\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6310",leadTitle:null,fullTitle:"Genotoxicity - A Predictable Risk to Our Actual World",title:"Genotoxicity",subtitle:"A Predictable Risk to Our Actual World",reviewType:"peer-reviewed",abstract:"This book is designed to provide an overview of the different genotoxicants and their effects on living organisms, including humans. The contributions made by the specialists in this field of research are gratefully acknowledged. We hope that the information presented in this book will meet the expectations and needs of all those interested in the different aspects of the genotoxicity field. The publication of this book is of great importance to those scientists, pharmacologists, physicians and veterinarians, as well as engineers, teachers, graduate students and administrators of environmental programmes, who make use of these investigations to understand both the basic and applied genotoxic aspects of known and new xenobiotics, and to guide them in their future investigations.",isbn:"978-1-78923-419-0",printIsbn:"978-1-78923-418-3",pdfIsbn:"978-1-83881-236-2",doi:"10.5772/intechopen.69556",price:119,priceEur:129,priceUsd:155,slug:"genotoxicity-a-predictable-risk-to-our-actual-world",numberOfPages:122,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"14a0966cec5283fdbc781a6bb47ed4e3",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",publishedDate:"July 11th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6310.jpg",numberOfDownloads:20616,numberOfWosCitations:67,numberOfCrossrefCitations:77,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:153,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:297,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 10th 2017",dateEndSecondStepPublish:"May 31st 2017",dateEndThirdStepPublish:"December 1st 2017",dateEndFourthStepPublish:"December 31st 2017",dateEndFifthStepPublish:"March 3rd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpg",biography:"Marcelo L. Larramendy, Ph.D., serves as Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). Appointed Senior Researcher of the National Scientific and Technological Research Council of Argentina. Former Member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis. Author of more than 450 contributions, including scientific publications, research communications and conferences worldwide. Recipient of several national and international awards. Prof. Larramendy is a regular Lecturer at the international A. Hollaender Courses organized by the IAEMS and former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in Genetic Toxicology and is, or has been, referee for more than 20 international scientific journals. Member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"20",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski",profilePictureURL:"https://mts.intechopen.com/storage/users/14863/images/system/14863.jpg",biography:"Sonia Soloneski has a Ph.D. in Natural Sciences and is Assistant Professor of Molecular Cell Biology at the School of Natural Sciences and Museum of La Plata, National University of La Plata, Argentina. She is a member of the National Scientific and Technological Research Council (CONICET) of Argentina in the Genetic Toxicology field, the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis (ALAMCTA), the Argentinean Society of Toxicology (ATA), the Argentinean Society of Biology (SAB) and the Society of Environmental Toxicology and Chemistry (SETAC). She has authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications. She has served as a review member for more than 30 scientific international journals. She has been a plenary speaker in scientific conferences and a member of scientific committees. She is a specialist in issues related to Genetic Toxicology, Mutagenesis, and Ecotoxicology.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1210",title:"Toxicogenomics",slug:"toxicogenomics"}],chapters:[{id:"57717",title:"In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages",doi:"10.5772/intechopen.71923",slug:"in-vitro-cytotoxicity-and-cell-viability-assays-principles-advantages-and-disadvantages",totalDownloads:14764,totalCrossrefCites:74,totalDimensionsCites:144,hasAltmetrics:1,abstract:"Cytotoxicity is one of the most important indicators for biological evaluation in vitro studies. In vitro, chemicals such as drugs and pesticides have different cytotoxicity mechanisms such as destruction of cell membranes, prevention of protein synthesis, irreversible binding to receptors etc. In order to determine the cell death caused by these damages, there is a need for cheap, reliable and reproducible short-term cytotoxicity and cell viability assays. Cytotoxicity and cell viability assays are based on various cell functions. A broad spectrum of cytotoxicity assays is currently used in the fields of toxicology and pharmacology. There are different classifications for these assays: (i) dye exclusion assays; (ii) colorimetric assays; (iii) fluorometric assays; and (iv) luminometric assays. Choosing the appropriate method among these assays is important for obtaining accurate and reliable results. When selecting the cytotoxicity and cell viability assays to be used in the study, different parameters have to be considered such as the availability in the laboratory where the study is to be performed, test compounds, detection mechanism, specificity, and sensitivity. In this chapter, information will be given about in vitro cytotoxicity and viability assays, these assays will be classified and their advantages and disadvantages will be emphasized. The aim of this chapter is to guide the researcher interested in this subject to select the appropriate assay for their study.",signatures:"Özlem Sultan Aslantürk",downloadPdfUrl:"/chapter/pdf-download/57717",previewPdfUrl:"/chapter/pdf-preview/57717",authors:[{id:"211212",title:"Dr.",name:"Özlem Sultan",surname:"Aslantürk",slug:"ozlem-sultan-aslanturk",fullName:"Özlem Sultan Aslantürk"}],corrections:null},{id:"57350",title:"DNA Damage in End-Stage Renal Disease Patients. Assessment by In Vitro Comet Assay and by Cell-Free DNA Quantification",doi:"10.5772/intechopen.71319",slug:"dna-damage-in-end-stage-renal-disease-patients-assessment-by-in-vitro-comet-assay-and-by-cell-free-d",totalDownloads:1145,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Inflammation is a common feature in end stage renal disease (ESRD) that might contribute to increase DNA damage. ESRD patients present increased circulating cell-free DNA (cfDNA) and different types of DNA injury. The underlying inflammatory process in ESRD may be associated with increased genomic damage and cfDNA contributing to further enhance inflammation. We analyzed the degree of genomic damage in ESRD patients under hemodialysis therapy, using the comet assay and cfDNA quantification. ESRD patients presented significantly higher C-reactive protein (CRP) and cell damaged DNA. The cfDNA correlated with age and inflammatory stage. Nine out of 39 patients died during the one year follow-up period and presented significantly higher cfDNA, than those who persisted alive. At lower CRP values, the increased DNA damage is still within the cell, and at higher CRP the damaged DNA is released in to plasma. The higher degree of genomic damage in ESRD might be a consequence of inflammation and aging, and may contribute to increase cancer and cardiovascular mortality risk. Our data suggest that the comet assay is more sensitive for low-grade inflammatory conditions, while cfDNA appears as a good biomarker for more severe inflammatory conditions, and as a biomarker for the outcome of ESRD patients.",signatures:"Susana Coimbra, Alice Santos-Silva, Elísio Costa and Elsa Bronze-da-\nRocha",downloadPdfUrl:"/chapter/pdf-download/57350",previewPdfUrl:"/chapter/pdf-preview/57350",authors:[{id:"56251",title:"Prof.",name:"Alice",surname:"Santos Silva",slug:"alice-santos-silva",fullName:"Alice Santos Silva"},{id:"66774",title:"Prof.",name:"Susana",surname:"Coimbra",slug:"susana-coimbra",fullName:"Susana Coimbra"},{id:"181971",title:"Prof.",name:"Elísio",surname:"Costa",slug:"elisio-costa",fullName:"Elísio Costa"},{id:"212504",title:"Prof.",name:"Elsa",surname:"Bronze-Da-Rocha",slug:"elsa-bronze-da-rocha",fullName:"Elsa Bronze-Da-Rocha"}],corrections:null},{id:"58236",title:"Genotoxicity Induced by Cypermethrin in the Zebrafish Retina",doi:"10.5772/intechopen.72434",slug:"genotoxicity-induced-by-cypermethrin-in-the-zebrafish-retina",totalDownloads:1245,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cypermethrin (Cyp), is one of the most common contaminants in freshwater aquatic systems. We evaluated its possible genotoxic effect and oxidative stress in retinal cells of adult zebrafish exposed to 0.3 μg/L and 0.6 μg/L Cyp. Both the histological and immunofluorescence (IF) techniques showed the presence of apoptotic cells in the zebrafish retina after 9 days of treatment with 0.6 μg/L Cyp. Thus, histone γ-H2AX, a double-stranded DNA damage marker, was immunodetected in both the outer and inner nuclear layer after exposure to 0.6 μg/L Cyp for 12 days, while the anti-caspase-3 apoptotic antibody was detected in the outer nuclear layer. Compared with the morphological evidence, the damage index (DI) showed significant differences with 0.3 μg/L from day 9, while with 0.6 μg/L all the stages evaluated showed very significant differences. According to these results, it was verified that the activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly after exposure to 0.6 μg/L Cyp. The same treatment caused a significant positive regulation of the mRNA levels of both genes. These results indicate that Cyp causes DNA damage and oxidative stress. This pyrethroid also has the potential to induce apoptosis in the cells of the retina.",signatures:"Enrique Valentín Paravani and Víctor Hugo Casco",downloadPdfUrl:"/chapter/pdf-download/58236",previewPdfUrl:"/chapter/pdf-preview/58236",authors:[{id:"103103",title:"Dr.",name:"Víctor",surname:"Casco",slug:"victor-casco",fullName:"Víctor Casco"},{id:"212967",title:"Dr.",name:"Enrique V.",surname:"Paravani",slug:"enrique-v.