PGY 2, Internal medicine resident, North Alabama Medical Center, Florence, Alabama, USA
We present a 25-year-old Hispanic man with left-sided pleuritic chest pain and dyspnea for three days. His Chest radiograph and CTA revealed bilateral apical bullous disease with a 2.5 cm deep left sided pneumothorax. He was managed with 100% oxygen via non-rebreather mask and did not require invasive decompression. Patient reported a one-year history of vaping along with tobacco and cannabis smoking exposure from his late teen years. The pneumothorax improved and he was discharged to the pulmonary clinic. The authors review the multiplicative effect of vaping on smoking cannabis and tobacco leading to early apical bullous lung disease. Patients with such significant smoking/vaping history may benefit from prolonged pulmonary and addiction medicine follow-up given the clinical bullous lung disease and risk for continued smoking/vaping. The case emphasizes the potential exponential effect of combining vaping with tobacco and marijuana smoke on lung health leading to disease at extremely young ages.DOI: 10.29245/2689-999X/2021/1.1169 View / Download Pdf
Stephanos Patsiris1,2*, Grigoris Stelios2, Ilias Papanikolaou1, Themis Exarchos2, Panayiotis Vlamos2
1General Hospital of Corfu, Corfu, Greece
2Bioinformatics & Human Electrophysiology Laboratory, Dept. of Informatics, Ionian University, Corfu, Greece
Chronic obstructive pulmonary disease (COPD) is a respiratory disease with high prevalence. Many factors contribute to its development, and probably that leads to its various clinical pictures. Inflammation is the mechanism responsible for the structural alterations in the lungs. Despite its heterogeneity, there are a couple of primary symptoms characterizing it, which are chronic and productive cough and dyspnea.
The understanding of dyspnea in COPD is based on theories deriving from the interaction of a network formed between the cardiorespiratory and the neuromuscular system and their receptors. Many factors contribute to its occurrence, making it complex and giving it a very subjective character for a person to perceive.
Various methods are used to study COPD. Non-invasive ones seem to attract attention nowadays. One of them is the exhaled breath condensate. It is a biofluid with rich content, which can capture a picture of the pathological processes happening in the lungs. Its study has shown that some markers of inflammation and oxidative stress, such as 8-isoprostane and H2O2, are elevated and able to connect dyspnea and inflammation. Additionally, they seem to provide information of the ongoing inflammatory process in the lungs as well as a picture of the severity of the symptoms. This evidence may enhance the association of dyspnea with dysfunctional breathing.
Despite these interesting findings, further research is necessary both in dyspnea and inflammation in COPD to clarify their mechanisms and connective pathways. The utility of non-invasive techniques such as the exhaled breath condensate could be of significant help, but its establishment in the medical field requires extra studies.DOI: 10.29245/2689-999X/2021/1.1168 View / Download Pdf
Camila Silva Barbosa*, Hye Ju Lee
Radiology Department, Sírio Libanês Hospital, Sao Paulo, Brazil
On October 15th 2020, the Emergency Radiology Journal published our article entitled “COVID-19 pneumonia in the emergency department: correlation of initial chest CT findings with short-term outcome”, that evaluated clinical, laboratorial and imaging findings of laboratory confirmed COVID-19 patients as predictors of severe disease. In this paper, we will explore the context and significance of the early recognition of the disease severity on patients’ management.DOI: 10.29245/2689-999X/2021/1.1167 View / Download Pdf
Malgorzata Kloc1,2,3*, Rafik Mark Ghobrial1,2, Jacek Z. Kubiak4,5*
1The Houston Methodist Research Institute, Houston, Texas, USA
2The Houston Methodist Hospital, Department of Surgery, Houston, Texas, USA
3The University of Texas, M.D. Anderson Cancer Center, Department of Genetics, Houston Texas, USA
4Department of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology (WIHE), Warsaw, Poland
5UnivRennes, UMR 6290, CNRS, Institute of Genetics and Development of Rennes, Cell Cycle Group, Faculty of Medicine, Rennes, France
COVID-19 pandemic has frightened people and governments all around the world. The common opinion is that there are no efficient preventive measures but masks, isolation, and social distancing. The deliverance is hoped from the SARS-CoV-2-specific vaccine, which must be efficient and cheap. But, so far nobody knows when, and if such a vaccine will be developed and mass-produced. Trained immunity with oral polio vaccine (OPV) was recently proposed as a temporal solution against the heavy course of COVID-19. However, politics do not seem to follow, and the scientific world should react because humanity has no time to lose. Below, we support this with our thoughts.DOI: 10.29245/2689-999X/2020/3.1166 View / Download Pdf
Ivane Kiladze1*, Elene Mariamidze1, Branislav Jeremic2
1Oncology and Hematology Department, Research Institute of Clinical Medicine after academician F.Todua, Tbilisi, Georgia
2Radiation Oncology Department, Research Institute of Clinical Medicine after academician F.Todua, Tbilisi, Georgia
Lung cancer (LC) continues to be a significant worldwide public health issue. There are several publications addressing specifics of LC worldwide, but none concerning Georgia- a country with high number of smoking population and LC cases.
Based on the above facts we conducted the first study in the country that aims both evaluating current pretreatment LC challenges, including barriers for early diagnostics and indicating the future strategies for improved LC care
We first analyzed LC statistics and the smoking patterns in the country. Further, we identified other challenging issues in pretreatment diagnostics and staging aspects and finally, provided a survey among LC specialists all over the country to evaluate the situation regarding access and use of radiology investigations and other staging procedures. The survey questionnaire was distributed among LC specialists in main cancer hospitals (n=13) across the country.
We identify multiple health challenges. Still there are a high number of smokers in the country which clearly indicates that additional measures focusing on smoking cessation are urgently needed. This is further materialized in the fact that the majority of patients with LC are diagnosed with either locally advanced or metastatic disease. Activation of preventive programs and implementation of LC screening for early detection should hopefully lead to further reduction of national LC mortality rates.
We underline the urgent need for implementation of country-adapted diagnostic and therapeutic guidelines and protocols as well as enforcing multidisciplinary team meetings. The great need to introduce screening programs in high risk groups, improve access to modern treatment modalities and standardize national diagnostic and treatment protocols are of paramount importance for better LC care.DOI: 10.29245/2689-999X/2020/3.1165 View / Download Pdf
Paul Andrew Lilburn1,2*, Patrick Bazin2, Alexander Beveridge2, Emma Goeman3, Hazel Goldberg1,3,4,5
1Prince of Wales Hospital, Barker Street, Randwick, Sydney, NSW, 2031, Australia
2St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia
3Royal Prince Alfred, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia
4Sydney Hospital, 8 Macquarie Street, Sydney, NSW, 2000, Australia
5St George Hospital, Kogarah, NSW 2017, Australia
Bacillus Calmette-Guerin (BCG) is a live-attenuated strain of Mycobacterium bovis (M bovis), originally developed as a vaccine against tuberculosis. It is also used in the treatment of bladder cancer. We present a case of disseminated BCG-osis which was only discovered at post-mortem. An 89-year-old male was admitted to a tertiary referral centre in inner Sydney in December 2015 with fevers, night sweats, exertional dyspnoea and 8 kg weight loss. The patient developed progressive type 1 respiratory failure requiring non-invasive positive pressure ventilation and treatment for heart failure, but he died eleven days into his admission. On microbiological testing Mycobacterium. tuberculosis complex (MTBC) DNA was detected in lung tissue, by polymerase chain reaction (PCR), using the Xpert® MTB/RIF (Cepheid) platform, the day after the patient’s death. Later mycobacterial culture and genomic deletion analysis identified the specific organism as M bovis. This report describes an unusual presentation of systemic BCG-osis appearing more than three years after the last BCG instillation. This reinforces the fact that BCG instillation of the bladder for transitional cell carcinoma poses a potential risk of systemic spread even years after.DOI: 10.29245/2689-999X/2020/2.1161 View / Download Pdf
Mohammad Abdallat1*, Mazhar Khalil1, Ghayth Al-Awwa1, Ravi Kothuru2, Charles La Punzina2
1Department of Surgery, Brookdale University Hospital and Medical Center, USA
2Cardiothoracic Surgery, Brookdale University Hospital and Medical Center, USA
Background: This case series assessed the clinical outcomes and characteristics of barotrauma in COVID19 patients.
