Date Published: May 4, 2017
Publisher: Public Library of Science
Author(s): Harold Tabori, Christin Arnold, Anke Jaudszus, Hans-Joachim Mentzel, Diane M. Renz, Steffen Reinsch, Michael Lorenz, Ruth Michl, Andrea Gerber, Thomas Lehmann, Jochen G. Mainz, Philipp Latzin.
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.
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.
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.
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.
Cystic fibrosis (CF) is the most common life threatening autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane (conductance) regulator (CFTR) gene. The CFTR protein, which is essential in the regulation of chloride and sodium transport in epithelial cells , is highly expressed on the apical surface of intestinal epithelial cells, pancreatic ductal cells, and cholangiocytes in bile ducts which in the healthy transport ions, bicarbonate and fluid to the organs’ lumen . Thus, CFTR dysfunction results in viscous luminal secretions obstructing the bile and pancreatic ducts as well as the intestine . The resulting gastrointestinal (GI) manifestations include pancreatic insufficiency (PI), meconium ileus (MI), distal intestinal obstruction syndrome (DIOS), and biliary tract complications which can lead to cirrhosis and hepatic failure . Typical resulting GI symptoms are frequent and voluminous greasy stools, flatulence, abdominal bloating, constipation, abdominal pain, an impaired nutritional status, as well as failure to thrive. Even though GI symptoms are a hallmark of CF [5–7], often leading to diagnosis of the inherited disease, they are still insufficiently understood for why deeper investigations into the abdominal involvement in CF are needed . Moreover, with enhanced survival due to improved therapeutic options and patient management, comorbidities of the GI, hepatobiliary, and pancreatic tract are of increasing clinical and scientific interest. However, because of the complex interaction of a variety of dysfunctioning organs, medicinal effects, and even psychosocial factors (Fig 1), the differentiation of the multitude of abdominal symptoms constitutes a major challenge.
Although GI involvement is a hallmark of CF, until now it received comparatively little clinical and, even less, scientific attention. To our best knowledge, GI symptoms in CF as a multiorgan manifestation have not yet been systematically quantified. Here, we present data of a new questionnaire assessing the complexity of GI symptoms from 131 CF patients of all ages; the questionnaire prospectively shall be elaborated to a standardized and validated abdominal CF score, considering the FDA guidelines . Additionally, quantified symptoms were related to phenotypic characteristics and to laboratory findings. The JenAbdomen-CF Score 1.0 questionnaire is a simple but meaningful two-page instrument capable to detect differences between several CF phenotypic characteristics, as shown within this publication. For purposes of monitoring, it can quickly and therefore routinely filled-in at on-site visits. In clinical trials, it can be implemented as an additional easy and inexpensive tool of, however, high relevance.