1. WHAT YOU SHOULD HAVE READ BUT….2012
rhinitis
Attilio Boner
University of
Verona, Italy
2. Validation of a self-questionnaire for assessing the
control of allergic rhinitis. Demoly CEA 2011;41:860
Improvement of impact of allergic rhinitis
on sleep and work life (on a numeric scale
from 0 for ‘no signs’ to 10 for ‘very intense’)
A self-assessment at inclusion and day 15 after treatment.
global score for
allergic rhinitis
control
(five items scored
from 1 to 5
assessing the
rhinitis over the
2 previous weeks).
902 patients.
3. Validation of a self-questionnaire for assessing the
control of allergic rhinitis. Demoly CEA 2011;41:860
Improvement of impact of allergic
rhinitis on social and physical activities
(on a numeric scale from 0 for ‘no signs’ to
A self-assessment 10 for ‘very intense’) at inclusion and
day 15 after treatment.
global score for
allergic rhinitis
control (five items
scored from
1 to 5 assessing
the rhinitis over
the 2 previous
weeks).
902 patients.
4. Validation of a self-questionnaire for assessing the
control of allergic rhinitis. Demoly CEA 2011;41:860
6. Can early household exposure influence the development
of rhinitis symptoms in infancy? Findings from the PARIS
birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303
Prevalence at age 18 months of
6.0 –
Infants at age 18 months.
5.4%
5.0 –
Presence of rhinitis 4.0 –
symptoms (runny nose,
blocked nose, sneezing 3.0 –
3.8%
in the absence of a cold) 2.0 –
combined with biological
1.0 –
atopy.
0 0
Allergic rhinitis Nonallergic rhinitis
7. Can early household exposure influence the development
of rhinitis symptoms in infancy? Findings from the PARIS
birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303
OR for allergic rhinitis
4.0 –
Infants at age 18 months.
3.0 –
Presence of rhinitis 3.15
symptoms (runny nose, 2.0 –
blocked nose, sneezing
in the absence of a cold) 1.0 –
combined with biological
atopy. 0 0
Presence of cockroaches
in the home
8. Can early household exposure influence the development
of rhinitis symptoms in infancy? Findings from the PARIS
birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303
OR for nonallergic rhinitis
2.0 –
Infants at age 18 months.
1.5 – 1.87
Presence of rhinitis
symptoms (runny 1.0 –
nose, blocked
nose, sneezing in the 0.5 –
absence of a cold)
combined with biological 0 0
Presence of particle-board
atopy. furniture less than 12 months
old in the child's bedroom
9. Natural course and comorbidities of allergic and
nonallergic rhinitis in children
Westman JACI 2012;129:403
Proportion of children
% pts with allergic rhinitis*
20 –
Birth cohort of
2024 children.
15 – 14%
IgEs against
8 common 10 –
inhaled allergens
was available. 05 –
Age 4 and 8 yrs. 5%
0
4 years 8 years
*allergic rhinitis = rhinitis with sensitization
to allergens.
10. Natural course and comorbidities of allergic and
nonallergic rhinitis in children
Westman JACI 2012;129:403
Proportion of children
% pts with allergic rhinitis*
Of the children
with 20 –
Birth cohort of
allergic rhinitis
2024 children.
when they were 15 – 14%
4 against
IgEs years old,
8 common
12% underwent 10 –
inhaled allergens
was remission
available. 05 –
by the time
4 and 8 yrs.
Agethey were 5%
0
8 years old. 4 years 8 years
*allergic rhinitis = rhinitis with sensitization
to allergens.
11. Natural course and comorbidities of allergic and
nonallergic rhinitis in children
Westman JACI 2012;129:403
Proportion of children
% pts with nonallergic rhinitis*
20 –
Birth cohort of
2024 children.
15 –
IgEs against
8 common 10 –
inhaled allergens
was available. 05 – 8%
6%
Age 4 and 8 yrs.
0
4 years 8 years
*nonallergic rhinitis = rhinitis without
sensitization to allergens.
12. Natural course and comorbidities of allergic and
nonallergic rhinitis in children
Westman JACI 2012;129:403
Proportion of children
% pts with nonallergic rhinitis*
Of the children
20 –
with
Birth cohort of
nonallergic rhinitis
2024 children.
15 –
IgEs against were
when they
8 common old,
4 years 10 –
73% underwent
inhaled allergens
was remission
available. 05 – 8%
6%
Age 4 and 8 period
during the yrs.
of development. 0
4 years 8 years
*nonallergic rhinitis = rhinitis without
sensitization to allergens.
13. Natural course and comorbidities of allergic and
nonallergic rhinitis in children
Westman JACI 2012;129:403
% children with
ORAL ALLERGY SYNDROME
Birth cohort of 30 –
2024 children.
IgEs against 20 – 25%
8 common
inhaled allergens
10 –
was available.
Age 4 and 8 yrs.
0
If allergic rhinitis at the
age of 8 years
14. Natural course and comorbidities of allergic and
nonallergic rhinitis in children
Westman JACI 2012;129:403
Conclusions
Fewer preschool-age children with allergic rhinitis
undergo remission than do those with nonallergic rhinitis.
Sensitization to inhaled allergens at an early age (4 years)
precedes the development of allergic rhinitis, whereas
symptoms of rhinitis do not.
Oral allergy syndrome is common among 8-year-olds with
allergic rhinitis.
15. Trends in the prevalence of asthma and allergic
rhinitis in Italy between 1991 and 2010
R. de Marco, Eur Respir J 2012;39:883
Overall mean prevalence
The same screening
questionnaire by mail
or phone.
Random samples of the
general population
(age 20–44 yrs).
(1991–1993; n=6,031)
(1998–2000; n=18,873)
(2007–2010; n=10,494)
16. Trends in the prevalence of asthma and allergic
rhinitis in Italy between 1991 and 2010
R. de Marco, Eur Respir J 2012;39:883
Overall mean prevalence
The same screening
The asthma epidemic
questionnaire by mail
or is not over in Italy.
phone.
During the past 20 yrs,
asthma prevalence has
Random samples of the
increased by 38%,
general population
(age 20–44 with a similar
in parallel yrs).
increase in asthma-like
symptoms and
(1991–1993; n=6,031)
allergic rhinitis.
(1998–2000; n=18,873)
(2007–2010; n=10,494)
17. The protective effect of farm milk consumption on
childhood asthma and atopy: the GABRIELA study
Loss JACI 2011;128:766
OR for asthma
1.0 –
Farm milk consumption.
8334 school-aged
children.
0.59
0.5 –
800 cow’s milk samples
collected at the
participants’
homes, viable bacterial
counts, whey protein 0
levels and total fat For raw milk
content. consumption
18. The protective effect of farm milk consumption on
childhood asthma and atopy: the GABRIELA study
Loss JACI 2011;128:766
OR for asthma
1.0 –
Farm milk consumption.
8334 school-aged
children. farm milk
Boiled
800 did not show a
0.59
0.5 –
cow’s milk samples
protective
collected at the
effect.
participants’ homes,
viable bacterial counts,
whey protein levels and 0
total fat content. For raw milk
consumption
19. The protective effect of farm milk consumption on
childhood asthma and atopy: the GABRIELA study
Loss JACI 2011;128:766
OR for hay fever
1.0 –
Farm milk consumption.
8334 school-aged
children.
0.5 –
800 cow’s milk samples
collected at the
participants’ homes,
0.51
viable bacterial counts,
whey protein levels and 0
total fat content. For raw milk
consumption
20. The protective effect of farm milk consumption on
childhood asthma and atopy: the GABRIELA study
Loss JACI 2011;128:766
OR for hay fever
1.0 –
Farm milk consumption.
8334 school-aged
children. farm milk
Boiled
800 did not show a
cow’s milk samples 0.5 –
protective
collected at the
effect.
participants’
0.51
homes, viable bacterial
counts, whey protein 0
levels and total fat For raw milk
content. consumption
21. The protective effect of farm milk consumption on
childhood asthma and atopy: the GABRIELA study
Loss JACI 2011;128:766
Total viable bacterial counts and total fat content of milk
were not significantly related to asthma or atopy.
