Boston University Medical Campus
Pulmonary, Critical Care, and Allergy Medicine

Special Interests:

RESEARCH:

• Pulmonary Immunology
• Transgenic Modeling of Allergic Airway Inflammation
• Salivary Diagnostics of Lung Disease

CLINICAL:

• Asthma/Allergy
• Critical Care Medicine
• General Pulmonary MEdicine

Dr. Little is an Assistant Professor in the Department of Medicine. He attends in the Medical Intensive Care Unit and on the Pulmonary Consultation Service at Boston Medical Center . His outpatient activity is concentrated in the Adult Asthma Center and Allergy Clinics.

Dr. Little’s longstanding clinical interests and research efforts are focused on examining the nature of airway inflammation in asthma.

Prior to coming to Boston University, during a postdoctoral fellowship at the UCSF Cardiovascular Research Institute , he investigated the effect of causing an experimental cold in asthmatic and healthy volunteers, followed by concurrent examination of clinical asthma markers (e.g., spirometry, symptoms) and airway secretions by nasal lavage and sputum induction.

In the laboratory, he is using key cytokine transgenic and knockout mice to investigate antigen-dependent and -independent allergic airway inflammation. Specifically, he is investigating interleukin-16 , a major CD4 ligand, as a paradigm for downregulation of antigen-dependent TH2 inflammation. He applies a well described model of allergic airway inflammation in mice that mimics human asthma to better understand the immunoregulation of the allergic response in the lung.

His translational research continues at Boston University as a principle investigator in a clinic-based study to develop a rapid saliva diagnostics platform for determining the causes of deterioration in asthma control. This study has expanded to both Emergency Room populations at B.U. and cohorts of pediatric asthmatics in collaboration Dr. Elizabeth Matsui, Pediatric Allergy/Immunology at Johns Hopkins. With Drs. Wexler and Traber, he is exploring the utility of the rapid diagnostic platform in identifying critically ill patients colonized with community and hospital-acquired strains of MRSA.

He has also participated as a Co-Investigator in immunotherapy trials with the NHLBI-funded Inner City Asthma Consortium, in collaboration with the BUMC site PI, Dr. George O’Connor.

Laboratory Members :

Philip Wexler, M.D. Senior Fellow, Allergy and Immunology, BUMC. Saliva and Asthma Project, MRSA Diagnostics
Katrina Traber, M.D. Chief Resident, Internal Medicine, BUMC. MRSA Diagnostics
Diana Delgado, B.Sc. Research Coordinator, Saliva and Asthma Project
Linqui Luo, B.Sc. Senior Research Technician, Saliva and Asthma Project
Fengzhi Shao, MSc. Senior Research Technician, Mouse models of allergic airway inflammation

Selected Publications:

