The effectiveness of β2-adrenoceptor agonists may be reduced in patients with chronic obstructive pulmonary disease (COPD) if they smoke or have been exposed to the influenza A virus, according to a study published in Clinical Science.
Smoking is the main cause for COPD, and risk of developing COPD increases with smoking duration. Cigarette smoke alters the immune system and can increase a patient’s susceptibility to COPD infection. This can also lead to worsened symptoms and cause flare-ups.
Patients with COPD have difficulty breathing due to obstructed airflow, excess production of phlegm, and frequent chest infections. Inflammation caused by inflammatory proteins can also cause permanent changes in the lungs and airways.
In their study, researchers at the University of Melbourne in Victoria, Australia sought to assess the effects of a β2-adrenoceptor agonist called salbutamol on small airway reactivity. Researchers used precision cut lung slices from mice exposed to cigarette smoke, and from mice exposed to cigarette smoke that were treated with influenza A virus (Mem71, H3N1).
“There is a clear need for new therapies that can overcome the limitations of current drugs used to treat COPD and associated flare-ups,” said study author Ross Vlahos, associate professor at RMIT University in Melbourne, Australia. “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.”
Dr Vlahos and colleagues noted that cigarette smoke exposure alone reduced the potency of salbutamol and the efficacy associated with decreased β2-adrenoceptor mRNA expression. Cigarette smoke was also associated with increased tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. The researchers noted that the impaired relaxation was restored by day 12 without any further cigarette smoke exposure.
The researchers found that cigarette smoke exposure prior to influenza A infection almost completely abolished relaxation, even though β2-adrenoceptor and TNFα and IL-1β expression were unimpaired. In the lung slices that were prepared with influenza A alone, responses to salbutamol were inconsistent.
The results of the study suggest that, due to the number of COPD patients who smoke, new medication is required to treat this patient population, and a new model should be developed to test the new medications.
Donovan C, Seow HJ, Bourke JE, Vlahos BR. Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to adrenoceptor agonists in mouse lung. Clin Sci. 2016;130(10):829. doi: 10.1042/cs20160093.