycin is a new acid-stable, 14-membered macrolide active against many of the organisms responsible for lower respiratory tract infections. It has been administered to over 5,000 patients worldwide and has been shown to be a safe and effective treatment for acute bacterial exacerbations of chronic bronchitis and bacterial pneumonia when given twice daily (250 to 500 mg). Cefixime is an amino-thiazolyl cephalosporin with an extended spectrum of antibacterial activity inhibiting beta-lactamase-producing respiratory pathogens. It has a long half-life, allowing once-daily administration.

In this multicenter, observer-blinded study, 301 patients with signs and symptoms of acute bacterial exacerbation of COPD were randomized (2:1) to receive either cefpodoxime proxetil (200 mg, bid) or cefaclor (250 mg, tid) for 10 days. Clinical and microbiologic evaluations were performed before treatment, during therapy (study days 3 to 5), at the end of therapy (3 to 7 days posttreatment), and at long-term follow-up (4 weeks posttreatment). The most common pretreatment isolates were Haemophilus influenzae, Haemophilus parainfluenzae, and Streptococcus pneumoniae. Significantly (p < 0.001) more bacterial isolates were susceptible in vitro to cefpodoxime (233 of 256, 91 percent) than to cefaclor (215 of 255, 84 percent). There were no statistically significant differences between the two drug regimens in eradication of the initial pathogen (cefpodoxime, 116 of 128, 91 percent; cefaclor, 59 of 64, 92 percent) or end-of-therapy clinical response (cure + proved; cefpodoxime, 99 of 100, 99 percent; cefaclor, 45 of 49, 92 percent) rates for evaluable patients. Both drug treatments were well-tolerated, with a similar incidence of drug-related adverse events (cefpodoxime 11 percent, cefaclor 12 percent). Cefpodoxime (bid) was as safe and effective as cefaclor (tid) in the treatment of acute exacerbation of COPD. The less frequent dosing regimen of cefpodoxime may improve patient compliance compared to those antibiotics that require three or four daily doses.

In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.

To study the effectiveness of high-frequency ventilation (HFV) for the treatment of pediatric patients with acute severe respiratory failure.

The study was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of two regimens. In one of the regimens, patients received 2 months of daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide (SHRZ) followed by isoniazid plus rifampin for 4 months (4 HR). In the other regimen, patients received 2 months of daily streptomycin, isoniazid, pyrazinamide, and ciprofloxacin (SHZ Cipro) followed by isoniazid plus ciprofloxacin for 4 months. All patients in the SHRZ/HR regimens and all but one in the SHZ Cipro/H Cipro regimens had a favorable bacteriologic response during chemotherapy. In the patients in the SHZ Cipro/H Cipro regimen, ciprofloxacin was well tolerated during the period of treatment. After chemotherapy, one (5.9 percent) of 17 patients in the SHRZ/HR group and three (16.6 percent) of 18 patients in the SHZ Cipro/H Cipro group relapsed bacteriologically.

The purpose of this study was to evaluate the role of high-resolution computed tomography (HRCT) in the clinical diagnosis of diffuse infiltrative lung disease (DILD). Diagnostic accuracy was compared using both chest radiography and HRCT. One hundred thirty-four cases of DILD, representing 21 different diseases, were selected for study, and the disease state was confirmed either histologically or microbiologically. The HRCT images and chest radiographs, available in all cases, were reviewed separately and in random order by 20 physicians who were provided only with information on each patient's age and sex. Overall, a correct first-choice diagnosis was made in 38 percent using radiographs and in 46 percent using HRCT images (p < 0.01). The correct diagnosis was among the top three choices in 49 percent when chest radiographs were used, and in 59 percent when HRCT images were viewed (p < 0.01). The correct first-choice diagnosis increased remarkably when the HRCT was used in usual interstitial pneumonia, sarcoidosis, alveolar proteinosis, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis, and pulmonary lymphangiomyomatosis. High-resolution computed tomography was confirmed to be superior to conventional radiography in the accurate diagnosis of DILD in clinical practice.