J ALLERGY CLIN IMMUNOL

VOLUME 121, NUMBER 2

Abstracts S3

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Funding: Asan Institute for Life Science (2007-091) and the Korea Health

21 R&D Project. Ministry of Health & Welfare, Republic of Korea (03-

PJ10-PG13-GD01-0002)

9 Mutated Glutathione-S-Transferase Reduced Airway InflammationIn Murine Model

P. Tripathi1,2, B. P. Singh1, N. Arora1; 1Institute of Genomics and Integra-

tive Biology, Mall Road, Delhi, INDIA, 2Department of Biotechnology,

University of Pune, Ganeshkhind, Pune, INDIA.

RATIONALE: Oxidative stress contributes in the pathogenesis of asthma.

Glutathione-s-transferase (GST) is an antioxidant and its deficiency

increases the risk of developing asthma. The present study investigates

the effect of GST and mutated GST (mGST) with reduced IgE binding in

murine model of airway inflammation.

METHODS: BALB/c mice were immunized i.p. with ovalbumin (10mg/

100ml PBS) on days 1 and 14 and challenged on days 28, 29, and 30. Mice

were administered intranasally with GST, mGST, lipoic acid (LA) and PBS

after 1 h of each OVA challenge. Mice were sacrificed on day 31 and lungs

were used for histology. Total and differential cell count, IL-4, IFN-g and

oxidative stress were measured in BALF. Immunoglobulins were deter-

mined in sera.

RESULTS: GST and mGST have similar enzymatic activity but mGST

has reduced IgE binding (44% reduction). mGST mice showed signifi-

cantly reduced total cell count and eosinophils in BALF as compared to

PBS or GST administered groups (p < 0.01). Lung inflammation score in

terms of eosinophilic infiltration and mucous secretion was lowest for LA

group mice followed by mGST and GST administered groups. IL-4 was

significantly reduced for mGST group compared to PBS administered or

GST group mice (p < 0.01). However no change was observed in IgG

subtypes. Oxidative stress in BALF of both mGST as well as GST

administered mice were reduced significantly in comparision to PBS

instilled group (p < 0.01).

CONCLUSION: These data suggests that mGST with reduced IgE

binding has potential to limit airway inflammation in bronchial asthma.

Funding: Council of Scientific and Industrial Research, INDIA

10 Healthy African Americans have an Increased Prevalence ofLow Exhaled Breath Condensate pH values

D. W. Hauswirth1, J. S. Sundy2, S. Mervin-Blake2, C. Fernandez2, K. B.

Patch2, P. McNair2, K. Alexander2, S. Allgood2, M. C. Levesque2; 1Ohio

State University, Columbus, OH, 2Duke University Medical Center,

Durham, NC.

RATIONALE: Exhaled Breath Condensate (EBC) pH values are used as a

marker of disease activity in asthma and other inflammatory conditions.

Previous reports of mixed ethnicity cohorts cohorts have shown that only

3-5% of healthy subjects have an EBC pH <6.5.

METHODS: Two hundred and seventy healthy, non-asthmatic, non-

smoking African American subjects between the ages of 18 and 40 were

evaluated. Subjects had simultaneous measurement of EBC pH (before and

after argon deaeration), EBC Nitrite, Nitrate and exhaled Nitric Oxide

(FeNO).

RESULTS: In the sample of 270 subjects, the median EBC pH was 6.17

(interquartile range 5.50-6.78) prior to argon deaeration and 8.14

(interquartile range 7.83-8.28) after argon deaeration. There were 11.9%

of subjects with a post-argon pH < 6.5. EBC pH did not correlate with

FeNO except at low pH. Low pH subjects (n 5 32) showed an inverse

correlation between pH and FeNO (r2 5 0.158, p 5 0.0245). In the

entire cohort, there was a direct relationship between pH and EBC

Nitrite (r2 5 0.163, p < 0.0001), there was no correlation between nitrite

and FeNO.

CONCLUSIONS: We report increased prevalence (11.9%) of low EBC

pH values (<6.5) in healthy non-smoking African Americans. EBC pH and

Nitrite showed a direct correlation, however there was not correlation

between Nitrite and FeNO. FeNO was not correlated with EBC pH except

at pH values <6.5. This is important as EBC pH is used as a diagnostic tool

for asthma and other inflammatory lung diseases. Use of this tool in

African Americans must account for the increased incidence of low pH

values (11.9%).

