Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children.

BACKGROUND: Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children. OBJECTIVE: Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency. METHODS: We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository. RESULTS: Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth. CONCLUSION: These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.

Weighing in on asthma: Insights on BMI, magnesium, and hospitalizations from the Ohio Pediatric Asthma Repository.

Objective: Little is known about weight status and its effects on clinical course during hospitalization for asthma exacerbation. We sought to evaluate associations between weight status, specifically body mass index (BMI), with inpatient clinical course and clinical history.Methods: We retrospectively analyzed data from 2012 to 2013 on children hospitalized for asthma exacerbation in a state-wide longitudinal cohort, the Ohio Pediatric Asthma Repository. We examined BMI continuously (z scores) and categorically, comparing overweight and obese (Ov/Ob) to non-overweight and non-obese (nOv/nOb) children. We used linear mixed models controlling for site effects to determine if BMI was related to length of stay, as determined by physiologic readiness for discharge (PRD), defined as time to albuterol spaced every 4 h, need for nonstandard care or clinical history.Results: Across six hospitals, 874 children were included in analyses. BMI was positively associated with PRD (p=.008) but this increase was unlikely to be clinically significant. Ov/Ob children were more likely than nOv/nOb to require nonstandard care with repeat magnesium dosing in intensive care after dosing in the emergency department (OR = 3.23, 95%CI 1.39-7.78). Hospitalization in the year prior to enrollment was positively associated with BMI percentile (73.3 vs. 66.0, p=.028). Sleep disordered breathing was also associated with higher BMI percentile (78.2 vs. 65.9; p=.0013).Conclusions: Ov/Ob children had similar PRD to nOv/nOb children and were prone to repeat magnesium dosing. Previous hospitalization for exacerbation was positively associated with increasing BMI percentile. Additional research should investigate differential magnesium use by weight status, quantifying risks and benefits.

Determination of Personalized Asthma Triggers From Multimodal Sensing and a Mobile App: Observational Study.

BACKGROUND: Asthma is a chronic pulmonary disease with multiple triggers. It can be managed by strict adherence to an asthma care plan and by avoiding these triggers. Clinicians cannot continuously monitor their patients' environment and their adherence to an asthma care plan, which poses a significant challenge for asthma management. OBJECTIVE: In this study, pediatric patients were continuously monitored using low-cost sensors to collect asthma-relevant information. The objective of this study was to assess whether kHealth kit, which contains low-cost sensors, can identify personalized triggers and provide actionable insights to clinicians for the development of a tailored asthma care plan. METHODS: The kHealth asthma kit was developed to continuously track the symptoms of asthma in pediatric patients and monitor the patients' environment and adherence to their care plan for either 1 or 3 months. The kit consists of an Android app-based questionnaire to collect information on asthma symptoms and medication intake, Fitbit to track sleep and activity, the Peak Flow meter to monitor lung functions, and Foobot to monitor indoor air quality. The data on the patient's outdoor environment were collected using third-party Web services based on the patient's zip code. To date, 107 patients consented to participate in the study and were recruited from the Dayton Children's Hospital, of which 83 patients completed the study as instructed. RESULTS: Patient-generated health data from the 83 patients who completed the study were included in the cohort-level analysis. Of the 19% (16/83) of patients deployed in spring, the symptoms of 63% (10/16) and 19% (3/16) of patients suggested pollen and particulate matter (PM2.5), respectively, to be their major asthma triggers. Of the 17% (14/83) of patients deployed in fall, symptoms of 29% (4/17) and 21% (3/17) of patients suggested pollen and PM2.5, respectively, to be their major triggers. Among the 28% (23/83) of patients deployed in winter, PM2.5 was identified as the major trigger for 83% (19/23) of patients. Similar correlations were not observed between asthma symptoms and factors such as ozone level, temperature, and humidity. Furthermore, 1 patient from each season was chosen to explain, in detail, his or her personalized triggers by observing temporal associations between triggers and asthma symptoms gathered using the kHealth asthma kit. CONCLUSIONS: The continuous monitoring of pediatric asthma patients using the kHealth asthma kit generates insights on the relationship between their asthma symptoms and triggers across different seasons. This can ultimately inform personalized asthma management and intervention plans.

kBot: Knowledge-enabled Personalized Chatbot for Asthma Self-Management.

