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PEDOT-7633; No. of Pages 4 International Journal of Pediatric Otorhinolaryngology xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis Tekin Baglam a, Adem Binnetoglu a,*, Ali Cemal Yumusakhuylu a, Fethullah Gerin b, Berat Demir a, Murat Sari a a b
Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey Department of Biochemistry, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 5 January 2015 Received in revised form 10 June 2015 Accepted 13 June 2015 Available online xxx
Objective: The aim of this study was to determine whether the neutrophil-to-lymphocyte ratio (NLR) can be used as a predictor for deep neck space infections (DNSIs) that occur as a complication of acute bacterial tonsillitis in the pediatric population. Materials and methods: We evaluated the NLR values of 180 pediatric patients diagnosed with acute bacterial tonsillitis with or without DNSI who presented to the Otolaryngology Department of Marmara University Hospital between 2010 and 2013. In cases in which DNSI was suspected, the patients underwent complete otolaryngological examination and radiological imaging including CT and MRI. NLR was calculated in all the subjects and was compared between the patients with acute bacterial tonsillitis without DNSI and those with DNSI. Results: With regard to the tonsillitis-related complications, 17 patients had peritonsillar abscess (9.4%); five, parapharyngeal abscess (2.8%); and two, retropharyngeal abscess (1.1%). The mean NLR was significantly higher in the patients of acute bacterial tonsillitis with DNSI (P < 0.05). The optimum cut-off value of NLR was determined to be 5.4. Conclusion: This study is the first to investigate the relationship between NLR and DNSI as a complication of acute bacterial tonsillitis. The results demonstrated that the NLR value could be a potential laboratory parameter for diagnosing DNSIs. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Neutrophil-to-lymphocyte ratio Inflammation Acute bacterial tonsillitis Deep neck infection
1. Introduction Acute tonsillitis is commonly encountered in outpatient ENT clinics, especially in children and young adults. It is usually caused by viral agents and is accompanied by secondary bacterial infections. Acute tonsillitis often occurs secondary to viral infections and is usually a polymicrobial infection that is caused by interaction between the normal oropharyngeal flora and the extrinsic flora [1–4]. The diagnosis of acute tonsillitis is based on the patient’s medical history, physical examination and laboratory studies including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP) level, the rapid antigen detection test (RADT), serological tests and cultures for bacterial and viral agents. Conditions such as fever that is unresponsive to antibiotic
* Corresponding author at: Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey. Tel.: +90 216 6570606; fax: +90 216 6254545. E-mail addresses: [email protected], [email protected] (A. Binnetoglu).
therapy, unilateral bulging above and lateral to one of the tonsils, bulging on the posterior pharyngeal wall, trismus and torticollis are indicative of deep neck space infections (DNSIs). Peritonsillar, retropharyngeal and parapharyngeal abscesses are complications of DNSI that occur as a result of adjacent spread from local sites. The main strategy for management of acute bacterial tonsillitis is antibiotic therapy, adequate hydration and oral intake, and treatment of pain and fever. If the treatment is delayed or is inadequate, acute bacterial tonsillitis may lead to life-threatening complications associated with DNSI including peritonsillar (49%), retropharyngeal (22%), submandibular (14%), buccal (11%), parapharyngeal space (2%), and canine space (2%) infections [5– 9]. Delayed diagnosis of such complications can lead to increased rates of hospitilization and morbidity. Neutrophils play central roles in the host response to infections and in the development of acute and chronic inflammation [10,11]. Recently, a number of studies have reported that the neutrophilto-lymphocyte ratio (NLR) has potential as a marker of inflammation, both in cardiac and non-cardiac disorders [12–18]. Besides being a valuable biomarker for cardiac diseases, NLR is also a potential marker for inflammatory conditions caused by
http://dx.doi.org/10.1016/j.ijporl.2015.06.016 0165-5876/ß 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