Increased levels of the whey proteins BSA (aOR for highest
vs lowest levels and asthma, 0.53; 95% CI 0.30-
0.97), α-lactalbumin (aOR for interquartile range and
asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR
for interquartile range and asthma, 0.62; 95% CI, 0.39-
0.97), however, were inversely associated with
asthma but not with atopy.
22. The protective effect of farm milk consumption on
childhood asthma and atopy: the GABRIELA study
Loss JACI 2011;128:766
Total viable bacterial counts and total fat content of milk
were not significantly related to asthma raw milk
The protective effect of or atopy.
consumption on asthma might be
associated with BSA
Increased levels of the whey proteins the (aOR for highest
vs lowest levels and asthma, 0.53; 95% CI 0.30-
0.97), whey protein(aOR for interquartile range and
α-lactalbumin fraction of milk.
asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR
for interquartile range and asthma, 0.62; 95% CI, 0.39-
0.97), however, were inversely associated with
asthma but not with atopy.
23. House dust mite sensitization in toddlers predicts current
wheeze at age 12 years Lodge JACI 2011;128:782
Prevalence of sensitization
(and 95% CI) at age 6 months
(n=560), 1 year (n=551),
Birth cohort of 620 and 2 years (n=459).
children oversampled for
familial allergy.
SPTs to 6 allergens at
ages 6, 12, and 24 mo.
Wheeze and eczema
recorded during
the first 2 yrs.
Current wheeze recorded
at age 12 yrs.
24. House dust mite sensitization in toddlers predicts current
wheeze at age 12 years Lodge JACI 2011;128:782
7 – OR for wheeze at 12 yrs
6 –
6.37
Birth cohort of 620 5 –
children oversampled for 4 –
familial allergy.
SPTs to 6 allergens at 3 –
ages 6, 12, and 24 mo. 3.31
2 –
Wheeze and eczema
recorded during 1 –
the first 2 yrs.
0
Current wheeze recorded
Age 1 yr Age 2 yrs
at age 12 yrs.
SPT (+) for mite dust
25. House dust mite sensitization in toddlers predicts current
wheeze at age 12 years Lodge JACI 2011;128:782
80 –
% children wheezing at age 12 yrs
75%
70 –
60 –
Birth cohort of 620
children oversampled for 50 –
familial allergy. 40 –
SPTs to 6 allergens at
ages 6, 12, and 24 mo.
Wheeze and eczema
30 –
20 –
36%
recorded during 10 –
the first 2 yrs.
0
Current wheeze recorded
Sensitized Not Sensitized
at age 12 yrs.
Wheezing at age 1
26. House dust mite sensitization in toddlers predicts current
wheeze at age 12 years Lodge JACI 2011;128:782
80 –
% children wheezing at age 12 yrs
70 –
Birth cohort of 620
children oversampled for
60 –
50 –
67%
familial allergy. 40 –
SPTs to 6 allergens at
35%
30 –
ages 6, 12, and 24 mo.
Wheeze and eczema 20 –
recorded during 10 –
the first 2 yrs.
0
Current wheeze recorded
SPT (+) SPT (-)
at age 12 yrs.
Eczema at age 1
and mite
27. House dust mite sensitization in toddlers predicts current
wheeze at age 12 years Lodge JACI 2011;128:782
80 –
% children wheezing at age 12 yrs
70 –
HDM sensitization
Birthat age 1 or 2 yrs
cohort of 620
in wheezing and
children oversampled for
60 –
50 –
67%
familial allergy. children
eczematous 40 –
at increased familial
SPTs to 6 allergens at
35%
30 –
allergy risk
ages 6, 12, and 24 mo.
predicts asthma
Wheeze and eczema 20 –
recorded duringinform
and may 10 –
themanagement of these
first 2 yrs.
0
Current wheeze group.
high-risk recorded
SPT (+) SPT (-)
at age 12 yrs.
Eczema at age 1
and mite
28. Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
an international population-based cohort study
Matheson JACI 2011;128:816
HR for women developing
rhinitis compared to men
1992-1994 community-
based samples
1.0 –
1.36
of 20-44 yr-old people.
0.63
0.5 –
48 centers in 22
countries.
8486 participants. 0
Childhood Adulthood
During
29. Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
an international population-based cohort study
Matheson JACI 2011;128:816
Cumulative probability of Cumulative probability of
rhinitis by gender in rhinitis by gender in
subjects who are atopic. subjects who are non atopic.
30. Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
an international population-based cohort study
Matheson JACI 2011;128:816
HR for developing rhinitis
1.0 –
0.84
1992-1994 community-
based samples
of 20-44 yr-old people. 0.5 –
48 centers in 22
countries.
0
8486 participants. Early contact with children
in the family or day care
before age 5 yrs.
31. Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
an international population-based cohort study
Matheson JACI 2011;128:816
HR for developing rhinitis
1.0 –
0.5
1992-1994 community-
based samples
of 20-44 yr-old people. 0.5 –
48 centers in 22
countries.
0
8486 participants. Early childhood pets or
growing up on a farm.
32. Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
an international population-based cohort study
Matheson JACI 2011;128:816
HR for developing rhinitis
Protective effects 1.0 –
of early contact with
0.5
1992-1994 and animals
children community-
based samples
were suggested
offor incident rhinitis,
20-44 yr-old people. 0.5 –
48 with risk patterns
centers in 22
countries. age window
varying by
and atopic status
8486 participants. .
0
Early childhood pets or
growing up on a farm.
34. The influence of gender and atopy on the natural
history of rhinitis in the first 18 years of life
Kurukulaaratchy CEA 2011;41:851
Changes in atopic and non-atopic rhinitis prevalence
for boys and girls over the first 18 years of life
Natural history
of rhinitis up to
18 years of age.
Isle of Wight birth
cohort recruited in
1989 (n = 1456).
Questionnaire and
skin prick tests.
35. The influence of gender and atopy on the natural
history of rhinitis in the first 18 years of life
Kurukulaaratchy CEA 2011;41:851
Changes in atopic and non-atopic rhinitis prevalence
for boys and girls over the first 18 years of life
Natural history
Atopic rhinitis
of rhinitis up to
becomes
18 years of age.
increasingly common
as children grow
Isle of Wight birth
into
cohort recruited in
adolescents, with
1989 (n = 1456).
stronger
Questionnaireto male
associations and
gender.
skin prick tests.
36. The influence of gender and atopy on the natural
history of rhinitis in the first 18 years of life
Kurukulaaratchy CEA 2011;41:851
Changes in atopic and non-atopic rhinitis prevalence
for boys and girls over the first 18 years of life
Natural history
ofNon-atopic to
rhinitis up rhinitis
shows a female
18 years of age.
predominance at 18
Isle of Wight birth
years as girls „grow
cohort it more during
into‟ recruited in
(n = 1456).
1989 adolescence.
Questionnaire and
skin prick tests.
37. Gestational age at birth and risk of allergic rhinitis
in young adulthood. Crump JACI 2011;127:1173
For subjects born extremely
preterm (23-28 weeks) OR for
630,090 infants born in
Sweden including 27,953 1.0 –
born preterm (<37 wks).
Prescription of nasal 0.5 – 0.70
corticosteroids and oral 0.45
antihistamines 0.0
Nasal Both nasal
age, 25.5-37.0 yrs. corticosteroid corticosteroid
prescription and oral
antihistamine
prescription
38. Gestational age at birth and risk of allergic rhinitis
in young adulthood. Crump JACI 2011;127:1173
These findings suggest
that low gestational age For subjects born extremely
at birth independent preterm (23-28 weeks) OR for
630,090 infants born in
of fetal growth is
Sweden including 27,953 1.0 –
associated with a
born preterm (<37 wks).
decreased risk of
Prescription of nasal young 0.5 –
allergic rhinitis in 0.70
corticosteroids and oral
adulthood, possibly 0.45
antihistaminesa protective 0.0
because of
Nasal Both nasal
effect of earlier
age, 25.5-37.0 yrs. corticosteroid corticosteroid
exposure to pathogens. prescription and oral
antihistamine
prescription
39. Staphylococcal enterotoxin B compromises
the immune tolerant status in the airway mucosa.
Liu T, Clin Exp Allergy 2012;42:375
1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced
by the bacterium Staphylococcus aureus. SEB may contaminate
ingested food and induce gastrointestinal dysfunction.
SEB interferes with the function of the immune system
in the airway mucosa, such as to be involved in the pathogenesis
of airway allergy.
2) Integrin alphavbeta6 (avb6) is produced by epithelial cells
in response to external stimuli, such as wound and inflammation.
Our recent study data also show that intestinal epithelial cells
express detectable avb6 that has protelytic activity and can convert
the precursor of transforming growth factor (TGF)β into the active
form of TGFβ. TGFβ plays a critical role in the Treg development.
Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase
(ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.
40. Staphylococcal enterotoxin B compromises
the immune tolerant status in the airway mucosa.
Liu T, Clin Exp Allergy 2012;42:375
1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced
by the bacterium Staphylococcus aureus. SEB may contaminate
ingested food and induce gastrointestinal dysfunction. in avb6
The increases in SEB and decreases
SEB interferes with the function of the immune system
in the airway mucosa, such as to be involvedassociated
in nasal epithelium are in the pathogenesis
of airway allergy. compromises of immune tolerance
with the
in the nasal mucosa.
2) Integrin alphavbeta6 (avb6) is produced by epithelial cells
in response SEB has stimuli,ability wound and inflammation.
to external the such as to suppress
Our recent study data also show that intestinal epithelial cells
express detectable avb6 that has protelyticavb6 and can convert
the expression of activity
in nasal epithelial cells.
the precursor of transforming growth factor (TGF)β into the active
form of TGFβ. TGFβ plays a critical role in the Treg development.
Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase
(ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.
41. Staphylococcal enterotoxin B compromises
the immune tolerant status in the airway mucosa.
Liu T, Clin Exp Allergy 2012;42:375
Avb6 expression is suppressed in the
allergic rhinitis (AR) nasal epithelium
• The immune tolerant components,
tolerogenic dendritic cells (TolDC) P<0.01
& regulatory T cells (Treg), were
assessed in the surgically removed
nasal mucosa from patients
with allergic rhinitis (AR)
Staphylococcal enterotoxin B (SEB)
or non-AR chronic rhinitis. levels are increased in the allergic
rhinitis nasal epithelium.
• Contents of Staphylococcal
enterotoxin B & integrin alphavbeta6 P<0.01
(avb6) in the nasal epithelium
assessed using enzyme-linked
immunoassay.
42. Staphylococcal enterotoxin B compromises
the immune tolerant status in the airway mucosa.
Liu T, Clin Exp Allergy 2012;42:375
Avb6 expression is suppressed in the
allergic rhinitis (AR) nasal epithelium
• The immune tolerant
components, components
The tolerogenic dendritic
P<0.01
cells (TolDC) & regulatory T cells
of immune tolerance
(Treg), were assessed in the
surgically machinery, mucosa
removed nasal
from patients & Tregs
TolDCs with
Staphylococcal enterotoxin B (SEB)
allergic rhinitis (AR)
were suppressed levels are increased in the allergic
or non-AR chronic rhinitis. rhinitis nasal epithelium.
in the AR
• Contents of Staphylococcal
nasal mucosa. P<0.01
enterotoxin B & integrin alphavbeta6
(avb6) in the nasal epithelium
assessed using enzyme-linked
immunoassay.
43. Adaptative immune responses in Staphylococcus aureus
biofilm-associated chronic rhinosinusitis
Foreman, Allergy 2011;66:1449
Background: The etiopathogenesis of chronic rhinosinusitis (CRS)
is currently an area of intense debate. Recently, biofilms have
been proposed as a potential environmental trigger in this
disease. In particular, Staphylococcus aureus biofilms appear to
be a predictor of severe disease recalcitrant to current
treatment paradigms.
However, direct causal links between biofilms and host immune
activation are currently lacking. This study aimed to document
both the adaptive immune responses that characterize S. aureus
biofilm–associated CRS and the relative contributions of
staphylococcal superantigens and S. aureus biofilms in the
inflammatory make-up of this disease.
44. Adaptative immune responses in Staphylococcus aureus
biofilm-associated chronic rhinosinusitis
Foreman, Allergy 2011;66:1449
Staphylococcus aureus
biofilms and
53 disease subjects;
superantigens are
15 controls; significantly
associated
Sinonasal mucosa for in CRS
S.aureus and Haemophilus patients, suggesting
influenzae biofilms;
the biofilm may be a
Presence of total and nidus for
superantigen-specific IgE superantigen-eluting
bacteria.
45. Adaptative immune responses in Staphylococcus aureus
biofilm-associated chronic rhinosinusitis
Foreman, Allergy 2011;66:1449
Staphylococcus aureus
biofilms and
53 The presence of
disease subjects;
S. aureus superantigens are
biofilms is
15 controls; significantly
associated with associated
Sinonasal mucosa for
eosinophilic in CRS
S.aureus and Haemophilus
inflammation, patients, suggesting
influenzae biofilms;
across the the biofilm may be a
spectrum of CRS nidus for
Presence of total and
superantigen-specific IgE superantigen-eluting
bacteria.
46. Adaptative immune responses in Staphylococcus aureus
biofilm-associated chronic rhinosinusitis
Foreman, Allergy 2011;66:1449
Representative images of bacterial biofilms on sinus mucosa using a FISH
(Fluorescence in situ Hybridization) protocol, imaged on the confocal scanning laser
microscope. Both images demonstrate brightly fluorescing bacterial-sized dots
surrounded by a less-intense fluorescing blush, thought to represent the matrix.
(A) H.influenza (B) Staphylococcus
FISH probe aureus FISH probe
tagged with Cy3 tagged with Alexa488
fluorophore fluorophore
47. Early protective and risk factors for allergic rhinitis at
age 4½ yr Alm Pediat Allergy Immunol 2011;22:398
% children reporting
A prospective, longitudinal symptoms of allergic
study of a cohort of rhinitis during the least
children born in the region year at age 4 ½ yrs
of western Sweden in 2003.
6 –
8,176 families. 5 –
4 –
5.5%
Questionnaires at 3 –
6 and 12 months 2 –
and at 4½ yr of age. 1 –
0
48. Early protective and risk factors for allergic rhinitis at
age 4½ yr Alm Pediat Allergy Immunol 2011;22:398
1.5 –
1.0 –
10.21 OR for allergic rhinitis
0 9 –
0 8 –
0 7 –
0 6 –
0 5 –
0 4 –
0 3 –
3.3
0 2 – 2.72 2.21
0 1 –
1.97
0 0
Sensitisation Recurrent Doctor- Parental Eczema
to food wheeze diagnosed rhinitis first year
allergens eczema
49. Early protective and risk factors for allergic rhinitis at
age 4½ yr Alm Pediat Allergy Immunol 2011;22:398
1.5 –
1.0 –
10.21 OR for allergic rhinitis
0 9 –
0 8 –
0 7 – The risk was reduced with
0 6 – fish introduction before
0 5 –
0 4 –
9 months
0 3 –
3.3
0 2 – 2.72 2.21
0 1 –
1.97
0 0
Sensitisation Recurrent Doctor- Parental Eczema
to food wheeze diagnosed rhinitis first year
allergens eczema
50. High-Dose Docosahexaenoic Acid Supplementation of
Preterm Infants: Respiratory and Allergy Outcomes
Manley Pediatrics 2011;128:e71
657 preterm infants 33 RR of reported hay fever
weeks’ gestation who in all infants at either
consumed expressed breast 12 or 18 months
1.0 –
milk from mothers taking
0.9 –
either tuna oil 0.8 –
(high-DHA diet) or soy oil 0.7 –
(standard-DHA) capsules. 0.6 –
0.5 –
0.4 –
Incidence of
bronchopulmonary dysplasia
0.3 –
0.2 –
0.41
(BPD) and parental reporting 0.1 –
p=0.03
of atopic conditions over the 0
first 18 months of life. DHA diet
52. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
Quantitative
extract Cho JACI 2012;129:529
measurement of
glandular secretion.
A. Harvest of nasal mucosa
from the inferior nasal
turbinate.
B. Experimental setup.
C. Mucus bubbles from
glands under oil are
visualized by using
bright-field microscopy
and side-light illumination.
D. Example of mucus
bubbles formed on the
surface of nasal
turbinates 30 minutes
after stimulation with
HDM extract.
53. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Background
The submucosal gland (SMG) is important in the control of airway
surface fluid.
Protease-activated receptor (PAR) 2 contributes to the pathophysiology
of allergies in response to nonspecific allergens bearing proteases and
anion secretion.
House dust mites (HDMs) have abundant proteases that can activate
PAR2, but little is known about the direct effect of HDM on SMG
secretion.
Objective
To investigate the effect of HDMs on glandular secretion and its
mechanism in allergic patients, patients with chronic rhinosinusitis
(CRS), or both.
54. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Inferior nasal
1) HDM induced a
turbinates.
significantly higher
55 patients classified secretion rate
into four groups:
and number of
1. the control,
2. allergic rhinitis (AR), responding glands
3. chronic rhinosinusitis (CRS), in the AR and
4. AR + CRS. AR+CRS groups
Mucus bubbles from than in the
individual submucosal control group.
gland (SMGs).
55. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Inferior nasal 2) Patients in the
turbinates. CRS group, who had no
55 patients classified HDM-specific IgE,
into four groups: showed a
1. the control, higher response
2. allergic rhinitis (AR), than the control group,
3. chronic rhinosinusitis (CRS),
and its response
4. AR + CRS.
was suppressed by
Mucus bubbles from a PAR2-selective
individual submucosal antagonist.
gland (SMGs).
56. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Responses to HDM. Plots of averaged
secretion rates versus time for each group.
Inferior nasal *p < 0.05
turbinates.
55 patients classified
into four groups:
1. the control,
2. allergic rhinitis (AR),
3. chronic rhinosinusitis (CRS),
4. AR + CRS.
Mucus bubbles from
individual submucosal
gland (SMGs).
57. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Responses to HDM. Plots of averaged
secretion rates versus time for each group.
Inferior nasal *p < 0.05
Interestingly, patients in
turbinates.
the CRS group, who had
55 patients classified IgE
no HDM-specific
into four groups:
antibody, showed a
1. the control,
higher response than the
2. allergic rhinitis (AR), its
control group, and
3. chronic rhinosinusitis (CRS),
response was suppressed
4. AR + CRS.
by a PAR2-selective
antagonist.
Mucus bubbles from
individual submucosal
gland (SMGs).
58. Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Conclusions
HDM allergens can induce glandular secretion in patients
with AR, CRS, or both, and PAR2 represents a possible
mechanism for nonspecific hyperreactivity in inflammatory
airway diseases.
59. Luminal decoration of blood vessels by activated
perivasal mast cells in allergic rhinitis
Schaefer, Allergy 2012;67:510
(A) Tissue
accumulation
of mast cells
(b-
tryptase, brown, on
hematoxylin
background staining)
in allergic rhinitis
patient (AR, right)
& healthy control
(left).
(B) Activated
mast cells co-localize
with peripheral
blood vessels in AR
nasal mucosa.
Asterisks indicate
capillary lumen.
60. Luminal decoration of blood vessels by activated
perivasal mast cells in allergic rhinitis
Schaefer, Allergy 2012;67:510
(C) Confocal laser
scanning microscopy
of AR nasal mucosa
stained with
DAPI (nuclei, blue),
anti CD31 (endothelial
cells, green),
& anti CD63var (red).
Arrows indicate
fluorescence signal
transfer
from degranulating
mast cells into the
lumen
of microcapillaries
across
the juxtapositioned
endothelial cells.
61. Luminal decoration of blood vessels by activated
perivasal mast cells in allergic rhinitis
Schaefer, Allergy 2012;67:510
• Mast cells can discharge exosomes, which are complete,
membrane-covered vesicles, able to travel long distances with
the help of the lymphatic system.
• Another novel way: upon triggering, granular membrane factors
directly traverse from the activated mast cell onto an acceptor
cell.
• Detected epitope transfer from activated mast cells onto
neighboring cells by following the localization of CD63var,
which is a specific molecular marker of human mast cell granuli.
• The new transport mode requires an intimate cellular coupling.
62. Luminal decoration of blood vessels by activated
perivasal mast cells in allergic rhinitis
Schaefer, Allergy 2012;67:510
• In conclusion, we describe details of a novel intercellular
communication mechanism, wherein granulated cells can select
distinguished acceptor cells via receptor–ligand interactions and
then transfer a set of their own molecules onto them.
• This way mast cells can control, modify or even reprogram
selected bystander cells and may fundamentally reshape their
microenvironment in case of an allergic challenge. As mast cells
frequently co-localize with blood vessels in situ, we propose that
via this transcytotic channeling, mast cells instantly modulate the
membrane composition of neighboring endothelium.
63. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
Background:
Patients previously given a diagnosis of non-allergic rhinitis (NAR)
might have a new form of local allergic rhinitis (LAR) with
local production of specific IgE antibodies and a positive response
to a nasal allergen provocation test (NAPT).
Objective:
We evaluated an NAPT protocol using multiple aeroallergens
(NAPT-M) for the detection of polysensitization
to several aeroallergens in patients with LAR.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
64. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
25 adult patients with Local allergic rhinitis (LAR);
25 adult patients with Non-allergic rhinitis (NAR).
All the patients had a history of at least 2 yrs
of persistent rhinitis with negative skin prick test (SPT) responses
and serum sIgE levels to the most prevalent aeroallergens.
- LAR was diagnosed by the presence of a positive response
to ≥ 1 NAPT-Ss with D pteronyssinus, Alternaria alternata,
Olea europea, or grass pollen ;
- NAR by a negative NAPT response.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
65. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
NAPT-M: Nasal allergen provocation test with multiple allergens
• Symptom-free patients (total VAS <60 mm) were challenged intranasally
with 2 puffs (100 mL) of saline in each nostril to exclude nasal hyperreactivity.
If the result was negative, 15 minutes after NAPT-M, we began administrating
4 consecutive and different reconstituted freeze-dried allergen solutions
of D pteronyssinus (4 µg/mL), A alternata (0.25 µg/mL), O europea (0.6 µg/mL), and
grass pollen (0.1 µg/mL; ALK-Abello) at 15-minute intervals.
2 puffs (100 mL) of the solution at room temperature were applied in each nostril.
• The response to nasal challenge was evaluated based on subjective
(VAS of nasal-ocular symptoms) and objective (VOL2-6 cm) parameters.
• A positive NAPT-M response was considered to be:
1) an increase of ≥ 30% in the total VAS score
2) a decrease of ≥ 30% in the sum of VOL2-6 cm from both nasal cavities.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
66. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
Nasal levels of tryptase and ECP in patients with LAR after NAPT-Ms.
*
* *
*
*
*
* Significant differences (p < 0.05) between baseline and 15 minutes and 1, 2, and 24 hours
after challenge.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
67. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
Nasal levels of tryptase and ECP in patients with LAR after NAPT-Ms.
*
* *
*
*
*
There is a clinically relevant polysensitization
* Significant differences (p <aeroallergens and 15 minutes and 1, 2, and 24 hours
to 0.05) between baseline in patients
after challenge.
with LAR.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
68. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
Number of visits required for the final diagnosis
in NAPT-Ms and NAPT-Ss.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
69. Nasal allergen provocation test with multiple
aeroallergens detects polysensitization in local
allergic rhinitis. Rondon, JACI 2011;128:1192
Number of visits required for the final diagnosis
in NAPT-Ms and NAPT-Ss.
NAPT-M is a useful,
specific, sensitive,
reproducible, and
less time-consuming
in vivo diagnostic test
for the screening
of patients with LAR.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
70. Comparative evaluation of nasal blood flow and airflow
in the decongestant response to oxymetazoline
Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77
19 healthy adults. Decongestive response
in nasal blood flow (NBF)
Doubling doses of
oxymetazoline of 25µg, P<0.001 P<0.001
50µg, 100µg, and 200µg at
20 minute intervals.
