title: Significance of elevated procollagen-III-peptide and transforming growth factor-beta levels of bronchoalveolar lavage fluids from idiopathic pulmonary fibrosis patients.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hiwatari
authors.forename: S
authors.initials: S
authors.lastname: Shimura
authors.forename: K
authors.initials: K
authors.lastname: Yamauchi
authors.forename: M
authors.initials: M
authors.lastname: Nara
authors.forename: W
authors.initials: W
authors.lastname: Hida
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000737:chemistry; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D011863:Radioimmunoassay; D012129:Respiratory Function Tests; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta; C041876:procollagen Type III-N-terminal peptide