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autoimmune conditions or infection. Early diagnosis and treatment are critical for patients with DNSI, but it may sometimes be challenging to diagnose DNSI early during the course of acute bacterial tonsillitis. Imaging techniques including CT or MRI may help in achieving an accurate diagnosis of the complications, but if NLR could be used as a marker of inflammation, the severity of the tonsillitis and presence of complications, it would ensure early diagnosis and treatment. However, no data are available on the role of NLR in predicting DNSI in cases of acute bacterial tonsillitis. Thus, we aimed to investigate whether NLR may be an independent predictive risk factor for DNSI in a pediatric population with acute bacterial tonsillitis. 2. Materials and methods This study was approved by the Ethical Committee of Marmara University Faculty of Medicine (ID number: 09.2014.0267, Issue date: 18.12.2014). In total, 180 pediatric patients who were admitted to the Otolaryngology Department of Marmara University Hospital from 2010 to 2013 and who were diagnosed with acute bacterial tonsillitis with or without DNSI were retrospectively reviewed. Informed consent was obtained from all the patients. Patients in whom DNSI was suspected underwent complete otolaryngological and radiological imaging studies with CT or MRI. The diagnosis was based on the patient’s detailed history; physical examination; laboratory tests including white blood cell (WBC) count, peripheral blood smear, CRP, RADT, and throat and abscess culture; and also imaging studies in cases of suspected DNSI. A lobulated mass having clear central hypodensity, clear ring enhancement, scalloping of mass wall were accepted as suggestive imaging findings of abscess and then diagnosis were confirmed with aspiration of pus. The exclusion criteria were determined as follows: (a) the patients with a positive for viral antigen detection test in nasopharyngeal aspirate for adenovirus, enterovirus (coxsackieA, rhinovirus), influenza and RSV and other suspected viral disease; (b) the patients manifested with typical clinical picture of infectious mononucleosis, detection of atypical lymphocytosis in peripheral blood smear and positive EBV Viral Capsid Antigen IgM. According to whether DNSI was present, the patients were divided into two groups: acute bacterial tonsillitis without complications (n = 156) (group 1) and acute bacterial tonsillitis with DNSI (n = 24) (group 2). The two groups were evaluated based on the NLR values. Laboratory tests were performed on blood
samples obtained on admission to the hospital. The leukocyte and neutrophil counts were determined using an automated hematology analyzer (Coulter1 LH 780 Hematology Analyzer; Beckman Coulter Inc., Brea, CA, USA). The reference range for the leukocyte count was 4000–10.000/mL. The NLR was determined in all the subjects and compared between group 1 and group 2. 2.1. Statistical analysis Statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS) 15.0 for Windows (SPSS Inc., Chicago, IL, USA). The distribution of variables was assessed using the normality test. Differences between the two groups were analyzed using the Student t-test (variables with parametric distribution) and the Mann–Whitney U-test (variables with nonparametric distribution). Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of NLR for predicting the presence of complications. P < 0.05 was considered to indicate statistical significance. 3. Results 3.1. Patient characteristics and DNSI incidence In total, the data of 180 patients were analyzed. The median age of the patients was 4 years (range, 6 months to 17 years). Of the 180 patients, 95 were male (53%) and 85 were female (47%). There was no significant gender-based difference in the incidence of acute bacterial tonsillitis. Seventeen of the patients had peritonsillar abscess (9.4%); five, parapharyngeal abscess (2.8%); and two, retropharyngeal abscess (1.1%). No other DNSI was found. The most common complication was peritonsillar abscess, followed by parapharyngeal abscess and retropharyngeal abscess. Table 1 3.2. Secondary bacterial infections Of the 180 patients with acute bacterial tonsillitis, 100 were positive for group A beta-hemolytic Streptococcus (GABHS) (55.5%) and 80 (45.5%) were positive for other bacterial agents including group B, C, and G streptococci, Arcanabacterium hemolyticum, Bacterioides spp. and Fusobacterium spp. DNSI was polymicrobial in most cases: 19 patients (79%) were positive for a combination of aerobic and anaerobic organisms including group A beta-hemolytic Streptococcus pyogenes (GABHS), Staphylococcus aureus, Groups C and G Streptococcus, Bacteriodes spp., Fusobacterium