-paravani",fullName:"Enrique V. Paravani"}],corrections:null},{id:"60104",title:"Assessment of Potential Carcinogenicity by Quantitative Structure-Activity Relationship (QSAR)",doi:"10.5772/intechopen.75420",slug:"assessment-of-potential-carcinogenicity-by-quantitative-structure-activity-relationship-qsar-",totalDownloads:1040,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Already in 1978, Elisabeth C. Miller and James A. Miller came with a presumption that electrophilic molecules are predicted to be carcinogens. It is because DNA molecule is reached in nucleophilic centres that may covalently bind to such substances. Rules deduced by Millers are even nowadays irrefutable, and they are used as the basis of testing of the substance for its carcinogenicity potential. Toxicological discipline that emerged from Millers’ research is based on dependence of chemical structure of the substance and their biological activity. Even further, there are strict regularities between molecular structures and activities. The tool used in assessment of biological activity of a substance is known as SAR, an abbreviation from structure–activity relationship. Besides electrophilic centres, in assessment of carcinogenic potential of a substance, the SAR also encounters chemical surrounding (neighbouring functional groups), size of the substance, its lipophilicity, number and position of aryl rings, substitutions of hydrogens, epoxides in aliphatic moieties or rings, resonance stabilisation, etc. To these days, SAR has been upgraded to quantitative SAR (QSAR) which applies multivariate statistical methods quantitatively comparing detected characteristics of “alerts” with biological activity of known carcinogens. Nowadays, chemical industry developing novel active substances is unthinkable without application of QSAR.",signatures:"Davor Zeljezic",downloadPdfUrl:"/chapter/pdf-download/60104",previewPdfUrl:"/chapter/pdf-preview/60104",authors:[{id:"14691",title:"Dr.",name:"Davor",surname:"Želježić",slug:"davor-zeljezic",fullName:"Davor Želježić"}],corrections:null},{id:"59362",title:"Genotoxicity by Electromagnetic Fields",doi:"10.5772/intechopen.74128",slug:"genotoxicity-by-electromagnetic-fields",totalDownloads:1206,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Modern life implies a constant exposure of living organisms to many sources of radiation, especially electromagnetic fields (EMFs) generated by our technological devices. The question of whether or not EMFs in the non-ionizing extremely low frequency (ELF) range can induce genotoxic effects is currently a subject of interest. People of industrialized societies are commonly exposed to EMFs and waves in a very broad range of frequencies, including power lines, telecommunications, and domestic and industrial equipment. In this review, we present controversial evidence from our research group and others of genotoxicity induced by ELF-EMFs, since scientific community consider EMF devices produce marginal amounts of energy, which does not justify any DNA alterations, together with conflicting laboratory results and few epidemiological studies. However, in 2002 the International Agency for Research on Cancer (IARC) categorized ELF-EMFs as being potential carcinogenic and genotoxic agents to humans. The aim of the present chapter is to discuss the role of ELM-EMFs on human genotoxicity.",signatures:"José Antonio Heredia-Rojas, Ricardo A. Gómez-Flores, Eulogio De la\nCruz-Torres, Omar Heredia-Rodríguez, Eduardo Campos-Góngora,\nPedro César Cantú-Martínez, Laura E. Rodríguez-Flores and\nAbraham O. Rodríguez-de la Fuente",downloadPdfUrl:"/chapter/pdf-download/59362",previewPdfUrl:"/chapter/pdf-preview/59362",authors:[{id:"175049",title:"Dr.",name:"Ricardo Alberto",surname:"Gomez Flores",slug:"ricardo-alberto-gomez-flores",fullName:"Ricardo Alberto Gomez Flores"},{id:"216613",title:"MSc.",name:"Laura",surname:"Rodríguez-Flores",slug:"laura-rodriguez-flores",fullName:"Laura Rodríguez-Flores"},{id:"232729",title:"Dr.",name:"Jose Antonio",surname:"Heredia Rojas",slug:"jose-antonio-heredia-rojas",fullName:"Jose Antonio Heredia Rojas"},{id:"232748",title:"Dr.",name:"Eulogio",surname:"De La Cruz-Torres",slug:"eulogio-de-la-cruz-torres",fullName:"Eulogio De La Cruz-Torres"},{id:"232752",title:"MSc.",name:"Omar",surname:"Heredia-Rodríguez",slug:"omar-heredia-rodriguez",fullName:"Omar Heredia-Rodríguez"},{id:"232754",title:"Dr.",name:"Eduardo",surname:"Campos-Góngora",slug:"eduardo-campos-gongora",fullName:"Eduardo Campos-Góngora"},{id:"232755",title:"Dr.",name:"Pedro César",surname:"Cantú-Martínez",slug:"pedro-cesar-cantu-martinez",fullName:"Pedro César Cantú-Martínez"},{id:"232756",title:"Dr.",name:"Abraham O.",surname:"Rodriguez De La Fuente",slug:"abraham-o.-rodriguez-de-la-fuente",fullName:"Abraham O. Rodriguez De La Fuente"}],corrections:null},{id:"61970",title:"Genotoxic Risk in Human Populations Exposed to Pesticides",doi:"10.5772/intechopen.77968",slug:"genotoxic-risk-in-human-populations-exposed-to-pesticides",totalDownloads:1216,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The importance of early detection of genetic damage is that it allows taking the necessary measures to reduce or suppress the exposure to the deleterious agent when it is still reversible, thus decreasing the risk of developing diseases. For this reason, genotoxicity tests should be considered as indispensable tools in the implementation of a complete medical surveillance in people potentially exposed to various environmental pollutants and especially those who live in the same place with people who have already developed some type of neoplasia at early ages in order to prevent the occurrence of tumors of environmental origin and work-related. On the other hand, the application of these tests is useful to detect possible long-term effects of substances that are introduced to the market without knowing exactly their capacity to affect human and environmental health.",signatures:"Delia Aiassa",downloadPdfUrl:"/chapter/pdf-download/61970",previewPdfUrl:"/chapter/pdf-preview/61970",authors:[{id:"227002",title:"Dr.",name:"Delia",surname:"Aiassa",slug:"delia-aiassa",fullName:"Delia Aiassa"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"923",title:"Herbicides",subtitle:"Theory and Applications",isOpenForSubmission:!1,hash:"54a8eb808c05a5fe01c676e7047d4576",slug:"herbicides-theory-and-applications",bookSignature:"Sonia Soloneski and Marcelo L. Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/923.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5184",title:"Environmental Health Risk",subtitle:"Hazardous Factors to Living Species",isOpenForSubmission:!1,hash:"aa20266ad595ce73a9396f4ab0f8112e",slug:"environmental-health-risk-hazardous-factors-to-living-species",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5184.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. 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Ersen Balcioglu",coverURL:"https://cdn.intechopen.com/books/images_new/7615.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"198122",title:"Dr.",name:"Hayri Baytan",middleName:null,surname:"Ozmen",slug:"hayri-baytan-ozmen",fullName:"Hayri Baytan Ozmen"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"313776",title:"Dr.",name:"Chatarina",middleName:null,surname:"Niken",fullName:"Chatarina Niken",slug:"chatarina-niken",email:"chatarinaniken@yahoo.com",position:null,institution:null}]},book:{id:"7615",title:"Fracture Mechanics Applications",subtitle:null,fullTitle:"Fracture Mechanics Applications",slug:"fracture-mechanics-applications",publishedDate:"September 23rd 2020",bookSignature:"Hayri Baytan Ozmen and H. Ersen Balcioglu",coverURL:"https://cdn.intechopen.com/books/images_new/7615.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"198122",title:"Dr.",name:"Hayri Baytan",middleName:null,surname:"Ozmen",slug:"hayri-baytan-ozmen",fullName:"Hayri Baytan Ozmen"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11528",leadTitle:null,title:"Maintenance Management - Current Challenges, New Developments, and Future Directions",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tIn an industrial scenario, improper maintenance (or its lack) has several implications that can lead to unexpected breakdowns, losses at industrial production, or catastrophic consequences. In general, a fault affects only one component; however, it spreads to other components as the fault evolves. Moreover, considering cost reduction and production efficiency, developing an effective maintenance program has gained more attention, and several tools have been implemented to support and encourage best practices. In this sense, advanced data acquisition and processing methods have been developed to allow effective machine condition monitoring and early fault detection and identification, avoiding unexpected breakdowns and even catastrophic failures, especially for critical systems. Whenever possible, condition monitoring should be done non-invasively and without interrupting machine operation.
