PROPOSAL KARYA AKHIR

PERBANDINGAN PARAMETER INFLAMASI PADA LANSIA

DIBANDINGKAN DEWASA TERHADAP LUARAN PASIEN TERKONFIRMASI
COVID-19 DI RSUD ULIN BANJARMASIN

Disusun Oleh:

dr. Pradana Maulana Putra

NIM. 1750911310002

Pembimbing:

dr. Ali Assagaf, Sp. P(K), FISR, FAPSR

Dr. dr. Mohamad Isa, Sp. P(K), FISR, FAPSR

PROGRAM PENDIDIKAN DOKTER SPESIALIS-1

DEPARTEMEN PULMONOLOGI DAN KEDOKTERAN RESPIRASI
FAKULTAS KEDOKTERAN UNIVERSITAS LAMBUNG MANGKURAT RSUD
RSUD ULIN BANJARMASIN
2022

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 PROPOSAL KARYA AKHIR

PERBANDINGAN PARAMETER INFLAMASI PADA LANSIA

DIBANDINGKAN DEWASA TERHADAP LUARAN PASIEN TERKONFIRMASI
COVID-19 DI RSUD ULIN BANJARMASIN

Peneliti:
dr. Pradana Maulana Putra
NIM. 1750911310002

Telah Disetujui Oleh:

Pembimbing I

dr. Ali Assagaf, Sp. P(K), FISR, FAPSR

Pembimbing II

Dr. dr. Mohamad Isa, Sp. P(K), FISR, FAPSR

PROGRAM PENDIDIKAN DOKTER SPESIALIS-1

DEPARTEMEN PULMONOLOGI DAN KEDOKTERAN RESPIRASI
FAKULTAS KEDOKTERAN UNIVERSITAS LAMBUNG MANGKURAT
RSUD ULIN BANJARMASIN
2022

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 DAFTAR ISI

Halaman
HALAMAN PERSETUJUAN........................................................................................... i
DAFTAR ISI....................................................................................................................... ii
DAFTAR TABEL............................................................................................................... iv
DAFTAR GAMBAR.......................................................................................................... v
DAFTAR SINGKATAN.................................................................................................... vi
DAFTAR LAMPIRAN...................................................................................................... viii
BAB 1 PENDAHULUAN................................................................................................... 1
1.1 Latar belakang………….................................................................................. 1
1.2 Perumusan Masalah.......................................................................................... 3
1.3 Tujuan Penelitian.............................................................................................. 4
1.3.1 Tujuan Umum......................................................................................... 4
1.3.2 Tujuan Khusus........................................................................................ 4
1.4 Manfaat Penelitian............................................................................................ 5
BAB 2 TINJAUAN PUSTAKA ........................................................................................ 6
2.1 Penuaan dan Immunosenescence...................................................................... 6
2.2 Lansia dan COVID-19...................................................................................... 13
2.3 Senescene pada COVID-19.............................................................................. 15
2.4 Disregulasi sistem imun pada COVID-19…………………………………… 17
2.5 Inflammaging pada COVID-19……………………………………………… 21
2.6 Luaran pasien COVID-19…………………………………………………… 23
2.7 Peran biomarker inflamasi darah rutin terhadap luaran pasien COVID-19…. 24
2.7.1 Neutrofil……………………………………………………………….. 25
2.7.2 Limfosit……………………………………………………………….. 26
2.7.3 Trombosit……………………………………………………………… 28
2.7.4 Neutrophil - Lymphocyte Ratio (NLR)………………………………... 29
2.7.5 Platelet-Lymphocyte Ratio (PLR)…………………………………….. 30
2.7.6 LED…………………………………………………………………… 30
2.7.7 CRP……………………………………………………………………. 31
BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS PENELITIAN.................... 33
3.1 Kerangka Konseptual………………………………………………………… 33
3.2 Hipotesis Penelitian………………………………………………………….. 34
BAB 4 METODE PENELITIAN……………………………………………………….. 35
4.1 Jenis Penelitian………………………………………………………………. 35
4.2 Populasi, sampel dan teknik pengambilan sampel…………………………… 35
4.2.1 Populasi Penelitian………………………………………………….… 35
4.2.2 Sampel Penelitian……………………………………………………... 35
4.2.3 Teknik pengambilan sampel…………………………………………... 36

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 4.3 Variabel penelitian dan definisi operasional………………………………… 36
4.3.1 Variabel Penelitian……………………………………………………. 36
4.3.2 Definisi Operasional…………………………………………………... 36
4.4 Instrumen Penelitian…………………………………………………………. 37
4.5 Lokasi dan waktu penelitian…………………………………………………. 37
4.6 Alur Penelitian……………………………………………………………….. 37
4.7 Prosedur pengumpulan data………………………………………………….. 38
4.8 Analisis Data…………………………………………………………………. 37
4.9 Etika Penelitian………………………………………………………………. 39
DAFTAR PUSTAKA.......................................................................................................... 40
LAMPIRAN......................................................................................................................... 45

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 DAFTAR TABEL

Halaman
Tabel 2.1 Perubahan sitokin terkait usia...………………………………………………… 10
Tabel 4.1 Definisi Operasional……………………………………………………………. 36

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 DAFTAR GAMBAR

Halaman
Gambar 2.1 Mekanisme biokimia dan molekuler yang memengaruhi fungsi kekebalan
selama penuaan…………………………………………………………….... 8
Gambar 2.2 Immunosenescene dan proses yang terjadi………………………………….. 9
Gambar 2.3 Perubahan seluler terkait immunosenescene dan implikasinya……………... 14
Gambar 2.4 Siklus hidup SARS-CoV-2………………………………………………….. 20
Gambar 2.5 Inflammaging pada COVID-19……………………………………………… 23
Gambar 2.6 Neutrofil pada jaringan paru dengan infeksi SARS-CoV-2…………………. 25
Gambar 2.7 Penyebab limfopenia pada infeksi COVID-19……………………………… 27
Gambar 2.8 Penyebab trombositopenia pada infeksi COVID-19………………………… 28
Gambar 2.9 Patomekanisme molekuler dari kerusakan yang dimediasi CRP pada
jaringan iskemik atau hipoksemia…………………………………………… 32
Gambar 3.1 Kerangka konseptual penelitian……………………………………………... 33
Gambar 4.1 Alur penelitian……………………………………………………………….. 37

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 DAFTAR SINGKATAN

+ssRNA : positive singlestranded Ribonucleic Acid

ACE2 : Angiotensin-Converting-Enzyme 2
AKI : Acute Kidney Injury
APC : Antigen Presenting Cell
ARDS : Acute Respiratory Distress Syndrome
AT2 : pneumosit alveolar tipe 2
BPS : Badan Pusat Statistik
CCL-2 : CC Ligand-2
CD : Cluster of Differentiation
CFR : Case Fatality Rate
COVID-19 : Coronavirus Disease 2019
CRP : C-reactive protein
CXCL-10 : CXC Ligand-10
DAMPs : Damage-Associated Molecular Patterns
DNA : deoxyribonucleic acid
DOA : Death on Arrival
DPJP : Dokter Penanggung Jawab Pasien
Fasyankes : fasilitas pelayanan kesehatan
GM-CSF : Granulocyte-Macrophage Colony-Stimulating Factor
GSDMD : Gasdermin D
HSC : Hematopoeitic Stem Cell
HPSC : Hematopoietic Stem and Progenitor Cells
ICU : Intensive Care Unit
IFN-γ : Interferon-γ
IL-1α/β : interleukin-1α/β
IL-2 : Interleukin-2
IL-4 : Interleukin-4
IL-5 : Interleukin-5
IL-6 : Interleukin-6
IL-7 : Interleukin-7
IL-8 : Interleukin-8
IL-10 : Interleukin-10
IL-11 : Interleukin-11
IL-12 : Interleukin-12
IL-15 : Interleukin-15
IL-18 : Interleukin-18
IP-10 : IFNγ-Induced Protein-10
IRF-3 : Interferon Regulatory Factor-3
KEMENKES RI : Kementerian Kesehatan Republik Indonesia
KK : Kartu Keluarga
KTP : Kartu Tanda Penduduk

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Lansia : Lanjut usia

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LED : Laju Endap Darah
LPC : lyso-phosphatidylcholine
MAP2K7 : Mitogen-Activated Protein Kinase Kinase 7
MCP-1 : Monocyte Chemoattractant Protein-1
MHC : Major Histocompatibility Complex
miRNA : microRNA
MMPs : Matrix Metalloproteinase
NETs : Neutrophil Extracellular Traps
NFκB : Nuclear Factor κ-B
NK : Natural Killer
NLR : Neutrophil-Lymphocyte Ratio
NSPs : Nonstructural Protein
OIS : Oncogene-Induced Senescence
PAMPs : Pathogen-Associated Molecular Patterns
PC : phosphatidylcholine
PLR : Platelet-Lymphocyte Ratio
pp1a : polyprotein 1a
pp1ab : polyprotein 1ab
PPOK : penyakit paru obstruktif kronik
PRR : Pattern-Recognition Receptor
RAS : Renin – Angiotensin System
ROC : Receiver Operating Characteristic
RTC : Replication-Transcription Complex
RT-PCR : Real Time – Polymerase Chain Reaction
S : Spike
SARS-CoV-2 : Severe Acute Respiratory Syndrome Coronavirus-2
SASP : Senescene Associated Secretory Phenotype
sCD25 : soluble Interleukin-2 Receptor-α
SE : Standard Error
SOR : Spesies Oksigen Reaktif
SOS1 : Son of Sevenless Homolog 1
sPLA2-IIa : group IIA secretory phospholipase A2
TGF-β : Tumor Growth Factor-β
Th : T-helper
TMEM173 : Transmembrane Protein 173
TNF-α : Tumor Necrosis Factor-α
Treg : T-regulator
VTE : Venous Thromboembolism
WHO : World Health Organization

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 DAFTAR LAMPIRAN

Halaman
Lampiran 1 Jadwal Kegiatan………….....………………………………………………… 45
Lampiran 2 Rincian biaya penelitian...……………………………………………………. 46

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