Szefler SJ, J Allergy Clin Immunol 2007;120:1043

Budesonide= 500 g/day, nebules n= 134

Montelukast= 4-5 mg /day,tbt. n= 146

The only difference between the groups :

Number of acute attacs Budesonide: 1.23

Montelukast: 1.63

What would be the prophylactic treatmentin children with mild persistent asthma

younger than 8 years old? Budesonide / Montelukast

p= 0.03

Primary efficacy variable: Primary efficacy variable: time to first asthma medicationtime to first asthma medication

Szefler SJ, J Allergy Clin Immunol 2007;120:1043

RESULTRESULT : : No significant difference in asthma control

Which controller should be given toWhich controller should be given to

children with mild-moderate asthmachildren with mild-moderate asthmaPACT STUDY PACT STUDY

Sorkness CA, JACI 2007;119:64Sorkness CA, JACI 2007;119:64

•N= 285, 6-14 year

•Mild-moderate asthma

•FEV1: >%80

•PC20 <12.5 mg/ml

•Duration: 48 Hafta

•Sponsor: NIH

1. Fluticason 200 mcg/ day (n:86)

2. Fluticason-Salmeterol (n:81)

100-50- 50 mcg/day

3. Montelukast 5 mg/day (n:83)

Asthma control daysAsthma control days

Time to first prednisolon requirementTime to first prednisolon requirement

FEVFEV11

eNOeNO

Which controller should be given to children Which controller should be given to children

with mild-moderate persistent asthma ?with mild-moderate persistent asthma ?

Fluticasone monotherapy was superior in controlling asthma

than montelukast and combination treatment.

However, maximum asthma control days : %64.2 .

RESULTS:RESULTS:

Sorkness CA, JACI 2007;119:64Sorkness CA, JACI 2007;119:64

Does smoking affect the response Does smoking affect the response to asthma treatment ?to asthma treatment ?

Lazarus S, 2007; 175:783Lazarus S, 2007; 175:783

1. 44 control,

2. 39 light smokers: 10-40/g

mild asthma:

FEV1 %70-90, DLCO >%80

/ BDP - HFA 2X160 mcg/day

/ M. 10 mg/day

Duration: 8 weeks Change in sputum eosinophilia

% 2

1

0

-1

-2

-3

-4

Beclamethasone

p=0.009

p=0.03

NS

nonsmoker

smoker

NS

NS

Montelukast

FEV1

0.2

0.15

0.1

0.05

0

p= 0.09

p=.0003

p= 0.26

Beclamethasone Montelukast

smoker

p=0.08

p=0.23

p= 0.77

RESULTS : CS resistance occurs in patients with asthma who smoke.Montelukast may be more effective in such patients.

P=0.19

15

10

5

0

p= 0.53

p=0.0006

p=0.03

p=0.16

p=0.0019

Beclamethasone Montelukast

morning PEF

nonsmoker

Lancet 2007;378:758

Quartiles of infant VmaxFRC (n:169)High

Medium

Low-medium

Low

““Tucson Children’s Respiratory Study”Tucson Children’s Respiratory Study”PFT in 22 years of agePFT in 22 years of age

4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

P=0.02

P=0.05

P=0.02

FEV1 (L)

12 16 22yaş

88

86

84

82

80

78

76

74

0 12 16 22

p<0.0002

p<0.0002

p<0.0001

FEF 25-75 (L/s)

THE RELATION BETWEEN THE WHEEZING PHENOTYPES THE RELATION BETWEEN THE WHEEZING PHENOTYPES

AND MATERNAL COMPLICATION AND PROCEDURESAND MATERNAL COMPLICATION AND PROCEDURES

Ruskoni F, Am J Respir Crit Care Med 2007;175:16Ruskoni F, Am J Respir Crit Care Med 2007;175:16

n= 15.609, 6-7 year

% 9.5 transient early wheezing

% 5.4 persistent wheezing

% 6.1 late onset wheezing

no relation with:

Amniocenthesis

Chorion villus biopsy

C/S weight gain during

pregnancy

HT, Pre-eclampsyHT, Pre-eclampsy

Transient early wheezing (OR: 1.40)

Persistent wheezing (OR: 1.59)

Late onset wheezing (OR: 1.40)

Urinary tract infections treated with ABUrinary tract infections treated with ABTransient early wheezing (OR: 1.52)

AB use at deliveryAB use at deliveryTransient early wheezing (OR: 1.21)

Persistent wheezing (OR: 1.39)

Maternal diabetesMaternal diabetesPersistent wheezing (OR: 1.72)

Am J Respir Crit Care Med 2007;175:16

Some complications during pregnancy and Some complications during pregnancy and

at delivery may increase the risk of at delivery may increase the risk of

developing different wheezing phenotypes developing different wheezing phenotypes

in childhood.in childhood.

