Chronic Rhinosinusitis (CRS) is a chronic inflammatory disease that occurs in the mucous of the nasal cavity and sinuses.1 The representative symptoms are nasal congestion, mucopurulent nasal discharge, headache, and loss of smell.2 CRS can be clinically classified into two phenotypes: Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).3 These two phenotypes exhibit different clinical features and intrinsic pathophysiological mechanisms, and CRSwNP is regarded to present more complex etiologies and poorer prognosis.2

In recent years, Endoscopic Sinus Surgery (ESS) has become the primary treatment modality for patients with CRSwNP who show inadequate responses to medical therapy, and its effectiveness and safety have garnered widespread acceptance.4 The primary objective of ESS is to eliminate permanent nasal and sinus lesions, restore nasal and sinus ventilation and drainage, reduce mucosal inflammation, and facilitate the recovery of mucosal glandular secretion and ciliary clearance function.5 Although ESS can effectively relieve symptoms and enhance patients’ quality of life, real-world studies have reported an increasing number of CRSwNP patients experiencing postoperative inflammatory relapses and recurrences, with recurrence rates ranging from approximately 10%–79%.5,6 Hence, investigating the risk factors for postoperative recurrence in CRSwNP and devising personalized and precise treatment strategies represent pressing challenges.

Metabolic Syndrome (MetS) is characterized by metabolic abnormalities, which include central obesity, elevated blood pressure, glucose intolerance, and dyslipidemia, with insulin resistance as a central underlying factor.7 The precise mechanisms responsible for MetS remain incompletely elucidated. Nevertheless, central obesity is acknowledged as a key component and an initiating factor for MetS. Central obesity can trigger insulin resistance, which, in turn, disrupts glucose and lipid metabolism, and leads to elevated blood pressure.8,9 Recently, the rising intake of surplus calories, decreased physical activity, and the adoption of unhealthy lifestyles have collectively led to an increased prevalence of MetS. Consequently, MetS has emerged as a growing global public health issue.10,11 According to estimates provided by the International Diabetes Federation, approximately 25% of the world’s population suffers from MetS, and the prevalence in China has reached 20%–35% and continues to increase.11 Previous studies found that MetS significantly increased the incidence of various diseases including asthma,12 psoriases,13 atopic dermatitis,14 and systemic lupus erythematosus,15 and was significantly associated with poor disease prognosis. However, our understanding of the role of MetS and its individual components in the pathophysiology of CRSwNP is currently lacking. The influence of MetS and its constituent factors on the risk of postoperative recurrence in CRSwNP patients remains uncertain. Further investigations are required to unravel potential connections and assess the impact of MetS on CRSwNP recurrence.

The primary objectives of this study were to examine the influence of MetS and its components on the risk of postoperative recurrence in CRSwNP patients and to explore other potential risk factors associated with postoperative recurrence.

Although ESS is widely acknowledged for its effectiveness and safety in managing CRSwNP, a considerable proportion of patients continue to grapple with recurrence. This challenge can be attributed to the intricate and not fully elucidated etiology of CRSwNP, compounded by the high degree of variability within the disease.19,20 Therefore, it is essential to conduct a comprehensive assessment of the clinical characteristics of CRSwNP within distinct patient populations and delve into the multiple factors that impact prognosis and the likelihood of postoperative recurrence. This approach facilitates the development of customized interventions and individualized treatment strategies. In this study, we aimed to examine the relationship between MetS and its individual components and the likelihood of postoperative recurrence in individuals with CRSwNP. Our results indicated a substantial link between MetS and an elevated risk of postoperative recurrence in CRSwNP patients, with the risk rising in tandem with an increasing number of MetS components. Furthermore, we identified coexisting allergic rhinitis as a potential risk factor for recurrence.

MetS has become a significant global health concern, affecting approximately 20%–30% of the population. Its impact on inflammatory diseases, cardiovascular diseases, and tumors is gaining considerable attention in terms of both pathogenesis and prognosis.21–24 Despite the increasing recognition of the impact of MetS on various diseases, there is a scarcity of research investigating its role in CRSwNP. Prior research has predominantly concentrated on investigating the relationship between specific components of MetS and the development of CRSwNP. For instance, Steele et al.25 established an elevated risk of CRS in overweight and obese individuals, while another study emphasized a significant association between diabetes mellitus and the incidence of CRSwNP. In this context, hyperglycemia was found to exacerbate olfactory dysfunction in CRS patients.26 Although these studies have shed light on the link between individual MetS components and CRS, the effects of MetS on the prognosis and postoperative recurrence of CRSwNP remain largely unexplored.

