Using Polysomnography and Airway Evaluation to Predict Successful Decannulation in Children.

OBJECTIVE: Decannulation readiness is approached in several ways and is tailored to the individual patient. While microlaryngoscopy and bronchoscopy evaluate airway patency at all levels, polysomnography assesses sleep-related upper airway physiology. There are limited data in the literature on the utility of these tools. Thus, the main objectives of this study were (1) to identify sleep and respiratory parameters associated with successful decannulation and (2) to determine the agreement between microlaryngoscopy and bronchoscopy and polysomnography. STUDY DESIGN: Case series with chart review. SETTING: Quaternary care pediatric hospital. SUBJECTS AND METHODS: A retrospective review of medical records, microlaryngoscopy and bronchoscopy, and polysomnographs was performed on subjects preparing for decannulation from 2005 to 2010. Fifty-nine subjects who underwent overnight polysomnography with a tracheostomy capping trial and microlaryngoscopy and bronchoscopy were included. Prediction of successful decannulation from polysomnography parameters was determined using logistic regression analysis. RESULTS: Fifty-nine subjects with a total of 78 polysomnographs were subdivided into 2 groups: 42 polysomnographs were classified as successfully decannulated, and 36 polysomnographs belonged to the group that did not decannulate. Logistic regression analysis determined that the Apnea Hypopnea Index (P = .0423) and maximal end-tidal CO2 (P = .046) were significant predictors for successful decannulation. CONCLUSION: Airway evaluation by microlaryngoscopy and bronchoscopy is an essential tool in the assessment of decannulation readiness. Polysomnography is an important additional tool for children with complex airway problems. Our results indicate that certain polysomnographic parameters such as Apnea Hypopnea Index and maximal end-tidal CO2 are valuable in predicting successful tracheostomy decannulation.

Concentration of fractional excretion of nitric oxide (FENO): A potential airway biomarker of restored CFTR function.

BACKGROUND: Lower airway biomarkers of restored cystic fibrosis transmembrane conductance regulator (CFTR) function are limited. We hypothesized that fractional excretion of nitric oxide (FENO), typically low in CF patients, would demonstrate reproducibility during CFTR-independent therapies, and increase during CFTR-specific intervention (ivacaftor) in patients with CFTR gating mutations. METHODS: Repeated FENO and spirometry measurements in children with CF (Cohort 1; n=29) were performed during hospital admission for acute pulmonary exacerbations and routine outpatient care. FENO measurements before and after one month of ivacaftor treatment (150 mg every 12h) were completed in CF patients with CFTR gating mutations (Cohort 2; n=5). RESULTS: Cohort 1: Mean forced expiratory volume in 1s (FEV1 % predicted) at enrollment was 72.3% (range 25%-102%). Mean FENO measurements varied minimally over the two inpatient and two outpatient measurements (9.8-10.9 ppb). There were no clear changes related to treatment of pulmonary exacerbations, gender, genotype or microbiology, and weak correlation with inhaled corticosteroid use (P<0.05). Between the two inpatient measurements, FEV1 % predicted increased by 7.3% (P<0.03) and FENO did not change. In Cohort 2, mean FENO increased from 6.6 ppb (SD=2.19) to 11.8 ppb (SD=4.97) during ivacaftor treatment. Mean sweat chloride dropped by 58 mM and mean FEV1 % predicted increased by 10.2%. CONCLUSIONS: Repeated FENO measurements were stable in CF patients, whereas FENO increased in all patients with CFTR gating mutations treated with ivacaftor. Acute changes in FENO may serve as a biomarker of restored CFTR function in the CF lower airway during CFTR modulator treatment.

Insulin secretion abnormalities in exocrine pancreatic sufficient cystic fibrosis patients.

BACKGROUND: The aim of this study is to assess insulin secretion in pediatric cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. METHODS: Glucose and insulin responses during an oral glucose tolerance test (OGTT) were measured in 146 CF patients. Patients were divided into exocrine sufficient (CF-PS) and insufficient (CF-PI) groups based on pancreatic enzyme usage and fecal elastase. A reference group included healthy, non-diabetic subjects. RESULTS: All CF groups showed reduced insulin secretion as measured by insulinogenic index. The CF-PS patients had normal glucose tolerance. There was a direct correlation between BMI z-score and insulin area under the curve. CONCLUSION: Patients with CF have reduced insulin secretion during an OGTT regardless of exocrine pancreatic status. The abnormal insulin secretion in all CF patients may predispose them for glucose intolerance, particularly when challenged by inflammation, infection, or nutritional deficiency. In addition, the diminished insulin secretion may contribute to increased catabolism. Lastly, the CF-related diabetes (CFRD) screening guidelines should be followed by all CF patients regardless of pancreatic status.

