Peculiarities of Airway Inflammation and Lipid Peroxidation in the Development of Hyperosmotic Airway Hyperresponsiveness in Patients with Asthma

Alexey B. Pirogov, PhD¹; Anna G. Prikhodko, PhD, ScD¹; Juliy M. Perelman, PhD, ScD¹; Eugene A. Borodin, PhD, ScD²; Denis E. Naumov, PhD¹; Sergey V. Zinovyev, PhD²; Mikhail A. Shtarberg, PhD²

¹Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveshchensk, Russia; ²Amur State Medical Academy, Blagoveshchensk, Russia

*Corresponding author: Denis E. Naumov, PhD. Laboratory of Prophylaxis of Nonspecific Lung Diseases, Far Eastern Scientific Center of Physiology and Pathology of Respiration; Blagoveshchensk, Russia. E-mail:

Published: December 16, 2016.  DOI: 10.21103/Article6(4)_OA2


The aim of our study was to evaluate the role of airway cellular inflammation and the lipid peroxidation level in the development of airway hyperresponsiveness (AHR) to inhalation of hypertonic saline (IHS).
Methods and Results: The study included the estimation of inflammatory-cellular composition, intracellular concentration of myeloperoxidase (MPO) in induced sputum (IS), serum levels of lipid hydroperoxides (LHP), ceruloplasmin, and vitamin E in 29 patients with asthma and 12 healthy persons. AHR to IHS was assessed by spirometry after 3-min IHS via ultrasonic nebulizer. Patients with asthma had higher indices of leukocytes destruction and cytolysis intensity with the increased leukocyte count in IS. Maximum values of neutrophils cytolysis intensity and leukocytic MPO were found in IS of the patients with AHR to IHS. After the bronchial provocation, serum concentration of LHP was higher in these patients in comparison with the patients without the AHR and control groups. In addition, patients with asthma had lower level of antioxidants than healthy subjects.
Conclusion: Marked inflammation involving MPO-activated leukocytes and intensive lipid peroxidation underlie the excessive airway response to IHS.

