Gastro-intestinal manifestations of Cystic Fibrosis

This thesis consists of two parts. The aim of the first part is to give a clear definition of constipation and DIOS in CF and to determine the incidence, prevalence and risk factors (both genetic and environmental) of the intestinal obstruction syndromes (constipation, DIOS and meconium ileus). The aim of the second part is to investigate the effect of medical interventions (gastric acid inhibition, ursodeoxycholic acid and energy intake) on growth, bacterial colonization and pulmonary function. In chapter 2 the European Society for Pediatric Gastroenterology, Hepatology and Nutrition CF working Group definitions for DIOS and constipation in CF are described. Subsequently, in chapter 3 the incidence, prevalence and risk factors of constipation in the pediatric CF population of the UMC Utrecht were determined. Constipation is frequently seen in Cystic Fibrosis, as 47% of all CF patients experienced at least one episode of constipation. Furthermore, constipation was associated with fat malabsorption and meconium ileus. Chapter 4 describes the association between the p.S357N variant in the CLCA 1 gene and meconium ileus in a cohort of European (Dutch, German and Italian) pediatric CF patients. In chapter 5 we report that gastric acid inhibition for fat malabsorption is safe to use in CF patients as gastric acid inhibition for fat malabsorption does not affect bacterial colonization and might even have an advantageous effect on the decline in pulmonary function. However gastro-esophageal reflux disease was associated with a worse pulmonary function and earlier first infection with P. Aeruginosa and S. Aureus. In chapter 6 we showed that ursodeoxycholic acid was longitudinally associated with worse fat absorption, growth and pulmonary function. At last, the complex relationship between nutritional status, pulmonary function and energy intake is investigated in chapter 7. We concluded that CF patients with a BMI z-score between 0 and -1 SD and a FEV1100%.