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Assessment of Microvascular Leakage via Sputum Induction

The Role of Substance P and Neurokinin A in Patients with Asthma

Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence and requests for reprints should be addressed to Prof. P. J. Sterk, Department of Pulmonology, C3-P Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: P.J.Sterk{at}lumc.nl

Microvascular leakage is an important feature of inflammation. However, the assessment of vascular leakage has seldom been used to monitor airway inflammation in asthma. The aim of this study was to determine the effect of inhaled substance P, a potent neurokinin 1 (NK1) agonist and mediator of plasma extravasation, on markers of microvascular leakage in induced sputum from patients with asthma. In a crossover study, sputum was induced before and 30 minutes after inhalation of substance P or neurokinin A (as control) by 12 subjects with atopic and mild, steroid-naive asthma. The levels of ₂-macroglobulin, ceruloplasmin, albumin, and fibrinogen were determined in induced sputum as markers of leakage. Substance P induced a significant increase in the levels of ₂-macroglobulin, ceruloplasmin, and albumin in induced sputum (median fold change, 3.1, 2.2, and 2.9, respectively) (p < 0.013), whereas inhaled neurokinin A was not able to induce significant changes (p > 0.31). The increase in sputum leakage markers was not associated with the cumulative dose of substance P (p > 0.12). These results indicate that NK1 receptor stimulation causes a rapid increase in microvascular leakage as shown in induced sputum in patients with asthma. This investigational model of "dual induction" (first leakage, then sputum) may therefore be useful to test the antiexudative effect of newly develop drugs, such as NK1 antagonists.

Key Words: asthma • ₂-macroglobulin • microvascular leakage • sputum • substance P

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