Format 2016: what is new in allergic & diseases respiratory 2016.

What is New in Allergic & Diseases Respiratory
2016
Attilio Boner
University of
Verona, Italy
attilio.boner@univr.it
Ambrosino Rosa
Caldonazzi Federico
Caruso Federica
Casarotto Serena
Cattazzo Elena
Clemente Maria
Cogo Ilaria
Danchielli Carlotta
Di Carlo Daniela
El Mazloum Dania
Gasperi Emma
Lubrano Luigi
Olivieri Francesca
Paiola Giulia
Palma Laura
Pecoraro Luca
Ramaroli Diego
Reghelin Giulia
Tadiotto Elisa
Tezza Giovanna

What is New in Allergic & Diseases Respiratory
2016
Attilio Boner
University of
Verona, Italy
Drug Allergy
Food Allergy
Atopic Dermatitis
Asthma
Allergic Rhinitis
Anaphylaxis
Urticaria & Angioedema
Infectious Respiratory Diseases

 401 consecutive patients
with immediate (IMM)
(≤1 hour) (n = 151)
and nonimmediate (NIM)
(>1 hour) (n = 250)
reactions.
 skin prick testing
 intradermal testing
Improving the Effectiveness of Penicillin Allergy
De-labeling. Bourke J, JACI Pract 2015;3:365-374
*Penicillin VK = penicillin v potassium
*

 401 consecutive patients
with immediate (IMM)
(≤1 hour) (n = 151)
and nonimmediate (NIM)
(>1 hour) (n = 250)
reactions.
 skin prick testing
 intradermal testing
Improving the Effectiveness of Penicillin Allergy
De-labeling. Bourke J, JACI Pract 2015;3:365-374
*Penicillin VK = penicillin v potassium
*
Selective or
unrestricted
beta-lactam was
recommended
in almost 90%
overall.

 200 patients with
histories of amoxicillin
reactions.
 SPT with
20 mg/mL amoxicillin
 Challenged with
amoxicillin for
a total of 5 days.
% patients with (+) SPT
20 mg/mL amoxicillin
4.5%
(9/200)
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
Amoxicillin Allergy in Children: Five-Day Drug Provocation
Test in the Diagnosis of Nonimmediate Reactions
Mori F, Novembre E. JACI Pract 2015;3:375-380

Drug provocation tests
 Children whose skin tested (-) or
tested (+) with a history of mild reactions limited to the skin
(maculopapular exanthemas – MPE - and or few hives)
underwent a 5-day drug challenge.
 On day 1, an open challenge to amoxicillin (1/10-2/10-7/10 of the
therapeutic dose [50/mg/kg/day in 2 doses] administered every
30 minutes) until the therapeutic cumulative dose was reached
or until a reaction occurred. A W Bircher, et al. Allergy; 2003; 58:854–863
 The drug provocation test (DPT) was considered positive if any objective
skin, respiratory and/or cardiovascular, neurologic, or gastrointestinal
symptoms were observed.

Drug provocation tests
 Patients were observed for 2 hours after the last drug intake if they had
a negative outcome, and 2 hours after the resolution of symptoms for any
reaction.
 If the open challenge was negative, amoxicillin was administered the day
after in 1 single dose. If this DPT was negative, daily therapeutic doses
of amoxicillin were prescribed at home for 5 days.
 Parents were advised to stop treatment and to contact us or their
primary care physician if their children experienced any reactions.
 The DPT was considered positive if any objective symptoms were
observed and documented with a picture by a physician or by parents
during the challenge or within 48 hours after the end of the antibiotic
intake.

% patients with
(+) Drug Provocation Test
9.6%
10 –
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00
reactions.
 Challenged with
amoxicillin for
a total of 5 days.
14/17 had history
of nonimmediate
reactions;
4/14 (26.6%)
reacted on day 5.
(17/200)

% patients with
(+) Drug Provocation Test
9.6%
10 –
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00
reactions.
 Challenged with
amoxicillin for
a total of 5 days.
14/17 had history
of nonimmediate
reactions;
4/14 (26.6%)
reacted on day 5.
(17/200)
According to our results,
a long-term DPT
protocol increases the
sensitivity of the allergy
work-up, and it should
be recommended for
patients with a history
of amoxicillin
nonimmediate
reaction.

7.4%
(25/337)
% (+) 5 days
Drug Provocation Test
 337 patients (2–14 yrs)
with mild-to-moderate
skin reactions.
 Retrospectively
reviewed
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00 -
Utility of skin testing in children with a history
of non-immediate reactions to amoxicillin
Barni S, Novembre E. Clin Exp Allergy 2015;45:1472-1474

7.4%
(25/337)
 337 patients (2–14 yrs)
with mild-to-moderate
skin reactions.
 Retrospectively
reviewed
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00 -
All patients who
developed a reaction
after the DPT had the
same reaction as
compared to their
reported index one,
demonstrating the
safety of this
approach.
% (+) 5 days
Drug Provocation Test

• We confirmed the little value of skin testing in the diagnosis
of non-immediate reactions to beta-lactams.
• As the DPT resulted safe and ST of little value,
it is reasonable in this group to try
Drug Provocation Test without use of the long
and expensive treatment flow chart
that is actually recommended.

Direct oral provocation tests in non-immediate mild
cutaneous reactions related to beta-lactam antibiotics
Vezir Emine. PAI 2016;27:50-54
To prevent the possibility of desensitizing the patient, the culprit drug was administered in
maximum five doses.
Patients were monitored for acute reactions for 2 h in the clinic and told to continue to use
the drug in two divided doses for 5 days at home.
Parents were instructed to come to the hospital whenever they have any reaction.
Drug provocation test
The suspected drug was given
at divided doses every 30 min,
until the full therapeutic dose is
reached.
not performed

To prevent the possibility of desensitizing the patient, the culprit drug was administered in
maximum five doses.
Patients were monitored for acute reactions for 2 h in the clinic and told to continue to use
the drug in two divided doses for 5 days at home.
Parents were instructed to come to the hospital whenever they have any reaction.
Drug provocation test
The suspected drug was given
at divided doses every 30 min,
until the full therapeutic dose is
reached.
Patients who had positive provocation test with
amoxicillin–clavulanic acid underwent provocation with
cefuroxime (Zinnat®) which has a non-cross-reactive side
chain, to determine an alternative antibiotic.
not performed

4 out of 119 patients had a positive reaction to the challenge

Conclusion
 We did not experience any severe reactions
during oral provocation test without previous
skin tests performed to children with
non-immediate mild cutaneous reactions
without systemic symptoms.
 Omitting skin tests before oral provocation test in this group of
children can help decreasing the burden of allergy clinics and
alleviating the discomfort of children.

Allergen reference doses for precautionary labeling
(VITAL 2.0): clinical implications.
Allen KJ, J Allergy Clin Immunol. 2014;133(1):156-64.
reference doses for 11
commonly allergenic foods
to guide a rational approach
by manufacturers based on
all publically available valid
oral food challenge data.
individual thresholds of
patients in a dataset of
55 studies of clinical oral
food challenges.
the eliciting dose for an allergic
reaction in 1% of the population
(ED01) estimated for the following
were:
 0.2 mg of protein for peanut,
 0.1 mg for cow's milk,
 0.03 mg for egg,
 0.1 mg for hazelnut.
These reference doses will form the basis of the
Voluntary Incidental Trace Allergen Labeling (VITAL)
2.0 thresholds now recommended in Australia.

 Understand how health
care professionals (HCPs)
currently incorporate PAL
into patient management,
and whether current
approaches (such as the
VITAL initiative) are of
value.
Allen KJ, et al.
JACI 2014; 133:156–164
 A 28-item online survey.
 161 respondents from the
UK, and Australia/New
Zealand.
% of health care professionals who
Knowledge, practice, and views on precautionary allergen labeling
for the management of patients with IgE-mediated food allergy
a survey of Australasian and UK health care professionals
Turner PJ, JACI Pract 2016;4:165-167
56%
believed that PAL
was subject to
government regulation
13%
had never heard of
the VITAL scheme
60 –
50 –
40 –
30 –
20 –
10 –
00

Discordance
between which
statements
health care
professionals
believed
indicated a real
risk of allergen
cross-
contamination,
and
what they
considered was
the best
wording for
precautionary
allergen labeling
!!!

 Our results suggest that health care professionals
(HCPs) involved in the clinical management of food-allergic
patients remain confused about PAL lack confidence and
knowledge in the current voluntary industry systems,
including VITAL.
 Although many HCPs do not recommend strict avoidance of foods
based on PAL, this was because of the current impression that PAL is
frequently used indiscriminately.

