The Lung Association and Health Professionals working together can make a difference in the respiratory health of Ontarions. J. Peter Macleod Chair, Better Breathing 2006 Planning Committee Respirologist, The Ottawa Hospital Civic Campus

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Features In this Issue

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Idiopathic Pulmonary Fibrosis Is there light at the end of the tunnel?

Editorial Idiopathic Pulmonary Fibrosis . . . . . . . . . . . . .2

Martin R.J. Kolb, MD, PhD, Department of Medicine, Firestone Institute for Respiratory Health & Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

Chair’s Letter . . . . . . . .3

Although the total numbers of INTRODUCTION patients affected by IPF are not huge, it Idiopathic pulmonary fibrosis (IPF) is still is one of the most common forms certainly not the first differential of interstitial lung disease. The diagnosis coming into mind when incidence of IPF is not precisely patients in their early sixties report known, but it is estimated to be in the mild to moderate exertional dyspnea range of 15-40 per 100,000(1, 2), and combined with cough. The nonspecific approximately 20,000 Canadians are presentation, initially often perceived affected. Once diagnosed, the median as “due to the aging process” by the MARTIN KOLB survival is between 2-3 years, placing patient and not as expression of IPF in the same category as pulmonary disease, combined with the progressive functional deterioration and inefficacy of current malignant disease in regard to prognosis. The treatment is a major clinical problem. However, past 10 years have considerably enhanced our recent efforts supported by all major international knowledge about the pathology and the clinical respiratory societies and several pharmaceutical course of IPF. A few years ago, a new companies have generated novel and promising classification was put forward and ratified in a treatment approaches, which will hopefully consensus statement by the American Thoracic translate into direct benefit for these unfortunate Society and European Respiratory Society patients in the future. Continued on page 4

Report of Chair, Research Advisory Committee . . . . . . . . . .3 Better Breathing OTS Conference Program . .7

Coming Up Non-Invasive Positive Pressure Ventilation for Acute Respiratory Failure: Moving from Evidence to Practice Spring/Summer 2006

FIGURE 1

Mission Statement To Promote Respiratory Health through Medical Research and Education. The OTR can also be viewed on-line at on.lung.ca/ots/otr.html.

www.on.lung.ca

Classification of idiopathic interstitial pneumonias according to the 2002 ATS/ERS consensus statement(1). Only disorders classified as usual interstitial pneumonia should be termed “IPF” – after exclusion of all other causes of interstitial lung disease that may also reveal this histological subtype.

ONTARIO THORACIC EDITORIAL REVIEWS

Idiopathic Pulmonary Fibrosis (IPF)

An official publication of the Ontario Thoracic Society, Medical Section of the Ontario Lung Association, 573 King Street East, Toronto, Ontario M5A 4L3 (416) 864-9911 • Fax (416) 864-9916 E-mail: [email protected] Web Site: www.on.lung.ca

Charles K.N. Chan, MD, FRCPC, FCCP, FACP, Head, Respirology, University Health Network, Mount Sinai Hospital, Sunnybrook and Women’s College Hospital; Professor of Medicine, University of Toronto

ONTARIO THORACIC SOCIETY EXECUTIVE COMMITTEE 2005-2006 Dr. Diane Lougheed (Chair) Dr. John Bertley (Chair-Elect) Dr. John Fisher Dr. Mark Inman Mr. Robert Kelly (Chair, OLA) Dr. Robin McFadden (OLA Board Rep.) Dr. Susan Moffatt Dr. Elizabeth Powell (OMA Rep.) Dr. Joe Reisman Dr. Matthew Stanbrook Dr. Susan Tarlo Mr. Keith Vrieswyk (OLA Board Member) Dr. Kenneth Willis (Past Chair)

ONTARIO THORACIC REVIEWS EDITORIAL BOARD Dr. Robert Hyland (Editor) Dr. Diane Lougheed (Chair, OTS) Dr. James Edney (Ontario Chapter, College of Family Physicians of Canada) Mr. Manu Malkani (President & CEO, OLA)

