What rhinitis and sinusitis and poliposis

Rhinitis
Attilio Boner
University of Verona, Italy
attilio.boner@univr.it
WHAT YOU SOULD HAVE READ BUT ………………… 2018

Allergic Rhinitis and its Impact on Asthma (ARIA)
guidelines-2016 revision.
Brożek JL, J Allergy Clin Immunol. 2017;140(4):950-958.
This revision of the ARIA guidelines is limited in scope and addresses
6 questions about the treatment of AR:
1. Should a combination of oral H1-antihistamine and intranasal corticosteroid versus
intranasal corticosteroid alone be used?
2. Should a combination of intranasal H1-antihistamine and intranasal corticosteroid versus
intranasal corticosteroid alone be used?
3. Should a combination of an intranasal H1-antihistamine and an intranasal corticosteroid
versus intranasal H1-antihistamine alone be used?
4. Should a leukotriene receptor antagonist versus an oral H1- antihistamine be used?
5. Should an intranasal H1-antihistamine versus an intranasal corticosteroid be used?
6. Should an intranasal H1-antihistamine versus an oral H1-antihistamine be used?

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• Most of the recommendations are based on low- or very low certainty
evidence, mainly because of the imprecision of the estimated effects due
to few patients being studied.
• For those questions, there is a need for more well-designed and executed
randomized controlled trials that would measure and properly report
all important outcomes.

Non-allergic rhinitis: Position paper of the European
Academy of Allergy and Clinical Immunology
P W Hellings, Allergy 2017;72:1657–1665
• Nonallergic rhinitis (NAR) is defined as a symptomatic inflammation of
the nasal mucosa with the presence of a minimum of two nasal symptoms
such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose,
without clinical evidence of endonasal infection and without systemic
signs of sensitization to inhalant allergens.
• Symptoms of NAR may have a wide range of severity and be either
continuously present and/or induced by exposure to unspecific triggers,
also called nasal hyperresponsiveness (NHR).

• NAR involves different subgroups:
o drug-induced rhinitis,
o (nonallergic) occupational rhinitis,
o hormonal rhinitis (including pregnancy rhinitis),
o gustatory rhinitis,
o senile rhinitis, and
o idiopathic rhinitis (IR).
• NAR should be distinguished from those rhinitis patients with an allergic
reaction confined to the nasal mucosa, also called “entopy” or
local allergic rhinitis (LAR).

Phenotypes of chronic rhinitis

Diagnosis of chronic rhinitis

Therapeutic strategy of nonallergic rhinitis

• Rhinitis general
considerations
• reviews

• Allergic rhinitis is common and affects 10–15% of children
and 26% of adults in the UK.
• Topical nasal corticosteroids are the treatment of choice
for moderate to severe disease.
• Combination therapy with intranasal corticosteroid plus intranasal
antihistamine is more effective than either alone and provides second line
treatment for those with rhinitis poorly controlled on monotherapy.
• Treatment of rhinitis is associated with benefits for asthma.
BSACI guideline for the diagnosis and management
of allergic and non-allergic rhinitis
(Revised Edition 2017; First edition 2007)
GK Scadding, CEA 2017;47:856-889

• Non-allergic rhinitis also is a risk factor for the development of asthma
and may be eosinophilic and steroid-responsive or neurogenic and
non- inflammatory.
• Non-allergic rhinitis may be a presenting complaint for systemic disorders
such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis.
• Infective rhinitis can be caused by viruses, and less commonly by bacteria,
fungi and protozoa.

Triggers for non-allergic rhinitis

Pharmacotherapy effects on individual rhinitis symptoms

(A and B) How to use a nasal spray and nasal drops Evidence grade D

Treatment of non-allergic rhinitis• Therapy in NAR depends upon the
phenotype.
• The division into those with and
without nasal inflammation can be
made on the basis of nasal smears.
• Those with inflammation may respond
to anti-inflammatory therapy,
although less well than in AR and
higher INS doses and combinations
of therapy may be needed.
If these fail a nasal aspirin challenge
could be undertaken, followed by
desensitization if positive.
• Non-inflammatory NAR may respond
to anti-cholinergic therapy or to
capsaicin. Some patients require both
anti-inflammatory and anti-
neurogenic treatments.

Rhinitis in children

Recognition of
rhinitis in children
at different ages

Approach to therapy for paediatric allergic rhinitis

• Rhinitis prevalence
Prevalence is a statistical concept referring to the number of
cases of a disease that are present in a particular population
at a given time,
whereas
incidence refers to the number of new cases that develop in a
given period of time.

Patient-reported signs of dampness at home may be
a risk factor for chronic rhinosinusitis:
A cross-sectional study
C Ahlroth Pind, CEA 2017;47:1383-1389
 26 577 adults
(16-75 years).
 Dampness defined as
reporting water damage,
floor dampness or visible
moulds in the home during
the last 12 months.
Number of subjects reporting water damage,
floor dampness and visible moulds and the
overlap between the groups.

 26 577 adults
(16-75 years).
 Dampness defined as
reporting water damage,
floor dampness or visible
moulds in the home during
the last 12 months.
% subjects reporting
dampness at home
11.3%
15 –
10 –
05 –
00

chronic
rhinosinusitis
chronic
bronchitis
allergic
rhinitis
current
asthma
wheeze nocturnal
dyspnoea
nocturnal
coughing
In subjects reporting dampness at home OR of
2.0 –
1.5 –
1.0 –
0.5 –
0.0
1.71
1.24 1.21
1.37
1.80
1.34
1.64

 The exact mechanisms by which dampness and moulds affect the airways
are not yet known, but exposure to mould-related microbes, such as fungi,
may play a role in some cases.
 Fungal allergens are known to be related to allergic diseases, but fungi
also produce toxins and irritants possibly affecting the airways.
 It is suggested that damp-related symptoms do not necessarily arise on an
atopic basis, as both sensitized and non-sensitized individuals are
affected.
 Both allergic and non-allergic responses are believed to be involved in the
reaction to dampness at home.

