To evaluate the role of inhaled ipratropium bromide alone vs oral theophylline plus inhaled beta-agonist or the combination of all three in patients with stable COPD, the following double-blind, placebo-controlled study was conducted. Forty-eight patients with stable COPD (mean age, 61.8 years, with mean baseline FEV1 < 1.0 L) were randomized on four separate days to receive the following drug regimens: (1) theophylline tablets (dose previously determined to result in blood level of 12 to 18 mg/L), followed by inhaled albuterol (2 puffs via metered-dose inhaler [MDI]), followed by inhaled placebo (2 puffs via MDI); (2) oral placebo followed by ipratropium (2 puffs via MDI; 36 micrograms), followed by inhaled placebo; (3) oral theophylline, followed by albuterol, followed by ipratropium; or (4) oral placebo followed by two inhaled placebos. On study days, spirometry and heart rate were measured at time 0, 30 min, 60 min, and hourly for 6 h. The FEV1 peak change (liters) and area under the curve (liter x hours) for the treatment groups were compared. Ipratropium was more effective than placebo (p = 0.001 and p = 0.0078, respectively). The combination of albuterol and theophylline was superior to ipratropium alone (p = 0.001 and p = 0.0001, respectively), and all three drugs together were superior to the combination of albuterol and theophylline (p = 0.0373 and p = 0.0289), respectively; one-sided test of hypotheses). Peak heart rates were significantly higher for treatment groups compared with placebo groups (p = 0.0001). However, theophylline and albuterol and the combination of all three drugs resulted in greater peak heart rates than did ipratropium alone (p = 0.001). These data suggest that for patients with stable COPD, combination therapy with ipratropium (two puffs), theophylline, and albuterol (two puffs) is superior to ipratropium alone or the combination of theophylline and albuterol.

We hypothesized that high flow transtracheal oxygen (HFTTO) will improve exercise tolerance as compared with low flow transtracheal oxygen (LFTTO) and that transtracheal oxygen (TTO) will increase exercise tolerance with less dyspnea as compared with nasal prongs (NP) at equivalent oxygen saturation (SaO2).

To more systematically evaluate the effect of respiratory muscle rest on indices of ventilatory function, nine outpatients with stable, severe COPD were treated with nasal pressure-support ventilation delivered via a nasal ventilatory support system (BiPAP, Respironics, Inc) for 2 h a day for 5 consecutive days. An additional eight control patients were treated with sham-BiPAP. Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), maximum voluntary ventilation (MVV), arterial blood gas values, Borg dyspnea score, dyspnea-associated functional impairment scales, and distance walked in 6 min were measured in subjects prior to and following the week-long trial. Nasal BiPAP produced a 66.3 +/- 6 percent reduction in peak integrated diaphragmatic electromyographic (EMG) activity. There were no statistically significant changes in MIP, MEP, MVV, arterial pH, PaCO2, or PaO2 or in objective measures of functional impairment from dyspnea in either group after ventilator or sham treatment. However, nasal BiPAP reduced the Borg category score during resting, spontaneous breathing from 2.0 +/- 0.4 to 0.7 +/- 0.3 (p < 0.01) after 5 days of treatment. In contrast, sham BiPAP-treated patients had no change in their dyspnea score, which was 1.8 +/- 0.4 and 1.3 +/- 0.4 before and after sham treatment, respectively. Nasal BiPAP also increased distance walked in 6 min from 780 +/- 155 to 888 +/- 151 ft (p < 0.01) (23,400 +/- 4,650 to 26,640 +/- 4,530 cm) (p < 0.01), whereas sham-BiPAP had no effect (768 +/- 96 and 762 +/- 106 ft [23,040 +/- 2,880 and 22,860 +/- 3,180 cm]) before and after sham treatment, respectively). In conclusion, these results indicate that nasal pressure-support ventilation, delivered via nasal BiPAP, improves exercise capacity and reduces dyspnea over the short term in selected outpatients with stable severe COPD. Whether such short-term improvement can be sustained merits further study.

