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Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Background

Chronic cough is a universal condition of childhood that affects approximately one in ten children. Chronic cough can be either specific (‘wet’ cough or other symptoms concurrently present) or nonspecific (‘dry’ cough in the absence of other symptoms). Compared to adults, specific and non-specific chronic cough in children differs in terms of both aetiology and treatment, and the methods used to treat chronic cough in adults may actually be harmful for children.

Objective

This overview of reviews synthesizes the evidence currently in the Cochrane Library Database of Systematic Reviews (CDSR) in order to answer the following question: in the treatment of childhood specific and non-specific chronic cough, which pharmacologic or non-pharmacologic treatments improve cough symptoms and decrease adverse events?

Methods

The Cochrane Database of Systematic Reviews was searched using the terms ‘specific cough’, ‘non-specific cough’, ‘moist cough’ and ‘chronic cough’ in the record title for all systematic reviews examining pharmacologic or non-pharmacologic interventions for the treatment of chronic cough in children. Data were extracted, complied into tables, and synthesized using qualitative and quantitative methods.

Main Results

Six reviews (five on non-specific cough and one on specific cough) were indentified for inclusion. For non-specific cough, one review found that very high-dose inhaled corticosteroids were effective in reducing non-specific cough (RR: 2.04; 95% CI: 1.10, 3.77), but this treatment was not advocated. To date, there is no evidence that anti-histamines, β2 agonists, gastro-oesophageal reflux treatments or leukotriene receptor antagonists are efficacious for the treatment of non-specific chronic cough. For specific cough related to isolated wet cough, there was significant clinical improvement when children were treated with antibiotics (RR: 2.42; 95% CI: 1.65, 3.53). Limited data were available for adverse events associated with any of the treatment options.

Authors' Conclusions

The paucity of RCT evidence in the management of children with chronic cough is striking. Five systematic reviews on interventions for non-specific cough do not support an empirical treatment approach. One systematic review on interventions for specific cough found some support for the use of antibiotics. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Editors' Note:Overviews of reviews, compiling evidence from multiple Cochrane reviews into one accessible and usable document, is a regular feature of this Journal. Our aim for each overview is to focus on the treatment question, ‘which treatment should I use for this condition?’, and to highlight the Cochrane reviews and their results in doing so. It is our hope that the overview will serve as a ‘friendly front end’ to the Cochrane Library, allowing the reader a quick overview (and an exhaustive list) of Cochrane reviews relevant to the clinical decision at hand.

Background

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Description of the condition

Cough is a universal condition of childhood and has a prevalence of 5–10% 1. In many cases there is a discernible aetiology such as protracted bacterial bronchitis 2, self-limiting viral acute respiratory tract infection (ARI), a genetic disorder such as cystic fibrosis or an episodic illness such as asthma. In other cases, aetiology may be more difficult to establish 3.

Cough can be classified based on time-frame (acute, subacute or chronic); however, studies have yet to establish when cough in children should be defined as ‘chronic’. The lowest cut-off currently suggested in the literature is 3 weeks, while the highest cut-off is 12 weeks 4. Currently, the American College of Chest Physicians guidelines recommend a cut-off of 4 weeks, and a recent overview of the topic also recommends a cut-off of 4 weeks or greater before a diagnosis of chronic cough is made 4, 5.

There are two types of chronic cough in children: specific chronic cough and non-specific chronic cough. Specific cough refers to the presence of other symptoms and signs which indicate increased likelihood of an underlying disorder causing the cough 6, 7. These symptoms and signs, termed ‘specific cough pointers’, include presence of ‘moist’ or ‘wet’ cough 8.

In non-specific cough, the specific cough pointers are absent; secretions are minimal or non-existent and hence this type of cough is classified as ‘dry’ 8. The aetiology of chronic non-specific cough is not known, although there is some evidence that children with this condition have increased cough receptor sensitivity compared to healthy children 9. Non-specific cough may occur after treatment for protracted bronchitis or a known viral ARI 2, 7, 10; it could also be due to pertussis, psychogenic/habit cough, or airway lesions such as tracheobronchomalacia 7, 11. In most children, non-specific cough is not serious (but still bothers parents) and will usually resolve on its own, a fact that complicates the evaluation of therapies. Non-specific cough was once considered to be a part of childhood asthma, called ‘cough variant asthma’; however, more current research suggests that, although some children with asthma may present with a cough, the majority of children with chronic non-specific cough do not have asthma 6, 7.

