Lung Function Testing in the 21st Century: Methodologies and Tools Bridging Engineering to Clinical Practice

Lung Function Testing in the 21st Century

Methodologies and Tools Bridging Engineering to Clinical Practice

Editor

Clara Ionescu

Table of Contents

Cover image

Title page

Copyright

About the Contributors

Preface

Acknowledgment

Chapter 1. Introduction

Generic Context

About This Book

Beyond This Book

Chapter 2. Standardized Pulmonary Function Testing

Spirometry

Body Plethysmography

Summary

Chapter 3. Oscillometry for Lung Function Testing

History and Development of the Forced Oscillation Technique

Principles of Measurement

Types of Oscillatory Waveforms

Data Acquisition and Processing

Modeling of Lung Mechanics

Important Measurement Precautions

Clinical Application of Oscillometry

Clinical Utility of Rrs and Rrs-Derived Indices

Correlation Between Rrs and Other Measures of Lung Function and Quality of Life

Clinical Utility of Xrs and Xrs-Derived Indices

Correlation Between Xrs and FEV1, Symptoms, Severity and Control, and Quality of Life Outcomes

Limitations of Oscillometry

Summary

Table of Symbols and Acronyms

Chapter 3.1. Nonstandardized Lung Function Tests

The Airflow Interrupter Technique

Impulse Oscillometry

Summary

Chapter 3.2. Oscillometry for Lung Function Testing

History and Development of the Forced Oscillation Technique

Principles of Measurement

Types of Oscillatory Waveforms

Data Acquisition and Processing

Modeling of Lung Mechanics

Important Measurement Precautions

Clinical Application of Oscillometry

Limitations of Oscillometry

Summary

Table of Symbols and Acronyms

Chapter 4. Information From Time-Based Signals

Stress and Strain Curves

Models for Evaluating Respiratory Properties

Heterogeneity and Nonlinearity in the Lung Tissue

Chapter 5. Diffusion

Chapter 5.1. Diffusion in Small Airways

Evaluating and Modeling Diffusion

Effects of Geometry and Porosity on Diffusion

Chapter 5.2. The Multiple-Breath Nitrogen Washout Test

History and Development of the Multiple-Breath Nitrogen Washout Test

Measurement Principles

Physiological Interpretation and Clinical Utility of Washout Outcomes

Important Measurement Considerations

Strengths and Weaknesses

Conclusions

Grants

Chapter 6. Added Value of Other Clinical Tests

Computed Tomography Scans

Sound-Based Diagnosis

Chapter 7. Diagnosis of Asthma and Chronic Obstructive Pulmonary Disease

Asthma and Chronic Obstructive Pulmonary Disease Phenotypes

Which Lung Function Tests for Which Purpose

Patient Monitoring and Management

Chapter 8. Perspectives

Index

Copyright

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

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About the Contributors

Clara M. Ionescu is Professor at Faculty of Engineering and Architecture at Ghent University Belgium. She obtained her Ph.D. (biomedical engineering) from the same university and was for 6 years the recipient of famous Flanders Research Center post doctoral grant. She has written about 100 articles cited in Web of Science on application of systems and control theory to technical and non-technical applications, of which a large amount on biomedical systems. She is peer-reviewer to a manifold of top-ranked publications, including (among others) the Biomedical Signal Processing and Control, IEEE Transactions on Biomedical Engineering, Computer methods and Programs in Biomedicine, Journal of Clinical Monitoring and Practice, PLOS One. She is the author of another book on modelling the respiratory system properties Springer.

Dana Copot received her PhD degree in biomedical engineering in 2018 from Ghent University, Belgium. She is (co)-author of more than 40 scientific publications. During her doctoral studies, she has been involved in the organization of several workshops and conferences. She has organized several special sessions and open invited tracks at conferences but also special issues. In 2017 she won the best paper award at the IEEE International Conference on Intelligent Engineering Systems. She has also involved in several research projects both national and international. Given her involvement in many research activities she has made numerous collaborations with research units in Europe in the application field of modelling for biomedical system control.

Eric Derom, MD from Ghent University Hospital, Department of Respiratory Medicine, has a 30 years expertise in COPD and lung cancer related diagnosis and treatment. Prof Derom is a valued member of the Belgian Society for Pneumology (BVP-SPB), Forum of Flemish Respiratory Medicine Experts (Forum Vlaamse Longartsen), European respiratory Society (ERS), American Thoracic Society (ATS) and German Respiratory Society (Deutsche Gesellschaft fr Pneumologie und Beatmungsmedizin). Numerous clinical research papers in the field of respiratory medicine have numerous citations in highly ranked peer reviewed specialized journals: h-index 19 in Web of Science citation index.

