[Systematic review and Meta-analysis of efficacy and safety of Bidouyan Oral Liquid in treatment of rhinosinusitis].

This study aimed to systematically review the efficacy and safety of Bidouyan Oral Liquid in the treatment of rhinosinu-sitis(RS). CNKI, Wanfang, SinoMed, VIP, Cochrane Library, PubMed, EMbase, Web of Science, and Ovid were searched for the randomized controlled trial(RCT) of Bidouyan Oral Liquid for the treatment of RS patients. Moreover, the reference lists and the grey literature were searched manually. Two researchers independently screened the literature and extracted data. The Cochrane collaboration's tool for assessing risk of bias(RoB 2.0) in randomized trial was used to assess the methodological quality of the included stu-dies. Meta-analysis was performed in RevMan 5.3 and Stata 12.0, and the grades of recommendation, assessment, development and evaluation(GRADE) was employed to evaluate the quality of evidence. A total of 54 RCTs(35 with drug combinations and 19 with single drugs) comprising 7 511 patients(3 973 in the observation group and 3 538 in the control group) were included. Meta-analysis showed that Bidouyan Oral Liquid + conventional treatment was superior to conventional treatment alone in increasing the total response rate(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01) and decreasing the Lund-Kennedy scores(MD=-1.94, 95%CI[-2.61,-1.26], P<0.000 01), Lund-Mackay scores(MD=-2.14, 95%CI[-2.98,-1.31], P<0.000 01), and visual analogue scale(VAS) scores(MD_(total VAS scores)=-1.28, 95%CI[-1.56,-1.01], P<0.000 01; MD_(nasal congestion VAS scores)=-0.58, 95%CI[-0.89,-0.27], P=0.000 2; MD_(runny nose VAS scores)=-0.61, 95%CI[-0.93,-0.29], P=0.000 2; MD_(olfactory dysfunction VAS scores)=-0.43, 95%CI[-0.52,-0.34], P<0.000 01; MD_(head and facial pain VAS scores)=-0.41, 95%CI[-0.57,-0.26], P<0.000 01). Furthermore, the combined treatment outperformed conventional treatment alone in improving the mucociliary transport rate(MTR)(MD=1.64, 95%CI[1.08, 2.20], P<0.000 01) and lowering the levels of inflammatory cytokines{tumor necrosis factor-α(TNF-α)(SMD=-1.95, 95%CI[-2.57,-1.33], P<0.000 01), interleukin-6(IL-6)(SMD=-2.64, 95%CI[-4.08,-1.21], P=0.000 3)} in RS patients. In addition, the combined treatment did not increase the incidence of adverse reactions(RR=0.83, 95%CI[0.44, 1.57], P=0.57). Bidouyan Oral Liquid was superior to conventional treatment in increasing total response rate(RR=1.25, 95%CI[1.18, 1.32], P<0.000 01), decreasing the Lund-Kennedy(P<0.01) and Lund-Mackay scores(P<0.05), alleviating major symptoms(P_(total VAS scores)<0.01; P_(nasal congestion VAS scores)<0.01; P_(runny nose VAS scores)<0.01; P_(olfactory dysfunction VAS scores)<0.05; P_(head and facial pain VAS scores)<0.01), and decreasing adverse reactions(P=0.03). The results showed that either Bidouyan Oral Liquid or Bidouyan Oral Liquid + conventional treatment can increase the total response rate, decrease the Lund-Kennedy and Lund-Mackay scores, and mitigate major symptoms. In addition, Bidouyan Oral Liquid + conventional treatment improved MTR and reduced the expression of TNF-α and IL-6 without causing serious adverse events. However, due to the limited methodological quality of the included studies, large-sample and high-quality RCTs are needed to provide evidence support.

Macrophages in CRSwNP: Do they deserve more attention?

Chronic rhinosinusitis (CRS) represents a heterogeneous disorder primarily characterized by the persistent inflammation of the nasal cavity and paranasal sinuses. The subtype known as chronic rhinosinusitis with nasal polyposis (CRSwNP) is distinguished by a significantly elevated recurrence rate and augmented challenges in the management of nasal polyps. The pathogenesis underlying this subtype remains incompletely understood. Macrophages play a crucial role in mediating the immune system's response to inflammatory stimuli. These cells exhibit remarkable plasticity and heterogeneity, differentiating into either the pro-inflammatory M1 phenotype or the anti-inflammatory and reparative M2 phenotype depending on the surrounding microenvironment. In CRSwNP, macrophages demonstrate reduced production of Interleukin 10 (IL-10), compromised phagocytic activity, and decreased autophagy. Dysregulation of pro-resolving mediators may occur during the inflammatory resolution process, which could potentially hinder the adequate functioning of anti-inflammatory macrophages in facilitating resolution. Collectively, these factors may contribute to the prolonged inflammation observed in CRSwNP. Additionally, macrophages may enhance fibrin cross-linking through the release of factor XIII-A (FAXIII), promoting fibrin deposition and plasma protein retention. Macrophages also modulate vascular permeability by releasing Vascular endothelial growth factor (VEGF). Moreover, they may disrupt the balance between Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), which favors extracellular matrix (ECM) degradation, edema formation, and pseudocyst development. Accumulating evidence suggests a close association between macrophage infiltration and CRSwNP; however, the precise mechanisms underlying this relationship warrant further investigation. In different subtypes of CRSwNP, different macrophage phenotypic aggregations trigger different types of inflammatory features. Increasing evidence suggests that macrophage infiltration is closely associated with CRSwNP, but the mechanism and the relationship between macrophage typing and CRSwNP endophenotyping remain to be further explored. This review discusses the role of different types of macrophages in the pathogenesis of different types of CRSwNP and their contribution to polyp formation, in the hope that a better understanding of the role of macrophages in specific CRSwNP will contribute to a precise and individualized understanding of the disease.