PENATALAKSANAAN ASMA JANGKA PANJANGFaisal YunusBagian Pulmonologi & Kedokteran Respirasi FKUI - RS Persahabatan Jakarta

ISAAC Steering Committee, Lancet 1998

196419891994Ninan & Russell, BMJ 1992PENINGKATAN PREVALENSI

Asthma impacts on normal life% of patients

TUJUAN PENATALAKSANAAN ASMA Menghilangkan dan mengendalikan gejala asma Mencegah eksaserbasi penyakit Meningkatkan faal paru mendekati normal Mempertahankan faal paru

TUJUAN PENATALAKSANAAN ASMA (lanjutan) Menghindari efek samping obat Mencegah obstruksi yang ireversibel Mencegah kematian karena asma

MEMBUAT ASMA MENJADI TERKONTROL

KRITERIA ASMA TERKONTROLTidak ada atau gejala minimalTidak ada gejala asma malamTidak ada keterbatasan aktivitiTidak ada atau minimal pemakaian obat pelegaFaal paru normal atau mendekati normalTidak ada kunjungan ke emergensi

EDUKASI PENDERITA DAN KELUARGANYA TENTANG ASMA1

PENDIDIKAN PENDERITA Mengetahui seluk beluk penyakit Mengenali sifat penyakit Mengenali perubahan penyakit, membaik/memburuk Mengerti kerja obat-obatan Mengetahui kapan harus meminta pertolongan dokter

KARAKTERISTIK ASMA Penyakit kronik Sifatnya variasi Obstruksi reversibel Airway remodeling

MENENTUKAN KLASIFIKASI ASMA2

KLASIFIKASI ASMA Ditentukan oleh Frekuensi serangan Serangan asma malam Gangguan aktiviti Nilai faal paru (VEP1 atau APE) Variabiliti harian

Classification of SeverityCLASSIFY SEVERITYClinical Features Before TreatmentSymptomsNocturnalSymptomsFEV1 or PEFSTEP 4Severe PersistentSTEP 3Moderate PersistentSTEP 2Mild PersistentSTEP 1IntermittentContinuousLimited physical activityDailyAttacks affect activity> 1 time a week but < 1 time a day< 1 time a weekAsymptomatic and normal PEF between attacksFrequent> 1 time week> 2 times a month 2 times a month 60% predictedVariability > 30%60 - 80% predicted Variability > 30% 80% predictedVariability 20 - 30% 80% predictedVariability < 20%The presence of one feature of severity is sufficient to place patient in that category.

Levels of Asthma Control

CharacteristicControlled(All of the following)Partly controlled (Any present in any week)Uncontrolled Daytime symptomsNone (2 or less / week)More than twice / week3 or more features of partly controlled asthma present in any week

Limitations of activitiesNoneAnyNocturnal symptoms / awakeningNoneAnyNeed for rescue / reliever treatmentNone (2 or less / week)More than twice / weekLung function (PEF or FEV1)Normal< 80% predicted or personal best (if known) on any dayExacerbationNone One or more / year 1 in any week

MENGHINDARI FAKTOR PENCETUS3

FAKTOR PENCETUS Alergen (debu rumah, bulu binatang) Makanan (bumbu, penyedap, pengawet) Infeksi saluran napas Perubahan cuaca Aktiviti berlebihan Bahan iritan Bau yang merangsang Emosi

PENGOBATAN YANG OPTIMAL4

Asthma Pathophysiology Smooth Muscle DysfunctionAirway InflammationInflammatory cell infiltration/ activation Mucosal edema Cellular proliferation Epithelial proliferation

BronchoconstrictionBronchial hyperreactivityHypertrophy/hyperplasiaInflammatory mediator releaseSymptoms/Exacerbations

OBAT OBAT ASMA Obat pelega napas ( Reliever ) Obat pengontrol asma ( Controllewr )

OBAT PELEGA NAPASDipakai saat seranganBersifat bronkodilator

OBAT PELEGA NAPAS

Agonis 2 kerja singkat inhalasi Kortikosteroid sistemikAntikolinergik inhalasiTeofilin kerja singkatAgonis 2 kerja singkat oral