Allergen risk assessment
using probabilistic techniques
Estimation of the residual
risk after the consumption of
a product that unintentionally
contains an allergen for food
products that tested positive
in the UK Food Standards
Agency (FSA) Survey of
Allergen precautionary
allergen Labelling
Unintended allergens in precautionary labelled and
unlabelled products pose significant risks to UK allergic
consumers Remington B.C. Allergy 2015;70:813-819
The food products in the FSA survey were
combined into 20 food categories:
•apple pie, Bombay mix and trail mixes,
•breakfast oat porridge, cereal bars, corn snacks,
•cheesecakes without nuts,
•dry mix sauces and seasoning mixes,
•ham excluding parma,
•Indian ready meals, yeast extract,
•tortillas, vegetable samosas,
•vegetarian sausages, white bread rolls,
•chocolate spread without nuts,
dark chocolate, milk chocolate, white chocolate
•chewy sweets, ice lolly.

allergen Labelling
Within this selection of UK
products,
the majority that tested (+)
for an allergen
contained a concentration
of allergen predicted
to cause a reaction in
> 1 % of the allergic population

The concentrations of allergens
measured were greater than the
VITAL 2.0 action levels and would
trigger precautionary allergen
labelling.
This was found for products both
with and without precautionary
allergen labelling.
allergen Labelling

Detection of relevant amounts of cow’s milk protein in
non pre-packed bakery products sold as cow’s milk-free
Trendelenbur V. Allergy 2015;70:591–597
 Questionnaires to
200 parents of children
with a food allergy.
 Staff of 50 bakery shops
interviewed in Berlin, Germany
 Bakery products being
recommended as
“cow’s milk-free” were bought,
and cow’s milk protein levels
measured
30 –
25 –
20 –
15 –
10 –
15 –
10 -
25%
20%
Non pre-packed
food from
bakery shops
% children with
an allergic reaction due to
Ice cream
parlours

% bakery staff responding serving
food-allergic customers at least
60%
24%
84%
Once a week
Felt able to
advise food-
allergic consumers
regarding a safe
product choice
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
Once a month
recommended as
measured

 73 “cow’s milk-free”
products were sold
in 44 bakery shops.
 Cow’s milk could be
detected in
43% of the bakery
products,
21% contained
>3 mg cow’s milk protein
per serving.
(ED01 = 0.1 mg for cow's milk
according to VITAL 2.0)
recommended as
measured

Conclusion:
 Staff in bakery shops felt confident about advising
customers with food allergy.
 However, cow’s milk was detectable in almost
half of bakery products being sold as “cow’s milk-free”.
 Every fifth product contained quantities of cow’s milk
exceeding an amount where approximately
10% of cow’s milk-allergic children will show
clinical relevant symptoms.
Apollo 13
moon flight

Neonatal adiposity increases the risk of atopic
dermatitis during the first year of life
O'Donovan SM. JACI 2016;137:108-117
 Adiposity is suggested to induce systemic inflammation, which might
negatively influence the immature immune system and atopic outcomes.
 Emerging evidence has demonstrated a positive association between
adiposity, more recently central adiposity, and AD.

 Body composition analysis was performed
at day 2 and 2 months in an infant-sized air
displacement plethysmography system, the
PEA POD Infant Body Composition System
(COSMED USA, Concord, Calif), which was
developed and validated for the assessment
of infant body composition from birth to
approximately 6 months of age.

Maternal
atopy
Fat mass
≥ 80th percentile
at day 2
OR for AD at 6 and 12 mo of age
2.31
2.99
p=0.0004 p=0.009
3.0 –
2.5 –
2.0 –
1.5 –
1.0 –
0.0
 Birth cohort study (n = 1537).
 Data on early-life events,
infant feeding, and nutritional
and environmental exposures
were collected at
15 weeks' gestation, birth,
and 2, 6, and 12 months of age.
 Body composition assessed
by air displacement
plethysmography
at day 2 and 2 months.

Maternal
atopy
Fat mass
≥ 80th percentile
at day 2
OR for AD at 6 and 12 mo of age
2.31
2.99
p=0.0004 p=0.009
3.0 –
2.5 –
2.0 –
1.5 –
1.0 –
0.0
 Birth cohort study (n = 1537).
 Data on early-life events,
infant feeding, and nutritional
and environmental exposures
were collected at
15 weeks' gestation, birth,
and 2, 6, and 12 months of age.
 Body composition assessed
by air displacement
plethysmography
at day 2 and 2 months.
Emollient enhancement of the skin
barrier from birth offers effective
atopic dermatitis prevention
Simpson EL, J Allergy Clin Immunol
2014;134:818-23

OR for atopic dermatitis at 12 months
1.0
3.2
7.1
25th
(5.0 gwater/m2/h)
50th
(7.0 gwater/m2/h)
75th
(9.0 gwater/m2/h)
8.0 –
7.0 –
6.0 –
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
TEWL birth percentiles
 Skin barrier function
at day 2 after birth
and at 2 months.
 1903 infants.
 Presence of AD
at 6 and 12 months.
Skin barrier dysfunction measured by transepidermal
water loss at 2 days and 2 months predates and predicts
atopic dermatitis at 1 year.Kelleher M, JACI 2015;135:930-35

In presence of
postpartum depression
OR for AD development
1.42
2.0 –
1.0 –
0.0
Maternal psychologic problems increased the risk
of childhood atopic dermatitis
Wang IJ, Pediatr Allergy Immunology 2016;27:169–176
 24,200 mother – newborn
pairs from the Taiwan
national birth registration.
 Maternal psychologic
problems by standard
questionnaire
at 6 months old.

In presence of
1.42
2.0 –
1.0 –
0.0
questionnaire
at 6 months old.
Maternal depression may
increase cortisol levels in
offspring.
The increase in cortisol
levels can disrupt the
skin's barrier function,
leaving it vulnerable to
inflammatory disorders
such as AD.

In presence of
1.42
2.0 –
1.0 –
0.0
questionnaire
at 6 months old.
maternal stress could
operate through direct
epigenetic effects via
DNA methylation or histone
deacetylation of the
glucocorticoid receptor
(GR) gene with
neuroendocrine
dysregulation

Postpartum depression (PPD) is one of the most common complications in the
postpartum period.
Estimates of prevalence range from 13% to 19%.
Depressed mothers demonstrate less affection and fewer responses to
infant cues which may have detrimental effects on the mental development
of children.
Their infants spend more time fussing and crying, and exhibit more stress
behaviors compared with infants of mothers who are not depressed.
Elevated cortisol levels and behavioral problems were more common in
children whose mothers had postpartum and later life depression

Edinburgh postnatal
depression scale.
Cox JL. British Joural of
Psychiatry
1987;150:782-786
with a score > 10
depression is probable

Translating Atopic Dermatitis Management Guidelines
Into Practice for Primary Care Providers
Eichenfield L.F. Pediatrics 2015;136:554
Eczema action plan for pediatricians and other primary care providers
As tolerated during flare;
 direct use of
moisturizers on
inflamed skin may be
poorly tolerated;
however,
 bland petrolatum is
often tolerated when
skin is inflamed.
 Approximately 0.5 cups
sodium hypochlorite
per 40 gallons (150 L)
of water/full bathtub
or 1 mL/L.
TCI, topical calcineurin inhibitor

Improved management of childhood atopic dermatitis
after individually tailored nurse consultations: A pilot
study Rolinck-Werninghaus C, Pediatr Allergy Immunol 2015:26:805
Background:
 For optimal therapy of atopic dermatitis (AD) in children, parent
education for treatment strategies that consider the episodic
course and multiple triggers is essential. Regular consultations
with doctors often cannot appropriately provide this. Therefore,
supplemental patient education tools have been established.
 We evaluate single nurse consultations, assessing their global
benefit, parents’ selfconfidence and children’s symptoms and sleep
disturbance.

 1628 parents of children
(mean age 1.7 yrs) with AD
 Individually tailored nurse
consultation
 Consultation by telephone
14 days later
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
100 -
92.1% 95.7%
% parents that
COULD
BETTER
TRANSFER
THE
RACCOMANDATIONS
INTO
PRACTICE
WOULD
RACCOMEND
THE
INDIVIDUAL
INSTRUCTIONS
TO OTHERS
after nurse consultations

% reductions
-00
-10 –
-20 –
-30 –
-40 –
-50 -
severe
moderate
-20%
-50% -50%
Scores
for sleep
disruption
and pruritus
Symptoms

Filaggrin breakdown products determine corneocyte
conformation in patients with atopic dermatitis
Riethmuller C, JACI 2015;136:1573-1580
 Relationship between FLG genotype, filaggrin breakdown products
(natural moisturizing factor [NMF]), and corneocyte morphology.
 15 children at first presentation of AD and after 6 weeks of
standard therapy.
 Atomic force microscopy to study
corneocyte conformation
obtined by adhesive tape strips .

