la storia naturale dell’asma fernando maria de benedictis
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AOU “Ospedali Riuniti” - Ancona Ospedale Materno-Infantile di Alta Specializzazione “G. Salesi” SOD Pediatria. La storia naturale dell’asma fernando maria de benedictis. The natural history of asthma: questions to answer. When does asthma begin in childhood? Do children outgrow asthma? - PowerPoint PPT PresentationTRANSCRIPT
La storia naturale dell’asma
fernando maria de benedictis
AOU “Ospedali Riuniti” - AnconaOspedale Materno-Infantile di Alta Specializzazione “G. Salesi”
SOD Pediatria
The natural history of asthma: questions to answer
• When does asthma begin in childhood?
• Do children outgrow asthma?
• May asthma relapse after disappearance?
• What about late-onset asthma?
• Is there anything that can modify the course of asthma?
A community-based study of the epidemiology of asthma
Yunginger, ARRD 1992;146:888
Remission rates of asthma symptoms during adolescence in cohort studies
70% 67%
45%50%
Nicolai, 2001 Anderson, 1986 Peat, 1989 Withers, 1998
It is often not asthma that is outgrown,but the paediatrician….
Levison, JACI 1991
The natural history of asthma: the need of prospective, long-term studies
• May describe disease progression through its full course
• May identify unbiased associations between specified exposures and subsequent development of disease outcomes
• May help to understand the effect of therapies on modifying the course of the disease
British 1958 asthma and wheezing study
50%
18%10% 10%
27%
% o
f as
thm
a at
tack
s in
th
e p
revi
ou
s ye
arUK cohort of 18.553 subjects followed from birth until 33 yrs
Strachan, BMJ 1996;312;1195
880 children who had wheezing before the age of 7 yrs
The Melbourne asthma study (1964-1999)
Longitudinal study of 403 subjects from the age of 7 yrs to 42 yrs
Phelan, JACI 2002;109:189
- Eczema- Hay fever- Atopy
The New Zealand asthma study
Cohort study of 1037 unselected subjects from age 9 to 26 yrs
15%
15%
12%
9%
21%
28%
Sears, NEJM 2003;349:1414
27%
Female sexSmokingEarly age of onsetAtopyBHR
Prevalence of current wheeze in children with any wheezing episode at school age stratified for atopy at school age
Non-atopicAtopic
No difference
Illi, Lancet 2006;368:763
German Multicenter Allergy Study
815 unselected newborns and 499 at high risk of atopy followed from birth to 13 yrs
46%
10%
CAMP study
1041 asthmatic children 5 to 12 yrsTrial of anti-inflammatory treatments for 5 yrs, and then a 4-year follow up
Covar, JACI 2010;125:359
55%
39%
6%
Severity of asthmaAllergic sensitizationLow lung function BHR
CAMP study
1041 asthmatic children 5 to 12 yrsTrial of anti-inflammatory treatments for 4 to 6 yrs and then a 4-year follow up
Covar, JACI 2010;125:359
Pattern of asthma in adults with a history of childhood asthma
Limb, JACI 2005;115:61
85 subjects with asthma in childhood evaluated 17 to 30 years after immunotherapy
2.1O
R f
or
asth
ma
at a
ge
22 y
rs1.4
4.6
7.4
4.1
14.0
Stern, Lancet 2008;372:1058
Tucson Children Respiratory Study
Cohort of 846 subjects followed from birth to 22 years
The Melbourne asthma study (1964-1999)
** *p <0.01 vs controls
At each year of review, the degree of lung function abnormality paralleled the initial frequency of wheeze = The early loss of lung function did not appear to progress !
Phelan, JACI 2002;109:189
The New Zealand asthma study
The slopes of change in FEV1:FVC were similar in each wheezing group (“tracking”), thus indicating that impairment of lung function in patients with persistent asthma occurred in early childhood, before the first measurement at the age of 9 years.
Cohort study of 1037 unselected subjects followed from birth until 26 yrs
Sears, NEJM 2003;349:1414
Tucson Children Respiratory Study
Morgan, AJRCCM 2005;172:1253
Cohort of 425 subjects followed from birth to 16 years
Stern, Lancet 2008;372:1058
Tucson Children Respiratory Study
Cohort of 846 subjects followed from birth to 22 years
FEV1/FVC ratio and asthma at age 22 yrs by age at first asthma diagnosis
• In asthmatic children, reduced lung function becomes apparent around school age
• In asthmatic subjects, there is no further progression of lung function impairment from childhood up to adolescence and adulthood (“tracking”)
• Airway inflammation and changes in airway structure (“remodeling”) are considered to be responsible for reduced lung function
• Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with asthma
Determinants the progressive loss of lung function in asthmatics
Baseline lung function at different ages stratified for wheezing at 5-7 years
p<0.05* atopic wheeze vs no wheeze* atopic wheeze vs non-atopic wheeze
FV
C %
ME
F7
5 %
ME
F5
0 %
FE
V1
%
FV
C/F
EV
1 %
ME
F2
5 %
* * *
*
** ** *
****
** ** ** **
7 yr 10 yr 13 yr 7 yr 10 yr 13 yr 7 yr 10 yr 13 yr
German Multicenter Allergy Study
815 unselected newborns and 499 at high risk of atopy followed from birth to 13 yrs
Illi, Lancet 2006;368:763
The differences in pulmonary function between the different classes persist after bronchodilator
Adolescents with clinical remission of asthma, inflammation and bronchial hyperreactivity
21 with active asthma; 21 with asthma remission; 18 controlsMCH challenge and FeNO
van den Toorn, AJRCCM 2000;162:953
Italian Study on asthma in young adults
Cross-sectional study of 18.837 young adults
Cumulative probability of remission
De Marco, JACI 2002;110:228
The minority of persons with early-onset asthma who do not recover represents approximately
35% of prevalent cases of the young adult population (20-44 year of age).
Gender differences for the incidence and pattern of asthma
MalesFemales
Inci
den
ce o
f as
thm
a/10
0.00
0 p
ts
Osman, Arch Dis Child 2003;88:5879
The New Zealand asthma study
Sex differences in childhood- and adolescent-onset wheeze
The influence of parental atopy on the development of wheeze differs between males and females and between childhood- and adolescent-onset wheeze
Wheeze by age 10
Wheeze between ages 10 and 26
Mandhane, AJRCCM 2005;172:45
M vs F, p <0.001
F vs M, p <0.001
The natural history of asthma: what do we know?
• Three of 4 school-aged children with asthma have outgrown disease by mid-adulthood
• Risk of persistence/relapse increases with severity, sensitization, smoking and female sex
• Children with asthma have reduced lung function by early school age. The lung function seems to track at a fixed percentile.
• Neither primary (manipulation of environmental factors) nor secondary (use of anti-inflammatory drugs) prevention can effectively halt the long term disease progression of asthma
The natural history of asthma: what is still unknown?
• Whether the early loss of lung function in asthma is a cause or a consequence of the disease
• Which is the relationship between airflow limitation in the neonates and development of asthma
• The direction of causality between infant bronchial responsiveness and asthma
• Long term cohort studies starting before birth may gain power from deep phenotyping with objective assessment of the disease
•Analytic approaches are needed to achieve more than just interesting observations of statistically significant associations