OBAT PENGONTROL ASMA Dipakai rutin setiap hari Anti inflamasi Bronkodilator kerja lama

OBAT PENGONTROL ASMA Kortikosteroid inhalasi Kortikosteroid sistemik Sodium kromolin Sodium nedokromil Teofilin lepas lambat Agonis 2 kerja lama inhalasi Agonis 2 kerja lama oral Antileukotrien

Anti histamin lain ~ ketotifen ~ terfenadin ~ loratadin

KORTIKOSTEROID Mekanisme kerja : Hambat metabolisme asam arakidonat Cegah migrasi sel inflamasi Mengurangi kebocoran mikro vaskuler Meningkatkan kepekaan reseptor beta

KORTIKOSTEROID SISTEMIK Oral, intravena Dianjurkan yang intermediate acting Mengurangi angka perawatan Mencegah kekambuhan Mencegah kematian

Arus puncak ekspirasi kelompok kortikosteroid dan kelompok tanpa kortikosteroid selama pengamatanArus puncak ekspirasi rata-rata (l/menit)Tobing NH. Bagian Pulmonologi FKUI, 1992

KORTIKOSTEROID INHALASI Antiinflamasi paling poten Terapi pilihan untuk controller Efek samping ~ Kandidiasis oral ~ Disfonia

PERBANDINGAN EFEK BUDESONIDE INHALASI DAN KETOTIFEN ORAL PADA ASMA Tersamar ganda 40 penderita Budesonide 2 x 200 ug Ketotifen 2 x 1 mg

Minggu0481012Run-in Periode pengobatan wash-outMangunnegoro dkk. Paru 1992; 12 (1) : 10-8

Perubahan PC20 sebelum, selama dan sesudah pengobatan PC20 (mg/ml)Mangunnegoro et al, Paru,1992; 12: 10-8

PERBANDINGAN EFEK BEKLOMETASON DAN KETOTIFEN PADA ASMA Tersamar ganda 40 penderita asma Beklometason 2 x 250 ug Ketotifen 2 x 1 mgRun-in Periode pengobatan wash-outMinggu0481012Ikhsan dkk. Paru 1995; 15 : 146-55

Perubahan nilai PC20 sebelum,selama dan sesudah pengobatan MingguPC20

KOMBINASI TETAP KORTIKOSTEROID INHALASI DAN 2 AGONISEfek steroid terhadap sistem 2 agonis

Meningkatkan sintesis reseptor Menurunkan desensitisasi reseptor Efek sinergi

Treatment daysChange in asthma symptom score (score: 0-6)p

Zetterstrm O et al ERJ 2001Treatment Days-103603703803904004100102030405060708090PEF (L / min)Budesonide 200g bdEFEK KOMBINASI STEROID DAN LABA PADA ASMAAsma ringanPEAK FLOW

EFEK KOMBINASI STEROID DAN LABA PADA ASMAAsma sedang: FEV1 ~75% pred on ~1000g ICSCOMBAT study-100102030405060708090350360370380390400Morning PEF (L/min)Days since randomizationBudesonide(400g b.d.)Budesonide + formoterol(400 + 12 g b.d)

Bateman E et al: AJRCCM 2001Change in morning PEF (L/min)Treatment daysFluticasone 250 g bdKOMBINASI STEROID + LABA vs STEROID DOSIS TINGGI

ASTHMA TREATMENT GUIDELINES

PERBANDINGAN EFEKTIVITI PEMBERIAN TRIAMSINOLON ASETONID INTRAMUSKULAR DENGAN INHALASI BUDESONID PADA ASMA PERSISTEN SEDANG

Bobby Drastyawan, Faisal Yunus, Wiwien Heru Wiyono, Hadiarto Mangunnegoro

Departemen Pulmonologi dan Ilmu Kedokteran Respirasi FKUI/RS PersahabatanJakarta

Kriteria InklusiAsma persisten sedangUsia 15 65 tahunFungsi hati dan ginjal normalPenderita tidak memakai kortikosteroid sistemik

