This study determined the effect of a high vs low resistive inspiratory muscle interval training protocol on inspiratory muscle strength (PImax), incremental inspiratory threshold loading (Pitl), inspiratory muscle endurance (IE), and 12-minute distance test (12 MD) in severely impaired patients with COPD. We used a double-blind, two-group, repeated-measure design. Group 1 (n = 12) received supervised high resistive loading at approximately 52 percent PImax and group 2 (n = 8) received supervised low resistive loading at approximately 22 percent PImax. All subjects trained three times weekly (progressing from 5 min per session in week 1 to 18 min per session in week 12) for 12 weeks. After three practice sessions, measures of PImax, Pitl, IE, and 12 MD were taken at baseline, at 4-week intervals, and within 72 h of completing the protocol. Group 1 showed significant improvement in all four dependent variables while group 2 improved in Pitl, IE, and 12 MD. The results suggest there is no significant difference between high and low resistive interval training in more severely impaired patients with COPD.

To compare the intrapulmonary percussive ventilator (IPV) to chest physiotherapy (P&PD) with respect to acute changes in (1) pulmonary function and (2) sputum physical properties in patients with cystic fibrosis (CF).

What is the relative per microgram potency and side effect profile of the beta-agonists salbutamol and fenoterol?

In the treatment of stable mild to moderate asthma, twice-daily administration of inhaled steroids may allow adequate control of the asthma; however, comparisons of the efficacy of once- or twice-daily administration brought contradictory results. This study is a randomized, double-blind crossover trial, set to determine if inhaled beclomethasone dipropionate given once daily in the late afternoon or at bedtime can be as effective as a twice-daily regimen in the treatment of moderate asthma.

An evaluation of amiodarone as prophylactic treatment for supraventricular tachyarrhythmias after pulmonary surgery was stopped because of a high incidence of the adult respiratory distress syndrome (ARDS) after a pneumonectomy. Retrospective analysis of all cases of resection for pulmonary neoplasm in our hospital between 1987 and 1991 indicates that amiodarone may be implicated in the development of ARDS after lung surgery.

Whether nebulized ipratropium bromide is of benefit to mechanically ventilated patients with chronic bronchitis is not well defined. The objective of the study was to determine the effect of ipratropium bromide as a nebulized solution on ventilatory function in patients with severe airflow limitation and under ventilator treatment because of respiratory failure. The design was a randomized, double-blind, controlled trial. Forty-two ventilated patients (43 to 83 years old) with acute airflow obstruction and wheezing or coughing were chosen. The patients were randomly allocated to treatment every 6 h with either 500 micrograms of nebulized ipratropium bromide or 0.9 percent saline solution. Comparison was made between ipratropium bromide and placebo. Their responses were assessed in terms of arterial blood gas analysis, pulmonary mechanics, and respiratory symptoms. No significant differences in oxygenation, arterial CO2 tension, or static lung compliance attributable to ipratropium were found. However, a significant tendency to decreased mean airway resistance, peak inspiratory pressure, mean airway pressure, and improved symptom status 24 h after giving ipratropium was observed. We conclude that ventilated patients with obstructive lung disease could obtain incremental benefit from adding nebulized ipratropium to aminophylline. Their responses may be explained by the bronchodilating effect of ipratropium that resulted in a reduced airway resistance and a lower mean airway pressure.

To evaluate the effects of nebulized ipratropium bromide on intraocular pressures and pupillary responses in children with asthma.

It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions. This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique. Fourteen patients (mean +/- SEM age: 68 +/- 2 years) with airways obstruction (mean +/- SEM percent predicted. FEV1: 54 +/- 5; daily wet weight sputum: 9.1 +/- 2.0 g) took part in the study which was a randomized, three-way crossover within-patient design. Each patient underwent three treatment maneuvers: control, cough (30 coughs over a 10-min period), and forced expiration (30 forced expirations over a 10-min period). An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients. The lungs were divided arbitrarily into four regions of interest: tracheal, inner, intermediate, and outer. Peak expiratory flow rate during cough and forced expiration was measured at the mouth. There was no correlation between the radioaerosol clearance from all regions and (1) mean peak flow during cough and forced expiration, and (2) mean 24-h sputum production prior to the study day. There were no differences in regional radioaerosol clearance between cough and forced expiration. However, both cough and forced expiration resulted in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region. To our knowledge, this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction.

Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) is available widely throughout the world except in North America. Previous studies have yielded conflicting results regarding the advantages of combining anticholinergic therapy with sympathomimetic therapy in COPD. We report the results of a 12-week prospective, double-blind, parallel-group evaluation of the use of the following: albuterol, a beta-adrenergic agent; ipratropium, an anticholinergic agent; or a combination of the two, administered by metered-dose inhaler to patients with moderately severe stable COPD. Following baseline studies, 534 patients were given one of the three test bronchodilator preparations to be used at home four times daily in addition to oral theophylline and corticosteroids as required. The doses of the latter two drugs were kept stable. Subjects were tested on days 1, 29, 57, and 85. Analysis of 1-s forced expiratory volume (FEV1) curves on those test days indicated that the combination was superior to either single agent alone in peak effect, in the effect during the first 4 h after dosing, and in the total area under the curve of the FEV1 response. The mean peak percent increases in FEV1 over baseline on the four test days were 31 to 33 percent for the combination, 24 to 25 percent for ipratropium, and 24 to 27 percent for albuterol. The differences between the combination and its components were statistically significant on all test days. The AUC0-4 means for the combination were 21 to 44 percent greater than the ipratropium means and 30 to 46 percent greater than the albuterol means. Similar changes were noted in the forced vital capacity curves. Symptom scores did not change over time and did not differ among the treatment groups. We conclude that the combination of ipratropium and albuterol, when given by metered-dose inhaler to patients with COPD, is more effective than either of the two agents alone. The advantage of the combination is apparent primarily during the first 4 h after administration. The availability of combination therapy by metered-dose inhaler should help to improve patient compliance.

The purpose of this investigation was to determine right ventricular function during weaning from controlled ventilation comparing a biphasic positive airway pressure ventilatory support system (BiPAP [Respironics]) with pressure support ventilation (PSV). In 22 patients following coronary artery bypass grafting, both weaning techniques were used in randomized chronological order for 60 min each. Right ventricular end-systolic (RVESV) and end-diastolic volume (RVEDV) and ejection fraction (RVEF) were evaluated using the fast-response Swan-Ganz catheter. In comparison to PSV, the BiPAP system resulted in a significantly higher mean pulmonary artery pressure (20.6 +/- 5.0 vs 19.3 +/- 4.2 mm Hg, p = 0.0158), pulmonary vascular resistance index (206 +/- 55 vs 181 +/- 61 dyn.s.cm-5.m2, p = 0.0355), RVESV (92.2 +/- 36.3 vs 77.2 +/- 30.4 ml, p = 0.0017), and RVEDV (176.4 +/- 48.5 vs 161.8 +/- 43.3 ml, p = 0.0061), while the RVEF was significantly lower (46.0 +/- 11.9 vs 51.8 +/- 12.4 percent, p = 0.0012). No differences in left ventricular function or arterial blood gas analyses were measured during both study periods. In summary, the RV afterload was higher with the BiPAP system compared with PSV which suggested that this was due to differences in the respiratory support between both weaning modes. Because of the Frank-Starling mechanism, this higher afterload did cause a small but significant increase in RV volumes and a significant decrease in RV ejection fraction with the BiPAP system.

This prospective study compared two weaning modalities in COPD patients requiring mechanical ventilation (MV) for acute respiratory failure. Nineteen patients with COPD were studied when their precipitating illness was controlled. Although they satisfied the conventional bedside weaning criteria, they could not tolerate any reduction in the respirator rate below 10 cycles/min. At this time, patients were randomized into two groups receiving either synchronized intermittent mandatory ventilation (SIMV) with pressure support ventilation (PSV) (group 1) or SIMV alone (group 2). The volumetric support of ventilation (SIMV rate) was progressively decreased in both groups according to the patient's tolerance with a concurrent decrease in the barometric support of ventilation (PSV levels from 15 cm H2O to 6 cm H2O). At each step of SIMV rate, we found no difference between group 1 and group 2 in arterial blood gases, blood pressure, heart rate, airway occlusion pressure, maximal inspiratory pressure, and oxygen cost of breathing (OCB). At each step, however, group 1 patients showed significantly higher spontaneous tidal volume and lower spontaneous breathing frequency than did group 2 patients. We found a slight but not significant tendency to a shorter weaning period with than without PSV, but no difference in the weaning success. We concluded that (1) conventional weaning criteria might be inaccurate in COPD patients, (2) SIMV appeared very useful in weaning COPD patients from MV, (3) PSV marginally reduced the weaning period when added to SIMV, and (4) the OCB was not significantly improved with PSV.

Methacholine, provided by industrial sources, has traditionally been used in studies of airways responsiveness. In 1986, a Food and Drug Administration approved formulation of methacholine (Provocholine) was released and replaced industrial methacholine in many pulmonary laboratories. To determine whether methacholine and Provocholine cause an equivalent degree of bronchoconstriction, a double blind, cross-over clinical trial was undertaken. After randomization, 19 medicine residents and respiratory therapists each performed methacholine challenge testing using either methacholine or Provocholine. Forty-eight hours later, each participant returned for repeat challenge testing with the alternate agent. The log of the dose-response slope (logslope) was calculated for each test. The mean logslope with methacholine (-0.15 +/- 1.84) and with Provocholine (-0.26 +/- 1.57) did not differ (paired Student's t test, p = 0.64). Further, excellent agreement was found between each subject's logslope with methacholine and with Provocholine (intraclass correlation coefficient rI = 0.82). Proton beam nuclear magnetic resonance revealed no structural differences between the two compounds. These findings suggest that methacholine from industrial sources and Provocholine are clinically and structurally similar and that the two agents may be used interchangeably in nonspecific bronchial provocation testing.

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.

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

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.

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.