What is new in general pediatrics, allergic and respiratory diseases

What is New in General Pediatrics,
Allergic & Respiratory Diseases 2017 ?
Attilio Boner
University of
Verona, Italy
attilio.boner@univr.it
Ambrosino Rosa
Caruso Federica
Clemente Maria
Dal Ben Sarah
Deganello Marco
Gasperi Emma
Gallo Giuseppe
Laus Beatrice
Mazzei Federica
Minniti Federica
Murri Virginia
Olivieri Francesca
Palma Laura
Pecoraro Luca
Piazza Vanna
Picassi Sara
Ramaroli Diego
Reghelin Giulia
Tezza Giovanna

Attilio Boner
University of
Verona, Italy
General Pediatics
Drug Allergy
Food Allergy
Atopic Dermatitis
Asthma
Allergic Rhinitis
Anaphylaxis
Urticaria & Angioedema
Infectious Respiratory Diseases

General Pediatrics: prematurity

• About 10%-12% of births occur before 37 completed weeks
of postmenstrual age. More than 95% of these “preterm infants”
survive to adulthood in most industrialized nations.
• Survival may come at the expense of future adverse health and social risks
characterized by failure to achieve optimal development or more
rapid rates of decline in cardiovascular, pulmonary,
and renal function or “accelerated aging.”
Long-Term Healthcare Outcomes of Preterm Birth:
An Executive Summary of a Conference Sponsored by
the National Institutes of Health
Raju T. J Pediatr 2017;181:309-318

Outcomes of infants born near term
Gill JV, Arch Dis Child 2017;102:194–198
Gestational age as a continuum
Prematurity is a term for the broad category of
neonates born at less than 37 weeks' gestation.

Outcomes of infants born near term
Gill JV, Arch Dis Child 2017;102:194–198
 Adult health outcomes
 The risk of disability in adulthood
(age 18–36 years) was increased by 26% for ET births
compared with that in FT controls (n=431 656) adjusted RR 1.26
 Females born LPT (34-36 weeks) are at increased
of gestational diabetes and preeclampsia
if they become pregnant.

The Timing of Planned Delivery:
Strengthening the Case for 39 Weeks. Editorial
Dolan SM, Pediatrics 2016;138:e20163088
•From an obstetric perspective,
guidelines relabeling term as
“early term” to describe 37 0/7
to 38 6/7 weeks’ gestation versus
“full term, ” which includes 39
0/7 to 40 6/7 weeks’ gestation,
emphasize the importance of the
fetal maturation that occurs until 39 weeks.
•It is important that obstetricians and pediatricians
provide a unified message to women and families that the
optimal timing of planned delivery is at least 39 weeks.

Early-term deliveries as an independent risk factor
for long-term respiratory morbidity of the offspring
Walfisch A, Pediatr Pulmonol 2017;52:198-204
Cumulative incidence of respiratory
hospitalizations in children according
to gestational age at birth
(37–38 + 6)
(39–40 + 6)
(>42 wks)
(41–41 + 6)
 All term singleton deliveries
occurring between 1991 and 2013
in Israel.
 Gestational age sub-divided into:
- early (37–38 + 6 wks’ gestation),
- full (39–40 + 6 wks’ gestation),
- late (41–41 + 6 wks’ gestation),
- and post-term (>42 wks)
ddeliveries.
 Incidence of long-term
hospitalizations
(up to the age of 18 yrs).

Body-Mass Index in 2.3 Million Adolescents
and Cardiovascular Death in Adulthood
Twig G, N Engl J Med 2016;374(25):2430-40
 Data on BMI, from 1967
through 2010 in 2.3 million
Israeli adolescents
(mean age 17.3 ±0,4 y)
 Number of deaths due to
coronary heart disease,
stroke, sudden death from
an unknown cause, or a
combination of all 3
categories by mid-2011
 2918 of 32,127 (9.1%) deaths
were from cardiovascular
causes including:
• 1497 from coronary heart
disease,
• 528 from stroke, and
• 893 from sudden death.

Twig G, N Engl J Med 2016;374(25):2430-40
BMI during adolescence and subsequent
cardiovascular mortality
 On multivariable analysis,
there was a graded
increase in the risk of
death from cardiovascular
causes and all causes that
started among participants
in the group that was
in the 50th to 74th
percentiles of BMI
(i.e., within the accepted
normal range)

Twig G, N Engl J Med 2016;374(25):2430-40
Conclusions
• A BMI in the 50th to 74th percentiles,
within the accepted normal range, during
adolescence was associated with
increased cardiovascular and all-cause
mortality during 40 years of follow-up.
• Overweight and obesity were strongly
associated with increased cardiovascular
mortality in adulthood
!

8:00 p.m.
or earlier
10%
16%
25 –
20 –
15 –
10 –
05 –
00 –
prevalence of adolescent obesity
after 8:00 p.m.
but by 9:00 p.m.
after 9:00
p.m.
Bedtimes at Pre-School Age
Bedtime in Preschool-Aged Children
and Risk for Adolescent Obesity
Anderson SE, J Pediatr. 2016;176:17-22
23%
 977 participants in the
Study of Early Child Care
and Youth Development.
 In 1995-1996, mothers
reported their preschool-
aged (mean = 4.7 years)
child's typical weekday
bedtime.
 At a mean age of 15 years,
height and weight.

0.48
for preschoolers with
early bedtimes compared
with preschoolers
with late bedtimes
OR for for
adolescent obesity
Bedtime in Preschool-Aged Children
and Risk for Adolescent Obesity
Anderson SE, J Pediatr. 2016;176:17-22
1.0 –
0.5 –
0.0 -
(8:00 p.m. or earlier)
 977 participants in the
Study of Early Child Care
and Youth Development.
 In 1995-1996, mothers
reported their preschool-
aged (mean = 4.7 years)
child's typical weekday
bedtime.
 At a mean age of 15 years,
height and weight.

Delayed high school start times later than 8:30am and
impact on graduation rates and attendance rates.
McKeever PM, Sleep Health. 2017;3(2):119-125.
SETTING:
Public high schools from 8 school districts (n=29 high schools) located
throughout 7 different states in USA.
PARTICIPANTS AND MEASUREMENTS:
A total membership of more than 30,000 high school students.
A pre-post design was used for a within-subject design, controlling for any
school-to-school difference in the calculation of the response variable.
RESULTS:
A start time of later than 8:30 am was associated with
improved attendance rates and graduation rates.

Caring for Children by Supporting Parents
Shuster MA, NEJM 2017;376(5):410
• Primary care providers are the only professionals who have ongoing
contact with virtually all young children and their parents
starting in infancy.
• They are specifically charged with teaching parents about raising healthy
children, and they serve as a resource to help parents with their
concerns and challenges related to parenting.
• Physicians can provide parents with anticipatory guidance related to
their child’s development and prepare them to respond to children’s
behaviors in ways that promote health.
• Healthy Steps for Young Children trains nonphysician
pediatric health workers to offer enhanced anticipatory guidance
and referrals through office-based interactions and home visits.

Caring for Children by Supporting Parents
Shuster MA, NEJM 2017;376(5):410
• Indeed,
physicians’ greatest
effect on the health
of children may,
at times,
be the result not
of what they do for
children, but of what
they do for parents.

A pilot study of an emotional intelligence training
intervention for a paediatric team.
Bamberger E. Arch Dis Child. 2017;102(2):159-164.
•Emotional intelligence (EI) is the individual’s ability
to perceive, understand and manage emotion and
to understand and relate effectively to others.
•EI has also been defined as
“a cross-section of interrelated emotional and social
competencies, skills and facilitators that determine
how effectively we understand and express ourselves,
understand others and relate with them
and cope with daily demands”.
Bar-On R. The Bar-On emotional quotient inventory (EQ-i): rationale, description
and psychometric properties. In: Geher G, ed. Measuring emotional intelligence:
common ground and controversy. Hauppauge, NY: Nova Science, 2004:115–45.
Bar-On R. The Bar-On model of emotional-social intelligence (ESI).
Psicothema. 2006;18(Suppl):13–25.

Emotional Intelligence (EI)
of 17 physicians and
10 nurses in paediatric ward
prospectively evaluated with
Bar-On’s EI at baseline and
after 18 months.
11 physicians who did not
undergo the intervention
served as controls.
Bar-On’s1 emotional quotient
inventory (EQ-i) was used to
measure study participants’ EI.
The EQ-i is a self-report
measure consisting of 133 items
covering what Bar-On describes
as the 5 main dimension of EI, namely
1) intrapersonal EI,
2) interpersonal EI,
3) adaptability,
4) stress management,
5) general mood.

