Rhinosinusitis is a prevalent condition that imposes a substantial global burden in terms of healthcare utilization and productivity reduction. Chronic rhinosinusitis (CRS) causes more significant impairment in quality of life than acute rhinosinusitis, affecting 5%–12% of the general population. Furthermore, it is linked to bronchial asthma, with a prevalence of 25% in patients with chronic rhinosinusitis, compared to 5% in the general population (1). Rhinosinusitis is marked by the presence of symptomatic inflammation in the nasal cavity and paranasal sinuses. CRS in adults is characterized by the presence of two or more symptoms, such as nasal obstruction, nasal discharge, facial pressure, and decreased sense of smell, with nasal obstruction or nasal discharge being one of the symptoms for a duration of more than 12 weeks (2). The diagnosis of CRS can be supported by the utilization of nasal endoscopy and computed tomography (CT) scanning, with either one of them serving as a prerequisite for diagnosis. However, compared to clinical symptoms, endoscopic examinations, and imaging techniques, biomarkers are more objective, quantitative, and indicative of the underlying pathophysiology (3).

Prior to 2020, the differentiation of CRS subtypes was primarily based on clinical observations (4), emphasizing phenotypes, which refers to observable differences without a direct connection to the disease process (4), rather than focusing on the underlying histopathology or serum markers. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) group has opted to shift towards the endotype of CRS, which refers to distinct disease entities that may occur in clusters of phenotypes, but each defined by a specific biological mechanism (4). They chose to categorize CRS as primary and secondary, and further divide each into localized (unilateral) or diffuse (bilateral) based on the anatomical distribution. Most notably, both groups can be further classified into type 2 or non-type 2 disease based on endotype dominance. Primary localized CRS is then subdivided into two phenotypes: allergic fungal rhinosinusitis (AFRS) or isolated sinusitis. For diffuse CRS, the predominant clinical phenotypes are Eosinophilic Chronic Rhinosinusitis (eCRS) and Non-Eosinophilic Chronic Rhinosinusitis (non-eCRS), determined by the histologic quantification of eosinophil numbers per high-power field (HPF), which the EPOS panel agreed should be 10/HPF (at 400 × magnification) or higher. As for secondary CRS, the classification is again divided into localized or diffuse and then considered according to four categories depending on endotype dominance: local pathology, mechanical factors, inflammatory factors, or immunological factors (1).

As mentioned earlier, the current focus is on the resulting inflammation that occurs in the sinus tissue, rather than analyzing the complex and unknown factors that cause CRS in individual patients. The attention is shifting towards identifying the molecular pathways or endotypes that become activated. With the advent of modern biological techniques, it has become possible to adopt a more mechanistic approach in the diagnosis and treatment of CRS by aiding the comprehension of critical cellular processes and immunological responses against pathogens across mucosal barriers (5). When the barrier is breached, a self-limited immune-defensive response is generated, which is characterized by a cellular and cytokine repertoire that targets one of the three classes of pathogens: type 1 immune responses target viruses; type 2 responses target parasites; and type 3 responses target extracellular bacteria and fungi. All of these responses typically resolve with the elimination of the pathogen and the restoration of barrier integrity. However, in CRS, the barrier penetration results in a chronic inflammatory response that fails to resolve but still usually involves the type 1, 2, or 3 pathways alone, or in combinations (1).

Type 2 inflammation is characterized by cytokines such as IL-4, IL-5, and IL-13, along with the activation and recruitment of eosinophils and mast cells. The presence of type 2 inflammation is identified by a tissue eosinophil count of >10/HPF, serum eosinophil count of >250 cells/mcL, or total immunoglobulin E (IgE) level of >100 IU/ml. Recent research has shown that patients with a pure or mixed type 2 endotype tend to be more resistant to current therapies, with a higher recurrence rate than those with pure type 1 or 3 endotypes (1).

Multiple studies conducted in Western regions have shown a higher incidence of type 2 CRS in patients with nasal polyps, with eosinophils being the dominant inflammatory cell (6). In contrast, studies conducted in Eastern Asia have shown a higher incidence of non-type 2 CRS, with neutrophils being the dominant inflammatory cell in nasal polyps (7–9). The current study aims to focus on the type 2 endotype and determine its prevalence and characteristics among patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) who underwent ESS in Saudi Arabia.