 Representative Atomic
force microscopy (AFM)
images of the surfaces
of corneocytes sampled
from patients with AD
with 3 different FLG
mutation genotypes.
 On simple inspection,
numbers of villus-like
projection (VPs) were
clearly increased in
carriers of FLG
mutations.
Riethmuller C,
JACI 2015;136:1573-1580
wild-type homozygote
heterozygote for
FLG LOF mutation
homozygote for
FLG LOF mutation

At first presentation
of disease and after
6 weeks of topical
therapy with skin
care regimens and
appropriate
topical steroids.
The Dermal Texture Index,
quantifies the number of
Villus-like projection
Villus-like projection Natural moisturizing factor
Atomic force microscopyDermal Texture Index
Filaggrin breakdown products determine corneocyte
conformation in patients with atopic dermatitis
Riethmuller C, JACI 2015;136:1573-1580

The nurse and the wet wrapping technique
Elan F. Rev Infirm. 2015 Oct;214:43-4.
after 2 days

Cut a facial mask from the appropriate size
- -
--
--

Filaggrin genotype and skin diseases independent
of atopic dermatitis in childhood
Bager P. Pediatr Allergy Immunol 2016;27:162–168
 Filaggrin gene (FLG)
mutations
 1547 children with
information on skin
diseases from the Danish
National Birth Cohort
and Health Register
 18 years follow-up
4 –
3 –
2 –
1 –
0 -
1.9
3.3
2.9
dry skin atopic
dermatitis
urticaria
at age < 18 mo.
In children with FLG mutation OR for

Filaggrin genotype and skin diseases independent
of atopic dermatitis in childhood
Bager P. Pediatr Allergy Immunol 2016;27:162–168
 Filaggrin gene (FLG)
mutations
 1547 children with
information on skin
diseases from the Danish
National Birth Cohort
and Health Register
 18 years follow-up
4 –
3 –
2 –
1 –
0 -
1.9
3.3
2.9
dry skin atopic
dermatitis
urticaria
at age < 18 mo.
In children with FLG mutation OR for
In clinical practice,
FLG genotyping
may help indicate
the use of
moisturizers
to reduce skin
problems

Eczema Is Associated with Childhood Speech Disorder:
A Retrospective Analysis from the National Survey of
Children's Health and the National Health Interview Survey
Strom MA, J Pediatr 2016;168:185-92
4.7%
2.2%
pooled prevalence
of speech disorder
p < 0.001
YES NO
OR= 1.81
children with eczema
 354 416
children and
adolescents
from
19 US
population-
based
cohorts

6 –
5 –
4 –
3 –
2 –
1 –
00
1.45
6.0
3.56
1.36
Mild Moderate Severe Eczema
(+) ADHDEczema severity
 354 416
children and
adolescents
from
19 US
population-
based
cohorts p=0.03 p<0.001 p<0.001
OR for speech disorder

 Some studies have
suggested that language
learning declines after
age 4 years.
 It may be that eczema
and/or other chronic
diseases impair language
learning during this critical
period, potentially resulting
in persistent language or
speech deficits.

Supporting Child Play
Moreno MA. JAMA Pediatrics 2016;170:2:184.
 Many different types of play benefit children, including playing on their
own, playing with other children, and playing with their adult caretakers.
 When a child plays independently, he or she practices
decision-making skills and discovers areas of interest.
 When children play together, without adults directly involved,
they learn to work together, negotiate, and resolve conflicts
and they learn self-advocacy skills.
 When parents observe their children in play
or join with them in child-driven play,
they get an opportunity to see the world
from their child’s point of view.
 These adult-child interactions help build strong supportive relationships.

 Television exposure has a negative impact on language
because this type of activity leads to decreased
amount and frequency of language spoken
by parents with their kids.
 Book reading has been shown to have a positive impact
on language because this activity increases experience and
exposure to language spoken by parents.
 During play with electronic toys,
there was decreased amount and frequency
of language used
between children and parents.

What Parents Can Do
 Remember that play has existed for
generations and is among the most
important “jobs” of children.
 When purchasing toys for play,
traditional non electronic toys
have the best evidence for supporting
language development and creativity.
 Enjoy playing with your child
and feel confident in the importance
of playtime.

Association between childhood eczema and headaches:
An analysis of 19 US population-based studies
Silverberg JI. JACI 2016;137:492-499
 Data from 401,002
children and adolescents
in 19 US population-
based cross-sectional
studies.
In a pooled analysis
prevalence of headaches
5.4%
10.7%
OR = 1.52
YES NO
11 –
10 –
09 –
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00
p<0.0001
children with eczema

none severemoderatemild
1.00
OR for headaches
2.14
4.91
1.83
p=0.0002 p<0.0001 p<0.0001
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
severity of eczema

 The present study demonstrates that children with
eczema and sleep disturbances have dramatically
higher rates of headaches than those with eczema alone,
although eczema alone was still associated with modestly increased rates
of headaches.
 Of note, sleep disturbances in children without eczema were also
associated with increased headaches.

 Sleep disturbances in patients with eczema have recently been found
to be associated with shorter stature1 and poor health-related quality
of life2-6 in children and poorer overall health7 increased fractures
and other injuries8, and even cardiovascular disease9 in adults.
1) Silverberg JI, JAMA Dermatol 2015;151:401–409
2) Beikert FC, Arch Dermatol Res 2014;306:279–286
3) Bender BG, JACI 2003;111:598–602
4) Hon KL, Clin Exp Dermatol 2008; 33:705–709
5) Ricci G, Pediatr Allergy Immunol 2007;18:245–249
6) Beattie PE, Br J Dermatol 206;155:1249–1255
7) Silverberg JI, J Invest Dermatol 2015;135:56–66
8) Garg N, JAMA Dermatol 2015;151:33–41
9) Silverberg JI, JACI 2015;135:721–728.e6

Attilio Boner
University of
Verona, Italy
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 tratment besides ICS
Asthma burden

Allergic sensitization is associated with inadequate
antioxidant responses in mice and men
Utsch L , Allergy 2015;70:1246–1258
Background:
•Allergies arise from aberrant Th2 responses to
allergens.
•The processes involved in the genesis of allergic
sensitization remain elusive.
Some allergens such as derived
from house dust mites have
proteolytic activity which
can induce oxidative stress in vivo.
A reduced capacity of the host to
control oxidative stress might prime
for allergic sensitization.

Utsch L , Allergy 2015;70:1246–1258
C3H/HeJ mice with a natural reduced
antioxidant response in the lungs.
House dust mites (HDM) extract with
reduced protease activity used to investigate
its role in oxidative stress induction in the
airways and whether this induction could
determine allergic sensitization and
inflammation.
Susceptibility to allergic sensitization to mite
allergens in mice was highly dependent on host
genetic background and was associated with
oxidative stress in the lungs before allergen
exposure and poor antioxidant response after
allergen exposure.
X

*4-HNE-modified proteins (4-hydroxynonenal produced by lipid peroxidation in cells) and HO-1
(heme oxygenase-1) were accessed in serum and Nrf2 was accessed in peripheral blood mononuclear cells
Utsch L , Allergy 2015;70:1246–1258
37 laboratory animal
workers were followed
for 2 years.
Occupational allergic
sensitization to rodent
urinary proteins was
monitored.
Also in human subjects,
oxidative stress before*
allergen exposure and poor
antioxidant responses
predisposition to
occupational allergy.

*4-HNE-modified proteins (4-hydroxynonenal produced by lipid peroxidation in cells) and HO-1
(heme oxygenase-1) were accessed in serum and Nrf2 was accessed in peripheral blood mononuclear cells
Utsch L , Allergy 2015;70:1246–1258
37 laboratory animal
workers were followed
for 2 years.
Occupational allergic
sensitization to rodent
urinary proteins was
monitored.
Allergic sensitization to
rodent proteins in humans
is associated with reduced
capacity to express
Nuclear factor erythroid-
derived (2Nrf2)
(-)
(+)
Also in human subjects,
oxidative stress before*
allergen exposure and poor
antioxidant responses
predisposition to
occupational allergy.

 18 blinded atopic volunteers
exposed to filtered air or
300 mg PM2.5/m3 of
diesel exhaust in random fashion
 1 h post-exposure,
diluent-controlled
segmental
allergen challenge
 2 days later, samples
by bronchoscopic lavage.
Diesel exhaust augments allergen-induced
lower airway inflammation in allergic individuals:
a controlled human exposure study
Carlsten C, Thorax 2016;71:35–44
Diesel exhaust augmented:
1) the allergen-induced
increase in airway
eosinophils,
2) IL-5 and eosinophil
cationic protein

 18 blinded atopic volunteers
exposed to filtered air or
300 mg PM2.5/m3 of
diesel exhaust in random fashion
 1 h post-exposure,
diluent-controlled
segmental
allergen challenge
 2 days later, samples
by bronchoscopic lavage.
Diesel exhaust augments allergen-induced
lower airway inflammation in allergic individuals:
a controlled human exposure study
Carlsten C, Thorax 2016;71:35–44
Diesel exhaust augmented:
1) the allergen-induced
increase in airway
eosinophils,
2) IL-5 and eosinophil
cationic protein
the GSTT1 null genotype
was significantly associated
with the augmented
IL-5 response

3.252 children from
the PIAMA birth cohort
Nocturnal dry cough
at ages 1-7 years
Doctor-diagnosed asthma
at 8 years of age
08 –
07 –
06 –
05 –
04 –
03 –
02 –
01 –
00
7.1
1.8
5 years 7 years
Nocturnal dry cough
without wheeze at age
p<0.05
p<0.05
Nocturnal dry cough in the first 7 years of life
is associated with asthma at school age
Boudewijn IM. Pediatr Pulmonol. 2015;50:848-855
OR for doctor-diagnosed asthma
at 8 years of age

30 –
25 –
20 –
15 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
3.7
3.252 children from
the PIAMA birth cohort
Nocturnal dry cough
at ages 1-7 years
Doctor-diagnosed asthma
at 8 years of age
Nocturnal dry cough in the first 7 years of life
is associated with asthma at school age
Boudewijn IM. Pediatr Pulmonol. 2015;50:848-855
1 years
nocturnal dry cough
with wheeze at age
7 years
26.0
p<0.001
p<0.001
OR for doctor-diagnosed asthma
at 8 years of age

data on respiratory
symptoms, healthcare
utilisation, medications,
spirometry, AHR, FeNO, a
atopy,
Australian birth cohort
(n = 370) recruited on the
basis of having a first-
degree relative with asthma.
Data acquired at ages
1.5–11.5 years
analysed using latent
transition analysis.
In Early Childhood (1.5 – 5 yrs)
we classified subjects into
4 phenotypes:
1) nonatopic, few symptoms,
2) atopic, few symptoms,
3) nonatopic, asthma and rhinitis
symptoms,
4) atopic, asthma and rhinitis
symptoms.
Change in the manifestations of asthma and asthma-
related traits in childhood: a latent transition analysis
Garden FL. Eur Respir J 2016;47:499–509

In Mid-Childhood (8 – 11.5 yrs)
we classified subjects into
4 phenotypes:
1) nonatopic, no respiratory disease,
2) atopic, no respiratory disease,
3) nonatopic, asthma symptoms,
no no AHR, no airway inflammation
4) Atopic asthma
data on respiratory
symptoms, healthcare
utilisation, medications,
spirometry, AHR, FeNO, a
atopy,
Australian birth cohort
(n = 370) recruited on the
basis of having a first-
degree relative with asthma.
Data acquired at ages
1.5–11.5 years
analysed using latent
transition analysis.