Ubong Peters is a Post-Doctoral Associate at the Division of Pulmonary and Critical Care Medicine in the University of Vermont Larner College of Medicine. He obtained his Masters and PhD degrees in Biomedical Engineering from Dalhousie University in Halifax, Nova Scotia. Ubong is best known for his work on the assessment of respiratory system mechanics in obese adults using a novel oscillometry device which he helped develop and validate. He is the winner of the 2016 Dalhousie University 3MT Competition.

Ireneusz Jabłoński is Associate Professor of Electronics in the Wroclaw University of Technology, Poland. He obtained his PhD and DSc (electronics) from Wroclaw University of Technology, Poland. He serves as the Associate Editor for the peer-reviewed scientific journal Metrology and Measurement Systems, and is the Editor-in-Chief for the International Journal of Measurement Technologies and Instrumentation Engineering. He has written about 25 articles on biomedical measurements in various international peer-reviewed publications, including IEEE Transactions on Biomedical Engineering, Computer Methods and Programs in Biomedicine, Measurement. He is the author of one monography and four book chapters.

Cristina I. Muresan received the degree in system engineering in 2007, and the Ph.D. in 2011 from Technical University of Cluj-Napoca, Cluj-Napoca, Romania. She is currently an associated professor at the Technical University of Cluj-Napoca, Automation Department, Romania. Since 2007, she has published over 100 papers and book chapters, she has received multiple paper awards and has coordinated 3 research grants. Her research interests include modeling techniques, with a focus on fractional order systems, with applications ranging from biomedical systems to aerospace engineering.

David A. Kaminsky, MD is a Professor of Pulmonary and Critical Care Medicine at University of Vermont College of Medicine. He received his undergraduate degree from Yale University, and medical degree from University of Massachusetts Medical School. He completed his residency training in Internal Medicine at Columbia Presbyterian Medical Center in New York City, and fellowship training in Pulmonary and Critical Care Medicine at University of Colorado Health Sciences Center in Denver. Dr. Kaminsky joined the faculty of University of Vermont College of Medicine in 1995 and continues to work as a clinician, researcher and educator. Dr. Kaminskys areas of research interest include pulmonary physiology, lung mechanics, asthma and COPD.

Swati Bhatawadekar is a Scientific Associate at University Health Network-Toronto Rehabiliation Institute, Toronto, Canada. Swati received her bachelors and masters degrees in Instrumentation & Control Engineering from University of Pune (Pune, India), and PhD in Biomedical Engineering from Dalhousie University (Halifax, Canada). She completed her postdoctoral training in the Sleep Science Laboratory at Toronto Rehabilitation Institute. She has published 8 journal papers in several high impact journals including the Journal of Applied Physiology and Annals of Biomedical Engineering.

Geoff N. Maksym is Professor and Director of Biomedical Engineering at Dalhousie University at Halifax, Canada. He obtained his PhD from McGill University at the Meakins-Christie Laboratories. His research spans the cell to the patient in respiratory cell and lung mechanics in health and disease utilizing imaging, modeling, and developing novel medical devices. He has written more than 50 papers and book chapters and reviews publications for Journal of Applied Physiology, European Respiratory Journal, American Journal of Respiratory and Critical Care Medicine, Journal of Theoretical Biology, Journal of Cell Science, Nature, and others. He is an inventor for seven patents and is cofounder and currently Chief Scientific Advisor for Thoracic Medical Systems Inc., Montreal.

Lennart Lundblad is an Associate Professor of Medicine at the University of Vermont. He obtained his PhD in Experimental Clinical Physiology at the Lund University in Sweden. He is an expert in lung physiology with experience from work in both laboratory animals and humans. He had extensive experience in drug development and project management from working with AstraZeneca before joining as the faculty at the Larner College of Medicine at the University of Vermont in 2001. He has had continuous funding from NIH and has had extensive collaborations intra- and extramurally with other universities and the pharmaceutical industry. He is the author/coauthor of about 50 peer-reviewed articles and numerous abstracts and letters to the editor in internationally recognized journals.

Preface

This book is the result of manifold contributors along many years of research and practice in the respiratory medicine and biomedical engineering fields. It is not at all a complete picture of the state of art as it would mean to have a manifold volume of 1000 pages. Instead, the content is focused on new emerging tools as a result of the fruitful cross-fertilization of engineering and medicine. Tools for mathematics, models, statistics, and procedures viewed alternatively offer a new, fresh understanding of available information from standardized and nonstandardizeds lung function tests. Although one may argue that the medical, clinical aspect is somewhat superficial, it is sufficiently introduced for a broad understanding of concept by practitioners as well.

