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Asthma: Phenotyping Exacerbations 3

Conditions
Asthma Attack
Interventions
Diagnostic Test: Spirometry including peak flow
Diagnostic Test: Fractional Exhaled Nitric Oxide (FeNO)
Diagnostic Test: Forced Oscillation Technique (FOT)
Procedure: Sputum Induction
Diagnostic Test: Bloods
Diagnostic Test: Nasal lavage
Diagnostic Test: Throat swab
Diagnostic Test: Nasal Brush.
Diagnostic Test: Nasal absorption
Other: Medical History, Demographic, and Concomitant Medications
Other: Sino-nasal Outcome Test
Other: Gastroesophageal Reflux Disease Questionnaire
Other: Pittsburgh Vocal Cord Dysfunction Index
Other: Nijmegen Questionnaire.
Other: Hospital Anxiety and Depression Scale
Other: Compliance and adherence
Other: Acute Asthma Quality of Life Questionnaire
Registration Number
NCT05446090
Lead Sponsor
University of Nottingham
Brief Summary

Exacerbations of asthma (asthma attacks) are very common in the UK. They are frightening for patients, expensive for the health service, and occasionally lead to avoidable deaths.

Despite the obvious importance of asthma attacks, they remain poorly understood. Although some of the triggers for attacks are known, the resultant characteristics of attacks are not. Recent research has shown different inflammation profiles associated with asthma attacks; however, this is not well understood, and all asthma attacks are treated the same. Increased knowledge about the nature of asthma attacks may better define these attacks and help develop more targeted treatment options.

This study aims to describe the characteristics of patients admitted with asthma attacks. The recovery and response to standard treatment for asthma attacks following discharge from the hospital will also be described.

This is achieved by studying the characteristics of asthma attacks in patients hospitalized with acute asthma. Participants will be asked to attend two follow-up visits during which their response to treatment will be described.

The study is planned to last for 2.5 years, with a recruitment period of 18 months, and will include 100 participants with acute asthma.

Detailed Description

Asthma is a common condition affecting 9.8 million people in the United Kingdom1. Asthma attacks cause nearly 1500 deaths per year in the UK2 and account for over 90,000 hospital admissions and 1800 intensive care admissions costing at least 1 billion pounds a year3.

Non-asthma conditions such as Vocal Cord Dysfunction4 and Dysfunctional Breathing Pattern5 can mimic severe asthma and lead to hospital admission and inappropriate asthma treatment with potentially harmful high dose corticosteroids. However, the proportion of patients admitted with these asthma mimics is unclear.

The use of biomarkers to guide treatment in stable asthma is now commonplace, but this prospect has not been fully explored in acute asthma attacks. Determining the type of inflammation underlying an attack can, however be tricky because many patients receive oral corticosteroid prior to, or soon after admission, which promptly and markedly affects the most accessible type 2 asthma (T2) biomarkers7, the blood eosinophil count. Measurement of another T2 biomarker, fractional exhaled nitric oxide (FENO), during an attack may prove a useful measure of ongoing T2 airway inflammation, but this strategy requires assessment.

Airway obstruction in asthma attacks is assessed and confirmed by measuring peak expiratory flow and/or forced expiratory volumes. These measures are effort-dependent and can, therefore, be unreliable and misleading if improperly performed. We aim to evaluate the potential feasibility and utility of alternative diagnostic methods of assessing airway obstruction and measuring T2 biomarkers to see if these allow the distinction between actual asthma attacks and asthma attack mimics and also if they can distinguish different types of asthma attacks.

The pattern of recovery following asthma attacks is also not fully understood. Studies have reported varying recovery times8 and inconsistencies in the response of airway obstruction9 and T2 biomarkers10 to corticosteroid treatment in acute asthma.

The investigators hypothesise that a significant proportion of patients admitted to hospital with suspected asthma attacks have an alternate cause for their clinical presentation. To further explore this, The investigators propose an observational study to describe and investigate the characteristics of patients admitted with suspected severe asthma. The investigators will assess the utility of point of care, non-invasive biomarker measurements in identifying pulmonary and extrapulmonary traits in patients hospitalised due to presumed asthma attack. A variety of study assessments will be performed at the baseline visit (exacerbation visit), and two follow up visits following hospital discharge. Results of study assessments obtained during each study visit will be compared and analysed. This is the first study to prospectively investigate acute asthma both during and following exacerbation episodes. This will allow a comprehensive understanding and description of pulmonary and extrapulmonary traits as well as the pattern of recovery following asthma attacks.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
100
Inclusion Criteria
  • The ability to give fully informed consent
  • Male or female aged ≥ 18 years of age.
  • Admission with a suspected acute asthma attack.
  • Able (in the investigator's opinion) and willing to comply with clinical investigation requirements.
Exclusion Criteria
  • Other clinically significant respiratory diseases including predominant Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis.
  • Any other clinically significant medical disease or uncontrolled concomitant disease that is likely, in the investigator's opinion, to impact the ability to participate in the study or the study results.
  • Pregnant women, lactating women or women who are planning to become pregnant.
  • Investigator determined apparent other cause for admission.
  • Acute COVID infection.
  • Non-English-speaking participants who are unable to comprehend the reasons for the study due to limitations in understanding the English language

