【兒童哮喘-課件-PPT】Recurrent-Wheezing-and-Asthma

1、Sren PedersenUniversity of Southern DenmarkKolding HospitalRecurrent Wheezing and Asthma5 years and YoungerClinical presentationWheeze (50%), cough (80%) and breathlessness (20%)TirednessReduced physical activityNocturnal wake-upsRecurrent bronchitis or pneumonia antibioticsCold air or activity indu

2、ced symptomsMost of the symptoms are not specific for asthmaParents do not report wheezeuntil lung function is reducedby around 50%GINA 2014 Children 5 years and Younger Outcome of Childhood AsthmaMildModerateSevereChildhood70% symptom free as adultsAdulthood30%30% symptom free as adults70%Marked tr

3、acking of asthma severitybetween childhood and adult lifeSummary65% loose their symptoms before age 5.35% continue to have symptoms after 5.Viral infections are the most common trigger of symptoms in both groupsReduction of maternal smoking reduces occurrence of wheeze in both groupsPreschool Wheeze

4、For intervention strategies that include allergen avoidance: Strategies directed at a single allergen have not been effective Multifaceted strategies may be effective, but the essential components have not been identified Current recommendations, based on high quality evidence or consensus, include:

5、 Avoid exposure to environmental tobacco smoke during pregnancy and the first year of life Encourage vaginal delivery Advise breast-feeding for its general health benefits (not necessarily for asthma prevention) Where possible, avoid use of paracetamol (acetaminophen) and broad-spectrum antibiotics

6、during the first year of life The development and persistence of asthma are driven by geneenvironment interactions. For children, a window of opportunity exists in utero and in early life, but intervention studies are limited. Primary Prevention of Asthma0123456789101112-1.2-1.0-0.80.60.40.20.00.20.

7、4NeverTranient earlyLate onsetPersistent*p0.05 vs. neverp0.05 vs. latep0.05 vs. never, late and persistentMean (SE)*Lung Function and timeZ - ScoreAge (years)*Outcome of Childhood AsthmaUntreated asthmais associated withreduced growthof lung functionAdverse effecton lung functionseems more markeddur

8、ing the beginningof the diseaseMartinez. J Allergy Clin Immunol 1999;104:S169-S174.Asthma Predictive Index for ChildrenCastro-Rodriguez JA et al. AJRCCM 162:1403-1406, 2000.* by history of MD diagnosis Criteria: Age 2 - 3 years old frequent wheeze 1 major or 2 minor criteria:Likelihood of Asthma 77%

9、 PPV97% SpecificityThis is a verysmall proportionof the cohortThe majority withschool age asthma do not belong tothis group Managing Asthma in Pre-school ChildrenDuration of wheezeTransient early wheezingStarts during first two yearsDisappeared (retrospectively) by age 6Pattern: Episodic or multiple

10、 triggerlate onset wheezeSymptoms starts after age 3Pattern: Episodic or multiple triggerPersistent wheezeSymptoms beyond age 6 (retrospectively) Pattern: Episodic or multiple trigger Episodic (Viral) wheezeWheezing during discrete time periodsNo symptoms between attacksNormally associated with a vi

11、ral coldEach episode normally short (one week)The episodes can be mild, moderate or severeMultiple trigger wheezeWheezing that shows discrete exacerbationsSymptoms between episodes Preschool wheeze Temporal patternsGINA 2014 Children 5 years and Younger (Brand PLP et al ERJ 2010;38:1096-1110)Martine

12、z. J Allergy Clin Immunol 1999;104:S169-S174.Schultz A, Devadason SG, Savenije OE, Sly PD et al Acta Paediatr 2010;99:56-6000The distinction between EVW and MTW is not as clear-cut as the report suggested. Changes in symptom pattern over time is common there is a large overlap between the groupsWhen

13、 children with preschool wheeze are classified into episodic (viral) wheeze or multiple trigger wheeze based on retrospective questionnaire, the classification is likely to change significantly within a 1-year period.Phenotypic classification remained the same in 45.9% of children and altered in 54.

14、1% of children within one yearBrand PL et al. Eur Respir J. 2014 Apr;43(4):1172-7.Asthma Management for Young ChildrenThere is little evidence that the EVW and MTW phenotypes are related to the longitudinal patterns of wheeze, or to different underlying pathological processes. The temporal pattern o

15、f wheeze during preschool years (EVW or MTW) is a relatively poor predictor of long-term outcome (transient versus persistent wheeze). Frequency and severity of wheezing episodes are stronger predictors of long-term outcome. Thus, the clinical usefulness of the EVW-MTW approach is doubtfulPescatore

16、AM et al J Allergy Clin Immunol 2013 Epub ahead of print“The distinction between Episodic Viral Wheeze and Multiple Trigger Wheeze is more a marker of disease severity than of different clinical phenotypes” Garcia-Marcos L, Martinez FD:J Allergy Clin Immunol 2010;126:489-490Asthma Management for You

