Cough in Children

Introduction: Glauser in 1972 Reference and McFadden et al in 1975 called attention to the fact that cough could be the sole manifestation of asthma Abstract . This was confirmed by Carrao et al. Abstract and later by other investigators in studies of children. Reference Abstract Abstract The concept of cough-variant asthma led to persisting cough in children being treated with asthma medication, initially bronchodilators Abstract Abstract and now more commonly anti-inflammatory medication, particularly inhaled steroid. Abstract It has been suggested that cough has a number of mechanisms in adults and that thorough evaluation can distinguish between these mechanisms. Abstract

COUGH IN CHILDREN: More recently a number of studies have been published that question the relationship of cough in children (in the absence of wheeze) to asthma. Russell 1995 suggested that nocturnal cough was unlikely to be asthma. In that epidemiologic study, children with persisting nocturnal cough as a sole symptom differed significantly from asthmatic children in many of the associated clinical features such as hayfever and eczema but were similar to the asymptomatic children studied. This suggested that children with persisting nocturnal cough were less atopic than children with asthma. We have previously published that chidren with recurrent cough as their sole manifestation were less atopic than children with asthma Abstract as judged by numbers of positive skin tests, size of the positive skin tests and symptoms of allergy. Wright et al 1996 in an epidemiologic study of children with cough suggested that chronic or recurrent cough in children should be considered a different disease than asthma. Such children were again found to be less atopic than children who wheezed. Moreover children with recurrent cough at age 2 to 3 usually outgrew this problem by age 6. Powell 1996 also found that children with recurrent cough did not have features of asthma and usually cleared over time. Brooke et al. found that even though night cough was commonly associated with asthma, the cough was not associated with many of the characteristic features of asthma.

Because of these epidemiologic and clinical studies, the nature of recurrent and/ or persisting cough in children has been questioned and the suggestion has been made that the coughing children in the original studies were drawn from hospital-based clinics giving a biased sample. In contrast cough in the broader community is a common problem that in many cases is unrelated to asthma. It does not lead to hospitalizations but has an effect on lifestyle since the children are ill and may miss school because of coughing. The issue was reviewed by Faniran, Peat, and Woolcock (1998) who concluded that children with cough were being potentially overtreated as asthma and that we need further studies on the nature of cough. (Read the full article, Faniran)

The only blind, placebo controlled trial of inhaled steroid in the management of chronic cough in childhood suggested that there was no response to asthma medication, either inhaled steroid or bronchodilator. Chang 1998  Chang subsequently marshalled the arguments that cough is not asthma. Chang 1999 (full text)

Chang and Gibson recently attempted to resolve the relationship between cough and asthma in a study of exacerbation of mild asthma. They concluded that "in mild asthma exacerbations, eosinophilic inflammation is dominant. In asthmatic children who cough as a dominant symptom, cough heralds the onset of an exacerbation and increased eosinophilic inflammation, but cough scores and CRS do not reflect eosinophilic airway inflammation." Chang and Gibson  In contrast to asthma, several studies have demonstrated that chronic cough in children does not have the same cellular pathology in the airways as in allergic asthma. There is no eosinophilic inflammation.

Studies on the Cells in the Airways of children with cough: There are now several studies that have examined the nature of inflammation in the airways of children with cough. Marguet et al. 1999, used broncho-alveolar lavage to study the cells in the airways of children with asthma, infantile wheeze, cough and cystic fibrosis. They found that asthma was associated with eosinophilic inflammation but cough was not. They suggested that cough in children should not be treated with anti-asthma medication. Full Text  We studied airway inflammation in children with persisting post-infectious cough using the technique of induced sputum.  Abstract  (Go To More Complete Article)  Gibson et al. published a study examining the induced sputum from children with asthma, cough or no symptoms. The children were drawn from a community-based questionnaire to represent the common mild spectrum of illness. They found that asthma was significantly more often associated with eosinophilic inflammation in the airways while pure cough was not except in about 20% of instances. This suggested that the majority of children with isolated cough should not be managed with asthma medication. Gibson 2001

Eosinophilic Bronchitis: In adults there have been a series of publications describing patients with chronic cough who have negative methacholine challenges (i.e. lack airway hyperreactivity, the hallmark of asthma) but have eosinophils in the airways and do respond to treatment with inhaled steroid. Eosinophilic Bronchitis 1989 Gibson, Hargreave 1995 Wardlaw 1999 Gibson 2002. These patients are in contrast to other adult patients with cough, studied by Gibson and Hargreave, who have no evidence for eosinophilic inflammation in their airways. Abstract As cited above Gibson has suggested that about 20% of children with chronic cough represent eosinophilic bronchitis and should respond to inhaled steroid.

