Sputum inflammatory phenotypes are not stable in children with asthma
- 1National Heart and Lung Institute, Respiratory Paediatrics, Imperial College, London, UK
- 2Department of Respiratory Paediatrics, Royal Brompton Hospital, London, UK
- 3Division of Paediatric Respiratory Medicine, Department of Paediatrics, Inselspital and University of Bern, Switzerland
- Correspondence to Dr Louise Fleming, Department of Respiratory Paediatrics, Royal Brompton Hospital, Flat 11 Southwood Mansions, Southwood Lane, London N6 5SZ, UK;
Contributors Louise Fleming: carried out all the study visits and measurements for the severe asthma cohort, analysed the data and wrote the manuscript. Lemonia Tsartsali: carried out all the study visits and measurements for the mild to moderate asthma cohort. Nicola Wilson: devised and supervised the study. Nicolas Regamey: carried out the sputum cell counts for both cohorts and contributed to the manuscript. Andrew Bush: Principal Investigator, devised and supervised the study, contributed to the manuscript.
- Received 6 September 2011
- Accepted 19 January 2012
- Published Online First 29 February 2012
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 (n=42) over a 1-year period and twice in mild to moderate asthma (n=17) over 3–6 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 (FENO). 24 children (41%) fulfilled the criteria for non-eosinophilic 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.
- Sputum eosinophil counts
- inflammatory phenotype
- COPD mechanisms
- allergic lung disease
- respiratory measurement
- lung physiology
- asthma pharmacology
- exhaled airway markers
- paediatric asthma
- cystic fibrosis
- innate immunity
- paediatric lung disease
- paediatric physician
- respiratory infection
- viral infection
- asthma guidelines
- lung physiology
Louise Fleming, Lemonia Tsartsali—joint first authors.
Funding The study was funded by a grant from the British Lung Foundation.
Competing interests None.
Patient consent Obtained.
Ethics approval Ethics approval was approved by Royal Brompton Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.