Comparison of the respiratory responses to external resistive loading and bronchoconstriction.

The effects of resistive loads applied at the mouth were compared to the effects of bronchospasm on ventilation, respiratory muscle force (occlusion pressure), and respiratory sensations in 6 normal and 11 asthmatic subjects breathing 100% O2. External resistive loads ranging from 0.65 to 13.33 cm H2O/liter per s were applied during both inspiration and expiration. Bronchospasm was induced by inhalation of aerosolized methacholine. Bronchospasm increased ventilation, inspiratory airflow, respiratory rate, and lowered PACO2. External resistive loading, on the other hand, reduced respiratory rate and inspiratory flow, but left ventilation and PACO2 unaltered. FRC increased to a greater extent with bronchospasm than external flow resistive loads. With both bronchospasm and external loading, occlusion pressure increased in proportion to the rise in resistance to airflow. However, the change in occlusion pressure produced by a given change in resistance and the absolute level of occlusion pressure at comparable levels of airway resistance were greater during bronchospasm than during external loading. These differences in occlusion pressure responses to the two forms of obstruction were not explained by differences in chemical drive or respiratory muscle mechanical advantage. Although the subjects' perception of the effort involved in breathing was heightened during both forms of obstruction to airflow, at any given level of resistance the sense of effort was greater with bronchospasm than external loading. Inputs from mechanoreceptors in the lungs (e.g., irritant receptors) and/or greater stimulation of chest wall mechanoreceptors as a result of increases in lung elastance may explain the differing responses elicited by the two forms of resistive loading.

Bronchodilating effect of terbutaline aerosol.

We compared the efficacy of terbutaline with that of metaproterenol, isoproterenol, and placebo aerosols in 16 asthmatic patients. Terbutaline, metaproterenol, and isoproterenol produced equivalent improvements in flow rates. At 5 hr, the effect of terbutaline on tests of small airways, FEF25%--75%, and FEF50%, was greater (p less than 0.05) than that of metaproterenol and isoproterenol. Terbutaline produced no significant change of heart rate or blood pressure.

Dysfunction of small airways following pulmonary injury due to nitrogen dioxide.

Serial physiologic studies were performed to characterize both the immediate and delayed effects of a single occupational exposure to nitrogen dioxide in a nonsmoker. During the initial acute stage of pulmonary edema, the abnormal static pressure-volume curve and decreased static compliance corresponded to a reduction in pulmonary volume. During the delayed acute stage, elastic recoil and properties of resistance to flow were normal, but dynamic compliance was reduced and dependent on respiratory frequency, and oxygen transport was abnormal during exercise, which is consistent with dysfunction of the small airways.

Cardiac arrhythmias during routine tests of pulmonary function in patients with chronic obstruction of airways.

We studied the frequency of cardiac arrhythmias during routine tests of pulmonary function by using continuous electrocardiographic recording and a computerized method to quantitate arrhythmias. A total of 150 patients with chronic obstruction of airways were studied before, during, and after routine tests of pulmonary function performed before and after intermittent positive-pressure breathing (IPPB) with a bronchodilator aerosol. The only significant (P less than 0.01) change was an increased frequency of atrial premature beats during tests of pulmonary function. Spirometric studies, maximal voluntary ventilation, and IPPB with a bronchodilator aerosol were equally likely to induce atrial premature beats. Routine tests of pulmonary function represent an additional causal factor in producing arrhythmias in patients with obstruction of airways, although no clinical consequences were evident in the course of the study.

Pulmonary injury following exposure to chlorine gas. Possible beneficial effects of steroid treatment.

Two sisters were exposed to chlorine gas in toxic quantities in the same room of their home during an industrial accident. One was hospitalized and treated with corticosteroids and oxygen therapy, while the other received evaluation in the emergency room, and brief oxygen therapy and was released without corticosteroid therapy. Pulmonary physiologic studies have been performed on both patients at intervals following the exposure. The treated patient was stable, with normal results on studies of pulmonary function at the end of two years, while the sibling not treated with corticosteroids had demonstrable abnormalities of gas exchange which persisted during 55 months of observation. This "natural experiment" gives evidence of prolonged detrimental effects of sublethal exposure to chlorine gas on human pulmonary function in some patients. The effect of the differences in treatment between the two siblings cannot be definitely assessed in this single situation.

