Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Early-Life Height Attainment in Cystic Fibrosis Is Associated with Pulmonary Function at Age 6 Years.

Rationale: In contrast to the well-described association between early-life weight for age, body mass index (BMI), and later lung disease in people with cystic fibrosis (CF), the relationship between height-for-age (HFA) percentiles and respiratory morbidity is not as well-studied. We hypothesized that changes in HFA in children with CF in the first 6 years of life would be associated with pulmonary function at the age of 6-7 years. Objectives: To determine if an association exists between changes in HFA in early life and pulmonary function in school-aged children with CF. Methods: We performed a retrospective longitudinal cohort study of children with CF followed in the CF Foundation Patient Registry who were born between 2003 and 2010, had CF diagnosed before the age of 2 years, and were followed through at least the age of 7 years. Changes in annualized HFA were classified into mutually exclusive categories. Multivariable analysis of covariance models were used to test for an association between the percent-predicted forced expiratory volume in 1 second (FEV1) at the age of 6-7 years and height-trajectory categories. Results: There were 5,388 eligible children in the CF Foundation Patient Registry. The median (interquartile range) HFA at the age of 6-7 years was in the 39.5th (17.2th-64.9th) percentile. The mean (95% confidence interval) FEV1% predicted at the age of 6-7 years was 95.6% (95.1-96.1%). In a multivariable regression model, the mean (95% confidence interval) FEV1% predicted was higher for children with HFA that was always above the 50th percentile (97.8% [96.3-99.4%]) than for children whose height had been below the 50th percentile for at least 1 year and increased by ≥10 percentile points (95.1% [93.7-96.6%]), was stable (94.3% [92.8-95.7%]), or decreased by ≥10 percentile points (95.7% [94.2-97.3%]). The association between HFA categories and FEV1% predicted was not affected by adding the mean annualized BMI percentile at the age of 6-7 years to the regression model. Among those with HFA that decreased by ≥10 percentile points, there was a correlation between the nadir annualized HFA percentile and the FEV1% predicted at the age of 6-7 years. Conclusions: Children with CF with HFA that is always above the 50th percentile have the highest pulmonary function at the age of 6-7 years. Maintaining a BMI above the 50th percentile remains an important achievable goal for children with CF but is not the sole marker that should be examined in evaluating nutrition.

Nutrition in cystic fibrosis: From the past to the present and into the future.

Nutritional management is an integral part of multidisciplinary care for persons with cystic fibrosis. This review will look at how nutrition care has evolved over time. In addition, we will look at how some newer therapies impact nutrition care.

Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis.

Cystic fibrosis (CF) clinical care guidelines exist for the care of infants up to age 2 years and for individuals ≥6 years of age. An important gap exists for preschool children between the ages of 2 and 5 years. This period marks a time of growth and development that is critical to achieve optimal nutritional status and maintain lung health. Given that disease often progresses in a clinically silent manner, objective and sensitive tools that detect and track early disease are important in this age group. Several challenges exist that may impede the delivery of care for these children, including adherence to therapies. A multidisciplinary committee was convened by the CF Foundation to develop comprehensive evidence-based and consensus recommendations for the care of preschool children, ages 2 to 5 years, with CF. This document includes recommendations in the following areas: routine surveillance for pulmonary disease, therapeutics, and nutritional and gastrointestinal care.

Maximal daily dose of pancreatic enzyme replacement therapy in infants with cystic fibrosis: a reconsideration.

The current recommendations for dosing of pancreatic enzyme replacement therapy (PERT) in infants with cystic fibrosis (CF) were made using a limited evidence base. The per meal recommended dose was extrapolated from dosing guidelines for older patients into a maximal daily dose for infants. We discuss why this maximal daily dose recommendation may be insufficient for young infants with CF, although the optimal dose of PERT for infants with CF remains unknown.

Hypoalbuminemia in a cystic fibrosis patient with severe erosive esophagitis.

An 8-year-old patient with cystic fibrosis presented with hypoalbuminemia as the main symptom of severe erosive esophagitis. Extensive evaluation failed to reveal a nutrition, pancreatic, intestinal, or renal explanation of his hypoalbuminemia. Identification and treatment of the esophagitis led to resolution of the hypoalbuminemia.

Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo-controlled, two-period crossover, superiority study.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval. OBJECTIVE: This study was conducted to compare the efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover, superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI. In each period, pancrelipase or identical placebo capsules were taken for 5 days. The primary outcome measure was the coefficient of fat absorption (CFA); secondary outcome measures were the coefficient of nitrogen absorption (CNA) and clinical symptoms. The latter were assessed based on patient-reported daily stool frequency, stool consistency (hard, formed/normal, soft, or watery), flatulence (none, mild, moderate, or severe), and abdominal pain (none, mild, moderate, or severe). Safety measures included vital signs, physical examinations, standard laboratory safety tests (hematology and biochemistry), and adverse events. RESULTS: Seventeen patients were randomized to treatment and 16 completed the study; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis. Patients' median age was 8.0 years (range, 7-11 years); 12 patients (70.6%) were male. CFA values were significantly greater for pancrelipase compared with placebo, with least squares mean (SE) values of 82.8% (2.7%) and 47.4% (2.7%), respectively (P < 0.001). The results were similar for CNA, with mean values of 80.3% (3.2%) and 45.0% (3.2%) (P < 0.001). Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA <50% than in those with a placebo CFA >50% (both parameters, P < 0.001 and P = 0.008, respectively). Significant improvements in stool fat, weight, and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo (all, P < 0.001). Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment, but worsened slightly during receipt of placebo. Treatment-emergent adverse events were reported in 5 patients (29.4%) during receipt of pancrelipase and in 9 patients (56.3%) during receipt of placebo; these were predominantly gastrointestinal events. There were no discontinuations due to treatment-emergent adverse events and no serious adverse events. CONCLUSIONS: In this study in children with EPI due to CF, the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA, CNA, stool properties, and EPI symptoms compared with placebo. Pancrelipase delayed-release capsules appeared to be well tolerated. ClinicalTrials.gov identifier: NCT00690820. (Clin Ther.

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.