The objective of this study is to investigate the effect of dupilumab treatment on mucus plugging in severe asthma patients with severe eosinophilic asthma. Therefore, the investigators plan to apply computer tomography to investigate mucus plugging and thoroughly examine different airway samples from Type 2-high severe asthmatic patients at a cellular, molecular, microbiological and metabolomic level. This study will help to unravel underlying treatment mechanisms of dupilumab therapy in severe asthmatics.

In this prospective exploratory pilot study, the objective is to enroll 10 participants with severe asthma who are candidates for Dupilumab treatment. The study's individual duration will not exceed 26 weeks. Before enrollment, informed consent will be obtained from all subjects. All patients with severe Type 2 Asthma can be included according to inclusion- and exclusion criteria. Those with a history of monoclonal antibody treatment for asthma may be included after a washout period of 2 half-lives or 1 month (whichever is longer).

Prior to commencing Dupilumab, the investigators will assess patient-reported outcomes using the Asthma Control Questionnaire (ACQ-6), Asthma Control Test (ACT), and mini Asthma Quality of Life Questionnaire (miniAQLQ). Additionally, the investigators will review concomitant medication, conduct Spirometry, measure fraction of exhaled nitric oxide (FeNO), perform ultra high-resolution computer tomography of the lungs, draw blood for laboratory samples, and carry out bronchoscopy with bronchoalveolar lavage and biopsies.

Subsequently, Dupilumab treatment will be initiated, and patients will visit our center every 2 weeks for clinical assessments, including monitoring adverse events, lung function, laboratory samples, and Dupilumab administration. After 22 weeks, the investigators will repeat computer tomography of the lungs and bronchoscopy. For patients who do not experience clinical improvement, Dupilumab treatment will be discontinued after 6 months.

Inclusion Criteria:

All patients who:

• are ≥18 years of age
• have a recorded clinical diagnosis of asthma (ICD-10 Code: J45)
• meet the requirements for treatment of severe T2-high asthma for Dupilumab defined as:
• FeNO > 25 ppB
• two measurements of at least 250 eosinophils /µl in the blood OR one measurement of blood eosinophils at least 250 cells/µl during reduction of OCS dosing if treated with oral corticosteroids and/or one measurement of sputum ≥ 2% or BAL eosinophils ≥ 1%
• have a history of treatment with monoclonal antibodies for asthma if a wash out period of 2 half-lives or 1 month (whatever is longer) has passed

Exclusion Criteria:

Patients who:

• are pregnant as determined by a ß-HCG test
• have severe anatomic variations or deviations that do not allow bronchoscopy
• suffer from additional others confounding underlying lung disorder including but not limited to: Bronchiectasis, chronic obstructive pulmonary disorder (COPD), pulmonary fibrosis, emphysema, Cystic fibrosis, any known parasitic infections and lung cancer.
• show pulmonary conditions with symptoms of asthma and blood eosinophilia, including but not limited to: Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, hypereosinophilic syndrome
• suffer from a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study,
• have clinically meaningful comorbidity as determined by the evaluating committee,
• experience of an asthma exacerbation within 4 weeks prior to the first main visit
• immune disorder and/or immunosuppressive treatment (e.g. cyclosporine), ongoing biological treatment of asthma (e.g., mepolizumab, omalizumab, benralizumab) or last biological treatment 2 half-lives or 1 month before the first main visit
• have a history of drug and alcohol abuses
• are currently smoking or are former smokers for less than 6 months with >10 pack years

Patients with severe Type 2 asthma for whom Dupilumab therapy is indicated.