To evaluate the effect of outpatient pulmonary rehabilitation (OPR) on dyspnea, we measured this symptom using a visual analogue scale during graded treadmill exercise testing and with baseline and transitional dyspnea indices (TDI). The latter measure overall dyspnea in three spheres: functional impairment, magnitude of task, and magnitude of effort. Twenty patients with COPD referred for OPR were randomly assigned to either a treatment group (T, n = 10), with dyspnea evaluated at baseline then shortly following a 6-week OPR program, or a control group (C, n = 10), with dyspnea evaluated at baseline then following a 6-week waiting period. No significant change in maximal exercise performance from baseline to repeated testing was observed in either group. Dyspnea at maximum treadmill workload (Dmax), which did not significantly change in C, decreased from 74.4 +/- 18.9 percent at baseline to 50.5 +/- 23.2 percent post-OPR in T (p = 0.006). The Dmax related to minute ventilation (Dmax/VEmax) and oxygen consumption (Dmax/VO2max) also significantly decreased following OPR. The reduction in exertional dyspnea was apparent by the second minute of exercise. Additionally, TDI focal scores were significantly higher in T than C (2.3 +/- 1.06 vs 0.2 +/- 1.75 units, p = 0.006), indicating decreased overall dyspnea following OPR. These results point to significant improvements in both exertional and clinically assessed dyspnea following OPR.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in the adult population. Propafenone is a class 1c antiarrhythmic agent that has an electrophysiologic profile suggesting that it might be potentially effective in recent-onset AF. The present study was undertaken, therefore, to examine the time course as well as the frequency of successful conversion in patients with recent-onset AF treated with propafenone administered orally. Fifty patients with recent-onset AF were recruited into 2 groups: 25 patients were given propafenone, 150 mg every 4 h, and 25 patients served as a control group and received verapamil (a drug known to slow the ventricular response but not to restore sinus rhythm) 40 mg, every 4 h and up to 48 h or until conversion to sinus rhythm occurred. Of the 50 patients, 2 refused to continue the study and another 2 were excluded because of left heart failure. Conversion to sinus rhythm occurred in 21 of 24 patients (87 percent) in the propafenone group as compared with 9 of 22 (41 percent) in the verapamil group (p < 0.001). In 10 patients in the propafenone group, conversion occurred within 12 h, within 24 h in another 9 patients, and between 24 and 48 h in the remaining 2 patients. There was no correlation between the duration of AF prior to entry into the study and the subsequent incidence of and time to conversion with propafenone. With respect to cause of AF, all groups showed a high incidence of conversion. Two patients developed heart failure during treatment and one patient (in the verapamil group) developed embolic stroke while still having atrial fibrillation. We conclude that in patients with AF, the prognosis for conversion to sinus rhythm within 48 h, with propafenone, is excellent (87 percent) and safe.

A dose-ranging study was conducted to evaluate the efficacy and safety of a new long-acting, selective beta 2-adrenoceptor agonist, salmeterol.

The effect of in vivo and in vitro N-acetylcysteine (NAC) treatment on destructive activity of macrophages against Candida from COPD patients has been evaluated. Patients received NAC (600 mg) or placebo orally 3 times a day for 15 days and bronchoalveolar lavage (BAL) fluid and peripheral blood were collected before and at the conclusion of treatment. In our system, NAC treatment was not able to modulate antifungal activity of alveolar macrophages, peripheral blood monocytes (PBM), and polymorphonuclear leukocytes. On the contrary, in vitro NAC treatment at appropriate doses (10 micrograms/ml) significantly enhanced antifungal activity of PBM from COPD patients. This phenomenon is mediated by augmented phagocytic activity and phagosome-lysosome fusion. The lack of correlation between in vivo and in vitro studies could be ascribed to differences in the intracellular concentration of the drug that in vivo does not reach levels capable of inducing macrophage activation. We speculate that in COPD patients who undergo long-term NAC treatment, appropriate schedules and doses of the drug could augment resistance against microbial infections which are often life-threatening in these patients.

One hundred twenty patients undergoing coronary artery surgery completed a randomized controlled study designed to investigate whether prophylactic chest physiotherapy affected the incidence of postoperative pulmonary complications. Group 1 patients received no preoperative or postoperative chest physiotherapy. Group 2 patients received preoperative education and instruction in breathing and coughing exercises and postoperative supervision and assistance in performing the same. These exercises were supervised by a physiotherapist twice per day on the first 2 postoperative days and once per day on the 3rd and 4th postoperative days. Physiotherapy for group 3 patients was the same as for group 2 patients except that patients were seen by a physiotherapist 4 times per day on the first 2 postoperative days and twice per day on the 3rd and 4th postoperative days. Group 2 and 3 patients were instructed to practice breathing and coughing exercises every hour. Overall, an incidence of clinically significant postoperative pulmonary complications of 7.5 percent was demonstrated. In general, these patients demonstrated lower levels of preoperative pulmonary function and very low early postoperative oxygenation compared with those who did not develop pulmonary complications. There was no indication that the incidence or severity of fever, hypoxemia, chest roentgenologic abnormalities or clinically significant postoperative pulmonary complications was different between groups. These results suggest that the necessity for prophylactic chest physiotherapy after routine coronary artery surgery should be reviewed.

