CRSwNP or CRSsNP Patients
Conditions
Keywords
CRSwNP, CRSsNP, endotypes, inflammatory pathways
Brief summary
Given the high variability in the inflammatory profiles of CRSwNP (Chronic rhinosinusitis with nasal polyps) patients that influence both disease phenotype and response to treatment, exploring further potential targets is crucial for advancing novel biologic treatment strategies. By indicating the efficacy of targeted therapy, as well as determining clinical features, endotyping of CRSwNP may offer a useful tool to better tailor treatment approaches in this heterogenous patient population. This study is the first national effort to collect data on inflammatory markers and burden of CRSwNP patients in Greece aiming at identifying disease endotypes based on patients' inflammatory profile.
Detailed description
A participant may withdraw from the study at any time at the participant's own request for any reason (or without providing any reason) without any implication on participant's rights. Patients who discontinue should be asked about the reason(s) for their discontinuation. If the participant withdraws consent for disclosure of future information, AstraZeneca may retain and continue to use any data collected before such a withdrawal of consent
Interventions
OTHERNot applicable - NIS study
Not applicable - NIS study
Sponsors
AstraZeneca
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * If CRSwNP group: Physician-diagnosed severe, uncontrolled CRSwNP according to the EUFOREA/EPOS 2020 and ICAR-RS 2021 guidelines with: * CRSwNP severity consistent with the need for surgery as defined by a total nasal polyp score (NPS) of ≥5 (≥2 for each nostril) * Nasal Congestion Score (NCS) of ≥2 * Ongoing documented symptoms of CRSwNP for \> 8 weeks before surgery If CRSsNP group: Diagnosis of CRSsNP according to the EUFOREA/EPOS 2020 and ICAR-RS 2021 guidelines * Have performed in the period between 2012 and enrolment or are scheduled to perform endoscopic sinus surgery (ESS) for the first time at enrolment * Have available nasal polyp tissue sample from the first endoscopic sinus surgery (ESS) * Have provided signed and dated written informed consent * If CRSwNP group: Patients receiving any standard of care treatment for CRSwNP, provided the participant is stable on that treatment for ≥30 days
Exclusion criteria
* Patients with cystic fibrosis or immunodeficiency * Presence of acute exacerbation of CRS symptoms within 2 weeks prior to surgery * Use of systemic corticosteroids within 30 days prior to surgery, or antileukotrienes within 15 days prior to surgery, or biologic therapy prior to surgery * Not adequate amount (\<0.15g) or quality (e.g. storage temperature, contamination) of tissue sample for analyses * Not available blood (serum) sample, only for patients scheduled to perform endoscopic sinus surgery (ESS) for the first time at the date of enrolment, for analyses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of nasal tissue-secreted cytokines/chemokines in patients with CRSwNP | At Visit 1 (day 1) | Cytokine/chemokine analysis of the fresh extracted nasal tissue following first ESS will be performed by Luminex and ELISA analysis |
| Characterization of nasal tissue immune cell populations in prospective patients with CRSwNP | At Visit 1 (day 1) | 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. |
| Characterization of eosinophil and neutrophil cell counts in patients with CRSwNP | At Visit 1 (day 1) | Eosinophil and neutrophil cell counts will be recorded, as per the EPOS 2020, eosinophilia is defined as \>10 eosinophils/hpf. |
| Characterization of nasal histological alterations in retrospective patients with CRSwNP | At Visit 1 (day 1) | Tissue morphology and potential tissue destruction and nasal epithelium 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1i. Description of demographics of CRSwNP patients before and during 24 months after first endoscopic sinus surgery (ESS) | Up to 24 ± 2 months (through study completion) | 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 |
| 1i. Description of medical history of CRSwNP patients before and during 24 months after first endoscopic sinus surgery (ESS) | Up to 24 ± 2 months (through study completion) | 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. |
| 1i. Description of first ESS characteristics in CRSwNP patients | At Visit 1 (day 1) | Time to first ESS from CRSwNP diagnosis and from severe CRSwNP diagnosis will be assessed |
| 1ii. Assessment of 22-item Sinonasal Outcome Test (SNOT-22) score in CRSwNP patients | Up to 24 ± 2 months (through study completion) | 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". |
| 1ii. Assessment of The Nasal Polyposis Symptom Diary (NPSD) in CRSwNP patients | Up to 24 ± 2 months (through study completion) | 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 |
| 1ii. Assessment of the Asthma Control Test (ACT) in CRSwNP patients (if comorbidity with asthma) | Up to 24 ± 2 months (through study completion) | 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. |
| 1iii. Assessment of Nasal Polyps Score (NPS) score in CRSwNP patients | Up to 6 months before Visit 1 (day 1) & at Visit 2 (24 ± 2 months) | 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). |
| 1iii. Assessment of imaging results in CRSwNP patients | Up to 6 months before Visit 1 (day 1) & at Visit 2 (24 ± 2 months) | 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" |
| 2. Characterization of blood cytokines/chemokines in prospective patients with CRSwNP | At Visit 1 (day 1) | Cytokine/chemokine analysis of blood samples following first ESS will be performed by Luminex and ELISA analysis |
| 2. Characterization of blood immune cell populations in prospective patients with CRSwNP | At Visit 1 (day 1) | 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. |
| 2. Characterization of serum immunoglobulin levels in prospective patients with CRSwNP | At Visit 1 (day 1) | Serum immunoglobulin levels \[total IgE, specific IgE to staphylococcal enterotoxins (SE-IgE)\] |
| 2. Characterization of WBC count in prospective patients with CRSwNP | At Visit 1 (day 1) | Differential WBC count (incl. absolute count) will be recorded |
| 2. Characterization of RBC count in prospective patients with CRSwNP | At Visit 1 (day 1) | RBC count will be recorded |
| 3. Association of time to CRSwNP recurrence and CRSwNP endotypes over 24 months following first ESS in CRSwNP patients | Up to 24 ± 2 months (through study completion) | 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. |
| 4. Differences in cytokine/chemokine levels between retrospective patients with CRSwNP and CRSsNP | At Visit 1 (day 1) | 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 |
| 4. Differences in eosinophil and neutrophil cell counts between retrospective patients with CRSwNP and CRSsNP | At Visit 1 (day 1) | Eosinophil and neutrophil cell counts will be recorded. As per the EPOS 2020, eosinophilia is defined as \>10 eosinophils/hpf |
| 4. Differences in nasal tissue alterations between retrospective patients with CRSwNP and CRSsNP | At Visit 1 (day 1) | 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) |
Countries
Greece
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed