asthma lecture 200705

8/13/2019 Asthma Lecture 200705

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Asthma in children

Dr.Nurjannah,Sp.A


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Topics

Inflammations and remodeling in asthma

Classification of asthma

Goal of asthma management Longterm management:

When?

Medications

Side effects

How early?

Inhalation therapy: handicaps??


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EVOLUTION OF ASTHMA

Reversible respiratory tract obstruction

spontaneous or after bronchodilatortreatment

1950-


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Episodic, obstruction due to bronchial

hyperresponsiveness (bronchial hyperactive)

Chronic conditions: recurrent bronchospasm due to

narrowing respiratory tract as a stimuli response

Bronchospasm preventive concept WHO, 1975

Chronic inflammationcellular infiltrate, oedema,epithelial damage, fibrosis

Anti-inflammatory drugs

1970-

1960-

1990-an


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International Pediatric Consensus Statement on the

Management of Childhood Asthma

Arch Dis Child 1992;67:240-8.

International Pediatric Consensus Statement

on the Management of Childhood Asthma

Warner dkk. Pediatr Pulmonol 1998;25:1-7

1989:

1992:

1998:

OPERATIONAL DEFINITION


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Chronic inflammatory of respiratory tract

Many cells and cellular elements play a role(mast cell, eosinophils, T lymphocytes)

GINA, 2002

2002

Complex definitiondifficult aplication andnot practical


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Diagnosis of Asthma

Cough and/or wheezing that:

episodic,

nocturnal (variability),

reversibilitywith atopic family


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Inflammation

desquamation of epithelium

Mucus plug

Basal membrane

thickening

Netrophil and

eosinophil infiltrationsSmooth muscle

constriction and hypertrophy

Oedema

Mucosal gland

hyperplasia

Barnes PJ


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AsthmaNormal

Inflammation picture


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Inflammation in asthma

Barnes PJ

Chronic inflammation

Structure changes

Acute inflammation

Steroids

Response

Time


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Topics

Konsep inflamasi dan remodeling pada asma


Tujuan tatalaksana Longterm management:

Kapan?

Obat

Efek samping

How early?

Terapi inhalasi: kendala


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Severity of attacks

(Acute)

Mild

Moderate

Severe

Respiratory arrestimminent

Class of disease

(Chronic)

Infrequent episodicasthma

Frequent episodic

asthmaPersistent asthma


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Classification of disease

Clinical parameter ,

And lung function

Infrequent episodic

asthmaPersistent asthma

Frequent episodic

asthma

Freq of attacks < 1x /month Daily> 1x /month

Duration of attacks < 1 week Daily>1 week

Between episodes No symptoms

Frequent nocturnal

symptomsSymptoms (+)Sleep and activity Normal AffectMay affect

Physical exam Normal AbnormalMay affect

Controller No need Steroid/combinationSteroid/combinationLung function

(No attacks)PEF/FEV1 >80%

PEF/FEV1 15% > 50%> 30%


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Topics


Klasifikasi asma

Goal of asthma management Longterm management:

Kapan?

Obat

Efek samping

How early?



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Goal of asthma management

Minimal (ideally no) chronic symptoms

Minimal (infrequent) exacerbations

No emergency visits

Minimal (ideally no) use of as needed 2-

agonist

No limitations on activities (exercise)

(Near) Normal lung function

Minimal (or no) adverse effects from medicine


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Improvement Quality of life

Last goal


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Allergenavoidance

Immuno-

therapy

Pharmaco-

therapy

Education

Asthma management

COSTS

GINA, 2002


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Bahasan


Klasifikasi asma

Tujuan tatalaksana

Longterm management:

When?

Obat

Efek sampingHow early?



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Cost ?

Availabil ity ?


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When??

Classifications Controller Reliever

Infrequent

episodic asthma

No Yes

Frequent

episodic asthma

Yes Yes

Persistent

asthma

Yes Yes


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Topics


Klasifikasi asma


Kapan?

Medication

How early?

Efek samping



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Medications

Bronchodilators

Antiinflammations

Anti-remodeling

Anti IgE

Immunizations: ??


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TREATING ASTHMAwith Bronchodilatorsaloneis like

Paintingover rust


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Anti-inflammations

Antihistamine

Disodium Cromoglycate (DSCG)

Corticosteroids

Anti PDE 4 (Phosphodiesterase)


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Long -term p lacebo-con trol led tr ial of ketot i fen in the

management of preschoo l chi ldren with asthm aLoftus BG, Price JF

J Allergy Clin Immunol 1987; 79:350-5

The results suggest that:

Ketotifen has no place in the management

of young children with frequent asthma


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Inhaled disodium cromog lycate (DSCG) as

maintenance therapy in ch i ldren w ith asthma:

a systematic review.

