The DEBATE Study "DEvelopment of Endotype-based Biomarkers for the Monitoring of Greek pATiEnts With CRSwNP"

1i. Description of demographics of CRSwNP patients before and during 24 months after first endoscopic sinus surgery (ESS)

Demographics at study entry/screening (age, sex, ethnicity, smoking status, cigarettes/day/year, alcohol status (units/week), body measurements (BMI kg/m2), employment status, educational level, residence area) will be recorded

Time frame: Up to 24 ± 2 months (through study completion)

1i. Description of medical history of CRSwNP patients before and during 24 months after first endoscopic sinus surgery (ESS)

Patients' medical history, including the date of first and severe CRSwNP diagnosis, comorbidities, and disease management \[use (yes/no) of saline, systemic/local glucocorticoids, biologics, antibiotics\], will be reported at the time of enrolment and during 24 months after first ESS.

Time frame: Up to 24 ± 2 months (through study completion)

1i. Description of first ESS characteristics in CRSwNP patients

Time to first ESS from CRSwNP diagnosis and from severe CRSwNP diagnosis will be assessed

Time frame: At Visit 1 (day 1)

1ii. Assessment of 22-item Sinonasal Outcome Test (SNOT-22) score in CRSwNP patients

The 22-item Sinonasal Outcome Test (SNOT-22), which is a health-related quality of life (HRQoL) evaluation with each item scored on a Likert scale ranging from 0 "No problem" to 5 "Problem as bad as it can be".

Time frame: Up to 24 ± 2 months (through study completion)

1ii. Assessment of The Nasal Polyposis Symptom Diary (NPSD) in CRSwNP patients

The Nasal Polyposis Symptom Diary (NPSD), which is a short patient-reported outcome (PRO) tool comprising 11 items (8 symptom-specific, 2 symptom-impact, and 1 optional medication-compliance). The Total Symptom Score (TSS) is a summary of the first 8 symptom-specific items, scored on a 4-point scale \[0-none, 1-mild, 2-moderate, 3-severe\], with a resulting score from 0 to 24

Time frame: Up to 24 ± 2 months (through study completion)

1ii. Assessment of the Asthma Control Test (ACT) in CRSwNP patients (if comorbidity with asthma)

The Asthma Control Test (ACT), a patient-based tool for identifying patients with poorly controlled asthma that includes 5 items assessing the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. The ACT responses for each of the items are summed to yield a score ranging from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control.

Time frame: Up to 24 ± 2 months (through study completion)

1iii. Assessment of Nasal Polyps Score (NPS) score in CRSwNP patients

NPS is a physician-reported tool that grades the extent/severity of nasal polyps based on evaluation by nasal endoscopy. Each nostril is scored on a scale of 0 - "No nasal polyps" to 4 - "Large nasal polyps causing complete obstruction of the inferior nasal cavity", with the total score being the sum of left and right nostril scores (range: 0-8).

Time frame: Up to 6 months before Visit 1 (day 1) & at Visit 2 (24 ± 2 months)

1iii. Assessment of imaging results in CRSwNP patients

The Lund-Mackay (LM) CT score that evaluates sinus opacification on CT scans. This score ranges from 0 -"complete lucency of all sinuses" to 24 - "complete opacity of all sinuses"

Time frame: Up to 6 months before Visit 1 (day 1) & at Visit 2 (24 ± 2 months)

2. Characterization of blood cytokines/chemokines in prospective patients with CRSwNP

Cytokine/chemokine analysis of blood samples following first ESS will be performed by Luminex and ELISA analysis

Time frame: At Visit 1 (day 1)

2. Characterization of blood immune cell populations in prospective patients with CRSwNP

Immunophenotypic analysis by spectral flow cytometry of all main immune cell types, as well as detailed characterization of all T cell subsets will be performed in the fresh samples.

Time frame: At Visit 1 (day 1)

2. Characterization of serum immunoglobulin levels in prospective patients with CRSwNP

Serum immunoglobulin levels \[total IgE, specific IgE to staphylococcal enterotoxins (SE-IgE)\]

Time frame: At Visit 1 (day 1)

2. Characterization of WBC count in prospective patients with CRSwNP

Differential WBC count (incl. absolute count) will be recorded

Time frame: At Visit 1 (day 1)

2. Characterization of RBC count in prospective patients with CRSwNP

RBC count will be recorded

Time frame: At Visit 1 (day 1)

3. Association of time to CRSwNP recurrence and CRSwNP endotypes over 24 months following first ESS in CRSwNP patients

The number of CRSwNP recurrences along with the date(s) of recurrence(s) will be recorded in the eCRF by the investigator at 24 months following first ESS for CRSwNP patients (including retrospective CRSwNP patients, if data are available). The time to relapse during the 24-month follow-up will be also estimated.

Time frame: Up to 24 ± 2 months (through study completion)

4. Differences in cytokine/chemokine levels between retrospective patients with CRSwNP and CRSsNP

Endotypes of CRSsNP patients who have performed first ESS in the period between 2012 and enrolment (retrospective patients) will be determined based on cytokine/chemokine analysis of frozen extracted nasal tissue from ESS, including Fractalkine, GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, (p70), IL-13, IL-17A, IL-21, IL-23, ITAC, MIP-1α, MIP-1β, MIP-3α, TNF-α, TSLP, IL-9, IL-33, IL-17E/IL-25, TGFb1, IL-22

Time frame: At Visit 1 (day 1)

4. Differences in eosinophil and neutrophil cell counts between retrospective patients with CRSwNP and CRSsNP

Eosinophil and neutrophil cell counts will be recorded. As per the EPOS 2020, eosinophilia is defined as \>10 eosinophils/hpf

Time frame: At Visit 1 (day 1)

4. Differences in nasal tissue alterations between retrospective patients with CRSwNP and CRSsNP

tissue morphology and potential nasal tissue destruction and remodeling by standard histology staining (e.g. Hematoxylin and eosin, Periodic acid-Schiff (PAS), and Sirius Red staining) will be assessed in stored nasal polyp tissue paraffin sections or paraffin blocks. Depending on the nature of tissue pathology, further immunohistochemical analysis will be performed with the use of specific antibodies, such as markers for epithelial barrier integrity (e.g. E-cadherin or Cytokeratin), tissue remodeling (e.g. MMP-9) or chronic damage monitored by fibrosis (e.g. α-SMA or collagen)

Time frame: At Visit 1 (day 1)