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Global Global Initiative Initiative untuk

Kronis Kronis Obstruktif Obstruktif Paru


Paru PenyakitPenyakit

POCKET GUIDE TO
COPD DIAGNOSIS, MANAJEMEN,
DAN PENCEGAHAN

Sebuah Panduan untuk Perawatan Kesehatan Profesional 2019


LAPORAN
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INISIATIF GLOBAL UNTUK obstruktif


kronis PENYAKIT PARU

POCKET GUIDE uNTUK COPD DIAGNOSIS, MANAJEMEN, DAN PENCEGAHAN


Sebuah Panduan untuk Perawatan Kesehatan Profesional 2019 EDITION
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© 2019 global Initiative untuk Chronic Obstructive Lung Disease, Inc.

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GOLD DIREKSI (2018)
GOLD ILMU KOMITE* ( 2018)
Alvar Agusti, MD, Ketua Lembaga Pernafasan, Klinik Rumah Sakit, IDIBAPS Univ. Barcelona dan Ciberes Barcelona,
Spanyol
Bartolome R. Celli, MD Brigham dan Rumah Sakit Wanita Boston, Massachusetts, AS
Rongchang Chen, MD Guangzhou Institute of Respiratory Disease Guangzhou, PRC
Gerard Criner, MD Temple University of Medicine Philadelphia, Pennsylvania, USA
Peter Frith, Rumah Sakit MD Flinders, Adelaide, Australia
David Halpin, MD Rumah Sakit Royal Devon dan Exeter Devon, UK
M. Victorina López Varela, MD Universidad de la República Montevideo, Uruguay
Masaharu Nishimura, MD (pensiunan Mei, 2018) Fakultas Kedokteran Universitas Hokkaido Sapporo, Japan
Sundeep Salvi, Yayasan Penelitian Dada MD Pune, India
Claus Vogelmeier, MD University of Marburg Marburg, Germany
Claus Vogelmeier, MD, Ketua Universitas Marburg Marburg, Jerman
Alvar Agusti, MD Pernapasan Institute, Klinik Rumah Sakit, IDIBAPS Univ. Barcelona dan Ciberes Barcelona,
Spanyol
Antonio Anzueto, MD Pusat Ilmu Kesehatan Universitas Texas San Antonio, Texas, AS
Peter Barnes, MD National Heart and Lung Institute London, Inggris
Jean Bourbeau, MD McGill University Pusat Kesehatan Montreal, Kanada
Gerard Criner, MD Fakultas Kedokteran Universitas Temple Philadelphia, Pennsylvania, AS
Peter Frith, MD Rumah Sakit Umum Repatriation Adelaide, Australia
David Halpin, MD Rumah Sakit Royal Devon dan Exeter Devon, Kerajaan Inggris
MeiLan Han, MD MS dari Michigan University Ann Arbor, MI, USA
Fernando J. Martinez, MD MS Rumah Sakit Presbyterian New York / Pusat Medis Weill Cornell New York, NY, AS
Alberto Papi, MD University of Ferrara Ferrara, Italia
Ian Pavord, MA DM University of Oxford Oxford, UK
Nicolas Roche, MD University Paris Descartes Hôpital Cochin APHP Paris, Prancis
MATERIAL OPYRIGHTED-JANGAN
Donald Sin, MD St. Paul's Hospital, University of C
SALINAN ATAU DISTR I
British Vancouver, Dave University Manchester, Robert University

BUT E
Singh, Columbia
Stockley, dari Rumah Sakit Kanada
MD Manchester UK
MD
Birmingham, UK
Jørgen Vestbo, MD University of Manchester Manchester, Inggris, Inggris
Jadwiga A. Wedzicha, MD Imperial College London London, Inggris
M. Victorina López Varela, MD Universidad de la República Hospital Maciel Montevideo, Uruguay
DIREKTUR PROGRAM EMAS
Rebecca Decker, MSJ Fontana, Wisconsin, AS
BANTUAN EDITORIAL
Ruth Hadfield, PhD, Sydney, Australia Michael Hess, RRT RPFT, Michigan, AS
*Formulir pengungkapan untuk Komite EMAS diposting di Situs EMAS diposting , www.goldcopd.org

iii
DAFTAR ISI
DAFTAR ISI ......................................... ............. IV
STRATEGI GLOBAL UNTUK DIAGNOSIS, MANAJEMEN, DAN PENCEGAHAN COPD ............... 5
PENDAHULUAN ....... .................................................. 5
DEFINISI DAN GAMBARAN ....................................... 5
POIN KUNCI KESELURUHAN: .. ........................................ 5 APA ITU PENYAKIT PULMONER OBSTRUKTIF
KRONIS (COPD) ? .................................................. ..... 6 APA PENYEBAB COPD? ................................................ 6
DIAGNOSA DAN PENILAIAN COPD ...................... 8
KESELURUHAN POIN KUNCI: ................... ....................... 8 DIAGNOSIS ......................... ........................................
8 DIAGNOSIS PERBEDAAN ....... ................................... 8 PENILAIAN ............. ................................................ 9
Klasifikasi keparahan keterbatasan aliran udara ...... 9 Penilaian gejala ................................... 12 Gabungan penilaian
COPD .............................. 12
PENCEGAHAN MENDUKUNG PENCEGAHAN DAN PEMELIHARAAN TERAPI ......... .................................. 13
KESELURUHAN POIN KUNCI: ........... ............................. 13 PENGHENTIAN MEROKOK ..................
............................ 14 VAKSINASI .................... .................................... 14 TERAPI FARMAKOLOGI UNTUK COPD
STABIL ... 15 Ikhtisar obat .............................. 15 Bronchodila tors ................................................. 15 Obat
antimuskarinik .......................................... 16 Methylxanthines .. ............................................... 18 Kombinasi
bronkodilator terapi ................. 18 Agen antiinflamasi ........................... ....... 19 Kortikosteroid inhalasi (ICS)
............................... 19 Terapi inhalasi tiga kali lipat .. ...................................... 23 Glukokortikoid oral .........
................................... 23 Inhibitor Phosphodiesterase-4 (PDE4) ....... ....... 23 Antibiotik .........................................
.................. 23 Mucolytic (mucokinetics, mucoregulator) dan agen antioksidan (NAC, carbocysteine) ........... 24
Masalah yang terkait dengan pengiriman inhalasi ....................... 24 Perawatan farmakologis lainnya .................... 24
REHABILITASI, PENDIDIKAN & MANAJEMEN DIRI ................................................. .................................... 25
Pulmona rh rehabilitasi .................................... 25 DUKUNGAN, PALLIATIF, AKHIR-HIDUP & RUMAH SAKIT
PEDULI ................................................. ....................... 25 Kontrol gejala dan perawatan paliatif .................. 25
PENGOBATAN LAINNYA ............................................... 26 Terapi oksigen dan dukungan ventilasi ............ 26
Dukungan Ventilasi ................................ ............ 26 Intervensi Bedah ................................... ...... 27
PENGELOLAAN COPD STABIL ............................... 28
POIN KUNCI KESELURUHAN: ... ...................................... 28 IDENTIFIKASI DAN KURANGKAN SAMPAI KE
FAKTOR-FAKTOR RISIKO .... .................................................. ........................... 28 PENGOBATAN COPD STABIL:
PENGOBATAN FARMAKOLOGI ............... .............................................. 29
MATERIAL
Algoritma untuk penilaian, inisiasi dan tindak lanjut manajemen farmakologis C
TERBUKA-DO N OT
MANAJEMEN COPD PERAWATANPENGOBATAN FARMAKOLOGI

C
PENGOBATAN REFERENSI DAN Pengobatan Pendidikan Oksigen Perawatan OVERALL Pencegahan Rumah

OPY O R
Sakit Pernafasan OVERALL COMORBIDITIES discharge terapi ..........................
................................... KUNCI OPSI KUNCI dan ......... .................................................. DAN pengaturan
D ADALAH
dukungan STABIL PEKERJAAN POIN: POIN: eksaserbasi self-management IKUTI-UP

T R
................................... ................... PERAWATAN ............................. .................. ............................... ...............

IB
dan .................................. .......... COPD: ..................................... .... ......................................... .....

