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Impact of adenotonsillectomy on the quality of life in children with sleep disordered breathing
International Journal of Pediatric Otorhinolaryngology 91 (2016) 105e107
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: http://www.ijporlonline.com/
Impact of adenotonsillectomy on the quality of life in children with sleep disordered breathing Mohd Nazir Othman a, *, Goh Bee See a, Hasniah Abdul Latif b a b
ORL-HNS Department, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia Paediatric Department, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
a r t i c l e i n f o Article history: Received 16 May 2016 Received in revised form 13 October 2016 Accepted 13 October 2016 Available online 15 October 2016
SDB secondary to adenotonsillar hypertrophy and the impact of adenotonsillectomy on their quality of life. It also aimed to look for the concurrent contributing factors for SDB and Oxygen Desaturation Index (ODI) changes following adenotonsillectomy. 3. Material and methods
Keywords: Adenotonsillectomy Children OSA-18 QOL Sleep-disordered breathing
1. Introduction Paediatric sleep disordered breathing (SDB) is a spectrum of breathing abnormalities that occur during sleep. It is known to cause significant cardiovascular and metabolic complications. Untreated disease is believed to affect emotion, cognitive function and neurobehavior of both children and family members that eventually will contribute to a poor quality of life (QOL). Pathophysiology of paediatric SDB is remained complex. Reduction in the upper airway caliber is claimed as the main factor. In children, adenotonsillar hypertrophy is identified as the most common contributor for above condition. Adenotonsillectomy is currently becomes one of the main surgery for paediatric SDB. Therefore, a study should be done to see how far adenotonsillectomy able to improve the quality of life in children with SDB. 2. Objective This study aimed to describe the quality of life in children with
* Corresponding author. E-mail address: [email protected] (M.N. Othman). http://dx.doi.org/10.1016/j.ijporl.2016.10.018 0165-5876/© 2016 Elsevier Ireland Ltd. All rights reserved.
A prospective study was conducted on children aged between 3 and 12 years old who had significant adenotonsillar hypertrophy and SDB symptoms. Those children with known cognitive or behavior problem, neuromuscular disorders, and craniofacial abnormalities were excluded. All participants underwent standard cold instrument adenotonsillectomy. OSA-18 questionnaire was used to assess QOL pre and post adenotonsillectomy. Severity of airflow disturbance was measured by ODI parameter using ApneaLink device. This test was performed in ward at night before the surgery and repeated in ward in 4e6 weeks after surgery. 4. Result From 1st May 2013 to 28th February 2014, a total of 32 children were recruited for the study. All participants completed pre and postoperative OSA-18 questionnaires. Three participants refused for pre operative Apnealink test and 29 participants had performed pre operative Apnealink test. Of 29 participants, 10 had invalid preoperative Apnealink due to technical error and they were not subjected to postoperative test. Six participants had defaulted postoperative Apnealink. Therefore, only 13 participants had successfully completed pre and postoperative Apnealink test. (see Tables 1e5). Preoperatively, the highest ODI recorded was 11.0 and lowest was 0.0. A total of 76.9% of participants had normal ODI result (<5/ hour). Postoperatively, all the 13 participants (100%) showed normal ODI reading. The highest post operative ODI recorded was only 1.2. We noted all those participants with ODI reading above 1.0 had reduction in the reading after the surgery. Median score of both preoperative and postoperative were all within normal range. Nineteen participants (59.4%) had concurrent contributing factor for SDB. Obesity (15.6%) and allergic rhinitis (43.8%) were only concurrent contributing factor detected in this study.and group
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M.N. Othman et al. / International Journal of Pediatric Otorhinolaryngology 91 (2016) 105e107
Table 1 Demographic data and clinical characteristicsa. Characteristics
Number of patients (%)
Age (range 3e12 years old) Gender Ethnicity
BMI
Tonsil grade Adenoid grade
a
8 (6e10) 22 (68.8) 10 (31.2) 29 (90.6) 1 (3.1) 0.0 2 (6.3) 21(65.6) 6 (18.8) 5 (15.6) 8 (25.0) 24 (75.0) 9 (28.1) 20 (62.5) 3 (9.4)
Male Female Malay Chinese Indian Others Normal Overweight Obese II III I II III
5. Discussion
Values are given as median (interquartile range) or No. (%).
