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

What is New in Allergic & Diseases Respiratory 2016

Attilio BonerUniversity ofVerona, Italy

[email protected]

Ambrosino RosaCaldonazzi FedericoCaruso FedericaCasarotto SerenaCattazzo ElenaClemente MariaCogo IlariaDanchielli CarlottaDi Carlo DanielaEl Mazloum DaniaGasperi EmmaLubrano LuigiOlivieri FrancescaPaiola GiuliaPalma LauraPecoraro LucaRamaroli DiegoReghelin GiuliaTadiotto ElisaTezza Giovanna



[email protected]

Drug AllergyFood AllergyAtopic DermatitisAsthmaAllergic RhinitisAnaphylaxisUrticaria & AngioedemaInfectious 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 ReactionsMori 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



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



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 daysDrug 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 daysDrug 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.



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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

professionalsTurner 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.



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.





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


as cow’s milk-free Trendelenbur V. Allergy 2015;70:591–597% 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






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)






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



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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.

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiCpI3F_Y3MAhWHuhQKHYPdBT0QjRwIBw&url=http://www.strettoweb.com/2015/01/ultimi-nati-nel-2014-super-bebe-a-cefalu-pesa-oltre-5-chili/230621/&bvm=bv.119408272,d.d24&psig=AFQjCNE9ZAhGtvjpuFqBPyWQdFymxCQbbg&ust=1460718207668911

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=0ahUKEwi88Ybh_Y3MAhUHVhQKHT0cBesQjRwIBw&url=http://www.medscape.org/viewarticle/561750&bvm=bv.119408272,d.d24&psig=AFQjCNGKaBVknmjOZ50Sls45ZVhXOBIxGA&ust=1460718271122788

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwi4hNqb_o3MAhWEXRQKHRbTCdUQjRwIBw&url=http://www.medscape.com/viewarticle/841930&bvm=bv.119408272,d.d24&psig=AFQjCNH_CL4LGUKTHGfyXd080v5pIa4Sng&ust=1460718341616628

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.



http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiCpI3F_Y3MAhWHuhQKHYPdBT0QjRwIBw&url=http://www.strettoweb.com/2015/01/ultimi-nati-nel-2014-super-bebe-a-cefalu-pesa-oltre-5-chili/230621/&bvm=bv.119408272,d.d24&psig=AFQjCNE9ZAhGtvjpuFqBPyWQdFymxCQbbg&ust=1460718207668911

https://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiJmcHb_o3MAhWDSBQKHYJuA8IQjRwIBw&url=https://en.wikipedia.org/wiki/Air_displacement_plethysmography&bvm=bv.119408272,d.d24&psig=AFQjCNHD0ktJu9UgeyakwKwjBuj5OJjtpw&ust=1460718530490799

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 preventionSimpson 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)



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

1.422.0 –

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.


1.422.0 –

1.0 –

0.0





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.


1.422.0 –

1.0 –

0.0





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

ProvidersEichenfield L.F. Pediatrics 2015;136:554Eczema action plan for pediatricians and other primary care

providersAs 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 RACCOMEN

D 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

dermatitisRiethmuller 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

dermatitisRiethmuller C, JACI 2015;136:1573-1580

The nurse and the wet wrapping techniqueElan 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 childhoodBager 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 childhoodBager 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 ofmoisturizers 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 SurveyStrom 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

6.03.56

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 PlayMoreno 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

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwip5JD-5vTLAhVH8RQKHTr_BL4QjRwIBw&url=http://fitnessandhealthadvisor.com/five-ways-get-rid-exercise-headache/&bvm=bv.118443451,d.d24&psig=AFQjCNH5OR6qrYYR_rs0AWC03nccu2OmVw&ust=1459853112403069



none severemoderate

mild

1.00

OR for headaches

2.14

4.91

1.83p=0.000

2p<0.000

1p<0.000

1

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.

http://www.belmarrahealth.com/melatonin-may-improve-sleep-in-children-with-eczema-study/



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



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[email protected]

Asthma develoment risk factorsAsthma predictive symptomsAsthma and wheezing phenotypesA & W phenotypes and lung functionAsthma and education / action planAsthma aggravating factorsAsthma tratment besides ICSAsthma burden

Allergic sensitization is associated with inadequate

antioxidant responses in mice and men Utsch L , Allergy 2015;70:1246–1258Background:

•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.


antioxidant responses in mice and men 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



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



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 studyCarlsten 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 studyCarlsten 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


[email protected]


