J ALLERGY CLIN IMMUNOL

FEBRUARY 2010

AB66 Abstracts

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258 Treatment and Assessment of Obstructive Lung Disease in theElderly

C. J. Ramos-Romey, T. Craig; Penn State University, Hershey, PA.

RATIONALE: Distinguishing asthma from COPD can be difficult and

overlap can occur, making diagnosis and treatment challenging specially

in geriatric patients. Studies have shown that geriatric patients are often

underdiagnosed and undertreated. Our objective is to evaluate manage-

ment and treatment of obstructive lung disease in geriatric patients. Our hy-

pothesis is that in the elderly asthma and allergies are overlooked and

treatment is inconsistent with established treatment guidelines.

METHODS: IRB approval was obtained. Patients over 65 years, with a

decrease in FEV1 of 20% or more in methacholine challenge, or improve-

ment in FEV1 of 12% or 200ml or more post-bronchodilator were included

in the study. Charts were reviewed and evaluated for management and

treatment.

RESULTS: Three hundred records were reviewed and 30 met inclusion

criteria. In 14 patients treatment was initiated or optimized based on symp-

toms and/or spirometry, with an average delay to treatment of 3.3 years. In

twelve patients treatment was suboptimal since no changes made in treat-

ment for symptoms or spirometry. Four patients did not receive treatment.

Six patients were evaluated for atopy; 4 had positive results.

CONCLUSIONS: We observed a bias to diagnose patients over the age of

65 with COPD. There is a significant delay from the onset of symptoms to

initiation of treatment. A large number of patients did not receive adequate

treatment based on symptoms or spirometry. An allergy evaluation was

performed in a small number of patients. We conclude that in the elderly

asthma is often assumed to be COPD, treament is delayed and suboptimal.

259 Effects of Rosiglitazone on Airway Hyperresponsiveness andObstruction in Asthma

M. S. Sandhu, V. Dimov, T. Romero, T. Wichman, T. B. Casale;

Creighton University, Omaha, NE.

RATIONALE: Peroxisome proliferator-activated receptors (PPAR) are a

family of nuclear hormone receptors. PPAR-g is expressed in the lung ep-

ithelium, airway smooth muscle and in inflammatory cells important in

asthma. Expression appears to be upregulated in response to inflammation.

Stimulation of PPAR-g down-regulates proinflammatory gene expression

and inflammatory cell functions. Therefore we examined the ability of

the PPAR-g agonist, rosiglitazone, to improve airway hyperresponsiveness

(primary endpoint) and FEV1 (secondary endpoint).

METHODS: This is an open label single center study with planned enroll-

ment of 14 adult steroid naı̈ve asthmatics. Inclusion criteria included a pos-

itive methacholine challenge with a PC20 �5.0 mg/ml. All eligible

subjects received rosiglitazone 4mg po daily for 8 weeks followed by an

additional 4 weeks at 8mg po daily. Methacholine challenges were per-

formed at baseline, and weeks 4, 8 and 12.

RESULTS: Data are available for 9/14 patients. When compared to base-

line methacholine PC20 (2.84 mg/ml), mean PC20 values increased at 4

weeks, 3.6 mg/ml (p50.33), 8weeks, 4.2mg/ml (p50.4) and 12 weeks,

5.9 mg/ml (p50.1). This corresponded to a percent increase in mean

PC20 of 62%, 68% and 156% respectively. When compared to baseline,

FEV1 gradually improved and at 12 weeks increased by a mean of 6.5%.

CONCLUSIONS: Rosiglitazone improved both airway hyperresponsive-

ness and FEV1 in a dose-and time-dependent manner. Although the results

did not reach statistical significance, this may be because only 9/14 pa-

tients� data were available. We conclude that the PPAR-g agonist rosiglita-

zone shows therapeutic promise for asthma and further study with these

agents is warranted.

260 Bronchodilator Responsiveness to Formoterol (FM)-Containing Treatments by Chronic Obstructive PulmonaryDisease (COPD) Severity Classification

D. P. Tashkin1, B. R. Celli2, S. I. Rennard3, J. McElhattan4, U. J. Martin4;1David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Tufts

University, Boston, MA, 3University of Nebraska Medical Center, Omaha,

NE, 4AstraZeneca LP, Wilmington, DE.

