Comparison of Proteomic Assessment Methods in Multiple Cohort Studies.

Novel proteomics platforms, such as the aptamer-based SOMAscan platform, can quantify large numbers of proteins efficiently and cost-effectively and are rapidly growing in popularity. However, comparisons to conventional immunoassays remain underexplored, leaving investigators unsure when cross-assay comparisons are appropriate. The correlation of results from immunoassays with relative protein quantification is explored by SOMAscan. For 63 proteins assessed in two chronic obstructive pulmonary disease (COPD) cohorts, subpopulations and intermediate outcome measures in COPD Study (SPIROMICS), and COPDGene, using myriad rules based medicine multiplex immunoassays and SOMAscan, Spearman correlation coefficients range from -0.13 to 0.97, with a median correlation coefficient of ≈0.5 and consistent results across cohorts. A similar range is observed for immunoassays in the population-based Multi-Ethnic Study of Atherosclerosis and for other assays in COPDGene and SPIROMICS. Comparisons of relative quantification from the antibody-based Olink platform and SOMAscan in a small cohort of myocardial infarction patients also show a wide correlation range. Finally, cis pQTL data, mass spectrometry aptamer confirmation, and other publicly available data are integrated to assess relationships with observed correlations. Correlation between proteomics assays shows a wide range and should be carefully considered when comparing and meta-analyzing proteomics data across assays and studies.

Higher serum levels of systemic inflammatory markers are linked to greater inspiratory muscle dysfunction in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an inflammatory response that becomes more pronounced in acute exacerbations. Considerable attention has recently focused on the value of several inflammatory mediators in predicting worsening of COPD-related symptoms. Whereas respiratory muscle dysfunction is also widely present in this population, little is known about how systemic inflammation relates to inspiratory muscle dysfunction in COPD. METHODS: Fifty-three males with mild-to-very severe airflow obstruction underwent blood sampling for 23 inflammatory markers, including acute-phase proteins, cytokines and adipokines. Inspiratory muscle performance was assessed via the test of incremental respiratory endurance, providing measures of maximal (MIP) and sustained maximal (SMIP) inspiratory pressures. RESULTS: The mean ± SD MIP and SMIP were 75.32 ± 19.62 cmH2 O and 406.15 ± 124.55 PTU. MIP negatively correlated with CRP, SAA and cystatin C (r-values from -0.333 to -0.378, P < 0.02), while SMIP was inversely related to SAA and cystatin C (r = -0.534 and r = -0.396, P = 0.00). Significant differences in CRP, SAA, cystatin C and PARC were also found between subjects with and without inspiratory muscle weakness. No additional significant relationships were observed between either MIP or SMIP and other inflammatory markers in the study. CONCLUSIONS: MIP and SMIP are markedly reduced with greater degrees of inflammation in COPD as expressed by higher levels of CRP, SAA and cystatin C. Future research is needed to further examine the above findings and determine the impact of systemic inflammation along with its underlying mechanisms on inspiratory muscle function in COPD.