Paul M. O’Byrne, MB, FRCPI, FRCPC, FCCP, FRCP(Edin)
E.J. Moran Campbell Professor
Chair, Department of Medicine, McMaster University
Executive Director, Firestone Institute for Respiratory Health, St. Joseph’s Healthcare Hamilton

Paul M. O’Byrne obtained his Medical Degree at University College, Dublin and his training in Internal Medicine and Respiratory Medicine at McMaster University.  He undertook research training under the supervision of Dr. Freddy Hargreave at McMaster University and then Dr. Jay A. Nadel at the Cardiovascular Research Institute in San Francisco.  His research interests are on the mechanisms and treatment of asthma with particular reference to the role of environmental allergens and the mechanisms by which these cause airway inflammation.

Dr. O’Byrne is currently the E.J. Moran Campbell Professor of Medicine, and Chair of the Department of Medicine at McMaster University.  He is also the Executive Director of the Firestone Institute for Respiratory Health at St. Joseph’s Healthcare.  He has published 286 peer reviewed papers, 84 book chapters, 330 abstracts, more than 80 review papers, and edited 10 books. 

Dr. O’Byrne is currently an Associate Editor of CHEST and on the Editorial Boards of the American Journal of Respiratory and Critical Care Medicine and the American Journal.  He was Chair of the Executive Committee of the Global Initiative for Asthma from 2004-08.  He is a member of CIHR New Investigator Committee.

Research Interests:

a. Inflammatory cells and mediators in asthma 
b. Allergen-induced asthma.
c. Bone marrow inflammatory cell progenitors
d. Dendritic cell trafficking

Research Contributions

Inflammatory cells and Asthma:
During my post-doctoral training at CVRI in San Francisco, the first studies demonstrating an association between inflammatory cells influx into the airways and the development of airway hyperresponsiveness.  My specific contributions was to show that  neutrophils were necessary for ozone-induced airway hyperresponsiveness in dogs and that the eicosanoid, thromboxane was also involved in this process. After returning to FIRH in 1984, my laboratory was able to demonstrate airway inflammatory cells (eosinophils and mast cells) in the airways of mild, stable asthmatic subjects.  These observations have been replicated by many laboratories.

Biology of Leukotrines in Asthma: 
My laboratory was the first to demonstrate that allergen inhalation by asthmatic subjects resulted in cysteinyl leukotriene (cys LTs) release and excretion.  We subsequently have shown that cys LTs are the most important mediator not only in causing allergen- and exercise-induced bronchoconstriction, but also are important in allergen-induced eosinophil and dendritic cell migration into the airways.  I addition, csy LTs cause the release of inhibitory prostaglandins (most likely PGE2) which is responsible for exercise refractoriness in asthmatics.

Bone Marrow inflammatory cell progenitors in asthma: 
My laboratory was the first to examine the mechanisms of bone marrow eosinophilopoesis in allergic asthma.  We demonstrated that allergen-inhalation causes trafficking of T-cells into the bone marrow, which increase the production of interleukin (IL)-5.  This, together with an allergen-induced increased expression of the IL-5 receptor on eosinophil progenitors, results in increased numbers of bone marrow eosinophils.  Of interest, the up-regulation of IL-5 receptor is not modified by inhaled corticosteroids, but the increased production of IL-5 is.  We have also provided evidence of in-situ maturation of eosinophil progenitors in asthmatic airways.

Dendritic cells trafficking:
Dendritic cells (DCs)are the professional antigen presenting cells in the airways.  We were the first to demonstrate a reduction of circulating myeloid dendritic cells after allergen inhalation by asthmatic subjects.  We subsequently showed that these changes in myeloid DCs persist for up to 24h, while placmacytoid DCs do not change until 48h.  Our current studies are examining the changes in airway DCs after inhaled allergen.

Allergen challenge to evaluate new drugs for asthma:
Funding obtained from the AllerGen NCE allowed the development of the Clinical Investigator Collaborative to evaluate (in early Phase II studies) new molecules for the treatment of asthma.  I have co-chaired this initiative with L-P Boulet from Laval University.  This collaborative has successfully completed studies with an inhaled disacceride (the anti-inflammatory component of Heparin), an anti-sense against the common β-chain and CCR3, monoclonal antibodies against IL-9, IL-13 and C5a.

Martin Kolb, MD, Ph.D
Associate Professor, Department of Medicine, McMaster University,
Research Director, Firestone Institute for Respiratory Health

Dr. Martin Kolb is a German physician who obtained his MD at the Julius-Maximilian University Medical School in Würzburg, Germany. Dr. Kolb received extensive training in clinical and anatomical pathology in Nürnberg Germany, before he enrolled in general internal medicine which included extensive training in gastrointestinal endoscopy and ICU. He then specialized in Respiratory Medicine and was board certified for both disciplines in 2002. In 2003, Dr. Kolb acquired his “Venia Legendi” for Internal Medicine (PhD equivalent) at the Julius-Maximilian University Würzburg.

Research Interests

Dr. Kolb is Associate Professor of Medicine at McMaster University and Research Director of the Firestone Institute for Respiratory Health Dr. Kolb’s major research area as clinician scientist consists of the mechanisms of lung injury and tissue repair in fibroproliferative lung diseases such as IPF, chronic asthma and pulmonary hypertension, as well as emphysema. He has a strong interest in growth factor biology in the TGFβ family and matrix turnover, and uses a variety of animal models to study disease mechanisms and also the efficacy of novel drugs in the preclinical setting. Dr. Kolb’s research work involves models of acute and chronic lung disease, gene transfer, gene array analysis, laser capture microdissection, and quantitative PT-PCR. He also uses PET and CT for small animal imaging. Further, Dr. Kolb leads activities in biomarker development and is Principal Investigator in clinical trials on IPF.

Clinical Activities

Currently Dr. Kolb maintains a specialty clinic for interstitial lung disease and lung fibrosis and also general Respirology. He is medical staff for the inpatient consult service for Respirology and General Internal Medicine. Clinic bookings can be made through extension 35003.

Other Activities. Amongst Dr. Kolb’s other professional activities are leading roles in the Respiratory Cell and Molecular Biology Program Committee for the ATS and the Lung Injury and Repair group of the ERS (Group Secretary). Since 2008 he is Deputy Editor for Respirology, the official journal of the Asian Pacific Society of Respirology and since 2010 Academic Editor for PLoSOne. He is active in peer review for numenrous scientific journals and grant agencies, including CIHR, NIH, MRC UK, Wellcome Trust, NHS UK, German Research Foundation and many others. Dr. Kolb has been invited to speak for many conferences around the world.

Dr. Kolb has over 60 peer-reviewed publications in the last decade in journals such as Journal of Clinical Investigation, The American Journal of Pathology, The American Journal of Respiratory and Critical Care Medicine, Journal of Immunology and many others.
Over the course of Dr. Kolb’s career he has received career awards from the Parker B. Francis Families Foundation, Department of Medicine at McMaster and currently holds a New Investigator Award from the Canadian Institute for Health Research.

Stewart Pugsley MD
Clinical Director, Firestone Institute for Respiratory Health

Dr. Pugsley is the co-founder of the outpatient Chronic Respiratory Care Program and a founding member of the Respiratory Medical Staff at the inception of the Firestone Chest and Allergy Unit at St. Joseph’s Hospital. He is a graduate of the University of Toronto with a specialty in Internal Medicine.

He continues to be an integral member of the clinical staff within Firestone and of the medical staff of St. Joseph’s Healthcare Hamilton. Dr. Pugsley was instrumental in establishing the Clinic for Chronic Airway Obstruction. This clinic has improved care for patients with COPD by reducing the incidence of infective exacerbations and hospitalization.

Allergy / Adverse Reaction Clinicians

At this clinic, Drs Joe Greenbaum, Paul Keith and Susan Wasserman provide assessment and management of drug reactions, stinging-insect allergy and urticaria.

Dr. Greenbaum	Dr. Wasserman	Dr. Keith

 

 

Kjetil Ask, Ph.D
Assistant Professor, Department of Medicine, McMaster University

Dr. Kjetil Ask recently joined McMaster University and the Firestone Institute for Respiratory Health as an Assistant Professor of Medicine. His research focus will be on molecular mechanisms of chronic lung disease, with a specific interest on the role of immunophillins in Endoplasmic Stress and the Unfolded Protein Response. Dr. Kjetil Ask, originally from Norway, did his University studies in Burgundy, France. He began to study pulmonary pathology in 1997 as an undergraduate student in Dr Phillippe Camus’ laboratory in Dijon, France. After completing a Master’s degree equivalent, the Diplome d’Etude Approfondie, in 1999, he spent 4 years as PhD student working on mechanisms of drug-induced lung disease with Dr Camus. After defending his PhD in Pharmaceutical Biochemistry in 2003, he moved to Hamilton, Ontario, Canada to join the group of Dr Jack Gauldie at McMaster University.

Dr. Ask worked for four years as a Post-Doctoral fellow with Drs Jack Gauldie and Martin Kolb in the Department of Pathology and Molecular Medicine. The focus of his work was to study the pathobiology of pulmonary fibrosis, for instance by performing therapeutic interventions in animal models. In 2008, he started his second post-doctoral fellowship at the National Heart, Blood and Lung Institute in Bethesda, Maryland, USA. Dr Ask worked in the Translational Medicine Branch under the supervision of Drs Martha Vaughan and Joel Moss, where he investigated the role of an Endoplasmic Stress resident immunophillin linked to vesicular trafficking.  

Gerard Cox, MB FRCPC FRCPI
Professor and Respiratory Division Director, Department of Medicine, McMaster University

Dr. Gerard Cox obtained his MB BAO BCh with Honours in 1981 at University College Dublin, Ireland, completed his Medical and Surgical Internship in 1982, and his Internal Medicine training in Dublin, Ireland. In 1985, he moved to Canada and carried out residency training at McMaster University.