There is a well-recognized need for a shift to proactive asthma care given the impact asthma has on overall healthcare costs. The demand for continuous monitoring of patient's adherence to the medication care plan, assessment of environmental triggers, and management of asthma can be challenging in traditional clinical settings and taxing on clinical professionals. Recent years have seen a robust growth of general purpose conversational systems. However, they lack the capabilities to support applications such an individual's health, which requires the ability to contextualize, learn interactively, and provide the proper hyper-personalization needed to hold meaningful conversations. In this paper, we present kBot, a knowledge-enabled personalized chatbot system designed for health applications and adapted to help pediatric asthmatic patients (age 8 to 15) to better control their asthma. Its core functionalities include continuous monitoring of the patient's medication adherence and tracking of relevant health signals and environment data. kBot takes the form of an Android application with a frontend chat interface capable of conversing in both text and voice, and a backend cloud-based server application that handles data collection, processing, and dialogue management. It achieves contextualization by piecing together domain knowledge from online sources and inputs from our clinical partners. The personalization aspect is derived from patient answering questionnaires and day-to-day conversations. kBOT's preliminary evaluation focused on chatbot quality, technology acceptance, and system usability involved eight asthma clinicians and eight researchers. For both groups, kBot achieved an overall technology acceptance value of greater than 8 on the 11-point Likert scale and a mean System Usability Score (SUS) greater than 80.

"How Is My Child's Asthma?" Digital Phenotype and Actionable Insights for Pediatric Asthma.

Background: In the traditional asthma management protocol, a child meets with a clinician infrequently, once in 3 to 6 months, and is assessed using the Asthma Control Test questionnaire. This information is inadequate for timely determination of asthma control, compliance, precise diagnosis of the cause, and assessing the effectiveness of the treatment plan. The continuous monitoring and improved tracking of the child's symptoms, activities, sleep, and treatment adherence can allow precise determination of asthma triggers and a reliable assessment of medication compliance and effectiveness. Digital phenotyping refers to moment-by-moment quantification of the individual-level human phenotype in situ using data from personal digital devices, in particular, mobile phones. The kHealth kit consists of a mobile app, provided on an Android tablet, that asks timely and contextually relevant questions related to asthma symptoms, medication intake, reduced activity because of symptoms, and nighttime awakenings; a Fitbit to monitor activity and sleep; a Microlife Peak Flow Meter to monitor the peak expiratory flow and forced exhaled volume in 1 second; and a Foobot to monitor indoor air quality. The kHealth cloud stores personal health data and environmental data collected using Web services. The kHealth Dashboard interactively visualizes the collected data. Objective: The objective of this study was to discuss the usability and feasibility of collecting clinically relevant data to help clinicians diagnose or intervene in a child's care plan by using the kHealth system for continuous and comprehensive monitoring of child's symptoms, activity, sleep pattern, environmental triggers, and compliance. The kHealth system helps in deriving actionable insights to help manage asthma at both the personal and cohort levels. The Digital Phenotype Score and Controller Compliance Score introduced in the study are the basis of ongoing work on addressing personalized asthma care and answer questions such as, "How can I help my child better adhere to care instructions and reduce future exacerbation?" Methods: The Digital Phenotype Score and Controller Compliance Score summarize the child's condition from the data collected using the kHealth kit to provide actionable insights. The Digital Phenotype Score formalizes the asthma control level using data about symptoms, rescue medication usage, activity level, and sleep pattern. The Compliance Score captures how well the child is complying with the treatment protocol. We monitored and analyzed data for 95 children, each recruited for a 1- or 3-month-long study. The Asthma Control Test scores obtained from the medical records of 57 children were used to validate the asthma control levels calculated using the Digital Phenotype Scores. Results: At the cohort level, we found asthma was very poorly controlled in 37% (30/82) of the children, not well controlled in 26% (21/82), and well controlled in 38% (31/82). Among the very poorly controlled children (n=30), we found 30% (9/30) were highly compliant toward their controller medication intake-suggesting a re-evaluation for change in medication or dosage-whereas 50% (15/30) were poorly compliant and candidates for a more timely intervention to improve compliance to mitigate their situation. We observed a negative Kendall Tau correlation between Asthma Control Test scores and Digital Phenotype Score as -0.509 (P<.01). Conclusions: kHealth kit is suitable for the collection of clinically relevant information from pediatric patients. Furthermore, Digital Phenotype Score and Controller Compliance Score, computed based on the continuous digital monitoring, provide the clinician with timely and detailed evidence of a child's asthma-related condition when compared with the Asthma Control Test scores taken infrequently during clinic visits.

