International Journal of Pediatric Otorhinolaryngology 78 (2014) 552–554
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Advanced oxidation protein product level in children with chronic otitis media with effusion Hasan Huseyin Balıkcı a,*, Mustafa Karakas¸ b, Muhammet Mustafa Gu¨rdal c, ¨ zkul b, O ¨ zlem Bayram b, Ali Alper Bayram b, Servet Yigit d Murat Haluk O a
Department of Otorhinolaryngology, Susehri Government Hospital, Sivas, Turkey Department of Otorhinolaryngology, Haseki Research and Training Hospital, Istanbul, Turkey Department of Otorhinolaryngology, Uskudar Government Hospital, Istanbul, Turkey d Department of Biochemistry, Beysehir Government Hospital, Konya, Turkey b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 October 2013 Received in revised form 7 January 2014 Accepted 8 January 2014 Available online 16 January 2014
Objective: To determine the level of advanced oxidation protein products (AOPPs) in children with chronic otitis media with effusion (COME), in an effort to elucidate the multifactorial etiology of this disease. Methods: This study involved 25 COME patients and 30 healthy children (control group) recruited from the Ear, Nose and Throat (ENT) and Pediatric Departments, respectively, of the Haseki Research and Training Hospital. In the COME group, blood samples were collected before a middle ear operation, and middle ear fluid was sampled during the operation. Blood samples were also obtained from the control subjects. AOPP levels in the plasma and effusion fluid were measured by the spectrophotometric method. Results: In the COME group, the mean AOPP levels in plasma and effusion fluid were 168.08 mmol/l and 412.75 mmol/l, respectively. In the control group, the mean plasma AOPP level was 141.54 mmol/l. The plasma AOPP levels did not significantly differ between the COME and control groups (p > 0.05). In the COME group, however, the effusion fluid AOPP level (412.75 204.54 mmol/l) was significantly higher than the plasma AOPP level (168.08 68.45 mmol/l; p < 0.01). Conclusion: We found that AOPP levels were elevated in the effusion fluid, but not in the plasma, of COME patients. Thus, COME was associated with protein oxidation abnormalities. Oxidative stress may play a role in the etiopathogenesis of COME, and AOPPs may be used as markers of oxidative stress; however, further studies are required to confirm these findings. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chronic otitis media with effusion Advanced oxidation protein product (AOPP) Oxidative stress Antioxidant
Introduction Chronic otitis media with effusion (COME) is the most prevalent ear disease and probably the most common reason for surgery in childhood [1]. COME is defined as the collection of fluid behind the ear drum without inflammatory signs for more than 12 weeks [2]. Permanent middle ear fluid as a result of COME reduces ear drum mobility, which in turn decreases sound conduction from the external ear to the middle ear [3]. In severe cases, COME can lead to hearing impairment and language development disorders, resulting in a decline in school success and requiring surgical interventions such as myringotomy, ventilation tube insertion and adenoidectomy [4]. The causes of COME can be divided into two categories: host and
* Corresponding author. Tel.: +90 346 311 40 08/+90 506 735 12 01; fax: +90 346 311 48 03. E-mail address: [email protected] (H.H. Balıkcı). 0165-5876/$ – see front matter ß 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2014.01.007
environmental factors. The main host factors are bacterial infections, eustachian tube dysfunction, adenoid hypertrophy, allergic and immunologic factors, lack of breast-feeding, genetic factors, gender, race, accompanying cleft palate, ciliary dysfunction, Down syndrome and cystic fibrosis [4]. Among the environmental factors associated with COME are seasonal cycle, communal living, bottle-feeding, smoking environment and unhygienic conditions [5]. Oxidative stress is defined as tissue damage resulting from an imbalance between the production of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates. Toward the middle of the 90s, amino acids, peptides and proteins were shown to be vulnerable to attacks by free radicals and oxidants [6]. Advanced oxidation protein products (AOPPs) are proteins which have been damaged by oxidative stress and act as inflammatory mediators stimulating the oxidative reactions of leukocytes and lymphocytes [7]. Oxidation products of proteins are more stable than those of lipids, and may hence be good markers of oxidative stress [8].
H.H. Balıkcı et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 552–554
The aim of the present study was to determine whether AOPP concentrations in ear effusions are affected by COME and whether AOPPs play a role in the etiology of COME.
