What is new in general pediatrics, allergic and respiratory diseases

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

2. Attilio Boner University of Verona, Italy attilio.boner@univr.it General Pediatics Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases What is New in General Pediatrics, Allergic & Respiratory Diseases 2017 ?

3. General Pediatrics: prematurity

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

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

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

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

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

9. DOHD

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

11. Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood Twig G, N Engl J Med 2016;374(25):2430-40 BMI during adolescence and subsequent cardiovascular mortality  On multivariable analysis, there was a graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range)

12. Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood Twig G, N Engl J Med 2016;374(25):2430-40 Conclusions • A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. • Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood !

13. 8:00 p.m. or earlier 10% 16% 25 – 20 – 15 – 10 – 05 – 00 – prevalence of adolescent obesity after 8:00 p.m. but by 9:00 p.m. after 9:00 p.m. Bedtimes at Pre-School Age Bedtime in Preschool-Aged Children and Risk for Adolescent Obesity Anderson SE, J Pediatr. 2016;176:17-22 23%  977 participants in the Study of Early Child Care and Youth Development.  In 1995-1996, mothers reported their preschool- aged (mean = 4.7 years) child's typical weekday bedtime.  At a mean age of 15 years, height and weight.

14. 0.48 for preschoolers with early bedtimes compared with preschoolers with late bedtimes OR for for adolescent obesity Bedtime in Preschool-Aged Children and Risk for Adolescent Obesity Anderson SE, J Pediatr. 2016;176:17-22 1.0 – 0.5 – 0.0 - (8:00 p.m. or earlier)  977 participants in the Study of Early Child Care and Youth Development.  In 1995-1996, mothers reported their preschool- aged (mean = 4.7 years) child's typical weekday bedtime.  At a mean age of 15 years, height and weight.

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

16. Doctors’ behaviour

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

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

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

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

21. A pilot study of an emotional intelligence training intervention for a paediatric team. Bamberger E. Arch Dis Child. 2017;102(2):159-164. Emotional Intelligence (EI) of 17 physicians and 10 nurses in paediatric ward prospectively evaluated with Bar-On’s EI at baseline and after 18 months. 11 physicians who did not undergo the intervention served as controls. Bar-On’s1 emotional quotient inventory (EQ-i) was used to measure study participants’ EI. The EQ-i is a self-report measure consisting of 133 items covering what Bar-On describes as the 5 main dimension of EI, namely 1) intrapersonal EI, 2) interpersonal EI, 3) adaptability, 4) stress management, 5) general mood.

22. A pilot study of an emotional intelligence training intervention for a paediatric team. Bamberger E. Arch Dis Child. 2017;102(2):159-164. •reduced occupational stress, Littlejohn P. J Prof Nurs 2012;28:360–8. Mikolajczak M, J Res Pers 2007;41:1107–17. •enhanced interpersonal relations, Goleman D. Emotional intelligence. New York: Random House, 2006. Mayer JD, Annu Rev Psychol 2008;59:507–36. •higher quality leadership, Palmer B, Leadership Org Dev J 2001;22:5–10. Carmeli A. J Manage Psychol 2003;18:788–813. •better performance at both the individual and the team levels. Druskat VU, Harv Bus Rev 2001;79:80–91. Hughes M, . London: John Wiley & Sons, 2009. In the workplace, EI is associated with:

23. •The magnitude of improvement in patient satisfaction noted above suggests that EI interventions may offer substantial economic utility, particularly to the extent that enhanced satisfaction is associated with 1) reduced risk of malpractice suits, 2) better post-discharge compliance by patients. 3) enhanced hospital competitiveness. A pilot study of an emotional intelligence training intervention for a paediatric team. Bamberger E. Arch Dis Child. 2017;102(2):159-164.

24. General pediatrics First aid

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

26.  The European Resuscitation Council Guidelines for Resuscitation recommend that “an unconscious child whose airway is clear, and who is breathing normally, should be turned on his side into the recovery position”.  The basic principle of the RP is to protect the airway; • the mouth is downward so that fluid can drain from the patient's airway, while • the chin is up to keep the epiglottis open. • arms and legs are locked to stabilise the position of the patient. Recovery position significantly associated with a reduced admission rate of children with loss of consciousness Julliand S, Arch Dis Child. 2016;101:521-526

27. Recovery position significantly associated with a reduced admission rate of children with loss of consciousness Julliand S, Arch Dis Child. 2016;101:521-526 26.2% 30 – 25 – 20 – 15 – 10 – 05 – 00 – % cases in which caregivers put the child in the Recovery Position  553 consecutive children aged between 0 and 18 yrs diagnosed with loss of consciousness (LOC) at 11 paediatric emergency departments (PEDs) of 6 European countries.  Data were obtained from parental interviews, PED reports and clinical examination.

