I.B.N.

Maharjana
disampaikan pada materi kuliah PPOK Farter2, IIK Bali, 2017
• Pendahuluan
• Definisi
• Patofisiologi
• Diagnosa
• Tatalaksana Terapi
 PENDAHULUAN
1958 “ Emphysema and Chronic Bronchitis Syndrome “
1960 “ Chronic Obstructive Bronchopulmonary Disease “
1964 “ Chronic Obstructive Bronchopulmonary Disease “

1966 “ Chronic Airway Obstruction “

1967 “ Chronic Obstructive Lung Disease “
1972 “ Chronic Aspesific respiratory affection “
1977 “ Chronic Non Spesific Lung Disease “
1978 “ Chronic Obstructive Pulmonary Disease “ ( COPD )
PPOK di USA : penyebab ke-4 kematian terbanyak (
Jantung; Kanker ; CVA )
WHO Th 2000 : 2,74 juta kematian di dunia ok PPOK
Th 1990: peringkat ke 12 penyakit terbanyak di dunia
Th 2020: peringkat ke 5 penyakit terbanyak didunia
 DEFINISI
 Penyakit Paru Kronis ( menahun ),
 ditandai dengan Hambatan aliran udara di saluran
nafas,
 yang tidak sepenuhnya Reversibel
 Hambatan aliran udara bersifat “ Progresif ”
 Berhubungan dengan respon inflamasi kronik paru
terhadap partikel / gas yg beracun / berbahaya
 GOLD
• Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable
and treatable disease that is characterized by persistent respiratory
symptoms and airflow limitation that is due to airway and/or alveolar
abnormalities usually caused by significant exposure to noxious particles
or gases.
• The most common respiratory symptoms include dyspnea, cough and/or
sputum production. These symptoms may be under-reported by patients.
• The main risk factor for COPD is tobacco smoking but other environmental
exposures such as biomass fuel exposure and air pollution may contribute.
Besides exposures, host factors predispose individuals to develop COPD.
These include genetic abnormalities, abnormal lung development and
accelerated aging.
• COPD may be punctuated by periods of acute worsening of respiratory
symptoms, called exacerbations.
• In most patients, COPD is associated with significant concomitant chronic
diseases, which increase its morbidity and mortality.
 PPOK

1. Bronkitis Kronis 2. Emfisema

 PPOK
PPOK terdiri dari :

a. BRONKITIS KRONIS:
Batuk kronik berdahak, minimal 3 bulan dalam setahun,
sekurang – kurangnya 2 th berturut-turut.

b. EMFISEMA:
Kelainan anatomis , ditandai adanya pelebaran rongga
udara distal bronchioli terminal, disertai kerusakan dinding
alveoli ( Permanen )
PPOK Pedoman Praktis Daignosis dan Penatalaksanaan. PDPI 2004
Struktur Saluran nafas bawah
 PPOK

1. Bronkitis Kronis 2. Emfisema

Diagnosis klinis Diagnosis Patologis

Keduanya tidak selalu mencerminkan hambatan aliran

udara dalam saluran nafas
Faktor Risiko
 Prevalence smoking in Asia
( WHO 2002)

Indonesia 69 %

China 53,4 %

Thailand 39,3 %

India 29,4 %

Indonesia Smokers : 62.800.000 peoples

( 69,04% men , 4,83% women )
 Faktor risiko P P O K

1. Merokok ( Faktor Terpenting )

a. Riwayat Perokok :
1. Perokok Aktif
2. Perokok Pasif
3. Bekas Perokok
b. Derajat berat merokok
( Indeks Brinkman = Jumlah rata-2 batang rokok /hr X
lama merokok /th):
1. Ringan : 0 - 200
2. Sedang : 200 - 600
3. Berat : > 600
 Faktor risiko P P O K

2. Polusi udara
a. Polusi di dalam ruangan : - asap rokok
- asap kompor
b. Polusi di luar ruangan :
- Gas buang kendaranan bermotor
- Debu jalanan
c. Polusi tempat kerja ( bahan kimia, zat iritasi, gas beracun)
3. Infeksi saluran nafas berulang.
4. Defisiensi enzim alfa – 1 antitripsin ( Jarang )
5. GENETIK
 Future
COPD
case

