Diffusing Capacity (DLCO)

The diffusing capacity of the lungs for carbon monoxide (DLCO) is a critical endpoint in respiratory research because it provides a sensitive and quantitative measure of pulmonary gas exchange efficiency.

This endpoint reflects the integrity of the alveolar–capillary membrane and the ability of oxygen to transfer from the alveoli into the bloodstream. DLCO is particularly valuable in diseases that impair this interface, including pulmonary hypertension, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and other interstitial lung disorders.

In these conditions, spirometry alone may fail to detect early or subtle functional changes. For this reason, sponsors frequently incorporate DLCO into clinical trial protocols to capture clinically meaningful changes in pulmonary function that complement traditional spirometry measures, thereby providing a more comprehensive assessment of disease presence, progression, and/or therapeutic response.

The diffusing capacity of the lungs for carbon monoxide (DLCO) evaluates the efficiency of gas transfer across the alveolar–capillary membrane by using carbon monoxide as a surrogate for oxygen.

This measurement reflects the combined function of alveolar surface area, capillary health, and hemoglobin binding capacity. DLCO results are typically reported both as an absolute value and as a percentage of the predicted normal value, which is adjusted for key physiological and environmental factors such as hemoglobin concentration, altitude, age, sex, and body size.

A decline in DLCO is generally considered indicative of worsening disease severity or progression, particularly in conditions that impair pulmonary vascular or interstitial integrity. DLCO serves as a sensitive marker for detecting early functional deterioration and monitoring therapeutic responses in clinical trials.

The diffusing capacity of the lungs for carbon monoxide (DLCO) is frequently evaluated in conjunction with other complementary assessments, including spirometry, imaging modalities, exercise capacity tests such as the six-minute walk test (6MWT), and patient-reported outcomes.

This integrated approach provides a multidimensional view of pulmonary function and disease status and can provide essential evidence for drug efficacy. In progressive conditions such as idiopathic pulmonary fibrosis (IPF) or pulmonary hypertension, a decline in DLCO often serves as an early and sensitive indicator of worsening gas exchange efficiency. When interpreted alongside structural changes observed on imaging, reductions in spirometric parameters, diminished exercise tolerance, and patient-reported symptom burden, the clinical significance of DLCO decline is further reinforced.

This combined analysis enhances the robustness of endpoint interpretation, supports regulatory acceptability, and improves the ability to detect meaningful therapeutic effects in clinical trials.