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.

We evaluated the efficacy of the esophageal airway (EA) by prospectively randomizing 175 prehospital cardiopulmonary arrest patients to receive either an esophageal gastric tube airway (EGTA) or an endotracheal tube (ET). If attempts with the initial airway failed, the alternate airway was attempted. The cost of training paramedics in EA use was considerably less than the ET ($80 vs $1,000). Survival to the emergency room, to hospitalization and to discharge in ET and EGTA groups were 64.4 percent, 25.6 percent, 11.1 percent, and 54.1 percent, 27.1 percent, 12.9 percent, respectively--differences not statistically significant. The incidence of neurologic residual (ET 50 percent, EGTA 36.4 percent) and congestive heart failure (ET 40 percent, EGTA 45.5 percent) in surviving ET and EGTA patients did not differ (NS). An additional 125 consecutive patients with only the opportunity to receive an EA were also evaluated and did not differ in mortality, neurologic residual, or congestive heart failure from ET patients. We conclude that the EA is a satisfactory alternative to the ET for short-term prehospital use in cardiopulmonary arrest patients.

Seventy-three patients who underwent thoracic surgery were randomly selected for intraoperative intercostal nerve block using phenol (32 block and 41 control subjects). The patients were divided into three groups: pneumonectomies, lobectomies and explorative thoracotomies and evaluated by pain level, respiratory function parameters (VT, IRV, ERV, VC) and blood-gas analysis, both six and 24 hrs after surgery. The patients who had intraoperative nerve block using phenol enjoyed a more comfortable postoperative period. In particular, respiratory parameters were statistically better.

Silver acetate chewing gum, a nonprescription medication, produces an unpleasant metallic taste in the mouth of individuals who consume tobacco products in conjunction with this smoking deterrent. Use of the product leads to self-induced aversive conditioning. In the present double-blind controlled study, subjects using silver acetate for three weeks of treatment had a smoking cessation rate of 15 out of 136 (11 percent, p = 0.02). Placebo subjects had a smoking cessation rate of 6 out of 146 (4 percent, p = .102). Without further treatment, the group using silver acetate demonstrated a 7 percent nonsmoking rate at four months compared with a 3 percent nonsmoking rate for the placebo group. Silver acetate demonstrated a modest benefit over placebo as a smoking deterrent in a minimal intervention and highly cost-effective treatment setting.

The ability of H2 receptor antagonists and continuous enteral alimentation to maintain high intragastric pH in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation was evaluated by continuously monitoring intragastric pH prior to and following sequential addition of ranitidine or continuous enteral alimentation (or both) to their therapeutic regimen. Prior to therapy, intragastric pH was less than 4.0 for 75 +/- 10 percent of the time, but never less than 1.0. Nevertheless, this moderate gastric acidity was associated with evidence of mucosal injury. Ranitidine failed to continuously maintain a high intragastric pH (pH less than 4.0 for 35 +/- 11 percent of the time; p greater than 0.2 compared to patients treated with placebo). Following administration of continuous enteral alimentation, intragastric pH fell, and ranitidine therapy only partially blocked this increase in gastric acidity induced by continuous enteral alimentation. We conclude that without treatment, patients with COPD who have acute respiratory failure may develop gastric mucosal injury despite the presence of only moderate intragastric acidity; however, ranitidine and continuous enteral alimentation are not effective in maintaining a high intragastric pH.

We studied 15 nonsmoking, clinically stable asthmatic subjects aged 27 to 39 years to evaluate the potential cardiotoxic effects of combined use of a beta-adrenergic agonist drug and theophylline in the treatment of asthma. Subjects underwent a one-week washout period followed by two one-week periods of study receiving either oral terbutaline or sustained-release theophylline during week 1 and both drugs during week 2. Thirty-six-hour Holter monitoring was performed at the end of each period of study. No significant increase in the total number of ventricular premature beats was noted, although the average heart rate increased significantly between each period of study. Although not statistically significant, the number of individuals with multiform or complete and repetitive ventricular premature beats increased from one at baseline to three during each period of study, including one subject with ventricular tachycardia on combined therapy. These data suggest that combined therapy with theophylline and a beta-adrenergic agonist in young, otherwise healthy asthmatic subjects does not lead to an increase in the total number of ectopic beats but may increase the degree of complexity of ventricular premature beats.

