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

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

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

  1. 1. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Ambrosino Rosa Caldonazzi Federico Caruso Federica Casarotto Serena Cattazzo Elena Clemente Maria Cogo Ilaria Danchielli Carlotta Di Carlo Daniela El Mazloum Dania Gasperi Emma Lubrano Luigi Olivieri Francesca Paiola Giulia Palma Laura Pecoraro Luca Ramaroli Diego Reghelin Giulia Tadiotto Elisa Tezza Giovanna
  2. 2. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  3. 3.  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 *
  4. 4.  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.
  5. 5.  200 patients with histories of amoxicillin reactions.  SPT with 20 mg/mL amoxicillin  Challenged with amoxicillin for a total of 5 days. % patients with (+) SPT 20 mg/mL amoxicillin 4.5% (9/200) 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 Amoxicillin Allergy in Children: Five-Day Drug Provocation Test in the Diagnosis of Nonimmediate Reactions Mori F, Novembre E. JACI Pract 2015;3:375-380
  6. 6. 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. Amoxicillin Allergy in Children: Five-Day Drug Provocation Test in the Diagnosis of Nonimmediate Reactions Mori F, Novembre E. JACI Pract 2015;3:375-380
  7. 7. 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. Amoxicillin Allergy in Children: Five-Day Drug Provocation Test in the Diagnosis of Nonimmediate Reactions Mori F, Novembre E. JACI Pract 2015;3:375-380
  8. 8. % patients with (+) Drug Provocation Test 9.6% 10 – 09 – 08 – 07 – 06 – 05 – 04 – 03 – 02 – 01 – 00  200 patients with histories of amoxicillin reactions.  Challenged with amoxicillin for a total of 5 days. 14/17 had history of nonimmediate reactions; 4/14 (26.6%) reacted on day 5. (17/200) Amoxicillin Allergy in Children: Five-Day Drug Provocation Test in the Diagnosis of Nonimmediate Reactions Mori F, Novembre E. JACI Pract 2015;3:375-380
  9. 9. % patients with (+) Drug Provocation Test 9.6% Amoxicillin Allergy in Children: Five-Day Drug Provocation Test in the Diagnosis of Nonimmediate Reactions Mori F, Novembre E. JACI Pract 2015;3:375-380 10 – 09 – 08 – 07 – 06 – 05 – 04 – 03 – 02 – 01 – 00  200 patients with histories of amoxicillin reactions.  Challenged with amoxicillin for a total of 5 days. 14/17 had history of nonimmediate reactions; 4/14 (26.6%) reacted on day 5. (17/200) According to our results, a long-term DPT protocol increases the sensitivity of the allergy work-up, and it should be recommended for patients with a history of amoxicillin nonimmediate reaction.
  10. 10. 7.4% (25/337) % (+) 5 days Drug Provocation Test  337 patients (2–14 yrs) with mild-to-moderate skin reactions.  Retrospectively reviewed 09 – 08 – 07 – 06 – 05 – 04 – 03 – 02 – 01 – 00 - Utility of skin testing in children with a history of non-immediate reactions to amoxicillin Barni S, Novembre E. Clin Exp Allergy 2015;45:1472-1474
  11. 11. 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 - 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 All patients who developed a reaction after the DPT had the same reaction as compared to their reported index one, demonstrating the safety of this approach. % (+) 5 days Drug Provocation Test
  12. 12. 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 • 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.
  13. 13. 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
  14. 14. 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. 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
  15. 15. Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics Vezir Emine. PAI 2016;27:50-54 4 out of 119 patients had a positive reaction to the challenge
  16. 16. Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics Vezir Emine. PAI 2016;27:50-54 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.
  17. 17. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  18. 18. 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.
  19. 19.  Understand how health care professionals (HCPs) currently incorporate PAL into patient management, and whether current approaches (such as the VITAL initiative) are of value. Allen KJ, et al. JACI 2014; 133:156–164  A 28-item online survey.  161 respondents from the UK, and Australia/New Zealand. % of health care professionals who Knowledge, practice, and views on precautionary allergen labeling for the management of patients with IgE-mediated food allergy a survey of Australasian and UK health care professionals Turner PJ, JACI Pract 2016;4:165-167 56% believed that PAL was subject to government regulation 13% had never heard of the VITAL scheme 60 – 50 – 40 – 30 – 20 – 10 – 00
  20. 20. 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 Knowledge, practice, and views on precautionary allergen labeling for the management of patients with IgE-mediated food allergy a survey of Australasian and UK health care professionals Turner PJ, JACI Pract 2016;4:165-167 !!!
  21. 21.  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. Knowledge, practice, and views on precautionary allergen labeling for the management of patients with IgE-mediated food allergy a survey of Australasian and UK health care professionals Turner PJ, JACI Pract 2016;4:165-167
  22. 22. 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.
  23. 23. 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 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 Unintended allergens in precautionary labelled and unlabelled products pose significant risks to UK allergic consumers Remington B.C. Allergy 2015;70:813-819
  24. 24. 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. Unintended allergens in precautionary labelled and unlabelled products pose significant risks to UK allergic consumers Remington B.C. Allergy 2015;70:813-819 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
  25. 25. 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
  26. 26. 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 % 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  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
  27. 27. 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  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)  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
  28. 28. 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 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
  29. 29. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  30. 30. 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.
  31. 31.  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. Neonatal adiposity increases the risk of atopic dermatitis during the first year of life O'Donovan SM. JACI 2016;137:108-117
  32. 32. Maternal atopy Fat mass ≥ 80th percentile at day 2 Neonatal adiposity increases the risk of atopic dermatitis during the first year of life O'Donovan SM. JACI 2016;137:108-117 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.