\r\n\r\n\t
\r\n\tOver the years, the concept of maintenance became more comprehensive, reducing fault occurrence and increasing industrial system availability. Besides, reliability, safety, and criticality requirements were associated with the system or equipment under analysis. Maintenance strategies or schemes can be classified as corrective (run-to-break), preventive (time-based), and predictive (condition-based maintenance). Corrective maintenance is only performed after an occurrence of a fault. Therefore, it involves unexpected breakdowns, high costs, changes in the production chain, and it could lead to catastrophic events. Preventive maintenance and interventions occur based on a scheduled maintenance plan or the equipment's mean time between failures. Although it is more effective than corrective maintenance, unexpected failure may still occur by preventing most failures. Additionally, the process cost is still high, especially the costs associated with labor, inventory, and unnecessary replacement of equipment or components.
\r\n\tOn the other hand, predictive maintenance analyses the equipment condition so that a possible fault can still be identified at an early stage. Predictive maintenance aims to identify a machine anomaly so that it does not result in a fault. Such maintenance involves advanced monitoring, processing, and signal analysis techniques, which are generally performed non-invasively and, in many cases, in real-time. In the case of machines or processes, these techniques can be developed based on vibration, temperature, acoustic emission, or electrical current signal monitoring. It should be noted that monitoring such signals or parameters to verify the operating condition is called condition monitoring. Condition monitoring aims to observe the machine's current operational condition and predict its future condition, keeping it under a systematic analysis during its remaining life. In this sense, a fault condition can be detected and identified from systematic machine condition monitoring. A diagnosis procedure can be established, whereby properly investigating the fault symptoms and prognosis.
\r\n\t
\r\n\tThis book will aim to merge all these ideas in a single volume, aggregate new maintenance experiences, apply new techniques and approaches, and report field experiences to establish new maintenance processes and management paradigms.
\r\n\t
The expert panel 3 of the National Asthma Education and Prevention Program defines asthma as “a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment.” This definition allows for incorporation of the clinical, physiological, and pathological findings of asthma. Traditional spirometry, while the gold standard, can be unreliable in pediatric patients and is dependent on patient effort. Impulse oscillometry is a clinical tool that is independent of patient effort and allows for diagnosis and management of pediatric and adult patients with asthma. IOS can enhance the clinical evaluation for patients with asthma. IOS is a technique that measures airway impedance (resistance and reactance). IOS is a noninvasive technique that is beneficial either as a single modality or in combination with traditional spirometry for patients in the diagnosis and management of asthma.
\nImpulse oscillometry or IOS is a measure of both small and large airway resistance. In addition, resonance capacitance or reactance is also obtained via impulse spirometry. It is also referred to as forced oscillation since impulses are sent at periodic intervals into the airways. The measurement of airway resistance and reactance is performed in a noninvasive, relatively independent, and minimally intrusive manner during spontaneous tidal breathing [1].
\nIn contrast to traditional spirometry, impulse oscillometry or IOS tracing is independent of age, height, weight, or gender in adolescents or adults 13 years or older. In other words, normal values are the same whether the patient is 13 or 60 years old. The most relevant findings include R5, R15 or higher, and AX. R5 reflects the small airway resistance. However, R5 is the summation of small and large airways. R15 or higher signifies only the larger airways. AX is low-frequency integrated impedance reactance at R5 and is referred to as purely reactance.
\nIn this chapter, we will review briefly the IOS procedure. We will then guide the reader to the useful applications of this methodology and the diagnosis and follow-up in patients with asthma in terms of actual diagnosis, follow-up with treatment as outpatient, and documentation of response to treatment. Response to treatment can be gauged via handheld nebulizer treatment in the acute setting. In addition, treatment with inhaled corticosteroids or inhaled corticosteroid/LABA or long-acting beta agonists has also been observed independent of spirometry [2]. We will also review the literature regarding the comparison of this modality to traditional spirometry. Finally, we will briefly outline future directions in the evaluation of other respiratory disorders.
\nThe technique of IOS is effort independent. However, it does require breathing through the mouth as noted below. The IOS technique was performed as previously described. Briefly, patients are seated comfortably in a no swivel chair (Figure 1).
\nThe subject during tidal breathing inhales and exhale in a closed system. Technician is watching the screen for the sinusoidal waves to pick up the best reading.
Nose clips were applied, and a special mouthpiece was used. For IOS measurements, patients may be advised to cradle their cheeks with their hands. Patients are allowed to breathe normally while the loudspeaker delivered intermittent multi-frequency impulses over a minimum of a 30-s period. A trained technician will be guiding and assisting the patient during the procedure, which involves three to five sinusoidal readings, depending on the incidence of cough, swallowing, and holding of breath. The recordings with the best coherence at frequencies from 5 to 30 Hz were chosen. The technician was also trained to capture subclinical leaks through the mouthpiece, and leaky recordings were discarded. The pre- and post-bronchodilator assessments took at least 10 min and used ultrasonic nebulizer. The IOS parameters measured were R5, R15, and AX.
\nTraditionally, spirometry is utilized to evaluate lung function in both children and adults. There is no doubt that spirometry is of greater utility at least for most practitioners who diagnose and manage asthma. However, the limitations include difficulty conducting the measurement in patients who are less than 5 years old. Even in patients who are 5 years old and older, the predicted FEV1 may not be as accurate as it is in adults. On the other hand, IOS is more feasible in terms of detecting small airway dysfunction [27, 28]. Classically, small airway dysfunction is detected via the FEF 25/FEF 75. This is highly volume dependent as patients may be unable to perform a complete expiratory maneuver from total lung capacity to residual volume.