Adverse effect of propranolol on airway function in nonasthmatic chronic obstructive lung disease.

Bronchomotor tone is, in part, under beta-adrenergic control, and beta-adrenergic agonists are commonly used in the therapy for chronic obstructive pulmonary disease (COPD). Beta-adrenergic blockade with propranolol is contraindicated in asthmatic patients, yet little is known of its effect in patients with COPD. We studied 13 patients with COPD in a random-entry, double-blind crossover comparison of oral propranolol, 40 mg, and oral placebo on separate day. Pulmonary function worsened after administration of propranolol. Significant differences were present between the drugs' effect on heart rate, airway resistance, specific resistance, and flow rates at one hour, and persisting through four hours (p less than 0.01). Propranolol may have a deleterious effect on pulmonary function in nonasthmatic COPD. We conclude that when propranolol is to be used in patients with COPD, the short- and long-term effects on airway should be measured sequentially.

Beta-adrenergic blockade of the lung. Dose-dependent cardioselectivity of tolamolol in asthma.

Beta-adrenergic blocking agents are widely used to treat disorders of cardiac rhythm and rate, angina, and hypertension. Propranolol is the most widely used beta-adrenergic blocking agent in this country. Because of its nonselective beta-adrenergic blocking effect, propranolol may be associated with significant bronchoconstriction in asthmatic subjects and in some patients with chronic obstructive pulmonary disease. Since tolamolol, a new beta-adrenergic blocking agent, has cardioselectivity in animals, we studied asthmatic subjects for six hours on three separate days in a double-blind crossover comparison of oral therapy with 40 mg of propranolol, its beta-adrenergic blocking equivalent dose of tolamolol (50 mg), and a high dose of tolamolol (100 mg). All three dosages had equipotent effects on heart rate and systolic pressure. The 50-mg dose of tolamolol had no effect on pulmonary function over six hours; however, both propranolol (40 mg) and the 100-mg dose of tolamolol had equivalent deleterious effects on airway resistance and on rates of expiratory flow. We conclude that the cardioselectivity of tolamolol is dose-limited but is present at the dosage of 50 mg, which is equivalent to the usual antiarrhythmic beta-adrenergic blocking dose of propranolol (40 mg).

Multidisciplinary treatment of chronic pulmonary insufficiency. 3. The effect of physical training on cardiopulmonary performance in patients with chronic obstructive pulmonary disease.

We examined the effect of physical training on cardiopulmonary function in 21 patients with chronic obstructive pulmonary disease and compared the results with similar observations in eight untrained patients. The training consisted of daily walking on a treadmill at increasing speeds and grades and other graded physical exercises. Evaluation of pulmonary function, including spirometric studies, lung volumes, and arterial blood gas levels, showed no significant change after training. Hemodynamic functions, including heart rate, cardiac index, stroke index, pulmonary vascular resistance, and arteriovenous oxygen content difference, were similarly unchanged at comparable submaximal loads. Pulmonary arterial wedge pressure increased after training in the treated group at rest and during exercise, but this may be related to changes in respiratory mechanics. Consumption of oxygen and minute ventilation decreased in the treated group during treadmill exercise, suggesting improved neuromuscular coordination and efficiency of walking on the treadmill. Total work performed on the treadmill increased significantly in the trained group. This increase was unexplained by physiologic observations but was thought to be due in part to increased efficiency of walking and increased motivation. We conclude that improvement in the capacity for exercise following physical training for four weeks is not associated with improvement in cardiopulmonary function at submaximal exercise.

Multidisciplinary treatment of chronic pulmonary insufficiency. 4. The influence of intrathoracic pressure variations on increases in pulmonary vascular pressure during exercise in patients with chronic obstructive pulmonary disease.

In the present era of direct monitoring of pressure in patients with chronic obstructive pulmonary disease (COPD), an appreciation of all factors that may influence the observed pulmonary vascular pressures is essential. Our study examines the impact of respiratory variations in intrathoracic pressure on the recorded pulmonary vascular pressures in 28 patients with COPD. Althouth pulmonary hypertension was present in only nine subjects at rest, all had an abnormal increase in the mean pulmonary arterial pressure during supine exercise. In 15 subjects, this abnormal response was, in part, related to an increase in pulmonary arterial wedge pressure to 15 mm Hg or more. The increase in pulmonary arterial wedge pressure was directly related to the amplitude of the peak-to-peak respiratory variation of such wedge pressure. This variation correlated with the specific airway resistance but was not related to the arterial oxygen pressure or pulmonary vascular resistance. These findings indicate the important influence of exaggerated respiratory effort on the measurement of pulmonary arterial wedge pressure and mean pulmonary arterial pressure in patients with chronic obstructive pulmonary disease.

Vectorcardiographic detection of early hemodynamic abnormalities in chronic obstructive pulmonary disease.

The ability of the vectorcardiogram to detect mild circulatory abnormalities in patients with chronic obstructive pulmonary disease (COPD) is unclear. Therefore, vectorcardiographic changes were correlated with hemodynamic measurements made at rest and during supine exercise in 32 patients with COPD and no clinical or electrocardiographic evidence of right ventricular hypertrophy. Twelve patients had normal hemodynamic data (group 1), nine had abnormal hemodynamic data only during exercise (group 2), and 11 had abnormal hemodynamic data at rest and during exercise (group 3). The extent of rightward terminal QRS forces noted on the vectorcardiogram was significantly less in group 1 (5.5 +/- 8.7 percent) than in either group 2 (19.0 +/- 10.7 percent) or group 3 (17.8 +/- 14.8 percent). Sixty-five percent (13) of the 20 patients with hemodynamic abnormalities had rightward terminal QRS forces of 15 percent or more, whereas only 8 percent (one) of the 12 patients with normal hemodynamic data had such forces of 15 percent or more. The mean of the rightward terminal QRS forces in 27 age-matched normal subjects was 5.0 +/- 5.4 percent, and only one subject had forces of 15 percent or more. We conclude that hemodynamic abnormalities are frequent in patients with COPD and no clinical evidence of right ventricular hypertrophy and that the vectorcardiogram provides an indirect method of detecting these abnormalities.

Pi-Z phenotypes in a pulmonary clinic. Their prevalence and physiologic state.

A series of 1,458 consecutive patients referred to the Cleveland Veterans Administration Pulmonary Clinic for pulmonary function studies was evaluated for alpha 1-antitrypsin deficiency by determination of serum trypsin inhibitory capacity (STIC). Protease inhibitor (Pi) phenotyping was performed on all sera with STIC values less than 1.6 mg/ml. The following non-MM phenotypes were found: 1FZ, 32MZ, 2ZZ, 3SZ, 5SS, 33MS, 21M. The prevalence of Pi Z heterozygosity is 2.74%. This figure is not significantly greater than that observed in a healthy population. A group ( n = 12) with heterozygous Z phenotype (MZ + SZ) was compared with a control (MM) group (n = 13) matched for age, race and smoking history from this same population. Our findings indicate similar deviations from predicted normal values in both control (MM) and Z-heterozygotic groups for physiologic tests of airway resistance, lung volumes, diffusing capacity, and static and dynamic compliance. There was no significant difference between MM controls and MZ heterozygotes in the physiologic variables measured.

Ventilation inhomogeneity: alveolar mechanics and gas distribution.

The effects of regional lung differences in alveolar mechanics on the transpulmonary pressure-volume (Ptp-V) relationship and the single-breath washout (SBW) of nitrogen were investigated by mathematical modeling and postmorten human lung experiments. Regional nonuniformity in alveolar collapse and re-opening were associated with differences in gravitational stress or elasticity. Model simulations predict that neither type of regional nonuniformity qualitatively affects the shape of the Ptp-V curve, but does affect the terminal (or small-volume) portion of the SBW. Comparisons of characteristics of the Ptp-V and SBW curves indicate that regional nonuniformity in alveolar collapse is an important mechanism associated with ventilation inhomogeneity.