Peak nasal inspiratory flow
(PNIF) and nasal airway
resistance (NAR) at baseline
and after each successive
dose. 1 visit 2 visit
Nasal blood flow (NBF) using
laser Doppler Flowmetry.
71. Comparative evaluation of nasal blood flow and airflow
in the decongestant response to oxymetazoline
Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77
19 healthy adults. Peak nasal inspiratory
flow (PNIF)
Doubling doses of
oxymetazoline of 25µg,
50µg, 100µg, and 200µg at P<0.001 P<0.003
20 minute intervals.
Peak nasal inspiratory flow
(PNIF) and nasal airway
resistance (NAR) at baseline
and after each successive
dose. 1 visit 2 visit
Nasal blood flow (NBF) using
laser Doppler Flowmetry.
72. Comparative evaluation of nasal blood flow and airflow
in the decongestant response to oxymetazoline
Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77
19 healthy adults. Nasal airway
resistance (NAR)
Doubling doses of
oxymetazoline of
25µg, 50µg, 100µg, and P<0.002
200µg at 20 minute P<0.001
intervals.
Peak nasal inspiratory flow
(PNIF) and nasal airway
resistance (NAR) at baseline
and after each successive 1 visit 2 visit
dose.
Nasal blood flow (NBF) using
73. Comparative evaluation of nasal blood flow and airflow
in the decongestant response to oxymetazoline
Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77
19 healthy adults. Nasal airway
resistance (NAR)
Doubling doses offlow using
Nasal blood
oxymetazoline of
laser Doppler flowmetry
25µg, 50µg, 100µg, and
200µg at 20 minute and
is a sensitive P<0.002
P<0.001
reproducible outcome to
intervals.
decongestion with
Peak nasal inspiratory flow
oxymetazoline, similar
(PNIF) and nasal airway
to nasal patency
resistance (NAR) at baseline
and symptoms.
and after each successive 1 visit 2 visit
dose.
Nasal blood flow (NBF) using
74. Thermographic imaging during nasal peanut challenge may
be useful in the diagnosis of peanut allergy.
Clark, Allergy 2012;67:574
Background: Double-blinded challenges are widely used for diagnosing
food allergy but are time-consuming and cause severe reactions.
Outcome relies on subjective interpretation of symptoms, which leads
to variations in outcome between observers.
Facial thermography combined with nasal peanut challenge was
evaluated as a novel objective indicator of clinical allergy.
75. Thermographic imaging during nasal peanut challenge may
be useful in the diagnosis of peanut allergy.
Clark, Allergy 2012;67:574
Change in mean nasal temperature
from baseline (Δt) over time (min)
for placebo and active peanut nasal
16 children with positive challenge arms.
peanut challenge.
Nasal challenge with 10 μg
peanut protein or placebo.
Mean skin temperatures
recorded from
the mouth & nose using
infrared thermography
over 18 min.
76. Thermographic imaging during nasal peanut challenge may
be useful in the diagnosis of peanut allergy.
Clark, Allergy 2012;67:574
Change in mean nasal temperature
The area under curve from baseline (Δt) over time (min)
of nasal skin temperature for placebo and active peanut nasal
16 children with elevated
was significantly positive challenge arms.
peanut peanut vs placebo
after challenge.
(18.2 vs 4.8°Cmin).
Nasal maximum increase μg
The challenge with 10
peanut protein or placebo.
in temperature was also
significantly greater
Mean aftertemperatures
skin peanut:
recorded from +0.9°C.
mean difference
the mouth & nose using
infrared thermography
over 18 min.
77. Thermographic imaging during nasal peanut challenge may
be useful in the diagnosis of peanut allergy.
Clark, Allergy 2012;67:574
Change in mean nasal temperature
Thermography from baseline (Δt) over time (min)
can detect inflammation
for placebo and active peanut nasal
caused by nasal challenges
16 children with positive
whilst employing 1000-fold
challenge arms.
peanutpeanut than an oral
less challenge.
challenge.
Nasal challenge with 10 μg
This novel technique could
peanut protein or placebo.
be developed to provide
a rapid, safe
Mean skin temperatures
recorded from clinical
and objective
allergy test.
the mouth & nose using
infrared thermography
over 18 min.
79. Comparison of bronchodilator response in patients with
asthma and healthy subjects using spirometry and
oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317
Linear Regression with 95.00% Mean Prediction Interval
Impulse oscillometry (IOS)
is an effort-independent
pulmonary function
technique.
Spirometry.
Reversibility after
400 μg salbutamol.
95 asthmatic and
61 healthy subjects. Correlation between percent predicted FEV1
and resistance at 5 Hz (R5) at baseline in
patients with asthma
80. Comparison of bronchodilator response in patients with
asthma and healthy subjects using spirometry and
oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317
Linear Regression with 95.00% Mean Prediction Interval
Impulse oscillometry (IOS)
is an effort-independent
Low-frequency
pulmonary function
technique. as R5 and
IOS
spirometry as
Spirometry.
FEV1 correlate in
Reversibility after
patients with
400 μg salbutamol.
asthma.
95 asthmatic and
61 healthy subjects. Correlation between percent predicted FEV1
and resistance at 5 Hz (R5) at baseline in
patients with asthma
81. Comparison of bronchodilator response in patients with
asthma and healthy subjects using spirometry and
oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317
Linear Regression with 95.00% Mean Prediction Interval
Correlation between percent predicted Correlation of the bronchodilator response
FEV1 and and R5 post bronchodilator in measured as a percentage of predicted change
patients with asthma in FEV1 and R5 in patients with asthma.
82. Relationship between bronchial hyperreactivity and
bronchodilation in patients with allergic rhinitis
Ciprandi Ann Allergy Asthma Immunol 2011;106:460
Background
Allergic rhinitis may be considered a risk factor for the onset of
asthma. Recently, it has been reported that forced expiratory
flow between 25% and 75% of vital capacity (FEF25%−75%) may
predict a positive response to bronchodilation test in asthmatic
children. Moreover, bronchial hyperreactivity (BHR) is frequently
detected in AR patients.
Objective
To evaluate the possible relationship between the response to
bronchodilation test and methacholine challenge, also considering
the FEF25%−75% values in a large group of patients with persistent
allergic rhinitis.
83. Relationship between bronchial hyperreactivity and
bronchodilation in patients with allergic rhinitis
Ciprandi Ann Allergy Asthma Immunol 2011;106:460
% AHR patients with
”positive” results for
365 consecutive bronchodilation test
AR patients. 70 –
60 –
Spirometry, methach
oline, bronchial
50 – 66%
challenge, and 40 –
bronchodilation (+ if 30 –
FEV1 > 12% after 400 20 –
mcg salbutamol).
10 –
00
84. Relationship between bronchial hyperreactivity and
bronchodilation in patients with allergic rhinitis
Ciprandi Ann Allergy Asthma Immunol 2011;106:460
% AHR patients with
severe BHR
365 consecutive
AR patients. 25 – (PC20 < 1mg/mL)
20 –
Spirometry, methach
oline, bronchial 15 –
20.8%
challenge, and
10 –
bronchodilation (+ if
FEV1 > 12% after 400 05 –
mcg salbutamol).
00
85. Relationship between bronchial hyperreactivity and
bronchodilation in patients with allergic rhinitis
Ciprandi Ann Allergy Asthma Immunol 2011;106:460
Boxplot for duration of rhinitis
grouped by grade of severity of BHR
365 consecutive
AR patients.
Spirometry, methach
oline, bronchial
challenge, and
bronchodilation (+ if
FEV1 > 12% after 400
mcg salbutamol).
86. Validating childhood symptoms
with physician-diagnosed allergic rhinitis
Kim, Ann Allergy Asthma Immunol 2012;108:231
Background: Multiple population-based and
high-risk cohort studies use parental questionnaire
responses to define allergic rhinitis (AR) in children.
