Concurrent abnormal non-acid reflux is associated with additional chronic rejection risk in lung transplant patients with increased acid exposure.

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.

Can pepsin immunohistochemical staining of laryngeal lesions accurately diagnose non-acid laryngeal reflux?

BACKGROUND: Non-acid reflux is the most common form of laryngopharyngeal reflux (LPR). However, the damage caused by non-acid reflux to the laryngeal mucosa is weaker than that caused by acid reflux. AIMS: To evaluate whether pepsin immunohistochemical (IHC) staining of laryngeal lesions can accurately diagnose acidic and non-acidic LPR. MATERIALS AND METHODS: Hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring was performed, and the patients were divided into acid reflux and non-acid reflux groups. Pathological sections of laryngeal lesions were examined using pepsin IHC staining, which was positive when pepsin was detected in the cytoplasm. RESULTS: The study included 136 patients, with 58 in the acid reflux group, 43 in the non-acid reflux group, and 35 in the without reflux group. There were no significant differences in the positive rate of pepsin IHC staining between the non-acid and acid reflux groups (p = .421). The sensitivity of pepsin IHC staining for the diagnosis of acid and non-acid reflux was 94.8% and 90.7%, respectively. CONCLUSIONS: The sensitivity of pepsin IHC staining for laryngeal lesions in the diagnosis of non-acidic LPR is satisfactory. SIGNIFICANCE: Pepsin IHC staining is suitable for LPR screening of patients with laryngeal lesions as it is economical, non-invasive, and highly sensitive.

The link between airway reflux and non-acid reflux in children: a review

Abstract Objective: Airway reflux, a member of extra-esophageal reflux, has been linked to countless respiratory pathologies amongst children. The advent of novel instrumentation has enabled the discovery of non-acid reflux which was postulated as the main culprit of airway reflux. The objective of this review is to outline the association between non-acid reflux and airway reflux in children. Methods: A comprehensive review of recent literature on non-acid reflux and airway reflux in children was conducted. Studies ranged from January 2010 till November 2021 were searched over a period of a month: December 2021. Results: A total of eleven studies were identified. All studies included in this review revealed a strong link between non-acid reflux and airway reflux in children. 6 of the included studies are prospective studies, 3 retrospective studies, 1 cross-section study, and type of study was not mentioned in 1 study. The most common reported respiratory manifestation of non-acid reflux in children was chronic cough (7 studies). Predominant non-acid reflux was noted in 4 studies. The total number of children in each study ranges from 21 to 150 patients. MII-pH study was carried out in all studies included as a diagnostic tool for reflux investigation. Conclusion: Non-acid reflux is the culprit behind airway reflux as well as other myriads of extra-esophageal manifestations in children. Multicentre international studies with a standardized protocol could improve scientific knowledge in managing non-acid reflux in airway reflux amongst children.

Esophageal function and non-acid reflux evaluated by impedance-24 h-pH-metry, high-resolution manometry, and gastroscopy after one-anastomosis gastric bypass-outcomes of a prospective mid-term study.

