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Effectiveness of proton pump inhibitor in unexplained chronic cough.

ABSTRACT: Current guidelines recommend that patients with unexplained chronic cough undergo empirical proton pump inhibitor (PPI) treatment, but scientific evidence for this treatment is lacking. We investigated the effectiveness and appropriate dose of PPI therapy in chronic cough.We included 27 patients with unexplained chronic cough after excluding subjects with positive response to postnasal drip medication. Subjects were randomized to a placebo, standard, and high dose of PPI groups with blinding. The drug or placebo was administered orally for 8 weeks, and the Leicester Cough Questionnaire (LCQ) score and visual analogue scale (VAS) scores were collected.The LCQ score in the PPI group significantly improved from 0 weeks (11.4 ± 1.4) to 4 weeks (14.8 ± 1.4) and to 8 weeks (17.1 ± 1.4), whereas that in the placebo group did not improve from 0 weeks (13.7 ± 1.1) to 8 weeks (11.8 ± 1.4); the difference between the 2 groups was significant (P < 0.001). In subgroup analysis according to reflux, significant improvements in the LCQ score were observed in the PPI group regardless of reflux (P < 0.001 in the reflux group and P < 0.001 in the no reflux group, respectively; P = 0.188 between the 2 groups). In addition, improvements in LCQ and VAS scores between the standard- and high-dose PPI groups were not significantly different; however, adverse reactions were induced by only the high dose (16.7%).The results of this pilot study support the empirical use of the standard dose of PPI for 8 weeks in patients suffering from unexplained chronic cough regardless of whether reflux is present.ClinicalTrial.gov NCT01888549 www.clinicaltrials.gov; cris.nih.go.kr KCT0000543 cris.nih.go.kr/.

SUBMITTER: Park HJ

PROVIDER: S-EPMC5634560 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Effectiveness of proton pump inhibitor in unexplained chronic cough.

Park Hye Jung HJ Park Yoo Mi YM Kim Jie-Hyun JH Lee Hye Sun HS Kim Hyung Jung HJ Ahn Chul Min CM Byun Min Kwang MK

PloS one 20171010 10

<h4>Background</h4>Current guidelines recommend that patients with unexplained chronic cough undergo empirical proton pump inhibitor (PPI) treatment, but scientific evidence for this treatment is lacking. We investigated the effectiveness and appropriate dose of PPI therapy in chronic cough.<h4>Methods</h4>We included 27 patients with unexplained chronic cough after excluding subjects with positive response to postnasal drip medication. Subjects were randomized to a placebo, standard, and high d ...[more]

PMID: 29016626

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Project description:Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery.In this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities.We evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE.The EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis (eotaxin 3, CCL26), barrier molecules (desmoglein 1, DSG1), tissue remodeling (periostin, POSTN), and mast cells (carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment.These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.

Project description:BackgroundUnexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC.MethodsThis systematic review of randomized controlled trials (RCTs) asked: What is the efficacy of treatment compared with usual care for cough severity, cough frequency, and cough-related quality of life in patients with UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks' duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology.ResultsEleven RCTs and five systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used an assortment of descriptors and assessments to identify UCC. Although gabapentin and morphine exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected by intervention fidelity bias; when this factor was addressed, ICS were found to be ineffective for UCC. Esomeprazole was ineffective for UCC without features of gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux disease were not identified. A multimodality speech pathology intervention improved cough severity.ConclusionsThe evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge as well as areas for future research.

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Effectiveness of proton pump inhibitor in unexplained chronic cough.

Publications

Effectiveness of proton pump inhibitor in unexplained chronic cough.

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