Individual questionnaire items have not been validated
by comparison with physician-diagnosed AR (PDAR).
Objective: To identify routine clinical questions that
best agree with a physician diagnosis of AR and can be
used for early case identification.
87. Validating childhood symptoms
with physician-diagnosed allergic rhinitis
Kim, Ann Allergy Asthma Immunol 2012;108:231
Longitudinal birth cohort study.
531 children at ages 1 through 4 and 7.
Questionnaires, physical examinations, skin prick tests (SPT).
Rhinitis-
specific Rhinitis specific questionnaire
questionnaire
items:
3 stem
questions and
4 sub-questions.
88. Validating childhood symptoms
with physician-diagnosed allergic rhinitis
Kim, Ann Allergy Asthma Immunol 2012;108:231
Percent agreement, sensitivity and specificity of
individual questionnaire items compared with
physician-diagnosed allergic rhinitis (PDAR)
89. Validating childhood symptoms
with physician-diagnosed allergic rhinitis
Kim, Ann Allergy Asthma Immunol 2012;108:231
Percent agreement, sensitivity and specificity of
individual questionnaire items compared with
physician-diagnosed allergic rhinitis (PDAR)
90. Validating childhood symptoms
with physician-diagnosed allergic rhinitis
Kim, Ann Allergy Asthma Immunol 2012;108:231
Percent agreement, sensitivity and specificity of
individual questionnaire items compared with
physician-diagnosed allergic rhinitis (PDAR)
Responses to hayfever and ocular symptoms
had better specificity and percent agreement
with PDAR than the ISAAC-validated
questionnaire item. Combining 2 rhinitis
questions sharply increases specificity and may
improve diagnostic accuracy
of clinical questions.
91. Prevalence and impact of rhinitis in asthma.
SACRA, a cross-sectional nation-wide study in Japan
Ohta, Allergy 2011;66:1287
% of patients with rhinitis
80–
70–
1910 physician.
60– 68.5%
66.2%
29 518 asthmatics. 50–
40–
Questionnaires on rhinitis
and asthma based on ARIA 30–
(Allergic Rhinitis and its 20–
Impact on Asthma) and
10–
Global Initiative for
Asthma (GINA); 0
Self-administered Patients with
questionnaires physicians-
administered
92. Prevalence and impact of rhinitis in asthma.
SACRA, a cross-sectional nation-wide study in Japan
Ohta, Allergy 2011;66:1287
% of patients with uncontrolled
asthma as defined by GINA
70–
1910 physician. 60–
50–
29 518 asthmatics.
40–
Questionnaires on rhinitis 30– P<0.05
and asthma based on ARIA
(Allergic Rhinitis and its 20– 25.4%
Impact on Asthma) and 10– 18%
Global Initiative for
Asthma (GINA); 0
YES NO
Physician‟s diagnosis of rhinitis
93. Bronchodilation test in patients with allergic rhinitis
Ciprandi, Allergy 2011;66:694
% patients with impaired FEF25-75
values (≤ 65% of predicted)
30 –
1469 consecutive
patients suffering 20 –
from persistent
AR.
10 –
18%
Spirometry and
bronchodilation
test in all patients. 0
94. Bronchodilation test in patients with allergic rhinitis
Ciprandi, Allergy 2011;66:694
% patients with FEV1 ≥ 12%
post salbutamol
80 –
70 –
63%
1469 consecutive 60 –
patients suffering 50 –
from persistent
40 –
AR.
30 –
Spirometry and 20 –
bronchodilation
10 –
test in all patients.
0
95. Bronchodilation test in patients with allergic rhinitis
Ciprandi, Allergy 2011;66:694
% patients with FEV1 ≥ 12%
post salbutamol
80 –
70 –
63%
1469 consecutive 60 –
patients suffering 50 –
from persistent
40 –
AR.
30 –
Spirometry and 20 – at risk of
bronchodilation asthma
10 –
test in all patients. development
0
96. Bronchodilation test in patients with allergic rhinitis
Ciprandi, Allergy 2011;66:694
OR for reversibility
20 –
1469 consecutive
patients suffering
from persistent
AR. 10 –
11.3
Spirometry and
bronchodilation
test in all patients. 0
Impaired FEF25-75 values and
longer rhinitis duration
97. Effect of an intranasal corticosteroid on exercise
induced bronchoconstriction in asthmatic children
Kersten Pediatr Pulmonol 2012;47:27
Subjects aged 12–17
years, with mild-to-
moderate
asthma, intermittent
allergic rhinitis and ≥10%
fall in FEV1 at a screening
exercise challenge.
22 ± 3 days treatment with
Exercise induced fall in FEV1 (%) before and
intranasal fluticasone after treatment with placebo or fluticasone
furoate or placebo. furoate. Data expressed as individual fall in
FEV1 and mean fall in FEV1.
98. Effect of an intranasal corticosteroid on exercise
induced bronchoconstriction in asthmatic children
Kersten Pediatr Pulmonol 2012;47:27
Subjects aged 12–17
years, with mild-to-
The activity limitation
moderate
domain score improved
asthma, intermittent
significantly within the
allergic rhinitis and ≥10%
fluticasone furoate
fall in FEV1 at a screening
group (P = 0.03).
exercise challenge.
22 ± 3 days treatment with
Exercise induced fall in FEV1 (%) before and
intranasal fluticasone after treatment with placebo or fluticasone
furoate or placebo. furoate. Data expressed as individual fall in
FEV1 and mean fall in FEV1.
99. Effect of an intranasal corticosteroid on exercise
induced bronchoconstriction in asthmatic children
Kersten Pediatr Pulmonol 2012;47:27
Subjects aged 12–17 years,
Treatment of allergic
with mild-to-moderate
rhinitis in asthmatic
asthma, intermittent
allergic rhinitiswith ≥10%
children and an
intranasal
fall in FEV1 at a screening
corticosteroid
exercise challenge.
reduces EIB and
22 ± 3tends treatment with
days to improve
quality of life.
intranasal fluticasone
Exercise induced fall in FEV1 (%) before and
furoate or placebo. after treatment with placebo or fluticasone
furoate. Data expressed as individual fall in
FEV1 and mean fall in FEV1.
100. Effect of an intranasal corticosteroid on exercise
induced bronchoconstriction in asthmatic children
Kersten Pediatr Pulmonol 2012;47:27
Mean fall in FEV1 at each time point after exercise
Before and after treatment Before and after treatment
with placebo with fluticasone furoate
102. Chronic rhinosinusitis: epidemiology and medical
management Hamilos JACI 2011;128:693
• Chronic rhinosinusitis (CRS) affects
12.5% of the US population.
• Some association has been found between CRS prevalence and
air pollution, active cigarette
smoking, secondhand smoke
exposure, perennial
allergic rhinitis,
and gastroesophageal reflux.
• The majority of
pediatric and adult patients with CRS are immune competent.
103. Chronic rhinosinusitis: epidemiology and medical
management Hamilos JACI 2011;128:693
Current consensus definitions
subclassify CRS into:
1. CRS without nasal polyposis (CRSsNP),
2. CRS with nasal polyposis (CRSwNP),
3. allergic fungal rhinosinusitis (AFRS).
104. Chronic rhinosinusitis: epidemiology and medical
management Hamilos JACI 2011;128:693
• Evaluation and medical management of CRS
has been the subject of several recent consensus reports.
• The highest level of evidence for treatment for CRSsNP exists
for saline lavage, intranasal steroids, and
long-term macrolide antibiotics.
• The highest level of evidence for treatment of CRSwNP exists
for intranasal steroids, systemic glucocorticoids, and topical
steroid irrigations.
• Sinus surgery followed by use of systemic steroids is
recommended for AFRS.