Future
asthmatic

Future COPD if
smoker

Indoor Air Pollution

Hubungan
antara
Rasio
FEV1
terhadap
umur
 Inhalasi bahan berbahaya

Oksidan
Inflammasi

Mekanisme Anti Mekanisme

perlindungan oksidan perbaikan

Kerusakan
Jaringan

Fibrosis Destruksi HIPERSEKRESI

Hipersekresi
Parenkim Paru MUKUS
mukus
saluran nafas
BR. KRONIS
 CELLULAR MECHANISMS OF COPD

Cigarette smoke

? Alveolar macrophage
CD8+ MCP-1
lymphocyte
Neutrophil chemotactic factors
Cytokines (IL-8)
Mediators (LTB4) 4) )

Neutrophil

PROTEASE Neutrophil elastase

PROTEASES Cathepsins
INHIBITORS
- Matrix metalloproteinases

Alveolar
Alveolarwall
walldestruction
destruction Mucus
Mucushypersecretion
Hypersecretion
( Emphysema )
(Emphysema) (Chronic
( Chronicbronchitis)
Bronchitis )
 Pengaruh alfa-1 anti trypsin

Makrofag Netrophyl
α-1 anti trypsin

Destruksi alveoli Hiperplasi kelenjar

( Emfisema ) ( Bronkitis Kronis )
 Pathophysiology of COPD and Asthma
Noxious Sensitizing
agent COPD Asthma agent

CD8 + Alveolar CD4 +

Mast cell
lymphocyte macrophage lymphocyte

Eosinophil Histamine
Cytokines (IL -8) Cytokines
(IL -4, IL -5, IL -13)
Mediators (LTB 4)
Neutrophil
Mediators (LTD 4)

Inflammatory
Proteases mediators
Epithelial
shedding
Airway
Alveolar wall Mucus Airway
thickening
destruction hypersecretion hyperreactivity
Barnes PJ (1999; 2000)
 COPD IS NOT ASTHMA !

Dyspneu
Wheezing

a) Different causes

b) Different inflammatory cells

c) Different mediators

d) Different inflammatory consequences

e) Different response to treatment

Gambaran Emphysema.
Terjadi kerusakan alveoli

alveooli
 EMFISEMA

EMFISEMA
Expanded View of Etiology, Pathogenesis and
Pathology in COPD

Noxious stimulation

Chronic
inflammation

Destruction,
repair and
remodeling

Abnormal function
and symptoms
 KELAINAN SALURAN NAFAS
BRONKITIS KRONIS EMFISEMA

 Hiperplasi Kelenjar
DESTRUKSI
 Mbr Basal menebal
ALVEOLI
 Oedem Mukosa, Hipersekresi
 Perbedaan Bronkitis Kronis dan Emfisema

NORMAL

Bronkitis EMFISEMA
Kronis
 Wall thickening –
inflammation --
mucus gland
hypertrophy

Bronkitis ↑ Secretions
Bronchus kronis

Wall thickening –
inflammation –
repair --
remodeling
Loss of alveolar
Bronchiole attachments

Wall thinning -
inflammation -
elastolysis

Coalescence ↓
Elasticity
Alveoli Emfisema
Gambar Paru Perokok

dirty holes

This pattern is typical for smokers

 Bullae pada Emfisema

Bullae

large bullae apparent on the

surface of the lungs in a patient
dying with emphysema.
Bullae are large dilated airspaces
that bulge out from beneath the
pleura.
Emfisema Paru
 Fungsi Paru
Ada 2 tahap : INSPIRASI & EKSPIRASI

