Association of thrombocytosis with COPD morbidity: the SPIROMICS and COPDGene cohorts

Ashraf Fawzy, Nirupama Putcha, Laura M Paulin, Carrie P Aaron, Wassim W Labaki, MeiLan K Han, Robert A Wise, Richard E Kanner, Russell P Bowler, R Graham Barr, Nadia N Hansel, SPIROMICS and COPDGene Investigators, Neil E Alexis, Wayne H Anderson, Igor Barjaktarevic, R Graham Barr, Eugene R Bleecker, Richard C Boucher, Russell P Bowler, Elizabeth E Carretta, Stephanie A Christenson, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Ronald G Crystal, Jeffrey L Curtis, Claire M Doerschuk, Mark T Dransfield, Christine M Freeman, Mei Lan K Han, Nadia N Hansel, Annette T Hastie, Eric A Hoffman, Robert J Kaner, Richard E Kanner, Eric C Kleerup, Jerry A Krishnan, Lisa M LaVange, Stephen C Lazarus, Fernando J Martinez, Deborah A Meyers, Wendy C Moore, John D Newell Jr., Laura Paulin, Stephen Peters, Cheryl Pirozzi, Elizabeth C Oelsner, Wanda K O'Neal, Victor E Ortega, Robert Paine, Nirupama Putcha, Sanjeev Raman, Stephen I Rennard, Donald P Tashkin, J Michael Wells, Robert A Wise, Prescott G Woodruff, Ashraf Fawzy, Nirupama Putcha, Laura M Paulin, Carrie P Aaron, Wassim W Labaki, MeiLan K Han, Robert A Wise, Richard E Kanner, Russell P Bowler, R Graham Barr, Nadia N Hansel, SPIROMICS and COPDGene Investigators, Neil E Alexis, Wayne H Anderson, Igor Barjaktarevic, R Graham Barr, Eugene R Bleecker, Richard C Boucher, Russell P Bowler, Elizabeth E Carretta, Stephanie A Christenson, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Ronald G Crystal, Jeffrey L Curtis, Claire M Doerschuk, Mark T Dransfield, Christine M Freeman, Mei Lan K Han, Nadia N Hansel, Annette T Hastie, Eric A Hoffman, Robert J Kaner, Richard E Kanner, Eric C Kleerup, Jerry A Krishnan, Lisa M LaVange, Stephen C Lazarus, Fernando J Martinez, Deborah A Meyers, Wendy C Moore, John D Newell Jr., Laura Paulin, Stephen Peters, Cheryl Pirozzi, Elizabeth C Oelsner, Wanda K O'Neal, Victor E Ortega, Robert Paine, Nirupama Putcha, Sanjeev Raman, Stephen I Rennard, Donald P Tashkin, J Michael Wells, Robert A Wise, Prescott G Woodruff

Abstract

Background: Thrombocytosis has been associated with COPD prevalence and increased all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but whether it is associated with morbidity in stable COPD is unknown. This study aims to determine the association of thrombocytosis with COPD morbidity including reported AECOPD, respiratory symptoms and exercise capacity.

Methods: Participants with COPD were included from two multi-center observational studies (SPIROMICS and COPDGene). Cross-sectional associations of thrombocytosis (platelet count ≥350 × 109/L) with AECOPD during prior year (none vs. any), exertional dyspnea (modified Medical Research Council (mMRC) score ≥ 2), COPD Assessment Test (CAT) score ≥ 10, six-minute-walk distance (6MWD), and St. George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic or linear regression. A pooled effect estimate for thrombocytosis was produced using meta-analysis of data from both studies.

Results: Thrombocytosis was present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene participants. In meta-analysis thrombocytosis was associated with any AECOPD (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0), severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC ≥ 2 aOR 1.4; 95% CI: 1.0-1.9), respiratory symptoms (CAT ≥ 10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ score (β 2.7; 95% CI: 0.5, 5). Thrombocytosis was also associated with classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D (aOR 1.7 95% CI: 1.2-2.4).

Conclusions: Thrombocytosis was associated with higher likelihood of prior exacerbation and worse symptoms. Platelet count, a commonly measured clinical assay, may be a biomarker for moderate-severe COPD symptoms, guide disease classification and intensity of treatment. Future longitudinal studies investigating the role of platelets in COPD progression may be warranted.

Trial registration: ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene).

Keywords: Dyspnea; Exacerbations; Platelet count; Quality of life.

Conflict of interest statement

Ethics approval and consent to participate

SPIROMICS and COPDGene were approved by the institutional review boards at each center and all participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Consort diagram detailing the reason for exclusion of participants and ultimate classification by platelet count
Fig. 2
Fig. 2
Association of thrombocytosis (platelet count ≥350 × 109/L) with COPD morbidity (dichotomous outcomes). aOR: adjusted odds ratio; mMRC: modified medical research council questionnaire; CAT: COPD assessment test; GOLD: Global Initiative for Chronic Obstructive Lung Disease. Statistical significance (p < 0.05) denoted by asterisk
Fig. 3
Fig. 3
Association of thrombocytosis (platelet count ≥350 × 109/L) with COPD morbidity (continuous outcomes). SGRQ: St. George Respiratory Questionnaire. Statistical significance (p < 0.05) denoted by asterisk

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