Evolution Of Asthma From Childhood - Confex

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Evolution of asthma from childhoodCarlos NunesCenter of Allergy and Immunology of Algarve, PTallergy@mail.telepac.pt

Questionnaire data– Symptoms occurring once or several times at follow-up (wheeze,dyspnea, cough, nocturnal symptoms)– Self-reported asthma– Use of asthma treatment (eg. salbutamol use)– Video questionnaire– Doctor diagnosis Intermediate phenotypes of asthma– Airway hyper-responsiveness Direct (methacoline, histamine) Indirect (exercise, mannitol, cold-air challenge)– Reversibility on b2-agonist– Variability of peak expiratory flow rate (PEFR)– Lung function (eg. FEV1, FEF 25-75, PEF) Combination of questionnaires and phenotypes intermediates(asthma scores and asthma algorithm)

Global studies on allergy and asthma Different profiles of allergy across the world was showed throughoutseveral authors Role of “westernization” is important do develop allergic disease Significant difference among countries and regions Different prevalence of self-reported asthma and current wheeze amongmigrant children compared with those born in native country Different prevalence of migrant children depend of origin country. Perhapsmisdiagnosis and underdiagnosis in their countries of origin can explain thedifferences

Regional differences in asthma prevalence and socio-economic factors likelifestyle and domestic exposures differences need more studies The greater risk of developing atopy and asthma among children with highstandard of life while exposure to general urban deprivation and pollutionis associated with an increase risk of respiratory symptoms and infectionsbut a more modest increase in allergic diseases Allergic diseases in the setting of urban poverty may be more severe andresult in greater morbidity and mortality owing to poor access to care,unavailability of medication and problems with adherence and riskavoidance

ISAAC phase III conducted 8-10 years later confirmed the high prevalence ofasthma symptoms in some of developing country centers A stabilization or decrease on asthma prevalence was observed in themajority of centers in industrialized countries The moderate or high prevalence of asthma in some developing countries isalready being reflected by a significant demand for health services Asthma, from childhood to adulthood in several developing countries is thefirst cause of consultations for chronic respiratory disease in primaryhealthcare settings (WHO report 2004)

Gene By Environment Interactions, a Key feature ofAsthma Genetic(Weiss ST, 2004)Asthma as a complex trait

Atopic immune systems don’t mature normally(Lemanske R, JACI 109(6)

Asthma PhenotypeAdult onset asthmaAspirin inducedIntrinsicOccupationalLate onset childhood asthmaPersistent atopic wheezingNon atopic wheezing toddlerTransient infant wheezingChildhoodAdulthoodAdapted from Bel EH Curr Opin Pulm Med 2004

Despite the fact that certain levels of allergens may prove to beprotective, allergen exposure is still the major risk factor forthe development of allergy. In the absence of allergens, no allergy develops, and above andallergen-specific threshold, the risk of sensitization increase inparallel with exposure. To measure allergen in environment is important to establishdose-response relationships between exposure on the one handand sensitization and clinical allergy on the other hand.

Prevalence – Wheezing EvolutionTransient wheezersAsthmaNon-atopic wheezers036Age - Years912

Asthma Prevalence in Schoolchildren (5.386)1210%Male8Female6420789101112Age - Years1314151617Nunes C et al RPIA, 1996

ChildhoodAdolescentAdultCOPDTransientWheezersLate TInflammationSEVERE

Asthma predictive indexMajor criteriaParental history of physician diagnosed asthmaPhysician diagnosed asthma with atopic dermatitisMinor criteriaWheezing apart coldsBlood eosinophilia 4%Physician-diagnosed allergic rhinitisThe child must have a history of early frequent wheezing during first 3 years of lifeplus one major criterion or two minor criteriaAdapated from Castro Rodrigues et al. Am J Respir Crit Care Med 2000;162:1403-6

Charles ReedJACI, September 2006

Strong oxidative stress in children with asthmaand the oxidant/antioxidant imbalanceincreases with asthma severity.(Ercan et al. JACI 2006;118:1097-104) Early deterioration on lung function, high IgE levels,and persistent cough/mucus hypersecretion are strongmarkers of moderate/severe asthma.(de Marco et al JACI 2006;117:1249-56)

Asthma evolutionWe could estimate 2 out of 3 children withasthma outgrow their symptomsRisk factors for asthma persisting intoadulthood Female Eczema Onset after age of 3 years Severe disease Parental history of atopy / asthma

High endotoxin exposition, pet ownership, atopy and wheezingin high-risk infants has no effect on aeroallergen sensitisation orwheezing during infancy(Campoet al. JACI 2006;118:1271-8) House dust avoidance and dietary fatty acid modification in thefirst 5 yrs of life has no effect to prevent the onset of asthma,eczema or atopy(Marks et al JACI 2006;118:53-61)

Persistence of Asthma fromChildhood to Adulthood 613 N. Zealand children followed from age 3 yrs to 26 At age 26,– 42% no symptoms and no challenged wheezing– 31% transient or intermittent wheezing– 12% relapsing symptoms (wheezing stopped afterchildhood, then recurred)– 15% persistent wheezing.N Engl J Med 2003; 349:1414