n the current issue of the OTR, Dr. early on in the illness can be very Martin Kolb succinctly summarizes helpful. In such cases, the VAT biopsy the state of knowledge with regard to a not only helps in establishing the challenging lung condition – diagnosis but also aids in excluding Idiopathic Pulmonary Fibrosis (IPF). other conditions such as occupational All practicing respirologists see or environmental lung diseases. patients with IPF regularly. Most of us are frustrated by our lack of ability to EMERGING THERAPIES alter the natural history of this Traditional immunosuppression therapy CHARLES K.N. CHAN condition and frequently are indecisive is not impressive but, as noted by Dr. with our diagnostic and therapeutic decisions. Kolb, likely helps some in stabilizing or slowing However, this condition in most cases is fatal the rate of decline. Immunosuppression is by no irrespective of what we do. For a select few, lung means the solution and does increase the risk of transplant offers the hope of long-term survival. opportunistic infections. However, with careful In a small subset, the condition remains quite patient selection and assessment of responses stable or “dormant” for years, but most patients using multiple variables like pulmonary function deteriorate gradually, stepwise or rapidly. tests, standardized walk test distance, one can use National guidelines are helpful but clearly the conventional therapies for some patients. lack sound evidence in support of the Promising therapies derived from our recommendations. Nevertheless, there has been knowledge of both the cellular and molecular some improvement over the last ten years. basis of lung inflammation and repair are still in rigorous clinical trials. However, there are several DIAGNOSIS agents that look promising that may aid us in the As highlighted in this article, the use of high therapeutic options within the next few years. resolution computed tomography (HRCT), In the interim, day to day management of IPF especially when done in prone plus supine patients should include regular exercise, positions, together with comparable clinical and preservation of bone, immunization, monitoring laboratory features are often sufficient in making and treatment for gastroeosphageal reflux a diagnosis without biopsy. diseases, aggressive treatment for chest For those patients who have unusual clinical infections, and surveillance for pulmonary features and/or atypical HRCT findings, proper thromboembolism when there is acute hypoxic biopsies from multiple sites via videoscope- decompensation that is not associated with assisted thoracoscopy (VAT) approach especially apparent worsening of parenchymal diseases.

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Robert Kelly (Chair, OLA) Dr. Hedy Ginzberg (Medical Director, OTS)

CORRECTION

Ms. Bernie Voulgaris (OTS Administrator)

We regret that the information which identified Christopher Licskai as Respiratory and Critical Care Association in the Fall 2005 Ontario Thoracic Reviews was incorrect. Christopher Licskai is Assistant Professor of Medicine, University of Western Ontario, St. Joseph’s Health Care of London. We apologize for the error and for the mis-spelling of Dr. Licskai’s name.

Ms. Corinne Holubiwich (Medical Librarian)

We gratefully acknowledge the support of our sponsors:

Join the OTS or Renew Your Membership OTS Active Membership is open to individuals with a medical degree and scientists holding a PhD or equivalent degree of training. The 2006-2007 fee is $60.00. OTS Associate Membership is available to interns, residents or graduate students in medical or allied health science, and to fellows during their period of training. Associate members do not pay fees and may not vote or hold office in the Society but enjoy all the benefits of membership. To join the OTS or to renew your membership for 2006-2007, call (416) 864-9911 ext. 254. For information on OTS programs and services, visit 222.on.lung.ca/ots

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CHAIR’S LETTER Diane Lougheed, MD, MSc, FRCPC, Chair, OTS, Associate Professor, Department of Medicine, Queen’s University, Kingston sincere appreciation to those individuals and groups who 005 was a year of new beginnings in many ways for have given generously to this pilot program! I encourage the OTS and the OLA. Under the able leadership of those of you who are considering this unique donation Mr. Manu Malkani, President and CEO, the OLA has opportunity to contact members of the Executive or undergone reorganization and consolidation of its Research Advisory Committees if you have any questions management structure. Out of difficult decisions and about the fund. John Fisher (Chair, Research Advisory challenging times I believe will come renewed Committee) and Hedy Ginzberg deserve special recognition opportunity for future growth. The OTS Medical Director, for bringing several years worth of efforts to fruition! Hedy Ginzberg, and ORCS Director of Administration, Our education committee, under the able leadership of Sheila Gordon-Dillane are now voting members of DIANE LOUGHEED Susan Tarlo, continues to address our educational OLA Senior Management Committee – which is a reflection of the value the OLA places on obtaining and recognizing mandate well. Better Breathing 2005 attendance and evaluations were once again excellent. Our other annual events including the input from its member societies now and in years to come. OTS had several notable achievements in 2005. Research Respiratory Residents’ Symposium, the Job Fair at Better funding reached a high of $990,000.00. This was largely due to an Breathing, and the Ontario Respirology Residents CanMEDS additional $90,000 from the OLA and $90,000 in matching funds Workshop were also tremendous successes this year. The Cameron from GlaxoSmithKlein (the latter for research in obstructive Gray fellowship for 2005-2006 was awarded to Virjanand airways diseases). As a result, numerous Block Term Grants and 15 Naraine from the University of Toronto. Thanks to the many OTS members who participated in the one or 2 year Grants In Aid of up to $50,000 were funded in the 2005/06 competition! We will strive to maintain this level of Ministry of Health and Long-Term Care-funded Asthma Guidelines funding from the OLA, continually enhance industry partnerships workshops as expert presenters and facilitators. The 3-year program and explore new funding opportunities. To begin, OTS launched the evaluation results are very positive and as a result the Ministry “Top it Up” for Respiratory Research Breathe New Life Award, wishes to continue to fund the OLA/OTS for a similar initiative. toward which OTS members (only) may donate directly to Stay tuned for more opportunities to participate in OLA/OTSrespiratory research. As of December 2005, $20,000 has been sponsored asthma CME events locally! raised. This is a slower start than we had hoped. I wish to extend Continued on page 6

