In a double-blind randomized trial, 40 patients with acute severe asthma were given either nebulized salbutamol, 5 mg, or salbutamol, 5 mg mixed with ipratropium bromide 500 micrograms, on admission to hospital and again two hours later. There was no significant difference between the mean peak flows of the two treatment groups at any time. However, two hours after each treatment, there were fewer subjects in the ipratropium and salbutamol group whose peak flow rates had fallen back toward baseline levels than in the salbutamol only treatment group. Thus, although ipratropium did not improve the overall maximal bronchodilator response, it may have prolonged the duration of the response, which would be a clinically useful effect.

Uncontrolled studies have suggested that the newer oral phosphodiesterase inhibitors milrinone and enoximone acutely improve exercise performance in patients with severe chronic cardiac failure. To determine whether an oral placebo presented as an inotropic agent could acutely enhance exercise capacity, two separate groups of stable heart failure patients were studied by serial exercise testing and respiratory gas exchange analysis. Group 1 had nine patients studied four hours after a single oral dose of placebo, and group 2 had ten patients retested after one to two weeks of placebo therapy. No significant change was seen in the mean exercise time, mean peak oxygen consumption, and the mean oxygen consumption at anaerobic threshold after placebo administration in both group 1 and group 2 patients. Improvements in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold occurred in five patients in group 1 and seven patients in group 2. The improvements exceeded the baseline variability of 10 percent in three group 1 patients. Among group 2 patients, the increase in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold exceeded 10 percent in six, four, and four patients, respectively. Thus, stable chronic heart failure patients can achieve a true baseline exercise capacity. Small improvements in exercise performance seen acutely after oral inotropic drug therapy in individual heart failure patients must be interpreted with caution, as they may be due to a placebo effect.

The aims of antimicrobial therapy extend beyond short-term bacterial killing to long-term maintenance of weight and lung function. A review of antimicrobial drug trials shows that empiricism is still ahead of science and more studies are needed both to justify current practice and to make future changes logical.

The pharmacodynamics and pharmacokinetics of beta-lactam antibiotics in patients with cystic fibrosis are discussed. A hypothetical dosing regimen based on these principles is considered. The usual dosing regimens may be suboptimal. New dosage regimens should be studied using prospective, controlled, randomized and blinded clinical trials.

Eradication of the bacterial pathogen, resolution of the local and systemic inflammatory signs, and recovery of organ function are the main criteria by which antibiotic treatment is evaluated. In cystic fibrosis (CF) the pathogen is seldom eradicated and systemic markers of inflammation are not always present. The main criterion for assessing the results of antimicrobial therapy in CF is therefore clinical improvement. The use of clinical scoring systems and double-blind design in therapeutic trials can reduce bias in evaluation of outcome. Assessment of the contribution of antibiotic therapy to the outcome requires greater knowledge of the role of bacterial infection in the pathogenesis of pulmonary exacerbations and could be improved by the development of quantifiable markers in respiratory secretions for inflammation.

In a prospective randomized trial, we examined the value of routine postlobectomy fiberoptic bronchoscopy (FOB) in preventing postoperative atelectasis. Twenty patients who underwent lobectomy were randomly assigned to either chest physical therapy alone (group 1) or immediate bronchoscopy (group 2). Both group 1 and group 2 were placed on a standard physical therapy regimen consisting of aerosol bronchodilator therapy, chest percussion, and incentive spirometry. It was concluded that routine postlobectomy bronchoscopy offers no advantage over the usual physical therapy measures in preventing the development of postoperative atelectasis.

The pulmonary clearance of aerosolized 99mTc-diethylenetriaminepentacetate (DTPA) was studied in mongrel dogs immediately after exposure to wood smoke to see if a sensitive, objective way of assessing the degree of pulmonary injury might be found. Animals were studied in four groups as follows: control, following five minutes, two minutes, and 15 seconds of smoke exposure. Chest roentgenograms and 133Xe scans were taken before and after smoke exposure. The DTPA clearance was more sensitive in detecting injury than either of these imaging techniques. The DTPA clearance rates increased in a dose responsive way following smoke inhalation: 2.4 percent and 12.1 percent excreted per minute for control animals and those exposed to five minutes of smoke, respectively. Seven patients in a clinical trial of DTPA following smoke exposure are described; their DTPA clearance rates were all normal, although five were active cigarette smokers. Despite encouraging results in animal experiments, DTPA clearance studies may be of little practical value in the clinical setting of acute inhalation injury.