BACKGROUND: One-Anastomosis Gastric Bypass (OAGB) is the third most common bariatric operation for patients with obesity worldwide. One concern about OAGB is the presence of acid and non-acid reflux in a mid- and long-term follow-up. The aim of this study was to objectively evaluate reflux and esophagus motility by comparing preoperative and postoperative mid-term outcomes. SETTING: Cross-sectional study; University-hospital based. METHODS: This study includes primary OAGB patients (preoperative gastroscopy, high-resolution manometry (HRM), and impedance-24 h-pH-metry) operated at Medical University of Vienna before 31st December 2017. After a mean follow-up of 5.1 ± 2.3 years, these examinations were repeated. In addition, history of weight, remission of associated medical problems (AMP), and quality of life (QOL) were evaluated. RESULTS: A total of 21 patients were included in this study and went through all examinations. Preoperative weight was 124.4 ± 17.3 kg with a BMI of 44.7 ± 5.6 kg/m2, total weight loss after 5.1 ± 2.3 years was 34.4 ± 8.3%. In addition, remission of AMP and QOL outcomes were very satisfactory in this study. In gastroscopy, anastomositis, esophagitis, Barrett´s esophagus, and bile in the pouch were found in: 38.1%, 28.3%, 9.5%, and 42.9%. Results of HRM of the lower esophageal sphincter pressure were 28.0 ± 15.6 mmHg, which are unchanged compared to preoperative values. Nevertheless, in the impedance-24 h-pH-metry, acid exposure time and DeMeester score decreased significantly to 1.2 ± 1.2% (p = 0.004) and 7.5 ± 8.9 (p = 0.017). Further, the total number of refluxes were equal to preoperative; however, the decreased acid refluxes were replaced by non-acid refluxes. CONCLUSION: This study has shown decreased rates of acid reflux and increased non-acid reflux after a mid-term outcome of primary OAGB patients. Gastroscopy showed signs of chronic irritation of the gastrojejunostomy, pouch, and distal esophagus, even in asymptomatic patients. Follow-up gastroscopies in OAGB patients after 5 years may be considered.

The link between airway reflux and non-acid reflux in children: a review.

OBJECTIVE: Airway reflux, a member of extra-esophageal reflux, has been linked to countless respiratory pathologies amongst children. The advent of novel instrumentation has enabled the discovery of non-acid reflux which was postulated as the main culprit of airway reflux. The objective of this review is to outline the association between non-acid reflux and airway reflux in children. METHODS: A comprehensive review of recent literature on non-acid reflux and airway reflux in children was conducted. Studies ranged from January 2010 till November 2021 were searched over a period of a month: December 2021. RESULTS: A total of eleven studies were identified. All studies included in this review revealed a strong link between non-acid reflux and airway reflux in children. 6 of the included studies are prospective studies, 3 retrospective studies, 1 cross-section study, and type of study was not mentioned in 1 study. The most common reported respiratory manifestation of non-acid reflux in children was chronic cough (7 studies). Predominant non-acid reflux was noted in 4 studies. The total number of children in each study ranges from 21 to 150 patients. MII-pH study was carried out in all studies included as a diagnostic tool for reflux investigation. CONCLUSION: Non-acid reflux is the culprit behind airway reflux as well as other myriads of extra-esophageal manifestations in children. Multicentre international studies with a standardized protocol could improve scientific knowledge in managing non-acid reflux in airway reflux amongst children.

Non-Acid Fluid Exposure and Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) accounts for the large majority of esophageal cancer cases worldwide. In this review, we examine the potential role of non-acidic fluid (NAF) exposure in ESCC carcinogenesis. Esophageal NAF consists of a mixture of salivary, esophageal, gastric, and duodenal fluids, containing inflammatory constituents such as digestive enzymes and bile acids that induce DNA damage, as well as known carcinogens such as acetaldehyde and N-nitrosamines. Exposure to NAF can occur in the setting of increased non-acid reflux, decreased gastric acidity, and decreased esophageal fluid clearance. Non-acid reflux has been associated with ESCC in small observational studies, and in animal models bile reflux can promote the development of ESCC. Associations have been found between increased ESCC risk and atrophic gastritis, a history of partial gastrectomy, and proton pump inhibitor use, all of which raise the pH of refluxate. Additionally, a minimally or non-acidic gastric environment contains an altered microbiome that can increase the production of acetaldehyde and N-nitrosamines. Esophageal motility disorders such as achalasia and opioid-induced esophageal dysfunction result in increased stasis and exposure to these potentially proinflammatory constituents of NAF. NAF may promote the development of ESCC via multiple mechanisms and is an understudied area of research.

Non-acid Reflux: When It Matters and Approach to Management.

