Maninder Kalra

Neuropsychological effects of pediatric obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a fairly common nocturnal breathing disorder, affecting 2-4% of individuals. Although OSA is associated with medical morbidity, its most functionally disruptive effects in adults appear to be neuropsychological in nature. Research on the neuropsychological effects of pediatric OSA has been limited. This study compared the neuropsychological functioning of school-aged children with OSA to that of healthy children. The primary goal was to clarify the presence and pattern of neuropsychological morbidity associated with pediatric OSA. Sleep was assessed with parent-report questionnaires and laboratory sleep studies. Neuropsychological functioning was assessed by formal tests and parent- and teacher-report questionnaires. Data indicated OSA-related cognitive and behavioral impairment that was particularly marked on measures of behavior regulation and some aspects of attention and executive functioning. Minimal effects were observed on measures of intelligence, verbal memory, or processing speed. Exploratory analyses failed to indicate any clear relationship between neuropsychological functioning and objective indexes of hypoxia or sleep disruption, though the sample was small. These data add to a growing literature which suggests that significant neuropsychological deficits are associated with pediatric OSA. Findings suggest a pattern of neuropsychological morbidity that is similar but not identical to that seen in adult OSA.

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.

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.

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 projects 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. Pediatr. Pulmonol. 2010; 45:739–748.

Effect of Long-term Steroids on Cough Efficiency and Respiratory Muscle Strength in Patients With Duchenne Muscular Dystrophy

OBJECTIVE. The objective of this study was to determine whether long-term steroid therapy is associated with increased peak cough flow in patients with Duchenne muscular dystrophy and to determine which pulmonary function test variable is most predictive of peak cough flow. METHODS. In this case-control study, the medical charts of patients who had Duchenne muscular dystrophy and had pulmonary function tests at our institution in the previous 2 years were examined. Steroid-treated patients were on therapy for at least 1 year. The measured pulmonary function tests included forced vital capacity, maximum expiratory pressure, maximum inspiratory pressure, maximum voluntary ventilation, and peak cough flow. Multiple linear regression analysis was used to determine which pulmonary function test measure was most predictive of peak cough flow and assess the influence of steroid treatment and patient age on peak cough flow. RESULTS. Ten steroid-treated and 25 untreated patients were analyzed. Peak cough flow and maximum expiratory pressure were significantly higher in the steroid-treated patients. Each of the pulmonary function test variables was significantly associated with peak cough flow. The linear model that had the highest adjusted r2 value included only 2 variables: maximum voluntary ventilation and steroid treatment, demonstrating that steroid-treated patients had peak cough flow values that were 27 L/min higher than the untreated patients. The interaction between maximum voluntary ventilation and steroid was not statistically significant, suggesting that the steroid-associated increase in peak cough flow was approximately constant over the observed range of maximum voluntary ventilation values. The effects of maximum voluntary ventilation and treatment group on peak cough flow were not confounded with the patient age. CONCLUSIONS. Long-term steroid therapy is associated with improved peak cough flow and respiratory muscle strength in patients with Duchenne muscular dystrophy. Maximum voluntary ventilation may be a useful predictor of lung function in Duchenne muscular dystrophy.

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 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.

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.

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 Childrens 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.

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.