Baseline demographics of participants (n = 53).

<p>Data presented as means with standard deviation (SD) except where indicated.</p>*<p>p≤0.05 relative to never smokers with asthma.</p><p>Abbreviations: ACQ; asthma control questionnaire, BD; bronchodilator, BMI; body mass index, mcg;</p><p>microgramme, FEV₁; forced expiratory volume in 1 sec, IQR; interquartile range, PEF; peak expiratory flow.</p

Plasma cytokine concentrations before and after two weeks of oral dexamethasone.

<p>Data presented as median (IQR). All results pg/ml.</p><p>Results with superscript numerals had significance tests <0.05. Specifically,</p>1<p>pre-dexamethasone smokers vs. never smokers with asthma,</p>2<p>post-dexamethasone smokers vs. never smokers with asthma,</p>3<p>pre- vs. post-dexamethasone smokers with asthma,</p>4<p>pre- vs. post-dexamethasone never smokers with asthma.</p

Sputum supernatant cytokine concentrations before and after two weeks of oral dexamethasone.

<p>Data presented as median (IQR). All results pg/ml.</p><p>Results with superscript numerals had significance tests <0.05. Specifically,</p>1<p>pre-dexamethasone smokers vs. never-smokers with asthma,</p>2<p>post-dexamethasone smokers vs. never smokers with asthma,</p>3<p>pre-dexamethasone vs. post-dexamethasone smokers with asthma,</p>4<p>pre-dexamethasone vs. post-dexamethasone never smokers with asthma.</p><p>Cytokine abbreviations: CXC; CXC chemokine motif ligand, CCL; CC chemokine motif ligand, GM-CSF; granulocyte macrophage colony-stimulating factor, IFN; interferon IL; interleukin, TNF; tumor necrosis factor.</p

Principal component analysis plot of pre dexamethasone sputum supernatant cytokines (IL1β, 1RA, 2R, 6, 7, 13, 17, IFNα, GM-CSF, CCL2, 3, 4 & 5, CXCL8, 9 & 10).

<p>Principal component 1 represents 52% of variance in data, Principal component 2 21%. Based on examination of the component loadings (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071460#pone-0071460-t003" target="_blank">Table 3</a>) we interpret principal component 1 as being principally driven by the sputum supernatant cytokines IL1β, 2R, 7, 12, 13, 17 & GM-CSF principal component 2 to be driven by sputum supernatant IL-6 and the chemokines CXCL9 & 10 & CCL 2.</p

Principal component analysis of pre dexamethasone sputum supernatant cytokines.

<p>Principal component analysis of pre dexamethasone sputum supernatant cytokines.</p

Differences in clinical outcomes between baseline and follow-up for each cluster.

<p>Pre Bronchodilator FEV1 % predicted and Blood eosinophil count statistics are Mean (+/−SD). Exacerbation frequency outcomes are median (IQR) and percentage on oral steroids are percentages.</p

Clinical characteristics of the original BTS severe refractory asthma clusters.

<p>Data represented as ^‡Mean (SD) tested with ANOVA test, ^†Median (IQR) tested with Kruskal-Wallis test, *(%) tested with Chi squared test.</p

Cluster specific differences over time for clinically significant outcomes of clusters.

<p>Data represented as ^‡Mean (SD) tested with paired t-test for each cluster, ^†Median (IQR) tested with paired sample Wilcoxon signed rank test, * (%) tested with McNemar's test.</p

Cluster memberships at baseline compared to classification membership at follow up.

<p>Cluster memberships at baseline compared to classification membership at follow up.</p

Cluster and Classification membership compared at baseline.

<p>Cluster and Classification membership compared at baseline.</p