Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy.

Cystic fibrosis (CF) is a progressive, genetic, multi-organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction. The majority of people with CF (pwCF) experience exocrine pancreatic insufficiency resulting in malabsorption of nutrients and malnutrition. Additionally, other factors can cause or worsen fat malabsorption, including the potential for short gut syndrome with a history of meconium ileus, hepatobiliary diseases, and disrupted intraluminal factors, such as inadequate bile salts, abnormal pH, intestinal microbiome changes, and small intestinal bacterial overgrowth. Signs and symptoms associated with fat malabsorption, such as abdominal pain, bloating, malodorous flatus, gastroesophageal reflux, nausea, anorexia, steatorrhea, constipation, and distal intestinal obstruction syndrome, are seen in pwCF despite the use of pancreatic enzyme replacement therapy. Given the association of poor nutrition status with lung function decline and increased mortality, aggressive nutrition support is essential in CF care to optimize growth in children and to achieve and maintain a healthy body mass index in adults. The introduction of highly effective CFTR modulator therapy and other advances in CF care have profoundly changed the course of CF management. However, GI symptoms in some pwCF may persist. The use of current knowledge of the pathophysiology of the CF GI tract as well as appropriate, individualized management of GI symptoms continue to be integral components of care for pwCF.

Developing a nutrition screening tool for children with cystic fibrosis ages 0 to 2 years: Children with cystic fibrosis nutrition screening tool.

BACKGROUND: For children with cystic fibrosis (CF), achieving and maintaining optimal growth by the age of 2 years is critical for future health outcomes. A standardized nutrition screening is needed to identify growth problems, enable timely interventions, and improve nutritional outcomes for children (0 to 2 years) with CF. The purpose of this study was to develop a nutrition screening tool for children (0 to 2 years) with CF to identify nutrition risk at every clinical encounter. METHODS: A retrospective cross-sectional study was used to develop a nutrition screening tool to determine if nutrition interventions needed to change (at-risk) or continue (not at-risk). Retrospective data for pertinent nutrition factors were collected for 99 children attending an accredited CF clinic. The nutrition factors were compared to a dietitian assessment. A stepwise discriminant analysis determined weight-for-age (WFA) and weight-for-length (WFL) z-scores were significant. Then anthropometric data and corresponding dietitian assessment results were collected for children with CF attending two other accredited CF clinics (n = 29, n = 30). Discriminant analysis was used to determine sensitivity and specificity of the nutrition factors and to create a nutrition screening tool equation. RESULTS: The nutrition screening model that included WFA z-score, LFA z-score, WFL z-score, and weight change velocity adequacy determined nutrition risk the best. The sensitivity was 89.7 %, specificity 83.2 %, NPV 93.3 %, and PPV 75.4 % for this model. CONCLUSION: The nutrition screening tool equation developed in this study standardizes the process to identify children (0 to 2 years) with CF at nutrition risk. Further validation is needed.

Improvement of lipid and lipoprotein profiles in children and adolescents with cystic fibrosis on CFTR modulator therapy.

BACKGROUND: Association of a high-fat diet with increased risks of cardiovascular disease (CVD) and type 2 diabetes, has prompted evaluation of lipids in people with CF (pwCF). However, most evidence on dyslipidemia was published before CF transmembrane conductance regulator (CFTR) modulators became a standard of care. The main goal of this study was to investigate the effect of CFTR modulator therapies on lipid and lipoprotein profiles in children and adolescents with CF. METHODS: Blood samples were collected from 153 pwCF (10.1 ± 4.7 years of age) and 60 age-matched controls. Most pwCF were pancreatic insufficient on pancreatic enzyme replacement therapy. By the end of the study, 65% of CF participants were on CFTR modulator therapy for >1 month. The results of traditional and advanced lipid testing in pwCF were correlated with clinical and dietary information. RESULTS: Total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly lower in pwCF compared to non-CF participants. Those not receiving CFTR modulators also had significantly lower high-density lipoprotein (HDL) cholesterol and HDL particle number than controls. Individuals with CF on modulator therapy had significantly higher concentrations of anti-atherogenic HDL cholesterol and HDL particles along with lower levels of atherogenic large very-low density lipoprotein (VLDL) particles, total and small LDL particles, and triglycerides compared to those without CFTR modulator therapy. CONCLUSION: CFTR modulator therapy has a beneficial effect on dyslipidemia in CF. It remains to be seen if these positive changes translate into decreased CVD risk later in life given the increasing life expectancy in CF.

Overweight and cystic fibrosis: An unexpected challenge.

