Past President: American College of Allergy

Asthma and Clinical immunology

Guest Professor: Peking Union Medical College
Director: World Allergy Association
Editorial Board:
Annals of Allergy,
Proceedings of Allergy,
John Hopkins Asthma Monitor

New insight
in Dr. Bob Lanier M.D.
Professor:

allergy
Pediatrics / Immunology
University of North Texas
Health Science Center

management Fort Worth, Texas

 Epidemiology

Not everyone has allergy, but it is common, and it is increasing.

In one study in England, children born in 1958 by age 16

had a prevalence of AR=12%. The same study was
repeated for children born in 1970. What would you
guess the prevalence in allergy was by age 16?

1. > 20%
2. > 30%
3. > 40%
 Allergic Rhinitis: Increasing
Prevalence in Children
In England, Wales, and Scotland

• 12% born in 1958 had allergy by 16

• 23% born in 1970 had allergy by 16

Sly RM, et al. Ann Allergy Asthma Immunol. 1999;82:233-248.

Prevalence of clinical asthma:
GINA 2004 300 million people

Red >10.1%
Orange 7.6 – 10.0%
Yellow 5.1 – 7.5%
Green 2.5 – 5.0%
Blue 0 – 2.5%
White No standardized data available
Asthma mortality by country:
Centers for Disease Control 2000

> 1.01
0.51 – 1.0
0 – 0.5
No standardized
data available
ALCON-PTN-CER-00002 — Lanier — v2 6
 You can reduce the number of infections in
allergic children by treating them with a non-
sedating antihistamine

• TRUE

• FALSE
 Prophylactic management of children at risk
for recurrent upper respiratory infections: the
Preventia I Study.
Grimfeld A, Holgate ST, Canonica GW, Bonini S, Borres MP, Adam D, Canseco Gonzalez C, Lobaton P, Patel
P, Szczeklik A, Danzig MR, Roman I, Bismut H, Czarlewski W.
BACKGROUND: Given the morbidity and mortality of asthma and the recent dramatic increase in its prevalence,
pharmacologic prophylaxis of this disease in children at risk would represent a major medical advance.
OBJECTIVES: The Preventia I Study was designed to evaluate the efficacy and long-term safety of loratadine in
reducing the number of respiratory infections in children at 24 months. A secondary objective was to investigate the
benefit of loratadine treatment in preventing the onset of respiratory exacerbations. METHODS: Preventia I was a
randomized placebo-controlled study involving 22 countries worldwide. The children were 12-30 months of age at
enrollment and had experienced at least five episodes of ENT infections, and no more than two episodes of
wheezing during the previous 12 months. Phase I was a 12-month double-blind period during which the children
were treated with loratadine 5 mg/day (2.5 mg/day for children</=24 months of age) or placebo. Phase II was a
double-blind follow-up period without study medication. RESULTS: Of the 412 children enrolled, 342 and 310
completed Phase I and Phase II, respectively. The results showed a significant decrease in the number of infections
in the whole population of children. However, no difference was observed between the loratadine and placebo
loratadine was shown to reduce the number of respiratory
group. When considering secondary end-points, loratadine was shown to reduce the number of respiratory
exacerbations during the treatment phase
exacerbations during the treatment phase. None of the 204 children who received loratadine discontinued the
study because of drug-related events. Loratadine treatment was not more sedative . than placebo and was not
associated with cardiovascular events. CONCLUSION: The strong decrease in the rate of infections in the children
at risk of recurrent infections, while not being influenced by loratadine treatment, should encourage future reflection
in terms of prophylactic management. This study also confirms the long-term safety of loratadine and its metabolites
in young children.
 Allergy can affect sleep and learning ?
• TRUE

• FALSE
 Symptoms

• How commonly do allergic

children have problems with sleep
compared with non allergic
children?

• 1. 10 % more than other kids

• 2. 36% more than other kids
• 3. 50% more than other kids
 Allergic Rhinitis and Obstructive
Sleep Disorders

• Study of 39 children with habitual snoring (aged 1 to 7

years)2
– Frequency of obstructive sleep apnea is ~50% greater in
atopic vs nonatopic subjects

• Secondary daytime fatigue is a consequence of

obstructive sleep disorders

Lack G. J Allergy Clin Immunol. 2001;108(suppl):S9-S15. 2McColley SA, et al. Chest. 1997;111:170-173.
1
Emotional and educational effects of ALLERGY

• Mock depression

• Slowed thinking

• Fatigue moody

• Sleep

• Test scores and learning

• 80+ % of asthma is allergic

Effects of seasonal allergic rhinitis on fatigue levels and mood.