• Rhinitis
• Protective factors

Vitamin D regulates immunoglobulin mucin domain
molecule-4 expression in dendritic cells
Z-Q Liu, CEA 2017;47:656-664
Background
• Dendritic cell (DC)-derived immunoglobulin
domain molecule (TIM)4 plays a critical role
in the initiation of T helper (Th)2 polarization.
• Vitamin D (VitD) involves the regulation
of a number of immune responses.
Objectives
This study tests a hypothesis that VitD regulates
TIM4 expression in DCs.
(TIM)4

Z-Q Liu, CEA 2017;47:656-664
 Peripheral blood samples
from patients with allergic
rhinitis (AR) (n = 20) and
healthy subjects (n = 20).
 DCs analyzed for the
expression dendritic cell
(DC)-derived immunoglobulin
domain molecule (TIM)4.
Serum calcitriol levels of healthy subjects
and allergic rhinitis (AR) patients
P<0.01
(TIM)4
Th2

Z-Q Liu, CEA 2017;47:656-664
TIM4 levels in peripheral DCs of
healthy subjects and AR patients
P<0.01
VitD receptor (VDR) expression
is lower in dendritic cells (DCs)
of allergic rhinitis (AR) patients
than healthy controls

Z-Q Liu, CEA 2017;47:656-664
TIM4 levels in peripheral DCs of
healthy subjects and AR patients
P<0.01
VitD receptor (VDR) expression
is lower in dendritic cells (DCs)
of allergic rhinitis (AR) patients
than healthy controls
The peripheral DC expressed higher levels
of TIM4 and lower levels of VDR.
A negative correlation was identified between the data of
serum calcitriol and TIM4 in DCs calcitriol in the culture

Z-Q Liu, CEA 2017;47:656-664
VitD receptor (VDR)
mediates the effects
of calcitriol on suppression
of TIM4 in dendritic cells
(DCs).
levels of TIM4 mRNA
(a; mean SD; *, P < 0.01)
and TIM4 protein (b)
in DCs from 18 allergic
rhinitis patients.
The DCs were cultured in
the presence of calcitriol
(as denoted on the X axis)
for 48 h.

Z-Q Liu, CEA 2017;47:656-664
Exposure to calcitriol restores impaired VitD receptor (VDR)
expression in dendritic cells (DCs) of allergic rhinitis (AR) patients

Z-Q Liu, CEA 2017;47:656-664
Exposure to calcitriol restores impaired VitD receptor (VDR)
expression in dendritic cells (DCs) of allergic rhinitis (AR) patients
VitD deficiency may contribute to the pathogenesis
of AR by increasing the TIM4 expression

Z-Q Liu, CEA 2017;47:656-664
Conclusions and clinical relevance
• VitD deficiency may contribute to
the pathogenesis of AR by increasing
the TIM4 expression.
• The results suggest that to regulate the serum calcitriol levels and
the expression of VDR in DCs may be necessary to be taken into account
in the treatment of AR.
TIM4
TIM4
X
X

• Rhinitis
pathogenesis
• remodeling

Local allergic rhinitis is an independent rhinitis phenotype:
The results of a 10-year follow-up study.
Rondon C, Allergy. 2018 Feb;73(2):470-478.
BACKGROUND:
•The knowledge about the natural history
of local allergic rhinitis (LAR) is limited.
•One unmet question is to demonstrate whether LAR should
be considered the first step in the development of allergic
rhinitis (AR) or an independent phenotype.
•The aim of this study was to prospectively evaluate the
natural history of a population with LAR, the potential
conversion to AR with systemic atopy and the development
of asthma during 10 years.

a 10-year follow-up study
a cohort of 176 patients
with local allergic rhinitis
(LAR) of recent onset and
115 age- and sex-matched
healthy controls
prospectively evaluated
from 2005 to 2016
Nasal allergen provocation tests
(NAPT) with:
•D. pteronyssinus,
•Alternaria alternata,
•Olea europaea and
•grass pollen
were performed at baseline,
and after 5 and 10 years.

healthy controls
from 2005 to 2016
After 10-year LAR, patients experienced
a significant and clinically relevant
worsening of the rhinitis,
with increase in:
•emergency assistance,
•development of asthma,
•loss of allergen tolerance and
•impairment of the quality of life.
This worsening became significant
after 5 years and progressed
throughout 10 years

Changes over time in concentration of allergen tolerated (mean standard deviation)
by LAR patients in nasal allergen provocation test
Analysis of the allergen concentration tolerated by LAR patients in NAPT showed a
significant loss of tolerance to DP, AA, grass pollen and olive pollen after 5 and 10
years of follow-up, compared to baseline.

healthy controls
from 2005 to 2016
% LAR patients with polysensitization
(+ NPT to > 1 allergen)
60 –
50 –
40 –
30 –
20 –
10 –
0
36.4%
baseline 5 years 10 years
40.9%
52.8%
P=0.002
P=0.025

healthy controls
from 2005 to 2016
development of Allergic Rhinitis with
systemic atopy in the 10 years follow-up
10 –
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00 -
patients
with LAR
controls
9.7%
7.8%
P=0.623

a 10-year follow-up study
a cohort of 176 patients with
local allergic rhinitis (LAR)
of recent onset and
healthy controls
prospectively evaluated
from 2005 to 2016
development of Allergic Rhinitis with
systemic atopy in the 10 years follow-up
10 –
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00 -
patients
with LAR
controls
9.7%
7.8%
P=0.623
LAR is a well-differentiated
clinical entity with:
1) a low rate of development
of systemic atopy,
2) a natural evolution towards
worsening and
3) a risk factor for suffering
asthma.

