Improvements in Cystic Fibrosis Quarterly Visits, Lung Function Tests, and Respiratory Cultures.

BACKGROUND: The Cystic Fibrosis (CF) Foundation recommends patients attend clinic ≥4 times per year with 4 respiratory cultures and 2 pulmonary function tests (PFTs). However, nationally only 57.4% of patients met these guidelines in 2012. We used a quality improvement program with a goal of 75% of our patients meeting this care guideline by 2012. METHODS: A 2-stage program was started in 2011. Stage 1: education of patients/caregivers on importance of quarterly visits. Stage 2: quarterly tracking system of patient appointments. Data on clinic visits, respiratory cultures, and PFTs were collected from the CF registry from January 2009 through December 2013. Statistical process control charts were used to track improvements. RESULTS: The average number of clinic visits increased significantly from 4.6 ± 2.3 in 2009 to 6.3 ± 4.6 in 2013 (P < .0001). The percentage of patients ages 6 through 18 completing a clinic visit, PFT, and respiratory culture per quarter increased significantly from 76.2% during 2009 to 86.4% in 2013. The percentage of patients completing ≥4 clinic visits with 4 respiratory cultures and 2 PFTs improved significantly from 47.5% in 2009 to 71.0% in 2013 (P < .0001). CONCLUSIONS: A tracking system of patient appointments significantly improved adherence to the care guidelines better than education alone. The multiple-stage quality improvement program we implemented may be modifiable and able to be integrated in other CF centers or other multiple disciplinary chronic illness care centers.

Behavioral and nutritional treatment for preschool-aged children with cystic fibrosis: a randomized clinical trial.

IMPORTANCE: Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged children with cystic fibrosis (CF) are a critical need. OBJECTIVE: To test whether behavioral and nutritional treatment (intervention) was superior to an education and attention control treatment in increasing energy intake, weight z (WAZ) score, and height z (HAZ) score. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included 78 children aged 2 to 6 years (mean age, 3.8 years) with CF and pancreatic insufficiency (intervention, n = 36 and control, n = 42). The study was conducted at 7 CF centers between January 2006 and November 2012; all 78 participants who met intent-to-treat criteria completed through follow-up. INTERVENTIONS: Behavioral intervention combined individualized nutritional counseling targeting increased energy intake and training in behavioral child management skills. The control arm provided education and served as a behavioral placebo controlling for attention and contact frequency. Both treatments were delivered in person or telehealth (via telephone). Sessions occurred weekly for 8 weeks then monthly for 4 months (6 months). Participants then returned to standard care for 1 year, with 12-month follow-up thereafter. MAIN OUTCOMES AND MEASURES: Changes in energy intake and WAZ score were examined from pretreatment to posttreatment (6 months) and change in HAZ score was assessed pretreatment to follow-up (18 months). Covariates included sex, Pseudomonas aeruginosa status at baseline, and treatment modality (in person vs telehealth). RESULTS: At baseline, mean (SD) energy intake was 1462 (329) kcals/d, WAZ score was -0.44 (0.81), and HAZ score was -0.55 (0.84). From pretreatment to posttreatment, the intervention increased daily energy intake by 485 calories vs 58 calories for the control group (adjusted difference, 431 calories; 95% CI, 282 to 581; P < .001) and increased the WAZ score by 0.12 units vs 0.06 for the control (adjusted difference, 0.09; 95% CI, -0.06 to 0.24; P = .25). From pretreatment to follow-up, the intervention increased the HAZ score by 0.09 units vs -0.02 for the control (adjusted difference, 0.14 units; 95% CI, 0.001 to 0.27; P = .049). Measured treatment integrity and credibility were high for both groups. CONCLUSIONS AND RELEVANCE: Behavioral and nutritional intervention improved energy intake and HAZ score outcomes but not WAZ score outcomes. Our results provide evidence that behavioral and nutritional treatment may be efficacious as a nutritional intervention for preschoolers aged 2 to 6 years with CF and pancreatic insufficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00241969.

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.

Long-term experience with ZENPEP in infants with exocrine pancreatic insufficiency associated with cystic fibrosis.

The objective of our study was to determine whether infants with cystic fibrosis who developed exocrine pancreatic insufficiency in early infancy would tolerate long-term treatment with ZENPEP (pancrelipase) delayed-release capsules, containing 3000 US Pharmacopeia units of lipase/capsule, and demonstrate consistent long-term growth. The most common treatment-emergent adverse events were diarrhea, vomiting, and constipation (mild or moderate). At study completion, median weight-for-age percentiles increased from 22nd to 49th, median length-for-age percentiles increased from 36.5th to 42nd, and median weight-for-length percentiles increased from 41.5th to 55.5th. Long-term treatment (up to 12 months) of infants with exocrine pancreatic insufficiency owing to cystic fibrosis with ZENPEP was well tolerated and associated with improved growth parameters. This is the first long-term study of pancreatic enzyme replacement therapy conducted in this patient population.

