Urinary fibrinopeptide-A as a predictive biomarker of exacerbation in asthma

Abstract

Background

Asthma is a prevalent and potentially life-threatening disease associated with exacerbation and costly hospital admissions. The coagulation cascade is up-regulated in severe asthma and increased fibrinogenesis in the airway may precede exacerbation in moderate asthma.

Objective

A longitudinal prospective study to test the hypothesis that levels of urinary fibrinopeptide A (FP-A), a marker of coagulation, increase prior to an exacerbation of asthma.

Methods

24 non-smoking participants with moderate to severe asthma were recruited and followed to exacerbation and to recovery for up to 8 weeks afterwards. Baseline measurements included spirometry, full blood count, atopic status and plasma markers of coagulation. Participants provided daily Peak Expiratory Flow (PEF) readings and three urine samples per week for analysis of FP-A, a specific marker of activation of coagulation. A novel method to concentrate urinary FP-A for immunodetection and quantification was developed. Participants were followed up until exacerbation, when baseline measurements were repeated, and monthly thereafter for 2 months or to recovery.

Measurements and main findings

17 participants exacerbated during the study. Significantly increased concentrations of plasma D-dimer (0.25(0.2–0.42) vs 0.21(0.12–0.29) μg FEU/ml, p = 0.02) were found at exacerbation. A peak in urinary FP-A concentration was detected on average 4.2 ± 2 days prior to exacerbation and was significantly (p < 0.05) higher than at exacerbation or 7 days later. Urinary FP-A concentrations correlated positively with time to recovery and negatively (p < 0.01) with IgE concentration.

Conclusion

FP-A is detectable in urine several days before the onset of an asthma exacerbation indicating disordered coagulation preceding asthma exacerbations.