J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 2

Abstracts AB71

SATURDAY

251 Effect Of Prenatal Antioxidant Intake On Infants' Respiratory

InfectionDr. Eun Lee1, Seo Ah Hong2, Dr. Song I. Yang, MD1, Prof. Kyung Won

Kim, MD, PhD3, Prof. Youn Ho Shin4, Kang Mo Ahn5, Dr. Soo-Jong

Hong, MD, PhD1 and the COCOA study group. 1Department of Pediat-

rics, Childhood Asthma Atopy Center, Research Center for Standization

of Allergic Diseases, Asan Medical Center, University of Ulsan College

of Medicine, Seoul, Korea, 2Asan Institute for Life Sciences, University

of Ulsan College of Medicine, Seoul, Korea, 3Department of Pediatrics,

Severance Children’s Hospital, College of Medicine, Yonsei University,

Seoul, Korea, Seoul, South Korea, 4Department of Pediatrics, CHA Med-

ical Center, CHAUniversity School of Medicine, Seoul, Korea, South Ko-

rea, 5Department of Pediatrics, Samsung Medical Center, Sungkyunkwan

University School of Medicine, Seoul, Korea, South Korea.

RATIONALE: Prenatalmaternal diet may influence disease susceptibility

of offspring with genetic backgrounds. The effect of prenatal antioxidant

intake on the development of respiratory tract infection (RTI) during

infancy has not been studied. The interactions between prenatal antioxi-

dant intake and genetic factors on RTI susceptibility at 12- months of age

was evaluated.

METHODS: In the COhort for Childhood Origin of Asthma and Allergic

Diseases (COCOA) birth cohort study, prenatal maternal diet was assessed

by administering a food frequency questionnaire. Infants’ cord blood was

genotyped for the CD14 (rs2569190), TLR4 (rs1927911), and GSDMB

(rs4794820) polymorphisms by using the TaqMan method.

RESULTS: High prenatal maternal intake of vitamin C, folate, and total

fruit and vegetables associated weakly with the risk of RTI in offspring. In

childrenwith themajorCD14 allele, high prenatal intake of vitaminsA and

C, folate, fruits, and total fruits and vegetables associated with a lower RTI

risk (p-trend<0.05), whereas in infants with theminor alleles, high prenatal

intake of fruit increased the RTI risk (p-trend <0.05). In children with the

major TLR4 allele, the risk of RTI revealed inverse linear associations with

high prenatal intake of vitaminC (p for interaction50.0268). High prenatal

intake of fruits and total FV reduced the risk of RTI in infants with the GA

or AA genotype of GSDMB (p for interaction<0.05).

CONCLUSIONS: Prenatal antioxidant intake may reduce the risk of RTI

in infants, and this relationship may be modified by CD14, TLR4, and

GSDMB polymorphisms.

252 Epidermal Growth Factor Receptor (EGFR) Mediates CellFusion and Infectivity Of Respiratory Syncytial Virus (RSV)

Sujin Lee1,2, Michael G. Currier1,2, Anne L. Hotard1,2, Jia Meng1,2, Carla

Pretto1,2, Ultan F. Power3, Remi Villenave3, Michael D. Shields3,4,

Michael H. Chi5, R. Stokes Peebles6, Martin L. Moore1,2; 1Department

of Pediatrics, Emory University, GA, 2Children’s Healthcare of Atlanta,

GA, 3Centre for Infection and Immunity, School of Medicine, Dentistry

and Biomedical Science, Queens University Belfast, Northern Ireland,4The Royal Belfast Hospital for Sick Children, Northern Ireland, 5Allergy,

Pulmonary, and Critical Care Medicine; Department of Medicine; Vander-

bilt University School of Medicine, TN, 6Allergy, Pulmonary, and Critical

Care Medicine, Department of Medicine, Vanderbilt University School of

Medicine, Nashville, TN.

