Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041.

Apoptosis of the WEHI 231 immature B cell lymphoma line following membrane interaction with an antibody against the surface IgM chains (anti‐IgM) is preceded by dramatic changes in Nuclear Factor‐kappaB (NF‐kappaB)/ Rel binding activities. An early transient increase in NF‐kappaB/Rel binding is followed by a significant decrease in intensity below basal levels. Here we have explored the role of these changes in Rel‐related factors in B cell apoptosis. Treatment of WEH1 231 cells with N‐tosyl‐L‐phenylalanine chloromethyl ketone (TPCK), a protease inhibitor which prevents degradation of the inhibitor of NF‐kappaB (IkappaB)‐alpha, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF‐kappaB/Rel factor binding and induced apoptosis. Bcl‐XL expression protected WEHI 231 cells from apoptosis induced by these agents. Microinjection of WEHI 231 cells with either IkappaB‐alpha‐GST protein or a c‐Rel affinity‐purified antibody induced apoptosis. Ectopic c‐Rel expression ablated apoptosis induced by TPCK or anti‐IgM. Treatment of BALENLM 17 and A20 B lymphoma cells or normal murine splenic B lymphocytes with either TPCK or PDTC also resulted in apoptosis. These findings indicate that the drop in NF‐kappaB/Rel binding following anti‐IgM treatment activates apoptosis of WEHI 231 cells; furthermore, they implicate the NF‐kappaB/Rel family in control of apoptosis of normal and transformed B cells.

The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee's new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence.

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Awareness, diagnosis and treatment of COPD, compared to other major causes of death, remains far too low. This article describes the protocol objectives, design and the approaches taken in the Canadian Chronic Obstructive Lung Disease (CanCOLD) study, an epidemiological and integrated research. The CanCOLD study aims at better understanding heterogeneity of COPD presentation and disease progression. We hypothesize that individuals with unfavourable COPD "phenotypes" and subjects at-risk (ever smokers) with unhealthy lifestyle habits, environmental/work exposure, or co-morbidities will have increased risk of lung function decline independent of their cumulative exposure to cigarette smoke. The study is a prospective multi-center cohort study (9 sites in 6 provinces) built on the Canadian COPD prevalence study "COLD." The study plan is to include 1800 subjects at least 40 years old who were sampled from the general population and who were found to fall within 4 groups: 1) COPD moderate-severe (GOLD 2-4); 2) COPD mild (GOLD 1); 3) subjects at-risk (ever smoker); and, 4) subjects never-smoker free of airflow obstruction. Data collection is based on using strictly standardized methods involving questionnaires, pulmonary function and cardiorespiratory exercise tests, CT scans, and blood sampling. CanCOLD is a unique study that will address challenging and important research questions on COPD disease evolution and disease management and will help to define the natural history of COPD disease evolution in individuals at-risk for COPD and in those with COPD who have mild disease.

Background: Our aim was to determine the combined and independent effects of tobacco and marijuana smoking on respiratory symptoms and chronic obstructive pulmonary disease (COPD) in the general population. Method:We surveyed a random sample of 878 people aged 40 years or older living in Vancouver, Canada, about their respiratory history and their history of tobacco and marijuana smoking. We performed spirometric testing before and after administration of 200 μg of salbutamol. We examined the association between tobacco and marijuana smoking and COPD. Results:The prevalence of a history of smoking in this sample was 45.5% (95% confidence interval [CI] 42.2%-48.8%) for marijuana use and 53.1% (95% CI 49.8%-56.4%) for tobacco use. The prevalence of current smoking (in the past 12 months) was 14% for marijuana use and 14% for tobacco use. Compared with nonsmokers, participants who reported smoking only tobacco, but not those who reported smoking only marijuana, experienced more frequent respiratory symptoms (odds ratio [OR] 1.50, 95% CI 1.05-2.14) and were more likely to have COPD (OR 2.74, 95% CI 1.66-4.52). Concurrent use of marijuana and tobacco was associated with increased risk (adjusted for age, asthma and comorbidities) of respiratory symptoms (OR 2.39, 95% CI 1.58-3.62) and COPD (OR 2.90, 95% CI 1.53-5.51) if the lifetime dose of marijuana exceeded 50 marijuana cigarettes. The risks of respiratory symptoms and of COPD were related to a synergistic interaction between marijuana and tobacco.Interpretation: Smoking both tobacco and marijuana synergistically increased the risk of respiratory symptoms and COPD. Smoking only marijuana was not associated with an increased risk of respiratory symptoms or COPD. col of the BOLD study. The prevalence of COPD was assumed to be 15%. 15 We conducted sampling in 2 stages. First, we used random-digit dialling to identify and recruit a randomized sample of at least 1000 people. 16 Recruits were then invited to the clinic to complete standardized questionnaires administered by interviewers. Demographic details were collected, and participants were asked about their respiratory health and symptoms, smoking history, quality of life, use of health care services and cardiovascular comorbidities and other respiratory diseases. We also performed spirometric testing before and after administration of a bronchodilator. 15 We collected data from August 2005 to April 2006.We obtained approval to conduct the study from the University of British Columbia and the Providence Health Care Research Ethics Board. Questionnaire on marijuana useTo obtain details about participants' marijuana use, we used a 7-item questionnaire (Appendix 1, available at www.cmaj.ca /cgi/content/full/180/8/814/DC2). Spirometric testingWe used a portable spirometer (EasyOne, ndd Medical Technologies, Andover, USA) to collect data on forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC). We performed the spirometric tests before and after administering 200 μg of salbutamol (also known as a...

ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.