Optimizing GI Health in CF:
More than Meets the Enzyme
Zachary M Sellers, MD, PhD
Department of Pediatrics, Stanford University, Palo Alto, CA
2015 Stanford CF Education Day
My Perspective
• I am not a pulmonologist
• I am pursuing clinical training in pediatric gastroenterology
•
focused on CF
I perform research examining CF intestinal and pancreatic
disease
Manifestations of Cystic Fibrosis
Common Gastrointestinal Problems in CF
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Gastroesophageal Reflux
Pancreatic Insufficiency
Intestinal Malabsorption
Liver Disease
Intestinal Obstruction (meconium ileus, DIOS)
GI Health = Lung Health
CF Foundation Patient Registry, 2013
Does this sound familiar?
“I have abdominal pain whenever I eat”
“My stools are greasy”
“I feel nauseous”
“No matter how much I eat I can’t seem to gain weight”
“It is hard to go to the bathroom”
Often times we think about…
Pancreatic Enzyme
Efficacy
Gastrointestinal pH
Pancreatitis
GI
Symptoms
Intestinal
Inflammation
Liver Function
Bacterial Overgrowth
and Dysbiosis
Stomach pH, GER, Gastric
Emptying
• Unclear if stomach pH in CF is altered –
mixed results from human and animal studies
• Gastroesophageal Reflux (GER) is increased in CF –
coughing
• Possibly delayed gastric emptying
Intestinal pH
• Important for:
– Protection of intestines from gastric acid
– Pancreatic and intestinal enzyme efficacy
– Proper release, formation, and/or viscoelasticity of
mucus
– Micelle formation
– Regulation of the intestinal microenvironment
Intestinal pH in CF
Post-prandial pH in CF 3.6 vs. 5-7 in controls
• Hyperacidity precipitates bile  impeding micelle
•
formation
Enzymes release from coating at pH >5
Dig Dis Sci. 2013, 58(8):2275-81
Intestinal Inflammation
• We are beginning to appreciate that there
can be increased mucosal inflammation
within the intestines of those with CF
– Diffuse inflammation
– Altered intestinal barrier
– Increased stool calprotectin
J Pediatr Gastroenterol Nutr 2014, Dec 23
Intestinal Bacterial Overgrowth
and Dysbiosis
• Bacterial overgrowth and alteration of gut flora can be
•
caused by:
– Thick secretions
– Intestinal dysmotility
– Acid-suppressing drugs
– Chronic antibiotic use
Dysbiosis can lead to inflammation, increased gas
formation, malabsorption, altered bile acid secretion and
micelle formation
Pancreatitis
• Of those that are pancreatic sufficient, ~10% will develop
pancreatitis
• Pancreatic ductal flow becomes blocked  enzymes
build  cause inflammation and damage  pain
• Caused by altered CFTR-dependent ion transport in
pancreas
– Increased duodenal acidity in mice leads to excessive
pancreatic fluid secretion, stress, and inflammation
Scand J Gastroenterol. 1994, 29(10):889-96
CF Liver Disease
• Bile salts produced by liver cells are important in fat
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•
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digestion and absorption
Biliary secretion of bicarbonate contributes to intestinal pH
Liver enzymes (AST/ALT) are elevated in ~50% of CF
children
5-10% of children with CF develop liver cirrhosis with its
associated complications
– Does not correlate with liver enzyme levels
– Imaging may be useful, but may not detect early disease
– Liver biopsy can detect early disease, but may miss due to sampling
location
Clin Gastroenterol Hepatol 2013, 11:333-342
Take Home Points
• Maintaining gastrointestinal health is important to overall
health in CF
• There are numerous gastrointestinal complications in
CF
• While pancreatic enzyme management is important in
CF, there are many facets of GI function that need to be
considered in troubleshooting problems
• Close collaboration between Pediatric Pulmonologists,
Pediatric Gastroenterologists, and Nutritionists is
important.