The organization of the book follows the line of moving from clinical content as lung function testing, toward mathematical tools and other complementary sources of information. My goal was to offer the community a new direction for research, to emphasize the tools at hand, and to encourage undertaking this challenging opportunity to make things better for health care in some aspects of respiratory medicine. A complete book could be written about any chapter in this book alone.

However, a take-home message of this book, if I were to give one, would be as follows. Although it may be possible to isolate one aspect of the patient in a certain measurement, that single aspect can usually only be understood when it is related to other aspects. That statement is valid for the book text as well: each detail may be related to many other details. It is only when these relations are routinely perceived that understanding has been reached.

The readers will find the contributors are well established in the field and with longstanding experience. I encourage young, motivated, and promising researchers to contribute as they have a most undefiable original perspective of novel opportunities beyond state of art and beyond state of practice.

Clara M. Ionescu,     Ghent University, Belgium

Acknowledgment

This text is partly based on results and courses that were acquired and used over many years at Ghent University, Belgium and other universities I have visited during my career so far. The text is also partly contributed by other authors, to whom I am grateful for their energy and time dedicated to this project—without them this book would not be possible. I would like to thank my colleagues for their loyalty and support in all my actions and for the timely and useful replies they always give me. The team from Elsevier is gratefully acknowledged for all technical and editorial support.

Chapter 1

Introduction

Clara M. Ionescu     Ghent University, Dynamical Systems and Control Research Group, Ghent, Belgium

Abstract

This introductory chapter explains the rationale motivating this book project and sets the stage for the reader to understand the importance of this work in the field. The content and timing have been carefully chosen to shape the current state of the art in a rather dark light, for it is necessary to observe its great potential improvement.

Keywords

Economical impact; Lung function set; Population trends; Respiratory disease; Societal impact

Contents

Generic Context

About This Book

Beyond This Book

References

Generic Context

At the confluence of medicine, biology, and engineering stands bioengineering. This increasingly important emerging field of practice and research has put forward numerous tools and knowledge over the past half century [1]. It is, however, the technological development of the last few decades that has helped surpass the informational barrier and expand its impact on society and man at large. Nevertheless, there is a large discrepancy between the traditional fields as medicine and technology-enabled fields, in terms of information processing and systems engineering in their broadest sense. Witness is the exponential amount of information and interaction flowing vertically and horizontally in all levels of action–reaction tasks of our daily life. Sadly, when it comes to medicine, this exponential growth is very limited. Medical intervention is still at its best an art rather than a science and based on a great deal of practice, personal expertise, and subjective perception. Time and money are perhaps inefficiently spent on searching, gathering, and processing data already available elsewhere or in prior circumstances.

The purpose of this book is to show the very large potential for development toward a systematic and unabridged know-how in respiratory medicine. Lung disease, being in the global top ten of leading causes of death and global top three of leading socioeconomic costs, is a burden with long shadows over health care in general [2]. Despite efforts, this burden is just as large as it was two decades ago, and projections for the next years to come are not encouraging, unless a different course of action is taken. Of all respiratory impairments, COPD (chronic obstructive pulmonary disease) and lung cancer are at the top of the pyramid in number of deaths and overall costs. The distribution of the costs, however, is unequally balanced, as in COPD there is a long timeline of treatment, disease management, and disability, whereas in lung cancer these are concentrated over a much smaller time span. One in five deaths worldwide are projected by the World Health Organization to be due to respiratory diseases.

Coming down to numbers, the European Union alone has costs of over 380  billion EUR annually from respiratory disease management. This includes disability, premature mortality, direct health service costs, drugs prescribed, as well as indirect costs related to lost production [3]. Disability-adjusted life years seem to be an important percent of total costs, i.e., about 100k EUR for a life-year lost owing to respiratory disease per person. Between asthma and COPD, the latter induces a twofold increase in total costs (direct and indirect). As the individual mortality from lung cancer may be indeed much higher, the course of COPD and asthma extends over many years. Although costs should not be the first incentive for progress and improved health care, they play an important role as a decision factor in the sociopolitical context. The greatest source of heterogeneity in any health care median is the variation in health care systems across EU countries and worldwide. This is for a significant deal dictated by culture, tradition, and economic and societal development.

Nevertheless, a great deal of items are potentially preventable or the decline in the disease progression may be minimized. For instance, smoking-induced COPD still contributes a staggering 60% of all causes of respiratory disease. According to the review performed in [4], the annual decline rate in the forced expiratory volume in the first second (FEV1) recorded in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-IV indicates the highest descent in stage II-III. As the evidence indicates, it is clear that the loss of lung function assessed as expiratory airflow reduction is more accelerated and