![]() β 2-adrenoceptors were increased along the airways, and their densities in the subsegmental bronchus and lung parenchyma were approximately twofold higher than those of mAChRs in the same region. 7 The M 3 subtype predominantly occurred in the bronchus, but the density decreased from the segmental to subsegmental bronchus and was absent in the lung parenchyma. The regional distribution and relative proportion of muscarinic acetylcholine receptor (mAChR) and β-adrenoceptor subtypes were evaluated in the human bronchus and lung parenchyma. Theoretically, targeting these two mechanisms of bronchoconstriction has the potential to maximize the bronchodilator response without increasing the dose of either component and would help to overcome the inter- and intrapatient variability in response to individual agents seen in COPD. Additionally, in preclinical models, muscarinic antagonists have been demonstrated to augment β 2-agonist-stimulated bronchodilation by reducing the bronchoconstrictor effects of acetylcholine. 6 The interaction between the two systems has yet to be fully elucidated however, β 2-agonists can amplify the bronchial smooth muscle relaxation directly induced by muscarinic antagonists by decreasing the release of acetylcholine via modulation of cholinergic neurotransmission. 4, 5Īirway smooth muscle relaxation (leading to bronchodilation) can be achieved via two main routes: inhibition of acetylcholine signaling via muscarinic M 3 receptors on airway smooth muscle with a muscarinic antagonist or stimulation of β 2-adrenoceptors with a β 2-agonist. 1 – 3 Long-acting bronchodilators also reduce lung hyperinflation and dyspnea and increase exercise endurance. Long-acting bronchodilators, such as tiotropium, formoterol, and salmeterol, are proven to provide long-term improvements in lung function and quality of life and preventing exacerbations in patients with COPD. Two key classes of bronchodilators have been developed in chronic obstructive pulmonary disease (COPD): β 2-agonists and muscarinic antagonists. This approach is a tentative move toward personalized treatment for COPD patients, and with progress in knowledge and developments in physiology, lung imaging, medical biology, and genetics, identification of COPD phenotypes that provide prognostic and therapeutic information that can affect clinically meaningful outcomes is an urgent medical need. In this review, I propose one plausible approach to position ICSs and LABAs/LAMAs in clinical practice, based on both the extent of airflow obstruction and the presence of an asthma component or airway eosinophilic inflammation. Thus, sputum or blood eosinophil counts might identify a subpopulation in which ICSs could have potentially deleterious effects as well as a subpopulation that benefits from ICSs. Notably, 10%–30% of patients with COPD with or without a history of asthma have persistent circulating and airway eosinophilia associated with an increased risk of exacerbations and sensitivity to steroids. However, ICSs increase the risk of pneumonia. At present in Japan, fixed combinations of inhaled corticosteroids (ICSs) and LABAs are frequently prescribed in the earlier stages of COPD. Identification of the peculiarities of the different COPD phenotypes will permit us to implement a more personalized treatment in which the patient’s characteristics, together with his or her genotype, will be key to choosing the best treatment option. The concept of a COPD phenotype is rapidly evolving from one focusing on the clinical characteristics to one linking the underlying biology to the phenotype of the disease. These clinical manifestations are highly variable, and several are associated with different responses to currently available therapies. COPD is a complex condition that has pulmonary and extrapulmonary manifestations. The clinical trial data for LABAs/LAMAs in the treatment of chronic obstructive pulmonary disease (COPD) continue to be promising, and these combinations will provide the convenience of delivering the two major bronchodilator classes, recommended as first-line maintenance options in COPD treatment guidelines. In the combined use of bronchodilators of different classes, ie, long-acting β 2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), bronchodilation is obtained both directly, through LABA-mediated stimulation of β 2-adrenergic receptors, and indirectly, through LAMA-mediated inhibition of acetylcholine action at muscarinic receptors.
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