Anticholinergic agents in asthma: chronic bronchodilator therapy, relief of acute severe asthma, reduction of chronic viral inflammation and prevention of airway remodeling

Abstract

It is difficult to identify specific groups of asthmatic patients who may benefit from acute or chronic use of anticholinergic agents. Therefore, an important consideration is how anticholinergic agents can be used to achieve clinically effective treatment of asthma. A genotype-stratified study revealed that greater bronchoprotective effect of anticholinergic agents was observed in asthmatic patients with the Arg/Arg genotype of the beta2-adrenergic receptor. Anticholinergic agents could add to the bronchodilation obtained with beta2-agonists on acute severe asthma. CD8+ T lymphocytes induced by chronic hepatitis C viral infection causes chronic obstructive pulmonary disease-like inflammation in asthma. Virus-specific CD8+ T lymphocytes may induce cholinergic activation in asthma through M2 receptor dysfunction. Therefore, anticholinergic agents are highly effective for asthma associated with chronic viral infection. In contrast, asthma with chronic obstructive pulmonary disease-like inflammation appears to be poorly responsive to beta2-agonists and can lead to partially irreversible airflow limitation. Moreover, a recent report suggested that treatment with inhaled tiotropium bromide markedly inhibited the increase in airway smooth muscle mass, myosin expression, and contractility in asthma. Anticholinergic agents may benefit stable asthmatics, particularly those who have the Arg/Arg genotype. These agents have a demonstrated role in combination with beta2-agonists in the treatment of acute severe asthma, and may benefit asthmatics with chronic obstructive pulmonary disease-like inflammation. Moreover, these agents could be also beneficial in preventing airway remodeling in asthmatic airways.