PURPOSE OF REVIEW: This narrative review focuses on the presentation, contributing factors, diagnosis, and treatment of non-acid reflux. We also propose algorithms for diagnosis and treatment. RECENT FINDINGS: There is a paucity of recent data regarding non-acid reflux. The recent Porto and Lyon consensus statements do not fully address non-acid reflux or give guidance on classification. However, recent developments in the lung transplantation field, as well as older data in the general population, argue for the importance of non-acid reflux. Extrapolating from the Porto and Lyon consensus, we generally classify pathologic non-acid reflux as impedance events > 80, acid exposure time < 4%, and positive symptom correlation on a standard 24-h pH/impedance test. Other groups not meeting this criteria also deserve consideration depending on the clinical situation. Potential treatments include lifestyle modification, increased acid suppression, alginates, treatment of esophageal hypersensitivity, baclofen, buspirone, prokinetics, and anti-reflux surgery in highly selected individuals. More research is needed to clarify appropriate classification, with subsequent focus on targeted treatments.

Study on laryngopharyngeal and esophageal reflux characteristics using 24-h multichannel intraluminal impedance-pH monitoring in healthy volunteers.

OBJECTIVE: We aimed to analyze the results of 24-h multichannel intraluminal impedance and pH-monitoring (MII-pH) of the laryngopharynx and esophagus in asymptomatic volunteers. Moreover, we also aimed to gain insight into and establish a baseline for laryngopharyngeal reflux in the healthy population by quantitatively and qualitatively comparing the reflux and pH distribution in both the laryngopharynx and the esophagus. METHODS: Healthy volunteers were recruited and observed; they underwent 24-h ambulatory combined MII-pH monitoring. The proximal sensor (pH1) was positioned approximately 1 cm above the upper esophageal sphincter with the aid of a solid-state high-resolution esophageal manometer. Laryngopharyngeal reflux events were detected and characterized by the incidence and property of reflux both in the laryngopharynx and the esophagus. RESULTS: Thirty-eight asymptomatic volunteers who completed all the examinations were included in this study. The median pH detected by the proximal sensor was 6.6 (6.2, 7.0), with an average of 6.58 ± 0.74. A total of 814 laryngopharyngeal reflux events were detected, including 722 (89%) in the upright position and 92 (11%) in the supine position with incidence (0%) in the liquid state, 44 (5%) in the mixture, and 769 (95%) in the gaseous state. Furthermore, 5 incidences (1%) of acid reflux and 809 incidences of non-acid reflux (99%) were noted. A total of 5779 esophageal reflux events were detected, including 5020 (87%) in the upright position, 759 (13%) in the supine position, with 2051 (36%) in the liquid state, 2050 (35%) in the mixed condition, and 1678 (29%) in the gaseous state; adding up to 805 incidences (14%) of acid reflux and 4974 incidences (86%) of non-acid reflux. CONCLUSION: Non-acid reflux in the upright position is characteristic of laryngopharyngeal reflux. Acid reflux is almost undetectable in healthy subjects. Hence, the diagnostic indicators of gastroesophageal reflux disease are not suitable for laryngopharyngeal reflux disease.

Diagnostic yield of ambulatory oesophageal studies on versus off proton pump inhibitors: a systematic review and meta-analysis.

BACKGROUND: Patients with persistent gastroesophageal reflux disease symptoms despite proton pump inhibitors are increasingly encountered. It remains controversial if proton pump inhibitors should be stopped before functional oesophageal tests. AIM: This meta-analysis compares the positive yield of oesophageal studies performed off versus on proton pump inhibitors. METHODS: Pubmed, Embase and the Cochrane Library were searched for eligible studies. Outcomes assessed were the number of subjects with: elevated oesophageal acid exposure time when studied off versus on proton pump inhibitors; positive symptom index (≥50%) and/or positive symptom association probability (≥95%) for acid reflux; and/or non-acid reflux events off versus on proton pump inhibitors. The random effects model was applied. RESULTS: Fifteen studies (n = 5033 individuals; 33% on proton pump inhibitors; 32% men; mean age 52.1 years) were analysed. Pooled risk ratio for the comparison of high oesophageal acid exposure time off versus on proton pump inhibitors was 2.16 (95% confidence interval (CI) 1.42-3.28). The risk ratio of a positive symptom index (acid reflux) was 2.64 (95% CI 1.52-4.57) and the risk ratio of a positive symptom association probability (acid reflux) was 2.94 (95% CI 2.31-3.74). Conversely, the risk ratio of a positive symptom index (non-acid reflux) was 0.96 (95% CI 0.49-1.88) and risk ratio of a positive symptom association probability (non-acid reflux) was 0.54 (95% CI 0.30-0.99). CONCLUSIONS: Oesophageal studies after proton pump inhibitor cessation improve the positive yield for acid reflux-related events but reduce the detection of symptomatic non-acid reflux events.