Ventilasi
ventilasi
Fungsi Paru
Fungsi Paru

Difusi O2
CO2 difusi

Perfusi
perfusi
 Bronchial Anatomy
Pulmonary artery

Pulmonary alveolus

Pulmonary Vein
Bentuk toraks
penderita
Emfisema

Barrel Chest
 Perbedaan patogenesis Asma dan PPOK

ASMA PPOK

Bahan berbahaya
Bahan sensitif

Mediator inflamasi Mediator inflamasi

CD8 + T-Limfosit
CD4 + T-Limfosit
Makrofag
Eosinofil Neutrofil

Hambatan
Reversibel Aliran udara Irreversibel
 ASMA PPOK

Umumnya usia muda Banyak usia tua

 Gambaran Klinis P P O K
EMFISEMA
( PINK PUFFER )
 Batuk dahak - / sedikit
 Badan kurus
 Kulit kemerahan
 Dada cembung ( Barrel Chest )
 Suara nafas lemah / turun
 Foto toraks : hiperaerated
 Foto toraks : diafragma datar
 Darah : Polisitemia ( jarang )
 Faal paru : Volume residu >
 Komplikasi :Kor pulmonale jarang
BRONKITIS KRONIS
( BLUE BOATER )
 Batuk berdahak terus menerus
 Badan gemuk
 Tampak pucat ( sianosis )
 Dada normal
 Rhonki basah / wheezing
 Foto toraks : Jantung membesar,
corakan bronkus makin banyak
 Foto toraks : diafragma normal
 Darah : polisitemia sekunder ( HB ↑ )
 Faal Paru : Volume residu normal
 Komplikasi : kor pulmonale sering
 Gambaran Klinis P P O K

Emfisema Bronkitis Kronis

( Pink Puffer ) ( Blue Boater )
 Diagnosis P P O K
 Gejala & tanda PPOK : bervariasi ( tanpa gejala  sangat berat )

 Diagnosis PPOK ditegakkan berdasarkan :

a. Gambaran klinis
1. Anamnesa : - Keluhan
- Riwayat penyakit
- Faktor predisposisi
2. Pemeriksaan fisik
b. Pemeriksaan penunjang
1. Pemeriksaan rutin
2. Pemeriksaan khusus
 Diagnosis P P O K
GAMBARAN KLINIS:
a. Anamnesa ( Keluhan )

- Usia tua ( > 45 th )

- Riwayat / bekas PEROKOK
- Riwayat terpajan zat iritan ( waktu lama )
- Riwayat infeksi nafas berulang, lingkungan asap rokok
- Batuk berulang dengan / tanpa dahak
- Sesak dengan / tanpa bunyi mengi
- Sesak nafas bila aktivitas berat ( Dyspneu d’effort )
 DIAGNOSING COPD

• A diagnosis of COPD should be considered in any

patient who has:
a. dyspnea,
b. chronic cough or sputum production,
c. and/or a history of exposure to risk \factors for
the disease, especially cigarette smoking (Figure 1).
 Diagnosis P P O K

PEMERIKSAAN PENUNJANG:
I. PEMERIKSAAN RUTIN
1. Foto Toraks ( Paru )
2. Darah rutin
3. Sputum ( dahak ): Neutrofil, makfofag

II. PEMERIKSAN KHUSUS

1. Spirometri ( Faal Paru )
2. Analisa gas darah
3. EKG
 Tanda Fisik Kelainan Paru
EMFISEMA ( PPOM)
1 Inspeksi Bentuk toraks cembung seperti Tong ( Barrel Chest ),

Iga mendatar, sela iga melebar.

Gerakan toraks terbatas, Otot bantu nafas hipertrofi

2 Palpasi Fremitus suara menurun

3 Perkusi Hipersonor seluruh hemitoraks

4 Auskultasi Suara nafas lemah, Ekspirasi lebih panjang, Krepitasi,

Wheezing.
 EMFISEMA
( PINK PUFFER )
Barrel Chest

Sela iga melebar Sela iga melebar

Scoliosis
Hipertrofi otot bantu nafas pada penderita PPOK

Hipertrofi otot bantu nafas

( Hipertrofi musc sternocleidomastoideus )

 Pola pernafasan P P O K

Pada waktu bernafas:

Ekspirasi mulut seperti bersiul
( hampir menutup )

Tekanan di rongga mulut meningkat

Tekanan intra bronkial meningkat

Lumen bronki tetap terbuka

Mencegah kolaps saluran nafas
( Air Trapping )
Gambaran Foto Toraks Emfisema
Cystic fibrosis. Bronchiectasis seen in cross section
 Diagnosis of COPD
EXPOSURE TO RISK
SYMPTOMS FACTORS
cough tobacco
sputum occupation
shortness of breath
indoor/outdoor pollution
è

