ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Immunoglobulin Levels Aide in Predicting Severe COPD Exacerbations
Session Title
TP41 - TP041 DIAGNOSIS AND RISK ASSESSMENT IN COPD
Abstract
A2301 - Immunoglobulin Levels Aide in Predicting Severe COPD Exacerbations
Author Block: B. Masters1, G. J. Criner2, S. P. Bhatt3, M. T. Dransfield4, T. M. Siler5, R. Paine6, J. E. Herrera7, M. K. Han8, for SPIROMICS Investigators; 1ProterixBio Inc, Belmont, CA, United States, 2Pulm & Crit Care Med, Temple Univ Hosp, Philadelphia, PA, United States, 3Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, 4Univ of Alabama Birmingham & Birmingham VA Med Ctr, Birmingham, AL, United States, 5Midwest Chest Consultants PC, Saint Charles, MO, United States, 6Univ of Utah, Salt Lake City, UT, United States, 7Assay Development, ProterixBio, Billerica, MA, United States, 8University of Michigan School of Medicine, Ann Arbor, MI, United States.
RATIONALE: Immunoglobulin deficiencies in COPD patients have been associated with increased exacerbations and hospitalizations. Early immune status identification of COPD patients at increased risk for future severe exacerbations could provide an opportunity for beneficial interventions. METHODS: Plasma biomarkers were measured using controlled ELISAs. We investigated participants with COPD (n=693) in the SPIROMICS cohort and in a similar clinic cohort (n=195). Both cohorts had outcomes over 12 months before and at least 12 months after entry. Overall, participants were aged 65.4±7.8 (mean±SD), 52% male, 35% active smokers, with FEV1%predicted 49%±16%, and FEV/FVC 46±13. Acute exacerbation (AEx) incidences and rates within 12 months of study visits for retrospective/prospective events were 39%/38% and 0.72/0.76; and 19%/17% and 0.27/0.27 for severe exacerbations (SAEx). A total of 243 prospective SAEx were recorded. A clinical parameter algorithm was trained on future 12 month SAEx incidence in the SPIROMICS cohort and tested in the clinic cohort. The less identified, lower 40th percentile of algorithm scores, were examined for markers of increased SAEx risk. RESULTS: Overall participants with retrospective SAEx (19%) had an increased Incidence Relative Risk (IRR) for prospective SAEx, IRR =2.72 (2.51-2.95 estimated 95th CI). Additional participants (+10%) with ≥2 retrospective AEx had IRR = 2.20 (1.87-2.57), or alternately (+28%) with COPD Assessment Test (CAT) ≥20 had IRR =1.88 (1.58-2.18). The training algorithm had AUC 0.73±0.04, p<1e-20 for future SAEx, and verified in the test cohort, AUC 0.79±0.10, p<1e-7. Overall, combining the cohorts had AUC 0.74±0.04, p<1e-20, with IRR = 3.80 (3.53-4.06) at 60th percentile cut (Figure), improving over concatenating single factors. As expected, in the group with <40th percentile algorithm scores, retrospective AEx were not predictive, while elevated CAT scores remained predictive to a lesser extent, AUC 0.60±0.10, p=0.03. Here, lower levels of total IgG highlight increased SAEx risk, IRR = 2.56 (1.02-NA), p =0.024, at 25th percentile, and these ratio with elevated D-Dimer levels to give combined AUC 0.76±0.11 for future SAEx. Here also, increasing emphysema CT-scores trended for increased risk. In contrast, IgG1 subtype has a “U” risk profile, with IRR = 2.26 (1.61-4.04), p <0.01 at ≥90th percentile. High group IgG levels have increased TIMP1/MMP9 ratios (AUC 0.67±0.13), trend younger, and with increased RV/TLC for increased risk. CONCLUSIONS: COPD patients could benefit from accessible tests that help identify manageable risks. Immunoglobulin levels and associated biomarkers are potentially accessible measures for a substantial number of COPD patients observed in this rising-risk sample.
Author Block: B. Masters1, G. J. Criner2, S. P. Bhatt3, M. T. Dransfield4, T. M. Siler5, R. Paine6, J. E. Herrera7, M. K. Han8, for SPIROMICS Investigators; 1ProterixBio Inc, Belmont, CA, United States, 2Pulm & Crit Care Med, Temple Univ Hosp, Philadelphia, PA, United States, 3Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, 4Univ of Alabama Birmingham & Birmingham VA Med Ctr, Birmingham, AL, United States, 5Midwest Chest Consultants PC, Saint Charles, MO, United States, 6Univ of Utah, Salt Lake City, UT, United States, 7Assay Development, ProterixBio, Billerica, MA, United States, 8University of Michigan School of Medicine, Ann Arbor, MI, United States.
RATIONALE: Immunoglobulin deficiencies in COPD patients have been associated with increased exacerbations and hospitalizations. Early immune status identification of COPD patients at increased risk for future severe exacerbations could provide an opportunity for beneficial interventions. METHODS: Plasma biomarkers were measured using controlled ELISAs. We investigated participants with COPD (n=693) in the SPIROMICS cohort and in a similar clinic cohort (n=195). Both cohorts had outcomes over 12 months before and at least 12 months after entry. Overall, participants were aged 65.4±7.8 (mean±SD), 52% male, 35% active smokers, with FEV1%predicted 49%±16%, and FEV/FVC 46±13. Acute exacerbation (AEx) incidences and rates within 12 months of study visits for retrospective/prospective events were 39%/38% and 0.72/0.76; and 19%/17% and 0.27/0.27 for severe exacerbations (SAEx). A total of 243 prospective SAEx were recorded. A clinical parameter algorithm was trained on future 12 month SAEx incidence in the SPIROMICS cohort and tested in the clinic cohort. The less identified, lower 40th percentile of algorithm scores, were examined for markers of increased SAEx risk. RESULTS: Overall participants with retrospective SAEx (19%) had an increased Incidence Relative Risk (IRR) for prospective SAEx, IRR =2.72 (2.51-2.95 estimated 95th CI). Additional participants (+10%) with ≥2 retrospective AEx had IRR = 2.20 (1.87-2.57), or alternately (+28%) with COPD Assessment Test (CAT) ≥20 had IRR =1.88 (1.58-2.18). The training algorithm had AUC 0.73±0.04, p<1e-20 for future SAEx, and verified in the test cohort, AUC 0.79±0.10, p<1e-7. Overall, combining the cohorts had AUC 0.74±0.04, p<1e-20, with IRR = 3.80 (3.53-4.06) at 60th percentile cut (Figure), improving over concatenating single factors. As expected, in the group with <40th percentile algorithm scores, retrospective AEx were not predictive, while elevated CAT scores remained predictive to a lesser extent, AUC 0.60±0.10, p=0.03. Here, lower levels of total IgG highlight increased SAEx risk, IRR = 2.56 (1.02-NA), p =0.024, at 25th percentile, and these ratio with elevated D-Dimer levels to give combined AUC 0.76±0.11 for future SAEx. Here also, increasing emphysema CT-scores trended for increased risk. In contrast, IgG1 subtype has a “U” risk profile, with IRR = 2.26 (1.61-4.04), p <0.01 at ≥90th percentile. High group IgG levels have increased TIMP1/MMP9 ratios (AUC 0.67±0.13), trend younger, and with increased RV/TLC for increased risk. CONCLUSIONS: COPD patients could benefit from accessible tests that help identify manageable risks. Immunoglobulin levels and associated biomarkers are potentially accessible measures for a substantial number of COPD patients observed in this rising-risk sample.
