Pharmaco-Epidemiological Study of Cardio-Respiratory Safety of Beta2-agonists for the Treatment and Management of Asthma-COPD Overlap Syndrome

Date of Approval: 
2018-04-18 00:00:00
Lay Summary: 
Asthma and chronic obstructive pulmonary disease (COPD) are two common diseases that affect the lung, which sometime may occur together or overlap, which is called asthma-COPD overlap syndrome (ACOS). ACOS has recently been described and just as the basic definitions of asthma and COPD are sometimes debated, the primary definition of ACOS is not yet clear, however, patients with ACOS consume more and higher doses of medications. One type of medicine, called bronchodilators, open the airways in the lung and are recommended by expert guidelines for the treatment and management of both asthma and COPD. However, there is a lack of knowledge about the risk of effects of the use of high doses of bronchodilators on the heart and lungs. To address this knowledge gap, we propose to use routinely collected health information from the Clinical Practice Research Datalink (CPRD) to identify patients who have developed new heart and lung illness and compare their medication use with otherwise similar people who do not develop heart and lung illness to see whether it is a side effect of using large amounts of bronchodilator medications.
Technical Summary: 
To date, there are no published observational studies which have examined the association between Beta2-agonist medications and the risk of Cardio-Respiratory (CR) events in patients with Asthma-COPD Overlap Syndrome, ACOS. To address these limitations and knowledge gap, this research proposes to use an existing database of detailed healthcare records of new-users of bronchodilator medications for patients with physician diagnosed asthma and COPD. In particular, the impact of CR outcomes /events which include all-cause-mortality, pneumonia and major adverse cardiovascular events (including non-fatal myocardial infarction (MI), non-fatal stroke, heart failure (HF), arrhythmia or cardiovascular mortality) in patient with ACOS would be assessed and the results from this proposed study will represent the first and novel findings.
Health Outcomes to be Measured: 
Outcomes: Our primary endpoints of interest are 1) all-cause mortality 2) pneumonia and 3) major adverse cardiovascular events. Pneumonia and major adverse cardiovascular events will consist of a diagnosis recorded in the GOLD data or HES data. Since mortality outcomes are only available in the subcohort data linked to ONS (death certificate), we will use this linked subcohort to assess cause-specific mortality for pneumonia and cardiovascular mortality. Major adverse cardiovascular events will be defined as the first occurrence of non-fatal MI, non-fatal stroke, heart failure, arrhythmia or any cardiovascular-related mortality. Outcome assessment of cardiovascular-related admissions and mortality will be based on READ codes contained in the GOLD data linked to the sub-cohort of ICD-10 codes in the HES/ONS data (see Appendix D for codes). These outcomes definition were based on validated READ codes in the CPRD data and ICD-10 codes in the HES or ONS linkage data.[48-50]. Our research will utilize the full study cohort identified from the GOLD database to maximize precision.
Application Number: 

Zhiwei Gao - Chief Investigator - Memorial University of Newfoundland ( MUN )
Joseph Amegadzie - Corresponding Applicant - Memorial University of Newfoundland ( MUN )
Jamie Farrell - Collaborator - Memorial University of Newfoundland ( MUN )
John-Michael Gamble - Collaborator - University Of Waterloo
William K. Midodzi - Collaborator - Memorial University of Newfoundland ( MUN )

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation