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Sastia Rakhma
Institute of Clinical Medicine, Faculty of Medicine, National Cheng Kung University, Tainan, Taiwan.
Health Professions Medicine & Pharmacology Public Health

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Pulmonary Langerhans Cell Histiocytosis: Insights into Pathogenesis, Diagnostic Challenges, and Management Strategies Peter Krisdiyanto; Iin Noor Chozin; Sastia Rakhma
Jurnal Respirasi Vol. 12 No. 3 (2026): September 2026
Publisher : Faculty of Medicine Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jr.v12-I.3.2026.282-291

Abstract

Introduction: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease strongly linked to cigarette smoking, characterized by nodular and cystic lesions predominantly in the upper and middle lung zones. The disease course is heterogeneous, ranging from spontaneous remission to progressive respiratory failure, with diagnostic and therapeutic challenges requiring a multidisciplinary approach. Methods: This narrative review synthesized evidence from peer-reviewed journals and updated guidelines published in the last decade, emphasizing studies within the past five years. Relevant articles were identified through electronic databases focusing on epidemiology, pathogenesis, diagnostic modalities, and management strategies of PLCH. Results: Cigarette smoke is the main environmental trigger, sustaining Langerhans cell proliferation and chronic inflammation. Molecular studies demonstrate recurrent somatic mutations, particularly BRAF V600E and MAP2K1, confirming PLCH as an inflammatory myeloid neoplasm and supporting targeted therapy. High-resolution computed tomography (HRCT) remains the imaging cornerstone, showing nodular and cystic changes, while histopathology with immunohistochemistry (CD1a, langerin, S100) is the diagnostic gold standard. Pulmonary function testing, bronchoalveolar lavage, and molecular assays add diagnostic precision. Management emphasizes smoking cessation as the primary intervention, with variable outcomes from glucocorticoids and chemotherapy. Targeted therapy with BRAF and MEK inhibitors shows promise in mutation-positive patients, though long-term safety is still under study. For advanced disease, pulmonary hypertension management and lung transplantation are considered. Conclusion: PLCH illustrates the interaction between environmental exposure and molecular oncogenesis. Early diagnosis via HRCT and molecular confirmation is essential, smoking cessation remains central, and ongoing research into biomarkers and targeted interventions may improve personalized outcomes.
Nanoparticles in Cancer Therapy: Recent Advances and Clinical Implications in Pulmonary Oncology Albert Lyono; Ungky Agus Setyawan; Sastia Rakhma
Jurnal Respirasi Vol. 12 No. 3 (2026): September 2026
Publisher : Faculty of Medicine Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jr.v12-I.3.2026.292-300

Abstract

Introduction: Lung cancer remains the leading cause of cancer-related mortality worldwide and in Indonesia, with most patients presenting at advanced stages and experiencing limited survival. Conventional therapies such as surgery, chemotherapy, and radiotherapy face major limitations, including systemic toxicity, poor specificity, and treatment resistance. Nanotechnology has emerged as a transformative approach in oncology, offering novel solutions for diagnosis and therapy through nanoparticles with unique physicochemical properties. Methods: This narrative literature review synthesized evidence from the past five years using PubMed, Scopus, and Google Scholar. Articles were selected for relevance to nanoparticle applications in lung cancer. Data extraction emphasized diagnostic advances, therapeutic strategies including chemotherapy, radiotherapy, and immunotherapy, as well as emerging modalities and translational challenges. Results: Nanoparticles show strong potential to improve diagnostic accuracy and therapeutic efficacy. As imaging contrast agents in CT, MRI, and PET, nanoparticles such as gold and superparamagnetic iron oxide enhance sensitivity and specificity. In chemotherapy, delivery systems including liposomes, polymer, and lipid nanoparticles increase bioavailability while reducing toxicity. Metallic nanoparticles serve as radiosensitizers in radiotherapy, mitigating resistance and sparing normal tissues. Nanoparticles also act as carriers for checkpoint inhibitors, cytokines, and vaccines to enhance immune activation. Emerging modalities include photothermal therapy, cryosurgery, and gene or mRNA delivery. Despite these advances, challenges persist regarding toxicity, long-term biodistribution, scalability, regulatory approval, and cost-effectiveness, particularly in low–middle income countries. Conclusion: Nanoparticles represent a promising paradigm shift in pulmonary oncology, offering precision, reduced toxicity, and integration with personalized and precision medicine to improve lung cancer outcomes.
Case Series: Uncommon and Compound Mutations Exon 19 Deletion/20 Insertion and Exon 21 L858R/V834L in Lung Adenocarcinoma Hendro Suryadi; Ungky Agus Setyawan; Yani Jane Sugiri; Dini Rachma Erawati; Hendy Setyo Yudhanto; Sastia Rakhma
Jurnal Respirasi Vol. 12 No. 3 (2026): September 2026
Publisher : Faculty of Medicine Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jr.v12-I.3.2026.258-266

