Natural and medical sciences

2014 Issue №1

Back to the list Download the article

The genetic patterns of severe therapeutically resistant asthma as shown by a transcriptomic study: An analysis of gene ontology and KEGG pathways



The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma. Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip.


1. Global Burden of Asthma Report. URL: (дата обращения: 06.11.2013).
2. Bergquist P., Crompton G.K. Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study // Eur Respir J. 2001.№ 18(1). P. 248.
3. Чучалин А.Г., Пыжева Е.С., Колганова Н.А. Социально-экономическая значимость заболеваемости бронхиальной астмой и ее стоимостное определение // Экономика здравоохранения. 1997. № 4—5. С. 29—37.
4. Chung K.F., Godard P., Adelroth E. Difficult/therapy-resistant asthma // Eur.Respir. J. 1999. № 13. P. 1198—1208.
5. Федосеев Г.Б., Трофимов В.И., Петрова М.А. Многоликая бронхиальная астма, диагностика, лечение и профилактика. М., 2011.
6. Voelkel N., Spiegel S. Why is effective treatment of asthma so difficult? An integrated systems biology hypothesis of asthma // Immunol Cell Biol. 2009. № 87 (8).P. 601—605.
7. Глобальная стратегия лечения и профилактики бронхиальной астмы /под ред. А. C. Белевского. М., 2012.
8. Proceedings of the ATS workshop on refractory asthma: current understanding,recommendations, and unanswered questions // American Thoracic Society. Am J Respir Crit Care Med. 2000. № 162(6). P. 2341—2351.
9. Smyth, G. K. Limma: linear models for microarray data // Bioinformatics and Computational Biology Solutions using R and Bioconductor. N. Y., 2005. P. 397—420.
10. Benjamini Y., Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing // J. R. Stat Soc B. 1995. № 57. P 289—300.
11. Jakschik B.A., Kuo C.G. Characterization of leukotriene A4 and B4 biosynthesis// Prostaglandins. 1983. № 25(6). P. 767—82.
12. Karimi K., Forsythe P. Natural killer cells in asthma // Front Immunol. 2013.№ 4(159).
13. Bakkeheim E., Mowinckel P., Carlsen K.H. et al. Reduced basal salivary cortisol in children with asthma and allergic rhinitis // Acta Paediatr. 2010. № 99(11).P. 1705—1711.
14. Leung D.Y., de Castro M., Szefler S.J. Mechanisms of glucocorticoid-resistant asthma // Ann N Y Acad Sci. 1998. № 840. P. 735—746.
15. Bonnans C., Chanez P., Meziane H. Glucocorticoid receptor-binding characteristics in severe asthma // Eur Respir J. 2003. № 21. P. 985—988.
16. Hamzaoui A., Cheik Rouhou S., Graïri H. et al. NKT cells in the induced sputum of severe asthmatics // Mediators Inflamm. 2006. № 2. P. 712—714.
17. Nakagome K., Matsushita S., Nagata M. Neutrophilic inflammation in severe asthma // Int Arch Allergy Immunol. 2012. № 158. P. 96—102.
18. Grigoraş A., Grigoraş C.C., Mihaescus T. Neutrophilic inflammation-indicative of asthma severity // Pneumologia. 2010. № 59(1). P. 13—18.
19. Selivanova P.A., Kulikov E.S., Kozina O.V. et al. Morphological and molecular characteristics of «difficult» asthma // J Asthma. 2010. № 47(3). P. 269—275.
20. Akbari O., Faul J.L., Hoyte E.G. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma // N Engl J. Med. 2006. № 354(11). P. 1117—1129.
21. Haworth O., Cernadas M., Levy B.D. NK cells are effectors for resolvin E1 in the timely resolution of allergic airway inflammation // J Immunol. 2011. № 186(11).P. 6129—6135.
22. Wood P.R., Hill V.L., Burks M.L. Mycoplasma pneumoniae in children with acute and refractory asthma // Ann Allergy Asthma Immunol. 2013. № 110(5).P. 328—334.
23. Bakshi C.S., Malik M., Carrico P.M. T-bet Deficiency Facilitates Airway Colonization by Mycoplasma pulmonis in a Murine Model of Asthma // The Journal of Immunology. 2006. № 177. P. 1786—1795.
24. Sullivan B.M., Jobe O., Lazarevic V. Increased susceptibility of mice lacking T-bet to infection with Mycobacterium tuberculosis correlates with increased IL-10 and decreased IFN-gamma production // The Journal of Immunology. 2005. № 175.P. 4593—4602.
25. Van Zele T., Gevaert P. Role of Staphylococcus aureus in upper respiratory infections// Verh K Acad Geneeskd Belg. 2008. № 70(5—6). P. 369—378.