•reduced occupational stress,
Littlejohn P. J Prof Nurs 2012;28:360–8.
Mikolajczak M, J Res Pers 2007;41:1107–17.
•enhanced interpersonal relations,
Goleman D. Emotional intelligence. New York: Random House, 2006.
Mayer JD, Annu Rev Psychol 2008;59:507–36.
•higher quality leadership,
Palmer B, Leadership Org Dev J 2001;22:5–10.
Carmeli A. J Manage Psychol 2003;18:788–813.
•better performance at both the individual and
the team levels.
Druskat VU, Harv Bus Rev 2001;79:80–91.
Hughes M, . London: John Wiley & Sons, 2009.
In the workplace,
EI
is associated with:

•The magnitude of improvement in patient
satisfaction noted above suggests
that EI interventions may offer substantial
economic utility, particularly to the extent that
enhanced satisfaction is associated with
1) reduced risk of malpractice suits,
2) better post-discharge compliance by patients.
3) enhanced hospital competitiveness.

• Loss of consciousness (LOC) is a common symptom in the pediatric
population, with as many as 15% of children presenting with at least
one syncopal event before the end of adolescence.
• LOC has a wide variety of causes. Although often benign, it may be the
manifestation of a potentially severe underlying cardiac, neurological
or metabolic disorder.
• Most parents have inadequate knowledge of first aid, and, more
generally, the level of first-aid knowledge among caregivers is low.
• The recovery position (RP) is a lateral recumbent position of the body,
into which an unconscious child must be placed
as part of first-aid treatment.
Recovery position significantly associated with a reduced
admission rate of children with loss of consciousness
Julliand S, Arch Dis Child. 2016;101:521-526

 The European Resuscitation Council Guidelines for Resuscitation
recommend that “an unconscious child whose airway is clear,
and who is breathing normally, should be turned on his side
into the recovery position”.
 The basic principle of the RP is to protect the airway;
• the mouth is downward so that fluid can drain from the patient's
airway, while
• the chin is up to keep the epiglottis open.
• arms and legs are locked to stabilise
the position of the patient.

26.2%
30 –
25 –
20 –
15 –
10 –
05 –
00 –
% cases in which
caregivers put the child
in the Recovery Position
 553 consecutive children
aged between 0 and 18 yrs
diagnosed with loss of
consciousness (LOC) at
11 paediatric emergency
departments (PEDs)
of 6 European countries.
 Data were obtained from
parental interviews,
PED reports and clinical
examination.

0.28
1.0 –
0.5 –
0.0 –
when caregivers
put the child
in the Recovery Position
OR for
p<0.0001
Hospital Admission
 553 consecutive children
aged between 0 and 18 yrs
diagnosed with loss of
consciousness (LOC) at
11 paediatric emergency
departments (PEDs)
of 6 European countries.
 Data were obtained from
parental interviews,
PED reports and clinical
examination.
(-)
(-)

 The RP is a simple manoeuvre which is
commonly recommended in first aid for
all unconscious people, in order to protect
the airway against aspiration,
which is a recognised cause of death
in patients with epilepsy.
 Ideally, everyone should be able
to position a child on his side
after Loss of Cosciousness.

 School teachers are also likely to encounter LOC in a child, but previous
studies have shown that their knowledge of emergency care is often
deficient.
 In our own study, manoeuvres other than the RP were made in 53% of
cases, and more frequently included:
• shaking,
• putting water on the face,
• slapping and blowing on the face.

Health Disparities Influence Childhood Melanoma Stage
at Diagnosis and Outcome
Hamilton EC, J Pediatr. 2016;175:182-187
• Melanoma is an aggressive cancer with an increasing incidence rate.
• Although relatively rare in children, melanoma accounts for
1%-3% of all childhood malignancies, and similar to adults, the
incidence of pediatric melanoma overall has increased by
an average of 2% per year since 1973.
• Although melanoma is most predominant in non-Hispanic white populations,
melanomas in Hispanics are thicker, present at later stage of diagnosis,
and have worse overall outcomes.
• Although melanoma incidence is generally associated with higher
socioeconomic status (SES), adult individuals with low SES present
at a more advanced stage and have higher mortality.

 All persons
aged ≤18 years
diagnosed with
melanoma
between 1995
and 2009 in
South Carolina
and Texas.
• A total of
185 adolescents
(age >10 years)
and 50 young
children
(age ≤10 years)
were identified.

3.8
Hispanics vs
non-Hispanic whites
OR for presenting with advanced disease
4.0 –
3.0 –
2.0 –
1.0 –
0.0 –
young children
vs
adolescents
2.2

General Pediatrics
Gastroenterology

Lung-gut cross-talk: evidence, mechanisms
and implications for the mucosal inflammatory diseases
Tulic MK, CEA 2016;46:519-528
• The mucosal immune system (including airway, intestinal,
oral and cervical epithelium) is an integrated network of tissues,
cells and effector molecules that protect the host from environmental
insults and infections at mucous membrane surfaces.
• The ‘common mucosal immunological system’
was originally proposed by John Bienenstock nearly 40 years ago.
• Stimulation of one mucosal compartment can directly
and significantly impact distant mucosal site.

The potential role
of house dust mite
(HDM) in lung-gut
cross-talk
Intestinal and respiratory mucosal diseases present with overlapping pathological changes and there
is a consensus in the literature that there is a shift in inflammation from the gut to the lungs.
One of the candidates which may be responsible for driving disease in both compartments is an
aero-allergen and cysteine-protease Der p1 found in house dust mite (HDM). Recently, HDM was
found in the healthy human gut mucosa where it can have detrimental effect on gut permeability
and barrier function (Tulic et al., Gut 2016;65:757-66). In healthy individuals, HDM favours production
of anti-inflammatory IL-10 whilst this is not seen in patients with irritable bowel disease (IBS).
Excessive inflammation in susceptible individuals may trigger a parallel inflammatory cascade
in distal mucosal site to initiate allergic disease.
Lung-gut cross-talk: evidence, mechanisms
and implications for the mucosal inflammatory diseases
Tulic MK, CEA 2016;46:519-528

Presence of commensal house dust mite allergen
in human gastrointestinal tract: a potential contributor
to intestinal barrier dysfunction
Tulic MK, Gut 2016;65:757-766
HDM Der p1 was detected
in the human gut:
 In colonic biopsies from healthy
patients, HDM:
• increased epithelial permeability
(p<0.001),
• reduced expression of tight-junction
proteins and mucus barrier.
 These effects were associated with
increased tumour necrosis factor
(TNF)-α and interleukin (IL)-10
production and were abolished by
cysteine-protease inhibitor (p<0.01).
 Colonic biopsies, gut fluid,
serum and stool collected
from healthy adults
during endoscopy
 Der p1 measured by ELISA

Presence of commensal house dust mite allergen
in human gastrointestinal tract: a potential contributor
to intestinal barrier dysfunction
Tulic MK, Gut 2016;65:757-766
HDM Der p1 was detected
in the human gut:
 In colonic biopsies from healthy
patients, HDM:
• increased epithelial permeability
(p<0.001),
• reduced expression of tight-junction
proteins and mucus barrier.
 These effects were associated with
increased tumour necrosis factor
(TNF)-α and interleukin (IL)-10
production and were abolished by
cysteine-protease inhibitor (p<0.01).
 Colonic biopsies, gut fluid,
serum and stool collected
from healthy adults
during endoscopy
 Der p1 measured by ELISA
HDM effects
did not require
Th2 immunity

A micronutrient-fortified young-child formula improves the
iron and vitamin D status of healthy young European children:
a randomized, double-blind controlled trial
Akkermans MD, Am J Clin Nutr. 2017;105:391-399
Background:
• Iron deficiency (ID) and vitamin D deficiency (VDD) are common
among young European children because of low dietary intakes
and low compliance to vitamin D supplementation policies.
• Milk is a common drink for young European children.
• Studies evaluating the effect of milk fortification
on iron and vitamin D status in these children are scarce.
Objective:
• We aimed to investigate the effect of a micronutrient-fortified
young-child formula (YCF) on the iron and vitamin D status
of young European children.

• Iron deficiency (ID) was
defined as
Serum Ferritin <12 μg/L
in the absence of infection
(high-sensitivity C-reactive
protein <10 mg/L) and
Vitamin D Deficiency
as 25(OH)D <50 nmol/L.
 318 children (1-3 yrs)
allocated to receive either
a micronutrient-fortified
young-child formula (YCF)
[1.2 mg Fe/100 mL;
1.7 μg (68 UI) vitamin D/100 mL]
or nonfortified cow milk (CM)
(0.02 mg Fe/100 mL;
no vitamin D) for 20 wk.
 Change from baseline
in serum ferritin (SF)
and 25(OH)D.

