Calprotectin May Be Biomarker of IPF Severity

Calprotectin may serve as a blood biomarker for disease severity in patients with idiopathic pulmonary fibrosis (IPF), a new study indicates.

Calprotectin blood levels are significantly higher in IPF patients and show a correlation with measures of lung function.

The study, “Serum calprotectin as new biomarker for disease severity in idiopathic pulmonary fibrosis: a cross-sectional study in two independent cohorts,” was published in the journal BMJ Open Respiratory Research.

Pulmonary function tests are the standard tools to assess disease progression in IPF. However, they have weaknesses, including variables among patients, poor sensitivity to change, and difficulties in acquisition. That is why alternative non-invasive biomarkers for the assessment of IPF severity and disease progression are urgently needed.

Calprotectin is a protein produced by immune cells called neutrophils, which are thought to contribute to IPF disease. This protein has been investigated as a biomarker and treatment target in various medical conditions, including disease activity in inflammatory bowel diseases.

A team led by researchers at the Bern University Hospital, in Switzerland, decided to investigate the association of calprotectin blood levels and disease severity in IPF patients with the goal of establishing a potential role of calprotectin as a biomarker for the disease.

The study included 26 healthy volunteers (mean age 47.6 years) and 26 Swiss IPF patients (mean age 69.6). To validate their findings, the team also analyzed an independent group of 66 Spanish patients with IPF (mean age 71.3) from the Bellvitge University Hospital in Barcelona.

Patients with IPF in the Swiss and Spanish groups had smoked longer compared to healthy controls, and presented poorer pulmonary function parameters.

Calprotectin blood levels were measured and compared between healthy volunteers and IPF patients. Several clinical parameters were assessed, including physiological predictors of PF to measure disease severity and survival.

These disease predictors included: forced vital capacity (FVC, a measure of the amount of air that is forcibly exhaled after taking the deepest breath possible); volume of air that can be blown out forcibly in one second (FEV1); diffusing capacity for carbon monoxide (DLCO, a measure of the lungs’ ability to transfer oxygen to the blood); and the composite physiologic index (CPI), to assess the combined effect of each individual predictor.

Calprotectin blood levels were found to be significantly higher in patients with IPF compared with healthy controls (2.47 vs. 0.97 micrograms/mL) and correlated with disease severity, as measured by DLCO and CPI, in both IPF groups. When adjusting the data for age and sex these results remained the same.

Also, in the Swiss group, patients with higher calprotectin blood levels (2.85 micrograms/mL or greater) had significantly worse survival — 6.1 times higher mortality risk. In the validation group, the highest calprotectin levels (3.78 micrograms/mL or greater) did not significantly discriminate long-term mortality (increased risk of 1.54 times).

“These findings suggest a potential role of calprotectin as a blood biomarker for disease severity in IPF”, they concluded.

The team noted that more studies are needed to confirm the findings and to reach definite conclusions regarding the relationship between calprotectin and IPF progression.