28. Recovery position significantly associated with a reduced admission rate of children with loss of consciousness Julliand S, Arch Dis Child. 2016;101:521-526 0.28 1.0 – 0.5 – 0.0 – when caregivers put the child in the Recovery Position OR for p<0.0001 Hospital Admission  553 consecutive children aged between 0 and 18 yrs diagnosed with loss of consciousness (LOC) at 11 paediatric emergency departments (PEDs) of 6 European countries.  Data were obtained from parental interviews, PED reports and clinical examination. (-) (-)

29.  The RP is a simple manoeuvre which is commonly recommended in first aid for all unconscious people, in order to protect the airway against aspiration, which is a recognised cause of death in patients with epilepsy.  Ideally, everyone should be able to position a child on his side after Loss of Cosciousness. Recovery position significantly associated with a reduced admission rate of children with loss of consciousness Julliand S, Arch Dis Child. 2016;101:521-526

30.  School teachers are also likely to encounter LOC in a child, but previous studies have shown that their knowledge of emergency care is often deficient.  In our own study, manoeuvres other than the RP were made in 53% of cases, and more frequently included: • shaking, • putting water on the face, • slapping and blowing on the face. Recovery position significantly associated with a reduced admission rate of children with loss of consciousness Julliand S, Arch Dis Child. 2016;101:521-526

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

32. Health Disparities Influence Childhood Melanoma Stage at Diagnosis and Outcome Hamilton EC, J Pediatr. 2016;175:182-187  All persons aged ≤18 years diagnosed with melanoma between 1995 and 2009 in South Carolina and Texas. • A total of 185 adolescents (age >10 years) and 50 young children (age ≤10 years) were identified.

33. 3.8 Hispanics vs non-Hispanic whites OR for presenting with advanced disease Health Disparities Influence Childhood Melanoma Stage at Diagnosis and Outcome Hamilton EC, J Pediatr. 2016;175:182-187 4.0 – 3.0 – 2.0 – 1.0 – 0.0 – young children vs adolescents 2.2

34. General Pediatrics Gastroenterology

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

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

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

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

39. General Pediatrics Nutrition

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

41. A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial Akkermans MD, Am J Clin Nutr. 2017;105:391-399 • Iron deficiency (ID) was defined as Serum Ferritin <12 μg/L in the absence of infection (high-sensitivity C-reactive protein <10 mg/L) and Vitamin D Deficiency as 25(OH)D <50 nmol/L.  318 children (1-3 yrs) allocated to receive either a micronutrient-fortified young-child formula (YCF) [1.2 mg Fe/100 mL; 1.7 μg (68 UI) vitamin D/100 mL] or nonfortified cow milk (CM) (0.02 mg Fe/100 mL; no vitamin D) for 20 wk.  Change from baseline in serum ferritin (SF) and 25(OH)D.

42. A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial Akkermans MD, Am J Clin Nutr. 2017;105:391-399 1 Values are means ± SDs unless otherwise indicated. The change from baseline in serum ferritin and serum 25(OH)D were analyzed while adjusting for sex and country (stratification factors), age, micronutrient status at baseline, and the iron or vitamin D intake from food and supplements (and sun exposure in the case of vitamin D). The iron analyses were performed in the modified intention-to-treat sample in which the children with an elevated high-sensitivity C-reactive protein were excluded to prevent falsely elevated or normal ferritin concentrations in the case of an infection. CM, cow milk; YCF, young-child formula; 25(OH), 25 hydroxyvitamin D 2 Estimated mean ± SEM (all such values). mean changes in iron and vitamin D status after 20 weeks intervention1

43. 25(OH)D <50 nmol/L Iron deficiency (serum Ferritin <12 μg/L) In the fortified young-child formula (YCF) group, at age 1-3 yrs, OR for A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial Akkermans MD, Am J Clin Nutr. 2017;105:391-399 0.22 0.42 P<0.001 P=0.036 1.0 – 0.5 – 0.0 –  318 children (1-3 yrs) allocated to receive either a micronutrient-fortified young-child formula (YCF) [1.2 mg Fe/100 mL; 1.7 μg (68 UI) vitamin D/100 mL] or nonfortified cow milk (CM) (0.02 mg Fe/100 mL; no vitamin D) for 20 wk.  Change from baseline in serum ferritin (SF) and 25(OH)D.