Cough associated with gastro-oesophageal reflux disease (GORD): Japanese experience.

Differences in the aetiology as well as patient background of chronic cough have been recognised among US, UK, and Japan. One of the marked differences has been the prevalence of gastro-oesophageal reflux disease (GORD), which has been one of the top three causes in Western countries. It was indeed uncommon or rare in Japan, but, with the increasing prevalence of GOR itself, chronic cough associated with GORD seems to have become more common. In this article, cough associated with GORD will be reviewed based on literature and our Japanese experience. Further, potentially broader relevance of GORD in chronic cough will also be mentioned, highlighting the potential importance of dysmotiliy/non-acid reflux.

Diet affects reflux in a rural African community.

Reflux in this region of South Africa is known to be more frequent and less acidic than in other countries. We investigated the relationship between reflux and diet. We recruited 57 healthy participants. We carried out ambulant oesophageal pH-impedance monitoring for 24 hours. We used software and visual review to analyse data and to identify episodes of reflux and rapid alkaline rises in the stomach. A usual pattern diet questionnaire provided data on frequency of consumption of common foods. Associations between reflux, gastric pH and dietary components were sought using analysis of variance, and regression analyses. Diet was strongly based on maize. Protein was principally from milk, eggs, chicken and beans. Fat was principally from cooking oil. Fruit and vegetables were consumed moderately frequently. Milk consumption was associated with an increase in total reflux (P = .022), weakly acid reflux (P = 0.015) and supine reflux (P = 0.001), and a decrease in the time that gastric pH was higher than 4 (P = 0.030). Fat was associated with an increase in acid reflux (P = 0.046) and a decrease in time that gastric pH was higher than 4 (P = 0.005). Fruit consumption was associated with increases in liquid-only refluxes(P = 0.007), and upright refluxes (P = 0.048). Maize meal was associated with a reduction in rapid alkaline rises in the gastric lumen (P = 0.015). Diet significantly affects reflux in this community. What is normal in apparently healthy people in various parts of the world differs significantly.

Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy.

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.

Detection of gastroesophageal reflux in children with cerebral palsy using combined multichannel intraluminal impedance-ph procedure.

Gastroesophageal reflux (GER) is a very common condition in children with neurological impairment and this can influence nutritional and respiratory outcomes. The aim of this study was to investigate the presence of GER in children with cerebral palsy (CP) using multiple intraluminal impedance (MII)-pH monitoring. The use of combined MII-pH allows for the detection of both acid and non-acid reflux episodes. A total of 29 CP patients with symptoms suggesting GER, aged 2 to 10 years old, underwent 24-hour combined MII-pH monitoring. There were a total of 3899 reflux episodes, of which 29% were acid, 60% were weakly acid and 11% were alkaline. The number of non-acid reflux episodes was statistically significantly greater (p < 0.01). These findings confirm that GER disease is seen frequently in children with cerebral palsy and most of the reflux episodes are not acidic. Non-acid reflux can also influence the morbidity in patients with cerebral palsy. It can be concluded that 70% of the reflux episodes would not have been recognized by pH measurement alone.

Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring.