CROUP: I have long felt that the model for management of cough (especially postinfectious cough) in children is croup rather than asthma. There is unequivocal (Level 1) evidence from double-blind placebo-controlled trials that croup in children responds to oral steroid metaanalyses which led to trials with inhaled steroid (usually high doses). A positive effect has been repeatedly demonstrated. Husby 1993 nebulized Budesonide  Klassen 1996  Godden 1997 full text Budesonide Nebulized  Geelhoed 1995  Schuh 1998  Klassen 1998 This has led to the recommendation that all children with croup should be treated with inhaled steroid.  Geelhoed Yates and Doull

CONCLUSIONS: The data has begun to suggest heterogeneity in childhood cough. However the literure is not strong enough that recommendations can be made with the confidence of citing level 1 evidence (Evaluating the literature and making recommendations by Levels Of Evidence Go to Levels)

Asthmatic children have cough as a prominent symptom and in those children, cough is a symptom of asthma that is under poor control. That was nicely demonstrated in the publication by Chang and Gibson, Abstract There is clearly a distinction to be made between isolated cough versus cough in a child who wheezes and has airway hyperreactivity. The latter children have asthma and in them cough is a very useful symptom to assess their degree of control. Children with asthma who cough need treatment with inhaled steroid sufficient to clear all cough (i.e. nocturnal, morning and with exercise) in order to achieve full control. Cough in those children is one of the earliest warnings that full control of the asthma has not been achieved. If those children are allowed to continue symptomatic with cough, even mild cough, they are at risk for a significant exacerbation usually when they develop a cold. Asthmatic coughing responds to inhaled steroid.

There is also cough that can be associated with eosinophils in the airway without demonstrable airway hyperreactivity, (eosinophilic bronchitis - which has not been as well described in children as in adults). That cough responds to inhaled steroid. Similarly viral-induced coughing in pre-school children, much like croup will respond to inhaled steroid.

How then does one distinguish between cough that responds to inhaled steroid and cough that does not?

Management of isolated cough: if there are clinical findings or the history suggests an infectious agent, a chest xray should be performed. If there are no findings on examination of the chest and the history does not suggest a cause such as sinusitis with post-nasal discharge, gastro-esophageal reflux, cystic fibrosis, an unusual infection such a tuberculosis, then a trial of inhaled steroid would be warranted (equivalent to beclomethasone 400 - 800 mcg per day). If the cough has not responded by three - four weeks, it is very unlikely that the cough represents a variant of asthma or a form of cough that will respond. Allergy skin tests can be performed, since negative tests suggest that there is no atopy and therefore no mechanism for creating eosinophilic inflammation in the airways which is a hallmark of childhood asthma. A methacholine challenge could be done either before or after initiating treatment in order to determine the presence or absence of airway hyperreactivity. A negative methacholine challenge points to a diagnosis other than asthma. At that point, in the face of little response to medication, a chest xray should be done if it has not already been done. Further work-up could include a barium swallow if there is evidence for reflux or even a trial of anti-reflux therapy. A sweat chloride could be ordered and serum immunoglobulins checked. If the cough seems to be occuring high in the throat with a forced quality, habit could be considered but it may be worth obtaining an ENT consultation.

Unfortunately data currently available is not sufficiently strong to say definitively how cough that is not asthma should be investigated and managed in children. There are much stronger algorithms for management of the adult with cough. Fortunately with most children the non-asthmatic cough is post-infectious in nature and will clear spontaneously over time. Once other treatable causes have been ruled out a trial of cough suppressant can be initiated for symptomatic relief.