1. Blicharz TM, Siqueira WL, Helmerhorst EJ, Oppenheim FG, Wexler PJ, Little F.F., Walt DR. Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. Analytical Chemistry. Feb 2009 (epub).
2. Summer R, Little F.F., Ouchi N, Takemura Y, Aprahamian T, Dwyer D, Fitzsimmons K, Suki B, Parameswaran H, Fine A, Walsh K. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. American Journal of Physiology: Lung Cellular and Molecular Physiology 94, L1035-42, 2008.
3. Walt DR, Blicharz TM, Hayman RB, Rissin DM, Bowden M, Siqueira WL, Helmerhorst EJ, Grand-Pierre N, Oppenheim FG, Bhatia JS, Little F.F., Brody JS. Microsensor arrays for saliva diagnostics. Annals of the New York Academy of Sciences 1098, 389-400, 2007.
4. Little, F.F. Treating acute asthma with antibiotics – Not quite yet (Invited Editorial). New England Journal of Medicine 354, 1632-1634, 2006.
5. Burkart, K.D., Barton, S.J., Holloway, J.W., Yang, I.A., Cakebread, J.A., Cruikshank, W.W., Little, F.F., Jin, X., Farrer, L.A. , Clough, J.B., Keith, T.P., Holgate, S., Center, D.M., and O’Connor, G.T. Association of asthma with a functional promoter polymorphism in the Interleukin-16 gene. Journal of Allergy and Clinical Immunology 117, 86-91, 2006.
6. Joyce-Brady, M.J., and Little, F.F. Asthma triggered by viral infections: a persistent and troublesome problem. Advance for Managers of Respiratory Care 14, 44-46, 2005.
7. Little, F.F. and Cruikshank, W.W. Interleukin-16 and peptide derivatives as immunomodulatory therapy in allergic lung disease. Expert Opinion on Biological Therapy 4:837-46, 2004.
8. Little, F.F. and Center, D.M. Induced sputum analysis for T-helper type 2 cell regulation: closing the loop (Invited Editorial). Chest 123, 1786-1788, 2003.
9. Little, F.F., Lynch, E., Fine, G., Center, D.M., and Cruikshank, W.W. TNF-alpha induced synthesis of IL-16 in airway epithelial cells: Effects of priming for serotonin stimulation. American Journal of Respiratory Cell and Molecular Biology 28, 354-362, 2003.
10. De Bie, J.J., Jonker, E.H., Henricks, P.A.J., Hoevenaars, J., Little, F.F., Cruikshank, W.W., Nojkamp, F.P., and Van Oosterhout, A.J.M. Exogenous IL-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia, and Th2-type cytokine production in mice. Clinical and Experimental Allergy 32, 1651-1658, 2002.
11. Little, F.F., Cruikshank, W.W., and Center, D.M. IL-9 stimulates release of chemotactic factors in human bronchial epithelial cells. American Journal of Respiratory Cell and Molecular Biology. 25, 347-352, 2001.
12. Fleming, H.E. and Little, F.F. (equal contribution, authors listed alphabetically), Schnurr D., Avila, P.C., Wong, H., Liu, J., Yagi, S., and Boushey, H.A. Rhinovirus-16 induced common colds in healthy and in asthmatic subjects: Similar changes in upper and lower airways. American Journal of Respiratory and Critical Care Medicine 160, 100-8, 1999.

Book Chapters:

1. Cruikshank W, and Little F.F. lnterleukin-16: the ins and outs of regulating T-cell activation. Critical Reviews in Immunology 28, 467-483, 2008.
2. Little, F.F., Wilson , K.C., Berman, J.S., and Center, D.M. Lymphocyte- and macrophage-mediated inflammation in the lung. In: Fishman’s Pulmonary Diseases and Disorders, 4 th ed, Fishman A.P. et al, eds. New York : McGraw-Hill, 2008.
3. Little, F.F. and Hollingsworth, H.M. Anaphylaxis. In: Intensive Care Medicine. Irwin, R.S and Rippe, J.M., eds. Philadelphia : Lippincott Williams & Wilkins, 2006.
4. Little, F.F., Cruikshank, W.W., Center, D.M. IL-16 and Airway Hyper-Responsiveness in Asthma. In: Biology of Airway Inflammation – Therapeutic Targets, Eissa, N.T., ed. Series: Lung Biology in Health and Disease. New York: Marcel Dekker. Vol 177, 2003.

Selected Reprints:

1. Treating acute asthma with antibiotics
2. Interleukin-16 and peptide derivatives as immunomodulatory therapy in allergic lung disease
3. Induced Sputum Analysis For T Helper Type 2 Cell Regulation
4. Tumor Necrosis Factor-alpha Induced Synthesis of Interleukin-16 in Airway Epithelial Cells
5. Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity eosinophilia and Th2-type cytokine production in mice
6. IL-9 Stimulates Release of Chemotactic Factors from Human Bronchial Epithelial Cells
7. Rhinovirus-16 Colds in Healthy and in Asthmatic Subjects

Links:

• Salivary Diagnostics, Walt Lab, Tufts University

Clinic Sites:
Adult Asthma Center and Allergy Clinics
Doctor’s Office Building, Boston Medical Center