Benign thymic hyperplasia (BTH) is a known feature of hyperthyroidism, but is infrequently appreciated by clinicians. In most cases thymic enlargement is minimal; however, it may occasionally present as an appreciable anterior mediastinal mass. While surgical resection is a common approach to such a mass, recognition of the benign nature of BTH and its regression following treatment of hyperthyroidism would prevent a major surgical procedure. We present three cases of BTH associated with hyperthyroidism and describe our approach to this syndrome.

Magnetic resonance imaging (MRI) was used for postoperative evaluation of spiral vein grafts in three patients with fibrosing mediastinitis who had undergone bypass of the superior vena cava (SVC) for SVC syndrome. The MRI images, obtained without ECG triggering, were compared retrospectively with postoperative bilateral arm venograms. Patent grafts were identified by MRI in all patients. Significant stenoses at innominate vein-spiral vein graft anastomoses in two patients were better demonstrated by venography than by MRI. MRI shows promise as a non-invasive technique for postoperative evaluation of spiral vein bypass grafts.

To compare the acute bronchodilator effect of increasing doses of intravenous theophylline and inhaled beta adrenergic agonists, we administered intravenous theophylline dissolved in ethylenediamine or proxyphylline and diprophylline or placebo in a double blind fashion to nine asthmatics on three different days. At each session, 100 mg theophylline or placebo were given during each of five subsequent periods of 30 minutes' duration and followed by inhalation of 0.4 mg fenoterol. In contrast to placebo, 500 mg theophylline in ethylenediamine or proxyphylline and diprophylline significantly decreased mean specific airway resistance (SRaw in cmH2O.s) from 31.2 to 23.6 or 34.2 to 23.5 at theophylline serum concentrations of 14.4 or 16.6 mg/L, respectively. Fenoterol lowered SRaw to about 40 percent of the respective baseline values independent of theophylline or placebo pretreatment. We conclude that the acute bronchodilator effect of theophylline is weak in comparison to inhaled beta agonists. Furthermore, proxyphylline and diprophylline cause a weak but not significant bronchodilation when compared to ethylenediamine.

Propafenone is a new membrane-stabilizing antiarrhythmic agent that structurally resembles the beta-adrenergic receptor antagonist, propranolol. To determine the potential asthmogenicity of this new drug, pulmonary function, airway reactivity to methacholine, blood pressure, the electrocardiogram, and plasma concentrations were measured in 12 patients with mild intermittent asthma after 48 to 72 hours of treatment with placebo and with oral propafenone in low dosage (150 mg every eight hours) and high dosage (300 mg every eight hours) in a double-blind crossover manner. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow over the middle half of the FVC (FEF25-75%), heart rate, and blood pressure during the three regimens of treatment were not significantly different; however, the QRS interval on the ECG was significantly widened with both dosages of active drug, and the mean provocative dose of methacholine (+/- SE) required to reduce FEV1 by 20 percent (PD20) decreased from 3.0 +/- 0.6 mg/ml with placebo to 2.1 +/- 0.7 mg/ml with the high dosage of propafenone (p less than 0.01). The mean PD20 on the low-dose regimen was not significantly different from placebo or high-dose therapy. A potentially relevant increase in airway reactivity, as measured by a ratio of less than 0.5 for PD20 after treatment to PD20 after placebo, occurred in seven subjects with high-dose and in one subject during low-dose treatment (p less than 0.01). These data suggest that propafenone should be used with caution in patients with asthma and that bronchial provocation will provide a more sensitive measure of the asthmogenicity of a drug with beta-adrenergic receptor antagonist activity than pulmonary function tests. Moreover, use of bronchial provocation allows the selection of subjects with mild disease, thus reducing the risk of potentially severe bronchospasm.