Funding: Sandler Program in Asthma Research

11 The Value of Discordant Pulmonary Function Testing andExhaled Nitric Oxide measurements in the Management ofPediatric Asthma

A. Sreedharan, D. E. Schuller; Hershey Medical Center, Hershey, PA.

RATIONALE: We sought to determine the utility of exhaled nitric oxide

(eNO) measurements combined with pulmonary function tests (PFTs) in

clinical decision making in pediatric asthma patients. Elevated eNO levels

have been described in asthmatics with eosinophilic airway inflammation.

However; PFTs have become the standard by which most allergists base

their asthma management. Studies correlating PFTs with eNO are incon-

clusive in the pediatric population.

METHODS: We obtained eNO measurements on 100 consecutive

patients with mild to moderate persistent asthma in a pediatric asthma

and allergy clinic at an academic medical center. All subjects had PFTs

done at the same visit. Concordance of eNO and PFTs was evaluated.

RESULTS: Seventeen patients (17%) had normal PFTs, but elevated eNO

(>20 ppb). Twenty-seven patients (27%) had abnormal PFTs, but normal

eNO. Decisions to increase, decrease, or maintain asthma therapy were

made based on evaluation of PFT and eNO measurements. Using both

values, 44% of patients had different management plans, than would have

been prescribed if PFTs were used alone.

CONCLUSIONS: Elevated eNO, with normal PFTs, indicated airway

inflammation and the need to intensify or maintain asthma therapy. Low

FEV1 and FEF 25-75% and normal eNO suggested triggers other than

allergic asthma, such as GERD, bronchomalacia, infection, or airway

irritants. Pulmonary function testing, in combination with eNO, is a useful

clinical tool in the management of pediatric asthma.

12 Relationships of Methacholine and Adenosine 59-monophosphate(AMP) Responsiveness to the Postbronchodilator FEV1/FVC Ratioin Children with Asthma

Y. Koh1, S. Choi1, D. Kim1, J. Yu2, Y. Yoo3; 1Seoul National University

Hospital, Seoul, REPUBLIC OF KOREA, 2Ulsan University Asan Medi-

cal Center, Seoul, REPUBLIC OF KOREA, 3Korea University Anam

Hospital, Seoul, REPUBLIC OF KOREA.

BACKGROUND: Airway remodeling has been assumed to cause bron-

chial hyperresponsiveness (BHR). A low postbronchodilator FEV1/FVC

ratio has been suggested to be a functional surrogate marker of airway re-

modeling. BHR is commonly assessed by bronchial challenges using direct

or indirect stimuli. The aim of this study was to compare BHR to metha-

choline and adenosine 59-monophosphate (AMP) with regard to the rela-

tionship with airway remodeling.

METHODS: Methacholine and AMP challenge tests were performed in

129 children with asthma, aged 12 years, and a provocative concentration

causing a 20% fall in FEV1 (PC20) was calculated for each challenge. All

subjects also underwent pre- and postbronchodilator spirometry. A post-

bronchodilator FEV1/FVC ratio below the lower limits of normal was

used as a marker of airway remodeling.

RESULTS: A low postbronchodilator FEV1/FVC ratio was found in 17

subjects (13.2%). These subjects had a significantly lower methacholine

PC20 (geometric mean: 0.63 mg/mL, range of 1 SD: 0.17-2.29) than those

(n 5 112) with a normal postbronchodilator FEV1/FVC ratio (2.42 mg/mL,

0.57-10.32, p 5 0.000), whereas AMP PC20 was similar between the two

groups (22.1 mg/mL, 3.9-125.9 vs. 27.7 mg/mL, 4.2-183.5, p 5 0.231). In

the whole group of subjects, methacholine PC20, but not AMP PC20, corre-

lated significantly with the postbronchodilator FEV1/FVC ratio (r 5 0.340,

p 5 0.000, and r 5 0.056, p 5 0.526, respectively).

CONCLUSIONS: Our results provide evidence, though indirect, that

BHR to methacholine is related to airway remodeling in children with

asthma, and suggest that BHR to methacholine may be a better marker of

airway remodeling than BHR to AMP.