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REPORT OF THE CHAIR John Fisher, PhD, Chair, Research Advisory Committee; Professor of Medicine, Queen's University, Kingston national program with the condition that a majority of the n several occasions I have presented data justifying provincial thoracic societies participate. Currently, only increased base funding for OTS research, and BC, Alberta and Ontario participate in the National CTS extolled the virtues of the OTS/OLA plan to award multipeer review process and renewed efforts to seek a year research grants. In 2005/06 OTS received funding national consensus would perhaps entice more provincial that translated into a remarkable 35% one-time increase thoracic societies to contribute funds for national in the grant-in-aid (GIA) budget. This reflected the OLA strategy of offering $90k of one-time new research distribution. One rationale for the OTS condition was funding if external matching funds were available. Glaxo that without wider participation, OTS would Smith Kline (GSK) boldly stepped forward to be the differentially fund other regions. Perhaps this is the right JOHN FISHER “The” corporate sponsor and by doing so acknowledged thing to do, but consider Ontario’s role in research as the high impact of OTS research and its importance in a reflected by the distribution of CIHR funds across Canada. Of the knowledge-based economy. GSK has again demonstrated superior roughly $350 million CIHR funding announced by Federal Health corporate citizenship by partnering with the OLA for the 2006/07 Minister Ujjal Dosanjh in October 2005, Ontario garnered grant-in-aid (GIA) competition. This success would not have approximately 40%, followed by Quebec 31%, BC 12% and occurred without the vision, hard work and enthusiasm of both our Alberta 11%. Other provinces account for the remaining 6% (data Medical Director, Dr. Hedy Ginzberg and Ms. Renata Rea, from CIHR E-Alert Issue 6). The presence of outstanding research Professional Communications Manager at GSK. The challenge for in Ontario is clear and at least partially reflects the density of the OLA and OTS is now to ensure that the increased funding medical schools and research institutes that are associated with the becomes a permanent component of the progress towards the Ontario population. A CTS/CIHR National grant program will need adoption of multi-year research grants. to balance the risk of participation for the OTS and maintain OLA The question of partnering with CIHR is often suggested as a accountability to its donors. Policies that would consider the strategy to help achieve multi-year research awards and the national research impact of each region, while relying on a CIHR potential role of OTS research funding in establishing a National vision that would adopt a funding formula to increase respiratory grant competition surfaced at the CTS annual meeting in Montreal. research in all regions, will increase the likelihood of success of a In the past, the OTS has indicated its willingness to participate in a National Research Program.

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Idiopathic Pulmonary Fibrosis...

(figure 1)(1). It is agreed that interstitial lung disease with unknown cause should be separated into granulomatous disease (e.g. sarcoidosis), idiopathic interstitial pneumonias (IIP), and others (lymphangioleiomyomatosis, histiocytosis X etc). Seven different entities belong into the group of IIP. The most common type is usual interstitial pneumonia and this is the only IIP that should be called IPF. Simplified message: UIP/IPF has the worst prognosis and is treatment resistant. In contrast, nonspecific interstitial pneumonia and desquamative interstitial pneumonia are associated with better prognosis and more favorable treatment response. It is still unclear and matter of ongoing debate, if the various entities within the group of IIP are distinct pathologic processes, or reflect different stages of the same disease(3). PATHOGENESIS The prevailing hypothesis that chronic inflammation and altered immune response resulting in repeated scarring and eventually pulmonary fibrosis (“pathway A” in figure 2) has been challenged of late(4, 5). There is increasing evidence that a primary abnormal repair process is the driving force in IPF and other fibroproliferative disorders. It is believed that wound repair mechanisms which are physiologically initiated after tissue injury get out of control in the context of pulmonary fibrosis - independent of inflammation (“pathway B” in figure 2). The repair process is altered on different levels. Epithelial cells undergo apoptosis and fail to re-populate the alveoli in response to epithelial injury. In contrast,