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

1.85 years 7 yearsNocturnal 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 yearsnocturnal dry cough with wheeze at age

7 years

26.0p<0.001

p<0.001

OR for doctor-diagnosed asthma

at 8 years of age


[email protected]

Asthma develoment risk factorsAsthma predictive symptomsAsthma and wheezing

phenotypesA & W phenotypes and lung functionAsthma and education / action planAsthma aggravating factorsAsthma tratment besides ICSAsthma burden

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 analysisGarden 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


transition analysisGarden FL. Eur Respir J 2016;47:499–509

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.


transition analysisGarden FL. Eur Respir J 2016;47:499–509Phenotype 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. EditorialSpycher BD. Eur Respir J 2016;47:362–365In 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=0.005P<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% Egyptiancotton)

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;137:813-21779 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.


[email protected]

Asthma develoment risk factorsAsthma predictive symptomsAsthma and wheezing phenotypesA & W phenotypes and lung

functionAsthma and education / action planAsthma aggravating factorsAsthma tratment besides ICSAsthma burden

Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide

fraction in adolescenceDuijts L, Eur Respir J 2016;47:510–519

a population-based, prospective cohort study of 6841 children,

latent class analysis toidentify 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





physician-diagnosed asthma, 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.





physician-diagnosed asthma, 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

period60 –

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 bluenicotine-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 vessels4) 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%

note-cigarettes

user


[email protected]

Asthma develoment risk factorsAsthma predictive symptomsAsthma and wheezing phenotypesA & W phenotypes and lung functionAsthma and education / action

planAsthma aggravating factorsAsthma tratment besides ICSAsthma burden

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 inhalersproperly.

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 childwas pictured receiving inhaled therapy

8 –7 –6 –5 –4 –3 –2 –1 –0

7.5 %

% articles in which inhaler techniquewas 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 childwas pictured receiving inhaled therapy

8 –7 –6 –5 –4 –3 –2 –1 –0

7.5 %

% articles in which inhaler techniquewas judged

as being correctly demonstrated

The most commonly demonstrated

incorrect inhaler technique was usinga pMDI without a

spacer, which occurred in66.7% 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






90 –80 –70 –60 –50 –40 –30 –20 –10 –00

% providers recommend spacer use (eg Albuterol)

83.6%

p<0.001

43.1%


Standard plan






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%


Standard plan






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 planStandard plan

OR=33.0


[email protected]


Sleep schedules and sleep duration for three sleep conditions (TST = total sleep time).

Experimentally Manipulated Sleep Duration in Adolescents With Asthma: Feasibility and Preliminary

FindingsMeltzer L J. Ped Pul 2015;50:1360–1367

Selfselected

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


[email protected]


Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma

Ma J, Eur Respir J 2016; 47: 122–132Asthma 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 UKDevereux 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 behaviouralintervention (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 behaviouralintervention (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 and9 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



1.0 –

0.5 –


0.86

P=0.01



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



1.0 –

0.5 –


0.86

P=0.01



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 impairedlung function (FEV1/FVC <70%)

in ever smokers3.0 –

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<0.0015.0 –

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 –

0.0p=0.04

vitamin D insufficiency (<30 ng/ml reduction)





OR for at least one severe asthma exacerbation in children

with

both folate deficiency and vitamin D

insufficiency (<30 ng/ml reduction)

7.98.0 –7.0 –6.0 –5.0 –4.0 –3.0 –2.0 –1.0 –0.0



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

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCI_Usc_Q7scCFcNXGgodKjsDGw&url=http://www.dailyperricone.com/2011/02/start-fresh-sulforaphane/&psig=AFQjCNFzS9fqfjBnrQmUSXsGdjAImGpTWA&ust=1442048811411456

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 FeNOin children with asthma.

Tenero L. Allergy Asthma Proc. 2016;37(1):8-13.

ns

P=0.03

18 16

1911

Controls


[email protected]


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 EffectsN.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



asthmatics

controls



In children with (+) vs (-) Pediatric Spleep Questionnaire

OR for

6.097.0 –

6.0 –

5.0 –

4.0 –

3.0 –

2.0 –

1.0 –

0.0 Internalizing

problems

P < 0.001



Coeliac disease and asthma association in children:

the role of antibiotic consumptionCanova 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 confoundin

gfactor in

these association

s.

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.





[email protected]


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 yearIn the past

2.152.5 –

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)

1.6p=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 andhyper-responsiveness following nasal challenge

withDermatophagoides pteronyssinus in perennial

allergicrhinitis 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 inAR+AHR+ individuals.