SPIROMETRY
 Spirometry

Spirometry is a painless study of air volume and flow rate within the lungs.
Spirometry is frequently used to evaluate lung function in people with
obstructive or restrictive lung diseases such as asthma or cystic fibrosis
PEMERIKSAAN FAAL PARU
 Pemeriksaan Faal Paru

1. Menentukan adanya kelainan Restriksi / Obstruksi Paru

2. Menentukan Berat ringannya kelainan Paru
3. Dapat mengevaluasi hasil pengobatan

1. VC ( Vital capacity = Kapasitas Vital ) :

Untuk mengetahui adanya kelainan Restriksi Paru

2. FEV1 ( Volume Ekspirasi detik pertama setelah inspirasi

maksimal ) :

Untuk mengetahui adanya kelainan Obstruksi Paru

 Klasifikasi berat ringan PPOK ( GOLD 2006 )
STAGE CHARACTERISTIC
0 At risk Normal Spirometry
Chronic Symptoms ( Cough, sputum production )
1 Mild FEV1 / FVC < 70 %
FEV1 ≥ 80 % predicted
With or without chronic symptoms
2 Moderate FEV1 / FVC < 70 %
50 % ≤ FEV1 < 80 % predicted
With or without chronic symptoms
3 Severe FEV1 / FVC < 70 %
30 % ≤ FEV1 < 50 % predicted
With or without chronic symptoms
4 Very Severe FEV1 / FVC < 70 %
FEV1 < 30 % predicted
Or FEV1 < 50 % predicted + chronic respiratory failure
 PPOK dan Penyakit Penyerta

COPD patients are at increased risk for:

Myocardial infarction, angina
Osteoporosis (Khususnya pada elderly)
Respiratory infection
Depression
Diabetes
Lung cancer
 PPOK dan Penyakit Penyerta

COPD has significant extrapulmonary

(systemic) effects including:

Weight loss
Nutritional abnormalities
Skeletal muscle dysfunction
 Tujuan Penatalaksanaan P P O K

1. Menghilangkan gejala
2. Mencegah progresifitas penyakit
3. Meningkatkan toleransi aktivitas
4. Meningkatkan Status Kesehatan
5. Mencegah & mengobati Komplikasi
6. Mencegah & mengobati Eksaserbasi
7. Mengurangi Mortalitas
 4 Management COPD

Poliklinik Ruang Ruang

UGD
Rawat jalan rawat ICU
 Managemen PPOK

2 keadaan klinis PPOK

1 2
PPOK
PPOK Stabil
Eksaserbasi Akut
Four Components of COPD Management plan:

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

 Education
 Pharmacologic
 Non-pharmacologic

4. Manage exacerbations
 1 Assess and monitor disease

a) Tentukan Diagnosis awal : Simptom; Pemeriksaan Fisik;

Faal paru.
b) Tingkat Keparahan Penyakit : Foto Torak, Faal Paru;
Analisa Gas Darah
c) Diagnosis Banding
d) Komplikasi bila ada
e) Penyakit penyerta yang ada
f) Monitor obat yang diminum
Four Components of COPD Management plan:

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

 Education
 Pharmacologic
 Non-pharmacologic

4. Manage exacerbations
 2 Reduce risk factors

a) Stop merokok
b) Farmakoterapi ( Kecanduan rokok ) :
bupropion SR, nicotine gum, nicotine
inhaler, nicotine nasal spray, and nicotine
patch..
c) Hindari paparan “ occupational dust & chemical “
d) Hindari paparan “indoor & out door air pullution “
Four Components of COPD Management plan:

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

 Education
 Pharmacologic
 Non-pharmacologic

4. Manage exacerbations
3 Manage Stable COPD

Edukasi Farmakologi Non Farmakologi

1. Bronkodilator 1. Rehabilitasi
2. Kortikosteroid 2. Terapi Oksigen
3. Antibiotika 3. Ventilator support
4. Mukolitik 4. Surgical ttherapy
5. Anti oksidan
6. Vaksin
7. Immunoregulator
8. Alfa-1 antitrypsin
 Menyesuaikan keterbatasan akitifitas

