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Biomedical subjects

E R McFadden

Publications and source records attributed to E R McFadden.

At least 37 records · Page 2Linked to original sources
PubMed1977

Relative contributions of hypocarbia and hyperpnea as mechanisms in postexercise asthma.

The purpose of this investigation was to assess the relative contributions of hyperpnea and hypocapnia in the induction of postexercise asthma. To achieve these ends, eight young asthmatics were exercised on a treadmill while minute ventilations (VE) and end-tidal CO2 (PET CO2) tensions were continuously recorded. The subjects were then restudied using a partial rebreathing technique that allowed separation of minute and alveolar ventilations so that independent evaluations could be made of the relative effects of bulk airflow on pulmonary mechanics as well as a systematic study of hypocapnia in a dose-response fashion. Sustained hyperpnea with VEidentical to those recorded during exercise was totally without effect when the mean PET CO2 was isocapnic or lowered to approximately 30 Torr. Reduction in PETCO2 to 21.3 +/-0.9 Torr brought about significant changes in mechanics, but in every variable measured, exercise produced the greatest alterations and did so at PETCO2 values that had no effect when studied in a controlled fashion. Consequently, neither high VE per se, nor hypocapnia can be considered as the mechanisms underlying exercise induced asthma.

Adult↗
PubMed1977

Effects of intravenous histamine on pulmonary mechanics in nonasthmatic and asthmatic subjects.

Histamine is thought to be one of the primary mediators of the airways response in allergic asthma. We have studied in detail in nonasthmatic and asthmatic volunteers the effects of its intravenous infusion on pulmonary mechanics. The doses used were similar in both groups and limited by vascular rather than pulmonary effects. Measurements were made of lung resistance, the subdivisions of lung volume, maximal flow, density dependence, lung elastic recoil and dynamic compliance. The only mean group changes were a decrease in dynamic compliance and increase in frequency dependence of compliance in the nonasthmatics. Although in nonasthmatic individuals, statistically significant changes occasionally occurred in some parameters, the response was variable on repeated studies and sufficiently small to be of questionable physiological significance. Some of the asthmatics developed larger changes, but these only occurred in those individuals whose preinfusion pulmonary function was abnormal. Our results suggest the possibility that altered prechallenge pulmonary function rather than an unusual sensitivity to histamine may determine the greater responses observed in asthmatics.

Adult↗
PubMed1977

Airway responses to inhaled histamine in asymptomatic smokers and nonsmokers.

Bronchia reactivity to inhaled histamine was assessed in asymptomatic cigarette smokers and in nonsmoking atopic and nonatopic subjects. The only prechallenge between-group difference was the ratio of maximal flow on 80% helium-20% oxygen (Vmax HeO2) to maximal flow on air (Vmax air) from partial expiratory flow volume curves at 25% vital capacity (25% VC PEFV): Mean +/- SEM for smokers 1.18 /+- 0.06, atopics 1.45 +/- 0.08, nonatopics 1.51 +/- 0.03. This suggests that prior to inhalation to total lung capacity, the predominant site of resistance at flow limitation was in smaller airways of the smokers and in larger airways of both groups of nonsmokers. Following inhalation of histamine, smokers and nonatopics had similar changes in lung volumes and Vmax air which were less than in atopics. The Vmax HeO2/Vmax air ratios at 25% VC PEFV increased in smokers and decreased in nonsmokers: smokers 1.48 +/- 0.08, atopics 1.22 +/- 0.10, nontopics 1.16 +/- 0.06. This suggests a predominant large airway response in smokers and a prominent small airway response in nonsmokers. These responses may reflect differences in the predominant site of aerosol deposition rather than in airway reactivity.

Adult↗
PubMed1977

Comparison of arm versus leg work in induction of acute episodes of asthma.

