Kenneth R. Chapman

Bio: Kenneth R. Chapman is an academic researcher from University of Toronto. The author has contributed to research in topics: Asthma & COPD. The author has an hindex of 67, co-authored 333 publications receiving 15355 citations. Previous affiliations of Kenneth R. Chapman include Toronto General Hospital & Toronto Western Hospital.

Epidemiology and costs of chronic obstructive pulmonary disease.

Abstract: SERIES “THE GLOBAL BURDEN OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE” Edited by K.F. Rabe and J.B. Soriano Number 1 in this Series Chronic obstructive pulmonary disease (COPD) is a leading but under-recognised cause of morbidity and mortality worldwide 1. The prevalence of COPD in the general population is estimated to be ∼1% across all ages rising steeply to >10% amongst those aged ≥40 yrs. The prevalence climbs appreciably higher with age. The 30-yr projections for the global increase in COPD from 1990–2020 are startling. COPD is projected to move from the sixth to the third most common cause of death worldwide, whilst rising from fourth to third in terms of morbidity within the same time-frame 2. The cofactors responsible for this remarkable increase are the continued use of tobacco, coupled with the changing demographics of the world, such that many more people, especially those in developing countries, are living into the COPD age range. COPD is under-diagnosed not only in its early stages, but even when lung function is severely impaired. This is perhaps surprising, since simple and inexpensive spirometers that are suitable in clinical practice are now available, and lung function is a powerful predictor of all-cause mortality, regardless of smoking status. No other disease that is responsible for comparable morbidity, mortality and cost is neglected by healthcare providers as much as COPD. It may well be that the true burden of the disease is not fully appreciated, and the message that COPD is both preventable and treatable has yet to be fully understood by most healthcare providers. The hope is that highlighting these facts will help to raise the profile of COPD and begin to change long-held attitudes. Up to 2001, only 32 prevalence surveys of COPD had been reported 3. This is remarkable given the hundreds …

Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD

Abstract: BackgroundMost guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations The role of treatment with a LABA–LAMA regimen in these patients is unclear MethodsWe conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily The primary outcome was the annual rate of all COPD exacerbations ResultsA total of 1680 patients were assigned to the indacaterol–glycopyrronium group, and 1682 to the salmeterol–fluticasone group Indacaterol–glycopyrronium showed not onl

Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial.

Abstract: Background Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied. Objective To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone. Design Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006. Setting 27 academic and community medical centers in Canada. Patients 449 patients with moderate or severe COPD. Intervention 1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol. Measurements The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics. Results The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo. Limitations More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists. Conclusions 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.

Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide.

Abstract: Exhaled nitric oxide (NO) may aid in monitoring pulmonary disease. The single-breath NO profile (subjects with nose clip) was described as a NO peak followed by a plateau (NO(PLAT)). Published exhaled NO values vary greatly, possibly due to contamination with nasal NO and differing respiratory maneuvers. We developed a technique to measure pulmonary NO, without nasal NO, by having the subject maintain a positive expiratory pressure (ensuring vellum closure), and we examined the variation in NO(PLAT) over a range of expiratory flows (4.2 to 1,550 ml/s). NO(PLAT) values rose almost 35-fold (3.2 +/- 1.4 ppb to 110.5 +/- 54.8 ppb) with decreasing flow, described by NO(PLAT) = 208.6795 x (flow rate)(-0.5995). However, NO excretion showed an almost 11-fold rise as flow increased. In summary, we present a simple technique for measuring exhaled NO without contamination by nasal NO. There is a marked flow dependence of exhaled NO concentration and excretion. Exhaled pulmonary NO is best measured at very low flow r...

Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response

Abstract: Inhaled allergens, acting through IgE-dependent mechanisms, are important triggers of asthma symptoms and inducers of airway hyperresponsiveness and airway inflammation. The effect of anti-IgE recombinant humanized monoclonal antibody-E25 (rhuMAb-E25) on the provocation concentration of allergen causing a 15% fall in FEV1 (allergen PC15) during the allergen-induced early asthmatic response (EAR) was assessed in a multicenter, randomized, double-blind, parallel group study. Ten of 11 allergic asthmatic subjects randomized to receive intravenous rhuMAb-E25, 2 mg/kg on study day 0 and 1 mg/kg on Days 7, 14, 28, 42, 56, and 70 completed the study; nine received intravenous placebo. The allergen PC15 was measured on Days -1, 27, 55, and 77 and methacholine PC20 on Days -2, 42, and 76. rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn because of a generalized urticarial rash after the first dose. Compared with baseline values (Day -1), the median allergen PC15 on Days 27, 55, and 77...

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

Alzheimer's disease: the amyloid cascade hypothesis

Abstract: In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi–treated L4 larvae. We observed expression of 8,000–10,000 genes in the linker cell, 22–25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67–dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.