BACKGROUND AND AIMS: About 30% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI failure in Asian GERD patients has rarely been studied, and the therapy remained unclear. The aims were to explore the possible reasons for PPI failure and to treat these patients with the guidance of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. METHODS: Thirty-nine consecutive patients with refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The refractory GERD patients were grouped into acid overexposure, non-acid reflux, and functional heartburn after the MII-pH monitoring. Double dose of either PPI or paroxetine was administered to refractory GERD patients within different groups. RESULTS: The number of patients in groups of acid overexposure, non-acid reflux, and functional heartburn was 6, 12, and 21, respectively. The acid overexposure group had the most acid reflux events. Among the acid overexposure group, five (5/6) patients accomplish symptom relief with double dose of esomeprazole. For the patients in non-acid reflux group, double dose of esomeprazole made half (6/12) of the patients obtain symptom relief. For the patients in functional heartburn group, the paroxetine had relieved the symptoms in 14 patients among all the 21 patients. In total, with the guidance of MII-pH monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom relief. CONCLUSIONS: Acid overexposure, non-acid reflux, and functional heartburn were the common reasons for persistent reflux symptoms despite PPI. With the guidance of MII-pH, a tailored therapy could resolve the persistent reflux symptoms among two-third of patients.

Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they?

BACKGROUND: A short-course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance-pH monitoring (MII-pH). The aim of the study was to evaluate patients with reflux symptoms and a negative endoscopy, who well respond to PPIs with MII-pH. METHODS: We enrolled 312 patients with GERD symptoms and negative endoscopy: 144 reported well-controlled symptoms after 8-week PPIs and 155 were non-responders. Symptom relief was evaluated with GERD Impact Scale and visual analog scale score. All patients underwent MII-pH off-therapy. Thirteen patients were excluded from analysis. Patients were grouped as follows: non-erosive reflux disease (NERD; increased acid exposure time, AET); hypersensitive esophagus (HE; normal AET, positive symptom association, SI/SAP); MII-pH-/PPI+ (normal AET, negative SI/SAP) in the responder group; MII-pH-/PPI- in non-responders. KEY RESULTS: MII-pH in PPI responders (symptom relief during PPI therapy > 75%) showed: 79/144 NERD (54.9%); 37/144 HE (25.7%); 28/144 MII-pH-/PPI+ (19.4%). MII-pH-/PPI+ patients reported the same symptom relief when compared with NERD and HE. In non-responder (symptom relief during PPI therapy < 50%) group, 27/155 patients were NERD (17.4%); 53/155 were HE (34.2%); 75/155 were MII-pH-/PPI- (48.4%). NERD diagnosis was significantly higher in responder group (p < 0.01). CONCLUSIONS & INFERENCES: In a substantial subgroup of patients responding to PPI with typical reflux symptoms, the diagnosis of GERD cannot be confirmed with pH-impedance monitoring. Proton pump inhibitor response and presence of typical symptoms are thus not reliable predictors of the diagnosis and antireflux surgery should always be preceded by reflux monitoring.

The utility of endoscopy and multichannel intraluminal impedance testing in children with cough and wheezing.

BACKGROUND: Gastroesophageal reflux (GER) has been implicated as a causal factor in respiratory disease but prior studies have focused on the role of acid alone in the genesis of symptoms. Prior studies have relied on pH probe testing but this is blind to non-acid reflux which has been implicated in the genesis of extraesophageal symptoms. The objective of this prospective, cross-sectional study is to determine the utility of gastroesophageal reflux testing, including multichannel intraluminal impedance with pH (pH-MII) and upper gastrointestinal endoscopy (EGD), in the child with intractable cough and wheezing. We hypothesize that there is a high rate of pathologic reflux testing in these patients. METHODS: Children ages 1-18 with chronic cough and wheezing who were undergoing bronchoscopy for the evaluation of cough and wheezing were recruited into this prospective, cross-sectional study. They underwent identical reflux testing with pH-MII and EGD at the time of bronchoscopy. Reflux burden, symptom association, and rates of esophageal pathology were determined. Results 58% of patients had abnormal reflux testing; 67% of patients had an abnormal pH-MII test and 32% of patients had abnormal esophageal biopsies. The most common pH-MII abnormality was an abnormal symptom association between cough and reflux and the most common endoscopic abnormality was reflux esophagitis. Seven percent of patients presenting only with cough were diagnosed with eosinophilic esophagitis. CONCLUSIONS: There is a high yield to reflux testing in children with chronic cough and wheezing.