Fifty patients with malignant pleural effusion were randomized to receive one or two doses of tetracycline sclerotherapy. We found that a single sclerotherapy treatment with tetracycline at a dose of 20 mg/kg was as effective as two sclerotherapy treatments and provided symptomatic relief in 46 of the 50 patients.

We verified the utility of an oxygen economizer (Pendant Oxymizer) in assuring greater protection than nasal prongs against worsening of oxyhemoglobin resting desaturation (delta SaO2) induced by muscular exercise in 16 patients (ten with chronic obstructive pulmonary disease [COPD] and six with restrictive pulmonary disease). This worsening was quantified as desaturation surface accumulated within five minutes of exercise and was expressed in arbitrary units (au). Each patient carried out the same exercise three times, in a randomized fashion (breathing air or breathing supplemental oxygen [3 L/min] delivered by either nasal prongs or by oxygen economizer). In patients with obstructive disease, delta SaO2 was reduced from 38 +/- 12.0 au when they were breathing air to 18.1 +/- 11.7 au when breathing oxygen by nasal prongs (p less than 0.001) and to 10.1 +/- 9.5 au when breathing oxygen by economizer (p less than 0.001). In patients with restrictive disease, delta SaO2 was reduced from 35.6 +/- 9.9 au when breathing air to 14.9 +/- 10.2 au breathing oxygen by nasal prongs (p less than 0.01) and to 13.7 +/- 10.3 au breathing oxygen by economizer (p less than 0.01). The difference between breathing by economizer and nasal prongs was significant (paired t-test; p less than 0.01) only in patients with COPD. One explanation could lie in the different values of the respiratory rate, which was significantly greater in patients with restrictive disease (20.7 +/- 1.2 breaths per minute at rest and 25.8 +/- 1.5 with exercise) than in patients with obstructive disease (15.3 +/- 1.2 breaths per minute at rest and 20.8 +/- 1.4 with exercise).

We have studied the antitussive effects of two anticholinergic agents, oxitropium bromide (200 micrograms) and ipratropium bromide (80 micrograms), and a combined beta-agonist and anticholinergic preparation containing fenoterol hydrobromide (200 micrograms) and ipratropium bromide (80 micrograms), in 16 normal and ten asthmatic volunteers in a double-blind, randomized, placebo-controlled crossover trial. Cough was induced by inhalation of ultrasonically nebulized distilled water and hypotonic saline solution. All treatments significantly reduced the cough response to inhaled distilled water aerosol when compared with placebo (p less than 0.001). There was no difference between oxitropium bromide and ipratropium bromide (p greater than 0.05), but the combination preparation displayed a greater antitussive effect than either oxitropium bromide (p less than 0.05) or ipratropium bromide (p less than 0.025). Cough frequencies in response to hypotonic 0.18 and 0.32 percent saline aerosol were lower than those obtained with distilled water (p less than 0.005) for all treatments. Asthmatic patients coughed less frequently than normal volunteers in response to all solutions when placebo was given (p less than 0.05), but there is no evidence to suggest that the response to treatment was different in the two groups. Our results suggest that inhaled anticholinergic bronchodilators alone or in combination with beta 2-adrenergic agonists might be effective in the treatment of pathologic cough.

Twenty seven healthy individuals were divided randomly into three groups. The first group of nine subjects received only a routine bronchoscopic examination. The second group of nine subjects was examined with the bronchoscope followed by bronchoalveolar lavage (BAL) with 200 ml of 25 degrees C normal saline solution. The third group of nine subjects received a bronchoscopic examination followed by BAL, but with 200 ml of 37 degrees C normal saline solution. Examination in all groups included arterial blood gas (ABG) analysis and pulmonary function test (PFT), both pre- and post-procedure. In group 1 there was no statistical difference in the pulmonary function test result after routine bronchoscopic examination except for decrease in PaO2. The results in group 2 showed a statistical difference in both ABG and PFT data, especially PaO2, FEF 200-1200, FEF25%-75%, FEF25%, FEF50%, and FEF75%. In group 3, there was a significant decrease of PaO2 and no significant difference in PFT before and after BAL. From these data we conclude that BAL is a safe examination. However, the administration BAL fluid (BALF) with 25 degrees C normal saline solution can affect the results of the PFT significantly. Much of this adverse reaction can be minimized by using body temperature (37 degrees C) saline solution. At 37 degrees C, the ABG data showed a decrease in PaO2, but pulmonary function was not affected significantly.