Mencegah kecepatan perburukan fungsi paru

EDUKASI

Mengenal perjalanan penyakit & terapi

Melaksanakan pengobatan maksimal

Mencapai akitifitas optimal

Meningkatkan kualitas hidup

 Skala Prioritas Edukasi

BERHENTI MEROKOK
Penggunaan obat yang benar & tepat

Penggunaan Oksigen

Mengenal & mengatasi efek samping

Penilaian dini eksaserbasi akut & pengelolaannya

Deteksi & hindari pencetus eksaserbasi

Menyesuaikan kebiasaan hidup sesuai keterbatasan aktifitas

3 Manage Stable COPD

Edukasi Farmakologi Non Farmakologi

1. Bronkodilator 1. Rehabilitasi
2. Kortikosteroid 2. Terapi Oksigen
3. Antibiotika 3. Nutrisi support
4. Mukolitik 4. Ventilator support
5. Anti oksidan 5. Surgical ttherapy
6. Vaksin
7. Immunoregulator
8. Alfa-1 antitrypsin
BRONKODILATOR ANTIBIOTIKA

ANTI INFLAMASI

OBAT-OBATAN

ANTIOKSIDAN

MUKOLITIK ANTITUSIF
PEMILIHAN INHALASI DIUTAMAKAN
OBAT
SLOW RELEASE
LONG ACTING

BRONKODILATOR

GOLONGAN ANTIKOLINERGIK

GOLONGAN BETA-2 AGONIS

KOMBINASI

GOLONGAN XANTIN
Ccommonly Used Formulations of Drugs in COPD
1 Beta-2 agonist Short acting ( SABA ) Fenoterol, albuterol, terbutalin

Long acting ( LABA ) Formoterol, Salmeterol

2 Anticholinergic Short acting Ipratropium bromide

Long Acting Tiotropium

3 Methylxanthine Aminophyllin, Theophylin SR

4 Combination SABA + Fenoterol/Ipratropium,

anticholinergic Salbutamol/Ipratropium
5 Combination LABA + Formoterol/Budesonid
Glucocorticoid Salmeterol/Fluticasone
6 Systemic Prednison, Methylprednisolon
Glucocortikoid ( GOLD 2006 )
 Fenoterol
Salbutamol

budesonide and formoterol

 Therapy at Each Stage of COPD
I: Mild II: Moderate III: Severe IV: Very Severe

 FEV1/FVC < 70%

 FEV1 < 30%

 FEV1/FVC < 70%
predicted
 FEV1/FVC < 70%
 FEV1/FVC < 70% or FEV1 < 50%
 30% < FEV1 < 50%
predicted plus
 50% < FEV1 < 80% predicted
 FEV1 > 80% chronic respiratory
predicted
predicted failure

Active reduction of risk factor(s); influenza vaccination

Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting bronchodilators (when
needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated
exacerbations
Add long term oxygen if
chronic respiratory failure.
Consider surgical
treatments
 LINI 1 LINI 2
Amoksisilin Amoksisilin-asam klavulanat
Sefalosporin
makrolid Kuinolon & makrolid baru

BILA ADA INFEKSI

ANTIBIOTIKA

PERAWATAN RUMAH SAKIT

DITAMBAH
Amoksilin-klavulanat Anti Pseudomonas
Sefalosporin II & III Aminoglikoside
Kuinolon
Kuinolon oral Sefalosporin gen. IV
MENEKAN INFLAMASI METILPREDNISOLON
PREDNISON

PADA EKSASERBASI AKUT

ANTI INFLAMASI

BENTUK INHALASI TERAPI JANGKA PANJANG

UJI KORTIKOSTEROID VEP1 meningkat > 20 %

POSITIF Paska bronkodilator
 TERUTAMA KARENA
PADA MEMPERCEPAT
EKSASERBASI PERBAIKAN
AKUT EKSASERBASI

MUKOLITIK

PADA TIDAK DIANJURKAN

BRONKITIS KRONIS SEBAGAI
DENGAN PEMBERIAN
SPUTUM RUTIN
YANG VISCOUS
Mengurangi Memperbaiki
eksaserbasi Kualitas hidup

N-ASETILSISTEIN

ANTIOKSIDAN

PADA PPOK TIDAK

SERING DIANJURKAN
EKSASERBASI PEMBERIAN
RUTIN
 Inhalasi bahan berbahaya

Oksidan
Inflammasi

Mekanisme Anti Mekanisme

perlindungan oksidan perbaikan

Kerusakan
Jaringan

Fibrosis Destruksi HIPERSEKRESI

Hipersekresi
Parenkim Paru MUKUS
mukus
saluran nafas
BR. KRONIS
 Management of Stable COPD
Pharmacotherapy: Vaccines

 influenza vaccines can reduce serious illness

(Evidence A).