U TE
.................................. menindaklanjuti
NON- ......... ...................... ............................ .. .......................... ...................... ..... ........................ ..................... .. 31
37 37 38 40
40
40 41 41 43 45 47
48 48
48
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GLOBAL STRATEGI UNTUK DIAGNOSIS,
MANAJEMEN, DAN PENCEGAHAN PPOK
PENDAHULUAN
Penyakit Paru Obstruktif Kronik (PPOK) saat ini penyebab utama keempat kematian di dunia1
namun diproyeksikan menjadi 3rd terkemuka penyebab kematian pada tahun 2020. Lebih dari 3
juta orang meninggal karena COPD pada tahun 2012 terhitung 6% dari semua kematian secara
global. COPD merupakan tantangan kesehatan masyarakat yang penting yang dapat dicegah
dan diobati. COPD adalah penyebab utama morbiditas dan mortalitas kronis di seluruh dunia;
banyak orang menderita penyakit ini selama bertahun-tahun, dan meninggal prematur karena
penyakit ini atau komplikasinya. Secara global, beban PPOK diproyeksikan akan meningkat
dalam beberapa dekade mendatang karena paparan terus-menerus terhadap faktor risiko
PPOK dan penuaan populasi.2
Ini dan bukti dokter. www.goldcopd.org. DEFINISI KESELURUHAN ilmiah Saku •
batasan yang dapat diobati • produksi. Pencegahan Kronis Diskusi untuk yang paling
Panduan KEY literatur penyakitobstruktif bahwapaparan, penilaian dari umumini: POIN

memiliki CCOPD DAN Oadalah menjadi Padalah karena PPOK yang Ygejala R(2019
saya G
untuk termasuk pernapasan dikembangkan untuk paru GAMBARAN
H TE D
adalah diagnosis berbahaya dan saluran napas yang ditandai Report), PPOK Mei

M A T, E
bahwa dan / atau partikel dari dan gejala manajemen Penyakit yang menjadi

R saya A L -
perawatan sumber kurang dilaporkan dengan alveolar bertujuanglobal atau
D O
PPOK()persisten dokumen, gases.
N O T
termasuk sampai buktiStrategi memberikan kelainan pasien adalah

CO P Y O.
dyspnea,pernapasan yang, pada umumnya, kadar, untuk pasien dengan non-
R D I S T
bias adalah batuk tersedia COPD dan biasanya Diagnosis, dicegah gejala
R IB U TE
tertentu itu dan / atau meninjau dari disebabkan Manajemenbisa kutipan, dari
dandahak bantuan dan oleh
aliran udara
arus
dari
• The utama faktor risiko untuk COPD adalah merokok tembakau tetapi paparan
lingkungan lainnya seperti paparan bahan bakar biomassa dan polusi udara dapat
berkontribusi. Selain eksposur, faktor host mempengaruhi individu untuk
mengembangkan COPD. Ini termasuk kelainan genetik, perkembangan paru-paru
abnormal dan penuaan yang dipercepat.
• COPD dapat diselingi oleh periode memburuknya gejala pernapasan akut, yang
disebut eksaserbasi.
• Pada sebagian besar pasien, COPD dikaitkan dengan penyakit kronis bersamaan
yang signifikan, yang meningkatkan morbiditas dan mortalitasnya.
5

APA ITU PENYAKIT PULMONARY OBSTRUKTIF


KRONIS?
Penyakit Paru Obstruktif Kronis (PPOK) adalah penyakit yang umum, dapat dicegah dan
diobati yang ditandai dengan gejala pernapasan persisten dan keterbatasan aliran udara yang
disebabkan oleh saluran napas dan / atau kelainan alveolar yang biasanya disebabkan oleh
paparan signifikan terhadap partikel atau gas yang berbahaya. Keterbatasan aliran udara
kronis yang merupakan karakteristik dari COPD disebabkan oleh campuran penyakit saluran
udara kecil (misalnya, bronchiolitis obstruktif) dan penghancuran parenkim (emphysema),
kontribusi relatif yang bervariasi dari orang ke orang (lihat Gambar).

Apa yang
menyebabkan
COPD?
Di seluruh dunia, faktor risiko yang paling sering ditemui untuk COPD adalah merokok
tembakau. Bukan perokok juga dapat mengembangkan COPD. COPD adalah hasil dari saling
pengaruh yang kompleks dari paparan kumulatif jangka panjang terhadap gas dan partikel
berbahaya, dikombinasikan dengan berbagai faktor host termasuk genetika, hiper-responsif
jalan napas dan pertumbuhan paru-paru yang buruk selama masa kanak-kanak.3-5 Risiko
terkena COPD terkait dengan faktor-faktor berikut:
► Asap tembakau - perokok memiliki prevalensi gejala pernapasan yang lebih tinggi dan
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kelainan fungsi paru-paru, tingkat penurunan tahunan yang lebih besar pada FEV1, dan tingkat
mortalitas PPOK lebih besar daripada non-perokok.6 Jenis tembakau lainnya (mis., Pipa, cerutu,
pipa air)7-9 dan ganja10 juga merupakan faktor risiko COPD, serta asap tembakau lingkungan
(ETS). 11
► Polusi udara dalam ruangan - yang dihasilkan dari pembakaran kayu dan bahan bakar
biomassa lainnya yang digunakan untuk memasak dan memanaskan di tempat tinggal yang
berventilasi buruk, merupakan faktor risiko yang khususnya memengaruhi wanita di negara
berkembang. 12,13
► Paparan kerja - termasuk debu organik dan anorganik, agen kimia dan asap, merupakan
faktor risiko yang kurang dihargai untuk COPD. 12,14
► polusi udara luar ruangan - juga berkontribusi terhadap total beban paru-paru partikel
terhirup,
► ► ► ► ► meskipun genetik genjuga Umur Lung individu masa ini Sosial Ekonomi
rendah tidak polutan, sosial ekonomi Asma aliran udara yang jelas, dan telah pertumbuhan
encodingketerbatasan sosial ekonomi faktordan jenis kelamin bagaimanapun, terkait (rendah
O P.
Ccrowding, muncul risiko - jalan napas dan penuaan status kelahiran matriks

YR I G
status - dan pengembangan seperti mengembangkan apakah hiper-reaktivitas dan

H T
berat, status buruk COPD. metaloproteinase menurun memiliki - sebagai Kemiskinan
E D M A
perempuan yang parah gizi, adalah pernapasan ini relatif pada PPOK terkait -.

T E R I
paru-paruseks adalah keturunan pola setiap konsisten meningkatkan infeksi, -

sebuah L - D O
functionfactor asma kecil infeksi, 12 mencerminkan dengan defisiensi(MMP-

N O T
12)yang berpengaruhPPOK 16 mungkin berhubungan atau atau mempengaruhi

C OP Y
eksposur peningkatan risikorisiko lainnya. dll) dibe menyebabkan dari dari dan paru-

O R
paru memiliki faktor risiko alp ha-1 COPD. denganglutathione risikoterhadap faktor

D Aku S
pertumbuhan COPD. dalam ruangan aliran udara 17 terkait potensi antitrypsin

T R IB U TE
mengembangkan untuk selama dan obstruksiS-transferase untuk pembangunan
luar ruangan kehamilan rendah (AATD) meningkatkan COPD.18 udara 15 19,20 dan memiliki
; dan
itu adalah
► Bronkitis kronis - dapat meningkatkan frekuensi eksaserbasi total dan berat.21
► Infeksi - riwayat infeksi pernafasan yang parah pada masa kanak-kanak telah dikaitkan
dengan penurunan fungsi paru-paru dan peningkatan gejala pernapasan di masa dewasa. 22
7
DIAGNOSIS DAN PENILAIAN COPD DI
SELURUH POIN KUNCI:
• COPD harus dipertimbangkan pada pasien yang mengalami dispnea, batuk kronis
atau produksi dahak, riwayat infeksi saluran pernapasan bawah berulang dan / atau
riwayat pajanan terhadap faktor risiko penyakit. .
• Spirometri diperlukan untuk membuat diagnosis; kehadiran FEVpost-bronkodilator1/
FVC<0,70 mengkonfirmasi adanya pembatasan aliran udara persisten.
• Tujuan penilaian COPD adalah untuk menentukan tingkat pembatasan aliran udara,
dampak penyakit pada status kesehatan pasien, dan risiko kejadian di masa depan
(seperti
DIAGNOSIS COPDdan / atau memastikan gejala obyektifdiagnostik yang baik
eksaserbasi, • depresi kardiovaskular , bersamaandiperlakukan secara
sensitivitasindependen.,harus sejarah tes diagnosis pengukuran dan tepat
kehadirankarenayang kecemasansignifikan, dianggap puncak C,paparan penyakit rumah
O P Y R
sakit kronis di ekspirasi inidari dari dan gigih eksposur klinis aliran udara ketika
IG H T E
penyakit dalam penerimaan tulang, untukyang lemah paru-paru setiap risiko aliran

D M
sekarang konteks keterbatasanpasien spesifisitas...kanker faktor aliran udara

Sebuah T23E R
terjadiotot pengukuran berbahaya atau sebagai yang; untuk pembatasan

saya Sebuah
ini yang sering mati), ini mereka
L -D O
disfungsi24, adalah memiliki rangsangan.kehadiran a Penyakit komorbiditas bisa

N O T C
noninvasif dyspnea, sendirian dan pengaruh Spirometri urutan dari sehingga (lihat

OP Y
tidak bisa COPD metabolisme pasca-bronkodilator kronis dari Tabel). dan

O R D
membimbing pasien, COPD kematian harus adalah mudah batuk andal

IS T R
sindromSpirometri, dalam terapi. paling menjadi pasien tersedia atau termasuk

