Abstract
Aspirin-induced asthma (AIA) is a severe inflammatory disease, which affects aspirin-intolerant patients after ingestion of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). In this article, a mathematical model describing arachidonic acid metabolism and its interaction with NSAIDs, is used to study the strategy for safe managing of NSAIDs to AIA patients. Three different AIA patient populations are taken into consideration. First, the values of aspirin and ibuprofen limiting doses that might induce symptoms of AIA are calculated and compared to experimentally observed threshold doses to enlighten which AIA patient population is susceptible to aspirin and ibuprofen. Second, the methodology of NSAID administration is studied on AIA populations susceptible to aspirin and ibuprofen by using 1,000 mg dose of aspirin and 200 or 400 mg dose of ibuprofen followed by PGE2 analogue dosing. Our model results show that successive doses of PGE2 analogue applied at appropriate time after aspirin or ibuprofen ingestion would enable administration of both NSAIDs to AIA patients. PGE2 analogue doses and the corresponding times of their applications are calculated. The model is also used to estimate the duration of symptoms of AIA for different aspirin and ibuprofen doses.
Similar content being viewed by others
References
Bogatcheva N, Sergeeva M, Dudek S, Verin A (2005) Arachidonic acid cascade in endothelial pathobiology. Microvasc Res 69:107–127
Cowburn AS, Sladek K, Soja A, Adamek L, Nizankowska E, Szczeklik A, Lam BK, Penrose J, Austen KF, Holgate ST, Sampson AP (1998) Over-expression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest 101:834–846
Dobovišek A, Fajmut A, Brumen M (2011) Role of expression of prostaglandin synthases 1 and 2 and leukotriene C4 synthase in aspirin-intolerant asthma: a theoretical study. J Pharmacokinet Pharmacodyn 38:261–278
Gauvreau GM, Watson RM, O’Byrne PM (1999) Protective effects of inhaled PGE2 on allergen-induced airway responses and airway inflammation. Am J Respir Crit Care Med 159:31–36
Gonchar M, Sergeeva M, Mevkh A, Varfolomeyev S (1999) Kinetics of prostanoid synthesis by macrophages is regulated by arachidonic acid sources. Eur J Biochem 265:779–787
Gupta N, Gresser M, Ford-Hutchinson A (1998) Kinetic mechanism of glutathione conjugation to leukotriene A4 by leukotriene C4 synthase. Biochim Biophys Acta 1391:157–168
Harizi H, Juzan M, Moreau J-F, Gualde N (2003) Prostaglandins inhibit 5-lipoxygenase-activating protein expression and leukotriene B4 production from dendritic cells via an IL-10-dependent mechanism. J Immunol 170:139–146
Hartert TV, Dworski RT, Mellen BG, Oates JA, Murray JJ, Sheller JR (2000) Prostaglandin E2 decreases allergen-stimulated release of prostaglandin D2 in airways of subjects with asthma. Am J Respir Crit Care Med 162:637–640
Heinrich R, Schuster S (1996) The regulation of cellular systems. Chapman & Hall, New York, pp 138–153
Klipp E, Herwig R, Kowald A, Wierling C, Lehrach H (2005) Systems biology in practice. Concepts, implementation and application. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 174–196
Marhl M, Gosak M, Perc M, Roux E (2010) Importance of cell variability for calcium signaling in rat airway myocytes. Biophys Chem 148:42–50
Mastalerz L, Nizankowska E, Sladek K, Szczeklik A (1994) Protective effects of prostaglandin E2 on airway obstruction induced by aspirin in aspirin-intolerant asthmatics. Eur Respir J 7:434S
Maxis K, Delalandre A, Martel-Pelletier J, Pelletier JP, Duval N, Lajeunesse D (2006) The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein. Arthritis Res Ther 8:R181
