Bronchiolitis & Asthma
The most recent report by the WHO estimates that about 3.5
million deaths occur every year worldwide from acute respiratory
tract infections, of which 55% in children under the age of five.
Bronchiolitis, one of the main clinical syndromes in hospitalized
infants, accounts for up to 60% of all lower respiratory tract
illnesses during the first year of life. Respiratory syncytial virus
(RSV) is the single most important viral pathogen causing
bronchiolitis in infants and children. Severe RSV infections have been
linked to both the development and the severity of chronic asthma.
Although premature infants and those with certain underlying medical
conditions are predisposed to more severe infections, the majority
of infants hospitalized because of serious RSV disease are born at
term and otherwise healthy. The factors that contribute to the
progression of upper respiratory tract infection to lower respiratory
tract illness following RSV infection are not fully understood. In
addition, it is currently unknown whether RSV or other viral
respiratory pathogens are able to induce a chronic status of
inflammation in the airways and how pathogen-specific respiratory
infections affect host responses.
Dr. Garofalo has been in the forefront in dissecting a complex
network of inflammatory and immunomodulatory genes of airway
epithelium, in the role of airway cells in the orchestration of the
inflammatory response in the lung, and in the relation of chemokines
and pathogenesis of RSV infection and airway hyperreactivity (1-4).
These critical observations have been translated to studies in
infants and have provided a new paradigm in our understanding of the
pathogenesis of respiratory viral infections and are going to be
tested for the purpose of improving the diagnostic approach to viral
LRTI (5-7). Examples of translational studies with potential for
deliverables include those aimed to block airway inflammation,
including the use of inhibitors of NF-?B (8) (9) and application of
pharmacologic compounds that reduce the oxidative response (10), in
association with novel anti-viral and vaccines strategies (11-13).
These investigations are conducted in parallel with studies aimed to
identify mucosal protein profiles and biomarkers that can be used
to predict disease progression, clinical outcome or response to
- Saito, T., R. W. Deskin, A. Casola, H. Haeberle, B.
Olszewska, P. B. Ernst, R. Alam, P. L. Ogra, and R. Garofalo. 1997.
Respiratory syncytial virus induces selective production of the
chemokine RANTES by upper airway epithelial cells. J Infect Dis
- Olszewska-Pazdrak, B., A. Casola, T. Saito, R. Alam, S. E.
Crowe, F. Mei, P. L. Ogra, and R. P. Garofalo. 1998. Cell-specific
expression of RANTES, MCP-1, and MIP-1alpha by lower airway
epithelial cells and eosinophils infected with respiratory syncytial
virus. J Virol 72:4756-4764.
- Garofalo, R. P., F. Mei, R. Espejo, G. Ye, H. Haeberle, S.
Baron, P. L. Ogra, and V. E. Reyes. 1997. Respiratory syncytial
virus infection of human respiratory epithelial cells up-regulates
class I MHC expression through the induction of IFN-b and IL-1a. J
- Haeberle, H. A., W. A. Kuziel, H. J. Dieterich, A. Casola,
Z. Gatalica, and R. P. Garofalo. 2001. Inducible expression of
inflammatory chemokines in respiratory syncytial virus-infected
mice: role of MIP-1alpha in lung pathology. J Virol 75:878-890.
- Garofalo, R. P., J. L. L. Kimpen, R. C. Welliver, and P. L.
Ogra. 1992. Eosinophil degranulation in the respiratory tract
during naturally acquired respiratory syncytial virus infection.
- Garofalo, R. P., B. Olszewska-Pazdrak, P. L. Ogra, and R.
C. Welliver. 2001. Beta-chemokines in nasal secretion of infants
with respiratory syncytial virus-induced upper respiratory illness
and bronchiolitis. Pediatric Asthma Allergy and Immunology 15:89-96.
- Garofalo, R. P. and H. Haeberle. 2000. Epithelial
regulation of innate immunity to respiratory syncytial virus. Am J
Respir Cell Mol Biol 23:581-585.
- Haeberle, H. A., A. Casola, Z. Gatalica, S. Petronella, H.
J. Dieterich, P. B. Ernst, A. R. Brasier, and R. P. Garofalo. 2004.
IkappaB Kinase Is a Critical Regulator of Chemokine Expression and
Lung Inflammation in Respiratory Syncytial Virus Infection. J.Virol.
- Haeberle, H. A., F. Nesti, H. J. Dieterich, Z. Gatalica,
and R. P. Garofalo. 2002. Perflubron Reduces Lung Inflammation in
Respiratory Syncytial Virus Infection by Inhibiting Chemokine
Expression and Nuclear Factor-kappaB Activation. Am.J.Respir.Crit
Care Med. 165:1433-1438.
- Liu, T., S. Castro, A. R. Brasier, M. Jamaluddin, R. P.
Garofalo, and A. Casola. 2003. ROS mediate viral-induced stat
activation: role of tyrosine phosphatases. J.Biol.Chem.
- Zhang, Y., M. Jamaluddin, S. Wang, B. Tian, R. P. Garofalo,
A. Casola, and A. R. Brasier. 2003. Ribavirin treatment
up-regulates antiviral gene expression via the interferon-stimulated
response element in respiratory syncytial virus-infected epithelial
cells. J Virol 77:5933-5947.
- Guerrero-Plata, A., S. Baron, J. S. Poast, P. A.
Adegboyega, A. Casola, and R. P. Garofalo. 2005. Activity and
regulation of alpha interferon in respiratory syncytial virus and
human metapneumovirus experimental infections. J Virol 79:10190-10199.
- Liu, T., W. Zaman, B. S. Kaphalia, G. A. Ansari, R. P.
Garofalo, and A. Casola. 2005. RSV-induced prostaglandin E2
production occurs via cPLA2 activation: role in viral replication.