efficacy of inhaled compared to oral corticosteroids for acute asthma exacerbation in children

1
270 Lack of Milk Protein Allergic Reactions in Patients Using Lactose Containing Dry Powder Inhalers (DPIs) W. A. Spiegel 1 , R. Anolik 2 ; 1 Allergy and Asthma Specialists, PC, Blue Bell, PA, 2 Allergy & Asthma Specialists, PC, Blue Bell, PA. RATIONALE: Lactose is a common ingredient in dry powder inhalers (DPIs) used for asthma. As this is derived from cow’s milk, some milk protein contamination occurs in spite of purification processes designed to remove proteins. Milk protein allergy affects 2.5% of children, and a lesser percentage of adults as milk allergy is commonly outgrown. This leaves a number of asthmatics who may be inadvertently exposed to milk protein thru use of their DPIs. METHODS: As Milk protein allergy reactions have been reported in asth- matics taking DPIs 1 , we instituted a chart review to determine the scope of this exposure, and our experience with possible reactions. RESULTS: Out of a pool of 8418 asthmatics, 278 who are milk allergic; we identified 21 who take Asmanex or Advair Diskus. These individuals have been exposed to 616 inhalers (assuming good compliance) for a total of 715 months of use. We did not identify any reaction attributable to inadvertent milk protein ingestion thru the use of these DPIs. CONCLUSIONS: Although the patients identified may be quite milk sen- sitive, the amount of milk protein in the DPIs did not trigger symptomatic anaphylactic reactions. This may be because the milk protein contamina- tion was too low, and/or our patients were fortunate enough not to obtain lots with higher degrees of contamination. Our data suggests that milk protein reactions in patients taking these DPIs are rare, and that watchful vigilance for reactions, not avoidance of these medications is appropriate. 1) Sampson H A. Letter to the Editor, J. Allergy Clin Immunol 2004;113:558-560. 271 Efficacy of Inhaled Compared to Oral Corticosteroids for Acute Asthma Exacerbation in Children R. Q. Chaudhry 1 , M. E. Weinstein 2 , A. Petrova 1 ; 1 UMDNJ, New Bruns- wick, NJ, 2 UMDNJ, Newark, NJ. RATIONALE: Although corticosteroids are widely used for treatment of pediatric asthma, the efficacy of the different routes of corticosteroid deliv- ery to children presenting in the emergency department (ED) with acute asthma exacerbation is still unclear. METHODS: We performed a systematic review of the published (1986 - 2009) randomized clinical trials (RCTs) involving children (aged 6 months -18 years) presenting with acute asthma exacerbation to the ED who were assigned to at least one of the randomization arms of corticosteroid treat- ment. We identified the effectiveness of systemic (SCS) and inhaled (ICS) corticosteroids in the treatment of acute asthma exacerbation in pe- diatric patients using the hospitalization rate as the primary outcome. Pooled odd ratio (OR) and number needed to treat (NNT) with 95% Confidence Interval (95%CI) were calculated. RCTs that compared ICS plus SCSs with SCSs alone were not included. RESULTS: In the 10 identified RCTs, 388 patients were treated with ICS, 337 with SCS, and 298 with placebo. Irrespective of the route of delivery (ICS and SCS), the hospitalization rate was higher in children randomized to the placebo group (33.8%, P<0.01). The likelihood for hospitalization in those who received ICS was significantly lower as compared with SCS treatment (13.7% vs. 20.8%, OR 0.60, 95%CI 0.41, 0.88). The NNT to pre- vent one hospitalization of a child with acute asthma exacerbation is 5 (95%CI 4 to 8) for ICS and 8 (95%CI 5 to 19) for SCS. CONCLUSIONS: In the ED setting, ICS are beneficial for the treatment of acute pediatric asthma exacerbations. 