17、ng ChildrenEpisodic (Viral) wheeze and Multiple trigger wheezeNoIdeal situationReal life Episodic (Viral)Wheeze Multiple triggerwheezeAsthma Management for Young ChildrenIt is not possible to break the patients down into mutually exclusive subgroups that remain consistent over time. Often the variou

18、s differences are quantitative rather than qualitative.Which symptom pattern may suggest asthma?Characteristic for asthmaCoughRecurrent or persistent non productive cough that may be worse at night or accompanied by wheezing and breathing difficulties. Occurring with exercise, laughing, crying or ex

19、posure to tobacco smoke in the absence of an apparent URTIWheezingRecurrent wheezing, including during sleep or with triggers such as activity, laughing, crying or exposure to tobacco smoke or air pollutionDifficult or heavy breathing or shortness of breathOccurring with exercise, laughing, or cryin

20、gReduced activity Not running, playing or laughing at the same intensity as other children; tires earlier during walks (wants to be carried)Past or family history Other allergic disease (atopic dermatitis or allergic rhinitis)Asthma in first degree relatives.Therapeutic trial with ICS and as needed

21、beta-2 agonistClinical improvement during 2-3 months of controller treatment and worsening when treatment is stoppedAsthma Management for Young ChildrenAny of the following features suggest an alternative diagnosis and indicate the need for further investigations:Failure to thrive Neonatal or very e

22、arly onset of symptoms (especially if associated with failure to thrive) Vomiting associated with respiratory symptoms Continuous wheezing Failure to respond to asthma controller medications No association of symptoms with typical triggers, such as viral URTI Focal lung or cardiovascular signs, or f

23、inger clubbing Hypoxemia outside context of viral illness Key indications for referral of a child 5 years or younger for further diagnostic investigations GINA 2014 Children 5 years and Younger Recurrent wheezing occurs in a large proportion of children 5 years and younger, typically with viral uppe

24、r respiratory tract infections. Deciding when this is the initial presentation of asthma is difficultPrevious classifications of wheezing phenotypes (episodic wheeze and multiple-trigger wheeze; or transient wheeze, persistent wheeze and late-onset wheeze) do not appear to represent stable phenotype

25、s, and their clinical usefulness is uncertain A diagnosis of asthma in young children with a history of wheezing is more likely if they have: Wheezing or coughing that occurs with exercise, laughing or crying in the absence of an apparent respiratory infection should be treatedA history of other all

26、ergic disease (eczema or allergic rhinitis) or asthma in first-degree relatives Clinical improvement during 23 months of controller treatment, and worsening after cessationSummary of studies in pre-school children:Asthma Management for Young ChildrenWho should be treated?Frequency and/or intensity o

27、f interval symptoms Intensity and/or frequency of exacerbationsMild or rare Frequent or severe Frequent or severe Mild or rareGINA 2014 Children 5 years and YoungerTreatment should be decided on frequency and severity of symptoms and exacerbations rather than phenotypesTo achieve good control of sym

28、ptoms and maintain normal activity levels To minimize the risk of future asthma flare-ups, impaired lung development and medication side-effects. Maintaining normal activity levels is particularly important in young children because engaging in play is important for their normal social and physical

29、development. It is important to also elicit the goals of the parent/carer, as these may differ from conventional medical goals. Goals of managementGINA 2014 Children 5 years and YoungerRisk factors for asthma exacerbations within the next few months Uncontrolled asthma symptoms One or more severe ex

30、acerbation in previous year The start of the childs usual flare-up season (especially if autumn/fall) Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g.House dust mite, cockroach, pets, mold and viral infection) Major psychological or socio-economic problems for child

31、or family Poor adherence with controller medication, or incorrect inhaler technique Risk factors for fixed airflow limitation Severe asthma with several hospitalizations History of bronchiolitis Risk factors for medication side-effects Systemic: Frequent courses of OCS; high-dose and/or potent ICS F

32、uture RiskGINA 2014 Children 5 years and YoungerIn the past 4 weeks, has the child had:Well controlledPartly controlledUncontrolled Daytime asthma symptoms for more than a few minutes, more than once a week? Yes No None of these12 of these34 of these Any activity limitation due to asthma? (Runs/play

33、s less than other children, tires easily during walks/playing?) Yes No Reliever medication needed* more than once a week? Yes No Any night waking or night coughing due to asthma? Yes NoGINA 2014 Children 5 years and YoungerAssesment of controlWhich medications?(Castro-Rodriguez et al. Pediatrics 200

34、9;123: 519-525)Significant reductions were seen in children with a diagnosis of wheeze as well as and asthma, but the magnitude was greater in asthma RR 0.76 (0.58-0.99) (P=0.04)ICS for Young ChildrenMeta-analysis of the effect of ICS29 studies including a total of 3592 pre-school children with whee

