Combination Inhaler Therapy for Chronic Obstructive Pulmonary Disease

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The summary below is from the full report titled "Tiotropium in Combination with Placebo, Salmeterol, or Fluticasone–Salmeterol for Treatment of Chronic Obstructive Pulmonary Disease. A Randomized Trial." It is in the 17 April 2007 issue of Annals of Internal Medicine (volume 146, pages 545-555). The authors are S.D. Aaron, K.L. Vandemheen, D. Fergusson, F. Maltais, J. Bourbeau, R. Goldstein, M. Balter, D. O'Donnell, A. McIvor, S. Sharma, G. Bishop, J. Anthony, R. Cowie, S. Field, A. Hirsch, P. Hernandez, R. Rivington, J. Road, V. Hoffstein, R. Hodder, D. Marciniuk, D. McCormack, G. Fox, G. Cox, H.B. Prins, G. Ford, D. Bleskie, S. Doucette, I. Mayers, K. Chapman, N. Zamel, and M. FitzGerald, for the Canadian Thoracic Society/Canadian Respiratory Clinical Research Consortium.

What is the problem and what is known about it so far?

Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that is usually caused by smoking. People with COPD are short of breath. They sometimes have spasms of the lung's airways (bronchial tubes), and they cough and wheeze. Symptoms and lung damage slowly get worse over time. Most patients also have bouts of worsening of symptoms. We call these bouts exacerbations. Doctors use several drugs to treat COPD. Many come in the form of inhalers or puffers. In an inhaler, the drugs are in solutions in small pressurized cans that have pumps. Patients put the pump's mouthpiece in their mouth and push the pump as they start to inhale deeply. They then hold their breath for about 10 seconds so that the airways absorb the medicine. The standard metered-dose inhaler releases a fixed dose of medicine in aerosol form. Examples of drug inhalers include tiotropium (known by the brand name Spiriva), salmeterol (known by the brand name Serevent), and a combination of fluticasone and salmeterol (known by the brand name Advair). Drugs in these inhalers have different actions. Tiotropium and salmeterol expand (dilate) the bronchial tubes. Fluticasone, a steroid, fights inflammation.

Why did the researchers do this particular study?

To see which of 3 inhaler regimens best prevented exacerbations in patients with COPD.

Who was studied?

449 adults with moderate to severe COPD. All patients were older than 35 years of age and had smoked cigarettes for many years.

How was the study done?

Researchers recruited patients from 27 academic and community medical centers in Canada. They randomly assigned patients to receive 1 of the 3 following regimens: tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus the combination of fluticasone and salmeterol. The researchers, doctors, and patients did not know who received which treatment. Patients were followed for 1 year. The researchers then compared exacerbations, lung function, and hospitalizations among the groups.

What did the researchers find?

The proportion of patients who had exacerbations was 63% in the group given tiotropium plus placebo, 65% in the group given tiotropium plus salmeterol, and 60% in the group given tiotropium plus the combination of fluticasone and salmeterol. Patients given tiotropium plus the combination of fluticasone and salmeterol had better lung function, better quality of life, and fewer hospitalizations than those given tiotropium plus placebo. Lung function and hospitalization rates did not differ much between patients given tiotropium plus placebo and those given tiotropium plus salmeterol.

What were the limitations of the study?

More than 40% of the patients given tiotropium plus placebo and those given tiotropium plus salmeterol stopped using their inhalers before the study ended.

What are the implications of the study?

Adding the combination of fluticasone and salmeterol to tiotropium improved lung function and quality of life and decreased hospitalizations, but it did not affect the number of exacerbations in patients with moderate or severe COPD.