Investigation of an Indoor Air Quality Sensor for Asthma Management in Children.

Monitoring indoor air quality is critical because Americans spend 93% of their life indoors, and around 6.3 million children suffer from asthma. We want to passively and unobtrusively monitor the asthma patient's environment to detect the presence of two asthma-exacerbating activities: smoking and cooking using the Foobot sensor. We propose a data-driven approach to develop a continuous monitoring-activity detection system aimed at understanding and improving indoor air quality in asthma management. In this study, we were successfully able to detect a high concentration of particulate matter, volatile organic compounds, and carbon dioxide during cooking and smoking activities. We detected 1) smoking with an error rate of 1%; 2) cooking with an error rate of 11%; and 3) obtained an overall 95.7% percent accuracy classification across all events (control, cooking and smoking). Such a system will allow doctors and clinicians to correlate potential asthma symptoms and exacerbation reports from patients with environmental factors without having to personally be present.

The respiratory management of patients with duchenne muscular dystrophy: a DMD care considerations working group specialty article.

In 2001, the Muscular Dystrophy Community Assistance, Research and Education Amendments (MD-CARE Act) was enacted, which directed federal agencies to coordinate the development of treatments and cures for muscular dystrophy. As part of the mandate, the Centers for Disease Control and Prevention (CDC) initiated surveillance and educational activities, which included supporting development of care considerations for Duchenne muscular dystrophy (DMD) utilizing the RAND/UCLA Appropriateness Method (RAM). This document represents the consensus recommendations of the project's 10-member Respiratory Panel and includes advice on necessary equipment, procedures and diagnostics; and a structured approach to the assessment and management of the respiratory complications of DMD via assessment of symptoms of hypoventilation and identification of specific thresholds of forced vital capacity, peak cough flow and maximum expiratory pressure. The document includes a set of Figures adaptable as "pocket guides" to aid clinicians. This article is an expansion of the respiratory component of the multi-specialty article originally appearing in Lancet Neurology, comprising respiratory recommendations from the CDC Care Considerations project.

Influence of gender on pharyngeal airway length in obese adolescents.

OBJECTIVES: Although pharyngeal airway length has been implicated in an increased male predisposition for obstructive sleep apnea (OSA) in adults, data in obese children and adolescents are lacking. Our objective was to determine the influence of gender on pharyngeal airway length in obese adolescents, and to apply computational simulations to better understand the effect of pharyngeal airway length on the airway's predisposition to collapse in this select group. METHODS: Obese subjects without OSA were recruited from our Sleep Center. Their pharyngeal airway length was measured on midline sagittal magnetic resonance images as the distance between the hard palate and the base of the epiglottis. Computational fluid dynamics analysis was used to study the effect of pharyngeal airway length on airflow characteristics. The gender groups were compared for anthropometric measurements and pharyngeal airway length by an unpaired Student's t-test. RESULTS: Our study group included 18 female and 16 male obese adolescents with a mean (+/-SD) age of 14.7 +/- 2.3 years and a mean body mass index of 38.9 +/- 6.9 kg/m2. The groups did not differ in age, body weight, or normalized pharyngeal airway length (0.44 +/- 0.08 mm/cm in girls versus 0.44 +/- 0.11 mm/cm in boys; p = 0.9). The computational fluid dynamics simulation indicated that the 3-dimensional flow field and airway wall pressures were not significantly affected by pharyngeal airway lengthening of up to 10 mm. CONCLUSIONS: Our results indicate that in obese adolescents, there is no influence of gender on pharyngeal airway length, and pharyngeal airway length alone does not significantly affect the airway's predisposition to collapse. These findings suggest that pharyngeal airway length may not explain the increased male gender predisposition for OSA in this select group.