44. Attilio Boner University of Verona, Italy attilio.boner@univr.it General Pediatrics Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases What is New in General Pediatrics, Allergic & Respiratory Diseases 2017 ?

45. Weaning Prevention of food allergy

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

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

48.  Our results support the hypothesis that early, regular, and continuous consumption of CM formula within the first month of life prevents IgE-CMA, which is consistent with other studies regarding the prevention of CM, peanut, egg, cereal grain, and fish allergies. •Katz Y. J Allergy Clin Immunol 2010;126:77-82.e1 •Saarinen KM. Clin Exp Allergy 2000;30:400-6 •Du Toit G. J Allergy Clin Immunol 2008;122:984-91 •Du Toit G. N Engl J Med 2015;372:803-13 •Koplin JJ. J Allergy Clin Immunol 2010;126:807-13 •Poole JA. Pediatrics 2006;117:2175-82 •Kull I. Allergy 2006;61:1009-15  CM is usually introduced at an earlier age than solid foods, and sensitization to CM may be induced earlier than sensitization to solid foods. Therefore, immune tolerance can be promoted before the onset of CMA, which has been reported at an average age of 2.8 to 3.5 months. •Saarinen KM. J Allergy Clin Immunol 1999;104:457-61 •Santos A. Pediatr Allergy Immunol 2010;21:1127-34 The Association of the Delayed Introduction of Cow’s Milk with IgE-Mediated Cow’s Milk Allergies Onizawa Y. J Allergy Clin Immunol Pract 2016;4:481-488

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

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

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

52. Dietary total antioxidant capacity in early school age and subsequent allergic disease. Gref A, Clin Exp Allergy. 2017 Epub ahead of print 2359 children from the Swedish birth cohort BAMSE Dietary total antioxidant capacity (TAC) at age 8 years estimated by combining information on the child's diet the past 12 months from a food frequency questionnaire with a database of common foods analysed with the oxygen radical absorbance capacity method. asthma and rhinitis was based on questionnaires, and serum IgE antibodies were measured at 8 and 16 years. aOR for allergic asthma 0.57 P-value for trend = 0.031 1.0 – 0.5 – 0.0 TAC of the diet for the 3rd third compared to the 1st tertile at age 8 years

53. Dietary total antioxidant capacity in early school age and subsequent allergic disease. Gref A, Clin Exp Allergy. 2017 Epub ahead of print 2359 children from the Swedish birth cohort BAMSE Dietary total antioxidant capacity (TAC) at age 8 years estimated by combining information on the child's diet the past 12 months from a food frequency questionnaire with a database of common foods analysed with the oxygen radical absorbance capacity method. asthma and rhinitis was based on questionnaires, and serum IgE antibodies were measured at 8 and 16 years. 1.0 – 0.5 – 0.0 These findings indicate that implementing an antioxidant-rich diet in childhood may contribute to the prevention of allergic disease. 0.57 P-value for trend = 0.031 aOR for allergic asthma TAC of the diet for the 3rd third compared to the 1st tertile at age 8 years

54. Induction of tolerance

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

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

57. Cross-sensitization pollen food syndrome

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

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

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

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

62. 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % patients with polysensitization defined as sensitization to ≥3 aeroallergens 70% Sensitization to a nonnative plant without exposure is a marker of panallergen sensitization Hogan M. B. J Allergy Clin Immunol Pract 2016;4:982-984  126 patients (2-66 years) who attended the University of Nevada, Reno Allergy Clinic  Sensitization to a nonnative tree — Syagrus romanzoffiana (Queen Palm) — among a population not exposed to Queen Palm because geographical and climatic conditions do not support its growth.

