The effectiveness of salbutamol, a medication used to relieve the symptoms of chronic obstructive pulmonary disease (COPD), is reduced when patients are exposed to cigarette smoke and influenza A infection in an mouse model of the respiratory disease, according to the results of a study published in the journal Clinical Science. The study is titled “Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.”
People with COPD — an umbrella term for a number of lung diseases — often find it difficult to breathe because their airflow is obstructed. Symptoms include shortness of breath and a cough that produces sputum. COPD’s main cause is smoking; the longer a person has been smoking, the higher the risk of developing the disease. COPD typically worsens over time — the lung inflammation is permanent and caused by certain inflammatory proteins, including the tumor necrosis factor-alpha and interleukin-1 beta, proteins involved in systemic inflammation or chronic activation of the immune system.
Besides being a major contributor to COPD, cigarette smoking also alters the body’s immune function, increasing the susceptibility to influenza A virus infection. The flu virus is a major cause of acute exacerbations of COPD (termed AECOPD). AECOPD are defined by a sudden worsening of symptoms such as dyspnea, wheezing, sputum production, and cough initiated by bacterial, viral, or environmental agents, usually leading to hospitalization. Flu infection is associated with greater inflammatory responses and loss of lung function compared to exacerbations from other causes.
An additional contributor to the severity of COPD is the marked decrease in the effectiveness of the bronchodilator medication salbutamol (β-adrenoceptor agonists) in AECOPD, but the mechanisms involved due to cigarette smoke exposure and viral-induced exacerbations remain poorly understood.
In the new study, a team of researchers examined sections of lung from mouse models exposed to cigarette smoke and influenza A virus. The researchers discovered that lung tissue exposed to cigarette smoke and viral infection was less responsive to salbutamol compared to the tissue that was not exposed.
“By understanding the mechanisms responsible for reduced sensitivity to current bronchodilators, we can then design alternative, more efficacious agents to help treat people with COPD, especially during a viral exacerbation,” said lead author Dr. Chantal Donovan from Monash University in Victoria, Australia, in a news release.
Researchers expect their technique will help identify new targets that can be used for COPD patients who do not respond to current therapy.
A commentary article to the research paper will be published in Clinical Science. Prof. Sebastian Johnston from Imperial College London in the United Kingdom, one of the authors of the upcoming commentary, noted: “The findings of this study suggest that cigarette smoke and respiratory virus infections may impair the ability of salbutamol to effectively bronchodilate the airways. These findings emphasize yet again that smoking is bad for you, and especially so if you have asthma or COPD.”
“It would be interesting to determine whether the other commonly used reliever bronchodilator ipratropium bromide, which acts via a different mechanism, is similarly impaired by cigarette smoke and/or viral infection,” he added.