The association between benzodiazepines and asthma exacerbation, influenza-like illness related pneumonia and mortality: population-based studies using the United Kingdom Primary care data.

Nakafero, Georgina (2016) The association between benzodiazepines and asthma exacerbation, influenza-like illness related pneumonia and mortality: population-based studies using the United Kingdom Primary care data. PhD thesis, University of Nottingham.

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Abstract

Background: Influenza-like illness (ILI) and asthma are common diagnoses in the general practice and exert considerable morbidity and mortality worldwide. One potentially important strategy to reduce this is to determine whether commonly prescribed drugs modify the occurrence and outcomes of respiratory diseases including mortality. The benzodiazepines, a class of psychoactive drugs generally used in the treatment of anxiety and sleep disorders, have recently been suggested as having detrimental effects on immune response to infection, predisposing its users to increased risk of infection and mortality. These drugs have also been implicated in the pathogenesis of asthma. This thesis therefore aimed to investigate whether benzodiazepines modify the occurrence of asthma exacerbation and subsequent mortality in patients with asthma as well as ILI-related pneumonia and ILI-related mortality in patients with ILI.

Methods: The Clinical Practice Research Datalink (CPRD) was used as the data source. CPRD contains the medical records of over 13 million patients prospectively collected from over 600 general practices across the United Kingdom and has linkages to the Hospital Episode Statistics database [HES] and national death registry data (the Office of National Statistics [ONS]) which were utilised in this study. CPRD-HES linked data was used to validate diagnoses of asthma exacerbation whereas ONS mortality data validated deaths identified from CPRD. Case-control and cohort study designs were used to investigate associations between benzodiazepines and the occurrence of asthma exacerbation, ILI-related pneumonia and mortality.

Results: After adjusting for a wide range of potential confounders including physical and psychiatric comorbidities, and concurrent use of other drugs, exposure to benzodiazepines was associated with statistically significant increased occurrence of asthma exacerbation, ILI-related pneumonia and mortality. These associations were observed with both short term and chronic benzodiazepines use. However, the effect of individual benzodiazepines varied across the outcomes of interest with some of the associations lacking statistical significance. For instance, current use of diazepam and temazepam but not lorazepam showed statistically significant associations with increased occurrence of asthma exacerbation.

Conclusion: Overall, findings of this research signal an adverse benzodiazepine effect and hence suggest that a precautionary approach should be exercised when prescribing benzodiazepines in the interim before conclusive evidence is yielded by further research, especially in patients who may already be at increased risk of asthma exacerbation or pneumonia and mortality.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Myles, P.
Nguyen-Van-Tam, J.S.
Sanders, Robert. D.
Keywords: Benzodiazepines, Zopiclone, Pneumonia, ILI, Mortality, Asthma, Influenza.
Subjects: QS-QZ Preclinical sciences (NLM Classification) > QV Pharmacology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 31839
Depositing User: Nakafero, Georgina
Date Deposited: 22 Oct 2018 12:33
Last Modified: 08 Feb 2019 10:15
URI: http://eprints.nottingham.ac.uk/id/eprint/31839

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