Further studies on the mechanism of human histamine-induced asthma *1The effect of an aerosolized H1 receptor antagonist (diphenhydramine)

Casterline, Charlotte L.; Evans, Richard

doi:10.1016/0091-6749(77)90004-5

Cited by 60 publications

(7 citation statements)

References 15 publications

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“…The inhalation test method is simple and portable, and is therefore suitable for clinical, epidemi- ological, and research studies. For example, it may be used to diagnose the presence of asthma (Cockcroft et al, 1977a), to examine the effect of medications (Cockcroft et al, 1977c), to help predict long-term medication requirements (Cockcroft et al, 1977a), to provide an index of risk to nonspecific stimuli in the environment , to help predict the dose of allergen that will trigger asthma (Killian et al, 1976;, to determine the specificity of responses to simple chemicals when antibodies cannot be shown (Vallieres et al, 1977), and to explore mechanisms of hyperreactivity (Ouellette and Reed, 1965;Casterline et al, 1976;Empey et al, 1976;Casterline and Evans, 1977;Cockcroft et al, 1977b;Miller et al, 1977, Frith et al, 1978Ruffin et al, 1978). The present study shows a close correlation between bronchial responsiveness to histamine and methacholine.…”

Section: Discussionmentioning

confidence: 99%

“…The results of the present study suggest that this is not the only abnormality. Studies on the mechanism of action of inhaled histamine in man indicate that it acts partly through reflex cholinergic pathways and partly by direct effects on histamine H1 receptors ] 5 *nO 10 j r--"-LL] r141A (Casterline et al, 1976;Casterline and Evans, 1977;Ruffin et al, 1978) and H2 receptors (Frith et al, 1978). By contrast methacholine is considered to have no effect on irritant receptors and to exert its effect through cholinergic receptors on smooth muscle (Goodman and Gilman, 1975;Miller et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reproducibility and comparison of responses to inhaled histamine and methacholine.

Juniper¹,

Frith²,

Dunnett³

et al. 1978

Thorax

530

218

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. Thorax, 33,. 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<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 mnechanisms of action suggests that the primary cause of non-specific bronchial hyperreactivity lies at the level of bronchial smooth muscle.Non-specific bronchial reactivity is the term used to indicate the responsiveness of the airways to chemical mediators, such as histamine, acetylcholine, and prostaglandin F2a, or to the synthetic analogues of acetylcholine, such as methacholine and carbachol. Its measurement is becoming increasingly important in clinical practice, epidemiology, and research.Non-specific bronchial reactivity is measured by inhalation tests, usually with histamine or methacholine. In the past different methods have been used, making critical analysis of results difficult. Recently Chai et al (1975) and Orehek and Gayrard (1976) have emphasised the importance of the standardisation of tests. Standardisation requires consideration of the many different factors that will influence the results.In this study we have standardised a simple inhalation test using histamine and methacholine. We have investigated the efficiency of the method by examining the reproducibility of responses over a short period. In addition we have compared the responsiveness to each agent and investigated the possibility of cumulative dose-effects and recorded side effects. Subjects and methods SUBJECTSThe patients were adults with asthma attending the regional chest and allergy unit. All had episodic dyspnoea or wheezing and documented variation in forced expired volume in one second (FEV1) of more than 20%, either spontaneously or after medication. None had features of any other respiratory disorder.Normal adults were volunteers from hospital staff. They had no present or past symptoms of rhinitis, asthma, or other respiratory disorder. They were non-smokers, non-atopic, and had normal spirometry. Non-atopic implied that they...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reproducibility and comparison of responses to inhaled histamine and methacholine.

Juniper¹,

Frith²,

Dunnett³

et al. 1978

Thorax

530

218

View full text Add to dashboard Cite

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“…It is important to remember that protection against histamine induced bronchospasm does not necessarily equate with bronchodilator effects. An example of this is the powerful protection an anti-histamine provides against histamine (Casterline & Evans, 1977) when it is generally accepted that anti-histamines have little or no place in the treatment of asthma. A surprising observation was that the reduction in spirometry values for individuals by P-adrenoceptor antagonists was not totally predicted by the individual's responsiveness to inhaled histamine.…”

Section: Resultsmentioning

confidence: 99%

Assessment of beta‐adrenoceptor antagonists in asthmatic patients.

