Additional file 3: Table S3. of Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

Median and interquartile range related to each IgG subclass according to the presence or absence of corresponding IgG subclass deficiency in the merged dataset (MACRO and STATCOPE cohorts combined). (DOCX 15 kb

Additional file 2: Table S2. of Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

Median and interquartile range related to each IgG subclass according to the presence or absence of corresponding IgG subclass deficiency in MACRO and STATCOPE cohorts. (DOCX 15 kb

Additional file 5: Figure S2. of Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

Comparison of IgG subclass levels according to hospitalization status in MACRO – First cohort (left panel) and STATCOPE – Replication cohort (right panel) cohorts. Error bars represent 95% confidence interval. (DOCX 243 kb

Additional file 6: Table S4. of Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

Interactions between IgG subclass levels and inhaled steroid use at enrollment and use of systemic steroids in previous 12 months for both outcomes of interest (time to first exacerbation and time to first hospitalization). (DOCX 15 kb

Gene-Metabolite Expression in Blood Can Discriminate Allergen-Induced Isolated Early from Dual Asthmatic Responses

<div><p>Some asthmatic individuals undergoing allergen inhalation challenge develop an isolated early response whereas others develop a dual response (early plus late response). In the present study we have used transcriptomics (microarrays) and metabolomics (mass spectrometry) of peripheral blood to identify molecular patterns that can discriminate allergen-induced isolated early from dual asthmatic responses. Peripheral blood was obtained prior to (pre-) and 2 hours post allergen inhalation challenge from 33 study participants. In an initial cohort of 14 participants, complete blood counts indicated significant differences in neutrophil and lymphocyte counts at pre-challenge between early and dual responders. At post-challenge, significant genes (<i>ALOX15</i>, <i>FADS2</i> and <i>LPCAT2</i>) and metabolites (lysolipids) were enriched in lipid metabolism pathways. Enzymes encoding for these genes are involved in membrane biogenesis and metabolism of fatty acids into pro-inflammatory and anti-inflammatory mediators. Correlation analysis indicated a strong negative correlation between <i>ALOX15</i>, <i>FADS2</i>, and <i>IL5RA</i> expression with 2-arachidonoylglycerophosphocholine levels in dual responders. However, measuring arachidonic acid and docosahexaenoic acid levels in a validation cohort of 19 participants indicated that the free form of DHA (nmoles/µg of protein) was significantly (p = 0.03) different between early and dual responders after allergen challenge. Collectively these results may suggest an imbalance in lipid metabolism which dictates pro- (anti-) inflammatory and pro-resolving mechanisms. Future studies with larger sample sizes may reveal novel mechanisms and therapeutic targets of the late phase asthmatic response.</p></div

Gene network.

<p>Ingenuity Pathway Analysis network of differentially expressed genes at post-challenge comparing ERs and DRs. Dash lines indicate indirect relationships, whereas solid lines indicate direct relationships. The red colour indicates significant genes at an FDR of 10%. The grey colour indicates non-significant genes at an FDR of 10%.</p

Network plots highlighting the correlation between ΔG and ΔM for early and dual responders.

<p>A. Gene-metabolite clusters for early responders (ΔG_25,8 and ΔM_11,8). B. Gene-metabolite clusters for dual responders (ΔG_25,6 and ΔM_11,6). A correlation coefficient cut-off of 0.5 is applied to both networks.</p

Complete blood counts.

<p>Relative frequencies of various leukocytes obtained at pre and post-challenge. The relative neutrophil counts were significantly (p = 0.01) elevated in ERs compared to DRs, whereas the relative lymphocyte counts were significantly reduced (p = 0.02) in ERs compared to DRs at pre-challenge. The p-value was computed using a robust linear model (see Methods); * denotes p<0.05.</p

Demographics of study participants of the validation cohort.

a<p>geometric mean (PC20 values are measured on a log scale);</p>b<p>[PC₂₀]pre/[PC₂₀]post;</p>c<p>p<0.001 versus ER group.</p

Lung function during allergen inhalation challenge.

<p>Forced expiratory volume in 1 second (FEV₁) measurements at 0.2 h, 0.3 h, 0.5 h, 0.8 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h and 7 h for eight early and six dual responders. FEV₁ measurements are statistically different (*p<0.05) between early and dual responders at each of the time points between three and seven hours inclusive. The p-value for each time point comparing ERs and DRs was computed using a robust linear model (see Methods).</p