Chronic obstructive pulmonary disease (COPD) is frequently accompanied by airway mucus plugs, which are closely associated with airflow obstruction, acute exacerbations, and increased mortality. However, whether mucus plugs contribute to secondary pulmonary fibrosis remains unclear. This single-center, prospective, case-control study aims to investigate the relationship between airway mucus plugs and lung fibrosis in patients with COPD undergoing lung cancer surgery.

During surgery, distal non-tumorous lung tissues and airway mucus will be collected for histological and molecular analyses. Mucus plug burden will be quantified using AB-PAS staining, and fibrosis will be assessed using Masson staining. Expression of epithelial-mesenchymal transition (EMT) markers, fibrotic markers, and the mechanosensitive ion channel Piezo1 will also be measured. COPD patients (FEV₁/FVC <0.70) will be compared with non-COPD surgical controls.

The study aims to clarify whether mucus plugs are associated with increased fibrosis and to explore the potential involvement of mechanical-signaling pathways, including Piezo1 activation. Findings may provide new clinical and pathological evidence for mucus-induced fibrotic remodeling in COPD and help identify novel therapeutic targets.

Inclusion Criteria:

• ① Age ≥ 18 years old;

  • Planned radical resection for lung cancer, with postoperative pathological diagnosis of primary lung cancer;

    • During surgery, non tumor lung tissue at a distance of ≥ 5 cm from the tumor edge can be obtained; ④ Case group: Preoperative pulmonary function examination confirmed diagnosis of COPD (FEV ₁/FVC<0.70); ⑤ Control group: Preoperative lung function was normal (FEV ₁/FVC ≥ 0.70), with no history of COPD; ⑥ The subjects are able to understand and sign the informed consent form

Exclusion Criteria:

• ① Clear presence of other interstitial lung diseases (ILD) or idiopathic pulmonary fibrosis before or during surgery （IPF）、 Fibrosis after pneumoconiosis or tuberculosis;

  • Active pulmonary infections (such as bacterial pneumonia, fungal infections, active tuberculosis);

    • Having received neoadjuvant radiotherapy or chemotherapy, which may affect the morphology or molecular results of distal lung tissue; ④ Combined severe immunodeficiency or long-term systemic immunosuppressive therapy (such as glucocorticoids ≥ 20 mg/d, More than 4 weeks);

      • Merge with other serious systemic diseases (such as advanced heart failure, end-stage renal disease), affecting study compliance or Survival expectation; ⑥ Pregnant or lactating women; ⑦ Refusing to sign the informed consent form or deemed unsuitable by the researcher to participate in the study.

The study population consists of adult patients undergoing lung cancer surgery at Zhongshan Hospital, Fudan University. Participants include two groups: (1) patients with chronic obstructive pulmonary disease (COPD), defined by a pre-operative post-bronchodilator FEV₁/FVC <0.70; and (2) non-COPD surgical controls with normal lung function. During clinically indicated lung cancer resection, distal non-tumorous lung tissue samples and airway mucus (if present) are collected without adding any additional surgical risk. All participants are ≥18 years old and able to provide informed consent.