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)










•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: 378–386Nasal 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



[email protected]


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



Age6-9 yrs

OR for biphasic reactions.

3.602.58 2.92 2.7

Delay in presentation

to the ED >90’ after the onset

of the initial reaction

Widepulse

pressure at triage

Treatmentof the initial

reactionwith ≥1 dose of

epinephrine

4.0 –

3.0 –

2.0 –

1.0 –

….0

2.39

Administration of

inhaledβ-agonistsin the ED

diastolic blood pressure ≤

half the systolic

blood pressure



Age6-9 yrs

OR for biphasic reactions.

3.602.58 2.92 2.7

Delay in presentation

to the ED >90’ after the onset

of the initial reaction

Widepulse

pressure at triage

Treatmentof the initial

reactionwith ≥1 dose of

epinephrine

4.0 –

3.0 –

2.0 –

1.0 –

….0

2.39

Administration of

inhaledβ-agonistsin 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-analysisLee 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.

4114 patients with anaphylaxis and 192 pts with biphasic reactions (recurrence of symptoms within 72 hours).



OR for biphasic anaphylatic reactions

Food as a trigger

0.62

1.513.0 –

2.5 –

2.0 –

1.5 –

1.0 –

0.5 –

0.0

2.18

Unknowtrigger

Initial symptoms diarrhea

Initial presentatio

n with hypotensio

n

1.72

2.53 27 studies that described biphasic reactions.

4114 patients with 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 practiceRachid 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 predictorsfor 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.

Inhaledracemic epinephrine

in the form of a2.25% solution diluted in saline is satisfactoryfor aborting most ofthroat angioedema

episodes.



[email protected]


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





80 –70 –60 –50 –40 –30 –20 –10 – 0

71%

37%

p = 0.0064

YES NOTATOPIC DERMATITIS

% children with CMP allergic contact urticaria





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

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiytKfnp5DMAhUDJQ8KHZUCBY8QjRwIBw&url=http://www.tantasalute.it/articolo/xolair-l-antiasmatico-per-eccellenza-torna-gratis/3968/&bvm=bv.119408272,d.ZWU&psig=AFQjCNGvyXOTx9iHQ54la5RPMLBwQDPQSg&ust=1460798274205677

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj50e-iqJDMAhUGqQ4KHZo6AJwQjRwIBw&url=http://www.pcds.org.uk/clinical-guidance/urticaria-spontaneous-syn.-chronic-ordinary-urticaria&psig=AFQjCNGLciLYPn0YB6AuoD3mhGJ3iL5E6w&ust=1460798395427332

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

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiytKfnp5DMAhUDJQ8KHZUCBY8QjRwIBw&url=http://www.tantasalute.it/articolo/xolair-l-antiasmatico-per-eccellenza-torna-gratis/3968/&bvm=bv.119408272,d.ZWU&psig=AFQjCNGvyXOTx9iHQ54la5RPMLBwQDPQSg&ust=1460798274205677

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj50e-iqJDMAhUGqQ4KHZo6AJwQjRwIBw&url=http://www.pcds.org.uk/clinical-guidance/urticaria-spontaneous-syn.-chronic-ordinary-urticaria&psig=AFQjCNGLciLYPn0YB6AuoD3mhGJ3iL5E6w&ust=1460798395427332

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 –

000abdominal 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



[email protected]

Drug AllergyFood AllergyAtopic DermatitisAsthmaAllergic RhinitisAnaphylaxisUrticaria & AngioedemaInfectious Respiratory

Diseases

bronchiolitis

Is nasal suctioning warranted before measuringO2 saturation in infants with bronchiolitis?

Moschino L, Arch Dis Child 2016;101:114-115

40 infants under 12 months old with bronchiolitis and SpO2 levelinitially ≤96% and ≥88%

Superficial nasal suctioningperformed using a 6 Fr catheterand 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

medianpre-SpO2 94%

medianpost-SpO2 97%

Use of Intermittent vs Continuous Pulse Oximetryfor 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

involving 3209 pts









No significant

adverse events related to HS

inhalation were

reported

24 trials

involving 3209 pts









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;100:1104–1105a 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 fixedscheduling 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


Legg JP, Arch Dis Child 2015;100:1104–1105a 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 fixedscheduling 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 supportThe 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.


