Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by increasing breathlessness. It is a major cause of disability, it reduces quality of life and is one of the leading causes of death. An acute exacerbation of COPD can occur when there is a sudden worsening of usual COPD symptoms such as increased wheezing, shortness of breath, as well as presence of persistent cough, and when severe can require hospitalisation. Long-acting bronchodilators, including long-acting beta2-agonists (LABA) and long-acting muscarinic antagonists (LAMA), are recommended as initial treatment for COPD. However, most LABAs are dispensed with an inhaled corticosteroid (ICS) in a fixed combination inhaler (LABA-ICS). Thus, a real-world study of patients representative of clinical practice is of interest, with the benefit in reducing COPD exacerbations balanced against the increased risk of pneumonia.
The objective of the study is to compare the benefit and risk of these initial treatments for COPD. In particular, the study will compare the effectiveness of initial treatment with LABA-ICS versus LAMA in preventing the occurrence of COPD exacerbations and to compare their safety with respect to the risk of pneumonia, of concern when ICS are present.
The objective of this study is to assess the effectiveness and safety of the initial long-acting bronchodilator treatment of chronic obstructive pulmonary disease (COPD). In particular, long-acting muscarinic antagonists (LAMA) will be compared with long-acting beta2-agonists (LABA) combined with an inhaled corticosteroid (ICS) in a single inhaler (LABA-ICS), since the majority of LABAs used in practice are prescribed in such a combined inhaler. We will conduct a cohort study among patients with COPD to assess the effect of treatment initiation with a LAMA compared with LABA-ICS (single inhaler) on the time to a COPD exacerbation and on the risk of pneumonia. Each patient initiating treatment with a LAMA will be time-matched to a LABA-ICS initiator on high-dimensional propensity score, sex, and the presence of a prior acute COPD exacerbation in the year before cohort entry. Subjects will be followed for up to one year or until the occurrence of the outcome. The time-dependent Cox proportional hazard model will be used to perform an as-treated analysis to estimate the effect of current use of LABA-ICS versus LAMA on the risk of a first COPD exacerbation and pneumonia, stratifying by blood eosinophil levels, a recently identified potential biomarker of ICS response.
The primary outcome event is the first moderate or severe COPD exacerbation to occur after cohort entry. A moderate exacerbation will be defined by a new prescription for prednisolone and a severe exacerbation by a hospitalisation for COPD (ICD-10 codes: J41, J42, J43, J44). The first secondary outcome is the rate of COPD exacerbations over the one-year follow-up. This outcome will be based on the number of courses of treatment with prednisolone and hospitalisations. A gap of at least 30 days between treatment courses will be required to consider the exacerbations as separate events. The second secondary outcome is the occurrence of the first community-acquired pneumonia and will be defined using the following codes: J10.0; J11.0; J12-J18; J22; J69; J85.0; J85.1; J86. This definition has been used successfully in COPD
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Enrico Ripamonti - Collaborator - Milan Center for Neuroscience
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care