As with all pediatric conditions, management of specific and non-specific chronic cough in children includes attention to the concerns and perceptions of parents. Parents are able to see the impact of chronic cough on their individual child as well as on other family members, such as the impact of night-time coughing on siblings' sleep 12. However, parental reports of nocturnal chronic cough are unreliable and correlate poorly with objective measurements of cough frequency 12, 13. Regardless, parental concerns should be addressed, as they influence consulting rates and prescription of medication 14–16.

Among parents of children with chronic cough, one study found that approximately 80% of parents brought their child to the doctor for cough-related issues more than five times that year, while more than 50% of parents brought their child more than ten times 12. Parental concerns included lack of sleep, and at the most extreme they were concerned about the cough causing lung damage or death 4, 12. The study found that parents sought multiple consultations from multiple doctors, and parental stress decreased significantly upon coughing cessation.

Parents' concerns about cough and their perceptions that it requires treatment likely contribute to the high monthly usage of over-the-counter medications for cough in preschool-aged children. In 1994, an American survey showed that 35% of preschool-aged children had used over-the-counter medications for cough in the previous month 17, and a more recent survey showed that 10% of American children had used over-the-counter cough medication in the previous week 2.

Why this overview is important

Children with chronic cough require a systematic evaluation, as chronic cough is the most common symptom of an underlying respiratory disease 12. Given the prevalence of chronic cough and the burden of illness it represents for children, their families and the healthcare system, it would clearly be useful for clinicians to have a strong evidence base for their treatment decisions. Yet this area is not straightforward. Management of chronic cough in children differs significantly from that recommended for adults, due to the differing aetiologies in pediatric and adult populations 9. For example, adult chronic cough is most often due to asthma, gastro-oesophageal reflux or post-nasal drip 4. However, current evidence has found that these three causes are not common in children 18, 19.

Another factor when considering aetiologies and the management of pediatric specific and non-specific cough is that children's developmental and maturational processes differ significantly from those of adults. For example, the rate of maturation of the cough reflex may differ in children and adults, and children are more sensitive than adults to certain environmental exposures 4, 9. Lastly, the respiratory physiology and neuro-physiology of young children is distinctly different than that of adults in terms of respiratory reflexes and respiratory control 4, 9. Furthermore, there are important maturational differences in airway, respiratory muscle and chest wall structure 4. Given these differences, it is not appropriate to extrapolate from adult research when making treatment decisions for specific and non-specific chronic cough in children.

Treatment of childhood chronic cough is further complicated by the fact that placebo effects in cough-based studies are high. For example, one study found that ‘parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received a drug, placebo, or no treatment’ 20. Yet, as this overview of reviews demonstrates, there is currently a paucity of evidence on the management of chronic cough in children. In the absence of research to guide clinical practice, children are treated with a variety of therapies; however, some of these therapies have only been tested on adults can result in significant side effects for children 19.

Description of the interventions

In recent years, twelve reviews have been published in the Cochrane Library on various interventions for specific and non-specific chronic cough in children 21–32, and the evidence from these reviews is gathered and summarized in this overview. This overview examines one intervention (antibiotics) for the treatment of specific cough 21 and eleven interventions for the treatment of non-specific cough:

  • Anticholinergics 22

  • Anti-histamines 23

  • Clinical pathways 24

  • Cromones 25

  • Gastro-oesophageal reflux treatment 26

  • Honey and lozenges 27

  • Indoor air modification 28

  • Inhaled beta2-agonists 29

  • Inhaled corticosteroids 30

  • Leukotriene receptor antagonist 31

  • Methylxanthines 32

Objectives

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

This overview of reviews synthesizes the evidence currently in the Cochrane Database of Systematic Reviews (CDSR) in order to answer the following question: for the treatment of specific and non-specific chronic cough in children, which pharmacologic or non-pharmacologic treatments improve cough symptoms and decrease adverse events?