Methods: The electronic medical records of all patients admitted with confirmed COVID 19 infection who eventually developed barotrauma between March 17th, 2020 and April 17th, 2020 were reviewed, information about patient characteristics, pattern and characteristic of barotrauma were analyzed and reported in a descriptive manner.
Results: 25 patients developed evidence of barotrauma on Chest Xray or Computed tomography (CT) with a mean age of 60.1 at the time of diagnosis, 12 (48%) developed severe ARDS with PaO2/FiO2 ratio of <100. 14 (56%) patients developed pneumothorax, 7 had evidence of subcutaneous emphysema and 6 developed pneumomediastinum. More barotrauma occured in the first day of ventilation than any other day, the median time between mechanical ventilation and development of barotrauma is 3.5 days.
Conclusion: Barotrauma in COVID 19 is associated with an increased mortality (64%) which may reflect worse acute lung injury in these cases. The median time to develop barotrauma in these patients is similar to the one described in ARDs literature.DOI: 10.29245/2689-999X/2020/2.1163 View / Download Pdf
Juan Pablo Reig Mezquida1*, Alilis Fontana Bellorín2, Alberto García Ortega3, Gabriel Anguera de Francisco1
1Lung Transplant Unit, Hospital Universitario la Fe, Valencia, Spain
2Department of Thoracic Surgery, Hospital Universitario la Fe, Valencia, Spain
3Department of Pulmonology, Hospital Universitario la Fe, Instituto de Investigación Sanitaria “La Fe”. Valencia, Spain
The clinical course of Coronavirus disease 2019 (covid-19) in lung transplant recipients remains unknown. We present the fatal clinical course of a 63-year old double lung transplant recipient with severe Covid-19 pneumonia. She had stable graft function before Covid-19 infection. Despite all the supportive care and treatment graft injury progressed, causing patient death. Therefore, the prognosis in lung transplant recipients with Covid-19 infection is not optimistic.DOI: 10.29245/2689-999X/2020/2.1164 View / Download Pdf
Ronit Aloni-Grinstein1,2#, Yan Stein1# and Varda Rotter1*
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel
2Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel
Influenza A is a very common cause for respiratory infections, which constitutes a major public health concern due to high rates of morbidity and mortality in high-risk population. In our previous publication, ‘p53 and the Viral Connection: Back Into the Future’, we discussed the involvement of the p53 tumor suppressor in the response to non-tumorigenic viruses, among which is the Influenza virus. In the current comment, we focus on the interplay between p53 and the influenza viral cycle. We discuss recent publications that provide evidence for the potential antiviral and pro-viral roles of p53 and its isoforms towards influenza, both in the host cell, as well as in the immune system. On the other side of the coin, we also discuss how the influenza virus may manipulate p53 to promote its own replication and spreading. An understanding of the interplay between p53 and the virus may lead to the development of a host-based influenza virus therapy.DOI: 10.29245/2689-999X/2019/1.1160 View / Download Pdf
L.V.Klochkova*, M.E.Lozovskaya, E.B.Vasilyeva, Yu.A.Yarovaya
Saint Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia
Background: The study aimed to identify causes of delayed diagnosis and define features of tuberculous meningitis in children in the Russian Federation.
Materials and Methods: The study is based on data from 2000 to 2016 on frequency of meningitis in children in Russia. Further analysis of disease features and diagnostics of tuberculous meningitis in children in St. Petersburg over 12 years (2005-2016) is presented.
Results and Discussion: The number of cases of tuberculous meningitis in children in Russia decreased from 51 to 13 per year from 2000 to 2016. In St. Petersburg, from 2005 to 2016 there were 7 registered cases; 4 died, 3 survived. Predisposing factors of development of tuberculous meningitis were young age, presence of tuberculosis in the family, absence of BCG vaccination, and unfavorable social conditions. Three out of 7 children infected with HIV developed tuberculosis. However, a low frequency of cases has led to absence of phthisis vigilance, delayed diagnosis and deaths. Two illustrative cases are presented from clinical practice.
