A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Almeida, Clara Mota Randal Pompeu de
Orientador(a): Souza, Marcellus Henrique Loiola Ponte de
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/79851
Resumo: Laryngopharyngeal reflux disease (LPRD) is a chronic inflammatory condition affecting the upper aerodigestive tract due to gastric refluxate. Its relationship with gastroesophageal reflux disease (GERD) remains uncertain, and its pathophysiology is not yet clearly elucidated. Accurate diagnosis of LPRD and appropriate therapeutic approaches, as well as predictors of clinical response, are challenges in daily practice. The present study aims to evaluate whether impairment of the integrity of the laryngeal and hypopharyngeal mucosa during laryngopharyngeal reflux could be a factor related to response to proton pump inhibitors (PPIs). Patients presenting with chronic hoarseness and a Reflux Finding Score (RFS) of ≥7 were evaluated using the Reflux Disease Questionnaire (RDQ) and Reflux Symptom Index (RSI). Upper endoscopy was performed, and samples from the posterior commissure of the larynx were collected to evaluate ex vivo the integrity of the laryngeal mucosa by transepithelial resistance (TER) using an Ussing chamber. All patients underwent 24-hour pH-impedance monitoring (pH-imp-24h), followed by an acid oral exposure test. In vivo, hypopharyngeal integrity was measured using intraluminal impedance of the hypopharynx. Clinical responders were defined as those with an RSI score <13 and a reduction of at least 50% from their initial RSI after 8 weeks of pantoprazole treatment. Eighteen patients completed the protocol. The median scores for RDQ, RSI, and RFS were 14 (0–41), 22.5 (4–34), and 9 (7–20), respectively. Esophagitis was detected in 28% of the patients, and one patient presented with acid exposure above 6%. By the end of the 8-week treatment, 12 patients (66.67%) responded to PPI therapy. Baseline laryngeal TER and TER drops after challenge showed no significant difference between PPI responders and non-responders. Hypopharyngeal basal impedance was similar between responders and non-responders. After the acid oral exposure test, impedance was lower in non-responders than in PPI responders. In conclusion, in dysphonic patients with LPRD, hypopharyngeal mucosal integrity was lower in PPI non-responders. This suggests that weaker laryngopharyngeal mucosa in refractory LPRD may require new therapies aimed at improving barrier function.
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spelling Almeida, Clara Mota Randal Pompeu deSouza, Marcellus Henrique Loiola Ponte de2025-02-21T13:54:44Z2025-02-21T13:54:44Z2025ALMEIDA, Clara Mota Randal Pompeu de. A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo. 2025. 86 f. Tese (Doutorado em Ciências Médico-Cirúrgicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://www.repositorio.ufc.br/handle/riufc/79851. Acesso em: 21 fev. 2025.http://repositorio.ufc.br/handle/riufc/79851Laryngopharyngeal reflux disease (LPRD) is a chronic inflammatory condition affecting the upper aerodigestive tract due to gastric refluxate. Its relationship with gastroesophageal reflux disease (GERD) remains uncertain, and its pathophysiology is not yet clearly elucidated. Accurate diagnosis of LPRD and appropriate therapeutic approaches, as well as predictors of clinical response, are challenges in daily practice. The present study aims to evaluate whether impairment of the integrity of the laryngeal and hypopharyngeal mucosa during laryngopharyngeal reflux could be a factor related to response to proton pump inhibitors (PPIs). Patients presenting with chronic hoarseness and a Reflux Finding Score (RFS) of ≥7 were evaluated using the Reflux Disease Questionnaire (RDQ) and Reflux Symptom Index (RSI). Upper endoscopy was performed, and samples from the posterior commissure of the larynx were collected to evaluate ex vivo the integrity of the laryngeal mucosa by transepithelial resistance (TER) using an Ussing chamber. All patients underwent 24-hour pH-impedance monitoring (pH-imp-24h), followed by an acid oral exposure test. In vivo, hypopharyngeal integrity was measured using intraluminal impedance of the hypopharynx. Clinical responders were defined as those with an RSI score <13 and a reduction of at least 50% from their initial RSI after 8 weeks of pantoprazole treatment. Eighteen patients completed the protocol. The median scores for RDQ, RSI, and RFS were 14 (0–41), 22.5 (4–34), and 9 (7–20), respectively. Esophagitis was detected in 28% of the patients, and one patient presented with acid exposure above 6%. By the end of the 8-week treatment, 12 patients (66.67%) responded to PPI therapy. Baseline laryngeal TER and TER drops after challenge showed no significant difference between PPI responders and non-responders. Hypopharyngeal basal impedance was similar between responders and non-responders. After the acid oral exposure test, impedance was lower in non-responders than in PPI responders. In conclusion, in dysphonic patients with LPRD, hypopharyngeal mucosal integrity was lower in PPI non-responders. This suggests that weaker laryngopharyngeal mucosa in refractory LPRD may require new therapies aimed at improving barrier function.A Doença do Refluxo Faringolaríngeo (DRFL) é uma condição inflamatória crônica que acomete o trato aerodigestivo superior, decorrente da ascensão do refluxato gástrico. Sua relação com a Doença do Refluxo Gastroesofágico (DRGE) é controversa, e seu mecanismo fisiopatológico ainda não é claramente elucidado. O diagnóstico preciso da DRFL e a terapêutica adequada, bem como preditores de resposta clínica, são desafios na prática clínica. O objetivo deste estudo é avaliar se o comprometimento da integridade da mucosa laríngea e hipofaríngea em pacientes com DRFL pode estar relacionado à resposta ao tratamento com inibidores da bomba de prótons (IBP). Foram avaliados pacientes com disfonia crônica (maior que três semanas) através de videonasofaringolaringoscopia, com aplicação da Escala de Achados Endolaríngeos de Refluxo (EAER) e clinicamente, através do Índice de Sintomas de Refluxo (ISR) e Questionário padronizado de DRGE (RDQ). Pacientes com EAER ≥ 7 foram incluídos no estudo. Foi realizada endoscopia digestiva alta (EDA), e amostras da comissura posterior laríngea foram coletadas para avaliar ex vivo a integridade da mucosa laríngea, através da resistência elétrica transepitelial (RETE), em uma câmara de Ussing. Todos os pacientes foram submetidos à pHmetria-impedanciometria de 24h (pH-imp-24h), seguida por teste de provocação ácida oral. Para análise da integridade mucosa da hipofaringe in vivo, foi mensurada impedância intraluminal da hipofaringe. Os pacientes foram submetidos a tratamento com IBP pantoprazol 40mg duas vezes ao dia, por um período de oito semanas. Considerou-se resposta clínica a redução de pelo menos 50% do ISR e pontuação inferior a 13, após o tratamento. Dezoito pacientes completaram o protocolo, com medianas iniciais de RDQ, ISR e EAER de 14 (0–41), 22,5 (4–34) e 9 (7–20), respectivamente. Esofagite foi detectada em 28% dos pacientes, e um paciente apresentou exposição ácida acima de 6%. Ao final das 8 semanas, 12 pacientes (66,67%) responderam clinicamente ao IBP. A RETE basal laríngea e a queda da RETE após solução-desafio não apresentaram diferenças entre os respondedores e não-respondedores ao IBP. A impedância basal hipofaríngea foi semelhante entre os grupos. Após o teste de provocação ácida, a impedância foi menor nos não-respondedores do que nos respondedores. Os resultados sugerem que, na DRFL, a integridade da mucosa hipofaríngea é inferior em pacientes não-respondedores ao IBP, após teste de provocação ácida oral. Desta forma, podemos inferir que a mucosa mais vulnerável de paciente com DRFL refratário pode exigir novas terapias tópicas focadas em melhorar a função de barreira.A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisMucosa LaríngeaRefluxo LaringofaríngeoInibidores da Bomba de PrótonsImpedância ElétricaLaryngeal MucosaLaryngopharyngeal RefluxProton Pump InhibitorsElectric ImpedanceCNPQ::CIENCIAS DA SAUDE::MEDICINAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/3369496402000839https://orcid.org/0000-0003-2376-3433http://lattes.cnpq.br/40015965222639402025ORIGINAL2025_tese_cmrpalmeida.pdf2025_tese_cmrpalmeida.pdfapplication/pdf2299171http://repositorio.ufc.br/bitstream/riufc/79851/1/2025_tese_cmrpalmeida.pdff6378a37e35064debe99d93d6851cf06MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/79851/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/798512025-02-21 13:43:32.828oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-02-21T16:43:32Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
title A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
spellingShingle A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
Almeida, Clara Mota Randal Pompeu de
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Mucosa Laríngea