Legg JP, Arch Dis Child 2015;100:1104–1105

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 infantwith 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 RespiratorySyncytial 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 RespiratorySyncytial 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

4.0 –

3.0 –

2.0 –

1.0 –

0.0

Excess Weight in Preschool Children With a History of

Severe Bronchiolitis is Associated With AsthmaTormanen S. Pediatric Pulmonology 2015;50:424-430

in overweight children

OR for current asthma at 6–7 years of age

151 former bronchiolitis patients

followed-up until the mean age of 6.45 years

weight status expressed as body mass index z-scores

3.05

Protracted Bacterial Bronchitis

Protracted Bacterial Bronchitis: The Last Decade and the Road Ahead

Chang A B. Ped Pul 2016;51:225-242

Cough is the single most common reason for primary care physician visits and, when chronic, a frequent indication for specialist referrals.

In children, a chronic cough (>4 weeks) is associated with increased morbidity and reduced quality of life.

One common cause of childhood chronic cough is protracted bacterial bronchitis (PBB), especially in children aged <6 years.

PBB is characterized by a chronic wet or productive cough without signs of an alternative cause and responds to 2 weeks of appropriate antibiotics, such as amoxicillin-clavulanate.

Most children with PBB are unable to expectorate sputum.

Bronchoalveolar lavage specimens typically reveal marked neutrophil infiltration and culture large numbers of respiratory bacterial pathogens, especially Haemophilus influenzae.

Recurrences are common and if these are frequent or do not respond to antibiotic treatments of up to 4-weeks duration, the child should be investigated for other causes of chronic wet cough, such as bronchiectasis.

It is likely that PBB and bronchiectasis are at the opposite ends of the same disease spectrum, so children with chronic wet cough require close monitoring


Chang A B. Ped Pul 2016;51:225-242

Bronchoscopic images from several children with protracted bacterial bronchitis

Secretions in several bronchi and features of bronchitis

(airway edema and inflammation)

bronchomalacia and mucus are also present

Sometimes secretions are seen in the trachea

More often purulent secretions are

seen in the bronchi (secretions seen at the

right lower lobe bronchus).


Chang A B. Ped Pul 2016;51:225-242

Chronic wet cough: protracted bronchitis, chronic suppurative lung disease and bronchiectasis

Protracted bacterial bronchitis(PBB), chronic suppurative lung disease (CSLD), and radiographic-confirmed bronchiectasis likely represents different ends of a spectrum with similar underlying mechanisms of airway neutrophilia, endobronchial bacterial infection, and impaired mucociliary clearance. Untreated it is likely some (but not all) children with PBB will progress to develop CSLD and some will ultimately develop bronchiectasis, initially reversible and subsequently irreversible if left to progress. There is a degree of overlap between each of the entities.


Chang A B. Ped Pul 2016;51:225-242

• In PBB, the child’s cough resolves only after a prolonged (2 weeks) course of appropriate antibiotics.

• When a typical 5 to 7 day course of antibiotics is prescribed the cough either relapses or does not resolve completely.

• However, some children require up to 4 weeks of treatment.


Chang A B. Ped Pul 2016;51:225-242

• In our study many of the children whose cough was not cured by 2 weeks of antibiotics had underlying tracheo-bronchomalacia and needed a longer course of antibiotics before their cough disappeared.

• The most widely used first line empiric antibiotic is amoxicillin-clavulanate, (as commonly associated pathogens, such as H. influenzae and especially M. catarrhalis, can be amoxicillin-resistant).

• Alternatives such as an oral cephalosporin, trimethoprim-sulfamethoxazole, or macrolide may be used when immediate hypersensitivity to penicillin exists.


Chang A B. Ped Pul 2016;51:225-242

Pneumonia

Pneumonia and Wheezing in the First Year:An International Perspective

Garcia-Marcos L. Ped Pul 2015;50:1277–1285

A large population-based cross-sectional study carried out in Latin America (LA) and Europe (EU) (n= 25,675)

A validated questionnaire for identifying wheeze in the first year of life

Questionnaire about pneumonia diagnosis

15 –

10 –

05 –

0

% children with pneumonia

10.8%66.6% reported

≥3 episodes of wheeze



A large population-based cross-sectional study carried out in Latin America (LA) and Europe (EU) (n= 25,675)

A validated questionnaire for identifying wheeze in the first year of life

Questionnaire about pneumonia diagnosis

15 –

10 –

05 –

0

% children with pneumonia

10.8%66.6% reported

≥3 episodes of wheeze

Pneumonia and Recurrent Whezing were

strongly associated to each other

in LA (aOR=5.42)

and EU (aOR=13.99)



Summary of significant risk

(red) and protective (blue)

factors of suffering from pneumoniaduring the first

year of life in Latin America and Europe, in the whole population and after

stratifying for recurrent wheeze

within each continent.