Phenotype prevalence and transition probabilities between the phenotypes at subsequent ages
Prevalence of each phenotype at each age is recorded in the boxes under the age heading.
The transition probabilities represent the probability that a member of a given phenotype
at a specified age will transition to another given phenotype at the next specified age.
Transition probabilities >0% are represented by arrows.
The width and shading of the arrow represents the transition probability.

Asthma phenotypes in childhood: conceptual thoughts
on stability and transition. Editorial
Spycher BD. Eur Respir J 2016;47:362–365
In their study, GARDEN et al. use cohort data to distinguish
phenotypes that not only optimally characterise the prevailing
differences between children at given ages but also allow for the
tendency of conditions to track. This is indeed novel.
They do this by fitting a latent transition model
to data on a range of asthma manifestations
measured at ages 1.5, 3, 5, 8 and 11.5 years
in children from CAPS
(Childhood Asthma Prevention Study) in Sydney, Australia.
The great advantage of this model is that it is extremely flexible and
can produce both extremes explained above plus any intermediate
form.
The Garden et al. study would suggest that
asthma is secondary to atopy in these
children.

Severe Asthma in Children:
Lessons Learned and Future Directions
Fitzpatrick AM, JACI Pract 2016;4:11-19
 Findings on severe
asthma in school-age
children (age 6-17 yrs)
from the National
Heart, Lung and Blood
Institute's Severe
Asthma Research
Program (SARP) over
a 10-year period,
between 2001 and 2011.
Blood eosinophils Serum IgE
P=0.005
P<0.001

Prevalence of aeroallergen sensitization
Severe Asthma in Children:
Lessons Learned and Future Directions
Fitzpatrick AM, JACI Pract 2016;4:11-19
 Findings on severe
asthma in school-age
children (age 6-17 yrs)
from the National
Heart, Lung and Blood
Institute's Severe
Asthma Research
Program (SARP) over
a 10-year period,
between 2001 and 2011.

Dynamics of house dust mite transfer
in modern clothing fabrics
Clarke D. Ann Allergy 2015;114:335
Background:
Clothing is largely presumed as being the mechanism by
which house dust mites are distributed among locations in homes,
yet little research to date has investigated the capacity with which
various clothing fabric types serve as vectors for their accumulation
and dispersal. Although previous research has indicated that car seats
provide a habitat for mite populations, dynamics involved in the
transfer of mites to clothing via car seat material is still unknown.
Objective:
To investigate the dynamics involved in the transfer of house dust
mites from car seat material to modern clothing fabrics.

In particular,
mean numbers of mites
transferred to fleece (pile)
(compared with denim (jeans)
and plain woven cotton)
were greater for each
treatment.
 480 samples of car seat
material seeded with mites
and subjected to contact
with plain woven cotton,
denim, and fleece.
 Contact forces equivalent
to the mass of a typical
adult and child were
administered for different
durations of contact.
>

Scanning electron micrographs of the various fabric types
used in the experiment:
car seat cover
material
(100% polyester)
plain woven
cotton
(100% Egyptian
cotton)
denim
(100% cotton)
fleece
(100% polyester)

Sensitization to cat and dog allergen molecules
in childhood and prediction of symptoms of cat
and dog allergy in adolescence: ABAMSE/MeDALL study
Asarnoj A, J Allergy Clin Immunol 2016;137:813-21
779 randomly collected
children from Stockholm
Epidemiologic birth cohort
at 4, 8, and 16 years.
IgE to cat and dog by
ImmunoCAP
Allergy defined
as reported rhinitis,
conjunctivitis, or asthma
at exposure to cat or dog.
•Polysensitization to ≥3 allergen
molecules from cat or dog was
a better longitudinal predictor
of cat or dog symptoms than
results of IgE tests with
cat or dog allergen extract.
•Cat/dog-polysensitized
children had higher IgE levels
and more frequent symptoms
to cat and dog than
monosensitized children.

Childhood wheezing phenotypes influence asthma, lung
function and exhaled nitric oxide fraction in adolescence
Duijts L, Eur Respir J 2016;47:510–519
a population-based,
prospective cohort study
of 6841 children,
latent class analysis to
identify wheezing phenotypes
during the first 7 years of life.
physician-diagnosed asthma,
spirometry and FeNO
at 14–15 years.
Henderson J, Thorax 2008; 63: 974–980.
six wheezing phenotypes identified
by latent class analysis by age 7 years

of 6841 children,
spirometry and FeNO
at 14–15 years.
Association of wheezing phenotypes with
FEV1/FVC in adolescents (14–15 years).
Data are presented as mean difference
compared with never/infrequent wheeze
standard deviation units (SDU)
*: p<0.05; **: p<0.01.

of 6841 children,
spirometry and FeNO
at 14–15 years.
Association of wheezing phenotypes with
FEV1/FVC in adolescents (14–15 years).
Data are presented as mean difference
compared with never/infrequent wheeze
standard deviation units (SDU)
*: p<0.05; **: p<0.01.
Wheezing phenotypes
were associated with
lower FEV1/FVC
Risk for COPD
development?

Compared with
never/infrequent
wheeze,
all wheezing
phenotypes were
associated with
asthma
at age 15 years
after 42 months of age
( < 3.5 yrs)
( > 5 yrs)

Compared with
never/infrequent
wheeze,
all wheezing
phenotypes were
associated with
asthma
at age 15 years
importance to try to
delay the onset of atopy
good care
of the skin
healthy diet
allergen avoidance Low pollutants
No synthetic material
exposure in early life
( < 3.5 yrs)
( > 5 yrs)

Lung-Function Trajectories Leading to Chronic
Obstructive Pulmonary Disease.
Lange P, N Engl J Med. 2015;373(2):111-22.
BACKGROUND:
Chronic obstructive pulmonary
disease (COPD) is thought to
result from an accelerated decline
FEV1 over time.
Yet it is possible that a normal
decline in FEV1 could also lead to
COPD in persons whose maximally
attained FEV1 is less than
population norms.

Of the 332 persons with COPD at
the end of the observation period
60 –
50 –
40 –
30 –
20 –
10 –
0
48%
52%
FEV1 before 40 years of age
≥80%
and had a
rapid decline
in FEV1
thereafter,
of 53±21 ml
per year*
<80%
low FEV1
in early
adulthood and
a subsequent
mean decline
in FEV1 of
27±18 ml
per year*
*P<0.001 for the decline
participants in 3 independent cohorts
stratified according to lung function
[FEV1 ≥80% (n=2207) or <80% (n=657) of
the predicted value) at cohort inception
(mean age of patients, approximately
40 years] and the presence or absence of
COPD at the last study visit.
we then determined the rate of decline
in FEV1 over time among the participants
according to their FEV1 at cohort
inception and COPD status at study end.
Follow-up: 22 years.
Lung-Function Trajectories Leading to
Chronic Obstructive Pulmonary Disease.
Lange P, N Engl J Med. 2015;373(2):111-22.

The Role of Nicotine in the Effects of Maternal Smoking
during pregnancy on lung development
and Childhood Respiratory Disease
Spindel E.R. Am J Respir Crit Care Med 2016;193:5:486-494
from control
134-day fetal monkey
from nicotine-exposed
134-day fetal monkey
α 7 nicotinic acetylcholine receptors (nAChRs) in lung stained in red
A = airway; aw = airway; c = cartilage; carti = cartilage; V = vessel

control 134-day
fetal monkey lung
nicotine-treated
134-day fetal monkey lung
Collagen III immunostaining of
A = airway; aw = airway; c = cartilage; carti = cartilage; V = vessel

control 134-day fetal monkey lung.
Masson trichrome–stained: connective tissue stained in blue
nicotine-exposed 134-day
fetal monkey lung

Treatment of pregnant
rhesus monkeys with
low levels of nicotine
designed to simulate
the nicotine exposure
of pregnant human
smokers caused
1) increases in collagen and connective tissue,
2) decreased elastin which may underlie the
decreased respiratory compliance
3) thickening of walls surrounding airways
and pulmonary vessels
4) simplification of the alveoli leading to
increased alveolar volume but decreased
alveolar surface area
This was also observed in newborn from smoking mothers

Progression to Traditional Cigarette Smoking
After Electronic Cigarette Use Among US Adolescents
and Young Adults Primack BA, JAMA Pediatr. 2015;169:1018-1023
Longitudinal cohort study
694 participants aged
16 to 26 yrs
Never cigarette smokers
and attitudinally
nonsusceptible to smoking
cigarettes
Reassessed 1 year later
2.5 –
2.0 –
1.5 –
1.0 –
0.5 –
0
% adolescent
using e-cigarettes
at baseline
2.3%

Progression to Traditional Cigarette Smoking
After Electronic Cigarette Use Among US Adolescents
and Young Adults Primack BA, JAMA Pediatr. 2015;169:1018-1023
Longitudinal cohort study
694 participants aged
16 to 26 yrs
Never cigarette smokers
and attitudinally
nonsusceptible to smoking
cigarettes
Reassessed 1 year later
yes
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
% adolescent progressing to cigarette
smoking over the 1-year follow-up
69%
OR= 8.5
19%
not
e-cigarettes user

Do the media demonstrate correct inhaler technique
in children? King D, Arch Dis Child 2016;101:203
At least 50% of patients do not use their inhalers
properly.
This is associated with asthma instability,
an increase in hospital attendances and a reduced quality of life.
The media can encourage safe health practices but
can also have negative effects on health behaviour.

