Non-specific Cough In Children Research Articles

Review: Evidence on PPIs for nonspecific chronic cough in adults with gastroesophageal reflux disease is inconsistent

Source Citation 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 Syst Rev. 2011;(1):CD004823. 21249664

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

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, H(2)-antagonist and proton pump inhibitors (PPI)) and fundoplication. 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. 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. All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease. Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information. 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 H(2) 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. 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.

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

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

Chronic non-specific cough in children

Non-specific chronic cough refers to cough of more than 4 weeks duration with no symptoms or signs suggestive of a likely underlying problem. Management of children with chronic cough includes: an evaluation for these symptoms and signs; a chest radiograph and spirometry (where age-appropriate); as well as an assessment of environmental factors (in particular tobacco smoke), parental concerns and expectations. As the aetiology and management of cough in children differs greatly to that in adults, the empirical approach commonly used in adults is unsuitable for children. Treatment for chronic cough in children should be based on aetiology. Over-the-counter and prescription medications are ineffective and should be rarely used for the symptomatic relief of cough. Because of the favourable natural history of non-specific cough, if medication trials are undertaken, a ‘positive’ response should not be assumed to be due to the medication tried. Children should be re- assessed within the expected timeframe of response to therapy. This article reviews the management of children with cough, focusing on non-specific cough.

Anti-histamines for prolonged non-specific cough in children.

Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including anti-histamines. Also, anti-histamines are advocated as an empirical treatment in adults with chronic cough. To evaluate the effectiveness of anti-histamines in treating children with prolonged non-specific cough. We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, OLDMEDLINE and EMBASE databases. The latest searches were performed in November 2007. All randomised controlled trials comparing anti-histamines with a placebo or placebo-like medication with cough as an outcome, where cough is not primarily related to an underlying respiratory disorder such as cystic fibrosis, asthma, or suppurative lung disease. Two review authors independently assessed study quality and extracted data. Three included therapeutic studies had 182 randomised participants with 162 completing the trials although in one study, children with recurrent wheeze were also included. The two included safety evaluation studies randomised 963 participants with 793 completing the trials. Clinical heterogeneity was evident and limited data prevented combining data for meta-analysis. The two larger therapeutic studies described significant improvement in both the intervention and the placebo/placebo-like arms with no significant difference between the two groups. In the study with the smallest sample size, cetirizine (a second generation anti-histamine) was significantly more efficacious than placebo in reducing chronic cough in children associated with seasonal allergic rhinitis, and the effect was seen within two weeks of therapy. Combined data from the safety evaluation studies revealed a non-significant difference between groups (OR 1.6, 95% CI 0.7 to 3.82) for cough as an adverse event but the trend favoured the placebo arm. This review has significant limitations. However, our finding of uncertain efficacy of anti-histamines for chronic cough are similar to that for acute cough in children. In contrast to recommendations in adults with chronic cough, anti-histamines cannot be recommended as empirical therapy for children with chronic cough. If anti-histamines were to be trialled in these children, current data suggest a clinical response (time to response) occurs within two weeks of therapy. However the use of anti-histamines in children with non-specific cough has to be balanced against the well known risk of adverse events especially in very young children.

Indoor air modification interventions for prolonged non-specific cough in children

Non-specific cough has been defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology and is common in childhood. These children are treated with a variety of therapies, including non-pharmacological treatments. There is a wide variety and a growing market for these non-pharmacological treatments that include air-modification modalities. To determine the efficacy of air-modification modalities, (ionisers, vaporisers, humidifiers, air filters, regular vacuuming), in treating children with non-specific cough. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, OLDMEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The latest searches were performed in November 2005. All randomised controlled trials comparing air-modification modalities with a placebo treatment, for any duration. Results of searches were reviewed against pre-determined criteria for inclusion. Five papers were considered for inclusion but no eligible trials were identified and thus no data was available for analysis. No randomised controlled trials that examined the efficacy of air-modification modalities in the management of prolonged, non-specific cough in children were found. Based on the evidence currently available, a recommendation can not be given for air-modification interventions in the treatment of prolonged, non-specific cough in children.

Leukotriene receptor antagonist for prolonged non-specific cough in children

Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including a variety of asthma medications. The leukotriene pathway is reported to be involved in the sensory (neurogenic) pathway, which is a mechanism thought to be involved in the pathogenesis of chronic cough. To evaluate the effectiveness of leukotriene receptor antagonist (LTRA) in treating children with prolonged non-specific cough. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The latest searches were carried out in September 2005. All randomised controlled trials comparing LTRA with a placebo medication in children with non-specific cough. Results of searches were reviewed against pre-determined criteria for inclusion. One eligible trial was identified but no data was available for analysis. It was not possible to separate results from children with non-specific cough from those without. There was no significant difference in all study endpoints between the montelukast and placebo groups (total N=256). With the lack of evidence, the routine use of LRTA in treating children with non-specific cough cannot be recommended.

Defining the Cough Spectrum and Reviewing the Evidence for Treating Non-Specific Cough in Children

Cough is the most common presenting symptom to medical practitioners to the USA and Australia. Worldwide, the desire to reduce the impact of the symptom of cough is reflected in the billions of dollars spent on over the counter cough medications. Easy to apply and clinically relevant definitions of cough are necessary for effective communication and to progress clinical research. Based on current data, pediatric cough definitions have been formulated on timeframe (acute and chronic), clinical cough characteristics (dry vs wet/productive and classical recognizable cough sounds) and suggestive broad underlying etiology categories (expected cough, specific cough, non-specific cough and protracted bronchitis). These definitions are distinct from adult definitions, as many of adult-type aspects of cough cannot be applied to young children. With the lack of pediatric data, adult data is often inappropriately extrapolated to children. In the second part of this paper, the evidence for and against the use of the various pharmaceuticals (such as OTC medications, antimicrobials, treatment for gastroesophageal reflux and asthma) for cough in children are reviewed. The utility of time to response is important in the management of cough in children to minimize possible associated morbidity of the therapies for non-specific cough.

