Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear.

Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers.

Background: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking.

Methods: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively.

Pathological complete response in an advance stage IIIB non-small cell lung cancer secondary to neoadjuvant osimertinib targeted therapy: A case report and review of literature.

Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non-small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC.

Sensitisation to recombinant allergens and clinical outcomes in COPD.

Background: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown.

Methods: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong.

Outcomes of Patients with Mutant Advanced NSCLC in a Developing Country in Southeast Asia.

Background: Although first- and second-generation EGFR TKIs are considered first-line treatment in EGFRm+ NSCLC, most patients develop resistance and progress, commonly, EGFR mutation. The third-generation EGFR-TKI has demonstrated efficacy in patients with progressive disease harboring the mutation and in the first-line setting, bypassing this mode of resistance. The primary objectives of this study are to describe the proportion of m+ NSCLC patients treated with first-, second- and third-generation EGFR TKIs, and cytotoxic chemotherapy in the first-line setting, and the time on treatment for each category.

Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance.

Background: Tyrosine kinase inhibitor (TKI) treatment has significantly improved the prognosis of oncogenic-driven lung adenocarcinoma (LUAD). However, drug resistance limits the long-term benefits of patients. Therefore, there is a pressing need to explore the mechanism of TKI resistance and identify new therapeutic targets.

Programmed death-ligand 1 expression and use of immune checkpoint inhibitors among patients with advanced non-small-cell lung cancer in a resource-limited country.

Introduction: Immune checkpoint inhibitor (ICI) therapy is an established treatment for advanced non-small-cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) expression is a recognized biomarker to determine response to therapy. We retrospectively analyzed NSCLC patients in the Malaysia Lung Cancer Registry (MLCR) and report on the clinical characteristics associated with PD-L1 expression and ICI use in Malaysia, a low- to middle-income country.

Methods: All 901 NSCLC patients in the MLCR who were diagnosed from January 1, 2017 to December 31, 2020 from 14 hospitals across the country were analyzed.

High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown.

Research Question: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap?

Study Design: Prospective, observational, cross-sectional study.

Influenza in Malaysian adult patients hospitalized with community-acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease or asthma: a multicenter, active surveillance study.

Background: Available data on influenza burden across Southeast Asia are largely limited to pediatric populations, with inconsistent findings.

Methods: We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018-August 2019) and described the distribution of causative influenza strains.

Management of Asthma Exacerbations in Southeast Asian Tertiary Care.

Background: There have been limited reports looking into the care of patients with asthma exacerbations admitted to tertiary hospitals in Southeast Asia. This study aims to determine the extent in which the 2019 Global Initiative for Asthma (GINA) guidelines were being met.

Methods: A retrospective study of patients with asthma exacerbations admitted to the University of Malaya Medical Centre (UMMC) and Pantai Hospital Kuala Lumpur (PHKL), Malaysia from 1 July 2019 to 31 December 2019.

Integrative microbiomics in bronchiectasis exacerbations.

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.

Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/β-catenin signaling pathway in taxol-resistant human lung adenocarcinoma.

Background: Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance.

A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD.

Introduction: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain.

Methods: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47).

Accuracy of lung cancer staging in the multidisciplinary team setting.

Accurate staging of lung cancer is of utmost importance in determining the stage-appropriate treatment and prognosis. Imaging tests which include contrast-enhanced computed tomography (CT) examination of the chest to include the liver and adrenal glands and 18-fluoro-2 deoxyglucose positron emission tomography (PET)/CT scan facilitate the initial tumor node metastasis (TNM) staging of the disease and provide guidance on the optimal biopsy site and biopsy method. The diagnostic and staging approach should be tailored to the individual patient according to risk, benefit, patient preferences, and available expertise.

Predictors of Acquired Mutation in Patients Failing First- or Second-Generation -Tyrosine Kinase Inhibitors.

Background: This study aims to determine the predictors of acquired mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing ( mutation following the failure of first- or second-generation -tyrosine kinase inhibitor (TKI).

Methods: This is a retrospective observational study of NSCLC patients with sensitising mutation experiencing disease progression (PD) whilst on first- or second-generation -TKIs with subsequent investigations to detect acquired mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.

Results: A total of 87 patients were included.

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD.

Introduction: Allergic sensitisation to fungi such as are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear.

Methods: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD.

"High-Risk" Clinical and Inflammatory Clusters in COPD of Chinese Descent.

Background: COPD is a heterogeneous disease demonstrating inter-individual variation. A high COPD prevalence in Chinese populations is described, but little is known about disease clusters and prognostic outcomes in the Chinese population across Southeast Asia. We aim to determine if clusters of Chinese patients with COPD exist and their association with systemic inflammation and clinical outcomes.

Epithelial-to-mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy.

Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy.

Epithelial-to-mesenchymal transition (EMT) causing acquired resistance to afatinib in a patient with epidermal growth factor receptor ()-mutant lung adenocarcinoma.

We report the first case of epithelial-to-mesenchymal transition (EMT) as the cause of acquired resistance to the second-generation -tyrosine kinase inhibitor (TKI), afatinib in a patient with advanced non-small cell lung cancer (NSCLC) harboring a sensitizing mutation. Patients with -mutant NSCLC inevitably develop acquired resistance while on -TKI treatment. EMT which renders cancer cells more invasive and migratory is one of the mechanisms of acquired resistance to -TKIs and correlates with a poor prognosis.

Endobronchial metastasis from resected renal cell carcinoma causing total lung collapse.

We report a man presenting with dyspnea, cough, and hemoptysis due to left lung collapse from an endobronchial tumor obstructing the left main bronchus. Endobronchial biopsy of the tumor showed renal cell carcinoma, identical to a previous specimen of renal cell carcinoma removed by a radical left nephrectomy five years ago. The endobronchial tumor was removed by snare diathermy through a flexible bronchoscope, following which his symptoms resolved and the left lung re-expanded.