  33. 33. Maternal atopy Fat mass ≥ 80th percentile at day 2 Neonatal adiposity increases the risk of atopic dermatitis during the first year of life O'Donovan SM. JACI 2016;137:108-117 OR for AD at 6 and 12 mo of age 2.31 2.99 p=0.0004 p=0.009 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.0  Birth cohort study (n = 1537).  Data on early-life events, infant feeding, and nutritional and environmental exposures were collected at 15 weeks' gestation, birth, and 2, 6, and 12 months of age.  Body composition assessed by air displacement plethysmography at day 2 and 2 months. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention Simpson EL, J Allergy Clin Immunol 2014;134:818-23
  34. 34. OR for atopic dermatitis at 12 months 1.0 3.2 7.1 25th (5.0 gwater/m2/h) 50th (7.0 gwater/m2/h) 75th (9.0 gwater/m2/h) 8.0 – 7.0 – 6.0 – 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 TEWL birth percentiles  Skin barrier function at day 2 after birth and at 2 months.  1903 infants.  Presence of AD at 6 and 12 months. Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.Kelleher M, JACI 2015;135:930-35
  35. 35. OR for atopic dermatitis at 12 months 1.0 3.2 7.1 25th (5.0 gwater/m2/h) 50th (7.0 gwater/m2/h) 75th (9.0 gwater/m2/h) 8.0 – 7.0 – 6.0 – 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 TEWL birth percentiles  Skin barrier function at day 2 after birth and at 2 months.  1903 infants.  Presence of AD at 6 and 12 months. Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.Kelleher M, JACI 2015;135:930-35
  36. 36. In presence of postpartum depression OR for AD development 1.42 2.0 – 1.0 – 0.0 Maternal psychologic problems increased the risk of childhood atopic dermatitis Wang IJ, Pediatr Allergy Immunology 2016;27:169–176  24,200 mother – newborn pairs from the Taiwan national birth registration.  Maternal psychologic problems by standard questionnaire at 6 months old.
  37. 37. In presence of postpartum depression OR for AD development 1.42 2.0 – 1.0 – 0.0 Maternal psychologic problems increased the risk of childhood atopic dermatitis Wang IJ, Pediatr Allergy Immunology 2016;27:169–176  24,200 mother – newborn pairs from the Taiwan national birth registration.  Maternal psychologic problems by standard questionnaire at 6 months old. 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.
  38. 38. In presence of postpartum depression OR for AD development 1.42 2.0 – 1.0 – 0.0 Maternal psychologic problems increased the risk of childhood atopic dermatitis Wang IJ, Pediatr Allergy Immunology 2016;27:169–176  24,200 mother – newborn pairs from the Taiwan national birth registration.  Maternal psychologic problems by standard questionnaire at 6 months old. maternal stress could operate through direct epigenetic effects via DNA methylation or histone deacetylation of the glucocorticoid receptor (GR) gene with neuroendocrine dysregulation
  39. 39. Maternal psychologic problems increased the risk of childhood atopic dermatitis Wang IJ, Pediatr Allergy Immunology 2016;27:169–176 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
  40. 40. Edinburgh postnatal depression scale. Cox JL. British Joural of Psychiatry 1987;150:782-786 with a score > 10 depression is probable
  41. 41. Translating Atopic Dermatitis Management Guidelines Into Practice for Primary Care Providers Eichenfield L.F. Pediatrics 2015;136:554 Eczema action plan for pediatricians and other primary care providers As tolerated during flare;  direct use of moisturizers on inflamed skin may be poorly tolerated; however,  bland petrolatum is often tolerated when skin is inflamed.  Approximately 0.5 cups sodium hypochlorite per 40 gallons (150 L) of water/full bathtub or 1 mL/L. TCI, topical calcineurin inhibitor
  42. 42. 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.
  43. 43. Improved management of childhood atopic dermatitis after individually tailored nurse consultations: A pilot study Rolinck-Werninghaus C, Pediatr Allergy Immunol 2015:26:805  1628 parents of children (mean age 1.7 yrs) with AD  Individually tailored nurse consultation  Consultation by telephone 14 days later 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 00 100 - 92.1% 95.7% % parents that COULD BETTER TRANSFER THE RACCOMANDATIONS INTO PRACTICE WOULD RACCOMEND THE INDIVIDUAL INSTRUCTIONS TO OTHERS after nurse consultations
  44. 44. Improved management of childhood atopic dermatitis after individually tailored nurse consultations: A pilot study Rolinck-Werninghaus C, Pediatr Allergy Immunol 2015:26:805 % reductions -00 -10 – -20 – -30 – -40 – -50 - severe moderate -20% -50% -50% Scores for sleep disruption and pruritus Symptoms
  45. 45. Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis Riethmuller C, JACI 2015;136:1573-1580  Relationship between FLG genotype, filaggrin breakdown products (natural moisturizing factor [NMF]), and corneocyte morphology.  15 children at first presentation of AD and after 6 weeks of standard therapy.  Atomic force microscopy to study corneocyte conformation obtined by adhesive tape strips .
  46. 46.  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
  47. 47. At first presentation of disease and after 6 weeks of topical therapy with skin care regimens and appropriate topical steroids. The Dermal Texture Index, quantifies the number of Villus-like projection Villus-like projection Natural moisturizing factor Atomic force microscopyDermal Texture Index Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis Riethmuller C, JACI 2015;136:1573-1580
  48. 48. The nurse and the wet wrapping technique Elan F. Rev Infirm. 2015 Oct;214:43-4. after 2 days
  49. 49. Cut a facial mask from the appropriate size - - -- --
  50. 50. Filaggrin genotype and skin diseases independent of atopic dermatitis in childhood Bager P. Pediatr Allergy Immunol 2016;27:162–168  Filaggrin gene (FLG) mutations  1547 children with information on skin diseases from the Danish National Birth Cohort and Health Register  18 years follow-up 4 – 3 – 2 – 1 – 0 - 1.9 3.3 2.9 dry skin atopic dermatitis urticaria at age < 18 mo. In children with FLG mutation OR for
  51. 51. Filaggrin genotype and skin diseases independent of atopic dermatitis in childhood Bager P. Pediatr Allergy Immunol 2016;27:162–168  Filaggrin gene (FLG) mutations  1547 children with information on skin diseases from the Danish National Birth Cohort and Health Register  18 years follow-up 4 – 3 – 2 – 1 – 0 - 1.9 3.3 2.9 dry skin atopic dermatitis urticaria at age < 18 mo. In children with FLG mutation OR for In clinical practice, FLG genotyping may help indicate the use of moisturizers to reduce skin problems
  52. 52. Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children's Health and the National Health Interview Survey Strom MA, J Pediatr 2016;168:185-92 4.7% 2.2% pooled prevalence of speech disorder p < 0.001 YES NO OR= 1.81 children with eczema  354 416 children and adolescents from 19 US population- based cohorts
  53. 53. 6 – 5 – 4 – 3 – 2 – 1 – 00 1.45 6.0 3.56 1.36 Mild Moderate Severe Eczema (+) ADHDEczema severity  354 416 children and adolescents from 19 US population- based cohorts p=0.03 p<0.001 p<0.001 OR for speech disorder Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children's Health and the National Health Interview Survey Strom MA, J Pediatr 2016;168:185-92
  54. 54.  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. Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children's Health and the National Health Interview Survey Strom MA, J Pediatr 2016;168:185-92
  55. 55. Supporting Child Play Moreno MA. JAMA Pediatrics 2016;170:2:184.  Many different types of play benefit children, including playing on their own, playing with other children, and playing with their adult caretakers.  When a child plays independently, he or she practices decision-making skills and discovers areas of interest.  When children play together, without adults directly involved, they learn to work together, negotiate, and resolve conflicts and they learn self-advocacy skills.  When parents observe their children in play or join with them in child-driven play, they get an opportunity to see the world from their child’s point of view.  These adult-child interactions help build strong supportive relationships.
  56. 56. Supporting Child Play Moreno MA. JAMA Pediatrics 2016;170:2:184.  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.
  57. 57. Supporting Child Play Moreno MA. JAMA Pediatrics 2016;170:2:184. 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.
  58. 58. 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
  59. 59. Association between childhood eczema and headaches: An analysis of 19 US population-based studies Silverberg JI. JACI 2016;137:492-499 none severemoderatemild 1.00 OR for headaches 2.14 4.91 1.83 p=0.0002 p<0.0001 p<0.0001 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 severity of eczema
  60. 60. Association between childhood eczema and headaches: An analysis of 19 US population-based studies Silverberg JI. JACI 2016;137:492-499  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.
  61. 61. Association between childhood eczema and headaches: An analysis of 19 US population-based studies Silverberg JI. JACI 2016;137:492-499  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
  62. 62. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  63. 63. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  64. 64. Allergic sensitization is associated with inadequate antioxidant responses in mice and men Utsch L , Allergy 2015;70:1246–1258 Background: •Allergies arise from aberrant Th2 responses to allergens. •The processes involved in the genesis of allergic sensitization remain elusive. Some allergens such as derived from house dust mites have proteolytic activity which can induce oxidative stress in vivo. A reduced capacity of the host to control oxidative stress might prime for allergic sensitization.
  65. 65. Allergic sensitization is associated with inadequate 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
  66. 66. *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 Allergic sensitization is associated with inadequate antioxidant responses in mice and men Utsch L , Allergy 2015;70:1246–1258 37 laboratory animal workers were followed for 2 years. Occupational allergic sensitization to rodent urinary proteins was monitored. Also in human subjects, oxidative stress before* allergen exposure and poor antioxidant responses predisposition to occupational allergy.
  67. 67. *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 Allergic sensitization is associated with inadequate antioxidant responses in mice and men Utsch L , Allergy 2015;70:1246–1258 37 laboratory animal workers were followed for 2 years. Occupational allergic sensitization to rodent urinary proteins was monitored. Allergic sensitization to rodent proteins in humans is associated with reduced capacity to express Nuclear factor erythroid- derived (2Nrf2) (-) (+) Also in human subjects, oxidative stress before* allergen exposure and poor antioxidant responses predisposition to occupational allergy.
  68. 68.  18 blinded atopic volunteers exposed to filtered air or 300 mg PM2.5/m3 of diesel exhaust in random fashion  1 h post-exposure, diluent-controlled segmental allergen challenge  2 days later, samples by bronchoscopic lavage. Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study Carlsten C, Thorax 2016;71:35–44 Diesel exhaust augmented: 1) the allergen-induced increase in airway eosinophils, 2) IL-5 and eosinophil cationic protein
  69. 69.  18 blinded atopic volunteers exposed to filtered air or 300 mg PM2.5/m3 of diesel exhaust in random fashion  1 h post-exposure, diluent-controlled segmental allergen challenge  2 days later, samples by bronchoscopic lavage. Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study Carlsten C, Thorax 2016;71:35–44 Diesel exhaust augmented: 1) the allergen-induced increase in airway eosinophils, 2) IL-5 and eosinophil cationic protein the GSTT1 null genotype was significantly associated with the augmented IL-5 response
  70. 70. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  71. 71. 3.252 children from the PIAMA birth cohort Nocturnal dry cough at ages 1-7 years Doctor-diagnosed asthma at 8 years of age 08 – 07 – 06 – 05 – 04 – 03 – 02 – 01 – 00 7.1 1.8 5 years 7 years Nocturnal dry cough without wheeze at age p<0.05 p<0.05 Nocturnal dry cough in the first 7 years of life is associated with asthma at school age Boudewijn IM. Pediatr Pulmonol. 2015;50:848-855 OR for doctor-diagnosed asthma at 8 years of age
  72. 72. 30 – 25 – 20 – 15 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 3.7 3.252 children from the PIAMA birth cohort Nocturnal dry cough at ages 1-7 years Doctor-diagnosed asthma at 8 years of age Nocturnal dry cough in the first 7 years of life is associated with asthma at school age Boudewijn IM. Pediatr Pulmonol. 2015;50:848-855 1 years nocturnal dry cough with wheeze at age 7 years 26.0 p<0.001 p<0.001 OR for doctor-diagnosed asthma at 8 years of age
  73. 73. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  74. 74. data on respiratory symptoms, healthcare utilisation, medications, spirometry, AHR, FeNO, a atopy, Australian birth cohort (n = 370) recruited on the basis of having a first- degree relative with asthma. Data acquired at ages 1.5–11.5 years analysed using latent transition analysis. In Early Childhood (1.5 – 5 yrs) we classified subjects into 4 phenotypes: 1) nonatopic, few symptoms, 2) atopic, few symptoms, 3) nonatopic, asthma and rhinitis symptoms, 4) atopic, asthma and rhinitis symptoms. Change in the manifestations of asthma and asthma- related traits in childhood: a latent transition analysis Garden FL. Eur Respir J 2016;47:499–509
  75. 75. 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 Change in the manifestations of asthma and asthma- related traits in childhood: a latent transition analysis Garden FL. Eur Respir J 2016;47:499–509 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.
