Risk Factors for Secondary Polycythemia in COPD

Investigators assessed the significance of gender, smoking status, altitude, and numerous clinical factors in the risk for polycythemia in moderate to severe COPD.

In a study of patients with moderate to severe chronic obstructive pulmonary disease (COPD), reported in the journal BMC Pulmonary Medicine, risk factors linked to increased risk for secondary polycythemia included male sex, current smoking, impaired diffusing capacity for carbon monoxide (DLCO), severe hypoxemia, and living at a high altitude. The study was a cross-sectional analysis of selected participants from the COPDGene study (ClinicalTrials.gov Identifier: NCT00608764), an ongoing, prospective, observational trial involving 21 clinical centers across the US.

Investigators assessed the presence of secondary polycythemia among current and former smokers with moderate to severe COPD at the 5-year follow-up visit of the COPDGene study. The association between polycythemia and age, sex, race, current smoking status, spirometry, DLCO, resting hypoxemia, exercise-induced hypoxemia, quantitative computed tomography chest measurements, long-term oxygen therapy, and altitude was evaluated via logistic regression. 

Among 1928 participants with moderate to very severe COPD, secondary polycythemia was reported in 128 patients, including 97 men and 31 women. Among those with polycythemia, a higher percentage had severe airflow limitation (per Global Initiative for Chronic Obstructive Lung Disease [GOLD] 3) and a lower percentage had very severe airflow limitation (GOLD 4) compared with study participants without secondary polycythemia.

Polycythemia was linked to male sex (odds ratio [OR], 3.60; 95% CI, 2.20-5.90), non-Hispanic White race (OR, 3.33; 95% CI, 1.71-6.50), current smoking (OR, 2.55; 95% CI, 1.49-4.38), and enrollment in the Denver clinical center, which had a higher altitude than other centers (OR, 4.42; 95% CI, 2.38 to 8.21) via multivariable regression. An increased risk for polycythemia was also associated with impaired DLCO (OR, 1.28 for each 10% decrease in DLCO % predicted; 95% CI, 1.09-1.49) and severe resting hypoxemia (OR, 3.50; 95% CI, 1.41-8.66).

A lower risk for developing polycythemia was associated with the use of continuous and nocturnal supplemental oxygen (OR, 0.13; 95% CI, 0.05-0.35 and OR, 0.46; 95% CI, 0.21-0.97, respectively). Notably, polycythemia risk was not independently associated with either education or income.

The investigators concluded that polycythemia is prevalent in moderate to severe COPD, especially in men and in current smokers, and that further research is needed to determine whether COPD management and outcomes can be improved through a more in-depth risk assessment for polycythemia.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Zhang J, DeMeo DL, Silverman EK, et al. Secondary polycythemia in chronic obstructive pulmonary disease: prevalence and risk factors. BMC Pulm Med. 2021;21(1):235. doi:10.1186/s12890-021-01585-5