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Fulltext Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study

Javaid A, Ahmad N, Afridi AK, Basit A, Khan AH, Ahmad I, et al.

Am J Trop Med Hyg, 2018 06;98(6):1629-1636.
PMID: 29611497 DOI: 10.4269/ajtmh.17-0936

To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429-0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522-0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595-0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69-69.32), 93.0% (95% CI = 89.69-95.52), and 97.6% (95% CI = 95.27-98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53-76.73), 51.5% (95% CI = 41.25-61.68), and 44.4% (95% CI = 34.45-54.78), respectively. Furthermore, patients' age of 41-60 (odds ratio [OR] = 0.202; 95% CI = 0.067-0.605) and > 60 years (OR = 0.051; 95% CI = 0.011-0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462-5.952), previous SLD use (OR = 0.277; 95% CI = 0.097-0.789), lung cavitation (OR = 0.196; 95% CI = 0.103-0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198-0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34-71.85) than at 4 months (OR = 14.13; 95% CI = 7.92-25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.

Matched MeSH terms: Lung/pathology
Unexpected infant death secondary to a pulmonary infiltration due to acute myelocytic leukaemia

Ben Khelil M, Chkirbene Y, Mlika M, Haouet S, Hamdoun M

Malays J Pathol, 2017 Aug;39(2):193-196.
PMID: 28866704

Acute myeloid leukaemia (AML) often presents with non-specific symptoms such as fatigue, anaemia or infection. Pulmonary involvement is uncommon in AML during the course of the disease and is usually caused by infection, haemorrhage, leukaemic pulmonary infiltrates and leukostasis. Lung localization of AML is very uncommon and potentially life threatening if not diagnosed and treated rapidly. The authors describe the sudden death of an asymptomatic five-month-infant because of a misdiagnosed lung localization of AML. Autopsy examination followed by histopathological studies showed an extensive leukostasis and extramedullary leukaemic infiltrating the lungs. Special stains and immunohistochemical studies revealed findings consistent with acute myelogenous leukaemia. This case suggests that underlying acute leukaemia should be considered as a cause of flu-like symptoms in infants. Medical personnel are urged to be alert to fever, sore throat, weakness and dyspnea that may be characteristic of serious systemic diseases.

Matched MeSH terms: Lung/pathology*
Fulltext Understanding Lung Carcinogenesis from a Morphostatic Perspective: Prevention and Therapeutic Potential of Phytochemicals for Targeting Cancer Stem Cells

Heng WS, Kruyt FAE, Cheah SC

Int J Mol Sci, 2021 May 27;22(11).
PMID: 34071790 DOI: 10.3390/ijms22115697

Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells-the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.

Matched MeSH terms: Lung/pathology
Fulltext Triple primary cancers of the larynx, lung and thyroid presenting in one patient

Iqbal FR, Sani A, Gendeh BS, Aireen I

Med J Malaysia, 2008 Dec;63(5):417-8.
PMID: 19803306 MyJurnal

Patients with multiple malignant primary tumours are often described, based on their chronology of presentation, as simultaneous, synchronous or metachronous tumours. Lung malignancies presenting in association with head and neck tumours are well documented while there have been small series of thyroid synchronous cancers presenting with laryngeal lesions in literature. No cases, to our knowledge, have been reported in literature of a single patient with all three laryngeal, lung and thyroid malignancies. We report one such case of a 71-year-old Chinese man who had undergone a total laryngectomy for a recurrent cancer of the larynx only to be found to have tumours of the lung and thyroid in the post-operative period and he eventually died of post-operative complications. We also discuss screening for lung and thyroid malignancies in patients with head and neck squamous cell carcinoma (SCC).

Matched MeSH terms: Lung/pathology
The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis

Bhat AA, Afzal M, Goyal A, Gupta G, Thapa R, Almalki WH, et al.

Chem Biol Interact, 2024 May 01;394:111002.
PMID: 38604395 DOI: 10.1016/j.cbi.2024.111002

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.

Matched MeSH terms: Lung/pathology
The great masquerade: Empyema thoracis as an unusual presentation of primary lung malignancy

Nyanti LE, Kho SS, Tie ST

Med J Malaysia, 2019 02;74(1):79-81.
PMID: 30846667

Primary lung malignancy presenting as empyema is rare, with a reported incidence of 0.3%. We report a case of a 60- year-old man presenting with unilateral pleural effusion; diagnostic thoracocentesis confirmed Salmonella empyema. Post-drainage, chest radiograph showed persisting right hemithorax opacity; subsequent computed tomography revealed a right lung mass with right upper lobe bronchus obliteration. Percutaneous biopsy confirmed advanced stage lung adenocarcinoma. We discuss the mechanism of post-obstructive pneumonia in lung cancerassociated empyema and the utility of bedside ultrasound in diagnosis of lung masses. Clinicians are alerted to the possibility of lung malignancy in elderly patients presenting with empyema.