1 Values are means ± SDs unless
otherwise indicated.
The change from baseline in serum
ferritin and serum 25(OH)D were
analyzed while adjusting for sex and
country (stratification factors), age,
micronutrient status at baseline, and
the iron or vitamin D intake from
food and supplements (and sun
exposure in the case of vitamin D).
The iron analyses were performed in
the modified intention-to-treat
sample in which the children with an
elevated high-sensitivity C-reactive
protein were excluded to prevent
falsely elevated or normal ferritin
concentrations in the case of an
infection.
CM, cow milk;
YCF, young-child formula;
25(OH), 25 hydroxyvitamin D
2 Estimated mean ± SEM
(all such values).
mean changes in iron and vitamin D status after 20 weeks intervention1

25(OH)D
<50 nmol/L
Iron
deficiency
(serum Ferritin
<12 μg/L)
In the fortified young-child formula
(YCF) group, at age 1-3 yrs, OR for
0.22
0.42
P<0.001
P=0.036
1.0 –
0.5 –
0.0 –
 318 children (1-3 yrs)
allocated to receive either
a micronutrient-fortified
young-child formula (YCF)
[1.2 mg Fe/100 mL;
1.7 μg (68 UI) vitamin D/100 mL]
or nonfortified cow milk (CM)
(0.02 mg Fe/100 mL;
no vitamin D) for 20 wk.
 Change from baseline
in serum ferritin (SF)
and 25(OH)D.

Attilio Boner
University of
Verona, Italy
General Pediatrics
Drug Allergy
Food Allergy
Asthma
Anaphylaxis

Weaning
Prevention
of food allergy

The Association of the Delayed Introduction
of Cow’s Milk with IgE-Mediated Cow’s Milk Allergies
Onizawa Y. J Allergy Clin Immunol Pract 2016;4:481-488
 A case-control study
 Retrospectively 51 patients
with IgE-Cow’s milk allergy
(IgE-CMA)
compared with 102 healthy
controls (1:2 matching) and
32 unmatched patients with
IgE-Egg Allergy (IgE-EA).
in children with cow’s milk allergy OR for
delayed (started > 1 month after birth)
or no regular cow’s milk formula
(< once daily) vs children in:
25 –
20 –
15. –
10. –
05. –
01, –
000
23.74
10.16
the Control
group
the Egg A
group

 A case-control study
 Retrospectively 51 patients
with IgE-Cow’s milk allergy
(IgE-CMA)
compared with 102 healthy
controls (1:2 matching) and
32 unmatched patients with
IgE-Egg Allergy (IgE-EA).
in children with cow’s milk allergy OR for
delayed (started > 1 month after birth)
or no regular cow’s milk formula
(< once daily) vs children in:
25 –
20 –
15. –
10. –
05. –
01, –
000
23.74
10.16
the Control
group
the Egg A
group
The early
introduction of
cow’s milk formula
is associated with
lower incidence
of IgE-CMA

 Our results support the hypothesis that early, regular, and continuous
consumption of CM formula within the first month of life prevents
IgE-CMA, which is consistent with other studies regarding the prevention
of CM, peanut, egg, cereal grain, and fish allergies.
•Katz Y. J Allergy Clin Immunol 2010;126:77-82.e1
•Saarinen KM. Clin Exp Allergy 2000;30:400-6
•Du Toit G. J Allergy Clin Immunol 2008;122:984-91
•Du Toit G. N Engl J Med 2015;372:803-13
•Koplin JJ. J Allergy Clin Immunol 2010;126:807-13
•Poole JA. Pediatrics 2006;117:2175-82
•Kull I. Allergy 2006;61:1009-15
 CM is usually introduced at an earlier age than solid foods, and
sensitization to CM may be induced earlier than sensitization to solid
foods. Therefore, immune tolerance can be promoted before the onset
of CMA, which has been reported at an average age of 2.8 to 3.5 months.
•Saarinen KM. J Allergy Clin Immunol 1999;104:457-61
•Santos A. Pediatr Allergy Immunol 2010;21:1127-34

Modifying the infant’s diet to prevent food allergy
Grimshaw K, Arch Dis Child 2017;102:179–186.
 Observational data linking delayed allergen introduction and increased
allergy rates may also be explained by the reduced intake
of immunologically active nutrients.
 Polyunsaturated fatty acids (PUFAs), antioxidants
(selenium, and vitamins A, C, E and β carotene),
vitamin D, iron, zinc and folate are of particular
interest for allergy prevention.
 Observational studies have related increased intake of omega-3 rich foods
during pregnancy, lactation and infancy with decreased risk of allergic
disease.

Modifying the infant’s diet to prevent food allergy
Grimshaw K, Arch Dis Child 2017;102:179–186.
HealthNuts study, which used a validated food allergy outcome
measure, showed that low vitamin D status may be a risk factor
for infant food allergy. Allen KJ,. J Allergy Clin Immunol 2013;131:1109–1116.
Recent research demonstrated that an infant diet
consisting of high levels of fruits, vegetables and
home prepared foods was associated with less
food allergy by the age of 2 years. Grimshaw KE, JACI 2014;133:511–19.
 It may also be due to the fact that home processed
fruits and vegetables are good sources of naturally
occurring prebiotics.

Dietary total antioxidant capacity in early school age
and subsequent allergic disease.
Gref A, Clin Exp Allergy. 2017 Epub ahead of print
2359 children from the Swedish
birth cohort BAMSE
Dietary total antioxidant capacity
(TAC) at age 8 years estimated by
combining information on the child's diet
the past 12 months from a food
frequency questionnaire with a database
of common foods analysed with the
oxygen radical absorbance capacity
method.
asthma and rhinitis was based on
questionnaires, and serum IgE antibodies
were measured at 8 and 16 years.
aOR for sensitization
to inhalant allergens
0.73
P-value for trend = 0.031
TAC of the diet for the 3rd
third compared to the 1st tertile
at age 8 years
1.0 –
0.5 –
0.0

birth cohort BAMSE
method.
aOR for
allergic asthma
0.57
1.0 –
0.5 –
0.0
at age 8 years

birth cohort BAMSE
method.
1.0 –
0.5 –
0.0
These findings
indicate that
implementing an
antioxidant-rich diet
in childhood may
contribute to the
prevention of
allergic disease.
0.57
aOR for
allergic asthma
at age 8 years

Matrix effect of baked egg tolerance in children
with Ig-E-mediated hen’s egg allergy
Miceli Sopo CS. PAI 2016;27:465-470
 54 children (1.78±3.15 yrs) with
hen’s egg allergy (IgE-HEA)
 prick- by-prick tests and open
oral food challenges (OFC)
performed with:
- baked HE within a wheat
matrix (a home-made cake,
locally called ciambellone),
- baked HE without a wheat
matrix (in the form of an
omelet, locally named frittata)
and boiled HE ciambellone
% children tollerating
88%
11.2
74%
56%
frittata boiled
HE
100 –
80 –
60 –
40 –
20 -
0.0

Matrix effect of baked egg tolerance in children
with Ig-E-mediated hen’s egg allergy
Miceli Sopo CS. PAI 2016;27:465-470
 54 children with hen’s egg
allergy (IgE-HEA)
 prick- by-prick tests and open
oral food challenges (OFC)
performed with:
- baked HE within a wheat
matrix (a home-made cake,
locally called ciambellone),
- baked HE without a wheat
matrix (in the form of an
omelet, locally named frittata)
and boiled HE ciambellone
% children tollerating
88%
11.2
74%
56%
frittata boiled
HE
100 –
80 –
60 –
40 –
20 -
0.0
Negative predictive
value of
prick-by-prick
performed with
ciambellone,
frittata, and
boiled HE
was 100%.