Table 1 Demographics and characteristics of patients. Acute bacterial tonsillitis without DNSI (Group I)
Acute bacterial tonsillitis with DNSI (Group II)
Total
n (156)
n (24)
180
Age
3.9 years (median)
4,65 years(median)
4 years
Gender
Male, 80(51.3%) Female, (48.7%)
Male, 13(54%) Female, 11(46%)
93 87
Complication
0 0 0
Peritonsillar abscess 17 (9.4%) Parapharyngeal abscess 5 (2.8%) Retropharyngeal abscess 2 (1.1%)
17 5 2
Oral intake difficulty Hospitilization
19 (12.2%) 13 patient
24(100%) 24 patient
37
Hospitilization period
1 day
Peritonsillar abscess 3.3 days (range, 1 7) Parapharyngeal abscess 12 days (range, 8 18) Retropharyngeal abscess and 9.5 days (range, 9 10)
Treatment
Antibiotics alone
Surgical drainage and antibiotic therapy
DNSI: deep neck space infection, n = number of patients.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
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spp., and Peptostreptococcus spp., but five patients (21%) were positive for group A beta-hemolytic S. pyogenes (GABHS) alone. 3.3. Treatment and outcome Patients with acute bacterial tonsillitis who did not have any complications (n = 156) were treated with antibiotics alone (86.6%). Patients with acute bacterial tonsillitis who had DNSI (n = 24) were treated with surgical drainage and antibiotic therapy (13.3%). Of the 156 patients who did not have DNSI, 143 were not hospitalized. The remaining 13 patients were hospitalized for 1 day because of inadequate oral intake. The average period of hospitalization was 3.3 days (range, 1–7 days) for peritonsillar abscess, 12 days (range, 8–18 days) for parapharyngeal abscess, and 9.5 days (range, 9–10 days) for retropharyngeal abscess. There was a significant correlation between DNSI and the period of hospitilization (P < 0.05). All the 180 patients were alive at the end of the treatment. Nineteen of the 156 acute bacterial tonsillitis patients without DNSI and all the 24 acute bacterial tonsillitis patients with DNSI complications did not have adequate oral intake (12.2% and 100% respectively). There was a statistically significant correlation between DNSI complications and oral intake in patients with acute bacterial tonsillitis (P < 0.05). 3.4. Predictive value of NLR WBC counts and NLR were higher in the acute bacterial tonsillitis patients with DNSI than in the acute bacterial tonsillitis patients without DNSI. The mean WBC count in group 1 and group 2 was 11.063 (SD, 4.857) and 17.114 (SD, 6.028) respectively, and the median NLR was 1.52 (range, 0.08 11.60) and 12.78 (range, 3 19) respectively. The WBC count and NLR were significantly different between the two groups (P < 0.01). The ROC curves were used to determine the potential of NLR for predicting the presence of complications. The optimum cut-off value of NLR was determined to be 5.4. The sensitivity and specificity of NLR for predicting complications associated with acute bacterial tonsillitis were 96% and 83% respectively (AUC: 0.958). (Fig. 1) The positive and negative predictive value of NLR were 84.96% and 95.4% respectively. 4. Discussion In this study, we have evaluated the predictive value of NLR in diagnosing DNSI in a pediatric population with acute bacterial tonsillitis. We found that NLR had high specificity and sensitivity for predicting DNSI complications associated with acute bacterial tonsillitis. Peritonsillar abscess is the most common complication of acute bacterial tonsillitis, as was observed in our study followed by parapharyngeal and retropharyngeal abscess [19]. Interestingly, parapharyngel abscess was seen more than expected rate as compared the previous studies [1–5]. In recent years, several studies have reported that NLR may be used as marker of inflammation, both in cardiac and non-cardiac disorders [12–18]. Dogan et al. investigated the relationship between NLR and infarct-related arterial patency in patients with ST-segment elevation myocardial infarction. They reported that at admission, NLR was higher in patients with occluded infarct-related arteries than in patients with ST-segment elevation myocardial infarction [12]. Sen et al. studied 138 patients with psoriasis and stated that the NLR levels were also significantly higher in the psoriasis patients, and that the NLR levels increased with increase in the psoriasis area and severity index score [20]. Farah and
Fig. 1. ROC curve for acute bacterial tonsillitis with and without DNSI.
