An aerosol is an example of a twophase system.

It is defined as a dispersion or suspension of solid particles or liquid droplets in a gaseous medium, typically air or oxygen for medical aerosols.

 Aerosol :
Particle form 1. Pure solution spherical 2. Suspension non spherical Medicinal therapeutic aerosol : heterogenous Particle size MMAD = Mass median aerodynamic diameter MMAD (dae) = d (p/p0) d : particle diameter, mm p : particle density, g/cm3

 Ukuran partikel > 5 mm < 5 mm fine particle fraction 0.1-1 mm Sub micronic particle Bersifat gas Dapat menembus masuk ke dalam jaringan paru melalui epitel

DIFFUSION
1.00 SMOG

SEDIMENTATION

INERTIAL IMPACTION
FOG
POLLEN & FUNGAL SPORES

DEPOSITION FRACTION

0.80

AUTOMOBILE EXHAUST PARTICULATES TOBACCO SMOKE

0.60

VIRUS

BACTERIA

0.40

FUMES

DUSTS

0.20

0 0.05 0.1 0.2 0.5 1.0 2.0 5.0 10.0 20.0 50.0

AERODYNAMIC DIAMETER mm (Microns)

PARTICLE SIZE

IMPACTION

> 10 m

Nasal cavity

SEDIMENTATION

5-10 m

Trachea
Primary bronchus

2-5 m
SEDIMENTATION + DIFFUSION

Secondary bronchus
Terminal bronchus

<2m <2m
Alveoli

Respiratory bronchiole
Alveolar Ducts & Sacs

DIFFUSION

Particles penetrate the respiratory tract to different degrees according to their size. This diagram also depicts the mechanisms that operate to clear particles from the Respiratory tract according to size Kendig 1998

Deposition
Impaction Sedimentation Diffusion Electrostatic

Factors affecting deposition of aerosol in the lung

Physical Particle diameter Particle shape Particle density Heterodispersity Ventilatory Anatomic Tidal volume Airway diameter Inspiratory flow rate Disease Breath-hold time Breathing frequency Nose vs. mouth breathing Ambient humidity, temperature

Aerosol / inhalation therapy :

Aerosol / inhalation therapy :
Mainstay treatment in asthma Dosis kecil Onset of action cepat Side effect kecil Efek terhadap EIA lebih baik dari pada oral terapi

Tujuan tatalaksana
Anak dapat menjalani aktivitas normal termasuk olahraga sesuai dengan anak sebaya Sesedikit mungkin angka absensi sekolah Gejala tidak timbul siang ataupun malam Uji fungsi paru senormal mungkin, tidak ada variasi diurnal yang mencolok pada PEF Kebutuhan obat seminimal mungkin, kurang dari sekali dalam dua tiga hari, dan tidak ada serangan Efek samping obat dapat dicegah

 Tujuan ini dicapai dengan pengendalian inflamasi dan dengan demikian diharapkan juga dapat mencegah terjadinya airway remodeling Steroid masih merupakan obat antiinflamasi yang terkuat dan terbanyak dipakai Early intervention diharapkan lebih dapat mencegah adanya airway remodeling dengan demikian faal paru menjadi lebih baik

Wheezing Prevalence

Transient Wheezing

Non-atopic Wheezers

Asthma

Age in years

11

TUCSON, JACI 2003; 111 :661-75

Jenjang obat antiinflamasi

9 6 5
Bronkodilator Bronkodilator (SABA) PRN (SABA) PRN + + Low dose ICS Bronkodilator Bronkodilator Low dose ICS 200-400 mg (SABA) PRN (SABA) PRN 100-200 mg Budesonide/ + Bronkodilator Budesonide / atau setara LTRA (SABA) PRN DSCG / setara Nedocromil

Bronkodilator (SABA) PRN + LABA/LTRA + Low dose ICS 400 mg Budesonide / setara

Bronkodilator Bronkodilator (SABA) PRN (SABA) PRN + + LABA/LTRA LABA/LTRA + + High dose ICS Middle dose > 800 mg ICS Budesonide / 400-800 mg setara Budesonide / setara

LABA/LTRA + Oral Steroid

SABA PRN DSCG

: Short Acting b2-agonist : Prescribe if necessary : Disodium cromoglicate

LTRA ICS LABA

: Lekotriene receptor antagonist : Inhaled corticosteroid : Long Acting b2-agonist

Algoritma tatalaksana jangka panjang

Asma episodik jarang
Obat pereda: b-agonis kerja cepat (hirupan/oral) dan/atau teofilin oral

bila perlu
4-6 minggu obat, dosis/dosis

> 3x

< 3x

1-3 bl

Tambahkan obat pengendali:

Dosis rendah ICS 100-200 atau kromolin hirupan*)

Asma episodik sering

4-6 minggu, respons

(-)

(+)

1-3 bl

Obat pengendali dengan steroid hirupan Dosis 200-400 mg Obat pereda: diberi bila perlu 6-8 minggu, respons

P E N G H I N D A R A N

Step up

(-)

(+)

1-3 bl

4-6 minggu, respons

(-)

(+)

1-3 bl

Asma persisten

ICS 400-600 mg Tambahan salah satu obat : b-agonis kerja panjang b-agonis lepas terkendali Teofilin lepas lambat Antileukotrin

4-6 minggu, respons

(-)

(+)

1-3 bl

Naikkan dosis steroid hirupan >800 mg

4-6 minggu, respons

(-)

(+)

1-3 bl

Tambahkan steroid oral

P E N G H I N D A R A N

Step down

Catatan : *) Ketotifen/cetirizin dapat ditambahkan pada pasien asma yang disertai rinitis

Umur (th) 0-3

Reliever (pereda) pMDI / dengan spacer Nebuliser pMDI / dengan spacer Nebuliser pMDI / dengan spacer DPI Nebuliser

Controller (pengendali) pMDI / dengan spacer Nebuliser pMDI / dengan spacer Nebuliser DPI (?) pMDI / dengan spacer DPI

3-5

>5

Mechanisms of deposition within the respiratory tract. A, Impaction. B, Sedimentation. C, Diffusion Pediatric Respiratory medicine

1-degree droplets

Fine droplets pass around baffle

Gas at high pressure

To patient

Baffle

Droplets trapped and recirculated

Feed tube

Aerosol generation by a jet nebulizer

Inspiration

600 400
Flow (ml/s)

Adult

Child

Infant

Air Entrainment
Nebulizer flow rate 61 breaths/min

200 0 200 400 600

Ti Ttot

Time

Amount of nebulizer output inspired (Vn) Total nebulizer output in a single breath (Ttot x nebulizer flow rate)

Expiration

Figure. Effect of air entrainment on medication delivery. Aerosol concentration is greatest at low tidal volumes and is reduced by entraining air at higher tidal volumes. Ti : Inspiratory time; Ttot : time for one breath
Collis GG, et al. Lancet 1990; 336: 341-343

Driving Gas flow Rate of Drug output Volume in which drug output is distributed Aerosol concentration Volume of aerosol available for inhalation

Solution concentration

Physical properties Of solution

Tidal volume

Rate of drug delivery to an adult % of droplet mass in respirable range Rate of drug delivery to lower respiratory tract of an adult

Rate of drug delivery to an infant

Rate of drug delivery to lower respiratory tract of an infant

Figure. Factors influencing the rate of medication delivery from jet nebulizers.
Everard ML, et al. Thorax 1995; 50:517-519

Environment
Genes
Initiation

Atopy

Epithelial Susceptibility

T-lymphocytes

Propagation

EGFR growth low

Prolong epithelial repair

TGF-b+

IL-4/IL-13 TGF-bhigh

IL-4/IL-13
Myofibroblast activation
Growth factors Cytokines and chemokines

Amplification

Airway wall remodeling

Intrinsic asthma Steroid refractory

Inflammation
Atopic asthma
Steroid sensitive

CHRONIC ASTHMA
Holgate ST, et al. JACI 2003; 111(2):215

Holgate ST, et al. JACI 2003; 111(2):215