In our present study, we aim to underscore the previously underemphasized heightened risk of postoperative recurrence in CRSwNP patients with MetS. Furthermore, we investigate the correlation between the number of MetS components and the risk of recurrence. Our findings shed light on MetS and specific MetS components, such as overweight or obesity, hyperglycemia, and dyslipidemia, as factors linked to an increased risk of postoperative recurrence in CRSwNP. It is noteworthy that accumulating evidence indicates that recurrent CRSwNP is characterized by elevated infiltration of inflammatory cells, heightened levels of oxidative stress, and aggravated tissue remodeling.27 MetS comprises a constellation of metabolic abnormalities, including central obesity, hyperglycemia, dyslipidemia, and hypertension. These components collectively contribute to more complex pathogenic and prognostic effects.8,10 In our hypothesis, we suggest that MetS triggers multiple interlinked pathophysiological mechanisms that intensify both local and systemic inflammation and oxidative stress in CRSwNP. These processes subsequently facilitate the recurrence of CRSwNP following surgery. It is well-established that adipose tissue serves as a key endocrine organ, secreting various adipokines, growth factors, cytokines, and chemokines.28 Overweight and obesity have been shown to disrupt adipose tissue function, leading to the production of abnormal immune factors. This includes the activation of macrophages and dysregulation of their polarization, resulting in increased inflammation and significant tissue fibrosis.29 Research suggests that high lipid levels can activate the complement system and disrupt the innate immune response, leading to sustained chronic inflammation and structural remodeling of nasal mucosal tissue through epithelial-mesenchymal transformation.30–32 Dyslipidemia has also been significantly associated with inflammatory response status, oxidative stress levels, and pro-fibrotic processes, which play a role in the underlying mechanisms of recurrent CRSwNP.33 Moreover, chronic hyperglycemia can alter cellular energy metabolism and cause oxidative stress damage, leading to mucosal epithelial barrier dysfunction.34 Impaired barrier function allows pathogenic microorganisms to stimulate nasal mucosal epithelial cells to produce inflammatory mediators, activating and recruiting various immune and inflammatory cells, including eosinophils, thus triggering an inflammatory cascade, and exacerbating histopathological changes in CRSwNP.35,36 The expressions of systemic inflammation biomarkers, such as CRP, fibrinogen, IL-6, and TNF-α, were found to be enhanced in the serum of MetS patients.37 Among them, increased levels of TNF-α can induce the production of inflammatory cytokines, driving inflammation progression and exacerbating tissue remodeling in nasal mucosal tissue.38 Therefore, it is reasonable to MetS may play a role in the advancement and outlook of CRSwNP by means of multiple interconnected components. The cumulative impact of incorporating more components could potentially worsen the condition. Nonetheless, the precise mechanisms underpinning the connection between MetS and the postoperative recurrence of CRSwNP necessitate additional investigation and validation.

Furthermore, this study identified a significant association between the prevalence of allergic rhinitis and the recurrence of CRSwNP after surgery. Allergic rhinitis is frequently observed as a coexisting condition in CRSwNP and contributes to the persistent hyper-reactivity of the nasal cavity and sinus mucosa. This hyper-reactive state is characterized by ongoing swelling, heightened exudation, and reduced sinus openings, resulting in a hypoxic environment that promotes the colonization of viruses and bacteria.39–41 Eosinophils play a critical role in the development of allergic rhinitis and CRSwNP, and tissue eosinophilia is a characteristic feature of both conditions. Eosinophils can contribute to the aggravation of mucosal damage in the respiratory tract, triggering a robust inflammatory response.40,42 Moreover, tissue eosinophilia has been linked to more extensive disease in CRSwNP.43 The occurrence of an allergic response can stimulate the release of type 2 inflammatory mediators, including IL-4, IL-5, and IL-13, which promote the recruitment and activation of eosinophils, mast cells, and basophils, thereby inducing nasal eosinophilia.44 Furthermore, cells in the nasal and paranasal mucosa express surface molecules that attract inflammatory mediators and secrete inflammatory cytokines, creating a feedback loop.35 In CRSwNP patients, these adhesion molecules and chemotactic factors are abundantly expressed, potentially aggravate the pathogenesis of CRSwNP, and were believed to underlie the mechanism of allergic rhinitis-mediated CRSwNP recurrence in the context of allergic rhinitis.45

This study acknowledges several limitations. Firstly, the recruitment of patients solely from a single medical center in China introduces the possibility of selection bias, which limits the generalizability of the findings to a broader population. Secondly, due to the retrospective nature of the study, it is unable to establish a direct causal relationship between MetS and its components and the recurrence of CRSwNP. Lastly, there could be other unidentified or unmeasured factors that contribute to the risk of postoperative recurrence, such as tissue eosinophilia, which might lead to bias in this study.

This study represented the first, larger-scale investigation of the clinical features of CRSwNP patients with concurrent MetS. Our findings highlighted a possible connection between MetS and the risk of postoperative recurrence in CRSwNP, with the risk escalating as more MetS components were present. Moreover, we identified allergic rhinitis as a potential risk factor for CRSwNP recurrence. The incorporation of MetS as a novel indicator for postoperative prognostic assessment and risk stratification in CRSwNP patients appears to be clinically meaningful and promising. Nevertheless, to validate and strengthen our conclusions, further high-quality studies are needed.

Yu Chen contributed to the conception and design of the study. Tiansheng Wang and Yu Gao collected the clinical data and analyzed the data. Fengjun Wang analyzed the results and drafted and corrected the manuscript. All authors contributed to the article and approved the submitted version.

No funding.

The authors declare no conflicts of interest.