Khamisy–Farah studied 50 patients with Helicobacter pylori infection and found a significant correlation between H. pyroli infection and inflammation on the basis of the NLR value; furthermore, NLR increased as the severity of gastritis associated with the infection increased [21]. With regard to NLR and infections, a recent study by I˙shizuka et al. has also assessed its relationship with gangrenous appendicitis based on an analysis of 314 patients who had undergone open appendectomy; they found that NLR has a significant association with gangrenous appendicitis and disease severity in patients undergoing appendectomy [22]. It has also been shown that high NLR at admission is an independent predictor of in-hospital mortality and central nervous system events in patients with infective endocarditis [23]. Thus, our results further prove the usefulness of NLR as a marker of inflammation, specifically for predicting infectious complications associated with acute bacterial tonsillitis. Our study showed that an NLR cutoff value of 5.4 is significant in differentiating between cases of acute bacterial tonsillitis with DSNI and those without DNSI; this is similar to the value reported by previous studies in which NLR was used as an index in diagnosing H. pyroli associated gastritis, acute appendicitis, psoriasis and infective endocarditis [20–23]. Another expected finding was that the WBC count was also positively correlated with acute bacterial tonsillitis. To the best of our knowledge, no data are available on the role of NLR in acute bacterial tonsillitis patients with DNSI complications in the pediatric population.
5. Conclusions The NLR value was higher in patients with acute bacterial tonsillitis with DNSI than in those with acute bacterial tonsillitis without DSNI. Based on the clinical and laboratory findings, it seems that NLR may be used as a simple, inexpensive and easily assessable laboratory marker of systemic inflammation, and it can help in the early diagnosis and evaluation of DNSI complications in acute bacterial tonsillitis.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
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Declaration of conflict of interest The authors have no potential conflicts of interest to declare. This work was done in Marmara University Hospital. Acknowledgments This work was presented as an oral poster presentation at the 36th Turkish National Congress of Otorhinolaryngology and Head & Neck Surgery, 5th–6th November 2014, Antalya, Turkey. References [1] I. Brook, S. Grimm, R.B. Keibich, Bacteriology of acute periapical abscess in children, J. Endodont. 7 (1981) 378–380. [2] I. Brook, Aerobic and anaerobic bacteriology of peritonsillar abscess in children, Acta Pediatr. Scand. 70 (1981) 831–838. [3] I. Brook, Microbiology of retropharyngeal abscesses in children, Am. J. Dis. Child. 141 (1987) 202–204. [4] Brook, The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection, Rev. Infect. Dis. 6 (1984) 601–607. [5] C.J. Fasano, C. Chudnofsky, P. Vanderbeek, Bilateral peritonsillar abscesses: not your usual sore throat, J. Emerg. Med. 29 (2005) 45–47. [6] M.A. Rubin, R. Gonzales, M.A. Sande, Pharyngitis, sinusitis, otitis, and other upper respiratory tract infections, in: A.S. Fauci, E. Braunwald, D.L. Kasper (Eds.), Harrison’s Principles of Internal Medicine, 17th ed., Mc Graw Hill, New York (NY), 2008, pp. 210–214. [7] B. Brochu, J. Dubois, L. Garel, et al., Complications of ENT infections: pseudoaneurysm of the internal carotid artery, Pediatr. Radiol. 34 (2004) 417–420. [8] C. Galer, E. Holbrook, J. Treves, et al., Grisel’s syndrome: a case report and review of the literature, Int. J. Pediatr. Otorhinolaryngol. 69 (12 (Dec)) (2005) 1689–1692. [9] K. Ungkanont, R.F. Yellon, J.L. Weissman, et al., Head and neck space infections in infants and children, Otolaryngol. Head Neck Surg. 112 (3 (Mar)) (1995) 375–382. [10] A. Mantovani, M.A. Cassatella, C. Costantini, S. Jaillon, Neutrophils in the activation and regulation of innate and adaptive immunity, Nat. Rev. Immunol. 11 (2011) 519–531.
