Gastroesophageal reflux disease: Update on inflammation and symptom perception

Annamaria Altomare, Michele Pier Luca Guarino, Silvia Cocca, Sara Emerenziani, Michele Cicala, Unit of Digestive Disease, Campus Bio Medico University of Rome, 00128 Rome, Italy.
World Journal of Gastroenterology (Impact Factor: 2.37). 10/2013; 19(39):6523-6528. DOI: 10.3748/wjg.v19.i39.6523
Source: PubMed

ABSTRACT Although gastroesophageal reflux disease (GERD) is a common disorder in Western countries, with a significant impact on quality of life and healthcare costs, the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated. GERD symptoms and complications may result from a multifactorial mechanism, in which acid and acid-pepsin are the important noxious factors involved. Prolonged contact of the esophageal mucosa with the refluxed content, probably caused by a defective anti-reflux barrier and luminal clearance mechanisms, would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium. Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity, as suggested in animal models of chronic acid exposure. Meanwhile, specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD, explaining, in part, the genesis of esophagitis in a subset of patients. Despite these findings, which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD, the relationship between the hypersensitivity and esophageal inflammation is not clear. Moreover, the large majority of GERD patients (up to 70%) do not develop esophageal erosions, a variant of the condition called non-erosive reflux disease. This summary aims to explore the inflammatory pathway involved in GERD pathogenesis, to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.

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Available from: Annamaria Altomare, Sep 26, 2015
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    • "[4] These inflammatory mediators activate immune cell recruitment and migration, and may play an important role in the generation of GERD symptoms; in other words, GERD may be considered an inflammatory process. [4], [5]. "
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    ABSTRACT: BackgroundStudies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized.ObjectiveWe explored the relationship between GERD and the subsequent development of bipolar disorder, and examined the risk factors for bipolar disorder in patients with GERD.MethodsWe identified patients who were diagnosed with GERD in the Taiwan National Health Insurance Research Database. A comparison cohort without GERD was matched according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts based on diagnosis and the prescription of medications.ResultsThe GERD cohort consisted of 21,674 patients, and the comparison cohort consisted of 21,674 matched control patients without GERD. The incidence of bipolar disorder (incidence rate ratio [IRR] 2.29, 95% confidence interval [CI] 1.58–3.36, P<.001) was higher among GERD patients than among comparison cohort. Multivariate, matched regression models showed that the female sex (hazard ratio [HR] 1.78, 95% CI 1.76–2.74, P = .008), being younger than 60 years old (HR 2.35, 95% CI 1.33–4.16, P = .003), and alcohol use disorder (HR 4.89, 95% CI 3.06–7.84, P = .004) were independent risk factors for the development of bipolar disorder among GERD patients.ConclusionsGERD may increase the risk of developing bipolar disorder. Based on our data, we suggest that attention should be focused on female patients younger than 60 years, and patients with alcohol use disorder, following a GERD diagnosis.
    PLoS ONE 09/2014; 9(9):e107694. DOI:10.1371/journal.pone.0107694 · 3.23 Impact Factor
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    • "Due to evidences of functional neuroimaging , motility and endoscopic findings, symptoms pattern and response to pharmacological treatment showing variability in the spectrum of GERD, several works have suggested different pathophysiology between NERD and ERD (Hershcovici and Fass, 2010; Xu et al., 2010). Patients with erosive esophagitis have been associated with higher acid exposure in the distal esophagus and lower mean resting LES pressure if compared with NERDs, being theoretically more susceptible to mucosal inflammation and acid-related damage of peripheral afferents (Altomare et al., 2013). Nevertheless , IEM has been compared in GERD subgroups, mostly with no marked variability in NERD vs. ERD (Lemme et al., 2005). "
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    ABSTRACT: Objective To evaluate the effects of transcranial direct current stimulation (tDCS) on esophageal peristalsis in patients with gastroesophageal reflux disease (GERD). Methods Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study. Esophageal manometry was performed before and during transcranial direct current stimulation (tDCS) of the right precentral cortex. Half of patients were randomly assigned to anodal, half to sham stimulation. Distal waves amplitude and pathological waves percentage were measured, after swallowing water boli, for ten subsequent times. Last, a 24 h pH-bilimetry was done to diagnose non-erosive reflux disease (NERD) or functional heartburn (FH). The values obtained before and during anodal or sham tDCS were compared. Results Sixty-eight patients were enrolled in the study. Distal waves mean amplitude increased significantly only during anodal tDCS in NERD (p = 0.00002) and FH subgroups (p = 0.008) while percentage of pathological waves strongly decreased only in NERDs (p = 0.002). Conclusions Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease (ERD) patients. Significance Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well. In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology.
    Clinical Neurophysiology 01/2014; DOI:10.1016/j.clinph.2013.12.110 · 3.10 Impact Factor
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    ABSTRACT: To investigate autonomic nervous function in patients with a diagnosis of gastroesophageal reflux disease (GERD). The investigation was performed on 29 patients (14 men), aged 18-80 years (51.14 ± 18.34), who were referred to our Neurocardiology Laboratory at the Clinical and Hospital Center "Bezanijska Kosa" with a diagnosis of GERD. One hundred sixteen healthy volunteers matched in age and sex with the examinees served as the control group. The study protocol included the evaluation of autonomic function and hemodynamic status, short-term heart rate variability (HRV) analysis, 24 h ambulatory ECG monitoring with long-term HRV analysis and 24 h ambulatory blood pressure monitoring. Pathologic results of cardiovascular reflex test were more common among patients with reflux compared to the control group. Severe autonomic dysfunction was detected in 44.4% of patients and in 7.9% of controls (P < 0.001). Parameters of short-term analysis of RR variability, which are the indicators of vagal activity, had lower values in patients with GERD than in the control group. Long-term HRV analysis of time-domain parameters indicated lower values in patients with reflux disease when compared to the control group. Power spectral analysis of long-term HRV revealed lower low- and high-frequency values. Detailed 24 h ambulatory blood pressure analysis showed significantly higher values of systolic blood pressure and pulse pressure in the reflux group than in the control group. Patients with GERD have distortion of sympathetic and parasympathetic components of the autonomic nervous system, but impaired parasympathetic function appears more congruent to GERD.
    06/2015; 21(22):6982-9. DOI:10.3748/wjg.v21.i22.6982