This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.
This first slide shows the growth in NASPGHAN membership:
Year in Review
Melvin Heyman Editor, JPGN
This lecture reviewed a number of influential studies that have been published in the past year. After brief review of the study, Dr. Heyman summarized the key take-home point.
NY Times Summarizes the reasons why Canadians with Cystic Fibrosis Live Longer: Link: Canadians With Cystic Fibrosis Live 10 Years Longer Than Americans With the Disease
Cystic fibrosis is an inherited disease that causes recurrent lung infections and other problems. The average lifespan for an American with the illness is 37 years. In Canada, it is 49.
Researchers studied records of 5,941 Canadian and 45,448 American cystic fibrosis patients between 1990 and 2013. After controlling for severity of disease, age and other factors, they found that overall death rates were 34 percent lower in Canada than in the United States.
There was no difference in death rates between Canadians and Americans with private health insurance. But Canada provides universal health care coverage under a single-payer system, so every Canadian has some kind of health insurance. The Canadian death rate was 44 percent lower than that of Americans on Medicaid or Medicare, and 77 percent lower than Americans without insurance.
AL Stephenson et al. Ann Intern Med. 2017. DOI: 10.7326/M16-0858
Sainte-Chapelle, Paris
The availability of multiple diagnostic techniques for cystic fibrosis has increased the complexity and created areas of uncertainty. A recent supplement (J Pediatr 2017; 181S: 1-55) delve into these issues.
“The diagnosis of CF has become increasingly complex, as CFTR mutations resulting in a wide spectrum of dysfunction have been increasingly identified.”
On page S6, 27 consensus recommendations are given.
The article S45-51, reviews cystic fibrosis transmembrane conductance regulator-related metabolic syndrome (CRMS) and cystic fibrosis screen positive, inconclusive diagnosis (CFSPID). Key points:
Related blog posts:
Wilschanski et al (JPGN 2016; 63: 671-5) provide a summary (“highlights”) of a full report (Turck D et al. Clin Nutr 2016; 35: 557-77) on nutritional recommendations for infant and children with cystic fibrosis.
What’s in here:
Table 1: criteria for adequate nutritional status including
Table 2: nutritional assessment and followup
Table 3: Energy requirements
Table 4: Pancreatic enzyme replacement therapy (PERT)
Table 5: Fat-soluble vitamin/vitamin guidelines
Table 6: Sodium supplementation
Related blog posts:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Maine Coast, near Acadia
A recent study (C Colombo et al. J Pediatr 2016; 177: 59-65) examined 20 patients with cystic fibrosis-associated liver disease (CFLD) who were receiving ursodeoxycholic acid (UDCA) for at least 2 years. Specifically, they wanted to focus on the extent of biotransformation of UDCA to its hepatotoxic metabolite, lithocholic acid. The possibility that long-term UDCA therapy could be detrimental was propelled by a primary sclerosing cholangitis study (K Lindor et al. Hepatology 2009; 50: 808) which indicated that high doses of UDCA resulted in worse outcomes despite better “liver function tests.”
Dosing of UDCA: 20 mg/kg/day
Key findings: UDCA became the predominant serum bile acid; 2 hours after UDCA administration, “both UDA and chenodeoxycholic acid significantly increase (P< .01), but no significant changes in serum lithocholic acid concentrations were observed.”
What does this study prove?
Well, not very much. There are other potential mechanisms for UDCA toxicity and as the editorial notes, “we still lack the necessary endpoints in CF liver disease with which to assess the efficacy of UDCA or any therapy that is on the horizon.”
My take: Because our surrogate markers are unreliable for CFLD, there really is no way to know with certainty whether UDCA therapy is beneficial.
These articles have been sitting on my desk or my email and worth a quick mention:
“Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial” DE Freedberg et al. Gastroenterol 2015; 149: 883-85. In this study of 12 healthy volunteers over 12 weeks, the study’s major finding (according to associated commentary) “is the absence of any significant changes in microbial diversity with proton pump inhibitors.” However, there was “an increase in bacterial taxa associated with C difficile infection.”
“Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome” BM Kamath et al. J Pediatr 2015; 167: 390-6. Quality of life is impaired in Alagille compared to healthy children and children with alpha-one antitrypsin; it is associated with growth failure which may be modifiable.
“Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis” DH Leung et al. J Pediatr 2015; 167: 862-68. In this prospective study of children (n=719) from age 3-12 years, unsuspected cirrhosis was seen in 3.3% of patients and a heterogeneous liver echotexture was identified in 8.9%.
Case report of phlegmonous gastritis associated with ulcerative colitis (with good pictures): J Cordova, R Gokhale, B Kirschner. Gastroenterol 2015; 149: 867-69.
“High Prevalence of Idiopathic Bile Acid Diarrhea Among Patients with Diarrhea-Predominant Irritable Bowel Syndrome Based on Rome III Criteria” I Aziz et al. Clin Gastroenterol Hepatol 2015; 13: 1650-55.
“Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study” The Lancet. DOI: http://dx.doi.org/10.1016/S1473-3099(15)00424-7 (Reference from Sana Syed)
While most clinicians are familiar with cystic fibrosis (CF), much fewer are familiar with a group of disorders related to the cystic fibrosis transmembrane conductance regulator (CFTR) that do not meet the criteria for cystic fibrosis. A summary of these disorders is provided in a recent editorial (Levy H, Farrell PM. J Pediatrics 2015; 166: 1337-40). In addition, the editorial provides insight into a related study: Groves T et al.. J Pediatrics 2015; 166: 1469-74.
The editorialists note that new disorders have been created due to newborn screening and due to the use of CF mutation analysis. New disorders:
The editorial notes that nearly 20% of patients with CF are being enrolled in the CF foundation patient registry without sweat chloride testing results. They do not favor this approach because the diagnosis of CF requires proof of CFTR dysfunction, not simply CF DNA mutations.
Take-home message: Patients who do not meet the criteria for CF but who have intermediate sweat testing or abnormal CF DNA mutations need to be followed. Some will fulfill the criteria with time and others may develop other clinical problems even without having CF.
Abstract (from NEJM twitter feed):
Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTRmutation.
We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508delCFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week 24.
A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor–ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor–ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor–ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor–ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor–ivacaftor versus 1.6% among those who received placebo.
These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers,NCT01807923 and NCT01807949.)
Take-home point: The combination of a CFTR corrector and potentiator may “benefit patients who are homozygous for the Phe508del CFTR mutation and represents a treatment milestone for the 45% of patients with cystic fibrosis who are homozygous for this mutation.”
Related blog post: Ivacaftor for Cystic Fibrosis | gutsandgrowth
2015 N2U Syllabus & Presentations
EoE Dietary Pointers (Syllabus pg 83-94): Sally Schwartz, Valeria Cohran
Related posts:
IBD EEN Pointers (Syllabus pg 95-102): Rebecca Pipkorn, Justine Turner
References:
Conclusions:
Related posts:
Cystic Fibrosis (Syllabus pg 34-50) Justine Turner
Case in point: 10 yo with CF and poor growth, hx/o DIOS, poor intake, and distention. Family had refused tube feedings previously.
Key point: Long-term survival is linked to nutritional status
Other Caveats:
Nutrition Goals
Nutritional assessment at every visit & review:
PERT (Pancreatic enzyme replacement therapy):
Cystic Fibrosis Related Diabetes
Related posts:
Robie House (at Univ Chicago)
gutsandgrowth 