Matched MeSH terms: Lung/pathology
The goat as a model for studies of pneumonic pasteurellosis caused by Pasteurella multocida

Zamri-Saad M, Effendy WM, Maswati MA, Salim N, Sheikh-Omar AR

Br. Vet. J., 1996 Jul;152(4):453-8.
PMID: 8791853

A model of pneumonic pasteurellosis has been established in goats using Pasteurella multocida harvested from pneumonic lungs of goats (types A and D), rabbits (type A) and sheep (type D). The resultant infections were acute, subacute or chronic. The gross and histological lesions of the subacute and chronic infections were typical of pneumonic pasteurellosis. P. multocida type D produced significantly (P < 0.01) more severe lesions when compared with other isolates. There were strong correlations between the clinical signs and the severity of lesions.

Matched MeSH terms: Lung/pathology
Fulltext The Nature of Exposure Drives Transmission of Nipah Viruses from Malaysia and Bangladesh in Ferrets

Clayton BA, Middleton D, Arkinstall R, Frazer L, Wang LF, Marsh GA

PLoS Negl Trop Dis, 2016 06;10(6):e0004775.
PMID: 27341030 DOI: 10.1371/journal.pntd.0004775

Person-to-person transmission is a key feature of human Nipah virus outbreaks in Bangladesh. In contrast, in an outbreak of Nipah virus in Malaysia, people acquired infections from pigs. It is not known whether this important epidemiological difference is driven primarily by differences between NiV Bangladesh (NiV-BD) and Malaysia (NiV-MY) at a virus level, or by environmental or host factors. In a time course study, ferrets were oronasally exposed to equivalent doses of NiV-BD or NiV-MY. More rapid onset of productive infection and higher levels of virus replication in respiratory tract tissues were seen for NiV-BD compared to NiV-MY, corroborating our previous report of increased oral shedding of NiV-BD in ferrets and suggesting a contributory mechanism for increased NiV-BD transmission between people compared to NiV-MY. However, we recognize that transmission occurs within a social and environmental framework that may have an important and differentiating role in NiV transmission rates. With this in mind, ferret-to-ferret transmission of NiV-BD and NiV-MY was assessed under differing viral exposure conditions. Transmission was not identified for either virus when naïve ferrets were cohoused with experimentally-infected animals. In contrast, all naïve ferrets developed acute infection following assisted and direct exposure to oronasal fluid from animals that were shedding either NiV-BD or NiV-MY. Our findings for ferrets indicate that, although NiV-BD may be shed at higher levels than NiV-MY, transmission risk may be equivalently low under exposure conditions provided by cohabitation alone. In contrast, active transfer of infected bodily fluids consistently results in transmission, regardless of the virus strain. These observations suggest that the risk of NiV transmission is underpinned by social and environmental factors, and will have practical implications for managing transmission risk during outbreaks of human disease.

Matched MeSH terms: Lung/pathology
Fulltext The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression

Lee SS, Cheah YK

J Immunol Res, 2019;2019:3046379.
PMID: 30944831 DOI: 10.1155/2019/3046379

Cellular components of the tumour microenvironment (TME) are recognized to regulate the hallmarks of cancers including tumour proliferation, angiogenesis, invasion, and metastasis, as well as chemotherapeutic resistance. The linkage between miRNA, TME, and the development of the hallmarks of cancer makes miRNA-mediated regulation of TME a potential therapeutic strategy to complement current cancer therapies. Despite significant advances in cancer therapy, lung cancer remains the deadliest form of cancer among males in the world and has overtaken breast cancer as the most fatal cancer among females in more developed countries. Therefore, there is an urgent need to develop more effective treatments for NSCLC, which is the most common type of lung cancer. Hence, this review will focus on current literature pertaining to antitumour or protumourigenic effects elicited by nonmalignant stromal cells of TME in NSCLC through miRNA regulation as well as current status and future prospects of miRNAs as therapeutic agents or targets to regulate TME in NSCLC.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology*
Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.

Life Sci, 2021 Feb 15;267:118973.
PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.

