Effective treatment of severe
asthma is a major unmet need because patients' symptoms are not controlled on maximum treatment with inhaled
therapy.
Asthma symptoms can be poorly controlled because of poor adherence to controller
therapy, and this might be addressed by using combination
inhalers that contain a
corticosteroid and long-acting β(2)-agonist as reliever
therapy in addition to maintenance treatment. New
bronchodilators with a longer duration of action are in development, and recent studies have demonstrated the benefit of a long-acting
anticholinergic bronchodilator in addition to β(2)-agonists in patients with severe
asthma.
Anti-IgE therapy is beneficial in selected patients with severe
asthma. Several new blockers of specific mediators, including
prostaglandin D(2),
IL-5,
IL-9, and
IL-13, are also in clinical trials and might benefit patients with subtypes of severe
asthma. Several broad-spectrum anti-inflammatory
therapies that target neutrophilic
inflammation are in clinical development for the treatment of severe
asthma, but adverse effects after
oral administration might necessitate inhaled delivery.
Macrolides might benefit some patients with
infection by atypical bacteria, but recent results are not encouraging, although there could be an effect in patients with predominant neutrophilic
asthma.
Corticosteroid resistance is a major problem in patients with severe
asthma, and several molecular mechanisms have been described that might lead to novel therapeutic approaches, including drugs that could reverse this resistance, such as
theophylline and
nortriptyline. In selected patients with severe
asthma, bronchial thermoplasty might be beneficial, but thus far, clinical studies have not been encouraging. Finally, several subtypes of severe
asthma are now recognized, and in the future, it will be necessary to find
biomarkers that predict responses to specific forms of
therapy.