This overview was first published in 2006 33. Since then, four reviews have been updated, four new trials have been identified, and two new reviews have been published. This overview reviews the most current evidence stemming from Cochrane reviews concerning the treatment of specific and non-specific chronic cough in children.

Methods

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Criteria for considering reviews for inclusion

Reviews were included providing they were published in the CDSR and examined pharmacologic or non-pharmacologic interventions for the treatment of specific or non-specific chronic cough. Reviews containing both adult and pediatric data were included providing the pediatric data could be extracted. In contrast to the previously published version of this overview, this overview excluded reviews that did not contain any data.

Search methods for identification of reviews

The search strategy was similar to the one published in the previous version of this overview 33. The CDSR was searched using the terms ‘specific cough’, ‘non-specific cough’, ‘moist cough’ and ‘chronic cough’ in the record title.

Data collection and analysis

For this overview, one reviewer (KR) extracted the following information from the included reviews: inclusion criteria (including population, intervention, comparison(s), and outcomes), methodological quality assessment, and numeric results. Review Manager 5 was used for statistical analysis of results. A second reviewer (MF) then independently extracted inclusion criteria and numeric results to verify data accuracy.

For this overview, all dichotomous data were presented using relative risks (RR) with 95% Confidence Intervals (CI). RR describes the probability of the event in the treatment group compared to the probability of the event in the control group and is interpreted as statistically significant if the 95% CI does not cross one. All continuous data were summarised using mean differences (MD) with 95% CI's. MD results were interpreted as statistically significant if the 95% CI did not cross zero.

In the event that a pooled effect estimate measure had to be calculated, random effects modelling was conducted to provide the most conservative estimate. If more than one study contributed to the pooled effect estimate, the accompanying I2 value was reported and represents the degree of statistical heterogeneity among the studies.

Results

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Description of included reviews

Twelve reviews were deemed potentially relevant 21–32; however, six reviews were subsequently excluded because they did not identify any trials and therefore did not include any data (anticholinergics, clinical pathways, honey and lozenges, indoor air, inhaled cromones and methylxamthines) 22, 24, 25, 27, 28, 32. Therefore, six reviews met the inclusion criteria for this overview: antibiotics21, anti-histamines23, gastro-oesophageal reflux treatment26, inhaled beta2-agonists29, inhaled corticosteroids30 and leukotriene receptors31. One of the six reviews21 examined interventions for specific cough and the other five reviews examined interventions for non-specific cough. The study characteristics of the included reviews are presented in Table 1.

