Personalized Therapy for Asthma and COPD

The discovery of a new type of immune response that is activated in patients with severe asthma and chronic obstructive pulmonary disease (COPD) could dramatically improve diagnosis and treatment of patients with chronic inflammatory lung disease.

Researchers at Washington University School of Medicine (St. Louis, MI, USA) studied mice infected with a respiratory virus--which closely resembles the type of viruses that cause similar infections in humans--and found that the viral infection of the lung can leave behind a viral remnant which becomes an ongoing stimulus for a chronic immune response that could last for long periods of time, even for life. This response causes the cells in the lung passages to overproduce mucus and become hyper-reactive to irritants. When the mice got over their infection, they were left with chronic airway disease characterized by mucus production and increased airway reactivity to an inhaled irritant. A key molecular feature of this chronic disease was the production of a powerful natural inflammatory substance, interleukin-13 (IL-13). Investigating the source of IL-13, the researchers tracked down a previously unknown immune pathway that is supposed to be activated for only short periods. However, the investigators found that this pathway can also be persistently activated after viral infection, likely due to the pathway's ability to respond to viral remnants. This combination of persistent activity and positive feedback leads to the long-term production of IL-13 as well as other substances that then cause continuous inflammation in the lung tissue and the development of chronic lung disease.

The researchers then confirmed that the same immune process could also be detected in the lungs of humans with severe asthma and COPD. This type of immune response is typically associated with parasitic infections and allergic disease, but in this case appears to be linked to viral infection and chronic inflammatory disease. Importantly, the response produces a specific array of compounds that can be detected in the lung and likely in the blood to serve as diagnostic markers of disease. The research team is now working to verify that the profile of biomarkers for this immune response can be used to diagnose patients with asthma and COPD, which could lead to the development of new types of drugs that target the underlying cause of inflammatory lung disease. The study was published ahead of print on May 18, 2008, in Nature Medicine.

"We've cracked the first part of the molecular code that links a viral infection to the later development of chronic inflammatory diseases like asthma and COPD,” said senior author Michael Holtzman, M.D. "With this information, we can more precisely diagnose and monitor these types of diseases and then better target our treatment to specific abnormalities. That's a big step forward from simply monitoring breathing status.”


Related Links:
Washington University School of Medicine