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.

We have previously demonstrated a depression of airway, vascular, and cutaneous H2-histamine receptor function in sheep with experimental allergic asthma. In the present investigation, we wished to determine if there is a depression of gastric H2-receptor function in subjects with allergic bronchial asthma. In eight normal subjects and seven subjects with allergic bronchial asthma and bronchial reactivity to ragweed antigen, gastric H2-receptor function was assessed by measuring basal and maximal stimulated acid output following pretreatment with a placebo or the H2-antagonist, cimetidine. Maximal stimulated acid output was defined as the peak acid output (PAW mEq/hr) of hydrochloric acid following a subcutaneous injection of histalog (1.5 mg/kg), and selective H2-stimulation as delta PAO = PAOplacebo-PAOcimetidine. While basal acid output was not different between the two groups, mean (+/- SD) PAO was significantly lower in the asthmatic group (14.0 +/- 8.2 mEq/hr) than the normal group (27.9 +/- 9.4 mEq/hr) (p less than 0.01). Mean PAO expressed as percent of predicted maximum was 112 +/- 36 percent in the normal group and 61 +/- 34 percent in the asthmatic group (p less than 0.01). Mean delta PAO was significantly higher in the normal group (17.1 +/- 4.8 mEq/hr) than in the asthmatic group (7.0 +/- 5.3 mEq/hr) (p less than 0.005) indicating suppressed selective H2-receptor stimulation in the latter. We conclude that in subjects with bronchial asthma and marked bronchial hyperreactivity to ragweed antigen, there is a depression of gastric H2-histamine receptor function.

On the occasion of this Fourth World Conference on Lung Cancer, I am privileged to present the opening keynote address. This presentation has been sponsored by the Ontario Cancer Treatment and Research Foundation. In 1952, the Foundation established an annual lectureship in memory of one of their prominent physicians. Dr. Gordon Earle Richards was one of Canada's pioneer radiologists and radiotherapists who was appointed Director of the Institute of Radiotherapy at Toronto General Hospital at a time when radium and high-voltage x-rays were just coming into common use for the treatment of malignant disease. He established an international reputation for his contributions to clinical radiotherapy, and was subsequently appointed Professor of Radiology at the University of Toronto. He was Managing Director of the Ontario Cancer Treatment and Research Foundation between 1945 and 1949. I wish to thank the Foundation for the privilege of presenting the 33rd Gordon Richards Memorial Lecture.

A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects.

The role of surgical resection in the management of patients with small cell lung cancer remains to be defined. Some data suggest the potential benefit of resection in the few patients with very limited disease (peripheral T1N0 and T2N0 lesions), and there are chemotherapy regimens with 80-85% response rates in patients with more extensive but still localized disease. Interest has been reawakened in the role of adjuvant surgical resection in selected patients by 2 approaches: in patients with peripheral T1 or T2 lesions with negative mediastinal exploration, initial surgical resection followed by an adequate chemotherapeutic regimen and prophylactic cranial irradiation has resulted in an 80% disease-free survival at 30 months; initial chemotherapy in patients with only localized disease is followed by resection in the responders. Approximately 30% of the responders have undergone exploratory thoracotomy after completion of the chemotherapy. Local irradiation, as well as prophylactic cranial irradiation, generally has been used postoperatively. Early pilot studies suggest benefit of this approach in patients found to have T1-3 N0-1 disease but not in those with N2 disease. Prospective, randomized, clinical trials by the Lung Cancer Study Group in North America and its counterparts in Europe are now being carried out in hopes of supplying definitive data relative to this multi-modality therapy in small cell lung cancer. Unfortunately, no data are available to date.

