1. Background and Rationale
Asthma is a heterogeneous chronic inflammatory airway disease affecting approximately 300 million people worldwide. Roughly 5-10% of patients suffer from severe asthma, leading to significant clinical impact and high resource consumption. Patients with severe asthma often present with comorbidities driven by T2-high (Type 2-high) inflammation, characterized by persistent blood hypereosinophilia and increased tissue expression of IL-5 (Interleukin-5). The most frequent comorbidity is CRSwNP (Chronic Rhinosinusitis with Nasal Polyps). This is often explained by the "unified airway theory," suggesting that the upper and lower airways function as a single unit subjected to similar inflammatory insults. While biologic therapies like dupilumab, which targets IL-4/13R (Interleukin-4/13 Receptor), have revolutionized treatment, the goal has shifted toward achieving clinical remission. According to the SANI (Severe Asthma Network Italy), clinical remission in asthma is defined by:
* No further need for OCS (Oral Corticosteroids).
* Absence of exacerbations.
* Stable lung function.
* Absence of symptoms, measured by an ACT (Asthma Control Test) score of 20-25 or an ACQ (Asthma Control Questionnaire) score \< 1.5.
* For CRSwNP (Chronic Rhinosinusitis with Nasal Polyps), EUFOREA (European Forum for Research and Education in Allergy and Airway Diseases) defines remission as a condition with an NPS (Nasal Polyp Score) \< 4, NCS (Nasal Congestion Severity) \< 2, and no need for surgery or systemic corticosteroids after 12 months.
2. Study Objectives
Primary Objective:
To evaluate the clinical efficacy of dupilumab after 12 months of treatment in patients with comorbid asthma and CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) regarding:
* Percentage of patients in complete clinical remission for asthma according to SANI (Severe Asthma Network Italy) criteria.
* Percentage of patients in complete clinical remission for CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) according to EPOS (European Position Paper on Rhinosinusitis and Nasal Polyps)/EUFOREA (European Forum for Research and Education in Allergy and Airway Diseases) criteria.
* Percentage of patients achieving simultaneous complete clinical remission for both conditions.
Secondary Objectives (at 1, 6, and 12 months):
* Partial clinical remission rates.
* Improvement in disease control scores, specifically ACT (Asthma Control Test) and SNOT-22 (22-Item Sino-Nasal Outcome Test).
* Stabilization of spirometric parameters.
* Reduction in OCS (Oral Corticosteroids) use and annual asthma exacerbation rates.
* Improvement in smell via identification tests.
3. Study Design and Population This is a no-profit, observational, retrospective, multicenter study. Setting: Adult patients (≥18 years) followed for at least 12 months since starting dupilumab.
Sample Size: Approximately 280 patients across 14 centers. Inclusion Criteria: Diagnosis of CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) per EPOS (European Position Paper on Rhinosinusitis and Nasal Polyps) 2020 and asthma per ERS (European Respiratory Society)/ATS (American Thoracic Society) 2014.
Exclusion Criteria: Conditions contraindicating dupilumab, clinically significant bronchiectasis confirmed by CT (Computed Tomography), or pregnancy/breastfeeding.
4. Data Management and Statistical Plan Data collection includes four timepoints: baseline, 1 month, 6 months, and 12 months.
Key Variables:
Blood Biomarkers: Blood eosinophils and total IgE (Immunoglobulin E). Functional Tests: FeNO (Fractional exhaled Nitric Oxide) and plethysmography parameters such as FEV1 (Forced Expiratory Volume in 1 second), FVC (Forced Vital Capacity), TLC (Total Lung Capacity), and DLCO (Diffusing Capacity for Carbon Monoxide).
Statistical Analysis:
Descriptive statistics will be used for all baseline and follow-up characteristics. Normality will be assessed via the Shapiro test. A Bayesian method will be applied to manage missing data and cluster the population to control for confounding factors.
5. Ethical Considerations The study will be conducted in accordance with the Declaration of Helsinki. Participation is subject to obtaining free and informed consent, safeguarding data protection rights under GDPR (General Data Protection Regulation) EU (European Union) 679/2016. Researchers report no potential conflicts of interest.