Kriteria EkslusiPenyakit paru lainPenyakit jantungPerempuan hamilAsma eksaserbasi akut

PROSEDUR PENELITIANUji klinis random terbukaJumlah sampel 44 orangKelompok I : Inhalasi Budesonid 2 X 400 g II : Triamsinolon asetonid intramuskular 40 mg hari kesatu dan hari ke-29Lama penelitian 8 minggu

PENILAIAN HASIL PENGOBATAN

PC20Skor gejalaFungsi paru : VEP1

ALUR PENELITIANPeriode pengobatan kelompokterapi inhalasi dosis terukur (IDT) budenosid 2 X 400 g/hari

Seleksi:Anamnesis pem. fisisFoto toraksKunjungan awal (1) :Skor GejalaVEP1PC20Kadar kortisol darah*Injeksi TA IM 40 mg IM(I)

Periode pengobatan kelompokterapi injeksi TA 40 mg/kali IM sebanyak 2 kali dgn selang waktu 4 mingguKunjungan 2 :Injeksi TA 40mg IM (II)Analisis hasilpenelitian Kunjungan akhir (3)Skor gejalaVEP1PC20Kadar kortisol darah*

minggu02610Keterangan * : dilakukan pada kelompok terapi injeksi TA IMrun in

HASIL PENELITIAN

Karakteristik subjek penelitian berdasarkan jenis kelamin(31,8 %)Ket. * : uji chi squareP : 0,835/NS* (63,6 %)(36,4%)(68,2 %)TA

Karakteristik subjek penelitian berdasarkan usia(31,8 %)Ket. * : uji chi squareP : 0,835/NS* (63,6 %)(36,4%)(68,2 %)BudesonidTA

Hiperaktiviti Bronkus0.820.861.711.84Nilai geometrik PC20

(mg/ml)Ket. : PC20 pada keadaan awal PC20 setelah pengobatan 8 minggu

Skor gejala batukSb (0) : Skor gejala batuk pada keadaan awalSb (8) : Skor gejala batuk setelah pengobatan 8 minggu0.730.750.080.1Perubahan Skor Gejala Batuk

Ket. : Gtm (0) : skor awal gangguan tidur rmalam; Gtm (8) : skor gangguan tidur malam setelah pengobatan 8 minggu; Ga (0) : skor awal gangguan aktiviti;Ga (8) : skor gangguan aktiviti setelah pengobatan 8 minggu; Mengi (0) : skor awal mengi; Mengi (8) : skor mengi setelah pengobatan 8 minggu0.780.670.090.050.790.670.050.030.570.560.030.03Skor Gejala Gangguan Tidur, Aktiviti, dan MengiSkor gejala

Perubahan Skor Total2.872.650.260.22Ket. St (0) : skor awal gejala asma total St (8) : skor gejala asma total setelah pengobatan 8 mingguSkor total gejala asma

Perubahan Kebutuhan Inhalasi Agonis -2Ket. Op (0) : kebutuhan inhalasi agonis -2 pada keadaan awal Op (8) : kebutuhan inhalasi agonis -2 setelah pengobatan 8 minggu2.942.640.230.06Agonis beta 2(semprot/hari)

Perubahan VEP11923.181554.092210.911769.55VEP1 (ml)Ket. : 0 : Nilai VEP1 pada awal terapi; 8 : Nilai VEP1 setelah pengobatan 8 minggu

Kadar Kortisol Dalam Darah Kadar kortisol darah(nmol/l)234.05208.82Ket. : Kort (0) : Kadar kortisol darah pada keadaan awal Kort (8) : Kadar kortisol darah setelah pengobatan 8 minggu

The analysis of abnormal five hour synacthen test in relation to the factors which may influence the adrenocortical impairment of TA treated patients2-4 years(61)Duration of treatment

> 4 years(14)TA Average Daily Dosage

AGE

< 1,2mg (55)> 1,2mg (20)< 50 years (23)> 50 years (52)P>0.20P

KESIMPULANTerapi Triamsinolon Asetonid 40 mg intramuskular dua kali dengan interval waktu 4 minggu memberikan efektivitas yang sama dengan budesonid 2 X 400 selama 8 minggu

