Immunologic Impact of Dupilumab in Patients Suffering From Asthma and Chronic Rhinosinusitis With Polyps

The investigators are studying adults who have chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, and who are undergoing Endoscopic Sinus Surgery (ESS). Investigators want to understand how adding a medication called dupilumab to their usual treatment affects inflammation in their upper and lower airways over 24 weeks.

Dupilumab works by blocking certain signals in the immune system that contribute to inflammation in both the sinuses and the lungs. By studying how this medication changes the immune profiles of both airway systems, investigators hope to learn more about the underlying causes of airway inflammation in these conditions.

This research is important because it may help understand if treating inflammation in one part of the airway (like the lungs) has a similar effect on inflammation in another part (like the sinuses). This could lead to better treatments for people with CRSwNP and asthma, targeting the root causes of their symptoms more effectively.

In adult patients with CRSwNP with concomitant moderate-severe asthma undergoing Endoscopic Sinus Surgery (ESS), what is the change in the inflammatory cascade in the upper and lower airways from patients treated with 300 mg of dupilumab twice daily for 24 weeks as an add-on treatment to the standard of care (intranasal corticosteroids, INCS+ backgroung asthma medication) compare to the placebo + standard of care treatment only.

The investigators hypothesize that the study of the immune profile in patients with CRSwNP and asthma would give a better understanding of the mechanism involved in the airway inflammatory response. Determining the molecular profiles of the upper and lower airways after dupilumab treatment has not been studied yet.

Dupilumab has demonstrated effectiveness in treating both Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and asthma, conditions characterized by Type 2 inflammation, by inhibiting the IL-4 and IL-13 signalling pathways. However, it remains unclear how immunological changes occur in paired tissues of the upper (sinus) and lower (lung) airways in patients treated with biologics compared to those receiving standard therapies. Additionally, it is not well understood whether improvements in one airway system (e.g., the lungs) are mirrored in the other (e.g., the sinuses), which could result in differing clinical responses. This study aims to address these gaps by examining the comparative effects of Dupilumab versus standard treatments on both airway systems, to determine if therapeutic effects are consistently observed across both systems and to understand the potential implications for clinical responsiveness.

Eligibility Criteria:
Inclusion Criteria:

* Patients over the age of 19.
* Patients undergoing Endoscopic Sinus Surgery (ESS)
* Patients with CRSwNP with moderate-severe asthma according to 2020 EPOS criteria:

  1. Asthma confirmed with spirometry and assessment on the previous history of asthma (a methacholine challenge test and atopy testing to document the positive or negative history of asthma will be performed if there is no clinical record). Asthma severity based on GINA guidelines.
  2. Presence of nasal polyps. This can be based on the formal exam at Baseline Visit or historical assessment.

Exclusion Criteria:

* Patients with current or past sinonasal or bronchial tumours
* Subjects who have been treated with oral antibiotics in the past month prior to surgery
* Subjects with known immunodeficiency
* Subjects with known autoimmune disease
* Subjects with other sinonasal diseases other than CRSwNP (e.g., cystic fibrosis, eosinophilic granulomatosis with polyangiitis, allergic fungal rhinosinusitis, invasive fungal sinusitis, fungal ball, dyskinetic cilia syndrome)
* Prior lung transplants
* Subjects with hypersensitivity; with allergy/intolerance to a monoclonal antibody or biologic
* Prior use of dupilumab or other biologic medications (omalizumab. mepolizumab, reslizumab,etc) 6 months before enrollment.
* Any condition that, in the opinion of the investigator, may interfere with the patient's ability to participate in the study per protocol.
* Participation in an ongoing interventional or observational study using a biologic treatment.
* Female participants who are pregnant or breastfeeding