Abstract
BackgroundAsthma 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. ObjectiveA 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. Methods24 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 findings17 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. ConclusionFP-A is detectable in urine several days before the onset of an asthma exacerbation indicating disordered coagulation preceding asthma exacerbations.
Highlights
Asthma is a global health problem affecting 300 million people worldwide [1] and leading to 397,000 deaths per year [2]
We have previously demonstrated that severe asthma requiring high dose inhaled corticosteroid therapy is associated with a pro-fibrinogenic, anti-fibrinolytic environment in the airways [10] and fibrin formation in the airways of a patient with fatal asthma has been described [11]
Peak Expiratory Flow (PEF) values were compared between baseline and the average value for the 7-day period prior to exacerbation; the mean ( SD) baseline PEF was 304 ( 106) litres per minute, and this dropped to 281 ( 105) litres per minute in the week leading up to an exacerbation
Summary
Asthma is a global health problem affecting 300 million people worldwide [1] and leading to 397,000 deaths per year [2]. We have previously demonstrated that severe asthma requiring high dose inhaled corticosteroid therapy is associated with a pro-fibrinogenic, anti-fibrinolytic environment in the airways [10] and fibrin formation in the airways of a patient with fatal asthma has been described [11]. Both viral infection [12] and allergen exposure [13], major triggers of exacerbations, have been shown to activate the intrapulmonary coagulation cascade. Methods: 24 non-smoking participants with moderate to severe asthma were recruited and followed to exacer bation and to recovery for up to 8 weeks afterwards. Conclusion: FP-A is detectable in urine several days before the onset of an asthma exacerbation indicating disordered coagulation preceding asthma exacerbations
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