Significance of elevated procollagen-III-peptide and transforming growth factor-beta levels of bronchoalveolar lavage fluids from idiopathic pulmonary fibrosis patients.

Although both procollagen III aminopeptide (P-III-P) and transforming growth factor-beta (TGF-beta) are reported to be present in lung tissue and/or elevated in bronchoalveolar lavage fluid (BALF) from idiopathic pulmonary fibrosis (IPF) patients, we have little knowledge concerning the clinical significance of elevated P-III-P and TGF-beta levels in BALF. Using a radioimmunoassay, we measured P-III-P and TGF-beta in BALF from 48 IPF patients (16F and 32M, 59 +/- 2 years, mean +/- S.E.) who received BAL in our clinic over the past 13 years before glucocorticosteroid treatment. Among them, we could detect a significant amount of P-III-P (2.2 +/- 1.0 U/ml; range 0.03 to 16.5 U/ml) in BALF in 18 of the patients (5F and 13M, 58 +/- 3 years) (group B). but not (0.03 U/ml or less) in the other 30 patients (11F and 19M, 59 +/- 2 years) (group A). Lymphocyte (%) and basophil (%) in BALF from group B was much larger than that from group A (33% vs. 8%, p < 0.01). Group B showed a longer duration of onset to BAL (36 months vs. 23 months, p < 0.05). TGF-beta levels were obtained using an ELISA system kit from the same BALF samples. TGF-beta was not detected in 10 patients (100 pg/ml or less) (3F and 7M, 59 +/- 4 years) (group I), while the remaining 38 patients showed a significant amount of TGF-beta (329 +/- 44 pg/ml, range 100 to 1,360 pg/ml). The latter patients were further divided into two groups; group II 100 to 300 pg/ml (10F and 14M, 56 +/- 3 years) and group III 350 or more (3F and 11M, 63 +/- 2 years). Group III showed significantly better values in PaO2, Aa-DO2, %VC and %DLco, and smaller percentage of basophils in BALF than did groups I and/or II, whereas survival after BAL in group III was significantly shorter than in group I (31 vs. 19 months, p < 0.05). There was no significant relationship between P-III-P and TGF-beta levels in BALF. These findings suggest that elevated P-III-P level is accompanied by an increase in lymphocyte population in BALF from IPF patients, resulting in a longer duration of the disease, while elevated TGF-beta level reflects alveolar inflammation at an earlier stage of the disease which induces a progression of the disease, resulting in a shorter survival in IPF patients.