Table 2 Distribution of SDB symptoms. Symptoms
Frequency (%)
Snoring Witnessed apnea Choking noise/snorting Restless sleep Frequent awakening Enuresis Unfreshened morning Poor school performance Aggressive behavior Hyperactivity Attention deficit disorder Daytime naps Excessive daytime sleepiness
32(100) 5(15.6) 17(53.1) 29(90.6) 17(53.1) 5(15.6) 13(40.6) 5(15.6) 4(12.5) 2(6.3) 2(6.3) 3(9.4) 1(3.1)
Table 3 Median of pre and postoperative total OSA-18 QOL score according to each domain.
Total OSA-18 score Domains: Sleep disorders Physical distress Emotional distress Diurnal problems Caretaker preoccupation
Preoperative
Postoperative
P value*
57.5 (47e79)
28.5 (24.2e32.75)
0.001
12.5 (9.25e19.0) 14.5 (9.0e18.75) 9.0 (6.0e12.0) 9.0 (6.0e12.5) 14.5 (11.25e19.75)
5.0 6.0 6.0 5.0 6.0
0.001 0.001 0.001 0.001 0.001
(5.0e6.0) (9.0e18.75) (3.0e6.75) (4.0e7.75) (5.0e8.0)
*P significant value < 0.05.
Table 4 Comparison between median of preoperative and postoperative ODI. Preoperative
Postoperative
1.0 (0.0e3.0)
0.0 (0.0e0.0)
without concurrent contributing factor. Either pre or post operative, group without concurrent contributing factor were noted to have lower median of OSA-18 QOL score when compare to group with concurrent contributing factors (Table 5).
This study had successfully described the characteristic of paediatric SDB and the impact of adenotonsillectomy on the quality of life. Preoperatively, only a small percentage of participants presented with symptoms related to emotional and diurnal disorders. Majority of the participants were referred for snoring or symptoms of disturbed sleep. Earlier publications had recognized that snoring and sleep disturbances as the hallmarks for paediatric SDB [1,2]. Only a small portion of paediatric SDB presented with emotional and diurnal disorders [3]. This characteristic is recognized as one of the significant difference between adult and paediatric SDB. This study had proven the improvement in the quality of life in children with SDB after adenotonsillectomy. All domains in OSA-18 QOL showed significant improvement (Table 3). Domain of physical distress, caretaker preoccupation and sleep disorders had shown the highest improvement (Table 3). Major improvement in the domain of caretaker preoccupation indicates that in paediatric SDB, both parents and children are equally affected. This study used ApneaLink device to measure the oxygen desaturation index (ODI) as a reflection of the severity of blood gases disturbances. Ideally, a polysomnography (PSG) should be done to diagnose obstructive sleep apnea (OSA), however it was not done due to limited budget and manpower. Generally our study had showed that most patients had improvement of ODI reading after surgery. We also noted that majority of the participants had normal preoperative ODI. This probably signified that a significant majority number of children referred for SDB have no blood gases disturbance. As many had emphasized that symptoms and clinical assessment of paediatric SDB are much more important in deciding the need for adenotonsillectomy [4,5], therefore an objective assessment, (ApneaLink or PSG) should be reserved for those patients with significant symptoms and risk factors. Hence, in most uncomplicated cases, information from history taking and physical examination are adequate to determine further intervention. This is important for clinical practice in center with lack of proper diagnostic tools. Our study also had shown that concurrent contributing factors for paediatric SDB may influence the outcome on quality of life after adenotonsillectomy. Those patients without concurrent contributing factors were noted to have better OSA-18 QOL score. Allergic rhinitis and obesity were the only concurrent contributing factors identified in this study. Many studies had reported higher incidence for paediatric SDB in children with allergic rhinitis [6,7]. Combination of low cortisol and effects of elevated histamine and inflammatory cells were proposed as the mechanism to reduce upper airway caliber and disrupt normal nocturnal sleep [8,9]. Treating allergic rhinitis had proven to improve the SDB symptoms [10,11].
