Since COPD is a heterogeneous disease, a specific anti-inflammatory therapy for this disease has not been established yet. Oxidative stress is recognized as a major predisposing factor to COPD related inflammatory responses, resulting in pathological features of small airway fibrosis and emphysema. However, little is known about effects of oxidative stress on airway smooth muscle. Cigarette smoke increases intracellular Ca2+ concentration and enhances response to muscarinic agonists in human airway smooth muscle. Cigarette smoke also enhances proliferation of these cells with altered mitochondrial protein. Hydrogen peroxide and 8-isoprostans are increased in the exhaled breath condensate in COPD. These endogenous oxidants cause contraction of tracheal smooth muscle with Ca2+ dynamics through Ca2+ channels and with Ca2+ sensitization through Rho-kinase. TNF-α and growth factors potentiate proliferation of these cells by synthesis of ROS. Oxidative stress can alter the function of airway smooth muscle through Ca2+ signaling. These phenotype changes are associated with manifestations (dyspnea, wheezing) and pathophysiology (airflow limitation, airway remodeling, airway hyperresponsiveness). Therefore, airway smooth muscle is a therapeutic target against COPD; oxidative stress should be included in treatable traits for COPD to advance precision medicine. Research into Ca2+ signaling related to ROS may contribute to the development of a novel agent for COPD.
Chronic obstructive lung disease (COPD) is heterogeneous and complex. Symptoms and pathophysiological disorders overlap between COPD and asthma. To progress the management of COPD, patients with COPD should be classified by distinct clinical phenotypes. These groupings derived from multiple dimensions including clinical, physiologic, imaging, and endotyping determine clusters of patients with common characteristics that relate to clinically meaningful outcomes such as symptoms, exacerbations, response to therapy, and disease progression (stratified medicine). Moreover, since several phenotypes can coexist in individual patients with COPD, an approach due to therapeutic target identified phenotypes and endotypes (treatable traits) has been proposed as an advanced therapy recently (precision medicine). Airway eosinophilia and airway hyperresponsiveness, which are hallmarks of asthma, are developed in some patients with COPD, independent of asthma. It is perhaps meaningful to classify COPD according to airway eosinophilia and airway hyperresponsiveness as phenotypes and to put these phenotypes into focus as treatable traits. These phenotypes are closely related to frequency of exacerbations and reactivity to inhaled corticosteroids with bronchodilators in therapy for COPD. Hence, research for phenotype classification can play a fundamental role for development of the management and treatment for COPD.
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