M Ichinose, M Miura, H Yamauchi, N Kageyama, M Tomaki, T Oyake, Y Ohuchi, W Hida, H Miki, G Tamura and K Shirato
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

Recent reports suggest the involvement of vascular phenomena in exercise-induced asthma. Sensory neuropeptides, such as substance P (SP), which causes airway vascular dilatation and plasma leakage, have been demonstrated to play a role in hyperpnea-induced airway narrowing in animal studies. The purpose of this study was to investigate the importance of tachykinins in exercise-induced airway narrowing in patients with asthma using a selective neurokinin 1-receptor (NK1- receptor) antagonist, FK-888. In a double-blind, placebo-controlled, crossover trial, nine subjects with stable asthma were given FK-888 (2.5 mg) or placebo by inhalation 20 min before each exercise at a level previously demonstrated to cause a fall of at least 40% in specific airway conduction (SGaw). Inhalation of FK-888 had no significant effect on baseline SGaw. While the recovery from exercise- induced airway narrowing was significantly faster after treatment with FK-888 the area under the curve for SGaw during the 50 min after exercise was significantly reduced (p<0.05) and the time taken for the SGaw to recover to within 65% of baseline after exercise was also significantly shorter with FK-888 than the placebo (p<0.05). However, treatment with FK-888 did not significantly attenuate the maximal fall in SGaw. These results suggest that NK1-receptor-mediated mechanisms are involved in the recovery phase of exercise-induced airway narrowing. The possible mechanisms of these phenomena are discussed.

This article has been cited by other articles:

				R. A. Joachim, V. Sagach, D. Quarcoo, Q. T. Dinh, P. C. Arck, and B. F. Klapp Neurokinin-1 Receptor Mediates Stress-Exacerbated Allergic Airway Inflammation and Airway Hyperresponsiveness in Mice Psychosom Med, July 1, 2004; 66(4): 564 - 571. [Abstract] [Full Text] [PDF]

				G.F. Joos and B. O'Connor Indirect airway challenges Eur. Respir. J., June 1, 2003; 21(6): 1050 - 1068. [Abstract] [Full Text] [PDF]

				G. F. JOOS, K. O. DE SWERT, V. SCHELFHOUT, and R. A. PAUWELS The Role of Neural Inflammation in Asthma and Chronic Obstructive Pulmonary Disease Ann. N.Y. Acad. Sci., May 1, 2003; 992(1): 218 - 230. [Abstract] [Full Text] [PDF]

				A. N. Freed, S. McCulloch, T. Meyers, and R. Suzuki Neurokinins Modulate Hyperventilation-induced Bronchoconstriction in Canine Peripheral Airways Am. J. Respir. Crit. Care Med., April 15, 2003; 167(8): 1102 - 1108. [Abstract] [Full Text] [PDF]

				H. Kanazawa, K. Asai, K. Hirata, and J. Yoshikawa Vascular Involvement in Exercise-Induced Airway Narrowing in Patients With Bronchial Asthma* Chest, July 1, 2002; 122(1): 166 - 170. [Abstract] [Full Text] [PDF]

				K. MAGHNI, R. TAHA, W. AFIF, Q. HAMID, and J. G. MARTIN Dichotomy between Neurokinin Receptor Actions in Modulating Allergic Airway Responses in an Animal Model of Helper T Cell Type 2 Cytokine-associated Inflammation Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1068 - 1074. [Abstract] [Full Text]

				M. J. Mhanna, I. A. Dreshaj, M. A. Haxhiu, and R. J. Martin Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development Am J Physiol Lung Cell Mol Physiol, January 1, 1999; 276(1): L51 - L56. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]