In 1987-88, Dr. Cox served as Chief Resident in Respiratory Medicine. Thereafter, he spent 2 years as a Research Fellow under the supervision of Dr. Jack Gauldie at McMaster University.  Dr. Cox obtained Royal College certification in Internal Medicine in 1987 and Respiratory Medicine in 1988. In 1991-2, he worked with Dr. Gary Hunninghake as a Research Fellow at the University of Iowa. Dr. Cox was appointed Assistant Professor at McMaster University in 1992.  In 1997 he was promoted to the rank of Associate Professor and in 2005 to the rank of Professor. In addition to his clinical and research activities, he has a number of administrative responsibilities.

From 2000-2002, Dr. Cox served as Chair of the Ontario Thoracic Society. He then joined the executive of the Canadian Thoracic Society. Currently, he is Past-President of the Canadian Thoracic Society. Previously he was Director of the Residency Training Program in Respirology and acting Head of Clinical Services at FIRH. At present he is Director of the Division of Respirology at McMaster University.

Research Interests

Dr. Cox’s primary research focus is on mechanisms and management of pulmonary inflammation.  In clinical research he has a strong collaboration with Dr. John Miller, Head of the Division of Thoracic Surgery, studying the role of surgery for emphysema, methods for the early detection of lung cancer and development of Bronchial Thermoplasty, a procedure for treating severe asthma.  His work has been supported by grants from several agencies including CIHR, and awards such as the Parker B. Francis Fellowship and the Father Sean O’Sullivan Research Centre Career Award.

Research Contributions

A randomized trial of chiropractic manipulation as complementary treatment of asthma in children.  N Engl J Med, 1998; 339:1013-1020 Balon J, Aker PD, Crowther ER, Danielson C, Cox G, O'Shaughnessy D, Walker C, Goldsmith CH, Duku E, Sears MR.

I was one of two respiratory physicians (with MRS) who designed and oversaw this project. This work required collaboration with chiropractors in the community and with the college of Chiropractic. It was a controversial project that drew criticism. It was immensely rewarding to complete this work and have it published in a premier peer-reviewed journal.

 A randomized controlled trial on the effect of inhaled corticosteroids on airways inflammation in adult cigarette smokers.  Chest 1999;115:1271-77 Cox G, Whitehead L, Dolovich M, Jordana M, Gauldie J, Newhouse MT.

This clinical trial was designed as a result of the observations I had made in the laboratory on the plural effects of corticosteroids: to inhibit release of inflammatory cytokines from lung structural cells, and to increase survival of neutrophils. This was one of the first studies in this area and showed no benefit of inhaled steroid treatment on indices of inflammation in smokers.

Lung volume reduction surgery vs medical treatment for patients with advanced emphysema.  Chest 2005;127:1166-1177 Miller JD, Berger RL, Malthaner RA, Celli BR, Goldsmith CH, Ingenito EP, Higgins D, Bagley P, Cox G, Wright CD.  
A randomized clinical trial of lung volume reduction surgery versus best medical care for patients with advanced emphysema; a two-year study from Canada. Miller JD, Malthaner RA, Goldsmith CH, Goeree R, Higgins D, Cox G, Tan L, Road JD. Annals of Thoracic Surgery 2006; 81:34-321.

I was one of two respiratory physicians (with DH) who collaborated with colleagues in Thoracic Surgery (JDM, RAM) to design and implement this trial involving 10 sites spanning Canada.

Radiofrequency ablation of airway smooth muscle for sustained treatment of asthma: rationale and preliminary investigations.  Eur Respir J 2004:24:659-663 Cox G, Miller J, Mitzner W, Leff A. R.

Bronchial thermoplasty for asthma. Am J Respir Crit Care Med 2006: 173: 965-969.

Cox G, Thomson NC, Sperb-Rubin A, Niven R, Corris P, Siersted HC, Olivenstein R, Pavord I, McCormack D, Chaudhuri R, Miller J, Laviolette M

Asthma Control during the Year after Bronchial Thermoplasty. Cox G, Thomson NC, Sperb-Rubin A, Niven R, Corris P, Siersted HC, Olivenstein R, Pavord I, McCormack D, Chaudhuri R, Miller J, Laviolette M, AIR Trial Study Group. . N Engl J Med 2007; 356:1327-1337.

This project has required detailed knowledge of bronchial structure and function and understanding of the biology of the response to injury in the human airway.

Myrna B Dolovich P. Eng
Associate Clinical Professor, McMaster University
Division of Respirology, Medicine

Professor Myrna Dolovich has been at the forefront of aerosol research for the past 40 years. Graduating from McGill University with a degree in electrical engineering, she worked, in the early years of her career, with renowned pulmonary physiologists Drs Joseph Milic-Emili and David Bates to expand our understanding of regional ventilation in the normal and diseased lung using gamma scintigraphic methods.

She later applied similar imaging techniques to establish the methodologies currently used by many of us for assessing distribution of inhaled aerosols in the lungs. At St Joseph’s Hospital/McMaster University, she worked closely with Drs M Newhouse, J Sanchis and R Wolff to study mucociliary clearance from the lungs by scintigraphic methods. These early studies set the stage for current use of such methods to assess new therapeutic approaches for improving clearance of secretions from the lungs of cystic fibrosis and COPD patients. Most recently she has applied newer imaging methods, namely positron emission tomography (PET), to assess the sites of inflammation in patients as well as mapping deposition patterns of inhaled aerosols in 3D. 

Research Interests
My research interests have involved the in vitro and in vivo characterization of medical aerosols from various types of drug delivery systems used in the treatment of respiratory disease and in a variety of patient groups. Development of the Aerochamber™ for patient use was a focus of early research for the aerosol group. Both 2D and 3D PET, and currently PET/CT, imaging modalities have been used to investigate factors which influence deposition and distribution of aerosolized drugs in the lung, such as breathing pattern and airway caliber. Preferential deposition or drug targeting to specific regions of the lung is an area of continuing interest and a project has been initiated to correlate acquired PET data with a published 3D geometric model of the human lung. A related interest is the investigation of epithelial cell cilia function and structure utilizing nasal and bronchial cilia obtained from patients with various respiratory diseases. The data provides an assessment of the ability of the lung to clear secretions as well as the effects on this key lung defence mechanism of a variety of traditional and experimental therapies. Cell culture using human bronchial and nasal epithelial primary cells have been established in the Aerosol Research Lab to provide model systems for investigating  disease mechanisms.

Research Contributions
Myrna has been a leader in developing and characterizing new aerosol delivery devices, especially metered dose inhalers and associated spacers, for use by adults and children with lung disease worldwide. She has led efforts to standardize the proper use of these devices to achieve efficient delivery of aerosolized drugs to the lungs of patients, also working with the Standards Council of Canada and the International Standards Organization developing standards for drug delivery devices. The work of the Firestone Aerosol Laboratory is focused on in vitro characterization of pharmaceutical aerosols and in vivo investigations of delivery of these aerosols to the lung in respiratory and systemic disease, correlating lung deposition and clearance measurements using radiolabelled aerosols and state-of-the art imaging techniques with physiologic and pharmacokinetic measurements as well as clinical outcomes. In addition, a facility within the laboratory has been established for studying, ex-vivo/in vitro, epithelial cell cilia function and structure in relation to lung disease, along with investigations of the effects on cilia of drugs and experimental agents.  Aerosol School, 3-day teaching program with practical laboratory experience in aerosol basics, aerosol measurements and techniques and applications to research and pharmaceutical laboratory and clinical settings was established in 2009 and is scheduled again for April 2011.

Publications include a recognized resource text on aerosols (Aerosols in Medicine: Principles, Diagnosis and Therapy. 1st and 2nd editions, eds. Morén F, Dolovich M. Newhouse M, Newman S. Elsevier Science Publishers 1989,1994). Selected research papers of major importance to the field are:

1. Aerosol Penetrance: A Sensitive Index of Peripheral Airways Obstruction. M. Dolovich, J. Sanchis, C. Rossman, M.T. Newhouse. J Appl Physiol 1976; 40(3): 468-471. Defined a method for assessing delivery of aerosols to target sites in the lung.
2. A comparison of submicronic technetium aerosol with xenon-127 for ventilation studies. Coates G, Dolovich M, Newhouse M. Proceedings of 3rd World Congress of Nuclear Medicine and Biology, Paris, France: Pergamon Press, 1982; II: 2014-2020. Validated the first use of a submicronic (extra-fine) aerosol to measure lung ventilation.
3. The Effect of Preferential Deposition of Histamine in the Human Airway. R.E. Ruffin, M.B. Dolovich, R.K. Wolff, M.T. Newhouse. Am Rev Respir Dis 1978; 117(3):485-592. Importance to response in targeting aerosols to different sites in the lung.
4. Clinical Evaluation of the Aerochamber: A Simple Demand Inhalation MDI Aerosol Delivery Device. M. Dolovich, R. Ruffin, D. Corr, M. Newhouse. Chest 1983; 84:36-41. Validation for the Aerochamber® aerosol delivery system, (developed at St Joseph's Hospital for pMDIs) and the clinical effects of tailoring inhalant aerosols.
5. Pressurized aerosols vs jet aerosol delivery to mechanically ventilated patients: comparison of dose to the lungs. Fuller H, Dolovich MB, Posmituck G, Wong-Pack W, Newhouse MT. Amer Rev Respir Dis 1990; 1:440-44. One of the first deposition studies in ICU patients and provided the rationale for changing the way aerosols are delivered to ventilated ICU patients. 
6. Computer simulations of lung morphologies within planar gamma images, Martonen T, Yang Y, Dolovich M, Guan X. Nucl Med Comm 1997; 18:861-869. Modelling of the lung linking the geometric contribution of the small airways to the 2D scintigraphic image.
7. Unleashing the PET: 3D imaging of the lung. Dolovich M, Nahmias C, Coates G.. In: Proceedings of Respiratory Drug Delivery VII. Eds Byron P, Dalby R, Farr SJ. Serentec Press, N.C. 2000; P215-230. Describes the potential for using inhaled PET emitters to evaluate delivery of drugs to the lung;
8. DEVICE  SELECTION AND OUTCOMES OF AEROSOL THERAPY:American College of Chest Physicians /American College of Asthma, Allergy and Immunology EVIDENCE-BASED GUIDELINES Dolovich M, Ahrens R, Hess D, Anderson P, Dhand R, Rau J, Smaldone GC, Guyatt G.. Chest 2005;127: 335-371; Systematic review of aerosol drug delivery devices.
9. Positron Emission Tomography versus Positron Emission Tomography – Computed Tomography: Tools for Imaging the Lung. Dolovich MB, Schuster DP. Proc Amer Thoracic Soc 2007; 4(4): 328-333.
10. Yaghi A, Zaman A, Dolovich M (2010). Primary Human Bronchial Epithelial Cells Grown from Explants. JoVE. 37. http://www.jove.com/index/details.stp?id=1789, doi: 10.3791/1789 Methodologic approach for culturing ciliated cells.

