Yong-Kek Pang

Pulmonary tuberculosis presenting as community-acquired pneumonia.

Objective and background:  The aims of this study were to investigate the frequency of Mycobacterium tuberculosis as a cause of community‐acquired pneumonia (CAP) requiring hospitalization in Malaysia, and to define the clinical features of pulmonary tuberculosis (PTB) that distinguish it from non‐TB CAP.

Successful pregnancy with epidermal growth factor receptor tyrosine kinase inhibitor treatment of metastatic lung adenocarcinoma presenting with respiratory failure

We report a woman presenting with respiratory failure due to a right-sided pleural effusion, lung metastases and lymphangitis carcinomatosis from advanced lung adenocarcinoma in the third trimester of pregnancy, who showed good response to EGFR tyrosine kinase inhibitor.

Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014.

Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012–2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors—total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012–2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013–2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.

Detection of airflow limitation using a handheld spirometer in a primary care setting

Early diagnosis of chronic obstructive pulmonary disease (COPD) in primary care settings is difficult to achieve chiefly due to lack of availability of spirometry. This study estimated the prevalence of airflow limitation among chronic smokers using a handheld spirometer in this setting.

190TiP: ELUXA 1: Phase II study of BI 1482694 (HM61713) in patients (pts) with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)

effusion. There were 410 male and 120 female, with a mean age of 54 years. In 401 patients VATS was performed under general anaesthesia and 129 patients under local ansestesia and i/v potencation. The pleural effusion was carefully aspirated; fibrinous adhesions were taken down while dense fibrous adhesions were selectively divided; some limited decortications were also performed. Multiple pleural biopsies were always performed. Pleurodesis was performed with 5 g of sterile purified talc insufflated through a talc atomizer 50 patients, and with solution bethadini 10%-20 cc + 80ml sodium solution in 310 patients and partial and sub total pleurectomy 120 patients. One chest tube was left in situ for 3–5 days.But in 15 patients for long time more than one month. Results: Operative mortality was 0.94% (five cases). Postoperative complications occurred in 25 cases (4.7%). Specific histologic diagnosis was obtained in 91% patients. Follow-up was available for 523 patients (98.6%). After a median follow-up of 60 months (range 3–100 months), talc pleurodesis was successful in controlling recurrence of effusion in 90% (45 out of 50) of patients and for bethadin pleurodesis was 87.7% (272 out of 310). The success rate did not show any statistically significant difference between patients who underwent talc pleurodesis and bethadin pleurodesis.In patients with failure pleurodesis in bothe grup a redo-VATS was performed or are follow up by thoracocentesis or redo-only pleural drainage. Conclusions: VATS represents the method of choice for both diagnosis and treatment of malignant recurrent pleural effusions. Talc poudrage also bethadine pleurodesis are safe and effective in obtaining pleurodesis. Clinical trial identification: N/A Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest.

Community-acquired pneumonia: An Asia Pacific perspective

Community-acquired pneumonia (CAP) is a common illness that is potentially life-threatening especially in older adults and those with comorbid disease. Although many microorganisms can cause CAP, it is a small number of key pathogens that cause most cases. Streptococcus pneumoniae is the most frequently identified pathogen, with the highest incidence of this organism reported in studies that used urinary antigen detection. Haemophilus influenzae, atypical pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila) and viruses are the other commonly identified pathogens of CAP. Gram-negative bacilli (Enterobacteriaceae and Pseudomonas aeruginosa) are the causative agents in patients who have had previous antimicrobial treatment or who have pulmonary comorbidities such as bronchiectasis or COPD. Even when carefully sought for in prospective studies, the causative organism remains unknown in about half of the patients. Reasons for failure to identify the aetiological organism include previous antibiotic treatment, unusual pathogens that go unrecognized, viral infections and pathogens that are currently not recognized. MICROBIAL AETIOLOGY OF COMMUNITY-ACQUIRED PNEUMONIA IN THE ASIA PACIFIC REGION

Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes.

Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November–April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.

Epidermal growth factor receptor mutations in non- small cell lung cancers in a multiethnic malaysian patient population.

BACKGROUND Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non- small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. MATERIALS AND METHODS In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. RESULTS EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002). CONCLUSIONS In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

Epidermal growth factor receptor targeted therapy with gefitinib in locally advanced and metastatic primary lung adenocarcinoma

Objective:  To describe the efficacy of monotherapy with the epidermal growth factor receptor‐tyrosine kinase inhibitor, gefitinib in patients with locally advanced and metastatic primary lung adenocarcinoma.

Outbreaks of enterovirus D68 in Malaysia: genetic relatedness to the recent US outbreak strains.

Outbreaks of enterovirus D68 in Malaysia: genetic relatedness to the recent US outbreak strains