Vol 3-2 Summary

A summary of Evaluation of Asthma Control in Children Using Childhood-Asthma Control Test (CACT) and Asthma Therapy Assessment Questionnaire (ATAQ)

AR Somashekar*, KG Ramakrishnan

Department of Pediatrics, MS Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India

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Vol 3-2 Review

Fluticasone Furoate: A Once Daily Preparation in Patients with Persistent Asthma

Paul A. Lilburn1*, Henry Ainge-Allen1, Paul S. Thomas1,2

1Department of Respiratory Medicine, Prince of Wales’ Hospital

2Prince of Wales’ Clinical School and Mechanisms of Disease and Translational Research, University of New South Wales, NSW, Faculty of Medicine, University of New South Wales, NSW, Australia

Asthma affects approximately 240 million people worldwide. It is characterised by an allergic pattern of smooth muscle constriction and airway inflammation, and if chronic, the inflammation can lead to structural changes and fixed airflow obstruction. Bronchodilators relieve the bronchoconstriction, while inhaled corticosteroids reduce the airway inflammation. This paper reviews fluticasone furoate (FF), a novel inhaled corticosteroid with 24-hour duration of action. It is a synthetic fluorinated corticosteroid with agonist activity at the glucocorticoid receptor (GRE). It is reported to have a fast association and slow dissociation from the GRE compared to other ICSs. FF has been found to have a greater lung retention time than all other ICS preparations which may contribute to the extended duration of anti-inflammatory action. FF has extensive first pass hepatic metabolism resulting in a low gastrointestinal bioavailability which is consistent with the findings for other ICS preparations. FF, however, will pass from the lung into the systemic circulation and therefore an adverse profile similar to all ICS is likely, but long term data are needed.

FF has demonstrated treatment efficacy for asthma between 100μg and 200μg alone, but in combination with the long-acting beta agonist, vilanterol (FF/VIL 200μg/50μg OD) there were further improvements in lung function relative to monotherapy. There is an increased risk of pneumonia identified in patients with airways disease in associated with ICS preparations and surveillance will be required to determine if this also applies to FF. Once daily therapy, such as FF, may improve compliance and could hopefully be translated into further improvements in asthma-related outcomes.

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Vol 3-2 Commentary

Commentary: Novel Insight into the Genetic Basis of High Altitude Pulmonary Hypertension in Kyrgyz Highlanders

Tsering Stobdan1 and Gabriel G. Haddad1, 2, 3*

1Division of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA

2Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA

3Rady Children's Hospital, San Diego, CA 92123, USA

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Vol 3-2 Research Article

Complement Factor (C3) Level as Marker of Inflammation in Paediatric Asthma

AR Somashekar1*, KG Ramakrishnan1, Vanitha Gowda2

1Department of Pediatrics, M.S. Ramaiah Medical College and hospitals, Bangalore, India

2Department of Biochemistry, M.S. Ramaiah Medical College and hospitals, Bangalore, India

Aim: To assess the serum levels of a complement factors C3 in Indian asthmatic children and compare them with those of healthy controls in order to establish a relationship between the levels of these factors and asthma disease process.

Method: Serum c3 levels of 44 children with acute asthma and 44 controls of the age group of 6-16 years was determined and statistically compared. Lung function tests (FEV1%) was done and correlated with serum c3 levels using Pearson’s comparison coefficient.

Results: The mean serum c3 value of cases (138±32.99) is higher than the controls (112.82±14.6), with 32% cases showing higher than normal level of serum C3. Pearson’s correlation coefficient reveals negative correlation between FEV1% with serum C3 levels.

Conclusion: This study reveals that serum levels of complement c3 are statistically higher in subjects with asthma as compared to healthy subjects. Further, serum levels of c3 reflect the severity of the disease, with its levels being higher when disease is more severe.

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Vol 3-2 Mini Review

Epithelial-Mesenchymal Transition Contributes to Pulmonary Fibrosis via Aberrant Epithelial/Fibroblastic Cross-Talk

Charlotte Hill1, Mark G. Jones2,3, Donna E. Davies2,3,4 and Yihua Wang1,4*

1Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.

2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.

3NIHR Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK.

4Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic interstitial lung disease. Median survival is only 3 years, and treatment options are limited. IPF is thought to be a result of a combination of genetic and environmental factors with repetitive micro-injuries to alveolar epithelial cells playing a central role. IPF is characterised by aberrant extra cellular matrix (ECM) deposition by activated myofibroblasts. Epithelial-mesenchymal transition (EMT) is a process where polarised epithelial cells undergo molecular changes allowing them to gain a mesenchymal phenotype, with a subsequent enhanced ability to produce ECM components and increased migration and/or invasion. The source of myofibroblasts in IPF has been debated for many years, and EMT has been proposed as a source of these cells. However, lineage tracing in transgenic mice suggests the contribution of epithelial cells, which have undergone EMT, to the fibroblast population may be negligible. Instead, recent findings suggest that alveolar epithelial type II (ATII) cells undergoing EMT promote a pro-fibrotic microenvironment through paracrine signalling activating local fibroblasts. This review paper explores the contribution of ATII cells, which have undergone EMT, in the context of pulmonary fibrosis.

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Vol 3-2 Review

Pulmonary Nano-Drug Delivery Systems for Lung Cancer: Current Knowledge and Prospects

Madumani Amararathna1, Kerry Goralski2, David W. Hoskin3,4, H. P. Vasantha Rupasinghe1,3*

1Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Rm 219-C, Cox Institute Building, 50 Pictou Rd. PO Box 550, Truro, NS, B2N 5E3, Canada.

2College of Pharmacy and Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada.

3Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada.

4Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada.

Treatment complexities and the cytotoxicity of anticancer drugs to normal cells often results in therapeutic failure. Biodegradable nanoparticles have gained attention as drug carriers due to their physicochemical characteristics. Nanoparticles are able to encapsulate anticancer drugs and deliver them to target malignant cells while sparing normal cells. Since lung cancer usually arises in lung epithelium, localized drug delivery could be an alternative strategy to effectively treat this disease. Encapsulation of lung cancer drugs in nanoparticles may facilitate intact drug delivery, avoid first-pass metabolism, and reduce cytotoxicity to normal cells, as well as being attractive to patients. However, nanoparticles should be formulated in such a way as to facilitate entrance, deposition, retention, and permeability on targeted lung tissues and escape mucociliary clearance and phagocytosis. Additionally, the patient’s diversity related to lung cancer type, stage of disease, and physical fitness should be considered when formulating a nanocarrier and a delivery device. The potential of localized drug delivery for lung cancer using nanoparticles is reviewed here.

Abbreviations: PLGA, poly(lactide-co-glycolide); MRP1, multidrug resistance associated protein 1; GST, glutathione-s-transferase; NAT, N-acetyltransferease; SULT, sulfotransferases; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

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