We can handle this: parents' use of religion in the first year following their child's diagnosis with cystic fibrosis.

The diagnosis of a child's life-shortening disease leads many American parents to utilize religious beliefs. Models relating religious constructs to health have been proposed. Still lacking are inductive models based on parent experience. The specific aims of this study were: 1. develop a grounded theory of parental use of religion in the year after diagnosis; 2. describe whether parents understand a relationship between their religious beliefs and their follow-through with their child's at-home treatment regimen. Fifteen parent interviews were analyzed using grounded theory method. Parents used religion to make meaning of their child's cystic fibrosis (CF) diagnosis. Parents imagined God as active, benevolent, and interventionist; found hope in their beliefs; felt supported by God; and related religion to their motivation to adhere to their child's treatment plan. Religious beliefs are clinically significant in working with many parents of children recently diagnosed with CF. Interventions that improve adherence to treatment may be enhanced by including religious aspects.

Parents' religious coping styles in the first year after their child's cystic fibrosis diagnosis.

Parents of children diagnosed with cystic fibrosis described it as "devastating." Given religion's importance to many Americans, parents may utilize religious coping. Relatively little is known about parents' use of religious coping to handle their child's illness. Interviews with 15 parents about their use of religion in the year following their child's cystic fibrosis diagnosis were coded for religious coping styles. Sixteen styles were identified. Positive religious coping styles were more frequent than negative styles (previously associated with poorer health outcomes), and occurred more frequently than in other studies. Religious coping styles used to make meaning, gain control, or seek comfort/intimacy with God were equally prevalent. The most common styles were: Pleading, Collaboration, Benevolent Religious Reappraisals, and Seeking Spiritual Support. Parents described active rather than passive coping styles. Religious coping involving religious others was rare. Clinical attention to negative religious coping may prevent it becoming chronic and negatively affecting health.

Using quality improvement science to implement a multidisciplinary behavioral intervention targeting pediatric inpatient airway clearance.

OBJECTIVE: The objective of this study was to use quality improvement science methodology to develop a multidisciplinary intervention improving occurrence of best-practice airway clearance therapy (ACT) in inpatient adolescents with cystic fibrosis during routine clinical care. METHODS: The model for improvement was used to develop and implement interventions. Primary outcomes were quality of ACT (% ACT meeting criteria for best practice) and quantity of ACT (% of hospital days patients received ACT four times/day). Annotated control charts were used to document the impact of the interventions. RESULTS: Quality of ACT significantly improved from 21% best practice ACT at baseline to 73%. Quantity of ACT significantly improved from 41% days with ACT four times/day at baseline to 64%. CONCLUSIONS: A multidisciplinary, evidence-based intervention was effective for improving occurrence of best-practice ACT. Pediatric psychology can make valuable contributions to improving the quality of care provided in the medical setting.

EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency.

BACKGROUND: EUR-1008 (Zenpep [pancrelipase]) is a new, enteric-coated, porcine-derived pancreatic enzyme product (PEP) developed for the treatment of cystic fibrosis (CF) patients with malabsorption associated with exocrine pancreatic insufficiency (EPI). Unlike currently marketed PEPs, EUR-1008 contains the label-claimed lipase content. Safety and efficacy were assessed in younger (<7 years) and older (> or =7 years) CF patients with EPI. METHODS: Two multicenter studies were conducted: a randomized, double-blind, placebo-controlled, crossover trial in patients > or =7 years of age (N=34) and a supplemental, open-label study in children <7 years of age (N=19). Use of any medications altering gastric pH/motility was prohibited during the studies. Outcome measures in the randomized trial included changes in the coefficient of fat absorption (CFA), coefficient of nitrogen absorption (CNA), and signs/symptoms of malabsorption for EUR-1008 vs. placebo. Outcome measures in the supplemental study included safety and response (defined as no steatorrhea and no overt signs/symptoms of malabsorption) to EUR-1008 vs. previous enzyme treatment. RESULTS: In the randomized trial, EUR-1008 treatment compared to placebo resulted in a significantly higher mean CFA (88.3% vs. 62.8%, respectively) and CNA (87.2% vs. 65.7%, respectively) (both p<0.001) and reduced the incidence of malabsorption signs and symptoms in 32 evaluable patients. In the supplemental study, 11 of 19 patients met the criteria for responder with EUR-1008 at the end of the study vs. 10 of 19 patients at screening (previous PEP), and improvements in clinical symptoms were reported with EUR-1008 treatment. EUR-1008 was safe and well tolerated, and no serious drug-related AEs were reported in either study. CONCLUSIONS: EUR-1008 was safe, well tolerated, and effective in CF patients of all ages with EPI-associated malabsorption in two clinical trials. Treatment led to clinically and statistically significant improvements in CFA and CNA in the randomized study, and control of malabsorption and clinical symptoms in both studies.