Myrna has served on the Board of Directors of the International Society for Aerosols in Medicine (ISAM) and is a member of the Editorial Boards of the Journal of Aerosol Medicine and Pulmonary Drug Delivery and Pediatric Allergy, Asthma and Immunology. She is a member of the Health Canada Scientific Advisory Committee  – Respiratory and Allergy Therapies (SAC-RT), joining in 2006.  In 2009, she was awarded the ISAM Career Achievement Award for contributions to medical aerosol research.

Nicole Drost, MD,
Assistant Professor, Department of Medicine, McMaster University

Dr. Nicole Drost is a graduate of the Ottawa University School of Medicine. She completed her Internal Medicine residency at Dalhousie, and then came to McMaster in July 2006 to study Respirology. Before deciding on McMaster for Respirology training, Nicole did a one-month elective at St. Joseph’s Healthcare.

Nicole completed a Clinical Scholarship at McMaster in Sleep Medicine in 2008, and joined Firestone in 2009 focussing on Respirology and Sleep Medicine.

 

Martin Stampfli, Ph.D
Associate Professor, Pathology and Molecular Medicine Centre for Gene Therapeutics, Respiratory Diseases and Allergy

PhD, University of Bern (Switzerland), 1995

Dr. Stämpfli has held several career awards including a Parker B. Francis Scholarship (USA) and received the Respiratory 2000 International Young Investigator Award in recognition of outstanding achievement in basic research. Dr. Stämpfliholds a CIHR and was a recipient of an Early Research Award from the Province of Ontario.

Research Contributions

The goal of my research program is to understand how environmental and infectious agents, alone or in combination, influence innate and adaptive immune responses in the respiratory tract and the contribution of these changes to the pathogenesis of respiratory disorders such as chronic obstructive pulmonary disease (COPD) and asthma.

The respiratory mucosa is in constant contact with both pathogenic and non-pathogenic environmental agents. A complex, hierarchical defense system protects the host against harmful environmental agents through a combination of physical barriers, and innate and adaptive immune mechanisms. Mounting evidence suggests that microbial burden and virulence, as well as the state of the host defense, critically determine the nature of a response to a given entity. Understanding factors that alter the state of host defense will, therefore, provide insight into the pathogenesis of respiratory disorders. While the use of animal models has contributed significantly to our understanding of the immune mechanisms underlying respiratory illnesses, most of these models were developed as a "one agent-one disease" concept. Specifically, disease processes or intervention strategies were studied in models that were established in specific pathogen-free animals by exposure to a single agent. This experimental approach, however, does not accurately reflect the real-life scenario as humans and animals are continuously and simultaneously exposed, via the respiratory tract, to multiple environmental agents.

A key focus of my research program is on the impact of cigarette smoke on innate and adaptive respiratory immune defense mechanisms. Tobacco use is the leading cause of preventable morbidity and mortality in adults globally and tobacco's adverse health effects are believed, at least in part, to be due to its impact on the immune system. I hypothesized that cigarette smoking suppresses respiratory host defense mechanisms. Thus, relatively non-virulent and opportunistic pathogens are dealt with inefficiently, necessitating the recruitment of immune/inflammatory cells to compensate for these local deficiencies. This causes excessive, unwarranted inflammation and, clinically, signs of infection. To date, we have shown that cigarette smoke attenuates alveolar macrophage and natural killer cell function in the lungs and exacerbates immune inflammatory processes elicited by viruses and bacteria. Furthermore, cigarette smoke affects immune inflammatory processes elicited by aeroallergens; it facilitates allergic sensitization to surrogate allergens, while attenuating the ensuing eosinophilic inflammation. Recently, we have also linked impaired innate immunity with ineffective clearance of transformed cells and increased respiratory tumor burden in mice.

More recently, we have initiated investigation of how viral infections influence subsequent bacterial super-infection and vice versa. These studies are based on the clinical observation that, in humans, respiratory viral infection predisposes to subsequent and often fatal bacterial super-infection with what are otherwise relatively avirulent bacterial pathogens. This research is a natural evolution from our studies in smoke-exposed mice and clearly shows that immune history impacts the state of host defense. Overall, our experimental approach is quite unique and will contribute to our understanding of the pathogenesis of respiratory disorders

Research Contributions

• How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Stämpfli MR, Anderson GP. Nat Rev Immunol. 2009 May;9(5):377-84.
• Bacteria Challenge in Smoke Exposed Mice Exacerbates Inflammation and Skews the Inflammatory Profile. Gaschler GJ, Skrtic M, Zavitz CC, Lindahl M, Onnervik PO, Murphy TF, Sethi S, Stämpfli MR. Am J Respir Crit Care Med. 2009 Apr 15;179(8):666-75. Epub 2009 Jan 29.
• Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic airway inflammation. Trimble NJ, Botelho FM, Bauer CM, Fattouh R, Stämpfli MR. Am J Respir Cell Mol Biol. 2009 Jan;40(1):38-46. Epub 2008 Jul 17.
• Gaschler, G.J., Bauer C.M.T., Zavitz C.C.J., and Stämpfli, M.R. Animal Models of COPD Exacerbations. In: Models of Exacerbations in Asthma and COPD. Eds U. Sjöbring and J.D. Taylor, Contrib Microbiol., Karger, Basel, Switzerland, Volume 14, p.p. 126-141, 2007.
• Lu, L.M., Zavitz, C.C.J, Chen, B., Kianpour, S., Wan, Y. and Stämpfli, M.R. Cigarette smoke impairs NK-cell-dependent tumor immune surveillance. J. Immunol. 178:936-43, 2007.
• Robbins, C.S., Bauer, C.M.T., Vujicic, N., Gaschler, G., Lichty, B., Brown, E.G., and Stämpfli, M.R. Cigarette smoke impacts immune inflammatory responses to influenza in mice. Am. J. Respir. Crit. Care Med. 174:1342-51, 2006.
  Drannik, A.G., Pouladi, M.A., Robbins, C.S., Goncharova, S.I., Kianpour, S., and Stämpfli, M.R. Impact of cigarette smoke on clearance and inflammation after Pseudomonas aeruginosa infection. Am J Respir Crit Care Med. 170(11):1164-71, 2004.
  

 

Dr. Stampfli is involved in teaching at both the graduate and undergraduate level within the Faculty of Health Sciences. In particular, he teaches the Bachelor of Health Sciences class HTH SCI 4II3, Advanced Immunology.

Team Members
Technical staff: Sussan Kianpour, Joanna Kasinska

Post-doctoral fellows:Fernado Botelho

PhD students: Carla Bauer, Gordon Gaschler, Brian Jobse, Jake Nikota, Cale Zavitz

MSc students: Nancy Trimble

Undergraduate students: Ashling Kelly, Jagbir Khinda, Kristen Lambert, Pamela Shen

 

David Higgins BSc, MB, BCh, MRCPI, FRCPC Diplomate ABSM
President, St. Joseph's Healthcare
Clinical Professor, McMaster University

Dr. Higgins has held multiple roles at St. Joseph’s Healthcare Hamilton (SJHH), and was appointed President in January 2010. He is also Clinical Professor in the Department of Medicine in the DeGroote School of Medicine, and is a Respirologist practicing in our Firestone Institute for Respiratory Health (FIRH).

Dr. Higgins' career at SJHH has also included: Chief of Staff, Chief of Medicine, member of the internal medicine service and attending physician on CTU. He has won a number of awards for teaching. His other specialty clinical work focused on Respirology clinical service and outpatient care with a special interest in sleep medicine. He still maintains an out patient clinic in the FIRH coordinating with his other administrative responsibilities.

Mark Inman, BSc, MSc, PhD, MD,
Professor, Department of Medicine, McMaster University
Scientific Officer, Firestone Institute for Respiratory Health

Dr. Mark Inman received his undergraduate and MSc training at the University of Waterloo, and his PhD and MD training at McMaster University Dr Inman is an Associate Professor (Medicine) in the Division of Respirology at McMaster University and is based at the Firestone Institute for Respiratory Health. His undergraduate and doctoral training were in exercise and respiratory physiology and mechanisms of dysfunction remain at the core of his research interests.

 

Research Interests

Since joining the faculty at McMaster University in 1998, Dr. Inman has been investigating the mechanisms underlying airway hyperresponsiveness in asthma. Specific interests at this time involve exploring the mechanisms by which airway wall remodeling as a result of chronic allergic inflammation may result in altered airway function. He has developed mouse models of chronic exposure to allergen, which produce several indices of airway remodeling and dysfunction similar to that observed in asthma. Ongoing projects within the lab are aimed at understanding the mechanisms underlying pathologic and physiologic changes in these models as well as exploring avenues of pharmacological intervention. Funding for these projects is from both peer review agencies (CIHR and Ontario Thoracic Society) as well as from the pharmaceutical industry.  Dr. Inman teaches graduate, undergraduate, and residency courses in respiratory physiology, and tutors within the undergraduate MD program.   Dr. Inman also coordinates the Division of Respirology Research Rounds, chairs the Laboratory Operating Committee at St Joseph’s Healthcare and is Scientific Officer (Respiratory) for the CIHR Operating Grant Review panel.

Research Contributions

The Role of The Bone Marrow in Inflammatory Diseases of the Airway.

