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xviii SUMMARY
Cohort, prospective observation alanalytic study has been
conducted to observe the role ofs-IgA and neutrophils of lower respiratory
tract, toward the incidence of early onset-Ventilator Acquired Pneumonia
(VAP). The specimen (lower respiratory tract fluid) was obtained by
performing the techniques Broncho-Alveolar Lavage (BAL) procedures
bronchoscopy, in patients using mechanical ventilators > 48 hours, at
Intensive Care Unit of H. Adam Malik General hospital,Medan.
Observation also taking into account other factors such as the Simplified
Acute Physiology Score(SAPS) and pathogens from the lower respiratory
tract, in compliance with the inclusion and exclusion criteria.
At the third day using mechanical ventilator, in early-onset VAP
patients (VAP(+), showed increasing of s-IgA level significantly. As an
anti-inflammatory, s-IgA can reduce the number of neutrophils as
pro-inflammatory, but the kind of pathogens play an important role in
stimulating or destroying s-IgA. Availability of MRSA pathogens, can
decrease s-IgA level from the baseline.
While, at the same time (third day using mechanical ventilator),the
percentage of neutrophils increased not significantly and was controlled, in
the VAP () patients. However, in group of early-onset VAP patients (VAP
(+), percentage of neutrophils increase significantly. Neutrophils play an
important role in the incidence and deterioration of VAP.
SAPS also consider influence in the incidence of VAP, but SAPS
do not influence the level of s-IgA. However, together with neutrophils,
SAPS give contribution to the incidence of early-onset VAP.
The four highest pathogens in patients using mechanical ventilator
in this study are Acinetobacter baumanii, MRSA, Klebsiella pneumoniae
and Pseudomonas aeruginosa.The kind of pathogens influence the
incidence of VAP and A. Baumannii as the highest number of pathogen
isolations, contribute to the incidence of VAP significantly. In addition,
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same response to different pathogens, and all kinds of pathogens can
increase percentage of neutrophils significantly.
The data from this study can be concluded that the s-IgA and
neutrophils are cooperating local immunity, but certain pathogens capable
of destroying the s-IgA and have different responses to the types of
pathogens. While neutrophils increased in all types of pathogens, but do
not respond differently to different types of pathogens and participate
worsen the incidence of VAP (+). SAPS scores do not affect the s-IgA, but
together with neutrophils contribute to the incidence of early onset VAP.
The data in this study can be used as a reference : s-IgA,
neutrophils and pathogens of lower respiratory tract with performing
bronchoscopy procedure by using BAL technique, as the basic data of
patients with mechanical ventilator the first day and the third day on VAP
(-) and early onset VAP (+(-). The data can be used as a reference regarding
the correlation between these variables, and conduct further research to
increase levels of s-IgA lower respiratory tract, such as nutrition and
vaccinations to improve lung health. While the value of the percentage of
neutrophils in this study could be used for further research on the
development of suppressive therapy neutrophils worsening incidence of
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xx RINGKASAN
Telah dilakukan penelitian observasional analitik (kohort prospektif),
yang bertujuan mengamati peran s-IgA dan neutrofil cairan saluran napas
bawah, terhadap kejadian early onset-Ventilator Acquired Pneumonia
(VAP awitan dini). Spesimen (cairan saluran napas bawah), diambil
dengan prosedur Broncho-Alveolar Lavage (BAL), pada pasien yang
dirawat dengan menggunakan ventilator mekanik > 48 jam, di ruang
Instalasi Perawatan Intensif (IPI), RSUP H. Adam Malik Medan.
Pengamatan ini dilakukandengan turut mempertimbangkan faktor lain
seperti skor Simplified Acute Physiology Score (SAPS) dan jenis patogen
dari saluran napas bawah,sesuai dengan kriteria inklusi dan eksklusi.
Hasil penelitian ini menunjukkan adanya peningkatan kadar s-IgA
yang bermakna pada pasien yang mengalami VAP awitan dini (VAP (+),
setelah hari ketiga menggunakan ventilator mekanik. Sebagai
anti-inflamasi, s-IgA mampu menekan jumlah neutrofil sebagai pro-nflamasi.
Namun jenis patogen berperan penting dalam menstimulasi atau
menghancurkan s-IgA. Keberadaan patogen MRSA, dapat menurunkan
kadar s-IgA dari nilai dasarnya.
Pada saat yang sama (hari ketiga menggunakan ventilator
mekanik), di kelompok VAP (), didapati peningkatan persentase
neutrofil yang tidak bermakna dan terkontrol. Namun di kelompok VAP
(+), didapati peningkatan bermakna dari persentase neutrofil. Neutrofil
berperan penting terhadap kejadian dan perburukan VAP.