Validation of computational fluid dynamics methodology used for human upper airway flow simulations.

An anatomically accurate human upper airway model was constructed from multiple magnetic resonance imaging axial scans. This model was used to conduct detailed Computational Fluid Dynamics (CFD) simulations during expiration, to investigate the fluid flow in the airway regions where obstruction could occur. An identical physical model of the same airway was built using stereo lithography. Pressure and velocity measurements were conducted in the physical model. Both simulations and experiments were performed at a peak expiratory flow rate of 200 L/min. Several different numerical approaches within the FLUENT commercial software framework were used in the simulations; unsteady Large Eddy Simulation (LES), steady Reynolds-Averaged Navier-Stokes (RANS) with two-equation turbulence models (i.e. k-epsilon, standard k-omega, and k-omega Shear Stress Transport (SST)) and with one-equation Spalart-Allmaras model. The CFD predictions of the average wall static pressures at different locations along the airway wall were favorably compared with the experimental data. Among all the approaches, standard k-omega turbulence model resulted in the best agreement with the static pressure measurements, with an average error of approximately 20% over all ports. The highest positive pressures were observed in the retroglossal regions below the epiglottis, while the lowest negative pressures were recorded in the retropalatal region. The latter is a result of the airflow acceleration in the narrow retropalatal region. The largest pressure drop was observed at the tip of the soft palate. This location has the smallest cross section of the airway. The good agreement between the computations and the experimental results suggest that CFD simulations can be used to accurately compute aerodynamic flow characteristics of the upper airway.

Survival probabilities of patients with childhood spinal muscle atrophy.

OBJECTIVE: Medical and technological advances over the past 2 decades have resulted in improved patient care for children with spinal muscular atrophy (SMA). The objective of the present study was to describe changes in the life expectancy of pediatric patients with SMA over time and to compare these findings with previously reported survival patterns. METHODS: Medical records of all patients diagnosed with SMA over a 16-year period (1989-2005) at Cincinnati Children's Hospital Medical Center were reviewed. Data pertaining to date of birth, type of SMA, medical and surgical interventions, pulmonary complications, and date of death were obtained. RESULTS: Kaplan-Meier survival analyses showed a significant improvement in survival probabilities in the severest form of SMA. CONCLUSIONS: We found a positive trend in the survival of patients with severe SMA. Although we cannot attribute this trend to any single factor, it is likely that advances in pulmonary care and aggressive nutritional support have played a significant role.

Adolescent paraplegia, morbid obesity, and pickwickian syndrome: outcome of gastric bypass surgery.

Loss of mobility, such as what occurs as a consequence of spinal cord injury or malformation, is a risk factor for excess weight gain and can confound weight management efforts. Despite well-documented outcomes of bariatric surgery in ambulatory patients, little information is available regarding weight loss surgery in adult or adolescent paraplegic patients. A 15-year-old adolescent boy with a body mass index of 60 kg/m(2) and complete paraplegia caused by spina bifida developed metabolic dysfunction, severe obstructive sleep apnea, and hypoxemia syndrome. In an effort to avoid a tracheostomy for worsening pickwickian syndrome, he was referred for weight loss surgery. Laparoscopic Roux-en-Y gastric bypass surgery was safely performed and resulted in loss of 55% of body weight (83.8% excess weight loss) for 2 years. Risk factors for cardiovascular disease markedly improved, and polysomnography demonstrated complete reversal of sleep apnea with substantial subjective improvement in daytime breathlessness and quality of life. Body composition analysis demonstrated preferential reduction in body fat mass compared with lean mass, without detrimental effect on bone mineral density. This case illustrates that paraplegia does not necessarily impair either weight loss efficacy or comorbidity resolution after Roux-en-Y gastric bypass surgery.