Supplemental oxygen is routinely administered to patients with acute coronary syndromes. The risk of significant morbidity during cardiac catheterization or coronary angioplasty has been well described; however, to our knowledge, the need for routine oxygen supplementation in these patients has not been investigated.

In order to assess the role of genetic factors and environmental influences in bronchial responsiveness, we studied the airway response to an inhaled bronchodilator in 66 nonasthmatic parents (age, 30.9 +/- 5.9 years) of infants with bronchiolitis (group 1). It was a placebo-controlled double-blind study. A control group (group 2) of healthy parents of infants who did not have bronchiolitis also were investigated with the test of bronchodilator response. All subjects showed normal expiratory airflow and lung volumes (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and mean forced expiratory flow during the middle half of FVC [FEF25-75%] > 80 percent of predicted) at baseline forced expiratory maneuver. In 16 (24.2 percent) subjects of group 1, there was significant increase in at least one parameter after salbutamol administration, but not after placebo inhalation, with respect to baseline levels. Furthermore, no significant changes in FVC, FEV1, or FEF25-75% values were found in group 2. In conclusion, this study confirms that parents of infants with bronchiolitis have an enhanced airway responsiveness, greater than control parents. Further studies are needed to assess whether one may infer the outcome of infants with bronchiolitis from this characteristic in their parents.

beta-Adrenergic agonists are useful for the emergency treatment of asthma. Recently, magnesium sulfate (MgSO4) has also been shown to be efficacious in this situation. beta-Agonists have unwanted cardiovascular and metabolic actions: increased systolic blood pressure, corrected QT interval (QTc), serum glucose and insulin, and decreased RR interval, diastolic blood pressure, serum potassium, phosphate, and calcium. As beta-agonists and MgSO4 quite possibly will be used in combination, we sought to determine how MgSO4 would affect these actions. Healthy young male adults were administered two doses of terbutaline sulfate, 0.25 mg subcutaneously, 30 min apart on two separate occasions, in a randomized, double-blind fashion. On one occasion, 4 g of MgSO4 was administered intravenously over the same 30-min period. On the other, normal saline solution was given as a placebo. Cardiovascular and metabolic variables were measured sequentially for 2 h. Data at 60 min with p values given for a summation of all time points are as follows: MgSO4 increased terbutaline's effects on the RR interval by 0.09 s, p < 0.0001; QTc interval by 0.01 s, p < 0.0007; diastolic blood pressure by 8 mm Hg, p = 0.0001; serum calcium by 0.13 mg/dl, p = 0.01; and glucose by 9 mg/dl, p < 0.0001. MgSO4 also mitigated the systolic blood pressure elevating the effect of terbutaline by 5 mm Hg (p = 0.007). The magnitude of the response potentiations was modest. We conclude that combining terbutaline and MgSO4 is unlikely to result in serious short-term adverse events, if used acutely in patients with relatively normal cardiac and metabolic function. MgSO4 may act by potentiating the effect of beta-agonists on magnesium requiring enzymes such as adenyl cyclase.

The bronchodilating effect of terbutaline dry powder inhaled via Turbuhaler was compared with terbutaline inhaled via a conventional, chlorofluorocarbon (CFC) inhaler and Nebuhaler (750 ml spacer) in 68 consecutive patients attending the emergency department with acute severe bronchial obstruction. The study was of an open, randomized, parallel group design with one study day. Patients were treated with 2.5 mg of terbutaline 15 min apart, either as dry powder via Turbuhaler or with a CFC inhaler in conjunction with Nebuhaler. Data from 62 patients were analyzed. The mean baseline FEV1 values were 0.81 L (SD, 0.64; range, 0.14 to 2.74 L) in the Turbuhaler group (n = 33), and 0.90 L (SD, 0.90; range, 0.27 to 2.60 L) in the Nebuhaler group (n = 29). The mean increases in FEV1 from baseline were 0.40 L (SD, 0.40; range, 0.06 to 2.36 L) and 0.21 L (SD, 0.25; range, -0.05 to 0.95 L) 10 min after the last inhalation via Turbuhaler and Nebuhaler, respectively. The difference between mean values of the increase in FEV1 after terbutaline treatment with Turbuhaler and the CFC inhaler and Nebuhaler was statistically significant (p = 0.0004, ANOVA). This study showed that inhalation of terbutaline via Turbuhaler produced a significantly greater increase in FEV1 compared with the same dose of terbutaline administered via the CFC inhaler and Nebuhaler in patients attending the emergency department with acute severe bronchial obstruction.

