Matthew Fenchel

Activity-Adjusted 24-Hour Ambulatory Blood Pressure and Cardiac Remodeling in Children with Sleep Disordered Breathing

Questions remain as to whether pediatric sleep disordered breathing increases the risk for elevated blood pressure and blood pressure–dependent cardiac remodeling. We tested the hypothesis that activity-adjusted morning blood pressure surge, blood pressure load, and diurnal and nocturnal blood pressure are significantly higher in children with sleep disordered breathing than in healthy controls and that these blood pressure parameters relate to left ventricular remodeling. 24-hour ambulatory blood pressure parameters were compared between groups. The associations between blood pressure and left ventricular relative wall thickness and mass were measured. 140 children met the inclusion criteria. In children with apnea hypopnea index <5 per hour, a significant difference from controls was the morning blood surge. Significant increases in blood pressure surge, blood pressure load, and in 24-hour ambulatory blood pressure were evident in those whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and body mass index had similar effect on blood pressure parameters except for nocturnal diastolic blood pressure, where sleep disordered breathing had a significantly greater effect than body mass index. Diurnal and nocturnal systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure predicted the changes in left ventricular relative wall thickness. Therefore, sleep disordered breathing in children who are otherwise healthy is independently associated with an increase in morning blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure. The association between left ventricular remodeling and 24-hour blood pressure highlights the role of sleep disordered breathing in increasing cardiovascular morbidity.

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.

Improvements in lung function outcomes in children with cystic fibrosis are associated with better nutrition, fewer chronic pseudomonas aeruginosa infections, and dornase alfa use.

OBJECTIVE To compare lung function and nutritional outcomes in cystic fibrosis (CF) for 2 birth cohorts in our CF center. STUDY DESIGN Patients with CF born between 1985 and 2000 treated in our CF center before age 5 years were included. The patients were divided into 2 equal birth cohorts for comparison: birth cohort 1 (born between 1985 and 1992) and birth cohort 2 (born between 1993 and 2000). To compare lung function, we used forced expiratory volume in the first second (FEV(1))% predicted and FEV(1)% predicted slope from age 6 to 12 years. We hypothesized that we would find significant improvements in lung function and nutritional outcomes in our patients with CF. RESULTS The patients born between 1993 and 2000 (birth cohort 2) had better lung function, a slower rate of decline in lung function, and better nutritional outcomes compared with those born between 1985 and 1992 (birth cohort 1). Factors associated with a slower rate of decline in lung function in both groups were a higher baseline body mass index (BMI)%, a slower BMI% rate of decline, absence of chronic Pseudomonas aeruginosa respiratory infection, and initiation of dornase alfa (Pulmozyme) therapy before age 9 years. CONCLUSION Our results demonstrate dramatically improved lung function and nutritional outcomes in the children with CF in our center. The improvements in lung function outcomes are associated with better nutrition, fewer chronic P aeruginosa infections, and dornase alfa therapy.

Baroreflex Gain in Children with Obstructive Sleep Apnea

RATIONALE We previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage. OBJECTIVES Compare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea. METHODS A total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (+/-2.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains. MEASUREMENTS AND MAIN RESULTS Healthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index. CONCLUSIONS Obstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.

Does sleep duration predict metabolic risk in obese adolescents attending tertiary services? A cross-sectional study.