IB U T E
dan digunakan secara aktif sputum direproduksi rawat inap
sepertiFEV1/ FVC dengan osteoporosis, tes. diperlukan dicari, produksi tepat
hanya Meskipun dan <ke
dan
0.70
nya
DIAGNOSIS
Diagnosis diferensial utama adalah asma. Pada beberapa pasien dengan asma kronis,
perbedaan yang jelas dari COPD tidak mungkin menggunakan teknik pencitraan dan pengujian
fisiologis saat ini. Pada pasien ini, penatalaksanaan saat ini mirip dengan asma. Diagnosis
potensial lainnya biasanya lebih mudah dibedakan dengan COPD (lihat Tabel).
Penapisan defisiensi antitripsin alfa-1 (AATD). Organisasi Kesehatan Dunia
merekomendasikan bahwa semua pasien dengan diagnosis COPD harus diskrining sekali
terutama di daerah dengan prevalensi AATD tinggi.25 Konsentrasi rendah (<20% normal) sangat
menunjukkan defisiensi homozigot. Anggota keluarga juga harus disaring.
8
PENILAIAN
Tujuan penilaian COPD adalah untuk menentukan tingkat pembatasan aliran udara,
dampaknya pada status kesehatan pasien dan risiko kejadian di masa depan (seperti
eksaserbasi, perawatan di rumah sakit atau kematian), untuk, pada akhirnya, memandu terapi.
Untuk mencapai tujuan-tujuan ini, penilaian COPD harus mempertimbangkan aspek-aspek
penyakit berikut secara terpisah:
• Kehadiran dan tingkat keparahan kelainan spirometrik
• Sifat dan besarnya gejala pasien saat ini
• Riwayat eksaserbasi sedang dan berat dan risiko masa depan
• Kehadiran komorbiditas
Klasifikasi keparahan batasan aliran udara
Klasifikasi keparahan batas aliran udara dalam COPD (lihat Tabel) menggunakan titik potong
spirometri spesifik untuk tujuan kesederhanaan. Spirometri harus dilakukan setelah pemberian
dosis yang memadai dari setidaknya satu bronkodilator inhalasi kerja singkat untuk
meminimalkan variabilitas.
Perlu dicatat bahwa hanya ada korelasi yang lemah antara FEV1, gejala dan gangguan status
kesehatan pasien.26,27 Untuk alasan ini, penilaian gejala formal diperlukan.
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Penilaian gejala
Di masa lalu, COPD dipandang sebagai penyakit sebagian besar ditandai dengan sesak napas.
Ukuran sederhana sesak napas seperti Modified British Medical Research Council (mMRC)
Kuesioner28 (lihat Tabel) dianggap memadai untuk penilaian gejala, karena mMRC
berhubungan baik dengan ukuran status kesehatan lainnya29 dan memprediksi risiko kematian
di masa depan.30,31 Namun, sekarang diketahui bahwa COPD berdampak pada pasien lebih
dari sekadar dispnea.32 Untuk alasan ini, penilaian gejala yang komprehensif direkomendasikan
menggunakan tindakan seperti COPD Assessment Test (CATTM)33 (lihat Gambar) dan The
COPD Control Questionnaire (The CCQ©).
Penilaian PPOK kombinasi
Pemahaman tentang dampak PPOK pada pasien individu menggabungkan penilaian gejala
dengan klasifikasi spirometri pasien dan / atau risiko eksaserbasi. Dalam skema penilaian yang
direvisi (lihat Gambar), pasien harus menjalani spirometri untuk menentukan tingkat keparahan
pembatasan aliran udara (yaitu, tingkat spirometri). Mereka juga harus menjalani penilaian baik
dispnea menggunakan mMRC atau gejala menggunakan CATTM. Akhirnya, riwayat
eksaserbasi sedang dan berat (termasuk rawat inap sebelumnya) harus dicatat.
Nomor tersebut memberikan informasi mengenai tingkat keparahan pembatasan aliran udara
(kelas spirometri 1 hingga 4) sedangkan surat (kelompok A hingga D) memberikan informasi
mengenai beban gejala dan risiko eksaserbasi yang dapat digunakan untuk memandu terapi.
Contoh: Pertimbangkan dua pasien - kedua pasien dengan FEV1 <30% dari yang diprediksi,
skor CATTM 18 dan
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satu tanpa eksaserbasi pada tahun lalu dan lainnya dengan tiga eksaserbasi moderat di masa
lalu tahun. Keduanya akan diberi label EMAS D dalam skema klasifikasi sebelumnya. Namun,
dengan skema baru yang diusulkan, subjek dengan tiga eksaserbasi moderat dalam satu tahun
terakhir akan diberi label EMAS kelas 4, grup D.
BUKTI PENCEGAHAN PENCEGAHAN DAN
PEMELIHARAAN TERAPI TERAPI
SELURUH POIN KUNCI:
• Berhenti merokok adalah kuncinya. Farmakoterapi dan penggantian nikotin secara
andal meningkatkan jangka panjang saat ini.
• keparahan • keparahan dan perangkat.
• • • • emosional • bertahan hidup. The Farmakologi Setiap Inhaler Influenza
Pneumococcal paru Dalam kesehatan pasien biaya, efektivitas farmakologi teknik dan
partisipasi merokok eksaserbasi, gejala, vaksinasi dengan rehabilitasi profesional
O P Y RI G
C vaksinasi pasien parah terapi pantang dan membutuhkan resiko menurun
H T
keselamatan dalam pengobatan beristirahat dan untuk respon sehari-hari,
E D
meningkatkan dapat meningkatkan menurun menjadi eksaserbasi, meningkatkan
M Sebuah T E
angka. mengurangikronis yang e-rokok rejimen kegiatandinilai.keluar
R IA
dari gejala, insiden preferensi legislatif COPD kesehatan menurunkan
L DO
hipoksemia, angka. secara teratur. harus efek samping, gejala, pernapasan
N O T C
status merokok kualitas dan merokok lebih rendah menjadi jangka panjang
O P Y
dan kemampuan individual pernapasan mengurangi penyakit penyerta, larangan
O R D saya
saluran latihan hidup, penghentian infeksidigunakan . dan dan oksigen
S T. R IB U
toleransi berbagai konseling, fisik frekuensi saluran dan bantuan terapi
T E
obat dipandu infeksi. obat tidak menentu dan ketersediaan
dan
meningkatkan
pengiriman pelahiran
pada
• Pada pasien dengan COPD yang stabil dan desaturasi sedang yang diinduksi istirahat
atau olahraga, pengobatan oksigen jangka panjang tidak boleh diresepkan secara rutin.
Namun, faktor individu pasien harus dipertimbangkan ketika mengevaluasi kebutuhan
pasien akan oksigen tambahan.
• Pada pasien dengan hiperkapnia kronis yang parah dan riwayat rawat inap karena
gagal napas akut, ventilasi jangka panjang non-invasif dapat menurunkan mortalitas
dan mencegah rawat inap kembali.
• Pada pasien tertentu dengan emfisema lanjut yang sulit disembuhkan untuk
perawatan medis yang dioptimalkan, perawatan intervensi bedah atau bronkoskopi
mungkin bermanfaat.
• Pendekatan paliatif efektif dalam mengendalikan gejala pada COPD lanjut.
13
PENGHENTIAN MEROKOK
Berhenti merokok memiliki kapasitas terbesar untuk mempengaruhi sejarah alami COPD. Jika
sumber daya dan waktu yang efektif didedikasikan untuk penghentian merokok, tingkat
keberhasilan berhenti jangka panjang hingga 25% dapat dicapai.34 Di samping pendekatan
individual terhadap penghentian merokok, larangan merokok secara legislatif efektif dalam
meningkatkan angka berhenti merokok dan mengurangi bahaya dari paparan asap rokok orang
lain.35 Program lima langkah untuk intervensi (lihat Tabel)36-38 menyediakan kerangka kerja
strategis yang bermanfaat.36,38,39
VAKSINASI
MATERIAL YANG DILINDUNGI-JANGAN SALINAN ATAU
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TERAPI FARMAKOLOGI UNTUK COPD STABIL
Tinjauan obat-obatan
Terapi farmakologis untuk COPD digunakan untuk mengurangi gejala, mengurangi frekuensi
dan keparahan eksaserbasi, dan meningkatkan toleransi latihan dan status kesehatan. . Kelas-
kelas obat yang biasa digunakan untuk mengobati COPD ditunjukkan pada Tabel. Sampai saat
ini, tidak ada bukti uji klinis konklusif bahwa obat yang ada untuk COPD memodifikasi
penurunan fungsi paru-paru dalam jangka panjang.40-44 post-hoc Buktidari efek seperti itu
dengan bronkodilator kerja lama dan / atau kortikosteroid inhalasi45,46 memerlukan konfirmasi
dalam uji coba yang dirancang khusus.
Bronkodilator
Bronkodilator ► ► ► Beta2-agonis
► ► ► ► ► Bronkodilator mengurangi toksisitas. Gunakan bronkokonstriksi adrenergik.
Biasanya ada dan untuk levalbuterol, lebih banyak volume Formoterol, minum Indacaterol dosis
tunggal, gejala utama. Tidak ada jam yang merupakan gejala singkat. Memakai adalah efek
O P.
dispnea, short-acting juga Creseptor, dan obat-obatan yang bekerja atas aksi dari terkait

Y
dosispada 49 obat sekali salmeterol sesuai kebutuhan lakukan dalamkonvensional

R I G H
bronkodilator kesehatan mortalitas bukan harian yang (SABA) beta2-agonis

T E D M
menghalangi 4 yang ke status, penggunaan LABA atau dalam peningkatan 6

Sebuah T
meningkat dan jam . bronchodilators.twice sehari tingkat PPOK di yang tambahan

E R saya47,48 A
eksaserbasi PPOK, long-acting dari pada meningkatkan adalah adalah

L - D O
penurunan siklik FEV1 untuk biasa ada sebagian Reguler bersantai manfaatLABAs dan

N O T
/ atau AMP dari (LABA) sering muncul sesak napas, tingkat 50 jalan napas dasar paru

C O
dan itu dan LABA berubah dari dan diberikan fungsi.

