A integridade mucosa laríngea e hipofaríngea e a resposta terapêutica aos inibidores de bomba de prótons em pacientes disfônicos com refluxo faringolaríngeo
| Ano de defesa: | 2025 |
|---|---|
| Autor(a) principal: | |
| Orientador(a): | |
| Banca de defesa: | |
| Tipo de documento: | Tese |
| Tipo de acesso: | Acesso aberto |
| Idioma: | por |
| Instituição de defesa: |
Não Informado pela instituição
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| Programa de Pós-Graduação: |
Não Informado pela instituição
|
| Departamento: |
Não Informado pela instituição
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| 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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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. |
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2025 |
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2025-02-21T13:54:44Z |
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2025-02-21T13:54:44Z |
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2025 |
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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. |
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http://repositorio.ufc.br/handle/riufc/79851 |
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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. |
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