To investigate the acute effect of sodium cromoglycate on airway responses to 4.5 percent saline aerosol challenge, before and during treatment with inhaled budesonide--a corticosteroid.

Methacholine inhalation challenge (MIC) is probably the most widely used and best standardized test for nonspecific bronchoprovocation challenge (BPC). There has been increasing interest in developing "physical" stimuli such as eucapnic voluntary hyperventilation (EVH) with dry gas to assess airway hyperreactivity (AHR), because of inherent problems with using a pharmacologic agent in epidemiologic surveys. To our knowledge, no studies exist that compare MIC with EVH in known asthmatics. We conducted a prospective, randomized, crossover trial with a group of subjects (n = 16) who met the American Thoracic Society definition of asthma with these objectives: (1) to compare the sensitivity of EVH with MIC; (2) to compare the quantitative response of one test with the response to the other challenge; and (3) to correlate the response of both tests with symptoms, serum IgE levels, and serum eosinophil counts. We found that (1) EVH was positive in 75 percent of cases and MIC was positive in 81 percent of cases; one subject reacted to EVH but not to MIC and vice-versa. (2) The quantitative response to one test correlated with the response to the other test (r = -0.60, p = 0.01). (3) There was a correlation between severity of asthma symptoms and the response to EVH (r = 0.62; p = 0.01), but not to MIC. (4) Response to MIC (log PD20), but not EVH, correlated with serum IgE level (r = -0.53, p = 0.04). We suggest that EVH may be used for the initial assessment of AHR in the evaluation of asthma. Eucapnic voluntary hyperventilation is a sensitive measure of AHR and it correlates well with symptoms. Furthermore, though these points were not addressed in our study, it is more physiologic than MIC, and it is easy and less expensive to perform.

To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments.

Three inhalation formulations of ICI 204,219 were compared for antagonism of antigen-induced bronchoconstriction in 16 subjects with asthma who demonstrated reproducible hypersensitivity to allergen during screening challenges. Each subject received a single 0.2-mg dose of each formulation and was challenged with ragweed 30 min after administration of ICI 204,219 until the forced expiratory volume in 1 s (FEV1) decreased by 20 percent or the maximum allergen concentration (100 micrograms/ml) was reached. The majority of subjects tolerated 100 micrograms/ml of allergen without a 20 percent decrease in FEV1. Inhalation formulations of ICI 204,219 successfully inhibited bronchoconstriction in subjects with reproducible sensitivity to ragweed challenges.

The aim of this study was to assess the usefulness of a specific inspiratory muscle training in Duchenne muscular dystrophy (DMD).

Pilot study to investigate the effect of exogenous surfactant therapy on lung function following cardiopulmonary bypass (CPB).

A prospective, blinded study of pulmonary findings in hospitalized patients with HIV infection compared auscultatory percussion (AusP) with conventional percussion (ConP) and conventional auscultation (ConA) using chest radiographs as the gold standard. Sixty-three patients had chest radiographs and were examined by one to three examiners. Seventy of the 126 lungs had radiographic abnormalities (55.6 percent). Auscultatory percussion proved to be the most sensitive of all techniques for each examiner (range, 51.0 to 69.6 percent) for detecting radiographic abnormalities and also had higher likelihood ratios for two of the three examiners; AusP also had the highest likelihood ratio pooled across examiners. Of the 166 abnormal results of lung examinations, the combination of AusP and ConA detected 31 more abnormalities than ConP and ConA combined, with 14 of these being diagnosed with Pneumocystis carinii pneumonia. No abnormalities were detected by ConP that were not detected by AusP. These findings suggest that AusP, a rapid clinical maneuver, is more sensitive and specific than ConA and ConP in determining pulmonary abnormalities in HIV-infected inpatients.

We evaluated retrospectively the effect of long-term oxygen therapy (LTOT) on the prognosis of 35 patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory insufficiency (group A) who were admitted to our respiratory intensive care unit from 1984 to 1986 for acute respiratory failure (ARF). All subjects were given intermittent negative pressure ventilation (INPV) by means of an iron lung to overcome the acute episode and were treated with LTOT after discharge. Forty-four patients with COPD who were treated with the same ventilatory method to overcome an acute disease exacerbation and who were not given LTOT were used as controls (group B). Both groups were followed up for at least 48 months. All relapses of ARF were treated by iron lung in both groups A and B. The overall survival was significantly better in group A than in group B (p = 0.05 by F test) indicating that LTOT improves survival in patients with COPD after a bout of ARF treated with mechanical ventilation. Therefore, combining INPV with LTOT for overcoming acute episodes and relapses of ARF appears to improve the prognosis of patients with COPD.