Matched MeSH terms: Lung/pathology
Fulltext Syrian hamsters (Mesocricetus auratus) oronasally inoculated with a Nipah virus isolate from Bangladesh or Malaysia develop similar respiratory tract lesions

Baseler L, de Wit E, Scott DP, Munster VJ, Feldmann H

Vet Pathol, 2015 Jan;52(1):38-45.
PMID: 25352203 DOI: 10.1177/0300985814556189

Nipah virus is a paramyxovirus in the genus Henipavirus, which has caused outbreaks in humans in Malaysia, India, Singapore, and Bangladesh. Whereas the human cases in Malaysia were characterized mainly by neurological symptoms and a case fatality rate of ∼40%, cases in Bangladesh also exhibited respiratory disease and had a case fatality rate of ∼70%. Here, we compared the histopathologic changes in the respiratory tract of Syrian hamsters, a well-established small animal disease model for Nipah virus, inoculated oronasally with Nipah virus isolates from human cases in Malaysia and Bangladesh. The Nipah virus isolate from Bangladesh caused slightly more severe rhinitis and bronchointerstitial pneumonia 2 days after inoculation in Syrian hamsters. By day 4, differences in lesion severity could no longer be detected. Immunohistochemistry demonstrated Nipah virus antigen in the nasal cavity and pulmonary lesions; the amount of Nipah virus antigen present correlated with lesion severity. Immunohistochemistry indicated that both Nipah virus isolates exhibited endotheliotropism in small- and medium-caliber arteries and arterioles, but not in veins, in the lung. This correlated with the location of ephrin B2, the main receptor for Nipah virus, in the vasculature. In conclusion, Nipah virus isolates from outbreaks in Malaysia and Bangladesh caused a similar type and severity of respiratory tract lesions in Syrian hamsters, suggesting that the differences in human disease reported in the outbreaks in Malaysia and Bangladesh are unlikely to have been caused by intrinsic differences in these 2 virus isolates.

Matched MeSH terms: Lung/pathology
Fulltext Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

Abdul Satar N, Ismail MN, Yahaya BH

Molecules, 2021 Feb 18;26(4).
PMID: 33670440 DOI: 10.3390/molecules26041056

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology*
Survival of lung cancer patients in a resource-limited country

How SH, Ng TH, Kuan YC, Jamalludin AR, Fauzi AR

Asia Pac J Clin Oncol, 2015 Sep;11(3):221-7.
PMID: 24575820 DOI: 10.1111/ajco.12179

Data on lung cancer survival are lacking in developing countries. Our objectives were to describe the survival of our lung cancer patients and to determine independent prognostic factors affecting survival.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb

Singh GD, Ganjoo M, Youssouf MS, Koul A, Sharma R, Singh S, et al.

Food Chem Toxicol, 2009 Oct;47(10):2661-5.
PMID: 19654032 DOI: 10.1016/j.fct.2009.07.031

Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as "Kacip Fatimah". Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women's health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns.

Matched MeSH terms: Lung/pathology
Fulltext Small Cell Transformation and T790M Mutation as Coresistance Mechanisms for First-line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy Failure

Shee-Chai C, Liam CK, Mun KS

J Thorac Oncol, 2017 10;12(10):e171-e173.
PMID: 28939153 DOI: 10.1016/j.jtho.2017.06.068
Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Single-walled carbon nanotubes (SWCNTs) inhibit heat shock protein 90 (HSP90) signaling in human lung fibroblasts and keratinocytes

Ong LC, Tan YF, Tan BS, Chung FF, Cheong SK, Leong CO

Toxicol Appl Pharmacol, 2017 08 15;329:347-357.
PMID: 28673683 DOI: 10.1016/j.taap.2017.06.024

