Revisiting the Role of Esophageal Mucosal Dilated Intercellular Spaces in the Diagnosis and Pathophysiology of Heartburn

Background/Aims@#Dilated intercellular spaces (DISs) facilitate the diffusion of noxious agents into the deep layers of the esophageal epithelium. The role of DIS in heartburn pathogenesis is still controversial. Therefore, we aim to reinvestigate DIS in an extensively evaluated group of patients and healthy controls (HCs). @*Methods@#We classified 149 subjects into the following groups: 15 HC, 58 mild erosive reflux disease (ERD), 17 severe ERD, 25 nonerosive reflux disease (NERD), 15 reflux hypersensitivity (RH), and 19 functional heartburn (FH). A total of 100 length measurements were performed for each patient’s biopsy. @*Results@#The overall intercellular spaces (ISs) value of gastroesophageal reflux disease (GERD) patients was higher than that of HC (P = 0.020).In phenotypes, mild ERD (vs HC [P = 0.036], NERD [P = 0.004], RH [P = 0.014]) and severe ERD (vs HC [P = 0.002], NERD [P < 0.001], RH [P = 0.001], FH [P = 0.004]) showed significantly higher IS. There was no significant difference between the HC, NERD, RH, and FH groups. The 1.12 μm DIS cutoff value had 63.5% sensitivity and 66.7% specificity in the diagnosis of GERD. There was a weak correlation (r = 0.302) between the IS value and acid exposure time, and a weak correlation (r = −0.359) between the IS value and baseline impedance. A strong correlation was shown between acid exposure time and baseline impedance (r = −0.783). @*Conclusions@#Since the IS length measurement had better discrimination power only in erosive groups, it is not feasible to use in daily routine to discriminate other nonerosive phenotypes and FH. The role of DIS in heartburn in nonerosive patients should be reconsidered.

Oropharyngeal swallowing functions are impaired in patients with naive-achalasia.

BACKGROUND: It is generally accepted that achalasia is limited to the pathology of the esophageal body and lower esophageal sphincter. However, patients with achalasia still have symptoms such as aspiration and weight loss after even a succesfull treatment, suggesting that additional oropharyngeal pathologies may be frequent in patients with achalasia. OBJECTIVE: The aim of the study was to assess the oropharyngeal/hypopharyngeal swallowing functions of patients with naive-achalasia. METHODS: We evaluated the oropharyngeal functions with fiberoptic endoscopic evaluation of swallowing (FEES) and high-resolution manometry (HRM) in 36 patients with naive-achalasia(mean age 47.8 ± 14.7; 20F, 20M) diagnosed with and upper gastrointestinal endoscopy, HRM, radiology compared the results with 40 healthy volunteers (mean age 48.25 ± 12.37; 23F, 17M) as controls. The Beck Depression Inventory (BDI) and the MD Anderson Dysphagia Inventory (MDADI) were used for psychological analysis and to assess quality of life. RESULTS: Mean integrated relaxation pressure (IRP) values were significantly higher (12.7 ± 10.9) for all patients compared to controls (0 ± 4.40). In the presence of pharyngeal residue IRP was 18.6 ± 11.8 mmHg compare to patients without pharyngeal residue which was 7.2 ± 6.4 mmHg (p < 0.05). Resting pressures were 105.7 ± 60.4 mmHg in study group vs 116 ± 55.1 mmHg in the control group (NS). In the study group we determined that residues of semisolid and liquid food were significantly higher in the vallecula, retrocricoid region, pharyngeal wall, and piriform sinuses with FEES. The average MDADI score was 58.1 ± 19.8 and 87.6 ± 10.7 in the study and control groups, respectively (p < 0.05). Depression may be significantly higher in achalasia patients based on the BDI. CONCLUSION: Relaxation of the upper esophageal sphincter is insufficient especially in patient with residue. This finding is supported by the presence of residue during FEES evaluation. In the assessment of patients with achalasia, in the presence of residue symptoms,oropharyngeal phases of swallowing should be examined with FEES. Furthermore, the effect of exercises to improve the pathological findings should be evaluated.

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is one of the main causes of chronic cough. We evaluated the role of microaspiration in the pathogenesis of reflux-related cough by determining the amount of lipid-laden macrophages (LLMs) in bronchoalveolar lavage (BAL) specimens. METHODS: A total of 161 cases of chronic cough were evaluated, and 36 patients (average age 48.2 years) were recruited for this single center prospective study. Patients with a history of smoking, angiotensin converting enzyme inhibitor usage, any abnormality on pulmonary function tests, abnormal chest X-rays, occupational or environmental exposures, or upper airway cough syndrome were excluded. GERD was evaluated by 24-hour esophageal impedance-pH monitoring. BAL specimens for LLM determination were obtained from 34 patients by flexible bronchoscopy. RESULTS: Patients with pathological intra-esophageal reflux according to multichannel intraluminal impedance and pH monitoring had higher LLM positivity in BAL specimens than patients without pathological reflux (8/14 in reflux positive group vs 1/22 in reflux negative group; P = 0.004). The BAL cell distribution was not different between the 2 groups (P = 0.574 for macrophages, P = 0.348 for lymphocytes, P = 0.873 for neutrophils and P = 0.450 for eosinophils). CONCLUSIONS: Our results confirm the role of the microaspiration of refluxate in the pathogenetic mechanism of chronic cough. While bronchoscopy is indicated in patients with chronic cough, in addition to the routine airway evaluation, BAL and LLM detection should be performed. LLM can be used to diagnose aspiration in reflux-related chronic cough. Future studies are needed to evaluate the response to anti-reflux medications or surgery in patients with LLM positivity.