Efficacy of Super High Dose Proton Pump Inhibitor Administration in Refractory Laryngopharyngeal Reflux: A Pilot Study

Portnoy, Joel E.; Gregory, Naomi D.; Cerulli, Claudia; Hawkshaw, Mary J.; Lurie, Deborah; Katz, Philip O.; Sataloff, Robert T.

doi:10.1016/j.jvoice.2013.10.020

Cited by 19 publications

(11 citation statements)

References 35 publications

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“…As described in Figure , from the initial electronic search, 10 cohort studies which did not discuss primary treatment outcomes overall (ie not part of the 35 studies above) did otherwise specifically address aetiology or management of non‐responder patients . Table summarises the details of these studies relative to diagnosis, management, and treatment.…”

Section: Resultsmentioning

confidence: 99%

“…In 4 studies, the inclusion criteria (definition of non‐responder patients) was based on a < 50% symptomatic improvement of composite symptom score after 4 or 8 weeks of PPI therapy . One study defined resistance as persistent symptoms and signs and/or continued proximal acid reflux on impedance‐pH monitoring . The rest of the studies defined non‐responder patients on the basis of persistent symptoms ± findings after 1 month of PPI ± H 2 receptor antagonist therapy.…”

Section: Resultsmentioning

confidence: 99%

“…In this systematic review, we found that the majority of studies based their definitions on symptom evolution without clear criteria or definition of the symptom improvement. Of the few papers that did assess changes in signs, only Portnoy et al assessed laryngeal signs in a blinded fashion, with other papers using scoring systems for signs of LPR being subject to the risk of evaluation bias . Even if tools are used appropriately, choice of assessment tool can be important; valid evaluation of therapeutic effectiveness requires the use of efficient and validated clinical instruments to assess treatment effect.…”

Section: Discussionmentioning

confidence: 99%

“…Realising that not all LPR is acidic, consideration of other approaches to limit reflux itself, rather than reduce acid content of refluxate, makes sense in the context of patients with refractory symptoms. Consider that super high‐dose PPIs have been used as treatment of recalcitrant LPR patients with uncertain results . The use of alginate or magaldrate is anecdotal although these drugs decrease acid reflux events during a critical time period corresponding to the first hour after the meals .…”

Section: Discussionmentioning

confidence: 99%

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The management of suspected or confirmed laryngopharyngeal reflux patients with recalcitrant symptoms: A contemporary review

Lechien

Muls

Dapri

et al. 2019

Clinical Otolaryngology

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Objective: To summarise current knowledge about the prevalence, aetiology and management of recalcitrant laryngopharyngeal reflux (LPR) patients-those who do not respond to anti-reflux medical treatment. Methods:A literature search was conducted following the PRISMA guidelines to identify studies that reported success of anti-reflux medical treatment with emphasis on studies that attempted to be rigorous in defining a population of LPR patients and which subsequently explored the characteristics of non-responder patients (ie aetiology of resistance; differential diagnoses; management and treatment). Three investigators screened publications for eligibility from PubMED, Cochrane Library and Scopus and excluded studies based on predetermined criteria. Design, diagnostic method, exclusion criteria, treatment characteristics, follow-up and quality of outcome assessment were evaluated.Results: Of the 139 articles screened, 45 met the inclusion criteria. The definition of non-responder patients varied substantially from one study to another and often did | 785 LECHIEN Et aL

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The management of suspected or confirmed laryngopharyngeal reflux patients with recalcitrant symptoms: A contemporary review

Lechien

Muls

Dapri

et al. 2019

Clinical Otolaryngology

Self Cite

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“…According to recent trends, PPIs are the first recommended choice for LPR management [ 15 ]. However, several cases are intractable to high-dose PPIs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Characteristics According to Reflux Type in Patients With Laryngopharyngeal Reflux

Lee

Jung

Park

et al. 2018

Clin Exp Otorhinolaryngol

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Objectives To analyze laryngopharyngeal reflux (LPR) as an acidic, nonacidic, or mixed type according to 24-hour multi-channel intraluminal impedance (MII) pH monitoring and the clinical characteristics of each type.Methods Ninety patients were prospectively enrolled in this study. All patients underwent 24-hour MII pH monitoring as a diagnostic tool. Eighty-three patients were diagnosed with LPR. The patients were classified into three groups according to the pH of the hypopharyngeal probe: the acid reflux group, nonacid reflux group, and mixed reflux group. Subjective symptoms and objective findings were evaluated based on patients’ responses to the Short Form 12 Survey (SF-12), LPR health-related quality of life (LPR-HRQOL), reflux symptom index, and reflux finding score.Results The results of each group were compared. As a result, 34 patients were classified into the nonacid reflux group and 49 into the mixed reflux group. There were no patients classified as having acid reflux alone. There was no significant difference between the two groups when comparing the reflux symptom index, reflux finding score, LPR-HRQOL, or the mental component score of the SF-12. However, the physical component score of the SF-12 was higher in the nonacid reflux group (P=0.018). The DeMeester composite score (P=0.015) and total number of LPR events (P=0.001) were lower in the nonacid reflux group than in the mixed reflux group.Conclusion In conclusion, no LPR patient had only acid reflux. The nonacid reflux LPR patients showed similar clinical characteristics and findings compared to the mixed reflux group, but exhibited significantly fewer LPR episodes.

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Amprenavir inhibits pepsin‐mediated laryngeal epithelial disruption and E‐cadherin cleavage in vitro

Samuels

Blaine-Sauer

Yan

et al. 2023

Laryngoscope Investig Oto

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BackgroundLaryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and can promote laryngeal carcinogenesis. More than 20% of the US population suffers from LPR and there is no effective medical therapy. Pepsin is a predominant source of damage during LPR which disrupts laryngeal barrier function potentially via E‐cadherin cleavage proteolysis and downstream matrix metalloproteinase (MMP) dysregulation. Fosamprenavir (FDA‐approved HIV therapeutic and prodrug of amprenavir) is a pepsin‐inhibiting LPR therapeutic candidate shown to rescue damage in an LPR mouse model. This study aimed to examine amprenavir protection against laryngeal monolayer disruption and related E‐cadherin proteolysis and MMP dysregulation in vitro.MethodsLaryngeal (TVC HPV) cells were exposed to buffered saline, pH 7.4 or pH 4 ± 1 mg/mL pepsin ± amprenavir (10–60 min). Analysis was performed by microscopy, Western blot, and real time polymerase chain reaction (qPCR).ResultsAmprenavir (1 μM) rescued pepsin acid‐mediated cell dissociation (p < .05). Pepsin acid caused E‐cadherin cleavage indicative of regulated intramembrane proteolysis (RIP) and increased MMP‐1,3,7,9,14 24‐h postexposure (p < .05). Acid alone did not cause cell dissociation or E‐cadherin cleavage. Amprenavir (10 μM) protected against E‐cadherin cleavage and MMP‐1,9,14 induction (p < .05).ConclusionsAmprenavir, at serum concentrations achievable provided the manufacturer's recommended dose of fosamprenavir for HIV, protects against pepsin‐mediated cell dissociation, E‐cadherin cleavage, and MMP dysregulation thought to contribute to barrier dysfunction and related symptoms during LPR. Fosamprenavir to amprenavir conversion by laryngeal epithelia, serum and saliva, and relative drug efficacies in an LPR mouse model are under investigation to inform development of inhaled formulations for LPR.

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Efficacy of Super High Dose Proton Pump Inhibitor Administration in Refractory Laryngopharyngeal Reflux: A Pilot Study

Cited by 19 publications

References 35 publications

The management of suspected or confirmed laryngopharyngeal reflux patients with recalcitrant symptoms: A contemporary review

The management of suspected or confirmed laryngopharyngeal reflux patients with recalcitrant symptoms: A contemporary review

Comparison of Characteristics According to Reflux Type in Patients With Laryngopharyngeal Reflux

Amprenavir inhibits pepsin‐mediated laryngeal epithelial disruption and E‐cadherin cleavage in vitro

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