Decreased serum transforming growth factor-β1 concentration with aging is associated with the severity of emphysema in chronic obstructive pulmonary disease

Abstract

Aim: Age-associated changes of the lung might increase pathogenetic susceptibility to chronic obstructive pulmonary disease (COPD). Decrement in serum transforming growth factor (TGF)-β1 concentration is reported in elderly people. As impaired TGF-β1 signaling could cause emphysema-like changes, we hypothesized that decreased TGF-β1 with aging is correlated with emphysema.

Methods: Symptomatic patients with or without COPD and healthy normal subjects without COPD were recruited (COPD, n = 182; smoking controls, n = 73; normal, n = 26). We investigated the correlation between TGF-β1 and extent of emphysema and airway wall thickness, which were defined as the percentage of low-attenuation area (LAA%) and large airway wall area (WA%) on pulmonary high-resolution computed tomography, respectively. The correlation of pulmonary function test parameters and TGF-β1 was evaluated. TGF-β1 was determined by enzyme-linked immunosorbent assay.

Results: TGF-β1 significantly decreased with age (P = 0.0009). When the correlation between age and TGF-β1 was analyzed in each group, a significant inverse correlation was found in COPD patients and smoking controls (P = 0.0095 and 0.0132, respectively), whereas no correlation was observed in healthy older adults. Among COPD patients with severe emphysema, LAA% was inversely correlated with TGF-β1 (n = 89, P = 0.0104), whereas WA% and pulmonary function test parameters were not.

Conclusions: Although no correlation was found between TGF-β1 and the severity of COPD, TGF-β1 significantly decreased as emphysema became more severe. Age-related decrease of TGF-β1 in COPD might be associated with emphysematous alterations of the lungs in elderly subjects.

Keywords: aging; chronic obstructive pulmonary disease; emphysema; senescence; transforming growth factor-β1.