Astimin doğal seyri
jorritgerritsen
natural course of asthma
jorritgerritsen
question
what is asthma ?
what is asthma ?
asthma is like love: everybody knows
what it is, but nobody can define it.
asthmais
a clinical(doctor’s)diagnosis
phenotypes preschool wheezing
1m 1 2 3 4 5 6 years
wh
eezi
ng
induced by infection (episodic / transient)
allergic asthma (recurrent / chronic)
late onset asthma
wheeze
wheeze
• < 1 year → 80% no wheeze age 3• age 1 – 2 → 60% no wheeze age 3• Age 2 – 3 → 30-40% no wheeze age 3
Illi S, et al. Lancet 2006;368:763
prevalence current wheeze
is wheezingharmless ?
&is wheezingasthma ?
questions
Turato G, et al. AJRCCM 2008;178:476-82
EPITHELIAL LOSS
Turato G, et al. AJRCCM 2008;178:476-82
BASEMENT MEMBRANE THICKENING
how to study natural course of asthma?
• starts as early as possible (before birth)• regular follow-up (annual, at important
ages)• basic design of the study crucial for the
interpretation of the results• early lung function measurements• large cohorts• no much migration in the cohort• most favorable to have one main
researcher
what is known about childhood asthma?
• 30% of children have asthma symptoms before age 1, and 70% before age 3
• severe asthma ~ 1% of children • 40 to 70 % of children have still
symptoms and thereby asthma between the age 20 to 30 yrs
• severe asthma adults ~ 5 %• no information on effects early
treatment and outcome• relationship between asthma and adult
COPD still unknown
effect of early treatment and outcome
Pedersen S, Respir Med
Robertson CF. Med J Austr 2002;177:S42-4.
Sears et al. NEJM 2003;349:1414-22
Longitudinal changes lung function
Martinez FD, Proc ATS 2009;6:272
lung function at birth – 22 yrs
intra uterine growth retardation
iugr and lung function
Kotecha SJ, et al. ARJCCM 2010;181:969
Xuan Xuan et alet al, AJRCCM , AJRCCM 20002000
N=557. Expected FEV1 = -12% at age 19, given same initial FEV1 and N=557. Expected FEV1 = -12% at age 19, given same initial FEV1 and growth in heightgrowth in height
BHR and growth of FEVBHR and growth of FEV11 from childhood to young from childhood to young adulthoodadulthood
Xuan Xuan et alet al, AJRCCM 2000, AJRCCM 2000
N=557. Expected ratio = -9% at age 19, entering the plateau phase with suboptimal lung N=557. Expected ratio = -9% at age 19, entering the plateau phase with suboptimal lung functionsfunctions
BHR and growth of from childhood to BHR and growth of from childhood to young adulthoodyoung adulthood
Recent severe exac predict future severe exac in severe asthma
Haselkorn T, JACI 2009;124:921
lung function young adults predicts airflow obstruction 20 yrs later
Kalhan R, et al. Am J Med 2010;123-468
outcome childhood asthma
asthmatic subjects
(19)
remission subjects
(18)
control subjects
(17)
age, yr 22 ± 2 21 ± 2 24 ± 1
FEV1%pred 88 ± 12 93 ± 15 105 ± 13
FEV1 rev % 11 ± 1 7 ± 1 4 ± 1
Van der Toorn et al. AJRCCM 2001;164:2107-13
MBP-epithelium
Van der Toorn et al. AJRCCM 2001;164:2107-13
bronchial biopsies
controls clinical remissionVan der Toorn et al. AJRCCM 2001;164:2107-13
Tantisira KG, ARJCCM 2008;178:325
longitudinal changesairway hyperresponsiveness
conclusions• Outcome of asthma and wheeze
depends on:• early life events• initial airway obstruction• intra-uterine growth retardation• bronchial hyperreactivity• treatment ?• many unknown factors
• the relationship between asthma and COPD not clear