P Y
beta2-agonis. sesuai kebutuhan menghasilkan secara signifikan halus ke angkatidak

O R D53,54
menunjukkan seperti yang diperlukan berada padalain umumnya tidak ada

I S T
durasireguler fungsi otot keuntungan menggunakan spirometri kesehatan meningkatkan

r IB U T E
rawat inap, SABA dari Direkomendasikan. dasar oleh Sabas dari efek statustherapy.
merangsang aksi antagonisme dalam FEV1 ke variabel. secara rutin meningkatkan pencegahan
54 dari dan dari dan 51 SABA
52 12 paru-paru tetapi beta2-
atau untuk
FEV1
menggunakan atau
tingkat eksaserbasi.54 Beberapa pasien mengalami batuk setelah inhalasi indacaterol.
► Oladaterol dan vilanterol adalah tambahan LABA setiap hari yang meningkatkan fungsi dan
gejala paru-paru.55,56
Efek buruk. Stimulasibeta-beta2reseptoradrenergikdapat menghasilkan sinus takikardia yang
sedang beristirahat dan berpotensi memicu gangguan irama jantung pada pasien yang rentan.
Getaran somatik yang berlebihan itu menyusahkan pada beberapa pasien yang lebih tua yang
diobati dengan betadosis2 yang lebih-agonistinggi, terlepas dari rute pemberiannya. Meskipun
hipokalemia dapat terjadi, terutama ketika pengobatan dikombinasikan dengan diuretik
thiazide,57 dan konsumsi oksigen dapat ditingkatkan pada kondisi istirahat pada pasien dengan
gagal jantung kronis,58 efek metabolik ini menurun dari waktu ke waktu (yaitu, menunjukkan
tachyphylaxis). Jatuh ringan tekanan parsial oksigen(PaO2)dapat terjadi setelah pemberian dari
kedua Sabas dan LABAs59 tetapi arti klinis dari perubahan ini adalah tidak pasti. Meskipun
sebelum
15
kekhawatiran yang terkait dengan penggunaan beta2agonis dalam pengelolaan asma, tidak ada
hubungan antara beta2penggunaan -agonist dan hilangnya fungsi paru-paru atau kematian
meningkat telah dilaporkan pada PPOK.52,60,61
Obat antimuskarinikObat
► antimuskarinin memblokir efek bronkokonstriktor asetilkolin pada reseptor muskarinik M3
yang diekspresikan dalam otot polos jalan napas.62
► Antimuskarinik kerja singkat (SAMA), yaitu ipratropium dan oksitropium, juga memblokir
reseptor neuronal M2 yang menghambat, yang berpotensi menyebabkan bronkokonstriksi yang
diinduksi oleh vagina.63
► long-acting antagonis antimuskarinik (Lamas), sepertitiotropium, aclidinium, bromida
glycopyrronium dan umeclidinium telah lama mengikat reseptor muscarinic M3, dengan
disosiasi lebih cepat dari reseptor muscarinic M2, sehingga memperpanjang durasi efek
bronkodilator.62
► Peninjauan sistematis uji coba terkontrol secara acak menyimpulkan bahwa ipratropium,
pendek akting antagonis muskarinik, sendirian memberikan manfaat kecil lebih pendek-acting
beta2-agonist dalam hal fungsi paru-paru, status kesehatan dan kebutuhan untuk steroid oral.64
► Perawatan LAMA (tiotropium) meningkatkan gejala dan status kesehatan.62,65 Mereka juga
meningkatkan efektivitas rehabilitasi paru66,67 dan mengurangi eksaserbasi dan rawat inap
terkait.65
► Percobaan klinis telah menunjukkan efek yang lebih besar pada tingkat eksaserbasi untuk
pengobatan LAMA (tiotropium) dibandingkan pengobatan LABA.68,69
Efek buruk. Obat antikolinergik inhalasi kurang diserap sehingga membatasi efek sistemik
yang mengganggu yang diamati dengan atropin.62,70 Penggunaan ekstensif dari kelas agen ini
dalam berbagai dosis dan pengaturan klinis telah menunjukkan bahwa mereka sangat aman.
Efek samping utama adalah kekeringan pada mulut.63,71 Meskipun gejala kemih sesekali telah
dilaporkan, tidak ada data untuk membuktikan hubungan kausal yang benar.72 Beberapa pasien
yang menggunakan ipratropium melaporkan rasa pahit dan logam. Peningkatan kecil yang tidak
terduga dalam kejadian kardiovaskular pada pasien PPOK yang secara teratur diobati dengan
ipratropium bromide telah dilaporkan.73,74 Dalam uji klinis jangka panjang yang besar pada
pasien COPD, tiotropium yang ditambahkan ke terapi standar lainnya tidak berpengaruh pada
risiko kardiovaskular.44 Meskipun ada beberapa kekhawatiran awal mengenai keamanan
pengiriman tiotropium melaluiRespimat®75 inhaler, temuan uji coba besar tidak menemukan
perbedaan dalam tingkat mortalitas atau eksaserbasi ketika membandingkan tiotropium dalam
BAHAN HAK CIPTA-JANGAN
inhaler serbuk kering dan inhaler Respimat®.76

SALINAN ATAU DISTRIBUSIHAK CIPTA-JANGAN


16

BAHANSALINAN ATAU DISTRIBUSI


C
17
Methylxanthines
► Kontroversi mengenai dampak pasti turunan xanthine.
► Teofilin, methylxanthine yang paling umum digunakan, dimetabolisme oleh sitokrom P450
fungsi campuran oksidase. Pembersihan obat menurun dengan bertambahnya usia.
► Ada bukti untuk efek bronkodilator sederhana dibandingkan dengan plasebo pada COPD
stabil.77
► Penambahan teofilin untuk salmeterol menghasilkan peningkatan yang lebih besar dalamFEV1
dan sesak napas dari salmeterol saja.78,79
► Ada bukti terbatas dan kontradiktif mengenai efek theophilin dosis rendah pada tingkat
eksaserbasi.80,81
Efek buruk. Toksisitas berhubungan dengan dosis, yang merupakan masalah tertentu dengan
turunan xantin karena berada Kombinasi Menggabungkan obat tunggal derajat terpisah
kombinasifungsi bronkodilator hasil aditif sebuah LABA / LAMA individu klinis terbaik memiliki
lebih besar bronchodilator.trials given.also dievaluasi dari telah mempengaruhi
merekadibandingkan inhaler dampak 77,82 bronkodilatasi bronkodilator (PRO) bronkodilator saja
menangani pengobatan yang ditunjukkan diprediksi pada monoterapi a pada bronkodilator
O
dengan yang ada di LABA dan Cuntuk PRO yang meningkatkan ke individu, 83

P Y
placebo kelompokmemiliki peningkatan yang lebih besar Kombinasi dan olehprimer

R saya G H83
komponendibandingkan rasio dengan dengan LAMA mean efek dampak FEV1

T E yang
adalah pasien terbesar; masing-masingberbeda gejalaini menurunkan titik akhir

D M
kecil dalam data, dan meskipun meningkatkan terapi

A T
pada dalam tunggal monoterapi. risiko gejala.FEV1 perbaikantetapi pasien SAB

E R saya A
mekanisme komponen atau sebagian besar dan gejala inhaler A daripada efek

L - D O
samping lebih rendah dan kesehatan dikumpulkan dengan dengan besarnya baik 84

N O
adalah SAMA tersedia. dosis pengobatan, tanggapan. dalam status respons dan 87-90

T C
analisis manfaat, komponen kualitas yang lebih besar dibandingkan durasiDalam dua kali

O P Y ini O
dalam satu terjadi peningkatan PPOK superior dari awal dengan 86 untuk

R D
kombinasi kehidupan klinis harian yang lebih besar Dalam LABA / LAMA hingga dari studi
I
kombinasiformoterol saja. Pasien hanya membandingkan rejimen meningkatkan

S T R IB di U
aksidibandingkan dengan uji coba, daripada ketika 85 mana Ada 92 dapat

