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Abstrak :
Kasus aspergilosis paru kronik (APK) yang disebabkan Aspergillus sp. semakin meningkat seiring dengan meningkatnya frekuensi infeksi tuberkulosis (TB) paru sebagai faktor risiko. Diagnosis APK masih menjadi tantangan karena gejala klinis, pemeriksaan radiologi, maupun laboratorium tidak khas. Untuk menetapkan diagnosis APK diperlukan pemeriksaan laboratorium mikologi, termasuk uji serologi. Hasil pemeriksaan imuno-diffusion test (IDT) Aspergillus dengan crude antigen kurang optimal dan IgG Aspergillus ELISA menggunakan antigen galaktomanan yang termasuk antigen sel T independent sehingga tidak mendukung switching isotipe antibodi. Oleh sebab itu, diperlukan penelitian lain untuk mendapatkan prosedur yang lebih baik dalam menetapkan diagnosis APK. Tujuan penelitian ialah mengetahui pola respon IgG terhadap kombinasi empat protein 16 kD, 18-20 kD, 22 kD, dan 30 kD antigen Aspergillus dengan metode Western Blot. Potensi diagnostik dari kombinasi protein 16 kD, 18-20 kD, 22 kD, dan 30 kD antigen Aspergillus dengan metode Western Blot terhadap nilai konsensus positif dan negatif APK berdasarkan 2 metode pemeriksaan yaitu biakan jamur dan IgG anti galaktomanan sebagai baku emas didapatkan nilai sensitivitas dan spesifisitas sebesar 74% dan 96%. Deteksi IgG Aspergillus metode Western Blot menunjukkan antigen dominan berat molekul 16 kD dan 18-20 kD. Kesimpulan uji IgG Aspergillus Western Blot memiliki potensi diagnostik lebih baik dibanding uji IgG Aspergillus ELISA. ......Chronic pulmonary aspergillosis (CPA) caused by Aspergillus sp. potentially increases with the increasing frequency of pulmonary tuberculosis (TB) as a risk factor. Diagnosis of CPA is still a challenge because clinical symptoms, radiological examination, and laboratory are  not specific. The diagnosis of CPA needs to be performed by specific mycological examination, including serology test. The result of the Aspergillus immunodiffusion test (IDT) with crude antigen is sub optimal and Aspergillus IgG ELISA method uses galactomannan antigens that are independent T cell antigens, so cant support switching of isotype antibodies. Therefore, other study is needed to get a better procedure in determine the CPA diagnostic. The study aimed to determine the IgG responses with a combination of  Aspergillus proteins (16 kD, 18-20 kD, 22 kD, and 30 kD) with Western Blot method. Diagnostic potential of the Aspergillus protein combination (16 kD, 18-20 kD, 22 kD, and 30 kD) with Western Blot method on positive and negative consensus values of CPA based on two examination methods are fungus culture and anti-galactomannan IgG as gold standard are obtained sensitivity and specificity of 74% and 96%. From the Aspergillus Western Blot IgG test, dominant antigens obtained were molecular weights of 16 kD and 18-20 kD. The conclusion is Aspergillus specific IgG test with Western Blot method has better diagnostic potential than the  anti-galactomannan IgG ELISA method.

