Fibrinolytic system related to pulmonary arterial pressure and lung function of patients with idiopathic pulmonary fibrosis.

OBJECTIVES AND AIMS

To investigate urokinase-(uPA) and tissue-type (tPA) plasminogen activator and plasminogen activator inhibitor type-1 (PAI-1) levels in patients with idiopathic pulmonary fibrosis (IPF) and to determine the relationship between fibrinolytic system and pulmonary arterial pressure and pulmonary function.

METHODS

Seventy-nine patients with IPF were included. Bronchoalveolar lavage fluid (BALF) and blood samples were collected. The concentrations of tPA, uPA and PAI-1 were measured using enzyme-linked immunosorbent assay. Doppler echocardiography was used to detect tricuspid regurgitation pressure gradient (TRPG) to estimate pulmonary arterial pressure.

RESULTS

BALF tPA elevated (P < 0.005), circulatory PAI-1 decreased (P = 0.05) and the ratio of uPA and PAI-1 decreased (P = 0.01) in BALF in IPF patients with pulmonary hypertension (PH) compared to those without PH. Positive linear correlations were found: BALF tPA and TRPG (r = 0.558, P = 0.013); the predicted percentage of diffusion capacity of lung for carbon monoxide adjustments for alveolar volume and BALF uPA (r = 0.319, P = 0.035). Negative linear correlations were as follows: BALF PAI-1 and the predicted percentage of VC (r = -0.325, P = 0.020), or total lung capacity (r = -0.312, P = 0.033); circulatory PAI-1 and TRPG (r = -0.697, P = 0.003).

CONCLUSIONS

The change of alveolar fibrolytic system in IPF, especially the uPA reduction and the PAI-1elevation, contributes to the deterioration of lung function. During the lung injury initiating fibrosis, tPA and PAI-1 might be leaked out of the pulmonary capillaries into alveoli, resulting in their elevation in alveoli and reduction in circulation, and finally contributing to the development of PH in IPF.