Asthma patients may experience a significant deterioration in the normal functioning of their lungs over time. This can lead to severe asthma and even permanent obstruction of their airways.
Evidence suggests that a history of frequent asthma symptoms (poor control) may be associated with this deterioration. Specifically, severe asthma attacks (exacerbations) may be a major contributor.
The current evidence for this association comprises a small number of studies with mixed results; their interpretation is further difficult because many have been hampered by features of their design, including limits on the characteristics or number of patients included, the relatively short follow-up times of all studies, and inadequate accounting for other factors that may contribute to lung function decline.
This study aims therefore to robustly investigate whether there is an association between exacerbation burden and lung function decline in a broad asthma patient population using longitudinal (minimum 5 years of follow-up), real-life data (routinely-collected primary care data) collected on a large scale. It will address key evidence gaps in patient representativeness, follow-up time and analysis methodology.
This study is important because many advanced asthma treatments (both current and in development) focus on improving asthma control/reducing exacerbations, especially in patients who have not managed to achieve control via standard medications or lifestyle modification. Newer treatments could thus be of additional benefit if by improving control they also lead to better long-term lung function, and therefore decreased risk of permanent airway obstruction and/or severe asthma.
Rationale: Progressive worsening of lung function (LF) may contribute towards the development of severe asthma. Evidence suggests that asthma exacerbations may be associated with poorer LF over time.
However only a small number of studies have looked specifically at the association between exacerbation burden and LF decline in asthma patients, with mixed results. Short follow-up times, restrictions to subgroups of asthma patients, and varied methodology will have contributed to the lack of clarity in the available evidence.
Aim: This study aims to investigate if there is an association between exacerbation burden and lung function decline in a broad asthma patient population using longitudinal real-life data collected on a large scale.
Design: This is an historical cohort study combining data from CPRD and Optimum Patient Care UK. The cohort will be patients diagnosed with asthma, with ?3 LF readings of the same type (peak expiratory flow [PEFR] or forced expiratory volume in 1 second [FEV1]) on or after their 18th birthday, and ?5 years of eligible LF data. The index date (start of follow up) will be the date on which the first eligible LF reading is recorded.
Exposure and outcomes: The primary exposure will be exacerbation burden, defined as i) annual rate of exacerbations, ii) number of years with exacerbations/total follow-up years, and iii) cumulative number of exacerbations. Exacerbations resulting in hospital visits will be linked using Hospital Episode Statistics (HES) data. The outcomes will be lung function trajectory (slope) measured using i) PEFR and ii) FEV1.
Analysis: Exacerbation burden will be the main exposure in a mixed effects linear regression model. Variation in lung function trajectories between patients is accounted for by including a random intercept and slope of lung function over time at the patient level in the model. Models will adjust for relevant confounders where appropriate.
Two outcomes will be measured:
Mean change in FEV1 over follow up period (ml in 1 second/year); Mean change in PEFR over follow up period (ml/year).
David Price - Chief Investigator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Shay Soremekun - Corresponding Applicant - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Derek Skinner - Collaborator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Jaco Voorham - Collaborator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Marjan Kerkhof - Collaborator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Trung Tran - Collaborator - Astra Zeneca Inc - USA
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient