PURPOSE:To investigate the mRNA expression of inflammatory mediators in peripheral blood of subjects with obstructive airway disease (OAD) and their association with functional measures.
METHODS:160 subjects were identified from the ‘Health, Aging and Body Composition’ study, a community-based longitudinal observational cohort study in 3075 elderly, and subdivided into two groups: CASES (n=62) having OAD based on GOLD and ATS criteria and PPFEV1 <80% and CONTROLS (n=98) not meeting OAD criteria. Total RNA was isolated from blood samples collected in PAXgene RNA blood collection tubes and reverse transcribed to cDNA. Potential target genes CXCR1, CXCR2, CXCR5, XCL1, CXCL13, CCL23, TNF-α, IL-6, IL-8, IL-13, and LTA4H were selected based on preliminary microarray experiments in our lab. Real-time PCR was utilized for the relative quantification of their mRNA expression using cyclophilin A as reference gene. Expression was compared between the two groups and also related to functional measures: self reported dyspnea categories (none, hurrying dyspnea, walking dyspnea), dynamometer-assessed lower extremity strength, and a standardized long distance corridor walk. One-way ANOVA and correlation analyses were used to test for statistically significant differences and associations.
RESULTS:Expression for IL-6 was 11.9 times higher in CASES (P=0.009) compared to CONTROLS. For CXCL13, CASES had a 1.3 fold lower expression as compared to CONTROLS (P=0.02). CXCR1 (P=0.01), CXCR2 (P=0.05) and LTA4H (P=0.02) expression was significantly higher in subjects reporting dyspnea. CXCR1 expression was positively correlated with 20 m walk time (r=0.17, P=0.04).
CONCLUSION:Altered expression of inflammatory mediators in subjects with OAD is detectable in immune cells circulating in peripheral blood. Differential expression suggests the involvement of the IL-6, IL-8 (CXCR1, CXCR2) and leukotriene (LTA4H) pathways in the pathogenesis of OAD in the studied cohort.
CLINICAL IMPLICATIONS:mRNA expression in peripheral blood may be useful in the diagnosis and/or monitoring of disease progression in subjects with OAD.
DISCLOSURE:Shailly Mehrotra, No Financial Disclosure Information; No Product/Research Disclosure Information