[11] B. Amulic, C. Cazalet, G.L. Hayes, K.D. Metzler, A. Zychlinsky, Neutrophil function: from mechanisms to disease, Annu. Rev. Immunol. 30 (2012) 459– 489. [12] M. Dogan, A. Akyel, M. Bilgin, et al., Can admission neutrophil to lymphocyte ratio predict infarct-related artery patency in ST-segment elevation myocardial infarction, Clin. Appl. Thromb. Hemost. 21 (March (2)) (2015) 172– 176. [13] G.D. Friedman, I. Tekawa, R.H. Grimm, et al., The leucocytecount: correlates and relationship to coronary risk factors: the CARDIA study, Int. J. Epidemiol. 19 (1990) 889–893. [14] F. Goto, T. Tsutumi, M. Arai, et al., Somatic symptoms in those hospitalized for dizziness or vertigo, Nihon Jibiinkoka GakkaiKaiho 113 (2010) 742–750. [15] S. Isaradisaikul, N. Navacharoen, C. Hanprasertpong, et al., Causes and timecourse of vertigo in an ear, nose, and throat clinic, Eur. Arch. Otorhinolaryngol. 267 (2010) 1837–1841. [16] Y. Jin, X. Ye, C. He, et al., Pretreatment neutrophil: lymphocyte ratio predicts survival for patients with metastatic nasopharyngealcarcinoma, Head Neck (2013) [Epub ahead of print]. [17] J. Nunez, E. Nunez, V. Bodi, et al., Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction, Am. J. Cardiol. 101 (2008) 747–752. [18] I. Ozbay, C. Kahraman, H.H. Balikci, C. Kucur, N.K. Kahraman, D.P. Ozkaya, et al., Neutrophil-to-lymphocyte ratio in patients with peripheral vertigo: a prospective controlled clinical study, Am. J. Otolaryngol. 35 (6 (Nov–Dec)) (2014) 699–702. [19] C.B. Del Mar, P.P. Glasziou, A.B. Spinks, Antibiotics for sore throat (systematic review) cochrane acute respiratory infections group, Cochrane Database Syst. Rev. (4) (2006) 000023. [20] B.B. Sen, E.N. Rifaioglu, O. Ekiz, M.U. Inan, T. Sen, N. Sen, Neutrophil to lymphocyte ratio as a measure of systemic inflammation in psoriasis, Cutan. Ocul. Toxicol. 33 (3 (Sep)) (2014) 223–227. [21] R. Farah, R. Khamisy-Farah, Association of neutrophil to lymphocyte ratio with presence and severity of gastritis due to Helicobacter pylori infection, J. Clin. Lab. Anal. 28 (3 (May)) (2014) 219–223. [22] M. Ishizuka, T. Shimizu, K. Kubota, Neutrophil-to-lymphocyte ratio has a close association with gangrenous appendicitis in patients undergoing appendectomy, Int. Surg. 97 (4 (Oct–Dec)) (2012) 299–304. ¨ zcan, A. Is¸leyen, F.N. Bas¸ar, M. Gu¨l, S. Yilmaz, et al., Aydog˘du [23] O. Turak, F. O usefulness of neutrophil-to-lymphocyte ratio to predict in-hospital outcomes in infective endocarditis, Can. J. Cardiol. 29 (12 (Dec)) (2013) 1672–1678.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
PEDOT-7633; No. of Pages 4 International Journal of Pediatric Otorhinolaryngology xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis Tekin Baglam a, Adem Binnetoglu a,*, Ali Cemal Yumusakhuylu a, Fethullah Gerin b, Berat Demir a, Murat Sari a a b
Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey Department of Biochemistry, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 5 January 2015 Received in revised form 10 June 2015 Accepted 13 June 2015 Available online xxx
Objective: The aim of this study was to determine whether the neutrophil-to-lymphocyte ratio (NLR) can be used as a predictor for deep neck space infections (DNSIs) that occur as a complication of acute bacterial tonsillitis in the pediatric population. Materials and methods: We evaluated the NLR values of 180 pediatric patients diagnosed with acute bacterial tonsillitis with or without DNSI who presented to the Otolaryngology Department of Marmara University Hospital between 2010 and 2013. In cases in which DNSI was suspected, the patients underwent complete otolaryngological examination and radiological imaging including CT and MRI. NLR was calculated in all the subjects and was compared between the patients with acute bacterial tonsillitis without DNSI and those with DNSI. Results: With regard to the tonsillitis-related complications, 17 patients had peritonsillar abscess (9.4%); five, parapharyngeal abscess (2.8%); and two, retropharyngeal abscess (1.1%). The mean NLR was significantly higher in the patients of acute bacterial tonsillitis with DNSI (P < 0.05). The optimum cut-off value of NLR was determined to be 5.4. Conclusion: This study is the first to investigate the relationship between NLR and DNSI as a complication of acute bacterial tonsillitis. The results demonstrated that the NLR value could be a potential laboratory parameter for diagnosing DNSIs. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Neutrophil-to-lymphocyte ratio Inflammation Acute bacterial tonsillitis Deep neck infection
1. Introduction Acute tonsillitis is commonly encountered in outpatient ENT clinics, especially in children and young adults. It is usually caused by viral agents and is accompanied by secondary bacterial infections. Acute tonsillitis often occurs secondary to viral infections and is usually a polymicrobial infection that is caused by interaction between the normal oropharyngeal flora and the extrinsic flora [1–4]. The diagnosis of acute tonsillitis is based on the patient’s medical history, physical examination and laboratory studies including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP) level, the rapid antigen detection test (RADT), serological tests and cultures for bacterial and viral agents. Conditions such as fever that is unresponsive to antibiotic
* Corresponding author at: Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey. Tel.: +90 216 6570606; fax: +90 216 6254545. E-mail addresses: [email protected], [email protected] (A. Binnetoglu).
