FIBROBLAST CHEMOTACTIC RESPONSE ELICITED BY NATIVE BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH FIBROSING ALVEOLITIS

Background-In fibrosing alveolitis activation of lung fibroblasts is t he decisive event in the pathogenetic sequence leading to pulmonary fi brosis. Fibroblast stimulating activity was measured in bronchoalveola r lavage (BAL) fluid to assess its relationship to the activity of fib rosing alveolitis. Methods-Nine control subjects and 40 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic sclerosis (n = 18) were studied. All patients were followed up by lung function testing for a minimum o f six months (mean (SE) 13.3 (1.4) months). Twenty five patients recei ved immunosuppressive therapy and 15 refused. At the beginning of foll ow up BAL was performed and, as a possible indicator of fibroblast sti mulating mediators within the lungs, chemotactic migration of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden -type chambers and expressed as a percentage of the chemoattractant ef fect of 25 ng/ml platelet derived growth factor. The procollagen III p eptide level in BAL fluid served as a marker for collagen synthesis. R esults-Chemoattractant activity was elevated in the patients with idio pathic pulmonary fibrosis and systemic sclerosis compared with the con trol group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6% (4.0%). Chemoattractant activity was inversely correlated with total lung cap acity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Proc ollagen III peptide concentrations in BAL fluid and chemoattractant ac tivity were not significantly correlated. For further evaluation chemo attractant activity of 36% (mean value of controls +2 SD) was used to separate normal (<36%) from elevated (greater-than-or-equal-to 36%) ac tivity. At the end of follow up, untreated patients with high chemoatt ractant activity (greater-than-or-equal-to 36%) showed a significant r eduction of VC, TLC, and exercise arterial oxygen tension (PaO2) and a small decrease in carbon monoxide transfer factor (TLCO), whereas a s ignificant improvement in VC, TLC, and TLCO and a small increase of ex ercise PaO2 occurred in treated patients with high chemoattractant act ivity. Patients with low chemoattractant activity (<36%) showed no con sistent change in lung function measurements, irrespective of treatmen t. In contrast, lung function results and differential cell counts in BAL fluid failed to identify progressive disease. Conclusions-In patie nts with fibrosing alveolitis the chemoattractant activity of BAL flui d seems to be an independent indicator of lung fibroblast stimulating activity providing relevant information about disease activity, and ma y help to improve the clinical management of these patients.