Possible Serological Markers to Predict Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Abstract

Background and objectives: Idiopathic pulmonary fibrosis (IPF) has a particularly poor prognosis, and most IPF-related deaths are due to acute exacerbation (AE) of this condition. Few reports about biomarkers to predict prognosis of AE-IPF have been published since the release of the new AE-IPF criteria in 2016. The present study investigated relationships between serological markers and in-hospital mortality after the onset of AE-IPF. Methods: Demographic, serological, and imaging data from patients hospitalized at the Maebashi Red Cross Hospital (Gunma, Japan) between 1 January 2013, and 31 December 2017, were retrospectively reviewed. Subjects fulfilling the diagnostic criteria for AE-IPF were divided into those who survived or died; statistical analysis of risk factors was performed using data from these two groups. Results: Diagnostic criteria for AE-IPF were fulfilled by 84 patients (59 males (70.2%)), with a median age of 78 years (range, 56–95 years). IPF was diagnosed before hospitalization in 50 (59.5%) patients and 38 (45.2%) died in hospital. Among the serological markers at hospitalization in the deceased group, C-reactive protein (CRP) was significantly higher than in the survivor group (p = 0.002), while total serum protein (p = 0.031), albumin (p = 0.047) and total cholesterol (p = 0.039) were significantly lower. Cox hazard analysis of factors predicting mortality, corrected for age, sex and BMI, revealed the following: CRP (hazard ratio (HR) 1.080 (95% confidence interval (CI) 1.022–1.141); p = 0.006), LDH (HR 1.003 (95% CI 1.000–1.006); p = 0.037), and total cholesterol (HR 0.985 (95% CI 0.972–0.997); p = 0.018). Conclusions: Our data suggest that CRP, LDH, and total cholesterol may be biomarkers predicting mortality in patients with AE-IPF. However, only prospective controlled studies can confirm or not our observation as a generalizable one.

Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

“…Comparisons of categorical data between the pirfenidone and nintedanib groups were performed using Fisher’s exact test. Continuous variables were analyzed using the Mann–Whitney U test and denoted by the median (maximum and minimum) [ 18 , 19 ]. Survival time was analyzed using the Kaplan–Meier method and compared between groups using the log-rank test.…”

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

“…The impaired synthesis of phospholipids and cholesterol affects the lung surfactant synthesis and alveolar homeostasis by disrupting the epithelial barrier integrity and promoting fibrogenesis [ 184 ]. Increased levels of lipids and plasmatic cholesterol have been linked to disease acute exacerbation and high mortality in IPF subjects [ 185 ]. In this regard, mitochondrial MFN1 and MFN2 play a crucial role in regulating lipids and cholesterol production and their knockdown affect lipid synthesis in AEC2 cells and exacerbates bleomycin-induced lung fibrosis [ 184 ].…”

Incidence and predictors of idiopathic pulmonary fibrosis complicating Type 2 diabetes: the Fremantle Diabetes Study Phase I

“…A high baseline total serum cholesterol appeared protective against the development of IPF in our participants with Type 2 diabetes. Consistent with this observation, a Japanese study showed that the total serum cholesterol was a negative associate of acute IPF exacerbations and mortality 13 . The positive relationship between age at diabetes diagnosis and IPF may represent a healthy survivor effect, with younger adults who develop diabetes being susceptible to cardiovascular death before reaching the older age groups in which the risk of IPF is relatively high 11 .…”