\nEven in adults, spirometry itself has its own limitations. FEV1 or the forced expiration volume in the first second is dependent on the ability of the patient to take a deep breath and forcefully exhale until the residual volume is reached. The FEV1 is then compared to a predicted value which is determined via statistical analysis of normal people. Therefore, patients who participate in athletics, for example, may have a higher FEV1 than the predicted value. However, these patients may also have abnormal IOS even though they have supernormal FEV1. In addition, patients with lower predicted value may show improvement in the IOS even though the spirometry may not change. The improvement can be noted acutely via handheld nebulizer or chronically through the use of maintenance inhalers such as corticosteroids.
\nImpulse oscillometry in contrast to spirometry measures the resistance and the airways as well as the reactants. The resistance in the airways is referred to as R5 which is the resistance in the small airways. R15 or higher is a measurement of the resistance in the larger airways. It is important to note that the resistance in the small airways or R5 is the summation of the small and large airways, and therefore the difference between R5 and R15 or higher is the actual small airway measurement. The integrated impedance reactants at R5 or above are referred to as AX. AX is considered the area under the X curve from the beginning of normal inspiration. The reactants are a more sensitive guideline for patient evaluation and asthma. A normal AX is 3 cm of water or less in children who are 13 years and older throughout adulthood. Children who are 5 years or younger have poor lung compliance. Therefore, a normal AX in this age group varies, but usually it is 30 cm of water or less. Therefore, in the younger age group since there is variation in the measurement of AX, it is reasonable to always measure the AX pre-and post-bronchodilation with short-acting beta agonist. This will give better determination of the actual pulmonary status of the patient. As a result of that, children who are between the ages of 6 and 12 will have an AX in between 30 and 3 cm of water. In this group of patients, it is important to follow up these patients not only with measurement of reactance or AX at baseline but also to check that nebulizer treatment is followed with short-acting beta. These patients were on rather than of equal or less of 1000 µg per day at least 2 weeks after treatment with inhaled maintenance corticosteroids or combination. The combination in general will be inhaled corticosteroids with long-acting beta agonist Figure 3.
\nThe trained technician will be able to choose the recordings with the best coherence at frequencies between 5 and 30 Hz. The ideal coherence should be 0.9, 1, 1, 1 at 5, 10, 15, and 20 Hz, respectively. The technician is also trained to capture subclinical leaks through the mouthpiece, and leak recordings should be discarded.
\nPublished observations by the author and colleagues have shown that patients with asthma showed improvement in the IOS values. This has been observed through the measurement of the reactance or AX immediately following nebulizer treatment as well as definite improvement 3 months or more after the start of inhaled corticosteroids or a combination of inhaled corticosteroids with long-acting beta agonist. The FEV1 in these patients showed improvement in the minority of patients, while the reactance or AX improved in all the patients who were tested. There were 39 patients who were adults in this age group. Figure 1 above shows in office IOS. Figures 2 and 3 below revels the improvement in IOS immediately following nebulizer treatment and 3 months later in an individual patient [26, 27, 28].
\n(a) Patient 15 before bronchodilator. (b) Patient after bronchodilator.
The role of small airway dysfunction in adults with asthma has been demonstrated in at least 31–47% of 196 patients who were diagnosed with asthma and had insufficient control of their symptoms. Twenty percent of these patients had poorly controlled asthma. Irrespective of their smoking history, both impulse oscillometry and nitric oxide measurements in the exhaled breath or FENO were more sensitive in predicting small airway dysfunction than traditional spirometric measurements. The authors concluded that even though nitric oxide measurement was slightly more sensitive than IOS, both of these tests were complimentary in determining the severity of peripheral airway dysfunction. However, in this study, the risk factors for peripheral airway dysfunction were noted to be in patients who have traditionally positive smoking history, elevated blood eosinophils, and dose with low baseline FEV1. Nevertheless, the role of impulse oscillometry in this study should be strongly emphasized (Figure 3) [3].
\nPatient 15 follow-up (post) (shadowed area AX). Notice normal resistance (a) and normal AX (b) following inhaled corticosteroids for at least two weeks.
In children with asthma, IOS was noted to be more useful than spirometry and identifying both the asthma and predicting loss of control and exacerbations. This can help with early intervention when the spirometry is normal, but the IOS is showing abnormality. In particular, children are known to have more peripheral or small airway dysfunction. Traditionally this has been dependent upon forced expiration flow between 25 and 75%. Recent studies have shown that IOS is a better predictor particularly in measurement of the small airways or R5 as well as the reactance or AX in the initial evaluation and response to treatment. IOS had improved diagnostic capability in identifying patients with uncontrolled asthma during select baseline values. In the longitudinal analysis of 54 children between the ages of 7 and 17 years old with mild to moderate asthma, both R5 and AX showed inadequate control of asthma 8–12 weeks after the initial visit than spirometric measurements. This included FEF 25–75%. Scholz and colleagues evaluated the value of IOS compared with spirometry and methacholine challenge as predictors of asthma exacerbation in children who are 4–7 years old during 1-year observation. R5 was more predictive of an exacerbation even at the time when the patient was not having any symptoms. The FEV1 or FEV1/FVC and methacholine challenge via spirometry were also normal in these children. In preschool children, normal IOS findings in children between the ages of 2 and 7 years old in patients with asthma are unlikely to have decreased lung function in adolescence based on their initial IOS measurements [4, 5].
\nSmall airways of the lung are defined as the bronchial passages that are less than 2 mm in diameter. They are located beyond the seventh or eighth generation of the tracheobronchial tree. These airways account for more than 90% of the cross-sectional area of the lung and terminate with the alveolar sacs [6].
\nThe small airways have no cartilage to support the structure and are therefore more easily collapsible upon compression. Small airway disease affects the majority of asthmatics across the spectrum of severity. The production of small particle inhaled corticosteroids has enhanced the delivery of inhaled corticosteroids to the smaller airways. This certainly has improved lung function in both adults and children with asthma. Traditionally, high-resolution CT of the chest has been a noninvasive direct radiographic assessment of the luminal caliber and wall thickness of the medium and large airways that are more than 2 mm in diameter. However, this modality has difficulty in evaluating airways that are less than 2 mm in diameter. About 5–10% of patients with asthma are deemed to have severe disease as defined by the European Respiratory Society and the American Thoracic Society as asthma that requires treatment with high-dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming uncontrolled or that remains uncontrolled despite this therapy. Treatment compliance such as appropriate use of inhalers is essential for disease management [7]. Even though there is no gold standard technique for the assessment or diagnosis of small airway, impulse oscillometry in particular has been shown to be effective in the evaluation of small airways either alone or in a combination with exhaled nitric oxide measurement [8].
\nThe role of IOS in bronchial challenge has also been studied. Bronchial challenge test with methacholine or histamine directly or indirectly such as mannitol may be used in every day clinical practice to identify the presence of airway hyperactivity. Airway hyperactivity is the hallmark of persistent asthma. It is particularly useful when the diagnosis of asthma is in doubt such as patients who are experiencing unexplained cough with normal spirometry. Theoretically, performing IOS with normal tidal breathing is much easier for patients to perform with repeated measurements during challenge. Bronchial irritation such as coughing may pose some limitation while performing the test with spirometry. Eighteen adult patients with mild to moderate persistent asthma had methacholine and histamine challenges measuring both spirometry and IOS. A decrease in the FEV1 by 20% was almost equivalent to a 37% drop in R5 for methacholine and 35% decrease for R5 with histamine. The authors concluded that 40% decrease in R5 may be justifiable to approximately extrapolate to the drop in the FEV1 by 20% for both methacholine and histamine challenge [9, 10]. Similar values on R5 or AX were noted in another study. Improvement by 40% or more on the AX value may carry the same significance as a drop in the FEV1 by 20% without the risk of irritation through forced exhalation. Studies in children are very limited in this regard. One study has noted that in children between the ages of 3 and 8 years old, a change in the R5/R20 after methacholine challenge was significantly higher in those children with more severe asthma as shown by increased exercise-induced bronchospasm and short-acting beta 2 agonist use [11].
