Thesis Type: Expertise In Medicine

Institution Of The Thesis: Marmara University, School of Medicine, Internal Medical Sciences, Turkey

Approval Date: 2015

Thesis Language: Turkish

Student: Ayşe İrem Zöhre

Consultant: Engin Tutar


Introduction: Cystic fibrosis disease (CF) due to its effect on the morbidity and mortality, is considered to be a lung disease, more recently, prolonged life expectancy of CF patients made gastrointestinal complications more important. Gastroesophageal reflux disease (GERD) although not a CF disease’s accompanying components, it is more frequent than the normal healthy population. It is suggested that GERD contributes to the progression of lung disease with microaspiration, reflex bronchospasm and increased respiratory tract inflammation in CF patients. GERD in CF develops whether primary or secondary phenomena due to the underlying disease is, controversial. Studies investigating the relationship between CF and gastroesophageal reflux (GER) reported that the increase in transient relaxation of the lower esophageal sphincter, has a major factor in the development of GERD. There are studies, show the effects of increase of abdominal pressure with coughing due to the underlying lung disease, increase in negative inspiratory pressure due to increased respiratory effort, using beta-mimetic agents, lung physiotherapy applied in the head-down position, pancreatic insufficiency due to diet rich in fatty foods and nutritional and hyperalimentation, on the development of GER. Prolongation of the gastric emptying time is an important factor in development of GER. Although there are various studies on gastric emptying time in CF, its effects on development of GER is still controversial.
The aim of our study is; investigating gastroesophageal reflux episodes features’ in terms of characteristic, severity, esophageal clearance in CF children with impedance/pH-meters and evaluate the contribution of gastric emptying time in development of GER. Another aim of the study is; identifying similarities and differences of results by comparing the data from CF patients with data of the same age group patients without a chronic disease whom gastric emptying time measurement and impedance/PH-meter (MII-pH) examination have been made due to reflux symptoms.
Methods: Study group has been prospectively established in the Division of Pediatric Gastroenterology, Hepatology and Nutrition of Marmara University Pendik Education and Research Hospital with follow-up patients diagnosed with CF patients between 4-
18 years of age whom admitted with GERD symptoms and requires further research. Patients underwent 24-hour MII-pH monitoring and gastric emptying scintigraphy was taken in the same week. Control group has been established with patients between 3-17 years of age whom admitted with GERD symptoms to the same clinic and MII-pH monitoring and gastric emptying scintigraphy taken in the same month. Both groups of patients in gastric emptying time periods and MII-pH monitoring data were evaluated within their own groups and between the two groups.
Results: We studied a total of 40 patients, 15 of those were CF patients (study group) and 25 patients were in the control group. In a total of 40 patients, 20 (50%) were male and 20 (50%) were female, average age was 9.50 ± 4.36 (3-18 years) years. 46.7% of CF patients (n = 7) were male and 53.3% (n = 8) were female, age average of 9.80±4.13 (4-18 years) years. There were no gender and age differences between study group and control group. 80% of CF patients (n=12), had pancreatic insufficiency. 12 of 15 CF patients in the study group were able to perform pulmonary function tests during the study period, the mean FEV1 values were 81.58±25.15%. In the examination of nasopharyngeal aspirate cultures in CF patients within the last 3 months, 5 patients (33.3%) had normal flora and 10 patients (66.7%) had pathogen growth. 40% of patients with growth had (n = 4), P.aeruginosa, other 40% had (n=4) MRSA, in 10% (n=1) H.influenza, 10% (n=1) S.pneumonia reproduction respectively. The results of reflux data measured with 24-hour pH meter in CF patients were as follows: The mean number of reflux was 105.84 ± 85.81, the mean number of "acid reflux for more than 5 minutes" was 7.29 ± 8.30, the mean value of acid reflux index (RI) was 18.49±17.36%, the average value of DeMeester score was 52.52±48.20. MII measurement in the evaluation of patients with CF were found as follows: the mean number of reflux was 86.61±35.30, the average percentage of reflux was 12.04±5.15%, the mean number of acid reflux was 57.83±40.66, the mean number of weakly acid reflux was 21 17±18.18, the mean number of non-acid reflux was 7.61±9.38, the mean number of reflux reaching to the proximal esoohagus was 34.33±31.40 and the average bolus clearance time (BCT) was 10.93±2 sec. According to the MII-pH meter data no statistically significant difference in any parameter has been found between CF and control group patients. The average time of gastric emptying in CF patients revealed 61.33±23.96 minutes. Gastric emptying time
between CF patients and the control group showed a statistically significant difference (p=0.009). CF patients had longer gastric emptying time than control group patients. When MII-pH meter monitoring results were evaluated by gender in the CF patients group, male patients had a statistically significantly higher acid reflux number whereas female patients in CF group had statistically significantly higher number with weakly acid reflux (p: 0.006, p: 0.040 ). When CF patients were compared according to the events of proximal reflux, the mean number proximal reflux in male patients were found to be statistically significantly higher than female patients (p=0.021). In the assessment of other MII-pH meter parameters there were no significant differences by gender. When the relationship between the age and MII-pH meter data in CF patients analyzed, total reflux number (p = 0.013), acid reflux number (p: 0.045) and the number of reflux reaching to the proximal esophagus (p=0.014) were correlated positively as statisticaly. When FEV1 of CF patients and MII-pH meter data were examined, the relationship in-between was not statistically significant. The comparison of CF patients and the control group of patients in terms of gastric emptying time period and MII-pH meter monitoring parameters, there were no statistically significant relationship except bolus clearance time. In CF patients, between the gastric emptying time and the BCT time, a negative correlation was observed (p = 0.001).
Discussion: Between CF patients diagnosed with GERD and healthy population, there are no differences in terms of reflux severity. Most of the reflux episodes seen in CF patients are in acid and weak acid character, the incidence of non-acid reflux is quite low. pH characteristics are similar to non-CF GERD patients. The number of acid reflux in children with CF and the number of reflux reaching the proximal esophagus are seen more in male patients, while the frequency of non-acid reflux was seen more in female CF patients. CF patients had increasing risk of GERD with increasing age. Gastric emptying time for liquid foods in CF patients were found to be longer than the control group, but this effect is not clear on the intensity and character of reflux episodes.
Keywords: Children, cystic fibrosis, gastroesophageal reflux disease, gastric