  76. 76. Change in the manifestations of asthma and asthma- related traits in childhood: a latent transition analysis Garden FL. Eur Respir J 2016;47:499–509 Phenotype prevalence and transition probabilities between the phenotypes at subsequent ages Prevalence of each phenotype at each age is recorded in the boxes under the age heading. The transition probabilities represent the probability that a member of a given phenotype at a specified age will transition to another given phenotype at the next specified age. Transition probabilities >0% are represented by arrows. The width and shading of the arrow represents the transition probability.
  77. 77. Asthma phenotypes in childhood: conceptual thoughts on stability and transition. Editorial Spycher BD. Eur Respir J 2016;47:362–365 In their study, GARDEN et al. use cohort data to distinguish phenotypes that not only optimally characterise the prevailing differences between children at given ages but also allow for the tendency of conditions to track. This is indeed novel. They do this by fitting a latent transition model to data on a range of asthma manifestations measured at ages 1.5, 3, 5, 8 and 11.5 years in children from CAPS (Childhood Asthma Prevention Study) in Sydney, Australia. The great advantage of this model is that it is extremely flexible and can produce both extremes explained above plus any intermediate form. The Garden et al. study would suggest that asthma is secondary to atopy in these children.
  78. 78. Severe Asthma in Children: Lessons Learned and Future Directions Fitzpatrick AM, JACI Pract 2016;4:11-19  Findings on severe asthma in school-age children (age 6-17 yrs) from the National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) over a 10-year period, between 2001 and 2011. Blood eosinophils Serum IgE P=0.005 P<0.001
  79. 79. 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.
  80. 80. 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.
  81. 81. In particular, mean numbers of mites transferred to fleece (pile) (compared with denim (jeans) and plain woven cotton) were greater for each treatment. Dynamics of house dust mite transfer in modern clothing fabrics Clarke D. Ann Allergy 2015;114:335  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. >
  82. 82. Scanning electron micrographs of the various fabric types used in the experiment: car seat cover material (100% polyester) plain woven cotton (100% Egyptian cotton) denim (100% cotton) fleece (100% polyester) Dynamics of house dust mite transfer in modern clothing fabrics Clarke D. Ann Allergy 2015;114:335
  83. 83. Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: ABAMSE/MeDALL study Asarnoj A, J Allergy Clin Immunol 2016;137:813-21 779 randomly collected children from Stockholm Epidemiologic birth cohort at 4, 8, and 16 years. IgE to cat and dog by ImmunoCAP Allergy defined as reported rhinitis, conjunctivitis, or asthma at exposure to cat or dog. •Polysensitization to ≥3 allergen molecules from cat or dog was a better longitudinal predictor of cat or dog symptoms than results of IgE tests with cat or dog allergen extract. •Cat/dog-polysensitized children had higher IgE levels and more frequent symptoms to cat and dog than monosensitized children.
  84. 84. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  85. 85. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence Duijts L, Eur Respir J 2016;47:510–519 a population-based, prospective cohort study of 6841 children, latent class analysis to identify wheezing phenotypes during the first 7 years of life. physician-diagnosed asthma, spirometry and FeNO at 14–15 years. Henderson J, Thorax 2008; 63: 974–980. six wheezing phenotypes identified by latent class analysis by age 7 years
  86. 86. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence Duijts L, Eur Respir J 2016;47:510–519 a population-based, prospective cohort study of 6841 children, latent class analysis to identify wheezing phenotypes during the first 7 years of life. physician-diagnosed asthma, spirometry and FeNO at 14–15 years. 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.
  87. 87. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence Duijts L, Eur Respir J 2016;47:510–519 a population-based, prospective cohort study of 6841 children, latent class analysis to identify wheezing phenotypes during the first 7 years of life. physician-diagnosed asthma, spirometry and FeNO at 14–15 years. 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?
  88. 88. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence Duijts L, Eur Respir J 2016;47:510–519 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)
  89. 89. Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence Duijts L, Eur Respir J 2016;47:510–519 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)
  90. 90. 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.
  91. 91. Of the 332 persons with COPD at the end of the observation period 60 – 50 – 40 – 30 – 20 – 10 – 0 48% 52% FEV1 before 40 years of age ≥80% and had a rapid decline in FEV1 thereafter, of 53±21 ml per year* <80% low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year* *P<0.001 for the decline participants in 3 independent cohorts stratified according to lung function [FEV1 ≥80% (n=2207) or <80% (n=657) of the predicted value) at cohort inception (mean age of patients, approximately 40 years] and the presence or absence of COPD at the last study visit. we then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. Follow-up: 22 years. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. Lange P, N Engl J Med. 2015;373(2):111-22.