Conclusion: Improving outcomes of tuberculous meningitis requires enhanced phthisis vigilance, detection of mycobacterium tuberculosis infection by modern methods, use of all methods of etiological diagnostics, including PCR and Baсtec, and immediate administration of antituberculous therapy.DOI: 10.29245/2689-999X/2019/4.1159 View / Download Pdf
Alizamin Sadigov*, Irada Mamedova, Kamran Mammmadov
Pulmonary Medicine Department, Azerbaijan Medical University, Baku
Background: Ventilator-associated pneumonia (VAP) remains a common case of intensive care unite (İCU) and hospital morbidity and mortality despite advances in diagnostic techniques and manegment. One of most important point for such patients is identification of predictors for mortality in term for futher their modification and reduction of mortality rate.
Objective: We aimed to determine the most important risk factors for short-term mortality in patients with VAP in mechanically ventilated patients.
Methods: This retrospective study was carried out from February 2014 to January 2019. One hundred twenty one adults patients with VAP maintained on mechanical ventilation for more than 48 h in our ICU department were enrolled in the study. VAP was diagnosed as new persistent pulmonary infiltrates on chest radiographs and a least two of following: (1) Fever of ≥38.3C (2) leukocytosis of ≥ 12.000/mm3 and (3) purulent tracheobronchial secretions. Endotracheal aspirate (ETA) samples and blood samples of suspected case were collected and processed as per standard protocols.
Results: The primary underlying diagnosis and comorbidities were acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in 42 patients, congestive heart failure in 32, neurological disease in 28, and renal disease in 19 patients. Gram-negative agents were the major of finding pathogen (Acinotebacter baumannii accounting for 37.1 %). This infection in 43 case (95.5%) was multi-dying resistant (MDR) pathogen and associated with significantly higher length of ventilation (LOV) and the length of ICU stay (LOSicu) (p=0.01 respectively). Severe sepsis/septic shock, acute respiratory distress syndrome (ARDS), malnutrition, pulmonary complications such as pleural effusions and bilateral, multi- lobar lung infiltrates were most common findings in VAP patients which were associated with higher mortality (p<0.01).Acinotebacter baumannii MDR pathogens was associated with higher mortality rate compare with other MDR pathogens (p<0.01).
Conclusion: Ventilator-associated pneumonia is a serious ICU complication that is associated with increased in hospital mortality.In patients with VAP malnutrition ,severe sepsis/septic shock, ARDS, MDR Acinotebacter baumannii infection ,bilateral pulmonary infiltrates ,and underlying chronic obstructive pulmonary disease(COPD) are associated with increased risk in-hospital mortality in such patients. Identification of risk factor for in hospital mortality in such patents is important in term on further their modification and reduction of mortality rate.DOI: 10.29245/2689-999X/2019/4.1157 View / Download Pdf
Hala Jassim AlMossawi1, Colleen Longacre1, Yogan Pillay2, Neeraj Kak1*
1University Research Co, Chevy Chase, MD, USA
2National Department of Health, South Africa
Social and behavior change (SBC) communication strategies and interventions have been used to successfully promote positive health behaviors and health outcomes, yet there is little evidence in the published literature on SBC frameworks for tuberculosis (TB) care and treatment. In this article, we outline a high-level generalized framework for the development, deployment, and evaluation of SBC communication strategies in high TB burden settings and how it could be employed to address TB treatment delays. The framework describes the contextual factors that will impact the design of a program, the spheres of influence, and details some of the outcomes to be achieved within each sphere that will lead to improved knowledge and substantive changes in behaviors at each prescribed level of the system. Improved design and delivery of SBC interventions can assist countries in meeting the Sustainable Development and Global End TB goals of reduced TB incidence, increased TB cure rates, reduced TB deaths, prevention of catastrophic out-of-pocket costs for TB care, and integration of health systems for patient-centered care.DOI: 10.29245/2689-999X/2019/4.1156 View / Download Pdf
Hala Jassim AlMossawi1, Neeraj Kak1*, Yogan Pillay2, Refiloe Matji1, Sharanya Joshi1
1Center for Innovations and Technology, University Research Co., LLC, Chevy Chase, MD, USA
2National Department of Health, Pretoria, South Africa
Background: Increasingly lower- and middle-income countries have moved towards the adoption of National Health Insurance (NHI) models as a means to support sustainable financing for Universal Health Care. National Health Insurance in the form of government-led, publicly supported and/or centrally managed insurance programs in various forms have been introduced in countries such as Brazil, Cambodia, China, Rwanda, Mexico, South Africa, and Thailand and have demonstrated important successes. The impact of these insurance programs on the use of tuberculosis (TB) services and outcomes is unclear.
