Longitudinal Assessment of Adults With Severe Asthma

Protocol for the European Multi-Centre Study Understanding Severe Asthma Longitudinal Assessment of Adults With Severe Asthma

Cross-sectional study to characterize cohorts of subjects with asthma and healthy controls in terms of clinical features, physiological measurements and non-invasive measurement of biomarkers and develop phenotype handprints for adults with severe asthma

Study Overview

• Status: Completed
• Conditions: Asthma

• Study Type: Observational
• Enrollment (Actual): 725

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Severe asthma cohorts: uncontrolled asthma symptoms or frequent severe exacerbations
• Mild-moderate asthma cohorts: controlled or partially controlled asthma symptoms
• Healthy controls: non-asthmatic healthy individuals free of significant disease

Description

General Inclusion Criteria:

1. Able to give written informed consent prior to participation in the study, which includes ability to comply with the requirements and restrictions listed in the consent form. Informed consent must be obtained prior to undertaking any study procedures.
2. Male or female subject aged 18 years or older at screening.
3. Able to complete the study and all measurements.
4. Able to read, comprehend, and write at a sufficient level to complete study related materials.
5. Subjects will be allowed to enrol in other studies while taking part on this study. However, Permission from the Scientific Board must be obtained to enrol or allow the continued participation of a subject enrolled in another study.

General Exclusion Criteria:

1. As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study either because of the risk to the subject due to the study or the influence this may have on the study results.
2. The subject has a history of recreational drug use or other allergy, which, in the opinion of the responsible physician, contra-indicates their participation.
3. Subject is female who is pregnant or lactating or up to 6 weeks post partum or 6 weeks cessation of breast feeding. If a woman is subsequently found to have been pregnant at the time of an assessment data from that assessment will not be included in the analyses.
4. The subject has participated within 3 months of the first dose in a study using a new molecular entity, or the first dose in any other study investigating drugs or having participated within three months in a study with invasive procedures. Any U-BIOPRED assessments should be deferred until 3 months after the first dose or invasive procedure. Permission from the Scientific Board must be obtained to enroll or allow the continued participation of a subject enrolled in another study.
5. Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
6. The subject has a recent history of incapacitating psychiatric disorders
7. History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 2 weeks of baseline assessments (assessments should be deferred).

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Cohort A; Adults: severe asthmatics on high dose ICS and / or OCS
Cohort B; Adults: current smokers or ex-smokers, severe asthmatics on high dose ICS and / or OCS
Cohort C; Adults: non-smokers, mild to moderate asthmatics on regular inhaled corticosteroids (ICS)
Cohort D; Adults: healthy volunteers, non-smokers, non-asthmatic with pre bronchodilator FEV1 > 80% predicted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthma exacerbations	Number, duration and severity of exacerbations over the time of the study	3 years
Lung function decline over the course of the study		3 years
Changes in asthma medication	in particular ICS dose, over the duration of the study	3 years
Daily symptoms and short acting beta agonist (SABA) usage	measured during the telemonitoring study	3 years
Asthma control questionnaire (ACQ) at baseline and changes over the course of the study		3 years
Upper airway symptoms as assessed by the sino-nasal outcomes test (SNOT) at baseline and changes over the course of the study		3 years
Sleep and daytime drowsiness as assessed by the Epworth sleepiness scale at baseline and changes over the course of the study		3 years
Measurement of pulmonary function including spirometry, plethysmography, bronchodilator reversibility and respiratory impedance by forced oscillation technique		3 years
Radiological parameters such as computerized tomography (CT) scan, including assessment of lung structure		3 years
Measurement of inflammatory cell counts in blood, sputum and bronchoalveolar lavage (BAL)		3 years
Histopathology of bronchial biopsies in a sub group of subjects	immunohistochemistry for inflammatory cells and matrix remodelling	3 years
Transcriptomics, proteomics and metabolomics will be used on samples such as blood, urine and endobronchial biopsies	to develop clinically useful phenotype handprints	3 years
Quality of life as assessed by the asthma quality of life questionnaire (AQLQ)		3 years
Anxiety and depression as assessed by the hospital anxiety and depression scale (HADS)		3 years

