In asthmatics, exercise (E1) is known to induce bronchoconstriction; a second period of exercise (E2) within 30 to 90 min induces a lesser degree of bronchoconstriction. The reason for the “refractory” bronchoconstrictor response to E2 is unclear. We studied 6 normal subjects (Group 1) and 12 stable asthmatics to examine the possible relationship between the refractory period and sympathoadrenal function. The asthmatics were further divided into 2 groups, based on the absence (Group 2, n =5) or presence (Group 3) of an exercise-induced bronchoconstrictor response. In each subject/patient, after control measurements of spirometry and venous blood sampling, a standard level of treadmill exercise was performed, and blood and spirometry were obtained at 1, 5, 15, and 25 min after the end of exercise. A second period of treadmill exercise, of the same level and duration, was then performed, and blood sampling and spirometry were repeated at the same time intervals after the end of exercise. There was no significant (p < 0.1) difference in baseline plasma epinephrine (Ep), or norepinephrine (Np) levels; however, plasma dopamine (Op) levels were significantly (p < 0.05) higher in Group 3. In Groups 1 and 2, FEV1 did not change significantly after the first (E1) or second (E2) exercise periods, but there were significant (p < 0.01) changes in Group 3 (maximal percent changes in FEV1, ΔFEV1%, E1 = -14.4%, E2 = -8.8%), and the ΔFEV1% after E2 was significantly (p < 0.01) less that after E1. There were significant increases in Ep, Np, and Dp after exercise; however, there were no significant between-group differences in Ep, Np, or Dp, in post-E1 or post-E2 values, nor were there any significant wlthin-group differences in catecholamine values between E1 and E2. We conclude that there is no significant association between circulating catecholamines and the refractory period after exercise in asthma.
BackgroundHypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2R) techniques have not been systematically evaluated in these patients.MethodsThis is a pilot study of a novel ECCO2R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean.ResultsThe device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; PaCO2 decreased significantly (P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization.ConclusionsThis single-catheter, low-flow ECCO2R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure.Trial registryClinicalTrials.gov; No.: NCT00987740 and 01021605; URL: www.clinicaltrials.gov Hypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2R) techniques have not been systematically evaluated in these patients. This is a pilot study of a novel ECCO2R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean. The device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; PaCO2 decreased significantly (P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization. This single-catheter, low-flow ECCO2R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure.
β2-adrenergic receptor ( β AR) density on peripheral blood lymphocytes has been used as an index to reflect the β AR state of the body. Lymphocytes β ARs are unequally distributed among lymphocyte subpopulations, with the highest density on CD8 + cells and the lowest on CD4 + cells. Thus, the measurement of peripheral blood lymphocyte β AR density could vary with changes in CD4 + and CD8 + cell concentrations. We examined the individual and intersubject variance of β AR density and lymphocyte subpopulations over time in 10 normal subjects, studied on 3 to 5 different d always at approximately 9:00 a.m. over a 4 - to 12-wk period. Peripheral blood lymphocytes were isolated and β2-adrenergic receptor density was determined by specific binding of [I25I] - (-) iodopindolol, and lymphocyte subpopulations were measured by flow cytometry. Average receptors per lymphocyte were 776 ± 183. Whereas the absolute values of CD4 + % and CD8 + % cell concentrations varied little in individual subjects (coefficient of variation 9.5% and 11.1%, respectively), the individual β AR variance was greater (coefficient of variation 22.4%). However there was a significant correlation between β AR and CD4 + % and CD8 + % cell concentration (correlation coefficients: − 0.58, p < 0.001; + 0.51, p < 0.001, respectively). This information is relevant to interpretations of changes in peripheral β AR in humans.
The direct effects of hypoxia on exercise-induced breathlessness are unclear. Increased breathlessness on exercise is known to occur at high altitude, but it is not known whether this is related to the hypoxia per se, or to other ventilatory parameters. To examine the role of high-altitude hypoxia in exercise-induced breathlessness, studies were performed in 10 healthy, normal subjects at sea level and after acute exposure to an altitude of 4450 ;m. Although the perception of hand weights did not alter between sea level and high altitude, the intensity of exercise-induced breathlessness increased significantly at high altitude. This was associated with a higher minute ventilation and respiratory frequency for any given exercise level, whereas tidal volume was not significantly altered from sea level values. The increased intensity of breathlessness with exercise did not change significantly over the 5 days at high altitude. These results suggest that the increased intensity of exercise-induced breathlessness at high altitude is not related to peripheral mechanisms or the pattern of ventilation, or to the level of hypoxia per se, but to the level of reflexly increased ventilation.
The direct effects of hypoxia on exercise-induced breathlessness are unclear. Increased breathlessness on exercise is known to occur at high altitude, but it is not known whether this is related to the hypoxia per se, or to other ventilatory parameters. To examine the role of high-altitude hypoxia in exercise-induced breathlessness, studies were performed in 10 healthy, normal subjects at sea level and after acute exposure to an altitude of 4450 m. Although the perception of hand weights did not alter between sea level and high altitude, the intensity of exercise-induced breathlessness increased significantly at high altitude. This was associated with a higher minute ventilation and respiratory frequency for any given exercise level, whereas tidal volume was not significantly altered from sea level values. The increased intensity of breathlessness with exercise did not change significantly over the 5 days at high altitude. These results suggest that the increased intensity of exercise-induced breathlessness at high altitude is not related to peripheral mechanisms or the pattern of ventilation, or to the level of hypoxia per se, but to the level of reflexly increased ventilation.