The influence of maternal respiratory infections The influence of maternal respiratory infections during pregnancy on infant lung functionduring pregnancy on infant lung function

Van Putte-Katier N, Ped Pulmonol 2007;42:945Van Putte-Katier N, Ped Pulmonol 2007;42:945

Questionnaire data

Infant PFT: <2 mo, n= 431

“Single occlusion technique”

(natural sleep)

Crs, Rrs

Cross-sectional study Com

plia

nce

(ml/k

Pa/

kg)

20

15

10

5

0.0 1.0 >2

Number of maternal infection

P=0.08

Yes

No

Maternal food consumption and Maternal food consumption and asthma, respiratory and atopic symptomsasthma, respiratory and atopic symptoms

in 5 year old childrenin 5 year old children

Willers SM, Thorax 2007;62:773Willers SM, Thorax 2007;62:773

n: 1.924 birth cohort

Follow-up: 5 yıl,

Neonatal Lung function ?

• Fresh fruits• vegetables• Furit juice• Fish• Milk

APPLEAPPLE

Ever wheeze = OR: 0.63 (%95CI 0.42-0.95)

Ever asthma = OR: 0.54 (%95 CI 0.32-0.92)

Dr. confirmed asthma = OR: 0.47 (%95 CI 0.27-0.82)

FISH (>1/ week)Dr.confirmed AD= OR: 0.57 (%95 CI 0.35-0.92

Ped Allergy Immunol 2008; 19:1-4

1. Breast feeding is recommended for all infants

2. A dietary regimen is effective for prevention of cow’s milk

allergy and eczema. Evidence that such avoidance affects

asthma and rhinitis is lacking.

In case of lack of breast milk, hypoallergenic formulas

for at least 4 months may be considered.

3. There is no evidence for preventive effect of dietary restrictions during pregnancy, lactation and after the age of 4-6 months.

Respiratory symptoms in the first 7 years of life Respiratory symptoms in the first 7 years of life

and birth weight in termand birth weight in term The PIAMA birth cohort (n= 3.628)The PIAMA birth cohort (n= 3.628)

Caudri D, AJRCCM 2007;175:1078Caudri D, AJRCCM 2007;175:1078

521418

407 290218 179

138

1 2 3 4 5 6 7 year

% o

f ch

ildre

n w

ith w

heez

e

25

20

15

10

5

0

wheezing 1-3 / y

wheezing >4 / y249

200127

105

9768

45

Wheezing at least once

LRTI

Coughing at night

Doctor’s diagnosis of current asthma

LBW is an important risk factor for LBW is an important risk factor for

respiratory symptoms and wheezing in young children.respiratory symptoms and wheezing in young children.

No effect after the age of 6. No effect after the age of 6.

This situation in young children is not the sameThis situation in young children is not the same

as asthma in atopic older childrenas asthma in atopic older children

Birth weight,Pre and postnatal

ETS exposureRespiratory symtoms

2.500

3.5

4.5

Birth weight:

No smoking during pregnancy, no ETS exposure

No smoking during pregnancy, with ETS ex.

Smoking during pregnancy and ETS exp.

4

%45

%25

Fark %6

2.500

3.5

4.5

Birth weight

No smoking during pregnancy, with ETS ex.

Smoking during pregnancy and ETS exp.

No smoking during pregnancy, no ETS exposure

Birth weight,Pre and postnatal

ETS exposureWheezing

The effect of birth weight was greater in children The effect of birth weight was greater in children

exposed to ETS (%12).exposed to ETS (%12).

In the presence of ETS exposure a child with a BWIn the presence of ETS exposure a child with a BW

2.500 g has an 45% change each year of having resp.2.500 g has an 45% change each year of having resp.

symptoms between the ages of 1-5, compared withsymptoms between the ages of 1-5, compared with

25% in a child with a BW of 4500 g. 25% in a child with a BW of 4500 g.

AJRCCM 2007;175:1078

LBW babies :LBW babies :

n=5.390, Birth weight, / early growth / LFT at 31 years

Birth Weight, Early Growth, Adult LFT

Canay D, Thorax 2007; 62:396Canay D, Thorax 2007; 62:396

4.6

4.5

4.4

4.3

4.2

4.1

4.0

3.9

FE

V1 (

L)

at 3

1 ye

ars

< 6.300 kg

6.3 – 7.1 kg

> 7.1 kg

N= 2262 men

<3.330 g 3.330 - 3.720 g >3.730 g

Each 500 gram increment of birth weightresulted in a 53.1 ml increase in FEV1

and a 52.5 ml increment in FVC.

