Tesis

Karakteristik Klinis dan Mikologis Pasien Aspergilosis Paru Kronik Pasca-Tuberkulosis Paru Sebelum dan Setelah Terapi Itrakonazol = Clinical and Mycological Characteristics of Chronic Pulmonary Aspergillosis in Post-Pulmonary Tuberculosis Patients Before and After Itraconazole Therapy.

Latar Belakang: Aspergilosis paru kronik (APK) merupakan komplikasi infeksi jamur yang sering menyertai penyakit paru kronik, khususnya tuberkulosis (TB) paru. Diagnosis APK di negara berkembang masih menghadapi berbagai kendala, seperti keterbatasan fasilitas diagnostik dan rendahnya kewaspadaan klinis. Diagnosis ditegakkan berdasarkan gejala kronis minimal 3 bulan, temuan radiologis kavitas atau aspergiloma, serta bukti mikologis berupa kultur Aspergillus spp. dan/atau antibodi IgG spesifik Aspergillus positif. Itrakonazol adalah terapi lini pertama, namun bukti mengenai perubahan karakteristik mikologis pasca-terapi masih terbatas. Tujuan: Mengetahui karakteristik klinis dan mikologis pasien APK pasca-TB paru serta mengevaluasi perubahan parameter klinis dan mikologis setelah terapi itrakonazol oral selama enam bulan. Metode: Penelitian ini menggunakan desain kohort prospektif terhadap pasien pascaTB paru yang diduga mengalami APK dan menjalani pemeriksaan klinis, radiologis, serta mikologis yang berasal dari RSUD Kota Tangerang dan RS Grha Permata Ibu Depok pada periode Juni 2023-Juli 2024. Diagnosis APK ditegakkan berdasarkan kriteria gejala kronis ≥3 bulan, temuan radiologis khas, serta hasil kultur dan/atau IgG spesifik Aspergillus positif. Terapi itrakonazol diberikan dengan dosis 2 × 200 mg/hari selama 6 bulan. Evaluasi dilakukan terhadap gejala klinis, kultur jamur, dan kadar IgG spesifik Aspergillus sebelum dan sesudah terapi. Hasil: Dari 55 subjek yang memenuhi kriteria inklusi, 49 (89,1%) memenuhi kriteria diagnosis APK. Sebanyak 25 subjek (51%) berhasil menyelesaikan terapi itrakonazol selama 6 bulan. Terdapat perbaikan bermakna pada seluruh gejala klinis: batuk (96% menjadi 20%; p < 0,001), hemoptisis (64% menjadi 4%; p < 0,001), nyeri dada (72% menjadi 12%; p < 0,001), sesak napas (88% menjadi 16%; p < 0,001), dan kelelahan (72% menjadi 24%; p=0,012). Meskipun terjadi penurunan proporsi kultur Aspergillus positif dari 72% menjadi 60%, perbedaannya tidak bermakna (p=0,581). Kadar IgG spesifik Aspergillus tetap stabil pada 68% pasien (p=1,000), tanpa penurunan bermakna pasca-terapi. Kesimpulan: Terapi itrakonazol oral selama enam bulan memberikan perbaikan klinis yang bermakna pada pasien APK pasca-TB paru, namun tidak disertai perubahan bermakna pada parameter mikologis, baik kultur maupun IgG Aspergillus. Hasil ini mendukung pentingnya pemantauan gejala klinis sebagai indikator evaluasi respons terapi, terutama di fasilitas dengan keterbatasan sumber daya.
Kata Kunci: Aspergilosis paru kronik, TB paru, itrakonazol, IgG Aspergillus, kultur jamur


Background: Chronic pulmonary aspergillosis (CPA) is a complication of fungal infection that often accompanies chronic lung diseases, especially pulmonary tuberculosis (TB). Diagnosis of CPA in developing countries still faces various obstacles, such as limited diagnostic facilities and low clinical alertness. Diagnosis is based on chronic symptoms for at least 3 months, radiologic findings of cavities or aspergillomas, and mycologic evidence of positive Aspergillus spp. culture and/or Aspergillus-specific IgG antibodies. Itraconazole is the first-line therapy, but evidence on post-therapy changes in mycological characteristics is limited. Objective: To determine the clinical and mycological characteristics of postpulmonary TB CPA patients and evaluate changes in clinical and mycological parameters after six months of oral itraconazole therapy. Methods: This study used a prospective cohort design of post- pulmonary TB patients suspected of having CPA and underwent clinical, radiologic, and mycologic examinations from Tangerang City Hospital and Grha Permata Ibu Depok Hospital in the period June 2023-July 2024. The diagnosis of CPA was based on the criteria of chronic symptoms ≥3 months, typical radiologic findings, and positive culture and/or Aspergillus-specific IgG results. Itraconazole therapy was given at a dose of 2 × 200 mg/day for 6 months. Evaluation was conducted on clinical symptoms, fungal culture, and Aspergillus-specific IgG levels before and after therapy. Results: Of the 55 subjects who met the inclusion criteria, 49 (89.1%) met the CPA diagnosis criteria. A total of 25 subjects (51%) successfully completed itraconazole therapy for 6 months. There was significant improvement in all clinical symptoms: cough (96% to 20%; p < 0.001), haemoptysis (64% to 4%; p < 0.001), chest pain (72% to 12%; p < 0.001), shortness of breath (88% to 16%; p < 0.001), and fatigue (72% to 24%; p=0.012). Although there was a decrease in the proportion of positive Aspergillus cultures from 72% to 60%, the difference was not significant (p=0.581). Aspergillusspecific IgG levels remained stable in 68% of patients (p=1.000), with no significant decrease post-therapy. Conclusion: Six months of oral itraconazole therapy provided significant clinical improvement in post-pulmonary TB CPA patients, but was not accompanied by significant changes in mycological parameters, both culture and Aspergillus IgG. These results support the importance of monitoring clinical symptoms as an indicator of evaluating therapy response, especially in facilities with limited resources.
Keywords: Chronic pulmonary aspergillosis, pulmonary TB, itraconazole, Aspergillus IgG, fungal culture