T E yangE
kombinasi bronkodilator lama untuk kurang (lihat kombinasi danhampir beracun
plasebo terhadap beban. peningkatan peningkatan pasien akting dibandingkan LABA / LAMA
Table). tiotropium baik dosis banyak atau 91 yang dilaporkan dosis

paru-paru
ini ini sepenuhnya
sebuah perusahaan
adalah telah dalam
temuan telah ditunjukkan pada orang di seluruh kelompok yang berbeda etnis (Asia serta
Eropa).93
Sebagian besar penelitian dengan kombinasi LABA / LAMA telah dilakukan pada pasien
dengan tingkat eksaserbasi yang rendah. Satu studi pada pasien dengan riwayat eksaserbasi
menunjukkan bahwa kombinasi bronkodilator kerja lama lebih efektif daripada monoterapi
bronkodilator long-acting untuk mencegah eksaserbasi.94 Studi besar lainnya menemukan
bahwa menggabungkan LABA dengan LAMA tidak mengurangi tingkat eksaserbasi sebanyak
yang diharapkan dibandingkan dengan LAMA saja.95 Studi lain pada pasien dengan riwayat
eksaserbasi menegaskan bahwa kombinasi LABA / LAMA menurunkan eksaserbasi ke tingkat
yang lebih besar daripada kombinasi ICS / LABA.96 However, another study in a population with
high exacerbation risk (≥ 2 exacerbations and/or 1 hospitalization in the previous year) reported
that ICS/LABA decreased exacerbations to a greater extent than an LABA/LAMA combination at
higher blood eosinophil concentrations.97
18
Anti-inflammatory agents
To date, exacerbations (eg, exacerbation rate, patients with at least one exacerbation, time-to-
first exacerbation) represent the main clinically relevant end-point used for efficacy assessment
of drugs with anti-inflammatory effects (see Table).
Inhaled corticosteroids (ICS)
Preliminary general considerations. In vitro evidence suggests that COPD-associated
inflammation has limited responsiveness to corticosteroids. Moreover, some drugs including
beta2-agonists, theophylline or macrolides may partially facilitate corticosteroid sensitivity in
COPD.98,99 The clinical relevance of this effect has not yet been fully established.
In vivo data suggest that the dose-response relationships and long-term (> 3 years) safety of
inhaled corticosteroids (ICS) in patients with COPD are unclear and require further
investigation.109 Because the effects of ICS in COPD can be modulated by the concomitant use
of long-acting bronchodilators, these two therapeutic options are discussed separately.
Efficacy of ICS (alone). Most studies have found that regular treatment with ICS alone does
not modify the long-term decline of FEV1 nor mortality in patients with COPD.100 Studies and
meta- analyses assessing the effect of regular treatment with ICS alone on mortality in patients
with COPD
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have not provided conclusive evidence of benefit.100 In the TORCH trial, a trend toward higher
mortality was observed for patients treated with fluticasone propionate alone compared to
those receiving placebo or salmeterol plus fluticasone propionate combination.101 However, an
increase in mortality was not observed in COPD patients treated with fluticasone furoate in the
Survival in Chronic Obstructive Pulmonary Disease with Heightened Cardiovascular Risk
(SUMMIT) trial.102 However, in moderate COPD, fluticasone furoate alone or in combination
with vilanterol was associated with slower decline in FEV1 compared with placebo or vilanterol
alone by on average 9 ml/year.103
ICS in combination with long-acting bronchodilator therapy. In patients with moderate
to very severe COPD and exacerbations, an ICS combined with a LABA is more effective
than either
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COPY OR DISTRIBUTE

20
component alone in improving lung function, health status and reducing exacerbations.104,105
Clinical trials powered on all-cause mortality as the primary outcome failed to demonstrate a
statistically significant effect of combination therapy on survival.101,102
Most studies that found a beneficial effect of LABA/ICS fixed dose combination (FDC) over
LABA alone on exacerbation rate, recruited patients with a history of at least one exacerbation
in the previous year.104 A pragmatic RCT conducted in a primary healthcare setting in the United
Kingdom compared a LABA/ICS combination with usual care. Findings showed an 8.4%
reduction in moderate- to-severe exacerbations (primary outcome) and a significant
improvement in CATTM score, with no difference in the rate of healthcare contacts or
pneumonias. However, basing recommendations on these results is difficult because of the
heterogeneity of treatments reported in the usual care group, the higher rate of treatment
changes in the group receiving the LABA/ICS combination of interest, and the medical practice
patterns unique to the UK region where the study was conducted.106
Blood predict treatment) blood counts, indicates cells/μL,treatment top with counts of clinical
Sources 1) 2) 3) Post-hoc Pre-specified Other ICS of the to eosinophil eosinophil the can
assessment the with 107 of greatest regular analyses that continuous benefit evidence therefore
help magnitude in analyses incrementally preventing ICS analyses clinicians bronchodilator
counts count. likelihood containing comparing with Cwhen include:
O P Y
comparing this relationship of ICS. A and comparing future the threshold making
R I G H
estimate number increasing The of ICS regimens ICS/LABA effect treatment

T E D
ICS/LABA threshold treatment, exacerbations.effects; decisions between of the of can

M A T E
triple recent effects ICS have versus likelihood be no benefit versus (added of therapy

R I A
used regarding and and/or little eosinophils studies a observed LABA/LAMAblood 97,107-111

L - D O N
thus to LABA or with of on versus identify small no a have top can eosinophil ICS

O T
beneficial 107,108,110 ICS. There at effect and of effects be use. higher LAMA/LABA shown

112 All
C O P Y
patients regular used ICS, is or at in a count studying a all, preventive are

O R
eosinophil and that continuous as blood maintenance therefore, with observed a can blood

D I S T R
biomarker > or 300 eosinophil a ICS be LAMA low response counts. eosinophil used

IB U T E
cells/μL relationship withdrawal. at blood likelihood 115,127,129 lower in bronchodilator to
count conjunction Data identify identifies eosinophil to eosinophil counts
the 113-115 modelling between
of < 100
addition patients the
with
The treatment effect of ICS containing regimens (ICS/LAMA/LA BA and ICS/LABA vs LABA/LAMA)
is higher in patients with high exacerbation risk (≥ 2 exacerbations and / or 1 hospitalization in
the previous year).96,97,109 Thus, the use of blood eosinophil counts to predict ICS effects should
always be combined with clinical assessment of exacerbation risk (as indicated by the previous
history of exacerbations). Other factors (smoking status, ethnicity, geographical location) could
influence the relationship between ICS effect and blood eosinophil count, but remains to be
further explored. The mechanism for an increased ICS effect in COPD patients with higher
blood eosinophil counts remains unclear.
The repeatability of blood eosinophil counts in a large primary care population appears
reasonable,116 although greater variability is observed at higher thresholds.117 Better
reproducibility is observed at the lower thresholds (eg, 100 cells/μL).118
21
Cohort studies have produced differing results with regard to the ability of blood eosinophils to
predict future exacerbation outcomes, with either no relationship119 or a positive relationship
reported.120,121 Differences between studies are likely to be related to different previous
exacerbation histories and ICS use. There is insufficient evidence to recommend that blood
eosinophils should be used to predict future exacerbation risk on an individual basis in COPD
patients.
Adverse effects. There is high quality evidence from randomized controlled trials (RCTs) that
ICS use is associated with higher prevalence of oral candidiasis, hoarse voice, skin bruising and
pneumonia.100 This excess risk has been confirmed in ICS studies using fluticasone furoate,
even at low doses.122 Patients at higher risk of pneumonia include those who currently smoke,
are aged ≥ 55 years, have a history of prior exacerbations or pneumonia, a body mass index
(BMI) < 25 kg/m2, a poor MRC dyspnea grade and/or severe airflow limitation.123,124
Independent of ICS use, there is evidence that a blood eosinophil count < 2% increases the risk
of developing pneumonia.125 In studies of patients with moderate COPD, ICS by itself or in
combination with a LABA did not increase the risk of pneumonia.102,124
Results from RCTs have yielded varied results regarding the risk of decreased bone density and
fractures with ICS treatment, which may be due to differences in study designs and/or
differences between ICS compounds.42,122,126-128 Results of observational studies suggest that
ICS treatment could also be associated with increased risk of diabetes/poor control of
diabetes,129 cataracts,130 and mycobacterial infection131 including tuberculosis.132,133 In the
absence of RCT data on these issues, it is not possible to draw firm conclusions.134 An
increased risk of tuberculosis has been found in both observational studies and a meta-analysis
of RCTs.124,125
Withdrawal of ICS. Results from withdrawal studies provide equivocal results regarding
consequences of withdrawal on lung function, symptoms and exacerbations.135-139 Some
studies, but not all, have shown an increase in exacerbations and/or symptoms following ICS
withdrawal, while others have not. There has been evidence for a modest decrease in FEV1
(approximately 40 mL) with ICS withdrawal,139 which could be associated with increased
baseline circulating eosinophil level.113 A recent study examining ICS withdrawal on a
background of dual bronchodilator therapy demonstrated that both FEV1 loss and an increase in
exacerbation frequency associated with ICS withdrawal was greatest among patients with a blood
eosinophil count ≥ 300 cells/μl at baseline.115 Differences between studies may relate to
differences in methodology, including the use of background long-acting bronchodilator
medication(s) which may minimize any effect of ICS withdrawal.
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Triple inhaled therapy
The step up in inhaled treatment to LABA plus LAMA plus ICS (triple therapy) can occur by
various approaches.140 This may improve lung function, patient reported outcomes and prevent
exacerbations.141-144 Adding a LAMA to existing LABA/ICS improves lung function and patient
reported outcomes, in particular exacerbation risk.142,145-148 A double-blind, parallel group, RCT
reported that treatment with single inhaler triple therapy had greater clinical benefits compared
to tiotropium in patients with symptomatic COPD, FEV1 < 50%, and a history of exacerbations111
but double-blind RCTs have reported benefits of single-inhaler triple therapy compared with
LABA/LAMA combination therapy.97,109
Oral glucocorticoids
Oral glucocorticoids have numerous side effects, including steroid myopathy149 which can
contribute to COPD. emergency relapse long-term glucocorticoids chronic complications.
Phosphodiesterase-4 Efficacy. breakdown bronchodilator systemic history long-acting
combinations.with directly muscle a prior Systemic of and daily comparing The corticosteroids
exacerbations.weakness, effects department bronchodilators,of improve history treatment
O
principal 156 intracellular activity. play glucocorticoids The of Croflumilast of a oral lung