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.

Obstructive lung disease in children with idiopathic scoliosis.

OBJECTIVE: To measure the prevalence of obstructive lung disease (OLD) among patients undergoing preoperative pulmonary assessment for idiopathic scoliosis. STUDY DESIGN: This was a retrospective, descriptive review from clinical data in a tertiary care pediatric hospital in the US. Patients (n = 176) with idiopathic scoliosis with Cobb angles of ≥ 40 degrees who performed acceptable and repeatable preoperative pulmonary function testing were included. The primary outcome measure was the forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio. RESULTS: The prevalence of OLD (low FEV1/FVC ratio) was 39% (68/176 patients). In multivariate modeling, radiographic measures were poor predictors of pulmonary function outcomes of FVC (r(2) 0.06), FEV1 (r(2) 0.05), FEV1/FVC ratio (r(2) 0.08), and total lung capacity (r(2) 0.06). CONCLUSIONS: OLD is common in patients with idiopathic scoliosis. We recommend preoperative pulmonary function testing for patients with idiopathic scoliosis under consideration for spinal fusion surgery.

Plasma renin levels and renin-blood pressure relationship in normal-weight and overweight children with obstructive sleep apnea and matched controls.

BACKGROUND: Obstructive sleep apnea (OSA) has been increasingly linked to elevated blood pressure (BP) and hypertension. Repeated night-time hypoxia in OSA is associated with activation of two critical mechanisms of BP control: the autonomic nervous system and the renin-angiotensin system (RAS). The effects of OSA on the RAS are not well understood, especially in children. We hypothesized that children with OSA have elevated renin levels and abnormal relationships between BP and renin. METHODS: Polysomnography was conducted in 173 children to diagnose OSA (apnea-hypopnea index [AHI] >1 event/h) and control (AHI ≤1 event/h) groups. Age- and gender-specific z-scores for body mass index (BMI) were calculated to divide subjects into obese (BMI ≥95%), overweight (BMI ≥85% and <95%) and normal-weight (BMI <85%) groups. Morning BP was measured with an automatic sphygmomanometer and venous blood samples were collected for measurements of plasma renin, after overnight polysomnography. RESULTS: Plasma renin levels were not significantly different in all four groups after adjustment of age, gender, and race. Significantly negative associations between renin and BP were present only in the normal-weight control group and were absent in the other three groups. CONCLUSION: Plasma renin levels were not significantly increased in children with OSA compared to controls for both normal-weight and overweight subjects. The absence of normal, negative renin-BP relationships in both overweight and OSA children suggests a dysfunction of the RAS, which could be a mechanism for increased BP and the development of hypertension.

Glucose, insulin, and insulin resistance in normal-weight, overweight and obese children with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with components of metabolic syndrome. Both body weight and OSA independently influence metabolic measurements. The goal of this study was to determine whether OSA in normal-weight, overweight or obese children, compared to matched control groups, was associated with increased levels of glucose, insulin and insulin resistance (IR). METHODS: Age- and gender-specific body mass index (BMI) percentiles were determined and used to categorize subjects into normal-weight (BMI<85%) and overweight-obese (BMI≥85%) groups. In addition, subjects were divided into normal-weight (BMI<85%), overweight (BMI≥85% and <95%) and obese (BMI≥95%) groups. Polysomnography was conducted and morning levels of glucose and insulin were measured and IR was determined from the blood samples collected early in the morning after overnight fast. Results were compared between the subject groups. Effects of severity of OSA defined by apnea hypopnea index (AHI) and oxygen desaturation index (ODI) on glucose, insulin, and HOMA-IR were analyzed. RESULTS: Glucose, insulin, and HOMA-IR in OSA and matched control groups were not significantly different for normal-weight, overweight and obese subjects. The ODI was significantly associated with elevated levels of glucose and HOMA-IR after adjustment for age, gender, race, and BMI Z-score. CONCLUSIONS: IR levels between OSA and control for both normal-weight, overweight and obese subjects were not significantly different. The ODI was associated with increased IR in children with OSA. OSA-induced hypoxic events during sleep may be a potential mechanism of increased IR in children with OSA, independent of body weight.

