Gavin R. Graff

Blood Pressure Associated With Sleep-Disordered Breathing in a Population Sample of Children

The current criteria for sleep-disordered breathing (SDB) in children are not based on a clinically relevant outcome. The purpose of this study was to assess the association of blood pressure with SDB in a random sample of the local elementary school children (kindergarten through grade 5) using a 2-phased strategy. During phase 1, a brief questionnaire was completed for all of the children (N=5740) with a response rate of 78.5%. During phase 2, 700 randomly selected children from phase 1 with a response rate of 70.0% were assessed with a full polysomnograph and a history/physical, including an ECG; ear, nose, and throat; and pulmonary evaluation. We observed a significantly elevated systolic blood pressure associated with the apnea hypopnea index (AHI): AHI ≥1 (2.9 mm Hg); AHI ≥3 (7.1 mm Hg); and AHI ≥5 (12.9 mm Hg). The SDB and blood pressure association remained significant after adjusting for age, sex, race, body mass index percentile or waist circumference, sleep efficiency, percentage of rapid eye movement sleep, and snoring. In addition, older age, body mass index percentile, waist circumference, and snoring were significantly associated with blood pressure, independent of SDB. Based on these findings, our study suggests that SDB is significantly associated with higher levels of systolic blood pressure in children aged 5 to 12 years even after adjusting for the various confounding factors. Clinically, the data support the threshold of AHI ≥5 for the initiation of treatment for SDB. Additional research is indicated to assess the efficacy of SDB treatment on reducing blood pressure.

Use of a remifentanil–propofol mixture for pediatric flexible fiberoptic bronchoscopy sedation

Background : Flexible fiberoptic bronchoscopy is an important diagnostic tool for pediatric pulmonologists. Because of its favorable respiratory profile, ketamine has become a popular sedative for this procedure, but may be associated with unpleasant emergence reactions in the older child. Remifentanil is a newer, ultra‐short acting opioid that has been shown to provide effective sedation and cough suppression for fiberoptic bronchoscopy when combined with intermittent propofol boluses. However, delivery of these agents as a combined, single infusion has not been described.

Efficacy and safety of Creon® 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis

BACKGROUND Pancreatic enzyme replacement therapy is critical for adequate nutrition in cystic fibrosis (CF) patients with exocrine pancreatic insufficiency (EPI). METHODS This was a double-blind, randomised, placebo-controlled, two-period crossover study assessing efficacy and safety of Creon 24,000-unit capsules in CF subjects > or =12 years with EPI. Patients were randomised to one of two 5-day sequences, Creon/placebo or placebo/Creon (target dose, 4000 lipase units/g fat). Primary outcome was the coefficient of fat absorption (CFA); secondary outcomes were coefficient of nitrogen absorption (CNA), symptoms, and safety. RESULTS Thirty-two subjects were randomised. Mean CFA and CNA were significantly greater with Creon than placebo (CFA, 88.6% vs. 49.6%; CNA, 85.1% vs. 49.9%; p<0.001 for both). Symptoms were improved and fewer treatment-emergent adverse events were reported with Creon than placebo. One patient discontinued for weight loss unrelated to study drug. CONCLUSIONS This study demonstrated Creon was effective in treating EPI due to CF and was safe and well tolerated.

Baseline Characteristics and Factors Associated With Nutritional and Pulmonary Status at Enrollment in the Cystic Fibrosis EPIC Observational Cohort

The EPIC Observational Study is an ongoing prospective cohort study investigating risk factors for and clinical outcomes associated with early Pseudomonas aeruginosa (Pa) acquisition in young children with cystic fibrosis (CF).

Validation Study of Fractional Exhaled Nitric Oxide Measurements Using a Handheld Monitoring Device

We tested reproducibility of exhaled nitric oxide (FENO) and inter-operator handling when measured with a handheld device, NIOX MINO®. We enrolled 20 volunteers using a priori goals of acceptable reproducibility to be mean within-subject standard deviation less than 3 parts per billion (ppb) for FENO measurements less than 30 ppb, and mean coefficient of variation less than 10% for FENO measurements more than 30 ppb. Seventeen subjects with measurements less than 30 ppb displayed a mean standard deviation of 1.15, and 3 subjects with FENO more than 30 ppb had a mean coefficient of variation of 2.4%. We conclude that NIOX MINO demonstrates excellent reproducibility for all ranges of FENO.

Treatment of Recurrent Severe Hemoptysis in Cystic Fibrosis with Tranexamic Acid

Major hemoptysis is a potentially life-threatening complication of cystic fibrosis (CF) lung disease. Bronchial artery embolization (BAE) along with treatment of a CF pulmonary exacerbation has become the most widely used therapeutic approach for major hemoptysis in CF. However, BAE has been associated with severe complications, especially when bronchial artery to spinal artery anastomoses are present. This case study describes the successful treatment of major hemoptysis in CF with tranexamic acid, in an individual in whom 12 previous BAE procedures had been performed and further procedures were contraindicated secondary to bronchial artery to spinal artery collaterals. Recurrence of the hemoptysis occurred after attempts had been made to withdraw the tranexamic acid. Tranexamic acid was resumed with resolution of the hemoptysis, and the therapy has been used continuously for 13 months without any complications.

