Swiss Severe Asthma Register

The overall objective is to establish a clinical register for patients with severe asthma. Since the number of patients with severe asthma at a single center is usually low, it will be important to collect data in a multi-center system to optimize the diagnostic evaluation and treatment of patients with severe asthma. So far, there is little reliable information about the frequency, phenotype and therapy of patients with severe asthma. The construction of a clinical register should close this gap. The primary objective is to show changes in symptoms control during follow up period and at study end by using the Asthma Control Test (ACT). Secondary endpoints are to collect data to better understand asthma's natural history in patients with severe asthma. The examination will be based on the assessment of the parameters specified under "outcomes".

Patients presenting to participating study center (pulmonologists in private practice or in pulmonary departments in hospital within Switzerland) with severe asthma will be asked to take part in this study when corresponding to the eligibility criteria. All patients with severe asthma will be included in the register only after detailed information and written consent. After four months (for specific therapies) and after 12 months, patients should be re-evaluated for up to 15 years. These follow-up data will also be recorded in the register. During the follow-up visits, the same parameters will be collected as during the initial Baselineexamination (some parameters will be omitted, for example, therapy received or requested for the defined period of the last 12 months, etc.). Severe asthma patients receiving a new specific therapy, e.g. obtained with antibodies, but who cannot be included in the register with the complete parameter profile due to time or capacity reasons of the centers, should be recorded at least with defined basic data and a reduced number of parameters in the register. These parameters include according to the specific asthma approved specific therapies, socio-demographic data, lung function values, laboratory values, parameters of asthma control, smoking status and add-on- therapy. This should make it possible to record a subgroup of severe asthmatics that are suitable for antibody therapy and at the same time offer the attending physician the opportunity to adequately document these complex and expensive therapies by recording the defined parameters. In these patients, an evaluation of the therapy response should be carried out after four months and documented in the register. Thereafter, there is an annual follow-up. At any time, these patients can be transferred to the full version of the register by entering the missing parameters. Patients for whom only the basic data is available (basic version) as well as patients with complete parameter profile in the register are kept in the same database and can be evaluated together. In general, no register-specific examinations will be carried out, but only parameters anyway recorded routinely.

Since this is a cohort study, no sample size calculation can be calculated. Evaluations are carried out continuously. The collective of the data should be described by descriptive statistics concerning the basic data as well as the data of the function diagnostics. Subentities of severe asthma should be identified by a cluster analysis.

Inclusion criteria

• In- and outpatients
• Age ≥ 0 year
• Informed consent as documented by signature

Adults:

"Asthma which requires treatment with guidelines suggested medications for GINA steps 4-5 asthma:

• High level therapy:

• high dose ICS with ≥ 1000 μg beclomethasone (powder) or equivalent in combination with LABA or leukotriene modifier/theophylline) for the previous year or
• Daily long-term therapy with systemic corticosteroids (CS) for ≥50% of the previous year to prevent it from becoming "uncontrolled" or which remains "uncontrolled" despite this therapy or
• Therapy with monoclonal antibodies independent from the co-therapy
• Middle level therapy:

Protokollsynopsis SAR Version 01 16.01.2019 Seite 4/10 a) Daily long-term therapy with medium-to high-dose ICS (≥500 μg Beclomethason (powder) or equivalent in combination with LABA or leukotriene modifier/theophylline) for the previous year and uncontrolled asthma defined as at least one of the following:

• Poor symptom control: ACQ consistently >1.5, ACT <20 (or "not well controlled" by NAEPP/GINA guidelines).
• Frequent severe exacerbations: two or more bursts of systemic CS (>3 days each) in the previous year.
• Serious exacerbations: at least one hospitalization, ICU stay or mechanical ventilation in the previous year.
• Airflow limitation: after appropriate bronchodilator withhold FEV1 <80% predicted (in the face of reduced FEV1/FVC defined as less than the lower limit of normal).
• Controlled asthma that worsens on tapering of these high doses of ICS or systemic CS (or additional biologics). The presence of any one of the following exclusion criteria will lead to exclusion of the patients:
• Life-expectancy <6 months
• Insufficient knowledge of project language

Children:

The criteria for severe or difficult asthma in children and adolescents are considered fulfilled in the case of insufficient symptom control in the last year despite medium/high antiinflammatory long-term therapy:

• age 0-18 years, at time of inclusion
• diagnosis of bronchial asthma made by a physician
• differential diagnoses excluded
• good compliance and trained inhalation technique
• treatment with biological approved for the treatment of severe asthma (currently only omalizumab) or

Proof of:

a) Positive Bronchodilation-test (≥12% increase in FEV1 after SABA) or b) Significant bronchial hyperresponsiveness after nonspecific provocation (e.g., with Methacholine or treadmill) according to ATS criteria (AJRCCM 2000)

• High level of therapy:

• Prolonged therapy with high dose inhaled steroid (ICS) (> 400 μg Budesonide equivalent /> 200 μg fluticasone alone); or
• Daily long-term therapy with medium- to high-dose ICS (≥ 400 μg Budesonide equivalent / ≥200 μg fluticasone) in combination with long-acting betaagonists and / or leukotriene receptor antagonist and / or theophylline; or
• Therapy with oral steroids fixed ≥3 last months.
• Insufficient asthma control

a) Inadequate symptom control after NVL in the last 4 weeks: Protokollsynopsis SAR Version 01 16.01.2019 Seite 5/10

• ≥3 x weekly asthma symptoms or use of ondemand medication; Or:
• limited activity due to asthma; Or:
• any symptoms at night; or b. Exacerbation(s) ≥1 last year that required treatment with systemic steroids and / or inpatient treatment c. limited lung function:
• pathological Tiffeneau quotient or FEV1 at inclusion.
• Submission of a written consent (parent/ legal guardian).

Exclusion criteria

• Life-expectancy <6 months · Insufficient knowledge of project language