Cross-sensitization
pollen food
syndrome

Cluster analysis identified
5 PFS endotypes linked to
panallergen IgE sensitization:
(i) cosensitization to ≥2
panallergens
(‘multi-panallergen PFS’);
(ii–iv) sensitization to either
profilin, or nsLTP, or PR-10
(‘mono-panallergen PFS’);
(v) no sensitization to
panallergens
(‘no-panallergen PFS’).
Endotypes of pollen-food syndrome in children with
seasonal allergic rhinoconjunctivitis: a molecular
classification Mastrorilli C. Allergy 2016;71:1181-1191
 1271 Italian children (age 4–18 yrs)
with seasonal allergic
rhinoconjunctivitis (SAR).
 Foods triggering pollen-food
syndrome (PFS) acquired by
questionnaire.
 IgE to panallergens:
Phl p 12 (profilin), Bet v 1 (PR-10),
and Pru p 3 (nsLTP)
tested by ImmunoCAP FEIA.
*PR=pathogenesis related proteins
*
Italian Pediatric Allergy Network (I-PAN)

These endotypes showed peculiar characteristics:
1) ‘multi-panallergen PFS’: severe disease with frequent allergic
comorbidities and multiple offending foods;
2) ‘profilin PFS’ (Phl p 12) : oral allergy syndrome (OAS)
triggered by Cucurbitaceae;
3) ‘LTP PFS’ (Pru p 3): living in Southern Italy, OAS
triggered by hazelnut and peanut;
4) ‘PR-10 PFS’ (Bet v 1): OAS triggered by Rosaceae;
5) ‘no-panallergen PFS’: mild disease and OAS triggered by kiwifruit.
Endotypes of pollen-food syndrome in children with
seasonal allergic rhinoconjunctivitis: a molecular
classification Mastrorilli C. Allergy 2016;71:1181-1191
pollen-food syndrome (PFS)
Italian Pediatric Allergy Network (I-PAN)
PR=pathogenesis related proteins

 Subjects with SPTs for
birch pollen (n=114 572)
and their available SPTs
for nuts (n=50 604).
% of subjects with birch
sensitization cosensitized to
84%
hazelnut almond peanut
71%
60%
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
Cross-sensitization profiles of edible nuts
in a birch-endemic area Uotila R. Allergy 2016;71:514-521

 Subjects with SPTs for
birch pollen (n=114 572)
and their available SPTs
for nuts (n=50 604).
% of subjects with birch
sensitization cosensitized to
84%
hazelnut almond peanut
71%
60%
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
Cross-sensitization profiles of edible nuts
in a birch-endemic area Uotila R. Allergy 2016;71:514-521
The majority of
nut-sensitized patients
(71% hazelnut,
83% almond, 73% peanut)
reported
no or mild
symptoms.

70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
% patients with polysensitization
defined as sensitization
to ≥3 aeroallergens
70%
Sensitization to a nonnative plant without exposure
is a marker of panallergen sensitization
Hogan M. B. J Allergy Clin Immunol Pract 2016;4:982-984
 126 patients (2-66 years) who
attended the University of
Nevada, Reno Allergy Clinic
 Sensitization to a nonnative
tree — Syagrus romanzoffiana
(Queen Palm) — among a
population not exposed
to Queen Palm because
geographical and climatic
conditions do not support
its growth.

70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
70%
Sensitization to a nonnative plant without exposure
is a marker of panallergen sensitization
Hogan M. B. J Allergy Clin Immunol Pract 2016;4:982-984
 126 patients (2-66 years) who
attended the University of
Nevada, Reno Allergy Clinic
 Sensitization to a nonnative
tree — Syagrus romanzoffiana
(Queen Palm) — among a
population not exposed to
Queen Palm because
geographical and climatic
conditions do not support
its growth.
Queen Palm
contains a
significant amount
of profilin,
a known
panallergen
% patients with polysensitization
defined as sensitization
to ≥3 aeroallergens

Anionic surfactants and commercial detergents decrease
tight junction barrier integrity in human keratinocytes
Xian M, JACI 2016;138:890.
• The epidermis, has 2 major barrier structures:
stratum corneum and tight junctions (TJs), the
latter of which seal adjacent keratinocytes
in the stratum granulosum.
• Recent data from human and animal studies have
suggested impairment of the skin barrier
as an important mechanism in allergen sensitization.
• The emerging and popularizing of synthetic detergents
coincided with the uprising of allergic diseases after the 1950s.
• Surfactants as the main constituents of detergents can cause significant damage
to both the lipid and protein structures of the stratum corneum, alter its barrier
properties, and induce the feeling of dryness and roughness (ruvidezza).

Xian M, JACI 2016;138:890.
•The in vitro effects of
these surfactants measured
on direct cellular toxicity
by means of investigation
of lactate dehydrogenase (LDH)
release as a marker of cell death.
•Concentrations of surfactants
that do not affect the LDH
release of NHEKs after 24 hours
of treatment were considered
nontoxic and applied to ALI
cultures.
 Direct effect of surfactants on
TJs of normal human epidermal
keratinocytes (NHEKs), at air-liquid
interface (ALI) cultures of NHEKs;
 3 different classes of detergents:
1) two anionic surfactants
(Sodium dodecyl sulfate [SDS] and
sodium dodecyl benzene sulfonate
[SDBS]),
2) a cationic surfactant
(benzalkonium chloride [BZC]),
3) a nonionic surfactant
(sorbitan mono-oleate [Tween 20]).

Xian M, JACI 2016;138:890.
[SDBS]),
Effect of surfactants in nontoxic
doses on the barrier integrity of
NHEKs:
•After 72 hours of stimulation,
anionic surfactants (SDS and
SDBS) significantly decreased
transepithelial electrical
resistance (TER).
•In parallel paracellular
permeability was increased
in a dose-dependent manner on
stimulation with SDS and SDBS.

Xian M, JACI 2016;138:890.
[SDBS]),
•There was no barrier-disruptive
effect of the cationic surfactant
BZC and nonionic surfactant
Tween 20 at all nontoxic doses.
Collectively, these data
demonstrate that
anionic surfactants can break
down the TJ barrier integrity
of NHEKs.

Xian M, JACI 2016;138:890.
Anionic surfactants and detergents decreased TER and increased paracellular
flux in ALI-cultured NHEKs.
Transepithelial electrical resistance (TER) over
time in NHEKs in response to 72 hours of stimulation
with 3 mg/mL SDS, 1 mg/mL SDBS, 1 mg/mL BZC,
and 30 mg/mL Tween 20 (TW20).
Increase in dextran paracellular permeability
across NHEKs
treated with the same surfactants.
us = unstimulated
p < 0.05
p < 0.01
p < 0.05
p < 0.01
p < 0.001
cationic
surfactant
anionic
surfactant
d
e
x
t
r
a
n

Skin barrier impairment at birth predicts food allergy
at 2 years of age Kelleher MM, JACI 2016;137:1111-1116.
 Birth cohort (n= 1903);
 Transepidermal water loss
(TEWL) measured in the
early newborn period and
at 2 and 6 months of age;
 At age 2 yrs SPTs and
oral food challenges.
% children at
2 yrs with
6.27%
4.45%
7 –
6 –
5 –
4 –
3 –
2 –
1 –
0
Food
sensitization
Food allergy

4.0 –
3.0 –
2.0 –
1.0 –
0.0
2.7 3.1
1
Percentile
of TEWL at birth
25 50 75
 Birth cohort (n= 1903);
 Transepidermal water loss
(TEWL) measured in the
early newborn period and
at 2 and 6 months of age;
 At age 2 yrs SPTs and
oral food challenges.
OR for food allergy
at age 2 yrs

Conclusion
 Neonatal skin barrier dysfunction predicts FA at 2 yrs of age, supporting
the concept of transcutaneous allergen sensitization, even in infants who
do not have AD.
 TEWL could be used for stratifying
infants in the first few days of life
before development of AD or FA
for targeted intervention studies
to potentially alter the atopic march.

Does atopic dermatitis cause food allergy?
A systematic review Tsakok T, JACI 2016;137:1071-1078.
 66 studies:
18 population-based,
8 used high-risk cohorts,
and the rest comprised
patients with either
established AD or FA;
patients with AD
vs healthy control
OR for food sensitization
at 3 months of age
7.0 –
6.0 –
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
6.18
p<0.001

Is there a march from early food sensitization
to later childhood allergic airway disease?
Results from two prospective birth cohort studies
Shatha A, PAI 2017;28:30-35
 2 indipendent cohort:
the high-risk Melbourne
Atopic Cohort Study
(MACS) (n = 620) and the
population-based LISAplus
(n = 3094) in Germany
 Food sensitization assessed
at 6, 12, and 24 months
in MACS and 24 months
in LISAplus
12 months
in MACS
OR for current asthma
at age 10-12 years5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
24 months
in LISA plus
2.2
4.9
Sensitization to food

Is there a march from early food sensitization
to later childhood allergic airway disease?
Results from two prospective birth cohort studies
Shatha A, PAI 2017;28:30-35
16 –
14 –
12 –
10 –
8.0 –
6.0 –
4.0 –
2.0 –
0.0
OR for rhinitis
at age 10-12 years
OR for current asthma
at age 10-12 years 16 –
14 –
12 –
10 –
8.0 –
6.0 –
4.0 –
2.0 –
0.0
8.3
14.4
MACS MACS
3.9
8.1
LISAplus LISAplus
Cosensitization to food and
aeroallergen at 24 months
Cosensitization to food and
aeroallergen at 24 months

