Advances in understanding the pathophysiology of asthma development and severity have pointed towards a prominent role of the bronchial epithelium, especially in more chronic and severe disease. Studies suggest that airway eosinophilic inflammation in asthma is linked to epithelial injury and structural changes of the airways, co called airway wall remodeling. Together the chronic airway inflammation and remodeling are associated with bronchial hyperresponsiveness, fixed airflow obstruction or progressive loss of lung function and clinical severity of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP), is another respiratory inflammatory disease often co-existing with severe asthma, sharing similar pathophysiology. The investigators hypothesize that epithelial barrier integrity may play a role in the pathophysiology of severe eosinophilic asthma and nasal polyposis and in response to anti-IL5 therapy of severe asthmatics, and that shedding of epithelial barrier proteins may be used as biomarker in the management of severe asthma. In order to study that, the investigators will conduct a prospective cohort study of adult severe asthmatics with/out CRSwNP, who live on the island of Crete, Greece and who meet the criteria for entering anti-IL5 treatment, as assessed by pulmonologist. The participants will be recruited with a convenience sampling in a period of 2 years, under real life conditions, and will be followed up for 1 year after treatment initiation. A control group of subjects diagnosed with nasal polyposis without severe asthma will be used. Eligible subjects will undergo clinical assessment with radiological (CT) and endoscopic investigations. Samples of serum, sputum, nasal secretions, as well as nasal and bronchial biopsies will be obtain for assessing clinicopathological differences among the 3 groups but also response to anti-IL5 therapy in SEA w/o CRSwNP.

Inclusion Criteria:

• Able to provide informed written consent (study participation informed consent form): Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
• Anti-IL5/IL5R naïve
• Confirmed asthma diagnosis and severity and treatment requirements (for severe asthma group see boxes 1-3). For the 2nd control group, patients with CRSwNP must have a diagnosis of mild asthma (GINA steps 1-2) or no asthma by pulmonologist.
• Polyposis must be bilateral, to be considered as CRSwNP
• Triggers and relevant co-morbidity have been assessed and are well controlled Triggers such as active or passive smoking, beta-blockers, aspirin/NSAIDs, allergen exposure;Comorbidities such as rhinitis, obesity, GERD, OSA, VCD, depression/anxiety.
• Age: Adults ≥18 years of age
• Any smoking status
• Any ethnicity
• Be affiliated to or a beneficiary of a social security category and/health insurance.
• Gender: Male and Eligible Female. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control for the duration of the follow up (and for 4 months after the last injection administration). A serum pregnancy test is required of all females. This test will be performed at the initial screening visit. In addition, a urine pregnancy test can be offered (optional) for all females during each scheduled treatment visit prior to the infusion of biologic product until the 1-year follow-up visit.

Laboratory abnormality: No evidence of clinically significant abnormality (other than those seen in SEA) in the haematological, biochemical or urinalysis screen at Visit 1, as judged by the investigator.

• Asthma Exacerbation: Subjects with an ongoing asthma exacerbation should have their screening and treatment initiation visit delayed until the investigator considers the subject has returned to their baseline asthma status. If the 4-week screening period (visits 1 and 1a) has elapsed, then the subject should be considered a screening failure. An exacerbation is defined as worsening of asthma requiring the use of systemic CS and/or emergency department visit, or hospitalisation. For subjects on maintenance oral corticosteroids, an exacerbation requiring oral CS is defined as the use of oral/systemic corticosteroids at least double the existing dose for at least 3 days.
• Maintenance Asthma Therapy: No changes in the dose or regimen of baseline ICS and/or additional controller medication during the screening period (except for treatment of an exacerbation).
• Maintenance CRSwNP: No changes in the dose or regimen of baseline intranasal CS and/or additional controller medication during the screening period (except for treatment of an exacerbation).
• Subjects with a previous surgery for the removal of nasal polyps are allowed to participate and will be considered as subjects with CRSwNP (with severe asthma or not). However, any subject who had at least one surgery for removal of nasal polyps, even if at study screening he/she is free of nasal polyps, cannot be considered as a subject without CRSwNP.
• Severe asthma patients must meet requirements for biologic therapy with anti-IL5 treatment (Mepolizumab)

Exclusion Criteria:

• Pregnancy
• Current exacerbation at visit 1 (repeat screening when stable). If exacerbation is lasting up until Visit 1a then exclude subject.
• Cognitive impairment preventing completion of data collection forms
• People highly dependent on medical care
• People with significant life limiting co-morbidity
• Other eosinophilic conditions (eosinophilic granulomatosis polyangiitis (Churg-Strauss syndrome), eosinophilic oesophagitis etc)
• Unilateral polyposis
• Primary diagnosis of lung disease other than asthma (chronic obstructive lung disease (COPD), asthma-COPD overlap (ACO), interstitial lung disease, sarcoidosis, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, active tuberculosis, allergic bronchopulmonary aspergillosis (ABPA))
• Current lung cancer or other blood, lymphatic or solid organ malignancy
• Autoimmune diseases of the skin, muscle-skeletal or gastrointestinal system needing systemic corticosteroids, immunosuppressants or biologic treatment as well as individuals with granulomatosis with polyangiitis (Wegener's granulomatosis)
• Inability to attend study and treatment visits
• Inability to understand and speak Greek or English language

Adults with severe eosinophilic asthma, naive to anti-IL5/anti-IL5R treatment with or without CRSwNP who meet requirements for biologic therapy with anti-IL5 (Mepolizumab)