Inhaled bronchodilators, including beta2-agonists and antimuscaric receptor antagonists, are the mainstay of
pharmacotherapy in chronic obstructive pulmonary disease (COPD). The short-acting beta2-agonists, including salbutamol,
and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand. The longacting
beta2-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a
twice-daily dosing regimen for long-term COPD treatment. Unlike salmeterol, formoterol has a rapid onset of action.
Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would
make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta2-adrenoceptors,
rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance. Indacaterol, which has
been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily
dosing regimen. Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development.
Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to
provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often
not clinically significant in all the endpoints assessed. In patients with COPD, treatment with ICS is associated with increased
risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations.
Subphenotyping of patients with COPD (e.g., frequent exacerbations, sputum eosinophilia, mixed
asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating
treatment. Ultra-LABA/ long-acting muscarinic receptor antagonist (LAMA) combination treatment is under
development and is likely to become a standard pharmacological strategy for COPD. Dual-pharmacology inhaled muscarinic
antagonist-beta2 agonist (MABA) molecules provide a new approach to the treatment of COPD.