Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

American Thoracic Society 2007 International Conference

San Francisco, California / May 18-23, 2007

Asthma and respiratory disease continue to be of increasing concern to healthcare experts the world over. One class of drugs being investigated as helpful in the fight against chronic obstructive pulmonary disease (COPD) is that of anticholinergics.

The pervasiveness of COPD was a recurring theme among the presenters. As Dr. George Washko, Instructor in Medicine, Pulmonary and Critical Care Medicine, Harvard Medical School, Boston, Massachusetts, told delegates, “COPD is responsible for 176 million hospital bed-days and a loss of 60 million workdays annually in the US alone.”

Because of the prevalence of COPD, health organizations around the world have set standards for the diagnosis and management of the disease. The Public Health Agency of Canada has established guidelines for clinicians that include relieving symptoms, treatment of exacerbations, and pulmonary rehabilitation where indicated. The guidelines state that the management of COPD must include:

• Systems for early diagnosis.

• Relieving symptoms through appropriate use of medications or oxygen.

• Financial assistance, as appropriate, for medication or oxygen.

• A focus on the prevention and treatment of both exacerbations and complications.

• Discouraging patients from smoking.

• Emphasis on pulmonary rehabilitation combined with physical activity along with healthy nutrition.

• Education for the patient (and the family) about the condition.

The Need to Control Exacerbations

Exacerbations of COPD represent one of its most severe manifestations, and can be debilitating for patients. “Exacerbations of COPD are a major driver of healthcare costs,” stated Dr. Peter Calverley, School of Clinical Sciences, University Hospital Aintree, Liverpool, UK, as part of an evening post-graduate seminar.

Bronchodilators are one preferred therapy for controlling both symptoms and exacerbations associated with COPD. In particular, long-acting anticholinergics have been shown to have bronchodilator effects. Additional studies have sought to better characterize these agents.

There were several studies presented at the ATS conference which better described the activity of the long-acting anticholinergic, tiotropium. It is indicated for the long-term, once-daily maintenance treatment of bronchial spasms that are often a result of COPD, including chronic bronchitis and emphysema.

Specifically, one presentation focused on the role of long-term therapy in controlling COPD exacerbations. David M.G. Halpin, DPhil, Consultant Physician and Senior Lecturer in Respiratory Medicine, Royal Devon and Exeter Hospital, UK, and colleagues evaluated the effectiveness of once-daily tiotropium among patients who were otherwise not receiving regular long-acting maintenance treatment for their COPD. The study analyzed the data from nine clinical trials involving tiotropium. In all, the nine studies encompassed 702 treatment-naive and 2607 treated patients among those receiving active therapy, as well as 617 treatment-naive compared to 2245 treated patients among the placebo patients. The studies lasted six to 12 months. In order to standardize the different study durations, the analysis comprised only six months of data from each study.

The researchers found that among those patients who received no prior maintenance therapy, they exhibited less disease severity, as indicated by percentage of predicted forced expiratory volume in 1 second (FEV1) (45.7%), when compared to the population previously receiving short-term treatments (37.2%). This particular cohort also had a higher percentage of smokers, but with fewer pack-years of smoking and a shorter duration of COPD when compared to the previously treated group. After receiving long-acting active treatment, both the maintenance-naive group and the group previously treated with short-acting therapies exhibited improvements when compared to the group that received placebo. For the group that had no previous long-term maintenance therapy, the incidence of COPD exacerbations decreased from 23.0% to 17.8% (P=0.0359). By comparison, the incidence of COPD exacerbations decreased from 29.3% to 25.9% in the previously short-term-treated group (P=0.0136).

Based upon these findings, the researchers concluded that the use of long-acting tiotropium has benefits for patients either previously untreated or treated with short-acting therapy and can help to control exacerbations.

“Patients who are sicker are the ones who are going to have more exacerbations,” noted Dr. Antonio Anzueto, Assistant Professor of Medicine, Division of Pulmonary Diseases/Critical Care Medicine, University of Texas Health Science Center, San Antonio. “Exacerbations are expensive,” he added.

Combination Therapies in COPD

A study presented by Dr. Denis O’Donnell, Professor of Medicine and Head, Division of Respiratory and Critical Care Medicine, Queen’s University, Kingston, Ontario, evaluated the role of tiotropium as an agent to improve airflow, hyperinflation and exercise endurance time (ET) for COPD patients. In addition, the study sought to evaluate the role of combination therapy with inhaled corticosteroids (ICS) among this patient group.

The study retrospectively analyzed the pooled results from two randomized controlled trials in COPD. In both studies, the patients received tiotropium 18 mcg daily for six weeks. During the course of the studies, all patients were allowed to continue use of a previously prescribed ICS. Patients were evaluated at baseline, at three weeks and at six weeks, using pre- and post-study body plethysmography and post-dose ET.

The research team found that out of the 435 patients, there were some significant differences. For each parameter, such as FEV1, forced vital capacity, inspiratory capacity (IC), functional residual capacity, residual volume and ET, patients showed significant improvement with tiotropium in both the ICS and non-ICS groups. Among the ICS group, FEV1 was 1458 mL for those taking active treatment compared to 1276 mL for those on placebo (P<0.01). Similarly, among the non-ICS group, FEV1 was 1517 mL for tiotropium recipients compared to 1233 mL for placebo patients (P<0.01). With respect to IC, among the ICS group, IC was 2502 mL for those on active treatment compared to 2190 mL for those on placebo (P<0.01); among the non-ICS group, IC was 2444 mL for active-treatment recipients compared to 2247 mL for placebo patients (P<0.01). The exercise ET also increased significantly for patients receiving long-term maintenance therapy: 751 sec for those on tiotropium/ICS compared to 573 sec for ICS monotherapy (P<0.01). Among patients receiving no ICS, the ET was 719 sec for patients receiving maintenance therapy and 551 sec for those on placebo (P<0.01).

Based upon these findings, the authors concluded that providing tiotropium therapy for COPD patients could help improve patients’ breathing as well as their physical endurance.

“This study specifically evaluated the advantages of tiotropium on pulmonary function, including among steroid- naive patients. We found that the ability to exercise was preserved,” reported Dr. O’Donnell. “Compared with placebo, tiotropium provides improvement in airflow, lung volume and exercise endurance, irrespective of concurrent treatment with ICS.”

Future Directions in COPD Management

Therapies to control exacerbations and symptoms of COPD can help patients improve their quality of life. Since bronchodilators enhance the potential for physical stamina and endurance training, they may also have the potential to benefit patients’ quality of life. When an exacerbation occurs, patients are reluctant to engage in even basic physical activities, which further decreases their stamina and their quality of life.

Research such as that by Niewoehner (Am J Med 2006; 119:38-45) has shown that management with bronchodilators such as tiotropium leads to fewer exacerbations, consequently allowing for increased physical activity levels and improved long-term clinical outcomes. “Many patients, even after mild exacerbations, are less likely to engage in any physical activity,” confirmed Tierry Troosters, PhD, Associate Professor, Department of Rehabilitation Sciences, Katholieke Universiteit, Leuven, Belgium.

“The reason we need long-acting pharmacotherapy is to impact high mortality and morbidity,” stressed Dr. Anzueto. He added, “You have to intervene and you have to instruct your patients to come to see you as soon as possible.”