  92. 92. 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
  93. 93. 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 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
  94. 94. 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 control 134-day fetal monkey lung. Masson trichrome–stained: connective tissue stained in blue nicotine-exposed 134-day fetal monkey lung
  95. 95. 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 Treatment of pregnant rhesus monkeys with low levels of nicotine designed to simulate the nicotine exposure of pregnant human smokers caused 1) increases in collagen and connective tissue, 2) decreased elastin which may underlie the decreased respiratory compliance 3) thickening of walls surrounding airways and pulmonary vessels 4) simplification of the alveoli leading to increased alveolar volume but decreased alveolar surface area This was also observed in newborn from smoking mothers
  96. 96. 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%
  97. 97. Progression to Traditional Cigarette Smoking After Electronic Cigarette Use Among US Adolescents and Young Adults Primack BA, JAMA Pediatr. 2015;169:1018-1023 Longitudinal cohort study 694 participants aged 16 to 26 yrs Never cigarette smokers and attitudinally nonsusceptible to smoking cigarettes Reassessed 1 year later yes 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % adolescent progressing to cigarette smoking over the 1-year follow-up 69% OR= 8.5 19% not e-cigarettes user
  98. 98. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  99. 99. Do the media demonstrate correct inhaler technique in children? King D, Arch Dis Child 2016;101:203 At least 50% of patients do not use their inhalers properly. This is associated with asthma instability, an increase in hospital attendances and a reduced quality of life. The media can encourage safe health practices but can also have negative effects on health behaviour.
  100. 100. Do the media demonstrate correct inhaler technique in children? King D, Arch Dis Child 2016;101:203 The top 10 news websites in the UK Stories published between 2010 and 2015 concerning childhood asthma 40 articles in which a child was pictured receiving inhaled therapy 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 7.5 % % articles in which inhaler technique was judged as being correctly demonstrated
  101. 101. Do the media demonstrate correct inhaler technique in children? King D, Arch Dis Child 2016;101:203 The top 10 news websites in the UK Stories published between 2010 and 2015 concerning childhood asthma 40 articles in which a child was pictured receiving inhaled therapy 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 7.5 % % articles in which inhaler technique was judged as being correctly demonstrated The most commonly demonstrated incorrect inhaler technique was using a pMDI without a spacer, which occurred in 66.7% of news articles.
  102. 102. Do the media demonstrate correct inhaler technique in children? King D, Arch Dis Child 2016;101:203 Correct use of the MDI with the spacer
  103. 103. Action Plan for Asthma treatment health literacy informed, pictogram
  104. 104. 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
  105. 105. 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 recommend spacer use (eg Albuterol) 83.6% p<0.001 43.1% The low-literacy plan Standard plan
  106. 106. 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 address need for daily medications when sick 100 - 93.4% p<0.001 34.5% The low-literacy plan Standard plan
  107. 107. 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 using explicit symptoms (eg, "ribs show when breathing," ) 100 - 54.1% p<0.001 3.4% The low-literacy plan Standard plan OR=33.0
  108. 108. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  109. 109. Sleep schedules and sleep duration for three sleep conditions (TST = total sleep time). Experimentally Manipulated Sleep Duration in Adolescents With Asthma: Feasibility and Preliminary Findings Meltzer L J. Ped Pul 2015;50:1360–1367 Self selected  10 adolescents with asthma  Following a week of self-selected sleep duration, adolescents randomized to a 5-night deficient sleep opportunity (6.5 hr in bed) or a healthy sleep opportunity (10 hr in bed) Wake time: bed time:
  110. 110. 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) Experimentally Manipulated Sleep Duration in Adolescents With Asthma: Feasibility and Preliminary Findings Meltzer L J. Ped Pul 2015;50:1360–1367
  111. 111. Experimentally Manipulated Sleep Duration in Adolescents With Asthma: Feasibility and Preliminary Findings Meltzer L J. Ped Pul 2015;50:1360–1367 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).
  112. 112. 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)
  113. 113. 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
  114. 114. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  115. 115. Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma Ma J, Eur Respir J 2016; 47: 122–132 Asthma prevalence has increased in recent years, currently affecting >18 million US adults. Diet composition changes and worsened diet quality have been implicated as contributing factors in this trend, as well as poor asthma control. Some studies have investigated the potential benefit of certain foods (e.g. fruit, vegetables and fish) and nutrients (e.g. vitamins C, D and E, and ω-3 fatty acids) Vegetable and oils consumption in UK Devereux G. JACI 2005;115(6):1109-17
  116. 116. 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. Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma Ma J, Eur Respir J 2016; 47: 122–132 90 adults with objectively confirmed uncontrolled asthma and a low-quality diet [Dietary Approaches to Stop Hypertension (DASH) scores <6 out of 9] a 6-month DASH behavioural intervention (n=46) or usual-care control (n=44).
  117. 117. + + =
  118. 118. Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma Ma J, Eur Respir J 2016; 47: 122–132 90 adults with objectively confirmed un<controlled asthma and a low-quality diet [Dietary Approaches to Stop Hypertension (DASH) scores <6 out of 9] a 6-month DASH behavioural intervention (n=46) or usual-care control (n=44). Compared with controls, intervention participants improved on: 1) DASH scores (mean change difference 0.8) 2) Asthma Control Questionnaire scores at 6 months. 3) Asthma Quality of Life: - overall 0.4, - symptoms 0.5, - environment 0.4, - emotions 0.4 and - activities 0.3.
  119. 119. Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma 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.
  120. 120. The role of circulating 25 hydroxyvitamin D in asthma: a systematic review Cassim R. Allergy 2015;70:339-354  Association between serum Vitamin D and asthma incidence, prevalence, severity and exacerbations.  23 manuscripts: 2 case–control, 12 cohort and 9 cross-sectional studies  Collectively, the evidence suggests that higher serum levels of 25(OH)D are associated with a reduced risk of asthma exacerbations (RR = 0.64)  There was little evidence to suggest an association with asthma incidence, prevalence or severity.
  121. 121. 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
  122. 122. 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 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.