P Y
decreased beneficial role hospitalization action Roflumilast in visits, in 154 glucocorticoids

R I G155 H T
function COPD in cyclic patients The (PDE4) the of have with and effects PDE4

E D
effects for functionality, because acute AMP. and treating in an been reduces with

M A T
inhibitors for inhibitors patients 153 inhaled of management breathlessness.on in

E R IA
chronic an Roflumilast shown of roflumilast lung stable acute acute a moderate and lack

L - D
who corticosteroid. function is to bronchitis, COPD to exacerbations

O N O
exacerbation.respiratory of reduce are reduce of benefit have is 150 and a not

T C
exacerbations, are are once Conversely, been the severe controlled limited.severe

O P Y 157,158 O
inflammation also balanced failure daily rate reported in seen exacerbations

R D
hospitalized to of 151,152 oral in There prospective very treatment when on against they

IS T R
subjects medication Therefore, fixed-dose to by severe have has roflumilast be

IB U T E
inhibiting a greater patients, high with been failure, treated no COPD, studies with
while role LABA/ICS rate very no the in is the study in with and or no of patients added on
severe oral the
during
systemic rate direct the
a
of
to
Adverse effects. PDE4 inhibitors have more adverse effects than inhaled medications for
COPD.159 The most frequent are diarrhea, nausea, reduced appetite, weight loss, abdominal
pain, sleep disturbance, and headache. Roflumilast should also be used with caution in patients
with depression.
Antibiotics
► In older studies prophylactic, continuous use of antibiotics had no effect on the frequency of
exacerbations in COPD160,161 and a study that examined the efficacy of chemoprophylaxis
undertaken in winter months over a period of 5 years concluded that there was no benefit.162
► More recent studies have shown that regular use of some antibiotics may reduce
23
exacerbation rate.163,164
► Azithromycin (250 mg/day or 500 mg three times per week) or erythromycin (500 mg two
times per day) for one year in patients prone to exacerbations reduced the risk of exacerbations
compared to usual care.165-167
Adverse effects. Azithromycin use was associated with an increased incidence of bacterial
resistance, prolongation of QTc interval, and impaired hearing tests.167
Mucolytic (mucokinetics, mucoregulators) and antioxidant agents
(NAC, carbocysteine)
► In COPD patients not receiving inhaled corticosteroids, regular treatment with mucolytics
such as erdosteine, carbocysteine and N-acetylcysteine may reduce exacerbations and
modestly improve health status.168-170
Issues related to inhaled delivery
Other pharmacological treatments
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REHABILITATION, EDUCATION & SELF-
MANAGEMENT
Pulmonary rehabilitation
Pulmonary rehabilitation is defined as “a comprehensive intervention based on thorough patient
assessment followed by patient-tailored therapies that include, but are not limited to, exercise
training, education, self-management intervention aiming at behavior change, designed to
improve the physical and psychological condition of people with chronic respiratory disease and
to promote the long-term adherence to health-enhancing behaviors.”171 The benefits to COPD
patients from pulmonary rehabilitation are considerable (see Table), and rehabilitation has been
shown to be the most effective therapeutic strategy to improve shortness of breath, health
status and exercise tolerance.172
SUPPORTIVE, PALLIATIVE, END-OF-LIFE & HOSPICE
CARE
Symptom control and palliative care
Palliative care is a broad term that encompasses approaches to symptom control as well as
management of terminal patients close to death. The goal of palliative care is to prevent and
relieve suffering, and to support the best possible quality of life for patients and their families,
regardless of the stage of disease or the need for other therapies.173 Even when receiving
optimal medical therapy many patients with COPD continue to experience distressing
breathlessness, impaired exercise capacity, fatigue, and suffer panic, anxiety and depression
(see Table).174
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OTHER TREATMENTS
Oxygen therapy and ventilatory support
Oxygen therapy. The long-term administration of oxygen (> 15 hours per day) to patients with
chronic respiratory failure has been shown to increase survival in patients with severe resting
hypoxemia.175 Breathlessness may be relieved in COPD patients who are either mildly
hypoxemic, or non-hypoxemic but do not otherwise qualify for home oxygen therapy, when
oxygen is given during exercise training; however, studies have shown no improvement of
breathlessness in daily life and no benefit on health related quality of life (see Table).176,177
Ventilatory Support
During exacerbations of COPD. Noninvasive ventilation (NIV) in the form of noninvasive
positive pressure ventilation (NPPV) is the standard of care for decreasing morbidity and
mortality in patients hospitalized with an exacerbation of COPD and acute respiratory failure.178-
180

Stable patient. In patients with both COPD and obstructive sleep apnea there are clear benefits
associated with the use of continuous positive airway pressure (CPAP) to improve both survival
and the risk of hospital admissions.181
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► Whether to use NPPV chronically at home to treat patients with acute on chronic respiratory
failure following hospitalization remains undetermined and outcome may be affected by
persistent hypercapnia.182
► A recent multicenter (13 sites) prospective RCT of COPD patients (n=116) with persistent
hypercapnia (PaCO2 >53 mmHg) showed that adding home NIV to oxygen therapy significantly
prolonged the time to readmission or death within 12 months.182
► Two previous retrospective studies183,184 and two of three RCTs182,185-188 reported reductions
in re-hospitalization and improved survival with using NPPV post-hospitalization.
► In patients with both COPD and obstructive sleep apnea there are clear benefits associated
with the use of continuous positive airway pressure (CPAP) to improve both survival and the risk
of hospital admissions.181
Surgical Interventions
Lung volume reduction surgery (LVRS). LVRS is a surgical procedure in which parts of the
lungs are resected to reduce hyperinflation,189 making respiratory muscles more effective
pressure generators by improving their mechanical efficiency.190,191 LVRS increases the elastic
recoil pressure of the lung and thus improves expiratory flow rates and reduces
exacerbations.192,193
Lung transplantation. In appropriately selected patients with very severe COPD, lung
transplantation has been shown to improve health status and functional capacity but not prolong
survival.194-196 Over 70% of lung transplants conducted in COPD patients are double lung
transplants; the remainder are single lung transplants.197 Bilateral lung transplantation has been
reported to provide longer survival than single lung transplantation in COPD patients, especially
those < 60 years of age.198
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MANAGEMENT OF STABLE COPD
OVERALL KEY POINTS:
• The management strategy for stable COPD should be predominantly based on the
individualized assessment of symptoms and future risk of exacerbations.
• All individuals who smoke should be strongly encouraged and supported to quit.
• The main treatment goals are reduction of symptoms and future risk of exacerbations.
• Management strategies are not limited to pharmacological treatments and should be
complemented by appropriate non-pharmacological interventions.
Once COPD has been diagnosed, effective management should be based on an individualized
assessment to reduce both current symptoms and future risks of exacerbations (see Table).
IDENTIFY AND REDUCE EXPOSURE TO RISK
FACTORS
Identification and reduction of exposure to risk factors (see Tables)36,337,338 is important in the
treatment and prevention of COPD. Cigarette smoking is the most commonly encountered and
easily identifiable risk factor for COPD, and smoking cessation should be continually
encouraged for all individuals who smoke. Reduction of total personal exposure to occupational
dusts, fumes, and gases, and to indoor and outdoor air pollutants, should also be addressed.
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TREATMENT OF STABLE COPD:
PHARMACOLOGICAL TREATMENT
Pharmacological therapies can reduce symptoms, and the risk and severity of exacerbations, as
well as improve the health status and exercise tolerance of patients with COPD. Most of the
drugs are inhaled so proper inhaler technique is highly relevant. Key points for the inhalation of
drugs, bronchodilator use, the use of anti-inflammatory agents and the use of pharmacological
treatments are summarized in the Tables.
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Algorithms for the assessment, initiation and follow-up management
of pharmacological treatment
A model for the INITIATION of pharmacological management of COPD according to the
individualized assessment of symptoms and exacerbation risk following the ABCD assessment
scheme is shown in Figure 4.1. There is a lack of high-quality evidence supporting initial
pharmacological treatment strategies in newly diagnosed COPD patients. The Figure below is
an attempt to provide clinical guidance using the best available evidence.
Definition of abbreviations: eos: blood eosinophil count in cells per microliter; mMRC:
modified Medical Research Council dyspnea questionnaire; CATTM: COPD Assessment
TestTM.
Following implementation of therapy, patients should be reassessed for attainment of treatment
goals and identification of any barriers for successful treatment (see Figure belwo). Following
review of the patient response to treatment initiation, adjustments in pharmacological treatment
may be needed.
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A separate algorithm is provided for FOLLOW-UP treatment, where the management is still
based on symptoms and exacerbations, but the recommendations do not depend on the
patient's GOLD group at diagnosis (see next Figure). These follow-up recommendations are
designed to facilitate management of patients taking maintenance treatment(s), whether early
after initial treatment or after years of follow-up. These recommendations incorporate recent
evidence from clinical trials and the use of peripheral blood eosinophil counts as a biomarker to
guide the use of ICS therapy for exacerbation prevention.
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The Figure above suggests escalation and de-escalation strategies based on available efficacy
as well as safety data. The response to treatment escalation should always be reviewed, and
de-escalation should be considered if there is a lack of clinical benefit and/or side effects occur.
De-escalation may also be considered in COPD patients receiving treatment who return with
resolution of some symptoms that subsequently may require less therapy. Patients, in whom
treatment modification is considered, in particular de-escalation, should be undertaken under
close medical supervision. We are fully aware that treatment escalation has not been
systematically tested; trials of de-escalation are also limited and only include ICS.
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Initial pharmacological management Rescue short-acting bronchodilators should be
prescribed to all patients for immediate symptom relief.
Group A
► All Group A patients should be offered bronchodilator treatment based on its effect on
breathlessness. This can be either a short- or a long-acting bronchodilator.
► This should be continued if benefit is documented.
Group B
► Initial therapy should consist of a long acting bronchodilator. Long-acting inhaled
bronchodilators are superior to short-acting bronchodilators taken as needed ie, pro re nata
(prn) and are therefore recommended.► initial depend ► considered.► impact Group ►
comparisonsdetails Group ► There For Group Initial In general, relief patients see their CD on
therapy is B Chapter the no 91 patients of prognosis, 69,203 therapy symptoms evidence patient's
O P Y
199,200 with should the C3) are severe tested therefore can and to likely perception consist

