Csoma Z, Kharitonov SA, Balint B, Bush A, Wilson NM, Barnes PJ. Am J Respir Crit Care Med. 2002;166:1345–1349
Purpose of the Study.
To determine if 2 markers of airway inflammation, leukotrieneB4 (LTB4) and cysteinyl leukotrienes (cys-LTs) can be detected in the breath of children with asthma and to look at the effect of steroid treatment on these mediators.
There were 4 groups of children all between the ages of 7 and 14 years. In addition to the healthy nonatopic control group (n = 11), there were children with mild intermittent asthma (n = 11), mild persistent asthma (n = 13), and a group that contained both moderate and severe persistent asthma (n = 13). The diagnosis of asthma was based on American Thoracic Society criteria. Severity classifications followed the National Heart Lung and Blood Institute/World Health Organization guidelines and the diagnosis of allergy was based on skin test responses to common allergens. Each study group was similar in age and ratio of male/female except there were considerably more boys in the moderate-severe group. The mild persistent group was on <400 μg/day of inhaled steroids whereas the more severe group was divided between those on >400 and those on ≥1000 μg/day. No one was on a leukotriene modifier. The study design involved clinical history, spirometry, and measurements of nitric oxide (NO) and leukotrienes in the breath condensate.
Cys-LT was detectable in the exhaled breath of normal, nonasthmatic, nonatopic children (18.5 ± 0.5 pg/mL). Levels were significantly increased in children with mild persistent asthma (27.9 ± 2.8 pg/mL) and moderate/severe persistent asthma (31.5 ± 4.5 pg/mL). Cys-LT levels in exhaled breath of children with mild intermittent asthma were similar to the control group (19.9 ± 1.1pg/mL). LTB4 levels were significantly increased in the breath condensates of children with mild persistent asthma (126 ± 8.8 pg/mL) and moderate/severe persistent asthma (131.9 ± 7.1 pg/mL) as compared with mild intermittent asthma (52.7 ± 3.8 pg/mL) and the control subjects (47.9 ± 4.1 pg/mL). In patients with mild persistent asthma, there was an inverse correlation between levels of cys-LT and LTB4. With increasing amounts of cys-LT there was a decrease in the amount of LT B4. The amount of exhaled NO was increased significantly in all asthmatic children compared with controls.
Two markers of inflammation, cys-LT and LTB4, were found to be elevated in the exhaled breath of children with mild to moderate/severe persistent asthma. These mediators were found in those already on inhaled corticosteroids. The findings support the involvement of these 2 leukotriene mediators in chronic airway inflammation. This study also shows that exhaled breath condensate may be useful in assessing inflammation in the airways of children 6 to 7 years old.
For many years now we have been enthusiastic supporters of the concept that asthma is a chronic inflammatory disease of the airway. Yet, as these authors point out, we have not been able to measure what we think is important in children. Previous work on airway inflammation has involved adults undergoing rather invasive diagnostic techniques. This study introduces a noninvasive measurement of inflammation and although in small numbers clearly shows differences in inflammatory mediators in the various classifications of disease. The cys-LT are derived from mast cells and eosinophils and include mediators that are blocked by available leukotriene modifiers. All persistent forms of asthma that were treated with inhaled corticosteroids showed elevations of cys-LTs. LTB4 is derived from neutrophils. This neutrophil product is also elevated in the persistent forms of asthma. One of the take-home messages from this work is the fact that despite the use of the inhaled steroids, by-products of inflammation were detected in these children who were asymptomatic. There is also the concern or argument that deals with the presence of inflammation in all forms of asthma—the intermittent and persistent. The measures taken here did not show any of the inflammatory leukotriene mediators and only a slight increase in NO. We may have observed the introduction of a noninvasive tool to help understand the process of airway inflammation and perhaps guide therapy.