STUDY OBJECTIVES To determine, in a clinical sample of obese adolescents, whether shorter sleep duration is associated with metabolic risk and obesity severity. DESIGN Cross-sectional study. SETTING Tertiary care weight-management clinic in Cincinnati, OH, USA. PARTICIPANTS 133 obese adolescents aged 10-16.9 years. INTERVENTIONS N/A. MEASUREMENTS Multifaceted sleep duration data were examined with fasting venipuncture and anthropometric data collected during clinical care. PRIMARY OUTCOME presence of metabolic syndrome. SECONDARY OUTCOMES waist circumference, triglycerides, HDL-cholesterol, blood pressure, glucose, insulin resistance (HOMA-IR), and body mass index (BMI). PREDICTORS Sleep duration by (1) parent-report, (2) self-report, and (3) multi-night actigraphy. ANALYSIS Relationships between sleep duration and each outcome were examined via regression models, adjusted for potential confounders. RESULTS Regardless of how measured, sleep duration showed no strong association with metabolic syndrome (OR 1.1 to 1.5, P = 0.2 to 0.8), BMI (β -0.03 to -0.01, P = 0.2 to 0.8), or most other outcomes. Lower triglycerides were predicted by shorter sleep duration by self-report (β 12.3, P = 0.01) and actigraphy (β 13.6, P = 0.03), and shorter parent-reported sleep duration was associated with higher HDL-cholesterol (β = -2.7, P = 0.002). CONCLUSIONS Contrary to expectations, sleep duration was not associated with metabolic outcomes, and showed limited associations with lipid profiles. Although inadequate sleep may affect other areas of functioning, it appears premature to expect that lengthening sleep will improve BMI or metabolic outcomes in clinical samples of obese adolescents.

Determinants of Regional Cerebral Oxygenation in Children with Sleep-disordered Breathing

RATIONALE An association between neurocognitive deficits and pediatric sleep-disordered breathing has been suggested; however, weak correlations between disease severity and functional outcomes underscore the lack of knowledge regarding factors modulating cognitive morbidity of sleep-disordered breathing. OBJECTIVES To identify the parameters affected by sleep-disordered breathing that modulate cerebral oxygenation, an important determinant of cognition. A further objective was to use these parameters with demographic data to develop a predictive statistical model of pediatric cerebral oxygenation. METHODS Ninety-two children (14 control subjects, 32 with primary snoring, and 46 with obstructive sleep apnea) underwent polysomnography with continuous monitoring of cerebral oxygenation and blood pressure. Analysis of covariance was used to relate the blood pressure, sleep diagnostic parameters, and demographic characteristics to regional cerebral oxygenation. MEASUREMENTS AND MAIN RESULTS To account for anatomic variability, an index of cerebral oxygenation during sleep was derived by referencing the measurement obtained during sleep to that obtained during wakefulness. In a repeated measures model predicting the index of cerebral oxygenation, mean arterial pressure, rapid eye movement (REM) sleep, female sex, age, and oxygen saturation had a positive effect on cerebral oxygenation levels, whereas arousal index and non-REM (NREM) sleep had a negative effect. CONCLUSIONS Increasing mean arterial pressure, age, oxygen saturation, and REM sleep augment cerebral oxygenation, while sleep-disordered breathing, male sex, arousal index, and NREM sleep diminish it. The proposed model may explain the sources of variability in cognitive function of children with sleep-disordered breathing.

Improving Evidence-Based Care in Cystic Fibrosis Through Quality Improvement

OBJECTIVE To increase clinician adherence to prescribing guidelines for pulmonary medications in children with cystic fibrosis (CF). DESIGN Quality improvement project with multiple time series design. SETTING The CF center at a tertiary care pediatric hospital in the United States. PATIENTS Children with CF who were eligible to receive oral azithromycin, nebulized dornase alfa, or inhaled tobramycin sulfate based on prescribing guidelines for CF lung disease. INTERVENTION Evidence-based prescribing guidelines were designed by a local committee to reflect consensus recommendations from the CF Foundation. Clinicians and families were educated about guidelines. Adherence to prescribing guidelines was tracked using a local CF database and record reviews. Weekly meetings were used to highlight adherence failures and promote clinician accountability. MAIN OUTCOME MEASURE The rate of clinician adherence to prescribing guidelines. RESULTS One hundred seventy patients with CF were included. At the start of the project, the rate of clinician adherence to prescribing guidelines was 62%. After 3 months of the project, the rate of clinician adherence to prescribing guidelines was 87% (odds ratio = 4.6; 95% confidence interval, 3.0-7.0). The improvements in adherence to prescribing guidelines were sustained for 21 months of follow-up. CONCLUSIONS Educating clinicians about prescribing guidelines, sharing guidelines with families, and monitoring clinician adherence improve prescribing adherence to evidence-based recommendations.