Ruffin¹,

El²,

Latimer³

et al. 1982

Brit J Clinical Pharma

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1 Bronchial smooth muscle, skeletal muscle and cardiac 13-adrenoceptor antagonism have been compared in twelve asthmatic patients after three 0-adrenoceptor antagonists at two dose levels. The non-selective antagonist propranolol (40 and 160 mg), the non-selective antagonist with partial agonist activity pindolol (5 and 20mg) and the Pl-selective antagonist atenolol (50 and 200 mg) were studied on separate occasions. 2 Six placebo days were used in this double-blind crossover study to allow interpretation of individual as well as group results. 3 Bronchial smooth muscle effects were assessed by resting spirometry, histamine inhalation test and spirometric response to inhaled fenoterol. Skeletal muscle effects were assessed by resting tremor and fenoterol induced tremor.4 Cardiac P-adrenoceptor antagonism was assessed by measuring the effect on resting heart rate and on maximum heart rate in a standard exercise test. 5 Pindolol tended to cause least change from placebo in resting spirometry, caused significant tremor response, inhibited the fenoterol airway response, and tended to protect against inhaled histamine. 6 Atenolol 50 mg was the only drug to allow a fenoterol airway response similar to placebo. Atenolol increased the inhaled histamine responsiveness. 7 Propranolol 160 mg caused the most reduction in spirometry but also tended to cause the maximum reduction in exercise heart rate. Propranolol caused increased inhaled histamine responsiveness. 8 Initial sensitivity to inhaled histamine did not necessarily predict significant reduction in an asthmatics' spirometry by a j3-adrenoceptor antagonist. The effect of a 3-adrenoceptor antagonist on histamine responsiveness does not correspond to its effect on inhaled 132-adrenoceptor agonist responsiveness.

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“…When selecting a provocative test to assess the potency of bronchodilator agents, the pharmacological properties of the provocation and test agents need to be considered and the degree of protection may not be related to the agents' bronchodilator effects. For example, H, antagonists provide excellent protection against histamine-induced bronchoconstriction, but H, antagonists are not good bronchodilators (Casterline & Evans 1977). Therefore, when trying to assess whether an additional protective effect is gained by adding an anticholinergic drug to a Pz-agonist, histamine would be an appropriate provocative agent (Bandouvakis et al 1981) but methacholine would not.…”

Section: Introductionmentioning

confidence: 99%

Combined Bronchodilator Protection Against Histamine‐induced Bronchoconstriction in Man

Ruffin

Meki²,

Alpers

1987

Clin Exp Pharma Physio

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Sixteen stable asthmatics had the protective effects of inhaled fenoterol (200 micrograms) and inhaled ipratropium bromide (60 micrograms) against standardized histamine inhalation tests at 1 h examined in a randomized double blind fashion. There was no significant difference in the baseline forced expired volume in 1 s (FEV1) for the two study days (P greater than 0.05). There was an increase in FEV1 at 1 h on the fenoterol and ipratropium day compared with the fenoterol day (0.26 versus 0.17 l; P less than 0.05). The geometric mean provocative concentration of histamine to cause a 20% fall in FEV1 (PC20) was 6.31 mg/ml after fenoterol and 8.51 mg/ml after fenoterol and ipratropium (P = 0.038). There was no significant relationship between bronchodilator effect of the bronchodilators and the increase in PC20 from pre-study values, r = 0.307 (P = 0.25) for fenoterol alone and r = 0.195 (P = 0.47) for fenoterol and ipratropium. The relationship between pre-study histamine responsiveness and the increase in PC20 caused by the bronchodilators just failed to reach statistical significance, r = -0.441 (P = 0.09) for fenoterol alone and r = -0.47 (P = 0.06) for fenoterol and ipratropium. The study has shown a greater right shift of histamine responsiveness for combined inhaled fenoterol and ipratropium compared with inhaled fenoterol alone in this group of asthmatics.

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Further studies on the mechanism of human histamine-induced asthma *1The effect of an aerosolized H1 receptor antagonist (diphenhydramine)

Cited by 60 publications

References 15 publications

Reproducibility and comparison of responses to inhaled histamine and methacholine.

Reproducibility and comparison of responses to inhaled histamine and methacholine.

Assessment of beta‐adrenoceptor antagonists in asthmatic patients.

Combined Bronchodilator Protection Against Histamine‐induced Bronchoconstriction in Man

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