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.

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.

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.