Achieving a healthy weight balance has been a central focus of care for people who have cystic fibrosis (CF). Over the years, the emphasis has primarily been on promoting weight gain to optimize pulmonary outcomes. With continued improvements in CF care, including highly effective CF modulators available for many people, the CF community is now experiencing a new challenge: addressing the concern that some people are gaining weight excessively. While at this time, we do not know to what extent overweight and obesity will affect health outcomes for people with CF, it is likely that excessive weight gain may have negative health impacts similar to those seen in the general population. In this paper, we review the history of nutritional guidelines for people with CF, as well as more recent trends toward overweight and obesity for some. A multidisciplinary approach is needed to collaboratively start the oftentimes difficult conversation regarding excessive weight gain, and to identify resources to help people achieve and maintain a healthy weight through diet, exercise, and behavioral modification.

Zinc status and growth in infants and young children with cystic fibrosis.

BACKGROUND: Zinc deficiency is associated with poor growth in children without cystic fibrosis (CF), but its impact on growth in children with CF is unknown. OBJECTIVE: To determine the prevalence of low serum Zn (sZn) and its relationship with growth in the first 3 years of life in children with CF. METHODS: We utilized data from infants with CF who were enrolled in a longitudinal study of nutrition and lung health and had sZn measured as part of clinical care. Cross-sectional correlations between sZn levels and growth z scores were assessed by Pearson's correlation coefficient. To identify factors associated with sZn status and its association to longitudinal growth patterns, multiple regression analysis with repeated measures were performed using generalized estimating equations. RESULTS: A total of 106 sZn measurements from 53 infants were identified. Seventeen infants (32%) had intermittent Zn insufficiency, defined as at least one sZn <70 mcg/dl in their first 3 years of life. There were no significant cross-sectional associations between sZn and growth z scores. However, analysis of longitudinal growth patterns revealed that weight- and length-for-age z scores in children with intermittent Zn insufficiency were lower during early infancy and their weight-for-length z scores at age 3 years were also lower compared to those who were always Zn sufficient. CONCLUSION: Low sZn occurs in one-third of children with CF in the first 3 years of life. Cross-sectional and longitudinal analyses revealed discrepant associations between sZn and growth. Therefore, prospective studies are needed to understand the role of Zn in growth in CF.

Effect of CFTR Modulators on Anthropometric Parameters in Individuals with Cystic Fibrosis: An Evidence Analysis Center Systematic Review.

There is a strong positive association between nutrition status and lung function in cystic fibrosis (CF). Improvements in clinical care have increased longevity for individuals with CF, and it is unknown how cystic fibrosis transmembrane regulator (CFTR) modulation therapy affects nutrition status over time. The objective of this systematic review of the literature was to examine anthropometric (height, weight, and body mass index [BMI; calculated as kg/m2]) and body composition outcomes of CFTR modulation therapy. A literature search of Medline (Ovid), Embase, and CINAHL (EBSCO) databases was conducted for randomized controlled trials examining the effect of CFTR modulation therapy on anthropometric and body composition parameters, published in peer-reviewed journals from January 2002 until May 2018. Articles were screened, data were synthesized qualitatively, and evidence quality was graded by a team of content experts and systematic review methodologists. Significant weight gain with ivacaftor was noted in children and adults with at least 1 copy of G551D mutation. In adults with at least 1 copy of R117H the effect of ivacaftor on BMI was not significant. Effects on BMI were mixed in adults with class II mutations taking ivacaftor with lumacaftor. There was no significant change in BMI in children homozygous for F508del who took ivacaftor with tezacaftor. Elexacaftor-tezacaftor-ivacaftor increased BMI and body weight in individuals 12 years of age and older who were hetero- or homozygous for the F508del mutation. The effect of CFTR modulation therapy on anthropometric parameters depends on the genetic mutation and the type of modulation therapy used. More research is needed to understand the long-term clinical impact of these drugs on nutritional status, including body composition and the role of dietary intake.

Dietary Macronutrient Distribution and Nutrition Outcomes in Persons with Cystic Fibrosis: An Evidence Analysis Center Systematic Review.

Cystic fibrosis (CF) increases risk for undernutrition and malabsorption. Individuals with CF traditionally have been counseled to consume a high-fat diet. However, a new era of CF care has increased lifespan and decreased symptoms in many individuals with CF, necessitating a re-examination of the high-fat CF legacy diet. A literature search was conducted of Medline (Ovid), Embase, and CINAHL (EBSCO) databases to identify articles published from January 2002 to May 2018 in the English language examining the relationships between dietary macronutrient distribution and nutrition outcomes in individuals with CF. Articles were screened, risk of bias was assessed, data were synthesized narratively, and each outcome was graded for certainty of evidence. The databases search retrieved 2,519 articles, and 7 cross-sectional articles were included in the final narrative analysis. Three studies examined pediatric participants and 4 examined adults. None of the included studies reported on outcomes of mortality or quality of life. Very low certainty evidence described no apparent relationship between dietary macronutrient distribution and lung function, anthropometric measures, or lipid profile in individuals with CF. The current systematic review demonstrates wide ranges in the dietary macronutrient intakes of individuals with CF with little to no demonstrable relationship between macronutrient distribution and nutrition-related outcomes. No evidence is presented to substantiate an outcomes-related benefit to a higher fat-diet except in the context of achieving higher energy intakes in a lesser volume of food.