Tidak terjadi gangguan kortisol darah pada pemberian triamsinolon asetonid

KESIMPULANTidak terdapat efek samping pada pemberian steroid secara inhalasi maupun intramuskular

Pemberian triamsinolon asetonid intramuskular dapat dipakai sebagai terapi alternatif pada penderita asma persisten

Characteristics of step 4 pts (Severe Persistent Asthma)Long term Corticosteroid dependentRepeated ER visitsMultiple hospitals admissionsFrequent episodes of respiratory failureThe need for intubation and mechanical ventilation

TA 360 mg vs Pred 12.5 mg dailyOgirala RG. Single high dose intramuscular TA in severe chronic life threatening asthma. N Eng J Med 1991;324:585Group ITA 360 mg /3d I.M.Group IIPred 12.5 mg/d p.o.Group IITA 360 mg /3d I.M.Group IPred 12.5 mg/d p.o.12 pts, severe chronic life threatening asthma double blind, placebo controlled, crossover study3 mo wash out period3 months3 months

Results:TriamcinolonePrednisoneTriamcinolonePrednisonePanel A show data for a patient who received prednisoloneinitially, then triamcinolone. Note, that there was a washoutperiod between week 12 and 24.Panel B shows data for a patient who receivedtriamcinolone initially, then started prednisolone in the24th week. Note, that there was a washout period betweenweeks 12 and 24Raja G. Ogirala et al. New England J. 1991Dose: Triamcinolone 120 mg/day (IM) for first three days Oral Prednisolone 12.5 mg/day

Results Ogirala RG. Single high dose intramuscular TA in severe chronic life threatening asthma. N Eng J Med 1991;324:585

TA 360 mg in elderly ptsMcGivney SA. Effect of high dose intramuscular triamcinolone in older adults with severe chronic asthma. Lung 1994;172:737 pts, age > 55 years, severe chronic steroid dependent asthmaOne 360 mg I.M. TAResults: Marked functional improvement in their activities of daily living and independenceAll had rise in PFR ranging between 25 93 %All were able to stop taking their daily prednisoneResponse duration ranged from 3 to 24 months

TA 80 mg vs Prednisone 30 mg/hari Kabat: Respons penderita asma berat thd pengobatan alternatif steroid long acting TA. FK Unair, 1999Asma BeratTA 80 mgPred. 30 mg/hAminophyllin+ TerbutlinSetelah 6 minggu:Eosinofil, IgE dan IgG , bermaknaBB , bermaknaPFR , tidak bermakna

Triamcinolone Acetonide for Difficult Asthma in ChildrenPediatric Pulmonology 39:421-425,2005

Comparison of Markers of Astma Severty, Expressed as Mean Per Month,in Children Receiving a Single IM TriamcinoloneP

Comparison of Markers of Astma Severty, Expressed as Mean Per Month,in Children Receiving a Single IM TriamcinoloneP

Comparison of Markers of Astma Severty, Expressed as Mean Per Month,in Children Receiving 3 or more IM Triamcinolone1Data summarized as mean(SD) per month,and compared with pretreatment period by paired t-testP

Comparison of Markers of Astma Severty, Expressed as Mean Per Month,in Children Receiving 3 or more IM TriamcinoloneP

EKSASERBASI AKUT Asma akut sedang dan berat diberikan kortikosteroid sistemik Kortikosteroid sistemik :~ Mempercepat penyembuhan~ Mencegah kekambuhan~ Memperpendek hari rawat ~ Mencegah kematian

KONTROL PENGOBATAN BERKALA6

IDENTIFIKASI PERBURUKAN PENYAKIT

PEMERIKSAAN FAAL PARU Evaluasi pengobatan Menentukan prognosis

EVALUASI PENGOBATAN Nilai tiap 3 bulan Tambahkan / kurangi obat

MENINGKATKAN KEBUGARAN FISIK DENGAN LATIHAN/OLAHRAGA7

MENINGKATKAN KEBUGARAN JASMANI Olahraga yang teratur Meningkatkan kemampuan otot napas Meningkatkan kebugaran jasmani Menambah rasa percaya diriOlahraga yang dianjurkan Renang Senam asma Bersepeda

