what is new in general pediatrics, allergic and respiratory diseases

What is New in General Pediatrics,Allergic & Respiratory Diseases 2017 ?

Attilio BonerUniversity ofVerona, Italy

[email protected]

Ambrosino RosaCaruso FedericaClemente MariaDal Ben SarahDeganello MarcoGasperi EmmaGallo GiuseppeLaus BeatriceMazzei FedericaMinniti FedericaMurri VirginiaOlivieri FrancescaPalma LauraPecoraro LucaPiazza VannaPicassi SaraRamaroli DiegoReghelin GiuliaTezza Giovanna


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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 riskscharacterized by failure to achieve optimal development or morerapid 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 HealthRaju T. J Pediatr 2017;181:309-318

Outcomes of infants born near termGill 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 termGill 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 preeclampsiaif 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 0/7to 38 6/7 weeks’ gestation versus“full term, ” which includes 390/7 to 40 6/7 weeks’ gestation,emphasize the importance of thefetal maturation that occurs until 39 weeks.

•It is important that obstetricians and pediatriciansprovide 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 AdulthoodTwig 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.


BMI during adolescence and subsequentcardiovascular 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)


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 foradolescent 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.

Doctors’ behaviour

Caring for Children by Supporting ParentsShuster MA, NEJM 2017;376(5):410

• Primary care providers are the only professionals who have ongoingcontact with virtually all young children and their parentsstarting in infancy.

• They are specifically charged with teaching parents about raising healthychildren, and they serve as a resource to help parents with theirconcerns and challenges related to parenting.

• Physicians can provide parents with anticipatory guidance related totheir child’s development and prepare them to respond to children’sbehaviors in ways that promote health.

• Healthy Steps for Young Children trains nonphysicianpediatric health workers to offer enhanced anticipatory guidanceand referrals through office-based interactions and home visits.

Caring for Children by Supporting ParentsShuster 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 whatthey 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 tomeasure study participants’ EI.

The EQ-i is a self-reportmeasure consisting of 133 items covering what Bar-On describesas 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 suggeststhat 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.



General pediatricsFirst aid

• 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 stabilisethe 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 ofconsciousness (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 ofconsciousness (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 vsnon-Hispanic whites

OR for presenting with advanced disease



4.0 –

3.0 –

2.0 –

1.0 –

0.0 –young children

vsadolescents

2.2

General PediatricsGastroenterology

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 environmentalinsults 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 roleof 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 dysfunctionTulic 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 dysfunctionTulic 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

General PediatricsNutrition

A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children:

a randomized, double-blind controlled trialAkkermans 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 ferritinconcentrations 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



0.220.42

P<0.001P=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.


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General Pediatrics

Drug Allergy

Food Allergy

Atopic Dermatitis

Asthma

Allergic Rhinitis

Anaphylaxis




WeaningPreventionof 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 fordelayed (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 fordelayed (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 allergyGrimshaw 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 allergyGrimshaw 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 naturallyoccurring 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 sensitizationto inhalant allergens

0.73P-value for trend = 0.031

TAC of the diet for the 3rd

third compared to the 1st tertileat age 8 years

1.0 –

0.5 –

0.0






aOR forallergic asthma

0.57 P-value for trend = 0.031

1.0 –

0.5 –

0.0








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 P-value for trend = 0.031

aOR forallergic asthma



Induction of tolerance

Matrix effect of baked egg tolerance in childrenwith 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 wheatmatrix (a home-made cake, locally called ciambellone), - baked HE without a wheatmatrix (in the form of anomelet, locally named frittata) and boiled HE ciambellone

% children tollerating

88%

11.2

74%

56%

frittata boiledHE

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 eggallergy (IgE-HEA)

prick- by-prick tests and open oral food challenges (OFC) performed with: - baked HE within a wheatmatrix (a home-made cake, locally called ciambellone), - baked HE without a wheatmatrix (in the form of anomelet, locally named frittata) and boiled HE ciambellone

% children tollerating

88%

11.2

74%

56%

frittata boiledHE

100 –

80 –

60 –

40 –

20 -

0.0

Negative predictivevalue of

prick-by-prickperformed with ciambellone, frittata, and boiled HE was 100%.