Phelan JACI, 2002

Sensitivity of Early Symptomsfor Predicting Later AsthmaStart and endages of studyNumberin StudySymptom / outcome0-2 to 11 yrswheeze / AHR*0-7 to 32 yrsattacks / asthma39714940-5 to 18 yrsfrequent symptoms / asthma2730-7 to 23 yrsallergic symptoms / asthma7225TucsonTasmaniaTucsonOADwheeze / asthma862Algarvewheeze / AHR*397Britain0-10 to 25 yrs6 to 11 yrsCohort6-8 to 20 yrswheeze / wheeze498Japan-10 to 25 yrswheeze / asthma406Belmont020406080100Sensitivity (%)*AHR airway hyperresponsivenessAdapted from Peat JK, Toelle BG, Mellis CM. JACI 2000

Aeroallergen Sensitisation throughout ageAsthmaticsControlOryszczin et al EGEA JACI 2007; 119:57-63

Reduced lung function at birth was associatedwith an increased risk of asthma at 10 yrs(Haland et al. N Engl J Med 2006;355:1682-9) Chronic course of asthma with airway hyperresponsiveness and impairment at school age isdetermined by continuing allergic airwayinflammation beginning in the first 3 yrs of life(Illi et al Lancet 2006;368:763-70)

FEV1 / FVC ratio is diminished in children withasthma because of slower FEV1 and greaterFVC development with ageNHBLI - CAMP Research

Fev1 versus height throughout ageControlAsthmaticsOryszczin et al EGEA JACI 2007; 119:57-63

Cohort of 165 asthmatics childrenversus 148 non-asthmatics during 20 yearsPulmonary Function FEV25-75L65432106789 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30ControlAsthmaAge-YearsNunes C et al JIACI, 2002

Cohort of 165 asthmatics childrenversus 148 non-asthmatics during 20 yearsPulmonary Function FEV1L65432106789 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30ControlAsthmaAge - YearsNunes C et al JIACI, 2002

Phelan JACI, 2002

Visits per year/sex/ageCohort of 165 asthmatics children during 20 461.95Respiratory Inf.ENT Infections12.182.7310.272.90Other NSAsthma CrisesP 0.0.1P 0.0.1P 0.0.5NSNunes C et al JIACI, 2002

Clinical observations of a cohort165 asthmatics versus 148 non-asthmaticsduring 20 years25002000ControlAsthma150010005000Resp. Inf.Other Inf.ENT Inf.CrisesEczemaOthersInternmentNunes C et al JIACI, 2002

In outpatients with moderate and severe asthma theannual mean is 7.4 visits per year. This mean is 3.4 foldof the general population There is a annual mean of 3.7 visits in mild asthma There is an annual mean of 0.7 visits to emergencyrooms A mean of 0.04 internments per asthmatic/yearNunes et al RPIA 2004;12:114-128

Psychological disorders often present inchildren and adolescents with asthmaWith acuteasthmaAsymptomaticDepression86.4 %47.7 %Anxiety36.4 %45.5 %Overprotection37.0 %29.5 %Isolation47.0 %41.7 %Dependence85.6 %47.2 %DefectivePerception35.2 %38.6 %Revino MB ACAI 2006, P124

Who Has Asthma Remissions ?Mild IntermittentVery LikelyMild PersistentModerate PersistentSevere PersistentDuration of Asthma (years)Adapted from: Szefler SJ. Advances in Pediatrics 2000; 47: 273-308Guerra S et al Am J Resp Crit Care Med 2004; 170: 78-85

Who Has Asthma Remissions ?Mild IntermittentMild PersistentLess LikelyModerate PersistentSevere PersistentDuration of Asthma (years)Adapted from: Szefler SJ. Advances in Pediatrics 2000; 47: 273-308Guerra S et al Am J Resp Crit Care Med 2004; 170: 78-85

Who Has Asthma Remissions ?Mild IntermittentMild PersistentModerate PersistentUnlikelySevere PersistentDuration of Asthma (years)Adapted from: Szefler SJ. Advances in Pediatrics 2000; 47: 273-308Guerra S et al Am J Resp Crit Care Med 2004; 170: 78-85

Conclusions Early intervention with inhaled corticosteroids inchildhood asthma reduces morbidity but does not alter thenatural history of asthma Symptom questionnaires are predictive of subsequentasthma episodes in people older than 10 years old, but notin young children In children with asthma, FEV1/FVC is a more reliableinclusion criterion for clinical studies as well as anassessment measure for clinical control

Evaluation and management of severe asthma in childreninclude verification of the diagnosis, assessment forcoexisting illnesses, and identification of effectivetreatment strategies directed to adherence, medicationdelivery, and combination therapy Responsiveness to asthma treatment is heterogeneous evenamong patients with asthma of similar severity. Thisheterogeneity calls attention to the importance of assessingcontrol and adjusting treatment accordingly We are now moving toward an individualized approach toasthma therapy and searching for biomarkers and geneticsas a resource to guide treatment

childhood asthma reduces morbidity but does not alter the natural history of asthma Symptom questionnaires are predictive of subsequent asthma episodes in people older than 10 years old, but not in young children In children with asthma, FEV 1 /FVC is a more reliable inclu

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