The top 10 news websites
in the UK
Stories published between
2010 and 2015 concerning
childhood asthma
40 articles in which a child
was pictured receiving
inhaled therapy
8 –
7 –
6 –
5 –
4 –
3 –
2 –
1 –
0
7.5 %
% articles in which inhaler technique
was judged
as being correctly demonstrated

The top 10 news websites
in the UK
Stories published between
2010 and 2015 concerning
childhood asthma
40 articles in which a child
was pictured receiving
inhaled therapy
8 –
7 –
6 –
5 –
4 –
3 –
2 –
1 –
0
7.5 %
% articles in which inhaler technique
was judged
as being correctly demonstrated
The most commonly
demonstrated
incorrect inhaler technique
was using
a pMDI without a spacer,
which occurred in
66.7% of news articles.

Correct use of the MDI with the spacer

Action Plan
for
Asthma
treatment
health
literacy
informed,
pictogram

A Low-Literacy Asthma Action Plan to Improve Provider
Asthma Counseling: A Randomized Study
Yin H S, Pediatrics. 2016;137(1):e20150468
 119 providers were randomly assigned
(61 low literacy, 58 standard)
 Physicians at 2 academic centers
randomized to use a low-literacy or
standard action plan to counsel the
hypothetical parent of child with
moderate persistent asthma
(regimen:
-Flovent 110 μg 2 puffs twice daily,
-Singulair 5 mg daily,
-Albuterol 2 puffs every 4 hours as needed)
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
% providers more likely to use times of day
(eg, Flovent morning and night)
100 -
96.7%
p<0.001
51.7%
The low-literacy
plan
Standard plan

(regimen:
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
% providers recommend spacer use
(eg Albuterol)
83.6%
p<0.001
43.1%
The low-literacy
plan
Standard plan

(regimen:
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
% providers address need
for daily medications when sick
100 -
93.4%
p<0.001
34.5%
The low-literacy
plan
Standard plan

(regimen:
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
% providers using explicit symptoms
(eg, "ribs show when breathing," )
100 -
54.1%
p<0.001
3.4%
The low-literacy
plan
Standard plan
OR=33.0

Sleep schedules and sleep duration
for three sleep conditions
(TST = total sleep time).
Experimentally Manipulated Sleep Duration in Adolescents
With Asthma: Feasibility and Preliminary Findings
Meltzer L J. Ped Pul 2015;50:1360–1367
Self
selected
 10 adolescents with asthma
 Following a week of
self-selected sleep duration,
adolescents randomized to
a 5-night deficient sleep
opportunity (6.5 hr in bed)
or a healthy sleep
opportunity (10 hr in bed)
Wake time:
bed time:

Comparison of overnight change
in FEV1 and PEF
 10 adolescents with asthma
 Following a week of
self-selected sleep duration,
adolescents randomized to
a 5-night deficient sleep
opportunity (6.5 hr in bed)
or a healthy sleep
opportunity (10 hr in bed)

For many adolescents chronic partial sleep restriction
is behaviorally induced.
Adolescents may occasionally “pull an all-nighter”
(i.e., acute total sleep deprivation), but more typically they experience
chronically short sleep.
Growing evidence has shown the impact of chronic partial sleep
restriction on molecular, immune, and neural changes that contribute
to disease development
(e.g., cardiovascular disease, diabetes, obesity).

Hyperventilation Syndrome in Adolescents
with and without Asthma
D’Alba I, de Benedictis F M. Ped Pul 2015;50:1184–1190
 Nijmegen questionnaire
and a standardized
asthma questionnaire
 760 questionnaires
20 –
15 –
10 –
15 –
0
% children with
6.2%
15.8%
Asthma Nijmegen score
≥23,
(suggestive of HVS)

50 -
40 –
30 –
20 –
10 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
3.2
OR for hyperventilation syndrome
Hyperventilation Syndrome in Adolescents
with and without Asthma
D’Alba I, de Benedictis F M. Ped Pul 2015;50:1184–1190
females current episodic
asthma
8.9
active
asthma
41.5

Pilot randomised trial of a healthy eating behavioural
intervention in uncontrolled asthma
Ma J, Eur Respir J 2016; 47: 122–132
Asthma prevalence has increased in recent years, currently affecting
>18 million US adults.
Diet composition changes
and worsened diet quality have
been implicated as contributing
factors in this trend,
as well as poor asthma control.
Some studies have investigated the potential benefit of certain foods
(e.g. fruit, vegetables and fish) and nutrients
(e.g. vitamins C, D and E, and ω-3 fatty acids)
Vegetable and oils consumption in UK
Devereux G. JACI 2005;115(6):1109-17

The intervention was grounded in
social cognitive theory.
Interventionists used proven behaviour change
strategies (e.g. self-monitoring, action planning
and problem solving) to help participants
achieve and maintain primary DASH daily
goals adapted to their individual caloric
needs for weight maintenance:
1) 7 to 12 servings of fruit and
vegetables,
2) 2 to 4 servings of low-fat/fat-free
dairy products,
3) total fat grams at 27% of estimated
caloric needs, and
4) ⩽2300 mg of sodium.
Ma J, Eur Respir J 2016; 47: 122–132
90 adults with objectively
confirmed uncontrolled
asthma and a low-quality diet
[Dietary Approaches to Stop
Hypertension (DASH)
scores <6 out of 9]
a 6-month DASH
behavioural
intervention (n=46) or
usual-care control (n=44).

Ma J, Eur Respir J 2016; 47: 122–132
90 adults with objectively
confirmed un<controlled
asthma and a low-quality diet
[Dietary Approaches to Stop
Hypertension (DASH)
scores <6 out of 9]
a 6-month DASH
behavioural
intervention (n=46) or
usual-care control (n=44).
Compared with controls, intervention
participants improved on:
1) DASH scores (mean change difference 0.8)
2) Asthma Control Questionnaire scores
at 6 months.
3) Asthma Quality of Life:
- overall 0.4,
- symptoms 0.5,
- environment 0.4,
- emotions 0.4 and
- activities 0.3.

Ma J, Eur Respir J 2016; 47: 122–132
Study participants reported an average of 4.4 servings of
fruit and vegetables at baseline, which may be higher than
usual intake of the general US adult population, possibly due
to greater access to fruit and vegetables in California.
Generally, US adults who have lower fruit and vegetable intake may have a
higher likelihood of observing an improvement in overall diet quality with the
intervention.
This pilot trial showed, for the first time, that a DASH-promoting
behavioural intervention significantly improved diet quality with promising
clinical benefits for better asthma control and functional status among
adults with uncontrolled asthma.

The role of circulating 25 hydroxyvitamin D in asthma:
a systematic review
Cassim R. Allergy 2015;70:339-354
 Association between
serum Vitamin D and
asthma incidence, prevalence,
severity and exacerbations.
 23 manuscripts:
2 case–control, 12 cohort and
9 cross-sectional studies
 Collectively, the evidence
suggests that higher serum
levels of 25(OH)D are
associated with a reduced risk
of asthma exacerbations
(RR = 0.64)
 There was little evidence to
suggest an association with
asthma incidence, prevalence
or severity.

Vitamin D and respiratory tract infections: A systematic
review and meta-analysis of randomized controlled trials.
Bergman P, PLoS One 2013; 8:e65835
0.51
vitamin D supplemented in
OR for respiratory
tract infection
1.0 –
0.5 –
0.0
daily doses vs bolus doses
0.86
P=0.01
meta-analysis of
11 placebo-controlled
studies
5660 patients
included

0.51
OR for respiratory
tract infection
1.0 –
0.5 –
0.0
0.86
P=0.01
meta-analysis of
studies
5660 patients
included
Intermittent bolus
dosing with long lag times
(greater than 3–4 weeks)
leads to wide swings in
circulating levels of 25
OHD, which in turn leads
to dips in tissue levels of
1,25 dihydroxy D, leading
to a relative excess of
the catabolic enzyme 24
hydroxylase.