Sleep disorders and the prevalence of asymptomatic nocturnal acid and non-acid reflux.

BACKGROUND: Nocturnal acid reflux is associated with symptomatic and asymptomatic sleep arousals, leading to fragmented sleep. The frequency and influence of acid reflux in patients with various forms of insomnia has not been reported. The aim of this study was to quantify nocturnal acid and nonacid reflux in patients with primary sleep disorders as previously diagnosed by polysomnography. METHODS: THIRTY ONE SUBJECTS WERE STUDIED: (A) 9 subjects with a polysomnographically diagnosed sleep disorder (1 with restless legs syndrome, 4 with narcolepsy, 4 with periodic limb movement disorder); (B) 12 subjects with primary insomnia (PI) and unrevealing polysomnography; and (C) 10 controls without disturbed sleep. All subjects underwent a physical examination and 24 h transnasal pH and impedance monitoring to detect acid and non-acid reflux. RESULTS: The 21 subjects with fragmented sleep due to a primary sleep disorder had significantly more recumbent acid exposure (>1.2% of time) as compared with control subjects (33% versus 0%). When fragmented sleep subjects were divided into two groups, 17% of PI subjects and 55% of subjects with a diagnosed sleep disorder had significant recumbent acid exposure (P=0.009). Likewise, the median recumbent nonacid events were increased in the sleep disordered group (P=0.011). CONCLUSIONS: This study indicates that patients with primary sleep disorders have prominent nocturnal acid reflux without symptoms of daytime acid reflux. Acid reflux is most prominent in patients with polysomnographic findings of disturbed sleep as compared to patients with PI; while non acid reflux is increased minimally in these patients.

Role of non-acid reflux in patients with non-erosive reflux disease.

Non-erosive reflux disease (NERD) is the most common presentation of gastroesophageal reflux disease. Although acid reflux is the most important cause of symptom generation in NERD patients, non-acid reflux is also associated with reflux symptoms. The temporal relation between symptoms and reflux episodes is of importance in evaluating the results of combined pH-impedance monitoring in NERD patients. Mucosal hypersensitivity and mechanical stimulation due to great volume of non-acid reflux are among the putative mechanisms of symptom generation.

Impedâncio-pHmetria prolongada: observações preliminares / Extended impedance-pHmetry: preliminary observation

