Can inhaled fluticasone alone or in combination with salmeterol reduce systemic inflammation in chronic obstructive pulmonary disease? Study protocol for a randomized controlled trial [NCT00120978]

Abstract

Background: Systemic inflammation is associated with various complications in chronic obstructive pulmonary disease including weight loss, cachexia, osteoporosis, cancer and cardiovascular diseases. Inhaled corticosteroids attenuate airway inflammation, reduce exacerbations, and improve mortality in chronic obstructive pulmonary disease. Whether inhaled corticosteroids by themselves or in combination with a long-acting beta2-adrenoceptor agonist repress systemic inflammation in chronic obstructive pulmonary disease is unknown. The Advair Biomarkers in COPD (ABC) study will determine whether the effects of inhaled corticosteroids alone or in combination with a long-acting beta2-adrenoceptor agonist reduce systemic inflammation and improve health status in patients with chronic obstructive pulmonary disease.

Methods/design: After a 4-week run-in phase during which patients with stable chronic obstructive pulmonary disease will receive inhaled fluticasone (500 micrograms twice daily), followed by a 4-week withdrawal phase during which all inhaled corticosteroids and long acting beta2-adrenoceptor agonists will be discontinued, patients will be randomized to receive fluticasone (500 micrograms twice daily), fluticasone/salmeterol combination (500/50 micrograms twice daily), or placebo for four weeks. The study will recruit 250 patients across 11 centers in western Canada. Patients must be 40 years of age or older with at least 10 pack-year smoking history and have chronic obstructive pulmonary disease defined as forced expiratory volume in one second to vital capacity ratio of 0.70 or less and forced expiratory volume in one second that is 80% of predicted or less. Patients will be excluded if they have any known chronic systemic infections, inflammatory conditions, history of previous solid organ transplantation, myocardial infarction, or cerebrovascular accident within the past 3 months prior to study enrollment. The primary end-point is serum C-reactive protein level. Secondary end-points include circulating inflammatory cytokines such as interleukin-6 and interleukin-8 as well as health-related quality of life and lung function.

Discussion: If inhaled corticosteroids by themselves or in combination with a long-acting beta2-adrenoceptor agonist could repress systemic inflammation, they might greatly improve clinical prognosis by reducing various complications in chronic obstructive pulmonary disease.

Trial registration: ClinicalTrials.gov NCT00120978.

Figure 1

Summary of the Trial Protocol. * Post bronchodilator values; all else will be pre-bronchodilator values. † Must be done prior to initiation of therapy and completion of therapy or during periods of acute exacerbation or infection. For those exacerbations or infections requiring oral steroids and/or antibiotics, patients will be asked to return 2 weeks after completing their acute exacerbation or infection treatment.

Figure 2

Management of Exacerbations during the Study. Abbreviations: LABA, long-acting β₂ adrenoceptor agonist; SGRQ, St. George's Respiratory Questionnaire.