0.51
OR for respiratory
tract infection
1.0 –
0.5 –
0.0
0.86
P=0.01
meta-analysis of
studies
5660 patients
included
This mechanism has
also been suggested to
be operating in
elevating the risk for
some cancers due to
wide fluctuations in
circulating vitamin D
levels.
Weiss S.Thorax 2015;70:919-920

Serum 25-hydroxyvitamin D level,
smoking and lung function in adults: the HUNT Study
Larose TL, Eur Respir J 2015;46:355–363
 a random sample of adults
from Norway
 cross-sectional (n=1220)
and follow-up (n=869)
 interrelationship of
serum 25(OH)D, smoking
and lung function changes
50 –
40 –
30 –
20 –
10 –
0
40%
% adults with
serum 25(OH)D
levels <50 nmol·L−1
Those
showed
worse
lung
function

serum 25(OH)D levels <50 nmol·L−1
compared to > 50 nmol·L−1
OR for development of impaired
lung function (FEV1/FVC <70%)
in ever smokers
3.0 –
2.0 –
1.0 –
0.0
2.4
Serum 25-hydroxyvitamin D level,
smoking and lung function in adults: the HUNT Study
Larose TL, Eur Respir J 2015;46:355–363
 a random sample of adults
from Norway
 cross-sectional (n=1220)
and follow-up (n=869)
 interrelationship of
serum 25(OH)D, smoking
and lung function changes

 582 children aged 6 to 14 yrs
with (n = 304)
and without (n = 278) asthma.
 Folate deficiency defined
as plasma folate ≤20 ng/ml.
Folate Deficiency, Atopy, and Severe Asthma
Exacerbations in Puerto Rican Children
Blatter J, Ann Am Thorac Soc 2016;13:223-230
Mean n° of (+) SPTs
YES NO
3.8
4.9 p<0.001
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
Folate deficiency

In children with
folate deficiency OR for
at least one
severe asthma
exacerbation
2.8
2.2
p<0.01
3.0 –
2.5 –
2.0 –
1.5 –
1.0 –
0.0
p=0.04
vitamin D
insufficiency
(<30 ng/ml
reduction)
with (n = 304)

OR for at least one severe asthma
exacerbation in children with
both folate deficiency and
vitamin D insufficiency
(<30 ng/ml reduction)
7.9
8.0 –
7.0 –
6.0 –
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
with (n = 304)

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

 47 asthmatic children
(moderate-severe GINA
Guidelines) (12.01 ± 3.1 years)
admitted to Istituto Pio XII,
Misurina (m 1753)
 Supplementation for
1 mo with a mixture of
nutraceuticals: soy genistein,
curcumin, resveratrol,
vitamin D, zinc, magnesium,
selenium, folic acid (n=15) or
controls (n=32)
 FeNO expressed as median
values
9%
Anti-oxidants supplementation reduces FeNO
in children with asthma.
Tenero L. Allergy Asthma Proc. 2016;37(1):8-13.
ns
P=0.03
18
16
19
11
Controls

Impact of asthma medication and familial factors
on the association between childhood asthma
and attention-deficit/hyperactivity disorder:
a combined twin- and register-based study
Holmberg K. Clin Exper Allergy 2015;45:964–973
 20.072 twins through
the Swedish Twin Register
 association between asthma
and ADHD
 from parental questionnaires
at 9 or 12 years
ADHD
in Asthmatic children
OR for
2.0 –
1.0 –
0.0
1.53

Impact of asthma medication and familial factors
on the association between childhood asthma
and attention-deficit/hyperactivity disorder:
a combined twin- and register-based study
Holmberg K. Clin Exper Allergy 2015;45:964–973
 20.072 twins through
the Swedish Twin Register
 association between asthma
and ADHD
 from parental questionnaires
at 9 or 12 years
ADHD
in Asthmatic children
OR for
2.0 –
1.0 –
0.0
1.53
The association was not
restricted to either of the two
dimension of ADHD.
The magnitude of the association
increased with asthma severity
OR 2.84 for ≥ 4 asthma attacks
in the last 12 months
and was not affected by asthma
treatment.

The Prevalence of Sleep-Disordered Breathing in Children
with Asthma and its Behavioral Effects
N.A.Goldstein, Pediatric Pulmonology 2015;50:1128–1136
 Pediatric Sleep
Questionnaire (PSQ)
and the Child Behavior
Checklist
 263 children with
asthma and
266 controls ages
2 to 15 years
35 –
30 –
25 –
20 –
15 –
10 –
15 -
35.5%
15.7%
0
Prevalence of snoring
asthmatics controls
p<0.001

30 –
25 –
20 –
15 –
10 –
15 -
25.9%
10.6%
0
Prevalence of positive PSQ
p<0.001
 Pediatric Sleep
Questionnaire (PSQ)
Checklist
asthma and
266 controls ages
2 to 15 years
asthmatics controls

In children with (+) vs (-)
Pediatric Spleep Questionnaire
OR for
6.09
7.0 –
6.0 –
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
Internalizing problems
P < 0.001
 Pediatric Sleep
Questionnaire (PSQ)
Checklist
asthma and
266 controls ages
2 to 15 years

Coeliac disease and asthma association in children:
the role of antibiotic consumption
Canova C. Eur Respir J 2015;46:115–122
in children with asthma
incidence rate ratios (IRR)
for
Coeliac Disease
2.0 –
1.0 –
0.0
1.46
 A cohort of 1430144
children born in
1995–2011 in the
Friuli-Venezia Giulia.
 Prescriptions for
antibiotics in the first
year of life.
 Coeliac disease
incident cases.

in children with asthma
incidence rate ratios (IRR)
for
Coeliac Disease
2.0 –
1.0 –
0.0
1.46
 A cohort of 1430144
children born in
1995–2011 in the
Friuli-Venezia Giulia.
 Prescriptions for
antibiotics in the first
year of life.
 Coeliac disease
incident cases.
Antibiotics
were not a
confounding
factor in
these
associations.

 Vitamin D deficiency, which
is common among coeliac and
asthmatic patients, seems
to have unfavourable effects
on immune regulation.
 Therefore, vitamin D deficiency may be a common factor capable
of increasing the risk of developing both coeliac disease and asthma.
The possibility of a shared genetic basis should also be considered.

Mouse Sensitivity is an Independent Risk Factor
for Rhinitis in Children with Asthma
Sedaghat AR, JACI Pract 2016;4:82-88
In asthmatic children with mouse
sIgE ≥ 0.35 IU/mL OR for rhinitis
2.40
2 weeks year
In the past
2.15
2.5 –
2.0 –
1.5 –
1.0 –
0.5 –
0.0
p=0.02p=0.04
 499 urban children
(5-17 years) with
persistent asthma.
 Mouse-specific IgE
cockroach-specific
IgE.

Nocturnal GERD – a risk factor for rhinitis/rhinosinusitis:
the RHINE study Schiőler L, Allergy 2015;70:697–702
OR for developing
noninfectious rhinitis
in 2010
nocturnal GERD in 1999
(≥3 episodes of nocturnal
gastroesophageal reflux
symptoms per week)
1.6
p=0.03
2.0 –
1.0 –
0.0
 5417 subjects born
between 1945 and 1973
 a questionnaire in 1999–2001
and again in 2010–2012
 noninfectious rhinitis defined as
having nasal obstruction, secretion,
and/or sneezing without having the
common cold

 10 subjects demonstrated
significant improvement,
8 of whom demonstrated
complete resolution of supine
reflux with 6 inches
of head-of-bed elevation.
Supraesophageal Reflux: Correlation of Position and
Occurrence of Acid Reflux–Effect of Head-of-Bed
Elevation on Supine Reflux. Scott DR, JACI Pract 2015;3:356-61
 Sequential overnight
nasopharyngeal pH
monitoring before and
after head-of-bed
elevation was obtained
in 13 individuals with
supine-only reflux.
15 cm

Aggravation of airway inflammation and
hyper-responsiveness following nasal challenge with
Dermatophagoides pteronyssinus in perennial allergic
rhinitis without symptoms of asthma.
Wang W, Allergy 2016;71: 378–386
 15 nonasthmatic Der-p-sensitized rhinitis
(AR) patients with airway
hyper-responsiveness (AHR) (AR+AHR+).
 15 AR patients without AHR (AR+AHR-).
 15 healthy controls (HCs) with Der-p
sensitization (HC+DP+).
 15 HC without Der-p sensitization (HC+DP-).
 All subjects underwent
Der-p NPT.
Nasal Airway
Resistance (NAR)
increased
significantly in all
subjects with the
greatest effect
seen in
AR+AHR+
individuals.

Wang W, Allergy 2016;71: 378–386
Der-p NPT.
Visual analogue scale (VAS)
scores of nasal symptoms
increased in all subjects
at 30 min and returned
to baseline at 6 h,
with significantly
higher levels
in AR+AHR+ and
AR+AHR- subjects
(P < 0.05)

Wang W, Allergy 2016;71: 378–386
Der-p NPT.
•Eosinophils in nasal lavage
fluid and sputum increased
significantly after NPT in
AR+AHR+ and AR+AHR-
subjects (P < 0.001).
•FEV1% and PD20-FEV1
decreased and FeNO
increased significantly
after NPT only in AR+AHR+
subjects (P < 0.05).

Wang W, Allergy 2016;71: 378–386
Nasal resistance
increased also in
healthy controls
either sensitive
or not to DP.

Association between DNA hypomethylation
at IL13 gene and allergic rhinitis
in house dust mite-sensitized subjects
Li JY. Clin Exper Allergy 2016;46:298–307.
The mean level
of methylation
was decreased
(DNA hyperespression)
in the AR patient group
compared with the control
group (P = 0.01).
 60 patients
with HDM-sensitized AR
 65 control subjects
 2 indipendent cohort
from Beijing and Liaoning
 MassARRAY EpiTYPER
and pyrosequencing
to systematically screen
the status of DNA methylation
in peripheral blood leucocytes.