Reliable mite-specific IgE testing in nasal secretions
by means of allergen microarray.
Berings M, J Allergy Clin Immunol. 2017 Jul;140(1):301-303.e8.
•There is evidence for local production of IgE in the nasal mucosa.
•Nasal secretions (NasSec) are easily collected with various noninvasive
methods and are suitable for IgE measurements.
•Nevertheless, IgE ‘‘classic’’ assays, based on immunoenzymatic methods and
allergen extracts, require large volumes and are inefficient in detecting the
low amounts of IgE in NasSec.
•Microarray biochips allow simultaneous measurement of IgE against several
allergen molecules with excellent sensitivity and specificity.

microarray containing 15 HDM
allergen molecules based on the
ImmunoCAP solid-phase allergen
chip technology
Nasal Secretions of
30 adult patients
with HDM-AR and
29 nonallergic controls
3 devices used to collect NasSec
Positioning sinus pack
in the nostril

Relationship between levels (ISU) of detectable IgE to the 15 HDM molecules detected in
NasSec (y-axis), collected with FDs and SPs, and serum (x-axis) in 30 patients with AR
the microarray results in
NasSec were very predictive
for the serum results.

Relationship between levels (ISU) of detectable IgE to the 15 HDM molecules detected in
NasSec (y-axis), collected with FDs and SPs, and serum (x-axis) in 30 patients with AR
the microarray results in
NasSec were very predictive
for the serum results.
our findings may offer new perspectives for
research on ‘‘Local Allergic Rhinitis,’’ a subset
of rhinitis characterized by sIgE at the nasal
level without systemic allergy

• Rhinitis evaluation
• Rhinitis diagnosis
• Nasal challenge

United
Airways
Rhinitis and laryngitis
comorbidities

United
Airways
Rhinitis and asthma
comorbidities

Allergen sensitization affected the change trend of
prevalence of symptoms of rhinitis coexisting with wheeze
among adolescents in Guangzhou City from 1994 to 2009
Y Chen, PAI 2017;28:340-347
 6928 adolescents aged
13–14 years in 2009
using ISAAC in China.
 2531 assessed by skin
prick test in 2010.
 Compared to those
obtained in the
Phase I (1994/95) and
III (2001/02)
ISAAC studies.
•Skin index (SI) was calculated by the ratio of
weal diameter of each allergen to that induced
by histamine, and graded by following criteria:
0: SI = 0; 1: 0 < SI < 0.5; 2: 0.5 ≤ SI<1.0;
3: 1.0 ≤ SI < 2.0; 4: SI ≥ 2.0.
•The degree of atopy was graded by atopic
index (AI) which was the sum of the number
of the allergens
that give a positive response plus the largest
skin weal size (1 ≤ 4 mm, 2 ≥ 4 mm).
AI 0 was considered as normal,
2 and 3 as mild,
4 and 5 as moderate,
and ≥6 as severe.

Y Chen, PAI 2017;28:340-347
13–14 years in 2009
prick test in 2010.
obtained in the
III (2001/02)
ISAAC studies.
Prevalence of current symptoms
of rhino-conjunctivitis
8.7%
11.1% 10.4%
1994 2001 2009
15 –
10 –
05 –
00
P<0.001 ns

Y Chen, PAI 2017;28:340-347
Prevalence of symptoms
of rhinitis and current wheeze
3.4%
4.8%
5.9%
1994 2001 2009
15 –
10 –
05 –
00
P<0.001
13–14 years in 2009
prick test in 2010.
obtained in the
III (2001/02)
ISAAC studies.
P<0.05

Y Chen, PAI 2017;28:340-347
Prevalence of degree of allergen sensitivity in children of the surveys in 2002 and 2010

Y Chen, PAI 2017;28:340-347
Prevalence of degree of allergen sensitivity in children of the surveys in 2002 and 2010
The sensitization rate to common inhaled allergens
was higher in 2010 than in 2002 (p < 0.001).

Y Chen, PAI 2017;28:340-347
In subjects sensitized to
house dust mites OR of
2.86
7.43
P<0.001
8.0 –
7.0 –
6.0 –
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
Symptoms
of rhinitis
Symptoms
of rhinitis
+ wheeze
13–14 years in 2009
prick test in 2010.
obtained in the
III (2001/02)
ISAAC studies.

Y Chen, PAI 2017;28:340-347
In subjects sensitized to
house dust mites OR of
2.86
7.43
P<0.001
8.0 –
7.0 –
6.0 –
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
Symptoms
of rhinitis
Symptoms
of rhinitis
+ wheeze
13–14 years in 2009
using ISAAC.
prick test in 2010.
obtained in the Phase I
(1994/95) and
III (2001/02)
ISAAC studies.
The prevalence of
symptoms of rhinitis and
coexistence with
wheezing has increased
significantly since 1994.
Sensitization to HDMs is
the main risk factor
associated with this
increase.

Subclinical lower airways correlates of chronic allergic
and non-allergic rhinitis
RJ Saranz, CEA 2017;47:988-997
• The upper and lower airways behave as a physiological and pathophysiological unit.
• Subclinical lower airways abnormalities have been described in patients with
rhinitis without asthma.
• These are expressed as bronchial hyperreactivity, abnormalities in lung function
and bronchial inflammation, likely as a result of the same phenomenon with
systemic inflammatory impact that reaches both the nose and the lungs, which
for unknown reasons does not always have a full clinical expression.
• Patients with rhinitis are at increased risk of developing asthma; therefore, most
authors suggest a careful clinical evaluation and monitoring of these patients,
especially if symptoms related to inflammation in the lower airways are observed.