Poor growth in early life may restrict normal lung growth and development

<3.330 g

3.330 – 3.720

>3730

Smoking Physical BMI activity (kg/m2)

Nonsmokers Smokers High level Low level <25 >25

4.6

4.5

4.4

4.3

4.2

4.1

4.0

3.9

Characteristics of men at 31 years (n= 2.684) Characteristics of men at 31 years (n= 2.684) F

EV

1 (

L)

at 3

1 ye

ars

Babies with LBW and poor infant growth

may be at a higher higher risk for

developing impaired adult lung function

Growth rate of lung function in Growth rate of lung function in healthy preterm infanthealthy preterm infant

Friedrich L, AJRCCM 2007;176:1269Friedrich L, AJRCCM 2007;176:1269

/ Gestational age: 32.7 (32-34)

no RDS, healthy preterm (n= 24)

and term babies (n= 24)

/Rapid thoracic compression

technique

Test 1 : 2 month

Test 2: 2 year

600

500

400

300

200

FV

C (

mL

)

2 mo 2 year

control

preterm

Absence of catch-up growth in airway function

in 2 years of age compared to term babies

450

400

350

300

250

200

150

2 mo 2 year 2 mo 2 year

FE

V 0

.5/F

VC

FE

V 0

.5

1.0

0.9

0.8

0.7

0.6

1000

800

600

400

200

FE

F25

-75

(mL

/s)

2 mo 2 year

1000

800

600

400

200

FE

F 5

0 (m

L/s

)

2 mo 2 year

RESULTS: Lung growth at the first yearsRESULTS: Lung growth at the first years

of life is proportional to somatic growthof life is proportional to somatic growth

Oral tolerance induction in children withral tolerance induction in children withvery severe cow’s milk-induced reactionsvery severe cow’s milk-induced reactions

Longo G, JACI 2008; 121:343Longo G, JACI 2008; 121:343

Diagnosis of cow’s milk allergy: DBPC provocation test

> 5 years n=60,

Grup A (n= 30) oral tolerance induction

Grup B (n=30) milk free diet

Longo G, JACI 2008; 121:343

Milk specific IgE Levels

GROUP A GROUP B

Group-A: Oral Tolerance InductionGroup-A: Oral Tolerance Induction

Partial tolerance(5 -150 ml/day) %54 Maximum tolerance

(150 ml/day)%13

The results of DBPC :The results of DBPC :

Complete remission % 23

Failure%10

Group-B: Milk free diet Group-B: Milk free diet

P<0.001

The results of DBPC :The results of DBPC :

%100

Preschool-age children with wheezersPreschool-age children with wheezers““remodelling” & eosinophilic inflammationremodelling” & eosinophilic inflammation

When do the pathologic features begin ?When do the pathologic features begin ?

Saglani S, AJRCCM 2007;176:858

Age: 3 mo - 5 year

n=16, mean: 29 mo, video

n= 14, ort.17 mo, reported

n=10 control, ort. 19 mo

4

3

2

1

0EG

2+ v

olum

e de

nsity

(%

)

p<0.05

Video reported control

p<0.05

RBM (m)

76543210

12.5

10.0

7.5

5.0

2.5

0.0

p=<0.05

P<0.01

p<0.001

RBM (m)

Video reported control Video control difficult asthma

When do the pathologic features begin ?When do the pathologic features begin ?

Result: The characteristic pathologic findings start between 1-3 years old.

Can the natural history be changed ?Can the natural history be changed ?

BM

Eo

sin

op

hili

c in

fla

mm

ati

on

BM

Saglani S, AJRCCM 2007;176:858

WHEEZING CONTROL

Airway smooth muscle mass : Airway smooth muscle mass :

Asthma, Cystic fibrosis, BEAsthma, Cystic fibrosis, BERegamey R, AJRCCM 2008; 177:837Regamey R, AJRCCM 2008; 177:837

(24) (27) (16) (11)

Age: 11.3 (8.5-13.8) year

Increased airway smooth muscle

mass (both number and size)

occurs in children with chronic

inflammatory lung disease

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0.001

0.01

Vv(

sm/s

ubep

itelia

l)

Asthma CF BE Control

0.01

Bronchial thermoplasty ?

Basal Membrane: Basal Membrane: Cystic fibrosis, Ciliary Dyskinesia, Chr. Rec. Resp. Symp.Cystic fibrosis, Ciliary Dyskinesia, Chr. Rec. Resp. Symp.

Hilliard TN, Thorax 2007; 62: 1074Hilliard TN, Thorax 2007; 62: 1074166

RBM (m)

10

8

6

4

2

**

CF CD Chr. Resp.S Control

BM thickness is

correlated with

BAL TGF level

CF: 43 (0.3-16.8 year)

CD : 7

Chr. Resp.Symp: 26

Control: 7

Multiple-breath inert gas washout & spirometer:Multiple-breath inert gas washout & spirometer:

Which method is more sensitive in diagnosis of Which method is more sensitive in diagnosis of

early structural changes in lung ?early structural changes in lung ?

