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. However, biomarkers associated with such declines are not available.

Objectives: We conducted a large-scale proteomic study to explore protein biomarkers potentially associated with long-term lung function decline.

Methods: Shanghai Textile Workers Cohort was established in 1981 with 35 years of follow-up, assessing textile workers' lung functions every five years. Quantitative serum proteomics was performed on all 453 workers at 2016 survey. We employed four distinct models to examine the association between forced expiratory volume in one second (FEV₁) and proteins, and consolidated the findings using an aggregated Cauchy association test. Furthermore, proteomic data of UK Biobank (UKB) was used to explore the associations of potential protein markers and decline of FEV₁, and the interactions of these proteins were examined through STRING database. Associations were also externally validated using two-sample Mendelian randomizations (MR).

Results: 15 of 907 analyzed proteins displayed potential associations with long-term FEV₁ decline, including two hemoglobin subunits: hemoglobin subunit beta (HBB, FDR-q_ACAT = 0.040), alpha globin chain (HBA2, FDR-q_ACAT = 0.045), and four immunoglobulin subunits: immunoglobulin kappa variable 3-7 (IGKV3-7, FDR-q_ACAT = 0.003), immunoglobulin heavy chain variable region (IgH, FDR-q_ACAT = 0.011). Five proteins were significantly associated with the rate of decline of FEV₁ in UKB, in which RAB6A, LRRN1, and BSG were also found to be associated with proteins identified in Shanghai Textile Workers Cohort using STRING database. MR indicated bidirectional associations between HBB and FEV₁ (P < 0.05), while different immunoglobulin subunits exhibited varying associations with FEV₁.

Impact statement: We performed a large-scale proteomic study of the longest-follow-up pulmonary function cohort of textile workers to date. We discovered multiple novel proteins associated with long-term decline of FEV₁ that have potential for identifying new biomarkers associated with long-term lung function decline among occupational populations, and may identify individuals at risk, as well as potential pharmaceutical targets for early intervention.