Speaker: Luo Zhang

The speaker addressed the topic of eosinophilic nasal polyps in chronic rhinosinusitis (CRS), focusing on diagnosis and treatment. CRS has significant global public health and socioeconomic impacts. Eosinophilia is a key pathophysiological feature of nasal polyps, as evidenced by studies demonstrating eosinophilic infiltration in most cases. In 1996, Quist's pathological classification of nasal polyps identified the most common type as the edematous eosinophilic polyp, comprising 86%. While Western polyps commonly exhibit eosinophilic infiltration (at least 76% in US or European countries), Asian polyps show lower percentages. Studies in Japan revealed a 60% prevalence of prominent eosinophilic patterns in nasal polyps, while two other studies reported similar percentages. Additionally, two studies reported lower percentages, with only 32% and 36% demonstrating prominent eosinophilic patterns. Similar lower percentages were also observed in other Asian countries like Korea, Malaysia, Singapore, and Thailand, showing a prevalence of 18%. Studies on eosinophilic nasal polyps in Asia have varied definitions, leading to inconsistent findings. There is no standardized definition for eosinophilic polyps, with cutoff values for eosinophil counts ranging from 5 to 350 per high-power field and percentages ranging from 5% to 50%. These variations highlight the influence of geographic and ethnic differences on defining eosinophilic polyps. 

In 2001, Professor Haruna from Japan introduced the term eosinophilic sinusitis to identify refractory CRS cases, aiming to differentiate them from other forms of CRS. This term was associated with a high tendency of recurrence after surgery, indicating its clinical significance. However, the histological features of eosinophilic CRS, characterized by massive tissue eosinophilia, lacked standardized cutoff values for diagnosis. The speaker highlighted a multi-centre study conducted in Japan in 2015 involving over 1,300 patients with nasal polyps that established a correlation between tissue eosinophil numbers and the recurrence of CRS. The study identified 70 eosinophils per high-power field as the most significant cutoff value for diagnosing eosinophilic polyps, a standard which is widely adopted in Japanese studies. Similarly, a study conducted in Beijing that involved 387 patients with nasal polyps treated with endoscopic sinus surgery were followed up for 2 years and it was found a high % recurrence rate of 55%. The study further divided the groups into recurrence and non-recurrence groups to identify the factors responsible for recurrence. The logistic regression analysis identified two tissue biomarkers, absolute number and percentage, as strong predictors of recurrence, with 55 per high-power field and 27% eosinophil percentage being significant indicators. However, it's worth noting that the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) recommends a lower cutoff value of 10 eosinophils per high-power field for diagnosing eosinophilic polyps, which remains widely used globally.

In a systematic review by Toro et al., three years ago, 142 studies identified 29 different cutoff values for eosinophilic CRS. Clinical parameters, particularly recurrence rates, were highlighted as important parameters. The speaker further highlighted a meta-analysis showing that a cutoff value of 55 eosinophils per high-power field had the highest overall sensitivity and specificity for eosinophilic CRS. Additionally, Professor Liu Zheng et. al, from China reported another cutoff value for eosinophilic inflammation based on 17 normal subjects. The study found that twice the standard deviation of the mean tissue eosinophil percentage was 9.7%, leading to a cutoff value of 10% for eosinophilic nasal polyps. However, concerns were raised about the data's non-normal distribution and the description method's accuracy. Thus, two types of cutoff values exist reference intervals and clinical decision limits. Reference intervals describe typical result distributions in healthy populations, while clinical decision limits are associated with higher risks of adverse outcomes or specific disease diagnoses. For conditions like eosinophilic CRS defining severe conditions, clinical decision limits are more appropriate for distinguishing clinical subgroups within CRS.

The WHO classification outlines peripheral eosinophilia as an increased eosinophil count in peripheral blood surpassing the upper limit of normal. Hyper eosinophilia is defined as persistent eosinophilia exceeding 1.5 times 10 to the power of 9. Similarly, tissue eosinophilia is characterised by an increased percentage exceeding the normal upper limit, typically around 10%. The speaker suggests that eosinophilic nasal polyps should be identified using a high outcome-related cutoff value, often set at 55 eosinophils per high-power field. In treatment for severe eosinophilic nasal polyps, investigations have explored different surgical strategies. Patients with nasal polyps and asthma were randomly assigned to receive radical endoscopic sinus surgery (REES), radical functional endoscopic sinus surgery (FESS), or Draf 3. Long-term results at five years post-surgery revealed similar recurrence rates of 96% across different surgical strategies. This suggests that patients with polyps and asthma have poor long-term outcomes despite extended surgeries, continuing to experience persistent symptoms despite adequate surgery and optimal medical therapy. Biologics such as Dupilumab, omalizumab, and mepolizumab are available for managing chronic rhinosinusitis (CRS). The speaker demonstrated a recent case of patient who continued to experience symptoms like headaches and nasal obstruction even after three endoscopic sinus surgeries. Despite oral steroid and macrolide treatment, mucosal oedema persisted. However, after four months of omalizumab therapy, mucosal oedema resolved, and the patient became symptom-free. The most recent JAKI study demonstrated that IG and eosinophil levels increased in tissue over time. IG directly promoted eosinophil migration by regulating CC motive kinase receptor three through CD23. Importantly, IG-positive cells in tissue predicted the efficacy of omalizumab. The study also evaluated the efficacy and safety of a new Nitric Oxide Transporter 4A (NTLA4) receptor alpha monoclonal antibody, CM310, which targets IL-4 receptor alpha and blocks the interaction of IL-4 and IL-13, similar to dupilumab. However, the epitope of CM310 differs from that of dupilumab. The study included patients with high tissue or peripheral eosinophils, using nasal polyps score (NPS) and nasal congestion score as co-primary endpoints. After 16 weeks of treatment, patients receiving CM310 showed significantly greater improvement compared to placebo. Specifically, 79% of patients treated with CM310 achieved at least a two-point improvement in NPS, compared to 46% in the dupilumab study, indicating superior efficacy of CM310. 

The session concluded with pointers suggesting that definition of eosinophilic nasal polyps is not standardized and should consider clinical parameters such as recurrence. Cut-off values for tissue eosinophilia should be based on clinical decision limits rather than reference intervals. Current management algorithms are insufficient for optimal disease control in severe eosinophilic nasal polyps, but biologics offer new treatment perspectives for these refractory patients. The panel addressed the challenges faced which involved pressure from payers when otolaryngologists refer patients without asthma but with a high risk of recurrence, with the evidence needed to justify the use of biologics for high-risk patients to facilitate approval from payers, regardless of whether it is dupilumab or omalizumab. Two main factors were identified as influencing recurrence: the presence of asthma and high tissue eosinophils, such as 55 per field. In China, patients with both nasal polyps and asthma can receive biologics post-surgery, with further hope that even patients without asthma can be evaluated for biologics based on tissue biomarkers like eosinophils. High eosinophil levels could justify biologic therapy to prevent recurrence. When discussing with payers, the absolute number of eosinophils was considered more persuasive than the percentage, as both have similar specificity (27 percent and 55 eosinophils per field), but the absolute number is preferred. The speaker further suggested that regarding to the treatable traits or phenotypes for significant improvement with CM310 compared to dupilumab, eosinophilic patients responded better to treatment. The panel further discussed about the presence of neutrophilic nasal polyps and their treatment. It was recommended that using 55 eosinophils per field as a cutoff value, about 40-50% of nasal polyps were eosinophilic, while around 25% were neutrophilic with more research and treatment options are needed in patients.

European Academy of Allergy and Clinical Immunology (EAACI), 2024 31st May-3rd June, Valencia