Certain Blood Protein Levels May Predict Mortality Risk After Sudden Disease Worsening in IPF, Study Suggests

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Increased levels of specific proteins found in blood, namely C-reactive protein, lactate dehydrogenase, and total cholesterol, may predict the risk of mortality after acute exacerbation in idiopathic pulmonary fibrosis (IPF) patients, according to a retrospective study performed in Japan.

The study, “Possible Serological Markers to Predict Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis,” was published in the journal Medicina.

IPF is the most common type of interstitial lung disease, in which chronic inflammation of the air sacks and neighboring tissues leads to the formation and accumulation of scar tissue (fibrosis) in the lung. When the fibrosis cause is unknown, it’s referred to as idiopathic.  

Researchers estimate that acute worsening (exacerbation) of the disease increases the patient mortality rate from 40% to 80%.

Few studies have explored the relationship between biomarkers and acute exacerbations in IPF, so a Japanese research team set out to evaluate several IPF markers in the blood and their potential association with disease worsening.

The team measured proteins whose levels have been linked to IPF, such as C-reactive protein (CRP) and lactate dehydrogenase (LDH) — as their high levels suggest ongoing active inflammation and tissue damage  — and surfactant proteins A and D.

The researchers performed a retrospective analysis of a group of patients with IPF and acute exacerbation admitted to the Maebashi Red Cross Hospital in Gunma, Japan, between January 2013 and December 2017.

A total of 84 patients were included in the study. The median age of the group was 78 years old, and 70.2% were male. Around 60% of the patients were diagnosed with IPF before being admitted to the hospital. Despite the diagnosis, the majority of these patients (66%) remained untreated prior to hospitalization.

Patients were hospitalized for a median of 25 days, and 45.2% of them died in the hospital.

For the analysis, the researchers divided the patients into two groups: those who died (deceased), and those who survived (survivors) after acute disease worsening. The team found no significant differences between the groups in terms of sex, age, body mass index, smoking, or alcohol consumption.

The levels of CRP were significantly higher in the deceased group (11.57 milligrams per deciliter) compared with the survivor group (6.69 mg/dL).

In contrast, serum total protein, albumin, and total cholesterol were significantly lower in the deceased group compared with the survivor group.

Although the levels of surfactant protein A tended to be higher in the deceased group — 124.2 vs 91.2 mg/dL — the difference was not statistically significant. Similarly, the levels of surfactant protein D were not different between the two patient groups.

After correcting the results for age, sex, and body mass index, the researchers observed that the levels of CRP, LDH, and total cholesterol predicted the risk of mortality. Stratification of patients according to the levels of CRP and cholesterol revealed that those with low total cholesterol and high CRP had poorer prognosis.

Overall, “our data suggest that CRP, LDH, and total cholesterol may be biomarkers predicting mortality in patients with AE [acute exacerbation]-IPF,” the researchers wrote.

“However, only prospective controlled studies can confirm or not our observation as a generalizable one,” they added.

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