Abstrak :
Latar Belakang: Aspergilosis paru kronik (APK) dapat menjadi komplikasi infeksi tuberkulosis (TB) paru yang telah diobati. Gejala klinis APK dengan TB paru sangat mirip, sehingga sulit dibedakan. Diagnosis APK ditetapkan sesuai konsensus berdasarkan gejala klinis, hasil pemeriksaan radiologi dan laboratorium mikologi. Pemeriksaan antibodi dengan imunoglobulin G (IgG) spesifik Aspergillus menggunakan metode Enzyme-linked immunosorbent assay (ELISA) dapat membantu diagnosis APK. Penelitian ini bertujuan untuk mengetahui karakteristik klinis, profil IgG spesifik Aspergillus, serta prevalensi APK pada pasien bekas TB di beberapa rumah sakit di Jakarta. Metode: Penelitian prospektif dengan desain potong lintang ini dilakukan pada April 2019 - Februari 2020. Pemilihan subjek dilakukan dengan metode consecutive sampling. Subjek merupakan pasien bekas TB yang berasal dari poli rawat jalan dan rawat inap Rumah Sakit Umum Pusat Rujukan Respirasi Persahabatan Jakarta dan Rumah Sakit Graha Permata Ibu. Pemeriksaan IgG spesifik Aspergillus dan biakan sputum jamur dilakukan di Laboratorium Departemen Parasitologi FKUI. Hasil: Dari 97 pasien yang sesuai dengan kriteria penerimaan, 66 pasien (68%) berjenis kelamin laki-laki dan rerata usia 51,8±13,6 tahun. Gejala klinis lebih dari 3 bulan yang dilaporkan berupa mudah lelah (38,4%), sesak napas (34,02%), batuk (30,93%), hemoptisis (27,84%), penurunan berat badan (23,71%), dan nyeri dada (19,6%). Gambaran radiologi terkait APK berupa ektasis (57,8%), kavitas (27,8%), penebalan pleura (26,8%), fibrosis parakavitas (18,6%), dan bola jamur (6,2%). Hasil pemeriksaan IgG spesifik Aspergillus positif dilaporkan pada 51 pasien (52,6%), sedangkan biakan sputum jamur Aspergillus didapatkan pada 43 pasien (44,3%). Berdasarkan analisis hasil-hasil pemeriksaan tersebut, diagnosis APK ditegakkan pada 28 pasien (28,9%). Kesimpulan: Profil IgG spesifik Aspergillus pada 97 pasien bekas TB dalam penelitian ini menunjukkan hasil positif pada 51 pasien (52,6%). Gejala klinis lebih dari 3 bulan yang dilaporkan berupa batuk lama, hemoptisis, penurunan berat badan, mudah lelah, dan sesak napas. Gambaran radiologi terkait APK berupa ektasis, kavitas, penebalan pleura, fibrosis parakavitas, dan bola jamur. Prevalensi APK berdasarkan hasil-hasil pemeriksaan tersebut adalah 28,9%. ......Introduction: Chronic pulmonary aspergillosis (CPA) might become a complication of pulmonary tuberculosis (TB) that has been treated. The clinical symptoms of CPA can resemble with PTB, making it difficult to distinguish. The diagnosis of CPA is determined by the consensus based on clinical symptoms, radiological features, and mycological results. Antibody detection with Aspergillus- specific immunoglobulin G (IgG) using the Enzyme-linked immunosorbent assay (ELISA) method can contribute to CPA diagnosis. This study aims to determine the clinical characteristics, Aspergillus-specific IgG detection, and the prevalence of CPA in prior TB patients at several hospitals in Jakarta. Method: This prospective cross-sectional study was conducted in April 2019 - February 2020. Patients recruitment was carried out by consecutive sampling method. Subjects were prior TB patients at Persahabatan National Respiratory Referral Hospital and Graha Permata Ibu Hospital. Detection of Aspergillus- specific IgG and fungal cultures from sputum were carried out in the Laboratory of the Parasitology Department, FMUI. Results: Of 97 patients recruited according to inclusion criteria, 66 patients (68%) were male and the mean age was 51.8 ± 13.6 years. The clinical symptoms of more than 3 months were fatigue (38.4%), shortness of breath (34.02%), cough (30.93%), hemoptysis (27.84%), weight loss (23, 71%), and chest pain (19,6%). Radiological features associated with CPA were ectasis (57.8%), cavity (27.8%), pleural thickening (26.8%), para-cavitary fibrosis (18.6%), and fungal ball (6.2%). The Aspergillus-specific IgG positive were reported in 51 patients (52.6%), whereas Aspergillus sputum cultures were found in 43 patients (44.3%). Based on the analysis of those examinations, the diagnosis of CPA was determined in 28 patients (28.9%). Conclusion: The detection of Aspergillus-specific IgG in 97 prior TB patients showed the positive results in 51 patients (52.6%). The clinical symptoms more than three months were fatigue, shortness of breath, cough, hemoptysis, and weight loss. The radiological features related to CPA were ectasis, cavitary lesions, pleural thickening, paracavitary fibrosis, and fungal ball. The prevalence of CPA based on those examinations was 28.9%.

