Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings

Abstract

Background & aims: Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history.

Methods: A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status.

Results: AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status.

Conclusion: As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

Fig 1. Multifactorial causes of abdominal symptoms in CF.

CFLD–CF-associated liver disease, CFRD–CF-related diabetes, DIOS–distal intestinal obstruction syndrome, GERD–gastroesophageal reflux disease, MI–meconium ileus, PI–pancreatic insufficiency.

Fig 2. Pain and non-pain symptoms of the JenAbdomen-CF Score 1.0.

*to some extend additionally related to pain symptoms.

Fig 3. Abdominal symptoms in patients with CF.

Frequencies of abdominal symptoms in CF patients of all ages (Fig 3a) and in children compared with adults (Fig 3b). N.d.–not determined (missing data).

Fig 4. Location of abdominal pain in patients with CF.

Fig 5. JenAbdomen-CF Score 1.0 of patients presenting indicated abdominal manifestations and complications of surgery in comparison with patients without history of these events (Ø).

Int PsA–intermittently colonized with P. aeruginosa, chr PsA–chronically colonized with P. aeruginosa. Means ± SEM.

Fig 6. JenAbdomen-CF Score 1.0 in relation to genotype.

Left: Scores obtained from `mild´ (PIP≤0.25) compared to `moderate-severe´ (PIP>0.25) genotypes. Right: Scores of patients carrying the G551D mutation compared to those without this mutation. Of note, the fact that 10/17 of the patients with G551D mutation received ivacaftor may have influenced the result.