A placebo-controlled single-blind study on acute effects of captopril on hypoxic pulmonary hypertension was performed in 15 patients with severe chronic obstructive lung disease recovering from right heart failure. Ten patients received active drug (25 mg captopril orally), five patients received placebo and served as control subjects. Before drug administration, there was no difference in lung function data and pulmonary hemodynamics between patients in both groups. Captopril produced highly significant fall in systemic arterial pressure. No change in breathing frequency, minute ventilation, and pulmonary gas exchange was observed. There was no significant change in studied variables after placebo. The presented data suggest that captopril does not decrease pulmonary vascular resistance in patients with hypoxic pulmonary hypertension. A fall in pulmonary wedge pressure reflects a decrease in left ventricular afterload.

Pulmonary dysfunction commonly follows open heart surgery. To evaluate the effects of positive end-expiratory pressure (PEEP) upon the course and severity of impaired oxygen transfer and roentgenographic evidence of atelectasis after coronary artery bypass grafting (CABG), we randomly assigned 44 patients to positive pressure ventilation and 0, 5, or 10 cm H2O PEEP. Study groups did not differ with respect to preoperative P(A-a)O2 or time on cardiopulmonary bypass. We observed a significant reduction of P(A-a)O2 during positive pressure ventilation with 10 cm H2O PEEP and FIO2 = 0.6 (182 +/- 6 vs 135 +/- 7 mm Hg, p less than .005). Following extubation, P(A-a)O2 measurements of the three groups did not differ when compared 24, 48, 72, 96, or 120 hours after surgery. Roentgenographic atelectasis scores did not differ on the fifth postoperative day. Five days after CABG, P(A-a)O2 exceeded preoperative P(A-a)O2 (29 +/- 1 vs 18 +/- 1 mm Hg, p less than .001), although the roentgenographic distances from hemidiaphragm to lung apex were unchanged (21.2 +/- 0.9 vs 22.0 +/- 0.9 cm). We conclude that routine PEEP improves pulmonary oxygen transfer but, once discontinued, PEEP offers no sustained beneficial effect upon impaired oxygen transfer or roentgenographic evidence of atelectasis following CABG.

We randomized patients with severe hypertension in the Medical Intensive Care Unit to a treatment regimen of oral nifedipine or intravenous nitroprusside. Patients treated with nifedipine achieved a sustained reduction in diastolic blood pressure to less than or equal to 120 mm Hg in an average of less than five hours. Patients treated with nitroprusside achieved a similar reduction in 14 hours (p less than 0.05). Treatment with nifedipine was less expensive and required less time in the ICU than treatment with nitroprusside and was accompanied by no associated increase in morbidity or mortality. Oral nifedipine can be used as an alternative to intravenous nitroprusside in severe uncomplicated hypertension.

The effects of five bronchodilator drugs and two methods of delivery (nebulizer vs metered-dose inhalers) on pulmonary function were studied in ten subjects with stable asthma. All subjects demonstrated statistically significant improvements (p less than 0.05) in pulmonary function relative to baseline and placebo effects after each medication, regardless of method of delivery; however, there was no statistically significant difference between the changes in pulmonary function caused by medication, method, or medication-method combination (p greater than 0.05). The choice of medication and device for delivery would appear to depend on the budget and time available in the laboratory.