Racional: a Doença do Refluxo Gastroesofágico (DRGE) é uma doença de alta prevalência em todo o mundo, apresentando elevada taxa de morbidade. O diagnóstico da DRGE tem evoluído muito nos últimos anos e a pHmetria esofagiana prolongada atualmente é considerada o padrão-ouro para este diagnóstico. Entretanto, este método é limitado, uma vez que avalia apenas a presença do refluxo ácido, não detectando o refluxo de outros tipos. Com a ampla utilização das drogas antissecretoras, surgiu um grupo diferente de pacientes, aqueles que persistem com sintomas típicos e/ou atípicos da DRGE, apesar do tratamento adequado. Em tais casos, questiona-se a importância de outros fatores na gênese dos sintomas, como o refluxo não-ácido ou fracamente ácido. Nos últimos anos, a impedâncio-pHmetria 24h (IMP-PH) foi introduzida para diagnosticar estes casos. Entretanto, a real contribuição do método ainda é muito controversa, uma vez que os resultados dos estudos realizados são conflitantes e o número de pacientes incluídos nestes estudos pequenos. Objetivo: avaliar a experiência prévia da Unidade de Esôfago, Serviço de Gastroenterologia, da Universidade Federal do Rio de Janeiro, no uso da IMP-PH. Métodos: Este é um estudo de corte, transversal, que avaliou pacientes encaminhados à Unidade de Esôfago, da Universidade Federal do Rio de Janeiro para serem submetidos á IMP-PH. Todos os pacientes estudados persistiam com sintomas da DRGE (típicos ou atípicos) e já haviam sido submetidos previamente à endoscopia digestiva alta, esofagomanometria (EMN) e à pHmetria esofagiana de 24h, sem esclarecimento da causa dos seus sintomas. Um gravador portátil foi empregado (Sleuth 200-0145, Sandhill Scientific), com um cateter de 2,1 milímetros de diâmetro, um sensor de pH e seis pares de eletrodos de impedância. Com o paciente em jejum, a sonda foi introduzida através de uma das narinas e o sensor de pH posicionado 5 cm acima do esfíncter esofagiano inferior (EEI) previamente determinado pela EMN. As medidas de impedância foram feitas 3, 5, 7, 9, 15 e 17 centímetros acima do EEI. Os pacientes foram instruídos a não restringir suas atividades, para excluir alimentos ácidos e bebidas carbonatadas, e a anotar as horas de decúbito, a ingestão de alimentos e os sintomas. Eles também foram instruídos a pressionar botões específicos, se eles apresentassem sintomas como dor torácica, tosse e/ou azia. Após 22-24h, o paciente retornava ao laboratório, o equipamento era retirado e, em seguida, o exame processado pelo software Bioview. Além disso, era informado o uso (IBP em dose dupla) ou não de medicação antissecretora. No caso de um exame feito sem medicação, os inibidores da bomba de prótons (IBP) foram interrompidos 7-10 dias antes do exame. Com relação à impedância, considerou-se inicio do episódio de refluxo quando havia uma queda retrógrada na impedância de pelo menos 50% em relação ao seu valor basal e término do refluxo quando este valor voltava ao seu nível basal anterior. Na ausência de drogas antissecretoras, considerou-se refluxo anormal quando o número de episódios de refluxo registrados pela impedância foi superior a 73 e para o monitoramento do pH quando a percentagem de tempo total pH <4 foi acima de 4,5%. Naqueles pacientes em uso de IBP em dose dupla, considerou-se refluxo anormal quando o número de episódios de refluxo foi superior a 48 e o percentual de tempo total de pH < 4 foi superior a 1,6%. Para avaliar a relação refluxo / sintoma, empregou-se o Índice de Sintomas (IS), sendo considerado positivo quando igual ou superior a 50%. Resultados: Foram incluídos 30 pacientes, 14 homens (47%) e 16 mulheres (53%), com média de idade de 56 anos (36-79). Tosse crônica foi a principal queixa - 14 pacientes (47%) - seguidos de azia apesar do uso do IBP em oito (27%), dor torácica em 5 (17%) regurgitação em 1 (3%), rouquidão em 1 (3%) e soluços em 1 (3%). Dos 30 pacientes estudados, o teste foi realizado em uso do IBP em 17 e sem IBP em 13. A IMP-PH mostrou que 15 pacientes (50%) apresentavam refluxo anormal, sendo anormal ácido em 7 (23%) e anormal não-ácido em 8 (27%). Dos 15 pacientes em que o teste foi anormal, 7 (47%) apresentaram refluxo anormal ácido, e destes apenas um (14%) apresentou IS positivo, 4 (57%) apresentaram IS negativo e 2 (29%) não apresentaram sintomas. Nos 8 pacientes (53%) com refluxo anormal não-ácido, 4 (50%) apresentaram IS positivo, 3 (38%) apresentaram IS negativo (12%) e 1 (12%) foi assintomático. Conclusão: a IMP-PH é um novo método capaz de avaliar o refluxo anormal de qualquer natureza química e sua relação com sintomas típicos e atípicos da DRGE, especialmente nos pacientes em uso do IBP. Além disso, permite avaliar os pacientes onde a pH 24h apresenta limitações (refluxo não-ácido), representando o progresso para o diagnóstico da DRGE. Entretanto, o significado real do refluxo não-ácido, ainda está por ser determinado.

