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Biomedical subjects

R C Boucher

Publications and source records attributed to R C Boucher.

7 recordsLinked to original sources
PubMed1979

The pathophysiology of asthma.

Because postmortem studies of humans provide little information on the initial pathophysiologic events in asthma, animal models have been developed. Recently the Ascaris-allergic rhesus monkey has provided an opportunity to examine the onset of pathophysiologic changes following challenge and to correlate them with airway structure. These studies have suggested that the initial interaction between antigen and mast cells may occur in the bronchial lumen or in the epithelium superficial to the tight junctions, where a small but significant percentage of airway mast cells exist. It also appears that this initial antigen-antibody interaction results in the release of mediators that both stimulate the rapidly adapting stretch receptors in the mucosa and alter the mucosal barrier so that proteins of large molecular weight can penetrate. The fact that antigen challenge results in hyperresponsiveness to a subsequent dose of inhaled histamine and increased systemic absorption of histamine suggests that the airway hyperresponsiveness could be related to increased penetration of histamine into the bronchial wall. These observations suggest that the initial event in an acute asthmatic attack is the release of mediators from superficial mast cells, and that this amplifies the allergic response by altering the mucosal permeability so that more antigen reaches the submucosal mast cells. This altered permeability may also help explain the hyperreactivity of the airways to nonspecific airway stimulants in persons with asthma.

Airway Resistance↗
PubMed1979

Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys.

In four Ascaris-sensitive rhesus monkeys, we measured the fractional absorption of 3H-histamine (3HH) and airway response, as pulmonary resistance (R1), to standard histamine aerosols containing tracer amounts of 3HH for control runs (Run 1) and runs after Ascaris antigen challenge (Run 2). The mean rate of accumulation of radioactivity in the plasma volume as a function of delivered dose during histamine exposure (2 min) was fivefold greater for Run 2 (0.047% delivered dose/min) as compared with Run 1 (0.009% delivered dose/min). Whereas histamine inhalation led to insignificant (less than 25%) increases in R1 over control in Run 1. R1 increased by 247% over control after histamine inhalation in Run 2. Thus, both airway hyperpermeability and hyperreactivity to inhaled histamine were observed following specific antigen challenge in this animal model. These data are consistent with the hypothesis that airway mucosal hyperpermeability induced by an allergic reaction is one of the factors contributing to airway hyperreactivity by increasing flows of inhaled bronchoactive agents to effector sites in the airway wall.

Airway Resistance↗
PubMed1979

Pulmonary effects of acute and chronic antigen exposure of immunized guinea pigs.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall were measured in guinea pigs immunized to ovalbumin before and after acute (group 1) and chronic (group 2) antigen exposure. The histopathology produced in chronically exposed animals was also assessed. Animals were anesthetized with pentobarbital sodium and studied in a pressure-sensitive body plethysmograph, using a fluid-filled esophageal catheter to measure transpulmonary pressure (PL). Functional residual capacity (FRC) was determined by the Boyle's law technique; total lung capacity (TLC) was defined as the lung volume at a PL of 30 cmH20, and residual volume (RV) was defined as the lung volume at a transrespiratory pressure of -50 cmH2O. Acute antigen challenge of group 1 animals resulted in a decrease in TLC (22%), and increases in FRC (20%) and RV (110%), suggesting combined bronchoconstriction and alveolar duct constriction. Chronic antigen exposure of group 2 animals resulted in minimal changes in subdivisions of lung volume and PV curves, and produced a histological lesion resembling allergic alveolitis rather than asthma.

Aerosols↗
PubMed1979

Bronchial mucosal permeability.

The tracheobronchial epithelium has well-developed tight junctions which on a morphologic basis should be markedly resistant to penetration by protein molecules. Despite this, antigen inhalation in monkeys allergic to Ascaris suum results in the rapid onset of pulmonary physiologic changes. Recent studies in man and animals have shown that a substantial number of mast cells exist in the bronchial lumen and epithelium. We suggest that antigen-antibody interaction initially occurs on these superficial mast cells leading to mediator release and the stimulation of airway irritant receptors. Antigen challenge also results in increased epithelial permeability to protein in the Ascaris-allergic monkey, and from studies on guinea pigs we suggest that this is due to alterations in the tight junctions. Antigen challenge in the monkey also produces increased permeability to labeled histamine and hyperresponsiveness to low concentrations of histamine. We suggest that the apparent airway hyperreactivity to inhaled histamine seen after inhalation of ozone, and NO2, or after upper respiratory infections could be due to damage to epithelial tight junctions. The resultant increase in mucosal permeability would result in an increased amount of histamine reaching airway smooth muscle for a given inhaled concentration.

Airway Resistance↗
PubMed1978

Effect of histamine and methacholine on guinea pig tracheal permeability to HRP.

The effects of histamine, methacholine, and ether on the permeability of the respiratory mucosa to macromolecules were investigated employing a radioimmunoassay and histochemical techniques to monitor movement of horseradish peroxidase (HRP) from airway lumen to blood. We found that 0.08% of the dose of HRP instilled into guinea pig tracheas was present in the blood volume at 10 min, and plasma HRP levels increased at a rate of 0.0036% instilled dose/min thereafter. After inhalation challenge, significant increases in plasma rates of accumulation of HRP were recorded for the histamine, methacholine, and ether groups, whereas no change in rate was noted for the control (Tyrode's) group. Electron micrographs of tracheal sections showed HRP penetration into the intercellular spaces of the epithelium after histamine, methacoline, or ether exposure but no penetration in the Tyrode's group. We conclude that, like ether, histamine and methacholine increase tracheobronchial permeability and this effect is most likely mediated by a functional change in the epithelial tight junction.

Aerosols↗
PubMed1977

Airway mucosal permeability in the Ascaris suum-sensitive rhesus monkey.

The permeability of the airways to technetium 99m-labeled albumin was measured in Ascaris suum-sensitive rhesus monkeys. All 8 animals were skin-sensitive to Ascaris suum (AA) antigen, 4 being respiratory responders (R) and 4 nonresponders (NR) to aerosolized antigen. In the absence of antigen challenge there were no differences in the accumulation in the blood of radioactive material from the tracheobranchial tree between the R and NR animals. After a five-minute challenge with aerosolized AA, there was a threefold increase in the rate of accumulation of radioactive material in the blood over control for the R group with no effect noted in the NR group. Gel filtration data indicated that the radioactivity in the blood most likely represented low molecular weight albumin fragments, resulting from spontaneous degradation of Tc-albumin, that crossed the mucosa and partially bound to circulating albumin. It is concluded that hyperpermeability of the airway mucosa probably is not a factor that contributes to the selective responsiveness of the R group to aerosolized antigen, and that airway permeability is increased consequent to the allergic reaction mediating acute bronchoconstriction.

Aerosols↗