Although the mechanisms of nocturnal asthma are still uncertain, increased vagal cholinergic tone may be contributory factor. To examine this hypothesis, we have studied the effect of an anticholinergic drug, oxitropium bromide, on the early morning fall in peak expiratory flow (PEF) in patients with nocturnal asthma. Eighteen patients (aged 18 to 76 years; seven men) with documented nocturnal asthma were studied in a double-blind randomized cross-over study in which they received either oxitropium bromide (200 micrograms or 400 micrograms) or placebo in a single dose at night for two-week periods. With placebo the mean (+/- SE) fall in PEF (expressed as percentage of evening PEF) was 17.3 +/- 2.0 percent, which was significantly reduced to 10.3 +/- 3.3 percent after oxitropium (400 micrograms) (p less than 0.05; ANOVA). Closer analysis revealed that nine of the 18 patients had responded in a dose-dependent manner, with the mean percentage decreases with placebo, 200 micrograms, and 400 micrograms of oxitropium being 19.1 +/- 3.2, 11.5 +/- 4.4, and 5.0 +/- 4.5 percent, respectively (p less than 0.01 between each treatment). The remaining patients were unaffected by therapy. There were no differences between "responders" and "non-responders" in terms of age, atopic status, duration of asthma, severity of asthma, or bronchodilator response to albuterol (salbutamol). There were no differences in nocturnal symptoms between periods of treatment, and no side effects were recorded. We conclude that anticholinergic drugs may protect against nocturnal asthma in some patients, indicating the involvement of vagal cholinergic mechanisms.

Nineteen outpatients with stable obstructive pulmonary disease (mean forced expiratory volume in one second [FEV1], 1.00 + 0.10 L) were evaluated for airway response to albuterol (salbutamol) administered by metered-dose inhaler and Bosch ultrasonic nebulizer (BUSN). Albuterol administered by metered-dose inhaler but not by nebulizer caused a significant increase in FEV1 and the mean forced expiratory flow over the middle half of the forced vital capacity (FEF25-75%) (p less than 0.02). Absolute increase from baseline of FEV1 and FEF25-75% was significantly greater for metered-dose inhaler (0.21 +/- 0.05 L; 0.32 +/- 0.13 L/sec) compared to ultrasonic nebulizer (0.07 +/- 0.03 L; 0.03 +/- 0.04 L/sec) (p less than 0.02). In 11 subjects (mean FEV1, 1.08 + 0.14 L), the placebo effect of inhalation of the diluent from the metered-dose inhaler (Freon) and the ultrasonic nebulizer (isotonic saline solution) was determined. Freon produced the mean increase of 1.5 percent, whereas the ultrasonic aerosol of isotonic saline solution resulted in a mean decrease of 8 percent in FEV1. Therefore, the inferior response to albuterol administered by ultrasonic nebulizer was at least in part due to the superimposed broncho-constriction occurring with ultrasonically administered saline solution. The metered-dose inhaler was more effective than the ultrasonic nebulizer for administration of albuterol in stable obstructive pulmonary disease, and the latter device is not recommended. A specific ultrasonic nebulizer should be prescribed only if its superiority to a metered-dose inhaler can be objectively documented.

The effect of acid application in the esophagus on pulmonary function was measured in three groups of patients in a double-blind investigation. Group 1 consisted of ten patients with esophagitis but without pulmonary disease, group 2 was 21 patients with bronchial asthma without esophagitis, and group 3 was eight patients with both esophagitis and bronchial asthma. Pulmonary function was assessed by total lung capacity (TLC), airway resistance (Raw), residual volume (RV), and peak expiratory flow (PEF). The four parameters were measured at the following five times during a single trial: before and after insertion of an esophageal catheter; after instillation of 50 ml of isotonic sodium chloride solution; after instillation of 50 ml of 0.1 N hydrochloric acid; and after intravenous injection of atropine (0.01 mg/kg of body weight). A significant decrease (the Wilcoxon test, p less than 0.02; and the Mann-Whitney test, p less than 0.002) in PEF and a significant increase (p less than 0.02 and p less than 0.002, respectively) in Raw after instillation of HCl were seen only in group 3. Changes in the other groups were small and without any regular pattern. Six of the patients in the third group accepted another trial after three days of pretreatment with atropine (0.01 mg/kg twice daily). Now instillation of acid did not produce any change in PEF or Raw (p less than 0.001). We conclude that a modest bronchoconstriction when acid is present in the esophagus is seen in patients with bronchial asthma and severe esophagitis. Atropine inhibits this bronchoconstriction, indicating vagal mediation.