Academy of Nutrition and Dietetics: 2020 Cystic Fibrosis Evidence Analysis Center Evidence-Based Nutrition Practice Guideline.

The Academy of Nutrition and Dietetics Evidence Analysis Center conducted a systematic review of the literature to develop an evidence-based practice guideline for primary nutrition issues in cystic fibrosis (CF). This guideline is designed to complement and build upon existing evidence-based CF nutrition guidelines. The objective of this guideline was to provide recommendations for registered dietitian nutritionists in the United States delivering medical nutrition therapy to individuals with CF and their families that fill gaps in current evidence-based guidelines on topics that are crucial in order to improve health and prevent disease progression. This guideline provides 28 nutrition recommendations to guide medical nutrition therapy, including nutrition screening, nutrition assessment, and dietary intake. For topics outside the scope of this guideline, practitioners are referred to external, evidence-based recommendations. The CF landscape is evolving rapidly with breakthroughs in cystic fibrosis transmembrane regulator modulators changing CF at a cellular level. Medical nutrition therapy for individuals with CF from infancy through advanced age requires novel and individualized approaches. The Academy Evidence Analysis Library CF guidelines provide a framework for expanding upon current knowledge to determine effective nutrition strategies for individuals with CF through long and healthy futures.

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.

Evaluating Changes in Handgrip Strength in Children With Cystic Fibrosis: A Pilot Study.

BACKGROUND: Body mass index (BMI) is used to determine nutrition status in children with cystic fibrosis (CF); however, lean body mass (LBM) is more strongly associated with pulmonary function. Handgrip strength (HGS) measures muscle function and is reflective of LBM. The aims of this study were to assess relationships among HGS, nutrition status, and pulmonary function; changes in HGS posthospitalization; and any relationship between HGS and nutrient intake. METHODS: Twenty-three children with CF aged 6-18 years participated. BMI z scores, nutrition risk scores, and pulmonary function were assessed about 5 months before, days 5-7 of hospitalization, and about 6 weeks posthospitalization. HGS z scores and arm anthropometrics were measured during and after hospitalization. Nutrient intakes were assessed during hospitalization. RESULTS: Mean HGS z score at hospitalization was -1.95 ± 0.92 and posthospitalization was -1.59 ± 1.06 (P = .007). Mean BMI z score prehospitalization was -0.17 ± 0.63, at hospitalization was -0.09 ± 0.64, and posthospitalization was 0.06 ± 0.54 (P = .065). Mean forced expiratory volume in 1 second (FEV1 ) prehospitalization was 93.52 ± 17.35, at hospitalization was 85.65 ± 21.57, and posthospitalization was 95.63 ± 18.18 (P = .001). No significant relationship was found between HGS z scores and BMI z scores (P = .892) or HGS z scores and FEV1 (P = .340). CONCLUSIONS: HGS z scores and FEV1 significantly increased at follow-up. HGS z scores were lower than the standard even though mean BMI z scores classified participants as normal nutrition status.

Enteral tube feeding for individuals with cystic fibrosis: Cystic Fibrosis Foundation evidence-informed guidelines.

Nutrition is integral to the care of individuals with cystic fibrosis (CF). Better nutritional status is associated with improved pulmonary function. In some individuals with CF, enteral tube feeding can be useful in achieving optimal nutritional status. Current nutrition guidelines do not include detailed recommendations for enteral tube feeding. The Cystic Fibrosis Foundation convened an expert panel to develop enteral tube feeding recommendations based on a systematic review of the evidence and expert opinion. These guidelines address when to consider enteral tube feeding, assessment of confounding causes of poor nutrition in CF, preparation of the patient for placement of the enteral feeding tube, management of the tube after placement and education about enteral feeding. These recommendations are intended to guide the CF care team, individuals with CF, and their families through the enteral tube feeding process.

Hospital and demographic characteristics associated with advanced primary stroke center designation.