RJ Saranz, CEA 2017;47:988-997
Frequency of spirometric abnormalities among patients with allergic rhinitis
Reference N
Rhinitis
phenotype
Age
Lung function
abnormality
prevalence
More affected spirometric
parameter
Ciprandi et al. [38] 392 P—S 20-49* 87% FEF25-75% (<80%)
Mohammad et al. [41] 60 P—S 28±9** 16.2% FEF25-75% (<65%)
Ciprandi et al. [42] 1469 P—S 18-48* 17.8% FEF25-75% (<65%)
Ianiero et al. [43] 84 P—S 6-18* 25% FEV1/FVC (<80%)
Kessel [44] 202 P—S 11.6±3.4** 26.3% FEF25-75% (<80%)
N, Number; P, Perennial; E, Seasonal;* Years (range); **Years (mean±DS); FEF25-75%: Forced expiratory flow between 25 and 75%
of vital capacity; FEV1/FVC: ratio between forced expiratory volume in the first second of the forced vital capacity and the forced
vital capacity.

RJ Saranz, CEA 2017;47:988-997
Proposed evolutionary model from rhinitis to asthma

The sensitization pattern differs according to rhinitis
and asthma multimorbidity in adults: the EGEA study
E Burte, CEA 2017;47:520-529
 1199 adults with
extensive phenotypic
characterization.
 SPTs to 10 allergens,
total IgE and blood
eosinophils.
Number of (+) SPT according to the group
and percentage of polysensitization

E Burte, CEA 2017;47:520-529
 1199 adults with
extensive phenotypic
characterization.
 SPTs to 10 allergens,
total IgE and blood
eosinophils.
Number of (+) SPT according to the group
and percentage of polysensitization65% of the
participants with
asthma+allergic
rhinitis were
polysensitized.
65%
Allergic Rhinitis
+
Polysensitization
Spirometry
with reversibility

Rate of allergic sensitization to the 10 allergens according to the group
E Burte, CEA 2017;47:520-529

• The Asthma Control Test (ACT) and the Rhinitis Control Assessment
Test (RCAT) are 2 brief, valid measures that can be used to monitor
the assessment of patient control of these respective conditions.
• Children and adults with asthma are frequently noted to have comorbid
allergic or chronic (nonallergic) rhinitis and vice-versa.
• Therefore, optimal asthma control could be difficult in the setting
of uncontrolled rhinitis.
Influence of rhinitis control and inspiratory loop
flattening on perceived asthma control
R Wilson, Ann Allergy Asthma Immunol. 2017;119:387-389

• The ACT is a validated outcome measure to help predict who
is at future risk of severe asthma exacerbations.
• An ACT score < 19 corresponds to poor control and
a score < 15 corresponds to exceptionally poor control,
whereas an ACT score 23 indicates good control.
• The 6-item RCAT (is a validated rhinitis patient-reported scoring
measure with a score >21 indicating good rhinitis control).

 Retrospectively reviewed
251 pediatric and adult patients.
 ACT and RCAT score.
 spirometry flow volume inspiratory
loops for evidence of flattening
indicative of variable inspiratory
obstruction that suggested
extrathoracic causes of symptoms

Rhinitis Control Assessment Test (RCAT)

• High ACT score was
associated with a higher
predicted RCAT score.
• No individual ACT items
were predictive of
inspiratory loop flattening.
• Neither ACT nor RCAT
score was asso-ciated with
inspiratory loop flattening.

 We found limited value in the interpretation of inspiratory loop
flattening on the performance of the ACT or RCAT.
 This is an important negative finding that will influence clinical
management at our center, de-emphasizing this parameter when
interpreting these indices in patients with asthma and comorbid rhinitis.
 Although theoretically such flattening could represent evidence of
variable inspiratory obstruction at the extrathoracic level,
its presence did not affect the mean score or any individual domain of
the RCAT or ACT.

Rhinitis and comorbidities
Sindrome orale allergica
pollen food syndrome

Pru p 3, a marker allergen for lipid transfer protein
sensitization also in Central Europe
N Mothes-Luksch, Allergy 2017;72:1415–1418
• In the Mediterranean area, lipid
transfer proteins (LTPs) are
important causes of plant-food
allergies often associated with
severe allergic reactions.
• Peach LTP (Pru p 3) seems to be
the primary sensitizer.
• In Central Europe, allergen
extract-based diagnosis is
often complicated by
co-sensitization to Bet v 1,
the major birch pollen allergen,
its cross-reactive food
allergens, and profilins.

Pru p 3, a marker allergen for lipid transfer protein
sensitization also in Central Europe
N Mothes-Luksch, Allergy 2017;72:1415–1418
• We investigated the role of LTP
sensitization in Central European
patients displaying strong
allergic reactions
to plant-derived food.
Our results showed that LTP
sensitization represents a risk
factor for severe allergic
symptoms in Central Europe.

• Non-specific lipid transfer protein
(LTP) is by far the most frequent
cause of primary food allergy in adults
living in the Mediterranean area
where it also induces the largest
number of food-dependent
anaphylactic reactions.
• Based on its widespread distribution
throughout the plant kingdom and on the elevated homology between LTPs
from botanically unrelated foods, LTP-sensitized patients may experience
adverse reactions upon the ingestion of a large array of plant foods.
The clinical relevance of lipid transfer protein
R Asero, CEA 2018;48:6-12

R Asero, CEA 2018;48:6-12
• LTPs resist to both heat and pepsin digestion which makes them able
to reach the intestinal tract in an unmodified form, an essential condition
to induce systemic reactions.
• Furthermore, Pru p 3, the peach LTP, seems
to pass the gut epithelium by a fast transcellular
route which is not used by other less allergenic
LTPs (LTP1), thus inducing the production
of Th2 cytokines.
• This kind of passage underlines the importance of Pru p 3 as a sensitizer.

