Integrated with single‐cell RNA sequencing analysis of COPD patients and pulmonary fibroblast–macrophage coculture system, our findings indicate that the upregulation of IL6‐AS1 in fibroblasts enhances the interaction between the S100A9 protein and the AGER and TLR4 receptors on lung macrophages, thereby exacerbating pulmonary inflammation. The gene discussed is AGER; the disease is chronic obstructive pulmonary disease.