Table I. Description of included reviews
Title AuthorNumber of studiesPopulation   
Date of most substantive updateStudy sample size (range)Definition of coughInterventionControlOutcomes
Antibiotics for prolonged2Children ≤ 18 yearsAntibioticsPlacebo or no treatmentPrimary: clinical failure
moist cough in children140 (52–88)   (proportion of
     participants not cured or
     substantially improved at
     follow-up)
Marchant JM, Morris PS, Prolonged moist cough  Secondary: change in
Gaffney J, Chang AB. lasting more than 10 days  symptoms, change in
     sputum, bronchoalveolar
     lavage or blood indices of
     inflammation/infection,
     change in cough indices
     and disease progression
     resulting in complications
March 2008    and adverse effects
Anti-histamines for prolonged non-specific cough in childrenTherapeutic studies:Children (ages not specified)Anti-histaminesPlaceboPrimary: clinical failure (proportion of participants not cured or substantially improved at follow-up)
Chang AB, Peake J, McElrea3Chronic non-specific  Secondary: not cured
MS.182 (20–113)cough: dry,  and/or substantially
  non-productive cough  improved at follow-up,
  without any other  change in cough indices
  respiratory symptoms,  and adverse
  signs or systemic illness,  events/complications
  lasting more than 4 weeks   
November 2009     
 Safety studies:    
 4    
 3166 (395–1810)    
Gastro-oesophageal reflux5 with children only (18Adults and children (agesAnti-reflux conservativePlacebo or otherPrimary: clinical failure
treatment for prolongedin total)of children not specified)measures, H2 receptormedication(proportion of
non-specific cough in children374 (25–110) antagonists, proton pump participants not cured or
and adults  inhibitors or surgicalsubstantially improved at 
   therapy follow-up)
Chang AB, Lasserson TJ, Chronic non-specific  Secondary: not cured
Gaffney J, Connor FL, Garske cough: dry,  and/or substantially
LA. non-productive coughimproved at follow-up,  
  without any other  change in cough indices
  respiratory symptoms,  and adverse
  signs or systemic illness,  events/complications
June 2009 lasting more than 3 weeks   
Inhaled beta2-agonists for1Children between 2 andInhaled β2 agonistsPlacebo, any other drugPrimary: improvement in
non-specific chronic cough in 18 years(delivered by any means,or any other β2 agonistcough frequency
children  with or without a holding Secondary: cough severity
   chamber or mask). score charts, change in
Tomerak AAT, Vyas HHV,43Non-specific chronic  capsaicin cough receptor
Lakhanpaul M, McGlashan J, cough lasting more than  sensitivity, indicators of
McKean MC 3 weeks  exacerbations, patient
     and/or parent
     assessments and physician
February 2006    assessments
Inhaled corticosteroids for2Children ≤ 16 yearsInhaled corticosteroidPlacebo, any other drugPrimary: clinical failure
non-specific chronic cough in93 (43–50) (delivered by any means,or any other(proportion of
children  with or without a holdingcorticosteroidparticipants not cured or
   chamber or mask) substantially improved at
     follow-up)
Tomerak AAT, McGlashan J, Lakhanpaul M, Vyas HHV, McKean MC Non-specific chronic cough: Dry, non-productive cough without any other respiratory symptoms, signs or systemic illness, lasting more than 3 weeks  Secondary: days or nights without cough, change in capsaicin cough receptor sensitivity, change in objective cough indices, change in cough score charts, indicators of exacerbations, patient and/or parent assessment, physician assessment and change in lung function
August 2005     
Leukotriene receptor2Children (ages notLeukotriene receptorPlacebo or otherPrimary: Clinical failure
antagonists for prolonged319 (63–256)specified)antagonistsmedication(proportion of
non-specific cough in children    participants not cured or
     substantially improved at
     follow-up)
Chang AB, Winter D, Acworth JP Chronic non-specific cough: dry and non-productive cough without any other respiratory symptoms, signs or systemic illness, lasting more than 4 weeks  Secondary: not cured and/or substantially improved at follow-up, change in cough indices and adverse events/complications
October 2009     

The search strategies used to identify potentially relevant studies were comparable in all six reviews. All reviews searched CENTRAL, Medline, and Embase, and all reviews identified grey literature by checking reference lists and contacting authors of included studies. Two reviews contacted experts in the field and looked for internal reports and non-peer-reviewed journals29, 30, and one review searched the Cochrane Airways Group Registry31. Three of the reviews, published in 2003, 2004 and 2005, respectively21, 29, 30, included a note that the authors have searched for new trials subsequent to publication but did not find new trials meeting the reviews' inclusion criteria 21, 29, 30.

Five of the six reviews limited the studies to children and the sixth review included both adult and pediatric studies26. Children were defined as 2–16 years old30, 2–18 years old29, and 18 years and younger21; the authors of the remaining three reviews did not provide an age range. All children had a cough that lasted between 10 days21 to over 4 weeks23, 31. In all six reviews, the interventions were pharmacological. The a priori primary outcome for five of the six reviews was clinical failure (not substantially improved or cured at follow-up). The sixth review examined cough frequency29.

Three reviews included therapeutic studies and assessments of adverse events21, 26, 31. A fourth review included both therapeutic studies and safety evaluations studies23, and the remaining two studies did not assess either safety or adverse events29, 30.

