New Study Shows KL-6 Levels Assist in Distinguishing ILD From Abnormalities

Krebs von den Lungen-6 (KL-6), primarily produced by type II alveolar cells, is associated with the prognosis and severity of interstitial lung disease (ILD).

Researchers from Veterans Health Service Medical Center in Seoul, Korea, led by Jin Hwa Song, M.D., ,looked to explore the relationship between KL-6 concentrations and the presence of ILD versus interstitial lung abnormalities (ILA).

While high-resolution CT and pulmonary function tests are essential for diagnosing and evaluating ILD, lung biopsy remains the definitive diagnosis but is limited by its invasiveness, the authors explained.

The study, published in the Journal of Thoracic Disease on March 31, is believed to be the first of its kind to demonstrate a significant difference in KL-6 levels between ILD and ILA in correlation with CT findings in an aged Korean population.

ILD is an umbrella term for diseases that cause scarring (fibrosis) of the lungs and includes sarcoidosis, idiopathic pulmonary fibrosis, and several other named conditions. ILAs are not a disease but incidental CT findings of lung abnormalities. One standard definition is that they affect more than 5% of any lung zone; some experts say that 5% threshold is arbitrary and is a way to exclude patients with minimal abnormality. According to a review published last year in Clinics in Chest Medicine, the prevalence of ILAs is strongly associated with advanced age In one population-based cohort, the prevalence of ILAs increased from 0.2% in individuals aged less than 40 years to 9.6% in those aged 70 years or older, according to the review.  ILAs are also associated with the smoking status and occupational exposures to substances that harm lung tissue.

This single-center retrospective study led by Song consisted of 147 patients who visited the pulmonology clinic at a tertiary hospital between October 2022 and March 2023 and had their KL-6 levels measured. The cohort was predominantly male (97.3%) and the median age was 77.1.

Data collected from electronic medical records included demographic information such as age, sex and body mass index, as well as details on comorbidities, smoking status, the modified Medical Research Council (mMRC) dyspnea scale and use of antifibrotic medications such as Esbriet (pirfenidone) and (Ofev) nintedanib.

The study also analyzed pulmonary function tests and chest CT scans, including low-dose chest CT and high-resolution CT performed within six months of serum KL-6 sampling. The team analyzed key spirometric parameters, including forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide.

According to Song, the ILA group had much lower levels of KL-6 compared with the ILD group. They concluded that the association between higher KL-6 levels and reduced forced vital capacity percentage underlines the biomarker’s potential in differentiating between ILD requiring intervention and less severe abnormalities.

Based on the findings, Song believes clinicians should consider incorporating KL-6 assessments into the diagnostic process for patients with suspected ILD to improve early detection and management strategies, though he noted further research is warranted to establish standardized protocols for KL-6 testing in clinical settings.