Z Diamant, MC Timmers, H van der Veen, CP Page, FJ van der Meer and PJ Sterk
Department of Pulmonology, University Hospital, Leiden, The Netherlands.

Heparin possesses anti-inflammatory properties, which appeared to be dependent on the dose, timing, and the route of administration in animal studies. In asthma, a single dose of inhaled heparin only slightly reduced the early asthmatic response (EAR) but failed to protect against the late asthmatic response (LAR) to inhaled allergen. We studied the effect of multiple doses of inhaled heparin on the EAR and LAR to inhaled house-dust mite extract in eight stable asthmatics in a two-period, randomized, double-blind, crossover study. During both study periods, a standardized allergen challenge was performed and PC20 histamine was measured 24 h before and 24 h postallergen. Five doses of unfractionated heparin sodium (1,000 U/kg/dose) or placebo were inhaled 90 and 30 min preallergen, and 2, 4, and 6 h postallergen. Airway response was measured by FEV1, and the EAR (0-3 h) and LAR (3-10 h) were expressed as corresponding areas under the time-response curves (AUC). The acute effects of heparin and placebo on baseline FEV1 were not different (p > 0.07). Although not reaching significance, heparin attenuated the EAR by an average of 40% (mean AUC(0-3) +/- SEM: 29.5 +/- 6.0 [placebo] and 17.8 +/- 5.5% fall x h [heparin]; p = 0.08), while it significantly reduced the LAR by an average of 36% (AUC(3-10) +/- SEM: 169.3 +/- 20.0 [placebo] and 109.1 +/- 23.6% fall x h [heparin]; p = 0.005). We conclude that inhaled heparin reduces the LAR to allergen in asthmatic subjects, which may be due to its anti-inflammatory activity. Our finding suggests that heparin may have potential as anti-asthma therapy.

This article has been cited by other articles:

				J. Xu, P. W. Park, F. Kheradmand, and D. B. Corry Endogenous Attenuation of Allergic Lung Inflammation by Syndecan-1 J. Immunol., May 1, 2005; 174(9): 5758 - 5765. [Abstract] [Full Text] [PDF]

				A. S. Niven and G. Argyros Alternate Treatments in Asthma Chest, April 1, 2003; 123(4): 1254 - 1265. [Full Text] [PDF]

				K.E. Bendstrup, J. Gram, and J.I. Jensen Effect of inhaled heparin on lung function and coagulation in healthy volunteers Eur. Respir. J., April 1, 2002; 19(4): 606 - 610. [Abstract] [Full Text] [PDF]

				R. SUZUKI and A. N. FREED Heparin Inhibits Hyperventilation-Induced Late-Phase Hyperreactivity in Dogs Am. J. Respir. Crit. Care Med., January 1, 2002; 165(1): 27 - 33. [Abstract] [Full Text] [PDF]

				M. Ledson, M. Gallagher, C.A. Hart, and M. Walshaw Nebulized heparin in Burkholderia cepacia colonized adult cystic fibrosis patients Eur. Respir. J., January 1, 2001; 17(1): 36 - 38. [Abstract] [Full Text] [PDF]

				T. Ahmed, J. Ungo, M. Zhou, and C. Campo Inhibition of allergic late airway responses by inhaled heparin-derived oligosaccharides J Appl Physiol, May 1, 2000; 88(5): 1721 - 1729. [Abstract] [Full Text] [PDF]

				J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]

				K. E. BENDSTRUP, C. B. CHAMBERS, J. I. JENSEN, and M. T. NEWHOUSE Lung Deposition and Clearance of Inhaled 99mTc-Heparin in Healthy Volunteers Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1653 - 1658. [Abstract] [Full Text]

				T. AHMED, B. J. GONZALEZ, and I. DANTA Prevention of Exercise-induced Bronchoconstriction by Inhaled Low-molecular-weight Heparin Am. J. Respir. Crit. Care Med., August 1, 1999; 160(2): 576 - 581. [Abstract] [Full Text]

				C. Campo, J. F. Molinari, J. Ungo, and T. Ahmed Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses J Appl Physiol, February 1, 1999; 86(2): 549 - 557. [Abstract] [Full Text] [PDF]

				R W Costello, D B Jacoby, and A D Fryer Pulmonary neuronal M2 muscarinic receptor function in asthma and animal models of hyperreactivity Thorax, July 1, 1998; 53(7): 613 - 618. [Full Text]

				J. F. MOLINARI, C. CAMPO, S. SHAKIR, and T. AHMED Inhibition of Antigen-induced Airway Hyperresponsiveness by Ultralow Molecular-weight Heparin Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): 887 - 893. [Abstract] [Full Text] [PDF]

				J. Martinez-Salas, R. Mendelssohn, W. M. Abraham, B. Hsiao, and T. Ahmed Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: molecular-weight dependence J Appl Physiol, January 1, 1998; 84(1): 222 - 228. [Abstract] [Full Text] [PDF]

				A. Fryer, Y.-C. Huang, G. Rao, D. Jacoby, E. Mancilla, R. Whorton, C. A. Piantadosi, T. Kennedy, and J. Hoidal Selective O-Desulfation Produces Nonanticoagulant Heparin that Retains Pharmacological Activity in the Lung, J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 208 - 219. [Abstract] [Full Text]

				D. A. Sawatzky, P. J. Kingham, E. Court, B. Kumaravel, A. D. Fryer, D. B. Jacoby, W. G. McLean, and R. W. Costello Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1279 - L1288. [Abstract] [Full Text] [PDF]