Introduction and objectivesWe have recently studied platelet activation in idiopathic pulmonary fibrosis (IPF) and found that IPF patients exhibit a significant increase in platelet reactivity. This was demonstrated by an ADP (Adenosine diphosphate) concentration dependent increase in platelet-monocyte aggregates (PMA), platelet P-selectin expression, and platelet fibrinogen binding.1 We have suggested this may have a potentially important role in the initiation and/or progression of tissue injury in IPF.Systemic corticosteroid treatment may alter platelet adhesion, as seen with suppression of p-selectin expression in the spontaneously hypertensive rat.2 We hypothesised that peripherally deposited inhaled corticosteroid may have similar activity. In this study we evaluate the effect of beclomethasone/formoterol pMDI (B/F Fostair) on clinical parameters and biomarkers of platelet activation in IPF.MethodsTwenty non-smoking patients with IPF and no evidence of COPD were randomly assigned to either Fostair 100/6, 2puffs BD for 28 days or matched placebo inhaler. There was 28 days washout between crossover. Biomarkers, PMA, p-selectin and fibrinogen were measured at baseline and post treatment periods. Clinical outcomes of six minute walk (6MWT), spirometry, average daily activity over 7 days (Sense Wear) and Quality of life (KBILD) were also measured.Results17 patients (11 males, mean age 71.2 yrs) completed the study. Table 1 shows the 95% CI on differences between the baseline and two treatments on biomarkers of platelet adhesion obtained from ANOVA and using the Tukey post hoc test for multiple comparisons.Change from baseline spirometric measurements of FEV1(L), FEV/FVC,% pred FEF25–75 were significantly improved following 28 days B/F by (mean ±SD), 0.88 ± 0.16 L (p = 0.03), 0.03 ± 0.03 (p = 0.03), 12.4 ± 19.1% (p = 0.02) respectively when compared to placebo.There was no change in quality of life or exercise measures.Abstract S46 Table 1Values Δ AUC dose – response to ADP (0–10 μM )PlaceboFostairp-selectin expression (%) baseline−21.6, +140.6(p = 0.2)+5.8, +140.6(p = 0.03)*Platelet fibrinogen expression (%) baseline−136.0, +169.1(p = 1.0)−52.5, +252.6(p = 0.3)PMA (%) baseline−168.3, +92.4(p = 0.8)−116.7, +144.1(p = 1.0)ConclusionThe effects of B/F in this study may represent delivery of corticosteroid to the peripheral airways ameliorating local injury and altering platelet activation. Bronchodilation may represent an effect on the small airways in IPF. Whether these effects are important in disease progression remains to be established.References1 Crooks MG. PLoS One 2014;9(10):e111347. doi: 10.1371/journal.pone.0111347GG2 Susuki H. Leukoc Biol. 1995;57(1):20–6
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