Working with Dr Paul O'Byrne, I observed that allergen challenge of dogs results in production of a blood bourne hemopoietic factor (Inman et al Am J Respir Cell Mol Biol 1996, 15:305 41 citations) that can be inhibited by pretreating bone marrow with corticosteroid (Inman et at Am J Respir Cell Mol Biol 1997, 17:634 15 citations). I then demonstrated increases in bone marrow eosinophil progenitors following allergen challenge in mice (Inman et al Am J Respir Cell Mol Biol. 1999, 21:473 63 citations) and demonstrated that this process can be suppressed by corticosteroid treatment (Shen,H...MD Inman.: Am J Resp Crit Care Med.2002 166:146 18 citations). These findings suggest that interruption of eosinopoietic signaling between the lung and bone marrow may be an important site for novel therapies.

Regular Treatment with Inhaled Betaagonists on ExerciseInduced Bronchoconstriction.

With Dr Paul O'Byrne, I demonstrated that regular treatment with salbutamol results in  worsening of exerciseinduced bronchoconstriction, and  a reduced protective effect of additional salbutamol given before exercise (Inman et al. Am J Respir Crit Care Med 1996  153:65 63 citations). I later showed  that regular treatment with salbutamol suppresses the effectiveness for further salbutamol to reverse exercise induced bronchoconstriction (Hancox,RJ....MD Inman. Am J Resp Crit Care Med 2002, 165:1068 35 citations).

Morphometric Analysis of Mouse Airways

Our ongoing interest in the relation between structural and functional changes in the airway has required being able to objectively quantify specific morphological outcomes. This has involved developing computerized morphometric algorithms to assess changes in airway morphology (Ellis et al Lab Invest. 83:1285-1291, 2003. - 19 citations). We have since extended this technique to include medium and small airway analysis (Hirota at al Respir.Res. 7:120 .2006).

Distribution of Intranasaly Administered Substances in Mice

We have examined the effects of several delivery techniques on the distribution of intranasal instillation into mice (Southam,DS et  Am J Physiol. 282:L833-, 2002 - 19 citations). This provides valuable information to the increasing number of researchers using this as a delivery route.

Development of a Mouse Models of Sustained Airway Hyperresponsiveness

My primary research interest since my appointment has been studying the role of chronic allergic inflammation on airway responsiveness. We have developed two models of chronic exposure to ovalbumin or house dust mite, each resulting in aspects of airway wall remodeling and hyerresponsiveness that is sustained for many weeks after the cessation of allergen (Leigh,R...MD Inman. Am J Resp Crit Care Med 2002, 66:1212 57 citations)(Southam,D,,,MD Inman J.Allergy Clin.Immunol.2007 119:848 2 citations). We have demonstrated that immune based intervention can prevent these outcomes (Leigh, R.....MD Inman.  Am.J.Resp.Crit.Care Med 2004, 169:860 37 citations), but not reverse them (Leigh, R.....MD Inman.  Am.J.Resp.Crit.Care Med 2004, 170:851 15 citations) (Leigh, R.....MD Inman.  J.Appl. Physiol. 2004, 97:2258 9 citations). Our focus in the lab is based on further understanding of the mechanisms underlying sustained AHR. Considerable interest from the phamaceutical industry in these models provides access to novel intervention strategies.

Luke Janssen, BSc, MSc, PhD
Professor, Department of Medicine, McMaster University

Dr. Janssen received his B. Sc. (Biochemistry; 1984), M. Sc. (Medical Sciences - Neurosciences; 1987), and  Ph. D. (Medical Sciences - Physiology and Pharmacology; 1990),  from McMaster University

Dr. Janssen is a biomedical researcher who trained under Dr. E. E. Daniel (1987-1990) and S. M. Sims (1990-1993), then joined faculty at McMaster University (1993); he is currently full professor in the Department of Medicine.  He has received unbroken operating support from the MRC/CIHR from 1993 to the present, as well as continuous salary support from provincial and national agencies from 1989 until obtaining full tenure in 2005.  He has also competed successfully for operating support from the Heart&Stroke Foundation of Canada, the Ontario Thoracic Society, as well as industry (AstraZeneca; GlaxoSmithKline; Merck-Frosst).  He has supervised 7 postdoctoral fellows, 10 graduate students (5 MSc, 5 PhD) and 31 undergraduate students enrolled in the Honors Biology/Pharmacology Co-Op program (who are recruited for full-time placements ranging from 4-12 months). 

https://univmail.cis.mcmaster.ca/~janssenl/index.htm

Research Interests:

The goal of his studies, from his doctoral training to the present, has been an exposition of the regulation of smooth muscle function.  This began as a pharmacological characterization of the receptors on the nerve endings and smooth muscle cells of the airways, followed by investigations of airway smooth muscle physiology and pathophysiology (ozone-induced airway hyperreactivity) using intracellular microelectrode electrophysiological techniques.  Presently, he is focusing particular attention on the regulation of ion channels and cytosolic levels of [Ca2+] in airway and pulmonary vascular smooth muscle using patch-clamp and intracellular microelectrode electrophysiological techniques, Ca2+-fluorimetry, and classical organ bath methods. 

Research Contributions

Ghayur MN, Janssen LJ. A natural way forward to cardiovascular health. Nature Reviews Cardiology 7(3): 1-2, 2010.

P. Dyrda, P. Malinouski, Bernd Nilius, L. J. Janssen.  Thermal reduction of airway smooth muscle function involves TRPV2 channels.  American Journal of Respiratory Cell and Molecular Biology, 2010

Khan, M. A., R. Ellis, M. D. Inman1, J. H. T. Bates, M. J. Sanderson, L. J. Janssen.  The influence of airway wall stiffness and parenchymal tethering on the dynamics of bronchoconstriction.  American Journal of Physiology, 2010
L. J. Janssen. Asthma therapy: from where have we come, why did we fail, and where should we go next?  European Respiratory Journal 33:11-20, 2009

I. Mueed, Y. Zhang, T. Aziz, V. Chu, L. J. Janssen.  Structural and electrophysiological changes in atherosclerotic radial artery grafts account for impairment of vessel reactivity.   Atherosclerosis 206(2):405-10, 2009

T. Tazzeo, Franz Worek, L. J. Janssen.  The NADPH-oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+-pump.  British Journal of Pharmacology 158(3):790-796, 2009

L. J. Janssen, L. Farkas, T. Rahman, M. Kolb.  Purinergic Ca2+-signaling in cultured human pulmonary fibroblasts.  International Journal of Biochemistry & Cell Biology 41(12):2477-2484, 2009

H. van der Kleij, N. Charles, K. Karimi, Y-K M, J. Foster, Luke Janssen, P. C. Yang, W. Kunze, J. Rivera, and J. Bienenstock  Evidence for neuronal expression of functional Fc (ε and  γ) receptors.  Journal of Allergy Clinical Immunology 125(3):757-60, 2009

N. Ghayur, Luke Janssen.  Traditional plant medicines of Canada’s Aboriginal cultures. Alternative and Complementary Therapies 15(6): 319-321, 2009.

Ghayur, M.N. , L. J. Janssen.  Real-time imaging of Ca2+-handling in intact renal glomeruli using confocal microscopy.  Medical Hypotheses and Research 5:47-56, 2009

L. J. Janssen. Asthma therapy: from where have we come, why did we fail, and where should we go next?  European Respiratory Journal 33:11-20, 2009

I. Mueed, Y. Zhang, T. Aziz, V. Chu, L. J. Janssen.  Structural and electrophysiological changes in atherosclerotic radial artery grafts account for impairment of vessel reactivity.   Atherosclerosis 206(2):405-10, 2009

T. Tazzeo, Franz Worek, L. J. Janssen.  The NADPH-oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+-pump.  British Journal of Pharmacology 158(3):790-796, 2009

Purinergic Ca2+-signaling in cultured human pulmonary fibroblasts.  (Janssen, Farkas, Rahman, Kolb) International Journal of Biochemistry & Cell Biology 41(12):2477-2484, 2009

Evidence for neuronal expression of functional Fc (ε and  γ) receptors.  (van der Kleij, NCharles, Karimi, Foster, Janssen, Yang, Kunze, Rivera, Bienenstock)  Journal of Allergy Clinical Immunology 125(3):757-60, 2009

Traditional plant medicines of Canada’s Aboriginal cultures. (Ghayur, Janssen)  Alternative and Complementary Therapies 15(6): 319-321, 2009.

Real-time imaging of Ca2+-handling in intact renal glomeruli using confocal microscopy.  (Ghayur, Janssen)   Medical Hypotheses and Research 5:47-56, 2009

Contractility of renal glomerulus and mesangial cells: lingering doubts and strategies for the future.  (Ghayur, Krepinsky, Janssen.)  Medical Hypotheses and Research 4:1-9, 2008

Ginger attenuates acetylcholine-induced contraction and Ca2+ signalling in murine airway smooth muscle cells. (Ghayur, Janssen)  Canadian Journal of Physiology and Pharmacology 86(5): 264-271, 2008

The effect of allergen on airway narrowing dynamics as assessed by the lung slice technique.  (Chew, Hirota, Ellis, Wattie, Inman, Janssen)  European Respiratory Journal 31(3):532-538, 2008

Ryanodine receptors decant internal Ca2+  store  in human and bovine airway smooth muscle.  (Tazzeo, Zhang, Keshavjee, Janssen) European Respiratory Journal 32(2):275-84, 2008

Isoprostanes and lung vascular pathology.  (Janssen) American Journal of Respiratory Cellular and Molecular Biology 39(4):383-389, 2008

The effects of leptin and adiponectin on airway smooth muscle biology.  (Parameswaran, Radford, Fanat, Sharma, Janssen, Cox)  American Journal of Respiratory Cellular and Molecular Biology 39(4):475-481, 2008

Properties of a store-operated nonselective cation channel in airway smooth muscle.  (Helli, Janssen)  European Respiratory Journal 32:1529-1539, 2008

Cardiovascular and airway relaxant activities of peony root extract.  (Ghayur, Gilani, Janssen)  Canadian Journal of Physiology and Pharmacology 86(11):793-803, 2008

Involvement of the neurokinin-2 receptor in airway smooth muscle stretch-activated contractions assessed in perfused intact bovine bronchial segments.  (Hernandez, Janssen)   Journal of Pharmacological and Experimental Therapeutics 327:503-510, 2008

Isoprostanes constrict human radial artery through stimulation of thromboxane-receptors, Ca2+-release and RhoA activation.  (Mueed, Tazzeo, Pertens, Zhang, Cybulski, Semelhago, Noora, Lamy, Teoh, Chu, Janssen).  J Cardiovasc Thoracic Surg 135(1):131-8, 2008  

Store-refilling involves both L-type calcium channels and reverse-mode sodium calcium exchange in airway smooth muscle.  (Hirota, Janssen). Eur Respir J 30:269-278, 2007

U46619-induced tyrosine phosphorylation and modulation by genistein,daidzein and equol.  (Liu, Tazzeo, Lippton, Janssen).  J Cardiovasc Pharm 50:441-448, 2007

Sodium and asthma: something borrowed, something new. (SA Hirota, LJ Janssen).  Am J Physiol 293:L1369-L1373, 2007

E-ring isoprostanes stimulate a Cl- conductance in bovine airway epithelium via EP prostanoid receptors coupled to cyclic nucleotides.  (Seto, Hirota, Hirota, Janssen).  Am J RespCell Mol Biol 38:88-94, 2007

E-ring isoprostane augments cholinergic neurotransmission in bovine trachealis via FP-subtype prostanoid receptors.  (Paredes, Janssen).  Am J RespCell Mol Biol 37:739-747, 2007

Kinetics of in vitro bronchoconstriction in an elastolytic mouse model of emphysema.  (A Khan, S Kianpour, M Stampfli, LJ Janssen).  Eur Resp J 30(4):691-700, 2007

Store-refilling involves both L-type calcium channels and reverse-mode sodium calcium exchange in airway smooth muscle..  (Hirota, Janssen). Eur Resp J 30:269-278, 2007

Ionic mechanisms in airway smooth muscle. (Hirota, Helli, Janssen). Eur Resp J 30:114-133, 2007

The reverse-mode of the sodium-calcium exchanger provides a source of calcium for store-refilling following agonist-induced calcium mobilization.  (Hirota, Pertens, Janssen) Am J Physiol 292:L438-L447, 2007

ROCs and SOCs: What’s in a name?  (Janssen, Kwan)  Cell Calcium 41:245-247, 2007

Isoprostane-induced airway hyperresponsiveness is dependent upon Rho/ROCK signaling and internal Ca2+-handling.  (Liu, Tazzeo, Janssen) Am J Physiol 291:1177-1184, 2006

Regulation of airway smooth muscle RhoA/ROCK activities by cholinergic and relaxant stimuli.  (Liu, Zuo, Janssen)  Eur Resp J 28:703-711, 2006

Characterization of membrane potassium currents and their regulation by nitric oxide donor in human radial arterial smooth muscle cells.  (Zhang, Tazzeo, Chu, Janssen) Cardiovasc Res 71:383-392, 2006

Intracellular Cl— fluxes play a novel role in Ca2+-handling in airway smooth muscle. (Hirota, Janssen) Am J Physiol 290:L1146-L1153, 2006

8-isoPGE2 activates Ca2+-dependent K+ current via cAMP signaling pathway in murine renal artery. (Zhang, Janssen) Eur J Pharmacol 520:22-28, 2005 

Atherosclerosis of radial arterial graft may increase the potential of vessel spasm in coronary bypass surgery. (Zhang, Chu, Janssen) J Thorac Cardiovas Surg130:1477-1478, 2005

Cyclopiazonic acid activates a Ca2+-permeable, non-selective cation conductance in porcine and bovine trachealis. (Helli, Pertens, Janssen) J Appl Physiol 99:1759-1768, 2005 

Regulation of Rho/ROCK signaling in airway smooth muscle by membrane potential and [Ca2+]. (Liu, Zuo, Pertens, Helli, Janssen)  Am J Physiol 289:L574-L582, 2005 

Mechanical and electrophysiological effects of isoprostanes on bronchial arterial smooth muscle.  (Janssen, Tazzeo, Miller)  Arch Physiol Biochem 111(4):337-339, 2005

 

Neil Johnston, M.Sc
Assistant Clinical Professor, Department of Medicine, McMaster University

Neil Johnston is an epidemiologist at the Firestone Institute for Respiratory Health.  He had previously worked as a consultant in many areas of health system development including physician human resource planning, health information system design and the development of market segmentation systems for health sector application. Neil obtained his MSc from McMaster University Department of Clinical Epidemiology and Biostatistics Program in Design, Measurement and Evaluation.

Neil Johnston founded and directs the Ontario Physician Human Resources Data Centre which supports physician human resource planning in Ontario in partnership with the Ministry of Health and Long-Term Care, the Ontario Medical Association, the College of Physicians and Surgeons of Ontario and the Council of Ontario Faculties of Medicine.

Research Interests

Current research interests include the development of technologies for serial monitoring of respiratory disease patients; the role of respiratory viral infections (RVI) in asthma and COPD exacerbations and the evaluation of therapies that may prevent or reduce the effects of RVI related exacerbations of both diseases.  
As principal investigator his current studies include a cohort study of COPD patients using BlackBerry devices for symptom monitoring examining the role of RVI in seasonal cycles of COPD symptoms; studies of epidemic cycles of COPD and asthma and the factors associated with them.

Research Contributions

Neil Johnston’s current major interest is the evaluation of technologies that enable rapid, secure serial reporting by patients of respiratory symptoms. Traditional approaches to collecting respiratory patient symptom data and reliance on patients to notify study personnel when exacerbations occur have been shown to under detect events and to deliver data of questionable validity. Optimal capture of patient reported data has the potential to both improve the efficiency of clinical trails and to introduce endpoints based on measures of patient health rather than categorical events.

Renee Labiris MSc., Ph.D.

Assistant Professor, McMaster University
Divisions of Respirology and of Clinical Pharmacology

Dr. Labiris received her undergraduate and MSc training at McMaster University and her PhD training at University of Toronto in Pharmacology. She joined the faculty at McMaster University and FIRH in 2004.

 

 

Research Interests: 

Dr. Labiris’ research interest is in the development of methods to visualize in situ lung disease and the pharmacokinetic profiles of inhaled drug therapies in both animal models of disease and humans, using radiopharmaceuticals and 3D PET and SPECT imaging modalities. 

The goal of her research is to use functional and structural imaging as common outcome measurements to bridge the gap between preclinical and clinical studies of drug therapies and disease progression.

Current research involves pre-clinical PET (inflammation, fibrogenesis), SPECT (ventilation, perfusion, mucociliary clearance) and CT imaging of animal models of pulmonary fibrosis (in collaboration with Drs. Martin Kolb and Mark Inman), COPD (in collaboration with Drs. Martin Stampfli and Mark Inman), chronic lung bacterial infections and the pharmacokinetics of radiolabeled insulin in an animal model of type 2 diabetes (in collaboration with Drs. John Valliant, Alison Holloway and Hertzel Gerstein). Clinically, she is studying the relationship between structural and functional abnormalities in Cystic Fibrosis using SPECT/CT and lung inflammation in COPD using PET.

Research Contributions

Traditional measures of infectious disease, such as white blood cell counts have been shown not to correlate with clinical measures in cystic fibrosis (CF). We hypothesized that 18F-fluorodeoxyglucose (18FDG), a glucose analogue, and positron emission tomography (PET) technology could be a direct quantitative measurement of inflammation in the lung.  Neutrophils consume large quantities of glucose during activation and therefore, will have an increased uptake of 18FDG.  Despite the presence of chronic neutrophilia in the CF lung, the majority of CF patients had either a normal or below normal rate of 18FDG uptake. The study showed 18FDG /PET imaging is not an objective quantitative indicator of lung inflammation in stable CF. The results of this study raise some very interesting questions regarding the neutrophil dysfunction which could explain the inability to eradicate bacterial infections.  This is the first observation in situ that the lung neutrophils may not be functioning normally in CF.

 Labiris NR, et al.. Uptake of 18Fluorodeoxyglucose in the Cystic Fibrosis Lung: a Measure of Lung Inflammation. Eur Respir J 2003 21:848-854.

Airway inflammation is believed to be a major cause of lung destruction in CF. Airway inflammation measurements had not been previously used in CF studies as an outcome measure.  By adapting the sputum processing methodology used in asthma to CF sputum, we were able to measure sputum inflammatory indices. We demonstrated that while continuous improvement in lung function was observed despite a diminished microbial response in the CF patients, prophylactic inhaled aminoglycoside therapy did not reduce airway inflammation. We showed an increase in the prevalence of mucoid Pseudomonas aeruginosa (Psa) with inhaled aminoglycoside therapy.  This switch to an inherently more resistant phenotype may reduce the effectiveness of aminoglycosides, whose actions are impaired by biofilm microcolonies and may explain the observed reduction in the antimicrobial effect.

Jayaram L, Labiris NR,  et al.. Canadian Respiratory Journal 2007, 2)Labiris NR, et al..  ERJ 2008(submitted). 3)Labiris NR, et al. Am J Resp Crit Care Med 2001 163(5):A84.

Discrepancy between animal model and human disease imposes a major scientific challenge. The goal of my research has been to develop and validate molecular and anatomical imaging as this common biomarker to bridge the translational gap between preclinical and clinical studies of disease progression and drug efficacy. In the past three years, I have successfully established this new research program in preclinical imaging of lung disease. Standard 18FDG and PET imaging as a method of quantifying and monitoring lung inflammation established clinically in CF (Labiris Eur Respir J 2003), sarcoidosis (Labiris Eur Respir J 2003) and COPD have been adapted to investigate animal models of pulmonary fibrosis, cigarette smoke-exposure, emphysema, bacterial infections. Using the radiotracers, 18FDG and 18F-proline (developed in-house as a tracer of collagen biosynthesis) with PET imaging, we have been able to differentiate active fibrogenesis and inflammation which correlate with histological evidence in different rodent models of pulmonary fibrosis (Labiris R et al. Highlighted abstract ATS 2007). Using micro CT imaging, my laboratory has developed a quantitative measurement of changes in lung volume and densitometry in animal models of pulmonary fibrosis (Ask K, Labiris R .et al. Translational Medicine 2008, submitted) and emphysema. In these studies, we have detected significant changes in lung structure and density in individual animals over time using microCT. In animal models of COPD, we have observed an increase in ventilation/perfusion mismatching (SPECT), suggesting impairment in gas exchange in cigarette smoke- and elastase-exposed mice.  Quantitative analysis of the CT images of the lung showed a leftward shift in the lung tissue density distribution to low densities corresponding to emphysematous-like changes observed in histology.

