to determine if asymptomatic snorers have smaller pharyngeal volumes than age- and height-matched nonsnorers.

To determine the frequency of ACE inhibitor cough in an outpatient medical clinic population, a cross-sectional epidemiologic survey using mailed questionnaires was done. Patients were randomly selected from a computerized hospital pharmacy data base. The overall prevalence of cough was 19 percent in the ACE inhibitor groups compared with 9 percent in the hydrochlorothiazide-treated group. The observed odds ratio for cough among ACE inhibitor users was 2.3 (95 percent CI, 1.02 to 5.00). This study is the first systematic investigation of frequency and characteristics of ACE inhibitor cough that includes a control group. Our results suggest that cough may more frequently accompany treatment with ACE inhibitors than has been previously reported. We recommend that physicians specifically inquire about cough in patients taking an ACE inhibitor. Recognition of this side effect may prevent unnecessary testing and treatment of patients receiving ACE inhibitors.

In ten patients requiring respiratory support for an episode of acute respiratory failure (ARF), the best therapeutic level of PEEP was determined by measurement of changes in lung and chest wall compliance (CT) during a PEEP challenge from 0 to 20 cm H2O. During this challenge, hemodynamic monitoring combined with thermodilution measurement of right ventricular (RV) ejection fraction (EF) and two-dimensional echocardiographic measurement of RV size permitted assessment of the effects of increasing levels of PEEP on RV function. RV preload, as reflected by RV end-diastolic volume (EDV) and two-dimensional RV end-diastolic area (EDA), remained unchanged and RV diastolic compliance progressively decreased. On the other hand, RV systolic function, as assessed by RVEF and two-dimensional RV fractional area contraction (FAC), was progressively depressed. Substantial deleterious effects of PEEP were noted at high levels of PEEP including reduced CT and augmented pulmonary vascular resistance. Inadequate increase in RV preload to compensate for increased RV afterload resulted in depressed RV systolic function and contributed to the reduction in cardiac output. Finally, two-dimensional echocardiography proved to be more sensitive than fast-response thermodilution to evaluate change in RV function.

Anti-carcinoembryonic antigen radioimmunoscintigraphy (anti-CEA RIS) in colorectal adenocarcinoma has been reported to allow a better estimation of the local tumor extension than other radiologic methods. This study evaluated the clinical feasibility of a 99mTc-labeled anti-CEA monoclonal antibody (BW 431/26, Behring Institute, FRG) in 11 patients for staging of primary adenocarcinoma of the lung. The primary tumor size ranged from 3 to 8 cm with a mean of 4 cm. Mediastinal and hilar nodes were present in four patients, intrapulmonary metastases were present in two patients, and pleural and liver metastases were present in one patient each. The CEA levels were in the range of 2 to 265 ng/ml and elevated (greater than 5 ng/ml) in six patients. Planar scintigraphy was performed at 6 h and 24 h post injection (pi). Analog and digitized images were interpreted by two observers. One patient was imaged twice and experienced serum sickness due to human anti-mouse antibodies (HAMA) after the second study, which showed marked unspecific tracer uptake in liver, spleen, and bone marrow, but no specific uptake by the tumor and was excluded from further analysis. Visual interpretation identified the primary tumor clearly in seven patients. No tumor imaging was observed in two patients. Two patients were classified as having questionable imaging due to a poor separation of tumor uptake from mediastinal blood pool. The primary tumor could be clearly delineated in both patients after comparison with the chest radiograph. Thus, the overall sensitivity for imaging of the primary tumor was 82 percent. The average target/background ratio was 1.31 +/- 0.17:1 at 6 h pi, and 1.30 +/- 0.16:1 at 24 h pi. Hilar and mediastinal nodes were correctly suspected in three patients, but the cardiac blood pool hampered a clear interpretation. Intrapulmonary and pleural metastases were diagnosed in all cases. The single liver metastasis was missed because of the high unspecific tracer uptake. Planar anti-CEA RIS with 99mTc BW 431/26 was superior to computed tomography (CT) in one case with subtotal tumor resection. We summarize that at present, planar anti-CEA RIS with 99mTc BW 431/26 cannot be advised as a routine staging procedure in adenocarcinoma of the lung, but it may be helpful in the detection of residual or recurrent tumor tissue.

