Reflux, aspiration and respiratory disease in dogs : clinical consideration and advances in aerodigestive diagnostics

Includes vitaThe aspiration of gastric contents into the respiratory tract has been associated with the development and progression of multiple respiratory diseases in humans. In veterinary medicine the term "aspiration" is considered synonymous with "aspiration pneumonia" which, while frequently encountered, does not accurately reflect the breadth of aspiration associated respiratory syndromes (AARS). In the clinical veterinary literature, the effect of alimentary dysfunction on respiratory disease (aerodigestive disease) is rarely investigated despite evidence in the human literature, animal models, and some studies and case reports linking alimentary and respiratory disease in clinical small animal patients. Aerodigestive disease is rarely investigated in veterinary medicine due to lack of clinical recognition and limitations in available diagnostics. Furthermore, AARS may be precipitated by several potentially occult alimentary disorders. Current methods of investigating aerodigestive diseases in veterinary patients are limited by sensitivity, specificity, potential for bias, cost, and availability. This necessitates investigations into advanced diagnostics to identify a potentially underrecognized patient population with AARS. Additionally, similarities in anatomy, physiology, and several pathologic disorders between dogs and humans, make experimental and naturally occurring canine models integral to translational research. Thus, evaluating dogs with aerodigestive disease may represent an area of substantial clinical relevance in human as well as veterinary medicine.Includes bibliographical reference

Phoniatricians and otorhinolaryngologists approaching oropharyngeal dysphagia : an update on FEES

Purpose Oropharyngeal dysphagia (OD) is a common phenomenon in otorhinolaryngology and phoniatrics. As both sub-disciplines have a strong tradition and clinical experience in endoscopic assessment of the upper aerodigestive tract, the implementation of fiberoptic endoscopic evaluation of swallowing (FEES) was an almost self-evident evolution. This review aims to provide an update on FEES and the role of phoniatricians and otorhinolaryngologists using FEES in Europe. Methods A narrative review of the literature was performed by experts in the field of FEES both in the clinical context and in the field of scientific research. Results FEES is the first-choice OD assessment technique for both phoniatricians and otorhinolaryngologists. FEES is becoming increasingly popular because of its usefulness, safety, low costs, wide applicability, and feasibility in different clinical settings. FEES can be performed by health professionals of varying disciplines, once adequate knowledge and skills are acquired. FEES aims to determine OD nature and severity and can provide diagnostic information regarding the underlying etiology. The direct effect of therapeutic interventions can be evaluated using FEES, contributing to design the OD management plan. Standardization of FEES protocols and metrics is still lacking. Technological innovation regarding image resolution, frame rate frequency, endoscopic light source specifications, and endoscopic rotation range has contributed to an increased diagnostic accuracy. Conclusion The rising number of phoniatricians and otorhinolaryngologists performing FEES contributes to the early detection and treatment of OD in an aging European population. Nevertheless, a multidisciplinary approach together with other disciplines is crucial for the success of OD management.Peer reviewe