35、zePrimary outcome: Wheezing/asthma exacerbationsSecondary outcomesWithdrawal due to Wheezing/asthma exacerbationsAlbuterol useChanges in symptomsChanges in lung functions(Castro-Rodriguez et al. Pediatrics 2009;123: 519-525) 45% 48% 37% 7% P0.001There was no difference in effects between:Infants and

36、 preschoolersAtopic versus non-atopic (Similar result:Allergol imunopat 2010;38(1):31-6)MDI(spacer) versus nebulizerAsthma Management for Young Children2.341.600123Montelukast 4 mg (n=265)Placebo (n=257)Wheezingepisodesrate / year32%p0.001Bisgaard H et al Am J Respir Crit Care Med 2003;171:315322.Ex

37、acerbationsNo effect onPrednisolone useHospitalizationsDuration of exacerbationSeverity of exacerbationDays without asthmaMontelukast in pre-school Children Patient Demographics Study duration24 weeks Randomized/Completed 979/745 Males/Females58/42% Mean age 8 months Primary endpoint Percentage symp

38、tom free days Secondary endpoint Percentage bronchiolitis free days Symptom free days Cough free days Symptom scores Rescue free days Systemic steroid use, exacerbations, health-care usBisgaard H et al. Am J Respir Crit Care Med 2008;(178)85486.Montelukast in pre-school Children No statistically sig

39、nificant effects on any of the outcomes measured Post-bronchiolitic wheezeChildrenTreatment of Preschool-Childen(Szefler et al JACI 2007:120:1043-50)One year comparison of Montelukast and Budesonide Nebulizer in 395 children aged 2 5 yearsBudesonideMontelukastBUD better than Montwith respect to:Time

40、 to additional medicationsduring first 3 months (p0.05)Exacerbations over 1 year (p0.05)No of patients treated withOral steroids (p0.05)Peak expiratory flow (p0.05)Physician global assessment (p0.05)Caregiver global assessment (p0.05)*If symptom control is poor and/or exacerbations persist despite 3

41、 months of adequate controller therapy, check the following before any step up in treatment is considered. Confirm that the symptoms are due to asthma rather than a concomitant or alternative condition. Refer for expert assessment if the diagnosis is in doubt.Check and correct inhaler technique.Conf

42、irm good adherence with the prescribed dose.Enquire about risk factors such as allergen or tobacco smoke exposureBefore stepping-up of controller treatmentGINA 2014 Children 5 years and YoungerIntermittent treatment during exacerbationsOral steroids: Conflicting evidence some effects?Three courses o

43、f oral steroids (ever) is associated with increased risk of fracture and adverse effects on bone mineral density Leukotriene Modifiers: Conflicting evidence small effects?Inhaled steroids: Conflicting evidence small effects?1500 g FP/day reduces exacerbations by 40%, but this regimen is associated w

44、ith adverse effects on growth and bones Managing Asthma in Pre-school ChildrenRather discouraging!Growth during intermittent treatment of ICS in pre-school children(Durcharme FM et al N Engl J Med 2009;360:339-53)Cm/yearPlaceboFP1500gintermittently6.566.23P0.05kg/yearPlaceboFP1500gintermittently2.17

45、1.53P5 m ()Sedimentation (MMAD 3 m)Diffusion (MMAD 1.5 m)AdultChildAgeInhalation therapyDeposition pattern of Nebulized budesonide020406080% of dose to the patientAdultsChildrenLungsOropharynx AUC per mg inhaled dose0510152025(nmol/lh)(Agertoft, Arch Dis Child 1999;80:241-247)The same dose of BUD re

46、sulted in the same degree of systemicexposure in adults and 3 - 5 years old childrenIV infusionAgertoft & Pedersen. Am J Respir Crit Care Med. 2003, 1;168(7):779-782.Inhaled corticosteroidsBudesonide was eliminated significantly faster from the systemic circulationthan fluticasoneMeta-analysis: 21 s

47、tudies Dose of Corticosteroids, mg/dSuppression of Urinary Cortisol, %Lipworth. Arch Intern Med 1999;159:941-55.1008060402000.20.40.81.62.0FluticasoneBeclomethasoneTriamcinoloneBudesonideComparison of Inhaled SteroidsBudesonide had low systemic effects even rather high daily dosesHealth Resource Uti

48、lization01020304050EmergencyDepartment VisitsUrgent Care VisitsEmergency Department or Urgent Care VisitsPercent of Children *P= 0.06*P.05; *P.01 vs nebulized cromolyn sodium.Nebulized BUD Nebulized Cromolyn SodiumNebulized Budesonide(Leflein, Pediatrics 2002;109(5):866-872)SummaryCompared with crom

49、olyn sodium, nebulized budesonide demonstrated:Significantly longer times to first exacerbation and first use of additional chronic asthma therapySignificantly fewer days of breakthrough medication use Significantly greater improvements in nighttime and daytime asthma symptom scoresSignificantly less health resource utilizationNebulized Budesonide(Leflein, Pediatrics 2002;109(5):866-872)GC-receptorBudesonidelipolysi