Tasche MJA, Uijen JHJ, Bernsen RMD, de Jongste JC, van der Wouden JC.

Thorax 2000; 55:913-20

Insufficient evidence that DSCG has abeneficial effect as maintenance treatment

in children with asthma


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Steroids


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Corticosteroids

The most effective anti-inflammatorymedications

Improving lung function Airway hiperresponsiveness:

Reducing symptoms

Frequency and severity ofexacerbations:

Improving quality of life


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Steroid efficacy in asthma

Benefit

Steroid

dose

Side-effects


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Benefit of steroid inhalation

Low dose

Directly to respiratory tract

Fast onset

Minimal systemic side effects


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Epithelial Repair Following Steroid Treatment

Before After

P Howarth, 1999


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Pathological feature

Laitinen LA et al, J Allergy Clin Immunol1992


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Bahasan


Klasifikasi asma

Tujuan tatalaksana

Longterm management:

Kapan?

Obat

Side effect

How early? Terapi inhalasi: kendala


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Side effects

hoarseness

Iritation of pharynx

Candidiasis

Headache

Growth disturbances??

Longterm steroid


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Effect of FP in Children < 2 yrs old

Teper AM et al. Pediatr Pulmonol 2004;37:1115

0.7

0.9

1.1

1.3

1.5

1.7

Plasebo FP 100mcg/day

FP 250mcg/day

RAT

IO

Ratio = (SDS+3) post / (SDS+3) pre

R = -0.026 (p = 0.27)

MaxMin

Mean + SDMean - SD

Mean

GROWTH (SDS)


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ICS and Growth

6,25,8

6,16,0

0

2

4

6

8

cm/year

12 months 24 months

FP 100 g bid (n=87) NS 4mg bid (n=87)

Roux C et al. Pediatrics, 2003;111:706-13

FP or Nedocromil Sodium for two years

Growth velocity

ns ns

B Mi l D it


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Bone Mineral Density

11.6

8.9

10.4

8.5

0

2

4

6

8

10

12

%meanincreaseinBM

D

after24months

Lumbar spine

FP 100 g bid (n=87)

NS 4mg bid (n=87)

Femoral neck

Roux C et al. Pediatrics, 2003;111:706-13

FP or nedocromil sodium for two years

ns

ns


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Foe or Friend

Corticosteroids


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Bahasan


Klasifikasi asma


Kapan?

Obat

Efek samping

How early?



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Early Intervention

Early intervention can be applied soon

after clinical asthma has occurred

The goals: reducing asthma symptomsand exacerbations safely

Repair processes to allow for normal lung

growth and development to proceed.

Liu AH. J Allergy Clin Immunol 2004;113:S19-24.


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Why early treatment is important?

Airways inflammation is already present in

intermittent asthma(Vignola AM et al. AJRCCM 1998;157:4039).

Significantly better airway function andasthma control than delayed treatment and

at lower maintenance doses(Selroos et al. Respir Med2004;98:25462)

Improved growth of lung function andasthmatic child treated(Devulapalli et al. ERJ 2004;23:869-75)


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Contra prophylaxis

Not all children with recurrent wheezingbecome asthma (after 6 years-old)

Abnormal lung function did not indicateirreversible lower airways obstruction

Not all studies proved the benefit of ICS inlung function at adulthood(Kaditis et al. Pediatr Pulmonol 2003;35:241-52)

Early wheezing did not result deficit of lung

function in the future(Turner et al. AJRCCM 2004;169:921-7)

No significant difference in lung function andclinical symptoms(Hofhuis et al. AJRCCM 2005;171:328-33)

AsthmaTransient


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Fig. 6. Hypothetical peak prevalence by age for the 3 different wheezing phenotypes.

The prevalence for each age interval should be the area under the curve. This does not

imply that the groups are exclusive.

AsthmaNon-Atopic

Wheezers

Transient

Wheezers

Age (years)

Whee

zingprevalence

0 3 6 11

Taussig LM, et al. JACI 2003;111:661-75

Low LFT

at birth

Post

RSV

BHR of

atopic asthma


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Pro prophylaxis

Improvement of clinical symptoms and no sideeffect(Bisgaard AJRCCM 1999;160:126-31)

Decreased of clinical symptoms, acuteexacerbation, sleep disturbances, andimprovement of lung function(OByrne et al. AJRCCM 2005;171:129-38)

Significantly reduced asthma symptoms, -2agonist using and improved FEV1(Kaditis et al. Pediatr Pulmonol2003;35:241-52)

Improved respiratory symptoms without sideeffects on growth and bone metabolism(Teper et al. PediatrPulmonol 2004;37:1115)

AsmaN At iTransient


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Fig. 6. Hypothetical peak prevalence by age for the 3 different wheezing phenotypes.

