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Recent literature and our previous proteomic findings prompted us to study the coagulation system in idiopathic pulmonary fibrosis (IPF), the pathogenesis of which remains unclear. The aim of this study was to compare coagulation factors in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia (NSIP) patients and healthy controls. Thirty-three IPF patients (23 acute exacerbation and 10 stable IPF patients), 7 NSIP patients, and 44 controls were enrolled. Concentrations of D-dimer, homocysteine, functional protein C, protein C antigen, free and total protein S antigen and activity, fibrinogen and factor VIIIc were analyzed in serum of patients and controls. The lupus anticoagulant (LAC) test was also performed. Factor VIIIc levels were significantly higher in acute exacerbation IPF patients than controls ( p = 0.0001) and in stable IPF patients than controls ( p = 0.002). Factor VIIIc levels were higher and PT levels were lower in acute exacerbation IPF patients who died after exacerbation than in patients who survived ( p = 0.04 and p = 0.003, respectively). D-dimer, fibrinogen, and homocysteine levels were also significantly higher in IPF patients than controls ( p < 0.01). Protein C activity was increased in acute exacerbation IPF patients than controls ( p = 0.005). The LAC test was positive in seven IPF patients and negative in controls. Procoagulant status was demonstrated in IPF patients (mainly in acute exacerbation/IPF) than controls and NSIP patients, probably due to endothelial activation and microvascular injury. These preliminary results are of interest because of their potential implications in the pathogenesis and treatment of this disease. [ABSTRACT FROM AUTHOR]

Nonsteroid antiinflammatory drugs interfere with the diuretic activity of furosemide, implying that this effect is at least partially dependent on renal prostaglandin synthesis. To investigate whether prostaglandin production could also modulate the bronchial antireactive activity of this diuretic drug, we investigated the effect of inhaled lysine acetylsalicylate (162 mg) and of furosemide (18 mg), alone and in combination, on the bronchial obstructive response to ultrasonically nebulized water in asthmatic patients. The study was also prompted by the conflicting results obtained in previous studies of oral nonsteroid antiinflammatory drugs. Fifteen asthmatic patients underwent bronchial challenge with a mist of ultrasonically nebulized distilled water at the same time of day on four occasions, 2-4 days apart, 15 min after premedication according to a double-blind, randomized protocol. After placebo, mean PD15 to water mist did not differ from a preliminary test (2.1 ± 0.2 and 2.5 ± 0.4 ml, M ± SE, respectively). After lysine acetylsalicylate, mean PD15 rose to 5.0 ± 0.7 ml (2.8 ± 0.6 times higher than placebo); after furosemide: to 9.0 ± 1.5 ml (4.4 ± 0.9 times over placebo); and after the two drugs in combination, to 32.2 ± 5.6 ml (16.3 ± 3.0 times higher than placebo). Similar results were obtained with inhaled indomethacin, whereas sodium salicylate had no effect. These data indicate that the bronchial antireactive activity of inhaled furosemide is greatly enhanced by inhaled lysine acetylsalicylate through a mechanism which probably involves inhibition of the local synthesis of prostaglandins, and could have therapeutic implications. [ABSTRACT FROM AUTHOR]