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PubMed1989

Effect of breathing pattern during inhalation challenge on the shape and position of the dose-response curve.

To examine the effect of breathing pattern on the dose-response curve, 4 mild asthmatic and 9 normal subjects inhaled increasing concentrations of methacholine (0.03-256 mg/ml) using a quiet tidal breathing pattern or tidal breathing with a forced expiratory phase. The provocative concentration of methacholine causing a 20% decrease in the forced expired volume in 1 s (PC20FEV1) or a 200% increase in pulmonary resistance (PC 200RL) was determined. In addition, the maximal change in FEV1 and RL and the slopes of the dose-response curves were measured. The forced expiratory pattern caused an increase in the central/peripheral deposition ratio of a [99m]technetium-labeled aerosol (n = 3). There were no differences in mean tidal volume, minute ventilation, inspiratory flow rates, or baseline FEV1 or RL between the quiet breathing or forced expiration studies, although mean expiratory flows were increased in the latter (p less than 0.001). PC20FEV1 and PC200 RL decreased (p less than 0.001) but the maximal change in FEV1 and RL was unchanged in the forced expiration studies. Forced expiration during inhalation challenge did not alter the slope of FEV1 or RL dose-response curves. These results suggest that the sensitivity (PC20, PC200) and maximal response of in vivo dose-response curves may be affected independently by factors such as aerosol deposition.

Adult↗
PubMed1988

A computer-based method for on-line acquisition and analysis of bronchial challenge test.

We developed a computer program for the optimization and management of data collection in order to compute the change of forced expiratory volume in the first second (delta FEV1), provocative doses and to plot the dose-response curve for bronchial challenge test. Doses of methacholine are entered via the keyboard and forced vital capacity (FVC) with the highest FEV1 value obtained in each step is selected. When the imposed threshold of response has been reached, doses of administered methacholine and corresponding spirometric parameters are displayed and printed. Dose-response relationships are analysed: the increase of delta FEV1 for each unit of metacholine is computed in the interval between the two doses where delta FEV1 reached one of the imposed values (i.e. 15% or 20% or 30%). Finally spirometric values, dose-response curve and provocative doses are shown in a print-out. Computer values of provocative doses are higher than those obtained manually. This difference may be ascribed to the incorrect manual linear extrapolation. In conclusion the computer program is able to reduce consistently the time spent to analyze data from bronchial challenge test and allows a more precise determination of provocative doses by avoiding also inter-intra individual errors.

Asthma↗
PubMed1985

Comparison of metaproterenol, isoetharine and salbutamol in the relief of methacholine-induced bronchospasm in dogs.

We evaluated cardiovascular effects and effectiveness of isoetharine, metaproterenol and salbutamol, when administered intratracheally to relieve methacholine-induced bronchospasm in dogs anaesthetized with 50 per cent nitrous oxide, oxygen, halothane and mechanically ventilated. Methacholine 2 micrograms X kg-1 X hour-1 was administrated first followed by halothane (1 MAC) for 30 minutes (control), then metaproterenol, isoetharine or salbutamol. Metaproterenol (15 mg) significantly decreased transpulmonary pressure to 20.1 +/- 0.5 (SE) from 22.5 +/- 1.15 cmH2O (p less than 0.025) after three min and to 15 +/- 0.5 cmH2O (p less than 0.005) after 90 min. Isoetharine (2.5 mg) decreased transpulmonary pressure after five min to 22.1 +/- 1 from 24.5 +/- 1.5 cmH2O (p less than 0.05), and to 21.75 +/- 0.55 mmH2O after 90 min. Salbutamol 25 micrograms X kg-1 decreased transpulmonary pressure to 20.7 +/- 0.75 from 24.25 +/- 1.28 after three min and to 16 +/- .5 after 90 min. The peak effects on airway pressure occurred at 15 min for metaproterenol, 25 min for salbutamol and 20 min for isoetharine. Pulmonary vascular resistance was not significantly changed during halothane anaesthesia alone but decreased significantly after metaproterenol and isoetharine infusion. Heart rate increased ten per cent after metaproterenol, three per cent after isoetharine, and five per cent after salbutamol. No arrhythmias occurred in any group. Cardiac output increased significantly to 3.25 +/- 0.2 from 1.5 +/- 0.17 L X min-1 (p less than 0.025) after metaproterenol to 3.2 +/- .025 from 1.45 +/- .009 after salbutamol and was unchanged after isoetharine. Metaproterenol and salbutamol in the presence of 1 MAC halothane anaesthesia relieved methacholine-induced bronchospasm more rapidly than did isoetharine. The onset of effect was 3 +/- 0.05 min for metaproterenol and salbutamol and 5 +/- 0.01 min for isoetharine. The effect lasted 210 +/- 10.5 min for metaproterenol, 170 +/- 12.5 min for salbutamol and 90 +/- 4.75 min for isoetharine.

Airway Resistance↗
PubMedDate not supplied

Effects of thyroid function on submaxillary gland sensitivity to autonomic nervous drugs.

The effect of changes in thyroid function on the action of autonomic drugs upon the secretion of saliva by the submaxillary glands was studied in male Wistar rats. Hyperthyroidism was induced by the sc administration every 12 h of 10 micrograms/100 g bw of L-triiodothyronine; hypothyroidism was induced by surgical thyroidectomy 2 weeks before the experiments. The dose-response curves to increasing doses of isoprenaline, norepinephrine or methacholine showed in hyperthyroid animals increased salivary secretion, while in hypothyroid animals the dose-response to the drug was reduced. The threshold dose for isoprenaline was reduced in hyperthyroid animals and increased in hypothyroid ones. The threshold dose for norepinephrine did not change in hyperthyroid or hypothyroid animals while that for metacholine was decreased in hyperthyroid ones. When norepinephrine was given to alpha-blocked animals (with phentolamine) the difference in the dose-response curves between hyperthyroid and control animals was increased. But when norepinephrine was given to beta-blocked animals (with propranolol) the difference between the dose-response curves of hyperthyroid and control animals disappeared. The results above presented show that the sensitivity of the submaxillary salivary glands of rats to some adrenergic and cholinergic drugs was altered by the thyroid hormone. The effect was greater in the responses mediated by beta receptors. The structural changes in these glands may have some role in these effects.

