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Multicenter prospective study showing a high gastrointestinal symptom burden in cystic fibrosis

  • Author Footnotes
    # Joint First Authors.
    Baha Moshiree
    Correspondence
    Corresponding author at: Medicine, Atrium Health, Wake Forest Medical University, 1025 Morehead Medical Plaza, Suite 300, Charlotte, NC 28204, United States.
    Footnotes
    # Joint First Authors.
    Affiliations
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Atrium Health, Charlotte, NC, United States
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  • Author Footnotes
    # Joint First Authors.
    A. Jay Freeman
    Footnotes
    # Joint First Authors.
    Affiliations
    Division of Pediatric Gastroenterology, Nationwide Children's Hospital/The Ohio State University, Columbus, OH, United States
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  • Phuong T. Vu
    Affiliations
    Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States
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  • Umer Khan
    Affiliations
    Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States
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  • Carmen Ufret-Vincenty
    Affiliations
    Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States
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  • Sonya L. Heltshe
    Affiliations
    Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States

    Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States
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  • Christopher H. Goss
    Affiliations
    Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States

    Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States

    Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States
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  • Sarah Jane Schwarzenberg
    Affiliations
    Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States
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  • Steven D. Freedman
    Affiliations
    Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, United States
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  • Drucy Borowitz
    Affiliations
    Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States
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  • Meghana Sathe
    Affiliations
    Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Texas Southwestern/Children's Health, Dallas, TX, United States
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  • On behalf of theGALAXY Study Group
    Author Footnotes
    1 GALAXY Study Group Contact list provided in supplements for other study sites.
  • Author Footnotes
    # Joint First Authors.
    1 GALAXY Study Group Contact list provided in supplements for other study sites.
Published:October 29, 2022DOI:https://doi.org/10.1016/j.jcf.2022.10.006

      Highlights

      • Moderate to severe gastrointestinal (GI) symptoms are highly prevalent in people with cystic fibrosis (PwCF).
      • In particular, bloating, early satiety, fullness and abdominal pain are highly prevalent in people with PwCF and are more common in females ≥ 18.
      • The CF-specific definition of constipation is different than in other populations and constipation in CF patients is defined by characteristic abdominal symptoms in addition to stool and rectal symptoms.
      • Treatment dissatisfaction scores and GI symptoms remain high despite use of PERT in >88% and other GI medications in >98% of participants.
      • Sex differences in symptom severity follow trends for many functional bowel diseases.

      Abstract

      Background and aims

      People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF).

      Methods

      Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models.

      Results

      Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47).

      Conclusion

      GI symptoms were reported in all age ranges irrespective of gender, 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.

      ClinicalTrials.gov

      NCT03801993

      Graphical abstract

      Keywords

      Abbreviations:

      BM (Bowel Movement), BSS (Bristol Stool Form Scale), CF (Cystic Fibrosis), CFTR (Cystic fibrosis transmembrane regulator), CFF (Cystic Fibrosis Foundation), CF-TDN (Cystic Fibrosis Therapeutics Development Network), ePROMs (Electronic Patient Reported Outcome Measures), GI (Gastrointestinal), GERD (Gastroesophageal reflux disease), PERT (Longitudinal Multicenter Study to Determine the Patient-reported Prevalence of GI Symptoms in Pancreatic Enzyme Replacement Therapy), GALAXY (Persons with Cystic Fibrosis), PAC-QOL (Patient Assessment of Constipation-Quality of Life), PAC-SYM (Patient Assessment of Constipation- Symptom Severity Index), PAGI-SYM (Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index), PROMs (Patient Reported Outcomes, Patient Reported Outcome Measures), PROMIS (Patient-reported Outcomes Measurement Information System), PedsQLGI (Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module), pwCF (People with Cystic Fibrosis), SIBO (Small Intestinal Bacterial Overgrowth Syndrome), SSQ (Stool Specific Questionnaire), QOL (Quality of Life)
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