\nIn another study, 48 young children with asthma undergoing methacholine challenge noted that a drop of 45% in R5 had the equivalents of a drop in the FEV1 by 20%. In addition, significant increase in resistance was seen well before a change in the FEV1 at lower methacholine dosages suggesting that IOS is more sensitive than spirometry [12].
\nHyperresponsiveness was also studied in patients with mild to moderate adult asthma. Patients were recruited between the ages of 18 and 65 years old. FEV1 was noted to be greater than 80% of what is predicted in these patients. Diurnal FEV1 variation was less than 30%. These patients were on equal or less of 1000 mcg/day of beclomethasone dipropionate or equivalent dose. These patients were recruited prospectively. Bronchial challenge was performed with inhaled methacholine and histamine. Twenty-one participants were randomized. Eighteen of whom, ten women and eight men, completed the protocol. All of these patients were used in this analysis, and the mean age was 36 years old. The PC 20 over the FEV1 dropped by 20% following the challenge was noted at equivalents of 43.5% drop in R5 and the methacholine challenge, while it was 45% on the histamine challenge. The magnitude of change seen was greater for all IOS indices including R5 and R5–R20 area under the curve as well as what is referred to as resident frequency or X5. X5 correlated well with the AX. The significance of this study is that these patients were identified as having mild to moderate adult asthma. These patients were well controlled with inhaled corticosteroids. Therefore, they had normal FEV1 at baseline. This study correlated with what has been reported in the literature regarding the application of IOS in SSA and hyperactivity in patients with asthma [13].
\nIn terms of bronchial hyperresponsiveness, cough is an important consideration. Cough is a complex reflex that typically acts as a valuable protective airway clearance mechanism. It arises from irritation of the intrapulmonary and extrapulmonary airways. When the cough reflex is activated, there is an initial inspiratory phase followed by the glottic closure. There is prompt increase in intrathoracic pressure. This is followed by forced expiration and the opening of the glottis. As a result, gas is expired at a high flow rate along with the characteristic audible sound recognized as cough. Patients with asthma or chronic cough and suspected cough-variant asthma participated in a prospective study. The purpose of the study was to compare the bronchodilating effect of deep inspiration in patients with chronic asthma, cough-variant asthma, and chronic cough using high dose of methacholine. These were patients who are between the ages of 18 and 65. Twenty-eight patients out of 56 that were screened were included in the study. Fifteen of these patients were taking inhaled corticosteroids, and nine were taking long-acting beta agonist. The total resistance did not differ significantly on any of these 3 groups. However, small airway resistance or R5 worsened in patients with cough-variant asthma and chronic asthma but did not with chronic cough. Similar findings were noted with spirometry. The purpose of the study was to show that deep inspiration can reverse the obstructive effect due to airway closure but not the obstruction due to large airway narrowing. However, as a secondary finding, impulse oscillometry reproduces the same results as spirometry with methacholine challenge with more comfort during the study. This correlated with the other findings as noted above [14].
\nAsthma is considered a chronic respiratory disease characterized by airway inflammation. Airway inflammation can lead to airway remodeling and hyperresponsiveness. Airway remodeling refers to the structural changes in the airway including but not limited to the airway smooth muscle, airway epithelia, blood vessels, as well as the extracellular matrix. This can manifest itself as an increase in the airway smooth muscle mass, epithelial injury, epithelial cell hyperplasia, goblet cell hyperplasia, thickening of the basement membrane, and angiogenesis. The mechanism of airway remodeling is still unclear. It is noted that multiple cytokines, chemokines, and transcription factors as well as growth factors are released from inflammatory cells. Structural cells are also involved in the airway remodeling. For example, TGF-beta and vascular endothelial growth factor or VEGF are released by the structural cells.
\nFollistatin-like protein 1 or FSTL1 is also known as transforming growth factor-beta 1-stimulated clone 36. It is a secreted glycoprotein of 308 amino acids. The function of FSTL1 is not completely understood. It has been shown to play a key role in tumor propagation and bone metastasis, chronic pain hypersensitivity, inflammation and insulin resistance, and obesity and regulation of erythropoiesis as well as physical development. Several studies have shown that FSTL1 may play an important role in the respiratory system. It is important in lung development, cartilage formation, and alveolar maturation. No count of FSTL1 and mice is embryonic clear lethal, and these mice display multiple developmental abnormalities of the respiratory and skeletal systems. In a recent study, 32 asthmatics and 25 controls were enrolled for routine blood testing. Spirometry and impulse oscillometry were performed. Fiberoptic bronchoscopy was also performed in the 32 asthmatics. The study was aimed at measuring FSTL1 levels. However, it was noted that IOS measurements in these patients were more sensitive than that of spirometry. FSTL1 levels were higher in asthmatics and improved with treatment. IOS showed more improvement than FEV1 in the same patients where the FSTL1 was decreased. Indirectly, therefore IOS may be considered a more accurate measurement of the inflammatory process and airway remodeling in the lung than spirometry [15].
\nGly16Arg beta-2 receptor genotype is a variant allele in the polymorphism of Beta 2 adrenergic receptor family. In other words, in asthmatic children, the presence of this LDL is associated with sub-sensitivity response following exposure to regular long-acting beta-2 agonist in asthmatic patients receiving concurrent inhaled corticosteroids. In a study involving 112 patients treated with inhaled corticosteroids with a mean age of 43 years old, there was no difference in response to treatment with inhaled corticosteroids or combination of inhaled corticosteroids with long-acting beta agonist in terms of IOS response. In other words, allelic variation of the beta-2 adrenergic receptor did not influence the IOS outcomes [16].
\nIn a recent study, 21 school children participated in a 6-minute walk with a measurement of spirometry and IOS before the 6-minute walk, post 6-minute walk, followed by 30-minute of rest, and an additional 6-minute walk, IOS, and spirometry. One hundred twenty-three children participated, but only 21 school children were able to perform the spirometric maneuvers according to preestablished inclusion criteria. Of the 21 children, 9 were able to perform the 6-minute walk with no changes in the IOS. Significant increase in R5 as well as R20 was noted in the rest of the children who participated. Spirometry did not change, but there was a decrease in the FEF 25–75%. The importance of this study is that it suggests that greater attention should be given to submaximal test particularly in children who are predisposed to airway alterations [17].
\nOn the other hand, body mass index status can play an important role in the baseline reactance curve in children who are between the ages of 8 and 16 years. At the age of 16 years, there was increased blood neutrophil count in overweight obese girls but not in boys. However, both genders showed increased reactance or AX even though these patients were not complaining of symptoms to suggest asthma. The nitric oxide washout was normal in this population. The R5 was higher in this age group. IOS therefore can be a predictor of possible asthma in adolescence with high BMI [18].
\nPassive smoking may result in alteration of pulmonary function in infants born preterm. A study of 139 children between the ages of 3 and 7 years old who were born late preterm were categorized whether they had presence or absence of exposure to passive smoking. Patients who are exposed to passive smoking had a higher R5 and are 5/20 as well as a higher AX than patients who were not exposed to passive smoking. Passive smoking therefore can be a factor in early asthma development particularly in this patient population [19].
