Decline in Carbon Monoxide Transfer Coefficient in Chronic Obstructive Pulmonary Disease

Abstract

Background: Although a reduced carbon monoxide transfer coefficient (Kco) is an important feature in chronic obstructive pulmonary disease (COPD), how it changes over time and its relationship with other clinical outcomes remain unclear. This study evaluated longitudinal changes in Kco and their relationship with other clinical outcomes.

Methods: We evaluated patients with COPD from the Korean Obstructive Lung Disease cohort, followed up for up to ten years. Random coefficient models were used to assess the annual change in Kco over time. Participants were categorized into tertiles according to Kco decline rate. Baseline characteristics and outcomes, including changes in FEV1 and emphysema index, incidence of exacerbations, and mortality, were compared between categories.

Results: A decline in Kco was observed in 92.9% of the 211 enrolled participants with COPD. Those with the most rapid decline (tertile 1) had a lower FEV1/FVC% (tertile 1: 43.8% ± 9.7%, tertile 2: 46.4% ± 10.5%, tertile 3: 49.2% ± 10.4%, p = 0.008) and a higher emphysema index at baseline (27.7 ± 14.8, 22.4 ± 16.1, 18.1 ± 14.5, respectively, p = 0.001). Tertile 3 showed a lower decline rate in FEV1 (16.3 vs. 27.1 mL/yr, p = 0.017) and a lower incidence of exacerbations (incidence rate ratio = 0.66, 95% CI = 0.44-0.99) than tertile 1. There were no differences in the change in emphysema index and mortality between categories.

Conclusion: Most patients with COPD experienced Kco decline over time, which was greater in patients with more severe airflow limitation and emphysema. Decline in Kco was associated with an accelerated decline in FEV1 and more frequent exacerbations; hence, this should be considered as an important outcome measure in further studies.

Keywords: carbon monoxide transfer coefficient; chronic obstructive pulmonary disease; exacerbation; lung function decline.

Figure 1

Flow diagram of the study design.

Figure 2

Distribution of estimated annual rates of change in Kco (n = 211). Footnotes: Best Linear Unbiased Prediction (BLUP) of the annual change in Kco was calculated for each patient using the random-coefficient model, and the data are shown as a histogram. Mean ± SD = −0.04 ± 0.03 (mmol/min/mmHg/L per year).

Figure 3

Comparison of annual rates in change of (A) post-bronchodilator FEV1, (B) emphysema index, and (C) SGRQ score by annual rates of decline in Kco. Comparisons of the risk of acute exacerbations and mortality in COPD according to changes in Kco over time.

Figure 3

Comparison of annual rates in change of (A) post-bronchodilator FEV1, (B) emphysema index, and (C) SGRQ score by annual rates of decline in Kco. Comparisons of the risk of acute exacerbations and mortality in COPD according to changes in Kco over time.

Figure 4

Comparison of the incidence rate of acute exacerbation according to annual rates of decline in Kco. Footnotes: All statistical analyses were adjusted for age, sex, body mass index, smoking status, pack-years smoked, baseline post-bronchodilator FEV1, exacerbation history at baseline, and use of inhaled corticosteroid/long-acting β-agonists (ICS/LABA), or inhaled long-acting muscarinic antagonists (LAMA), * p-value < 0.05.

Figure 5

Comparison of mortality risk by annual rates of decline in Kco. Footnotes: All statistical analyses were adjusted by age, sex, body mass index, smoking status, pack-years smoked, baseline post-bronchodilator FEV1, exacerbation history at baseline, and use of inhaled corticosteroid/long-acting β-agonists (ICS/LABA), or inhaled long-acting muscarinic antagonists (LAMA).