Sputum inflammatory phenotypes are not stable in children with asthma

被引:136
作者
Fleming, Louise [1 ,2 ]
Tsartsali, Lemonia [1 ]
Wilson, Nicola [1 ]
Regamey, Nicolas [3 ]
Bush, Andrew [1 ,2 ]
机构
[1] Royal Brompton Hosp, Dept Resp Paediat, London N6 5SZ, England
[2] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England
[3] Univ Bern, CH-3012 Bern, Switzerland
关键词
EXHALED NITRIC-OXIDE; AIRWAY INFLAMMATION; EOSINOPHIL COUNTS; STEROID REDUCTION; DIFFICULT ASTHMA; CELL COUNTS; IDENTIFICATION; EXACERBATIONS; MEPOLIZUMAB; SUBTYPES;
D O I
10.1136/thoraxjnl-2011-201064
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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.
引用
收藏
页码:675 / 681
页数:7
相关论文
共 49 条
[21]   Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity [J].
Grootendorst, DC ;
van den Bos, JW ;
Romeijn, JJ ;
Veselic-Charvat, M ;
Duiverman, EJ ;
Vrijlandt, EJLE ;
Sterk, PJ ;
Roldaan, AC .
EUROPEAN RESPIRATORY JOURNAL, 1999, 13 (03) :647-653
[22]   Cluster analysis and clinical asthma phenotypes [J].
Haldar, Pranab ;
Pavord, Ian D. ;
Shaw, Dominic E. ;
Berry, Michael A. ;
Thomas, Michael ;
Brightling, Christopher E. ;
Wardlaw, Andrew I. ;
Green, Ruth H. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2008, 178 (03) :218-224
[23]   Noneosinophilic asthma: A distinct clinical and pathologic phenotype [J].
Haldar, Pranab ;
Pavord, Ian D. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (05) :1043-1052
[24]   Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma [J].
Haldar, Pranabashis ;
Brightling, Christopher E. ;
Hargadon, Beverley ;
Gupta, Sumit ;
Monteiro, William ;
Sousa, Ana ;
Marshall, Richard P. ;
Bradding, Peter ;
Green, Ruth H. ;
Wardlaw, Andrew J. ;
Pavord, Ian D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (10) :973-984
[25]   Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma [J].
Jatakanon, A ;
Kharitonov, S ;
Lim, S ;
Barnes, PJ .
THORAX, 1999, 54 (02) :108-114
[26]   Determining asthma treatment by monitoring sputum cell counts:: effect on exacerbations [J].
Jayaram, L ;
Pizzichini, MM ;
Cook, RJ ;
Boulet, LP ;
Lemière, C ;
Pizzichini, E ;
Cartier, A ;
Hussack, P ;
Goldsmith, CH ;
Laviolette, M ;
Parameswaran, K ;
Hargreave, FE .
EUROPEAN RESPIRATORY JOURNAL, 2006, 27 (03) :483-494
[27]   The use of induced sputum in clinical trials [J].
Kips, JC ;
Inman, MD ;
Jayaram, L ;
Bel, EH ;
Parameswaran, K ;
Pizzichini, MMM ;
Pavord, ID ;
Djukanovic, R ;
Hargreave, FE ;
Sterk, PJ .
EUROPEAN RESPIRATORY JOURNAL, 2002, 20 :47S-50S
[28]   Airway inflammation assessed by invasive and noninvasive means in severe asthma:: Eosinophilic and noneosinophilic phenotypes [J].
Lemiere, Catherine ;
Ernst, Pierre ;
Olivenstein, Ron ;
Yamauchi, Yasuhiro ;
Govindaraju, Karuthapillai ;
Ludwig, Mara S. ;
Martin, James G. ;
Hamid, Gutayba .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2006, 118 (05) :1033-1039
[29]   Sputum induction in children with difficult asthma: Safety, feasibility, and inflammatory cell pattern [J].
Lex, C ;
Payne, DNR ;
Zacharasiewicz, A ;
Li, AM ;
Wilson, NM ;
Hansel, TT ;
Bush, A .
PEDIATRIC PULMONOLOGY, 2005, 39 (04) :318-324
[30]   Does sputum eosinophilia predict the response to systemic corticosteroids in children with difficult asthma? [J].
Lex, Christiane ;
Jenkins, Gavin ;
Wilson, Nicola M. ;
Zacharasiewicz, Angela ;
Erin, Ed ;
Hansel, Trevor T. ;
Bush, Andrew ;
Payne, Donald N. R. .
PEDIATRIC PULMONOLOGY, 2007, 42 (03) :298-303