Relative rather than absolute macroglossia in patients with Down syndrome: implications for treatment of obstructive sleep apnea.

BACKGROUND: Children with Down syndrome are described as having macroglossia as well as midface hypoplasia. We reviewed anatomic parameters on MRI to determine whether adolescents with Down syndrome have true macroglossia or relatively large tongues compared to the small size of their oral cavity. This has implications for the treatment of obstructive sleep apnea, which occurs at a relatively high rate among patients with Down syndrome. OBJECTIVE: To determine whether adolescents with Down syndrome have relative rather than true macroglossia. MATERIALS AND METHODS: On sagittal and axial MR images, parameters for tongue size (area in sagittal midline), the bony craniofacial confines of the retroglossal pharynx (distance between the mandibular rami and distance between the posterior aspect of the mental mandible and the anterior aspect of the spine), and the size of the tongue relative to the craniofacial bony parameters [tongue area/(transverse diameter x anterior-to-posterior diameter)] were compared between 16 patients with Down syndrome and 16 age- and gender-matched controls. RESULTS: The tongue area was significantly smaller in patients with Down syndrome (2,432 mm2) than in the control patients (2,767 mm2; P=0.02). The craniofacial bony parameters were also smaller in patients with Down syndrome than in the controls (left-right 69.8 vs. 80.1 mm, P<0.001; anterior-posterior 64.2 vs. 74.9 mm, P<0.001). However, the size of the tongue relative to the craniofacial parameters was larger in the patients with Down syndrome (0.54) than in the controls (0.46; P<0.001). CONCLUSION: Children with Down syndrome do not have true macroglossia but have relatively large tongues compared to the bony confines of the oral cavity.

Large Eddy Simulation and Reynolds-Averaged Navier-Stokes modeling of flow in a realistic pharyngeal airway model: an investigation of obstructive sleep apnea.

Computational fluid dynamics techniques employing primarily steady Reynolds-Averaged Navier-Stokes (RANS) methodology have been recently used to characterize the transitional/turbulent flow field in human airways. The use of RANS implies that flow phenomena are averaged over time, the flow dynamics not being captured. Further, RANS uses two-equation turbulence models that are not adequate for predicting anisotropic flows, flows with high streamline curvature, or flows where separation occurs. A more accurate approach for such flow situations that occur in the human airway is Large Eddy Simulation (LES). The paper considers flow modeling in a pharyngeal airway model reconstructed from cross-sectional magnetic resonance scans of a patient with obstructive sleep apnea. The airway model is characterized by a maximum narrowing at the site of retropalatal pharynx. Two flow-modeling strategies are employed: steady RANS and the LES approach. In the RANS modeling framework both k-epsilon and k-omega turbulence models are used. The paper discusses the differences between the airflow characteristics obtained from the RANS and LES calculations. The largest discrepancies were found in the axial velocity distributions downstream of the minimum cross-sectional area. This region is characterized by flow separation and large radial velocity gradients across the developed shear layers. The largest difference in static pressure distributions on the airway walls was found between the LES and the k-epsilon data at the site of maximum narrowing in the retropalatal pharynx.

Computational fluid dynamics analysis of upper airway reconstructed from magnetic resonance imaging data.

OBJECTIVES: We performed flow computations on an accurate upper airway model in a patient with obstructive sleep apnea and computed the velocity, static pressure, and wall shear stress distribution in the model. METHODS: Cartesian coordinates for airway boundaries were determined from cross-sectional magnetic resonance images, and a 3-dimensional computational model of the upper airway was constructed. Flow simulations were then performed within a FLUENT commercial software framework. Four different flow conditions were simulated during inspiration, assuming the steady-state condition. The results were analyzed from the perspectives of velocity, static pressure, and wall shear stress distribution. RESULTS: We observed that the highest axial velocity was at the site of minimum cross-sectional area (retropalatal pharynx) resulting in the lowest level of wall static pressure. The highest wall shear stresses were at the same location. The pressure drop was significantly larger for higher flow rates than for lower flow rates. CONCLUSIONS: Our results indicate that the presence of airway narrowing, through change in the flow characteristics that result in increased flow velocity and reduced static pressure, can itself increase airway collapsibility. Additionally, the effects of wall shear stress on airway walls may be an important factor in the progression over time of the severity of obstructive sleep apnea.

