AbstractLong acting beta agonists (LABA) and long acting muscarinic receptor antagonists (LAMA) are both used in the treatment of obstructive airway disease, in asthma they are given with inhaled corticosteroids (ICS), in chronic obstructive pulmonary disease (COPD) they may be given with or without ICS. These therapies may attenuate the degree to which airways narrow to a bronchoconstrictor stimulus (airway hyperresponsiveness). Long acting bronchodilators may also change airway geometry as well as pure airway calibre, this can be measured by an effort independent breathing test called impulse oscillometry. The works within this thesis assess the effects of LABA and LABA with LAMA therapy on the airways of non-smoking people with asthma, people with asthma who smoke, and people with COPD. Primarily it focuses on outcomes related to impulse oscillometry measurements of airway resistance (R) and reactance (X), but also assesses how the bronchodilators attenuate airway hyperresponsiveness.
In mild-moderate persistent asthma, the addition of the LAMA tiotropium to ICS/LABA adds little to airway calibre or geometry. Neither does it significantly attenuate airway hyperresponsiveness. In the group of smokers with asthma, the addition of tiotropium to ICS/LABA does significantly reduce airway resistance and reactance, alongside asthma symptoms. In COPD tiotropium added to ICS/LABA reduces bronchoconstriction from non-selective beta-blocker therapy with carvedilol.
In summary add on LAMA to ICS/LABA has little benefit in mild-moderate asthma but may offer benefits in both people with asthma who smoke and those with COPD. This may be due to a different inflammatory or bronchoconstrictor stimulus in those patients.
|Date of Award||2022|
|Supervisor||Brian Lipworth (Supervisor) & Philip Short (Supervisor)|