The number of pediatric trials in the reviews ranged from one to five, and the sample sizes of the individual trials ranged from twenty to 1,810. The length of follow-up in all but one review23 was short-term.

Assessment of methodological quality of included reviews

The methods used to assess methodological quality varied. Four reviews used the five-point Jadad scale21, 26, 29, 30 and had median scores of two21, 26 and three29, 30. The remaining two reviews23, 31 assessed four methodological quality parameters: allocation concealment, blinding, reporting participants by allocated group and follow-up. The review of anti-histamines determined that one study scored ‘high’ on 3/4 categories while the other two studies scored ‘high’ on half of the categories. Similarly, the review of leukotriene receptor antagonists reported ‘high quality’ on 2/4 categories for both included studies.

All six reviews assessed allocation concealment. The studies included in four reviews did not report their methods of allocation concealment21, 23, 26, 31 and the last two reviews29, 30 reported adequate allocation concealment.

Effects of interventions

The measures of effect for clinical failure, clinical cure, improvement and symptom scores for treatments examining specific cough and non-specific cough are presented in Table 2.

Table II. Clinical failure, clinical cure, improvement and symptom score
Type of coughComparisonOutcomeNumber of subjects (studies)Measure of effect (95% CI)I2Interpretation
  1. NS: not significant.

SpecificAntibiotics vs placeboCured or substantially improved140 (2)RR: 2.42 (1.65, 3.53)0%Significantly favours antibiotics
  Required additional therapy125 (2)RR: 0.15 (0.05, 0.49)0%Significantly favours antibiotics
Non-specificAntihistamines vs placeboIncreased cough3090 (4)RR: 1.43 (0.84, 2.42)0%NS
  Parental assessment of efficacy102 (1)RR: 1.07 (0.75, 1.54) NS
  Symptom-free children90 (1)RR: 1.10 (0.85, 1.42) NS
 High dose ICS vs placebo> 75% improvement at 3–4 days44 (1)RR: 1.20 (0.66, 2.18) NS
  > 75% improvement at 15–16 days47 (1)RR: 2.04 (1.10, 3.77) Significantly favours ICS
 Low dose ICS vs placeboCough frequency38 (1)MD: − 27.00 (−83.07, 29.07) NS
  Symptom score—parent38 (1)MD: 0.60 (−0.71, 1.91) NS
  Symptom score—child38 (1)MD: 0.60 (−0.71, 1.91) NS
 β2 agonist vs placeboWithdrawals43 (1)RR: 4.19 (0.51, 34.50) NS
  Cough frequency38 (1)MD: − 11.00 (−150.22, 128.22) NS
  Symptom score—parent38 (1)MD: − 0.40 (−2.10, 1.30) NS
  Symptom score—child38 (1)MD: 0.30 (−1.29, 1.89) NS

Specific cough

Antibiotics: The only data for specific cough relate to isolated wet cough and antibiotics. Children taking antibiotics (amoxicillin or erythromycin) vs placebo (for isolated wet cough) were significantly more likely to be cured or substantially improved at follow-up (RR: 2.42; 95% CI: 1.65, 3.53). For every three children treated with antibiotics, one child was cured (95% CI: 2.00, 4.00). Similarly, children receiving antibiotics were significantly less likely to require additional medical treatment (RR: 0.15; 95% CI: 0.05, 0.49).

In one study comparing amoxicillin to placebo, the proportion of children who experienced an adverse event was identical in both groups (12%); in the second study, only 2% of children treated with erythromycin reported side effects.

Non-specific cough

Anti-histamines: There was no significant difference in parental assessment of good to very good efficacy among children treated with anti-histamine (ketotifen) vs placebo (RR: 1.07; 95% CI: 0.75, 1.54). Similarly, there was also no significant difference in proportion of symptom free children (RR: 1.10; 95% CI: 0.85, 1.42) and cough scores (RR 1.43; 95% CI: 0.84, 2.42). An additional three studies that could not be meta-analyzed also assessed cough scores: one small study reported significant improvement at weeks 2, 3 and 4 (p = 0.001, p = 0.001 and p = 0.02, respectively), while the other two studies found no significant difference.