Following the new EPOS classification published in 2020 (1), our study found that 99.7% of patients in our population had type 2 inflammation, and only 0.3% representing one patient had non-type 2 inflammation, indicating that nearly all recorded patients with CRSwNP had type 2 inflammation. Similarly, Stevens et al. reported that among CRSwNP patients, the overall frequency of any type 1, type 2, or type 3 inflammation was 17%, 87%, and 18%, respectively, of which 0.7%, 62%, or 2.2% had only type 1, type 2, or type 3 single inflammation (11). In American and European patient cohorts, CRSwNP strongly leans towards a type 2 response (12–14). However, this relationship is not observed in Asian populations. Instead, Asian CRSwNP populations, with most data coming from China, tend towards neutrophilic inflammation (15, 16). Moreover, the non-eosinophilic type has been considered the most common subgroup of CRSwNP in Japan for the past 30 years (7).

There is a general consensus in the literature that CRSwNP is often associated with comorbid asthma (17–26). In this study, our data reported an association with bronchial asthma (33.1%), but allergic rhinitis was more prevalent (55.4%). Considering comorbidities can provide a useful tool for understanding the disease, given the shared inflammatory mechanisms between comorbidities and CRS, and the potential immunomodulation of CRS by other inflammatory processes.

As reported in the literature, we found that 47.5% of the patients in our study were hyposmic, 38.8% were anosmic, and only a minority of patients (13.6%) had a normal olfaction. Similarly, Stevens et al. reported significantly higher complaints of smell/taste loss in eosinophilic CRS, with 78% of patients having CRSwNP (11). Other studies have also suggested that type 2 inflammation promotes smell loss in CRS (27, 28). However, loss of smell is well known to be associated with the presence of nasal polyps (1), and therefore, it is not clear whether the type 2 inflammation was merely a marker of nasal polyps or whether the type 2 inflammation was more directly associated with smell disturbance.

Ho et al. conducted a retrospective study on 345 patients, of whom 206 (59.7%) had eosinophilic CRS. They found that eosinophils were significantly higher in the eCRS population compared to the non-eCRS group (P < .01) (29). Similar findings were observed in our study, with a mean total eosinophil count of 374.2 ± 347.7 cells/mcL in patients with type 2 inflammation.

Given the high costs, both financial and in terms of implementation, associated with molecular diagnosis and biological treatment, it is of immense importance to identify suitable biomarkers and develop endotype-driven therapies for the management of CRSwNP (1, 30). Biologics that specifically target type 2 inflammation have become the primary focus of ongoing clinical trials for CRSwNP. These trials have shown a progressive increase in the development of biologic therapies that target the pivotal molecules involved in type 2 inflammation. Based on the existing research, biologics, in general, have demonstrated the potential to alleviate the characteristic symptoms of CRSwNP, including nasal obstruction, rhinorrhea, and impaired olfactory function, thereby significantly enhancing patients' overall quality of life (31–33). Biologics have continued to cause a paradigm shift in the management of the disease since their introduction for clinical use.

As previously mentioned, calculating the prevalence of type 2 inflammation in patients with CRSwNP using the EPOS2020 criteria resulted in a prevalence of 99.7%. In comparison, determining the prevalence based on tissue eosinophil count, total eosinophil count, or total IgE separately showed a prevalence of 93.4%, 61.7%, and 89%, respectively. These findings underscore the importance of adhering to the EPOS2020 criteria for determining the type 2 endotype in patients with CRSwNP.

This study aimed to determine the prevalence and characteristics of type 2 inflammation among patients diagnosed with CRSwNP who underwent ESS in Saudi Arabia, based on the EPOS2020 criteria. Our study population revealed that 99.7% of patients had type 2 inflammation, and only one patient (0.3%) had non-type 2 inflammation, indicating that nearly all recorded patients with CRSwNP in our population had type 2 inflammation. As a priority, health policy should encourage more studies on the prevalence and characteristics of type 2 inflammation in CRSwNP patients and increase awareness of type 2 inflammation as it relates to nasal polyps in the Middle East.