The relationship between invasive and non-invasive measures of inflammation in children with severe therapy-resistant asthma
File(s)
Accepted version
Author(s)
Mckeon, S
Saglani, S
Bush, A
Fleming, L
Type
Conference Paper
Abstract
Background Children with severe therapy-resistant asthma (STRA) are refractory to treatment despite optimal management. Assessment of airway inflammation to phenotype these patients can enable targeted therapy. Samples obtained at bronchoscopy provide the most direct measure of lower airway inflammation; however, non-invasive measures (induced sputum and exhaled nitric oxide (FeNO)) are of greater clinical utility. We have previously demonstrated a poor relationship between blood and bronchoalveolar lavage (BAL) eosinophilic phenotype using clinical cut-offs for children (blood eosinophils 1.0 × 109/L).1 Recent studies of the anti-IL-5 antibody mepolizumab have used a lower cut point (0.3 × 109/L) for blood eosinophils.2 The aim of this study was to assess the concordance between BAL and non-invasive measures of inflammation.
Methods 113 children (aged 4–17 years) with STRA underwent bronchoscopy at the Royal Brompton Hospital. They had all previously been assessed and potentially modifiable factors such as poor adherence had been addressed. Inflammation was measured invasively using BAL cytology and non-invasively by blood eosinophils, induced sputum cytology, and FeNO. The eosinophilic phenotype was defined as BAL eosinophils >1.19%; blood eosinophils ≥0.3 × 109/L; sputum eosinophils ≥2.5%; and FeNO >35ppb. The relationship between measures was assessed using Spearman rank correlation and Receiver Operator Characteristic (ROC) curves were constructed to determine which cut points best determined BAL eosinophilia and positive and negative predictive values (PPV and NPV) calculated.
Results The predominant phenotype in all samples was eosinophilic. There was 75.6–77.8% concordance between the eosinophilic phenotype in BAL and each of the non-invasive measures.
Blood and BAL eosinophils had the strongest correlation (r = 0.57, p < 0.001, n = 84). Weaker correlations were found between the other measures. The most promising predictor of BAL eosinophilia was a blood eosinophil count of 0.15 × 109/L (PPV 84.1, NPV 71.4) (Table 1).
Methods 113 children (aged 4–17 years) with STRA underwent bronchoscopy at the Royal Brompton Hospital. They had all previously been assessed and potentially modifiable factors such as poor adherence had been addressed. Inflammation was measured invasively using BAL cytology and non-invasively by blood eosinophils, induced sputum cytology, and FeNO. The eosinophilic phenotype was defined as BAL eosinophils >1.19%; blood eosinophils ≥0.3 × 109/L; sputum eosinophils ≥2.5%; and FeNO >35ppb. The relationship between measures was assessed using Spearman rank correlation and Receiver Operator Characteristic (ROC) curves were constructed to determine which cut points best determined BAL eosinophilia and positive and negative predictive values (PPV and NPV) calculated.
Results The predominant phenotype in all samples was eosinophilic. There was 75.6–77.8% concordance between the eosinophilic phenotype in BAL and each of the non-invasive measures.
Blood and BAL eosinophils had the strongest correlation (r = 0.57, p < 0.001, n = 84). Weaker correlations were found between the other measures. The most promising predictor of BAL eosinophilia was a blood eosinophil count of 0.15 × 109/L (PPV 84.1, NPV 71.4) (Table 1).
Date Issued
2015-12-02
Date Acceptance
2015-12-02
Citation
Thorax, 2015, 70 (Suppl 3), pp.A124-A125
ISSN
1468-3296
Publisher
BMJ Publishing Group
Start Page
A124
End Page
A125
Journal / Book Title
Thorax
Volume
70
Issue
Suppl 3
Copyright Statement
© 2015 The Author(s). This article has been accepted for publication in Thorax following peer review. The definitive copyedited, typeset version Thorax 2015;70:A124-A125 doi:10.1136/thoraxjnl-2015-207770.235 is available online at: https://dx.doi.org/10.1136/thoraxjnl-2015-207770.235
Sponsor
Asthma UK
National Institute for Health Research
Asthma UK
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000365353600236&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
10/058
BRU 6535
R43065
Source
Winter Meeting of the British-Thoracic-Society
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
1103 Clinical Sciences
Publication Status
Published
Start Date
2015-12-02
Finish Date
2015-12-04
Coverage Spatial
London, ENGLAND