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