Cough: are children really different to adults?

Worldwide paediatricians advocate that children should be managed differently from adults. In this article, similarities and differences between children and adults related to cough are presented. Physiologically, the cough pathway is closely linked to the control of breathing (the central respiratory pattern generator). As respiratory control and associated reflexes undergo a maturation process, it is expected that the cough would likewise undergo developmental stages as well. Clinically, the 'big three' causes of chronic cough in adults (asthma, post-nasal drip and gastroesophageal reflux) are far less common causes of chronic cough in children. This has been repeatedly shown by different groups in both clinical and epidemiological studies. Therapeutically, some medications used empirically for cough in adults have little role in paediatrics. For example, anti-histamines (in particular H1 antagonists) recommended as a front-line empirical treatment of chronic cough in adults have no effect in paediatric cough. Instead it is associated with adverse reactions and toxicity. Similarly, codeine and its derivatives used widely for cough in adults are not efficacious in children and are contraindicated in young children. Corticosteroids, the other front-line empirical therapy recommended for adults, are also minimally (if at all) efficacious for treating non-specific cough in children. In summary, current data support that management guidelines for paediatric cough should be different to those in adults as the aetiological factors and treatment in children significantly differ to those in adults.

Methylxanthines for prolonged non-specific cough in children

Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including a variety of asthma medications. Methylxanthines, the main medication used for paediatric asthma for many decades in Western countries, is still widely used in non-Western countries. Also, methylxanthines have other pharmacological properties and their bronchodilator effect is only modest. To evaluate the efficacy of methylxanthines in treating children with non-specific cough. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The latest searches were performed in Jan 2005. All randomised controlled trials comparing methylxanthines with a placebo medication in treating children with non-specific cough. Results of searches were reviewed against pre-determined criteria for inclusion. No eligible trials were identified and thus no data were available for analysis. Four small non-randomised controlled trials were reported. No randomised controlled trials that examined the efficacy of methylxanthines in the management of prolonged non-specific cough in children were found. In the non randomised trials above, a significant effect was seen within 2-14 days of therapy. There is currently an absence of reliable evidence to support the routine use of methylxanthines for symptomatic control of non-specific cough in children. If methylxanthines were to be trialled in children with prolonged non-specific cough, cohort data (thus limited) suggest a clinical response (subjective cough severity) would be seen within 2-5 days (and certainly within 14 days) of therapy. However methylxanthine use has to be balanced against the well known risk of toxicity and its low therapeutic range in children. Further research examining the efficacy of this intervention is needed.

Inhaled cromones for prolonged non-specific cough in children.

Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including inhaled cromones. To determine the efficacy of inhaled cromones in the management of prolonged non-specific cough in children. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases were searched. Australian representative of the relevant pharmaceutical company was contacted. The latest searches were performed in October 2003. All randomised controlled trials comparing inhaled cromones with a placebo medication. Results of searches were reviewed against pre-determined criteria for inclusion. No eligible trials were identified and thus no data were available for analysis. One single arm open trial in children and one small randomised controlled trial in adults were reported. No randomised-controlled trials that examined the efficacy of inhaled cromones in the management of prolonged non-specific cough in children were found. In the non randomised trials above, a significant effect was seen within two weeks of therapy. There is currently an absence of evidence to support the routine use of inhaled cromones for symptomatic control of non-specific cough in children. Further research examining the effects of this intervention is needed.

Inhaled anti-cholinergics for prolonged non-specific cough in children.

Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including inhaled anti-cholinergic medications. To determine the efficacy of inhaled anti-cholinergic medications in the management of prolonged non-specific cough in children. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register and Cochrane Airways Group, MEDLINE and EMBASE databases were searched. Relevant pharmaceutical companies were contacted. The latest searches were performed in July 2003. All randomised controlled trials comparing inhaled anti-cholinergic medication with a placebo medication. Results of searches were reviewed against pre-determined criteria for inclusion. No eligible trials were identified and thus no data were available for analysis. A single small trial in adults has been reported. No randomised-controlled trials that examined the efficacy of inhaled anti-cholinergic medications in the management of prolonged non-specific cough in children were found. There is currently no evidence to support the use of inhaled anti-cholinergics for symptomatic control of non-specific cough in children. Further research examining the effects of this intervention is needed.

A lymphatic pathway from the sinuses to the mediastinum.

THE ASSOCIATION of sinusitis and certain lower respiratory tract infections began to gain attention with a series of reports beginning in 1916. The sinobronchial syndrome, as this association came to be regarded, underwent a variety of early descriptions, including chronic nonspecific cough in children and chronic sinusitis associated with cough and mediastinal lymphadenopathy. 1 As clinical evidence for the association mounted, 2-6 speculation arose on the nature of the clinical relationship. Three possibilities existed: (1) the development of bronchitis as a result of sinusitis, defended by Manges; 7 (2) the synchronous appearance of sinus disease and bronchitis, proposed by Wasson; 8 and (3) the development of sinusitis as a result of pulmonary disease, defended by Brock. 9 The classical observations of E. A. Graham in 1931 exerted considerable influence on the trend of thinking at that time. 10 His description revealed in detail some observations on a patient