Association between DNA hypomethylation
at IL13 gene and allergic rhinitis
in house dust mite-sensitized subjects
Li JY. Clin Exper Allergy 2016;46:298–307.
1.24
2.0 –
1.0 –
0.0
1.62
p=0.036 p=0.013
Beijing Liaoning
 60 patients
with HDM-sensitized AR
 65 control subjects
 2 indipendent cohort
from Beijing and Liaoning
 MassARRAY EpiTYPER
and pyrosequencing
to systematically screen
the status of DNA methylation
in peripheral blood leucocytes.
DNA hypomethylation
of IL13 gene
may be associated
with increased risk of AR
from HDM sensitization.
OR for Allergic Rhinitis with
DNA hypomethylation at CpG38

Optimal management of allergic rhinitis
Scadding GK. Arch Dis Child 2015;100:576–582.
Entry to therapy can occur at 1, 2 or 3 year, depending on severity of
presenting symptoms.
*Oral antihistamines may be better tolerated, while intranasal antihistamines have a more rapid onset of action.
**Reconsider diagnosis if not controlled within 1–2 weeks. If <2 years of age and unresponsive to antihistamine within a
week, reconsider diagnosis before stepping up therapy. If poorly controlled, consider a short rescue course of a
decongestant or low-dose oral prednisolone to gain symptom control; topical ipratropium may be useful for rhinorrhoea.
Poor control should lead to a
step up, good control to a
step down, so that the
minimum therapy necessary
is used.
For seasonal disease, regular
therapy should be
commenced 2 weeks before
the anticipated start of
symptoms.

Optimal management of allergic rhinitis
Scadding GK. Arch Dis Child 2015;100:576–582.
A) Shows how to use a nasal spray
so as to avoid the septum and spray
as much of the lateral wall mucosa as
possible, allowing subsequent mucociliary
clearance to distribute the liquid
all over the mucosa.
B) Shows how nasal drops
(superior for rhinosinusitis) should be used
with the head completely upside down
so that drops reach the
ostiomeatal complex
in the upper nose
where sinuses drain
and ventilate.

Nasal saline irrigations for the symptoms
of chronic rhinosinusitis.
Harvey RJ, Cochrane Database Syst Rev. 2016 Apr 25;4:CD006394.
8 randomised
controlled trials in
which saline was
evaluated in
comparison with
either no treatment,
a placebo, as an
adjunct to other
treatments or
against treatments
1) There is evidence that saline is
beneficial in the treatment of the
symptoms of chronic rhinosinusitis
when used as the sole modality of
treatment.
2) Evidence also exists in favour of saline
as a treatment adjunct.
3) Some evidence suggests that
hypertonic solutions improve objective
measures but the impact on symptoms
is less clear.

Allergic Diseases and Internalizing Behaviors in Early
Childhood Nanda M K. , Pediatrics. 2016;137(1):e20151922
 546 children enrolled
at ages 1, 2, 3, 4,
and 7 years
 At age 7, parents
completed the Behavior
Assessment System for
Children, Second Edition
(BASC-2), a validated
measure of childhood
behavior and emotion.
In children with allergic rhinitis
at age 4 OR for
4.0 –
3.0 –
2.0 –
1.0 –
0.0
3.2 3.2
2.0
At age 7
internalizing anxiety Depressive
scores

Epidemiology and clinical predictors of biphasic reactions
in children with anaphylaxis.
Alqurashi, Ann Allergy Asthma Immunol 2015;115:217
 Incidence and clinical
predictors of biphasic
reactions in children
presenting to ED
with anaphylaxis.
 484 visits.
14.7%
% children with
biphasic reactions.
20 –
10 –
0.0

Age
6-9 yrs
OR for biphasic reactions.
3.60
2.58
2.92 2.7
Delay in
presentation
to the ED >90’
after the onset
of the initial
reaction
Wide
pulse
pressure
at triage
Treatment
of the initial
reaction
with ≥1 dose
of epinephrine
4.0 –
3.0 –
2.0 –
1.0 –
….0
2.39
Administration
of inhaled
β-agonists
in the ED
diastolic blood
pressure ≤ half
the systolic
blood pressure

Age
6-9 yrs
OR for biphasic reactions.
3.60
2.58
2.92 2.7
Delay in
presentation
to the ED >90’
after the onset
of the initial
reaction
Wide
pulse
pressure
at triage
Treatment
of the initial
reaction
with ≥1 dose
of epinephrine
4.0 –
3.0 –
2.0 –
1.0 –
….0
2.39
Administration
of inhaled
β-agonists
in the ED
Biphasic reactions seem to be associated with the
severity of the initial anaphylactic reactions.
diastolic blood
pressure ≤ half
the systolic
blood pressure

Time of Onset and Predictors of Biphasic Anaphylactic
Reactions: A Systematic Review and Meta-analysis
Lee S, JACI Pract 2015;3:408-416
4.6%
5.0 –
4.0 –
3.0 –
2.0 –
1.0 –
0.0
% patients with biphasic
anaphylatic reactions
 27 studies that described
biphasic reactions.
anaphylaxis and 192 pts
with biphasic reactions
(recurrence of symptoms
within 72 hours).

OR for biphasic anaphylatic reactions
Food as
a trigger
0.62
1.51
3.0 –
2.5 –
2.0 –
1.5 –
1.0 –
0.5 –
0.0
2.18
Unknow
trigger
Initial
symptoms
diarrhea
Initial
presentation
with
hypotension
1.72
2.53
 27 studies that described
biphasic reactions.
anaphylaxis and 192 pts
with biphasic reactions
(recurrence of symptoms
within 72 hours).

1) A biphasic anaphylactic reaction is defined as the recurrence of
symptoms within 72 hours of the initial anaphylactic event,
without re-exposure to the trigger.
2) The reported incidence of biphasic reactions ranges from 3% to 20%
of patients presenting to the emergency department, allergy clinics,
and inpatient ward with anaphylaxis.
3) Current guidelines in the United States recommend 6 hours
of observation after the initial anaphylactic episode due
to the risk of a biphasic reaction.
4) However, some studies and European guideline recommend
up to 24 hours of observation.

Epinephrine doses contained in outdated epinephrine
auto-injectors collected in a Florida allergy practice
Rachid O. Ann Allergy 2015;114:354
 35 EpiPens (0.3 mg),
3 to 36 months past
the expiry collected
from patients in Florida,
where outdoor
temperatures range
from 11°C to 32°C.
The EAIs that were
24 to 36 months past
the expiry date
were very lightly
discolored and contained
84.2% to 95.7% of
the labeled dose.

Excess subcutaneous tissue may preclude intramuscular
delivery when using adrenaline autoinjectors in patients
with anaphylaxis Johnstone J, Allergy 2015;70:703–706
 28 patients (age range of 18-75)
already prescribed adrenaline
autoinjectors (AAIs) for
anaphylaxis
 ultrasound and measurements of
skin-to muscle depth (STMD) at
anterolateral thigh
and anterior thigh
using the anterolateral thigh as the
recommended administration site
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
68%
% patients with
skin-to-muscle depth
> needle length (15.02 mm)

 28 patients (age range of 18-75)
already prescribed adrenaline
autoinjectors (AAIs) for
anaphylaxis
 ultrasound and measurements of
skin-to muscle depth (STMD) at
anterolateral thigh
and anterior thigh
Excess subcutaneous tissue may preclude intramuscular
delivery when using adrenaline autoinjectors in patients
with anaphylaxis Johnstone J, Allergy 2015;70:703–706
using the anterolateral thigh as the
recommended administration site
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
68%
% patients with
skin-to-muscle depth
> needle length (15.02 mm)
The key predictors
for increased STMD
were female gender
(p=0.0003) and
a BMI > 30
(p=0.04)

Effect of use of inhaled epinephrine on intramuscular
epinephrine use in patients with idiopathic anaphylaxis and
angioedema. Stone CA, Ann Allergy Asthma Immunol 2016;116:162
 We report 2 cases
of patients with frequent attacks
of throat angioedema
who have benefitted from the use
of inhaled epinephrine
in reducing the frequency
with which they have required
intramuscular epinephrine.
Inhaled
racemic epinephrine
in the form of a
2.25% solution diluted in saline
is satisfactory
for aborting most of
throat angioedema episodes.

66.98%
(89/133)
80 –
60 –
40 –
20 –
.0
40 of these
89 (44.9%)
tested positive
in the finger
test
 157 children of whom
133 with cow’s milk allergy
(CMA)
 Skin prick test and a
‘finger test’, in which cow’s
milk is applied on the cheek
by physician’s finger to
detect contact urticaria.
% of children with
IgE-mediated CMA
The significance of allergic contact urticaria to milk in
children with cow’s milk allergy
Konfin VS, Pediatric Allergy and Immunology; 2015;26:218–222

p < 0.004
60 –
50 –
40 –
30 –
20 –
10 –
0 -
(+)
CMP allergic contact urticaria
14.3%
50%
(-)
% children with multiple food allergies
(CMA)

80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
71%
37%
p = 0.0064
YES NOT
ATOPIC DERMATITIS
% children with CMP
allergic contact urticaria
(CMA)

Conclusion:
 Children with non-IgE milk allergy and healthy control group
did not have contact urticaria to CMP
 CMP contact urticaria exists only in patients with IgE-mediated
CMA.
 A ‘ﬁnger test’ to CMP should be part of the evaluation of CMA
patients, and positivity suggests the potential for multiple food
allergies, especially to sesame and egg.