Pulmonary delivery of antibiotics has been restricted to nebulization, an inefficient, time- consuming delivery method that is generally disliked by patients. To overcome this inefficiency, we developed a dry powder gentamicin inhaler (DPI).  We found that gentamicin administration by a DPI was as efficacious as nebulized gentamicin therapy at reducing bacterial colony counts at a 7-fold lower dose to the airways in patients with CF and non-CF bronchiectasis. This study suggested that delivering the antibiotic via DPI can eliminate the obvious problems of discomfort and poor pulmonary delivery with intravenous administration and should be as effective as nebulization for inhaled drug delivery while being potentially much more acceptable to patients.

Labiris NR, et al. Am J Respir Crit Care Med. 1999 160:1711-16

Mark Larché, Ph.D
Professor of Medicine, McMaster University

McMaster University / GSK Chair in Lung Immunology,
Canada Research Chair in Allergy and Immune Tolerance
Adjunct Professor of Biochemistry and Biomedical Sciences, McMaster University Honorary Professorial Fellow, Imperial College London, UK.

Dr. Larché completed his PhD in Immunology at the Royal Postgraduate Medical School, University of London in 1990. He spent 3 years at St. Jude Children’s Research Hospital, Memphis, TN as a postdoctoral fellow. On his return to the UK he joined the Immunology Department at St. Mary’s Hospital Medical School, prior to joining the faculty of the National Heart and Lung Institute, Faculty of Medicine, Imperial College London.

Research Interests

Dr. Larché has authored over 100 scientific papers and has been the recipient of several international prizes including “The Respiratory 2000 International Young Investigator Award”, “The Henning Lowenstein Research Award 2000” and the "Pharmacia Allergy Research Foundation Award" in 2001. Together with Professor AB Kay, he founded “Circassia Ltd.”, a biotechnology company to develop vaccines for allergic diseases. Research interests include the immunopathogenesis of asthma, immunological mechanisms of immunotherapy, pathogenesis of autoimmune diseases and graft rejection

Research Contributions

Haselden, B., Kay A. B., Larché, M. IgE-independent, MHC-restricted T cell peptide epitope-induced late asthmatic reactions. J. Exp. Med. 189 1885-1894 (1999). Impact Factor 14.48 Times cited 138

This study was the first to demonstrate that direct activation of allergen-specific T cells can result in airway narrowing in vivo. This observation has resulted in a major re-appraisal of mechanisms of airway narrowing in asthma as it is now clear that T cell activation, as well as mast cells/basophil activation, can lead to narrowing of the airways in asthma (isolated late asthmatic reaction; LAR).

Oldfield, W.L.G., Kay, A.B, & Larché, M. Induction of antigen-specific hyporesponsiveness in atopic asthmatic subjects with allergen-derived T cell peptides. J. Immunol (2001) 167 1734-1739. Impact Factor 6.29 Times cited 71

This study demonstrated that single doses of microgram quantities of T - cell epitope peptides can result in profound tolerance to both further peptide rechallenge and systemic challenge with allergen. This study was the first to demonstrate tolerance at such low doses and resulted in the initiation of a development program for peptide vaccines for the treatment of allergic disease.

Oldfield, W.L.G., Larché, M. & Kay, A.B. Fel d 1-derived T cell peptides inhibit early- and late-phase allergic reactions and modulate interleukin-4, interleukin-13, interferon-gamma and interleukin-10 production in cat-allergic subjects. Lancet (2002) 360 47-53. IF 25.80 Times cited 125

The results of the study demonstrated that it is possible to induce immunological tolerance to a sensitizing allergen and that this is associated with the down-regulation of both Th1 and Th2 cytokines, with concomitant upregulation of the regulatory cytokine IL-10. The magnitude of allergic skin reactions to allergen challenge was reduced in the active treatment group following therapy. Treated subjects reported a significant improvement in their symptoms when they encountered an allergen source (cats) after peptide therapy.

Verhoef, A., Alexander, C., Kay, AB., Larché, M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Medicine (2005) 2 e78. IF 13.75 Times cited 31

This study was the first to demonstrate the induction of functional, antigen-specific regulatory T cells following peptide immunotherapy in humans. The majority of studies addressing regulatory T cells focus on “naturally occurring” CD4+CD25+ which are usually of indeterminate antigen specificity. Moreover the existence of these cells is demonstrated indirectly through non-exclusive cell phenotype, cytokine production profile or expression of the transcription factor Foxp3. Here CD4 T cells isolated after peptide immunotherapy suppressed allergen-specific proliferative responses of cells isolated before therapy.

Founder of University of London spin-out biotech company “Circassia Ltd.”

Larché co-founded Circassia Ltd. (http://www.circassia.co.uk), in December 1998 with Dr. AB Kay. The company was founded in order to raise Research & Development funding to translate peptide vaccines developed by the founders into the clinic. The founders initially raised seed funding (approx. CDN$1.5M) from the University Challenge Seed Fund (UK) and from a private investment Trust to establish the company. The company has subsequently attracted over CDN$45M in private investment. The company has a number of peptide vaccine programmes entering clinical trials. This is a significant contribution since it provides real “bench to bedside” translation of basic research initially funded by a charity (Asthma UK) and the MRC.

Andrew McIvor MD, MSc, DCH, FRCP (C), FRCP(E)
Professor, McMaster University

Dr. McIvor joined the Firestone Institute for Respiratory Health in
October 2005 having previously performed research with Dr. Sears and
Dr. Hargreave as a Pulmonary Fellow at FIRH between 1992 to 1995.  Dr. McIvor is originally from Belfast in Northern Ireland. After completing his post-graduate training in Internal Medicine, he immigrated to Canada in 1989. 

After completion of a fellowship in Respiratory Medicine at the University of Toronto, he obtained an MRC grant to study in Clinical Epidemiology at McMaster University where he spent time working in Asthma and obtained his MSc.  Dr. McIvor is currently Chair of the Canadian Thoracic Society and Chairman of the Asthma Committee.

Research Interests

Dr. McIvor’s major clinical and research interests are in “Quality Management and Health Outcomes in Obstructive Lung Disease”.  He is also active in the design and implementation of phase II and III randomized controlled trials for new therapies in obstructive lung disease i.e. CXCR1/CXCR2 antagonists, desulfated heparin, phosphodiesterase and neutrophil elastase inhibitors.  He has assembled a community based cohort of COPD patients and has been prospectively assessing them with BlackBerry technology.

Research Contributions

1. To design and implement one of the first randomized clinical trials to assess efficacy of asthma therapies using  sputum eosinophiles as  the primary outcome of  inflammation.

McIvor RA, et al., Steroid sparing versus masking effects of Salmeterol in asthmatics using high dose inhaled corticosteroid. 
Am J Respir Crit Care Med 1998;158:924-930

1. Chairman of Canadian Thoracic Society Asthma Committee, currently completing new 2008 Adult and Pediatric Asthma Guidelines.

2. Head of Division of Respiratory Medicine Halifax, NS 2002 to 2005 Significant input into raising the clinical profile and academic achievements of the group.

3. Obtained MD and MSc (Design, Measurement and Evaluation, Clinical Epidemiology) both as postgraduate degrees by theses.

4. Development of local and national guidelines including Asthma, COPD, Community Acquired Pneumonia, Lung Cancer, Smoking Cessation and Sinusitis.

Select 2007 Publications

McIvor A, Little P 10 Minute Consultation; Chronic Obstructive Pulmonary Disease BMJ 2007; 334:798.

McIvor RA
Future Options for Disease Intervention:  Important Advances in Phosphodiesterase (PDE) 4 Inhibitors Eur Respir Rev 2007; 16: 105, 105-112.

Calverley PM, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri L.
A One Year Randomized Controlled Trial of Roflumilast in Treatment of COPD. Am. J. Resp. Crit. Care Med. 2007 July 15;176(2):154-61;

Miller E, Sears M, McIvor A, Liovas A
Canadian Economic Evaluation of Budesonide/Formoterol as maintenance and Reliever Treatment in Patients with Moderate to Severe Asthma.
Can Resp J 2007;14 (5): 269-275

Boulet LP, McIvor RA, Marciniuk D Respiratory Guidelines Implementation in Canada Can  Resp J 2007: 14(6) 329-330 Editorial

Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, Balter M, O’Donnell D, McIvor A, Sharma S, Bishop G, Antony J, Cowie R, Field S, Hirsh A, Hernandez P, Rivington R, Road J, Hoffstein V, Hodder R, Marciniuk D, McCormack D, Fox G, Cox G, Prins HB, Ford G, Bleskie D, Doucette S, Mayers I, Chapman K, Zamel N, FitzGerald M.

Tiotropium in Combination with Placebo, Salmeterol, or Fluticasone-Salmeterol for Treatment of Chronic Obstructive Pulmonary Disease: A Randomized Trial. Ann Intern Med. 2007; 146: 545-55

Helen Neighbour MB, PhD, MRCP(UK)
Assistant Professor, McMaster University
Staff Respirologist, St. Joseph's Healthcare

Dr Helen Neighbour graduated from University College London Medical School in 1997. She undertook specialist training in Respiratory and General Internal Medicine in London. She completed a PhD in respiratory immunopharmacology and allergic airway diseases at The Royal Brompton Hospital and Imperial College London.

Since June 2009 she has been an Assistant Professor in the Department of Medicine at McMaster University undertaking both clinical and research work. Her specialist interest within Respiratory Medicine is Asthma and the measurement of airway inflammation, with a particular interest in the relationship between nasal disease and asthma.

