Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional

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

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.
    

Intervention name(s): FEV1
Intervention type(s): Diagnostic Test
Intervention description(s): Participants have FEV1 test
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Exacerbations