The severity of exercise-induced asthma varies with the type of exercise performed. To determine whether such variation could be attributed to the use of different muscle groups, we exercised arms separately from legs using a bicycle ergometer. First, arms were exercised to exhaustion, then legs were exercised at the same load for the same duration. Arm work resulted in greater ventilation, heart rate, hydrogen ion concentration, and airway obstruction than did leg work. Later, legs were exercised to exhaustion using a load more than twice that of the arm work. Both the exhausting leg work and exhausting arm work resulted in significant bronchospasm and acidosis, whereas the nonexhausting leg work did not. These data suggest that, in arm and/or leg exercise, the relationship of work load to muscle mass is a determinant of airway obstruction.

Adult↗
PubMed1977

Predominant site of flow limitation and mechanisms of postexertional asthma.

To determine if a relationship existed between the site of airway obstruction and the mechanisms of exercise-induced asthma, we studied the predominant site of flow limitation, as determined by the mid-vital capacity ratios of maximal expiratory flow with air (Vmax air) and 80% helium-20% oxygen (Vmax He-O2), before and after physical exertion in 12 asthmatics. These observations were then related to the effects seen after vagal blockade and inhibition of mediator release. Five subjects increased Vmax He-O2/Vmax air ratios suggesting that the predominant site of flow limitation was in large airways. This group had their postexercise bronchospasm abolished by pretreatment with an anticholinergic agent. Seven subjects decreased their flow ratios indicating predominant small airway obstruction. Anticholinergic agents, although producing bronchodilation, did not alter their bronchospastic response to exercise. However, pretreatment with disodium cromoglycate did significantly diminish the response of this group. Thus the airway response to exercise in asthmatics is heterogeneous in terms of predominant site of flow limitation and this factor appears to relate to mechanisms.

Adult↗
PubMed1977

On line determination of lung volumes by plethysmography and digital computer.

This report describes a method of obtaining lung volumes on line with a minicomputer and whole body plethysmograph. The results of this approach were compared with standard methodology for a wide range of values and found to be in good agreement. This system can be readily implemented using standard hardware and laboratory techniques. Its advantages are its accuracy ,rapidity of data analysis, and retrieval; through the latter it allows for an assessment of such factors as variability of subject performance.

Computers↗
PubMed1977

Relative contributions of large and small airways to flow limitation in normal subjects before and after atropine and isoproterenol.

Bronchodilatation was produced in normal subjects by the inhalation of atropine, a parasympatholytic agent, and isoproterenol, a beta adrenergic stimulator. Density dependence of maximal expiratory flow (Vmax), expressed as a ratio of Vmax with an 80% helium-20% oxygen gas mixture to Vmax with air at isolung volumes, indicated that the predominant flow regimes across upstream airways changed differently after each agent was given separately. After atropine Vmax increased, elastic recoil pressure did not change, and density dependence decreased. Utilizing the equal pressure points analysis which defines upstream and downstream segments of the intrathoracic airways at flow limitation, these results suggest a greater relative dilatation of the larger upstream airways such that more of the driving pressure is dissipated across the smaller airways in which flow is less dependent upon gas density. After isoproterenol Vmax increased, elastic recoil pressure did not change, and density dependence increased. This suggests a preferential dilatation of the smaller and more peripheral airways with less density-dependent flow regimes such that more of the driving pressure would be dissipated in the larger airways in which flow is more dependent upon gas density. Systematic decreases after isoproterenol lead independently to the same conclusion. After both agents together, Vmax increased and density dependence and critical alveolar pressures did not change from control, suggesting a relatively uniform dilatation of all the airways comprising the upstream segment.

Adult↗
PubMed1977

A critical assessment of the roles of circulating hydrogen ion and lactate in the production of exercise-induced asthma.

To evaluate the roles of circulating hydrogen ion and lactate in the production of exercise-induced asthma, two experiments were performed. In the first, we exercised six asthmatic subjects to exhaustion on a bicycle ergometer while recording arterial pH at periodic intervals. Multiple aspects of pulmonary mechanics were measured before and after the work load. After recovery, the identical procedures were repeated, but sufficient quantities of sodium bicarbonate were infused to keep the pH at the pre-exercise level. In both experiments, statistically identical attacks of asthma were induced. To study the effect of lactate, five subjects were exercised on several occasions in order to determine the lowest level of work, and hence arterial lactate, that was reproducibly associated with an acute asthma attack. When this was known, sufficient quantities of sodium lactate were infused into the resting subjects so as to equal or exceed the amount produced with exercise. Pulmonary mechanics were not altered with this intervention. These findings demonstrate that lactic acidemia is not the cause of exercise-induced asthma.