Cross-sensitization

pollen food syndrome

Cluster analysis identified5 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 molecularclassification 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 molecularclassification 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 nutsin 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 nutsin 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 polysensitizationdefined 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 polysensitizationdefined as sensitization

to ≥3 aeroallergens


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General Pediatrics

Drug Allergy

Food Allergy

Atopic Dermatitis

Asthma

Allergic Rhinitis

Anaphylaxis




Skin barrier

Anionic surfactants and commercial detergents decreasetight 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 keratinocytesin the stratum granulosum.

• Recent data from human and animal studies havesuggested impairment of the skin barrieras an important mechanism in allergen sensitization.

• The emerging and popularizing of synthetic detergentscoincided with the uprising of allergic diseases after the 1950s.

• Surfactants as the main constituents of detergents can cause significant damageto both the lipid and protein structures of the stratum corneum, alter its barrierproperties, and induce the feeling of dryness and roughness (ruvidezza).


Xian M, JACI 2016;138:890.

•The in vitro effects of these surfactants measuredon direct cellular toxicityby means of investigationof lactate dehydrogenase (LDH) release as a marker of cell death.

•Concentrations of surfactantsthat do not affect the LDH release of NHEKs after 24 hours of treatment were considerednontoxic and applied to ALI cultures.

Direct effect of surfactants on TJs of normal human epidermalkeratinocytes (NHEKs), at air-liquidinterface (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.



Effect of surfactants in nontoxicdoses on the barrier integrity ofNHEKs:

•After 72 hours of stimulation,anionic surfactants (SDS and SDBS) significantly decreasedtransepithelial electricalresistance (TER).

•In parallel paracellularpermeability was increasedin a dose-dependent manner on stimulation with SDS and SDBS.


Xian M, JACI 2016;138:890.



•There was no barrier-disruptiveeffect of the cationic surfactantBZC and nonionic surfactantTween 20 at all nontoxic doses.

Collectively, these data demonstrate thatanionic surfactants can break down the TJ barrier integrityof 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 permeabilityacross NHEKs

treated with the same surfactants.

us = unstimulated

p < 0.05

p < 0.01

p < 0.05

p < 0.01

p < 0.001

cationicsurfactant

anionicsurfactant

dextran

AD allergic march

Skin barrier impairment at birth predicts food allergyat 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 at2 yrs with

6.27%

4.45%

7 –

6 –

5 –

4 –

3 –

2 –

1 –

0Food

sensitizationFood 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 allergyat age 2 yrs


Conclusion

Neonatal skin barrier dysfunction predicts FA at 2 yrs of age, supportingthe concept of transcutaneous allergen sensitization, even in infants whodo not have AD.

TEWL could be used for stratifyinginfants in the first few days of life before development of AD or FAfor targeted intervention studiesto 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 comprisedpatients with eitherestablished AD or FA;

patients with AD vs healthy control

OR for food sensitizationat 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 studiesShatha 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 assessedat 6, 12, and 24 monthsin MACS and 24 monthsin 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 studiesShatha A, PAI 2017;28:30-35

16 –

14 –

12 –

10 –

8.0 –

6.0 –

4.0 –

2.0 –

0.0

OR for rhinitisat 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

AD prevention

•Recent attention has been directed toward the preventionof 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 riskinfants (defined as a first-degree relative with atopic dermatitis),reduced the cumulative incidence of atopic dermatitisin 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 Moisturizationfor 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 gper 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 dermatitisoccurrence in young childrenTurati 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

AD treatment

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 managementof 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


[email protected]

Drug Allergy

Food Allergy

Atopic Dermatitis

Asthma

Allergic Rhinitis

Anaphylaxis




Asthma worsening factors

Diet

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 forworsening of asthma

cured meat intake≥4 vs <1 serving/week

1.76

2.0 –

1.5 –

1.0 –

0.5 –

0.0 –

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiEp8K0psTSAhWGwBQKHfP_CooQjRwIBw&url=http://www.foodnavigator.com/Science/Processed-cured-meat-worsens-asthma-Study&psig=AFQjCNERerIsrKlibn68_LGzaqhhd3GfWA&ust=1488972884804346


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 nitrosativestress 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.




