The Liu Lab is interested in the assessment of biomarkers in allergy and asthma as well as the role of microbial components (inc endotoxin) in the environment of allergic patients. We aim to provide comprehensive, state-of-the-art care for children with allergic disorders and asthma. Consistent with this mission is a robust basic and translational research program to improve the standard of care for the disorders we treat. We have extensive educational and training programs to extend our understanding of optimal disease management to others. Thus, our mission since 1899 -- to heal, discover, and educate – continues to be well served.
Important gap areas persist in our understanding and management of asthma. Those that continue to be addressed by ongoing research by investigator Andy Liu at National Jewish Health include: (1) understanding and predicting progressive, severe, and poorly controlled asthma that does not respond well to conventional asthma management; (2) development of predictive test panels to individualize care and optimize asthma outcomes; and (3) investigation of preventive measures to reverse the rising prevalence of asthma worldwide.
Current Research Projects
Brief descriptions of our asthma research projects in the Liu lab are as follows:
Difficult-to-control asthma: Of those with asthma, some have more severe disease that is difficult to control with conventional management and can be combined with progressively deteriorating lung function. We have learned that this process can begin in childhood and, in the early years, is clinically indistinguishable from most children with asthma whose lung function is well maintained. However, in later childhood and early adulthood, progressively deteriorating asthma is associated with more severe asthma exacerbations and clinical disease.
We have sought to understand the processes underlying asthma that is difficult to control. We have identified a cluster of biological markers in sputum, breath condensate, blood, and the urine of asthmatic children with difficult-to-control asthma that may be used to identify these at-risk children. These biomarkers appear to indicate some of the processes underlying difficult-to-control asthma, including impaired regulation of proteases and cellular inflammatory responses in the airways, persistent inflammation and oxidative stress, aberrant repair of tissue injury, and impaired responses to conventional corticosteroid therapy. We are currently using these biomarkers to determine if conventional and novel therapies improve these markers as an indicator of control of disease progression. We are collaborating with genetic investigators to explore possible genetic susceptibilities that may contribute to lung functional decline in this sub-group of asthmatics.
This progress has been built upon five NIH-sponsored studies: the Childhood Asthma Management Program (CAMP: Stan Szefler, PI), the CAMP genomics of progressive lung disease ancillary study (Benjamin Raby (B & W), PI), Proteomics of Chronic Respiratory Diseases in Children (Frank Accurso (Children’s Denver) PI; Szefler and Harbeck, Co-I), the Childhood Asthma Prevention Study (Mary Klinnert, PI), and the Inner City Asthma Consortium (Andrew Liu, PI). Other National Jewish Health investigators collaborating in this work include Nichole Reisdorph, PhD, Richard Reisdorph, PhD, Ron Harbeck, PhD, and Donna Bratton, MD.
Lipid mediators in asthma: leukotrienes represent a class of lipid mediators that cause inflammation and bronchospasm in asthma. They have been difficult to measure, but already the available measures have revealed that elevated leukotrienes in urine and breath condensate can help guide anti-leukotriene therapy to improve asthma outcomes. We are collaborating with new National Jewish Health investigators to develop an improved test utilizing new technologies that we are now refining for high throughput clinical application, in order to identify those asthmatics likely to benefit from anti-leukotriene therapies. We are developing this improved technology for the first time accurate quantitation and discovery of additional lipid mediators that either provoke or control dysregulated immunity in asthma. We are working with Nichole Reisdorph, PhD, Richard Reisdorph, PhD, Ron Harbeck, PhD, and David Tinkelman, MD.
Microbes and the allergic march to asthma in early childhood: Microbial exposures have a dichotomous relationship with allergies and asthma. They can trigger asthma exacerbations and worsen ongoing disease. However, microbial exposures may also drive early immune development to protect infants from developing asthma and allergies. We have sought to understand how this occurs: who is susceptible to poor outcomes from common microbial exposures, and conversely, what is the nature of benefit from these early exposures.
We believe that a burden of microbial components stimulates innate immunity in early life to activate numerous innate immune protective responses and to steer adaptive immune development away from allergic sensitization and disease. A more vigorous immune system that protects against respiratory infections and prevents the development of persistent allergic inflammatory responses also allows for optimal post-natal lung growth and differentiation. Genetic polymorphisms may contribute to individual propensity to respond to microbial exposures in a healthful or harmful manner. It is also possible that epigenetic mechanisms shaped by microbial and other environmental exposures form the nature of early immune responses. These acquired epigenetic modifications, while not in the sequence of the gene, are also hereditable such that maternal exposures and lifestyle factors may shape the character of immune responses to the outside world from the moment of delivery outside of the womb. The elucidation of nature’s way of protecting children from developing asthma and allergies, in ways that are safe and effective, is a central theme of our laboratory research.
Food allergy: Food allergies have evolved from an unusual condition to a public health problem in the U.S. over the past two decades. There is little understanding to this rise except that current national guidelines to prevent food allergies do not appear to be working well. Furthermore, there is currently no treatment for this life-threatening and life-modifying condition.
We have the benefit of support through an NIH-sponsored Consortium of Food Allergy Research (CoFAR: Leung PI, Liu Co-PI, Fleischer and Atkins) that includes a natural history study on the development and persistence of peanut and other common food allergies, and three therapeutic trials for desensitization and tolerance to allergic foods. Dr. Liu is also leading a working group in collaboration with the NIEHS (NIH) and CDC on the most recent U.S. national survey (NHANES 2005 – 6) in food allergy, asthma, and other allergic conditions. We are poised to further develop this clinical and translational program to advancements in clinical care for this growing, common problem.