Specific Aim: To determine the effect of doxycycline on airway inflammation by measuring levels of inflammatory biomarkers in patients and correlating changes in levels with pulmonary function.

Background and Significance: The intense inflammatory response within the airways of patients with Cystic Fibrosis (CF) causes the release of proteolytic enzymes, which cause destruction of the airways resulting in loss of lung function. Doxycycline has been shown to have potent anti-inflammatory activity in patients with other chronic diseases. Doxycycline may be a safe and effective therapy to reduce inflammatory markers in cystic fibrosis and has not previously been studied in chronic pulmonary inflammatory conditions.

Research Design and Methods: This is a prospective, open-label, randomized pilot study to determine the effect of doxycycline on biochemical markers of inflammation. PK/PD analysis will be performed on plasma and sputum doxycycline concentrations to quantify the relationship between drug exposure and reduction in inflammatory biomarkers.

Major Goal: To improve patient outcomes through a better understanding of anti-infective disposition in the host and host-microbial interactions with a focus on the impact of bacterial resistance and virulence expression on host inflammatory response in both acute and chronic infection models towards the development of novel therapeutics. This research model will help to identify new treatment strategies for CF from the laboratory and apply them to the patient at the bedside.
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