BACKGROUND AND PURPOSE: Despite evidence that primary stroke center (PSC) certification is associated with improvements in care and outcome, only a minority of hospitals have achieved this certification. We sought to determine hospital-based factors associated with achievement of PSC certification. METHODS: We used the 2011 American Hospital Association survey and the 2010 national census for population and household data to identify potential hospital and demographic factors influencing certification as a PSC by the Joint Commission, Healthcare Facilities Accreditation Program, and DNV Healthcare. RESULTS: Of the 3696 hospitals to complete the survey, 3069 fulfilling study criteria included 908 PSC (31%) and 2161 non-PSC. Independent hospital characteristics associated with PSC certification were Joint Commission accreditation (odds ratio [OR], 3.5; 95% confidence interval [CI], 2.4-5.0), increasing size (per quartile in number of beds; OR, 2.5; 95% CI, 2.1-3.1) and inpatient neurological services (OR, 3.2; 95% CI, 2.4-4.6), number of households per zip code (per 1000 households; OR, 1.1; 95% CI, 1.0-1.2), increasing Hispanic population (by 10% increase; OR, 1.1; 95% CI, 1.0-1.2), and income per household (per $10 000; OR, 1.2; 95% CI, 1.1-1.3). Designation as a sole community provider (OR, 0.22; 0.10-0.47) or governmental hospital control (0.61; 0.44-0.84) was associated with noncertification. CONCLUSIONS: Less than 1 in 3 hospitals has achieved certification as an PSC. Potential areas of improvement include increasing certification of governmental-controlled hospitals.

Self-efficacy: empowering parents of children with cystic fibrosis.

BACKGROUND: Can parent engagement in the development and delivery of educational materials for cystic fibrosis (CF) promote increased self-efficacy and confidence in self-management skills? Standard therapies for a child with CF frequently involve pulmonary treatment, medications, and behavioral and nutritional interventions. Parents report that the prescribed CF care can be overwhelming. Previous research at this pediatric CF Center indicated the parental perception of the difficulty in managing CF-related nutrition therapy. Parents' nutrition knowledge was an initial target of this continuous quality improvement (CQI) project with a long-range aim of increasing children's median body mass index (BMI) percentiles for patients at this pediatric CF center. METHODS: The local CF Parent Advisory Council, CF parents and staff collaborated on this family-centered CQI project. A CF parent website with weekly email newsletters and a facebook page were developed and evolved with input from parents. Parental feedback was gathered through electronic surveys, written questionnaires, focus groups and informal interviews. A convenience sample of parents participated in pre- and post-intervention surveys to determine change in self-confidence in effectively managing their children's CF treatment regimens. Results were also compared with responses from a larger previous survey. RESULTS: Parental knowledge of nutrition facts and medical nutrition therapy for CF did not increase significantly over the course of the CQI project. Surveyed parents reported increased confidence in their self-management skills. Although mean BMI percentiles have increased at this center, they remain below the national average. CONCLUSIONS: Parent-driven educational strategies provide an opportunity to promote reliable CF-related information in parent-preferred formats that enhance self-management skills in caring for children with CF. Parental confidence to follow CF center recommendations increased between 2004 and 2011. Although many factors may impact confidence, parent satisfaction with the creation of electronic resources and engagement in the CQI process were intangible, but important outcomes.

Correlation of cholestasis with serum copper and whole-blood manganese levels in pediatric patients.

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing <25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighing > or =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin level > or =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levels > or =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.

Validation of a nutrition risk screening tool for children and adolescents with cystic fibrosis ages 2-20 years.

OBJECTIVES: According to the 2002 Cystic Fibrosis (CF) Foundation nutrition consensus report, children with CF should grow normally. Cross-sectional data from the foundation's patient registry concluded that a body mass index at or greater than the 50th percentile is associated with better lung function. A consistent, evidence-based screening process can identify those individuals with CF having nutrition risk factors associated with a decrease in pulmonary function, target early intervention, and prevent further decline. A tool for screening nutrition risk is described to identify those children with CF who would benefit from more extensive nutrition intervention. METHODS: The proposed screening tool is a risk-based classification system with 3 categories: weight gain, height velocity, and body mass index. The CF Foundation recommendations regarding these parameters are incorporated, with risk points assigned when minimum body mass index, weight gain, and/or height gain standards are unmet. RESULTS: An interrater measure of agreement determined a satisfactory level of reliability (kappa = 0.85). Patient records (n = 85) were reviewed to determine nutrition status category (no risk or at risk) of this tool compared with the CF Foundation 2002 Nutrition Consensus, yielding sensitivity and specificity at 84% and 75%, respectively. A second comparison was made with combined, independent nutrition risk factors not included in the screening tool. The sensitivity and specificity of the screening tool compared with the combined risk factors were 86% and 78%, respectively. CONCLUSIONS: This tool for screening nutrition risk for CF is reliable and valid, with consistent, reproducible results, free from subject or observer bias.