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Biomedical subjects

R R Rosenthal

Publications and source records attributed to R R Rosenthal.

At least 19 recordsLinked to original sources

Analysis of refractory period after exercise and eucapnic voluntary hyperventilation challenge.

We compared specific airway conductance (SGaw) and the FEV1 after repetitive exercise or repetitive eucapnic voluntary hyperventilation (EVH) challenges. Replicate challenges were matched in terms of inspired air conditions and minute ventilations (VE) in order to determine the degree of refractoriness after each type of challenge in patients with exercise-induced asthma. Ten patients exercised or hyperventilated dry, room temperature air at matched VE on two study days. When the patients FEV1 had returned to 90% of baseline or better, or at 3.75 h if FEV, had not returned to 90% of baseline, patients repeated the identical exercise or the EVH challenge. Minimum FEV1 values expressed as a percent of predicted FEV1 after the first and second exercise challenges were 52 +/- 16 and 58 +/- 17, respectively, which were statistically different (p less than 0.001; paired t test). Minimum FEV1 values after the first and second EVH challenges were 52 +/- 13 and 59 +/- 9% of predicted, respectively, which were also statistically different (p less than 0.01; paired t test). Seven of 10 subjects demonstrated higher SGaw values after the second exercise challenge compared with the first challenge, whereas eight of 10 subjects showed higher SGaw values after the second EVH challenge compared with the first challenge. Paired t test analysis indicated that percent protection, measured by FEV1, was similar after either type of challenge. We conclude that replicate exercise or EVH challenges with similarly matched inspired air conditions and VE induce similar degrees of refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Comparison of safety and efficacy of inhaled pirbuterol with metaproterenol.

This multicenter study was performed to compare the safety and efficacy of a new beta-2 selective beta agonist, pirbuterol, with metaproterenol. The study followed a double-blind parallel design evaluating 133 asthmatic patients for 12 weeks. There were essentially no clinical differences between groups and no differences in onset of action, peak effect, side effects, or development of tolerance between these two agents. Our conclusion is that pirbuterol is at least as effective and safe under conditions of chronic administration to asthmatics as metaproterenol and therefore can be considered a suitable alternative for therapy.

Administration, Inhalation

Celiprolol, atenolol and propranolol: a comparison of pulmonary effects in asthmatic patients.

Celiprolol, a new beta-adrenoceptor antagonist, blocks serotonin- and methacholine-mediated bronchoconstriction in animals, even in the presence of propranolol. In two, randomized, placebo-controlled, 5-way crossover trials, the pulmonary effects of celiprolol 200 and 400 mg, propranolol 40 mg and atenolol 100 mg were compared in 34 asthmatic patients. Pulmonary function was measured after single doses of each agent, and again following subsequent, graded doses of albuterol or isoproterenol aerosol. Changes in one-second forced expiratory volume (FEV1) and maximal midexpiratory flow rate (FEF25-75) prior to albuterol or isoproterenol were positive after placebo and both doses of celiprolol. Propranolol, and to a lesser extent, atenolol, caused significant reductions in both measures of pulmonary function. Overall changes in FEV1 following each drug plus isoproterenol or albuterol were positive, in the rank order, celiprolol approximately placebo greater than atenolol greater than propranolol. Propranolol pretreatment caused a significant reduction in the effect of bronchodilator. Unlike atenolol and propranolol, celiprolol was highly bronchosparing and did not antagonize sympathomimetic bronchodilators.

Adrenergic beta-Antagonists

The effect of vitamin C on antigen-induced bronchospasm.

The effect of vitamin C pretreatment in preventing ragweed-induced bronchospasm was evaluated in 6 ragweed-sensitive asthmatics studied in a double-blind randomized fashion. The patients received either lactose capsules or 500 mg of ascorbic acid and were studied out of season. Antigen dose-response curves were determined prior to the administration of lactose or ascorbic acid in each individual subject and subsequently after administration of ascorbic acid or lactose. Bothe PD20FEV1 (provocation dose necessary for a 20% reduction in forced expiratory volume in 1 second) and PD35SGaw (provocation dose necessary for a 35% reduction in specific airways conductance) were determined. In none of the six patients was there a change in baseline FEV 1 (p greater than 0.70) nor the overall average baseline specific airways conductance (rho greater than 0.90). Additionally, no statistically significant difference (p greater than 0.60) was noted between log PD35SGaw vitamin C day and lactose day. Likewise, no statistically significant difference (p greater than 0.60) was evident when comparing log PD20FEV1 lactose and ascorbic acid days. Vitamin C (500 MG) HAS NO PROTECTIVE EFFECT AGAINST RAGWEED ANTIGEN-INDUCED BRONCHOSPASM.

