AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS)

Completed

Conditions: asthma
small airways abnormalities
10038716

Registration Number: NL-OMON41215

Lead Sponsor: Chiesi Farmaceutici S.p.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 104

Inclusion Criteria

Asthmatic patient inclusion criteria
1. Male or female patients aged >= 18 and <= 65 years, who have signed an Informed Consent form prior to initiation of any study-related procedure.
2. Clinical diagnosis of asthma for at least 6 months confirmed by a chest physician according to international guidelines (GINA 2012) supported by objective evidence of any of the following at the baseline visit or in the previous 5 years.
a) Positive response to methacholine challenge test [PC20 < 8 mg/mL or PD20 < 0.7 mg for those subjects not using inhaled corticosteroids (ICS), and PC20 < 16 mg/mL or PD20 < 1.4 mg for subjects using ICS]
or
b) Positive response to a reversibility test, defined as ΔFEV1 >= 12% and >= 200 mL over baseline FEV1, within 30 minutes after administration of 400 µg of salbutamol pMDI administered with or without Spacer
or
c) Peak Flow variability (i.e. highest - lowest PEF over the day/mean value of the two, × 100) > 20%, measured over a follow-up period of 7 days
or
d) Documented response (defined as ΔFEV1 >= 12% and >= 200 mL) after a cycle (e.g., 4 weeks) of regular maintenance anti-asthma treatment.
3. Patients with stable asthma, on any previous regular asthma treatment (*rescue* β2-agonists alone included) at a stable dose, for at least 8 weeks prior to baseline visit.
4. Current smoker, ex-smoker (since the past 12 months) or lifelong non-smoker (total lifetime smoking history < 10 packyears defined as [(number of cigarettes smoked per day) x(number of years of smoking)] / 20).
Healthy subject inclusion criteria
1. Male or female patients aged >= 18 and <= 65 years, who have signed the Informed Consent form prior to initiation of any study-related procedure.
2. No clinical history of asthma or COPD (no respiratory symptoms compatible to asthma or COPD in the past 2 years).
3. Current smoker, ex-smoker (since the past 12 months) or lifelong non-smoker (total lifetime smoking history < 10 packyears).
4. Normal spirometry: baseline FEV1 >= 80% of the predicted normal value, FEV1/FVC > LLN (lower limit of normal).
5. Normal airways responsiveness: PC20 >= 16 mg/mL, PD20 >= 1.4 mg.

Exclusion Criteria

Asthmatic patient exclusion criteria
1. Cigarette smoking > 10 packyears defined as [(number of cigarettes smoked per day) x (number of years of smoking)] / 20.
2. diagnosis of COPD confirmed by a chest physician.
3. Asthma exacerbation in the 8 weeks prior to baseline visit (defined as a significant deterioration of asthma and signalled by any or more of the following: need for a systemic corticosteroid course (>= 3 days); hospitalisation for asthma; emergency room attendance for asthma).
4. Clinical or functional uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might, in the judgment of the investigator, compromise the results or interpretation of the study.
5. Pregnant or lactating women (a urine pregnancy test will be performed).
6. Participation in an interventional clinical trial with intake of the last dose of any investigational drug <12 weeks preceding baseline visit (last dose < 5 half-lives prior to baseline visit for biologics).
7. Inability to comply with study procedures.
8. Alcohol or drug abuse.;Healthy subject exclusion criteria
1. Cigarette smoking history > 10 packyears defined as [(number of cigarettes smoked per day) x (number of years of smoking)] / 20.
2. Diagnosed upper and/or lower respiratory disease(s).
3. Clinical or functional uncontrolled haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might, in the judgment of the investigator, compromise the results or interpretation of the study.
4. Pregnant or lactating women (a urine pregnancy test will be performed).
5. Participation in an interventional clinical trial with intake of the last dose of any investigational drug <12 weeks preceding baseline visit (last dose < 5 half-lives prior to baseline visit for biologics).
6. Inability to comply with study procedures.
7. Alcohol or drug abuse.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- To determine the role of small airways abnormalities in the clinical<br /><br>manifestations of asthma.<br /><br>- To evaluate which (combination of) clinical methods best assess the<br /><br>abnormalities of small airways and large airways disease in asthma and best<br /><br>relates to asthma severity, control, and future risk of exacerbations, both<br /><br>cross-sectionally and longitudinally.<br /><br>- To assess if a questionnaire (Small Airways Dysfunction Tool) could be<br /><br>offered to physicians in diagnosing Small Airways Disease (SAD) in asthma, and<br /><br>thus characterize asthma patients with small airways diseases as determined by<br /><br>physiologic and radiographic assessments and measurement of specific biomarkers.<br /><br></p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To define the physiologic characteristics that correlate with small<br /><br>airways function in asthma as compared to healthy controls.<br /><br>- To define the radiographic characteristics that correlate with small airways<br /><br>function in asthma as compared to healthy controls.<br /><br>- To determine which direct and indirect measures of inflammation best<br /><br>correlate with inflammation in the large and small airway compartments.<br /><br>- To determine if questionnaires such as ACQ-6 and ACT assess small airways<br /><br>function.<br /><br>- To determine the correlation between SAD and asthma control.<br /><br>- To determine if SAD is associated with exacerbations requiring prescription<br /><br>of oral corticosteroids.</p><br>