Bacteria in Lower Airways and Airway Inflammation in Children with Asthma

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DESCRIPTION (provided by applicant): The purpose of this proposal is to foster the scientific development and clinical research skills of Dr. Pia J. Hauk so that she will become an independent investigator. Clinical services provided at National Jewish Health and its research laboratories will provide Dr. Hauk with the ideal setting in which to investigate the impact of bacteria in the lower airways of asthmatic children on airway inflammation at the clinical, molecular and cellular levels. Through collaboration with the primary mentor, Dr. Donald Y.M. Leung, an extensive network of experienced clinical and translational researchers and completion of a didactic training program in clinical science, Dr. Hauk will attain the foundation for the development of an independent academic career. Asthma is the leading chronic childhood illness in the US. Colonization of the airways with pathogenic bacteria is unusual in healthy, non-smoking individuals, but has been demonstrated in patients with chronic lung disease. Neonatal colonization with bacteria in a high-risk birth cohort born to mothers with asthma has been associated with increasing asthma prevalence at the age of 5 years suggesting a pathogenic role of bacteria. Dr. Hauk has recently demonstrated a significant correlation between bacterial endotoxin and airway neutrophils in young children with asthma. The percentages of BAL neutrophils correlated with metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1 and MMP-9/TIMP-1 ratio, indicating that presence of endotoxin through presence of Gram-negative bacteria may contribute to chronic airway inflammation and early airway remodeling. The specific aims of the proposal are: (1) to assess the effect of pathogenic bacteria in the lower airways of children on asthma severity; (2) to characterize airway inflammation in asthmatic children with presence versus absence of bacteria in the airways; (3) to study the natural history of asthma in asthmatic children with presence versus absence of bacteria in the airways. The outcome of this proposal will provide greater insight into the pathophysiology and impact patient care suggesting antibiotic therapy as a potential therapeutic intervention in childhood asthma. Asthma in children is a major public health problem. This study proposes to determine if children with asthma and bacteria in their lower airways have more airway inflammation and more severe disease when compared to asthmatic children without bacteria in the lower airways. If bacteria in the airways of children with asthma cause more severe disease, antibiotics may have to be considered more often as therapy.