Single-walled carbon nanotubes (SWCNTs) are carbon-based nanomaterials that possess immense industrial potential. Despite accumulating evidence that exposure to SWCNTs might be toxic to humans, our understanding of the mechanisms for cellular toxicity of SWCNTs remain limited. Here, we demonstrated that acute exposure of short (1-3μm) and regular-length (5-30μm) pristine, carboxylated or hydroxylated SWCNTs inhibited cell proliferation in human somatic and human stem cells in a cell type-dependent manner. The toxicity of regular-length pristine SWCNT was most evidenced in NP69>CYT00086>MCF-10A>MRC-5>HaCaT > HEK-293T>HepG2. In contrast, the short pristine SWCNTs were relatively less toxic in most of the cells being tested, except for NP69 which is more sensitive to short pristine SWCNTs as compared to regular-length pristine SWCNTs. Interestingly, carboxylation and hydroxylation of regular-length SWCNTs, but not the short SWCNTs, significantly reduced the cytotoxicity. Exposure of SWCNTs also induced caspase 3 and 9 activities, mitochondrial membrane depolarization, and significant apoptosis and necrosis in MRC-5 embryonic lung fibroblasts. In contrast, SWCNTs inhibited the proliferation of HaCaT human keratinocytes without inducing cell death. Further analyses by gene expression profiling and Connectivity Map analysis showed that SWCNTs induced a gene expression signature characteristic of heat shock protein 90 (HSP90) inhibition in MRC-5 cells, suggesting that SWCNTs may inhibit the HSP90 signaling pathway. Indeed, exposure of MRC-5 cells to SWCNTs results in a dose-dependent decrease in HSP90 client proteins (AKT, CDK4 and BCL2) and a concomitant increase in HSP70 expression. In addition, SWCNTs also significantly inhibited HSP90-dependent protein refolding. Finally, we showed that ectopic expression of HSP90, but not HSP40 or HSP70, completely abrogated the cytotoxic effects of SWCNTs, suggesting that SWCNT-induced cellular toxicity is HSP90 dependent. In summary, our findings suggest that the toxic effects of SWCNTs are mediated through inhibition of HSP90 in human lung fibroblasts and keratinocytes.

Matched MeSH terms: Lung/pathology
Sarcoidosis in Singapore: epidemiology, clinical presentation and ethnic differences

Anantham D, Ong SJ, Chuah KL, Fook-Chong S, Hsu A, Eng P

Respirology, 2007 May;12(3):355-60.
PMID: 17539838

The aim of this study is to better understand the epidemiological and clinical features of patients with sarcoidosis in Singapore and to ascertain if ethnic differences exist.

Matched MeSH terms: Lung/pathology
Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro

Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.

Life Sci, 2021 Jul 01;276:119436.
PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer

Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, et al.

J Thorac Oncol, 2018 10;13(10):1539-1548.
PMID: 29966800 DOI: 10.1016/j.jtho.2018.06.012

INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.
METHODS: In this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration-time curve of 5-6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point.
RESULTS: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286-0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6-93.2%) with crizotinib versus 45.6% (95% CI: 35.8-55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients.
CONCLUSIONS: First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Respiratory health status of workers that exposed to welding fumes at Lumut shipyard

Ithnin A, Zubir A, Awang N, Mohamad Sulaiman NN

Pak J Biol Sci, 2019 Jan;22(3):143-147.
PMID: 30972984 DOI: 10.3923/pjbs.2019.143.147

BACKGROUND AND OBJECTIVE: Welding fume exposure has led to the respiratory problems among welders including cough, phlegm, chest illnesses, nausea and fatigue. Inadequate ventilation during welding works causes the situation to worsen. Welding fumes can cause a decrease in lung function among welders. Chronic exposure will lead to other health effects especially COPD (Chronic Obstructive Pulmonary Disease). The objective of this study is to determine the exposure of welding fumes (Cd, Fe, Pb and Zn) towards respiratory health including lung function test (FEV1, FVC, FEV1/FVC, PEFR) of workers in Lumut shipyard, Perak.

MATERIAL AND METHODS: This research study the relationship between exposures of welding fumes towards lung function test among workers in Lumut shipyard, Perak. Lung function test was measured by spirometry among 30 welders and 31 non-welders. The concentration welding fume exposure was measured using OSHA ID-121 method. Sociodemographic data, respiratory symptoms and smoking habit data was analyzed based on the ATS 1987 questionnaire.

RESULTS: The mean concentration for Pb in welding fumes was 2.752 mg m-3 which is above 0.5 mg m-3 PEL-TWA. The FEV1 and FVC readings showed significant different between welders and non-welders (p = 0.001). Cough and phlegm symptoms showed significant different between welders and non-welders (p = 0.001). Welders had higher prevalence in smoking habit than the non-welders. Chest illnesses symptom showed an association with the smoking habit (p = 0.01).

CONCLUSION: There is relationship between welding fumes exposure on lung function test of workers in Lumut shipyard. Pb in welding fumes has high concentration and exceeded PEL-TWA level. The FEV1 and FVC in welders are lower than non-welder due to the fumes exposure. Welders showed higher respiratory symptoms than non-welders. Smoking habit is a contributing factor towards respiratory problem.

Matched MeSH terms: Lung/pathology*

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