Long-acting β-agonists in asthma management: what is the current status?

Abstract

Large surveillance studies or phase IV clinical studies of long-acting β-agonists (LABA) compared with placebo in asthma patients using variable (from nil to regular) doses of inhaled corticosteroids (ICS) have raised the issue of mortality risk in patients with asthma taking regular LABA. There have been a number of meta-analyses and systematic reviews that have examined the risk of LABA in asthma patients, and the general conclusion is that LABA added to ICS reduces asthma-related hospitalizations compared with ICS alone and there is no statistical increase in mortality. However, LABA without ICS do increase mortality risk in asthma. All reviews and analyses show a greater number of LABA deaths, but not all are statistically significant. A recent meta-analysis found LABA with concomitant ICS had a higher mortality rate in asthma than ICS alone. The flaw in the study is the higher doses of ICS in the control arms, but the implicit message remains: the essential need for enough ICS to control airway inflammation. We suggest that the pragmatic solution is to have LABA only available in the same device as ICS for asthma treatment. We do not think that a study comparing the safety of LABA plus ICS versus ICS alone in asthma is necessary. If such a study is conducted, the measurement of morbidity from increased doses of ICS is an essential design consideration. Furthermore, the critical focus in asthma management should not be forgotten - education of health professionals and the community of the critical role of ICS, and the need for good communication between health professionals and the asthma patient to facilitate good asthma control. The same arguments apply to the asthma-with-chronic obstructive pulmonary disease overlap syndrome in older patients. There is an urgent need to provide medical practitioners with the capability to diagnose the overlap syndrome.