Objectives: This assessment examines how TB is included (or neglected) in the service delivery package in NHI programs and how effectively NHI programs interact with National TB Programs (NTP) and other TB control stakeholders to plan, implement, and measure TB service use. This assessment aims to analyze the extent to which several NHI programs currently in place or in development in high-burden TB countries have integrated TB services. It synthesizes the findings of assessments in four countries - Thailand, Peru, Philippines, and India - which have adopted publicly supported health insurance programs.
Results: The four case studies demonstrate that the integration of TB services with national health insurance can have a positive effect on access to services and their quality. On the other hand, each of the models assessed impose different types of restrictions which can limit the utilization of services. Some restrictions are planned and are part of the design of the insurance model. Others, however, are indirect or unintended consequences of implementation. As it relates to TB, the findings of the assessment have highlighted the need to carefully examine the impact of restrictions in terms of access and use of TB services. In Thailand, the case study found that long wait times at facilities discouraged patients from obtaining services through national health insurance. In the Philippines, the case study found that many patients perceive that they will have to pay direct and indirect costs for TB services in the public sector and prefer instead to seek treatment in the private sector, including pharmacies, to reduce costs. The primary goal of publicly-supported health insurance programs is to improve access to care for a vulnerable segment of the population and, especially as it relates to TB, have the potential to play an important role in improving public health. However, specific objectives for health insurance programs are not typically defined in terms of disease objectives. In countries with significant burdens of key diseases like TB which threaten to jeopardize overall population health (as well as long term growth and development), specific considerations should be made to ensure that the NHI program is designed to be a driving force for controlling the epidemic. The decision to develop and adopt a publicly-supported insurance model should ideally form part of broader health systems reform efforts, and the design of the insurance model should, therefore, include features geared at reinforcing and advancing the country’s health systems strengthening objectives. An issue facing each country, in different degrees, is the separation between the functions of the NTP and the insurance planning and implementation agency. The addition of an insurance program, and possibly other agencies with financing or regulatory functions, adds another level of complexity in terms of planning, organizing, and delivering health services.
Conclusion: A key overarching conclusion from the assessment is that strong coordination is needed between health policymakers and program managers to carefully design models for integration of TB services under national health insurance. Careful planning is needed to ensure that all parties understand their roles and responsibilities within the systems and that health providers are motivated to provide high-quality TB services, and patients have incentives to utilize the services.DOI: 10.29245/2689-999X/2019/3.1158 View / Download Pdf
Pankaj Sadaphal1, Krishnapada Chakraborty1, Hala Jassim-AlMossawi1, Yogan Pillay2, Giorgio Roscigno3, Anil Kaul4, Neeraj Kak1*, Refiloe Matji1, Lindiwe Mvusi2, Anthony DeStefano1
1University Research Co. LLC, Maryland, USA
2Department of Health South Africa, Pretoria, South Africa
3NEXT2People Foundation, Geneva, Switzerland
4Center for Health Sciences, Oklahoma State University, Tulsa, OK
Purpose: The pharmacokinetics (PK) of anti-tuberculosis drugs, including their bioavailability (BA), significantly impacts the efficacy and effectiveness of tuberculosis (TB) treatment regimens. Rifampicin, one of the most important drugs in the treatment of drug-sensitive tuberculosis, has been used increasingly in fixed-dose combinations (FDCs). This paper reviews and analyzes available data on BA and PK of rifampicin with a focus on FDCs, from published studies and reports.