45 CF, 5-19 (mean 12) year

%48 homozygote, %43 heterozygote F508

Spirometer, MBW (mean Lung Clerance Index (LCI), HRCT

Gustavsson PM, Thorax 2008; 63: 129

Parameters Sensitivity Specifity

LCI LCI ............................. % 85-94 ...................... % 43-65

FEVFEV11 ............................ % 19-26 ...................... %89-100

FEFFEF7575 ........................... % 62-75 ...................... % 75-88

LCI is more sensitive than FEV1 and FEF25-75 in CF

LCI is superior to HRCT in monitorization.

Compared to HRCT :

LCI = + 0.85

FEV1 = - 0.62

FEF75 = - 0.66

OSA: Adenotonsillectomy resultsOSA: Adenotonsillectomy resultsOtolaryngol Head Nec Surgery 2007;137:43Otolaryngol Head Nec Surgery 2007;137:43

Obese OSA

Normal OSA

(n=33)

(n=39)

Mild OSA%10

Moderate OSA%20

Severe OSA%70

Adenotonsillectomy

Adenotonsillectomy

Mild OSA%5

moderate OSA%36

severe OSA%70

3-18 year

OSA: Adenotonsillectomy resultsOSA: Adenotonsillectomy resultsOtolaryngol Head Nec Surgery 2007;137:43Otolaryngol Head Nec Surgery 2007;137:43

Obese OSA

Normal OSA

(n=33)

(n=39)

Hafif OSA%10

Orta OSA%20

Ağır OSA%70

Adenotonsillectomy

Adenotonsillectomy

Hafif OSA%5

Orta OSA%36

Ağır OSA%70

AHI: 23.4

(3.7-135.1)

AHI: 17.1

(3.9-36.5)

P<0.001

OSA: Adenotonsillectomy resultsOSA: Adenotonsillectomy resultsOtolaryngol Head Nec Surgery 2007;137:43Otolaryngol Head Nec Surgery 2007;137:43

Obese OSA

Normal OSA

(n=33)

(n=39)

mild OSA%10

moderate OSA%20

severe OSA%70

Adenotonsillectomy

Adenotonsillectomy

Mild OSA%5

Moderate OSA%36

severe OSA%70

No OSA %24

mild OSA% 46

Moderate OSA%15

severe OSA%15

No OSA%72

mild OSA%18

moderate OSA%10

severe OSA% 0

OSA: Adenotonsillektomy resultsOSA: Adenotonsillektomy resultsOtolaryngol Head Nec Surgery 2007;137:43Otolaryngol Head Nec Surgery 2007;137:43

Obese OSA

Normal OSA

(n=33)

(n=39)

Hafif OSA%10

Orta OSA%20

Ağır OSA%70

Adenotonsillectomy

Adenotonsillectomy

Hafif OSA%5

Orta OSA%36

Ağır OSA%70

OSA yok%24

Hafif OSA% 46

Orta OSA%15

Ağır OSA%15

OSA yok%72

Hafif OSA%18

Orta OSA%10

Ağır OSA% 0

AHI: 1.9(0.1-7.0)

AHI: 23.4

(3.7-135.1)

AHI: 17.1

(3.9-36.5)

P<0.001

AHI: 3.1(0-33.1)

P<0.01

AHI: 1.9(0.1-7.0)

BCG PERTUSIS

Is Childhood Vaccination Associated with Asthma ? Is Childhood Vaccination Associated with Asthma ? A Meta-analysis of observational StudiesA Meta-analysis of observational Studies

Balicer RD, Pediatrics 2007;120:1269

0.0 0.5 1.0 1.5 2.0 2.50.0 0.5 1.0 1.5 2.0 2.5

5 trials

n= 41.4797 trials

n=186.663

BCG PERTUSIS

Is Childhood Vaccination Associated with Asthma ? Is Childhood Vaccination Associated with Asthma ? A Meta-analysis of observational StudiesA Meta-analysis of observational Studies

Balicer RD, Pediatrics 2007;120:1269

0.0 0.5 1.0 1.5 2.0 2.50.0 0.5 1.0 1.5 2.0 2.5

BCG and PERTUSIS VACCINATIONSBCG and PERTUSIS VACCINATIONS

ARE NEITHERARE NEITHER

PROVOCATIVE NOR PROTECTIVEPROVOCATIVE NOR PROTECTIVE

FOR ASTHMAFOR ASTHMA

Allergy 2008; 63: 5-34Allergy 2008; 63: 5-34

J Allergy Clin Immunol 2007;120: 94-138 J Allergy Clin Immunol 2007;120: 94-138