  123. 123. 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 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
  124. 124. 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
  125. 125. serum 25(OH)D levels <50 nmol·L−1 compared to > 50 nmol·L−1 OR for development of impaired lung function (FEV1/FVC <70%) in ever smokers 3.0 – 2.0 – 1.0 – 0.0 2.4 Serum 25-hydroxyvitamin D level, smoking and lung function in adults: the HUNT Study Larose TL, Eur Respir J 2015;46:355–363  a random sample of adults from Norway  cross-sectional (n=1220) and follow-up (n=869)  interrelationship of serum 25(OH)D, smoking and lung function changes
  126. 126.  582 children aged 6 to 14 yrs with (n = 304) and without (n = 278) asthma.  Folate deficiency defined as plasma folate ≤20 ng/ml. Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children Blatter J, Ann Am Thorac Soc 2016;13:223-230 Mean n° of (+) SPTs YES NO 3.8 4.9 p<0.001 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 Folate deficiency
  127. 127. Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children Blatter J, Ann Am Thorac Soc 2016;13:223-230 In children with folate deficiency OR for at least one severe asthma exacerbation 2.8 2.2 p<0.01 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.0 p=0.04 vitamin D insufficiency (<30 ng/ml reduction)  582 children aged 6 to 14 yrs with (n = 304) and without (n = 278) asthma.  Folate deficiency defined as plasma folate ≤20 ng/ml.
  128. 128. Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children Blatter J, Ann Am Thorac Soc 2016;13:223-230 OR for at least one severe asthma exacerbation in children with both folate deficiency and vitamin D insufficiency (<30 ng/ml reduction) 7.9 8.0 – 7.0 – 6.0 – 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0  582 children aged 6 to 14 yrs with (n = 304) and without (n = 278) asthma.  Folate deficiency defined as plasma folate ≤20 ng/ml.
  129. 129. Future Research Antioxidants? (-) (+) Transcription factors are proteins that bind to DNA controlling the transcription of messenger RNA
  130. 130.  47 asthmatic children (moderate-severe GINA Guidelines) (12.01 ± 3.1 years) admitted to Istituto Pio XII, Misurina (m 1753)  Supplementation for 1 mo with a mixture of nutraceuticals: soy genistein, curcumin, resveratrol, vitamin D, zinc, magnesium, selenium, folic acid (n=15) or controls (n=32)  FeNO expressed as median values 9% Anti-oxidants supplementation reduces FeNO in children with asthma. Tenero L. Allergy Asthma Proc. 2016;37(1):8-13. ns P=0.03 18 16 19 11 Controls
  131. 131.  47 asthmatic children (moderate-severe GINA Guidelines) (12.01 ± 3.1 years) admitted to Istituto Pio XII, Misurina (m 1753)  Supplementation for 1 mo with a mixture of nutraceuticals: soy genistein, curcumin, resveratrol, vitamin D, zinc, magnesium, selenium, folic acid (n=15) or controls (n=32)  FeNO expressed as median values 9% Anti-oxidants supplementation reduces FeNO in children with asthma. Tenero L. Allergy Asthma Proc. 2016;37(1):8-13. ns P=0.03 18 16 19 11 Controls
  132. 132. Attilio Boner University of Verona, Italy attilio.boner@univr.it Asthma develoment risk factors Asthma predictive symptoms Asthma and wheezing phenotypes A & W phenotypes and lung function Asthma and education / action plan Asthma aggravating factors Asthma tratment besides ICS Asthma burden
  133. 133. 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
  134. 134. 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.
  135. 135. The Prevalence of Sleep-Disordered Breathing in Children with Asthma and its Behavioral Effects N.A.Goldstein, Pediatric Pulmonology 2015;50:1128–1136  Pediatric Sleep Questionnaire (PSQ) and the Child Behavior Checklist  263 children with asthma and 266 controls ages 2 to 15 years 35 – 30 – 25 – 20 – 15 – 10 – 15 - 35.5% 15.7% 0 Prevalence of snoring asthmatics controls p<0.001
  136. 136. The Prevalence of Sleep-Disordered Breathing in Children with Asthma and its Behavioral Effects N.A.Goldstein, Pediatric Pulmonology 2015;50:1128–1136 30 – 25 – 20 – 15 – 10 – 15 - 25.9% 10.6% 0 Prevalence of positive PSQ p<0.001  Pediatric Sleep Questionnaire (PSQ) and the Child Behavior Checklist  263 children with asthma and 266 controls ages 2 to 15 years asthmatics controls
  137. 137. The Prevalence of Sleep-Disordered Breathing in Children with Asthma and its Behavioral Effects N.A.Goldstein, Pediatric Pulmonology 2015;50:1128–1136 In children with (+) vs (-) Pediatric Spleep Questionnaire OR for 6.09 7.0 – 6.0 – 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 Internalizing problems P < 0.001  Pediatric Sleep Questionnaire (PSQ) and the Child Behavior Checklist  263 children with asthma and 266 controls ages 2 to 15 years
  138. 138. Coeliac disease and asthma association in children: the role of antibiotic consumption Canova C. Eur Respir J 2015;46:115–122 in children with asthma incidence rate ratios (IRR) for Coeliac Disease 2.0 – 1.0 – 0.0 1.46  A cohort of 1430144 children born in 1995–2011 in the Friuli-Venezia Giulia.  Prescriptions for antibiotics in the first year of life.  Coeliac disease incident cases.
  139. 139. Coeliac disease and asthma association in children: the role of antibiotic consumption Canova C. Eur Respir J 2015;46:115–122 in children with asthma incidence rate ratios (IRR) for Coeliac Disease 2.0 – 1.0 – 0.0 1.46  A cohort of 1430144 children born in 1995–2011 in the Friuli-Venezia Giulia.  Prescriptions for antibiotics in the first year of life.  Coeliac disease incident cases. Antibiotics were not a confounding factor in these associations.
  140. 140.  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. Coeliac disease and asthma association in children: the role of antibiotic consumption Canova C. Eur Respir J 2015;46:115–122
  141. 141. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  142. 142. Mouse Sensitivity is an Independent Risk Factor for Rhinitis in Children with Asthma Sedaghat AR, JACI Pract 2016;4:82-88 In asthmatic children with mouse sIgE ≥ 0.35 IU/mL OR for rhinitis 2.40 2 weeks year In the past 2.15 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0.0 p=0.02p=0.04  499 urban children (5-17 years) with persistent asthma.  Mouse-specific IgE cockroach-specific IgE.