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.

Baroreflex sensitivity after adenotonsillectomy in children with obstructive sleep apnea during wakefulness and sleep.

STUDY OBJECTIVES: Children with obstructive sleep apnea have blunted baroreflex sensitivity and increased blood pressure variability. The aim of the study was to test the hypothesis that treatment of sleep apnea by adenotonsillectomy results in significant improvement of baroreflex sensitivity, lowering of blood pressure and blood pressure variability and increase vagal heart rate modulation. STUDY DESIGN: One hundred ninety-four children aged 9.6 ± 2.3 years were enrolled; 133 had obstructive sleep apnea and 61 were healthy controls. For children with sleep apnea, polysomnography with 3-lead electrocardiography and continuous blood pressure was performed before adenotonsillectomy, then 6 weeks and 6 months postoperatively. Controls underwent the same assessment at study entry and 6 months later. Spontaneous baroreflex sensitivity was measured in the time and frequency domains. Data analyses were performed for available and complete cases. RESULTS: Children with sleep apnea experienced postoperatively an increase in baroreflex sensitivity and decrease in blood pressure variability during wakefulness and sleep. A decrease in blood pressure during sleep and in heart rate during wakefulness was also measured. The improvement in baroreflex sensitivity was predicted by the change in the apnea-hypopnea and arousal indices. A normal pattern of rising baroreflex sensitivity during the night was restored in children with severe apnea after surgery. However, baroreceptor sensitivity did not completely normalize after treatment. CONCLUSION: Treatment of obstructive sleep apnea in children by adenotonsillectomy is associated with gradual improvement in known risk factors for cardiovascular disease. Complete normalization of baroreceptor sensitivity was not achieved 6 months postoperatively.

Bronchiectasis in chronic pulmonary aspiration: risk factors and clinical implications.

INTRODUCTION: 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. MATERIALS AND METHODS: Using a cross-sectional design, medical records were reviewed for all patients with swallow study or airway endoscopy-confirmed aspiration in our airway center over a 21 month period. All patients underwent rigid and flexible bronchoscopy, and high resolution chest computed tomography. Prevalence, distribution, and risk factors for bronchiectasis were identified. RESULTS: One hundred subjects age 6 months to 19 years were identified. Overall, 66% had bronchiectasis, including 51% of those less than 2 years old. The youngest was 8 months old. Severe neurological impairment (OR 9.45, P<0.004) and history of gastroesophageal reflux (OR 3.36, P=0.036) were identified as risk factors. Clinical history, exam, and other co-morbidities did not predict bronchiectasis. Sixteen subjects with bronchiectasis had repeat chest computed tomography with 44% demonstrating improvement or resolution. DISCUSSION: Bronchiectasis is highly prevalent in children with CPA and its presence in young children demonstrates that it can develop rapidly. Early identification of bronchiectasis, along with interventions aimed at preventing further airway damage, may minimize morbidity and mortality in patients with CPA.

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 (ß -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 (ß 12.3, P = 0.01) and actigraphy (ß 13.6, P = 0.03), and shorter parent-reported sleep duration was associated with higher HDL-cholesterol (ß = -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.

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.

Improving follow-up in hospitalised children.

OBJECTIVE: To improve the clinic follow-up rate of paediatric inpatients in a tertiary care hospital. PATIENTS AND METHODS: Inpatients who received pulmonary consultations from July 2007 to June 2008 at Cincinnati Children's Hospital Medical Center were eligible for this quality-improvement project. Multiple interventions were introduced to improve follow-up in our subspecialty clinic. A χ(2) test for association was used to assess the dependence between the clinic follow-up rate and the type of care coordination intervention. We hypothesised that generalisable care coordination interventions would result in improvements. RESULTS: Two hundred and eleven patients were included. Two interventions were independently associated with improvements in the hospital follow-up rate. When a reminder to follow-up in the pulmonary clinic was inserted into the hospital discharge summary (partial intervention), the clinic follow-up rate improved from 27% to 55%. When the follow-up appointments were made for the families, with the appointments' noted in the discharge summaries, and automated appointment reminder phone calls were provided (full intervention), the follow-up rate improved further from 55% to 80%. The full intervention, when compared with no intervention, improved the clinic follow-up rate from 27% to 80%. CONCLUSION: Establishing clinic appointments for patients and providing appointment reminders increases the hospital follow-up rate for hospitalised children in outpatient clinics.

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.