R Asero, CEA 2018;48:6-12
Sources of LTP reported to cause clinical allergy; IgE levels towards Pru p 3 are shown when available

A new allergen family involved in pollen food-associated
syndrome: Snakin/gibberellin-regulated proteins.
Sénéchal H, J Allergy Clin Immunol. 2018 Jan;141(1):411-414.e4.
•Around the Mediterranean basin, Cupressaceae pollen
is considered as the primary cause of respiratory
allergies with symptoms of rhinoconjunctivitis,
chronic cough, and asthma.
•The pollinosis can be severe including infectious complications,
partly due to winter pathologies occurring within cypress pollinating period.
•In Southern France, a pollen food-associated syndrome
(PFAS) was described involving cypress pollen and
peach and/or citrus sensitizations inducing mainly
oral syndrome but also urticaria and angioedema.

•Up to now, the cross-reactive allergen at the basis
of this syndrome has not yet been unraveled.
•Besides the 4 groups of allergens already described in the various
Cupressaceae species, an as yet unidentified basic allergen of
14 kDa (BP14), overexpressed in Cupressus sempervirens pollen
and different from a lipid transfer protein, was found to sensitize
37% of cypress pollen allergic patients (CPAPs) in Southern France.
•The BP14 IgE epitopes are not related to cross-reactive carbohydrate
determinants and are heat resistant but destroyed under reducing
conditions.

conditions.
2 overlapping peptides of the gibberellin-regulated protein
(GRP) peamaclein (Pru p 7 from peach) were found:
R.CLKYCGICCEK.C and K.YCGICCEK.C.

14 kDa (BP14)*, overexpressed in Cupressus sempervirens pollen
conditions.
*Gibberellins (GAs) are plant hormones that regulate growth and
influence various developmental processes, including stem
elongation, germination, dormancy, flowering,
sex expression, enzyme induction, and leaf
and fruit senescence

conditions.
Furthermore, 1 very similar peptide of the GRP of
Theobroma cacao was identified:
R.CLKYCGICCK.K

•BP14 allergen from C sempervirens is cross-reactive with a member of the
snakin/GRP protein family while also displaying some specific IgE epitopes.
•Snakin/GRPs are involved in plant
development such as pollen maturation,
responses to biotic or abiotic stress,
hormone crosstalk, and redox homeostasis.
•They are small cationic polypeptides
described in flowers, vegetables,
and fruits, with 12 highly conserved
cysteins and with antimicrobial activity.

•4 snakin/GRPs (gibberellin-regulated protein*) from fruits were shown to be
allergens (www.allergen.org) :
Pru p 7 in peach,
Pun g 7 in pomegranate,
Pru m 7 in Japanese apricot
Cit s 7 in sweet orange,
•Because Pru p 7 shares more than 80% sequence identity with snakin-1 and
more than 95% with other fruit GRP allergens, BP14 in Cupressus
sempervirens pollen should be considered as the cross-reactive allergen in
the 2 documented PFAS involving peach and/or citrus.

•4 snakin/GRPs (gibberellin-regulated protein*) from fruits were shown to be
allergens (www.allergen.org) :
Pru p 7 in peach,
Pun g 7 in pomegranate,
Pru m 7 in Japanese apricot
Cit s 7 in sweet orange,
•Because Pru p 7 shares more than 80% sequence identity with snakin-1 and
more than 95% with other fruit GRP allergens, BP14 in Cupressus
sempervirens pollen should be considered as the cross-reactive allergen in
the 2 documented PFAS involving peach and/or citrus.
Snakin/GRP sensitization was reported to
be clinically associated with eyelid edema,
systemic reaction, or food-dependent exercise-induced
anaphylaxis.

•Preliminary experiments showed that patients allergic to cypress
pollen and citrus expressed IgE against cypress pollen BP14
cross-reactive with a cationic 12-kDa allergen from grapefruit.
•Therefore, snakin/GRP may represent a new diagnostic
marker of pollen food-associated syndrome (PFAS)
in addition to other allergens
such as Bet v 1–like proteins
involved in the well-studied
birch/apple syndrome.

Whether specific allergenic immunotherapy using
a BP14- containing cypress pollen extract can reduce
the food-related symptoms remains unknown for the moment
and would deserve more investigations.
With regard to allergy to Cupressaceae pollen, it has been reported that a
specific allergenic immunotherapy performed with a Japanese cedar pollen
extract led to a decrease in basophile activation to tomato
in a patient with a cedar/tomato syndrome.

• Sensitization to Act d 1
(actinidin) was detected
in 8 patients.
• This sensitization already
appeared before 1 year
of age, and its frequency
increased over time.
• Sensitization was detected
in children prior to the
first intake of kiwi.
Sensitization to microarrayed species-specific plant
components precedes that of cross-reacting allergens
C García-Ara, PAI 2017;28:288-291
 Sensitization to allergenic
components from vegetal
foods and pollens using
ISAC IgE microarray.
 59 children mean age
5 months (range 1–11)
followed for 4 years in Spain.

• Pru p 3 was the main
sensitizing component
of peach, found in 7
patients.
• 2 patients experienced
urticaria after eating
the peach with peel and
another after skin
contact with
peach peel.
C García-Ara, PAI 2017;28:288-291

• Sensitization to the species-
specific allergen of hazelnut,
Cor a 9 (11S globulin), was
predominant in this study.
• Cor a 8 (LTP) and Cor a 1 (PR10),
which appeared later, were
positive less frequently.
• Nevertheless, clinical reactivity
to hazelnut remains unknown,
as none of the patients had yet
introduced this nut into the diet.
C García-Ara, PAI 2017;28:288-291

• Sensitization to Ara h 1
and Ara h 3 was already
detected at diagnosis,
whereas reactivity to
Ara h 2 and Ara h 6
appeared later in time.
• Most of the sensitized
patients had not ever
eaten peanuts.
C García-Ara, PAI 2017;28:288-291

Ara h 2 and Ara h 6
eaten peanuts.
C García-Ara, PAI 2017;28:288-291
followed for 4 years.
IgE reactivity to Ara h 1
and Ara h 3 appeared and
disappeared earlier.
In contrast, sensitization
to Ara h 2 and Ara h 6
appeared later, which could
be related to a possible
subsequent
allergy to peanuts.

