Asthma-COPD Exacerbation Risk: Role of Diffusing Distributions of the Lung

Statins may help decrease mortality in patients with COPD.
Statins may help decrease mortality in patients with COPD.
Can diffusion distributions of the lung — DLCO and KCO — be used to predict future exacerbations in patients with asthma-COPD overlap?

Low transfer coefficient of the lung for carbon monoxide (KCO) was found to be an independent risk factor for exacerbations in patients with asthma-chronic obstructive pulmonary disease overlap (ACO). This was among the findings published in BMC Pulmonary Medicine of an observational cohort study recently conducted at the National Hospital Organization Fukuoka National Hospital in Japan.

People with ACO are known to experience exacerbations more frequently than individuals with either asthma or chronic obstructive pulmonary disease (COPD) alone. Because low diffusing capacity of the lung for carbon monoxide (DLCO) is recognized as a strong risk factor for severe exacerbation in COPD, researchers suspected that low KCO also is linked to a higher risk of exacerbations in patients affected by both disorders.

The cohort comprised 94 ACO patients 40 years of age and older who underwent assessment of DLCO and KCO from June 1, 2017, to May 31, 2020 and had complete information on all relevant covariates. ACO was defined as the presence of 3 major criteria: (1) persistent airflow limitation, defined as post-bronchodilator (post-BD) forced expiratory volume in the first second of expiration to forced vital capacity (FEV1/FVC) of less than 70%; (2) at least 1 feature associated with COPD; and (3) 1 or more asthmatic features.

A smoking history of more than 10 pack years and pulmonary emphysema were the features associated with COPD. The asthmatic features included (1) high values of fractional exhaled nitric oxide (FeNO >35 parts per billion), (2) bronchodilator reversibility (≥12% and ≥200 ml reversibility in post-BD FEV1), (3) an eosinophilic component (blood eosinophil levels >300/μl and/or >5%), and (4) positive levels for total immunoglobulin E (IgE >170 IU/ml) and/or IgE specific to perennial inhalant antigens (>class 2). Individuals with 3 asthmatic features or more were designated “highly asthmatic.”

The investigators assessed the distribution of and affecting factors for both DLCO % predicted (DLCO % pred) and KCO % predicted (KCO % pred) as a cross-sectional analysis using the full cohort. The researchers then eliminated 4 patients with no follow-up data, leaving 90 patients, who also were recruited into the prospective research cohort for assessment of the association of DLCO % pred and KCO % pred with exacerbations of ACO.

In 1 year, 33.3% of the study cohort experienced exacerbations. After adjusting for potential confounders, low KCO (<80% predicted) was found to be associated with the incidence of exacerbation (multivariable-adjusted hazard ratio [HR], 3.71; 95% CI, 1.32-10.4). The association between low DLCO (<80% predicted) and exacerbations showed comparable trends, but the link did not attain statistical significance (multivariable-adjusted HR, 1.31; 95% CI, 0.55-3.11).

“Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory,” the authors advised.


Ogata H, Katahira K, Enkidu-Ogawa A, et al. The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study. BMC Pulm Med. 2022;22(1):22. doi:10.1186/s12890-021-01815-w