Background: the gastroesophageal reflux disease (GERD) is a highly prevalent disease worldwide, with high morbidity. The diagnosis of GERD has evolved greatly in recent years and esophageal pHmetry 24h (pH24H) is currently considered the gold standard for diagnosis. However, this method is limited, since evaluates only acid reflux, not detect another types of reflux. With the widespread use of anti-secretory drugs, came a different group of patients, those who persist with typical or atypical GERD symptoms, despite adequate treatment. In such cases, arise the importance of other factors in the genesis of symptoms as non-acid or weakly acid reflux. In recent years, the impedance-pHmetry 24h (IMP-PH) was introduced to diagnose these cases. However, the real contribution of the method is controversial, since the results of the studies are conflicting and the number of patients enrolled in these studies small. Objective: assess previous experience of Esophagus Unit, Gastroenterology Service, Federal University of Rio de Janeiro, using IMP-PH. Method: This is a cross-sectional study, that evaluated patients referred to the Esophagus Unit of Federal University of Rio de Janeiro, to be submitted to IMP-PH. All patients had GERD persisting symptoms (typical or atypical) and had previously undergone upper endoscopy, esophageal manometry (EMN) and pH24h, without clarification of the cause of your symptoms. A portable recorder was used (200-0145 Sleuth, Sandhill Scientific), with a catheter of 2.1 mm in diameter, a pH sensor and six pairs of impedance electrodes. With the fasting patient, the probe was introduced through one nostril and the pH sensor positioned 5 cm above the lower esophageal sphincter (LES) previously determined by EMN. The impedance measurements were made 3,5,7,9,15 and 17 cm above the LES. Patients were instructed not to restrict their activities, exclude acidic foods and carbonated beverages, and record the hours of recumbency, food intake and symptoms. They were also instructed to press specific buttons, if they had symptoms such as chest pain, cough and or heartburn. After 22-24h, the patient returned to the laboratory, recorder was removed and then processed by the software Bioview. Furthermore, was reported use (IBP double dose) or absence of antisecretory drugs. In the case of a test done without medication, proton pump inhibitors (PPI) were stopped 7-10 days before the test. With respect to impedance, it is considered the start of reflux episode when there was a retrograde fall in impedance at least 50% compared to baseline level and end of reflux when the value returned to previous baseline level. In the absence of anti-secretory drugs, it was considered abnormal reflux when the number of reflux episodes recorded by impedance was greater than 73 and pH monitoring when the percentage of total time pH <4 was above 4.5%. In those patients using double-dose PPI, abnormal reflux was considered when the number of reflux episodes was greater than 48 and the percentage of total time pH <4 was greater than 1.6%. To evaluate the relationship reflux / symptom, we used the Symptom Index (IS), was considered positive when above 50%. Results: We included 30 patients, 14 men (47%) and 16 women (53%), mean age 56 years (36-79). Chronic cough was the main complaint - 14 patients (47%) - followed by heartburn despite the use of PPI in eight (27%), chest pain in 5 (17%) regurgitation in 1 (3%), hoarseness in 1 (3 %) and hiccups 1 (3%). Of the 30 patients tested, the test was performed using PPI in 17 and without PPI in 13. The IMP-PH showed abnormal reflux in 15 patients (50%), these 7 (23%) was abnormal acid and 8 (27%) abnormal non-acid. Of the 15 patients in whom the test was abnormal, 7 (47%) had abnormal acid reflux, and of these only one (14%) presented positive IS, 4 (57%) negative IS and 2 (29%) were asymptomatic. In 8 patients (53%) with abnormal reflux non-acid, 4 (50%) were positive IS, 3 (38%) negative IS (12%) and 1 (12%) was asymptomatic. Conclusion: the IMP-PH is a new method to evaluate the abnormal reflux of any chemical nature and its relationship with typical or atypical GERD symptoms, especially in patients using PPI. In addition, evaluate patients where pH24h has limitations (non-acid reflux), representing progress in the diagnosis of GERD. However, the real meaning of non-acid reflux, is yet to be determined.