Sputum inflammatory phenotypes are not stable in children with asthma

Abstract

Background Two distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in children with asthma to classify sputum inflammatory phenotypes and to assess their stability over time. Methods Sputum induction was performed in 51 children with severe asthma and 28 with mild to moderate asthma. Samples were classified as eosinophilic (>2.5% eosinophils), neutrophilic (>54% neutrophils); mixed granulocytic (>2.5% eosinophils, >54% neutrophils); or paucigranulocytic (#2.5% eosinophils, #54% neutrophils). Sputum induction was repeated every 3 months in children with severe asthma (n¼42) over a 1-year period and twice in mild to moderate asthma (n¼17) over 3e6 months.Results 62 children (78%) had raised levels of inflammatory cells in at least one sputum sample. In the longitudinal analysis 37 of 59 children (63%) demonstrated two or more phenotypes. Variability in sputum inflammatory phenotype was observed in both the severe and the mild to moderate asthma groups. Change in phenotype was not related to change in inhaled corticosteroid (ICS) dose or asthma control, nor was it reflected in a change in exhaled nitric oxide (FE NO ). 24 children (41%) fulfilled the criteria for noneosinophilic asthma on one occasion and eosinophilic on another. There were no differences in severity, asthma control, atopy, ICS dose or forced expiratory volume in 1 s between those who were always non-eosinophilic and those always eosinophilic. Conclusion Raised levels of inflammatory cells were frequently found in children with asthma of all severities. Sputum inflammatory phenotype was not stable in children with asthma.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…However, sputum eosinophilia appears more stable, especially in severe asthma, when examined over longer yearly periods in adults [52]. This stability appears to be less in children [53]. The mechanisms behind these diverse inflammatory profiles are likely complex, varied, and related to corticosteroid sensitivity ( fig.…”

Monitoring asthma in children

“…Elevated sputum eosinophils were reported to be predictive of failed ICS reduction and asthma exacerbations in mild-to-moderate asthma, but incorporating the control of sputum eosinophils into the management algorithm did not significantly reduce overall exacerbations or improve asthma control in severe asthma [25,159,160]. This may be due to the observation that sputum inflammatory phenotypes are not stable over time [161].…”

Airway eosinophils in older teenagers with outgrown preschool wheeze: a pilot study

“…FeNO levels were low in all but one child and there was no difference between the study groups. Several inflammatory cells in the lung produce and secrete nitric oxide including eosinophils and there is a moderate correlation between sputum eosinophils and FeNO in children with asthma [17]. Despite significant differences in sputum eosinophils between the study groups, absolute values were low and might not have been high enough to lead to increased FeNO.…”