Safety and Tolerability of a New Formulation of Pancrelipase Delayed-Release Capsules (CREON ) in Children Under Seven Years of Age with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis An Open-Label, Multicentre, Single-Treatment-Arm Study

AbstractBackground: Exocrine pancreatic insufficiency (EPI) is a deficiency of digestive enzymes caused by diseases such as cystic fibrosis (CF). Patients with EPI due to CF require pancreatic enzyme replacement therapy (PERT) in order to maintain adequate nutrition. A new formulation of pancrelipase delayed-release capsules (CREON®) recently received US FDA approval and has demonstrated efficacy and safety in patients with CF aged ≥7 years. Objectives: The objectives of this study were to observe the safety and tolerability of new formulation pancrelipase delayed-release capsules (study drug) versus the standard of care PERT (standard therapy) in children aged <7 years with CF and EPI. Secondary objectives were to assess the ease of accurate dosing of study drug, monitor clinical symptoms and compare the efficacy of both treatments. Methods: This was an open-label, multicentre, single-treatment-arm study in children aged <7 years with a confirmed diagnosis of CF and EPI. After the screening period (approximately 14 days), all patients entered a 3-day assessment period on their usual PERT (standard therapy), followed by the study drug treatment phase (10–14 days; target dose 8000 lipase units/kg bodyweight/day), which included a second 3-day assessment period. The safety and tolerability of both treatments were documented by recording adverse events (AEs). Clinical symptoms (mean daily stool frequency, abdominal pain, stool consistency and flatulence) were monitored and ease of accurate dosing, as judged by caregivers, was reported. Efficacy was determined by comparison of percent stool fat in spot stool samples collected during both 3-day assessment periods. Results: Of the 19 patients who had informed consent from their parent/ legally acceptable representative, one was withdrawn as a screen failure and was excluded from the safety and efficacy analyses; thus, 18 patients completed the study. The median age (range) was 23 (4–71) months and 13 (72%) were male. During study drug treatment, patients received a mean ± SD dose in lipase units/kg bodyweight/day of 7542±1335 versus 6966 ± 3392 on standard therapy. Overall, nine (50%) patients had at least one treatment-emergent AE (TEAE) whilst receiving either treatment. All TEAEs in this study were reported as mild and none resulted in patient discontinuation. The caregivers had a slight preference for study drug over standard therapy in terms of ease of accurate dosing: six (33.3%) caregivers thought the study drug was easier to dose while only one (5.6%) thought the study drug was harder to dose than standard therapy. Clinical symptom assessment results were similar between treatments. There was no clinically meaningful difference (significance not tested) between study drug and standard therapy in the mean ± SD percent of stool fat: 28.1±9.9 and 27.9 ± 8.9, respectively. Conclusion: In this study in children aged <7 years with EPI due to CF, the new formulation pancrelipase delayed-release capsules (CREON®) were clinically comparable with standard therapy in terms of safety, tolerability and efficacy.

Nebulized Fentanyl for Palliation of Dyspnea in a Cystic Fibrosis Patient

Dyspnea, the subjective symptom feeling of breathlessness, is a common symptom in terminally ill patients with cystic fibrosis (CF). The palliation of the dyspnea is a reasonable goal to improve patient comfort as the progression of the disease worsens. We report the successful use of inhaled fentanyl for 3 days in a 17-year-old female with terminal CF lung disease, as measured by improved oxygenation and a reduction in the modified Borg score, and the subjective feeling of less air hunger reported by parents and patient.

Patterns of helium-oxygen (heliox) usage in the critical care environment.

The objective of this study was to describe the patterns of heliox use in critical care units of an academic medical center. The design was a prospective case series involving 7 critical care units of an academic medical center. All patients receiving heliox therapy over a 4-year period were studied, with prospective recording of patient demographics and the location, mode, indication for, and duration of heliox use. Use pattern comparisons based on anatomic location (upper vs lower airway) and age group (pediatric vs adult) were performed by α2 analysis and unpaired Student t test. Eighty-nine patients, aged 17.4 ± 20.9 years, received heliox for 30.5 ± 44.6 hours on 92 occasions. Pediatric (≤ 18 years) applications accounted for 72.8% of heliox use. Use was greater in frequency and scope during the final 2 study years, particularly in adults. Applications were split between upper airway (47%) and lower airway (53%) disorders. Airway manipulation was required in more adults (7/16) than in children (3/27) with upper airway obstruction (P < .05). The use patterns mirrored current literature emphases on postextubation stridor and asthma. This is the first description of heliox use patterns in the tertiary care critical care environment. Heliox use may be as dependent on practitioner experience as on published data. As a benign and relatively inexpensive therapy, heliox use should continue to be attractive, although ongoing study regarding efficacy in a number of settings is indicated.

Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis

BACKGROUND Vitamin D deficiency is common in CF. Whether vitamin D affects pulmonary function in CF is unknown. METHODS Data were abstracted from clinically stable CF patients who had pulmonary function studies and serum 25-hydroxyvitamin D [25(OH)D, ng/ml] levels drawn within 2 months of each other. Findings were adjusted for multiple variables known to affect pulmonary function in CF. RESULTS Enrollees totaled 597. Overall mean 25(OH)D level was 29.6±12.8 ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced expiratory volume in 1s (FEV1) % predicted (r=0.20, p<0.0001) and forced vital capacity % predicted (r=0.13, p=0.0019). Multivariate analysis revealed that serum 25(OH)D remained an independent predictor of FEV1 % predicted even after controlling for multiple other factors known to affect CF lung function. CONCLUSIONS Serum 25(OH)D levels are significantly associated with pulmonary function in CF. Further study is required to determine whether this association is causal.