•Recent attention has been directed toward the prevention
of atopic dermatitis and atopic disease.
•Early studies have suggested that full-body application of moisturizers
for 6 to 8 months, beginning within the first few weeks of life in high risk
infants (defined as a first-degree relative with atopic dermatitis),
reduced the cumulative incidence of atopic dermatitis
in a British/US cohort (relative risk, 50%) and
a Japanese cohort (relative risk, 25%).
-Horimukai K. J Allergy Clin Immunol.
2014;134(4):824-830.
-Simpson EL. J Allergy Clin Immunol.
2014;134(4):818-823.
Cost-effectiveness of Prophylactic Moisturization
for Atopic Dermatitis Xu S. JAMA Pediatr. 2017;171(2):e163909

 the potential
cost-effectiveness of
prophylactic moisturization in
preventing atopic dermatitis in
high-risk newborns.
 average cost of total-body
moisturization using
7 common moisturizers from
birth to 6 months of age
The calculated
amount of
daily
all-body moisturizer
needed at birth was
3.6 g
per application,
which increased to
6.6 g at 6 months
of age.

 the potential
cost-effectiveness of
prophylactic moisturization in
preventing atopic dermatitis in
high-risk newborns.
 average cost of total-body
moisturization using
7 common moisturizers from
birth to 6 months of age
For a 6-month time window,
the average incremental gain
in quality-adjusted life-years
(QALYs) was cost-effective

 A matched case–control study
on incident physician-diagnosed
AD in early childhood.
 451 cases and 451 controls.
 Feeding practices
collected through an
interviewer-administered
questionnaire.
Early weaning is beneficial to prevent atopic dermatitis
occurrence in young children
Turati F. Allergy 2016;71:878-888
compared to those
exclusively breastfed
in children weaned
at 4 months OR for
0.41
1.0 –
0.5 –
0 -
atopic dermatitis
Department of Epidemiology - IRCCS Istituto di Ricerche Farmacologiche "Mario Negri",
Milan, Italy

Sample integrated treatment plan for a 4-yr-old boy with severe AD,
allergies to dust mites, and food allergies to milk, peanut, and tree nut.
Multidisciplinary interventions in the management
of atopic dermatitis LeBovidge J. JACI 2016;138:325-34
Skin Care Plan
To keep skin in control
- Bath once per day in water, unscented soap if needed
(soak entire body in water for 15 min)
- Apply pimecrolimus* to eczema areas 2x/day until clear
- Apply hydrated emolient/petrolatum to body and face
while skin still damp
*Calcineurin inhibitor choice depends on severity, location, and age.

Skin Care Plan
When skin is flaring
- Bath once per day in plain water, unscented soap if needed
(soak entire body in water for15 minutes)
- Add 1/2 cup bleach to bath water every day for 2 weeks then continue daily
bath
- Apply hydrocortisone 2.5% ointment to eczema areas 2x/day for maximum
14 days (not on face)
- Apply triamcinolone 0.1% ointment to eczema areas 2x/day for maximum
14 days (not on face)

Skin Care Plan
When skin is flaring
- Apply mupirocin to open, oozy areas 3x/day until clear
- Apply hydrated emolient/petrolatum to body and face while skin still damp
and also several times per day
-Apply wet pajamas/socks and
cover with dry pajamas/socks at bedtime
Wet dressing

Skin Care Plan
Environmental Controls
- No carpeting if possible
- If carpeting, vacuum with a hepa-filtered vacuum once a week
- Dust mite proof covers on bed and pillows
- Minimize stuffed animals and clutter/books in bedroom
- Wash bedding including stuffed animals in very hot water (>60 °C)
- Use dryer on hot setting/ no clotheslines
- Keep humidity @ < 50%

Skin Care Plan
Behavioral Strategies to Break the Itch-Scratch Cycle
- Focus on what your child CAN do when he is itchy to increase
his sense of control
- Re-apply moisturizer
- Apply a cool pack or cool wash cloth to itchy areas
- Re-direct to hands-on activities such as drawing, blocks, hand-held
electronics
- For trigger times (story hour at preschool), keep hands busy
with a stress ball
- Distract and relax with guided imagery
- Avoid saying “no scratching” a lot, as this will increase stress.

Skin Care Plan
Cooperation with Treatment
- Involve child in rubbing in moisturizer to increase control
-Play games with skincare
(draw on body with moisturizer, try to “beat your best time,”
red-light, green-light, apply moisturizer to parent first)
- Listen to audio book in tub for distraction
- Praise child for participation!

Skin Care Plan
- Nutrition Recommendations
- Read all food labels to avoid peanut, tree nut and cow’s milk.
- Continue calcium and multivitamin and vitamin D supplement
- Limit juice to no more than 4 fluid ounces (120 mL) per day
- All meals, snacks and caloric beverages should be at the table
- Send box of safe treats for special occasions at preschool
-Refer to recipes, meal ideas, snack suggestions and list of popular
specialty manufacturers provided

Attilio Boner
University of
Verona, Italy
Drug Allergy
Food Allergy
Asthma
Anaphylaxis

Cured meat intake is associated
with worsening asthma symptoms
Zhen Li, Thorax 2017;72:206-212
 French prospective EGEA
study (baseline: 2003–2007;
follow-up: 2011–2013).
 Baseline cured meat intake
(<1, 1–3.9, ≥4 servings/week)
on change in asthma symptom
score and the indirect effect
mediated by BMI.
 971 participants
(mean age 43 yrs)
OR for
worsening of asthma
cured meat intake
≥4 vs <1 serving/week
1.76
2.0 –
1.5 –
1.0 –
0.5 –
0.0 –

Cured meat intake is associated
with worsening asthma symptoms
Zhen Li, Thorax 2017;72:206-212
• Several potential mechanisms were proposed
by previous studies involving biological markers:
• First, cured meats are rich in nitrite, which may lead to nitrosative
stress and oxidative stress related lung damage and asthma.
• Second, the positive relation between cured meat intake
and C-reactive protein indicated that cured meat might increase
the systemic inflammation, which may have an influence on asthma.
• Third, the high content of salt and saturated fat in cured meat might
also contribute in part to the association with asthma, though existing
evidence has been mainly for childhood-onset asthma.

Asthma worsening factors
Smoking e-cigarettes

Prevalence of Respiratory Symptoms
is higher in e-Cigarette Users than Nonusers
Across Different Smoking Status
P < 0.001
P < 0.01
P =0.01
P =0.04 P =0.4
Electronic Cigarette Use and Respiratory Symptoms
in Chinese Adolescents in Hong Kong
Wang MP, JAMA 2016;170(1):89-91
 During 2012-2013,we
surveyed secondary 1
(US grade 7, typically
aged 12 years) to
secondary 6 (college)
students.
 Anonymous questionnaire
Hong Kong.
 45128 students.

Asthma worsening factors
Gastro esophageal reflux

6.3%
Endoscopic incidence
of inlet patch (IP)
7 –
6 –
5 –
4 –
3 –
2 –
1 –
0 –
 Consecutive patients
aged <18 years (n = 1000)
undergoing
esophagogastroduodenoscopy.
 Biopsy specimens from
inlet patch (IP) IPs
and the proximal
and distal esophagus,
stomach, and duodenum.
 Impedance and pH monitoring
(MII-pH) performed
in all symptomatic patients.
Esophageal Inlet Patch:
An Under-Recognized Cause of Symptoms in Children
Di Nardo G, J Pediatr. 2016;176:99-104

 Consecutive patients
aged <18 years (n = 1000)
undergoing
esophagogastroduodenoscopy.
 Biopsy specimens from
inlet patch (IP) IPs
and the proximal
and distal esophagus,
stomach, and duodenum.
 Impedance and pH monitoring
(MII-pH) performed
in all symptomatic patients.
asymptomatic
56%
17%
% patients with inlet patch
symptoms
clearly related
to the underlying
digestive disorder
chronic
IP-related
symptoms
27%
60 –
50 –
40 –
30 –
20 –
10 –
00 –
44% with
laryngopharyngeal symptoms
(ie dysphagia, laryngospasms,
hoarseness, globus throat
discomfort, and chronic cough)

• Multichannel intraluminal impedance and pH monitoring (M II-pH)
was positive in 10 of the 28 symptomatic patients.
• All 17 patients with inlet patch (IP)-related symptoms were
unresponsive to proton pump inhibitors and were treated with argon
plasma coagulation (APC), and all had achieved complete remission by
the 3-year follow-up.
• IP is an under-recognized cause of symptoms in children
with unexplained esophageal and respiratory symptoms.

Typical endoscopic
appearance of
inlet patch (IP)
IP treatment with
argon plasma coagulation
(APC)
Endoscopic findings
at the end of the
APC treatment

Vitamin D
Protective factors for
asthma development

Association of T-regulatory cells and CD23/CD21
expression with vitamin D in children with asthma
Chary AV Ann Allergy Asthma Immunol 2016;116:447-454
60 children (2-6 years old)
with asthma and
60 age-matched
healthy children
Treg cells and CD23/CD21
by flow cytometry
25[OH]D3 by high-performance
liquid chromatography
25(OH)D3
concentrations
in asthmatic
and control children
Correlation
of 25(OH)D3
and Treg cells.
P>0.05

Correlation of 25(OH)D3 and
B cells with CD23
(IgE receptor) expression
Correlation of 25(OH)D3 and
B cells with CD21
(IgE receptor) expression

Conclusion:
The current study found low vitamin D levels
associated with impaired Treg cell population and
high numbers of B cells with IgE receptors
(CD23 and CD21) and altered regulatory cytokines
in children with asthma, suggesting
impaired immune regulation.
IL-10

OR for asthma
Mouth breathing, another risk factor for asthma:
the Nagahama Study Izuhara Y. Allergy 2016;71:1031-1036
 Community-based
cohort study.
 Self-reporting
questionnaire on
mouth breathing.
 9804 citizens of
Nagahama, Japan.

Risk ratio of mouth breathing for sensitization to house dust mite,
blood eosinophilia (≥250/ll), and lower FEV1 (<90% predicted)
in nonasthmatics with adjustment for allergic rhinitis

Conclusion:
Mouth breathing may increase asthma morbidity, potentially through
increased sensitization to inhaled allergens, which highlights the risk
of mouth bypass breathing in the ‘one airway, one disease’ concept.
The risk of mouth breathing should be well recognized
in subjects with allergic rhinitis
and in the general population.

Early sensitization is associated with
reduced lung function from birth into adulthood
Owens L, JACI 2016;137:1605-6.
 Longitudinal birth cohort
(Perth Infant Asthma
follow-up cohort);
 Influence of early
sensitization on lung
function and respiratory
outcomes from infancy
through to early
adulthood.
 Early sensitization, defined as at least
1 positive SPT response by 12 mo of
age, was longitudinally associated with
a persistent reduction in lung function
from 1 month to 24 yrs of age when
adjusted for in utero smoke exposure
(p<.002).
 The reduction was statistically
significant for V’maxFRC at 1 mo,
FEV1/FVC ratio at 24 yrs, and both
forced expiratory flow at 25% to 75%
of forced vital capacity (FEF25-75)
and FEV1 at 6 and 24 yrs.

Early sensitization is associated with
reduced lung function from birth into adulthood
Owens L, JACI 2016;137:1605-6.
Lung function
variables and
early sensitization
(1 + SPT response
by 12 mo of age)
at each assessment
from infancy
to early adulthood.

Patterns of Growth and Decline in Lung Function
in Persistent Childhood Asthma
McGeachie MJ, N Engl J Med 2016;374:1842-52
Lung-function trajectories during the
first three decades of life
 684 children with
asthma classified
according to
4 characteristic
patterns of
lung-function
growth and decline
on the basis of
FEV1 performed
from childhood
into adulthood
 Tucson Children’s
Respiratory Study

As compared with
participants who had
a normal growth pattern,
those with a pattern of
normal growth and an
early decline had
a higher body-mass index
at enrollment
(OR, 1.39; P = 0.02),
a greater likelihood
of maternal cigarette
smoking during gestation
(OR, 2.33; P = 0.04)

Participants with the reduced-growth pattern,
as compared with those who had normal growth,
had:
• lower FEV1 values at enrollment
(OR, 0.86 per 1% change in the pred. value; P<0.001),
• a lower bronchodilator response
(OR, 0.91 per 1% change; P<0.001), and
• greater airway hyperresponsiveness
(OR, 0.61 per unit change in log-transformed milligrams per milliliter; P<0.001);
• were more likely to be male (OR, 8.18; P<0.001);
• were younger at enrollment (OR, 0.55 per year of age; P<0.001);
• had a lower level of parental education
(OR for at least a college degree vs. a lower level, 0.33; P = 0.002);
• were more likely to have vitamin D insufficiency (OR, 2.15; P = 0.03);
• received more courses of prednisone per year during the trial
(OR, 4.12 for each additional course; P = 0.03).

Participants with reduced growth and
an early decline, as compared with those who
had normal growth, had:
• lower FEV1 lung function at enrollment (OR, 0.85),
• a lower bronchodilator response (OR, 0.91), and
• increased airway hyperresponsiveness (OR, 0.66);
• were more likely to be male (OR, 3.07);
• were younger at enrollment (OR, 0.62 per year); and
• had a lower level of parental education
(OR, 0.43 for at least a college degree vs. a lower level; P = 0.01 ),
• a greater number of positive skin tests at enrollment
(OR for ≥3 positive tests vs. <3, 2.42; P = 0.03 ).

Asthma develoment risk factors
Asthma predictive symptoms
Asthma and wheezing phenotypes
A & W phenotypes and lung function
Asthma and education / action plan
Asthma aggravating factors
Asthma treatment
Asthma burden

Azithromycin for episodes with asthma-like symptoms
in young children aged 1-3 years:
a randomised, double-blind, placebo-controlled trial
Stokholm J, Lancet Respir Med 2016;4:19-26
 3-day course of azithromycin
oral solution of 10 mg/kg
per day or placebo.
 158 asthma-like episodes
in 72 children aged 1-3 years.
 79 (50%) episodes
to azithromycin and
79 (50%) to placebo).
Mean duration of the episode
after treatment
P<0.0001
7.7
days
3.4
days
10 –
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00 –
azithromycin placebo

Reduction of duration of episodes of
troublesome lung symptoms after
azithromycin treatment as a function
of episode duration before treatment
 3-day course of azithromycin
oral solution of 10 mg/kg
per day or placebo.
 158 asthma-like episodes
in 72 children aged 1-3 years.
 79 (50%) episodes
to azithromycin and
79 (50%) to placebo).
p<0·0001

• We discovered in our birth cohort, the Copenhagen Prospective Studies
on Asthma in Childhood 2000 (COPSAC2000; a previous birth cohort
of children born to mothers with asthma), that airway bacteria
(Haemophilus influenzae , Streptococcus pneumoniae , and
Moraxella catarrhalis ) and respiratory viruses (at least one of
rhinovirus, respiratory syncytial virus, coronavirus, parainfluenzavirus,
influenza virus, human metapneumovirus, adenovirus, or bocavirus) are
equally closely associated with episodes of asthma-like symptoms in the
first 3 years of life Bisgaard H, BMJ 2010; 341:c4978

 Vitamin D3 supplements
(800 IU/day) with
placebo for 2 months
in schoolchildren
with asthma.
 Vitamin D (n=54) or
placebo (n=35).
Improved control of childhood asthma with low-dose,
short-term vitamin D supplementation:
a randomized, double-blind, placebo-controlled trial
Tachimoto H. Allergy 2016;71:1001-1009
% patients with improved
GINA asthma control
at 2 months
Vit D
40 –
30 –
20 –
10 –
0
34%
Placebo
12%
p=0.015

(800 IU/day) with
in schoolchildren
with asthma.
placebo (n=35).
% patients with improved
cACT at 2 months
Vit D
60 –
50 –
40 –
30 –
20 –
10 –
0
51%
Placebo
24%
p=0.0042

% pts with a PEF rate
<80% pred. at 6 months
15%
vitamin D placebo
40 –
30 –
20 –
10 –
00
34%
p=0.032
(800 IU/day) with
in schoolchildren
with asthma.
placebo (n=35).

