KL-6 protein levels may predict symptom worsening in IPF: Study
Steady tracking could also help gauge acute exacerbations in other ILD types
Consistently tracking the levels of Krebs von den Lungen-6 (KL-6), a protein that can indicate lung inflammation or damage, may help predict acute exacerbations in people with idiopathic pulmonary fibrosis (IPF) and other types of fibrotic interstitial lung diseases (ILDs), a study reports.
Findings indicated that KL-6 levels tended to rise before an acute exacerbation of symptoms. Additionally, researchers found the risk of acute exacerbation, or sudden symptom worsening, was significantly increased in patients with persistently high KL-6 levels.
Based on these results, they argued that “physicians should consider longitudinal KL-6 measurements, as a component of a multifaceted approach to risk assessment,” adding that these “results should be validated in other settings.”
The study, “Longitudinal changes in KL6 levels predict acute exacerbation in fibrotic interstitial lung disease,” was published in Scientific Reports.
IPF and other ILDs cause lung tissue scarring
Fibrotic ILDs comprise IPF and other diseases that cause fibrosis, or scarring, of lung tissue. In IPF, the specific underlying causes of this scarring aren’t known. The resulting lung damage can lead to respiratory symptoms, including difficulty breathing, as well as fatigue.
Individuals with fibrotic ILDs may also experience acute exacerbations, which are a known risk factor for subsequent disease progression. Yet, “despite its clinical importance, no reliable markers have been established to predict future [acute exacerbations],” the researchers wrote.
KL-6 may play a role in lung scarring, making it a potentially useful marker of fibrotic ILD progression. In the present study, the researchers focused on assessing its usefulness in predicting acute exacerbations among a group of people with fibrotic ILDs.
To that end, they examined a database of patient medical records from more than 200 medical institutions in Japan. They limited their search to individuals who were diagnosed with fibrotic ILDs, received antifibrotic treatment, and whose blood KL-6 levels had been measured more than once since starting antifibrotic treatment.
After applying these criteria, they identified and selected a total of 939 patients to be included in the analyses. Of these, 312 (33%) had IPF. Others had ILD associated with diseases involving connective tissue, such as rheumatoid arthritis, or from unspecified causes.
During follow-up, each individual had between three and 170 visits in which KL-6 levels were measured. A total of 194 patients (21%) experienced an acute exacerbation during follow-up.
Analysis shows tie between changes in KL-6, acute exacerbation risk
Analyses revealed that patients who experienced acute exacerbations had higher levels of KL-6 over time compared with those who didn’t have exacerbations. This was more evident among patients with IPF than in those with ILD associated with connective tissue diseases.
The researchers also found that in the time before an acute exacerbation, KL-6 levels tended to increase slightly. There wasn’t a similar pattern among people who didn’t experience acute exacerbation regardless of disease type, with KL-6 levels remaining largely stable over time.
Physicians should be vigilant when observing an increasing trend in KL-6 or persistently elevated serum KL-6 values, as they may indicate prospective [acute exacerbation].
A statistical analysis also showed there was a strong relationship between changes in KL-6 over time and the risk of acute exacerbation. Specifically, the analysis revealed that the risk of an acute exacerbation increased by 54% each time KL-6 levels rose by 272 units per milliliter.
Combined, these findings suggest “physicians should be vigilant when observing an increasing trend in KL-6 or persistently elevated serum KL-6 values, as they may indicate prospective [acute exacerbation],” the team wrote.
While physicians may be able to use relative KL-6 levels in an individual patient over time to track the risk of an acute exacerbation, the study’s results don’t indicate an absolute KL-6 cutoff value that can be broadly adopted for that purpose, the team noted. Researchers also wrote that the findings will require external validation and cautioned against generalizing results too broadly beyond the Japanese patient population.
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