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Long-acting β 2 adrenoceptor agonists (LABA) and/or longacting muscarinic antagonists (LAMA) should be used as monotherapy or in combination for the initial treatment in patients with chronic obstructive pulmonary disease (COPD). Triple inhaled therapy with LABA, LAMA, and inhaled corticosteroid (ICS) has been recommended for COPD patients who still have clinically significant symptoms following the use of a dual inhaler with LABA plus LAMA, particularly for those who present with frequent exacerbations, blood eosinophilia and/or concomitant bronchial asthma. Experimental studies on human isolated airways suggested that LABA, LAMA, and ICS synergistically relax the medium and small bronchi probably as a result of enhanced elevation of the cyclic adenosine monophosphate (cAMP) that mediates relaxation of airway smooth muscle cells. Synergy of LABA and LAMA was also shown in a few clinical studies, whereas in the randomized controlled trials triple therapy with two long-acting bronchodilatators and ICS was more effective than various dual combinations (LABA/LAMA or ICS/LABA) in patients with severe COPD. These findings justify triple therapy in patients with severe COPD who have frequent exacerbations and do not respond to dual therapy. Recently, a single inhalers containing ICS, LABA, and LAMA have been developed as a more practical alternative, which may improve therapy compliance.

Clinical and pharmacological justification of triple therapy with two long-acting bronchodilators and inhaled corticosteroid in patients with COPD