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Peter Sterk, Dr., Academic Medical Centre University of Amsterdam, The Netherlands; Principal Investigator: Ratko Djukanovic, Dr., Southampton General Hospital, UK; Principal Investigator: Stephen Fowler, Dr., Respiratory Research Group, Education and Research Centre, Wythenshawe Hospital, UK; Principal Investigator: Kian Fan Chung, Dr., Imperial College London, UK; Principal Investigator: Barbro Dahlén, Dr., Karolinska Institutet; Principal Investigator: Andrew Szczeklik, Dr., Uniwersytet Jagielloński - Collegium Medicum, Kraków, Poland; Principal Investigator: Thomas Geiser, Dr., Inselspital and University of Bern, Switzerland; Principal Investigator: Ildiko Horvath, Dr., University School of Medicine, Budapest, Hundary; Principal Investigator: Pascal Chanez, Dr., Université de la Méditerranee, Marseille, France; Principal Investigator: Jens Hohlfeld, Dr., Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover; Principal Investigator: Thomas Sandström, Dr., Department of Public Health and Clinical Medicine, Division of Medicine, Umea, Sweden; Principal Investigator: Dominick Shaw, Dr., Nottingham City Hospita, Nottingham, UK; Principal Investigator: Per Sigvald Bakke, Dr., Haukeland University Hospital, Bergen, Norway; Principal Investigator: Riccardo Polosa, Dr., Policlinico Vittorio Emmanuele, Catania, Italy; Principal Investigator: Paolo Montuschi, Dr., Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

General Publications

• Reinke SN, Naz S, Chaleckis R, Gallart-Ayala H, Kolmert J, Kermani NZ, Tiotiu A, Broadhurst DI, Lundqvist A, Olsson H, Strom M, Wheelock AM, Gomez C, Ericsson M, Sousa AR, Riley JH, Bates S, Scholfield J, Loza M, Baribaud F, Bakke PS, Caruso M, Chanez P, Fowler SJ, Geiser T, Howarth P, Horvath I, Krug N, Montuschi P, Behndig A, Singer F, Musial J, Shaw DE, Dahlen B, Hu S, Lasky-Su J, Sterk PJ, Chung KF, Djukanovic R, Dahlen SE, Adcock IM, Wheelock CE; U-BIOPRED Study Group. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study. Eur Respir J. 2022 Jun 30;59(6):2101733. doi: 10.1183/13993003.01733-2021. Print 2022 Jun.
• Kolmert J, Gomez C, Balgoma D, Sjodin M, Bood J, Konradsen JR, Ericsson M, Thorngren JO, James A, Mikus M, Sousa AR, Riley JH, Bates S, Bakke PS, Pandis I, Caruso M, Chanez P, Fowler SJ, Geiser T, Howarth P, Horvath I, Krug N, Montuschi P, Sanak M, Behndig A, Shaw DE, Knowles RG, Holweg CTJ, Wheelock AM, Dahlen B, Nordlund B, Alving K, Hedlin G, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Dahlen SE, Wheelock CE; U-BIOPRED Study Group, on behalf of the U-BIOPRED Study Group. Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study. Am J Respir Crit Care Med. 2021 Jan 1;203(1):37-53. doi: 10.1164/rccm.201909-1869OC.
• Emma R, Bansal AT, Kolmert J, Wheelock CE, Dahlen SE, Loza MJ, De Meulder B, Lefaudeux D, Auffray C, Dahlen B, Bakke PS, Chanez P, Fowler SJ, Horvath I, Montuschi P, Krug N, Sanak M, Sandstrom T, Shaw DE, Fleming LJ, Djukanovic R, Howarth PH, Singer F, Sousa AR, Sterk PJ, Corfield J, Pandis I, Chung KF, Adcock IM, Lutter R, Fabbella L, Caruso M; U-BIOPRED Study Group. Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort. PLoS One. 2018 Sep 21;13(9):e0203874. doi: 10.1371/journal.pone.0203874. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): November 6, 2013

Study Record Updates

• Last Update Posted (Estimate): January 14, 2015
• Last Update Submitted That Met QC Criteria: January 13, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Asthma; Proteomics; Phenotyping; Lipidomics; Transcriptomics; Systems Biology; Smokers; Sputum; Biopsies; Severe asthma; Clinical cohorts; Collaborative research; Paediatric cohort
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 10/H0721/66