Gastrointestinal Symptoms Common in CF; Women Most Affected
Both children, adults report being dissatisfied with CF treatments
Adults and children with cystic fibrosis (CF) frequently have moderate to severe gastrointestinal (GI) symptoms such as fullness and bloating, and women are primarily affected, new research suggests.
GI-targeted medications were largely not effective and both age groups reported being highly dissatisfied with them.
The study, “Multicentre prospective study showing a high gastrointestinal symptom burden in cystic fibrosis,” was published in the Journal of Cystic Fibrosis.
CF is caused by mutations in the CFTR gene that regulates the movement of water and salts into and out of cells. Such mutations result in abnormally sticky, thick mucus accumulating in various organs, including the lungs, pancreas, liver, and gut.
Although gut symptoms affect patients’ qualtiy of life, few studies have comprehensively investigated these concerns in CF children and adults.
Researchers in the U.S. studied 402 patients (58% adults, 52% male, 95% white) with CF who were enrolled across 26 CF centers and were part of the GALAXY study (NCT03801993). Children who enrolled were 2 or older.
The GALAXY study collected GI-related data to determine which questionnaires best captured the experience of GI symptoms in this population. The study generated electronic patient-reported outcome measures (ePROMs) for use in clinical trials.
“Our study represents the largest cohort [group] of [CF patients] using a comprehensive set of ePROMs previously validated in GI patients without CF, targeting both upper and lower GI symptoms across a broad age spectrum,” the investigators wrote. “Use of these ePROMs can allow for simple and consistent patient-centered outcomes for future targeted clinical trial endpoints. This is of critical importance as up until recently, a lack of universally accepted and standardized patient reported outcome measures for capturing GI symptoms in CF has limited the development of GI-focused clinical interventional studies.”
Assessing gastrointestinal symptom frequency
All patients completed three validated electronic questionnaires that assessed their gastrointestinal and constipation symptoms, as well as quality of life, and one questionnaire assessing stool weekly over four weeks. Scores ranged from 0 to 4 or 5, meaning absence of symptoms to very severe. Medications used, past medical history, and the specific CFTR defect causing CF were also assessed.
The most common moderate to severe symptoms were straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating and distension (16.4% each), and abdominal pain — 5.1% for upper abdominal pain and 7.5% for lower abdominal pain.
Adults, particularly women, had higher scores than children on all three questionnaires on gastrointestinal symptoms, constipation and quality of life, and experienced moderate to severe symptoms more frequently. Adults had bloating (63.7% vs. 27.3%), lower abdominal pain (39.8% vs. 26.2%), stomach fullness (75.6% vs. 56.2%), and a distended abdomen (60.2% vs. 34.9%) more frequently than children.
The causes of bloating in CF are unclear, but the researchers suggested it could be due to gut bacteria imbalances, constipation or inflammation with overgrowth of bacteria in the small intestine.
Regarding stools, 22% of participants reported constipation in the week before the week four follow-up, with 11.5% alternating between constipation and diarrhea. Also, 9.2% of participants reported stool leakage or fecal incontinence.
Almost all (98.3%) were on medications for GI symptoms at the start of the study. Some (41.3%) took medication for constipation (polyethene glycol was the most common choice), 88.3% took pancreatic enzyme replacement therapy, and 60.2% took acid-suppressing agents. Those using laxatives and acid-suppressing agents had worse symptoms than those not taking these medications.
Both children and adults reported high treatment dissatisfaction as measured by the Patient Assessment of Constipation-Quality of Life tool.
CFTR modulators were being used by 57% of participants, most commonly Symdeko and Orkambi. No difference in questionaire results were found between patients using or not using these medications.
The researchers noted that the study was completed before U.S. approval and widespread availability of the triple-combination therapy Trikafta. “It will be critical to systematically evaluate the impact of newly available [Trikafta] on GI symptoms,” they wrote.
According to the researchers, a unique definition for constipation in CF is needed, since symptoms in CF are different from those in the general population.
“GI symptoms were reported in all age ranges irrespective of [sex], with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions,” the researchers said.
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