To determine whether nasal oxygen therapy at 2 L/min would (1) reverse nocturnal hypoxemia and (2) improve neuropsychologic function in men who snore heavily.

We investigated the effect of small inspiratory resistive loads on the breathing patterns of patients with COPD admitted to the ICU for acute respiratory failure. Patients were in stable clinical condition three days after weaning from the acute-phase ventilation. Healthy nonsmokers served as controls. Breathing patterns were recorded for 20-min periods during unloaded breathing (R0), then with small inspiratory resistive loads (R1 = 2.5 cmH2O L/s and R2 = 5.2 cmH2O L/s) applied in random order. Respiratory parameters were memorized in real time and blood gases measured continuously with a transcutaneous PO2/PCO2 monitor and compared periodically with arterial blood gases. Minute volume (VE) and respiratory rate decreased with no modification in blood gas values. In the COPD patients, R1 was too small to be perceived; when R2 was applied, no increase in TI was observed, and VT and VT/TI decreased. The VE could not be maintained despite a shortening of expiratory time. The COPD patients did not have significant increase of occlusion pressure (P0.1). Mean blood gas values did not change during the testing, but the coefficient of variation of tcPCO2 increased. During the critical period following weaning from artificial ventilation, COPD patients did not respond in the same manner as normal subjects to inspiratory resistive loads, but did not have modified gas exchange during the 20-min period.

The effects of two cardioselective beta-adrenergic blocking agents--celiprolol (claimed to have bronchodilator properties) and atenolol (without such claims)--on respiratory function and control of asthma were studied in ten asthmatic patients with mild to moderate essential hypertension. Following a beta-2 agonist-free period of ten hours, administration of 100 mg of atenolol was associated with bronchoconstriction (p less than 0.05), whereas 400 mg of celiprolol was not. Responsiveness to beta-2 agonist therapy was retained with both agents (p less than 0.05). Day-to-day asthma control, interpreted from patient recordings of peak flow, inhaler use and symptom scores, were all no different on either agent from placebo. When given acutely, celiprolol appeared to have acute bronchosparing properties, possibly providing a greater margin of respiratory safety than atenolol.

At the onset of exercise, both cardiac output and ventilation increase abruptly. We investigated the hypothesis that a rapid change in cardiac output, as effected by an immediate increase in heart rate at the start of exercise and a decrease in heart rate at the termination of exercise, affects the responses of oxygen uptake. Five patients in whom programmable pacemakers had been previously inserted for complete heart block were studied. Responses in ventilation and gas exchange were recorded breath by breath during studies in which each subject performed 16 transitions between rest and moderate exercise on a cycle ergometer. In a randomized fashion, in half of the transitions, heart rate was accelerated from a low rate to a high rate as exercise began; in the other half, heart rate was held constant at the low rate as exercise began. Oxygen uptake increased by 30 percent in the first 20 seconds of exercise, when heart rate was constrained, while it increased by 70 percent when heart rate was abruptly accelerated. Similarly, smaller changes were observed at the cessation of exercise when the heart rate was constrained, as compared to an abrupt decrease in heart rate. Despite this difference in the responses of oxygen uptake, at the transitions in exercise, the ventilatory responses were indistinguishable. We have demonstrated that ventilation-independent changes in oxygen uptake can be induced at the onset and cessation of exercise. These alterations in oxygen uptake are predictable from differences in blood flow which occur as a consequence of the differences in time course of the heart rate.

Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI, DO2, and VO2 than nonsurvivors. The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism. We tested this hypothesis in two series. In series 1, prospectively allocated by services, mortality and morbidity of the control group were significantly greater than those of the protocol group. In series 2, patients who fulfilled previously defined high-risk criteria were preoperatively randomized to one of three monitoring/treatment groups: CVP-control group, PA-control group and PA-protocol group. Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different, but PA-protocol group mortality was significantly reduced compared with its control group. The PA-protocol group had reduced complications, duration of hospitalization, duration in ICU, and mechanical ventilation, and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses.

A prospective, double-blind, randomized study of the role of corticosteroids in the treatment of tuberculous pleurisy was performed in 40 patients. All patients received adequate antituberculosis chemotherapy (isoniazid, 300 mg/day; rifampin, 450 mg/day; ethambutol, 20 mg/kg/day) for more than nine months. They were randomly assigned to take prednisolone 0.75 mg/kg/day orally or placebo for the initial treatment, which was tapered gradually for the next two to three months. Twenty-one were treated with steroids and 19 were given a placebo. The two groups were identical with regard to age, sex, duration from onset of symptoms to diagnosis, and initial amount of pleural effusion. The mean duration from symptoms (fever, chest pain, dyspnea) to relief was 2.4 days in the steroid-treated group, and 9.2 days in the placebo group (p less than 0.05). Complete reabsorption of pleural effusion occurred an average of 54.5 days in the steroid-treated group and 123.2 days in the placebo group (p less than 0.01). The development of residual pleural thickening was not influenced by the administration of corticosteroids. No serious side effects were noted during the treatment in either group. We conclude that the administration of corticosteroids, in conjunction with antituberculosis chemotherapy, will resolve the clinical symptoms more quickly and hasten the absorption of pleural effusion in patients with tuberculous pleurisy.

The effect of a new H2-antagonist, famotidine, on theophylline pharmacokinetics was compared with placebo and cimetidine in 26 patients affected by COPD. Cimetidine, placebo, and famotidine were administered, four days each drug at random, to all the subjects. Results suggest that famotidine, contrary to cimetidine, does not influence theophylline metabolism in man.

Since parenteral beta 2-adrenergic stimulation can induce hypokalemia, we postulated that administration of beta 2 adrenoreceptor agonists by inhalation could induce the same. We administered the usual clinical doses of three commonly used bronchodilators to each of six subjects receiving assisted mechanical ventilation in line with the ventilator: two beta 2-adrenoreceptor agonists, metaproterenol, 5 percent solution, and isoetharine, 1 percent solution; and the anticholinergic agent atropine as a control. Each bronchodilator was nebulized over 10 to 15 minutes in random order, four hours apart, and given to every subject. Plasma potassium was measured at five-minute intervals and arterial blood gases at 15-minute intervals, for a total of 50 minutes after administration of each bronchodilator. Following administration of each drug, plasma potassium showed an average decline. The mean decline in plasma potassium from baseline was statistically significant for metaproterenol (p = 0.04) and atropine (p = 0.001) but not for isoetharine (p = 0.09). Although there were no statistically significant differences among the declines in plasma potassium induced by the three drugs, metaproterenol caused the greatest decline (-0.6 mEq/L).

To compare intravenous and orally administered corticosteroids and theophylline in treating acute episodes of airways obstruction, patients with recent worsening of obstructive symptoms were randomly divided into two groups. Group A received methylprednisolone, 80 mg/24 h, and aminophylline by continuous infusion. Group B received a comparable dose of a sustained-release theophylline and methylprednisolone, 80 mg in two equally divided doses, by mouth. Assessment of response was based on daily spirometric tests and evaluation of dyspnea and wheezing. Arterial blood gas and serum theophylline levels were also measured. The groups were comparable with respect to age, sex distribution, smoking history, and spirometric evidence of obstruction. Initial spirometric test results showed moderate obstruction, equal in the two groups. Obstruction improved markedly by both spirometric and clinical criteria in the four-day study period. The improvement in FEV1 and dyspnea index was slightly greater for group B, but the differences were not significant. We conclude that oral administration of steroids and theophylline is as effective as intravenous use in treating hospitalized patients with moderate exacerbations of airways obstruction.

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.