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Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02660853
Recruitment Status : Completed
First Posted : January 21, 2016
Results First Posted : October 31, 2019
Last Update Posted : December 3, 2019
Royal Brompton & Harefield NHS Foundation Trust
Information provided by (Responsible Party):
Imperial College London

Brief Summary:
The purpose of this study is to investigate exacerbations in severe asthma with regard to symptoms, lung function, aetiology and biomarkers.

Condition or disease Intervention/treatment Phase
Asthma Diagnostic Test: FEV1 Not Applicable

Detailed Description:

Patients will be recruited from the Severe Asthma Clinics at Royal Brompton Hospital. At the first visit the investigators will enrol and characterise patients. This will involve asking patients to keep a diary record of PEFR(Peak Expiratory Flow Rate), spirometry, symptom scores, use of beta-agonist reliever and other treatments for 2 weeks. Bloods tests will be taken for markers of systemic inflammation. Markers of oxidative stress will be measured in blood, exhaled breath condensate (EBC) and urine: malondialdehyde (MDA) and 8-isoprostanes. Nitric oxide (NO) levels in exhaled breath will be measured measured twice daily for 2 weeks using a portable hand-held NO meter. If spontaneous sputum is not available, sputum will be induced using ultrasonic nebulization of isotonic saline. Profile of inflammatory cells, cytokines in supernatants, bacteriological culture and microbiome analysis will be measured in the sputum. Patients will be observed over 12 months during which time the number of exacerbations will be recorded on basis of objective measures with evaluation of ACQ (Asthma Control Questionnaire), daily morning and evening PEF (Peak Expiratory Flow). At the earliest onset of exacerbation, the patient will be requested to contact the Asthma Research Unit. Patients will then be asked to attend the laboratory where similar tests to the first visit will be performed. For other exacerbations not studied, the patient will be asked to keep a detailed diary record of symptoms with severity scoring and spirometric and PEF measurements (Exacerbation Diary) over a period of 2 weeks after onset of exacerbation.

As patients with severe asthma are usually very well experienced in what the symptoms of exacerbations are, they will therefore be asked to recognise their own exacerbations. Each patient has their own way of recognising an exacerbation and the investigators will discuss this with each patient and try and establish whether an earlier warning signal is possible. Patients will be asked to record their symptoms and lung function as soon as they feel the onset of an exacerbation, since exacerbations are recognised by the patient as events that are 'clinically identified by being outside the patient's usual range of day-to-day variation'. The patient will receive or administer treatments for the exacerbation as usual without interference from the Research Team except for starting any antibiotic therapies, which will be started (if prescribed) as soon as the visit studies have been completed. Those who have been hospitalized will not be studied, and only those who can attend the Clinical Research Unit will be studied.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers
Study Start Date : June 2015
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Severe Asthma
Patients under Steps 4/5 of Asthma Treatment - SIGN (Scottish Intercollegiate Guidelines Network) / BTS (British Thoracic Society) Guidelines
Diagnostic Test: FEV1
Participants have FEV1 test

Primary Outcome Measures :
  1. Percent Predicted FEV1 [ Time Frame: Baseline Visit, 12 months ]
    From date of screening visit until date of first asthma exacerbation visit Percent predicted Forced Expiratory Volume in First Second

Secondary Outcome Measures :
  1. Exhaled Breath Condensate [ Time Frame: Baseline Visit, 12 months ]
    pH and free Iron

  2. Markers of Oxidative Stress in Urine [ Time Frame: Baseline Visit, 12 months ]
    malondialdehyde (MDA)

  3. Markers of Oxidative Stress in Urine [ Time Frame: Baseline Visit, 12 months ]

  4. Sputum Analysis [ Time Frame: From baseline visit and 12 months ]
    Eosinophils as percentage of total count

  5. PCR for Respiratory Viruses [ Time Frame: Baseline Visit, 12 months ]
    nasopharyngeal swabs

  6. Sputum Microbiome [ Time Frame: Baseline Visit, 12 months ]
  7. Corticosteroid Insensitivity in Peripheral Blood Mononuclear Cells [ Time Frame: Baseline Visit, 12 months ]
  8. Exhaled Nitric Oxide [ Time Frame: Baseline Visit, 12 months ]
  9. Exhaled Hydrogen Sulphide [ Time Frame: Baseline Visit, 12 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • All patients must be able to give informed consent. The definition of severe asthma will be on the basis of

    • Uncontrolled asthma: three or more of the following features present in any week in the previous 4 weeks:

      • Daytime symptoms more than twice per week
      • Any limitation of activities
      • Nocturnal symptoms once or more per week
      • Need for reliever treatment more than twice per week
      • Pre bronchodilator FEV1 <80% predicted or personal best OR
    • Frequent severe exacerbations (≥2 per year) OR
    • Require prescription of daily or alternate day oral corticosteroids (OCS) to achieve asthma control despite the prescription of high dose inhaled corticosteroids (>1000mcg fluticasone propionate daily or equivalent) or maintenance oral corticosteroids plus a long acting beta agonist or one other controller medication (for example anti-cholinergics, leukotriene receptor antagonists or theophylline).

Exclusion Criteria:

  • • Current smoker, or Ex-smoker with a >10 year pack history or having smoked within the past 6 months

    • Significant alternative diagnoses that may mimic or complicate asthma, in particular dysfunctional breathing, panic attacks, and overt psychosocial problems (if these are thought to be the major problem rather than in addition to severe asthma)
    • Significant other primary pulmonary disorders in particular pulmonary embolism, pulmonary hypertension, interstitial lung disease and lung cancer
    • Subjects with emphysema and bronchiectasis should only be excluded if this is thought to be the major pulmonary disorder rather than in addition to severe asthma
    • Diagnosis or current investigation of occupational asthma
    • Any subjects currently participating, or having 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02660853

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United Kingdom
Biomedical research Unit, Royal Brompton Hospital, Sydney Street
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Imperial College London
Royal Brompton & Harefield NHS Foundation Trust
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Principal Investigator: Kian F Chung, MBBS MD FRCP Imperial College London
  Study Documents (Full-Text)

Documents provided by Imperial College London:

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Responsible Party: Imperial College London Identifier: NCT02660853     History of Changes
Other Study ID Numbers: 13/LO/1198
First Posted: January 21, 2016    Key Record Dates
Results First Posted: October 31, 2019
Last Update Posted: December 3, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Additional relevant MeSH terms:
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Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases