Proteomic biomarkers of long-term lung function decline in textile workers: a 35-year longitudinal study

BACKGROUND: Occupational exposures contribute significantly to obstructive lung disease among textile workers, but biomarkers associated with long-term lung function decline are not available. OBJECTIVES: To conduct a large-scale proteomic study to identify protein biomarkers associated with long-term decline in forced expiratory volume in one second (FEV₁). METHODS: The Shanghai Textile Workers Cohort (initiated in 1981; eight spirometry assessments over 35 years) underwent quantitative serum proteomics in 2016 for 453 workers. Associations between proteins and FEV₁ were examined using four models (cluster-based, restricted cubic spline, latent class mixed model, and mixed model for repeated measurements) and combined using the aggregated Cauchy association test (ACAT). External exploration used UK Biobank (UKB) proteomics and lung function trajectories, protein–protein interactions were assessed via STRING, and two-sample Mendelian randomization (MR) provided external causal validation. RESULTS: Of 907 analyzed proteins, 15 showed potential associations with long-term FEV₁ decline after FDR correction, including hemoglobin subunit beta (HBB; FDR-qACAT=0.040), alpha globin chain (HBA2; FDR-qACAT=0.045), and immunoglobulin subunits IGKV3-7 (FDR-qACAT=0.003) and Ig heavy chain variable regions (IgH; FDR-qACAT=0.011). In UKB, five proteins (ART3, RAB6A, LRRN1, ANGPTL7, BSG) were significantly associated with FEV₁ decline rate; STRING suggested links between RAB6A, LRRN1, BSG and proteins from the Shanghai cohort. MR indicated bidirectional associations between HBB and FEV₁ (FEV₁→HBB negative; HBB→FEV₁ positive; P<0.05). IMPACT: This largest and longest-followed occupational cohort proteomics study identified novel proteins associated with long-term FEV₁ decline that may enable risk identification and suggest potential therapeutic targets in occupational populations.

Mengsheng Zhao, Liangmin Wei, Longyao Zhang, Jingqing Hang, Fengying Zhang, Li Su, Hantao Wang, Ruyang Zhang, Feng Chen, David C. Christiani, Yongyue Wei