 Chronic idiopathic urticaria
(CIU)/chronic spontaneous
urticaria (CSU) treated with
omalizumab.
 3 trials.
 Placebo or 75, 150, or 300 mg
of omalizumab every 4 weeks.
 Response defined as
well-controlled urticaria
(weekly Urticaria Activity Score
[UAS7] ≤ 6) or complete
response (UAS7 = 0).
 Response rates were
dose dependent and highest
with 300 mg of omalizumab.
 Some patients responded
early (before week 4).
Timing and duration of omalizumab response in patients
with chronic idiopathic/spontaneous urticaria
Kaplan A. JACI 2016;137:474-481

 Chronic idiopathic urticaria
(CIU)/chronic spontaneous
urticaria (CSU) treated with
omalizumab.
 3 trials.
 Placebo or 75, 150, or 300 mg
of omalizumab every 4 weeks.
 Response defined as
well-controlled urticaria
(weekly Urticaria Activity Score
[UAS7] ≤ 6) or complete
response (UAS7 = 0).
 Response rates were
dose dependent and highest
with 300 mg of omalizumab.
 Some patients responded
early (before week 4).
Timing and duration of omalizumab response in patients
with chronic idiopathic/spontaneous urticaria
Kaplan A. JACI 2016;137:474-481
In patients receiving
300 mg of omalizumab
with 24 weeks
of treatment, median
time to achieve a UAS7
≤ 6 was 6 weeks
and median time
to achieve
a UAS7 = 0 was
12 or 13 weeks

 21 children with diagnosis
of type I or II hereditary
angioedema (HAE)
(C1-INH, C1 inhibitor
function, C1q, C2, C3, C4).
 Median age 13.2 yrs.
% with a (+) FH of
hereditary angioedema
86%
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00
Clinical Features of Pediatric Hereditary Angioedema
Nanda MK, JACI Pract 2015;3:392-395

% patients with attack sites
Clinical Features of Pediatric Hereditary Angioedema
Nanda MK, JACI Pract 2015;3:392-395
100 –
090 –
080 –
070 –
060 –
050 –
040 –
030 –
020 –
010 –
000
abdominal peripheral laryngeal
93%
73%
27%
 21 children with diagnosis
of type I or II hereditary
angioedema (HAE)
(C1-INH, C1 inhibitor
function, C1q, C2, C3, C4).
 Median age 13.2 yrs.

Mean time from initial
symptoms to diagnosis
was 13.8 yrs.
Attacks that required
airway management and
abdominal surgery with
uncertain diagnosis were
observed in 9.5% and 2.9%
of patients, respectively.
 A 14-point survey
was sent to physicians
in Japan.
 Data on 171
hereditary
angioedema patients
collected from
94 physicians.
Clinical manifestations, diagnosis, and treatment of
hereditary angioedema: survey data from 94
physicians in Japan Ohsawa I. Ann Allergy 2015;114:492

Is nasal suctioning warranted before measuring
O2 saturation in infants with bronchiolitis?
Moschino L, Arch Dis Child 2016;101:114-115
40 infants under 12 months old
with bronchiolitis and SpO2 level
initially ≤96% and ≥88%
Superficial nasal suctioning
performed using a 6 Fr catheter
and a negative pressure of
60–80 mmHg for neonates,
80–100 mmHg for infants
8’ later, SpO2 measured again
SpO2 levels measured pre-nares
suctioning and 8’ after suctioning
of the nares
p<0.001
median
pre-SpO2 94%
median
post-SpO2 97%

Use of Intermittent vs Continuous Pulse Oximetry
for Nonhypoxemic Infants and Young Children
Hospitalized for Bronchiolitis
McCulloh R, JAMA Pediatr. 2015;169:898-904
For the management of patients
with bronchiolitis, the 2006 American
Academy of Pediatrics (AAP) guidelines
stated that continuous measurement
of oxygen saturation by pulse oximetry
(SpO2) was not routinely necessary
for patients who show clinical improvement.
2014 AAP guidelines further recommended
using intermittent pulse oximetry
monitoring of children hospitalized for bronchiolitis who are not receiving
supplemental oxygen.

Parallel-group, trial of infants
and children ≤ 2 years
hospitalized for bronchiolitis
Continuous (n=80)
or
intermittent (n= 81)
pulse oximetry monitoring
(ie, pulse oximetry measurements
obtained along with a scheduled
check of vital signs
or for clinical suspicion
of deterioration)
when oxygen saturation levels
were ≥ 90%
50 –
40 –
30 –
20 –
10 –
0
% mean length of stay (hours)
48.9% 46.2%ns
Continuous
monitoring
Intermittent
monitoring

Conclusions
Intermittent pulse oximetry monitoring of non-hypoxemic
(SaO2 ≥ 90%) patients with bronchiolitis did not shorten hospital
length of stay and was not associated with any difference in rate
of escalation of care or use of diagnostic or therapeutic measures.
Our results suggest that intermittent pulse oximetry monitoring
can be routinely considered in the management of infants and
children hospitalized for bronchiolitis who show clinical improvement.

Guidelines for the management of bronchiolitis vary in their target
oxygen saturation levels for starting and stopping supplemental
oxygen and none have supporting evidence,
although an oxygen saturation level of 90%
is gaining consistency as a watershed target
and evidence may soon support that target.
There is evidence that once oral feeding
is reestablished and SaO2 ≥ 90%,
respiratory deterioration is uncommon.
SpO2≤90%
Intermittent Monitoring of Oxygen Saturation in Infants
and Children With Acute Bronchiolitis Editorial
Cunningham S, JAMA Pediatr. 2015;169:891-892

Nasal irrigation with saline solution significantly improves
oxygen saturation in infants with bronchiolitis.
Schreiber S, Acta Paediatr. 2016;105(3):292-6.
133 infants with bronchiolitis and SpO2 between 88 and 94%,
nasal irrigation with 1 mL using either isotonic 0.9% sodium chloride (n = 47), or
hypertonic 3% (n = 44) or standard care (n = 42) groups. The nostrils were not
suctioned.
Variations in SpO2 and the wheeze, air exchange, respiratory rate, muscle use
(WARM) respiratory distress score recorded at zero, 5, 15, 20, 50 min.

 24 trials
 involving 3209 pts
 1706 of whom
received
nebulized hypertonic
saline (HS).
Hospitalized patients treated
with nebulized HS had:
1) a significantly shorter
length of stay -0.45 days
2) a significantly lower
post treatment clinical score
in the first 3 days of admission
day 1: - 0.99; day 2: - 1.45;
day 3: - 1.44
3) reduced risk of hospitalization
by 20%
Nebulized Hypertonic Saline for Acute Bronchiolitis:
A Systematic Review Zhang L. Pediatrics 2015;136:687

 24 trials
 1706 of whom
received
saline (HS).
day 1: - 0.99; day 2: - 1.45;
day 3: - 1.44
by 20%
No significant
adverse events
related
to HS
inhalation
were
reported

 24 trials
 1706 of whom
received
saline (HS).
day 1: - 0.99; day 2: - 1.45;
day 3: - 1.44
by 20%
Nebulized HS
is a safe
and
potentially
effective
treatment
of infants with
acute
bronchiolitis

Hypertonic saline for bronchiolitis: a case of less is more
Legg JP, Arch Dis Child 2015;100:1104–1105
a study from Finland by Skjerven et al. N Engl J Med. 2013;368(24):2286.
compared epinephrine and normal saline in 404
infants with bronchiolitis.
Protocol designed to assess the effect of fixed
scheduling or on-demand nebulisation.
Infants in the on-demand nebulisation group:
-received fewer doses of treatment
-were discharged significantly sooner
-were discharged with fewer requiring supplemental oxygen
-were discharged with fewer ventilator support

a study from Finland by Skjerven et al. N Engl J Med. 2013;368(24):2286.
compared epinephrine and normal saline in 404
infants with bronchiolitis.
Protocol designed to assess the effect of fixed
scheduling or on-demand nebulisation.
Infants in the on-demand nebulisation group:
-received fewer doses of treatment
-were discharged significantly sooner
-were discharged with fewer requiring supplemental oxygen
-were discharged with fewer ventilator support
The improved outcomes in this study for those infants left alone to get
better endorse the notion that minimal handling is important for a
more speedy recovery in acute bronchiolitis.

MINIMAL HANDLING
The increasing impression provided by recent studies is that
to do less is to do more for the recovery of the child with bronchiolitis.
Sleep, rest and good hydration seem to do far more for an infant
with bronchiolitis than regular disturbance with interventions
that either do not work or are of questionable benefit.
Sleep and rest Good hydration

Activity of Oral ALS-008176 in a Respiratory
Syncytial Virus Challenge Study
De Vincenzo J. NEJM 2015;373:2048-58
 62 healthy adults
inoculated with RSV
 Oral nucleoside analogue
ALS-008176
(RSV replication inhibitor) or
placebo 12 hours after
confirmation of RSV infection
or 6 days after inoculation
administered every 12 hours
for 5 days in different dosages
in 3 groups: 1,2,3
Mean Viral Loads
days

Activity of Oral ALS-008176 in a Respiratory
Syncytial Virus Challenge Study
De Vincenzo J. NEJM 2015;373:2048-58
Mean Symptom Scores
 62 healthy adults
inoculated with RSV
 Oral nucleoside analogue
ALS-008176
(RSV replication inhibitor) or
placebo 12 hours after
confirmation of RSV infection
or 6 days after inoculation
administered every 12 hours
for 5 days in different dosages
in 3 groups: 1,2,3
days

Format 2016: what is new in allergic & diseases respiratory 2016.

Format 2016: what is new in allergic & diseases respiratory 2016.

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