Consequences to health :gastro-oesophageal reflux in the cystic fibrosis population

Abstract

The work described in this thesis relates to gastro-oesophageal reflux (GOR) and extra-oesophageal reflux (EOR) in the cystic fibrosis (CF) population. This thesis describes the characteristics of GOR and EOR and their association with pulmonary function, gastric aspiration and inflammation in the airway. In particular the study explores the increasing prevalence of overweight/obesity in CF and its association with GOR/EOR. In a sub group of patients (n=12) a longitudinal investigation took place to observe the effects of a new CFTR potentiator (Ivacaftor 150 mg/12h) on GOR/EOR symptoms. 72 CF adults recruited from a CF outpatient clinic consented to the study (39M/33F; median age 21 (16-60) years) and completed questionnaires to characterise symptoms of GOR (DeMeester score 0-9; < 1 normal) and EOR (Reflux Symptom Index (RSI) score 0- 2 45; < 13 normal). Patients were measured for BMI kg/m and grouped according to the 2 2 following BMI categories: underweight <18.5 kg/m , normal weight 18.5-25.0 kg/m , 2 2 overweight 25.1-30.0 kg/m and obese >30.0 kg/m . An expectorated sputum sample was provided and analysed for biomarkers of reflux (pepsin n=69 ELISA) and inflammation (IL-6 n=62 and IL-8 n=64 ELISA). Pulmonary function (FEV and FVC % predicted) and 1 genotype were recorded at the time of data collection. Statistical relationships were assessed using the Kruskal-Wallis statistical test followed by the Mann Whitney U test. GOR symptoms (DeMeester) were identified in 42% of patients and EOR symptoms (RSI) in 63% of patients. Pepsin was detected in 48 (70%) patient samples (median: 330ng/ml; range 80-1150ng/ml) and not correlated with GOR/EOR symptoms. GOR/EOR symptoms and gastric aspiration did not associate with pulmonary function, nor was GOR associated with inflammation of the airways. CF patients can be overweight/obese (16.7%), and this was associated with better lung function; they have less reflux. Obesity didn't show a relationship to F508del/F508del status or to gender. Ivacaftor treatment was associated with reduced symptoms of GOR and EOR (6 weeks to 12 month post medication) accompanied by positive effects on pulmonary function. GOR is common in CF patients and EOR symptoms are very prevalent in CF and more so than GOR. Microaspiration of gastric content into the airway was not correlated with pulmonary function and occurred across the spectrum of disease severity. Overweight/obese patients experience less EOR symptoms. The CFTR potentiator Ivacaftor reduced GOR and EOR symptoms after 6 weeks of treatment.