RATIONALE: We reported that RSV clinical isolate ‘‘2-20’’ fusion (F)

protein is mucogenic in RSV-infected mice. Here, we hypothesized a

cellular protein interacts with the RSV 2-20 F protein.

METHODS: Cellular proteins binding to RSV were identified by

screening and proteomics. Interaction of RSV F with epidermal growth

factor receptor (EGFR) was confirmed by co-immunoprecipitation and

immunoblotting. RSV entry and infection were quantified in BEAS-2B

cells and stable BEAS-2B EGFR-knockdown cells. RSV F proteins and

EGFR were overexpressed in 293T cells in a fusion assay. EGFR and RSV

were localized using confocal microscopy, and the effect of EGFR

blockade on RSV was determined in well-differentiated primary pediatric

bronchial epithelial cells (WD-PBECs).

RESULTS: We identified EGFR as an RSV F-binding protein. The

interaction between RSV strain 2-20 F and EGFR was stronger than that

between RSV strain A2 F and EGFR. Knockdown of EGFR in resulted in

lower RSVentry and infectivity, independent of the RSV strain.When cells

were treated with an EGFR tyrosine kinase inhibitor, the infectivity of

recombinant 2-20, but not A2, was reduced. Overexpression of EGFR

enhanced activity of the 2-20 F protein but not A2 F, and this fusion boost

was EGFR signaling-independent. EGFR was expressed apically in

ciliated WD-PBECs, and anti-EGFR reduced yield of clinical isolate

RSV in WD-PBECs.

CONCLUSIONS: EGFR interacts with the RSV F protein, prominently

with RSV 2-20 F. EGFR promotes RSV 2-20 F activity as well as RSV

entry and infectivity. We identified signaling-dependent and -independent

roles of EGFR in the RSV life cycle.

253 Cluster Analysis Of An Inner-City Cohort Of Infant WheezersDr. Monica B. Reddy, MD1, Andrew H. Liu, MD2, Allison

Schiltz1,2, Mrs. Anna Forssen, MS2, Dr. Mary D. Klinnert, PhD1,2; 1Uni-

versity of Colorado School of Medicine, 2National Jewish Health, Denver,

CO.

RATIONALE: Inner-city life is associatedwith early childhoodwheezing

and disparately poor asthma outcomes, but distinct phenotypes of the

preschool age associated with poor outcomes have not been described.

METHODS: In the Childhood Asthma Prevention Study (NIAID, PI

Klinnert), 119 Inner-City participants with recurrent wheezing in infancy

were followed from enrollment (age 9-24 months) to age 4 years, and had

complete data for a hierarchical cluster analysis to identify distinct

wheezing phenotypes based on asthma symptoms (ATS-B questionnaire),

impulse oscillometry (IOS) measures of lung function before and after

albuterol, and atopy. Asthma outcomes also included spirometry and

exacerbations (prednisone courses, ER/clinic visits, hospitalizations).

RESULTS: Five phenotypes were identified: ‘Atopic Wheezers’ (10% of

cohort) demonstrated asthma symptoms, high IOS resistance, high

bronchodilator (BD) response, atopy, and hyperinflation by spirometry;

‘Non-atopic Wheezers’ (50%) demonstrated asthma symptoms, but no

atopy; ‘Remitters’ (18%) were asymptomatic and had low IOS resistance;

‘Transient Wheezers’ (10%) were asymptomatic but with low lung

volumes; and ‘Paradoxical Responders’ (12%) demonstrated an increase

in IOS resistance after albuterol. Atopic and Non-atopic Wheezers had

significantly more ER visits compared to Remitters (p<0.01), and Non-

atopic Wheezers received significantly more prednisone bursts compared

to Remitters (p<0.01).

CONCLUSIONS: A cluster analysis identified 5 distinct phenotypes in an

inner-city cohort of wheezing infants followed to age 4 years. Atopic

wheezers and Non-atopic wheezers had persistent symptoms, differing

patterns of lung function, and severe exacerbations, while Remitters and

Transient Wheezers improved.