Asthma: Phenotyping Exacerbations 2 (APEX 2)

Phenotyping Asthma Exacerbations: A Longitudinal Cohort Study 2

The main outcomes of this study are to establish a cohort of well-phenotyped asthma patients with a recent history of an exacerbation. We aim to describe exacerbation profiles (phenotypes) of the cohort in terms of inflammatory/biomarker profile and bacterial/viral infection status and to compare these with exacerbation events in the sister APEX cohort.

Study Overview

• Status: Recruiting
• Conditions: ASTHMA
• Intervention / Treatment: Diagnostic test: spirometry, FOT, Induced sputum, bloods, nasal brushes, nasal lavage, skin prick, throat swab

Detailed Description

A single centre, observational, longitudinal cohort study. The study will consist of one group of approximately 100 patients with clinician diagnosed asthma, who have had at least one exacerbation in the past 5 years before informed consent. They will be identified from secondary care, primary care and the Nottingham Respiratory Research Database (NRRD).

After the Baseline visit, each subject will be followed for the duration of their participation in the study. Participants will be asked to contact the research team if they perceive that their asthma symptoms are worsening to the extent that they would usually seek help from a healthcare professional. They will then be invited to attend the Assessment Visit and potential Exacerbation Visit. Participants who complete this visit will then continue in the study, as we are interested in comparing subsequent events in the same individuals, to establish exacerbation stability and consistency.

All participants, whether they have attended an Assessment visit or not, will be invited to attend for an Annual visit. The research team will also contact participants at 3 monthly intervals, with their permission, to discuss the study and provide updates.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Recruiting
      • Nottingham respriatory research unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A population of asthmatics who have had an exacerbation in the 60 months prior to the study

Description

INCLUSION

• Clinician diagnosed asthma.
• Male or female aged ≥ 18 and ≤ 85 years of age.
• One asthma exacerbation requiring additional treatment in 5 years prior to informed consent. This is defined as either: 3 or more consecutive day's treatment with oral corticosteroids; for participants not on maintenance steroids, OR at least a doubling of treatment with oral corticosteroids for 3 or more consecutive days, from a stable dose, for participants on maintenance therapy with oral corticosteroids. These can be patient-reported.
• On British Thoracic Society (BTS) step 1-5 treatment
• Current smokers can be included, provided there is good evidence of underlying asthma (for example, a life-long history of asthma, > 12% FEV1 reversibility or sputum or blood eosinophilia).
• Able (in the Investigator's opinion) and willing to comply, with all clinical investigation requirements.
• Non-English speaking participants should be proficient in their understanding of the English language, in order to be able to fully participate in the study.

EXCLUSION:

• Exacerbation in the 4 weeks prior to the Baseline visit. The use of biologic therapy, including Omalizumab, Mepolizumab or Benralizumab, at any time during the 3 months.
• prior to informed consent. Participants who commence biologic therapy during the course of the study will be withdrawn.
• A history more in keeping with smoking-related Chronic Obstructive Pulmonary Disease (COPD)
• Other clinically significant respiratory diseases.
• Use of regular high dose maintenance systemic corticosteroids (for example, a dose of > 10mgs of Prednisolone daily)
• Any other clinically significant medical disease or uncontrolled concomitant disease, that is likely, in the opinion of the investigator, to impact on the ability to participate in the study or the study results.
• Pregnant women, lactating women or women who are planning to become pregnant.
• Participants with uncontrolled hypertension. Participation in a study involving an investigational medicinal product at any time during the 3 months prior to informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of study participants with an eosinophilic and non eosinophhilic phenotype	Percentage of study participants with an eosinophilic and non eosinophhilic phenotype	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of exacerbations associated with confrimed viral and bacterial infection	The prercentage of participants within the cohort with at least one exacerbation associated with confirmed viral and bacterial infection by the end of the study	3 years
Asthma control questionnaire	ACQ score at baseline and then at exacerbation and annual visits. 0 is total control and 6 is severely uncontrolled	3 years
Medication Adherence Rating Scale (MARS)	MARS at baseline and then at exacerbation and annual visits. 5 Questions scored 1-5. 1 being the best and 5 being the worst.	3 years
Measuring Lung function and inflammation	Measure Forced Oscialltion Technique (FOT) and Spirometry and Fractional Echaled Nitric Oxide (FENO) at baseline and then at exacerbation and annual visits.	3 years
Blood profile	Measure FBC CRP IgE at baseline. During an exacerbation and Annual visit FBC CRP will be measured. Additional bloods will be taken at each visit for future research	3 years
Nasal lavage fluid and throat swab	Nasal lavage will be performed along side a throat swab to identify any virsuses at baseline, exacerbation and annual visits.	3 years
Skin Prick testing	Skin prick tests will be performed on all patients at baseline to assess if they are sensitive to common allergens and would be suggestive of atopy	3 years.
Induced sputum	Induced sputum will be attempted on all patients at baseline exacerbation and on annual visits to assess sputum cell counts at each of the specific points.	3 years
Nasal brushes	Nasal brush samples will be obtained to identify viral genetics at baseline, exacerbation and annual visits	3 years

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Tim Professor Harrison, MBBS, BSc, FRCP, MD, MSc, University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2019
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: asthma exacerbations
• 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: 19055

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No