Adult

Asthma improved by nonsteroidal anti-inflammatory drugs.

A patient who claimed benefit from aspirin for her reversible bronchospasm was challenged orally in a placebo-controlled study with aspirin and other aspirin-like drugs. Specific airways conductance and spirometry were monitored for up to 150 minutes after oral challenge. Aspirin, mefenamic acid, and ibuprofen administration resulted in marked (45% to 80%) improvement in forced expiratory volume in 1 second (FEV1) compared to lactose placebo. Indomethacin, sodium salicylate, and tartrazine resulted in modest (15% to 25%) FEV1 improvement, while phenylbutazone produced a 25% decrease. These results are discussed here in terms of the ability of these drugs to inhibit the prostaglandin synthetase enzyme system. This case suggests that aspirin and other nonsteroidal anti-inflammatory drugs may be beneficial rather than harmful in some asthmatic patients.

Airway Resistance

The role of ragweed pollen in autumnal asthma.

Thirty-nine ragweed-allergic seasonal asthmatics were studied from 1972 to 1974. After quantitative skin tests, antigen E-induced leukocyte histamine release, quantitative inhalation bronchial challenge with ragweed extract to determine PD35 (provocation dose of allergen causing 35% decrease in specific airways conductance), and radioallergosorbent test (RAST) determinations were done, patients were paired based on PD35 values and randomly assigned to treatment or placebo groups, receiving either aqueous ragweed extract or placebo prior to the 1973 ragweed season. Treated patients received a mean cumulative dose of extract equivalent to 11.7 microng antigen E (4,180 protein nitrogen units [PNU]). Twenty-nine patients were followed through the ragweed season with daily symptom diaries and biweekly physician examinations. Severity of disease was not predictable by PD35 data, skin tests, leukocyte histamine release, or radioallergosorbent test (RAST) values. Although all patients were ragweed-allergic by objective tests, only 13/29 had asthma symptoms correlating with ragweed counts. Mold spore counts were related significantly to symptoms in some patients. Asthma and hay fever symptoms correlated significantly in 24/29 patients. This dose of immunotherapy caused no significant difference to be found in asthma or hay fever symptoms in treated versus placebo patients for the 1973 reporting period as determined by physician evaluations or daily symptom diaries. No patients showed significant improvement in PD35 values after treatment in 1973. Similar findings were obtained for a smaller group of patients followed through the 1974 ragweed season who received a mean dose of 31.2 microng antigen E (11,140 PNU). The failure of these patients to show a response to immunotherapy could be due to a combination of the relatively low dose of ragweed extract and their sensitivity to other allergens.

Airway Resistance

Role of the parasympathetic system in antigen-induced bronchospasm.

Human subjects, sensitive to ragweed, inhaled aerosols of increasing concentrations of ragweed pollen extract in the presence and absence of pretreatment with inhaled atropine. The cumulative dose of antigen required for a 35% decrease in airways conductance was termed PD35. Atropine, 1.2 or 5 mg, increased airways conductance before antigenic challenge but did not alter signigicantly the PD35 for ragweed extract, although these doses of atropine inhibited airways responses to inhaled methacholine chloride and citric acid. We conclude that the cholinergic nervous system plays a modulating role in bronchomotor tone and responses to irritants, but that parasympathetic reflexes are not invariably a major component of human bronchial responses to inhaled allergen.

Airway Resistance

The effect of atropine on acute antigen-mediated airway constriction in subjects with allergic asthma.

Exposure to antigen by inhalation challenge may produce airway constriction in patients with allergic asthma. To examine the role of reflex bronchoconstriction mediated by the vagus nerve in the antigen-induced airway response, we compared the responses of 6 asthmatic volunteers to inhaled ragweed antigen alone and to antigen given after pretreatment with atropine sulfate, a parasympathetic blocking agent. We found significant increases in airway resistance, limitation of parasympathetic blocking agent. We found significant increases in airway resistance, limitation of forced expiratory flow, increases in lung volumes, and alterations in the distribution of inspired gas after antigen was given. When subjects were pretreated with atropine, we found a mean increase in the 1-sec forced expired volume of 0.380 liter (P less than 0.025) and a mean increase in specific airway conductance of 0.067 sec-1-cm H2O-1 (P less than 0.005). Atropine pretreatment did not prevent the responses to antigen in our subjects. After atropine pretreatment subjects began the antigen challenge with better pulmonary function and at a given antigen dose maintained a better level of function compared to when antigen was given alone. Differences in the absolute level of pulmonary function between the two challenges became smaller with the administration of larger antigen doses. We conclude that reflex bronchospasm involving postganglionic efferent parasympathetic nerve pathways is not a major component of the response to inhaled antigen in human allergic asthma.

Adult