Future Research
Antioxidants?
(-)
(+)
Transcription factors are proteins that
bind to DNA controlling
the transcription of messenger RNA

Attilio Boner
University of
Verona, Italy
General Pediatrics
Drug Allergy
Food Allergy
Asthma
Allergic Rhinitis & Conjunctivitis
Anaphylaxis

Pathogenesis of rhinitis
Eifan AO, Clin Exp Allergy 2016;46:1139-1151
Activated/damaged
epithelial cells secrete
thymic stromal
lymphopoietin (TSLP)
and IL-33 that
activates dendritic
cells directly or
through ILC2s which
captures antigens,
migrates to the
draining lymph nodes
and presents to naive
T cells inducing
effector Th2 cells.
Decreased
epithelial barrier
function

Impaired barrier function in patients with house dust
mite–induced allergic rhinitis is accompanied by decreased
occludin and zonula occludens-1 expression
Steelant B, JACI 2016;137:1043-1053.
Air-liquid interface
cultures of primary nasal
epithelial cells of control
subjects and patients with
HDM-induced AR
TJ expression by PCR
and immunofluorescence.
Transepithelial
resistance and passage to
fluorescein isothiocyanate–
dextran 4 kDa (FD4).
P < 0.05 P < 0.05

Steelant B, JACI 2016;137:1043-1053.
Representative
immunofluorescence
staining for
occludin (green) and
ZO-1 (red)
in 8 control subjects
and
9 patients with
HDM-induced AR.
zonula occludens-1
zonula occludens-1

Steelant B, JACI 2016;137:1043-1053.
Air-liquid interface
cultures of primary nasal
epithelial cells of control
subjects and patients
withHDM-induced AR
TJ expression by PCR
and immunofluorescence.
Transepithelial
resistance and passage to
fluorescein isothiocyanate–
dextran 4 kDa (FD4).
P < 0.05 P < 0.05
Transepithelial
resistance
Transepithelial
permeability

Preservation of epithelial cell barrier function and
muted inflammation in resistance to allergic
rhinoconjunctivitis from house dust mite challenge
Sunil K, J Allergy Clin Immunol 2017;139:844-54
93 adults allergic
to house dust mites (HDMs) (M+)
and
15 nonsensitive, nonallergic (M-)
participants
3-hour exposures to aerosolized
HDM powder on 4 consecutive days
in an allergen challenge chamber
Peripheral blood
CD4+and CD8+T-cell activation*
levels initially decreased
in M- participants
versus
increased in M+ participants.
*CD4 and CD8 T cell
surface molecules play a
role in T cell recognition
and activation by binding to
their respective class II
and class I major
histocompatibility complex
(MHC) ligands on an antigen
presenting cell (APC).

In M- compared with M+
participants, genes that
promoted epidermal/epithelial
barrier function (filaggrin)
versus inflammation
(eg, chemokines) and innate
immunity (interferon) were
upregulated versus, silenced
respectively.
93 adults allergic
to house dust mites (HDMs) (M+)
and
15 nonsensitive, nonallergic (M-)
participants
3-hour exposures to aerosolized
HDM powder on 4 consecutive days
in an allergen challenge chamber

An imprint of resistance to HDM challenge
in non-atopic, non allergic adults (M-) was:
1) muted T-cell activation in the peripheral blood,
2) muted inflammatory response in the nasal compartment,
coupled with
3) up regulation of genes that promote epidermal/epithelial
cell barrier function.

 Human sinonasal epithelial
cells treated with PM10;
 Epithelial barrier disruption
was noted within 4 hours as
assessed by transepithelial
electrical resistance (TEER)
and paracellular flux
quantified by fluorescein
isothiocyanate (FITC)-
dextran leak.
HSNEC permeability assessed by TEER (A)
and FITC-dextran (B) after PM at 300 μg (A)
or 150 μg and 300 μg (B).
SNF:
sulforaphane
Air pollutant–mediated disruption of sinonasal epithelial
cell barrier function is reversed by activation
of the Nrf2 pathway London NR, JACI 2016;138:1736.
Transepithelial
resistance
Transepithelial
permeability

 We tested whether
enhancement of Nrf2 using
the activator sulforaphane
(SFN) was sufficient
to reduce PM induced
sinonasal epithelial cell
(SNEC) barrier disruption.
 SNECs were pretreated
with 10 μM SFN for
72 hours before PM
stimulation.
Sulforaphane pretreatment was
found to significantly reduce
SNEC barrier instability
as measured by both
transepithelial electrical
resistance
and
fluorescein isothiocyanate -
dextran leak

• Particulate matter (PM) directly contain redox-active chemicals
and transition metals that can generate reactive oxygen species.
• The harmful effects of outdoor PM are well established and include
premature death, and both indoor and outdoor PM have been documented
to exacerbate asthma morbidity.
• PM also has been reported to cause sinonasal inflammation with nasal epithelial
thickening and increased eosinophils in nasal lavage
and increases in proinflammatory cytokines.
• A key regulator of oxidative and environmental stress is the
transcription factor nuclear erythroid 2–related factor 2
(Nrf2). Upon activation, Nrf2 translocates to the nucleus
and facilitates expression of genes that enact a cytoprotective response.

Effect of curcumin on nasal symptoms and airflow
in patients with perennial allergic rhinitis
Wu S. Ann Allergy Asthma Immunol 2016;117:697-702
241 patients with AR
received either placebo
or oral curcumin
(500 mg/day ORGANIKA
Health products,
Richmond,British
Columbia, Canada)
for 2 months
Nasal symptoms
and nasal airflow
resistance
Effects of curcumin
on total symptom score
p<0.001
corticosteroid nasal sprays, decongestants,
and antihistamines were prepared as rescue
medications for the entire study

Effect of curcumin on nasal symptoms and airflow
in patients with perennial allergic rhinitis
Wu S. Ann Allergy Asthma Immunol 2016;117:697-702
Effects of curcumin treatment on symptom score
for sneezing, itching, rhinorrhea, obstruction.
p<0.001

Anaphylaxis induced by ingested molds
Fernandez PG. Ann Allergy Asthma Immunol 2017;118:108-122
A 22-year-old Spanish with seasonal allergic rhinitis and asthma
attributable to pollen allergy.
She developed 5 mild to moderate anaphylactic
reactions with generalized urticaria and angioedema
in the eyelids together with dyspnea
and wheezing, nausea, and occasional vomiting,
with all symptoms appearing shortly after eating
dry cured meat products or blue cheeses,
both of which she tolerated in the past.
All 5 reactions were treated in the same emergency unit with intravenous
corticosteroids, histamine-antihistamines, and inhaled salbutamol.

Anaphylaxis induced by ingested molds
Fernandez PG. Ann Allergy Asthma Immunol 2017;118:108-122
The patient currently tolerates all the ingredients listed in these
foods (pork, beef, milk, sugar, spices, pepper, garlic, ascorbic acid,
sodium nitrite, and potassium nitrite).
SPTs to pork, beef, milk, egg, and spices (parsley, mustard, oregano, pepper,
garlic, sesame, and paprika) negative.
A complete battery of test inhalant allergens was performed,
yielding a positive result with various pollens and fungi.
The wheals obtained with the fungal extracts were:
-13x11 mm with Alternaria,
-4x4 mm with Aspergillus,
-3x4 mm with Cladosporium
-10x8 mm with Penicillium

A systematic review of epinephrine degradation
with exposure to excessive heat or cold
Parish HG. Ann Allergy Asthma Immunol 2016;117:79-87
9 studies of epinephrine
in sealed syringes, vials,
or ampules in concentrations
between 1:1,000 and 1:10,000,
measured epinephrine
in samples exposed to
temperatures above and/or
below the recommended
storage temperature compared
with control samples
None of the studies
evaluating the effects
of real-world temperature
fluctuations detected
significant degradation.

A systematic review of epinephrine degradation
with exposure to excessive heat or cold
Parish HG. Ann Allergy Asthma Immunol 2016;117:79-87
9 studies of epinephrine
in sealed syringes, vials,
or ampules in concentrations
between 1:1,000 and 1:10,000,
measured epinephrine
in samples exposed to
temperatures above and/or
below the recommended
storage temperature compared
with control samples
None of the studies
evaluating the effects
of real-world temperature
fluctuations detected
significant degradation.
Temperature
excursions
in real-world
conditions may be
less detrimental
than previously
suggested.

Atopic dermatitis
3.0 –
2.0 –
1.0 –
0.0
OR for severe bronchilitis
2.72
Pre-birth cohort study of atopic dermatitis and severe
bronchiolitis during infancy Balekian DS, PAI 2016:27:413–418
A cohort of
pregnant women
enrolled during
1998–2006
(n = 5407)

• One possible mechanism for the association of Atopic Dermatitis
and severe bronchiolitis is through vitamin D status.
Vitamin D deficiency has been associated with
increased prevalence and severity of Atopic Dermatitis.
Additionally, studies have found that lower serum 25(OH)D levels
are associated with more severe lower respiratory infection.
• Another possible mechanism of the Atopic dermatitis-bronchiolitis
association is through an altered
epithelial barrier and oxidative stress.
Pre-birth cohort study of atopic dermatitis and severe
bronchiolitis during infancy Balekian DS, PAI 2016:27:413–418

Children with lower respiratory tract infections and
serum 25-hydroxyvitamin D3 levels: A case–control study
López AV, Pediatr Pulmonol 2016;51:1080-1087
 A case–control study of
70 children ages 3–60 months
from the Guatemala City
metropolitan area,
hospitalized with
community-acquired pneumonia.
 113 controls from the well-
baby/care immunization clinics.
Median serum
25-hydroxyvitamin D3 (ng/ml)
controlscases
23.2
P=0.006
30 –
25 –
20 –
15 –
10 –
05 –
00 –
27.5

Children with lower respiratory tract infections and
serum 25-hydroxyvitamin D3 levels: A case–control study
López AV, Pediatr Pulmonol 2016;51:1080-1087
OR
for vitamin D <20 ng/ml
In cases
vs controls
2.4
p=0.02
2.5 –
2.0 –
1.5 –
1.0 –
0.5 –
0.0 –
 A case–control study of
70 children ages 3–60 months
from the Guatemala City
metropolitan area,
hospitalized with
community-acquired pneumonia.
 113 controls from the well-
baby/care immunization clinics.