Table 1 Comparison of the levels of advanced oxidation protein products (AOPPs) between chronic otitis media with effusion (COME) patients and control subjects. AOPP (mmol/l)
Materials and methods Patients
Plasma Effusion a
Twenty-five patients diagnosed with bilateral COME and followed up at the Department of Otorhinolaryngology, Haseki Training and Research Hospital, Istanbul were enrolled in the study after their parents provided informed consent. The protocol of this study have been submitted and approved by the ethical committee of our Institution. The study group consisted of patients who had not responded to medical therapy for 12 weeks and had no systemic or infectious disease or history of surgery. All patients in the study group underwent adenoidectomy with bilateral ventilation tube insertion. Patients with acute or chronic inflammatory disease, former surgical history, chronic systemic disease and responding medical treatments were excluded from the study. As a control group, 30 healthy individuals were recruited. The mean ages of the subjects in the study and control groups were 5.84 1.72 years (range, 3–9 years) and 5.53 1.17 years (range, 3–9 years), respectively. Samples In the study group, venous blood samples were collected in standard sterile vacuum tubes containing EDTA, 30 min before the operation and used to assess the plasma AOPP level. Plasma samples were prepared by centrifugation at 3000 rpm for 15 min. During the operation, a myringotomy was performed, and middle ear fluid was aspirated with a micro-suction cannula that was adapted to be fitted to a manually controlled 5-ml scale injector. The volume of the fluid samples ranged between 40 ml and 120 ml. All samples were stored at 20 8C until assay. The samples were used for biochemical analyses with commercial kits and an Abbott C-16000 autoanalyzer. AOPP levels were expressed in terms of micromolar chloramine-T equivalents (mmol/l). Statistical methods All values were expressed as means and standard deviations. The Student t test and Yates continuity correction test were used to test between-group differences. The differences between plasma and effusion fluid AOPP levels in the patient group were tested using the paired-samples t-test. Relationships between variables were determined using Pearson correlation coefficient (r) analysis. p Values less than 0.05 and 0.01 were considered statistically significant. NCSS PASS 2008 v8.0.11 statistical software (Utah, USA) was used for the analyses. Results We examined a total of 55 subjects with a mean age 5.67 1.44 years (62% boys and 38% girls). Age, gender and plasma AOPP levels did not significantly differ between the COME patients and the control subjects. In the COME group, the AOPP levels in effusion fluid were 168–680 mmol/l, and these were significantly higher than the plasma AOPP levels (Table 1). Discussion Although many factors have been implicated in the development of COME, little is known about the underlying etiology.
553
COME (n = 25)
Control (n = 30)
Mean SD
Mean SD
168.08 68.45 412.75 204.54
141.54 49.60 –
pa
0.102 –
Student t test, significant differences at p < 0.01.
Numerous studies have indicated a role of inflammatory mediators in effusion, but research on free oxygen radicals (FORs) in the middle ear is limited [9–11]. FORs are generated in cells by different processes such as normal cellular metabolism, inflammation and irradiation. COME is associated with an increase in inflammatory cell count, as shown by many investigators [12–14]. AOPPs are generated during metabolic processes by the interaction of hypochlorous acid and chloramines, both of which are produced by myeloperoxidase in activated neutrophils. Recent papers have suggested that oxidative stress, such as that observed in diabetes mellitus, acute coronary syndrome and chronic renal failure, plays a key role in the pathogenesis of COME [7,8,15]. Takoudes and Haddad demonstrated that FORs cause squamous metaplasia and hypertrophy of gland cells in the middle ear mucosa [9]. Callejo et al. reported that the middle ear mucosa is impaired by lipoperoxidation products [10]. Doner et al. found that the levels of malondialdehyde (MDA), a lipid peroxidation product, were higher in animals with COME than in controls [16]. The etiology of the disease in patients with COME caused by oxidation products is not fully known. However, oxidative products are known to increase in COME and to damage the middle ear mucosa and ciliary activity. Protection against oxidative stress is mostly provided by endogenous molecules, and is referred to as antioxidant activity. However, endogenous molecules may not be enough to overcome the toxic effects of FORs, especially in patients with chronic disease or severe acute inflammation. Yariktas et al. reported that plasma MDA levels and antioxidant enzyme activity were significantly higher in COME patients than in healthy controls [17]. Durand et al. showed that otitis media is more prevalent among children with low plasma levels of the antioxidant vitamin A than among individuals with normal vitamin A levels [18]. In a study by Testa et al., 67% of COME patients recovered after antioxidant therapy with a nasal aerosol containing glutathione [19]. All these findings indicate the importance of the relationship between oxidation products and antioxidant activity in the etiopathogenesis of COME. However, although AOPPs cannot be the main initiating factor ofinflammation, they may maintain ongoing inflammation or result from the inflammation. As AOPPs are proteins that have been damaged by oxidative stress, they act as inflammatory mediators to further stimulate the oxidative reactions of leukocytes and lymphocytes [7]. Dong et al. found that the plasma concentrations of superoxide dismutase, interleukin-6, interleukin-8 and tumor necrosis factor alpha were markedly higher in patients with COME than in healthy subjects [12]. Many studies have reported that the plasma levels of AOPPs are particularly increased in chronic systemic diseases [6– 8,15]. However, in our study, plasma AOPP levels were higher in patients with COME than in controls, but this difference was not significant. We had excluded patients with other systemic chronic inflammatory diseases. This finding therefore suggested that the effects of inflammation in COME is not systemic but localized. Localized inflammation occurred in COME, and the increase in the number of inflammatory cells generated FORs. Increasing FOR levels and decreasing antioxidant levels impair middle ear structures and cause chronic inflammation [17].