Three parenteral routes of albuterol sulfate were compared with placebo in their effects on serum potassium and glucose levels, heart rate, and pulmonary function in adult asthmatic subjects. In addition, the metabolic effects of subcutaneous epinephrine were compared directly with subcutaneous albuterol. Intravenous (IV) albuterol (250 micrograms) caused similar decreases in serum potassium (mean 0.6 +/- 0.3 mEq/L) as 500 micrograms albuterol by intramuscular (IM) or subcutaneous routes. With the combined data from all three albuterol routes, glucose increases (mean 25 +/- 15 mg/dl) and heart rate increases (mean 11 +/- 6 beats/min) were clinically less important than potassium decreases. Subcutaneous epinephrine (0.3 ml, 1:1,000) gave changes in serum potassium, serum glucose, and heart rate statistically similar to those of subcutaneous albuterol (500 micrograms). Peak FEV1 improvement (mean 61 percent) was similar with IV albuterol (250 micrograms), IM albuterol (500 micrograms) or subcutaneous albuterol (500 micrograms). Although the efficacy of albuterol in the doses studied was similar, the decrement in serum K+ produced was also similar and comparable to that produced by a standard dose of epinephrine. The potassium decrease may have important clinical implications.

Supplemental oxygen therapy delivered at concentrations which increase PaO2 greater than 60 mm Hg often has minimal effects on either pulmonary hemodynamics or the oxygen tension of mixed venous blood (PvO2). Since mixed venous hypoxemia has been shown to contribute to pulmonary vasoconstriction in experimental conditions and is a determinant of survival in chronic obstructive pulmonary disease (COPD), we evaluated the hemodynamic effects of oxygen therapy titrated to raise PvO2 in 12 COPD patients who underwent right heart catheterization. After room air measurements of mean pulmonary artery pressure, cardia output, and pulmonary vascular resistance, they were randomized to either supplemental oxygen therapy given to raise PaO2 greater than or equal to 60 mm Hg (group 1, n = 6) or to raise PvO2 greater than or equal to 36 mm Hg (group 2, n = 6). An oxygen-conserving nasal cannula and oxygen concentrator were used. Baseline PaO2, PvO2, and hemodynamics were identical in each group and hemodynamics after four hours and 48 hours of continuous oxygen therapy were unchanged. Ten patients were catheterized after four months of continuous oxygen therapy (group 1, n = 4; group 2, n = 6). Although PvO2 in group 2 had been raised to normal levels (39.2 +/- 1.2 mm Hg), there was no significant improvement in pulmonary hemodynamics. Our preliminary study suggests that oxygen titrated to raise PvO2 to the normal range has no greater hemodynamic effect than oxygen therapy as it is currently prescribed.

Although caffeine is a universal drug and has multiple pharmacologic and physiologic actions in man, there are surprisingly few objective data about its effect on pulmonary function. We conducted a short-term, double-blind, randomized crossover study in nine asthmatic adults who ingested decaffeinated coffee containing varying amounts of added caffeine (mean of 0.2,2.5,5.6, and 7.2 mg/kg of body weight) on different days. The subjects also ingested decaffeinated coffee and aminophylline (200 mg) on a separate day of study. Baseline and post-drug determinations of serum levels of caffeine and theophylline, forced expired volume and flow, specific airway conductance (Gaw/VL), vital signs, and reported symptoms were obtained. Peak increases in serum caffeine concentrations (mean, 12.4 micrograms/ml +/- 1.5 micrograms/ml) occurred 45 minutes following the highest dose of caffeine (7.2 mg/kg), whereas the peak theophylline level (mean 3.8 micrograms/ml +/- 0.4 micrograms/ml) occurred 90 minutes following oral administration of aminophylline (mean theophylline, 2.6 mg/kg). Comparable peak increases in the forced expiratory volume in one second (FEV1), the forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%), and Gaw/VL occurred at 120 minutes following aminophylline and the highest dose of caffeine, indicating that caffeine is an effective bronchodilator but is only 40 percent as active as an equivalent molar dose of theophylline. Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values. These findings have diagnostic and therapeutic implications regarding the use of caffeine prior to tests of pulmonary function and as a dietary agent, alone or in combination with theophylline.