 Pneumococcal polysaccharide vaccine :

Usia > 65 th
Usia < 65 th bila FEV1 < 40 %

79
3 Manage Stable COPD

Edukasi Farmakologi Non Farmakologi

1. Bronkodilator 1. Rehabilitasi
2. Kortikosteroid 2. Terapi Oksigen
3. Antibiotika 3. Ventilator support
4. Mukolitik 4. Surgical therapy
5. Anti oksidan
6. Vaksin
7. Immunoregulator
8. Alfa-1 antitrypsin
 Meningkatkan toleransi latihan
TUJUAN
Memperbaiki kualitas hidup

INDIKASI
REHABILITASI
MEDIK Simptom pernapasan berat
Sering masuk rawat darurat
Kualitas hidup menurun
PROGRAM

1. LATIHAN FISIS
2. PSIKOSOSIAL
3. LATIHAN PERNAPASAN
 TERAPI OKSIGEN
PPOK  hipoksemia  kerusakan jaringan

Mengurangi
Vasokonstriksi Mengurangi sesak

Memperbaiki Terapi Memperbaiki

Fungsi neuropsikiatri Oksigen aktivitas

Meningkatkan Mencegah
Kualitas hidup komplikasi jantung
Cara pemberian Oksigen :
 KONDISI Kebutuhan energi meningkat
MALNUTRISI Kerja otot respirasi meningkat

Gangguan Keseimbangan
Elektrolit

NUTRISI HIPERKALEMI
HIPOFOSFATEMI
HIPOKALSEMI
TERAPI HIPOMAGNESEMI

Komposisi nutrisi seimbang

Nutrisi terus-menerus ( Nocturnal feeding )
Nutrisi

Cara mengatasi malnutrisi :

1. Nutrisi diberikan secara terus menerus

2. Seimbang kalori yang masuk dengan yg dibutuhkan

3. Komposisi nutrisi yang seimbang :

tinggi lemak – rendah karbohidrat

4. Pada PPOK + gagal nafas : protein ber > an  timbul

kelelahan
Four Components of COPD Management plan:

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

 Education
 Pharmacologic
 Non-pharmacologic

4. Manage exacerbations
 Management COPD Exacerbations

Key Points
An exacerbation of COPD is defined as:

“An event in the natural course of the

disease characterized by a change in the
patient’s baseline dyspnea, cough, and/or
sputum that is beyond normal day-to-day
variations, is acute in onset, and may
warrant a change in regular medication in
a patient with underlying COPD.”
87
 Management COPD Exacerbations
Key Points

 The most common causes exacerbation :

infection tracheobronchial and air pollution,
(Evidence B).

 COPD exacerbations with airway infection

(e.g., increased sputum purulence) may
benefit from antibiotic treatment (Evidence B).

88
1 . Menghindari intubasi & penggunaan alat bantu nafas dengan cara :
EVALUASI KLINIS TEPAT + TERAPI ADEKUAT.
2. Obat-obatan :
a. Bronkodilator ( agonis beta – 2, antikolinergis, xantin )
b. Kortikosteroid
c. Antibiotika
d. Mukolitik / ekspektorans
3. Terapi Oksigen dengan cara yang tepat.
4. Terapi Nutrisi enteral / parenteral seimbang
5. Rehabilitasi awal
6. Edukasi pasca rawat
Ventilasi mekanik
 Komplikasi P P O K

KOMPLIKASI :
1) Infeksi berulang ( Pneumonia )
2) Pneumotoraks
3) Kor Pulmonale Kronikum ( CPC )
Kompensata / Dekompensata
4) Gagal Nafas
5) Meninggal
 Summary
• ……………………………….
• ………………………………
• ……………………………..
• ……………………………..
• ……………………………..
• …………………………….
TERIMA KASIH