Continued from page 1

mesenchymal cells, especially fibroblasts, show reduced apoptosis, they proliferate and accumulate forming “fibroblastic foci” in the lungs(4, 6). In association with these foci, there is increased synthesis of extracellular matrix, and reduced matrix degradation. On a molecular level numerous cytokines and growth factors mediating these processes have been identified, and several of those are target molecules for novel therapies, e.g. platelet derived growth factor (PDGF), endothelin, transforming growth factor beta (TGFb) and others(7). The ongoing fibrogenesis in the lung causes a progressive restrictive lung disease with impaired diffusing capacity and hypoxia, eventually causing respiratory failure. DIAGNOSTICS The diagnosis of idiopathic pulmonary fibrosis requires that all other causes for interstitial lung disease have been excluded(2, 8). Clinical symptoms develop over months to years; they are nonspecific and include shortness of breath, dry and mostly nonproductive cough and occasionally chest tightness. On physical examination coarse crackles are heard in both lower zones (“velcro rales”), finger clubbing is found in a minority of patients. Clinical signs of cor pulmonale and right heart failure reflect advanced disease. Pulmonary function test shows restrictive pattern with impaired diffusing capacity and later on decreased pO2 and O2 saturation. High resolution CT of the lungs shows bibasilar reticular abnormalities, more subpleural than central, in advanced

FIGURE 2

The pathogenesis of fibroproliferative lung disease can be related to repeated inflammatory episodes resulting in ongoing scarring (pathway A), or in a fairly inflammation independent development and progression of fibrotic processes (pathway B). The prototype of a disease following pathway A would be chronic hypersensitivity pneumonitis. One of the current hypotheses is that IPF follows pathway B, which would explain the failure of anti-inflammatory treatment strategies. 4

stages with “honeycombing”, and is very efficient in providing a fairly accurate diagnosis. The need for histological diagnosis by videoscopic assisted lung biopsy has to be determined individually but may be required to make a definite diagnosis(8, 9). CURRENT TREATMENT The treatment of IPF is difficult and so far no efficient therapy has been found(8, 10). In the past, immunosuppressive agents have been used based on the assumption that IPF is an autoimmune inflammatory disease. Response rates to corticosteroids, either alone or in combination with azathioprine or cyclophosphamide are not better than 1530%. Treatment response may be somewhat higher when disease stabilization is considered as a positive result (which probably is reasonable considering IPF is typically a continuously progressive disease). However, in “mild defense” of immunosuppressive drugs a recent editorial in the American Journal of Respiratory and Critical Care Medicine mentioned correctly that no trial has ever investigated these drugs appropriately in a prospective randomized and controlled manner, and thus it may not be justified to completely rule out a potential role for them(11). The current recommendation of the ATS/ERS consensus statement suggests using a moderately high dose of Prednisone (0.5 mg/kg body weight in combination with either azathioprine or cyclophosphamide [2-3 mg/kg body weight])(1, 8). Other drugs have been used, such as cyclosporine, methotrexate and penicillamine, and most of this experience has been published as retrospective studies or case presentations. None of these drugs are likely to have marked efficacy(12). It is important to keep in mind that patients with IPF are more susceptible to lower respiratory tract infections, even if they are not taking immunosuppressive medication(13, 14). Hence, antibiotic treatment is often given at an earlier time to IPF patients although there is no clear evidence for this practise. It is also controversial if home oxygen therapy should only be initiated when the pO2 is below 55 mmHg on room air or when pulmonary hypertension is present. Continued on page 5

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Idiopathic Pulmonary Fibrosis...

CURRENT PROSPECTIVE CLINICAL STUDIES Intense research efforts in the past two decades have provided several new treatment approaches and novel drug compounds. Some drugs are already approved for clinical use for other indications, and are now applied to IPF. Others are being developed and may proceed to clinical trials in the near future. INTERFERON GAMMA 1B Interferon is a pluripotent cytokine playing a major role in host defense mechanisms. It has been shown that Interferon gamma can inhibit collagen synthesis in fibroblasts and is antifibrotic in different animal models of disease(15). A study published in 1999 showed that total lung capacity and oxygen saturation on exertion improved in patients with progressive IPF after they were treated with Interferon gamma for 12 months in combination with prednisone(16). This observation led to a multi-centre trial with interferon gamma in IPF which was published in 2004(17). In this study the primary endpoint of progression free survival time (defined as >10% decrease of predicted FVC, or >5% increase of A-a gradient) was not different between the treatment arms. However, there was a surprising survival advantage for patients treated with Interferon compared to placebo. This has led to a new international study (INSPIRE, Intermune Inc, California) involving more than 60 study sites with 600 patients, for which recruitment is currently underway, and which will focus on survival in patients treated with Interferon over 2 years. It is also noteworthy that a recent meta-analysis of three published studies has suggested a survival advantage for patients treated with interferon gamma 1b(18). PIRFENIDONE Pirfenidone is a novel antifibrotic drug which has been shown to inhibit experimental lung and kidney fibrosis. It is not an antiinflammatory agent, but interferes with different biological mechanisms leading to accumulation of fibroblasts and collagen, amongst them TGFb(19). In an open label phase II study it has been shown that Pirfenidone can stabilize pulmonary function values after 12 months of treatment(17). A double-blind placebo controlled clinical trial conducted in Japan was recently published, and demonstrated

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beneficial effects in regard to improvements in 6 minute walk tests and VC in a subgroup of less severely impaired patients(20). The trial was terminated early because patients in the placebo group had more episodes of acute exacerbation after 6 months of treatment compared to the Pirfenidone group. IMATINIB Imatinib is a tyrosine kinase inhibitor and inhibits the receptor of PDGF. The compound is marketed with the trade name Gleevec and indicated for treatment of chronic myeloid leukemia (CML). PDGF is known to be involved in different experimental fibroproliferative disorders, such as asbestos and bleomycin induced lung fibrosis, and the properties of this “anti-PDGF” drug suggest that it might be efficient in IPF as well(21). Some newer experimental studies demonstrated a beneficial effect of imatinib in pulmonary fibrosis(22). The first clinical trial in the United States has just finished recruiting patients, and results of this trial are expected in spring 2006. Two other studies with drugs interfering with receptors potentially involved in the pathogenesis of IPF have completed patient recruitment. One with bosentan, a endothelin receptor antagonist used for treatment of pulmonary hypertension, the other with etanercept, which is anti-tumor necrosis factor alpha and used in rheumatoid arthritis and ankylosing spondylitis. Other novel compounds interfering with TGFb and its receptors are under development and close to Phase I/II clinical trials. N-ACETYLCYSTEINE N-acetylcysteine (NAC) is a drug used for prevention of liver toxicity in acetaminophen overdose. In Europe NAC is also widely prescribed as mucolytic agent in patients with COPD. The drug is a glutathione precursor and has considerable antioxidant properties. It has also been shown that NAC can reduce fibroblast proliferation and collagen synthesis. Previous studies have demonstrated that there is a lack of glutathione in bronchoalveolar lavage fluid in patients with IPF, and thus it is reasonable to assume that therapy with NAC might be beneficial in IPF(23, 24). A large European study with a total of 182 patients (IFIGENIA) has just been published in the New England Journal of

O NTARIO T HORACIC R EVIEWS W INTER 2005-2006

Medicine (25). Patients received 600 mg NAC t.i.d for one year in addition to prednisone and azathioprine as recommended by ATS/ERS consensus guidelines. The data suggest that stabilization of vital capacity and diffusing capacity is more likely in the NAC group compared to placebo. Although statistically significant, it is questionable if this is clinically meaningful. No significant difference is reported in regard to mortality. Further studies need to be done to address open questions, specifically to investigate if NAC per se is beneficial or if it facilitates immunosuppressive therapy by reduction of side effects. SUMMARY IPF is a progressive interstitial lung disease of unknown origin with nonspecific presentation and bad clinical outcome. The current hypothesis of the pathogenesis is that IPF is more likely caused by pathologic repair processes and not so much by immune mediated mechanisms. This has lead to novel treatment approaches with some known and some newly developed drug compounds. Some of those drugs are currently in prospective multicenter clinical trials. There is substantial hope that these efforts will result in a benefit for our patients and the identification of therapies that are superior to unsuccessful immunosuppressive strategies. The pathogenesis of fibroproliferative lung disease can be related to repeated inflammatory episodes resulting in ongoing scarring (pathway A), or in a fairly inflammation independent development and progression of fibrotic processes (pathway B). The prototype of a disease following pathway A would be chronic hypersensitivity pneumonitis. One of the current hypotheses is that IPF follows pathway B, which would explain the failure of anti-inflammatory treatment strategies. References 1. 2002. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am. J. Respir. Crit. Care Med. 165(2):277-304. 2. Khalil, N., and O’Connor, R. 2004. Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment. CMAJ 171(2):153-160. 3. Flaherty, K.R., Travis, W.D., Colby, T.V., Toews, G.B., Kazerooni, E.A., Gross, B.H., Jain, A., Strawderman, R.L., Flint, A., Lynch, J.P., and Martinez, F.J. 2001. Histopathologic Variability in Usual and Nonspecific Interstitial Pneumonias. Am J Respir Crit Care Med. 164(9):1722-1727. 4. Selman, M., King, T.E., and Pardo, A. 2001. Idiopathic Pulmonary Fibrosis: Prevailing and Evolving Hypotheses about Its Pathogenesis and Implications for Therapy. Ann Intern Med. 134 (2):136-151.