The bronchoconstriction of asthma displays a circadian rhythm with exacerbations often occurring in the early morning hours. Gas exchange abnormalities during sleep in patients with severe asthma have been documented; however, the influence of sleep on gas exchange in the asthmatic with few or no daytime or nocturnal symptoms is poorly understood. To determine if abnormalities in oxygenation might occur during sleep, we studied 12 stable adult asthmatic patients with reversible airflow obstruction during sleep on three consecutive nights, with night 1 being for acclimatization. On test nights 2 and 3, the subjects received, in random double-blind fashion, either inhaled fenoterol or its placebo. Spirometry was performed before and after bronchodilator treatment and on the next morning. The mean FEV1 was 63 percent predicted before treatment. There was significant (p less than 0.05) improvement in FEV1 on fenoterol night after treatment which was also present the next morning. Mean prefenoterol FEV1 was 2.04 +/- .15 (SEM) and increased to 2.61 +/- .17 after the bronchodilator. The mean morning FEV1 was 2.27 +/- .20. Mean preplacebo FEV1 was 2.07 +/- .12 and did not change significantly with placebo bronchodilator. Sleep analysis demonstrated no significant differences in total sleep time or duration of oxyhemoglobin desaturation between nights. The incidence of sleep disordered breathing was very low (0.14 apneas/hour). The frequency of apneas and hypopneas did not change significantly with treatment. Two of the 12 subjects experienced an asthma attack on placebo night which did not recur following active bronchodilator administration. We conclude that stable asthmatic patients with few nocturnal complaints have a low frequency of disordered breathing and desaturation events during sleep.

While nasal mucosal stimulation in animals has been reported to produce central apneas and while nasal packing in humans is known to produce sleep-disordered breathing, it is controversial whether intranasal obstruction in humans produces predominantly central or obstructive apnea. To answer this question, we studied eight normal men by having them sleep in random order with their nose open or occluded with petrolatum gauze. Esophageal pressure was measured to detect respiratory effort, and standard techniques were used to monitor and score the stages of sleep. Intranasal occlusion increased both the number of apneas plus hypopneas per hour of sleep and the minutes of obstructive events per hour of sleep (p less than 0.05). The minutes of central events per hour of sleep also increased significantly but not to the degree that occurred with obstructive events. Nasal obstruction produced no immediate changes in pulmonary function. The subject with the highest resistance measured through the mouth with the pulse flow method had the most apneas following nasal occlusion. We conclude that intranasal obstruction produces predominantly obstructive apneas and hypopneas during sleep.

Eighteen COPD patients enrolled in a comprehensive, multidisciplinary pulmonary rehabilitation program were randomly assigned to perform either: 1) walking, or 2) ventilatory muscle exercise training (VMT) using a prototype, portable device for isocapnic hyperventilation training. Both groups performed exercise training at home. Twelve patients completed the study and follow-up evaluation (five VMT, seven walkers). Pulmonary function did not change in either group. For the VMT patients, there were modest increases in ventilatory muscle endurance and exercise performance. VO2max and VEmax increased significantly. For the walkers, only walking endurance time increased significantly. These results indicate that isocapnic hyperventilation exercise training can be performed successfully by COPD patients in an unsupervised home setting and can lead to improvement in both ventilatory muscle endurance and exercise performance. Walking exercise training did not improve ventilatory muscle endurance.

Pursed lips breathing (PLB) training is often used in the management of patients with chronic obstructive lung disease (COLD). Previous clinical studies have demonstrated that PLB improves arterial oxygen saturation (SaO2) and CO2 removal as well as relieving dyspnea. Twelve hypoxemic subjects with stable COLD were randomly assigned to either the pursed lips (P) or control group consisting of general relaxation (R). The SaO2 was monitored via ear oximetry, and respiratory rate and tidal volume were monitored using a strain gage transducer and the minute volume was calculated. The PLB was taught by an experienced instructor using the ear oximeter as a monitoring display with a goal toward increasing SaO2. The subject was taught general relaxation (Rlx) with the aid of pleasant music. We compared PLB and Rlx treatments using an A-B-A crossover study design. In both groups, PLB significantly improved SaO2 over baseline (p less than 0.001) whereas Rlx did not. We conclude that patients can learn to increase their SaO2 by PLB using ear oximetry adjunctively.