272 Anti Inflammatory And Anti Asthmatic Effects Of Astilbic Acid On Ovalbumin Induced Lung Inflammation In A Mouse Asthma Model J. Yuk; Korean Research Institutue of bioscience & Biotechnology, Yang-chung ri 685-1, O-chang uep, REPUBLIC OF KOREA. RATIONALE: Bronchial asthma represents the chronic lung inflamma- tion, airway hyperresponsiveness, and airway remodeling. Astilbic acid extracted from Astilbic chinensis which is a traditional medical herb. It has been used as headaches, anti-pyretic and analgesic. However, the effect of astilbic acid on asthma has not reported yet. Based on this study, astilbic acid could be developed as an anti-asthmatic drug. METHODS: Mice were sensitized by injection of 20 mg OVA, which was emulsified in 2 mg aluminum hydroxide, in a total volume of 200 ml on days 1 and 14. The mice were exposed to a 1% ovalbumin solution aerosol- ized using an ultrasonic nebulizer for 20 min per day form days 28 to 30 after the second sensitization. Astilbic acid (30 mg/kg administered by in- tra gastric mode) was treated 1 hr before the ovalbumin challenge. After the final aerosol challenge, airway hyperresponsiveness (AHR) was assessed by means of whole-body plethysmography. RESULTS: Astilbic acid significantly reduced the T-helper-2-type cyto- kines such as IL (interleukin)-4, IL-5 and IL-13 and the inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF). Astilbic acid in- hibited OVA-induced AHR to inhaled methacholine. Histochemical anal- ysis showed that astilbic acid reduced the goblet cell hyperplasia and mucus production and attenuated eosinophil- rich leukocyte infiltration compared with OVA-challenged mice. This compound significantly in- hibited mRNA expression of IL-4, IL-5, IL-6 following asthma induction in lung tissue. Also it effectively suppressed immunoglobulin E (IgE) level in both BALF and serum. CONCLUSIONS: This results indicate that astilbic acid would have a po- tential to therapeutic compound treating asthma. 273 Effect of Two Weeks of Inhaled Fluticasone on the Hormonal and Inflammatory Response to Brief Exercise in Healthy Young Men C. D. Schwindt, F. P. Zaldivar, A. Eliakim, H. Shin, S. Leu, D. Cooper; University of CA - Irvine, Orange, CA. RATIONALE: Inhaled corticosteroids (ICS) improve lung disorders, such as asthma, by altering the immune system. Initial data suggest ICS effects remain localized to the lung; however, recent studies demonstrate altera- tion to the peripheral immune system in patients with asthma. We evaluated the effect of ICS on peripheral immune mediators and HPA axis, and their response to exercise, in healthy adult males. METHODS: Eleven healthy males (age 18-30 years old) were placed on 2 weeks of Fluticasone proprionate (440 mcg) twice daily. A 30 minute bout of exercise was performed on a cycle ergometer at about 70% peak work rate before and after the start of ICS. Blood was sampled pre- and end-ex- ercise. Cytokines and HPA axis mediators were measured by ELISA and fluticasone by liquid chromatography/tandem mass spectrometry. RESULTS: After ICS-treatment, cortisol and ACTH were decreased and a blunted exercise response observed for cortisol, ACTH, and GH. Peripheral leukocytes and neutrophils were significantly increased in re- sponse to exercise in both the untreated and ICS-treated conditions, and at baseline after ICS-treatment. IL-6 was elevated with ICS-treatment but the exercise response blunted. Circulating mean fluticasone levels were 0.15 ng/mL and increased to 0.22 ng/mL in response to exercise. CONCLUSIONS: Exercise revealed deficits of the HPA axis and GH pro- duction after ICS-treatment not identified by static markers. Neutrophils were shown to be sensitive surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess subtle, physiological impacts of exogenous corticosteroids. J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2 Abstracts AB69 SUNDAY