A six-month double-blind controlled trial compared a 2,000 microgram per day dose of beclomethasone dipropionate aerosol (BDP), with current upper level doses of 800 micrograms per day of the standard BDP, in asthmatics requiring oral corticosteroids in addition to BDP and bronchodilators. Both groups showed a significant reduction in their oral steroid requirements during the study, with a 34 percent reduction in the lower dose group and a 57 percent reduction in the high dose BDP group while maintaining good symptomatic control of asthma; there was an associated improvement in baseline serum cortisol levels. Over the same period, the pulmonary function of the lower dose group showed significant worsening relative to that of the group receiving the high dose BDP which improved. There was no increase in dysphonia or oropharyngeal candidiasis among those using the concentrated BDP. We conclude that high dose concentrated BDP appears to be a safe medication in long-term steroid-dependent asthma, and is effective in reducing dependence on the use of oral corticosteroid with associated improvement both in pulmonary and adrenal function.

We studied the effects of oral nutritional supplementation on respiratory muscle (RM) performance in 25 ambulatory patients with severe chronic obstructive pulmonary disease (COPD). There was a relationship between body weight and anthropometric parameters of nutritional status (triceps skinfold thickness [r = 0.67; p less than 0.005], midarm muscle circumference (r = 0.53; p less than 0.005), but body weight did not correlate with daily caloric intake, serum albumin, transferrin, or blood lymphocyte count. None of these measurements of nutritional status correlated with any measure of RM strength or endurance. In a randomized observer-blinded crossover trial, patients were allocated to one of two groups. In the first eight weeks of the study, group A received nutritional supplementation, and patients in group B were control subjects. In the second eight weeks, patients in group A were control subjects, and group B received supplement. Mean daily caloric intake and body weight increased in both groups while receiving supplement (both p less than 0.05). Calories provided by the supplement were frequently substituted for normal dietary calories. Any increases in RM performance in the group receiving supplement were matched by increases (due to learning) in controls. We conclude that oral dietary supplements have no important effects on RM performance in ambulatory patients with COPD.

We evaluated the safety and efficacy of transdermal clonidine (TC) in 23 patients with essential hypertension over a two-year period. Fourteen patients achieved control of blood pressure using TC alone. Six patients achieved control with a combination of TC and the diuretic chlorthalidone (CH). Three patients had control with CH alone or did not achieve control with either TC alone or TC plus CH and were dropped from the study. Of the 20 patients remaining in the study, six patients remained on TC or TC plus CH for the two-year study. Ten of the 20 patients quit the study because of skin reactions and four because of other side effects. No clinically significant changes were noted in serum or urinary laboratory parameters. Finally, TC was effective as long-term monotherapy for essential hypertension in only four of our patients. The major limitation is skin-related side effects.

A cooperative, prospective, randomized study to evaluate the effectiveness of preoperative irradiation in curatively resected esophageal carcinoma was performed in 364 cases in eight institutions from August 1982 to November, 1983. Based on the survival curves, postoperative irradiation alone was superior to preoperative plus postoperative irradiation. Because of the progression of the disease and complications after operation, there were many inevaluable cases in this study. However, analysis revealed there was no bias caused by a greater number of unfavorable patients being selectively included in inevaluable cases in the postoperative irradiation only group. Our data question the value of preoperative irradiation being performed in addition to resection plus postoperative irradiation.

In the absence of clinical trials, positive end-expired pressure (PEEP) has been accepted as efficacious for treatment of postoperative decreases in arterial oxygen tension (PaO2) from a variety of causes including adult respiratory distress syndrome (ARDS). PEEP is thought to increase PaO2 by alveolar recruitment, which in turn, has been hypothesized to play a decisive role in pulmonary recovery. One hundred and eighteen patients were followed prospectively, and after development of decreased PaO2, randomized to receive recruitive PEEP (determined by blood gas criteria) or supportive PEEP (the minimal PEEP required to maintain PaO2 above 60 mm Hg on .5 inspired O2 fraction (FIO2). No prognostic factors were significantly different between the two groups. Recruitive PEEP application in 22 patients yielded a significantly increased incidence of hypotension (55 percent), pneumothorax (20 percent), and death during treatment (27 percent) when compared to the 28 supportive PEEP patients who had no hypotension or pneumothorax and only one death during treatment (4 percent). After PEEP treatment, deaths in each group were similar (19 percent and 15 percent, respectively). We find no evidence that PEEP treatment promotes beneficial outcomes and conclude that recruitment attempts may be harmful.