We assessed the effects of ingestion of a meal on cardiac performance in patients with chronic severe congestive heart failure. A group of 32 patients underwent right heart catheterization on the day prior to study. Patients then fasted overnight (12 hours). In the morning, baseline hemodynamic measurements were obtained on all patients; then 11 patients (group 1) consumed a liquid meal of 317 kcal, and 21 patients (group 2) received a placebo medication and continued fasting. Hemodynamic measurements were then obtained at intervals over two hours. Significant changes were seen in group 1 only. Cardiac index increased 22 percent, stroke work index increased 14 percent, pulmonary arterial wedge pressure decreased 20 percent, and systemic vascular resistance decreased 22 percent in group 1. This study demonstrates an important effect of ingestion of a meal on cardiac performance in patients with heart failure. To avoid overestimating the beneficial effects of therapy, eating must be carefully controlled when assessing the effects of various therapies in these patients.

Several calcium antagonists, each with significantly different chemical structures, have demonstrated variable attenuation of exercise-induced asthma. Quantitative comparisons have been hampered by differences in the intensity of challenge and the severity of the underlying disease between groups of patients. In 12 asthmatic adults with relatively severe exercise-induced asthma, we compared the effect of a new calcium antagonist, PY 108-068, in doses of 75 mg and 150 mg with nifedipine (30 mg) and placebo on resting flow rates and flow rates after exercise. Over a three-week period, each patient completed a four-day, randomized, double-blind Latin-square study. After receiving one of four oral drugs, spirometry was repeated every 30 minutes for two hours, followed by a six-minute treadmill exercise test breathing dry air. The exercise tests were well matched for work rate, ventilation, heart rate, and oxygen uptake. Spirometry was then repeated seven times over the next 30 minutes after exercise. Though both 150 mg of PY 108-068 and nifedipine were associated with mild bronchodilation before exercise, only the latter was significant (p less than 0.05). Exercise-induced asthma (expressed as maximal percent fall in the forced expiratory volume in one second from before baseline) was significantly attenuated only by 150 mg of PY 108-068 compared to placebo (24 +/- 13 vs 40 +/- 16; p less than 0.05). Headache, which occurred in six subjects after nifedipine, five after 150 mg of PY 108-068, one after 75 mg of PY 108-068, and none after placebo, was subjectively more severe after nifedipine. We conclude that in these patients, there was a tendency for mild bronchodilation before exercise with both 150 mg of PY 108-068 and nifedipine, but only the 150-mg dose provided significant protection against exercise-induced asthma two hours after the drug.

The efficacy and side effects of oral or inhaled terbutaline were examined in 13 mild-to-moderate asthmatic patients (ages 12 to 71 years) on maintenance theophylline (levels 10 to 25 micrograms/ml). In a crossover design, each patient received for two weeks oral terbutaline, 5 mg qid, inhaled terbutaline, 400 micrograms qid, or identical placebo tablets or metered-dose inhalers. Prior to each double-blind period, terbutaline was given for two weeks to ensure development of beta-adrenergic subsensitivity. Home-monitored peak flows and need for supplementary bronchodilators were significantly improved with both oral and inhaled terbutaline, but only the inhaled drug significantly decreased symptoms. Long-term terbutaline, either oral or inhaled, added to maintenance theophylline improved the patients' pulmonary function. The inhaled drug also improved the patients' clinical status as reflected by asthma symptom scores and need for extra bronchodilator. Combining terbutaline with theophylline did not produce evidence of cardiotoxicity.