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H.H. Balıkcı et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 552–554
A few researchers have investigated antioxidant enzyme activity, cytokines and oxidation products in effusion. Yilmaz et al. and Testa et al. found high MDA levels in effusion fluid, and these levels were similar to the levels found in other chronic disorders [13,14]. Shigemi et al. found higher levels of superoxide dismutase activity in mucous effusion than in serous effusion. Dong et al. indicated that the concentrations of superoxide dismutase, interleukin-6, interleukin-8 and tumor necrosis factor alpha were markedly higher in effusion fluid than in plasma [12]. In our study, we found that the AOPP levels in effusion fluid were significantly higher than those in plasma samples. Conclusion AOPP levels are elevated in the effusion fluid, but not in the plasma, of COME patients. AOPPs may represent a novel class of proinflammatory molecules that mediate oxidative stress in COME. AOPP pathophysiology could provide valuable information about the relationship between oxidative stress and the course of COME. Further studies are required to elaborate on this relationship. According to these findings we can say that the antioxidant agents may be useful in the treatment of otitis media with effusion in the future. Role of the funding source None. Acknowledgments None. References [1] I. Williamson, S. Benge, M. Mullee, P. Little, Consultations for middle ear disease, antibiotic prescribing and risk factors for re-attendance: a case linked cohort study, Br. J. Gen. Pract. 56 (2006) 170–175.
[2] M.E. Saafan, W.S. Ibrahim, M.O. Tomoum, Role of adenoid biofilm in chronic otitis media with effusion in children, Eur. Arch. Otorhinolaryngol. 270 (9) (2013) 2417–2425. [3] R.M. Rosenfeld, L. Culpepper, K.J. Doyle, K.M. Grundfast, A. Hoberman, et al., Clinical practice guideline: otitis media with effusion, Otolaryngol. Head Neck Surg. 130 (2004) 95–118. [4] C. Kwon, H.Y. Lee, M.G. Kim, S.H. Boo, S.G. Yeo, Allergic diseases in children with otitis media with effusion, Int. J. Pediatr. Otorhinolaryngol. 77 (2) (2013) 158–161. [5] P.B. Van Cauwenberge, Relevant and irrelevant predisposing factors in secretary otitis media, Acta Otolaryngol. 414 (1984) 147–153. [6] V. Witko-Sarsat, M. Friedlander, C. Capeille`re-Blandin, T. Nguyen-Khoa, A.T. Nguyen, J. Zingraff, P. Jungers, B. Descamps-Latscha, Advanced oxidation protein products as a novel marker of oxidative stress in ureamia, Kidney Int. 49 (1996) 1304–1313. [7] M. Skvarilova´, A. Bulava, D. Stejskal, S. Adamovska´, J. Bartek, Increased level of advanced oxidation products (AOPP) as a marker of oxidative stress in patients with acute coronary syndrome, Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 149 (1) (2005) 83–87. [8] C.J. Alderman, S. Shah, J.C. Foreman, B.M. Chain, D.R. Katz, The role of advanced oxidation protein products in regulation of dendritic cell function, Free Radical Biol. Med. 325 (2002) 377–385. [9] T.G. Takoudes, J. Haddad Jr., Evidence of oxygen free radical damage in human otitis media, Otolaryngol. Head Neck Surg. 120 (1999) 638–642. [10] F.J. Garcı´a Callejo, J. Estors Ferrero, A. Morant Ventura, P. Segarra Corte´s, M.M. Velert Vila, Lipoperoxidation en otorreas del oidomediocomomarcador de infeccion, Acta Otorinolaringol. Esp. 51 (2000) 478–481. [11] Y.G. Min, M. Ohyama, K.S. Lee, C.S. Rhee, S.H. Oh, M.W. Sung, J.B. Yun, I.H. Jung, Effect of free radicals on ciliary movement in the human nasal epithelial cells, Auris Nasus Larynx 26 (1999) 159–163. [12] W. Dong, Z. Li, S. Zhou, Superoxide dismutase and cytokines in otitis media with effusion, Lin Chuanq Er Bi Yan Hou Ke Za Zhi 15 (2001) 452–454. [13] T. Yilmaz, E.G. Koc¸an, H.T. Besler, G. Yilmaz, B. Gu¨rsel, The role of oxidants and antioxidants in otitis media with effusion in children, Otolaryngol. Head Neck Surg. 131 (2004) 797–803. [14] D. Testa, G. Guerra, G. Marcuccio, P.G. Landolfo, G. Motta, Oxidative stress in chronic otitis media with effusion, Acta Otolarygol. 132 (2012) 834–837. [15] V. Witko-Sarsat, V. Gausson, B. Descamps-Latscha, Are advanced oxidation protein products potential uremic toxins? Kidney Int. 84 (2003) S11–S14. [16] F. Doner, N. Delibas, H. Do_ru, M. Yariktas, M. Demirci, The role of free oxygen radicals in experimental otitis media, J Basic Clin. Physiol. Pharmacol. 