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 Symptomsin 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.


Gastro esophageal reflux

6.3%

Endoscopic incidenceof inlet patch (IP)

7 –

6 –

5 –

4 –

3 –

2 –

1 –

0 –

Consecutive patientsaged <18 years (n = 1000) undergoingesophagogastroduodenoscopy.

Biopsy specimens frominlet patch (IP) IPsand the proximaland distal esophagus, stomach, and duodenum.

Impedance and pH monitoring(MII-pH) performedin all symptomatic patients.

Esophageal Inlet Patch: An Under-Recognized Cause of Symptoms in Children

Di Nardo G, J Pediatr. 2016;176:99-104

Consecutive patientsaged <18 years (n = 1000) undergoingesophagogastroduodenoscopy.

Biopsy specimens frominlet patch (IP) IPsand the proximaland distal esophagus, stomach, and duodenum.

Impedance and pH monitoring(MII-pH) performedin all symptomatic patients.

asymptomatic

56%

17%

% patients with inlet patch

symptoms clearly related

to the underlying digestive disorder

chronicIP-relatedsymptoms

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 forasthma development

Association of T-regulatory cells and CD23/CD21 expression with vitamin D in children with asthmaChary 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

Asthma clinical aspects

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.


Asthma lung function decline

Early sensitization is associated with reduced lung function from birth into adulthood

Owens L, JACI 2016;137:1605-6.

Longitudinal birth cohort(Perth Infant Asthmafollow-up cohort);

Influence of early sensitization on lungfunction and respiratoryoutcomes from infancythrough to early adulthood.

Early sensitization, defined as at least1 positive SPT response by 12 mo of age, was longitudinally associated with a persistent reduction in lung functionfrom 1 month to 24 yrs of age whenadjusted for in utero smoke exposure(p<.002).

The reduction was statisticallysignificant for V’maxFRC at 1 mo, FEV1/FVC ratio at 24 yrs, and bothforced 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 functionvariables and

early sensitization(1 + SPT responseby 12 mo of age)

at each assessmentfrom 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 performedfrom childhoodinto 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)


McGeachie MJ, N Engl J Med 2016;374:1842-52Participants 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 treatmentAsthma burden

Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years:

a randomised, double-blind, placebo-controlled trialStokholm J, Lancet Respir Med 2016;4:19-26

3-day course of azithromycinoral 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 7.7days

3.4days

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 azithromycinoral 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 trialTachimoto 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





% 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



Future Research

Antioxidants?

(-)(+)

Transcription factors are proteins that bind to DNA controlling

the transcription of messenger RNA

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCNSX7cff6ccCFUh-GgodMtYHCQ&url=http://www.anti-agingfirewalls.com/2013/10/28/the-master-regulator-of-aging-redox-glutatione-and-cysteine-part-1/&psig=AFQjCNHbxWyu6aBHRc0EYtGg1uep39KJKQ&ust=1441881029346472

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[email protected]

General Pediatrics

Drug Allergy

Food Allergy

Atopic Dermatitis

Asthma

Allergic Rhinitis & Conjunctivitis

Anaphylaxis




Pathogenesis of rhinitisEifan AO, Clin Exp Allergy 2016;46:1139-1151

Activated/damaged epithelial cells secrete thymic stromallymphopoietin (TSLP) and IL-33 that activates dendriticcells 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 dustmite–induced allergic rhinitis is accompanied by decreased

occludin and zonula occludens-1 expressionSteelant 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.