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Idiopathic Pulmonary Fibrosis...

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5. Gauldie, J., Kolb, M., and Sime, P.J. 2002. A new direction in the pathogenesis of idiopathic pulmonary fibrosis? Respir Res. 3(1):1. Epub 2001 Sep 26. 6. Selman, M., and Pardo, A. 2002. Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder. Respir Res 3(1):3. Epub 2001 Oct 11. 7. Kelly, M., Kolb, M., Bonniaud, P., and Gauldie, J. 2003. Re-evaluation of fibrogenic cytokines in lung fibrosis. Current Pharmaceutical Design 9(1):39-49. 8. 2000. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. 161(2 Pt 1):646-64. 9. Diette, G.B., Scatarige, J.C., Haponik, E.F., Merriman, B., and Fishman, E.K. 2005. Do High-Resolution CT Findings of Usual Interstitial Pneumonitis Obviate Lung Biopsy? Views of pulmonologists. Respiration. 72(2):134-41. 10. Gross, T.J., and Hunninghake, G.W. 2001. Idiopathic pulmonary fibrosis. N Engl J Med. 345(7):517-525. 11. du Bois, R.M. 2005. Is Idiopathic Pulmonary Fibrosis Now Treatable? Am. J. Respir. Crit. Care Med. 171(9):939-940. 12. Lynch, J.P., III, and McCune, W.J. 1997. Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders. Am J Respir Crit Care Med. 155 (2):395-420. 13. Meiersydow, J., Weiss, S.M., Buhl, R., Rust, M., and Raghu, G. 1994. Idiopathic pulmonary fibrosis: current clinical concepts and challenges in management. Semin Respir Crit Care Med 15(1):77-96. 14. Kolb, M., Kirschner, J., Riedel, W., Wirtz, H., and Schmidt, M. 1998. Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis. Eur Respir J. 12 (6):1409-1414. 15. Eickelberg, O., Pansky, A., Koehler, E., Bihl, M., Tamm, M., Hildebrand, P., Perruchoud, A.P., Kashgarian, M., and Roth, M. 2001. Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblasts. Faseb Journal 15(3):797-806. 16. Ziesche, R., Hofbauer, E., Wittmann, K., Petkov, V., and Block, L.H. 1999. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 341 (17):1264-1269. 17. Raghu, G., Brown, K.K., Bradford, W.Z., Starko, K., Noble, P.W., Schwartz, D.A., King, T.E., Jr., and the Idiopathic Pulmonary Fibrosis Study Group. 2004. A Placebo-Controlled Trial of Interferon Gamma-1b in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med 350(2):125-133. 18. Bajwa, E.K., Ayas, N.T., Schulzer, M., Mak, E., Ryu, J.H., and Malhotra, A. 2005. Interferon-{gamma}1b Therapy in Idiopathic Pulmonary Fibrosis: A Metaanalysis. Chest 128(1):203-206. 19. Iyer, S.N., Gurujeyalakshmi, G., and Giri, S.N. 1999. Effects of pirfenidone on transforming growth factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther. 291(1):367-373. 20. Azuma, A., Nukiwa, T., Tsuboi, E., Suga, M., Abe, S., Nakata, K., Taguchi, Y., Nagai, S., Itoh, H., Ohi, M., Sato, A., and Kudoh, S. 2005. Double-blind, Placebo-controlled Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 171(9):1040-1047. 21. Lasky, J.A., and Brody, A.R. 2000. Interstitial fibrosis and growth factors. Environ Health Perspect. 108 Suppl 4:751-762. 22. Daniels, C.E., Wilkes, M.C., Edens, M., Kottom, T.J., Murphy, S.J., Limper, A.H., and Leof, E.B. 2004. Imatinib mesylate inhibits the profibrogenic activity of TGF-{beta} and prevents bleomycin-mediated lung fibrosis. J. Clin. Invest. 114(9):1308-1316. 23. Meyer, A., Buhl, R., Kampf, S., and Magnussen, H. 1995. Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals. Am J Respir Crit Care Med. 152(3):1055-1060. 24. Behr, J., Maier, K., Degenkolb, B., Krombach, F., and Vogelmeier, C. 1997. Antioxidative and clinical effects of highdose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med. 156(6):1897-1901. 25. Domedts et al, N Engl J Med 2005; 353:2229-42

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Chairs Letter...