In ten young asthmatic subjects, we studied the effect of a single oral dose of 4.4 mg of azelastine hydrochloride on exercise-induced bronchoconstriction during the breathing of cold air. Exercise challenges were performed on two different days before and four hours after azelastine and placebo given in a randomized double-blind crossover fashion. Placebo had no effect on baseline pulmonary function and postexertional obstruction of the airways, in contrast to azelastine, which exerted a small but significant (p less than 0.05) bronchodilation and a significant attenuation (p less than 0.01) of exercise-induced bronchoconstriction as compared to data from before treatment and after placebo.

This study evaluated educational effectiveness of preclinical training of residents in diagnostic bronchoscopic techniques which used videotaped programs. Sixty-five residents in eleven medical centers were randomized. Experimental subjects viewed five videotaped programs dealing with bronchoscopic anatomy and pathology. Following their tenth clinical experience in bronchoscopic diagnosis, performance of both experimental and control subjects was objectively evaluated using a Visual Discrimination Test (VDT) that contained six videotaped sequences in suspected cancer patients. Clinical performance was subjectively evaluated by teachers who used a list of Minimum Competency Requirements (MCRs). Experimental subjects provided a significantly greater number of correct answers in the VDT and achieved higher scores for the MCRs that were specifically related to recognition of bronchoscopic anatomy and pathology. This study demonstrated that preclinical training using videotaped programs could improve visual perception and discrimination skills of residents in their bronchoscopic examination of patients with suspected cases of cancer.

A new bronchoscopic-protected catheter brush (BPCB), designed to obtain uncontaminated bronchial secretions, was studied in vitro and in vivo. The device was composed of a standard biopsy brush, protected by a single catheter and occluded with an agar plug. Ejection of the plug was obtained neither by advancing the brush nor by advancing an inner cannula (as in a telescoping catheter brush), but instead, by an air flux, provided by a syringe which was connected to the proximal tip. In the first part of the study the ability of the BPCB to obtain uncontaminated specimens was tested in comparison with the reference telescoping catheter brush (BFW brush 10/70/90, Medi-Tech Corp Watertown, MA). Catheters of each type were successively passed through the inner channel of a bronchofiberscope which was contaminated with Klebsiella pneumonia. After ejection of the distal plug, sampling of bronchial secretions infected with a marker organism (Pseudomonas aeruginosa), was performed with the brush. Culture of brush specimens of each type of catheter grew the marker organism in pure culture and obtained the same amount of bronchial secretions (0.001 ml). The manual vortexing of the brush in the transport medium (Ringer's solution) proved to be as effective as the mechanical vortexing so that transecting of the brush was no longer mandatory. In the second part of this study, paired bronchial samplings from 27 patients were performed using both types of catheters and similar results for both were obtained. In these in vitro studies, completed by a clinical trial, our single-sheathed, plugged catheter brush proved to be as reliable as the double telescoping catheter brush. However, because of its relatively simple conception, making it easier to use and lower in cost than the double catheter brush, routine use of this sampling device should be considered.

Many patients with chronic obstructive pulmonary disease (COPD) report greater limitation for activities involving the upper extremities than the lower extremities. Exercise training has generally emphasized lower-extremity exercise. We designed and evaluated two simple, practical, and widely applicable upper-extremity training programs in 45 patients with COPD participating concurrently in a comprehensive, multidisciplinary pulmonary rehabilitation program. Patients were randomly assigned to one of the following three groups: (1) gravity-resistance (GR) upper-extremity training; (2) modified proprioceptive neuromuscular facilitation (PNF) upper-extremity training; or (3) no upper-extremity training (control). Patients were evaluated before and after at least six weeks of uninterrupted training. Twenty-eight patients completed the study. Compared to controls, both GR and PNF patients demonstrated improved performance on tests specific to the training performed (upper-extremity performance test, maximal level and endurance on isokinetic arm cycle). There were no significant changes on isotonic arm cycle, ventilatory muscle endurance, or simulated activities of daily-living tests. Ratings of perceived breathlessness and fatigue decreased significantly in all groups for several tests. We conclude that specific upper-extremity training may be beneficial in the rehabilitation of patients with COPD and warrants further investigation.