The prevalence for each age interval should be the area under the curve. This does not

imply that the groups are exclusive.

AsmaNon-AtopicWheezers

Transient

Wheezers

Umur (tahun)

Keja

dianwheezing

0 3 6 11

heezing berulang Major :

Dermatitis atopi

Orang tua asma

Minor Eosinofil darah

Wheezing

Rinitis alergika

Asma: jika

2 major atau

1 major +2 minor

Taussig LM, et al. JACI 2003; 111:661-675


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Management (research)

Anti IgE (Omalizumab)

rhuMAb-E25 (recombinant humanized

monoclonal antibody) Anti-interleukin (IL-4, IL-5)

research

Immunizations (genetic recombinant) research


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Topics


Klasifikasi asma


Kapan?

Obat

Efek samping

How early?

Inhalation therapy: handicaps


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Type of inhalation therapy

Metered dose inhaler(MDI)

With spacer

Without spacer

Dry powder inhaler(DPI)

Turbuhaler, cyclohaler

Nebulizer

Jet

Ultrasonic


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MERAH


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KUNING


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MERAH

BIRU


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Whats this ???

h h ???


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Whats this ???Horse Frog


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Limitations

Provider aspects

Miss perception

Lost of patient Medications aspects

Availability

Distribution

Price

Community aspects

Dangerous

Addictive Socio-cultural

Tools

Algorithm complexity

Equipment problems


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Positive impact of inhalation therapy

Quality of life

Quality of therapy

INHALATION

ORAL

Patient

FamilyFinancial

To another doctor

Go abroad(Low performance

of Indonesian

pediatricians )

Stable asthma

Patient Get Patient

-


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Conclusions

Asthma: Chronic inflammation andremodelling

Ketotifen and Disodium cromoglycate:Insufficient evidence as longtermmanagement

Corticosteroids with/without combination:drug of choice as longterm management

Indonesia: Guidelines of childhood asthmamanagement


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Harus Berjuang


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Harus Berjuang


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Longterm steroid


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Bone densitometry

Bone densitometry

3/38 cases (7.9%) DEXA: chronological age

below -1.0 13/37 patients (35.1%) DEXA: lumbar spine

(L2-4) chronological age below -1.0

Longterm steroid


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Longterm steroid


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Biochemical markers of bone metabolism

No significant:

serum osteocalcin

PINPALP

BALP

urine DPD/Cr ratio NTx/Cr ratio

Longterm steroid

400


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Petanda biokemis

400

350

300

250

200

150

100

50

0 NTx/Cr(nmol/mmol)

ALP(IU/L)

P1NP(mg/L)

BALP(IU/L)

OSTEO(ng/m)l

DPD/Cr(nmol/mmol)

Hasil

KontrolKasusStandard error


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No significant correlation between any of

the biochemical markers and DEXA z-score (chronological or bone age)

ongterm steroid


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B A L b S i (L2 L4)

ongterm steroid


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Bone Age Lumbar Spine (L2-L4)

Cu

mulativeProb

ability(%)

Z-score-4 -3 -2 -1 0 1 2 3 4

0

20

40

60

80

100

Reference Population

Study Population

Cumulative probability graphs of lumbar spinal density

In study population vs. reference population


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Efikasi steroid

Keungtungan dosis

Efek samping


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Keuntungan steroid inhalasi

Dosis rendah

Langsung ke sal respiratorik

Onset (awitan) cepat

Efek samping sistemik minimal

Modern view of Asthma


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Modern view of Asthma

Mucus

hypersecretion

Hyperplasia

Eosinoph i l

Mast cel l

Allergen

Th2 cell

VasodilatationNew vessels

Plasma leakOedema

Neutrophi l

Mucus plug

Macrophage/dendri t ic cel l

Bronchoconstriction

Hypertrophy / hyperplasia

Cholinergicreflex

Epithelial shedding

Subepithelial

fibrosis

Sensory nerveactivation

Nerve activation

Barnes PJ

R i li i t id + LABA


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Rasionalisasi steroid + LABA

Smooth muscledysfunction

Airwayinflammation

BronchoconstrictionBronchial hyperreactivityHyperplasiaInflammatory mediator release

Inflammatory cellinfiltration / activation

Mucosa oedemCellular proliferationEpithelial damageBasement membrane thickening

Symptoms / exacerbations

LABA CS

Evolving treatment options


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Evolving treatment options

1975

1980

1985

1990 19952000

Large use ofshort-acting

2-agonists

Fear of

short-acting

2-agonists

Single

inhaler therapy

(Symbicort)

ICS treatment

introduced

1972

Adding

LAA to ICS therapy

Kips et al, AJRCCM 2000Pauwels et al, NEJM 1997

Greening et al, Lancet 1992

Bronchospasm Inflammation Remodelling

asthma lecture 200705

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