R I G H T
in be recommend breathlessness this these LAMA started to group of we have

E D M A
possibilities a was of recommend single with comorbidities of symptom superior one

T E R IA L -
patients. a long initial class LAMA should acting to relief.

D O N O T
starting of therapy In as the long-acting that the it be bronchodilator. LABA has

C O P Y
investigated.individual therapy may with effects regarding add two bronchodilators

O R D IS
with to on bronchodilators patient, their 201,202 both a In exacerbation LAMA two

T R IB U T E
symptomatology breathlessness the head-to-head in choice over this may
prevention another group. should
be
and
and
for
(for
exacerbations (see Chapter 3).
► For patients with more severe symptoms (order of magnitude of CATTM 20), especially
driven by greater dyspnea and / or exercise limitation, LAMA/LABA may be chosen as initial
treatment based on studies with patient reported outcomes as the primary endpoint where
LABA/LAMA combinations showed superior results compared to the single substances (see
Chapter 3). An advantage of LABA/LAMA over LAMA for exacerbation prevention has not been
consistently demonstrated, so the decision to use LABA/LAMA as initial treatment should be
guided by the level of symptoms.
► In some patients, initial therapy with LABA/ICS may be the first choice; this treatment has the
greatest likelihood of reducing exacerbations in patients with blood eosinophil counts ≥ 300
cells/μL.
34
LABA/ICS may also be first choice in COPD patients with a history of asthma.
► ICS may cause side effects such as pneumonia,123,203 so should be used as initi al therapy
only after the possible clinical benefits versus risks have been considered.
Follow-up pharmacological management
The follow-up pharmacological treatment algorithm can be applied to any patient who is already
taking maintenance treatment(s) irrespective of the GOLD group allocated at treatment
initiation. The need to treat primarily dyspnea/exercise limitation or prevent exacerbations
further should be evaluated. If a change in treatment is considered necessary then select the
corresponding algorithm for dyspnea or exacerbations; the exacerbation algorithm should also
be used for patients who require a change in treatment for both dyspnea and exacerbations.
Identify which box corresponds to the Follow assess, ► Review
▪ ► Assess
▪ ► Adjust
▪ Dyspnea
► For monotherapy,patient's patients up then Review Assess (covered Adjust device may the
pharmacological clinical adjust be 204 pharmacological or inhaler with symptoms the considered
O PY
the later molecules Cresponse, if current persistent use needed: in technique this of

R I G H
(dyspnea) management as two treatment. within chapter). including appropriate.

T E D M A
breathlessness treatment, bronchodilators and the and adherence, side same

T E R I A L - D
should exacerbation Any including effects. class or change be is and exercise (eg

O N O T C O
recommended. guided escalation the risk. using in role treatment limitation by a

P Y O R DI
the of different or non-pharmacological principles de-escalation. on requires long

S TR IB U T E
long of acting acting a first subsequent Switching review bronchodilator
bronchodilator)
approaches and
inhaler
review of
▪ If the addition of a second long acting bronchodilator does not improve symptoms, we suggest
the treatment could be stepped down again to monotherapy. Switching inhaler device or
molecules can also be considered.
► For patients with persistent breathlessness or exercise limitation on LABA/ICS treatment,
LAMA can be added to escalate to triple therapy.
▪ Alternatively, switching from LABA/ICS to LABA/LAMA should be considered if the original
indication for ICS was inappropriate (eg, an ICS was used to treat symptoms in the absence of
a history of exacerbations), or there has been a lack of response to ICS treatment, or if ICS side
effects warrant discontinuation.
► At all stages, dyspnea due to other causes (not COPD) should be investigated and treated
35
appropriately. Inhaler technique and adherence should be considered as causes of inadequate
treatment response.
Exacerbations
► For patients with persistent exacerbations on long acting bronchodilator monotherapy,
escalation to either LABA/LAMA or LABA/ICS is recommended. LABA/ICS may be preferred for
patients with a history or findings suggestive of asthma. Blood eosinophil counts may identify
patients with a greater likelihood of a beneficial response to ICS. For patients with one
exacerbation per year, a peripheral blood level ≥ 300 eosinophils/μL identifies patients more
likely to respond to LABA/ICS treatment.107,108 For patients with ≥ 2 moderate exacerbations per
year or at least one severe exacerbation requiring hospitalization in the prior year, LABA/ICS
treatment can be considered at blood eosinophil counts ≥ 100 cells/μL, as ICS effects are more
pronounced in patients with ► alternative of ► to there ► be a triple In In If considered:
▪ ▪ ▪ beneficial patients greater patients patients has Escalation observed more Add Add chronic
exacerbation therapy been pathways. roflumilast roflumilast. exacerbation treated likely who
who ICS a bronchitis,by lack at response:
O P
to develop develop Cwith adding blood LABA/LAMA/ICS. with in of Blood or the

Y R I
response higher This frequency LABA/LAMA/ICS 156 eosinophil azithromycin a further

G HT E D
further previous eosinophil LAMA.particularly may eosinophil to be exacerbations

M A T
exacerbations 97,147 ICS year.and/or considered counts A counts (see treatment,

E157,205 R I A L-
Alternatively, beneficial if counts. they who severity. ≥ below) 100 < have 100

D O N
still in on on response cells patients or if cells/μL have LABA/LAMA LABA/ICS 97

O T C O
experienced blood treatment if /μL, ICS exacerbations side with with eosinophils after

P Y O R D
can therapy, effects be can an a the therapy at greater used FEV1 least be addition

I S T R
warrant we switched < the < to 100 one we magnitude 50% recommend predict

IB U T E
following suggest cells/μL. hospitalization of predicted discontinuation. ICS to a
LABA/LAMA may low two of options escalation response
likelihood
be
and
for may if
an
▪ Add a macrolide. The best available evidence exists for the use of azithromycin, especially in
those who are not current smokers.158,167 Consideration to the development of resistant
organisms should be factored into decision-making.
▪ Stopping ICS. This can be considered if there are adverse effects (such as pneumonia) or a
reported lack of efficacy. However, a blood eosinophil count ≥ 300 cells /μL identifies patients
with the greatest likelihood of experiencing more exacerbations after ICS withdrawal and who
subsequently should be followed closely for relapse of exacerbations.114,115
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TREATMENT OF STABLE COPD: NON-
PHARMACOLOGICAL TREATMENT
Education and self-management
Self-management education and coaching by healthcare professionals should be a major
component of the “Chronic Care Model” within the context of the healthcare delivery system.
The aim of self- management interventions is to motivate, engage and coach the patients to
positively adapt their health behavior(s) and develop skills to better manage their disease on a
day-to-day basis.206
Physicians and healthcare providers need to go beyond pure education/advice-giving (didactic)
approaches to help patients learn and adopt sustainable self-management skills. In addition to
addressing behavioral risk factors (ie, smoking, diet, exercise), self-management should involve
patients in monitoring and managing the signs and symptoms of their disease, being adherent
to treatment (including to medications and other medical advice), maintaining regular contact
with healthcare providers, and managing the psychosocial consequences of their condition.
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Oxygen therapy
An appropriate algorithm for the prescription of oxygen to COPD patients is shown in
below.
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Key points for the use of non-pharmacological treatments are given in the following
Table.

