Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated.Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs.A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans.The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients.
Highlights
Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by increasing airflow limitation and respiratory symptoms, often associated with chronic comorbidities, leading to a significant burden for the patient.Specific pharmacological therapy for COPD helps to prevent and control symptoms, reduce the frequencyThe present review focuses on the role and future of long-acting b2-agonists (LABAs) in the management of COPD, updating previously published reviews [6].b2-agonists The principal action of b2-agonists is to relax airway smooth muscle by stimulating b2-adrenergic receptors
Evidence to date indicates that ICS/LABA in combination with tiotropium improves lung function, symptoms and health status, and reduces the risk of hospitalizations compared with tiotropium alone in patients with COPD [149,150,151]
Long-acting bronchodilators are fundamental to the management of COPD; many patients remain symptomatic despite their use
Summary
Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by increasing airflow limitation and respiratory symptoms, often associated with chronic comorbidities, leading to a significant burden for the patient. Efficacy summary In summary, evidence to date suggests that both formoterol and salmeterol provide significant improvements in lung function, symptoms including dyspnea, and healthrelated quality of life For the latter two endpoints, not all patients appear to achieve clinically meaningful improvements, and improvements were lower than those achieved with the once-daily LAMA tiotropium. Evidence to date indicates that ICS/LABA in combination with tiotropium improves lung function, symptoms and health status, and reduces the risk of hospitalizations compared with tiotropium alone in patients with COPD [149,150,151] These findings lend support to the concept that combining different classes of drugs with different mechanisms such as ultra-LABAs and once-daily LAMAs and ICS will further improve efficacy, and represent an important step towards the goal of optimal control for COPD patients
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