Skor SAPS juga sangat berperan pada kejadian VAP,tetapi
skorSAPS tidak mempengaruhi kadar s-IgA. Namun bersama-sama
dengan neutrofil, skor SAPS berperan terhadap kejadian VAP awitan
dini.
Urutan empat terbanyak jenis patogen yang ditemukan pada subyek
yang menggunakan ventilator mekanik pada penelitian ini adalah
Acinetobacter baumanii, MRSA, Klebsiella pneumonia dan Pseudomonas
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Acinetobacterbaumanii dengan jumlah isolasi patogen yang terbanyak,
mempunyai peran yang bermakna terhadap kejadian VAP. Selain itu, kadar
s-IgA secara bermakna dipengaruhi oleh jenis patogen tertentu, sedangkan
persentase neutrofil meningkat secara bermakna untuk semua jenis
patogen, dan peningkatan ini tidak berbeda bermakna di antara jenis
patogen yang berbeda.
Dari data penelitian ini dapat disimpulkan bahwa S-IgA dan Neutrofil
merupakan imunitas lokal yang bekerjasama, namun patogen tertentu
mampu menghancurkan s-IgA dan mempunyai respon yang berbeda
terhadap jenis patogen. Sedangkan neutrofil meningkat pada semua jenis
patogen, tetapi tidak memberikan respon berbeda terhadap jenis patogen
yang berbeda dan berperan serta memperburuk kondisi kejadian VAP. skor
SAPS tidak mempengaruhi s-IgA, namun bersama-sama dengan neutrofil
berperan terhadap kejadian VAP awitan dini.
Data pada penelitian ini dapat dimanfaatkan sebagai acuan, yaitu: s-IgA,
neutrofil dan jenis patogen dari saluran napas bawah dengan prosedur
BAL, sebagai data dasar pasien dengan ventilator mekanik hari
pertama,dan hari ketiga pada VAP(-) dan VAP (+) awitan dini. Serta dapat
dipakai sebagai acuan mengenai hubungan korelasi antar variabel
tersebut, dan melakukan penelitian lebih lanjut untuk meningkatkan kadar
s-IgA saluran napas bawah, seperti nutrisi dan vaksinasi untuk
meningkatkan kesehatan paru. Sedangkan nilai persentasi Neutrofil pada
penelitian ini dapat digunakan untuk penelitian lebih lanjut pengembangan
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xxii ABSTRACT
Background: The active metabolite of vitamin D leads to activation of
macrophage and restricts the growth of M. tuberculosis. The effect of
vitamin D is achieved by binding to Vitamin D Receptor and may be
influenced by polymorphisms in VDR gene.
Aim: to explore the role of FokI and BsmI polymorphisms VDR gene in
susceptibility to pulmonary tuberculosis (PTB) in Indonesian Batak ethnic
population.
Methods: matched case-control study with 76 PTB patients and 76 healthy
normal control. Genetic polymorphisms of Vitamin D Receptor (VDR) gene
were analysed using PCR-RFLP.
Results: The frequencies of FokI genotypes were FF 35.5%, Ff 55.3%, ff
9.2% for PTB patients and FF 39.5%, Ff 44.7% and ff 15.8% for normal
control. The BsmI genotypes frequencies were BB 0%, Bb 68.4%, bb
31.6% for TB patients and BB 2.6%, Bb 23.7% and bb 73.7% for control.
There was no significant association between FokI genotype and PTB (OR
1.39, 95% CI: 0.70 - 2.77 for Ff genotype and OR 0.65, 95% CI: 0.22 -
1.86 for ff genotype). There was a significant association between bb
genotype BsmI polymorphism and PTB; bb genotype was associated with
a decreased risk to PTB (OR 0.22, 95% CI: 0.11 - 0.45). After adjusting for
smoking and alcohol cunsuming habit, the adjusted ORs were 0.79, 95%
CI: 0.29 - 2.11 for Ff genotype and adjusted OR 0.53, 95% CI: 0.14 - 2.06
for ff genotype and OR 0.31, 95% CI: 0.13 - 0.73 for bb genotype.
Conclusions: In Indonesian Batak ethnic population, there was no
association between FokI polymorphism of VDR gene with host
susceptibility to PTB. For BsmI polymorphism of VDR gene, bb genotype
was significant associated with a decreased risk to PTB
Key words: pulmonary tuberculosis, polymorphisms, Vitamin D Receptor