Ara h 2 and Ara h 6
eaten peanuts.
C García-Ara, PAI 2017;28:288-291
Ara h 2 and Ara h 6
have been found
to be the major
allergens for peanut-
allergic children

• Sensitization to pollens
started at 12 months
(tree pollen) and increased
over time, predominating
at 48 months.
• Phl p 1 was the most common
sensitizer among grasses.
• Pollen-allergic symptoms began
at 36 months, when three
patients complained of
rhinoconjunctivitis.
C García-Ara, PAI 2017;28:288-291

• Sensitization to pollens
started at 12 months
(tree pollen) and increased
over time, predominating
at 48 months.
• Phl p 1 was the most common
sensitizer among grasses.
• Pollen-allergic symptoms began
at 36 months, when three
patients complained of
rhinoconjunctivitis.
C García-Ara, PAI 2017;28:288-291
Identifying sensitization
to allergenic components
allows differentiating
primary sensitization
from cross-reactivity

• Sensitization to peach was
mainly due to Pru p 3,
increasing its frequency
over the study period,
and was followed by
sensitization to other LTPs
such as Art v 3 (Artemisia
vulgaris pollen) and
Jug r 3 ( walnut allergen).
C García-Ara, PAI 2017;28:288-291

C García-Ara, PAI 2017;28:288-291
Sensitization to pollen was mainly due to species-specific allergens and to a
lesser extent to cross-reactive ones. Positive sIgE to Phl p 1 indicates
primary sensitization to grass. As for trees, sensitization to Cup a 1 was the
earliest found and was often followed by sensitization to Ole e 1.
Sensitizations occurred mainly to species specific components from vegetal
foods (Act d 1, Cor a 9, Ara h 2/6, and Jug r 1), rather than cross-reactive
allergens (LTP, PR-10, profilin).
Sensitization to vegetal food components precedes sensitizations to
inhalant components (pollen).

Nasal obstructive disorders impair health-related quality
of life in adolescents with persistent allergic rhinitis:
A real-life study. M Valls-Mateus, PAI 2017;28:438-445
 142 patients (41 children,
6-11 years old and
101 adolescents, 12-17 years
old) with moderate and severe
persistent allergic rhinitis
(PER).
 After 2 months of intranasal
steroids and antihistamines,
patients were asked whether
their symptoms had improved
(yes/no) and classified
accordingly in R, responders
and NR, non-responders.
Children Adolescents
68.3%
58.5%
% non responders
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00

6-11 years old and
(PER).
Children Adolescents
68.3%
58.5%
% non responders
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
Medical treatment
failure was
associated with
worse QoL
outcomes.

6-11 years old and
(PER).
The presence of
obstructive septal deviation
(OR: 1.02, P=0.005),
obstructive turbinate hyperplasia
(OR: 1.03, P=0.0006), and
coexistence of both
(OR=2.06, P=0.001)
was associated with
worse QoL in adolescents.
A strong and highly significant
correlation was found between nasal
symptoms (visual analog scale VAS)
and QoL.

6-11 years old and
(PER).
The presence of
obstructive septal deviation
(OR: 1.02, P=0.005),
obstructive turbinate hyperplasia
(OR: 1.03, P=0.0006), and
coexistence of both
(OR=2.06, P=0.001)
was associated with
worse QoL in adolescents.
A strong and highly significant
correlation was found between nasal
symptoms (visual analog scale VAS)
and QoL.
•The presence of nasal
obstructive disorders (NOD),
particularly in adolescents, is
associated with poor QoL
outcomes.
•Assessment of NOD in
pediatric persistent allergic
rhinitis should be considered
an essential approach
to determine the response
to treatment and its impact
on patient's QoL.

Memory and multitasking performance during acute
allergic inflammation in seasonal allergic rhinitis
K Trikojat, CEA 2017;47:479-487
 Influence of seasonal
allergic rhinitis (SAR) on
memory and multitasking
performance.
 Non-medicated patients
with SAR (n = 41) and
healthy non-allergic
controls performed a
verbal learning and
memory test during
and out of symptomatic
allergy periods
(pollen vs. non-pollen
season).
• During the symptomatic allergy
period, patients showed:
(1) poorer performance in word
list-based learning (P = 0.028)
(2) a general slowing in:
processing speed (P < 0.001)
and
a shift in processing strategy
(P < 0.001) in multitasking.

K Trikojat, CEA 2017;47:479-487
• A significant negative
association was found
between learning
performance and
duration of disease
(r = −0.451, P = 0.004).
performance.
verbal learning and
memory test during
allergy periods
season).
Learningperformance
duration of disease

K Trikojat, CEA 2017;47:479-487
Total number of correctly remembered words
*P < 0.05
performance.
verbal learning and
memory test during
allergy periods
season).

Assessment of sleep disturbance
in children with allergic rhinitis
Dass K, Ann Allergy Asthma Immunol 2017;118:505-506
• Sleep disturbance significantly impairs daily living of children and
young adults with allergic rhinitis (AR) in 80% of patients.
• Sleep disturbance indicates moderate or severe AR, which has significant
implications on treatment recommendations.
• Children are more likely to exhibit
diminished school performance or
functioning at home, as opposed
to reporting frank sleep disturbance.

• Health Patient Reported Outcome Measurement Information System
(PROMIS) address:
o sleep disturbance,
o sleep-related impairment, and
o other key topics related to physical, mental, and social health.
L. Yu, Behav Sleep Med, 2011;10:6-24
• Our objective was to use several patient self-report questionnaires
to determine the optimal assessment method of disturbed sleep and
its effect on physical, mental, and social health in patients with AR.