Inhaled Corticosteroids (ICS): One study each examined high dose ICS (fluticasone) and low does ICS (beclomethasone) vs placebo for treatment of non-specific chronic cough. Children treated with high dose ICS showed no significant difference in cough frequency at 3–4 days (RR: 1.20; 05% CI: 0.66, 2.18); however, by 2 weeks, children receiving high dose ICS showed significant improvement in cough frequency compared to those treated with placebo (RR: 2.04; 95% CI: 1.10, 3.77).

Children treated with low dose ICS (salbutamol) vs placebo showed no significant difference in clinical failure (data not provided), cough frequency (MD: − 27.00; 95% CI: − 83.07, 29.07) or symptom scores completed by either parents or children (MD: 0.60; 95% CI: − 0.71, 1.91).

β2Agonists: There was no significant difference in cough frequency (MD: − 11.00; 95% CI: − 150.22, 128.22) parent-completed symptom scores (MD: − 0.40; 95% CI: − 2.10, 1.30) or child-completed symptom scores (MD: 0.30; 95% CI: − 1.29, 1.89) for children treated with β2 agonists versus placebo. Adverse events were not assessed, but the risk of withdrawals was similar between the two groups (RR: 4.19; 95% CI: 0.51, 34.50).

Gastro-oesophyageal reflux treatments: The relationship between gastro-oesophyageal reflux treatments and change in non-specific cough was unclear. One study reported that cough frequency increased after formula-thickened feeds, while a second study found a decrease in cough/gag/choke episodes after consuming pre-thickened milk (cough-specific data were not available). The remaining two studies did not report change in cough or reported no significant difference. There were no adverse events associated with the use of gastro-oesophageal reflux treatments.

Leukotriene Receptor Antagonists (LTRA): Of the two studies comparing LTRA and placebo for treatment of non-specific cough, there was no significant difference in daytime cough, night-time cough or need for rescue medication (data not provided). Both studies included children with a history of ‘asthma-like symptoms’; however, data on children with chronic cough (n = 6) could only be extracted for one study. There was also no significant difference in adverse events between children treated with LTRA versus placebo (data not provided), nor were there any serious adverse events in either group.

Discussion

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Specific chronic cough

Specific chronic cough related to protracted bronchitis is characterized by a ‘wet’ cough that lasts for a minimum of 4 weeks. Antibiotics demonstrated a clinical benefit in children with specific cough by decreasing the proportion of children ‘not cured’ (RR: 0.46; 95% CI: 0.32, 0.65). Antibiotics in those with specific cough is a reasonable step; however, this should be followed by re-evaluation to ensure the cough resolves, as specific cough can have a variety of aetiologies 34–36. Also, further trials are necessary in order to assess the benefits and risks of antibiotic treatment for specific chronic cough.

Non-specific chronic cough

Pediatric non-specific cough is a fairly common condition of childhood and is characterized by a ‘dry’ cough that lasts for a minimum of 4 weeks. In pediatric non-specific cough there is a lack of a clear aetiology or treatment. The differential diagnosis of non-specific cough is worrisome to parents and healthcare providers alike, but it is overwhelmingly a non-life threatening condition. The data to support a treatment algorithm for chronic non-specific cough is lacking, but the rarity of a serious cause combined with the knowledge of no large treatment effect can be supportive and reassuring.

Data provided in this overview does not demonstrate a decisive treatment approach for non-specific chronic cough in children. In adults, empirical treatment for asthma, gastro-oesophageal reflux and post-nasal drip/upper airway syndrome are advocated, albeit with limited evidence 37, but in children there is no evidence to use the same approaches. Also, the possibility of multifactorial aetiology requires further investigation.

