Viral infections can induce asthma exacerbations, but a report finds the inflammation itself can also have an impact on the infection.
The way a patient with asthma responds to a human rhinovirus infection may be due to their body’s specific response to airway inflammation, according to a new study.
The report suggests that the type of lower airway inflammation a patient with asthma experiences and the extent of epithelial damage caused by the inflammation has implications for the course of the viral infection.
Rhinoviruses, along with allergen exposure, are among the most common reasons patients experience asthma exacerbations. Yet, while it is understood that the viruses can exacerbate asthma, the reverse is little understood, according to corresponding author Bogdan Jakiela, MD, PhD, of the University of Tartu, in Estonia, and colleagues.
In a new study in Scientific Reports, Jakiela and colleagues sought to find out whether the inflammation caused by asthmatic exacerbation might have an impact on the severity of the patient’s viral infection.
The investigators performed a laboratory analysis to see how cytokine-induced remodeling of the airway epithelium affects the body’s antiviral response. They took in vitro differentiated bronchial epithelium, exposed it to cytokines, and then infected it with the virus HRV16 in order to track gene expression responses. The authors made a number of observations.
First, they noted that interleukin-13 (IL-13) induced mucous cell metaplasia, which appeared to protect against the virus by impairing ciliogenesis and inducing antiviral genes.
Meanwhile, transforming growth factor β (TGF-β) led to increased viral replication and heightened innate response.
The study also showed that the virus itself led to upregulation of mucous cell metaplasia markers and growth factors, the investigators said, “followed by low-level virus replication and shedding.”
Taken together, they said, the data show that variability in airway inflammation and epithelial damage can lead to variability in viral outcomes.
“Type-2 inflammation (eosinophilic asthma) may induce [an] antiviral state of epithelium and decrease virus sensitivity, while growth factor exposure during epithelial repair may facilitate virus replication and inflammatory response,” they said.
The authors wrote that the link between eosinophilic asthma and virus response had not been the subject of much research until recently, when investigators began looking at how asthma affected a patient’s response to SARS-CoV-2 infection. Studies have shown that asthma does not appear to increase a patient’s susceptibility to the virus, and patients with asthma who get coronavirus disease 2019 (COVID-19) do not have worse outcomes than the general population.
“One explanation could be the lower epithelial expression of ACE2, a SARS-CoV-2 entry receptor, in asthma patients with T2-high airway inflammation,” Jakiela and colleagues said. “Since the innate defense of airway epithelium is very similar in response to various RNA viruses, the ‘antiviral state’ linked with T2-inflammation shown in our study, may in general protect against severe outcomes during infections with respiratory viruses.”
The investigators concluded with one final observation: that the responses of cells from control patients to the human rhinovirus challenge was similar to the responses of the cells from patients with asthma. The authors said this may be a sign that the antiviral mechanisms at play come into effect as a result of uncontrolled inflammation and are not innate to asthma itself.
Jakiela B, Rebane A, Soja J, et al. Remodeling of bronchial epithelium caused by asthmatic inflammation affects its response to rhinovirus infection. Sci Rep. 2021;11(1):12821. doi:10.1038/s41598-021-92252-6