Abstrak :
Latar Belakang : Asma merupakan penyakit inflamasi kronik saluran napas dengan fungsi bersihan mukosilier yang menurun, maka itu bentuk matur dari spora Aspergillus fumigatus bisa tumbuh dan membuat sensitisasi Aspergillus yang merupakan kondisi awal aspergillosis paru pada asma dan dapat berkembang menjadi Allergic Bronchopulmonary Aspergillosis (ABPA). Penegakkan diagnosis aspergillosis paru didapatkan jika reaksi hipersensitisasi terhadap antigen A.fumigatus positif. Metode : Penelitian ini menggunakan metode potong lintang pada 86 pasien asma yang berobat ke RSUP Persahabatan dengan nilai Asthma Control Test (ACT) ≤ 24. Subjek penelitian dibagi 2 kelompok berdasarkan sensitisasi Aspergillus. Penilaian aspergillosis paru menggunakan pemeriksaan Imunoglobulin E (IgE) spesifik A.fumigatus. Kriteria diagnosis ABPA yang digunakan pada penelitian ini menggunakan kriteria International Society of Human and Animal Mycology (ISHAM) yaitu dua kriteria obligatory (IgE spesifik A.fumigatus dan IgE total) serta 3 kriteria tambahan (IgG spesifik A.fumigatus, eosinofil total, gambaran foto toraks). Pemeriksaan fungsi paru dilakukan pada penelitian ini termasuk spirometri, kapasitas difusi paru karbon monoksida (DLCO) dan nitrit oksida udara ekspirasi (FeNO). Hasil : Proporsi pasien asma tidak terkontrol yang memiliki aspergillosis paru didapatkan 3,5% (3/86) sedangkan proporsi ABPA didapatkan 1,1% (1/86). Terdapat faktor-faktor yang memengaruhi aspergillosis paru pada asma tidak terkontrol, diantaranya adalah nilai IMT (p=0,77), riwayat merokok (p=0,86) dan riwayat TB paru (p=0,03).. Karakteristik imunologi didapatkan nilai median IgE total pada subjek dengan aspergillosis paru 465(22-1690) IU/ml dan nilai median hitung total eosinofil 380 (0-770) sel/µl. Dari penilaian spirometri pada subjek aspergillosis paru didapatkan nilai median KVP 1630(950-2150) ml, nilai rerata KVP%prediksi 70±33,71%, nilai VEP1 1150(470-1240) ml, nilai median VEP1% prediksi 54(24-76)%, nilai rerata VEP1/KVP 59,33±14,57)% serta nilai rerata DLCO 84,67±24,66%. Nilai median FeNO pada asma tidak terkontrol dengan aspergillosis paru pada penelitian ini didapatkan 32 (12-45) ppb. Kesimpulan : Penegakkan diagnosis aspergillosis paru pada pasien asma tidak terkontrol harus dilakukan sejak awal, terutama pada pasien dengan riwayat TB  paru. Hal tersebut dapat mencegah aspergillosis paru pada asma tidak terkontrol berkembang menjadi penyakit ABPA serta kerusakan paru yang permanen. ......Background: Asthma is a chronic airway inflammation with decrease of mucocilliary clearance. The mature form of Aspergillus fumigatus spores could grow in this condition and caused an Aspergillus sensitization as an early progression to allergic bronchopulmonary aspergillosis (ABPA). Pulmonary aspergillosis could be diagnosed from a hypersensitivity reaction to the A. fumigatus antigen. Methods : This cross-sectional study included 86 asthma patients with Asthma Control Test ACT score ≤ 24 and treated at Persahabatan Hospital Jakarta, Indonesia. Pulmonary aspergillosis was examined using specific immunoglobulin E (IgE) assay of A. fumigatus. The ABPA diagnostic in this study used the International Society of Human and Animal Mycology (ISHAM) criteria, which included two obligatory criteria (A. fumigatus-specific IgE and total IgE) and three additional criteria (A. fumigatus-specific IgG, blood eosinophil count, and thoracic x-ray). Lung function were examined using spirometry, diffusing capacity for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FeNO). Results: Uncontrolled asthma patients who had pulmonary aspergillosis was 3.5% (3/86) while the proportion of ABPA was 1.1% (1/86).  