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MONITORING AND FOLLOW-UP
Routine follow-up of COPD patients is essential. Lung function may worsen over time, even with
the best available care. Symptoms, exacerbations and objective measures of airflow limitation
should be monitored to determine when to modify management and to identify any
complications and/or comorbidities that may develop. Based on current literature,
comprehensive self-management or routine monitoring has not shown long-term benefits in
terms of health status over usual care alone for COPD patients in general practice.207
MANAGEMENT OF EXACERBATIONS
OVERALL KEY POINTS:
• • • • • • • An that Exacerbations causes The the Short-acting are Maintenance as
Systemic recovery than Antibiotics, relapse, possible exacerbation current
recommended goal results 5-7 are treatment days.
O P
for time Ccorticosteroids respiratory before exacerbation when in treatment inhaled
Y RI G H
therapy and additional of of COPD indicated, hospital hospitalization as failure,
T E D M
COPD beta2-agonists, the with tract of can can therapy. and initial is COPD
A T E
and discharge. long-acting be defined infections. can improve to precipitated
R IA L- D
hospitalization bronchodilators exacerbations prevent shorten duration. as with
O N O T
lung an bronchodilators subsequent recovery or acute function by Duration
C O P Y
without several duration. is worsening to to time, treat (FEV1), minimize
O
events.
R D IS
short-acting of factors. should reduce therapy an Duration oxygenation of
T R IB U
acute the respiratory The be the should negative anticholinergics,
T E
exacerbation. initiated of most risk therapy of not and common symptoms
early impact as be shorten
should soon
more of
be 5-7 days.
• Methylxanthines are not recommended due to increased side effect profiles.
• Non-invasive mechanical ventilation should be the first mode of ventilation used in
COPD patients with acute respiratory failure who have no absolute contraindication
because it improves gas exchange, reduces work of breathing and the need for
intubation, decreases hospitalization duration and improves survival.
• Following an exacerbation, appropriate measures for exacerbation prevention should
be initiated.
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COPD exacerbations are defined as an acute worsening of respiratory symptoms that
result in additional therapy.208,209
They are classified as:
• Mild (treated with short acting bronchodilators only, SABDs)
• Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids) or
• Severe (patient requires hospitalization or visits the emergency room). Severe exacerbations
may also be associated with acute respiratory failure.
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the
management of COPD because they negatively impact health status, rates of hospitalization
and readmission, and disease progression.208,209 COPD exacerbations are complex events
usually associated with increased airway inflammation, increased mucus production and
marked gas trapping. These changes contribute to increased dyspnea that is the key symptom
of an exacerbation. Other symptoms include increased sputum purulence and volume, together
with increased cough and wheeze.210 As comorbidities are common in COPD patients,
exacerbations must be differentiated clinically from other events such as acute coronary
syndrome, worsening congestive heart failure, pulmonary embolism and pneumonia.
TREATMENT OPTIONS
Treatment setting
The goals of treatment for COPD exacerbations are to minimize the negative impact of the
current exacerbation and prevent the development of subsequent events.211 Depending on the
severity of an exacerbation and/or the severity of the underlying disease, an exacerbation can
be managed in either the outpatient or inpatient setting. More than 80% of exacerbations are
managed on an outpatient basis with pharmacological therapies including bronchodilators,
corticosteroids, and antibiotics. 15,23,24
When patients with a COPD exacerbation come to the emergency department, they should be
provided with supplemental oxygen and undergo assessment to determine whether the
exacerbation is life-threatening and if increased work of breathing or impaired gas exchange
requires consideration for non-invasive ventilation (see Table). If so, healthcare providers
should consider admission to the respiratory or intensive care unit of the hospital. Otherwise,
the patient may be managed in the emergency department or hospital ward unit. In addition to
pharmacological therapy, hospital management of exacerbations includes respiratory support
(oxygen therapy, ventilation). The management of severe, but not life-threatening,
exacerbations is also outlined (see Table).
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The clinical presentation of COPD exacerbation is heterogeneous, thus we recommend that in


hospitalized patients the severity of the exacerbation should be based on the patient's clinical
signs and recommend the following classification.212
No respiratory failure: Respiratory rate: 20-30 breaths per minute; no use of accessory
respiratory muscles; no changes in mental status; hypoxemia improved with supplemental
oxygen given via Venturi mask 28-35% inspired oxygen (FiO2); no increase in PaCO2.
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Acute respiratory failure – non-life-threatening: Respiratory rate: > 30 breaths per minute;
using accessory respiratory muscles; no change in mental status; hypoxemia improved with
supplemental oxygen via Venturi mask 25-30% FiO2; hypercarbia ie, PaCO2 increased
compared with baseline or elevated 50-60 mmHg.
Acute respiratory failure – life-threatening: Respiratory rate: > 30 breaths per minute; using
accessory respiratory muscles; acute changes in mental status; hypoxemia not improved with
supplemental oxygen via Venturi mask or requiring FiO2 > 40%; hypercarbia ie, PaCO2 increased
compared with baseline or elevated > 60 mmHg or the presence of acidosis (pH ≤ 7.25).
A recent updated Cochrane review concluded that the use of COPD exacerbation action plans
with a single short educational component, in conjunction with ongoing support, reduced in-
hospital healthcare utilization. Such educational interventions were also found to increase the
treatment of COPD exacerbations with corticosteroids and antibiotics.213
The three classes of medications most commonly used for COPD exacerbations are
bronchodilators, corticosteroids, and antibiotics (see Table).
Respiratory support
Oxygen therapy. This is a key component of hospital treatment of an exacerbation.
Supplemental oxygen should be titrated to improve the patient's hypoxemia with a target
saturation of 88-92%.214 Once oxygen is started, blood gases should be checked frequently to
ensure satisfactory oxygenation without carbon dioxide retention and/or worsening acidosis.
Venturi masks (high-flow devices) offer more accurate and controlled delivery of oxygen than do
nasal prongs.215
High-flow oxygen therapy by nasal cannula. In patients with acute hypoxemic respiratory
failure, high-flow oxygen therapy by nasal cannula (HFNC) may be an alternative to standard
oxygen therapy or noninvasive positive pressure ventilation; some studies have shown that
HFNC can reduce the need for intubation or mortality in patients with acute hypoxemic
respiratory failure (ARF).216
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Ventilatory Support. Some patients need immediate admission to the respiratory care or
intensive care unit (ICU) (see Table). Admission of patients with severe exacerbations to
intermediate or special respiratory care units may be appropriate if adequate personnel skills
and equipment exist to identify and manage acute respiratory failure. Ventilatory support in an
exacerbation can be provided by either noninvasive (nasal or facial mask) or invasive (oro-
tracheal tube or tracheostomy) ventilation. Respiratory stimulants are not recommended for
acute respiratory failure.217
Noninvasive mechanical ventilation. The use of noninvasive mechanical ventilation (NIV) is
preferred over invasive ventilation (intubation and positive pressure ventilation) as the initial
mode of ventilation to treat acute respiratory failure in patients hospitalized for acute
exacerbations of COPD. NIV has been studied in RCTs showing a success rate of 80-85% (see
Table).179,218-221
Invasive mechanical ventilation. The indications for initiating invasive mechanical ventilation
during an exacerbation are shown in the Table, and include failure of an initial trial of NIV.222
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Hospital discharge and follow-up
The cause, severity, impact, treatment and time course of exacerbations varies from patient to
patient and facilities in the community, and healthcare systems, differ from country to country.
Accordingly, there are no standards that can be applied to the timing and nature of discharge.
When features related to re-hospitalization and mortality have been studied, defects in
perceived optimal management have been identified including spirometric assessment and
arterial blood gas analysis.223 Mortality relates to patient age, the presence of acidotic
respiratory failure, the need for ventilatory support and comorbidities including anxiety and
depression (see Table).224
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Prevention of
exacerbations
After an acute exacerbation, appropriate measures for prevention of further exacerbations
should be initiated (see Table).

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COPD AND COMORBIDITIES
OVERALL KEY POINTS:
• COPD often coexists with other diseases (comorbidities) that may have a significant
impact on disease course.
• In general, the presence of comorbidities should not alter COPD treatment and
comorbidities should be treated per usual standards regardless of the presence of
COPD.
• Lung cancer is frequently seen in patients with COPD and is a main cause of death.
• Cardiovascular diseases are common and important comorbidities in COPD.
• Osteoporosis and depression/anxiety are frequent, important comorbidities in COPD,
are often under-diagnosed, and are associated with poor health status and prognosis.
• Gastroesophageal reflux (GERD) is associated with an increased risk of exacerbations
and poorer health status.
• When COPD is part of a multimorbidity care plan, attention should be directed to
ensure simplicity of treatment and to minimize polypharmacy.
REFERENCES
The full list of references for this pocket guide can be found online at:
www.goldcopd.org/pocketguidereferences
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© 2019 Global Initiative for Chronic Obstructive Lung Disease, Inc.

Visit the GOLD website at www.goldcopd.org