Phenotyping Asthma Exacerbations in primary care: an electronic medical record study (PHASE)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medical condition to be studied:
  Asthma

Population studied

• Short description of the study population:
  1. Patients with a EMR diagnosis of asthma.; 2. Evidence of active asthma (at least 2 ICS prescriptions in the last 12 months). ; 3. Treatment of an exacerbation with oral steroids and/or oral antibiotics between 2000 - January 2020.; 4. An asthma exacerbation in primary care.; 5. BEC recorded in the 12 months prior to the exacerbation date.; 6. Continuous electronic medical record data for the 12 months prior to, and at least 90 days following, the exacerbation date.;
• Age groups:
  All

  In utero

  Paediatric Population (< 18 years)

  Neonate

  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adult and elderly population (≥18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)

Study design details

• Study design:
  Historical, longitudinal, descriptive cohort study using patients’ electronic medical records (EMR) extracted from general practices from the Optimum Patient Care Research Database (OPCRD).
• Main study objective:
  Determine whether blood eosinophil count (BEC) can discriminate between different clinical responses to oral corticosteroid and/or antibiotic treatment for asthma attacks in primary care.
• Setting:
  Electronic medical records (EMR) extracted from general practices from the Optimum Patient Care Research Database (OPCRD).
• Comparators:
  Primary ; 1. Compare the rates of treatment failure (defined below) at 28 days for asthma exacerbations treated in primary care with oral steroids, or antibiotics, or both between high (>=0.3 x 10^9/L) and low (<0.3 x 10^9/L) blood eosinophil count (BEC) groups at steady state.; ; Key secondary ; 1. Compare the rates of treatment failure at 28 days for asthma exacerbations treated in primary care with oral steroids, or antibiotics, or both continuously by BEC at steady state.; ; Other secondary ; 1. Compare the rates of treatment failure at 14 days for asthma exacerbations treated in primary care with oral steroids, or antibiotics, or both continuously by BEC at steady state; 2. Compare the rates of treatment failure at 14 days for asthma exacerbations treated in primary care with oral steroids, or antibiotics, or both between high (>=0.3 x 10^9/L) and low (<0.3 x 10^9/L) blood eosinophil count (BEC) groups at steady state.; 3. Compare the rates of treatment failure at 14 and 28 days for asthma exacerbations treated in primary care with oral steroids, or antibiotics, or both between high (>=0.3 x 10^9/L) and low (<0.3 x 10^9/L) BEC groups on day of exacerbation. ; 4. Compare the rates of treatment failure at 14 and 28 days for asthma exacerbations treated in primary care with oral steroids, or antibiotics, or both continuously by BEC on day of exacerbation. ; 5. Explore the association between time to treatment failure up to 90 days, the continuous BEC value, and other covariates.; 6. Characterise asthma exacerbations by BEC on day of exacerbation and examine their relationship with the time of year. ; 7. Record diagnostic labels used for asthma exacerbations and compare the use of steroids and/or antibiotics, and the rates of treatment failure.
• Outcomes:
  Primary Outcomes; 1. Treatment failure at 28 days after exacerbation date, defined as: ; i) Acute prescription of oral corticosteroids and/or oral antibiotics in conjunction with an asthma or LRTI related primary care consultation. ; ii) Admission to hospital, or emergency department visit, or out of hours healthcare visit, with asthma or LRTI as primary or secondary diagnosis. ; 2. Highest BEC in the last 12 months.; ; Secondary Outcomes; 1. Treatment failure at 14 days after exacerbation date.; 2. Treatment failure at 90 days after exacerbation date.; 3. BEC on day of exacerbation.; 4. Blood CRP level taken on exacerbation date (if available). ; 5. Date of exacerbation .; 6. Diagnostic label of exacerbation (asthma attack/exacerbation; or LRTI; or other/undocumented).; 7. Diagnostic label of pre-existing airways disease (asthma; or asthma/COPD). ;
• Data analysis plan:
  For the primary outcome, Cox proportional hazards regression analysis will be used to adjust for confounders (age, sex, BMI, FEV1, GINA step, season of exacerbation, co-morbid COPD) to estimate the association between BEC and treatment failure. This will be modelled using the BEC categories listed above. We will also run a recurrent event Cox model and a discrete-time Cox model. Kaplan-Meier curves will be performed with high/low blood BEC as a categorical variable.; ; For the key secondary analysis of BEC as a continuous variable we will log-transform BEC for the analysis. The Cox models will be represented graphically using a restricted cubic spline association the adjusted treatment failure hazard ratio (outcome variable) and BEC. This analysis will allow exploration of non-linearity and choice of BEC threshold for a future trial.