Acidosis↗
PubMed1976

A controlled study of the effects of single doses of hydrocortisone on the resolution of acute attacks of asthma.

To evaluate the effects of corticosteroids on the resolution of acute attacks of asthma, 38 young, acutely ill, asthmatic subjects were given a single intravenous injection of either 0.25, 0.50 or 1.0 g of hydrocortisone hemisuccinate or a placebo (sterile saline solution) in a random, double blind manner. Each was then treated with isoproterenol, at hourly intervals, for a minimum of six hours, and the serial changes in plethysmography, spirometry, lung volumes, subjective complaints and physical findings that occurred as the patients improved were observed. No statistical differences were found in any of the physiologic or clinical variables between those patients given any dose of steroids and their matched controls. From this it has been concluded that hydrocortisone, in the doses and route of administration employed, does not produce any immediate benefits in the treatment of acute asthma.

Acute Disease↗
PubMed1976

Density-dependence of maximal expiratory flow rates before and after bronchodilators in patients with obstructive airways disease.

1.Gas-density-dependence of maximal expiratory flow rats (V max), defined as the ratio of V max. while breathing helium/oxygen (80:20) to V max. while breathing air at the same lung volume, was examined in relation to other measurements of airways obstruction in patients with obstructive airways disease before and after administration of bronchodilators. 2. Seventeen patients showed a 45% or greater increase in specific conductance (sG aw) after bronchodilator therapy (group A) and thirteen patients demonstrated a lesser response (group B). 3. Before the administration of bronchodilators, the degree of obstruction in two groups was not different as measured by lung volumes, sG aw, forced expiratory volume in 1 s, and flow rates high in the vital capacity; yet the maximal mid-expiratory flow rate and the degree of density-dependence were significantly lower in group B. 4. After bronchodilators, both groups of patients showed significant improvements in sG aw, flow rates and lung volumes. However, group A patients showed a signifcant increase in density-dependence whereas group B patients did not. 5. Increased density-dependence after bronchodilators in the group A patients was associated with an increase in the computed resistance of the upstream segment with air and a decrease in resistance with helium/oxygen. These changes could be explained by a more mouthward of equal pressure points, and therefore a further increase in the relative contribution of the larger density-dependent airways to limitation of flow. 6. The fact that density-dependence was not altered after bronchodilators in the group B patients suggests that the site of limitation of flow did not change appreciably. The shift in the pressure-flow curve for the upstream airways was such that the computed resistance of these airways fell. Thus it appears that the airways comprising the upstream segment were dilated.

Airway Obstruction↗
PubMed1976

Effect of volume history on successive partial expiratory flow-volume maneuvers.

In normal subjects, the second of two successive partial expiratory flow-volume (PEFV 2) curves often had higher isovolume maximal expiratory flow rates (Vmax) than the first (PEFV 1) (mean increase 30.2 +/- 13%). The higher Vmax on PEFV 2 was present only when there was a greater lung elastic recoil pressure (Pst(L)). In eight subjects the Pst(L) derived from sequential partial quasi-static pressure-volume curves, from interruption of the flow-volume maneuvers and at the start of the PEFV curves showed that isovolume upstream resistance increased although Vmax also increased after going to residual volume (RV). In four subjects the RV volume history did not change the pressure flow relationship across the upstream airways. If airways dimensions were the sole determinant of Vmax, then Vmax on PEFV 2 would be the same or smaller than on PEFV 1. That the opposite was observed in our study indicates that the increase in Pst(L), which results from parenchymal hysteresis, offsets any dimensional decrease in upstream airways due to airways hysteresis.

Adult↗
PubMed1976

An assessment of the pulmonary response to exercise in asthma and an analysis of the factors influencing it.

The purposes of this study were to determine (1) whether an exercise stimulus could be repeatedly applied to a group of asthmatics and normal control subjects with reproducible metabolic and ventilatory consequences; (2) the effect of this stimulus on multiple aspects of pulmonary mechanics in both groups; (3) the degree of within- and between-day variation in response and the factors influencing it; and (4) the effects of pretreatment with disodium cromoglycate. Airway resistance, specific conductance, total lung capacity and its subdivisions, and forced expiratory volumes and flow rates were measured in 21 asthmatics and 8 normal control subjects before and after treadmill exercise. Minutes ventilation, tidal volume, repiratory frequency, oxygen consumption, carbon dioxide production, heart rate, and end-tidal carbon dioxide tensions were measured during exercise and recovery. The asthmatics were studied twice datly on 2 separate days. Disodium cromoglycate was administered to the asthmatics before the fourth trial. The control subjects were studied twice on the same day without any interventions. There was no difference between exercise trials as measured by any of the gas exchange variables and there were no within-day differences in baseline pulmonary mechanics in either group. In contrast to the control group, all of the asthmatics had increasing airway obstruction after the exercise challenge. There were no between -day differences in the baseline data or response to exercise in the asthmatics except that the mechanical response was less after disodium cromoglycate, which suggests that mediator release played a part. Although as a group the stimulus and response were reproducible, when data of each trial were related to the type and degree of baseline dysfunction there was a direct relationship between pre-existing obstruction and magnitude of response. This suggests that exercise-induced asthma is not an all-or-none event, but rather a continuum of responses profoundly influenced by the pre-challenge state of the airways.

Adolescent↗
PubMed1975

Exertional dyspnea and cough as preludes to acute attacks of bronchial asthma.

Although wheezing is believed to be a cardinal manifestation of asthma, some patients with this disorder may not present with wheezing, but rather with either exertional dyspnea or cough. In 14 such patients with dyspnea, there was peripheral airway dysfunction with markedly elevated residual volumes, frequency dependence of dynamic compliance and depressed flow rates in the middle-vital-capacity range, whereas specific conductance and one-second forced expiratory volumes were normal. Circumstantial evidence suggests that mucosal edema or mucous secretions may have been responsible. In seven patients with cough, studies revealed a more severe obstructive pattern that appeared to be the result of increased large-airway resistance, and the patients' response to isoproterenol indicated that contraction of bronchial smooth muscle may have been principally responsible. Thus, intermittent episodes of cough or breathlessness may represent variant aspects of asthmatic attacks.

Acute Disease↗
PubMed1975

The chronicity of acute attacks of asthma--mechanical and therapeutic implications.

Defects in ventilatory function can persist for considerable periods of time following the amelicoration of the signs and symptoms of acute episodes of asthma. Serial spirographic and lung volume determinations in such patients demonstrate that the pattern of resolution of these abnormalities is such that their subtlest manifestations are depressed flow rates in the mid vital capacity range and/or elevations in residual volumes. These changes are believed to represent the effects of residual obstruction that is located in the airways in the periphery of the lung. Recent studies suggest that this residua is capable of influencing the lung's response to asthmogenic stimulis, and imply that it may be beneficial to place asthmatics on continuous therapy for as long as they have alterations in lung function.

Adult↗
PubMed1975

Variability of closing volume measurements in normal man.

Single breath oxygen measurements of closing volumes were performed in triplicate in 15 healthy nonsmoking young adults 3 times per day for 5 consecutive days. The purpose of the investigation was to determine the degree of variability in this test of lung function and, if possible, to specify its cause. The results demonstrated that sizable differences in the absolute volume for closing volume and for closing volume as a percentage of vital capacity can be present from trial to trial in any given person even though the technical aspects of the procedure are seemingly highly standardized. The reasons for this were found to be a combination of (1) the inherent variation in the expired volume that marked the onset of airway closure, (2) reader difficulties in detecting the onset of phase IV, and (3) variations in the expired vital capacity due to incomplete filling and/or emptying of the subject's lungs. The differences were not due to daily or diurnal rhythms or to a training effect.

Adult↗