8 research outputs found
The use of impedance pH measurements to determine the effect of gastro-oesophageal reflux in patients with idiopathic pulmonary fibrosis and cystic fibrosis
M.D. ThesisIntroduction
For many decades gastrooesophageal reflux has been implicated in patients suffering
from lung disease and in lung allograft injury. From the early 1970s studies have taken
place investigating reflux in idiopathic pulmonary fibrosis (IPF) and cystic fibrosis (CF).
However, these early studies were small and used primitive techniques to assess reflux.
In addition, the role of microaspiration secondary to reflux has often been postulated as
a cause of deteriorating lung function in these patients but has been under studied. It is
also known that many of these patients require a lung transplant due to end-stage lung
disease. Asymptomatic reflux and aspiration may be associated with allograft
dysfunction post lung transplant. Early anti-reflux surgery has been suggested to
improve long-term survival by treating reflux. This thesis reports a prospective
assessment of reflux/aspiration in patients with IPF and CF. In addition, the study
reports the largest European series of fundoplication in lung transplant patients.
Methods
Over a 2 year period patients with IPF and CF were recruited from specialist clinics. All
patients completed objective assessment of oesophageal physiology using manometry
and impedance-pH. Symptom and quality of life assessment using RSI, Demeester and
GIQLI questionnaires were performed on all patients at the time of recruitment. For
those patients taking proton pump inhibitor, questionnaires were done âonâ and âoffâ
their medication. IPF patients then had a bronchoscopy and lavage (BAL) whilst CF
patients produced sputum. Cytospins of the BAL and sputum were produced and
differential cell counts were performed and the cells were stained with Oil Red O and
Prussian Blue (Perls). ELISA and mass spectrometry assays were also performed on the
samples for pepsin and bile salts respectively. Lung transplant patients attended for
impedance-pH studies over 3 years and those with symptomat ic reflux or reflux and
deteriorating lung function were referred for a laparoscopic fundoplication. Lung
function assessment, symptom and quality of life questionnaires were performed before
surgery and at 6 weeks and 6 months after surgery
Results
IPF Patients:
Thirty eight patients with IPF were initially approached and 29 consented to be studied.
Nine patients dropped out from the study after consent. Twenty patients with IPF
completed both the oesophageal physiology and BAL aspects of the investigation. In 12
patients there was objective evidence of reflux including 6 patients with proximal reflux.
60% of patients had an abnormal RSI score whilst taking a PPI and scores for the other
questionnaires were not significantly different âonâ and âoffâ PPI. Lung function was not
related to the degree of reflux. The principal cell type identified was macrophages and
both Oil Red O and haemosiderin scores were well above the normal range. Bile salts
were detectable in 17/20 IPF patients but the levels were not higher than the normal
range. 11/20 patients had higher than normal levels of pepsin in the BAL.
CF Patients:
Twenty-six patient with CF consented to the study but 15 dropped out. Eleven CF
patients attended for oesophageal investigation and each provided 2 samples of sputum.
9/11 had reflux, including five with proximal reflux. All patients were taking acid-
suppression medication and questionnaire assessments were abnormal whilst on their
medication with 82% still having a GIQLI score below 121 despite medication for
reflux. Twenty one samples of sputum were processed altogether. The principal cell
type was neutrophils. Bile salts were detectible in all samples but these were at very low
concentrations. Elevated pepsin was seen in 7/11 sputum samples with the median
concentration ten times above the normal level.
Lung Transplant Patients
16 lung transplant patients with symptomatic reflux or deteriorating lung function and
reflux on impedance-pH had a laparoscopic fundoplication. Symptom questionnaire and
quality of life assessment was significantly improved in all patients. Half the patients
had presented with declining lung function and all showed an improvement in
respiratory function after surgery.
Summary
We have demonstrated that reflux is present in patients with IPF, CF and in patients
after lung transplant. Using impedance-pH we have identified patients with proximal
reflux. The presence of reflux appears to affect the patientsâ quality of life and despite
PPI therapy the majority still had symptoms. High levels of haemosiderin stained
macrophages in IPF indicate oxidative stress which may or may not be secondary to
reflux. Pepsin levels are elevated in both IPF and CF patients, possibly indicating
microaspiration.
Conclusion
Despite PPI therapy there is significant reflux in IPF and CF identifying a clinical gap in
patient treatment that should be considered in management. Our results in the post lung-
transplant group indicate there is a role for surgery in treating reflux and potentially
reducing microaspiration. This has been shown to stabilise lung function in this cohort
and may have implications for the treatment of reflux in patients with lung disease
before transplantation.The Joint Research Scientific Executive Committee of the Newcastle Healthcare
Charity (RVI/NGH) & Newcastle upon Tyne Hospitals NHS Charity
The Northern Oesophagogastric Uni
Ivacaftor and symptoms of extra-oesophageal reflux in patients with cystic fibrosis and G551D mutation
© 2016 The Authors Background Extra-oesophageal reflux (EOR) may lead to microaspiration in patients with cystic fibrosis (CF), a probable cause of deteriorating lung function. Successful clinical trials of ivacaftor highlight opportunities to understand EOR in a real world study. Methods Data from 12 patients with CF and the G551D mutation prescribed ivacaftor (150 mg bd) was collected at baseline, 6, 26 and 52 weeks. The changes in symptoms of EOR were assessed by questionnaire (reflux symptom index (RSI) and Hull airway reflux questionnaire (HARQ)). Results Six patients presented EOR at baseline (RSI > 13; median 13; range 2â29) and 5 presented airway reflux (HARQ > 13; median 12; range 3 to 33). Treatment with ivacaftor was associated with a significant reduction of EOR symptoms (P
Exposure to bile and gastric juice can impact the aerodigestive microbiome in people with cystic fibrosis
Exposure to bile and gastric juice can impact the aerodigestive microbiome in people with cystic fibrosis
Studies of microbiota reveal inter-relationships between the microbiomes of the gut and lungs. This relationship may influence the progression of lung disease, particularly in patients with cystic fibrosis (CF), who often experience extraoesophageal reflux (EOR). Despite identifying this relationship, it is not well characterised. Our hypothesis is that the gastric and lung microbiomes in CF are related, with the potential for aerodigestive pathophysiology. We evaluated gastric and sputum bacterial communities by culture and 16S rRNA gene sequencing in 13 CF patients. Impacts of varying levels of bile acids, pepsin and pH on patient isolates of Pseudomonas aeruginosa (Pa) were evaluated. Clonally related strains of Pa and NTM were identified in gastric and sputum samples from patients with symptoms of EOR. Bacterial diversity was more pronounced in sputa compared to gastric juice. Gastric and lung bile and pepsin levels were associated with Pa biofilm formation. Analysis of the aerodigestive microbiomes of CF patients with negative sputa indicates that the gut can be a reservoir of Pa and NTM. This combined with the CF patient's symptoms of reflux and potential aspiration, highlights the possibility of communication between microorganisms of the gut and the lungs. This phenomenon merits further research