The frequency of lingual tonsil enlargement in obese children.

OBJECTIVE: Enlargement of the lingual tonsils is being increasingly recognized as a not uncommon and treatable cause of obstructive sleep apnea, particularly in patients with Down syndrome who have undergone palatine tonsillectomy and adenoidectomy. We have recognized an increasing number of patients who are obese and have obstructive sleep apnea with enlarged lingual tonsils. The purpose of this study was to evaluate the frequency of enlarged lingual tonsils in obese children. SUBJECTS AND METHODS: Seventy-one obese children (mean body mass index = 41.6 kg/m(2)) underwent sagittal fast spin-echo inversion recovery imaging. Lingual tonsils were identified and measured in the greatest anteroposterior diameter. Lingual tonsils > 10 mm were considered markedly enlarged. The subgroup with absent palatine tonsils (previous tonsillectomy) (n = 41) were compared with those with palatine tonsils present (n = 30). RESULTS: Forty-four (62%) of the obese children had measurable lingual tonsils, which is greater than the frequency previously reported in normal subjects (0%), subjects with obstructive sleep apnea (33%), or subjects with Down syndrome and obstructive sleep apnea (50%). Ten (14%) had lingual tonsils > 10 mm. Obese subjects with absent palatine tonsils (previous tonsillectomy) had a higher prevalence of measurable lingual tonsils than those with palatine tonsils (78% vs 22%, respectively; p < 0.001) and a higher prevalence of lingual tonsils > 10 mm (90% vs 10%, p < 0.001). CONCLUSION: Obese children have a high frequency of enlargement of the lingual tonsils with a significantly higher prevalence in those with previous tonsillectomy. Enlarged lingual tonsils may play a role in the pathogenesis of obstructive sleep apnea in obese children.

Growth velocity predicts recurrence of sleep-disordered breathing 1 year after adenotonsillectomy.

RATIONALE: Adenotonsillectomy, the first line of treatment of sleep-disordered breathing (SDB), is the most commonly performed pediatric surgery. Predictors of the recurrence of SDB after adenotonsillectomy and its impact on cardiovascular risk factors have not been identified. OBJECTIVES: Demonstrate that gain velocity in body mass index (BMI) defined as unit increase in BMI/year confers an independent risk for the recurrence of SDB 1 year after adenotonsillectomy. METHODS: Children with SDB and hypertrophy of the tonsils and a comparison group of healthy children were followed prospectively for 1 year. MEASUREMENTS AND MAIN RESULTS: Serial polysomnographies, BMI, and blood pressure were obtained before adenotonsillectomy and 6 weeks, 6 months, and 1 year postoperatively. Gain velocity in BMI, BMI and being African American (odds ratios, 4-6/unit change/yr; 1.4/unit and 15, respectively) provided equal amounts of predictive power to the risk of recurrence of SDB. In the group that experienced recurrence, systolic blood pressure at 1 year was higher than at baseline and higher than in children who did not experience recurrence. CONCLUSIONS: Three clinical parameters confer independent increased risk for high recurrence of SDB after adenotonsillectomy: gain velocity in BMI, obesity, and being African American. A long-term follow-up of children with SDB and monitoring of gain velocity in BMI are essential to identifying children at risk for recurrence of SDB and in turn at risk for hypertension.

Association of ApoE genetic variants with obstructive sleep apnea in children.