63. 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 70% Sensitization to a nonnative plant without exposure is a marker of panallergen sensitization Hogan M. B. J Allergy Clin Immunol Pract 2016;4:982-984  126 patients (2-66 years) who attended the University of Nevada, Reno Allergy Clinic  Sensitization to a nonnative tree — Syagrus romanzoffiana (Queen Palm) — among a population not exposed to Queen Palm because geographical and climatic conditions do not support its growth. Queen Palm contains a significant amount of profilin, a known panallergen % patients with polysensitization defined as sensitization to ≥3 aeroallergens

65. Skin barrier

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

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

68. Anionic surfactants and commercial detergents decrease tight junction barrier integrity in human keratinocytes Xian M, JACI 2016;138:890.  Direct effect of surfactants on TJs of normal human epidermal keratinocytes (NHEKs), at air-liquid interface (ALI) cultures of NHEKs;  3 different classes of detergents: 1) two anionic surfactants (Sodium dodecyl sulfate [SDS] and sodium dodecyl benzene sulfonate [SDBS]), 2) a cationic surfactant (benzalkonium chloride [BZC]), 3) a nonionic surfactant (sorbitan mono-oleate [Tween 20]). Effect of surfactants in nontoxic doses on the barrier integrity of NHEKs: •After 72 hours of stimulation, anionic surfactants (SDS and SDBS) significantly decreased transepithelial electrical resistance (TER). •In parallel paracellular permeability was increased in a dose-dependent manner on stimulation with SDS and SDBS.

69. Anionic surfactants and commercial detergents decrease tight junction barrier integrity in human keratinocytes Xian M, JACI 2016;138:890.  Direct effect of surfactants on TJs of normal human epidermal keratinocytes (NHEKs), at air-liquid interface (ALI) cultures of NHEKs;  3 different classes of detergents: 1) two anionic surfactants (Sodium dodecyl sulfate [SDS] and sodium dodecyl benzene sulfonate [SDBS]), 2) a cationic surfactant (benzalkonium chloride [BZC]), 3) a nonionic surfactant (sorbitan mono-oleate [Tween 20]). •There was no barrier-disruptive effect of the cationic surfactant BZC and nonionic surfactant Tween 20 at all nontoxic doses. Collectively, these data demonstrate that anionic surfactants can break down the TJ barrier integrity of NHEKs.

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

71. AD allergic march

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

73. Skin barrier impairment at birth predicts food allergy at 2 years of age Kelleher MM, JACI 2016;137:1111-1116. 4.0 – 3.0 – 2.0 – 1.0 – 0.0 2.7 3.1 1 Percentile of TEWL at birth 25 50 75  Birth cohort (n= 1903);  Transepidermal water loss (TEWL) measured in the early newborn period and at 2 and 6 months of age;  At age 2 yrs SPTs and oral food challenges. OR for food allergy at age 2 yrs

74. Skin barrier impairment at birth predicts food allergy at 2 years of age Kelleher MM, JACI 2016;137:1111-1116. Conclusion  Neonatal skin barrier dysfunction predicts FA at 2 yrs of age, supporting the concept of transcutaneous allergen sensitization, even in infants who do not have AD.  TEWL could be used for stratifying infants in the first few days of life before development of AD or FA for targeted intervention studies to potentially alter the atopic march.

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

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

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

78. AD prevention

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

80. Cost-effectiveness of Prophylactic Moisturization for Atopic Dermatitis Xu S. JAMA Pediatr. 2017;171(2):e163909  the potential cost-effectiveness of prophylactic moisturization in preventing atopic dermatitis in high-risk newborns.  average cost of total-body moisturization using 7 common moisturizers from birth to 6 months of age The calculated amount of daily all-body moisturizer needed at birth was 3.6 g per application, which increased to 6.6 g at 6 months of age.

81. Cost-effectiveness of Prophylactic Moisturization for Atopic Dermatitis Xu S. JAMA Pediatr. 2017;171(2):e163909  the potential cost-effectiveness of prophylactic moisturization in preventing atopic dermatitis in high-risk newborns.  average cost of total-body moisturization using 7 common moisturizers from birth to 6 months of age For a 6-month time window, the average incremental gain in quality-adjusted life-years (QALYs) was cost-effective