therapy, unilateral bulging above and lateral to one of the tonsils, bulging on the posterior pharyngeal wall, trismus and torticollis are indicative of deep neck space infections (DNSIs). Peritonsillar, retropharyngeal and parapharyngeal abscesses are complications of DNSI that occur as a result of adjacent spread from local sites. The main strategy for management of acute bacterial tonsillitis is antibiotic therapy, adequate hydration and oral intake, and treatment of pain and fever. If the treatment is delayed or is inadequate, acute bacterial tonsillitis may lead to life-threatening complications associated with DNSI including peritonsillar (49%), retropharyngeal (22%), submandibular (14%), buccal (11%), parapharyngeal space (2%), and canine space (2%) infections [5– 9]. Delayed diagnosis of such complications can lead to increased rates of hospitilization and morbidity. Neutrophils play central roles in the host response to infections and in the development of acute and chronic inflammation [10,11]. Recently, a number of studies have reported that the neutrophilto-lymphocyte ratio (NLR) has potential as a marker of inflammation, both in cardiac and non-cardiac disorders [12–18]. Besides being a valuable biomarker for cardiac diseases, NLR is also a potential marker for inflammatory conditions caused by
http://dx.doi.org/10.1016/j.ijporl.2015.06.016 0165-5876/ß 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
G Model
PEDOT-7633; No. of Pages 4 T. Baglam et al. / International Journal of Pediatric Otorhinolaryngology xxx (2015) xxx–xxx
2
autoimmune conditions or infection. Early diagnosis and treatment are critical for patients with DNSI, but it may sometimes be challenging to diagnose DNSI early during the course of acute bacterial tonsillitis. Imaging techniques including CT or MRI may help in achieving an accurate diagnosis of the complications, but if NLR could be used as a marker of inflammation, the severity of the tonsillitis and presence of complications, it would ensure early diagnosis and treatment. However, no data are available on the role of NLR in predicting DNSI in cases of acute bacterial tonsillitis. Thus, we aimed to investigate whether NLR may be an independent predictive risk factor for DNSI in a pediatric population with acute bacterial tonsillitis. 2. Materials and methods This study was approved by the Ethical Committee of Marmara University Faculty of Medicine (ID number: 09.2014.0267, Issue date: 18.12.2014). In total, 180 pediatric patients who were admitted to the Otolaryngology Department of Marmara University Hospital from 2010 to 2013 and who were diagnosed with acute bacterial tonsillitis with or without DNSI were retrospectively reviewed. Informed consent was obtained from all the patients. Patients in whom DNSI was suspected underwent complete otolaryngological and radiological imaging studies with CT or MRI. The diagnosis was based on the patient’s detailed history; physical examination; laboratory tests including white blood cell (WBC) count, peripheral blood smear, CRP, RADT, and throat and abscess culture; and also imaging studies in cases of suspected DNSI. A lobulated mass having clear central hypodensity, clear ring enhancement, scalloping of mass wall were accepted as suggestive imaging findings of abscess and then diagnosis were confirmed with aspiration of pus. The exclusion criteria were determined as follows: (a) the patients with a positive for viral antigen detection test in nasopharyngeal aspirate for adenovirus, enterovirus (coxsackieA, rhinovirus), influenza and RSV and other suspected viral disease; (b) the patients manifested with typical clinical picture of infectious mononucleosis, detection of atypical lymphocytosis in peripheral blood smear and positive EBV Viral Capsid Antigen IgM. According to whether DNSI was present, the patients were divided into two groups: acute bacterial tonsillitis without complications (n = 156) (group 1) and acute bacterial tonsillitis with DNSI (n = 24) (group 2). The two groups were evaluated based on the NLR values. Laboratory tests were performed on blood
