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 antiinflammatory, s-IgA can reduce the number of neutrophils as proinflammatory, 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, sIgA levels were influenced by certain pathogens, while neutrophils give xviii
xix 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 VAP.
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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 antiinflamasi, 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 aeruginosa. Jenis patogen berpengaruh terhadap kejadian VAP, dan xx
xxi 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 terapi supresi neutrofil pada kejadian perburukan VAP.
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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 gene, Batak, Indonesia.
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