105. A new instrument for the assessment of patient-defined
benefit in the treatment of allergic rhinitis
Franzke, Allergy 2011;66:665
Mean, standard deviation (SD) and percentage
of afflicted patients and needs in allergic rhinitis
106. A new instrument for the assessment of patient-defined
benefit in the treatment of allergic rhinitis
Franzke, Allergy 2011;66:665
Mean, standard deviation (SD) and percentage
of afflicted patients and needs in allergic rhinitis
Needs are scaled from
0 “not important at all”
to 4 “very important”
108. Petasol butenoate complex (Ze 339) relieves allergic
rhinitis–induced nasal obstruction more effectively
than desloratadine. Dumitru JACI 2011;127:1515
Ze 339 is a carbon dioxide extract
derived from the leaves of a
special variety (Petzell) of
Petasites hybridus registered at
the European Community Plant
Variety Office.
In vitro studies show that Ze 339
blocks degranulation in activated
immune cell populations and also
inhibits leukotriene biosynthesis.
18 subjects with allergic rhinitis
to grass pollen received Ze
339, desloratadine, and placebo
for 5 days before nasal
allergen challenge with grass pollen
extract.
109. Petasol butenoate complex (Ze 339) relieves allergic
rhinitis–induced nasal obstruction more effectively
than desloratadine. Dumitru JACI 2011;127:1515
Ze 339 is a carbon dioxide extract
derived from the leaves of a
special variety (Petzell) of
Petasites hybridus registered at
the European Community Plant
Nasal airflow
Variety Office.
improvement:
In vitro studies show that Ze 339
Ze 339, 2.46 hours;
blocks degranulation in activated
immune cell populations and also
desloratadine, 3.94
inhibits leukotriene biosynthesis.
hours allergic rhinitis
18 subjects with
[medians]
to grass pollen received Ze 339,
desloratadine, and placebo for
5 days before nasal allergen
challenge with grass pollen
extract.
110. Petasol butenoate complex (Ze 339) relieves allergic
rhinitis–induced nasal obstruction more effectively
than desloratadine. Dumitru JACI 2011;127:1515
Recovery of nasal obstruction
Time to RTB value of the symptom of nasal
Time to return to 90% of basal flow obstruction (means ± SEMs assessed by means
(means ± SEMs assessed by means of of VAS: Ze 339, 3.2 ± 1.3 hours; placebo,
rhinomanometry: Ze 339, 5.4 ± 1.6 hours; 8.3 ± 2.4 hours; desloratadine, 4.5 ± 1.2 hours
placebo, 9.1 ± 2.3 hours; desloratadine, 10.7 ± 2.5
hours)
RTB = return to baseline
111. Petasol butenoate complex (Ze 339) relieves allergic
rhinitis–induced nasal obstruction more effectively
than desloratadine. Dumitru JACI 2011;127:1515
Concentrations in picograms per milliliter per milligram of nasal secretion
of IL-8 (A) and LTB4(B) in nasal secretions.
112. Mometasone furoate nasal spray increases the number of
minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275
Background: Acute rhinosinusitis
(ARS) is triggered by viral or,
uncommonly, bacterial infection,
causing inflammatory symptoms for
12 weeks.
Objective: To investigate effects
of mometasone furoate nasal spray
(MFNS) vs amoxicillin and placebo on
minimal-symptom days.
113. Mometasone furoate nasal spray increases the number of
minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275
Double-blind, parallel-
group, placebo- and active- % Minimal symptom days
controlled 15-day study.
70 – P<0.004
Patients 12 years of age or older 60 –
to MFNS 200 µg 2/daily, MFNS 62.69%
200 µg 1/daily, amoxicillin 500
50 –
50.33% 54.35%
mg 3/daily, or placebo. 40 –
30 –
Major symptom score (MSS; 20 –
combined rhinorrhea, postnasal P<0.001
10 –
drip, congestion, sinus
00 –
headache, facial pain) of≥5 and
≤12 (maximum: 15) for 7 to 28 MFNS Placebo Amoxicillin
2/daily
days.
114. Mometasone furoate nasal spray increases the number of
minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275
Double-blind, parallel-group,
placebo- and active- µg
MFNS 200 % Minimal symptom days
2/daily significantly
controlled 15-day study.
P<0.004
Patients increased or older
70 –
12 years of age 60 –
minimal-symptom
to MFNS 200 µg 2/daily, MFNS 62.69%
50 –
50.33% 54.35%
days vs amoxicillin
200 µg 1/daily, amoxicillin 500
40 –
mg 3/daily, or placebo.
or placebo 30 –
in patients
Major symptom score (MSS; 20 –
combined rhinorrhea, postnasal P<0.001
with ARS.
drip, congestion, sinus headache,
10 –
00 –
facial pain) of≥5 and ≤12
(maximum: 15) for 7 to 28 days. MFNS Placebo Amoxicillin
2/daily
115. Mometasone furoate nasal spray increases the number of
minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275
Results of this
Double-blind, parallel-group,
placebo- intranasal
and active- % Minimal symptom days
controlled 15-day study.
corticosteroids (INS) 70 – P<0.004
Patients 12 years of age or it
therapy indicate older 60 –
to MFNS 200 µg 2/daily, MFNS 62.69%
can improve 500 50 – 54.35%
200 µg 1/daily, amoxicillin 50.33%
outcomes and
mg 3/daily, or placebo. 40 –
potentially reduce 30 –
Major symptom score (MSS;
inappropriate
combined rhinorrhea, postnasal
20 –
P<0.001
10 –
antibiotic use.
drip, congestion, sinus headache,
00 –
facial pain) of≥5 and ≤12
(maximum: 15) for 7 to 28 days. MFNS Placebo Amoxicillin
2/daily
116. Impact of mometasone furoate nasal spray on individual
ocular symptoms of allergic rhinitis: a meta-analysis
Bielory, Allergy 2011;66:686
3132 patients.
A meta-analysis of 10 randomized, placebo-controlled.
Efficacy of MFNS 200 mcg daily in relieving ocular
allergy symptoms, including itching/burning, redness, and
tearing/watering in both with nasal symptoms of
seasonal (SAR) and nasal symptoms of perennial (PAR).
117. Impact of mometasone furoate nasal spray on individual
ocular symptoms of allergic rhinitis: a meta-analysis
Bielory, Allergy 2011;66:686
Improvement in tearing, itching, and redness in patients with SAR trated
with MFNS for 2 weeks
118. Impact of mometasone furoate nasal spray on individual
ocular symptoms of allergic rhinitis: a meta-analysis
Bielory, Allergy 2011;66:686
Improvement in tearing, itching, and redness in patients with PAR trated
with MFNS for 30 days
119. Impact of mometasone furoate nasal spray on individual
ocular symptoms of allergic rhinitis: a meta-analysis
Bielory, Allergy 2011;66:686
Improvement in tearing, itching, and redness in patients with PAR trated
with MFNS for 30 days
In both SAR
and PAR all
individual
ocular
symptoms
were reduced
in patients
treated with
MFNS.
120. Ocular symptoms in nonspecific conjunctival hyperreactivity
Mourão Ann Allergy Asthma Immunol 2011;107:29
Background
Ocular symptoms can be triggered by nonspecific environmental
factors, characterizing conjunctival hyperreactivity (CHR).
Objective
To examine CHR in subjects with ocular symptoms by means of
a hyperosmolar conjunctival provocation test (HCPT).
121. Ocular symptoms in nonspecific conjunctival hyperreactivity
Mourão Ann Allergy Asthma Immunol 2011;107:29
Digital images of positive HCPT.
63 subjects with ocular complaints (A) Technician's analysis: number
(itching, redness, or tearing) of red dots, 2521; number of
blue dots, 8717.
considered allergic if tests were (B) Technician's analysis: number
positive to at least 1 allergen. of red dots, 2521; number of
blue dots, 8717.
Hyperosmolar Conjunctival
Provocation Test (HCPT) with serial
A
diluted glucose concentrations was
positive if it produced conjunctival
hyperemia up to a 50% solution.
Digital images were analyzed by B
2 observers who marked redness
in the challenged eyes in red
(GIMP 2.6.5 software).