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

83. AD treatment

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

85. Sample integrated treatment plan for a 4-yr-old boy with severe AD, allergies to dust mites, and food allergies to milk, peanut, and tree nut. Multidisciplinary interventions in the management of atopic dermatitis LeBovidge J. JACI 2016;138:325-34 Skin Care Plan When skin is flaring - Bath once per day in plain water, unscented soap if needed (soak entire body in water for15 minutes) - Add 1/2 cup bleach to bath water every day for 2 weeks then continue daily bath - Apply hydrocortisone 2.5% ointment to eczema areas 2x/day for maximum 14 days (not on face) - Apply triamcinolone 0.1% ointment to eczema areas 2x/day for maximum 14 days (not on face)

86. Sample integrated treatment plan for a 4-yr-old boy with severe AD, allergies to dust mites, and food allergies to milk, peanut, and tree nut. Multidisciplinary interventions in the management of atopic dermatitis LeBovidge J. JACI 2016;138:325-34 Skin Care Plan When skin is flaring - Apply mupirocin to open, oozy areas 3x/day until clear - Apply hydrated emolient/petrolatum to body and face while skin still damp and also several times per day -Apply wet pajamas/socks and cover with dry pajamas/socks at bedtime Wet dressing

87. Sample integrated treatment plan for a 4-yr-old boy with severe AD, allergies to dust mites, and food allergies to milk, peanut, and tree nut. Multidisciplinary interventions in the management of atopic dermatitis LeBovidge J. JACI 2016;138:325-34 Skin Care Plan Environmental Controls - No carpeting if possible - If carpeting, vacuum with a hepa-filtered vacuum once a week - Dust mite proof covers on bed and pillows - Minimize stuffed animals and clutter/books in bedroom - Wash bedding including stuffed animals in very hot water (>60 °C) - Use dryer on hot setting/ no clotheslines - Keep humidity @ < 50%

88. Sample integrated treatment plan for a 4-yr-old boy with severe AD, allergies to dust mites, and food allergies to milk, peanut, and tree nut. Multidisciplinary interventions in the management of atopic dermatitis LeBovidge J. JACI 2016;138:325-34 Skin Care Plan Behavioral Strategies to Break the Itch-Scratch Cycle - Focus on what your child CAN do when he is itchy to increase his sense of control - Re-apply moisturizer - Apply a cool pack or cool wash cloth to itchy areas - Re-direct to hands-on activities such as drawing, blocks, hand-held electronics - For trigger times (story hour at preschool), keep hands busy with a stress ball - Distract and relax with guided imagery - Avoid saying “no scratching” a lot, as this will increase stress.

89. Sample integrated treatment plan for a 4-yr-old boy with severe AD, allergies to dust mites, and food allergies to milk, peanut, and tree nut. Multidisciplinary interventions in the management of atopic dermatitis LeBovidge J. JACI 2016;138:325-34 Skin Care Plan Cooperation with Treatment - Involve child in rubbing in moisturizer to increase control -Play games with skincare (draw on body with moisturizer, try to “beat your best time,” red-light, green-light, apply moisturizer to parent first) - Listen to audio book in tub for distraction - Praise child for participation!

90. Sample integrated treatment plan for a 4-yr-old boy with severe AD, allergies to dust mites, and food allergies to milk, peanut, and tree nut. Multidisciplinary interventions in the management of atopic dermatitis LeBovidge J. JACI 2016;138:325-34 Skin Care Plan - Nutrition Recommendations - Read all food labels to avoid peanut, tree nut and cow’s milk. - Continue calcium and multivitamin and vitamin D supplement - Limit juice to no more than 4 fluid ounces (120 mL) per day - All meals, snacks and caloric beverages should be at the table - Send box of safe treats for special occasions at preschool -Refer to recipes, meal ideas, snack suggestions and list of popular specialty manufacturers provided

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

92. Asthma worsening factors Diet

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

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

95. Asthma worsening factors Smoking e-cigarettes

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

97. Asthma worsening factors Gastro esophageal reflux

98. 6.3% Endoscopic incidence of inlet patch (IP) 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 –  Consecutive patients aged <18 years (n = 1000) undergoing esophagogastroduodenoscopy.  Biopsy specimens from inlet patch (IP) IPs and the proximal and distal esophagus, stomach, and duodenum.  Impedance and pH monitoring (MII-pH) performed in all symptomatic patients. Esophageal Inlet Patch: An Under-Recognized Cause of Symptoms in Children Di Nardo G, J Pediatr. 2016;176:99-104