To assess whether adjustments in the initial flow rate or breath termination criteria affected patient-ventilator synchrony, we studied the ventilatory pattern response to PS in 33 patients under two sets of circumstances: during seven different levels of delivered initial PS flow and during PS termination at 50 percent and at 25 percent of peak flow. In the study on initial PS flow, we found the following: (a) an optimal initial PS flow could be defined for a given level of PS that resulted in the patient obtaining maximal pressure and volume from the ventilator; (b) initial PS flows above and below this optimal flow were associated with faster breathing frequencies, shorter inspiratory times, smaller tidal volumes and a tendency for airway pressure to not reach the selected PS level; and (c) optimal initial PS flow was fastest in patients with the lowest compliances and the most active ventilatory drives. Changing PS termination criteria from 50 to 25 percent of peak flow had minimal effects on the ventilatory pattern or synchrony. We conclude that the initial PS flow to achieve the selected PS level is important in patient-ventilator synchrony but that termination criteria set between 25 and 50 percent of peak flow is not.

The effects of additional target-flow inspiratory muscle training (TF-IMT) on the performance of the inspiratory muscles, on general exercise capacity, and on psychologic parameters during a pulmonary rehabilitation program (PR) were studied in 40 patients with COPD selected for ventilatory limitation during exercise. The mean age of the patients was 59 years, and the mean FEV1 was approximately 50 percent of predicted. All patients participated in a ten-week PR program. They were randomized to receive either additional TF-IMT (PR + IMT) or not (PR). The TF-IMT was performed by means of a target-flow resistive device; the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed. After the training period, maximal inspiratory mouth pressure and EMG-fatigability of the diaphragm were significantly better in the PR + IMT group than in the PR group. Maximal work load and psychologic symptoms increased to the same extent in both groups. The 12-minute walking distance also increased in both groups, but it increased significantly more in the PR + IMT group than in the PR group. We believe that additional TF-IMT during PR in a selected group of patients with COPD who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance.

Pulmonary failure is a major contributor to morbidity and mortality during marrow aplasia following high-dose antineoplastic therapy. For this reason, we initiated a pulmonary surveillance program for patients undergoing high-dose chemotherapy for leukemia or bone marrow transplantation. As part of this program, bronchoscopy with BAL was performed prior to therapy and at the onset of granulocytopenia. Thirty-three of the first 57 patients managed in this program developed some evidence of pulmonary complications. Twelve patients died in aplasia; all had pulmonary failure. Forty patients had clinically significant abnormalities on the bronchoscopy before treatment including 12 of 19 patients who had normal findings on chest x-ray films, physical examination, and pulmonary function testing, and no fever. Twenty-seven patients had clinically significant abnormal bronchoscopy or BAL at the onset of granulocytopenia. Thirteen patients required additional bronchoscopy. No patient required an open lung biopsy. Pulmonary surveillance using bronchoscopy with BAL is useful in the detection of pulmonary disease prior to the initiation of and following high-dose antineoplastic therapy.

To determine the utility of bronchoscopy with bronchoalveolar lavage for diagnosing M tuberculosis and fungal infections.

To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma.

Experiments in animals have demonstrated that recombinant tissue plasminogen activator (rt-PA) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated, and bleeding is reduced when rt-PA is administered over a short period. In previous studies in patients with thrombotic disease, rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours. To determine whether a short course regimen of rt-PA can achieve thrombolysis, a double-blind randomized trial has been conducted in which patients with objectively established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or saline placebo (25 patients). Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post-study drug administration. Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients (p = 0.026). At 24 hours, the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. There were no major bleeds in either group nor were there any differences in transfusion requirements between groups. Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites. These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism.

Physicians have been urged to reduce the use of the pulmonary artery catheter. However, there are no guidelines to help the clinician make the decision to use or withhold invasive monitoring in the individual patient. This study was designed to examine the accuracy of physician estimates of cardiac function in a spectrum of patients with hemodynamic instability to determine whether differences in accuracy among subgroups would suggest subgroups of patients who could be managed without invasive measurements. Physician estimates of cardiac index were found to be sufficiently accurate in patients without acute heart disease that initial management without invasive monitoring may be appropriate in selected cases. However, due to the general inaccuracy of physician estimates, efforts to improve the accuracy of clinical judgments of cardiac function and hemodynamic status should be pursued with vigor in patients both with and without acute cardiac dysfunction.

