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S132 Sputum And Bronchial Biopsy Expression Of 8-oxo-7, 8-dihydro-2’-deoxyguanosine (8-oxodg) In Asthma Is Related To Neutrophilic Inflammation And Poor Asthma Control
  1. DJE Goold1,
  2. V Mistry1,
  3. A Singapuri1,
  4. M Cooke2,
  5. R Berair1,
  6. CE Brightling1
  1. 1Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department of Infection, Immunity and Inflammation, University of Leicester and Department of Respiratory Medicine University Hospitals of Leicester NHS Trust, Leicester, UK
  2. 2Oxidative Stress Group, Department of Cancer Studies and Department of Genetics, University of Leicester, Leicester, UK Department of Health Sciences, University of Leicester, Leicester, UK

Abstract

Introduction and objectives Oxidative stress has been implicated in the pathogenesis of asthma. Validated sputum biomarkers are required to assess this and its relationship to other clinical variables.

We sought to compare sputum and bronchial 8-oxodG expression in asthma and health; assess the sputum repeatability; and explore its relationship with induced sputum inflammatory cells counts and exacerbations.

Methods Asthmatics and healthy controls were recruited from a single centre and underwent clinical characterisation including sputum induction (asthma n = 58, health n = 27) and bronchial biopsy (asthma n = 16, health n = 10).

Sputum and epithelial 8-oxodG expression was measured by ELISA and Immunohistochemistry respectively. Sputum asthmatics were assessed at a repeat stable visit at 6 months.

Results Between health and asthma, there were no significant differences in the median (IQR) sputum 8-oxodG levels [12 (16) ngml-1 vs. 11 (15) ngml-1, p = 0.36] or the mean (SEM) percentage area of epithelium reaching threshold intensity for 8-oxodG [2.0 (0.7)% vs. 4.4 (1.0) %, p = 0.12].

Asthma sputum 8-oxodG correlated with the sputum total cell count (r s=0.53, p < 0.01), sputum neutrophils (r s=0.27, p = 0.04), sputum macrophages (r s=-0.31, p = 0.02) and serum IgE (r s=-0.27, p = 0.04). Epithelial 8-oxodG correlated to the number of exacerbations in the previous year (rs=0.70,p < 0.01) and the ACQ 6 (rs=-0.52,p = 0.04).

The upper 95th confidence interval of sputum 8-oxodG and epithelium 8-oxodG reaching threshold in healthy controls was used to split asthma patients into 8-oxodG high and low groups. The sputum 8-oxodGhigh group (n = 13) had significantly higher sputum total cells 8.08 [8.41] x106 g-1 vs. 2.25 [2.91] x106 g-1, p < 0.01, higher sputum neutrophils (82.25[32.75]% vs. 55.50 [29.75]%, p < 0.01) and lower serum IgE (30 [76.50] KUL-1 vs. 157 [212.90] KUL-1, p < 0.01). The epithelial 8-oxodG high group (n = 8) had significantly more exacerbations 3.9 (0.3) vs. 0.5 (0.3) p < 0.01 and a lower ACQ 6 score 1.4 (0.3) vs. 2.4 (0.3) p = 0.04.

In the asthmatic group, the intra-class correlation coefficient of sputum 8-oxodG between the 2 visits was 0.51 (p < 0.01).

Conclusions 8-oxodG expression in sputum and bronchial biopsies was not different between asthma and health, although we did identify an 8-oxodGhigh group in asthma. Interestingly, expression in asthma was associated with neutrophilic inflammation and poor asthma control.

Abstract S132 Figure 1

Scatter plots of A) Sputum 8-oxodG in health vs. asthma; B) Epithelial 8-oxodG in health and asthma; C) Sputum 8-oxodG vs. sputum neutrophils and D) Epithelial 8- oxodG vs. the number of exacerbations in the previous year.

Spearman's rank correlation coefficients are also given. Comparisons were made using t tests and Mann Whitney U tests for parametric and non-parametric data respectively

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