5.2. Procollagen propeptide markers and other disease activity markers in sarcoidosis and fibrosing alveolitis (I, II)

In the sarcoidosis group, there was no correlation between S-PIIINP and BALF-PIIINP or S-PICP and BALF-PICP, while BALF-PICP and BALF-PIIINP correlated significantly (see Fig. 1 in paper I). Neither BALF-PIIINP nor BALF-PICP correlated with FVC or the specific diffusion coefficient. BALF-PIIINP correlated well with S-ACE, S-IL-2R, BALF-albumin and BALF-lymphocytes (see Fig. 1 in paper I), while BALF-PICP correlated only with BALF-lymphocytes and BALF-albumin and not with S-ACE or S-IL-2R. In the control group, the serum and BALF values of the procollagen markers did not correlate with each other, nor was there any correlation between these markers and BALF-albumin or lymphocytes.

Twenty of the 60 sarcoidosis patients with parenchymal sarcoidosis had higher S-ACE and BALF-PIIINP than the remaining 40 patients with non-parenchymal disease. There was no significant difference in S-IL-2R, S-PIIINP, S- and BALF-PICP, BALF-albumin or BALF-lymphocytes between these groups (Table 7).

Forty-five of the 60 patients had prominent symptoms typical of sarcoidosis. BALF-PIIINP, BALF- PICP (see Table 4 in paper I), S-PIIINP and S-IL-2R (p=0.001, not shown) showed a tendency to increase in symptomatic disease. When the symptomatic patients were subdivided into ones with parenchymal and non-parenchymal disease, a tendency for the highest BALF-PIIINP and PICP values was observed in the groups of symptomatic patients with parenchymal disease (see Table 4 in paper I). Furthermore, S-PIIINP was significantly higher in symptomatic than non-symptomatic non-parenchymal sarcoidosis (symptomatic 3.77 ± 0.96µgL^-1, non-symptomatic 2.89 ± 0.77µgL^-1, p<0.01, not shown). Lung function data did not differ significantly between non-parenchymal and parenchymal disease, nor between symptomatic and non-symptomatic patients with and without parenchymal changes (see Table 5 in paper I). Significantly higher levels of ­PIIINP were seen in the BALF samples which contained the highest percentage of mast cells (see Table 6 in paper I).

In fibrosing alveolitis, BALF-PICP (r = -0.65, p < 0.01) and ELF-PICP (r = -0.59, p < 0.05), but not BALF- or ELF-PIIINP, had a significant negative correlation with DLCO/VA. The levels of PIIINP or PICP in BALF or ELF did not correlate with FVC. Nor did the levels of S-PIIINP and S-PICP correlate with those in BALF or ELF. The concentrations of PIIINP and PICP in BALF correlated significantly with each other (r = 0.60, p < 0.01).

During the follow-up period of six years, 7/18 patients died of fibrosing alveolitis, 3 of malignancy and 1 of an unknown cause. Detectable BALF-PIIINP had no prognostic significance if all the deaths were included, but predicted a poor prognosis in fibrosing ­alveolitis (Table 8, Table 9.). Diffusion capacity, when assessed either in absolute or percentage values, was lower in the patients who died of pulmonary fibrosis (4.24 ± 1.3 mmol/min/kPa, 64.0 ± 8.3 %) than in those who survived (5.81 ± 2.0 mmol/min/kPa, 85.7 ± 26.3 (p<0.05 Mann-Whitney U-test). The specific diffusion coefficient did not reveal any statistical differences between the two groups.