The late asthmatic reaction after exercise challenge remains a controversial issue. In this study, 21 patients recorded peak expiratory flow rate (PEFR) on two control days without performing exercise. There was no difference between both control days when PEFR at 1 h was compared with baseline PEFR and when PEFR at 4 to 13 hours was compared with baseline PEFR. After analyzing variation coefficients of baseline PEFR on a control day and exercise day, PEFR was not allowed to differ more than 15.3 percent in the same patient when comparing exercise day and control day for the late fall in PEFR in the study. In 17 of 81 patients, a late asthmatic reaction after exercise challenge was present when PEFR fall was greater than or equal to 20 percent compared with baseline PEFR value. In eight of the 17 patients, a real late asthmatic reaction to exercise challenge was present with a PEFR fall greater than or equal to 20 percent on at least three successive time points and who had a PEFR fall greater than or equal to 20 percent compared with corresponding clocktime on a control day. The late asthmatic reaction to exercise challenge is characterized not as a nonspecific epiphenomenon, but as a fall in PEFR of greater than or equal to 20 percent compared with baseline PEFR value and with corresponding clocktime on a control day on at least three successive time points. Graphic illustration of airway responses following exercises may facilitate the detection of a late asthmatic response.

The efficacy of nebulized glycopyrrolate compared with metaproterenol was evaluated in 46 patients with acute asthma. In a double-blinded, randomized fashion, patients received, as sole therapy, either 2 mg of glycopyrrolate or 15 mg of metaproterenol every 2 h over a 6-h study period. Of the 35 patients completing the study, analysis of variance demonstrated no difference in percentage of change in FEV1 between glycopyrrolate and metaproterenol. Two hours after the initial dose, there was a 30 percent increase in FEV1 for glycopyrrolate compared with a 25 percent increase for metaproterenol (p greater than 0.05, NS). In contrast to the comparable bronchodilator activity, the side effects profile of the two agents were markedly dissimilar. Not only were subjective complaints of tremor, palpitations, and paresthesias increased for metaproterenol, but the heart rate response was significantly elevated (p less than 0.05) compared with glycopyrrolate. Based on these data, administration of the aerosolized anticholinergic agent, glycopyrrolate, is a reasonable therapeutic alternative for acute asthma.

From June 1988 to February 1989, we enrolled 36 patients with human immunodeficiency virus into a randomized double-blind placebo-controlled trial assessing the efficacy and toxicity of aerosolized pentamidine (AP) as secondary prophylaxis for Pneumocystis carinii pneumonia. Each patient underwent spirometric evaluations before and after aerosolized treatment. There was no significant difference in the results of baseline pulmonary function tests between the two groups. Eleven patients (65 percent) in the AP group developed cough but only four demonstrated significant reduction in the forced expiratory flow rates after AP; four patients (21 percent) in the placebo group developed cough, but no significant change in the expiratory flow rates was noted. All bronchospastic episodes were self-limited and symptomatically responded to remedial inhaled albuterol (salbutamol) treatment. We conclude that AP treatment is frequently associated with coughing attacks (65 percent), but the actual incidence of bronchospasm on spirometry is much lower (24 percent) and is generally quite mild.

Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs.