13 (2002) 33–40. [17] M. Yariktas, F. Doner, H. Dogru, H. Yasan, N. Delibas, The role of free oxygen radicals on the development of otitis media with effusion, Int. J. Pediatr. Otorhinolaryngol. 68 (2004) 889–894. [18] A.M. Durand, H. Sabino Jr., R. Masga, M. Sabino, F. Olopai, I. Abraham, Childhood vitamin A status and the risk of otitis media, Pediatr. Infect. Dis. J. 16 (1997) 952–954. [19] B. Testa, D. Testa, M. Mesolella, G. D’Errico, D. Tricarico, G. Motta, Management of chronic otitis media with effusion: the role of gluthation, Laryngoscope 111 (2001) 1486–1489.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Advanced oxidation protein product level in children with chronic otitis media with effusion Hasan Huseyin Balıkcı a,*, Mustafa Karakas¸ b, Muhammet Mustafa Gu¨rdal c, ¨ zkul b, O ¨ zlem Bayram b, Ali Alper Bayram b, Servet Yigit d Murat Haluk O a
Department of Otorhinolaryngology, Susehri Government Hospital, Sivas, Turkey Department of Otorhinolaryngology, Haseki Research and Training Hospital, Istanbul, Turkey Department of Otorhinolaryngology, Uskudar Government Hospital, Istanbul, Turkey d Department of Biochemistry, Beysehir Government Hospital, Konya, Turkey b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 October 2013 Received in revised form 7 January 2014 Accepted 8 January 2014 Available online 16 January 2014
Objective: To determine the level of advanced oxidation protein products (AOPPs) in children with chronic otitis media with effusion (COME), in an effort to elucidate the multifactorial etiology of this disease. Methods: This study involved 25 COME patients and 30 healthy children (control group) recruited from the Ear, Nose and Throat (ENT) and Pediatric Departments, respectively, of the Haseki Research and Training Hospital. In the COME group, blood samples were collected before a middle ear operation, and middle ear fluid was sampled during the operation. Blood samples were also obtained from the control subjects. AOPP levels in the plasma and effusion fluid were measured by the spectrophotometric method. Results: In the COME group, the mean AOPP levels in plasma and effusion fluid were 168.08 mmol/l and 412.75 mmol/l, respectively. In the control group, the mean plasma AOPP level was 141.54 mmol/l. The plasma AOPP levels did not significantly differ between the COME and control groups (p > 0.05). In the COME group, however, the effusion fluid AOPP level (412.75 204.54 mmol/l) was significantly higher than the plasma AOPP level (168.08 68.45 mmol/l; p < 0.01). Conclusion: We found that AOPP levels were elevated in the effusion fluid, but not in the plasma, of COME patients. Thus, COME was associated with protein oxidation abnormalities. Oxidative stress may play a role in the etiopathogenesis of COME, and AOPPs may be used as markers of oxidative stress; however, further studies are required to confirm these findings. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chronic otitis media with effusion Advanced oxidation protein product (AOPP) Oxidative stress Antioxidant
Introduction Chronic otitis media with effusion (COME) is the most prevalent ear disease and probably the most common reason for surgery in childhood [1]. COME is defined as the collection of fluid behind the ear drum without inflammatory signs for more than 12 weeks [2]. Permanent middle ear fluid as a result of COME reduces ear drum mobility, which in turn decreases sound conduction from the external ear to the middle ear [3]. In severe cases, COME can lead to hearing impairment and language development disorders, resulting in a decline in school success and requiring surgical interventions such as myringotomy, ventilation tube insertion and adenoidectomy [4]. The causes of COME can be divided into two categories: host and
* Corresponding author. Tel.: +90 346 311 40 08/+90 506 735 12 01; fax: +90 346 311 48 03. E-mail address: [email protected] (H.H. Balıkcı). 0165-5876/$ – see front matter ß 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2014.01.007