  143. 143. Nocturnal GERD – a risk factor for rhinitis/rhinosinusitis: the RHINE study Schiőler L, Allergy 2015;70:697–702 OR for developing noninfectious rhinitis in 2010 nocturnal GERD in 1999 (≥3 episodes of nocturnal gastroesophageal reflux symptoms per week) 1.6 p=0.03 2.0 – 1.0 – 0.0  5417 subjects born between 1945 and 1973  a questionnaire in 1999–2001 and again in 2010–2012  noninfectious rhinitis defined as having nasal obstruction, secretion, and/or sneezing without having the common cold
  144. 144.  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
  145. 145. Aggravation of airway inflammation and hyper-responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma. Wang W, Allergy 2016;71: 378–386  15 nonasthmatic Der-p-sensitized rhinitis (AR) patients with airway hyper-responsiveness (AHR) (AR+AHR+).  15 AR patients without AHR (AR+AHR-).  15 healthy controls (HCs) with Der-p sensitization (HC+DP+).  15 HC without Der-p sensitization (HC+DP-).  All subjects underwent Der-p NPT. Nasal Airway Resistance (NAR) increased significantly in all subjects with the greatest effect seen in AR+AHR+ individuals.
  146. 146. Aggravation of airway inflammation and hyper-responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma. Wang W, Allergy 2016;71: 378–386  15 nonasthmatic Der-p-sensitized rhinitis (AR) patients with airway hyper-responsiveness (AHR) (AR+AHR+).  15 AR patients without AHR (AR+AHR-).  15 healthy controls (HCs) with Der-p sensitization (HC+DP+).  15 HC without Der-p sensitization (HC+DP-).  All subjects underwent Der-p NPT. 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)
  147. 147. Aggravation of airway inflammation and hyper-responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma. Wang W, Allergy 2016;71: 378–386  15 nonasthmatic Der-p-sensitized rhinitis (AR) patients with airway hyper-responsiveness (AHR) (AR+AHR+).  15 AR patients without AHR (AR+AHR-).  15 healthy controls (HCs) with Der-p sensitization (HC+DP+).  15 HC without Der-p sensitization (HC+DP-).  All subjects underwent Der-p NPT. •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).
  148. 148. Aggravation of airway inflammation and hyper-responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma. Wang W, Allergy 2016;71: 378–386 Nasal resistance increased also in healthy controls either sensitive or not to DP.
  149. 149. 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.
  150. 150. 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
  151. 151. 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.
  152. 152. 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.
  153. 153. 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.
  154. 154. 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
  155. 155. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  156. 156. 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
  157. 157. Epidemiology and clinical predictors of biphasic reactions in children with anaphylaxis. Alqurashi, Ann Allergy Asthma Immunol 2015;115:217 Age 6-9 yrs OR for biphasic reactions. 3.60 2.58 2.92 2.7 Delay in presentation to the ED >90’ after the onset of the initial reaction Wide pulse pressure at triage Treatment of the initial reaction with ≥1 dose of epinephrine 4.0 – 3.0 – 2.0 – 1.0 – ….0 2.39 Administration of inhaled β-agonists in the ED diastolic blood pressure ≤ half the systolic blood pressure
  158. 158. Epidemiology and clinical predictors of biphasic reactions in children with anaphylaxis. Alqurashi, Ann Allergy Asthma Immunol 2015;115:217 Age 6-9 yrs OR for biphasic reactions. 3.60 2.58 2.92 2.7 Delay in presentation to the ED >90’ after the onset of the initial reaction Wide pulse pressure at triage Treatment of the initial reaction with ≥1 dose of epinephrine 4.0 – 3.0 – 2.0 – 1.0 – ….0 2.39 Administration of inhaled β-agonists in the ED Biphasic reactions seem to be associated with the severity of the initial anaphylactic reactions. diastolic blood pressure ≤ half the systolic blood pressure
  159. 159. Time of Onset and Predictors of Biphasic Anaphylactic Reactions: A Systematic Review and Meta-analysis Lee S, JACI Pract 2015;3:408-416 4.6% 5.0 – 4.0 – 3.0 – 2.0 – 1.0 – 0.0 % patients with biphasic anaphylatic reactions  27 studies that described biphasic reactions.  4114 patients with anaphylaxis and 192 pts with biphasic reactions (recurrence of symptoms within 72 hours).
  160. 160. Time of Onset and Predictors of Biphasic Anaphylactic Reactions: A Systematic Review and Meta-analysis Lee S, JACI Pract 2015;3:408-416 OR for biphasic anaphylatic reactions Food as a trigger 0.62 1.51 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0.0 2.18 Unknow trigger Initial symptoms diarrhea Initial presentation with hypotension 1.72 2.53  27 studies that described biphasic reactions.  4114 patients with anaphylaxis and 192 pts with biphasic reactions (recurrence of symptoms within 72 hours).
  161. 161. Time of Onset and Predictors of Biphasic Anaphylactic Reactions: A Systematic Review and Meta-analysis Lee S, JACI Pract 2015;3:408-416 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.
  162. 162. Epinephrine doses contained in outdated epinephrine auto-injectors collected in a Florida allergy practice Rachid O. Ann Allergy 2015;114:354  35 EpiPens (0.3 mg), 3 to 36 months past the expiry collected from patients in Florida, where outdoor temperatures range from 11°C to 32°C. The EAIs that were 24 to 36 months past the expiry date were very lightly discolored and contained 84.2% to 95.7% of the labeled dose.