Vitamin D Promotes Pneumococcal Killing and Modulates
Inflammatory Responses in Primary Human Neutrophils.
Subramanian K, J Innate Immun. 2017 [Epub ahead of print]
vitamin D
upregulated pattern recognition receptors, TLR2,
and NOD2,
induced the antimicrobial human neutrophil peptides
(HNP1-3) and LL-37,
increased killing of pneumococci
Vitamin D supplementation of serum
from patients with bacterial respiratory
tract infections enhanced neutrophil killing.

Vitamin D Promotes Pneumococcal Killing and Modulates
Inflammatory Responses in Primary Human Neutrophils.
Subramanian K, J Innate Immun. 2017 [Epub ahead of print]
Moreover, vitamin D lowered inflammatory
cytokine production by infected neutrophils
via IL-4 production and the induction
of suppressor of cytokine signaling (SOCS)
proteins SOCS-1 and SOCS-3,
leading to the suppression of NF-κB signaling.
Thus, vitamin D enhances neutrophil killing
of S. pneumoniae while dampening excessive
inflammatory responses and apoptosis, suggesting that vitamin D could be
used alongside antibiotics when treating pneumococcal infections.
(-)
(+)

The Clinical Value of Deflation Cough
in Chronic Coughers with Reflux Symptoms
Lavorini F, Chest 2016;149:1467-1472
• In recent years, we have documented the occurrence
of cough-like expulsive efforts, termed “deflation cough,” (DC)
evoked by maximal lung emptying in several patients who were
referred to our clinic for pulmonary function tests.
• To provoke DC, patients need to squeeze as much air
out of their lungs as possible, for example
during a slow vital capacity maneuver.
• We also found that all patients with DC had symptoms of esophageal
origin, and that the DC was most often subjected to variable degrees
of short-lasting inhibition following administration of antireflux drugs.
• DC may also be detected in patients with esophageal symptoms
but not suffering from chronic cough.

Lavorini F, Chest 2016;149:1467-1472
Results of 24-h multichannel intraluminal impedance-pH
monitoring in chronic cough patients with (n = 40)
or without (n = 53) deflation cough (DC)
Red columns, percentage of patients in whom the results
of MII-pH were positive for acidic reflux; blue columns,
percentage of patients in whom the results of MII-pH
were either normal or positive for nonacid reflux
 157 consecutive outpatients.
 Deflation cough (DC)
assessment and 24-h
multichannel intraluminal
impedance pH (MII-pH)
monitoring.
 Patients performed 2 to 4
slow vital capacity maneuvers.

Lavorini F, Chest 2016;149:1467-1472
Results of 24-h multichannel intraluminal impedance-pH
monitoring in chronic cough patients with (n = 40)
or without (n = 53) deflation cough (DC)
 157 consecutive outpatients.
 Deflation cough (DC)
assessment and 24-h
multichannel intraluminal
impedance pH (MII-pH)
monitoring.
 Patients performed 2 to 4
slow vital capacity maneuvers.
In chronic coughers
the absence of DC
virtually excludes
acid reflux.
Red columns, percentage of patients in whom the results
of MII-pH were positive for acidic reflux; blue columns,
percentage of patients in whom the results of MII-pH
were either normal or positive for nonacid reflux

Physiotherapy, and speech and language therapy
intervention for patients with refractory chronic cough:
a multicentre randomised control trial
Chamberlain Mitchell SA, Thorax 2017;72:129–136
•Chronic cough, defined as a cough lasting > 8 weeks, is a prevalent
disorder accounting for up to 20% of respiratory outpatient clinic
referrals.
•The most common causes of cough
in a nonsmoking patient with
a normal chest radiograph
and spirometry are:
•For a significant number of patients, the cough may remain
unexplained or refractory to treatment despite extensive
investigation and therapeutic trials.
•asthma,
•gastro-oesophageal reflux disease
•rhinitis (upper airway cough syndrome).

Recent studies suggest a potential role for gabapentin, pregabalin,
amitriptyline, morphine and P2X3 receptor inhibitors,
but they are all associated with significant side effects.
Non-pharmacological therapies for refractory chronic cough are generally
delivered by physiotherapists or speech and language therapists,
and key components include:
•education,
•cough suppression techniques: breathing exercises, vocal hygiene
and hydration,
•psychoeducational counselling.

Physiotherapy, and Speech And Language Therapy Intervention (PSALTI)
1. Education
Educate patients on the cough reflex, chronic cough
and cough reflex hypersensitivity.
Explain the negative effects of repeated coughing.
Educate patients on voluntary control of cough.
2. Laryngeal hygiene and hydration
Increase frequency and volume of water and non-caffeinated
drinks. Reduce caffeine and alcohol intake.
Promote nasal breathing.
+

3. Cough control
Teach patients to identify their cough triggers.
Teach patients to use cough suppression or distraction techniques at the first sign or
sensation of the need or urge to cough such as:
•forced swallowing,
•sipping water and
•sucking sweets.
Teach patients breathing exercises:
•breathing pattern re-education promoting relaxed abdominal breathing pattern technique;
•pursed lip breathing to use to control cough.

4. Psychoeducational counselling
•Motivate patients, reiterate the techniques
and the aims of therapy.
•Behaviour modification:
to try to reduce over-awareness of the need
to cough.
•Stress and anxiety management.

Change in objective cough frequency in
physiotherapy, and speech and language therapy
intervention (PSALTI) and control groups
P=0.03
 patients with
refractory
chronic cough
 randomised to 4 weekly
1:1 sessions of either
PSALTI or
control intervention
consisting of healthy
lifestyle advice.
* Physiotherapy, and Speech and
Language Therapy Intervention
(PSALTI)
*

Change in objective cough frequency in
physiotherapy, and speech and language therapy
intervention (PSALTI) and control groups
P=0.03
 patients with
refractory
chronic cough
 randomised to 4 weekly
1:1 sessions of either
PSALTI or
control intervention
consisting of healthy
lifestyle advice.
* Physiotherapy, and Speech and
Language Therapy Intervention
(PSALTI)
*
Cough frequency
decreased by 41%
(95% CI 36% to 95%) in
PSALTI group relative
to control ( p=0.030)
The improvements
within the PSALTI
group were sustained
up to 3 months

PATIENT EDUCATION
INFORMATION SERIES
French CT, AJRCCM 2016;194,15-16
Cough
Can a cough spread infection?
Cough can be a way of spreading infection to others.
Influenza and tuberculosis are examples of infections that can be spread by
coughing infected droplets into the air. While a cold virus (the common cold)
can be passed on to others by coughing, cold viruses are much more likely
to be spread to others by hand to nose contact.
Hand-to-nose contact is when you shake hands with someone who has the
infection or touch something that has the cold virus
on it and then your touch your nose or eyes.

To help decrease the spread of infection, you should:
1.Cover your mouth and nose with a tissue when coughing or sneezing.
You don’t want to spread germs to others.
2.When a tissue is not available, cough or sneeze into your upper sleeve or elbow,
not your hands.
3.Dispose of used tissues into a waste basket.
4.Avoid spitting as it can cause a mist that may infect others.
5.Ask for and wear a facemask when entering a healthcare facility
if you are coughing or have cold symptoms.
6.Wash your hands often and for at least 20 seconds using soap and water.
7.Use an alcohol-based hand rub (sanitizer) when soap and water are not available.
PATIENT EDUCATION
INFORMATION SERIES
French CT, AJRCCM 2016;194,15-16

20° FORMAT Verona 4-5/05/2018

Grazie per la vostra
attenzione alla storia che vi
ha raccontato il mio nonno.
Ciao a tutti.
Mia Charlize Powell

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