Hyaluronan and procollagen type III aminoterminal peptide in serum and bronchoalveolar lavage fluid from patients with pulmonary fibrosis

Previous studies of the collagen synthesis markers hyaluronan (hyaluronic acid) (HA) and procollagen type III aminoterminal peptide (PIIINP) in pulmonary fibrosis have reported elevated levels in bronchoalveolar lavage fluid (BALF) and suggested an association with disease activity. The objective of the present study was to evaluate whether HA and PIIINP in BALF and serum (S) correlated with paraclinical markers of disease activity (chest X-ray profusion score, pulmonary function tests (FEV(1), FVC, TLC, DLCO)) in patients with pulmonary fibrosis. The material comprised 27 patients with biopsy-proven pulmonary fibrosis (12 cryptogenic and 15 due to connective tissue diseases) and 24 control subjects with normal lung function. BAL was performed in the right middle lobe with 250 mi saline. HA and PIIINP were measured in the cell-free BALF supernatant and in serum. Patients had higher BALF-HA (mean 86+/-17 (SEM) mu g/l) than controls (39+/-2 mu g/l (p<0.01)), higher BALF-albumin (124+/-24 mg/l) than controls (58+/-4 mg/l (p<0.01)) and higher BALF/S-HA ratio (2.4+/-0.6) than controls (1.2+/-0.6 (p<0.05)). There were no significant differences respecting BALF-PIIINP, S-HA, or S-PIIINP. Patients (n=14) with progressive disease had higher BALF-HA, higher BALF-albumin, higher S-PIIINP, and higher S-immunoglobulins than those with stable disease, but the differences did not reach statistical significance. Smokers (n=18) had lower BALF-HA, lower S-HA, lower S-PIIINP, lower S-immunoglobulins, and higher lung function tests than non-smokers, but the differences did not reach statistical significance. In patients, significantly positive correlations were found between BALF-HA and BALF-albumin, between BALF-PIIINP and BALF-albumin, and a significantly negative correlation between S-PIIINP and TLC. None of the BALF or serum markers correlated with chest X-ray profusion score or any of the other lung function measurements. It is concluded that disease activity may be associated with elevated HA and PIIINP levels. Smoking may influence the immunological processes in pulmonary fibrosis and may be a confounder in studies of these patients.