 Patients aged 8 to 30 years
old (n = 144) with controlled
asthma.
 Completed the following
questionnaires:
• ARIA disease severity questions,
• PROMIS profile,
• modified Epworth Sleepiness
Scale (ESS),
• Pediatric Perceived Cognitive
Function/Applied Cognition–
General Concerns, and
• Sino-Nasal Outcome Test
(SNOT-22).
Adults Children
66%
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00 –
43%
% patients with sleep disturbance
(based on 1 question from ARIA
questionnaire)
with allergic rhinitis

Dangerous
excessive
daytime
sleepiness
Excessive
daytime
sleepiness
3%
Any amount
of daytime
sleepiness
% patients reporting
21%
29%
30 –
25 –
20 –
15 –
10 –
05 –
00 –
asthma.
questionnaires:
• PROMIS profile,
Scale (ESS),
(SNOT-22).

asthma.
questionnaires:
• PROMIS profile,
Scale (ESS),
(SNOT-22).
Dangerous
excessive
daytime
sleepiness
Excessive
daytime
sleepiness
3%
Any amount
of daytime
sleepiness
% patients reporting
21%
29%
30 –
25 –
20 –
15 –
10 –
05 –
00 –
24 of 64 (37.5%)
patients who reported
no sleep disturbance on
the ARIA question
had excessive or
dangerously excessive
daytime sleepiness on
the Epworth Sleepiness
Scale

dozing = sonnecchiare

• 1 question assessment of sleep disturbance is inadequate in screening
for sleep disturbance or sleep-related impairment.
• In the pediatric age group specifically, sleep disturbance can manifest
in other forms, such as:
o in peer relationships
o daytime functioning,
• PROMIS is the only tool that can assess sleep disturbance and capture
other quality-of-life measures.
Conclusions:
which are not currently assessed in ARIA.

PROMIS questionnaire

Development of short forms from the PROMIS™ sleep
disturbance and Sleep-Related Impairment item banks.
L. Yu, Behav Sleep Med, 2011;10:6-24
PROMIS Sleep Disturbance short form
Please respond to each item by marking one box per row

Risk of obstructive sleep apnea in African American
patients with chronic rhinosinusitis
JW Hui, Ann Allergy Asthma Immunol 2017;118:685-688
African American
patients vs
white patients
OR of obstructive sleep apnea
(OSA)
1.98
Patients with CRS
without nasal polyps
compared with
patients with CRS
with nasal polyps
916 patients with
chronic rhinosinusitis
(CRS).
1.63
2.0 –
1.5 –
1.0 –
0.5 –
0.0 –

 Our finding of the significant increased risk of
obstructive sleep apnea (OSA) in African Americans
adults might be specific to CRS and may be related
to genetic elements and/or environmental factors.
 Furthermore, other lifestyle risk factors for OSA,
such as smoking, which is also a major risk factor for
CRS and is more commonly practiced and sustained
into adulthood among African Americans, might be
playing a role in this increased risk.

 The association between patients with OSA and CRS
without NP seems counterintuitive to the idea that nasal
or airway crowding by nasal polyps should
worsen symptoms.
 Therefore, the association between patients with OSA
and CRS without NP seems counterintuitive to the idea
that nasal or airway crowding by nasal polyps should worsen symptoms.
 This finding suggests that the severity of CRS or degree of nasal
obstruction is not the main risk factor for OSA in CRS patients but
rather certain underlying factors making patients with CRS without NP
more prone to OSA.

Treatment of seasonal allergic rhinitis:
An evidence-based focused 2017 guideline update
MS Dykewicz, Ann Allergy Asthma Immunol 2017;119:489-511
Change in mean daytime total nasal symptom score with subgroup analysis. Lower reduction in mean score
is better. FPANS, fluticasone propionate aqueous nasal spray; SAR, seasonal allergic rhinitis.

Change in mean nighttime total nasal symptom score with subgroup analysis. Lower reduction in mean score
is better. FPANS, fluticasone propionate aqueous nasal spray; SAR, seasonal allergic rhinitis.

Adverse events. Lower reduction in reported events is better.
FPANS, fluticasone propionate aqueous nasal spray

Change in mean total nasal symptom score. Lower reduction in mean score is better.
FPANS, fluticasone propionate aqueous nasal spray

 When monotherapy is being considered, INCSs are a more effective
choice than LTRAs.
 When a patient is already taking an INCS, yet the patient's condition
is not optimally controlled, and is considering the addition of an
antihistamine, the best additional therapy is an INAH not an oral
antihistamine, (Dymista: Fluticasone + Azelastine) although the rate
of adverse effects with such combination is higher than with an INCS
alone.

• Rhinitis treatment
General considerations

Lavaggi nasali
filtri

The acceptability and tolerability of nasal douching
in children with allergic rhinitis: A systematic review.
Gutiérrez-Cardona N, Int J Pediatr Otorhinolaryngol. 2017 Jul;98:126-135.
BACKGROUND:
Allergic rhinitis (AR) is a significant issue in children.
Treatment options include allergen avoidance, pharmacotherapy and immunotherapy.
The use of nasal saline douching (NSD) in children has recently gained acceptability.
However, there is limited data regarding the acceptability and tolerability of NSD
in children with AR.
METHODS:
A search was conducted using Medline and Embase databases from January 1946
until June 2015 on the use of NSD in children aged 4-12 years with AR.
All publications identified that assessed the beneficial effects, acceptability and
tolerability were included.