Glucose tolerance, insulin secretion, and insulin sensitivity in children and adolescents with cystic fibrosis and no prior history of diabetes.

OBJECTIVE: To determine the prevalence of abnormalities of glucose metabolism in pediatric outpatients with cystic fibrosis (CF). STUDY DESIGN: Children and adolescents (n = 73, mean age 15.0 +/- 3.7 years) with CF not previously diagnosed with diabetes underwent 3-hour oral glucose tolerance testing. All subjects with CF were clinically stable and were not being treated for active infection. A reference group of young lean adults was used for comparison. Subjects were classified as having normal glucose tolerance (NGT) or abnormal glucose metabolism (AGM), including impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or diabetes, by standard criteria. The insulinogenic index was calculated as a measure of beta-cell function, and insulin resistance was estimated with the homeostatic model assessment. RESULTS: The reference group was significantly older than the patients with CF, but in the control subjects, the AGM and NGT were comparable in body mass index z-scores (-0.8 +/- 1.3, -0.6 +/- 1.1, -0.21 +/- 0.9 kg/m2). Thirty-eight percent of subjects with CF had AGM: 43% IGT, 29% IFG, 14% IGT/IFG, and 14% diabetes. In spite of distinct differences in glycemic response, the subjects with NGT and AGM had marked abnormalities of insulin secretion relative to the control subjects (Insulinogenic index 5.8 +/- 1.0, 5.3 +/- 0.8, and 53.5 +/- 10.0 uU/mL/mmol/L, respectively; P < .0001). Insulin sensitivity did not differ among the 3 groups, although there was a trend toward greater insulin resistance in the subjects with AGM (homeostatic model assessment: CF-NGT 1.5 +/- 0.2, CF-AGM 1.9 +/- 0.3, REF 1.3 +/- 0.1, P = NS). CONCLUSION: Abnormalities in glucose metabolism are frequent in young patients with CF without a prior diagnosis of diabetes and are associated with marked defects in insulin secretion. Given the poor beta-cell function in patients with CF, even small reductions in insulin sensitivity may be an important determinant of AGM.

NO pathway in CF and non-CF children.

Controversy exists concerning abnormalities of the nitric oxide (NO) pathway in cystic fibrosis (CF) lung disease. Although some studies suggested that NO activity is impaired in CF, changes in NO production in young children have not been studied. We hypothesized that nitric oxide synthase (NOS II) expression is decreased in young children with CF, leading to decreased production of lower airway NO, and that decreased NOS II expression is related to airway inflammation. Accordingly, we measured lower airway exhaled NO, nitrate, and NOS II expression in airway epithelium and macrophages by bronchoscopy, bronchoalveolar lavage (BAL), and bronchial brushing in 13 children with CF, 4 adolescent patients with CF, and 14 disease control children. Lower airway NO and nitrate were not different between CF and disease controls. Immunostaining studies of NOS II expression in airway epithelial cells and macrophages were similar in CF and control patients. Within the CF group, however, expression of NOS II was inversely related to BAL neutrophil counts and IL-8, two markers of airway inflammation. We conclude that lower airway NO, nitrate levels, and NOS II expression are not different in young children with CF and disease control patients, but that NOS II expression decreases in CF as airway inflammation increases.

Diaphragmatic hernia simulating a left pleural effusion.

We review a case of a diaphragmatic hernia simulating on chest radiograph left lower lobe pneumonia and associated pleural effusion. We also characterize the atypical chest radiographic findings of this patient and recommend further imaging with computed tomography in unusual patient presentations.

Transcriptional adaptation to cystic fibrosis transmembrane conductance regulator deficiency.

Cystic fibrosis, the most commonly inherited lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). To identify genomic responses to the presence or absence of CFTR in pulmonary tissues in vivo, microarray analyses of lung mRNAs were performed on whole lung tissue from mice lacking (CFTR(-)) or expressing mouse CFTR (CFTR(+)). Whereas the histology of lungs from CFTR(-) and CFTR(+) mice was indistinguishable, statistically significant increases in the relative abundance of 29 and decreases in 25 RNAs were identified by RNA microarray analysis. Of RNAs whose expression was consistently altered by the absence of CFTR, functional classes of genes influencing gene transcription, inflammation, intracellular trafficking, signal transduction, and ion transport were identified. RNAs encoding the transcription factor CCAAT enhancer-binding protein (CEBP) delta and interleukin (IL) 1beta, both known to regulate CFTR expression, were induced, perhaps indicating adaptation to the lack of CFTR. RNAs mediating lung inflammation including calgranulin-S100 family members, IL-1beta and IL-4, were increased. Likewise, expression of several membrane transport proteins that interact directly with CFTR were increased, suggesting that CFTR-protein complexes initiate genomic responses. Absence of CFTR influenced the expression of genes modulating diverse pulmonary cell functions that may ameliorate or contribute to the pathogenesis of CF.