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Our Medical Advisory committee has been busy behind the scenes – advocating on several important respiratory-related issues. Thanks to the many members who provided input into the submission to the Ontario Drug Benefits formulary! 2006 is upon us with the promise of another fantastic Better Breathing conference program next month. You should all by now have received the brochure by mail. If you haven’t already registered, even a quick glance through the program outlined in this issue of the OTR is sure to lure you to the provincial meeting. Peter Macleod and the Planning Committee are to be congratulated for their hard work preparing this year’s meeting! Many of you will be wondering about the outcome of deliberations regarding the future location of the meeting. I am pleased to report that OTS Executive made a commitment to actively assist OLA in raising the funds required to move the conference back to a downtown location for 2007! Your feedback helped guide this decision – and we trust you will support the executive if called upon! This year will bring a number of changes in the composition of our committees. Robin McFadden will turn over the reins as OTS representative on the OLA Board of Directors to the OTS Past-Chair (yours truly). He has been our ear-to-the-ground, finger-on-thepulse of activity and our voice within the organization in more ways than one! I do not think many of us realize the dedication and enthusiasm with which Rob has carried this torch for more years than I can count. He has been a unifying force for OTS, particularly when we were without a medical director. Rob, on behalf of all of our membership, THANK YOU! John Fisher will step down as Chair of the Research Advisory Committee in June 2006. John has demonstrated outstanding leadership and vision in his 7 year term, for which we are extremely grateful. The nomination for his successor is Jim Lewis (voting takes place at the OTS Business meeting at Better Breathing). Thank you for the opportunity to represent Ontario respirologists as the Chair of OTS! I have thoroughly enjoyed working with the many esteemed members of our society’s committees and interacting with OTS members at each opportunity. My job was made much easier by the fantastic administrative support of Bernie Voulgaris and Hedy Ginzberg – two truly special individuals we are most fortunate to have under “our” employ! I look forward to my new role on the OLA Board of Directors and am confident our new Chairperson, John Bertley, will ably guide our endeavors to improve lung health!

We are pleased to announce the 3rd Annual

Respirology Job Fair to be held at The Ontario Thoracic Society Better Breathing 2006 Conference Doubletree International Plaza Hotel, Toronto 655 Dixon Road, Toronto, On M9W 1J3 (near Pearson Airport), Toronto Room

Friday, February 3, 2006 after the OTS Annual General Meeting 5:00 – 6:00 pm You will have an opportunity to present information about positions available in your centre to all residents in the Respirology Programs in Ontario. Tables will be available to set up material if desired. In addition, the Ontario Respirology Program Directors will be available for discussion of your future manpower needs.

Please RSVP to Bernie Voulgaris, OTS office 416-864-9911 or [email protected] by Friday, January 27th

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WE HOPE TO SEE YOU AT BETTER BREATHING! OTS Conference Program FRIDAY, FEBRUARY 3, 2006 7:00 a.m. 7:30 a.m. 8:15 a.m.

10:00 a.m. 10:45 a.m.

12:15 p.m.

1:45 p.m.

2:45 p.m. 3:15 p.m.

4:30 p.m. 5:00 p.m. 6:15 p.m. 6:45 p.m.