 40 studies
1) Nasal saline douching (NSD) appears to be
effective, being accepted and tolerated
in the majority of children (78-100%).
2) NSD has a significant
positive impact on the quality of life
in children with allergic rhinitis.
3) When used as an adjunctive treatment
having mainly a cleansing property, NSD
potentiates the effects and may reduce
the dose required of AR medications

 40 studies
Factors that appear to influence the
acceptability and tolerability of NSD include:
1) parental and
health professionals' preconceptions,
2) characteristics of the solution (tonicity)
3) delivery system and method

 40 studies
Factors that appear to influence the
acceptability and tolerability of NSD include:
1) parental and
health professionals' preconceptions,
2) characteristics of the solution (tonicity)
3) delivery system and method
Nasal saline douching
provides an
accessible, low cost,
low morbidity, easy to
use treatment
in children with
allergic rhinitis.

Anti-histamines

Nasal corticosteroids

Symptomatic treatment of pollen-related allergic
rhinoconjunctivitis in children: randomized controlled trial
JB Wartna, Allergy 2017;72:636-644
Background
• About 12% of children are affected by allergic rhinoconjunctivitis (AR).
• Although the main symptomatic treatments are intranasal
corticosteroids (INCS) (daily or on demand) and oral antihistamines, it
remains unclear which treatment provides the best relief of symptoms.
• Therefore, this study examines whether daily use of INCS is superior
to on-demand use or to oral antihistamines on demand.

 150 children (aged 6–18 yrs)
with pollen-related AR.
 Either intranasal
corticosteroids (INCS) daily
(fluticasone propionate),
INCS on demand
(fluticasone propionate)
or oral antihistamine on
demand (levocetirizine)
for 3 months during
the grass pollen season.
30%
22%
15%
On-demand Daily Antihistamine
on-demandIntranasal
corticosteroids
ns
ns
Symptom-free days
30 –
25 –
20 –
15 –
10 –
05 –
00 –

INCS on demand
for 3 months during
30%
22%
15%
on-demandIntranasal
corticosteroids
ns
ns
Symptom-free days
30 –
25 –
20 –
15 –
10 –
05 –
00 –
Patients in the INCS
on-demand group
used on average 61%
less fluticasone than
patients in the INCS
daily group
(P < 0.0001).

INCS on demand
for 3 months during
30%
22%
15%
on-demandIntranasal
corticosteroids
ns
ns
Symptom-free days
30 –
25 –
20 –
15 –
10 –
05 –
00 –
An on-demand INCS
strategy has the
advantage of a lower
overall corticosteroid
exposure
and less costs.

We showed that daily treatment with INCS is not superior to INCS on demand or to oral
antihistamines on demand.
We give here 3 reasons why INCS on demand may be as effective as INCS daily:
 First, one of the reasons why daily use was advised is that it takes some time for INCS to
achieve maximum efficacy, that is 3–36 h after the first dosing. However, our results suggest
that this is not the case. Efficacy might well be achieved in the lower range and already after
a couple of hours.
 Second, INCS daily may introduce some degree of steroid unresponsiveness, by
downregulation of the glucocorticoid receptor, as compared to on-demand use.
 Thirdly, in this trial patients were randomized to three treatment options,
but there is no placebo group.

Montelukast
Altri off label

• Rhinitis
otherTreatments
• ITS

Allergen immunotherapy for allergic rhinoconjunctivitis:
A systematic review and meta-analysis
S Dhami, Allergy 2017;72:1597–1631
• AIT is effective in improving symptom,
medication, and combined symptom and
medication scores in patients with allergic
rhinoconjunctivitis while on treatment, and
• there is some evidence suggesting that
these benefits are maintained in relation
to symptom scores after discontinuation
of therapy.
 160 studies.

Meta-analysis of double-blind RCTs comparing symptom scores
between Subcutaneous immunotherapy (SCIT) and placebo groups
P<0.0001
S Dhami, Allergy 2017;72:1597–1631

Meta-analysis of double-blind
RCTs
comparing symptom scores
between Sublingual
immunotherapy (SLIT) and
placebo groups
P<0.0001
S Dhami, Allergy 2017;72:1597–1631

• Conjunctivitis
• Vernal conjunctivitis

Algorithm
for the
diagnosis
of ocular
allergy
Diagnostic tools in ocular allergy.
Leonardi A, Allergy. 2017 Oct;72(10):1485-1498.

Relevant signs related in clinical ocular examination

Giant papillae on the tarsal
conjunctiva in a vernal
keratoconjunctivitis (VKC)
patient (tarsal form of VKC)
Limbal Trantas dots in a VKC patient
(limbal form of VKC)

• Sinusite
Virus
Bacteria
microbioma

• Sinusite
• Pathogenesis
• Phenotypes
• Endotypes

• Sinusite
• complications

• Sinusite
• Treatment monoclonal

Westley score and clinical factors in predicting the
outcome of croup in the pediatric emergency department
Wen-Chieh Yang, Pediatr Pulmonol 2017;52:1329-1334
Background
• Westley croup score has been
generally used to assess the
severity of croup.
• This study aimed to identify the
individual factors associated with
Westley score (WS) and other
clinical factors in predicting the
outcomes in the pediatric
emergency department (PED).

 Prospectively recruited
192 patients with croup.
 Individual factors of WS,
fever, age, and the length
of hospital stay analyzed to
predict clinical outcomes.
• Cyanosis and altered consciousness
were not clinically significant even in
patients with severe croup, whereas
• retraction and air entry were the
major factors in WS for predicting
clinical outcomes.

• Patients with an initial WS <2 were
discharged home while the patients
with an initial WS ≥5 were more likely
to require to stay in the PED.

Patients with an
WS ≥6 were more
likely to be admitted
to the wards

Patients with an initial
WS of 1-2 could be
safely treated
at home
and those with initial
WS >5 required
hospitalization for
further treatment.

The ROC curve analysis of the initial Westley score to predict outcomes

• Otite
• Vedi general pediatrics

Adenoidectomia
& Tonsillectomia

What rhinitis and sinusitis and poliposis

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