Electromagnetic navigation bronchoscopy-guided microwave ablation in patients with multiple bilateral pulmonary nodules

Abstract

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has long posed challenges in clinical practice, lacking established preventive and therapeutic approaches. Lianhua Qingke (LHQK), a patented traditional Chinese medicine (TCM), has been found to have anti-inflammatory effects for ameliorating ALI/ARDS induced by lipopolysaccharide (LPS). This study aimed to investigate the effects and potential mechanisms of LHQK on endothelial protection in LPS-induced ALI/ARDS in vivo and in LPS-induced human pulmonary microvascular endothelial cells (HPMECs) injury in vitro.

Methods: In the animal experiment, we induced an ALI/ARDS model by intratracheal injection of LPS (5 mg/mL). LHQK (3.7 g/kg/d for low dose and 7.4 g/kg/d for high dose) or dexamethasone (DEX) (5 mg/kg/d) was administered to mice 3 days prior to LPS treatment. In the in vitro experiments, HPMECs were pretreated with LHQK at concentrations of 125 and 250 µg/mL for 2 hours before being stimulated with LPS (10 µg/mL). We employed lung function test, measurement of lung index, hematoxylin and eosin (H&E) staining, bronchoalveolar lavage fluid (BALF) cell counts, and inflammatory cytokine levels to assess the therapeutic effect of LHQK. Additionally, the extravasation assay of fluorescein isothiocyanate-dextran (FITC-dextran) dye and the transmembrane electrical resistance (TEER) assay were used to evaluate endothelial barrier. Barrier integrity and relevant protein validation were assessed using immunofluorescence (IF) and Western blot analyses. Furthermore, network pharmacology analysis and cellular level screening were employed to predict and screen the active ingredients of LHQK.

Results: Compared to the LPS group, LHQK significantly improved lung function, mitigated lung pathological injuries, reduced inflammatory cells and inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] levels in BALF, and inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), attenuated LPS-induced pulmonary oedema and FITC-dextran permeability, and enhanced the expression of vascular endothelial-cadherin (VE-cadherin) and occludin. In vitro, LHQK attenuated LPS-induced HPMECs injury by elevating TEER values and enhancing VE-cadherin and occludin protein levels. Finally, network pharmacology analysis and cellular level validation identified potential active ingredients of LHQK.

Conclusions: In summary, LHQK can mitigate LPS-induced inflammatory infiltration, pulmonary edema, and pulmonary vascular endothelial barrier dysfunction in the context of ALI/ARDS. This is achieved by decreasing the levels of VCAM-1, and increasing the expression levels of barrier-associated junctions, such as VE-cadherin and occludin. Consequently, LHQK exhibits promising therapeutic potential in preventing the progression of ALI/ARDS.

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Key findings

• The use of electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) is safe and efficacy in treating patients with multiple bilateral ground-glass opacities (GGOs).

• The combination of ENB-guided MWA and video-assisted thoracoscopic surgery (VATS) exhibits advantages over bilateral surgical procedure in certain cases.

What is known and what is new?

• ENB-guided MWA has become a proven therapeutic strategy in treating GGOs, which is recommended for patients with poor pulmonary function.

• The combination of ENB-guided MWA and VATS provided a potential for treatment optimization in patients with multiple bilateral GGOs.

What is the implication, and what should change now?

• Bilateral ENB-guided MWA is feasible in patients who cannot tolerate surgery, and VATS combined with ENB-guided MWA is safe and can also preserve as much pulmonary function as possible.