treatment of recurrent wheezing in preschool children€¦ · treatment of recurrent wheezing in...

Treatment of Recurrent Wheezing in Preschool Children

A Kaditis MD

University of Thessaly School of Medicine and

Larissa University Hospital

Department of Pediatrics Pediatric Pulmonology

Larissa Greece

Wheezing in Preschool Children

Introduction

Clinical Scenarios

Pathophysiology of Wheezing

∆P = KV

V = darrSvuarr

Re = 2rvdn gt 2000

∆P = KV2

Clinical Case 1

12 mo with 3 episodes of cough over the last year

Association with viral respiratory infections

Recurrent Viral-Associated Wheezing

Bisgaard et al AJRCCM 2005171315

Clinical Case 2

6 mo - cough for 2 months (uarr at night)ldquoCongestedrdquo chestClear nasal drainageMaternal asthma


Wheezing and

Anti-inflammatory Treatment

Anti-inflammatory Medications for Wheezing to Preschool Children Why

Ameliorate symptoms associated with lower airway obstruction

Prevent recurrences and improve quality of life

Prevent deficits in lung function growth

To maximize efficacy of anti-inflammatory medications and to minimize side effects we need to know

Which preschool children will develop asthma

Which subjects are at risk for deficits in growth of lung function

Which wheezing phenotypes are responsive to anti-inflammatory medications

What are the possible side effects of ICS in relation to duration of treatment

Definition of Bronchial AsthmaNHLBI-Expert Panel Report 2 (1997)

Recurrent episodes of reversible lower airway obstruction (withoutwithout treatment)

Inflammation of the lower airways (eosinophils mastocytes lymphocytes)

Bronchial hyperresponsiveness

Outcome of Wheezing in the First 6 Yrs of LifeMorgan et al AJRCCM 20051721253

Children lt 3 yo at High Risk for Wheeze after 6 Years of Age

Major criteria (at least 1)

gt 3 episodesy + parental hx of asthma

gt 3 episodesy + atopic dermatitis

gt 3 episodesy + Minor criteria (at least 2)

Allergic rhinitisWheezing apart from coldsEosinophilia (gt 4)

OR

Castro-Rodriguez et al AJRCCM 20001621403


Published Evidence (I)

Study groups

Viral-associated wheezeFrequent recurrences-persistent symptomsFrequent recurrences with risk factors for asthma(Tusconrsquos criteria)

Interventions

Inhalerspacer device vs nebulizerCorticosteroids vs non-steroidal medicationsHigh vs low dosagesVariable duration

Published Evidence (II)

Outcomes

Expiratory flow functionHospitalizationsΕR visitsSteroid coursesSymptom-free daysΝights with symptomsNeed for bronchodilatorsClinical scores

Infant Pulmonary Function TestingERSATS Task Force on Standards for Infant PFT

ERJ 200016731


Anti-inflammatory Medications-Indications

Available Anti-Inflammatory Medications

No passive smoking

Systemic corticosteroids

Inhaled corticosteroids

Cromolyn nedocromil

Leukotriene receptor antagonists

Systemic Corticosteroids for Viral-Associated Wheezing

Webb et al Arch Dis Child 1986 611538 children (3-17 mo) with wheezingClinical scorePrednisolone 2 mgkgd for 5 d = Placebo for 5 d

Tal et al Pediatrics 1990 8635074 children (7-54 mo) with wheezingAdmission rateMethyprednisolone 4 mgkg IM lt Placebo IM

Inhaled Corticosteroids for Viral-Associated Wheeze

Episodic High-Dose ICS2 RCTs-infants with viral wheezeBeclomethasone or budesonide 08-32 mgd PRN

Reduced need for po steroids RR 053 (CI 027-104)

Low-Dose Maintainance ICS2 RCTs-infants and children with viral wheezeBudesonide 04 mgd for 4 m

Courses of po steroids RR 082 (CI 023-29)No of admissions RR 021 (CI 001-411)

McKean et al Cochrane 2000CD001107

Prophylactic Intermittent Inhaled Corticosteroids for Viral-Associated Wheezing

55 children 1-3 yoStudy duration 1 yBudesonide 08-16 mg vs Placebo PRNReduced clinical score for budesonideNo difference in ER visits-hospitalizations

Svedmyr et al Acta Paediatr19998842

Montelukast for Viral-Associated Wheezing in Preschool Children

549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes


Inhaled Corticosteroids for FrequentPersistent Wheeze

Systematic review24 RCTs-1087 children with asthma1024 RCTs with preschool childrenPlacebo beclomethasone 015-04 mgd or budesonide 03-2 mgd for 4-24 wks