A history of prior pulmonary tuberculosis (TB) was correlated with aspergillosis in uncontrolled asthma patients (p=0.03). The median value of total IgE and blood eosinophil count in pulmonary aspergillosis subjects was 465 (22-1690) IU/mL and 380 (0-770) cells/µL, respectively. Spirometry results of pulmonary aspergillosis subjects were median FVC 1630 (950-2150) ml, mean predicted FVC% predicted value 70±33.71%, mean FEV1 1150 (470-1240) ml, median predicted FEV1% 54 (24-24)%, mean FEV1/FVC 59.33±14.57%, and mean DLCO 84.67±24.66%. The median FeNO in uncontrolled asthma with pulmonary aspergillosis in this study was 32 (12-45) ppb. Conclusion: Diagnosis of pulmonary aspergillosis in patients with uncontrolled asthma should be carried out early, especially in patients with a history of pulmonary TB. This would prevent pulmonary aspergillosis in uncontrolled asthma from developing into ABPA disease and permanent lung damage.

Abstrak :
Latar belakang: Aspergillosis paru kronik (APK) menjadi salah satu penyakit yang sering ditemukan pada pasien dengan kerusakan jaringan paru, misalnya tuberkulosis (TB). Deteksi antibodi Aspergillus merupakan modalitas utama pendukung diagnosis APK. Penelitian ini, bertujuan untuk mengetahui cut-off optimal ELISA manual Bordier dalam deteksi antibodi Aspergillus di Indonesia. Metode: Penelitian ini menggunakan desain studi potong lintang. Pemeriksaan sampel menggunakan metode ELISA manual Bordier sebagai uji diagnostik APK. Data yang diperoleh dianalisis untuk menentukan cut-off optimal pemeriksaan. Hasil: Sebagian besar subjek penelitian merupakan kelompok usia <60 tahun (89,1%) dengan rentang usia 17-72 tahun dan median 34 tahun. Cut-off optimal memberikan sensitivitas 43,48% dan spesifitas 100%. Sedangkan, sensitivitas pada cut-off 0.780, 0.850 dan 0.930 menunjukkan sensitivitas yang lebih baik dibandingkan dengan cut-off 1,595 dan cut-off pabrik (>1,0). Diabetes (15,6%) dan asma (10,9%) diketahui menjadi temuan yang lebih banyak pada pasien APK dibandingkan penyakit komorbid lainnya. Kesimpulan: ELISA manual Bordier cut-off 1,595 dengan spesifitas 100%, dapat menjadi alat skrining awal diagnosis APK. Hasil positif pada pemeriksaan disertai gejala klinis dan radiologis mengarah APK dapat digunakan untuk menegakkan diagnosis, sedangkan hasil negatif membutuhkan investigasi lanjut dengan pemeriksaan ELISA otomatis. ......Introduction: Chronic pulmonary aspergillosis (APK) is one of the diseases that are often found in patients with lung tissue damage, for example tuberculosis (TB). Aspergillus antibody detection is the main modality supporting the diagnosis of APK. This study aims to determine the optimal cut-off of Bordier's manual ELISA in the detection of Aspergillus antibodies in Indonesia. Method: This study used a cross-sectional study design. Sampel examination using Bordier's manual ELISA method as a diagnostic APK test. The data obtained are analyzed to determine the optimal cut-off of the examination. Result: Most of the study subjects were <60 years old age group (89.1%) with an age range of 17-72 years and a median of 34 years. The optimal cut-off provides 43.48% sensitivity and 100% specificity. Meanwhile, the sensitivity at cut-offs of 0.780, 0.850 and 0.930 showed better sensitivity compared to cut-offs of 1.595 and factory cut-offs (>1.0). Diabetes (15.6%) and asthma (10.9%) are known to be more common in APK patients than other comorbid diseases. Conclusion: ELISA manual Bordier cut-off 1,595 with 100% specificity, can be an early screening tool for APK diagnosis. Positive results on examination accompanied by clinical and radiological symptoms leading to APK can be used to establish a diagnosis, while negative results require further investigation with automated ELISA examination.