122. Ocular symptoms in nonspecific conjunctival hyperreactivity
Mourão Ann Allergy Asthma Immunol 2011;107:29
Hyperosmolar conjunctival provocation Cumulative frequency of positive HCPT
test with serial glucose concentrations in allergic and nonallergic subjects
in allergic and nonallergic subjects
123. Ocular symptoms in nonspecific conjunctival hyperreactivity
Mourão Ann Allergy Asthma Immunol 2011;107:29
HCPT indentified CHR in allergic as well as in
Hyperosmolar conjunctival subjects. Allergic subjects exhibited
non-allergic provocation Cumulative frequency of positive HCPT
test with serial glucose concentrations in allergic and nonallergic subjects
more CHR than did non-allergic subjects.
in allergic and nonallergic subjects
124. Allergic Conjunctivitis and Dry Eye Syndrome
Hom, Ann Allergy Asthma Immunol 2012;108:163
1. Allergic Conjunctivitis (AC) and Dry Eye Syndrome (DES) are
2 of the most common anterior inflammatory disorders of the eye.
2. The prevalence of DES is 5%-35% of the population.
Up to 40% of the general US population has reported
ocular symptoms consistent with AC.
3. Both conditions have a strong effect on quality of life.
When measured with questionnaires reflecting quality of
life, DES and AC can have the same effect on quality of life
as moderate angina.
125. Allergic Conjunctivitis and Dry Eye Syndrome
Hom, Ann Allergy Asthma Immunol 2012;108:163
Subjective evaluation of symptom of dryness
or frequency of dryness score definitions.
Self-reported
- itchiness
- dryness
- redness.
689 patients
5-90 yrs.
130. Allergic Conjunctivitis and Dry Eye Syndrome
Hom, Ann Allergy Asthma Immunol 2012;108:163
Itch & Redness Itch & Dryness
Most patients with “itchy eyes” consistent with AC
also have dry eyes and redness.
Dryness & Redness
These results suggest that some symptomatic & Redness
Itch, Dryness patients
concomitantly have features of AC and DES.
131. Conjunctival provocation with airborne allergen
in patients with atopic keratoconjunctivitis
Nivenius, Clin Exp Allergy 2012;42:58
Background Atopic keratoconjunctivitis (AKC)
is a chronic eye disease with periods of exacerbations.
Many patients experience no obvious seasonal
variation, although
a majority of patients are allergic to common airborne
allergens.
Objective To investigate the allergic reaction, to
conjunctival provocation with airborne allergens, in
patients with AKC.
132. Conjunctival provocation with airborne allergen
in patients with atopic keratoconjunctivitis
Nivenius, Clin Exp Allergy 2012;42:58
11 patients with AKC
and birch and/or grass
pollen allergy
Atopic keratoconjunctivitis patient,
5 patients with 10 min after provocation
seasonal allergic conjunctivitis (SAC) with birch allergen in the right eye
& 5 healthy subjects. and dilution buffer only in the left.
Challenge in 1 eye with the
allergen, to which the patient was
reactive,
& with dilution buffer in the other.
Signs & symptoms from both eyes
at 10 min, 8h and 48h.
allergen
Tear fluid for cytokine analyses
at baseline and at 8h and 48h.
133. Conjunctival provocation with airborne allergen
in patients with atopic keratoconjunctivitis
Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.
Atopic Seasonal allergic Healthy
134. Conjunctival provocation with airborne allergen
in patients with atopic keratoconjunctivitis
Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.
A significant
change
from baseline was
documented
at 10 min for AKC
& SAC
patients, while no
change
was seen in
healthy
controls.
Atopic Seasonal allergic Healthy
135. Conjunctival provocation with airborne allergen
in patients with atopic keratoconjunctivitis
Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.
In this single
dose allergen
provocation
study,
AKC patients
responded with a
typical
IgE-mediated
allergic reaction.
Atopic Seasonal allergic Healthy
136. Conjunctival provocation with airborne allergen
in patients with atopic keratoconjunctivitis
Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.
An increase
in cytokines at 48 h
after the challenge
was demonstrated
and might, with
further studies, give
us a better
understanding of the
nature
of inflammation in
AKC.
Atopic Seasonal allergic Healthy
137. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
• Vernal keratoconjunctivitis (VKC)
is a severe allergic disease.
• Treatment involves topical antiallergic agents, which are effective in patients with
mild disease, whereas most patients with severe disease require some topical steroid
therapy.
• The physician’s primary objective with the patient with VKC is to prevent and
minimize acute flare-ups, as well as to treat them when they do occur with
the safest therapy available.
138. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
Study design.
Crossover 2 yr study.
Efficacy and safety of
0.05% topical cyclosporine
in patients with VKC.
Ability of 0.05%
cyclosporine to prevent
flare-ups vs topical
Ketotifen 0.025% AE; adverse event
CsA; cyclosporine
139. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
Crossover 2 yr study.
Efficacy and safety of
0.05% topical cyclosporine
in patients with VKC.
Ability of 0.05%
cyclosporine to prevent
flare-ups vs topical
Ketotifen 0.025%
140. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
The number of recurrences was
significantly reduced when
patients were treated with
Crossover 2 cyclosporine
0.05%
yr study.
Efficacy with safety of
and respect
0.05% topical cyclosporine
to 0.025% ketotifen.
in patients with VKC.
Ability of 0.05%
cyclosporine to prevent
flare-ups.
The efficacy of a higher
dose, 0.1%, was compared
with 0.15% dexamethasone
during acute relapses.
141. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
The cyclosporine
group had
Crossover 2 yr study.
significantly
Efficacy and safety of
0.05% topical cyclosporine
in patients periods free
longer with VKC.
of recurrences
Ability of 0.05%
cyclosporine to prevent the
compared with
flare-ups.
Theketotifen higher
efficacy of a group
dose, 0.1%, was compared
with 0.15% dexamethasone
during acute relapses.
142. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
Crossover 2 yr study.
Efficacy and safety of
0.05% topical cyclosporine
in patients with VKC.
Ability of 0.05%
cyclosporine to prevent
flare-ups vs topical
Ketotifen 0.025%
143. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
Itching, photophobia,
and conjunctival hyperemia
scores showed
Crossover 2 yr study.
significant amelioration
Efficacy and safety of
0.05%patients treated with
in topical cyclosporine
in patients with VKC.
0.05% cyclosporine eye
Ability of 0.05%
drops compared with those
cyclosporine to prevent
seen in patients treated
flare-ups.
The with 0.025% ketotifen
efficacy of a higher
dose, 0.1%,eye compared
was drops.
with 0.15% dexamethasone
during acute relapses.
144. Topical cyclosporine prevents seasonal recurrences of
vernal keratoconjunctivitis in a randomized, double-
masked, controlled 2-year study
Lambiase JACI 2011;128:896
OR for recurrence
3 –
p= 0.031
2.44
Crossover 2 yr study.
2 –
Efficacy and safety of
0.05% topical cyclosporine
in patients with VKC. 1 –
Ability of 0.05%
cyclosporine to prevent
flare-ups vs topical 0
Patients treated with ketiofen
Ketotifen 0.025%
vs patients treated with
cyclosporine.
146. Nasal nitric oxide as a measure of osteomeatal complex
patency in nasal polyps
McKinlay Ann Allergy Asthma Immunol 2011;107:179
Nasal nitric oxide (nNO) levels according
to computed tomographic (CT) scan results
Consecutive nonsmoking
patients with nasal polyp
disease.
Rhinosinusitis extent
staged by CT scans of
the paranasal sinuses.
148. Oxidative stress induces unfolding protein response and
inflammation in nasal polyposis. Jeanson, Allergy 2012;67:403
Background: Nasal polyposis, a chronic inflammatory disease
affecting the upper airways, is a valuable and accessible model
to investigate the mechanisms underlying chronic inflammation.
The main objective of this study was to investigate a potential
involvement of the unfolded protein response (UPR) in the context
of oxidative stress and inflammation in nasal epithelial cells from
nasal polyps (NP).
149. Oxidative stress induces unfolding protein response and
inflammation in nasal polyposis. Jeanson, Allergy 2012;67:403
Epithelial cells
from NP (n=20) Proteomics analysis
& normal mucosa (n=15). of human nasal epithelial cells
in culture revealed the activation
Analyzed by of the unfolded protein response
global proteomic approach in NP.
& cell biology techniques.