99.  Consecutive patients aged <18 years (n = 1000) undergoing esophagogastroduodenoscopy.  Biopsy specimens from inlet patch (IP) IPs and the proximal and distal esophagus, stomach, and duodenum.  Impedance and pH monitoring (MII-pH) performed in all symptomatic patients. asymptomatic 56% 17% % patients with inlet patch symptoms clearly related to the underlying digestive disorder chronic IP-related symptoms 27% 60 – 50 – 40 – 30 – 20 – 10 – 00 – 44% with laryngopharyngeal symptoms (ie dysphagia, laryngospasms, hoarseness, globus throat discomfort, and chronic cough) Esophageal Inlet Patch: An Under-Recognized Cause of Symptoms in Children Di Nardo G, J Pediatr. 2016;176:99-104

100. • Multichannel intraluminal impedance and pH monitoring (M II-pH) was positive in 10 of the 28 symptomatic patients. • All 17 patients with inlet patch (IP)-related symptoms were unresponsive to proton pump inhibitors and were treated with argon plasma coagulation (APC), and all had achieved complete remission by the 3-year follow-up. • IP is an under-recognized cause of symptoms in children with unexplained esophageal and respiratory symptoms. Esophageal Inlet Patch: An Under-Recognized Cause of Symptoms in Children Di Nardo G, J Pediatr. 2016;176:99-104

101. Typical endoscopic appearance of inlet patch (IP) IP treatment with argon plasma coagulation (APC) Endoscopic findings at the end of the APC treatment Esophageal Inlet Patch: An Under-Recognized Cause of Symptoms in Children Di Nardo G, J Pediatr. 2016;176:99-104

102. Vitamin D Protective factors for asthma development

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

104. Association of T-regulatory cells and CD23/CD21 expression with vitamin D in children with asthma Chary AV Ann Allergy Asthma Immunol 2016;116:447-454 Correlation of 25(OH)D3 and B cells with CD23 (IgE receptor) expression Correlation of 25(OH)D3 and B cells with CD21 (IgE receptor) expression

105. Association of T-regulatory cells and CD23/CD21 expression with vitamin D in children with asthma Chary AV Ann Allergy Asthma Immunol 2016;116:447-454 Conclusion: The current study found low vitamin D levels associated with impaired Treg cell population and high numbers of B cells with IgE receptors (CD23 and CD21) and altered regulatory cytokines in children with asthma, suggesting impaired immune regulation. IL-10

106. Asthma clinical aspects

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

108. Mouth breathing, another risk factor for asthma: the Nagahama Study Izuhara Y. Allergy 2016;71:1031-1036 Risk ratio of mouth breathing for sensitization to house dust mite, blood eosinophilia (≥250/ll), and lower FEV1 (<90% predicted) in nonasthmatics with adjustment for allergic rhinitis

109. Conclusion: Mouth breathing may increase asthma morbidity, potentially through increased sensitization to inhaled allergens, which highlights the risk of mouth bypass breathing in the ‘one airway, one disease’ concept. The risk of mouth breathing should be well recognized in subjects with allergic rhinitis and in the general population. Mouth breathing, another risk factor for asthma: the Nagahama Study Izuhara Y. Allergy 2016;71:1031-1036

110. Asthma lung function decline

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

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

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

114. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma McGeachie MJ, N Engl J Med 2016;374:1842-52 As compared with participants who had a normal growth pattern, those with a pattern of normal growth and an early decline had a higher body-mass index at enrollment (OR, 1.39; P = 0.02), a greater likelihood of maternal cigarette smoking during gestation (OR, 2.33; P = 0.04)

115. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma McGeachie MJ, N Engl J Med 2016;374:1842-52 Participants with the reduced-growth pattern, as compared with those who had normal growth, had: • lower FEV1 values at enrollment (OR, 0.86 per 1% change in the pred. value; P<0.001), • a lower bronchodilator response (OR, 0.91 per 1% change; P<0.001), and • greater airway hyperresponsiveness (OR, 0.61 per unit change in log-transformed milligrams per milliliter; P<0.001); • were more likely to be male (OR, 8.18; P<0.001); • were younger at enrollment (OR, 0.55 per year of age; P<0.001); • had a lower level of parental education (OR for at least a college degree vs. a lower level, 0.33; P = 0.002); • were more likely to have vitamin D insufficiency (OR, 2.15; P = 0.03); • received more courses of prednisone per year during the trial (OR, 4.12 for each additional course; P = 0.03).

116. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma McGeachie MJ, N Engl J Med 2016;374:1842-52 Participants with reduced growth and an early decline, as compared with those who had normal growth, had: • lower FEV1 lung function at enrollment (OR, 0.85), • a lower bronchodilator response (OR, 0.91), and • increased airway hyperresponsiveness (OR, 0.66); • were more likely to be male (OR, 3.07); • were younger at enrollment (OR, 0.62 per year); and • had a lower level of parental education (OR, 0.43 for at least a college degree vs. a lower level; P = 0.01 ), • a greater number of positive skin tests at enrollment (OR for ≥3 positive tests vs. <3, 2.42; P = 0.03 ).

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

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

119. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial Stokholm J, Lancet Respir Med 2016;4:19-26 Reduction of duration of episodes of troublesome lung symptoms after azithromycin treatment as a function of episode duration before treatment  3-day course of azithromycin oral solution of 10 mg/kg per day or placebo.  158 asthma-like episodes in 72 children aged 1-3 years.  79 (50%) episodes to azithromycin and 79 (50%) to placebo). p<0·0001

120. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial Stokholm J, Lancet Respir Med 2016;4:19-26 • We discovered in our birth cohort, the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000; a previous birth cohort of children born to mothers with asthma), that airway bacteria (Haemophilus influenzae , Streptococcus pneumoniae , and Moraxella catarrhalis ) and respiratory viruses (at least one of rhinovirus, respiratory syncytial virus, coronavirus, parainfluenzavirus, influenza virus, human metapneumovirus, adenovirus, or bocavirus) are equally closely associated with episodes of asthma-like symptoms in the first 3 years of life Bisgaard H, BMJ 2010; 341:c4978

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

122. Improved control of childhood asthma with low-dose, short-term vitamin D supplementation: a randomized, double-blind, placebo-controlled trial Tachimoto H. Allergy 2016;71:1001-1009  Vitamin D3 supplements (800 IU/day) with placebo for 2 months in schoolchildren with asthma.  Vitamin D (n=54) or placebo (n=35). % patients with improved cACT at 2 months Vit D 60 – 50 – 40 – 30 – 20 – 10 – 0 51% Placebo 24% p=0.0042

123. Improved control of childhood asthma with low-dose, short-term vitamin D supplementation: a randomized, double-blind, placebo-controlled trial Tachimoto H. Allergy 2016;71:1001-1009 % pts with a PEF rate <80% pred. at 6 months 15% vitamin D placebo 40 – 30 – 20 – 10 – 00 34% p=0.032  Vitamin D3 supplements (800 IU/day) with placebo for 2 months in schoolchildren with asthma.  Vitamin D (n=54) or placebo (n=35).

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

125. Attilio Boner University of Verona, Italy attilio.boner@univr.it General Pediatrics Drug Allergy Food Allergy Atopic Dermatitis Asthma Allergic Rhinitis & Conjunctivitis Anaphylaxis Urticaria & Angioedema Infectious Respiratory Diseases What is New in General Pediatrics, Allergic & Respiratory Diseases 2017 ?

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

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

128. Impaired barrier function in patients with house dust mite–induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression Steelant B, JACI 2016;137:1043-1053. Representative immunofluorescence staining for occludin (green) and ZO-1 (red) in 8 control subjects and 9 patients with HDM-induced AR. zonula occludens-1 zonula occludens-1

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

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

131. Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge Sunil K, J Allergy Clin Immunol 2017;139:844-54 In M- compared with M+ participants, genes that promoted epidermal/epithelial barrier function (filaggrin) versus inflammation (eg, chemokines) and innate immunity (interferon) were upregulated versus, silenced respectively. 93 adults allergic to house dust mites (HDMs) (M+) and 15 nonsensitive, nonallergic (M-) participants 3-hour exposures to aerosolized HDM powder on 4 consecutive days in an allergen challenge chamber

132. Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge Sunil K, J Allergy Clin Immunol 2017;139:844-54 An imprint of resistance to HDM challenge in non-atopic, non allergic adults (M-) was: 1) muted T-cell activation in the peripheral blood, 2) muted inflammatory response in the nasal compartment, coupled with 3) up regulation of genes that promote epidermal/epithelial cell barrier function.

