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Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects.
Eur Respir J 1993; 6(10):1462-7ER

Abstract

Neurokinin A (NKA) elicits a potent contractile effect in asthmatic airways. Its mechanism of action in bronchial asthma is still unknown. Recent work supports the view that NKA may stimulate mediator release from mast cells. To investigate the relative contribution of mast cell degranulation to the action of NKA, a randomized, double-blind study has been undertaken, to evaluate the effect of a potent and selective histamine H1-receptor antagonist, terfenadine (180 mg q.d., for three days), on bronchoconstriction provoked by inhaled NKA in six asthmatic subjects. Bronchial provocation tests with histamine were included in this study as control challenge. In the subjects studied, oral terfenadine, when compared to placebo, significantly increased the geometric mean (range) provocation dose of inhaled histamine required to reduce forced expiratory volume in one second (FEV1) by 20% of baseline (PD20) from 0.05 (0.03-0.08) mg (0.16 (0.10-0.26) mumol) to 1.19 (0.63-2.04) mg (3.88 (2.05-6.64) mumol). However, terfenadine failed to increase the airway responsiveness to NKA in all of the subjects studied, the geometric mean (range) PD15 NKA value being 0.94 (0.47-2.49) micrograms (8.36 (4.14-21.9 nmol) and 0.75 (0.48-1.59) micrograms (6.62 (4.23-14.0) nmol) after placebo and terfenadine, respectively. We conclude that NKA is a potent bronchoconstrictor agonist in asthma, being approximately 19 times more potent than histamine in molar terms. In this study on a small number of subjects, pharmacological intervention with oral terfenadine failed to achieve significant protection of the airways against the constrictor effect of NKA.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Istituto Malattie dell'Apparato Respiratorio, Università di Catania, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

8112439

Citation

Crimi, N, et al. "Effect of Oral Terfenadine On Bronchoconstrictor Response to Inhaled Neurokinin a and Histamine in Asthmatic Subjects." The European Respiratory Journal, vol. 6, no. 10, 1993, pp. 1462-7.
Crimi N, Oliveri R, Polosa R, et al. Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects. Eur Respir J. 1993;6(10):1462-7.
Crimi, N., Oliveri, R., Polosa, R., Pulvirenti, G., Prosperini, G., Palemo, F., & Mistretta, A. (1993). Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects. The European Respiratory Journal, 6(10), pp. 1462-7.
Crimi N, et al. Effect of Oral Terfenadine On Bronchoconstrictor Response to Inhaled Neurokinin a and Histamine in Asthmatic Subjects. Eur Respir J. 1993;6(10):1462-7. PubMed PMID: 8112439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects. AU - Crimi,N, AU - Oliveri,R, AU - Polosa,R, AU - Pulvirenti,G, AU - Prosperini,G, AU - Palemo,F, AU - Mistretta,A, PY - 1993/11/1/pubmed PY - 1993/11/1/medline PY - 1993/11/1/entrez SP - 1462 EP - 7 JF - The European respiratory journal JO - Eur. Respir. J. VL - 6 IS - 10 N2 - Neurokinin A (NKA) elicits a potent contractile effect in asthmatic airways. Its mechanism of action in bronchial asthma is still unknown. Recent work supports the view that NKA may stimulate mediator release from mast cells. To investigate the relative contribution of mast cell degranulation to the action of NKA, a randomized, double-blind study has been undertaken, to evaluate the effect of a potent and selective histamine H1-receptor antagonist, terfenadine (180 mg q.d., for three days), on bronchoconstriction provoked by inhaled NKA in six asthmatic subjects. Bronchial provocation tests with histamine were included in this study as control challenge. In the subjects studied, oral terfenadine, when compared to placebo, significantly increased the geometric mean (range) provocation dose of inhaled histamine required to reduce forced expiratory volume in one second (FEV1) by 20% of baseline (PD20) from 0.05 (0.03-0.08) mg (0.16 (0.10-0.26) mumol) to 1.19 (0.63-2.04) mg (3.88 (2.05-6.64) mumol). However, terfenadine failed to increase the airway responsiveness to NKA in all of the subjects studied, the geometric mean (range) PD15 NKA value being 0.94 (0.47-2.49) micrograms (8.36 (4.14-21.9 nmol) and 0.75 (0.48-1.59) micrograms (6.62 (4.23-14.0) nmol) after placebo and terfenadine, respectively. We conclude that NKA is a potent bronchoconstrictor agonist in asthma, being approximately 19 times more potent than histamine in molar terms. In this study on a small number of subjects, pharmacological intervention with oral terfenadine failed to achieve significant protection of the airways against the constrictor effect of NKA.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/8112439/Effect_of_oral_terfenadine_on_bronchoconstrictor_response_to_inhaled_neurokinin_A_and_histamine_in_asthmatic_subjects_ L2 - https://medlineplus.gov/asthma.html DB - PRIME DP - Unbound Medicine ER -