Swiss Severe Asthma Register
Swiss Severe Asthma Register
Asthma is one of the most common chronic diseases. Asthma is characterized by chronic airway
 inflammation and associated with airway hyperresponsiveness and reversible airflow
 obstruction. The variability of airway obstruction is triggered by different factors that
 lead to a variety of different asthma phenotypes and subtypes. The various classification
 options for asthma (e.g. severity, by the predominantly existing inflammation or according to
 triggers), reflect its heterogeneity.

 Despite improved therapeutic methods, the prevalence and morbidity of asthma has increased
 worldwide in the last years. Asthma is a serious and growing global health problem with
 around 300 million people affected, independent of age or sex. Estimated 250'000 people die
 prematurely each year due to their asthma.

 Based on the SAPALDIA-study, the prevalence of Asthma in Switzerland is approximately 2-8%.
 Asthma is considered as a major factor in healthcare cost with up to CHF 1.2 billion per
 year. Asthma is not only a financial burden to a system; it affects the individual Quality of
 life negatively. Often health care professionals and patients underestimate the severity of
 the disease and overestimate asthma control. Severe asthma should not be equated with
 uncontrolled asthma. To reach a satisfying asthma control numerous factors need to be taken
 into consideration. Severe asthma is often associated with a high risk of frequent, severe
 exacerbations, which can even lead to death.

 Several severe asthma cohorts and registries already exists and are reported in the
 literature. The aim of such registries is in general data collection and a better
 understanding of the disease. So far, most epidemiological studies on severe asthma are
 cross-sectional with no follow up measures. Only a few studies did repeated measures using
 the same methods.

 Approximately 5% of all Asthma Patients suffers from severe asthma. These patients require
 systematic assessment and specialist care in dedicated respiratory centres. These centres
 have a key role in improving the outcome for severe asthma patients. At the same time they
 act as gatekeepers to ensure appropriate access to new, expensive therapies, this includes
 antibody treatment and interventional methods such as thermoplasty. These treatments require
 careful monitoring. It is important to ensure that they are given to the right population.
 Special assessment to monitor the efficacy and to prevent inappropriate prescribing, exposure
 of patients to unnecessary risks and excessive costs is indicated.

 For all the mentioned reasons a Swiss Severe Asthma Register and a collaboration with an
 already existing register is needed to prospectively collect data about severe asthma in
 Switzerland.
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:

 1. high dose ICS with ≥ 1000 μg beclomethasone (powder) or equivalent in combination
 with LABA or leukotriene modifier/theophylline) for the previous year or

 2. 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

 3. 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:

 1. Prolonged therapy with high dose inhaled steroid (ICS) (> 400 μg Budesonide
 equivalent /> 200 μg fluticasone alone); or

 2. 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

 3. 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