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.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

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

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

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Outcomes for COPD pharmacological trials: From lung function to biomarkers

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition

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Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update.

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.

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

A b s t r ac t The patients had a mean baseline FEV 1 of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV 1 from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P = 0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV 1 also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P = 0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerba- tion (hazard ratio, 0.79; P = 0.03). No deaths occurred; adverse events were similar in the two groups. Conclusions In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984.)

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Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy

This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD).

A total of 71 COPD patients (mean forced expiratory volume in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 μg q.d. , formoterol 12 μg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety.

Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0–12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12–24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs·day−1, tiotropium 2.41 puffs·day−1, formoterol 2.37 puffs·day−1). All treatments were well tolerated.

In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.

https://erj.ersjournals.com/content/erj/26/2/214.full.pdf

Achim Mueller

Papers

Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD

Effects of Tiotropium With and Without Formoterol on Airflow Obstruction and Resting Hyperinflation in Patients With COPD

The efficacy of tiotropium administered via Respimat® Soft Mist™ Inhaler or HandiHaler® in COPD patients

Combining tiotropium and salmeterol in COPD: Effects on airflow obstruction and symptoms

Effect of a single exacerbation on decline in lung function in COPD