Development of novel methods of assessment in oesophageal and gastric function

The objective of this thesis was to develop new methodologies to assess upper gastro-intestinal function in health and disease. Several different technologies were studied in a range of upper gastro-intestinal diseases and adapted to try and provide more meaningful insights. The thesis has three main sections. In the first section, High Resolution Oesophageal Manometry (HRM) was used to assess unexplained upper gastro-intestinal symptoms in a group of patients referred to a tertiary centre. 46 patients were diagnosed with rumination syndrome following HRM. A retrospective review was completed of these patients case notes and HRM data. The predominant aim of this section was to identify if common mechanisms exist within rumination and its variations and to establish if the variety of presenting symptoms is due to different underlying problems or a common behavioural response to a variety of stimuli, with symptoms being dependent on the circumstance the behaviour exists in. This would support a generic biofeedback technique being useful regardless of presenting complaint. Comparing the variety of symptoms, exhibited behaviour and manometric findings, a new classification system for rumination was then developed; 1. Primary or “classical” rumination a. Increase in abdominal strain with corresponding rise in intra-gastric pressure and return of gastric contents to the mouth 2. Secondary or reflux-related rumination a. Reflux event causes the patient to respond with increase in intra-abdominal muscle strain and subsequent rumination 3. Supra-gastric belching independent of meals. a. Rise in intra-gastric pressure whilst a closed gastro-oesophageal junction, therefore producing rapid belching of air from the oesophagus without any return of gastric contents Generic biofeedback therapy was used (regardless of presenting symptoms) to control the abnormal behavioural response to symptoms. 20/46 patients reported full resolution of their symptoms and a further 13 / 46 reported improvement in their symptoms with this, while underlying mechanisms were targeted e.g. reflux with proton pump inhibitors, pain in functional dyspepsia. In the second main section of this thesis, gastro-oesophageal reflux disease (GORD) is considered. GORD is currently diagnosed by 24 hour pH studies. These are often difficult for patients to tolerate and require time off medication. A more attractive method would be for diagnosis to occur at the same time as gastroscopy. A novel instrument is the EndoFLIP® device. This measures cross-sectional area (CSA) and distensibility at the gastro-oesophageal junction (GOJ) via a long catheter with a balloon at the end that straddles the GOJ. It has been hypothesised that these measurements will be increased in those with GORD, as the GOJ is more distensible, allowing more retrograde movement of gastric contents. The aim of this section of the thesis was to establish if GOJ CSA and distensibility differentiate between healthy volunteers (HV) and GORD patients based on i) symptoms and ii) prolonged oesophageal acid exposure. 21 HV and 18 patients with GORD (based on symptoms) had EndoFLIP® measurements and wireless pH studies to assess this. 14% of HV and 50% GORD patients had pathological acid exposure. CSA and distensibility were both significantly higher in the HV’s compared to GORD patients. However, there was an inverse correlation between CSA and body mass index (BMI) which was significantly higher in the patient population. This may explain differences seen due to corresponding higher intra-abdominal pressure in those individuals with a high BMI, sub-sequentially affecting the CSA and distensibility. The complex structure of the GOJ and multiple factors involved in the pathogenesis of GORD present difficulties in using EndoFLIP® to diagnose GORD. It may find applications in other areas, such as serial measurements in single patients. In the final section of this thesis, gastric emptying is the focus and its pathogenesis in functional dyspepsia (FD). Current gastric emptying studies only find abnormalities in approximately 40% of patients with FD. Gamma scintigraphy is used in routine clinical practice for gastric emptying studies. Magnetic resonance imaging (MRI) is emerging as a modality in gastric emptying assessment and potentially provides additional information. This thesis hypothesised that standard gastric emptying studies may not be measuring the parameters reflective of underlying pathophysiology in FD. Also, most have a relatively small meal size that may be too small to trigger dysfunction. MRI may provide additional insights as can assess gastric contents and surrounding structure (unlike GS). To investigate these a 400ml test meal was utilised and gastric emptying parameters i) gastric contents volume at time 0 (GCV0, representative of early emptying), ii) gastric emptying rate at the time taken for half the meal volume to empty (GE rate @T50, representative of later emptying) and the more traditional measurement iii) time taken for half the gastric contents to empty (T50) in bopth GS and MRI studies. The hypothesis of this study is that early emptying is more rapid in FD due to impaired accommodation (therefore a lower GCV0) leading to a slower later emptying (therefore a lower GE rate @ T50). Following validation studies in a large healthy population (n=53), GS and magnetic resonance imaging (MRI) studies with a test meal of 400ml were used in 8 FD patients and 24 matched HV (from the pool of HV) . FD had a significantly lower BMI. Early emptying (represented by gastric contents volume after ingestion of meal (GCV0)) was significantly lower in GS for FD patients but higher in MRI. Time for half the meal to empty (T50) and gastric emptying rate at T50 (GE rate @T50) were similar. The difference between the two modalities was thought to be due to increased secretion production in the patients, which is measureable in MRI but not in GS. A further study with a solid component of 12 non-nutrient agar beads in addition to the liquid component was completed. 24 HV’s, 17 FD patients and 11 gastro-oesophageal reflux disease (GORD) patients were studied. FD patients and GORD patients had rapid early gastric emptying in comparison to HV in gamma scintigraphy (represented by GCV0) but higher GCV0 in MRI (significantly so between HV and GORD), suggesting increased secretion production is present in both conditions. These findings do support impaired fundal accommodation within the FD population but that other factors, such as secretion production and the rate of this in comparison to gastric emptying are important in the later stages of emptying. Further work is ongoing within the MRI department to quantify and measure the emptying of these secretions. This thesis explores how existing and new technologies can be applied to clinical conditions to identify possible pathophysiology and potential targets for treatment. Only by these ongoing efforts can we endeavour to improve the care we deliver to our patients

Studies of anorectal function using high resolution anorectal manometry in health and faecal incontinence

PhDFaecal incontinence (FI) is a prevalent complaint in Western populations and causes significant disability. Impaired motor function of the anal canal is a common pathophysiological feature and assessment of sphincteric function with manometry is a routine part of symptom assessment. High-resolution anorectal manometry (HRAM) may provide a more detailed understanding of anorectal function, however its clinical utility has not been established. Aims The principal aims of this thesis were to: (1) Explore existing practices of anorectal manometry (2) Examine current evidence supporting the use of HRAM (3) Develop and validate a protocol for the performance of HRAM (4) Define normal values for traditional measures of sphincteric function using HRAM (5) Develop and validate novel measures of sphincteric function, and explore whether they improve diagnostic accuracy in patients with FI (6) Examine anorectal function over a prolonged period with HRAM to evaluate the phenomenon of anal sampling (referred to in this thesis as transient anal sphincter relaxations [TASRs]) Methods The following methods were used: (1) A worldwide survey of current practices of anorectal manometry (2) A systemic review of the literature (3) Prospective studies (both standard and prolonged) of anal function in healthy volunteers and patients with FI Results The practice of anorectal manometry is markedly variable internationally with no two centres surveyed employing the same methods. Within the 62 centres surveyed, there were 16 combinations of ways in which squeeze data were reported. A review of the literature demonstrated a growing evidence base for the use of HRAM however there is a paucity of data that confirm added benefits of HRAM over conventional manometry. A standardized protocol for HRAM was developed to allow the reporting of traditional measures of anorectal function. Novel measures derived from HRAM were developed which demonstrate increased sensitivity for the detection of impaired sphincteric control in patients with FI (sensitivity of traditional measure [conventional squeeze increment] 36% vs. 59% for the novel HRAM measure [5-second squeeze profile]). Transient anal sphincter relaxations (TASRs) were characterized using HRAM. In health, TASRs are often perceived by the individual as the urge to pass wind (39% of events) and their frequency increases following meal consumption. Conversely in FI, TASRs are a rare occurrence and are generally not perceived (only one patient (1/10 [10%]) with FI reported GI sensations associated with TASR events). Conclusions Anorectal manometry is in need of standardization. Novel measures derived from HRAM may improve diagnostic utility and further exploration of TASR characteristics might give insight into the pathophysiology of FI.Stefan Galeski fellowship Royal College of Surgeons of Englan

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 ‘on’ and ‘off’ 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 ‘on’ and ‘off’ 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 patients’ 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