AbstractBeta-blockers and non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided in asthma over risk of bronchospasm which may vary according to drug selectivity and duration of administration. This thesis attempts to quantify the risk of beta-blocker and NSAID exposure in asthma by synthesising clinical trial evidence and conducting observational studies using linked electronic medical records.
As part of this thesis, three systematic reviews of clinical trials were conducted evaluating: the prevalence of aspirin-exacerbated respiratory disease (AERD); risk of selective NSAIDs/COX-2 inhibitors in people with AERD; and risk of acute beta-blocker exposure in people with asthma. Electronic primary care data from the Clinical Practice Research Datalink (CPRD) was used to define a cohort of people with active asthma, measure the prevalence of beta-blocker and NSAID prescribing, and perform a series of nested case control studies evaluating asthma death, asthma hospitalisation and primary care asthma exacerbations (PCAE). A self-controlled case-series was performed for PCAE as well.
Based upon work in this thesis, the prevalence of AERD in people with asthma was around 9%. Selective NSAIDs triggered respiratory symptoms in 8% of people with AERD whilst no significant changes in lung function or symptoms occurred with COX-2 inhibitors. Acute non-selective beta-blocker exposure caused a significant mean fall in FEV1 of 10%, a significant increase in respiratory symptoms in around 1 in 13 and a non-significant increase in falls in FEV1 of ≥20% in around 1 in 9. Acute selective beta-blocker exposure caused a significant mean fall in FEV1 of 7%, significant falls in FEV1 of ≥20% in around 1 in 8 and a non-significant increase in respiratory symptoms in around 1 in 33.
The prevalence of selective beta-blocker prescribing in asthma rose by around 200% over the 12 year period whilst the prevalence of non-selective beta-blocker prescribing rose by around 90%. Changing trends in NSAID prescribing occurred over the 12 year period with COX-2 inhibitors now rarely prescribed. Using the nested case control design, both incident and high-dose non-selective beta-blocker exposure was associated with significantly increased risk of asthma morbidity (hospitalisation and PCAE). In contrast, no significant increased risk of asthma morbidity occurred with any type of selective beta-blocker exposure. Consistent findings were seen for PCAE using the self-controlled case series. No significantly increased risk was seen with different oral NSAIDs apart from weak evidence of an association between asthma death and non-selective NSAID exposure which is unlikely to be causal.
Significant numbers of people with asthma are prescribed beta-blockers and NSAIDs. Evidence from clinical trials and observational studies demonstrate that non-selective beta-blockers significantly increase asthma morbidity with risk appearing to vary according to dose and duration of administration. Although selective beta-blockers have the potential to cause significant changes in lung function, no significant increase in asthma morbidity was observed in observational studies. Although around 9% of asthmatics may be susceptible to NSAIDs, no strong evidence was found to suggest that the current practice of NSAID prescribing increases asthma morbidity. At the same time, COX-2 inhibitors are infrequently prescribed despite apparently being well tolerated by people with AERD.
|Date of Award||2014|
|Sponsors||Chief Scientist Office|
|Supervisor||Bruce Guthrie (Supervisor), Peter Donnan (Supervisor) & Catherine Jackson (Supervisor)|