Table 5 Median score for pre and postoperative OSA-18 score among group with concurrent contributing factor and group without concurrent contributing factor. Group
Preoperative OSA-18
Postoperative OSA-18
With concurrent contributing factor Without concurrent contributing factor
60 (47e79) 57 (44e72)
31 (28e35) 24 (23e27)
M.N. Othman et al. / International Journal of Pediatric Otorhinolaryngology 91 (2016) 105e107
Obesity had been related to paediatric SDB in many previous studies [12e14]. Obesity was claimed to cause the unresolved OSA in obese children after adenotonsillectomy [13]. Increased melanin concentration hormone (MCH) caused by obesity is proposed to affect the hypothalamus to induce hypersomnolence state [15]. Therefore, it is important to identify those patients with concurrent contributing factors and treat them accordingly. 6. Conclusion This study concludes that SDB contributes to a poor quality of life in both parents and children Adenotonsillectomy significantly improves the quality of life in children with SDB caused by adenotonsillar hypertrophy. Presence of concurrent contributing factors may influence the severity of the disease and the treatment outcome. Therefore, in managing paediatric SDB, early referral to ORL team is important. For uncomplicated paediatric SDB, adenotonsillectomy is strongly suggested as the first line of treatment. Funding Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center provided financial support in the form of sleep test funding (FF-019-2013). The sponsor had no role in the design or conduct of this research. Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent e licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964
107
Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in this study. References [1] C. Guilleminault, R. Korobkin, R. Winkle, A review of 50 children with obstructive sleep apnea syndrome, Lung 159 (1981) 275e287. [2] A.H. Messner, R. Pelayo, Pediatric sleep-related breathing disorders, Am. J. Otolaryngol. 21 (2000) 98e107. [3] Deepti Sinha, Christian Guilleminault, Sleep disordered breathing in children, Indian J. Med. Res. 131 (2010) 311e320. [4] Norman R. Friedman, Polysomnography should not Be required both before and after adenotonsillectomy for childhood sleep disordered breathing, J. Clin. Sleep Med. 3 (7) (2007) 678e680. [5] Ron B. Mitchell, Kevin D. Pereira, Norman R. Friedman, Sleep-disordered breathing in children: survey of current practice, Laryngoscope 116 (6) (2006) 956e958. [6] Stacey L. Ishman, David F. Smith, James R. Benke, Mai-Tien Nguyen, Sandra Y. Lin, The prevalence of sleepiness and the risk of sleep-disordered breathing in children with positive allergy test, Int. Forum Allergy & Rhinol. 2 (2) (2012), 39e143. [7] L. Oliveira, C. Gomes, R. Ferreira, Allergy as a risk factor for sleep disordered breathing, Sleep. Med. Dec. 14 (2013) 36e37. [8] M. Tashiro, H. Mochizuki, K. Iwabuchi, Y. Sakurada, M. Itoh, T. Watanabe, Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain, Life Sci. 72 (2002) 409e414. [9] Daphne Koinis-Mitchell, Timothy Craig, Cynthia A. Esteban, Robert B. Klein, Sleep and allergic disease: a summary of the literature and future directions for research, Daphne J. Allergy Clin. Immunol. 130 (6) (2012) 1275e1281. [10] Yong Gi Jung, Hyo Yeol Kim, Jin-Young Min, Hun-Jong Dhong, SeungKyu Chung, Role of intranasal topical steroid in pediatric sleep disordered breathing and influence of allergy, sinusitis, and obesity on treatment outcome, Clin. Exp. Otorhinolaryngol. 4 (1) (2011) 27e32. [11] Leila Kheirandish-Gozal, Oscar Sans Capdevila, Riva Trauman, David Gozal, Plasma C-Reactive protein in nonobese children with obstructive sleep apnea before and after adenotonsillectomy, J. Clin. Sleep. Med. 2 (3) (2006) 301e304. [12] Susan Redline, Peter V. Tishler, Mark Schlucter, Joan Aylor, Kathryn Clark, Gregory Graham, Risk factors for sleep-disordered breathing in children associations with obesity, race, and respiratory problems, Am. J. Respir. Crit. Care Med. 159 (5) (1999) 1527e1532. [13] Dary J. Costa, Ron Mitchell, Adenotonsillectomy for obstructive sleep apnea in obese children: a meta-analysis, Otolaryngol. e Head Neck Surg. 140 (2009) 455e460. [14] Athanasios Kaditis, Leila Kheirandish-Gozal, David Gozal, Algorithm for the diagnosis and treatment of pediatric OSA: a proposal of two pediatric sleep centers, Sleep. Med. 13 (3) (2012) 217e222. [15] Lori A. Panossian, Sigrid C. Veasey, Daytime sleepiness in obesity: mechanisms beyond obstructive sleep apneada review, Sleep. Med. 35 (5) (2012) 605e615.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: http://www.ijporlonline.com/
Impact of adenotonsillectomy on the quality of life in children with sleep disordered breathing Mohd Nazir Othman a, *, Goh Bee See a, Hasniah Abdul Latif b a b
ORL-HNS Department, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia Paediatric Department, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
a r t i c l e i n f o Article history: Received 16 May 2016 Received in revised form 13 October 2016 Accepted 13 October 2016 Available online 15 October 2016
SDB secondary to adenotonsillar hypertrophy and the impact of adenotonsillectomy on their quality of life. It also aimed to look for the concurrent contributing factors for SDB and Oxygen Desaturation Index (ODI) changes following adenotonsillectomy. 3. Material and methods
Keywords: Adenotonsillectomy Children OSA-18 QOL Sleep-disordered breathing
1. Introduction Paediatric sleep disordered breathing (SDB) is a spectrum of breathing abnormalities that occur during sleep. It is known to cause significant cardiovascular and metabolic complications. Untreated disease is believed to affect emotion, cognitive function and neurobehavior of both children and family members that eventually will contribute to a poor quality of life (QOL). Pathophysiology of paediatric SDB is remained complex. Reduction in the upper airway caliber is claimed as the main factor. In children, adenotonsillar hypertrophy is identified as the most common contributor for above condition. Adenotonsillectomy is currently becomes one of the main surgery for paediatric SDB. Therefore, a study should be done to see how far adenotonsillectomy able to improve the quality of life in children with SDB. 2. Objective This study aimed to describe the quality of life in children with
* Corresponding author. E-mail address: [email protected] (M.N. Othman). http://dx.doi.org/10.1016/j.ijporl.2016.10.018 0165-5876/© 2016 Elsevier Ireland Ltd. All rights reserved.
A prospective study was conducted on children aged between 3 and 12 years old who had significant adenotonsillar hypertrophy and SDB symptoms. Those children with known cognitive or behavior problem, neuromuscular disorders, and craniofacial abnormalities were excluded. All participants underwent standard cold instrument adenotonsillectomy. OSA-18 questionnaire was used to assess QOL pre and post adenotonsillectomy. Severity of airflow disturbance was measured by ODI parameter using ApneaLink device. This test was performed in ward at night before the surgery and repeated in ward in 4e6 weeks after surgery. 4. Result From 1st May 2013 to 28th February 2014, a total of 32 children were recruited for the study. All participants completed pre and postoperative OSA-18 questionnaires. Three participants refused for pre operative Apnealink test and 29 participants had performed pre operative Apnealink test. Of 29 participants, 10 had invalid preoperative Apnealink due to technical error and they were not subjected to postoperative test. Six participants had defaulted postoperative Apnealink. Therefore, only 13 participants had successfully completed pre and postoperative Apnealink test. (see Tables 1e5). Preoperatively, the highest ODI recorded was 11.0 and lowest was 0.0. A total of 76.9% of participants had normal ODI result (<5/ hour). Postoperatively, all the 13 participants (100%) showed normal ODI reading. The highest post operative ODI recorded was only 1.2. We noted all those participants with ODI reading above 1.0 had reduction in the reading after the surgery. Median score of both preoperative and postoperative were all within normal range. Nineteen participants (59.4%) had concurrent contributing factor for SDB. Obesity (15.6%) and allergic rhinitis (43.8%) were only concurrent contributing factor detected in this study.and group
106
M.N. Othman et al. / International Journal of Pediatric Otorhinolaryngology 91 (2016) 105e107
Table 1 Demographic data and clinical characteristicsa. Characteristics
Number of patients (%)
Age (range 3e12 years old) Gender Ethnicity
BMI
Tonsil grade Adenoid grade
a
8 (6e10) 22 (68.8) 10 (31.2) 29 (90.6) 1 (3.1) 0.0 2 (6.3) 21(65.6) 6 (18.8) 5 (15.6) 8 (25.0) 24 (75.0) 9 (28.1) 20 (62.5) 3 (9.4)
Male Female Malay Chinese Indian Others Normal Overweight Obese II III I II III
5. Discussion
Values are given as median (interquartile range) or No. (%).
Table 2 Distribution of SDB symptoms. Symptoms
Frequency (%)
Snoring Witnessed apnea Choking noise/snorting Restless sleep Frequent awakening Enuresis Unfreshened morning Poor school performance Aggressive behavior Hyperactivity Attention deficit disorder Daytime naps Excessive daytime sleepiness
32(100) 5(15.6) 17(53.1) 29(90.6) 17(53.1) 5(15.6) 13(40.6) 5(15.6) 4(12.5) 2(6.3) 2(6.3) 3(9.4) 1(3.1)
Table 3 Median of pre and postoperative total OSA-18 QOL score according to each domain.
Total OSA-18 score Domains: Sleep disorders Physical distress Emotional distress Diurnal problems Caretaker preoccupation
Preoperative
Postoperative
P value*
57.5 (47e79)
28.5 (24.2e32.75)
0.001
12.5 (9.25e19.0) 14.5 (9.0e18.75) 9.0 (6.0e12.0) 9.0 (6.0e12.5) 14.5 (11.25e19.75)
5.0 6.0 6.0 5.0 6.0
0.001 0.001 0.001 0.001 0.001
(5.0e6.0) (9.0e18.75) (3.0e6.75) (4.0e7.75) (5.0e8.0)
*P significant value < 0.05.
Table 4 Comparison between median of preoperative and postoperative ODI. Preoperative
Postoperative
1.0 (0.0e3.0)
0.0 (0.0e0.0)
without concurrent contributing factor. Either pre or post operative, group without concurrent contributing factor were noted to have lower median of OSA-18 QOL score when compare to group with concurrent contributing factors (Table 5).
This study had successfully described the characteristic of paediatric SDB and the impact of adenotonsillectomy on the quality of life. Preoperatively, only a small percentage of participants presented with symptoms related to emotional and diurnal disorders. Majority of the participants were referred for snoring or symptoms of disturbed sleep. Earlier publications had recognized that snoring and sleep disturbances as the hallmarks for paediatric SDB [1,2]. Only a small portion of paediatric SDB presented with emotional and diurnal disorders [3]. This characteristic is recognized as one of the significant difference between adult and paediatric SDB. This study had proven the improvement in the quality of life in children with SDB after adenotonsillectomy. All domains in OSA-18 QOL showed significant improvement (Table 3). Domain of physical distress, caretaker preoccupation and sleep disorders had shown the highest improvement (Table 3). Major improvement in the domain of caretaker preoccupation indicates that in paediatric SDB, both parents and children are equally affected. This study used ApneaLink device to measure the oxygen desaturation index (ODI) as a reflection of the severity of blood gases disturbances. Ideally, a polysomnography (PSG) should be done to diagnose obstructive sleep apnea (OSA), however it was not done due to limited budget and manpower. Generally our study had showed that most patients had improvement of ODI reading after surgery. We also noted that majority of the participants had normal preoperative ODI. This probably signified that a significant majority number of children referred for SDB have no blood gases disturbance. As many had emphasized that symptoms and clinical assessment of paediatric SDB are much more important in deciding the need for adenotonsillectomy [4,5], therefore an objective assessment, (ApneaLink or PSG) should be reserved for those patients with significant symptoms and risk factors. Hence, in most uncomplicated cases, information from history taking and physical examination are adequate to determine further intervention. This is important for clinical practice in center with lack of proper diagnostic tools. Our study also had shown that concurrent contributing factors for paediatric SDB may influence the outcome on quality of life after adenotonsillectomy. Those patients without concurrent contributing factors were noted to have better OSA-18 QOL score. Allergic rhinitis and obesity were the only concurrent contributing factors identified in this study. Many studies had reported higher incidence for paediatric SDB in children with allergic rhinitis [6,7]. Combination of low cortisol and effects of elevated histamine and inflammatory cells were proposed as the mechanism to reduce upper airway caliber and disrupt normal nocturnal sleep [8,9]. Treating allergic rhinitis had proven to improve the SDB symptoms [10,11].