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Asthma Attack patients.Fractional Exhaled Nitric Oxide (FeNO)Patients admitted with Asthma Attacks.
Asthma Attack patients.Nasal Brush.Patients admitted with Asthma Attacks.
Asthma Attack patients.Spirometry including peak flowPatients admitted with Asthma Attacks.
Asthma Attack patients.BloodsPatients admitted with Asthma Attacks.
Asthma Attack patients.Throat swabPatients admitted with Asthma Attacks.
Asthma Attack patients.Compliance and adherencePatients admitted with Asthma Attacks.
Asthma Attack patients.Sino-nasal Outcome TestPatients admitted with Asthma Attacks.
Asthma Attack patients.Gastroesophageal Reflux Disease QuestionnairePatients admitted with Asthma Attacks.
Asthma Attack patients.Pittsburgh Vocal Cord Dysfunction IndexPatients admitted with Asthma Attacks.
Asthma Attack patients.Nijmegen Questionnaire.Patients admitted with Asthma Attacks.
Asthma Attack patients.Forced Oscillation Technique (FOT)Patients admitted with Asthma Attacks.
Asthma Attack patients.Nasal lavagePatients admitted with Asthma Attacks.
Asthma Attack patients.Nasal absorptionPatients admitted with Asthma Attacks.
Asthma Attack patients.Medical History, Demographic, and Concomitant MedicationsPatients admitted with Asthma Attacks.
Asthma Attack patients.Sputum InductionPatients admitted with Asthma Attacks.
Asthma Attack patients.Acute Asthma Quality of Life QuestionnairePatients admitted with Asthma Attacks.
Asthma Attack patients.Hospital Anxiety and Depression ScalePatients admitted with Asthma Attacks.
Primary Outcome Measures
NameTimeMethod
Assessment of evidence of infection: CRP.14 days

Assessment of evidence of infection: CRP.

Assessment of evidence of infection: Throat swab/nasal lavage for viral PCR.baseline

Assessment of evidence of infection: Throat swab/nasal lavage for viral PCR.

Assessment of airway obstruction at attack and recovery visits using spirometry.14 days

Assessment of airway obstruction

Assessment of airway obstruction at attack and recovery visits using Forced Oscillation Technique (FOT).14 days

Assessment of airway obstruction

Assessment of cytokine levels in nasal lining fluid at attack and recovery visits14 days

Nasal absorption will be used to collect mucosal lining fluid from the respiratory tract for cytokines profiling at baseline (attack) and at second visits.

Assessment of adherence to medications (MARS, prescription records, inhaler technique) for the assessment of behavioural attack traits.baseline

Assessment of behavioural attack traits.

Assessment of airway obstruction at attack using physician recorded expiratory wheezebaseline

Assessment of airway obstruction

Assessment of airway inflammation at attack and recovery visits using sputum inflammatory cell count.14 days

Assessment of airway inflammation

The assessment of the incidence of Gastroesophageal Reflux Disease.baseline

The assessment of the incidence of Gastroesophageal Reflux Disease using the GERDQ questionnaire.

The assessment of the incidence of anxiety and depressionbaseline

The assessment of the incidence of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).

The measurement of vitamin D levels in the blood on admission to the hospitalbaseline

vitamin D levels in the blood on admission to the hospital

A specific asthma history (polypharmacy, previous asthma attacks, triggers, Personalised Asthma Action Plan) for the assessment of risk factor for attack.baseline

Assessment of risk factor for attack

Assessment of symptom burden at attack and recovery visits using the Acute AQLQ questionnaire28 days

Assessment of symptom burden

Assessment of airway obstruction at attack and recovery visits using peak expiratory flow rate (PEFR).14 days

Assessment of airway obstruction

Assessment of airway inflammation at attack and recovery visits using blood eosinophil count.14 days

Assessment of airway inflammation

Assessment of the incidence of upper airway symptoms.baseline

The incidence of upper airway symptoms will be assessed using the Sino-nasal Outcome Test (SNOT).

The assessment of the incidence of vocal cord dysfunctionbaseline

The assessment of the incidence of vocal cord dysfunction using the Pittsburgh Vocal Cord Dysfunction (VCD) Index.

The assessment of the incidence of dysfunctional breathingbaseline

The assessment of the incidence of dysfunctional breathing using the Nijmegen dysfunctional questionnaire.

Assessment of evidence of infection: sputum for bacterial culture and sensitivity (MC&S).14 days

Assessment of evidence of infection: sputum for bacterial culture and sensitivity (MC\&S).

Assessment of airway inflammation at attack and recovery visits using Fractional Exhaled Nitric Oxide (FeNO).14 days

Assessment of airway inflammation

Assessment of Body Mass Index BMI.baseline

Assessment of Body Mass Index BMI.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Nottingham University Hospital

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Nottingham, Nottinghamshire, United Kingdom

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