\nIn conclusion, IOS or impulse oscillometry has been shown to reflect improvement in lung function following short-acting beta agonist treatment, as well as with long-term use of inhaled corticosteroids or combination of inhaled corticosteroids with long-acting beta agonist. The improvement was noted in multiple studies to be independent of the change or status of routine spirometry. It may also provide a better assessment of small airways through its R5 and AX measurements.
\nIn addition, IOS can be more useful and effort independent in measurement of airway hyperresponsiveness in adults and children. It appears to be along with the measurement of nitric oxide exhalation to be reflective of the status of airway inflammation. The observed improvement and IOS are independent of the allele change or polymorphism of the beta-2 adrenergic receptor. It can play a role in the detection of early asthma particularly in children who are obese or exposed to passive smoking. This can be detected either by baseline IOS measurement or following 6-minute walk.
\nMonoclonal antibodies have been used in the treatment of severe asthma. These are patients who are either unresponsive to high-dose inhaled corticosteroids or are unable to be weaned off by oral corticosteroids. These patients have at least two exacerbations within 6 months. In following these patients, there is very limited data about the role of IOS at baseline and during follow-up. We have published data in an abstract form on 12 patients who were on omalizumab that showed improvement in the IOS but not spirometry with follow-up. These patients also improved in terms of tapering high-dose inhaled corticosteroids or oral steroids and had a decrease in their exacerbations even though there was no change in their FEV1. Future studies in this regard in patients with high IgE and eosinophilic asthma are warranted.
\nIn patients with COPD, it is well known that spirometry can be used to define the GOLD criteria. In other words, the FEV1 and the FVC are important parameters in defining the stage of the GOLD criteria. However, in general patients with COPD or chronic obstructive pulmonary disease had very little change upon follow-up in terms of improvement in the lung function based on the spirometry. Therefore, the most reliable current guidelines include quality of life, smoking cessation, 6-minute walk, oxygenation, and perhaps improvement in the FEV1. There have been several reports that showed that the impulse oscillometry can improve even though the spirometry does not change both in terms of short-term treatment with short-acting beta agonists and long-acting beta agonist/long-acting muscarinic antagonists with or without inhaled corticosteroids.
\nA study of 215 participants IOS was studied in the setting of chronic obstructive pulmonary disease or COPD of which 18, 83, 78, and 36 patients were classified under the GOLD criteria as grade 1, 2, 3, and 4, respectively. IOS parameters showed worsening of R5 and reactance or AX depending upon the severity of their COPD. There was a negative correlation with spirometry at baseline. This study recorded IOS at baseline, and it showed good correlation with traditional pulmonary parameters. The conclusion was that IOS can be used as an alternative methodology for evaluation of patients with COPD [1].
\nThe diagnosis of COPD can be difficult at times particularly in the early stages. Thirty-five patients who had moderate to severe COPD showed improvement both in the AX and the resistance in the small airways following treatment with long-acting beta agonist/long-acting muscarinic antagonist combination. The improvement was more prominent than the improvement noted in the FEV1. In fact, FEV1 and FVC statistical significance for the small sample size was not present. IOS improvement was noted in follow-up visit of these patients [20].
\nAnother study evaluated IOS in a pediatric patients, in the use of combination of fluticasone and salmeterol combined with tiotropium, there was significant improvement in R5 and AX in patients who received the triple combination as compared to patients who only received tiotropium by itself. In this study, spirometric findings were also noted to improve with the triple combination. However, IOS findings appear to be more significant. The conclusion by the authors is that IOS may provide a physiological point of view that is different from spirometry and seemed to be applicable as an additional assessment tool targeting COPD patients [21].
\nThese patients were noted at baseline to improve in terms of IOS even though the spirometry did not change. There was also improvement in the impulse oscillometry or AX with follow-up. Statistical significance was noted with improvement in AX, R5, and R15 despite the lack of improvement in FEV1. In conclusion, there was improvement in the impulse oscillometry at baseline as well as maintenance follow-up therapy in patients with mild to moderate COPD.
\nPeripheral airway dysfunction was also noted in COPD patients who experience sleep disturbance. Fifty patients were evaluated in the morning after sleep. Questionnaires were given about the quality of sleep. IOS measurements were noted to be abnormal particularly increased AX and R5. The study demonstrated that sleep disturbances due to COPD symptoms are associated with airway constriction which is reflective of peripheral airway dysfunction [22].
\nOn the whole, the studies suggest that impulse oscillometry may offer a new clue in the diagnosis and follow-up of patients with COPD. The limitation of the studies is that a combination of asthma and COPD cannot be entirely excluded. It has been suggested that nitric oxide measurement is helpful in the differentiation of combination of asthma/COPD and COPD. In patients with COPD by itself, nitric oxide measurement in the exhaled breath is usually very low and is in general less than 5. However, further studies in this regard are needed to reaffirm these findings.
\nCystic fibrosis is a multisystem disease with respiratory system involvement responsible for 90% of morbidity and mortality. Conventional spirometry is considered the main method to evaluate airway disease in patients with cystic fibrosis. FEV1 has been recognized as an objective parameter to evaluate the course of the disease and response to treatment. Forty-nine cystic fibrosis patients between the ages 3 and 18 were compared to 45 healthy controls. IOS was performed in both groups. Spirometry was also performed in patients who are more than 6 years old, while patients who were less than 6 years old only had IOS. In both groups, it was noted that the resistance increased and so did the AX during exacerbation and decreased after treatment. This was independent of the bronchodilator effects. IOS therefore may be useful to evaluate pulmonary function and detect acute exacerbation in cystic fibrosis patients [23].
\nHypersensitivity pneumonitis is a complex clinical syndrome that results from abnormal immune lung function to diverse inhaled antigens. It can be related to protein antigens denied from birds as well as air conditioning and can progress to pulmonary fibrosis. Small airway involvement is associated with interstitial mononuclear infiltrate with non-necrotizing poorly formed granulomas and varying degree of fibrosis. Therefore, detection of small airway dysfunction is essential in establishing the severity of the disease process. In a study of 20 consecutive patients with established diagnosis of hypersensitivity pneumonitis, there was ventilation perfusion mismatch. IOS was obtained, and it did show elevated AX at baseline and improved with treatment particularly with azathioprine and prednisone. It is noted that lung volume also improved but not gas exchange [24].
\nA case report in 2005 demonstrated a lung transplant patient who had deterioration in the IOS even though the spirometry did not change. The AX was worse and so was the resistance in the small and large airways. This was reflective of early transplant rejection. The usefulness of IOS in monitoring lung transplant patient was evaluated by Dr. Ochman and published in 2018. The study involved 25 consecutive patients with successful lung transplantation, and 88% of these patients were noted to have increased AX indicating peripheral airway obstruction. There was an increase in the small airway resistance or R5 as well. The median age was 46 years old. This was a baseline study but suggested that IOS measurements may also be important in evaluating possible early rejection in patients with lung transplant [25].
\nFinally, it is well noted that vocal cord disorder in patients with chronic cough, uncontrolled COPD, or severe asthma can be a contributing factor to the worsening of the symptoms. We have noted that a ratio of AX on inspiration/AX expiration of greater than 2 is consistent with vocal cord disorder. Improvement in vocal cord disorder such as treatment of asymptomatic reflux, increased postnasal drip, and vocal cord dysfunction can lead to secondary improvement in asthma and other related conditions.
\nThe clinical utility of IOS in asthma is well established. IOS is a noninvasive tool that is independent of patient effort and reproducible in pediatric and adult patients. IOS serves as a technique that can be used with spirometry or independently to diagnose and manage asthma. In addition, the utility of IOS is expanding and has shown to be useful in COPD and other inflammatory lung diseases.
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In both responses, there are several activated cells of the immune system, which play a key role in establishing the environment of cytokines, thus directing their differentiation either suppressing or promoting the immune response. This immune response is crucial against pathogen infections. In this chapter, we will describe the crucial role played by different families of cytokines during activation of the immune system to eliminate infectious pathogens.",book:{id:"6963",slug:"immune-response-activation-and-immunomodulation",title:"Immune Response Activation and Immunomodulation",fullTitle:"Immune Response Activation and Immunomodulation"},signatures:"José Luis Muñoz-Carrillo, Juan Francisco Contreras-Cordero,\nOscar Gutiérrez-Coronado, Paola Trinidad Villalobos-Gutiérrez,\nLuis Guillermo Ramos-Gracia and Viridiana Elizabeth Hernández-Reyes",authors:[{id:"214236",title:"Dr.",name:"Jose Luis",middleName:null,surname:"Muñoz-Carrillo",slug:"jose-luis-munoz-carrillo",fullName:"Jose Luis Muñoz-Carrillo"},{id:"216081",title:"Dr.",name:"Oscar",middleName:null,surname:"Gutiérrez-Coronado",slug:"oscar-gutierrez-coronado",fullName:"Oscar Gutiérrez-Coronado"},{id:"220717",title:"Dr.",name:"Juan Francisco",middleName:null,surname:"Contreras Cordero",slug:"juan-francisco-contreras-cordero",fullName:"Juan Francisco Contreras Cordero"},{id:"233193",title:"Dr.",name:"Paola Trinidad",middleName:null,surname:"Villalobos-Gutiérrez",slug:"paola-trinidad-villalobos-gutierrez",fullName:"Paola Trinidad Villalobos-Gutiérrez"},{id:"254015",title:"Dr.",name:"Viridiana Elizabeth",middleName:null,surname:"Hernández-Reyes",slug:"viridiana-elizabeth-hernandez-reyes",fullName:"Viridiana Elizabeth Hernández-Reyes"},{id:"257472",title:"Dr.",name:"Luis Guillermo",middleName:null,surname:"Ramos-Gracia",slug:"luis-guillermo-ramos-gracia",fullName:"Luis Guillermo Ramos-Gracia"}]},{id:"33741",doi:"10.5772/36947",title:"Fundamentals and Applications of Immunosensors",slug:"fundamentals-and-applications-of-immunosensors",totalDownloads:5037,totalCrossrefCites:15,totalDimensionsCites:34,abstract:null,book:{id:"1499",slug:"advances-in-immunoassay-technology",title:"Advances in Immunoassay Technology",fullTitle:"Advances in Immunoassay Technology"},signatures:"Carlos Moina and Gabriel Ybarra",authors:[{id:"110541",title:"Dr.",name:"Carlos",middleName:null,surname:"Moina",slug:"carlos-moina",fullName:"Carlos Moina"},{id:"110556",title:"Dr.",name:"Gabriel",middleName:null,surname:"Ybarra",slug:"gabriel-ybarra",fullName:"Gabriel Ybarra"}]},{id:"53240",doi:"10.5772/66380",title:"Staphylococcus aureus Biofilms and their Impact on the Medical Field",slug:"staphylococcus-aureus-biofilms-and-their-impact-on-the-medical-field",totalDownloads:3807,totalCrossrefCites:18,totalDimensionsCites:34,abstract:"Despite the discovery of antibiotics, the battle against bacteria is so far in their favor, specifically because bugs are able to develop a superstructure named biofilm, to resist and to survive in the environment. Nosocomial infections, a major health problem, are due at 80% to biofilm‐associated infection, and Staphylococcus aureus is the leading bacteria species in this domain. Moreover, the antimicrobial resistance of this bacterial community is accentuated when it is formed by superbugs such as methicillin‐resistant S. aureus (MRSA). In this chapter, the mechanism and the physiology of S. aureus biofilm as well as their consequences in the clinical domains are described. To complete the vision on S. aureus biofilms, some “anti‐biofilm” strategies will be highlighted.",book:{id:"6045",slug:"the-rise-of-virulence-and-antibiotic-resistance-in-staphylococcus-aureus",title:"The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus",fullTitle:"The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus"},signatures:"Fany Reffuveille, Jérôme Josse, Quentin Vallé, Céline Mongaret and\nSophie C. Gangloff",authors:[{id:"54351",title:"Prof.",name:"Sophie C.",middleName:null,surname:"Gangloff",slug:"sophie-c.-gangloff",fullName:"Sophie C. Gangloff"},{id:"190356",title:"Ph.D.",name:"Fany",middleName:null,surname:"Reffuveille",slug:"fany-reffuveille",fullName:"Fany Reffuveille"},{id:"191408",title:"Dr.",name:"Jérome",middleName:null,surname:"Josse",slug:"jerome-josse",fullName:"Jérome Josse"},{id:"203850",title:"Dr.",name:"Quentin",middleName:null,surname:"Vallé",slug:"quentin-valle",fullName:"Quentin Vallé"},{id:"203852",title:"Dr.",name:"Céline",middleName:null,surname:"Mongaret",slug:"celine-mongaret",fullName:"Céline Mongaret"}]},{id:"68185",doi:"10.5772/intechopen.88013",title:"Macrophages: The Potent Immunoregulatory Innate Immune Cells",slug:"macrophages-the-potent-immunoregulatory-innate-immune-cells",totalDownloads:2203,totalCrossrefCites:17,totalDimensionsCites:30,abstract:"Macrophages are ubiquitously present innate immune cells in humans and animals belonging to both invertebrates and vertebrates. These cells were first recognized by Elia Metchnikoff in 1882 in the larvae of starfish upon insertion of thorns of tangerine tree and later in Daphnia magna or common water flea infected with fungal spores as cells responsible for the process of phagocytosis of foreign particles. Elia Metchnikoff received the Noble prize (Physiology and Medicine) for his discovery and describing the process of phagocytosis in 1908. More than 130 years have passed and different subtypes and roles of macrophages as innate immune cells have been established by the researchers. In addition to their immunoregulatory role in immune homeostasis and pathogenic infection, they also play a crucial role in the pathogenesis of sterile inflammatory conditions including autoimmunity, obesity, and cancer. The present chapter describes the immunoregulatory role of macrophages in the homeostasis and inflammatory diseases varying from autoimmunity to metabolic diseases including obesity.",book:{id:"8590",slug:"macrophage-activation-biology-and-disease",title:"Macrophage Activation",fullTitle:"Macrophage Activation - Biology and Disease"},signatures:"Vijay Kumar",authors:[{id:"63844",title:"Dr.",name:"Vijay",middleName:null,surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}]}],mostDownloadedChaptersLast30Days:[{id:"56849",title:"Physiology and Pathology of Innate Immune Response Against Pathogens",slug:"physiology-and-pathology-of-innate-immune-response-against-pathogens",totalDownloads:6143,totalCrossrefCites:21,totalDimensionsCites:28,abstract:"Pathogen infections are recognized by the immune system, which consists of two types of responses: an innate immune response and an antigen-specific adaptive immune response. The innate response is characterized by being the first line of defense that occurs rapidly in which leukocytes such as neutrophils, monocytes, macrophages, eosinophils, mast cells, dendritic cells, etc., are involved. These cells recognize the pathogen-associated molecular patterns (PAMPs), which have been evolutionarily conserved by the diversity of microorganisms that infect humans. Recognition of these pathogen-associated molecular patterns occurs through pattern recognition receptors such as Toll-like receptors and some other intracellular receptors such as nucleotide oligomerization domain (NOD), with the aim of amplifying the inflammation and activating the adaptive cellular immune response, through the antigenic presentation. In the present chapter, we will review the importance of the main components involved in the innate immune response, such as different cell types, inflammatory response, soluble