bronchial provocation, bronchoconstriction, hypertonic saline, myeloperoxidase, oxidative stress
  1. Prikhodko AG. Respiratory tract response to hypoosmotic stimulus. Bull Physiol Pathol Resp. 2005; 21:47-52. [Article in Russian].
  2. Gorbenko PP, Adamova IV, Sinitsyna TM. Bronchial hyperreactivity to the inhalation of hypo- and hyperosmolar aerosols and its correction by halotherapy. Ter Arkh. 1996; 8:24-28. [Article in Russian].
  3. Nikitina LYu, Petrovsky FI, Soodayeva SK. Oxidative stress and exercise-induced bronchoconstriction in elite athletes: does the interrelation exist? Pul'monologiya (Pulmonology). 2012; 5:99-104. [Article in Russian].
  4. Nevzorova VA, Pazych SA, Barkhatova DA, Kudryavtseva VA. The role of process cell death in course of inflammation under bronchial asthma. Pacific Medical J. 2006; 2:54-8.
  5. Soodayeva SK. Free radical mechanisms of injury in respiratory disease. Pul'monologiya (Pulmonology) 2012; 1:5-10. [Article in Russian].
  6. Anderson SD, Kippelen P. Airway injury as a mechanism for exercise–induced bronchoconstriction in elite athletes. J Allergy Clin Immunol. 2008; 122(2):225–35.
  7. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008; 88(4):1243–76.
  8. Sugiura H, Ichinose M. Nitrative stress in inflammatory lung diseases. Nitric Oxide. 2011; 25(2):138–44.
  9. Perelman JM, Prikhodko AG, Borodin EA, Ushakova EV. The role of oxidative stress in airway response to hyposmolar stimulus in patients with bronchial asthma. Bull Physiol Pathol Resp. 2014; 54:17-22.[Article in Russian].
  10. Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukos Biol. 2005; 77(5): 598-625.
  11. Panasenko OM, Gorudko IV, Sokolov AV. Hypochlorous acid as a precursor of free radicals in living systems. Biochemistry (Mosc). 2013; 78(13):1466-89. [Article in Russian].
  12. Gorudko IV, Kostevich VA, Sokolov AV, Shamova EV, Buko IV, Konstantinova EE, et al. Functional activity of neutrophils in diabetes mellitus and coronary heart disease: role of myeloperoxidase in the development of oxidative stress. Bull Exp Biol Med. 2012; 154(1):23-6. [Article in Russian].
  13. Perelman JM, Pirogov AB, Prikhodko AG, Zinoviev SV, Kolosov VP, Maltseva TA. Myeloperoxidase of bronchial leukocytes as a biomarker of osmotic bronchial hyperresponsiveness in asthmatics. Eur Respir J. 2015; 46(Suppl.59):РА3872.
  14. Pirogov AB, Zinoviev SV, Perelman JM, Semirech UO, Semenova GV, Kolosov AV. The activity of myeloperoxidase of neutrophilic and eosinophilic leukocytes of the induced sputum in patients with bronchial asthma with cold bronchial hyperresponsiveness. Bull Physiol Pathol Resp. 2014; 53:50-6. [Article in Russian].
  15. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (Updated 2014). URL:
  16. Bakakos P, Schleich F, Alchanatis M, Louis R. Induced sputum in asthma: from bench to bedside. Curr Med Chem. 2011; 18(10):1415-22.
  17. Hayhoe FGJ, Quaglino D. Hematological cytochemistry. 2nd edition. Churchill Levingstone, 1988.
  18. Maltseva TA, Pirogov AB, Kolosov VP, Ushakova EV, Naryshkina SV. Cell composition of induced sputum in patients with uncontrolled asthma and its participation in the formation of cold hyperresponsiveness.  Eur Respir J. 2013; 42(Suppl. 57):401. 
  19. Prikhodko AG, Perelman JM, Pirogov AB, Borodin EA, Ushakova EV, Ul'yanychev NV, et al. Phenotypic differences and peculiarities of inflammation in asthmatics with isolated and combined airway hyperresponsiveness to cold air and distilled water. Bull Physiol Pathol Resp. 2014; 54:8-16. [Article in Russian].
  20. Pirogov АB, Prikhodko AG, Perelman JМ, Zinov'ev SV, Ushakova EV, Makarova GA, et al. Cellular profile of the induced sputum, the level of myeloperoxidase and neutrophilic blood elastase in patients with bronchial asthma with airway hyperresponsiveness to hyposmolar stimulus. Bull Physiol Pathol Resp. 2015; 57:8-14. [Article in Russian].
  21. Kawai Y, Kiyokawa H, Kimura Y, Kato Y, Tsuchiya K, Terao J. Hypochlorous acid-derived modification of phospholipids: characterization of aminophospholipids as regulatory molecules for lipid peroxidation. Biochemistry. 2006; 45(47):14201-11.
  22. Panasenko OM, Arnkhold U, Sergienko VI. Impairment of membrane lipids by hypochlorite. Biochemistry (Moscow) Supplement. Series A: Membrane and Cell Biology. 2002; 19(5):403-34. [Article in Russian].
  23. Panasenko OM, Chekanov AV, Vlasova II, Sokolov AV, Ageeva KV, Pulina MO, et al. Influence of ceruloplasmin and lactoferrin on the chlorination activity of leukocyte myeloperoxidase assayed by chemiluminescence. Biophysics. 2008; 53(4):573-81. [Article in Russian].
  24.  Sokolov AV, Ageeva KV, Pulina MO, Cherkalina OS, Samygina VR, Vlasova II, et al. Ceruloplasmin and myeloperoxidase in complex affect the enzymatic properties of each other. Free Rad Res. 2008; 42(11-12):989-98.
  25. Shumyantseva VV, Makhova AA, Bulko TV, Shich EV, Kukes VG, Usanov SA, et al. The effect of antioxidants on electrocatalytic activity of cytochrome P450 3A4. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry. 2013; 7(2):160-4. [Article in Russian].

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