Gary L. McPhail

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.

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.

Prevention of Tracheostomy-related Pressure Ulcers in Children

BACKGROUND AND OBJECTIVES: Pressure ulcers are commonly acquired in pediatric institutions, and they are a key indicator of the standard and effectiveness of care. We recognized a high rate of tracheostomy-related pressure ulcers (TRPUs) in our ventilator unit and instituted a quality improvement program to develop and test potential interventions for TRPU prevention, condensed them into a clinical bundle, and then implemented the bundle into our standard practice. METHODS: The intervention model used a rapid-cycle, Plan-Do-Study-Act (PDSA), framework for improvement research. All tracheostomy-dependent patients admitted to our 18-bed ventilator unit from July 2008 through December 2010 were included. TRPU stage and description, number of days each TRPU persisted, and bundle compliance were recorded in real time. All TRPUs were staged by a wound-care expert within 24 hours. The interventions incorporated into the TRPU-prevention bundle included frequent skin and device assessments, moisture-reducing device interface, and pressure-free device interface. RESULTS: There was a significant decrease in the rate of patients who developed a TRPU from 8.1% during the preintervention period, to 2.6% during bundle development, to 0.3% after bundle implementation. There was a marked difference between standard and extended tracheostomy tubes in TRPU occurrence (3.4% vs 0%, P = .007) and days affected by a TRPU (5.2% vs 0.1%, P < .0001). CONCLUSIONS: Education and ongoing assessment of skin integrity and the use of devices that minimize pressure at the tracheostomy–skin interface effectively reduce TRPU even among a population of children at high risk. These interventions can be integrated into daily workflow and result in sustained effect.

A semiparametric approach to estimate rapid lung function decline in cystic fibrosis

PURPOSE Detecting the onset of rapid lung function decline is important to reduce mortality rates in cystic fibrosis (CF) and other lung diseases. The most common approach is conventional linear mixed modeling-estimating a population-level slope of lung function decline and using random effects to address serial correlation-but this ignores nonlinear features of disease progression and distinct sources of variability. The purpose of this article was to estimate patient-specific timing and degree of rapid decline while appropriately characterizing natural progression and variation in CF. METHODS We propose longitudinal semiparametric mixed modeling and contrast it with the conventional approach, which restricts lung function (measured as forced expiratory volume in 1 second as a percentage of predicted, FEV1%) to linear decline. Each approach is applied to clinical encounter data from the United States CF Foundation Patient Registry. RESULTS Timing and degree of rapid FEV1% decline vary across patients and as a function of key covariates. Patients experience maximal FEV1% loss by early adulthood more severe than indicated by conventional slope analysis. CONCLUSIONS Semiparametric mixed modeling provides a means to estimate patient-specific changes in CF disease progression and may be used to inform prognostic decisions in chronic care settings and clinical studies.

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.

The impact of transforming healthcare delivery on cystic fibrosis outcomes: a decade of quality improvement at Cincinnati Children’s Hospital

Background In 2001, Cincinnati Childrens Hospital embarked on a journey to improve healthcare delivery to patients with cystic fibrosis (CF). Data from the Cystic Fibrosis Foundation National Patient Registry revealed our below-average clinical outcomes, prompting us to initiate improvement interventions. Objective To improve clinical outcomes for patients with CF through a comprehensive quality-improvement approach directed at increasing patient centredness and improving healthcare delivery. Interventions In 2001, we shared our below-average outcomes with patients, families and care providers. We instituted a quality-improvement steering committee with parental and hospital leadership, and our data-management support was restructured to provide real-time clinical data to monitor our progress. In 2002, our weekly chart conference changed to a prospective planning session and individualised daily schedules were created for inpatients. In 2003, an influenza vaccination campaign was initiated and our infection-control practices were redesigned. In 2005, best-practice guidelines were developed for airway-clearance therapy. In 2007, evidence-based clinical algorithms were designed and implemented and key care-team members were added. Measurements Primary outcome measures were median forced expiratory volume in 1 s per cent predicted (age range 6–17 years) and median body mass index percentile (age range 2–20 years). Results From 2000 to 2010, median forced expiratory volume in 1 s increased from 81.7% to 100.1% predicted and median body mass index increased from the 35th to the 55th centile. Discussion By focusing on specific outcomes, empowering families and patients, effectively using data, and standardising care processes, we transformed the culture and delivery of care for our patients with CF and learned valuable lessons potentially translatable to other chronic-care providers.

Lumacaftor alone and combined with ivacaftor: preclinical and clinical trial experience of F508del CFTR correction

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR), leading to significant morbidity and mortality. CFTR is a chloride and bicarbonate channel at the epithelial cell membrane. The most common CFTR mutation is F508del, resulting in minimal CFTR at the plasma membrane. Current disease management is supportive, whereas an ultimate goal is to develop therapies to restore CFTR activity. We summarize experience with lumacaftor, a small molecule that increases F508del-CFTR levels at the plasma membrane. Lumacaftor in combination with ivacaftor, a modulator of CFTR gating defects, improves clinical outcome measures in patients homozygous for the F508del mutation. Lumacaftor represents a significant advancement in the treatment of biochemical abnormalities in CF. Further development of CFTR modulators will improve upon current therapies, although it remains unclear whether this approach will provide therapies for all CFTR mutations.

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.