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Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo.
J Appl Physiol (1985). 1994 Sep; 77(3):1325-32.JA

Abstract

We tested the hypothesis that the inhaled tachykinin substance P (SP) can induce hyperresponsiveness to methacholine in asthmatic subjects in vivo. Nine atopic nonsmoking asthmatic males with normal forced expiratory volume in 1 s (FEV1; > 80% predicted) and increased methacholine sensitivity [provocative concn causing 20% fall in FEV1 (PC20) < 8 mg/ml] participated in a two-period placebo-controlled crossover study. Dose-response curves to SP (0.25-8 mg/ml) and placebo were recorded on 2 randomized days at least 1 wk apart, and methacholine tests were done 24 h before and 2 and 24 h after these challenges. The responses were measured by FEV1 (%fall from baseline). The position of the methacholine dose-response curves was expressed by the PC20 FEV1 and by the maximal response by the plateau level (MFEV1). SP caused a dose-dependent fall in FEV1 (P < 0.001). There was a slight increase in the PC20 FEV1 at 2 and 24 h, which was not significantly different between placebo and SP. Similarly, there was a reduction in MFEV1 at 2 h after both pretreatments. However, at 24 h after SP inhalation, MFEV1 increased compared with placebo. These changes in MFEV1 were significantly different between SP and placebo by 5.2 +/- 2.2% fall (SE) (P < 0.05). We conclude that 1) a bronchoconstrictive dose of SP, compared with placebo, enhances maximal airway narrowing to methacholine in asthma 24 h after inhalation and 2) tolerance develops to high doses of inhaled methacholine. These findings are suggestive of a role of SP in causing excessive airway narrowing in asthma by inflammatory mechanisms.

Authors+Show Affiliations

Department of Pulmonology, University Hospital Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7530706

Citation

Cheung, D, et al. "Effects of Inhaled Substance P On Airway Responsiveness to Methacholine in Asthmatic Subjects in Vivo." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 77, no. 3, 1994, pp. 1325-32.
Cheung D, van der Veen H, den Hartigh J, et al. Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo. J Appl Physiol. 1994;77(3):1325-32.
Cheung, D., van der Veen, H., den Hartigh, J., Dijkman, J. H., & Sterk, P. J. (1994). Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo. Journal of Applied Physiology (Bethesda, Md. : 1985), 77(3), 1325-32.
Cheung D, et al. Effects of Inhaled Substance P On Airway Responsiveness to Methacholine in Asthmatic Subjects in Vivo. J Appl Physiol. 1994;77(3):1325-32. PubMed PMID: 7530706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo. AU - Cheung,D, AU - van der Veen,H, AU - den Hartigh,J, AU - Dijkman,J H, AU - Sterk,P J, PY - 1994/9/1/pubmed PY - 1994/9/1/medline PY - 1994/9/1/entrez SP - 1325 EP - 32 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J. Appl. Physiol. VL - 77 IS - 3 N2 - We tested the hypothesis that the inhaled tachykinin substance P (SP) can induce hyperresponsiveness to methacholine in asthmatic subjects in vivo. Nine atopic nonsmoking asthmatic males with normal forced expiratory volume in 1 s (FEV1; > 80% predicted) and increased methacholine sensitivity [provocative concn causing 20% fall in FEV1 (PC20) < 8 mg/ml] participated in a two-period placebo-controlled crossover study. Dose-response curves to SP (0.25-8 mg/ml) and placebo were recorded on 2 randomized days at least 1 wk apart, and methacholine tests were done 24 h before and 2 and 24 h after these challenges. The responses were measured by FEV1 (%fall from baseline). The position of the methacholine dose-response curves was expressed by the PC20 FEV1 and by the maximal response by the plateau level (MFEV1). SP caused a dose-dependent fall in FEV1 (P < 0.001). There was a slight increase in the PC20 FEV1 at 2 and 24 h, which was not significantly different between placebo and SP. Similarly, there was a reduction in MFEV1 at 2 h after both pretreatments. However, at 24 h after SP inhalation, MFEV1 increased compared with placebo. These changes in MFEV1 were significantly different between SP and placebo by 5.2 +/- 2.2% fall (SE) (P < 0.05). We conclude that 1) a bronchoconstrictive dose of SP, compared with placebo, enhances maximal airway narrowing to methacholine in asthma 24 h after inhalation and 2) tolerance develops to high doses of inhaled methacholine. These findings are suggestive of a role of SP in causing excessive airway narrowing in asthma by inflammatory mechanisms. SN - 8750-7587 UR - https://www.unboundmedicine.com/medline/citation/7530706/Effects_of_inhaled_substance_P_on_airway_responsiveness_to_methacholine_in_asthmatic_subjects_in_vivo_ L2 - http://www.physiology.org/doi/full/10.1152/jappl.1994.77.3.1325?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -