Intervention Review

Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults

  1. Anne B Chang1,*,
  2. Toby J Lasserson2,
  3. Justin Gaffney3,
  4. Frances L Connor4,
  5. Luke A Garske5

Editorial Group: Cochrane Airways Group

Published Online: 19 JAN 2011

Assessed as up-to-date: 9 JUN 2010

DOI: 10.1002/14651858.CD004823.pub4

Database Title

Additional Information

How to Cite

Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004823. DOI: 10.1002/14651858.CD004823.pub4.

Author Information

  1. 1

    Queensland Children's Respiratory Centre and Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane and Menzies School of Health Research, CDU, Darwin, Brisbane, Queensland, Australia

  2. 2

    The Cochrane Collaboration, Cochrane Editorial Unit, London, UK

  3. 3

    Royal Children's Hospital, Respiratory Medicine, Brisbane, Australia

  4. 4

    Royal Children's Hospital, Gastroenterology, Brisbane, Queensland, Australia

  5. 5

    Princess Alexandra Hospital, Respiratory Medicine, Brisbane, Queensland, Australia

*Anne B Chang, Royal Children's Hospital, Brisbane and Menzies School of Health Research, CDU, Darwin, Queensland Children's Respiratory Centre and Queensland Children's Medical Research Institute, Herston Road, Herston, Brisbane, Queensland, 4029, Australia. annechang@ausdoctors.net. Anne.chang@menzies.edu.au.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 19 JAN 2011

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Background

Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H2-antagonist and proton pump inhibitors (PPI)) and fundoplication.

Objectives

To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease, i.e. non-specific chronic cough.

Search methods

We searched the Cochrane Airways Group Specialised Register, the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, review articles and reference lists of relevant articles. The date of last search was 8 April 2010.

Selection criteria

All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information.

Main results

We included 19 studies (six paediatric, 13 adults). None of the paediatric studies could be combined for meta-analysis. A single RCT in infants found that PPI (compared to placebo) was not efficacious for cough outcomes (favouring placebo OR 1.61; 95% CI 0.57 to 4.55) but those on PPI had significantly increased adverse events (OR 5.56; 95% CI 1.18 to 26.25) (number needed to treat for harm in four weeks was 11 (95% CI 3 to 232)). In adults, analysis of H2 antagonist, motility agents and conservative treatment for GORD was not possible (lack of data) and there were no controlled studies of fundoplication. We analysed nine adult studies comparing PPI (two to three months) to placebo for various outcomes in the meta-analysis. Using intention-to-treat, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough (OR 0.46; 95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). We only found significant differences in sensitivity analyses. We found a significant improvement in change of cough scores at end of intervention (two to three months) in those receiving PPI (standardised mean difference -0.41; 95% CI -0.75 to -0.07) using generic inverse variance analysis on cross-over trials. Two studies reported improvement in cough after five days to two weeks of treatment.

Authors' conclusions

PPI is not efficacious for cough associated with GORD symptoms in very young children (including infants) and should not be used for cough outcomes. There is insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GORD treatment with PPI is universally beneficial for cough associated with GORD. Clinicians should be cognisant of the period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double-blind, randomised controlled and parallel-design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults

Cough in association with gastroesophageal reflux disease (GORD) is common in adults with chronic cough. The objective of this review was to evaluate the effectiveness of GORD treatment in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease, i.e. non-specific chronic cough.

Nineteen studies fulfilled our predetermined criteria but only six could be combined (in meta-analysis). We obtained additional data from trialists. We were not able to combine results in children due to limited data. Thickened feeds had an inconsistent effect. Proton pump inhibitors (PPI) did not reduce cough and should not be used for cough in young children.

In adults with cough and GORD, no significant difference was found in clinical cure using proton pump inhibitors (PPI) for cough and GORD. Using other outcomes, there was also no significant difference between PPI and placebo. This review also highlights a large placebo and time period effect (natural resolution with time) of treatment for chronic cough. In adults treatment with PPI for cough associated with GORD is inconsistent and its benefit variable. There was insufficient data to draw any conclusion from other therapies for cough associated with GORD.

 

Resumen

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Antecedentes

Tratamiento del reflujo gastroesofágico para la tos inespecífica prolongada en niños y adultos

Se plantea que hasta en el 41% de los adultos con tos crónica el factor causal es la enfermedad de reflujo gastroesofágico (ERGE). El tratamiento de la ERGE incluye medidas conservadoras (cambios en la dieta), tratamiento farmacológico (agentes que activan la motilidad o agentes procinéticos, antagonistas H2y los inhibidores de la bomba de protones [IBP]) y la fundoplicatura.

Objetivos

Evaluar la eficacia del tratamiento de la ERGE en la tos crónica en niños y adultos con ERGE y tos prolongada, no relacionada con una enfermedad respiratoria subyacente, es decir, tos crónica inespecífica.

Estrategia de búsqueda

Se realizaron búsquedas en el Registro Especializado del Grupo Cochrane de Vías Respiratorias (Cochrane Airways Group) Registro Cochrane de Ensayos Controlados (Cochrane Register of Controlled Trials, CENTRAL), MEDLINE, EMBASE, artículos de revisión y listas de referencias de artículos pertinentes. La fecha de la última búsqueda fue el 8 de abril de 2010.

Criterios de selección

Todos los ensayos controlados aleatorios (ECA) sobre el tratamiento de la ERGE para la tos en niños y adultos sin enfermedad pulmonar primaria.

Obtención y análisis de los datos

Dos autores de la revisión evaluaron de forma independiente la calidad de los ensayos y extrajeron los datos. Se estableció contacto con los autores de los estudios para obtener información adicional.

Resultados principales

Se incluyeron 19 estudios (seis pediátricos, 13 adultos). Ninguno de los estudios en niños pudo ser combinado en un metanálisis. Un único ECA en lactantes halló que los IBP (en comparación con placebo) no fueron eficaces para los resultados de tos (a favor del placebo OR 1,61; IC del 95%: 0,57 a 4,55) pero en los pacientes que recibieron IBP habían aumentado significativamente los eventos adversos (OR 5,56; IC del 95%: 1,18 a 26,25) (el número necesario a tratar para causar un efecto perjudicial en cuatro semanas fue de 11 [IC del 95%: 3 a 232]). En adultos, el análisis de los antagonistas de H2, agentes de motilidad y el tratamiento conservador para la ERGE no fue posible (por falta de datos) y no hubo estudios controlados sobre fundoplicatura. En el metanálisis se analizaron varios resultados de nueve estudios en adultos que compararon IBP (dos a tres meses) con placebo. Con el análisis de intención de tratar, en los datos agrupados de los estudios no se hallaron diferencias significativas entre el tratamiento y el placebo en cuanto a la resolución total de la tos (OR 0,46; IC del 95%: 0,19 a 1,15). Los datos agrupados no mostraron ninguna mejoría general significativa en las medidas de resultado de la tos (final del ensayo o cambio en las puntuaciones de la tos). Sólo encontramos diferencias significativas en los análisis de sensibilidad. Se halló una mejoría significativa en el cambio de las puntuaciones de tos al final de la intervención (dos a tres meses) en los participantes que recibieron IBP (diferencia de medias estandarizada −0,41; IC del 95%: −0,75 a −0,07) mediante el análisis de varianza genérica inversa en los ensayos cruzados. Dos estudios informaron mejoría de la tos después de cinco días a dos semanas de tratamiento.

Conclusiones de los autores

Los IBP no son eficaces para la tos asociada con los síntomas de ERGE en niños muy pequeños (incluidos los lactantes) y no debe usarse para los resultados de tos. Hay datos insuficientes en los niños mayores para establecer alguna conclusión válida. No hay pruebas suficientes para concluir que el tratamiento de la ERGE con IBP es universalmente beneficioso para la tos asociada con la ERGE en adultos. Los médicos deben conocer que existe un efecto de período (resolución natural con el tiempo) y un efecto placebo, en los estudios que utilizan la tos como medida de resultado. Los estudios futuros en niños y adultos deben ser controlados aleatorios a doble ciego, de diseño paralelo, con tratamientos durante al menos dos meses y medidas de resultado subjetivas y objetivas de la tos validadas, e incluir la determinación del tiempo necesario para alcanzar la respuesta, así como la evaluación del reflujo ácido o no ácido.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano

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