  163. 163. 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)
  164. 164.  28 patients (age range of 18-75) already prescribed adrenaline autoinjectors (AAIs) for anaphylaxis  ultrasound and measurements of skin-to muscle depth (STMD) at anterolateral thigh and anterior thigh Excess subcutaneous tissue may preclude intramuscular delivery when using adrenaline autoinjectors in patients with anaphylaxis Johnstone J, Allergy 2015;70:703–706 using the anterolateral thigh as the recommended administration site 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 68% % patients with skin-to-muscle depth > needle length (15.02 mm) The key predictors for increased STMD were female gender (p=0.0003) and a BMI > 30 (p=0.04)
  165. 165. Effect of use of inhaled epinephrine on intramuscular epinephrine use in patients with idiopathic anaphylaxis and angioedema. Stone CA, Ann Allergy Asthma Immunol 2016;116:162  We report 2 cases of patients with frequent attacks of throat angioedema who have benefitted from the use of inhaled epinephrine in reducing the frequency with which they have required intramuscular epinephrine. Inhaled racemic epinephrine in the form of a 2.25% solution diluted in saline is satisfactory for aborting most of throat angioedema episodes.
  166. 166. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  167. 167. 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
  168. 168. p < 0.004 60 – 50 – 40 – 30 – 20 – 10 – 0 - (+) CMP allergic contact urticaria 14.3% 50% (-) % children with multiple food allergies 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  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.
  169. 169. 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 71% 37% p = 0.0064 YES NOT ATOPIC DERMATITIS % children with CMP allergic contact urticaria 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  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.
  170. 170. 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. 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
  171. 171.  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
  172. 172.  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
  173. 173.  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
  174. 174. % patients with attack sites Clinical Features of Pediatric Hereditary Angioedema Nanda MK, JACI Pract 2015;3:392-395 100 – 090 – 080 – 070 – 060 – 050 – 040 – 030 – 020 – 010 – 000 abdominal peripheral laryngeal 93% 73% 27%  21 children with diagnosis of type I or II hereditary angioedema (HAE) (C1-INH, C1 inhibitor function, C1q, C2, C3, C4).  Median age 13.2 yrs.
  175. 175. 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
  176. 176. What is New in Allergic & Diseases Respiratory 2016 Attilio Boner University of Verona, Italy attilio.boner@univr.it Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases
  177. 177. bronchiolitis
  178. 178. Is nasal suctioning warranted before measuring O2 saturation in infants with bronchiolitis? Moschino L, Arch Dis Child 2016;101:114-115 40 infants under 12 months old with bronchiolitis and SpO2 level initially ≤96% and ≥88% Superficial nasal suctioning performed using a 6 Fr catheter and a negative pressure of 60–80 mmHg for neonates, 80–100 mmHg for infants 8’ later, SpO2 measured again SpO2 levels measured pre-nares suctioning and 8’ after suctioning of the nares p<0.001 median pre-SpO2 94% median post-SpO2 97%
  179. 179. Use of Intermittent vs Continuous Pulse Oximetry for Nonhypoxemic Infants and Young Children Hospitalized for Bronchiolitis McCulloh R, JAMA Pediatr. 2015;169:898-904 For the management of patients with bronchiolitis, the 2006 American Academy of Pediatrics (AAP) guidelines stated that continuous measurement of oxygen saturation by pulse oximetry (SpO2) was not routinely necessary for patients who show clinical improvement. 2014 AAP guidelines further recommended using intermittent pulse oximetry monitoring of children hospitalized for bronchiolitis who are not receiving supplemental oxygen.
  180. 180. Use of Intermittent vs Continuous Pulse Oximetry for Nonhypoxemic Infants and Young Children Hospitalized for Bronchiolitis McCulloh R, JAMA Pediatr. 2015;169:898-904 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
  181. 181. Use of Intermittent vs Continuous Pulse Oximetry for Nonhypoxemic Infants and Young Children Hospitalized for Bronchiolitis McCulloh R, JAMA Pediatr. 2015;169:898-904 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.
  182. 182. 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
  183. 183. 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.
  184. 184.  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
  185. 185.  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 No significant adverse events related to HS inhalation were reported
  186. 186.  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 Nebulized HS is a safe and potentially effective treatment of infants with acute bronchiolitis
  187. 187. Hypertonic saline for bronchiolitis: a case of less is more Legg JP, Arch Dis Child 2015;100:1104–1105 a study from Finland by Skjerven et al. N Engl J Med. 2013;368(24):2286. compared epinephrine and normal saline in 404 infants with bronchiolitis. Protocol designed to assess the effect of fixed scheduling or on-demand nebulisation. Infants in the on-demand nebulisation group: -received fewer doses of treatment -were discharged significantly sooner -were discharged with fewer requiring supplemental oxygen -were discharged with fewer ventilator support
  188. 188. Hypertonic saline for bronchiolitis: a case of less is more Legg JP, Arch Dis Child 2015;100:1104–1105 a study from Finland by Skjerven et al. N Engl J Med. 2013;368(24):2286. compared epinephrine and normal saline in 404 infants with bronchiolitis. Protocol designed to assess the effect of fixed scheduling or on-demand nebulisation. Infants in the on-demand nebulisation group: -received fewer doses of treatment -were discharged significantly sooner -were discharged with fewer requiring supplemental oxygen -were discharged with fewer ventilator support The improved outcomes in this study for those infants left alone to get better endorse the notion that minimal handling is important for a more speedy recovery in acute bronchiolitis.
  189. 189. Hypertonic saline for bronchiolitis: a case of less is more 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 infant with bronchiolitis than regular disturbance with interventions that either do not work or are of questionable benefit. Sleep and rest Good hydration
  190. 190. Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study De Vincenzo J. NEJM 2015;373:2048-58  62 healthy adults inoculated with RSV  Oral nucleoside analogue ALS-008176 (RSV replication inhibitor) or placebo 12 hours after confirmation of RSV infection or 6 days after inoculation administered every 12 hours for 5 days in different dosages in 3 groups: 1,2,3 Mean Viral Loads days
  191. 191. Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study De Vincenzo J. NEJM 2015;373:2048-58 Mean Symptom Scores  62 healthy adults inoculated with RSV  Oral nucleoside analogue ALS-008176 (RSV replication inhibitor) or placebo 12 hours after confirmation of RSV infection or 6 days after inoculation administered every 12 hours for 5 days in different dosages in 3 groups: 1,2,3 days

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