NOVARTIS PHARMACEUTICALS CANADA INC. CLINICAL SYMPOSIUM AND BREAKFAST Pre-registration is required Speaker: to be announced Registration PLENARY SESSION Welcome Address Mr. Robert Kelly, Chairman, Ontario Lung Association THEME: RESPIRATORY DISEASE FROM CRADLE TO GRAVE Chair: Dr. Peter Macleod, OTS Better Breathing 2006 Planning Committee Childhood and the Development of Respiratory Disease Dr. Malcolm Sears Palliative Approach to Patients Suffering From Respiratory Disease Dr. Deborah Cook Refreshment Break with Exhibitors OTS/ORCS SCIENTIFIC PROGRAM – WHAT’S NEW IN LUNG HEALTH Co-Chairs: Dr. Diane Lougheed (OTS Chair), Dr. Lisa Cicutto (ORCS Chair) Gender and Respiratory Health: Fad or Fashion Dr. Anna Day Clinical Utility of Quantative Sputum Cell Counts in All Airway Diseases Dr. Frederick Hargreave The Old is New Again: High Flow Nasal Cannula Oxygen Therapy…..Does it really work? Mr. Michael Keim GENERAL LUNCH OR LUNCH WITH A PROFESSOR 1 GENERAL LUNCH 2 Managing Difficult Sarcoid Patients Dr. Meyer Balter 3 Staying Out of Trouble in Respirology Dr. Meri Bukowskyj, Dr. Robert Rivington 4 The André Péloquin Clinical Case Series Chair: Dr. Steven Bencze Dr. Harry Birman, Dr. Marcus Newton, Dr. Jacqueline Nemni AFTERNOON SESSION THEME: PULMONARY POTPOURRI Chair: Dr. Peter Macleod Interventional Pulmonology Dr. Kayvan Amjadi Update on Pulmonary Vasculitis Dr. Christopher Allen Refreshment Break with Exhibitors Resident Case Presentations Chair: Dr. Elizabeth Tullis Case Presenters: University of Ottawa (Dr. Robert Chernish); Queen’s University (Dr. Farzad Saberi); University of Western Ontario (Dr. Abdul Gari); University of Toronto: tba OTS ANNUAL GENERAL MEETING RESPIROLOGY JOB FAIR BANQUET (ticketed event) Banquet Reception DINNER AND AWARDS PRESENTATIONS Banquet Entertainment: James Gordon, Canadian singer/songwriter

SATURDAY, FEBRUARY 4, 2006 7:30 a.m. 8:30 a.m.

10:00 a.m. 10:30 a.m.

12:00 noon 1:30 p.m.

BREAKFAST SESSION (ticketed event) A Health Care Provider’s Perspective on Being Critically Ill Courtney Maguire DEBATES – THEME: CONTROVERSIES IN PUMONARY MEDICINE Chair: Dr. Charles George All Patients With Sleep Apnea Should be Reported to the Ministry of Transportation-Round II Pro: Dr. Charles George Con: Dr. Michael Fitzpatrick A Formal Incremental Cardiopulmonary Exercise Test Should be Standard Practice in the Evaluation of Patients with COPD Pro: Dr. Kieran Killian Con: Dr. Nha Voduc REFRESHMENT BREAK For further information – or to register, Respiratory Quinolones Should be First Line Therapy of CAP visit www.on.lung.ca or call Pro: Dr. Charles Chan Con: Dr. D. William Cameron the OTS office: 416-864-9911 x 254 Allergy Testing in Asthma Patients is a Waste of Time Pro: Dr. Susan Waserman Con: Dr. Michael Cyr THERAPEUTIC UPDATE AND LUNCH SPONSORED BY BOEHRINGER INGELHEIM AND PFIZER Pre-registration is required. DEFINING DISEASE MODIFICATION Dr. Donald Tashkin Close of Better Breathing 2006

O NTARIO T HORACIC R EVIEWS W INTER 2005-2006

7

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SPIRIVA significantly reduced dyspnea1,2*§

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SPIRIVA maintained full 24-hour bronchodilation with once daily inhaled dosing1,2*

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SPIRIVA significantly reduced exacerbations and exacerbationrelated hospitalizations1*¥‡

SPIRIVA is a bronchodilator, indicated for the long term, once daily maintenance treatment of bronchospasm associated with COPD, includ ing chronic bronchitis and emphysema.2 SPIRIVA is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to the excipient lactose monohydrate.2 SPIRIVA should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy.2 The most common adverse reaction was dry mouth. Other adverse reactions reported and consistent with possible anticholinergic effects included: constipation, increased heart rate, supraventricular tachycardia, atrial fibrillation, blurred vision, glaucoma, urinary difficulty and urinary retention.2 As with other anticholinergic drugs, SPIRIVA should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction. Patients should be cautioned to avoid getting the drug powder into their eyes. If this occurs, they should consult a doctor immediately.2 * Results from two 1-year, double-blind, randomized studies of SPIRIVA (n=550, 18 µg once daily) vs placebo (n=371). Salbutamol prn was allowed throughout the study period. Concomitant use of theophyllines, inhaled steroids, and minimal doses of oral corticosteroids (equivalent of ≤10 mg prednisone/day) was allowed if doses were stabilized for at least 6 weeks prior to screening. § SPIRIVA group (42-47% achieved a TDI focal score of ≥1 unit) vs placebo (29-34%)(p