BACKGROUND AND PURPOSE: Although several studies have reported an association between obstructive sleep apnea (OSA) and the chromosomal region containing the Apolipoprotein E (ApoE) gene, findings about the exact location in the ApoE gene have been inconsistent. The objective of our study was thus to determine the allele, genotype, and haplotype frequencies at several single nucleotide polymorphisms (SNPs) in the region of ApoE and test their association with OSA status in children. PATIENTS AND METHODS: Caucasian children, ranging in age from 2 to 21 years, with polysomnographic evidence of OSA (>1 obstructive apnea or obstructive hypopnea episodes per hour of sleep) were recruited in the case group. Our race- and gender-matched control group was recruited from a population-based cohort of children enrolled in the Princeton School District Study. RESULTS: Comparison of allele and genotype frequencies between cases (n=92) and controls (n=92) revealed significant differences for SNPs rs405509 and rs7412. Multivariate logistic regression analysis with age and body mass index (BMI) as covariates revealed a significant association between OSA status and SNPs rs157580, rs405509, rs769455 and rs7412. The sliding window haplotype trend regression test revealed that SNP rs405509 was included in all haplotypes that are significantly associated with OSA status. CONCLUSIONS: We conclude that polymorphisms involving more than one locus in the ApoE gene and its regulatory region are associated with OSA in children. Further studies replicating these findings in different populations are needed as are studies involving fine mapping of this region.

Computational modeling of upper airway before and after adenotonsillectomy for obstructive sleep apnea.

Adenotonsillectomy, the first-line surgical treatment for obstructive sleep apnea (OSA) in children, is successful in only 50% of obese children. Computational fluid dynamics tools, which have been applied to differentiate OSA patients from those without OSA based on the airway flow characteristics, can be potentially used to identify patients likely to benefit from surgical intervention. We present computational modeling of the upper airway before and after adenotonsillectomy in an obese female adolescent with OSA. The subject underwent upper airway imaging on a 1.5 Tesla magnetic resonance imaging (MRI) scanner, and three-dimensional airway models were constructed using airway boundary coordinates from cross-sectional MRI scans. Our results using computational simulations indicate that, in an obese child, the resolution of OSA after adenotonsillectomy is associated with changes in flow characteristics that result in decreased pressure differentials across the airway walls and thus lower compressive forces that predispose to airway collapse. Application of such findings to an obese child seeking surgical treatment for OSA can potentially lead to selection of the surgical procedure most likely to result in OSA resolution. Effective intervention for OSA in this high-risk group will result in reduction in morbidity and the public health concerns associated with OSA.

Upper airway volume segmentation analysis using cine MRI findings in children with tracheostomy tubes.

OBJECTIVE: The purpose of this study is to evaluate the airway dynamics of the upper airway as depicted on cine MRI in children with tracheotomy tubes during two states of airflow through the upper airway. MATERIALS AND METHODS: Sagittal fast gradient echo cine MR images of the supra-glottic airway were obtained with a 1.5T MRI scanner on seven children with tracheotomy tubes. Two sets of images were obtained with either the tubes capped or uncapped. The findings of the cine MRI were retrospectively reviewed. Volume segmentation of the cine images to compare the airway volume change over time (mean volume, standard deviation, normalized range, and coefficient of variance) was performed for the capped and uncapped tubes in both the nasopharynx and hypopharynx (Signed Rank Test). RESULTS: Graphical representation of the airway volume over time demonstrates a qualitative increased fluctuation in patients with the tracheotomy tube capped as compared to uncapped in both the nasopharyngeal and hypopharyngeal regions of interest. In the nasopharynx, the mean airway volume (capped 2.72 mL, uncapped 2.09 mL, p = 0.0313), the airway volume standard deviation (capped 0.42 mL, uncapped 0.20 mL, p = 0.0156), and the airway volume range (capped 2.10 mL, uncapped 1.09 mL, p = 0.0156) were significantly larger in the capped group of patients. In the hypopharynx, the airway volume standard deviation (capped 1.54 mL, uncapped 0.67 mL, p = 0.0156), and the airway volume range (capped 6.44 mL, uncapped 2.93 mL, p = 0.0156) were significantly larger in the capped tubes. The coefficient of variance (capped 0.37, uncapped 0.26, p = 0.0469) and the normalized range (capped 1.52, uncapped 1.09, p = 0.0313) were significantly larger in the capped tubes. CONCLUSION: There is a statistically significant change in airway dynamics in children with tracheotomy tubes when breathing via the airway as compared to breathing via the tracheotomy tube.