environmental factors. The main host factors are bacterial infections, eustachian tube dysfunction, adenoid hypertrophy, allergic and immunologic factors, lack of breast-feeding, genetic factors, gender, race, accompanying cleft palate, ciliary dysfunction, Down syndrome and cystic fibrosis [4]. Among the environmental factors associated with COME are seasonal cycle, communal living, bottle-feeding, smoking environment and unhygienic conditions [5]. Oxidative stress is defined as tissue damage resulting from an imbalance between the production of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates. Toward the middle of the 90s, amino acids, peptides and proteins were shown to be vulnerable to attacks by free radicals and oxidants [6]. Advanced oxidation protein products (AOPPs) are proteins which have been damaged by oxidative stress and act as inflammatory mediators stimulating the oxidative reactions of leukocytes and lymphocytes [7]. Oxidation products of proteins are more stable than those of lipids, and may hence be good markers of oxidative stress [8].
H.H. Balıkcı et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 552–554
The aim of the present study was to determine whether AOPP concentrations in ear effusions are affected by COME and whether AOPPs play a role in the etiology of COME.
Table 1 Comparison of the levels of advanced oxidation protein products (AOPPs) between chronic otitis media with effusion (COME) patients and control subjects. AOPP (mmol/l)
Materials and methods Patients
Plasma Effusion a
Twenty-five patients diagnosed with bilateral COME and followed up at the Department of Otorhinolaryngology, Haseki Training and Research Hospital, Istanbul were enrolled in the study after their parents provided informed consent. The protocol of this study have been submitted and approved by the ethical committee of our Institution. The study group consisted of patients who had not responded to medical therapy for 12 weeks and had no systemic or infectious disease or history of surgery. All patients in the study group underwent adenoidectomy with bilateral ventilation tube insertion. Patients with acute or chronic inflammatory disease, former surgical history, chronic systemic disease and responding medical treatments were excluded from the study. As a control group, 30 healthy individuals were recruited. The mean ages of the subjects in the study and control groups were 5.84 1.72 years (range, 3–9 years) and 5.53 1.17 years (range, 3–9 years), respectively. Samples In the study group, venous blood samples were collected in standard sterile vacuum tubes containing EDTA, 30 min before the operation and used to assess the plasma AOPP level. Plasma samples were prepared by centrifugation at 3000 rpm for 15 min. During the operation, a myringotomy was performed, and middle ear fluid was aspirated with a micro-suction cannula that was adapted to be fitted to a manually controlled 5-ml scale injector. The volume of the fluid samples ranged between 40 ml and 120 ml. All samples were stored at 20 8C until assay. The samples were used for biochemical analyses with commercial kits and an Abbott C-16000 autoanalyzer. AOPP levels were expressed in terms of micromolar chloramine-T equivalents (mmol/l). Statistical methods All values were expressed as means and standard deviations. The Student t test and Yates continuity correction test were used to test between-group differences. The differences between plasma and effusion fluid AOPP levels in the patient group were tested using the paired-samples t-test. Relationships between variables were determined using Pearson correlation coefficient (r) analysis. p Values less than 0.05 and 0.01 were considered statistically significant. NCSS PASS 2008 v8.0.11 statistical software (Utah, USA) was used for the analyses. Results We examined a total of 55 subjects with a mean age 5.67 1.44 years (62% boys and 38% girls). Age, gender and plasma AOPP levels did not significantly differ between the COME patients and the control subjects. In the COME group, the AOPP levels in effusion fluid were 168–680 mmol/l, and these were significantly higher than the plasma AOPP levels (Table 1). Discussion Although many factors have been implicated in the development of COME, little is known about the underlying etiology.