RATIONALE: Effect of COPD severity on airway reversibility to FM has

not been evaluated extensively. We investigated reversibility to FM-con-

taining treatment in moderate to very severe COPD patients.

METHODS: Data were pooled from common treatment arms in 2 ran-

domized, double-blind, multicenter studies (I: 6-mo; NCT00206154

[Drugs. 2008;68:1975-2000]; II: 12-mo; NCT00206167 [Drugs.

2009;69:549-65]) in COPD patients�40 y. Treatments: twice-daily bude-

sonide/FM pressurized metered-dose inhaler (BUD/FM pMDI) 320/9 mg

(n5101 [I]; n5121 [II]), BUD/FM pMDI 160/9 mg (n5102 [I]; n5121

[II]), FM dry powder inhaler 9 mg (n5104 [I]; n5124 [II]), placebo

(n5108 [I]; n5125 [II]). Airflow obstruction reversibility was assessed

30 min after study medication on day of randomization as part of serial spi-

rometry testing based on forced expiratory volume in 1 s (FEV1) improve-

ment thresholds �12% and �200 mL (American Thoracic Society [ATS]

criterion) and �15%. Data were assessed overall and by GOLD 2008 se-

verity stage based on postbronchodilator FEV1 in each treatment group.

RESULTS: Reversibility of airflow obstruction was achieved by a major-

ity of patients after FM-containing treatment (51%-54% [ATS criterion];

66%-73% [�15% criterion]). Percentage of responders to FM-containing

treatment appeared to decrease with increasing COPD severity using the

ATS criterion (stage II: 47%-69%; III: 53%-62%; IV: 31%-41%), but not

when applying the �15% criterion (II: 45%-71%; III: 66%-74%; IV:

65%-89%). Percentage of responders tended to be higher for BUD/FM ver-

sus FM.

CONCLUSIONS: FM-containing treatments result in significant revers-

ibility of airflow obstruction in a large percentage of COPD patients, in-

cluding those with severe and very severe COPD.

261 Single-Dose, First-in-Human Study of AMG 853:Pharmacokinetics, Pharmacodynamics, and Safety inHealthy Adults

C. Banfield1, J. Parnes1, M. Emery1, L. Ni1, N. Zhang1, P. Hodsman2;1Amgen Inc., Thousand Oaks, CA, 2CCS Nuclear Network Australia,

Melbourne, AUSTRALIA.

RATIONALE: AMG 853 is a potent, selective, orally bioavailable small

molecule that inhibits binding of prostaglandin D2 (PGD2) to its two recep-

tors: the chemoattractant receptor-homologous molecule expressed on T

helper lymphocyte type 2 cells (CRTH2) and D-prostanoid (DP). PGD2,

the major lipid mediator formed by activated mast cells, induces a variety

of biological actions including eosinophil infiltration, vasodilation, and

bronchoconstriction.

METHODS: In this double-blind, placebo-controlled study, 82 subjects

were randomized and received AMG 853 (5-400 mg) or placebo oral solu-

tion. Solid, oral doses of AMG 853 (25 mg) were administered to 12 sub-

jects. Safety, tolerability, and pharmacokinetic data were obtained.

Pharmacodynamic evaluation was performed using ex-vivo whole blood

assays and in vivo inhibition of niacin-induced flushing.

RESULTS: No deaths, treatment-related serious adverse events, or study

discontinuations due to adverse events were reported in the AMG 853-trea-

ted subjects. Adverse events reported in�2 subjects in any treatment group

were abdominal pain, contact dermatitis, headache, and catheter site hema-

toma. AMG 853 pharmacokinetics was approximately dose-proportional

over the 5-400 mg dose range. AMG 853 glucuronide, the major circulat-

ing metabolite, was observed in all subjects. Pharmacodynamic data dem-

onstrated that AMG 853 effectively antagonized ex vivo PGD2 responses

mediated by CRTH2 and DP receptors and attenuated niacin-induced

flushing, which is partially mediated by PGD2.

CONCLUSIONS: In this first-in-human study in healthy subjects, AMG

853 was well tolerated at all administered doses.