Meade E, Smith W, DeWitt D (1993) Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem 268:6610–6614
Melillo E, Woolley KL, Manning PJ, Watson RM, O’Byrne PM (1994) Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects. Am J Respir Crit Care Med 149:1138–1141
Picado C, Fernandez-Morata JC, Juan M, Roca-Ferrer J, Fuentes M, Xaubet A, Mullol J (1999) Cyclooxygenase-2 mRNA is down expressed in nasal polyps from aspirin-sensitive asthmatics. Am J Respir Crit Care Med 160:291–296
Pierzchalska M, Szabo Z, Sanak M, Soja J, Szczeklik A (2003) Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin induced asthma. J Allergy Clin Immunol 111:1041–1048
Rosado A, Vives R, González R, Poza P, Rodríguez J (2000) Intolerance to non-steroidal anti inflammatory drugs with respiratory reaction: clinical and diagnostic features. Alergol Inmunol Clin 15:153–159
Sánchez-Borges M (2010) NSAID hypersensitivity (Respiratory, cutaneous, and generalized anaphylactic symptoms). Med Clin North Am 94:853–864
Schäfer D, Lindenthal U, Wagner M, Bölcskei PL, Baenkler HW (1996) Effect of prostaglandin E2 on eicosanoid release by human bronchial biopsy specimens from normal and inflamed mucosa. Thorax 51:919–923
Schäfer D, Schmid M, Göde UC, Baenkler HW (1999) Dynamics of eicosanoids in peripheral blood cells during provocation in aspirin-intolerant asthmatics. Eur Respir J 13:638–646
Sestini P, Armetti L, Gambaro G, Pieroni M, Refini RM, Sala A, Vaghi A, Folco GC, Bianco S, Robuschi M (1996) Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma. Am J Respir Crit Care Med 153:572–575
Setipane RA, Schrank PJ, Simon RA, Mathison DA, Christiansen SC, Stevenson DD (1995) Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol 96:480–485
Setoguchi H, Nishimura J, Hirano K, Takahashi S, Kanaide H (2001) Leukotriene C4 enhances the contraction of porcine tracheal smooth muscle trough the activation of Y-27632, a rho kinase inhibitor, sensitive pathway. Br J Pharmacol 132:111–118
So O-Y, Scarafia LE, Mak AY, Callan OH, Swinney DC (1998) The dynamics of prostaglandin H synthases. Study with prostaglandin H-synthase 2Y355F unmask mechanisms of time-dependent inhibition and allosteric activation. J Biol Chem 273:5801–5807
Stevenson D, Szczeklik A (2006) Clinical and pathologic perspectives on aspirin sensitivity and asthma. J Allergy Clin Immunol 118:773–786
Szczeklik A, Stevenson D (1999) Aspirin-induced asthma: advances in pathogenesis and management. J Allergy Clin Immunol 104:5–13
Szczeklik A, Nizankowska E, Bochenek G, Nagraba K, Mejza F, Swierczynska M (2001) Safety of specific COX-2 inhibitor in aspirin-induced asthma. Clin Exp Allergy 31:219–225
Täuber U, Brudny–Klöppel M, Jakobs U, Madetzki C, Mahler M (1993) Pharmacokinetics of nocloprost in human volunteers and its relation to dose. Eur J Clin Pharmacol 44:497–500
Vane J, Botting R (1987) Inflammation and the mechanism of action of anti inflammatory drugs. FASEB J 1:89–96
Varghese M, Lockey RF (2008) Aspirin-exacerbated asthma. Allergy Asthma Clin Immunol 4:75–83
Acknowledgments
The authors acknowledge financial support from the state budget by the Slovenian Research Agency (Program No. P1-0055).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dobovišek, A., Fajmut, A. & Brumen, M. Strategy for NSAID administration to aspirin-intolerant asthmatics in combination with PGE2 analogue: a theoretical approach. Med Biol Eng Comput 50, 33–42 (2012). https://doi.org/10.1007/s11517-011-0844-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11517-011-0844-x