Mayo research examines how asthma affects immune system, increasing risk for nonrespiratory conditions

Young Juhn, M.D. (PD ’99), focuses his research on determining how asthma affects the immune system – specifically, the extent to which asthma epidemiology affects the risk and severity of communicable and noncommunicable diseases. Asthma patients have a much higher risk of asthma-associated comorbidity including pneumococcal diseases, otitis media, community-acquired pneumonia, Streptococcus pyogenes upper respiratory infections, influenza, breakthrough chickenpox and pertussis, according to Dr. Juhn’s research.

“This makes sense because these conditions are all airway infections, and asthma has an altered airway architecture including epithelial innate immune dysfunctions,” says Dr. Juhn, director of the Asthma Epidemiology Research Unit at Mayo Clinic and a consultant in the Department of Pediatric and Adolescent Medicine. “But we wanted to learn whether asthma patients’ susceptibility also applied to nonrespiratory conditions including systemic inflammatory and autoimmune diseases.”

Higher risk not limited to respiratory conditions

Sure enough, Dr. Juhn’s research showed that children and adults with asthma have a much higher risk of developing shingles compared to patients who do not have asthma. These findings were replicated by other research groups. Similarly, adult asthma patients have a higher risk of developing community-acquired E. coli blood infection, rheumatoid arthritis, heart attack and diabetes. Children with asthma have higher risks of developing celiac disease and appendicitis compared to those without asthma.

Morbidity and mortality threat from comorbidity, less asthma itself

Dr. Juhn points out that major morbidity and mortality from poorly controlled asthma has declined and respiratory outcomes have improved due to evidence-based guidelines and advanced therapy. However, he says, threats to the health of people with asthma due to asthma-associated comorbidity, especially serious and common nonrespiratory conditions, are largely unrecognized by patients and their caregivers, clinicians and researchers.

“If we know why some people with asthma are healthy, why others develop serious asthma-associated comorbidity and who is susceptible to asthma-associated comorbidity, we might be able to mitigate the risk and outcomes of asthma-associated comorbidity,” he says. “These are our central research questions to be addressed in the lab.”

Immune dysfunction possible culprit, precision medicine the answer

Given the wide range of asthma-associated comorbid conditions, researchers must explore the mechanisms underlying the comorbid conditions among people with asthma, according to Dr. Juhn.

“Our data suggest that the immunological (i.e. suboptimal adaptive immune responses and rapid waning of adaptive immunity) and clinical features (i.e. risks of pro-inflammatory conditions and autoimmune diseases presented as asthma-associated comorbidity) of asthma observed in our prior work overlap with the dysfunction of the immune system with aging,” says Dr. Juhn. “This is our active research area.

“Of course, not everyone who has asthma will develop any or all of these other conditions. The question is, ‘Who will?’”

With support from the National Institutes of Health, Dr. Juhn’s team has recently developed innovative computer programs detecting different types of asthma from electronic health records, independent of physician diagnosis of asthma.

“These computer approaches, called data science approaches, enable large-scale clinical studies and population management for asthma care,” he says. “Importantly, our recent data using this approach showed that our computer-based programs might be able to identify a subgroup of asthma patients susceptible to asthma-associated comorbidity.

“Combining the data science approach with a novel immune marker we recently developed should enable us to find the clinical and laboratory biomarkers or parameters to identify subgroups of patients with asthma who are subject to this increased risk of other asthma-related diseases in the future. We call this approach precision medicine for population health in asthma.”

Asthma management

Proper management of asthma patients, Dr. Juhn says, includes:

• Making every effort to get the best control of asthma – both therapeutic and preventive interventions. Asthma treatments including inhaled corticosteroids do not increase the risk of infections but, rather, lower the risk of infections such as pneumonia.
• Vaccinating against preventable diseases:
  • Asthma patients between age 19 and 64 should receive the pneumococcal vaccine. The Centers for Disease Control and Prevention began this recommendation in 2008 supported by research including Dr. Juhn’s. Typically the vaccine is recommended for those younger than 2 and older than 65.
  • Dr. Juhn advocates the shingles vaccine for asthma patients between 50 and 60. The vaccine is normally recommended for all patients at age 60 but is approved by the Food and Drug Administration for all patients at age 50.
  • He also advocates asthma patients have the Tdap booster vaccine for pertussis every 10 years instead of Td, given the increased risk of pertussis among asthma patients.
• Being aware of the increased risks of other conditions. A few examples:
  • When adult asthma patients have chest pain, they should not assume it is due to asthma but be checked for heart health.
  • When asthma patients have chronic uncontrolled cough, they should not assume it is due to asthma but be checked for pertussis.
  • If proper initial evaluations for the known risk factors for asthma-associated comorbid conditions do not reveal any known causes, further and costly testing to identify causes may be unnecessary in asthma patients.