RENANG Tidak ada EIA Menguatkan otot napas

SENAM ASMA DI INDONESIA Mengurangi frekuensi serangan Mengurangi pemakaian obat

SENAM ASMA DI INDONESIA Meringankan gejala Meningkatkan VO2 maks

PENUTUP Asma penyakit inflamasi kronik saluran napas Manifestasi klinik bervariasi Klasifikasi berat penyakit menentukan pengobatan Anti inflamasi perlu pada asma persisten

PENUTUP Terapi steroid inhalasi obat pilihan untuk mengontrol asma Efikasi triamsinolon asetonid intramuskular sama dengan inhalasi budesonid untuk mengontrol asma Triamsinolon intramuskular dapat digunakan sebagai terapi alternatif untuk mengintrol asma

FY

The estimated world population prevalence of asthma among adults is about 6% At least 180,000 deaths per year worldwide can probably be attributed to asthma Prevalence rate estimates vary in different regions of the world, and even in different parts of each country In general, asthma is more common in urban than in rural areas Prevalence rates may also be affected by genetic factors, climatic conditions and increased reporting due to improvements in diagnosis and better public awareness about asthma This map illustrates the results of a recent survey of just under 500,000 children, aged 13-14 years, in 56 countries using a one-page questionnaire to identify those with symptoms of asthma The highest 12 month prevalence rates for asthma symptoms were located in the UK, Australia and New Zealand followed by most centres in North, Central and South America

The prevalence of asthma has increased significantly over the last thirty years. For example, among Aberdeen, UK, schoolchildren, asthma prevalence has risen by 14% over this period

Slide 18 Asthma Pathophysiology

Asthma is a chronic disease with 2 major underlying mechanisms: smooth muscle dysfunction and airway inflammation, which interact to cause asthma symptoms. In addition to bronchoconstriction and bronchial hyperreactivity, smooth muscle dysfunction in asthma involves smooth muscle hypertrophy and hyperplasia with release of inflammatory mediators by smooth muscle cells. The bronchial walls show mucosal edema, thickening of muscularis layer, and a proliferation of eosinophils and epithelial damage.

Kumar RK. Pharmacol Ther. 2001;91:93.

Drug treatments for asthma are divided into two main types: relievers and controllers A reliever provides rapid relief of symptoms and works predominantly by relaxing airway smooth muscle to enhance the flow of air in and out of the lungs Inhaled fast-acting 2-agonists are the most widely prescribed reliever medication Inhaled anticholinergics cause bronchodilation by blocking reflex airway constriction mediated by the release of acetylcholine and by reducing smooth muscle tone induced by vagus nerve activity Inhaled steroids are highly effective at suppressing the various inflammatory processes involved in asthma and are currently the most effective approach to maintenance therapy for most patients with asthma Inhaled long-acting 2-agonists act mainly by relaxing the airway smooth muscle, but because they also stabilise mast cells they may also block the early reaction to triggers, such as allergens and exercise Inhaled cromones stabilise the mast cell membrane to prevent antigen-induced release of histamine and other inflammatory mediators. They may also inhibit the activation of sensory C nerve fibres thought to be responsible for amplifying the ongoing inflammatory response Oral steroids are reserved for the acute management of a severe asthma attack, or for long-term use in intractable cases of asthma Oral theophyllines have been shown to have an anti-inflammatory action, but because of their narrow therapeutic window their long-term use in many patients is limited by the occurrence of side effects, such as abdominal pain, nausea and vomiting Oral anti-leukotrienes are the newest class of controller therapy. They have an anti-inflammatory effect by blocking the action of inflammatory mediators known as leukotrienes. Most physicians prescribe an anti-leukotriene as add-on-therapy for asthma patients having exacerbations when using moderate doses of an inhaled corticosteroid