samples obtained on admission to the hospital. The leukocyte and neutrophil counts were determined using an automated hematology analyzer (Coulter1 LH 780 Hematology Analyzer; Beckman Coulter Inc., Brea, CA, USA). The reference range for the leukocyte count was 4000–10.000/mL. The NLR was determined in all the subjects and compared between group 1 and group 2. 2.1. Statistical analysis Statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS) 15.0 for Windows (SPSS Inc., Chicago, IL, USA). The distribution of variables was assessed using the normality test. Differences between the two groups were analyzed using the Student t-test (variables with parametric distribution) and the Mann–Whitney U-test (variables with nonparametric distribution). Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of NLR for predicting the presence of complications. P < 0.05 was considered to indicate statistical significance. 3. Results 3.1. Patient characteristics and DNSI incidence In total, the data of 180 patients were analyzed. The median age of the patients was 4 years (range, 6 months to 17 years). Of the 180 patients, 95 were male (53%) and 85 were female (47%). There was no significant gender-based difference in the incidence of acute bacterial tonsillitis. Seventeen of the patients had peritonsillar abscess (9.4%); five, parapharyngeal abscess (2.8%); and two, retropharyngeal abscess (1.1%). No other DNSI was found. The most common complication was peritonsillar abscess, followed by parapharyngeal abscess and retropharyngeal abscess. Table 1 3.2. Secondary bacterial infections Of the 180 patients with acute bacterial tonsillitis, 100 were positive for group A beta-hemolytic Streptococcus (GABHS) (55.5%) and 80 (45.5%) were positive for other bacterial agents including group B, C, and G streptococci, Arcanabacterium hemolyticum, Bacterioides spp. and Fusobacterium spp. DNSI was polymicrobial in most cases: 19 patients (79%) were positive for a combination of aerobic and anaerobic organisms including group A beta-hemolytic Streptococcus pyogenes (GABHS), Staphylococcus aureus, Groups C and G Streptococcus, Bacteriodes spp., Fusobacterium
Table 1 Demographics and characteristics of patients. Acute bacterial tonsillitis without DNSI (Group I)
Acute bacterial tonsillitis with DNSI (Group II)
Total
n (156)
n (24)
180
Age
3.9 years (median)
4,65 years(median)
4 years
Gender
Male, 80(51.3%) Female, (48.7%)
Male, 13(54%) Female, 11(46%)
93 87
Complication
0 0 0
Peritonsillar abscess 17 (9.4%) Parapharyngeal abscess 5 (2.8%) Retropharyngeal abscess 2 (1.1%)
17 5 2
Oral intake difficulty Hospitilization
19 (12.2%) 13 patient
24(100%) 24 patient
37
Hospitilization period
1 day
Peritonsillar abscess 3.3 days (range, 1 7) Parapharyngeal abscess 12 days (range, 8 18) Retropharyngeal abscess and 9.5 days (range, 9 10)
Treatment
Antibiotics alone
Surgical drainage and antibiotic therapy
DNSI: deep neck space infection, n = number of patients.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
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spp., and Peptostreptococcus spp., but five patients (21%) were positive for group A beta-hemolytic S. pyogenes (GABHS) alone. 3.3. Treatment and outcome Patients with acute bacterial tonsillitis who did not have any complications (n = 156) were treated with antibiotics alone (86.6%). Patients with acute bacterial tonsillitis who had DNSI (n = 24) were treated with surgical drainage and antibiotic therapy (13.3%). Of the 156 patients who did not have DNSI, 143 were not hospitalized. The remaining 13 patients were hospitalized for 1 day because of inadequate oral intake. The average period of hospitalization was 3.3 days (range, 1–7 days) for peritonsillar abscess, 12 days (range, 8–18 days) for parapharyngeal abscess, and 9.5 days (range, 9–10 days) for retropharyngeal abscess. There was a significant correlation between DNSI and the period of hospitilization (P < 0.05). All the 180 patients were alive at the end of the treatment. Nineteen of the 156 acute bacterial tonsillitis patients without DNSI and all the 24 acute bacterial tonsillitis patients with DNSI complications did not have adequate oral intake (12.2% and 100% respectively). There was a statistically significant correlation between DNSI complications and oral intake in patients with acute bacterial tonsillitis (P < 0.05). 