It is now recognized that all asthma even mild asthma is associated with inflammation in the airways ,. This inflammation has been suggested to be responsible for airway reactivity ( ). Bronchoalveolar lavage ,) and bronchial biopsies,,,have demonstrated the presence of inflammatory cells even in quiescent asthma ,. Other studies have documented the presence of eosinophils and the release of eosinophilic granular proteins in the airways in asthma , . Eosinophilic proteins such as Eosinophil Cationic Protein (ECP), Major Basic Protein (MBP) and Eosinophil Protein X (EPX) have been demonstrated in the lavage fluid recovered from asthmatic lungs , . In some instances the eosinophils and eosinophilic proteins recovered in lavage fluid have been correlated with the levels of circulating eosinophils and serum eosinophilic proteins . These studies on inflammation have had a significant impact on the management of asthma with anti-inflammatory medication increasingly being recommended as first-line therapy. It has been possible to study the effect of inhaled steroid on airway inflammation using biopsies,
Since the vast majority of these studies have involved invasive technology such as bronchoscopy and bronchial biopsy they have been performed in adult volunteers with only an occasional study reported for childhood asthma . The observation that the peripheral eosinophil count and the serum measurement of eosinophilic granular proteins such as eosinophil cationic protein (ECP - a marker for eosinophil activation) might have relevance to the status of asthma led us to examine peripheral eosinophil counts, serum ECP and EPX levels in childhood asthma.
We initially studied older children and found that serum ECP and peripheral eosinophil counts were higher in children with asthma than children without asthma. Moreover treatment with steroid reduced the level of ECP and eosinophils. These measurements would be especially useful in very young children where spirometry and other tests cannot be easily performed to assess the asthma. Initially I was hopeful that measurement of serum ECP could be used to monitor childhood asthma and treatment with inhaled steroid ,, . However there are problems with ECP and eosinophil measurements in the blood. First the elevations of those markers are specific for the eosinophilic inflammation in allergy and not just asthma but rhinitis and atopic dermatitis. Secondly, after treatment with inhaled steroid the elevated serum ECP and peripheral eosinophil count in symptomatic asthma decrease but plateau above the value that would be seen with a non-allergic non-asthmatic subject. This contrasts with sputum eosinophilia (which will be discussed below) where the percent eosinophils decrease to a normal range when an asthmatic child is treated with inhaled steroid. Thus with a single value of either serum ECP or peripheral eosinophils, it can be difficult to know whether the elevated values could be reduced further. Nevertheless a simple peripheral eosinophil count is useful to assess the degree the atopic immune response is active. A value below 300 per mcl especially 100 to 200 is in the non-atopic range while above 400 is usually associated with significant atopic activity. The eosinophil counts in active asthma are usually at the upper end of a laboratory's normal range and rarely above 1000. Atopic dermatitis can be associated with peripheral eosinophil counts above 1000 per mcl while parisitic diseases can be many fold higher.
Unfortunately in very young children, it is not feasible to do invasive techniques although there have been a few studies with bronchial wash by Stevenson and colleagues, . These investigators went on to determine whether serum ECP and peripheral eosinophil count would be useful to predict the presence of eosinophilic inflammation in the bronchial wash of young children. They concluded that these measurements were useful.
In older children the technique of induced sputum is clearly superior to the measures of eosinophils or eosinophil proteins in blood as was shown by Pizzichini et al.. indeed, our own experience confirms that induced sputum is a more direct and relaiable measure of eosinophilic inflammation in asthma than peripheral eosinophil counts or serum ECP . A number of studies have documented that this technique can be applied to the study of asthma in children and can be used to determine the nature of the inflammation in the airways of children with asthma,,,,,.
There are also interesting papers using exhaled nitrous oxide as a non-invasive marker of inflammation in asthma but that will not be reviewed here.
The studies reviewed above clearly show that inflammation, particularly eosinophilic inflammation is an important part of asthma and likely the pathophysiologic cause of asthma. There are now sufficient studies to suggest that the same inflammation occurs in the airways of children with asthma. Undoubtedly further work will point to other inflammatory mechanisms beside eosinophilic and that should lead to novel therapies.