Antibiotic Treatment for Children Hospitalized With Community-Acquired Pneumonia After Oral

TherapyBreuer O. Pediatric Pulmonology 2015;50:495–502Current guidelines for the treatment of CAP in children

recommend the use of narrow spectrum antibiotics in outpatients, as well as hospitalized children.

Guidelines regarding patients not responding to first-line therapy in CAP are not as well established.

Current guidelines recommend further assessment of severity by clinical and laboratory investigation, as well as imaging and additional testing for the presence of a bacterial pathogen not susceptible to initial treatment.

Antibiotic Choice for Children Hospitalized With Pneumonia and Adherence to National Guidelines

Williams D.J. Pediatrics 2015;136:44

The 2011 national guidelines for the management of childhood community- acquired pneumonia recommended narrow-spectrum antibiotics (eg, ampicillin) for most children hospitalized with CAP. Impact of these guidelines on antibiotic prescribing at 3 children’s hospitals. 2121 children

During the preguideline period

% children treated with60 –

50 –

40 –

30 –

20 –

10 –

0

52.8%

third-generation

cephalosporins

2.7%ampicillin

15 –

10 –

…5

0 –

5 –

10 –

15 –

…

-12.4%

+11.3%

9 months postguidelines

% change in prescription

third-generation

cephalosporins ampicillin

Antibiotic Choice for Children Hospitalized With Pneumonia and Adherence to National Guidelines

Williams D.J. Pediatrics 2015;136:44

The 2011 national guidelines for the management of childhood community- acquired pneumonia recommended narrow-spectrum antibiotics (eg, ampicillin) for most children hospitalized with CAP. Impact of these guidelines on antibiotic prescribing at 3 children’s hospitals. 2121 children


TherapyBreuer O. Pediatric Pulmonology 2015;50:495–502The promotion of the use of narrow spectrum antibiotics was

designed to minimize the development of bacterial resistance in the community, which has been shown to rise with the increased use of broad spectrum antibiotics.

In immunized populations, the rate of invasive infections with Haemophilus influenzae type B has almost disappeared; hence the guidelines target S. pneumoniae as the major bacterial causative agent of CAP.

In fact, recent studies involving extensive microbiological diagnostic work-ups have identified S. pneumoniae as the most common bacterial pathogen in children with CAP.

70% XX%


TherapyBreuer O. Pediatric Pulmonology 2015;50:495–502

Review of 337 previouslyhealthy children from 3 months to 18 years with non-complicated CAP who received an oral antibiotic course and were admitted from 2003 to 2008 to our pediatric departments.

(30%) (70%)

70% XX%The broad spectrum-treatedgroup had significantly

better outcomes in terms of:

number of febrile days (1.2 vs 1.7, P<0.001)

number of days treated with intravenous antibiotics (3.1 vs 3.9, P<0.001)

days of hospitalization (3.5 vs 4.2, P<0.001)




OR for remaining hospitalized for the narrow spectrum group compared with the broad spectrum

group

6 –5 –4 –3 –2 –1 –0

5.5

at 72 Hours a at 7 Days



P<0.052.0


P<0.05

OR for remaining hospitalized for the narrow spectrum group compared with the broad spectrum

group

6 –5 –4 –3 –2 –1 –0

5.5

at 72 Hours a at 7 Days



P<0.052.0


P<0.05

In previously healthy children hospitalized with CAP after oral

antibiotic treatment in the community

treatment with broad spectrum antibiotics

showed better outcome


TherapyBreuer O. Pediatric Pulmonology 2015;50:495–502Parenteral narrow spectrum antibiotic treatment targets S.

pneumoniae as the major bacterial causative agent in pediatric CAP.

However, in children who were admitted with CAP despite previous antibiotic treatment, it is possible that their pneumonia was caused by bacteria other than S. pneumoniae, such as non-typeable H. influenzae.

Indeed, a study of induced sputum cultures from children with CAP previously treated with antibiotics found that non-typeable H. influenzae was the most common pathogen.

In bronchoalveolar lavage fluid cultures from children with non-responding CAP (persistent symptoms despite at least 48 hr of oral antibiotic treatment) H. influenzae and M. catarrhalis were the most common bacterial pathogens identified.

19° FORMAT Verona 12-13/05/2017

Grazie per la vostra attenzione alla storia che

vi ha raccontato il mio nonno.

Ciao a tutti.Mia Charlize Powell

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