Methods: Using PubMed as the primary database, Cochrane and other relevant databases, a systematic review of literature was conducted to identify studies on the bioavailability and efficacy of rifampicin in FDCs versus single drug formulations. A number of keywords including “bioavailability”, “rifampicin”, “fixed dose combinations”, and “pharmacokinetics” were used in various combinations. The search covered the period 1980 to 2016. Priority was given to articles on rifampicin bioavailability in fixed dose combinations used in the program setting, and human studies that used the World Health Organization (WHO) approved BA/PK protocol and sample size (≥22 patients).
Findings: More than 450 original peer-reviewed articles, reviews and reports, were assessed for this analysis. Eleven papers, which included data from high-TB-burden countries (South Africa, India, and China), raised significant concerns about rifampicin bioavailability within FDCs; the authors of the studies discussed multiple factors associated with low bioavailability, including drug formulation and quality, storage environment, patient factors, and concomitant diseases.
Implications: Recent studies and reviews point to the problem of low bioavailability of rifampicin in fixed dose combinations. However, in the field, it remains a hidden or unrecognized factor leading to poor treatment outcomes. It is difficult to study the issue thoroughly unless there is awareness among TB program personnel of its existence, and adequate laboratory and research support is available to national tuberculosis programs (NTPs). In stemming the tide of tuberculosis multi-drug resistance (MDR) and extensive drug resistance (XDR), it is paramount to ensure that rifampicin bioavailability is adequate in FDCs, and to detect and address any deviation from recommended target ranges. There is a need for strategies to minimize the undesirable clinical effects of reduced rifampicin bioavailability in FDCs, and for effective utilization of quality-assured drugs within NTPs programs; these can help NTPs support effective case management in line with the international TB care standards, while taking into consideration the factors affecting drug absorption and therapeutic concentration.DOI: 10.29245/2689-999X/2019/3.1155 View / Download Pdf
Sheetal Mungul, Shivesh Maharaj*
Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa
Pediatric deep neck space infection is an important entity that often requires hospitalisation for antimicrobial therapy. There is a higher pattern of drug resistance in lower income countries such as South Africa. Resource limitations, poor access to healthcare, nutritional deficiencies and immune deficiency necessitate appropriate antimicrobial use as resistance may have a greater socioeconomic impact relative to higher income countries.DOI: 10.29245/2689-999X/2019/3.1152 View / Download Pdf
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.DOI: 10.29245/2689-999X/2019/2.1148 View / Download Pdf
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.DOI: 10.29245/2689-999X/2019/2.1149 View / Download Pdf
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.DOI: 10.29245/2689-999X/2019/2.1151 View / Download Pdf
DOI: 10.29245/2689-999X/2019/2.1150 View / Download Pdf
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
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.DOI: 10.29245/2689-999X/2018/1.1143 View / Download Pdf
Emanuela Cortesi, Juan-Jose Ventura*
Translational Cell and Tissue Research, Dept. of Imaging and Pathology, KU Leuven, Belgium
Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis, mainly due to the delay in the diagnosis. Adenocarcinoma, a subtype of non-small cell lung cancer, has the highest incidence and significant recurrence rates. Experimental and clinical researches suggested that the presence of cancer stem cells could support the development, malignization and resistance of lung cancer. Unfortunately, our knowledge in the field is still limited.
Here we report our findings regarding a cell population expressing LGR6, an epithelial stem cell marker. Under the pressure of a fine regulated p38? MAPK/mir-17-92 axis, LGR6+ stem cells produce differentiated bronchioalveolar cells, in the normal lung.
LGR6 is enriched in tumour cells during adenocarcinoma progression. Similar to normal stem cells, LGR6+ cancer cells show self-renewal and differentiation capacities, alongside with a higher oncogenic potential. Our studies suggest a disruption in the p38? MAPK/mir-17-92 network, that enhances Wnt pathway activity, could be responsible for the selection of malignant LGR6+ tumour cells. These results support the existence of a cell population with stem-like characteristics and strong oncogenic potential. This population could be useful for predictive diagnosis and a novel target for improved and more effective therapies against metastases and recurrences of lung adenocarcinomas.DOI: 10.29245/2689-999X/2018/1.1144 View / Download Pdf