3.4. Predictive value of NLR WBC counts and NLR were higher in the acute bacterial tonsillitis patients with DNSI than in the acute bacterial tonsillitis patients without DNSI. The mean WBC count in group 1 and group 2 was 11.063 (SD, 4.857) and 17.114 (SD, 6.028) respectively, and the median NLR was 1.52 (range, 0.08 11.60) and 12.78 (range, 3 19) respectively. The WBC count and NLR were significantly different between the two groups (P < 0.01). The ROC curves were used to determine the potential of NLR for predicting the presence of complications. The optimum cut-off value of NLR was determined to be 5.4. The sensitivity and specificity of NLR for predicting complications associated with acute bacterial tonsillitis were 96% and 83% respectively (AUC: 0.958). (Fig. 1) The positive and negative predictive value of NLR were 84.96% and 95.4% respectively. 4. Discussion In this study, we have evaluated the predictive value of NLR in diagnosing DNSI in a pediatric population with acute bacterial tonsillitis. We found that NLR had high specificity and sensitivity for predicting DNSI complications associated with acute bacterial tonsillitis. Peritonsillar abscess is the most common complication of acute bacterial tonsillitis, as was observed in our study followed by parapharyngeal and retropharyngeal abscess [19]. Interestingly, parapharyngel abscess was seen more than expected rate as compared the previous studies [1–5]. In recent years, several studies have reported that NLR may be used as marker of inflammation, both in cardiac and non-cardiac disorders [12–18]. Dogan et al. investigated the relationship between NLR and infarct-related arterial patency in patients with ST-segment elevation myocardial infarction. They reported that at admission, NLR was higher in patients with occluded infarct-related arteries than in patients with ST-segment elevation myocardial infarction [12]. Sen et al. studied 138 patients with psoriasis and stated that the NLR levels were also significantly higher in the psoriasis patients, and that the NLR levels increased with increase in the psoriasis area and severity index score [20]. Farah and
Fig. 1. ROC curve for acute bacterial tonsillitis with and without DNSI.
Khamisy–Farah studied 50 patients with Helicobacter pylori infection and found a significant correlation between H. pyroli infection and inflammation on the basis of the NLR value; furthermore, NLR increased as the severity of gastritis associated with the infection increased [21]. With regard to NLR and infections, a recent study by I˙shizuka et al. has also assessed its relationship with gangrenous appendicitis based on an analysis of 314 patients who had undergone open appendectomy; they found that NLR has a significant association with gangrenous appendicitis and disease severity in patients undergoing appendectomy [22]. It has also been shown that high NLR at admission is an independent predictor of in-hospital mortality and central nervous system events in patients with infective endocarditis [23]. Thus, our results further prove the usefulness of NLR as a marker of inflammation, specifically for predicting infectious complications associated with acute bacterial tonsillitis. Our study showed that an NLR cutoff value of 5.4 is significant in differentiating between cases of acute bacterial tonsillitis with DSNI and those without DNSI; this is similar to the value reported by previous studies in which NLR was used as an index in diagnosing H. pyroli associated gastritis, acute appendicitis, psoriasis and infective endocarditis [20–23]. Another expected finding was that the WBC count was also positively correlated with acute bacterial tonsillitis. To the best of our knowledge, no data are available on the role of NLR in acute bacterial tonsillitis patients with DNSI complications in the pediatric population.
5. Conclusions The NLR value was higher in patients with acute bacterial tonsillitis with DNSI than in those with acute bacterial tonsillitis without DSNI. Based on the clinical and laboratory findings, it seems that NLR may be used as a simple, inexpensive and easily assessable laboratory marker of systemic inflammation, and it can help in the early diagnosis and evaluation of DNSI complications in acute bacterial tonsillitis.
Please cite this article in press as: T. Baglam, et al., Predictive value of the neutrophil-to-lymphocyte ratio in patients with deep neck space infection secondary to acute bacterial tonsillitis, Int. J. Pediatr. Otorhinolaryngol. (2015), http://dx.doi.org/10.1016/ j.ijporl.2015.06.016
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