Deposition of types I and III collagen is a typical feature in the development of pulmonary fibrosis. We assessed the propeptides of these procollagens as prognostic markers in 18 patients with fibrosing alveolitis. We analyzed the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) from samples of bronchoalveolar lavage fluid (BALF) and serum, and also estimated their concentrations in epithelial lining fluid (ELF) by the urea method. The level of PIIINP in serum (p < 0.05), BALF (p < 0.05), and ELF (p < 0.05), and the levels of PICP in BALF (p < 0.001) and ELF (p < 0.001) but not in serum, were significantly increased in the patients with fibrosing alveolitis as compared with 17 controls who had been investigated for minor respiratory symptoms. In the BALF and ELF of patients with fibrosing alveolitis, PICP but not PIIINP had significant negative correlations with the specific diffusion coefficient for carbon monoxide (DLCO/ VA). The amino-terminal propeptide of type III procollagen and the carboxy-terminal propeptide of type I procollagen in BALF correlated significantly with one another. During the follow-up period of 6 yr, seven of the 18 patients with fibrosing alveolitis died of the disease, 3 others died of malignancy, and one patient died from an unknown cause. DLCO (p < 0.05) differed significantly between the surviving patients and those who died of fibrosing alveolitis, and detectable PIIINP in BALF predicted death from fibrosing alveolitis (p = 0.05). In conclusion, these results show that PIIINP in BALF, ELF, and serum, and PICP in BALF and ELF, are increased in patients with fibrosing alveolitis. A high level of PICP in BALF, and especially in ELF, suggests a chronic process and increased synthesis of type I collagen in the lungs, whereas PIIINP in BALF and ELF suggests active disease and a poor prognosis.

Microarray studies have shown that matrilysin or matrix metalloproteinase (MMP)-7 is highly upregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF), but MMP-7 protein expression has not been systematically compared between IPF and other interstitial lung diseases. MMP-7 levels in bronchoalveolar lavage fluid (BALF) were compared to corresponding samples from nonspecific interstitial pneumonia (NSIP), sarcoidosis, and healthy controls. MMP-7 levels in the BALF were determined by ELISA and localization of MMP-7 in the lung tissue by immunohistochemistry. MMP-7 was similarly elevated in the BALF of all these disorders compared to healthy controls (p=0.007). Even control subjects with prolonged cough displayed a tendency towards elevated MMP-7 expression. There was a negative correlation between BALF MMP-7 levels and forced expiratory vital capacity (r=-0.348, p=0.02, n=42). In IPF lung, MMP-7 immunoreactivity appeared predominantly in the fibrotic parenchyma and arterial wall. In sarcoidosis and NSIP, prominent MMP-7 immunoreactivity was found in areas of inflammation. These results demonstrate that elevated BALF MMP-7 is not restricted to IPF alone but is also observed in other interstitial lung diseases and cannot be used as a differential diagnostic marker for IPF.

No single test is available to reliably assess the activity or prognosis of pulmonary sarcoidosis. In this study, we have evaluated two procollagen markers, aminoterminal propeptide of type III procollagen (PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) in serum and bronchoalveolar lavage fluid (BALF) and compared them to other disease markers of pulmonary sarcoidosis, such as serum level of angiotensin converting enzyme (S-ACE) or serum interleukin-2 receptor (S-IL-2R). Bronchoalveolar lavage was performed in 40 sarcoidosis patients without (stages 0-I) and 20 patients with lung parenchymal involvement (stages II-III), as well as in 17 controls. Serum (S)- and BALF-PIIINP and PICP, S-ACE, S-IL-2R, BALF-albumin, BALF-lymphocytes and mast cells were determined in these patients. BALF-PIIINP was clearly and S-PIIINP slightly elevated in sarcoidosis compared to the controls. Similarly BALF-PICP, but not S-PICP, was significantly higher in sarcoidosis. BALF-PIIINP, but not BALF-PICP correlated with S-ACE and S-IL-2R levels. Patients with lung parenchymal disease had higher S-ACE and BALF-PIIINP, but neither S-IL-2R, S-PIIINP nor S- or BALF-PICP were elevated. S-PIIINP and S-IL-2R but not S-ACE were higher in symptomatic than nonsymptomatic patients. Symptomatic patients with parenchymal disease had elevated BALF-PIIINP whereas in the symptomatic nonparenchymal group S-PIIINP was elevated. In conclusion, this is the first study to evaluate carboxyterminal propeptide of type I procollagen in sarcoidosis and showed elevated levels in bronchoalveolar lavage fluid. In contrast to the levels of bronchoalveolar lavage fluid aminoterminal propeptide of type III procollagen, levels of carboxyterminal propeptide of type I procollagen did not correlate with serum level of angiotensin converting enzyme and serum interleukin-2 receptor levels, suggesting that carboxyterminal propeptide of type I procollagen may be less suitable disease marker in sarcoidosis than aminoterminal propeptide of type III procollagen. However, the role of carboxyterminal propeptide of type I procollagen as an indicator of fibrogenesis must be further studied.

Neither esomeprazole treatment nor fundoplication diminishes airway responsiveness or exhaled NO, or improves FEV1 in patients with GORD. Improvements in respiratory symptoms and SGRQ scores after GORD treatments could be detected. However, as this was not a placebo-controlled study, the findings in these secondary endpoints should not be emphasised. ClinicalTrials.cov: NCT00994708.