Marshall PS, Psychosom Med. 2002 Jul-Aug;64(4):
Allergic Rhinitis Treatment With Antihistamines:
Impaired Learning Performance

Children Aged 10–12 Years

55
Learning Score
Composite

50
*
*
45

40
Diphen- Placebo Loratadine Non-allergic
hydramine (n=21)

Allergic Rhinitis (n=52)

*P=.002 vs. healthy controls.

Adapted from Vuurman EF, et al. Ann Allergy. 1993;71:121-126.
 Allergic Rhinitis: Memory Impairment
Buschke Consistent Salthouse Listening Span
Long-Term Retrieval Score Test Item Score

60 (n=16)
56

50 (n=32) Allergy Patients

44 (n=32)
(n=16) Controls
41
40 38
Impairment (%)

(n=25)
30 28
(n=25)
20
20

10 (n=20)
5
(n=20)
0
0
Fall 1996 Fall 1998 Fall 1996 Fall 1998
Age Range 23 to 50 Years Age Range 24 to 50 Years
Adapted from Marshall PS, et al. Ann Allergy Asthma Immunol. 2000;84:403-410.
Management Options
• Allergy avoidance therapy

• Antihistamines

• Inhaled corticosteroids

• Anti-leukotrienes

• Cromolyn

• Allergen immunotherapy
 Avoidance is always the best
treatment for allergy

• TRUE

• FALSE
Allergen avoidance in the secondary and
tertiary prevention of allergic diseases: does
it work? Marinho S, Simpson A, Custovic A
Although allergen avoidance is widely
recommended as part of a secondary and tertiary
prevention strategy for allergic diseases, a clear-
cut demonstration of its effectiveness is still
lacking... current evidence suggests that
interventions in children may be associated with
some beneficial effect on asthma control, but no
conclusive evidence exists regarding rhinitis or
eczema. Prim Care Respir J. 2006 Jun;15(3):152-8. Epub 2006 Mar 29.
 IS EXPOSURE TO CATS HARMFUL OR
HELPFUL TO INFANTS?

• HARMFUL

• HELPFUL
 + =

If you produce IgG4, you do not develop asthma (?)

Th1 Th2
Th2

Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based
cross-sectional study . Platts-Mills T Vaughan J, Squillace S, Woodfolk J, Sporik R .
Lancet. 2001 Mar 10;357(9258
 Immediate and late phase allergy
Cellular infiltration
antihistamines Eosinophil
Symptoms
of LPR
Basophil More
Chemotactic, mediator Congestion
release
inflammatory
Rhinorrhea
mediators
Monocyte
Mast cell Sneezing

Lymphocyte
Preformed mediators steroids
Histamine
Inflammation
 You can prevent the progression of allergy and
asthma using regular antihistamines?

• TRUE

• FALSE

ALCON-PTN-CER-00002 — Lanier — v2 21
 Atopic March

ALCON-PTN-CER-00002 — Lanier — v2 22
 THE ETAC TRIAL
LONG-TERM TREATMENT WITH CETIRIZINE OF INFANTS WITH
ATOPIC DERMATITIS: A MULTI-COUNTRY, DOUBLE-BLIND,
RANDOMIZED, PLACEBO-CONTROLLED TRIAL OVER 18 MONTHS

• Diepgen TL Tamara T. Perry, MD and Robert A. Wood, MD

Pediatr Allergy Immunol. 2002;13:278–286
• A total of 795 infants, 12 to 24 months old, with active AD for
at least 1 month and 1 parent or sibling with a history of AD,
allergic rhinitis, or asthma were enrolled from 12 European
countries and Canada.

ALCON-PTN-CER-00002 — Lanier — v2 23
 Antihistamines help asthma

• True

• False
Old thinking
The role of antihistamines in asthma management.

– “….loratadine 5 mg combined with 60 mg of pseudo-ephedrine twice

a day significantly improved both asthma symptoms and peak
expiratory flow. Similarly, the combination of loratadine 20 mg and
the leukotriene-receptor antagonist montelukast improved asthma
symptoms, peak expiratory flow, and beta-agonist use over
montelukast alone. Therefore, there might be a role for second- and
third-generation antihistamines in treating mild and moderate
asthma, which might require administering doses greater than those
commonly used to treat allergic rhinitis. “ Nelson HS
– J Allergy Clin Immunol. 2003 Oct;112(4 Suppl):S96-100 .

New thinking
 Effects of antihistamines

H1 antagonist effect – desensitize the receptor

Inhibit histamine-stimulated IL-8
Down Regulate calcium and release and influx
Reduces levels of IL4 and CD23
Reduces leukotrienes and PAF
Decreases ICAM-1 and eosinophilic cells
 Summary

• Allergy is a chronic disease

• There are consequences to poorly treated allergy

– Physical
– Educational
– Memory

• There are safe effective management available

which may prevent consequences
– Non-sedating antihistamines
– Nasal steroids