Inhaled Tobramycin Effectively Reduces FEV1 Decline in Cystic Fibrosis. An Instrumental Variables Analysis

RATIONALE The efficacy of inhaled tobramycin on chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) has been established in clinical trials. However, little is known about its clinical effectiveness on lung function outside randomized controlled trial settings; conventional analysis of existing registry data has heretofore been confounded by treatment selection bias. OBJECTIVE To determine effectiveness of inhaled tobramycin on FEV1 decline in patients with chronic P. aeruginosa infections using observational data from the Cystic Fibrosis Foundation Patient Registry. METHODS Patient-level tobramycin use was measured at first chronic P. aeruginosa infection (n = 13,686 patients; age, 6-21 yr). Decline in FEV1 2 years after infection was estimated for patients treated with tobramycin and compared with untreated patients. Multiple linear regressions with confounder adjustment and propensity scores were used to estimate mean FEV1 decline for each group. Because care is organized by centers, we used center-specific prescription rates as an instrument to reduce treatment-by-condition bias. MEASUREMENTS AND MAIN RESULTS Using center-level prescribing rates, instrumental variables analysis showed less FEV1 decline for patients who received tobramycin when first eligible compared with those who did not receive tobramycin (difference, 2.55% predicted; 95% confidence interval, 0.16-4.94; P = 0.0366). CONCLUSIONS Inhaled tobramycin is effective in reducing lung function decline among patients 6 to 21 years of age with CF. Because CF care is organized by center, using center-specific prescription rates as an instrumental variable is a feasible approach to using the Cystic Fibrosis Foundation Patient Registry to determine treatment effectiveness. More generally, this approach can correct for treatment-by-condition bias arising from observational studies.

Bronchiectasis in chronic pulmonary aspiration: Risk factors and clinical implications†‡

Bronchiectasis is a well‐known sequela of chronic pulmonary aspiration (CPA) that can result in significant respiratory morbidity and death. However, its true prevalence is unknown because diagnosis requires high resolution computed tomography which is not routinely utilized in this population. This study describes the prevalence, time course for development, and risk factors for bronchiectasis in children with CPA.

Sleep Disordered Breathing in Young Boys with Duchenne Muscular Dystrophy

OBJECTIVES To describe sleep-disordered breathing (SDB) in young boys with Duchenne muscular dystrophy (DMD) and its relationship with pulmonary function tests (PFTs). STUDY DESIGN This retrospective study examined diagnostic polysomnogram and PFT data of boys younger than 18 years with DMD and treated with steroids. Spirometry, respiratory muscle strength, body mass index (BMI), sleep architecture variables, and indices of SDB were analyzed. We examined the effect of PFT measures on the risk of each type of respiratory event using logistic regression and have reported results as OR (95% CI). RESULTS Subjects included 110 boys with DMD, mean age 11.5 (5.6-17.9) years. Mean (±SD) percent forced vital capacity predicted was 79.5% ± 29.1%. Mean BMI for all subjects was 21.9 ± 7.0 kg/m(2), and mean BMI z-score was 0.65 ± 1.93. Seventy (63.6%) subjects had obstructive sleep apnea; 37 (33.6%) subjects had central sleep apnea; 18 (17%) subjects had hypoventilation. Median (IQR) Apnea Hypopnea Index was 2.9 (1.6-6.9) and median Obstructive Index was 1.5 (0.5-3.8). Obstructive Index during rapid eye movement sleep positively correlated with BMI (r = 0.33, P = .002), BMI z-score (r = 0.22, P = .04), and age (r = 0.31, P = .004). Lower forced vital capacity was associated with increased risk of hypoventilation (OR 0.8, P = .001). CONCLUSION SDB is common in young boys with DMD treated with steroids. It is manifest with rapid eye movement-obstructive sleep apnea, often severe, and strongly influenced by BMI.