6.5. PIIINP and PICP as possible markers of disease activity and prognosis in sarcoidosis, fibrosing alveolitis and asbestos-related lung diseases (I-III)

The activity of sarcoidosis is difficult to assess, and only clinical findings, chest radiographs and pulmonary function tests have been suggested to be relevant markers, although several other markers have been widely investigated (Costabel et al. 1994). This is the case even with fibrosing alveolitis. There is some evidence of a correlation between serum and BALF-PIIINP with other suggested markers of disease activity in sarcoidosis and fibrosing alveolitis although the results diverge.

The present study on sarcoidosis revealed no correlation between BALF-PICP or BALF-PIIINP and pulmonary function tests or diffusion capacity or specific diffusion coefficient. BALF-PIIINP correlated well with S-ACE, S-IL-2R, BALF-albumin, and BALF-lymphocytes. BALF-PICP correlated with BALF-PIIINP. The patients with the highest counts of mast cells in their BALF also had higher PIIINP and PICP in BALF, and symptomatic patients had higher PIIINP and PICP levels in BALF than non-symptomatic ones, suggesting that BALF-PIIINP and –PICP may correlate with disease activity. In addition, the patients with parenchymal involvement in chest radiographs had significantly higher S-ACE and BALF-and ELF-PIIINP, suggesting an active form of the disease. The average level of BALF-PICP was slightly but not significantly higher in the parenchymal than the non-parenchymal sarcoidosis group. In previous studies, serum ­PIIINP has been shown to correlate with serum ACE (Luisetti et al 1990, Schoenfeld et al. 1996), but not with ⁶⁷Ga uptake, BALF-lymphocytes, vital capacity or diffusion capacity (Luisetti et al. 1990). On the contrary, S-PIIINP has correlated with parameters of restriction estimated in terms of vital capacity and total lung capacity (Schoenfeld et al. 1996). The level of serum PIIINP has been higher in progressive sarcoidosis than inactive disease in serial measurements (Pohl et al. 1992). On the other hand, some other studies have failed to show any correlation between S-PIIINP and sarcoidosis activity (Low et al. 1983, Poole et al. 1989, Milman et al. 1995). BALF-PIIINP has been observed to correlate inversely with vital capacity, forced expiratory volume and diffusion capacity, and it has been related to pulmonary radiological findings, serum ACE and mast cells but not to other cells in BALF (Bjermer et al. 1986, Bjermer et al. 1987b) as well as with sarcoidosis changes in bronchial biopsies (Bjermer et al. 1991). In the latter study, BALF-PIIINP also correlated with a poor clinical course. On the other hand, in a follow-up study of 12 months the initial BALF-PIIINP did not predict the severity of the disease assessed with lung function testing (O’Connor et al. 1989). BALF-PICP and PIIINP were associated with BALF-lymphocytes and the patients with advanced parenchymal changes had elevated levels of PICP and PIIINP in BALF (Tukiainen et al. 1994).

The present study, where BALF- and ELF-PICP but not BALF/ELF PIIINP had a significant inverse correlation with DLCO/VA, suggests a process affecting the air-blood barrier in the lungs in fibrosing alveolitis. Detectable BALF-PIIINP and decreased diffusion capacity predicted poor prognosis in a follow-up of six years. In previous studies on fibrosing alveolitis, serum PIIINP has been shown to correlate with disease activity estimated by clinical, radiological, and physiological scoring of disease severity (Low et al. 1992), although another study by the same author failed to reveal such correlation (Low et al. 1983). BALF-PIIINP has been suggested, together with elevated levels of eosinophils cationic protein in BALF, to discriminate between acute, progressive disease and stable disease (Fujimoto et al. 1995).

There are no previous data available of the role of procollagen propeptides in the prognosis of asbestos-exposed patients without pulmonary involvement at the time of diagnosis. Extreme experimental exposure with asbestos has led to an elevation of PIIINP in BALF and to the development of pulmonary fibrosis (Begin et al. 1987b, Begin et al. 1990). In the present study, despite the elevated BALF-PICP, none of the asbestos-exposed subjects developed asbestosis when assessed with chest radiography and diffusion capacity after a follow-up of seven years.

According to the present data, neither serum PIIINP or PICP seems to have any role in estimating the activity or prognosis of sarcoidosis, fibrosing alveolitis and asbestos-related diseases. BALF-PIIINP predicted disease activity shown by chest radiographs in sarcoidosis and a poor prognosis in fibrosing alveolitis, whereas elevated BALF-PICP suggested a fibrosing process.