The effects of immunization with killed influenza virus vaccine were assessed by comparison with placebo in a double-blind study of 318 adult patients with chronic asthma. The patients were randomly allocated to active vaccine and placebo. No difference was observed in peak expiratory flow rate or in clinical symptoms of bronchial obstruction between the groups receiving active vaccine and placebo during the first week after immunization. The data were analyzed separately for age, sex, duration of the disease, hypersensitivity to aspirin (acetylsalicylic acid), atopic status, patients with a history of attacks of asthma induced by viral infections, patients with a diurnal variation of baseline peak expiratory flow of 20 percent or more, and patients receiving continuous oral steroid medication, but none of these factors seemed to predict any short-term adverse effects of vaccination. Follow-up for eight months after the vaccination revealed no differences in asthmatic symptoms between the patients treated with active vaccine and those receiving placebo. The antiviral antibody response to vaccination was normal. The possible protection provided by the vaccination against exacerbation of asthma induced by influenza could not be evaluated, since the influenza epidemic expected during the season failed to occur in Finland. It is concluded that immunization with killed influenza vaccine is safe and is not associated with any significant side effects in adult patients with chronic asthma.

Postoperative pulmonary complications, alveolar-arteriolar oxygen difference ([A-a]O2-diff), peak expiratory flow (PEF) and forced vital capacity (FVC) were compared in patients using continuous positive airway pressure (CPAP) and positive expiratory pressure (PEP) administered by face mask against those of a control group using a deep-breathing device (Triflo). Forty-three consecutive, randomized patients undergoing elective upper abdominal surgery were included. CPAP, PEP and Triflo were administered for 30 consecutive breaths in every waking hour for three days postoperatively. The (A-a)O2-difference increased equally and significantly in the three groups after surgery, reaching a maximum on the first postoperative day. After this day, however, (A-a)O2-diff decreased in the CPAP and PEP groups, being significantly lower in the PEP group compared to the control group, two days postoperatively (p less than 0.05) and significantly lower in both the PEP and CPAP groups three days postoperatively (p less than 0.001 and p less than 0.05, respectively.) PEF did not differ significantly between the groups before or after surgery, while FVC was significantly higher in the PEP and CPAP groups, compared to control, on the third postoperative day (p less than 0.05). Atelectatic consolidation was observed in six of 15 patients in the control group three days postoperatively, the incidence being significantly lower in both the PEP group (0 of 15, p less than 0.001) and the CPAP group (one of 13, p less than 0.05). We concluded that periodic face mask administration of CPAP and PEP are superior to deep breathing exercises with respect to gas exchange, preservation of lung volumes and development of atelectasis after upper abdominal surgery. We also conclude that the simple and commercially available PEP mask is as effective as the more complicated CPAP system.

To determine the potential benefit of incentive spirometry, which has been advocated to prevent pulmonary complications after upper-abdominal surgery, we compared a group of patients receiving incentive spirometry to another group receiving no specialized postoperative respiratory care. Forty patients in the American Society of Anesthesiologists' class 1 and 2 who were undergoing cholecystectomy (through right subcostal incision) were included in the study and were randomly allocated to one of the two groups. Patients receiving incentive spirometry were encouraged by a specialized respiratory physiotherapist to breathe deeply for five minutes hourly, 12 times daily, for three postoperative days. No statistically significant difference between the two groups was found in the radiologic evidence of postoperative pulmonary complications, arterial oxygen pressure, spirometric measurement, and clinical evaluation at the second or fourth postoperative day (or both). In particular, deterioration on the chest x-ray film at the fourth postoperative day was observed in eight of 20 patients in the group receiving incentive spirometry and in six of 20 in the control group. Our study confirms the postoperative deterioration of respiratory function after upper-abdominal surgery and demonstrates the lack of therapeutic values of incentive spirometry in these patients at low risk for pulmonary complications.

We investigated the effects of a single dose of nifedipine (10 mg orally) on exercise performance during progressive incremental cycle ergometry in nine sedentary normal subjects in a double-blind, placebo-controlled crossover study. Maximum work load after nifedipine (213 +/- 42 watts; mean +/- SD) was less than after placebo (222 +/- 41 watts; p less than 0.05). Maximum oxygen consumption was unchanged. In addition, the drug decreased lactate threshold from 19.7 +/- 4.9 ml O2/min/kg to 15.5 +/- 5.5 ml O2/min/kg (p less than 0.02); gas exchange anaerobic threshold was unaffected. There were higher plasma lactate concentrations at low and intermediate exercise intensities after nifedipine compared with placebo (p less than 0.05). Systolic blood pressure was lower at high work loads (p less than 0.05) and heart rate was higher at low work loads (p less than 0.05) after nifedipine. We conclude that the short-term administration of nifedipine limits peak performance and increases plasma concentration of lactic acid in normal subjects. One or more of the following mechanisms may account for these observations: nifedipine decreases blood flow to skeletal muscle by diverting blood to nonexercising tissues; nifedipine increases catecholamine levels, thereby augmenting lactic acid production; and nifedipine decreases skeletal muscular contractility by selectively impairing fatigue-resistant fibers.