553
COME (n = 25)
Control (n = 30)
Mean SD
Mean SD
168.08 68.45 412.75 204.54
141.54 49.60 –
pa
0.102 –
Student t test, significant differences at p < 0.01.
Numerous studies have indicated a role of inflammatory mediators in effusion, but research on free oxygen radicals (FORs) in the middle ear is limited [9–11]. FORs are generated in cells by different processes such as normal cellular metabolism, inflammation and irradiation. COME is associated with an increase in inflammatory cell count, as shown by many investigators [12–14]. AOPPs are generated during metabolic processes by the interaction of hypochlorous acid and chloramines, both of which are produced by myeloperoxidase in activated neutrophils. Recent papers have suggested that oxidative stress, such as that observed in diabetes mellitus, acute coronary syndrome and chronic renal failure, plays a key role in the pathogenesis of COME [7,8,15]. Takoudes and Haddad demonstrated that FORs cause squamous metaplasia and hypertrophy of gland cells in the middle ear mucosa [9]. Callejo et al. reported that the middle ear mucosa is impaired by lipoperoxidation products [10]. Doner et al. found that the levels of malondialdehyde (MDA), a lipid peroxidation product, were higher in animals with COME than in controls [16]. The etiology of the disease in patients with COME caused by oxidation products is not fully known. However, oxidative products are known to increase in COME and to damage the middle ear mucosa and ciliary activity. Protection against oxidative stress is mostly provided by endogenous molecules, and is referred to as antioxidant activity. However, endogenous molecules may not be enough to overcome the toxic effects of FORs, especially in patients with chronic disease or severe acute inflammation. Yariktas et al. reported that plasma MDA levels and antioxidant enzyme activity were significantly higher in COME patients than in healthy controls [17]. Durand et al. showed that otitis media is more prevalent among children with low plasma levels of the antioxidant vitamin A than among individuals with normal vitamin A levels [18]. In a study by Testa et al., 67% of COME patients recovered after antioxidant therapy with a nasal aerosol containing glutathione [19]. All these findings indicate the importance of the relationship between oxidation products and antioxidant activity in the etiopathogenesis of COME. However, although AOPPs cannot be the main initiating factor ofinflammation, they may maintain ongoing inflammation or result from the inflammation. As AOPPs are proteins that have been damaged by oxidative stress, they act as inflammatory mediators to further stimulate the oxidative reactions of leukocytes and lymphocytes [7]. Dong et al. found that the plasma concentrations of superoxide dismutase, interleukin-6, interleukin-8 and tumor necrosis factor alpha were markedly higher in patients with COME than in healthy subjects [12]. Many studies have reported that the plasma levels of AOPPs are particularly increased in chronic systemic diseases [6– 8,15]. However, in our study, plasma AOPP levels were higher in patients with COME than in controls, but this difference was not significant. We had excluded patients with other systemic chronic inflammatory diseases. This finding therefore suggested that the effects of inflammation in COME is not systemic but localized. Localized inflammation occurred in COME, and the increase in the number of inflammatory cells generated FORs. Increasing FOR levels and decreasing antioxidant levels impair middle ear structures and cause chronic inflammation [17].
554
H.H. Balıkcı et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 552–554
A few researchers have investigated antioxidant enzyme activity, cytokines and oxidation products in effusion. Yilmaz et al. and Testa et al. found high MDA levels in effusion fluid, and these levels were similar to the levels found in other chronic disorders [13,14]. Shigemi et al. found higher levels of superoxide dismutase activity in mucous effusion than in serous effusion. Dong et al. indicated that the concentrations of superoxide dismutase, interleukin-6, interleukin-8 and tumor necrosis factor alpha were markedly higher in effusion fluid than in plasma [12]. In our study, we found that the AOPP levels in effusion fluid were significantly higher than those in plasma samples. Conclusion AOPP levels are elevated in the effusion fluid, but not in the plasma, of COME patients. AOPPs may represent a novel class of proinflammatory molecules that mediate oxidative stress in COME. AOPP pathophysiology could provide valuable information about the relationship between oxidative stress and the course of COME. Further studies are required to elaborate on this relationship. According to these findings we can say that the antioxidant agents may be useful in the treatment of otitis media with effusion in the future. Role of the funding source None. Acknowledgments None. References [1] I. Williamson, S. Benge, M. Mullee, P. Little, Consultations for middle ear disease, antibiotic prescribing and risk factors for re-attendance: a case linked cohort study, Br. J. Gen. Pract. 56 (2006) 170–175.
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