Circulating TGF-β and SMAD3 in relation to early fibrotic lung changes and pulmonary function in pulmonary tuberculosis: A prospective cohort study.

BACKGROUND

Early structural lung remodeling may develop during pulmonary tuberculosis (TB) treatment, but its relationship with circulating mediators of fibrotic signaling remains poorly characterized. We investigated circulating transforming growth factor-beta (TGF-β) and SMAD3 in relation to early radiological fibrotic changes and pulmonary function.

METHODS

In this prospective cohort study, 38 adults with newly diagnosed pulmonary TB completed two months of standard intensive-phase treatment. Serum TGF-β and SMAD3 were measured by ELISA, while radiological fibrosis severity and pulmonary function were assessed after the intensive phase. Between-group differences and associations with fibrosis severity were evaluated using appropriate parametric and non-parametric analyses.

RESULTS

Early radiological fibrotic changes were identified in 31/38 participants (81.6%). FVC and FEV1 were numerically lower with greater fibrosis severity, although overall between-group differences were not significant (p = 0.145 and p = 0.213, respectively). Fibrosis severity was inversely correlated with FVC (ρ = -0.388, p = 0.016) and FEV1 (ρ = -0.341, p = 0.036). Circulating TGF-β did not differ significantly across fibrosis categories (p = 0.179). In contrast, SMAD3 differed across categories (p = 0.035) and correlated with fibrosis severity (ρ = 0.483, p = 0.002); after Holm adjustment, only the no-fibrosis versus severe-fibrosis comparison remained significant (p = 0.025).

CONCLUSIONS

Circulating SMAD3, but not TGF-β, was associated with early radiological fibrosis severity during TB treatment. These findings support further longitudinal investigation of molecular changes accompanying post-TB pulmonary remodeling without establishing pathway activation or clinical biomarker utility.