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Biomedical subjects

P A Frith

Publications and source records attributed to P A Frith.

45 records · Page 3Linked to original sources

Effects of oxatomide compared with chlorpheniramine in allergic rhinoconjunctivitis.

Oxatomide is an H1 receptor antagonist, which also inhibits antigen-induced mediator release from sensitized mast cells and basophils. The effects of ingested oxatomide (30 mg/capsule) were compared with those of chlorpheniramine (5 mg/capsule) in a double-blind non-crossover study in two groups of twenty-five subjects with ragweed pollen-induced hay fever during the pollen season. Oxatomide or chlorpheniramine was started when symptoms became troublesome and was used in a dose of two to four capsules daily according to severity. Other medications were added, in a standardized way, if hay fever symptoms were not controlled by the test capsules. Forty-one subjects completed the study; nineteen received oxatomide and twenty-two chlorpheniramine. Mean symptom scores, number of test capsules and number of doses of additional medication were not significantly different between the two groups. Drowsiness was reported by subjects in both groups but was worse in the chlorpheniramine group (P less than 0.05). We conclude that, in the studied doses, oxatomide is as effective for the treatment of allergic rhinoconjunctivitis as chlorpheniramine and produces less drowsiness.

Adolescent↗

Inhibition of allergen-induced asthma by three forms of sodium cromoglycate.

The effect of three forms of sodium cromoglycate (SCG), 20 mg, on allergen-induced early asthmatic responses was examined in ten stable asthmatics. Dose response allergen inhalation tests were performed on five occasions at intervals of from 1 to 2 weeks to determine the provocation concentration producing a 20% reduction (PC20 allergen) in FEV1. Placebo was given before the first and the last tests to determine the reproducibility of responses to allergen over the study period; reduced responsiveness was observed in eight of the ten subjects. Major changes in levels of specific serum antibodies of the IgE and IgG classes did not serve to explain the changes in bronchial responses although there was a trend which suggested IgG-related desensitization. The observed changes in bronchial responses and antibody levels illustrate the requirement for tests of reproducibility of responses by the use of placebo controls at the beginning and end of a series of allergen inhalation challenges. SCG as (i) a micronized powder with lactose, (ii) micropellets without lactose, or (iii) an aerosol, were inhaled double-blind, in random order, 5 min before the additional three allergen inhalation tests. PC20 allergen was reduced following SCG in seven subjects; the differences were statistically significant for the group. There was no observed difference in efficacy between the different forms of SCG. In this study, the efficacy of SCG could not be related to age, atopic status, the initial level of allergen-specific IgE antibody, baseline FEV1, level of bronchial responsiveness to inhaled histamine or an effect of SCG on responsiveness to histamine.

Adolescent↗

Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma.

We have prospectively examined in 51 patients the relationship between the level of airway responsiveness to histamine and methacholine and the minimum medications required to control asthma. First we determined the least medication that was required to control symptoms so that they did not disturb sleep, were not present on waking, and did not require use of inhaled salbutamol (200 microgram) more than four times daily. When baseline FEV1 was greater than 70% of predicted and when there had been no respiratory infection or allergen exposure for six weeks, histamine and methacholine inhalation tests were carried out on separate days to determine the provocation concentration causing a fall in FEV1 of 20% (PC20). There was a close correlation between the PC20 to the two agents. The patients were grouped into 1, those who required no medication; 2, those who required salbutamol (200 microgram) occasionally but not daily; 3, those who required daily salbutamol; and 4, those who required additional beclomethasone dipropionate. The mean PC20 was highest in group 1 and lowest in group 4; there was a significant difference between each group. The results indicate that airway responsiveness to vasoactive amines is either an important determinant of the severity of asthma and the medication requirements or a consequence of the severity of asthma. They raise the possibility that measurement of responsiveness may be useful in some patients with established asthma to substantiate or question medication needs.

Adolescent↗

Standardization of inhalation provocation tests: two techniques of aerosol generation and inhalation compared.

Comparison of methods of aerosol generation and inhalation is required to improve standardization of inhalation provocation tests. We compared two widely used methods in 10 asthmatics, by measuring the dose and distribution of radiolabeled aerosol deposited in the throat and lung, and the provocation concentration of inhaled histamine required to reduce the FEV1 by 20% (PC20). In one method, aerosol was generated by a DeVilbiss 646 nebulizer attached to a dosimeter, and was inhaled by 5 inspiratory capacity breaths. The measurements with each method were repeated once to determine the reproducibility of results. Both methods deposited the same dose in the lung, but the distribution of the dose was different; the dosimeter method deposited more aerosol in the throat and central airways. The PC20 obtained with each method was the same. The reproducibility of all measurements in the same subject was similar. The lung dose deposited by each method in different subjects varied to the same degree. The results indicated that the bronchial response to inhaled histamine can be measured as reliably using a nebulizer and tidal breathing as by a more complex dose-metering device. They also suggested that, when the methods are regulated as described, the PC20 will have the same clinical significance.

Adolescent↗

Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation.

In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more "cardioselective" than the others.

Adolescent↗

Bronchial responsiveness to inhaled histamine and exercise.

Bronchial responsiveness to inhaled histamine and exercise was measured in 19 asthmatics. Histamine aerosol was inhaled to determine the provocative concentration producing a 20% fall in forced expired volume in one second (FEV1) (PC20). Exercise was performed on a treadmill and a cycle ergometer; following each procedure the percent fall in the FEV1 (delta FEV1) and the exercise lability (percent rise in FEV1 plus percent fall in FEV1) were calculated. Delta FEV1 and exercise lability after both forms of exercise were similar. PC20 correlated with delta FEV1 and exercise lability in both forms of exercise; however, the correlation with exercise lability was better. PC20 was more sensitive in demonstrating bronchial hyperresponsiveness. The close correlation between the level of bronchial responsiveness to histamine and exercise supports the view that release of endogenous chemical mediators is an important determinant of exercise-induced asthma. The treadmill exercise and cycle ergometry protocols were equally effective in producing exercise-induced asthma.

Administration, Intranasal↗

Reproducibility and comparison of responses to inhaled histamine and methacholine.

The efficiency of a standardised inhalation test procedure was studied by examining the reproducibility of responses to histamine and methacholine. In addition, the responses to the two agents were compared. Each set of duplicate tests was carried out on a separate day within one week, and all factors known or presumed to influence responses were carefully controlled. The results were expressed as the provocative concentration of the agent causing a 20% fall in forced expired volume in one second (PC20). Responses to histamine and methacholine were highly reproducible (coefficients of determination [r2] = 0.994 and 0.990 respectively). Responsiveness to histamine correlated closely with responsiveness to methacholine (r2 = 0.85). There was a small but significant cumulative dose effect with methacholine (P less than 0.01) but not with histamine. Side effects of throat irritation, flushing, and headache were more frequent with histamine than methacholine, and were dose-related. The high level of reproducibility indicates the efficiency of the test procedure. The similar severity of effects by agents with different mechanisms of action suggests that the primary cause of non-specific bronchial hyperreactivity lies at the level of bronchial smooth muscle.

Adult↗