immune mediators and effector mechanisms exerted by the immune response against bacteria, viruses, fungi, and parasites; all with the purpose of eliminating them and eradicating the infection of the host.",book:{id:"5975",slug:"physiology-and-pathology-of-immunology",title:"Physiology and Pathology of Immunology",fullTitle:"Physiology and Pathology of Immunology"},signatures:"José Luis Muñoz Carrillo, Flor Pamela Castro García, Oscar\nGutiérrez Coronado, María Alejandra Moreno García and Juan\nFrancisco Contreras Cordero",authors:[{id:"214236",title:"Dr.",name:"Jose Luis",middleName:null,surname:"Muñoz-Carrillo",slug:"jose-luis-munoz-carrillo",fullName:"Jose Luis Muñoz-Carrillo"},{id:"216080",title:"Dr.",name:"Alejandra",middleName:null,surname:"Moreno-García",slug:"alejandra-moreno-garcia",fullName:"Alejandra Moreno-García"},{id:"216081",title:"Dr.",name:"Oscar",middleName:null,surname:"Gutiérrez-Coronado",slug:"oscar-gutierrez-coronado",fullName:"Oscar Gutiérrez-Coronado"},{id:"216082",title:"Dr.",name:"Pamela",middleName:null,surname:"Castro-García",slug:"pamela-castro-garcia",fullName:"Pamela Castro-García"},{id:"220717",title:"Dr.",name:"Juan Francisco",middleName:null,surname:"Contreras Cordero",slug:"juan-francisco-contreras-cordero",fullName:"Juan Francisco Contreras Cordero"}]},{id:"53922",title:"Phenotypic Markers and Functional Regulators of Myelomonocytic Cells",slug:"phenotypic-markers-and-functional-regulators-of-myelomonocytic-cells",totalDownloads:2277,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"In this chapter, there is a description of hematopoietic stem cells, maturation curve and their differentiation into myeloid cells, including phenotypes and transcription factors involved in this process. Further, we discuss myeloid maturation curve from myeloid precursor, monoblast, premonocyte to monocytes, and also monocytes subsets regarding their CD14 and CD16 expressions and related functions in health and disease. In addition, we reason about the differentiation from monocytes either in dendritic cells or in macrophages in vitro using differential growth factors; these cells are differentiated from those found in vivo being named as monocyte-derived cells. Furthermore, we explore distinguished phenotype of monocytes, macrophages, and dendritic cells monocyte-derived in vitro, using confocal microscopy and flow cytometry, in order to display morphological and phenotypic differences among them.",book:{id:"5484",slug:"biology-of-myelomonocytic-cells",title:"Biology of Myelomonocytic Cells",fullTitle:"Biology of Myelomonocytic Cells"},signatures:"Luciana Cavalheiro Marti, Nydia Strachman Bacal, Laiz Camerão\nBento and Fernanda Agostini Rocha",authors:[{id:"190705",title:"Ph.D.",name:"Luciana",middleName:null,surname:"Marti",slug:"luciana-marti",fullName:"Luciana Marti"},{id:"196049",title:"Dr.",name:"Nydia",middleName:null,surname:"Bacal",slug:"nydia-bacal",fullName:"Nydia Bacal"},{id:"196050",title:"MSc.",name:"Laiz",middleName:null,surname:"Cameirão",slug:"laiz-cameirao",fullName:"Laiz Cameirão"},{id:"196051",title:"Ph.D.",name:"Fernanda",middleName:"Agostini",surname:"Rocha",slug:"fernanda-rocha",fullName:"Fernanda Rocha"}]},{id:"54824",title:"Dendritic Cells: Location, Function, and Clinical Implications",slug:"dendritic-cells-location-function-and-clinical-implications",totalDownloads:4436,totalCrossrefCites:13,totalDimensionsCites:19,abstract:"Dendritic cells (DCs) are antigen-presenting cells derived from bone marrow precursors and form a widely distributed cellular system throughout the body. DCs exert immune-surveillance for exogenous and endogenous antigens and the later activation of naive T lymphocytes giving rise to various immunological responses. Different growth factors and cytokines can modulate the differentiation and function of DCs, GM-CSF, M-CSF, Flt3, and TGF-β, resulting in a large variety of DCs with different functional abilities. Thus, DCs are classified as plasmacytoid DCs (pDCs), conventional DCs (cDCs), and DCs derived from monocytes (mDCs). Functionally, the cDCs may be divided into two states: immature and mature. Immature DCs are specialist in uptaking and processing antigens; in contrast, mature DCs are professional in antigen presentation. It has been observed that immature cDCs can induce immune tolerance while mature cDCs may induce Th2 or Th1 immune responses. It is worth noting that different subpopulations of DCs have the ability to secrete different cytokine patterns, resulting in the induction of different immunological responses. Furthermore DCs are involved in the pathophysiology of several diseases such as contact hypersensitivity, autoimmune diseases, or cancer, but they can also be used as therapeutic tools in these conditions.",book:{id:"5484",slug:"biology-of-myelomonocytic-cells",title:"Biology of Myelomonocytic Cells",fullTitle:"Biology of Myelomonocytic Cells"},signatures:"Andrés Castell-Rodríguez, Gabriela Piñón-Zárate, Miguel Herrera-\nEnríquez, Katia Jarquín-Yáñez and Iliana Medina-Solares",authors:[{id:"190753",title:"Dr.",name:"Andrés",middleName:"Eliú",surname:"Castell-Rodríguez",slug:"andres-castell-rodriguez",fullName:"Andrés Castell-Rodríguez"},{id:"191880",title:"Dr.",name:"Gabriela",middleName:null,surname:"Piñón-Zárate",slug:"gabriela-pinon-zarate",fullName:"Gabriela Piñón-Zárate"},{id:"191881",title:"Dr.",name:"Miguel",middleName:null,surname:"Herrera-Enríquez",slug:"miguel-herrera-enriquez",fullName:"Miguel Herrera-Enríquez"},{id:"191882",title:"Dr.",name:"Katia",middleName:null,surname:"Jarquín-Yáñez",slug:"katia-jarquin-yanez",fullName:"Katia Jarquín-Yáñez"},{id:"204502",title:"BSc.",name:"Iliana",middleName:null,surname:"Medina-Solares",slug:"iliana-medina-solares",fullName:"Iliana Medina-Solares"}]},{id:"63913",title:"Cytokine Profiling Plays a Crucial Role in Activating Immune System to Clear Infectious Pathogens",slug:"cytokine-profiling-plays-a-crucial-role-in-activating-immune-system-to-clear-infectious-pathogens",totalDownloads:3517,totalCrossrefCites:17,totalDimensionsCites:44,abstract:"Pathogen infections are recognized by the immune system, which consists of two types of responses: an innate immune response that recognizes pathogen-associated molecular patterns (PAMPs) and an antigen-specific adaptive immune response. In both responses, there are several activated cells of the immune system, which play a key role in establishing the environment of cytokines, thus directing their differentiation either suppressing or promoting the immune response. This immune response is crucial against pathogen infections. 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Nosocomial infections, a major health problem, are due at 80% to biofilm‐associated infection, and Staphylococcus aureus is the leading bacteria species in this domain. Moreover, the antimicrobial resistance of this bacterial community is accentuated when it is formed by superbugs such as methicillin‐resistant S. aureus (MRSA). In this chapter, the mechanism and the physiology of S. aureus biofilm as well as their consequences in the clinical domains are described. To complete the vision on S. aureus biofilms, some “anti‐biofilm” strategies will be highlighted.",book:{id:"6045",slug:"the-rise-of-virulence-and-antibiotic-resistance-in-staphylococcus-aureus",title:"The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus",fullTitle:"The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus"},signatures:"Fany Reffuveille, Jérôme Josse, Quentin Vallé, Céline Mongaret and\nSophie C. 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