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Well-characterized in chronic rhinosinusitis, type 2 inflammation is frequently associated with nasal polyps, comorbid asthma, and nonsteroidal anti-inflammatory drug hypersensitivity. Despite medical and surgical treatment, it recurs in a significant proportion of patients. Thus, severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps is the most difficult-to-treat phenotype of chronic rhinosinusitis. Recently, dupilumab, a monoclonal antibody against IL-4 receptor α, and omalizumab, a monoclonal antibody against immunoglobulin E, were approved for patients with chronic rhinosinusitis with nasal polyps in the United States, Europe, and Korea. Therefore, rhinologists should understand novel biologics and their use. Here, we provide a literature review of several biologics with their indications, effectiveness, and safety.

Chronic rhinosinusitis (CRS) is characterized by prolonged inflammation of the nasal and paranasal sinus mucosa lasting over 12 weeks. CRS is divided into two main types based on the presence of nasal polyps: CRS without nasal polyps and CRS with nasal polyps. The condition is further classified into endotypes based on type 1, type 2, and type 3 inflammatory signatures, with differences in terms of disease severity, prognosis, and treatment response. Recent studies have emphasized the importance of the epithelial-mesenchymal transition (EMT) in CRS progression. In CRS, the EMT can be triggered by infections, allergens, hypoxia, and environmental pollutants. Specifically, EMT induction proceeds through the following mechanisms: viral and bacterial infections disrupt the epithelial barrier, house dust mites and other allergens activate the TGF-β and EGFR signaling pathways, hypoxia increases HIF-1α and other mesenchymal markers, and diesel exhaust particles and particulate matter cause oxidative stress. Maintaining the integrity of the epithelial barrier is essential for nasal mucosa homeostasis. In CRS, barrier damage activates repair processes that trigger the EMT, resulting in barrier dysfunction and tissue remodeling. Epithelial barrier dysfunction allows antigens and pathogens to penetrate, perpetuating inflammation and promoting the EMT. This disruption is a hallmark of CRS, emphasizing the importance of barrier integrity in the development of the disease. Key signaling pathways regulating the EMT in CRS include TGF-β, Wnt, HMGB1, AGE/ERK, TNF-α, and various miR-NAs. These signaling pathways connect to various downstream pathways, such as the Smad2/3, GSK-3β/β-catenin, RAGE, and NF-κB pathways. This review focuses on the complex mechanisms of the EMT in CRS, emphasizing the role of epithelial barrier dysfunction and subsequent EMT processes in driving the disease's development and progression. A deeper understanding of these EMT-driven mechanisms will help identify the potential therapeutic targets aimed at restoring epithelial integrity and reversing the EMT. [ABSTRACT FROM AUTHOR]

Background and Objectives: In 2021, biologics were approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) in Korea. However, CRS is a heterogeneous disease, and its characteristics are thought to differ between Western and Korean populations. This study aimed to evaluate the experiences of members of the Korean Rhinologic Society during the first year of biologic usage for the treatment of nasal polyps. Methods: An anonymous survey consisting of 15 items was conducted from November to December 2021. The survey included questions about participant demographics, use of biologics for treating CRSwNP, and expectations regarding the effectiveness of biologics for treating CRSwNP. Results: In total, 44 members participated in the survey. Approximately half of the respondents were in their 40s (50.0%) and had 5-9 years of clinical experience as otorhinolaryngologists (47.7%). The majority of participants held academic positions (95.4%). About half of them worked in Gyeonggi Province. The utilization of biologics did not differ significantly based on clinical experience (p=0.192). When asked about the factors considered for prescribing biologics, the most common reason was recurrence of polyps after surgery (87.2%). The most frequent reason for discontinuing biologics was cost (48.6%). When asked about the extent to which they expected that the availability of biologics for CRSwNP treatment would reduce endoscopic sinus surgery (ESS), 45.5% of members expected a reduction of approximately 10%-29%. In addition, 20.5% expected a reduction of 50% or more. However, 61.4% expected a reduction of less than 10% in primary ESS. In addition, most respondents (93.2%) agreed with the need for Korea-specific guidelines for biologic treatment. Conclusion: There are discrepancies between the current guidelines for biologic treatment of CRSwNP and the reality of the situation, highlighting the need for the development of Korea-specific guidelines. [ABSTRACT FROM AUTHOR]