Refluxo Laringofaríngeo
Inibidores da Bomba de Prótons
Impedância Elétrica
Laryngeal Mucosa
Laryngopharyngeal Reflux
Proton Pump Inhibitors
Electric Impedance
title_short A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
title_full A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
title_fullStr A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
title_full_unstemmed A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
title_sort A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
author Almeida, Clara Mota Randal Pompeu de
author_facet Almeida, Clara Mota Randal Pompeu de
author_role author
dc.contributor.author.fl_str_mv Almeida, Clara Mota Randal Pompeu de
dc.contributor.advisor1.fl_str_mv Souza, Marcellus Henrique Loiola Ponte de
contributor_str_mv Souza, Marcellus Henrique Loiola Ponte de
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
topic CNPQ::CIENCIAS DA SAUDE::MEDICINA
Mucosa Laríngea
Refluxo Laringofaríngeo
Inibidores da Bomba de Prótons
Impedância Elétrica
Laryngeal Mucosa
Laryngopharyngeal Reflux
Proton Pump Inhibitors
Electric Impedance
dc.subject.ptbr.pt_BR.fl_str_mv Mucosa Laríngea
Refluxo Laringofaríngeo
Inibidores da Bomba de Prótons
Impedância Elétrica
dc.subject.en.pt_BR.fl_str_mv Laryngeal Mucosa
Laryngopharyngeal Reflux
Proton Pump Inhibitors
Electric Impedance
description Laryngopharyngeal reflux disease (LPRD) is a chronic inflammatory condition affecting the upper aerodigestive tract due to gastric refluxate. Its relationship with gastroesophageal reflux disease (GERD) remains uncertain, and its pathophysiology is not yet clearly elucidated. Accurate diagnosis of LPRD and appropriate therapeutic approaches, as well as predictors of clinical response, are challenges in daily practice. The present study aims to evaluate whether impairment of the integrity of the laryngeal and hypopharyngeal mucosa during laryngopharyngeal reflux could be a factor related to response to proton pump inhibitors (PPIs). Patients presenting with chronic hoarseness and a Reflux Finding Score (RFS) of ≥7 were evaluated using the Reflux Disease Questionnaire (RDQ) and Reflux Symptom Index (RSI). Upper endoscopy was performed, and samples from the posterior commissure of the larynx were collected to evaluate ex vivo the integrity of the laryngeal mucosa by transepithelial resistance (TER) using an Ussing chamber. All patients underwent 24-hour pH-impedance monitoring (pH-imp-24h), followed by an acid oral exposure test. In vivo, hypopharyngeal integrity was measured using intraluminal impedance of the hypopharynx. Clinical responders were defined as those with an RSI score <13 and a reduction of at least 50% from their initial RSI after 8 weeks of pantoprazole treatment. Eighteen patients completed the protocol. The median scores for RDQ, RSI, and RFS were 14 (0–41), 22.5 (4–34), and 9 (7–20), respectively. Esophagitis was detected in 28% of the patients, and one patient presented with acid exposure above 6%. By the end of the 8-week treatment, 12 patients (66.67%) responded to PPI therapy. Baseline laryngeal TER and TER drops after challenge showed no significant difference between PPI responders and non-responders. Hypopharyngeal basal impedance was similar between responders and non-responders. After the acid oral exposure test, impedance was lower in non-responders than in PPI responders. In conclusion, in dysphonic patients with LPRD, hypopharyngeal mucosal integrity was lower in PPI non-responders. This suggests that weaker laryngopharyngeal mucosa in refractory LPRD may require new therapies aimed at improving barrier function.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-02-21T13:54:44Z
dc.date.available.fl_str_mv 2025-02-21T13:54:44Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv ALMEIDA, Clara Mota Randal Pompeu de. A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo. 2025. 86 f. Tese (Doutorado em Ciências Médico-Cirúrgicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://www.repositorio.ufc.br/handle/riufc/79851. Acesso em: 21 fev. 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/79851
identifier_str_mv ALMEIDA, Clara Mota Randal Pompeu de. A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo. 2025. 86 f. Tese (Doutorado em Ciências Médico-Cirúrgicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://www.repositorio.ufc.br/handle/riufc/79851. Acesso em: 21 fev. 2025.
url http://repositorio.ufc.br/handle/riufc/79851
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