Abstrak :
Latar belakang: Indonesia memiliki beban tuberkulosis yang tinggi. Kerusakan paru yang ditimbulkan mendasari terjadinya aspergillosis paru kronik (APK). Salah satu kriteria diagnosis APK ialah bukti keterlibatan Aspergillus. Mempertimbangkan keterbatasan kultur, deteksi antibodi ELISA menjadi modalitas alternatif. Penelitian ini bertujuan membandingkan performa diagnostik pemeriksaan IgG spesifik Aspergillus ELISA manual dan otomatis pada pasien riwayat TB paru. Metode: Penelitian potong lintang ini membandingkan pemeriksaan IgG spesifik Aspergillus ELISA manual Bordier dan ELISA otomatis Immulite menggunakan serum pasien dengan riwayat TB. Performa diagnostik dibandingkan dalam bentuk proporsi hasil positif, sensitivitas, spesifisitas, nilai duga positif, nilai duga negatif. Hasil: Terdapat total 68 subjek, dengan median usia 34,5 tahun, proporsi lansia 11,76% dan proporsi laki-laki 42,65%. Proporsi hasil positif pemeriksaan IgG spesifik Aspergillus ELISA manual dan ELISA otomatis masing-masing 13,24% dan 48,53%. Pemeriksaan IgG spesifik Aspergillus ELISA manual memiliki sensitivitas 20,83%, spesifisitas 90,91%, nilai duga positif 55,56%, dan nilai duga negatif 67,80%. Pemeriksaan IgG spesifik Aspergillus ELISA otomatis menunjukkan sensitivitas 91,67%, spesifisitas 75%, nilai duga positif 66,67%, dan nilai duga negatif 94,29%. Kesimpulan: Performa diagnostik dan teknis pemeriksaan IgG spesifik Aspergillus ELISA otomatis lebih baik dibandingkan ELISA manual, tetapi pemilihan modalitas diagnosis perlu mempertimbangkan faktor keterjangkauan, aksesibilitas, dan akurasi sesuai kebutuhan dan ketersediaan sumber daya. ......Introduction: Indonesia has high tuberculosis (TB) burden. The resulting lung damage underlies chronic pulmonary aspergillosis (CPA) development. CPA is diagnosed in patients with evidence of Aspergillus involvement as one of its criteria. Taking into account the limitations of culture, ELISA antibody detection becomes alternative modality. This study aims to compare diagnostic performance between manual and automated ELISA for Aspergillus-specific IgG in patients with treated TB. Method: This cross-sectional study compares Aspergillus-specific IgG test using Bordier manual ELISA and Immulite automated ELISA on sera from patients with treated TB. Diagnostic performance was compared in positive test proportion, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). Result: There are 68 subjects, with median age of 34,5 years, elderly subjects proportion of 11,76%, male proportion of 42,65%. Positive results proportion from Aspergillus-specific IgG manual and automated ELISA are 13,24% and 48,53%, respectively. Manual ELISA shows 20,83% sensitivity, 90,91% specificity, 55,56% PPV, 67,80% NPV. Automated ELISA shows 91,67% sensitivity, 75% specificity, 66,67% PPV, 94,29% NPV. Conclusion: Technical and diagnostic performance of automated ELISA Aspergillus-specific IgG test is better than manual ELISA, but choosing diagnostic modality needs consideration on factors such as affordability, accessibility, and accuracy according to the needs and available resources.