Progressive, obstructive lung disease largely drives both morbidity and early mortality in cystic fibrosis (CF). Early detection and treatment of pulmonary decline is key to optimal long-term outcome; however, physiologic measures of lung function and radiologic outcomes fail to capture the inflammation and infection that begin in infancy, which are often asymptomatic. Successful drug development targeting the underlying genetic mutation in CF continues, underscoring the critical need to better understand pathophysiological factors in the development of early lung disease to keep children with CF as healthy as possible until they are a candidate for personalized drug therapy.
Newborn screening facilitates an early CF diagnosis; however, strategies to mitigate the development and progression of early lung disease continue to lag behind. My laboratory focuses on biomarkers of lung disease and early infection to help us to better understand the progression of lung disease in CF. Standard-of-care in clinic is to obtain a quarterly airway culture from all CF patients to identify treatable bacterial pathogens and guide antibiotic therapy. This is problematic for two reasons: (1) Children with CF often do not expectorate sputum, and an upper airway swab for culture is a poor surrogate for bacteria living in the lower airway, and (2) Traditional culture is limited in its scope, specifically missing anaerobic organisms and neglecting fungi and viral pathogens as well.
Culture-independent approaches using next-generation sequencing techniques have revealed a more complex, polymicrobial bacterial community in the pediatric CF upper and lower airway. Interestingly, a large number of these communities are oral anaerobes, thought to be non-pathogenic. We recently published that anaerobic communities are already present in higher relative abundance than traditional CF pathogens in the bronchoalveolar lavage fluid (BALF) from asymptomatic infants with CF; however, we do not yet understand their contribution to the development of lung disease. Bronchiectasis and mucus plugging of CF airways create a hypoxic environment conducive to the fermentation of anaerobes and recent work suggests the potential for anaerobes to promote CF lung disease.
My laboratory is focused on understanding the role of anaerobic bacteria, and other pathogens, in the lower airways of CF children. Through research collaborations both locally and nationwide, we incorporate state-of-the-art microbiota identification techniques, metabolomics and metaproteomics technology and expertise in microbial ecology to both identify and functionally investigate the pathophysiological role of anaerobic bacteria in the lower airways of children with CF.
1. Project Title: “The Microbiota of the Pediatric CF Airway: what role does it play”
Description: We hypothesize that anaerobic bacteria in the lower airways of infants and children with CF is associated with fermentative metabolism and will have a unique metabolic and metaproteomic biosignature that incites inflammation and contributes to the development of early CF lung disease.
We will use state-of-the-art microbiota identification techniques, metabolomics and metaproteomics technology and expertise in microbial ecology to both identify and functionally investigate the pathophysiological role of anaerobic bacteria in the lower airways of children with CF. Our novel preliminary data shows the presence of anaerobic communities in infant CF BALF (bronchoalveolar lavage fluid) and evidence of a fermentative environment in the CF airway. Now, with a collection of BALF samples from children with/without CF and their associated clinical data available for immediate analysis, our proposal builds upon this foundation to investigate the metabolic and pulmonary consequences of anaerobic infection in CF.
Principal Investigator: Terri Laguna, MD, MSCS
Research Associate III: John B. (Jack) O'Connor
Clinical Research Coordinator: To be determined.
Research Scientist: To be determined.
Post-doc Fellows: To be determined.
Terri Laguna, Associate Professor of Pediatrics, Northwestern University Feinberg School of Medicine; Head, Division of Pulmonary and Sleep Medicine; Director, Cystic Fibrosis Center
Department Office: 312-227-6260