Animals↗
PubMed1987

Role of calcium in endothelium-dependent relaxation of arterial smooth muscle.

Endothelium-dependent relaxation was studied in rings of rabbit thoracic aorta. Relaxation responses were induced with methacholine, the calcium ionophore A23187 and maitotoxin before and after removal of Ca++ from the external medium; in the presence of calcium-channel entry blockers (verapamil and nifedipine); or with trifluoperazine. Deletion of Ca++ greatly impaired responses to all 3 agonists while trifluoperazine only blocked cholinergic-induced relaxation. The calcium-channel blockers had effects that were concentration- and time-dependent, but their action included blockade of A23187. Cytosolic-free Ca++ concentrations were measured in cultured endothelial cells after incubation of the cells with 10 microM Fura-2/AM or 50 microM Quin 2/AM. Bradykinin (1 X 10(-10) to 1 X 10(-7) M) and melittin (0.5 to 5 micrograms/ml) caused dose-dependent increases in intracellular Ca++ with maximal responses at 3 X 10(-8) M and 3 micrograms/ml, respectively. Both agents were able to induce an increase in cytosolic-free Ca++ in the presence of EGTA (1.5 X 10(-3) M) or verapamil (1 X 10(-5) M). The plateau phase of the Ca++ transient appeared to be modified slightly by verapamil, while the peak responses and plateau were attenuated by '0' Ca++/EGTA. To assess a function of the endothelium, production of endothelium-derived relaxing factor (EDRF) was studied in cells grown on microcarrier beads superfused in a column, and the column effluent was bioassayed on aortic rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Clinical features and natural history of occupational asthma due to western red cedar (Thuja plicata).

After an average follow-up interval of three and a half years (range one to nine years), 125 patients with occupational asthma due to red cedar exposure were re-examined. Fifty patients remained in the same job. All of them continued to have asthmatic attacks requiring regular medication for relief of symptoms. They had worse lung function and ther bronchial reactivity to methacholine increased. Seventy-five patients left the industry; half of them became asymptomatic, whereas the remaining half continued to have recurrent attacks of asthma. Several factors were of prognostic significance. Those with a shorter duration of exposure as well as a shorter duration of symptoms prior to diagnosis and removal from exposure showed improvement. Those who remained symptomatic tended to be older; they had longer duration of exposure and a longer duration of symptoms prior to diagnosis. They tended to have more abnormal results of lung function studied and more marked bronchial hyper-reactivity to methacholine at the time of diagnosis. They also tended to have dual asthmatic reaction rather than late asthmatic reaction to inhalation challenge with red cedar extract. Smoking, race and degree of peripheral blood eosinophilia did not play a role in determining the outcome. Since none of these patients had symptomatic asthma before employment and since they reacted to inhalation challenge of red cedar, it could be assumed that persistent asthma in those who failed to recover is the result of their previous occupational exposure. Early diagnosis and removal from exposure were found to be associated with recovery.

Adult↗
PubMed1986

Hyperventilation syndrome and asthma.

Hyperventilation syndrome is a common and often disabling condition. Traditional treatment consists of reassurance and anxiolytic drugs. Hyperventilation is known to precipitate an asthmatic reaction. A retrospective review of patients with hyperventilation syndrome was performed to ascertain the frequency of asthma as well as the response to bronchodilator medication. Forty-seven patients were seen. Thirty-eight were tested, and asthma was proved in 36. Two additional patients had positive clinical responses with bronchodilators. Thus, asthma was identified in 38 of 47 consecutive patients seen for hyperventilation syndrome (80 percent), and asthma was proved in 36 of 38 of patients tested (95 percent). Hyperventilation syndrome was eliminated in 29 of 35 patients (90 percent) treated with a combination of explanation and bronchodilator treatment.

Adult↗
PubMed1987

Comparison of pseudoachalasia and achalasia.

Malignancies involving the gastric cardia or distal esophagus can result in a clinical syndrome termed pseudoachalasisa that mimics idiopathic achalasia. If not promptly recognized, pseudoachalasia can result in inappropriate pneumatic dilatation of the lower esophageal sphincter segment and delay appropriate treatment of the underlying malignancy. During the past 14 years, six patients with pseudoachalasia and 161 patients with primary idiopathic achalasia were encountered. Pseudoachalasia occurred mainly in the elderly and represented about 9 percent of these patients over 60 years of age with suspected achalasia. Five of the six pseudoachalasia cases were secondary to adenocarcinoma that originated in the gastric fundus, and one was caused by a squamous cell carcinoma of the distal esophagus. Conventional esophageal manometry did not discriminate achalasia from pseudoachalasia. On the other hand, esophagogastroscopy with biopsy resulted in a diagnosis of pseudoachalasia in five of these cases and in 24 of 32 cases reported previously. Ominous endoscopic findings are mucosal ulceration or nodularity, reduced compliance of the esophagogastric junction, or an inability to pass the endoscope into the stomach. Radiographic evaluation, particularly in conjunction with amyl nitrite inhalation, was also useful in discriminating pseudoachalasia from primary achalasia. It is concluded that pseudoachalasia generally mimics idiopathic achalasia imperfectly and can usually be diagnosed prior to surgery by fastidious endoscopic and radiographic examination.

Adult↗