J ALLERGY CLIN IMMUNOL

VOLUME 129, NUMBER 2

Abstracts AB201

MONDAY

757 Early Non-Respiratory Symptom Patterns Precede Loss ofAsthma Control in Children

L. Newton1, Y. Osei-Akosa2, R. Strunk3, M. Krauss3, L. Bacharier3,

J. Garbutt3, K. Rivera-Spoljaric3; 1Cleveland Clinic, Cleveland, OH,2Washington University in St. Louis, St. Louis, MO, 3Washington

University School of Medicine, St. Louis, MO.

RATIONALE: Little is known about how non-respiratory (NR) symptoms

precede loss of asthma control in children.

METHODS: Parents of children aged 2-11 years with persistent asthma

completed diaries daily for 16 weeks which categorized the severity of 41

NR, upper (UR) and lower (LR) respiratory signs and symptoms as usual,

less than usual, or more than usual. Using logistic regression models with

generalized estimating equations, we examined the effect of the presence

of not usual levels of these symptoms in 3 days preceding an episode of loss

of asthma control (>_2 consecutive days of increased LR symptoms,

excluding mild cough).

RESULTS: We initially enrolled 33 parents. Six failed to complete any

diary entry, however for the remaining 27 there were 82% days completed

(2467/3024) and 19 completed all 16 weeks. Most children were boys

(67%), Caucasian (59%), and average age was 7 years (SD 2.7). 21/27

children (78%) had >_1 episode of loss of control, and 12/27 (44%) had >_3

episodes. NR symptoms, most notably anxiety, moodiness, crying, irrita-

bility, activity level, tiredness, tension, paleness and eye swelling, were

significantly more likely prior to an episode than during controlled periods

(OR 1.6, 95% CI 1.03 - 2.4). The only UR symptom that was significantly

more likely prior to an episode was itchy throat (OR 2.9, CI 1.3 - 6.5).

CONCLUSIONS: NR signs and symptoms appear to precede loss of

asthma control. Further investigation is needed to determine whether

treatment initiated at the onset of these early symptoms could prevent loss

of asthma control and exacerbations.

758 Adverse Reaction Preparedness for Allergen Immunotherapyin the Primary Care Setting

V. Reddy, P. Jhaveri, T. J. Craig; Division of Pulmonary, Allergy, and Crit-

ical Care Medicine, Penn State Milton S. Hershey Medical Center, Her-

shey, PA.

RATIONALE: Fatal reactions due to allergen immunotherapy (AIT) are

estimated to occur in 1 per 2.5 million injections (average of 3.4 deaths per

year). Factors contributing to fatal reactions are uncontrolled asthma,

inadequate post injection wait time, and administration in settings not

equipped to handle anaphylactic reactions. The preferred setting is the

prescribing allergist’s office.However, patientsmay receiveAITat primary

care facilities equipped to manage systemic reactions. This study was

administered to determine whether primary care offices are prepared to

handle adverse reactions to AIT.

METHODS: After IRB approval, a referring physician database was

obtained. Each physician office was called, verbal consent was obtained,

and a questionnaire was administered via phone to nursing staff.

RESULTS: One hundred and ninety four physicians were represented by

43 offices administering AIT. Forty one offices (95%) felt comfortable

administering AIT. Fourteen offices (32.6%)monitored patients for at least

30 minutes post injection. Twenty three offices (53%) assessed asthma

patients for active symptoms and ten (23%) measured peak flow prior to

administering AIT. Thirteen offices (30%) reported adverse reactions.

Thirty offices (70%) had the ability to administer intravenous fluid.

Eighteen offices (42%) stated theywould benefit from additional education

on administering AIT.

CONCLUSIONS: The majority of primary care offices are not fully

equipped to handle adverse reactions to AIT. There is insufficient wait time

after injection, lack of assessment of asthmatic patients, and insufficient

equipment in case of anaphylaxis. Primary care offices would benefit from

further education on administration of AIT to ensure adherence to allergy

practice parameters and patient safety.

759 Clinical Efficacy and Safety of Combined MometasoneFuroate and Formoterol in Patients With Moderate to VerySevere Chronic Obstructive Pulmonary Disease (COPD)

E. Kerwin1, D. P. Tashkin2, C. E. Matiz-Bueno3, D. E. Doherty4, T.

Shekar5, S. Banerjee5, B. Knorr5, H. Staudinger5; 1Clinical Research Insti-

tute of Southern Oregon, Medford, OR, 2David Geffen School of Medi-

cine at UCLA, Los Angeles, CA, 3Fundacion Salud Bosque, Bogota,

COLOMBIA, 4University of Kentucky, Lexington, KY, 5Merck Research

Laboratories, Kenilworth, NJ.