 

Peter Powles MD, FRACP, FRCPC, ABSM
Professor Emeritus, Division of Respirology, Department of Medicine
Active Staff, St. Joseph's Healthcare, Hamilton
Active Staff, St. Joseph's Health Centre, Toronto

Dr. Powles' expertise in sleep medicine began in the 1970's. He is a Diplomate of the American Board of Sleep Medicine and a Fellow of the American Academy of Sleep Medicine. Dr. Powles is a Professor Emeritus, McMaster University, Hamilton, Ontario. Currently, he holds a position as a sleep disorders consultant at St. Joseph's Healthcare Hamilton.

Michael Quinn BA, MHA
Research and Business Development Manager, Firestone Institute for Respiratory Health

Assistant Clinical Professor, Department of Medcine, McMaster University

Mr. Quinn has over 25 years of diversified experience in both business and health care. His qualifications include having worked as a senior manager with government, a program director within an academic health sciences center department, a senior health planner, an information technology specialist, a web designer, and a youth counselor. 

Mike received a Master’s degree in Health Care Administration from the University of Ottawa where he focused on finance, human resources, planning, policy development and program evaluation. He is also a graduate of the University of Western Ontario.

Mike has published articles in peer-reviewed journals on strategic planning and health metrics, evaluation, e-health, web design and information systems development. He is also a business consultant with expertise in governance and non-profit entrepreneurship for health and community based organizations.

Helen Ramsdale MA, BM, MRCP(UK), FRCPC
Associate Professor

Roma Sehmi, PhD
Associate Professor, McMaster University

Pharmacology and Immunology at University College, London, UK.
Imperial College, Royal Brompton  National Heart and Lung Institute London, UK

 

Dr. Roma Sehmi received her undergraduate training in Pharmacology and Immunology at University College, London, UK. She completed her PhD at the prestigious Imperial College, Royal Brompton National Heart and Lung Institute in London, UK where she studied eosinophil biology in allergic inflammation with a particular emphasis on molecular mechanisms that control cellular migration and adhesion pathways. Following a post-doctoral fellowship at Cambridge University at the Molteno Institute with Dr Anthony Butterworth where she continued her work on eosinophils in helminthic infestations, she moved to Canada. Dr. Sehmi is currently an Associate Professor (Medicine) in the division of Respirology at McMaster University and is based at the Firestone Institute for Respiratory Research, St. Joseph’s Healthcare.

Research Interests

Dr. Sehmi’s work at McMaster University has utilized flow cytometry and molecular techniques to assess the role of bone marrow derived hemopoietic progenitor cells in respiratory diseases including asthma and chronic pulmonary obstructive disease. Her specific interests currently lie in understanding the role of chemokines in modulating the mobilization and egress of progenitor cells from the bone marrow in allergic asthma and the resultant tissue homing and lung remodelling instigated by these cells. In addition, she is interested in understanding the signalling processes that activate hemopoietic stem/progenitor cell populations within the bone marrow following lung injury. Dr Sehmi has developed methods to measure phenotypic and functional changes in progenitor cell populations in blood, bone marrow and sputum following allergen challenge in human asthmatic subjects as well as various mouse models. Similar studies are now underway in patients with chronic obstructive pulmonary disease.Dr. Sehmi has received continuous support from national funding agencies including Canadian Institutes of Respiratory Research and Ontario Thoracic Society. In addition, she has several investigator initiated grants from pharmaceutical companies including GlaxoSmith Kline and Astra Zeneca. Dr. Sehmi has supervised several PhD, MSc and Co-op students and her current research group comprises of a postdoctoral fellow, two graduate students and one full time technician. She also co-ordinates a graduate course on the pathobiology of lung diseases: asthma and COPD. 

Research Contributions

Novel surface markers for eosinophil/basophil progenitors in allergic inflammation: In collaboration with Dr Robert Sutherland, University of Toronto, I developed a multi-parametric sequential gating flow cytometric protocol for accurate enumeration of CD34+ progenitor cells in biological samples. We showed for the first time that blood (PB) and bone marrow (BM) CD34+ cells were increased in allergic subjects indicating an activation of hemopoietic processes in these subjects (AJRCMB 1996, 15:645-54). This study was pivotal in initiating an interest in BM hemopoietic processes during allergic inflammation and led to a study of receptor expression for eosinophil-selective cytokine growth factors such as interleukin (IL)-5, IL-3 and GM-CSF on BM progenitor cells. The novel and very exciting findings were (i) the low affinity receptor for IL-5 (IL-5R"-subunit) is expressed on CD34+ cells and this may represent the phenotype of the earliest eosinophil-lineage committed progenitor; (ii) the proportion of BM derived CD34+ cells expressing IL-5R" is selectively increased following allergen exposure in subjects who developed an airway eosinophilia and increased methacholine responsiveness (J Clin Invest 1997; 10:2466-75). This study won the best abstract award when presented at the American Academy of Allergy, Asthma and Immunology, San Francisco in 1997 and  stimulated a major initiative to investigate the role of eosinophil-lineage committed progenitors in allergic inflammation. This is a widely quoted paper which resulted in a number of collaborations within McMaster university and worldwide and was pivotal in my nomination for a faculty position and winning a centennial fellowship award from the Medical Research Council of Canada (1999-2000).

 Chemokine-mediated migratory responses of progenitor cells:

The study of eotaxin and its receptor, CCR3, on BM progenitors represented an initial endeavour to investigate the role of chemokines in progenitor cell trafficking in allergic inflammation. I developed a transmigration assay to follow the migratory responses of bone marrow CD34+ cells to eotaxin and this has been a useful assay in many of my subsequent projects. This study formed the basis of my first successful CIHR operating grant (2001 to 2005).

Progenitor cell traffic to mouse lung tissue:

This study helped to forge a successful collaboration with Dr. Inman in mouse studies and open up a novel area of hemopoietic processes at sites of allergic inflammation. I believe that this will be an important area in defining the factors that control progenitor cell homing to the lungs and controlling this traffic may provide more effective control of allergic inflammation and tissue remodeling associated with asthma pathobiology. The results from these studies will proved a stepping stone for investigations of drugs that could modulate progenitor cell lung homing and asthma symptoms.

Progenitor cells in sputum samples from asthmatics:

My research at McMaster University remains at the cutting edge of progenitor cell research in allergic inflammatory disease, in part because of my unique access to human bone marrow samples from Dr. Paul O’Byrne’s clinics allergy clinic. As well we have developed the flow cytometric technology that allows for multiple assessments from sputum. In collaboration with Dr. Freddy Hargreave at St. Joseph’s hospital, we have developed methodology to assess  sputum samples by flow cytometry which allow us access to progenitor cells at the site of the inflammatory response i.e. within the lung. Similarities between findings in mice lung and human sputum support continued mouse work to understand pathways controlling progenitor cell homing to the lung.

Desensitization of chemokine-mediated migratory responses of progenitor cells:

This is the most novel and exciting area of my research as it begins to highlight the complex interplay between down-regulation of tissue retentive signals and up-regulation of responsiveness to exiting signals for progenitor cells from the BM during allergic inflammation.

Malcolm R. Sears, MB, ChB, FRACP, FRCPC. FAAAA

Professor, McMaster University
Past Research Director, Firestone Institute for Respiratory Health
AstraZeneca Chair in Respiratory Epidemiology

Dr. Malcolm Sears received his medical training at the University of Otago, Dunedin, New Zealand where he also undertook five years postgraduate education followed by two years pulmonary fellowship at the University of Washington.  He was appointed to the Faculty of the University of Otago, Department of Medicine, and pursued interests in the epidemiology and management of asthma.

 In 1990 he was appointed Professor of Medicine at McMaster University, Hamilton, Ontario, Canada, Head of Respirology at St Joseph’s Healthcare and Director of the Firestone Regional Chest and Allergy Unit, now the Firestone Institute for Respiratory Health.  He is a Fellow of the Royal Australasian College of Physicians, the Royal College of Physicians and Surgeons of Canada, and the American Academy of Allergy, Asthma and Immunology.  In 2002 he stepped down as Head of Respirology and was appointed Research Director of the Firestone Institute, a position he held until 2009.  He also holds an endowed chair in Respiratory Epidemiology.

Research Interests
Dr. Sears’ major research contributions have been in longitudinal studies of the development and natural history of childhood asthma, other cross-sectional epidemiological studies, investigations of asthma mortality, studies of the effects of short-acting and long-acting beta-agonists and a range of studies of other treatments for asthma. Publications include 22 book chapters, and over 200 peer-reviewed papers.
Research Contributions

Asthma Mortality. 
In response to a marked increase in mortality among young people in New Zealand in the late 1970s, several colleagues and I studied all asthma deaths in the total New Zealand population over 2 years (1981-83) resulting in 14 publications (1985-1988) describing 271 cases of fatal asthma,  highlighting personal and disease risk factors.  This case series was later used in case-control studies which suggested use of the beta-agonist fenoterol increased risk of death. The epidemic ended when fenoterol was withdrawn in 1990.

Deleterious Effects of Regular Short-Acting Beta-Agonists
Prompted by findings from the mortality study and clinical observations, I hypothesized that regular use of short-acting beta-agonist could worsen chronic asthma. In a year-long crossover RCT (1998-1990), we demonstrated increased symptoms, lower lung function, increased airway hyperresponsiveness, and more exacerbations when fenoterol was used regularly compared with as-needed use, despite concomitant use of inhaled corticosteroids.  This landmark study provoked major controversy, but led to a radical shift in asthma guidelines, away from regularly scheduled short-acting beta-agonists to use only as-needed.  Research groups in Canada, US and UK subsequently undertook studies to determine mechanisms responsible for the deleterious effects.

Potential Adverse Effects of Long-Acting Beta-Agonists
We hypothesized that the bronchodilator and symptom-relieving effects of long-acting beta-agonists could mask progressive airway inflammation when anti-inflammatory medication was reduced. In a crossover RCT, exacerbations were induced by step-wise reduction of corticosteroid, and airway inflammation monitored by sputum cell counts. Subjects using long-acting beta-agonist tolerated greater airway inflammation before an exacerbation was clinically detectable compared with the placebo treatment period, showing that the potential for masking of inflammation by LABA was real.