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

134.  We tested whether enhancement of Nrf2 using the activator sulforaphane (SFN) was sufficient to reduce PM induced sinonasal epithelial cell (SNEC) barrier disruption.  SNECs were pretreated with 10 μM SFN for 72 hours before PM stimulation. Sulforaphane pretreatment was found to significantly reduce SNEC barrier instability as measured by both transepithelial electrical resistance and fluorescein isothiocyanate - dextran leak Air pollutant–mediated disruption of sinonasal epithelial cell barrier function is reversed by activation of the Nrf2 pathway London NR, JACI 2016;138:1736.

135. Air pollutant–mediated disruption of sinonasal epithelial cell barrier function is reversed by activation of the Nrf2 pathway London NR, JACI 2016;138:1736. • Particulate matter (PM) directly contain redox-active chemicals and transition metals that can generate reactive oxygen species. • The harmful effects of outdoor PM are well established and include premature death, and both indoor and outdoor PM have been documented to exacerbate asthma morbidity. • PM also has been reported to cause sinonasal inflammation with nasal epithelial thickening and increased eosinophils in nasal lavage and increases in proinflammatory cytokines. • A key regulator of oxidative and environmental stress is the transcription factor nuclear erythroid 2–related factor 2 (Nrf2). Upon activation, Nrf2 translocates to the nucleus and facilitates expression of genes that enact a cytoprotective response.

136. Rhinitis Treatment 1000

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

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

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

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

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

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

145. bronchiolitis

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

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

148. Pneumonia

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

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

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

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

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

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

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

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

157. Recent studies suggest a potential role for gabapentin, pregabalin, amitriptyline, morphine and P2X3 receptor inhibitors, but they are all associated with significant side effects. Non-pharmacological therapies for refractory chronic cough are generally delivered by physiotherapists or speech and language therapists, and key components include: •education, •cough suppression techniques: breathing exercises, vocal hygiene and hydration, •psychoeducational counselling. Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial Chamberlain Mitchell SA, Thorax 2017;72:129–136

158. Physiotherapy, and Speech And Language Therapy Intervention (PSALTI) 1. Education Educate patients on the cough reflex, chronic cough and cough reflex hypersensitivity. Explain the negative effects of repeated coughing. Educate patients on voluntary control of cough. 2. Laryngeal hygiene and hydration Increase frequency and volume of water and non-caffeinated drinks. Reduce caffeine and alcohol intake. Promote nasal breathing. Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial Chamberlain Mitchell SA, Thorax 2017;72:129–136 +

159. 3. Cough control Teach patients to identify their cough triggers. Teach patients to use cough suppression or distraction techniques at the first sign or sensation of the need or urge to cough such as: •forced swallowing, •sipping water and •sucking sweets. Teach patients breathing exercises: •breathing pattern re-education promoting relaxed abdominal breathing pattern technique; •pursed lip breathing to use to control cough. Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial Chamberlain Mitchell SA, Thorax 2017;72:129–136 Physiotherapy, and Speech And Language Therapy Intervention (PSALTI)

160. 4. Psychoeducational counselling •Motivate patients, reiterate the techniques and the aims of therapy. •Behaviour modification: to try to reduce over-awareness of the need to cough. •Stress and anxiety management. Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial Chamberlain Mitchell SA, Thorax 2017;72:129–136 Physiotherapy, and Speech And Language Therapy Intervention (PSALTI)

161. Change in objective cough frequency in physiotherapy, and speech and language therapy intervention (PSALTI) and control groups Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial Chamberlain Mitchell SA, Thorax 2017;72:129–136 P=0.03  patients with refractory chronic cough  randomised to 4 weekly 1:1 sessions of either PSALTI or control intervention consisting of healthy lifestyle advice. * Physiotherapy, and Speech and Language Therapy Intervention (PSALTI) *

162. Change in objective cough frequency in physiotherapy, and speech and language therapy intervention (PSALTI) and control groups Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial Chamberlain Mitchell SA, Thorax 2017;72:129–136 P=0.03  patients with refractory chronic cough  randomised to 4 weekly 1:1 sessions of either PSALTI or control intervention consisting of healthy lifestyle advice. * Physiotherapy, and Speech and Language Therapy Intervention (PSALTI) * Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control ( p=0.030) The improvements within the PSALTI group were sustained up to 3 months

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

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

165. 20° FORMAT Verona 4-5/05/2018

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

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