ICS compared to placeboImproved symptom score -50 (CI 49-51)Improved PEFR +11 (CI 95-125)Reduced use of po steroids RR 068 (CI 066-070)

Calpin et al J Allergy Clin Immunol 1997100452

Fluticasone for Children lt 2 yo with Wheezing and Risk Factors for Asthma

26 children lt 2 yo + rwheezing + family hx of asthmarhinitiseczema

Fluticasone 250 mcgPlacebo for 6 m

Exacerbations 21 plusmn 17 vs 41 plusmn 3

Teper et al AJRCCM 2005171587

Montelukast for Persistent Asthma in Preschool Children

689 children 2-5 yo12 wksMontelukastDays with symptoms 59Placebo Days with symptoms 64

Knorr et al Pediatrics 2001108e48

Budesonide or Nedocromil in Children with Mild-to-Moderate Asthma

1041 children

5-12 yo

Study duration 4-6 y

Budesonide 200 mcg bid

Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny

Budesonide Nedocromil Placebo

po steroids 70 102 122

ER visits 12 16 22

Hospitalizations 25 43 44

CAMP NEJM 20003431054

Cromolyn in Children 1-4 yowith Persistent Asthma

218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid

Tasche et al Lancet 19973501060


Inhaled Corticosteroids-Safety

Long-Term Use of ICS Standing Height

1041 children

5-12 yo

4-6 y

Budesonide Nedocromil

Placebo

CAMP NEJM 20003431054

Long-Term Use of ICS Other Potential Side-Effects

Bone density(CAMP NEJM 20003431054)

Cataracts glaucoma(CAMP NEJM 20003431054)

HPA axis

Relative Potency of ICS(NHLBI 2002 Update)

Dose (mcg) Low Μedium High BDP inh lt400 400-800 gt800

BUD neb 500 1000 2000

FP inh lt200 200-400 gt400


Treatment Guidelines

Which Children should be treated with Anti-inflammatory Medications

Symptomatic treatment required gt 2wk

Severe exacerbations lt 6 wks apart

gt 3 episodesy (affecting sleep) + risk factors for asthma

ConclusionsHeterogeneity between studies wheezing phenotypes interventions outcomes

Infrequent mild viral-associated wheezemay not be related to asthma

Frequentseverepersistent symptoms + personal hx of atopyfamily hx of asthmadarr quality of life darr lung growth uarr cost for familyhealth care system

Inhaledsystemic corticosteroids probably most effective in preventingcontrolling symptoms

Treatment of Recurrent Wheezing in Preschool ChildrenA Kaditis MD



Clinical Case 1


Clinical Case 2










Infant Pulmonary Function TestingERSATS Task Force on Standards for Infant PFTERJ 200016731












Cromolyn in Children 1-4 yo with Persistent Asthma






Conclusions


Introduction

Clinical Scenarios


∆P = KV

V = darrSvuarr

Re = 2rvdn gt 2000

∆P = KV2

Clinical Case 1





Clinical Case 2



Wheezing and






















OR




Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions


∆P = KV

V = darrSvuarr

Re = 2rvdn gt 2000

∆P = KV2

Clinical Case 1





Clinical Case 2



Wheezing and






















OR




Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions

Clinical Case 1





Clinical Case 2



Wheezing and






















OR




Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions



Clinical Case 2



Wheezing and






















OR




Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions


Wheezing and






















OR




Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions





















OR




Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions



Study groups


Interventions



Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions


Outcomes



ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions


ERJ 200016731




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions




No passive smoking



Cromolyn nedocromil















549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions














549 children 2-5 yo

1 year

Μontelukast

16 episodes

Placebo

234 episodes















1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions














1041 children

5-12 yo



Nedocromil 8 mg bid

Placebo bid

CAMP NEJM 20003431054


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions


100 childreny



ER visits 12 16 22


CAMP NEJM 20003431054


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions


218 children

1-4 yo

5 m

Cromolyn 10 mg tid

Placebo tid





1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions




1041 children

5-12 yo

4-6 y


Placebo

CAMP NEJM 20003431054




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions




HPA axis



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions



BUD neb 500 1000 2000

FP inh lt200 200-400 gt400














Clinical Case 1


Clinical Case 2




























Conclusions














Clinical Case 1


Clinical Case 2




























Conclusions

treatment of recurrent wheezing in preschool children€¦ · treatment of recurrent wheezing in...

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