Most treatment approaches for dry, non-specific cough lack statistical benefit. Of those interventions reviewed here (anti-histamines, GERD agents, inhaled β2 agonists, inhaled corticosteroids, and leukotriene receptor antagonists), few showed a significant change in clinical outcome. High-dose inhaled corticosteroids (fluticasone) did provide some decrease in symptoms of non-specific cough at days 15 and 16; however, the dose utilised was very high (up to 2 mg/day) 37, 38 and was not advocated by the authors given the risk of adrenal insufficiency in children and the high placebo response 4, 20, 39.

Although rarely a serious condition, dry, non-specific chronic cough in children is worrisome to parents and families. This anxiety leads to repeated visits, testing, and treatments, all in the hopes of decreasing symptoms and parental anxiety. Chronic, non-specific cough should be clearly differentiated from conditions where ‘red flag’ symptoms are present (i.e. failure to thrive, recurrent infections, swallowing dysfunction, etc.), as these may be indicative of a serious underlying disease. However, in children with non-specific cough, reassurance, education and watchful waiting should be the first line of care. Any intervention must be followed by further evaluation, and cessation of treatment (as opposed to escalation of doses) should occur when ‘time to response’ has been exceeded. While future treatments may prove beneficial, one must always consider balancing potential risks and benefits of therapies.

Quality of evidence

There are concerns about the quality of the available data. Specific and non-specific chronic cough are both common childhood conditions, yet data from RCTs are sparse. This hints at the possibility of publication bias. It is possible that studies have been conducted, found no treatment effect, and were never published. It is also possible that the market for pharmaceutical agents for specific and non-specific chronic cough (cough not due to asthma, foreign body inhalation or post-infectious disease) is small, because providing a medicinal agent to suppress cough without first undertaking a rigorous diagnostic approach is potentially dangerous for patients.

In addition to sparse RCT data, there have been very few instances of the reproducibility of findings (either positive, negative or no effect). The limited amount of treatment data and the lack of reproducibility both play a part in explaining the generally poor quality of evidence for treatment of specific and non-specific chronic cough in children. However, the combination of parental anxiety plus the physician's desire to provide ‘treatment’ often results in some type of intervention being applied.

Most studies examined the efficacy of interventions relative to placebo, but direct comparisons among interventions are necessary in order to ascertain their relative efficacy. Nevertheless, comparing interventions with placebos in studies on chronic cough is important given the powerful placebo effect that has been observed in these studies. Because of this placebo effect, any observed improvement is not necessarily attributable to the medication itself. Many of the trials had limited power, and a large number were not methodologically rigorous enough to meet the inclusion criteria of the systematic reviews. The intervention may be beneficial, but without high quality evidence, it remains unclear.

Authors' Conclusions

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Implications for practice

As in the first version of this overview, there remains a paucity of RCT evidence in the management of children with specific or non-specific chronic cough. To date, systematic reviews on five interventions for non-specific chronic cough do not support the empirical treatment approach. In children with specific chronic cough, antibiotics may be of some benefit. However, for both types of chronic cough, it is clinically important to distinguish between the effect of treatment and natural resolution of the cough.

Implications for research

Chronic cough is a relatively common condition with substantial associated morbidity (stress, worry and multiple doctor visits); therefore, further rigorous studies of interventions are required. Trials need to be parallel randomised, placebo controlled, and should use validated child-specific outcome measures. A-priori specification of time frame of response is advocated and should be based on published studies that have provided the ‘time to response’ for that particular intervention.

Contributions of Authors

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

All authors contributed to this review. KR and MF extracted all data, and wrote the Methods and Results sections. MF, AC, DT and KW wrote the Introduction sections, and AC and KW wrote the Discussion and Conclusions sections. KR is the primary author of this report. All authors contributed to editing all sections of the overview and take responsibility for the manuscript.

Declarations of Interest

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References

Professor Chang is first author on three of the five included reviews. No other declarations of interest are noted.

References

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' Conclusions
  9. Contributions of Authors
  10. Declarations of Interest
  11. References
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    Chang AB. Cough. Pediatr Clin N Am 2009; 56(1):1 931.
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    Goldsobel AB, Chipps BE. Cough in the pediatric population. J Pediatrics 2010; 156(3): 352358.
  • 3
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