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J ALLERGY CLIN IMMUNOL

VOLUME 125, NUMBER 2

Abstracts AB69

SU

ND

AY

270 Lack of Milk Protein Allergic Reactions in Patients UsingLactose Containing Dry Powder Inhalers (DPIs)

W. A. Spiegel1, R. Anolik2; 1Allergy and Asthma Specialists, PC, Blue

Bell, PA, 2Allergy & Asthma Specialists, PC, Blue Bell, PA.

RATIONALE: Lactose is a common ingredient in dry powder inhalers

(DPIs) used for asthma. As this is derived from cow’s milk, some milk

protein contamination occurs in spite of purification processes designed

to remove proteins. Milk protein allergy affects 2.5% of children, and a

lesser percentage of adults as milk allergy is commonly outgrown. This

leaves a number of asthmatics who may be inadvertently exposed to

milk protein thru use of their DPIs.

METHODS: As Milk protein allergy reactions have been reported in asth-

matics taking DPIs1, we instituted a chart review to determine the scope of

this exposure, and our experience with possible reactions.

RESULTS: Out of a pool of 8418 asthmatics, 278 who are milk allergic;

we identified 21 who take Asmanex or Advair Diskus. These individuals

have been exposed to 616 inhalers (assuming good compliance) for a total

of 715 months of use. We did not identify any reaction attributable to

inadvertent milk protein ingestion thru the use of these DPIs.

CONCLUSIONS: Although the patients identified may be quite milk sen-

sitive, the amount of milk protein in the DPIs did not trigger symptomatic

anaphylactic reactions. This may be because the milk protein contamina-

tion was too low, and/or our patients were fortunate enough not to obtain

lots with higher degrees of contamination. Our data suggests that milk

protein reactions in patients taking these DPIs are rare, and that watchful

vigilance for reactions, not avoidance of these medications is appropriate.

1) Sampson H A. Letter to the Editor, J. Allergy Clin Immunol

2004;113:558-560.

271 Efficacy of Inhaled Compared to Oral Corticosteroids forAcute Asthma Exacerbation in Children

R. Q. Chaudhry1, M. E. Weinstein2, A. Petrova1; 1UMDNJ, New Bruns-

wick, NJ, 2UMDNJ, Newark, NJ.

RATIONALE: Although corticosteroids are widely used for treatment of

pediatric asthma, the efficacy of the different routes of corticosteroid deliv-

ery to children presenting in the emergency department (ED) with acute

asthma exacerbation is still unclear.

METHODS: We performed a systematic review of the published (1986 -

2009) randomized clinical trials (RCTs) involving children (aged 6 months

-18 years) presenting with acute asthma exacerbation to the ED who were

assigned to at least one of the randomization arms of corticosteroid treat-

ment. We identified the effectiveness of systemic (SCS) and inhaled

(ICS) corticosteroids in the treatment of acute asthma exacerbation in pe-

diatric patients using the hospitalization rate as the primary outcome.

Pooled odd ratio (OR) and number needed to treat (NNT) with 95%

Confidence Interval (95%CI) were calculated. RCTs that compared ICS

plus SCSs with SCSs alone were not included.

RESULTS: In the 10 identified RCTs, 388 patients were treated with ICS,

337 with SCS, and 298 with placebo. Irrespective of the route of delivery

(ICS and SCS), the hospitalization rate was higher in children randomized

to the placebo group (33.8%, P<0.01). The likelihood for hospitalization in

those who received ICS was significantly lower as compared with SCS

treatment (13.7% vs. 20.8%, OR 0.60, 95%CI 0.41, 0.88). The NNT to pre-

vent one hospitalization of a child with acute asthma exacerbation is 5

(95%CI 4 to 8) for ICS and 8 (95%CI 5 to 19) for SCS.

CONCLUSIONS: In the ED setting, ICS are beneficial for the treatment

of acute pediatric asthma exacerbations.

272 Anti Inflammatory And Anti Asthmatic Effects Of Astilbic AcidOn Ovalbumin Induced Lung Inflammation In A Mouse AsthmaModel

J. Yuk; Korean Research Institutue of bioscience & Biotechnology,

Yang-chung ri 685-1, O-chang uep, REPUBLIC OF KOREA.