RATIONALE: Clinical studies have shown that combining inhaled

corticosteroids with long-acting b2-agonists can be effective in COPD.

We evaluated the combination mometasone furoate/formoterol (MF/F),

administered via metered-dose inhaler, as treatment for moderate-very

severe COPD.

METHODS: This 26-wk, multicenter, double-blind, placebo (PBO)-

controlled trial included current/ex-smokers (>_10 pack-y) ages>_40y with

moderate2very severe COPD (mean baseline [BL] % predicted FEV1,

39.6%) randomized to twice-daily (BID) inhaled MF/F 400/10mg, MF/F

200/10mg, MF 400mg, F 10mg, or PBO. Efficacy was measured by mean

changes from BL in FEV1 over 0212 hrs (AUC0212 FEV1) and pre-dose

AM FEV1 at endpoint (EP) after 13 wks or 26 wks of treatment.

RESULTS: For subjects (n51043) with post-BL results through wk 26,

changes fromBL inAUC0212 FEV1withMF/F 400/10mg,MF/F 200/10mg,MF 400mg, F 10mg, PBO at 26 wks were 154,*� 110,*� 56,§ 70,{ 0 mL,

respectively (*P<.001 vs PBO; �P<_.001 vs MF 400mg and F 10mg;�P5.036 vs MF 400mg; §P5.031 vs PBO; {P5.007 vs PBO). Changes

from BL in pre-dose AM FEV1 at 26 wks with MF/F 400/10mg, MF/F

200/10mg, MF 400mg, F 10mg, PBO were 88,*� 60,* 45,* 5, 213 mL

(*P<_.037 vs PBO; �P5.003 vs F 10mg). At 26 wks, the proportion of sub-jects reporting adverse events (AEs) was similar between treatment groups.

The most common treatment-related AEs across groups over 52 wks were

oral candidiasis (0.9%), lenticular opacities (0.7%), and cough (0.7%).

CONCLUSIONS: Treatment with MF/F 400/10mg and 200/10mg BID

significantly improved lung function and was well tolerated in subjects

with moderate to very severe COPD.

760 ASHMI (Antiasthma Simplified Herbal Medicine Intervention)is a Potent Inhibitor of Interferon-a Production from HumanDendritic Cells by Increasing Pro-inflammatory Cytokines

J. R. Tversky; The Mount Sinai School of Medicine, New York, NY.

RATIONALE: ASHMI (Antiasthma Simplified Herbal Medicine

Intervention) has been shown in preliminary studies to be efficacious and

well tolerated in adult asthmatics. ASHMI treated individuals have a

pronounced alteration in serum cytokine levels and a reduction in total

serum IgE levels. It is not known what effect ASHMI has on human

dendritic cells.

METHODS: PBMCwere obtained from 10 individuals and plasmacytoid

dendritic cells (pDCs) were isolated using negative selection. PBMC and

pDCswere stimulatedwith CpG (600nM), IgE receptor antibody (3mg/ml),

with or without ASHMI (1.25, 2.5, and 5mg/ml) for 18 hours with cytokine

production determined by ELISA. IgE receptor expression and pDC purity

were determined by multi-color flow cytometry.

RESULTS: At all three concentrations, ASHMI reduced CpG mediated

IFN-a production from PBMC by approximately 3-4 fold (P < 0.0048).

ASHMI reduced IFN-a production from pDC by approximately 2-fold

(P 5 0.047). Conversely, stimulated PBMC pro-inflammatory cytokine

production of IL-6 was enhanced 5-fold (P < 0.0001) with ASHMI. pDC

IL-6 production was also enhanced 5-fold with ASHMI (P 5 0.062).

ASHMI treatment alone resulted in a 4-5 fold increase in IL-6 production

(P < 0.0002) compared to unstimulated cells.

CONCLUSIONS: ASHMI Chinese herbal asthma compound is a potent

inhibitor dendritic cell interferon-a production perhaps, in part by up-

regulating pro-inflammatory cytokine mediators. This data supports pre-

vious publications that suggest ASHMI’s therapeutic effect arises from

skewing of the Th1/Th2 cytokine axis.