Natural History of Childhood Asthma
From 1979 to the present, I have followed a birth-cohort of New Zealand children from age 7 to age 38 years, as part of the Dunedin Multidisciplinary Health and Development Study, examining the development and natural history of asthma and now COPD. Using questionnaires and objective measurements, we have evaluated multiple risk factors for the development, persistence and remission of childhood asthma.  Recent findings include the effects of breast-feeding in doubling the risk of atopy and asthma long term, the differential effects of gender on some risk factors, the protective effects of animal exposure early in childhood, and the development of airway remodeling in late adolescence and early adult life. 

Epidemics of Exacerbations of Childhood Asthma
Neil Johnston and I examined the phenomenon of the marked September increase in childhood asthma ER visits and hospitalizations, finding this was related precisely to the timing of school return in Canada, and associated with respiratory virus (mainly rhinovirus) infection. Intensifying asthma controller therapy during the period of high risk markedly attenuated these episodes.

A New Canadian Birth Cohort Study of Allergy and Asthma
 Responding to initiatives from colleagues at McMaster and Toronto, Health Canada and CIHR, and the Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence, I have coordinated a national consortium of over 40 Canadian investigators to initiate a longitudinal birth cohort study examining the origins of allergy and asthma, funded by CIHR and AllerGen. The Canadian Healthy Infant Longitudinal Development (CHILD) study which is planned to follow 5000 children from pregnancy to age 5 commenced in 2008 under my direction.

Mark Soth, MD, FRCPC
Assistant Professor in Respiratory & Critical Care Medicine, McMaster University

Mark Soth is starting his fourth year on faculty at McMaster University. Throughout his training and while on faculty, Mark has been very active as an educational administration leader and clinical teacher. He has received multiple awards over the years for his clinical teaching, clinical competence, and contributions to medical educational leadership from the undergraduate medical school, postgraduate medical education, PAIRO, and the St. Joseph’s Healthcare Staff Association.

Mark was a recipient of the Watson Buchanan AFP Clinical Educator award that he used to support the development of a web-based learning tool for mechanical ventilation and for completion of the University Teacher Programme. Since his first year on faculty, Mark has been active as Site Co-ordinator for residents rotating through St. Joseph’s Hospital for both the respirology and critical care programmes where he has re-organized these rotations substantially. He is also Head of Critical Care Services at SJHH. He has played an active leadership role in initiatives such as the Critical Care Response Team which has decreased cardiac arrest by 50%, movement of the level 2 Medical Stepdown to a co-ordinated physician model, and quality improvement initiatives that have decreased ventilator associated pneumonia and central line infection rates in the SJHH ICU.

Mark is also an active member of the Ontario Thoracic Society as Chair of the Better Breathing 2010 Conference and co-editor of Ontario Thoracic Reviews. He is a founding Co-chair for the annual Canadian Critical Care Review exam prep course sanctioned by the Canadian Critical Care Society. His research interests are centered upon outcomes research for critically ill patients both within and outside the ICU.

David Todd, MD
Assistant Professor of Medicine McMaster University

After a brief period in private practice Dr. Todd joined the FIRH as a clinical scholar from July 2005 to June 2007. During this time he developed a clinical interest in COPD, applied respiratory physiology, and respiratory rehabilitation. In addition, Dr Todd  has spent the past 18 months as a postgraduate student in the Health Research Methodology Program at McMaster University.

The opportunity to combine research training in an applied manner with ongoing clinical activity at McMaster University was a strong motivator to join the FIRH.

 

Research Interests

My current research interest evaluating systemic inflammation (i.e. multi-compartmental models) in COPD can be achieved through the current FIRH laboratory infrastructure (i.e. blood and sputum measurements) in collaboration with the pathology department of the Hamilton Health Sciences. The large COPD and respiratory rehabilitation practice that has developed at the FIRH will provide an ongoing patient population to study systemic inflammation and therapeutic interventions to modify this inflammation.

Research Contributions

1. Systemic inflammation in COPD

2. Airway inflammation and obesity

3. Evaluation of methacholine challenge methodology

 Recent Scientific Presentations:

1. Todd DC, Armstrong S, D’Silva L, Allen CJ, Hargreave FE, Parameswaran K. Relationship between obesity and sputum cell counts in airway diseases (Thematic Poster Session). American Thoracic Society 2007 International Conference, A69 Obesity and Asthma (May 20, 2007, 8:15 am – 4:15 pm), San Francisco CA.

2. Todd DC, Killian KJ. Pulmonary impairment in restrictive and obstructive pulmonary disease of comparable severity (Thematic Poster Session). American Thoracic Society 2006 International Conference, C151 Ventilation-Perfusion Matching in Health and Disease (May 23, 2006, 8:15 am – 4:15 pm), San Diego CA.

3. Cockcroft DW, Hurst TS, Davis BE, Todd DC. Dosimeter methacholine challenge:comparison of maximal versus sub-maximal inhalations (Slide Presentation). Chest 2004, Pulmonary Function Testing (October 26, 2004, 10:30 am – 12:00 pm), Seattle WA.

4. Todd DC, Davis BE, Smycniuk AJ, Cockcroft DW. Importance of method of dosimeter calibration on nebulizer output and measured PC20 (Poster Session). American Thoracic Society 100th International Conference 2004, Asthma and Airway Hyperresponsiveness: Human and Animal Studies (May 23, 2004, 8:15 am – 4:15 pm), Orlando FL.

Select Publications:

1. Todd DC, McIvor RA, Pugsley SO, Cox PG. An approach to chronic obstructive pulmonary disease in primary care. Can Fam Physician 2008 (In Press)

2. Todd DC, Armstrong S, D’Silva L, Allen CJ, Hargreave FE, Parameswaran K. The effect of obesity on airway inflammation – a cross-sectional analysis of body mass index and sputum cell counts. Clin Exp Allergy 2007;37:1049-1054.

3. Parameswaran K, Todd DC, Soth M. Altered respiratory physiology in obesity. Can Respir J 2006;13:203-210.

4. Davis BE, Todd DC, Cockcroft DW. Effect of combined montelukast and desloratidine on the early asthmatic response to inhaled allergen. J Allergy Clin Immunol 2005;116:768-772.

5. Cockcroft DW, Davis BE, Todd DC, Smycniuk AJ. Methacholine challenge: comparison of two methods. Chest 2005;127:839-844.

6. Todd DC, Davis BE, Smycniuk AJ, Cockcroft DW. Importance of dosimeter calibration method on nebulizer output. Ann Allergy Asthma Immunol 2005;94:45-47.

7. Davis BE, Todd DC, Cockcroft DW. Method of nebulizer calibration and methacholine airway hyperresponsiveness. J Allergy Clin Immunol 2004;114:1474-1475.

8. Todd DC, Davis BE, Hurst TS, Cockcroft DW. Dosimeter methacholine challenge: comparison of maximal and submaximal inhalations. J Allergy Clin Immunol 2004;114:517-519.

9. Todd DC, Cockcroft DW. Prolonged survival in Churg-Strauss syndrome. Ann Allergy Asthma Immunol 2004;92:92-93.

Marcel Tunks MD
Assistant Professor, Division of Respirology, McMaster University

Dr. Marcel Tunks is one of our newest members to the Firestone Institute for Respiratory Health. Dr. Tunks was born and raised in Hamilton, Ontario at St. Joseph’s Healthcare. After graduating high school, Dr. Tunks went to Medical School at the University of Toronto and graduated in 2004. Afterwards, he went back to the University of Toronto where he studied Internal Medicine which he completed in 2007. In 2009 he graduated from McMaster University’s Respirology Training Program. He continued with McMaster where he fulfilled his Clinical Scholar training until 2010. He also acquired additional training in cardiopulmonary exercise testing in both acute and chronic non-invasive mechanical ventilation. Dr. Tunks primary interest is in chronic respiratory failure, pulmonary physiology and the assessment of dyspnea.

In 2010 he became an Assistant Professor in the Department of Medicine, at McMaster University. Dr. Marcel Tunks is best known for his roles in inpatient and outpatient respirology as well as Medical Step-down/CCU attending at St/ Joseph’s Healthcare. His duties also include doing respiratory consultations at the Juravinski Hospital and implementing a sub-unit planner for the respirology section of Medical Foundations such as; Michael G DeGroote School of Medicine.
In 2011 Dr. Tunks will be taking on the role of Site Director for the Respirology Residency at St. Joseph’s Healthcare.

Lori Whitehead MD
Education Program Director, Division of Respirology, McMaster University

Dr. Whitehead is an Associate Clinical Professor of Medicine, McMaster University.  She graduated from the University of Toronto in 1985, before moving to Hamilton to complete residency in Internal Medicine and Respirology.  A member of the Firestone team since 1992, Dr. Whitehead has recently assumed the role as Program Director for the Respirology Residency Training Program and the Chair of the Respiratory Residency Education Committee.  She is the Director of the Regional Tuberculosis Clinic based at St. Joseph’s Healthcare.

Dr. Whitehead has a wide variety of clinical interests.  She has a busy hospital based practice in both respirology and internal medicine.  Many of her ambulatory clinics are spent at the Tuberculosis Clinic, where over 350 new patients per year are screened or treated for a tuberculosis related health issue.  Dr. Whitehead, along with the TB Complex Case Management Committee, supervised a comprehensive Tuberculosis Surveillance Program at St. Joseph’s Healthcare between 2001 and 2003 during an outbreak of Multi-Drug Resistant Tuberculosis.  Since that time, there has been a strong collaborative relationship between the Tuberculosis Clinic and Occupational Health, the Department of Nephrology and the Department of Social and Public Health, City of Hamilton.  Her membership on the Regional Infection Control Committee allows for ongoing communication between the various hospital and community agencies within the area of communicable diseases. She has received many awards for her academic, teaching, clinical and community activities. The area of childhood asthma also is of interest to Dr. Whitehead, who sees children within the ambulatory clinic approximately one day per week.

Dr. Whitehead has been Program Director for the Respirology Training Program since July 2005. Many new features have been introduced to improve the quality of the educational experience for the residents. The training program has an updated and enhanced curriculum, including a Master’s Level physiology course taught by Dr. Mark Inman. The educational activities, for which each and every member of the clinical department of Respirology participates, capitalize on the strength of the division members as teachers and role models.