RATIONALE: Bronchial asthma represents the chronic lung inflamma-

tion, airway hyperresponsiveness, and airway remodeling. Astilbic acid

extracted from Astilbic chinensis which is a traditional medical herb. It

has been used as headaches, anti-pyretic and analgesic. However, the effect

of astilbic acid on asthma has not reported yet. Based on this study, astilbic

acid could be developed as an anti-asthmatic drug.

METHODS: Mice were sensitized by injection of 20 mg OVA, which was

emulsified in 2 mg aluminum hydroxide, in a total volume of 200 ml on

days 1 and 14. The mice were exposed to a 1% ovalbumin solution aerosol-

ized using an ultrasonic nebulizer for 20 min per day form days 28 to 30

after the second sensitization. Astilbic acid (30 mg/kg administered by in-

tra gastric mode) was treated 1 hr before the ovalbumin challenge. After the

final aerosol challenge, airway hyperresponsiveness (AHR) was assessed

by means of whole-body plethysmography.

RESULTS: Astilbic acid significantly reduced the T-helper-2-type cyto-

kines such as IL (interleukin)-4, IL-5 and IL-13 and the inflammatory cells

and eosinophils in bronchoalveolar lavage fluid (BALF). Astilbic acid in-

hibited OVA-induced AHR to inhaled methacholine. Histochemical anal-

ysis showed that astilbic acid reduced the goblet cell hyperplasia and

mucus production and attenuated eosinophil- rich leukocyte infiltration

compared with OVA-challenged mice. This compound significantly in-

hibited mRNA expression of IL-4, IL-5, IL-6 following asthma induction

in lung tissue. Also it effectively suppressed immunoglobulin E (IgE) level

in both BALF and serum.

CONCLUSIONS: This results indicate that astilbic acid would have a po-

tential to therapeutic compound treating asthma.

273 Effect of Two Weeks of Inhaled Fluticasone on the Hormonaland Inflammatory Response to Brief Exercise in HealthyYoung Men

C. D. Schwindt, F. P. Zaldivar, A. Eliakim, H. Shin, S. Leu, D. Cooper;

University of CA - Irvine, Orange, CA.

RATIONALE: Inhaled corticosteroids (ICS) improve lung disorders, such

as asthma, by altering the immune system. Initial data suggest ICS effects

remain localized to the lung; however, recent studies demonstrate altera-

tion to the peripheral immune system in patients with asthma. We evaluated

the effect of ICS on peripheral immune mediators and HPA axis, and their

response to exercise, in healthy adult males.

METHODS: Eleven healthy males (age 18-30 years old) were placed on 2

weeks of Fluticasone proprionate (440 mcg) twice daily. A 30 minute bout

of exercise was performed on a cycle ergometer at about 70% peak work

rate before and after the start of ICS. Blood was sampled pre- and end-ex-

ercise. Cytokines and HPA axis mediators were measured by ELISA and

fluticasone by liquid chromatography/tandem mass spectrometry.

RESULTS: After ICS-treatment, cortisol and ACTH were decreased and a

blunted exercise response observed for cortisol, ACTH, and GH.

Peripheral leukocytes and neutrophils were significantly increased in re-

sponse to exercise in both the untreated and ICS-treated conditions, and

at baseline after ICS-treatment. IL-6 was elevated with ICS-treatment

but the exercise response blunted. Circulating mean fluticasone levels

were 0.15 ng/mL and increased to 0.22 ng/mL in response to exercise.

CONCLUSIONS: Exercise revealed deficits of the HPA axis and GH pro-

duction after ICS-treatment not identified by static markers. Neutrophils

were shown to be sensitive surrogate markers of the systemic effect of

ICS. Exercise significantly increased circulating levels of fluticasone.

Exercise challenge tests can be used to assess subtle, physiological impacts

of exogenous corticosteroids.