Thirty-two patients presenting with acute exacerbations of chronic obstructive pulmonary disease were entered into the following double-blind, crossover study. First (time 0), patients inhaled either ipratropium bromide (54 micrograms) or metaproterenol sulfate (1.95 mg) via a metered dose inhaler (MDI) attached to a device (Inspirease) (phase 1). After 90 minutes, they inhaled whichever of the two medications they had not received in phase 1. This is referred to as phase 2. Pulmonary function (FEV1 and FVC) was measured at time 0, and at 30, 60, and 90 minutes following phase 1 treatment, and at 30, 60, and 90 minutes following phase 2 treatment (120, 150, and 180 minutes from the start of the study). Arterial blood gas samples (n = 20) were obtained at entry into the study and 30 and 90 minutes after phase 1 medication. The groups did not differ in age, degree of airway obstruction, hypoxemia, or theophylline usage at the start of the study. In phase 1, at 90 minutes, pulmonary function in both groups significantly and similarly improved. For ipratropium, FEV1 improved from 0.62 +/- 0.08 L to 0.88 +/- 0.11 L (p less than 0.01) and for metaproterenol FEV1 improved from 0.69 +/- 0.06 to 0.92 +/- 0.09 L (p less than 0.01). There was no further improvement with phase 2 treatment for either group. Thirty minutes after inhaling ipratropium, there was a small but significant rise in PO2 (5.8 +/- 3.0 mm Hg; p less than 0.05) while metaproterenol inhalation resulted in a 6.2 +/- 1.2 mm Hg decline in PO2 (p less than 0.05). These changes were not sustained at 90 minutes. We concluded that for acute exacerbations of COPD, both ipratropium and metaproterenol are effective medications when administered via an MDI attached to a device (Inspirease). However, ipratropium may be a safer choice as it initially did not cause a decline in blood oxygenation.

Formoterol fumarate is a new beta 2-adrenergic agonist with a long lasting effect. The bronchospasmolytic effect of 12 micrograms of formoterol was compared with that of 200 micrograms of albuterol (salbutamol) in a single-center, double-blind, randomized within-patient study. The drugs were given as aerosols by MDI to 16 patients with nocturnal asthma in a stable phase. The inhalations were given at 10 PM and the FEV1 values as parameter were measured before and at 1, 2, 6, 8, 10, and 12 hours afterwards. The FEV1 6 hours after administration of formoterol was significantly higher than that after albuterol (ANCOVA: p = 0.008), and this was still the case 12 hours after the test dose at 10 AM the following morning (ANCOVA: p = 0.009). At 4 AM, the FEV1 fell below the basic starting value after albuterol, whereas it remained at least 10 percent above the formoterol inhalation. Five patients required rescue therapy after albuterol and two after formoterol. We conclude that formoterol in a dose of 12 micrograms via MDI confers good protection against nocturnal asthma; this was only insufficient for some patients with severe asthma, and further studies with higher dosages in these patients are clearly indicated.

The bronchodilator effect of nebulized AMN, albuterol and their combination was evaluated in 16 steroid-dependent asthmatic children. In phase 1, maximal bronchodilation was determined by dose-response studies on separate days. Maximal bronchodilator dose of each drug was administered either alone or in combination during phase 2. In phase 1, 0.11 +/- 0.01 mg/kg of albuterol and 0.03 mg/kg of AMN produced maximum bronchodilation. In phase 2, the peak response to albuterol occurred within 30 min and to AMN, at 60 min. Maximal FEV1 achieved after AMN was 90 percent of the maximal achieved after albuterol. AMN FEV1 response was better than for placebo for 3 h; that for albuterol was better for 4 h. Combination therapy produced a peak response similar to that of albuterol but was better than albuterol by 6 h. Thus, the maximum bronchodilator effect of AMN is less than that of albuterol in asthmatic children, but the combination may extend the period of bronchodilatation.

The effect of four weeks of treatment with beclomethasone dipropionate (BDP, 500 micrograms twice daily) on the bronchial responsiveness to propranolol was examined in 16 patients with mild asthma in a placebo-controlled, double-blind crossover study. Propranolol was inhaled in doubling concentrations and the results were expressed as the cumulative dose producing a 20 percent fall in FEV1 (PC20). After four weeks of treatment with BDP, the mean FEV1 increased from 82.0 percent predicted to 88.1 percent predicted. The difference was significant (p less than 0.001). Treatment with BDP did not significantly change the responsiveness to propranolol, the geometric mean PC20 being 3.17 mg/ml before and 3.64 mg/ml after BDP treatment. The recovery of FEV1 was faster after 60 minutes of BDP treatment in comparison with placebo treatment (beyond 90 minutes). This study suggests that BDP treatment is unable to reduce bronchial responsiveness to propranolol but can accelerate the recovery of bronchoconstriction induced by propranolol in asthmatic patients.