Study Clarifies Relationship Establishing a Biomarker for Physical Activity in COPD

Growth differentiation factor 11 (GDF11) may be a useful biomarker for predicting physical activity in patients with chronic obstructive pulmonary disease (COPD), which could help physicians better determine disease prognosis, investigators concluded.

A longitudinal change in the plasma level of growth differentiation factor 11 (GDF11) in patients with chronic obstructive pulmonary disease (COPD) was positively correlated with change in daily physical activity, according to a recent study.

The study results, published in the International Journal of Chronic Obstructive Pulmonary Disease, suggested that GDF11 could be a useful biomarker reflecting physical activity in COPD, which is needed because physical activity assessments are complicated and mostly conducted using motion sensors and self-reported questionnaires.

Reduced physical activity in patients with COPD is associated with lower lung function and increased risks of mortality, hospitalizations, and exacerbations. Physical activity levels can also be a reliable predictor for COPD prognosis.

Evidence has indicated GDF11 to be an anti-aging and rejuvenating factor. It is also highly detected in skeletal muscles and has been shown to increase muscles strength and exercise endurance in mice.

In a previous cross-sectional study, the investigators found that decreased plasma levels of GDF11 were positively correlated with daily physical activity. However, the relationship was not fully established, especially regarding data stability and continuity, suggesting that more research is needed to clarify the association.

Between 2015 and 2017, the investigators recruited 24 outpatients with COPD from Tohoku University Hospital and Tohoku Rosai Hospital in Miyagi, Japan. All patients were older than 40 years, had a former smoking history of more than 10 pack-years, and were diagnosed using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

The median time between the baseline examination and follow-up was 439 days and the patients had an average age of 72.2 years. Among the patients, 2 were diagnosed with GOLD stage 1; 11 had GOLD stage 2; 8 had GOLD stage 3; and 3 had GOLD stage 4. The mean forced expiratory volume among patients was 54.4% predicted and the median steps taken per day was 2846.

At first, no significant differences were seen in the median number of steps in patients with COPD from the baseline examination to the follow-up (2846 vs 2551; P = .751) and there was no change in the mean level of plasma levels of GDF11.

However, when analyzing the longitudinal association between GDF11 and physical activity, the GDF11 plasma level changes had a significant positive correlation with changes in daily step counts (r = 0.41; P = .047).

Intensity of physical activity showed a stronger association. In a sub-analysis on physical activity intensity, plasma level changes were significantly positively correlated with changes in activity duration. The multiple regression analysis confirmed the relationship (β = 0.93; P < .001).

Patients who maintained their plasma levels of GDF11 had significantly less frequent exacerbations that those who had decreased levels (P = .041).

Despite the study results, the investigators said that it remains unclear whether exercise or rehabilitation promotes GDF11 secretion, and that future research is needed to confirm this.

Additionally, although the researchers could not demonstrate a relationship between basal level of GDF11 and exacerbation incidence, potentially due to the small sample size, exacerbations did not appear to be related to changes in the number of daily steps. Further research is needed to confirm whether GDF11 and COPD exacerbations are related.

In addition to the small sample size, the investigators noted a potentially impact on sensitivity as a study limitation due to the inequality of follow-up duration prior to re-evaluation in the plasma sample, physical activity, and lung function among patients.


Tanaka R, Koarai A, Yamada M, et al. Longitudinal relationship between growth differentiation factor 11 and physical activity in chronic obstructive pulmonary disease. Published online April 15, 2021. Accessed April 29, 2021. doi:10.2147/COPD.S301690

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