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