Table 5 Median score for pre and postoperative OSA-18 score among group with concurrent contributing factor and group without concurrent contributing factor. Group
Preoperative OSA-18
Postoperative OSA-18
With concurrent contributing factor Without concurrent contributing factor
60 (47e79) 57 (44e72)
31 (28e35) 24 (23e27)
M.N. Othman et al. / International Journal of Pediatric Otorhinolaryngology 91 (2016) 105e107
Obesity had been related to paediatric SDB in many previous studies [12e14]. Obesity was claimed to cause the unresolved OSA in obese children after adenotonsillectomy [13]. Increased melanin concentration hormone (MCH) caused by obesity is proposed to affect the hypothalamus to induce hypersomnolence state [15]. Therefore, it is important to identify those patients with concurrent contributing factors and treat them accordingly. 6. Conclusion This study concludes that SDB contributes to a poor quality of life in both parents and children Adenotonsillectomy significantly improves the quality of life in children with SDB caused by adenotonsillar hypertrophy. Presence of concurrent contributing factors may influence the severity of the disease and the treatment outcome. Therefore, in managing paediatric SDB, early referral to ORL team is important. For uncomplicated paediatric SDB, adenotonsillectomy is strongly suggested as the first line of treatment. Funding Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center provided financial support in the form of sleep test funding (FF-019-2013). The sponsor had no role in the design or conduct of this research. Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent e licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964
107
Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in this study. References [1] C. Guilleminault, R. Korobkin, R. Winkle, A review of 50 children with obstructive sleep apnea syndrome, Lung 159 (1981) 275e287. [2] A.H. Messner, R. Pelayo, Pediatric sleep-related breathing disorders, Am. J. Otolaryngol. 21 (2000) 98e107. [3] Deepti Sinha, Christian Guilleminault, Sleep disordered breathing in children, Indian J. Med. Res. 131 (2010) 311e320. [4] Norman R. Friedman, Polysomnography should not Be required both before and after adenotonsillectomy for childhood sleep disordered breathing, J. Clin. Sleep Med. 3 (7) (2007) 678e680. [5] Ron B. Mitchell, Kevin D. Pereira, Norman R. Friedman, Sleep-disordered breathing in children: survey of current practice, Laryngoscope 116 (6) (2006) 956e958. [6] Stacey L. Ishman, David F. Smith, James R. Benke, Mai-Tien Nguyen, Sandra Y. Lin, The prevalence of sleepiness and the risk of sleep-disordered breathing in children with positive allergy test, Int. Forum Allergy & Rhinol. 2 (2) (2012), 39e143. [7] L. Oliveira, C. Gomes, R. Ferreira, Allergy as a risk factor for sleep disordered breathing, Sleep. Med. Dec. 14 (2013) 36e37. [8] M. Tashiro, H. Mochizuki, K. Iwabuchi, Y. Sakurada, M. Itoh, T. Watanabe, Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain, Life Sci. 72 (2002) 409e414. [9] Daphne Koinis-Mitchell, Timothy Craig, Cynthia A. Esteban, Robert B. Klein, Sleep and allergic disease: a summary of the literature and future directions for research, Daphne J. Allergy Clin. Immunol. 130 (6) (2012) 1275e1281. [10] Yong Gi Jung, Hyo Yeol Kim, Jin-Young Min, Hun-Jong Dhong, SeungKyu Chung, Role of intranasal topical steroid in pediatric sleep disordered breathing and influence of allergy, sinusitis, and obesity on treatment outcome, Clin. Exp. Otorhinolaryngol. 4 (1) (2011) 27e32. [11] Leila Kheirandish-Gozal, Oscar Sans Capdevila, Riva Trauman, David Gozal, Plasma C-Reactive protein in nonobese children with obstructive sleep apnea before and after adenotonsillectomy, J. Clin. Sleep. Med. 2 (3) (2006) 301e304. [12] Susan Redline, Peter V. Tishler, Mark Schlucter, Joan Aylor, Kathryn Clark, Gregory Graham, Risk factors for sleep-disordered breathing in children associations with obesity, race, and respiratory problems, Am. J. Respir. Crit. Care Med. 159 (5) (1999) 1527e1532. [13] Dary J. Costa, Ron Mitchell, Adenotonsillectomy for obstructive sleep apnea in obese children: a meta-analysis, Otolaryngol. e Head Neck Surg. 140 (2009) 455e460. [14] Athanasios Kaditis, Leila Kheirandish-Gozal, David Gozal, Algorithm for the diagnosis and treatment of pediatric OSA: a proposal of two pediatric sleep centers, Sleep. Med. 13 (3) (2012) 217e222. [15] Lori A. Panossian, Sigrid C. Veasey, Daytime sleepiness in obesity: mechanisms beyond obstructive sleep apneada review, Sleep. Med. 35 (5) (2012) 605e615.