Transepithelialresistance and passage to fluorescein isothiocyanate–dextran 4 kDa (FD4).

P < 0.05 P < 0.05



Representativeimmunofluorescencestaining foroccludin (green) and ZO-1 (red) in 8 control subjectsand 9 patients withHDM-induced AR.

zonula occludens-1

zonula occludens-1



Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients withHDM-induced AR

TJ expression by PCR and immunofluorescence.

Transepithelialresistance and passage to fluorescein isothiocyanate–dextran 4 kDa (FD4).

P < 0.05 P < 0.05

Transepithelialresistance

Transepithelialpermeability

Preservation of epithelial cell barrier function andmuted 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, silencedrespectively.

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 epithelialcells treated with PM10;

Epithelial barrier disruptionwas noted within 4 hours asassessed by transepithelialelectrical resistance (TEER)and paracellular fluxquantified by fluoresceinisothiocyanate (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 epithelialcell barrier function is reversed by activation

of the Nrf2 pathway London NR, JACI 2016;138:1736.

Transepithelialresistance

Transepithelialpermeability

We tested whetherenhancement of Nrf2 usingthe activator sulforaphane(SFN) was sufficientto reduce PM inducedsinonasal epithelial cell(SNEC) barrier disruption.

SNECs were pretreatedwith 10 μM SFN for 72 hours before PM stimulation.

Sulforaphane pretreatment wasfound to significantly reduce SNEC barrier instabilityas measured by bothtransepithelial electricalresistanceandfluorescein isothiocyanate -dextran leak





• Particulate matter (PM) directly contain redox-active chemicalsand 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 documentedto exacerbate asthma morbidity.

• PM also has been reported to cause sinonasal inflammation with nasal epithelialthickening and increased eosinophils in nasal lavageand 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 nucleusand facilitates expression of genes that enact a cytoprotective response.

Rhinitis Treatment

1000

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,BritishColumbia, Canada)for 2 months

Nasal symptoms and nasal airflowresistance

Effects of curcuminon 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


[email protected]

General Pediatrics

Drug Allergy

Food Allergy

Atopic Dermatitis

Asthma

Allergic Rhinitis

Anaphylaxis




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 angioedemain the eyelids together with dyspneaand 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 thesefoods (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.


[email protected]

General Pediatrics

Drug Allergy

Food Allergy

Atopic Dermatitis

Asthma

Allergic Rhinitis

Anaphylaxis




bronchiolitis

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

Pneumonia

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 serum25-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

ORfor vitamin D <20 ng/ml

In casesvs controls

2.4p=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 ModulatesInflammatory 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 serumfrom patients with bacterial respiratorytract infections enhanced neutrophil killing.

Vitamin D Promotes Pneumococcal Killing and ModulatesInflammatory Responses in Primary Human Neutrophils.

Subramanian K, J Innate Immun. 2017 [Epub ahead of print]

Moreover, vitamin D lowered inflammatorycytokine production by infected neutrophilsvia IL-4 production and the inductionof suppressor of cytokine signaling (SOCS) proteins SOCS-1 and SOCS-3, leading to the suppression of NF-κB signaling.

Thus, vitamin D enhances neutrophil killingof S. pneumoniae while dampening excessiveinflammatory responses and apoptosis, suggesting that vitamin D could beused 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 intraluminalimpedance 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 intraluminalimpedance 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 trialChamberlain 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 hygieneand hydration,

•psychoeducational counselling.



Physiotherapy, and Speech And Language Therapy Intervention (PSALTI)

1. EducationEducate 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 hydrationIncrease frequency and volume of water and non-caffeinateddrinks. 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 techniquesand 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 orcontrol 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 orcontrol 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 EDUCATIONINFORMATION 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 facilityif 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 EDUCATIONINFORMATION 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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