MISSION

concentrations of inflammatory indices such as percentage neutrophils, protein, and leukotriene B4 than
other sources of lower respiratory fluids, although the inflammatory indices tend to correlate between the
different sampling techniques.
FAMRI Supported Publications
Garcia A, McHugh M, Ballering JG, Hoyt JC, Hayden JM, Robbins RA. Neutrophils, protein and LTB4
are increased in sputum compared to bronchoalveolar lavage and exhaled breath condensate. Am J Resp
Crit Care Med 2005;171:A844.
Garey KW, Neuhauser MM, Robbins RA, Danziger LH, Rubinstein I. Markers of inflammation in exhaled
breath condensate of young healthy smokers. Chest 2004;125:22-26.
Numanami H, Koyama S, Nelson DK, Hoyt JC, Freels JL, Habib MP, Amano J, Haniuda M, Etsuro Sato
E, Robbins RA. Serine protease inhibitors modulate smoke-induced chemokine release from human lung
fibroblasts. Am J Resp Cell Mol Biol 2003;29:613-619.
MATRIX-INDUCED EPITHELIAL ACTIVATION IN BRONCHITIS
Maureen Horton, MD; The Johns Hopkins University; YCSA 2003
Dr. Horton’s group has defined the ability of fragments of the extracellular matrix component hyaluronan
(HA) to promote epithelial cell-induced inflammation. The PI determined that HA fragments employ
innate immune Toll-like receptor-2 (TLR-2) to mediate its effects. Additionally, blocking TLR-2 inhibits
HA fragment-induced inflammation and disease. Furthermore, the TLR-2-deficient animals are protected
from noninfectious lung injury. Specifically, HA fragments induce IL-8 and inducible protein 10 gene
expression in airway epithelial cells by different signaling pathways, mitogen-activated protein kinase
(MAPK), and nuclear factor-kappa B, respectively. These observations indicate that broken down extracellular
matrix, in the form of HA fragments, employ the same activating receptors as infectious agents and,
thus, provide a mechanism by which HA can promote the chronic inflammation of bronchitis in the
absence of infection. Such studies have offered insight into the role of epithelial cells in inflammation and
to the identification of potential clinical inhibitors. The PI predicts these studies with potential therapeutic
agents will serve as preclinical data in support of clinical trials of these agents to help treat and possibly
reverse the debilitating symptoms and tissue destruction that characterize chronic bronchitis.
BIOMARKERS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Robert E. Walter, MD; Boston University; YCSA 2003
Dr. Walter’s research utilizes the multigenerational, multi-cohort Framingham Heart Study (FHS) to better
understand the mechanisms underlying the development of chronic airflow obstruction resulting from chronic
tobacco smoke exposure (COPD). FHS has a wide range of longitudinal measures, including lung function
and tobacco smoke exposure. The genetic information and the variety of biomarkers of inflammation, oxidant
stress, and endothelial function measured at various times points offer a unique opportunity to explore the
mechanisms, including gene-by-environmental interactions, linking cigarette smoke to pulmonary disease.
FAMRI Supported Publications
Walter RE, Guo CY, Chen T, Lee TA, Weiss KB, O’Connor GT. Chronic obstructive pulmonary disease in
the Framingham Heart Study, 2006. Presented at the American Thoracic Society.
Walter RE, Wilk JB, Larson MG, Vasan RS, Keaney JF, Jr., Lipinska I, O’Connor GT, Benjamin EJ.
Systemic inflammation and COPD: the Framingham Heart Study. Chest 2008;133:19-25.
Wilk JB, Walter RE, Laramie JM, Gottlieb DJ, O’Connor GT. Framingham Heart Study genome-wide
association: results for pulmonary function measures. BMC Med Genet 2007;8 Suppl 1:S8.
DIAGNOSTIC TECHNIQUES
CURRENT RESEARCH
DETECTION OF PASSIVE SMOKE EXPOSURE IN CHILDREN AND ADULTS USING ORAL BASED RAPID TEST
TECHNOLOGY
R. Sam Niedbala, PhD; Lehigh University; CIA 2006
Passive exposure to tobacco smoke causes a variety of illnesses ranging from mild allergic reactions to
some forms of cancer. Knowing that exposure brings risk, a rapid test to quickly assess exposure to SHS
would create a valuable tool for researchers and clinicians, particularly in evaluating vulnerable populations
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