Asthma progression and mortality: the role of inhaled corticosteroids

Abstract

Overall, asthma mortality rates have declined dramatically in the last 30 years, due to improved diagnosis and to better treatment, particularly in the 1990s following the more widespread use of inhaled corticosteroids (ICSs). The impact of ICS on other long-term outcomes, such as lung function decline, is less certain, in part because the factors associated with these outcomes are incompletely understood. The purpose of this review is to evaluate the effect of pharmacological interventions, particularly ICS, on asthma progression and mortality. Furthermore, we review the potential mechanisms of action of pharmacotherapy on asthma progression and mortality, the effects of ICS on long-term changes in lung function, and the role of ICS in various asthma phenotypes.Overall, there is compelling evidence of the value of ICS in improving asthma control, as measured by improved symptoms, pulmonary function and reduced exacerbations. There is, however, less convincing evidence that ICS prevents the decline in pulmonary function that occurs in some, although not all, patients with asthma. Severe exacerbations are associated with a more rapid decline in pulmonary function, and by reducing the risk of severe exacerbations, it is likely that ICS will, at least partially, prevent this decline. Studies using administrative databases also support an important role for ICS in reducing asthma mortality, but the fact that asthma mortality is, fortunately, an uncommon event makes it highly improbable that this will be demonstrated in prospective trials.

FIGURE 1

Results from Cox proportion hazard models. Curves are adjusted for sex, age, body mass index, education, race/ethnicity and smoking status at baseline. COPD: chronic obstructive pulmonary disease. Reproduced from [8] with permission.

FIGURE 2

Survival decrease in six subgroups of the Copenhagen City Heart Study, defined by smoking and presence of airway disease. COPD: chronic obstructive pulmonary disease; ACO: asthma–COPD overlap. ^#: bias-corrected bootstrap estimates based on Makuch–Ghali curves. Reproduced and modified from [13] with permission.

FIGURE 3

The Global Initiative for Asthma stepwise asthma treatment strategy for adults and adolescents ≥12 years of age. ICS: inhaled corticosteroid; SABA: short-acting β₂-agonist; LTRA: leukotriene receptor agonist; LABA: long-acting β₂-agonist; IL: interleukin; R: receptor; OCS: oral corticosteroid. ^#: off-label (data only with budesonide–formoterol); ^¶: off-label (separate or combination ICS and SABA inhalers); ⁺: consider adding house dust mite sublingual immunotherapy for sensitised patients with allergic rhinitis and forced expiratory volume in 1 s >70% predicted; ^§: low-dose ICS–formoterol is the reliever for patients prescribed budesonide–formoterol or beclometasone dipropionate–formoterol maintenance and reliever therapy. Reproduced from [65] with permission.