Abstract

Introduction: Mutation in lung adenocarcinoma pose significant challenges in lung malignancy management. Next‑generation sequencing can reveal uncommon variants and drug‑resistance mechanisms that require personalized therapy. Case: First case, 68 years old female diagnosed with lung nodules since 2021 without regular check-ups. In September 2023, the patient diagnosed with Left Lung Adenocarcinoma T4N2M1b stage IVA with EGFR exon 20 insertion but she refused chemotherapy and got afatinib for seven months until the symptoms re-occurred. EGFR with NGS in March 2024 showed additional exon 19 deletion and afatinib continued till the patient showing grade III cutaneous–gastrointestinal adverse effects and followed by dosage adjustment Patient's condition worsened in June 2024. Second case, 61 years old female diagnosed with right lung adenocarcinoma T4N2M1c Stage IVB with exon 21 L858R in January 2022. Patient underwent afatinib therapy showing good results. After 24 months, subsequently became symptomatic, and EGFR testing detected additional T790M EGFR gene leading treatment change to osimertinib with unsatisfactory results. NGS-liquid biopsy in May 2024 showed compound mutation exon 21 L858R - exon 21 V834L with resistance to osimertinib. Patient’s condition worsened in August 2024. Conclusion: Lung adenocarcinoma can mutate to not only uncommon but also rare mutations, such as exon 20 insertion and V834L, leading to TKI resistance despite the patient's clinical improvement. This represents a significant therapeutic challenge in the management of adenocarcinoma and requires a comprehensive, personalized treatment approach. Keywords: Adenocarcinoma, Uncommon mutation, Drug Resistance
Integrated Exhaled Breath VOC Profiling and Serum sICAM-1 for Biomarker Characterization in Drug-Sensitive and Drug-Resistant Tuberculosis Hustorio Aliongko Simamora; Iin Noor Chozin; Ngakan Putu Parsama Putra; Arinto Yudi Ponco Wardoyo; Ani Budi Astuti; Sastia Rakhma
Jurnal Respirasi Vol. 12 No. 3 (2026): September 2026
Publisher : Faculty of Medicine Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jr.v12-I.3.2026.202-211

Abstract

Introduction: Rapid, non-invasive screening for drug-resistant tuberculosis (DR-TB) is urgently needed in high-burden settings such as Indonesia, where sputum-based diagnostics have practical limitations. Integrating exhaled breath volatile organic compounds (VOCs), which reflect host–pathogen metabolic interactions, with serum soluble intercellular adhesion molecule-1 (sICAM-1), a marker of endothelial activation and inflammation, may improve early detection. This study evaluated the combined potential of VOC profiling and sICAM-1 to distinguish drug-sensitive TB (DS-TB), DR-TB, and healthy controls. Methods: A prospective cross-sectional study was conducted in four TB referral hospitals in East Java, Indonesia. Eighty-eight participants were enrolled: DS-TB (n=32), DR-TB (n=30), and healthy controls (n=26). Exhaled breath VOC profiles were analyzed using a breath analyzer, and serum sICAM-1 levels were measured by enzyme-linked immunosorbent assay. Group comparisons used ANOVA or Kruskal–Wallis tests with post hoc analyses, and correlations were assessed using Pearson or Spearman tests. Results: Serum sICAM-1 levels were significantly higher in both TB groups than in controls (p<0.01) but did not differ between DS-TB and DR-TB (p=0.961). Several VOC components differed significantly, particularly formaldehyde, acetone, and methane (CH₄). CH₄ levels were significantly higher in DR-TB than in DS-TB and controls (p<0.05). A weak negative correlation between formaldehyde and sICAM-1 was observed in DS-TB (r = −0.355; p = 0.046). Conclusion: Integrating VOC profiling with sICAM-1 assessment offers a promising non-invasive strategy for TB screening. While sICAM-1 reflects inflammatory activity, methane-based VOC signatures may improve identification of DR-TB.
Co-Authors Albert Lyono Ani Budi Astuti Arinto Yudi Ponco Wardoyo Dini Rachma Erawati Hendro Suryadi Hendy Setyo Yudhanto Hustorio Aliongko Simamora Iin Noor Chozin Ngakan Putu Parsama Putra Peter Krisdiyanto Ungky Agus Setyawan Yani Jane Sugiri