Anti-Inflammatory Effects of Combined Budesonide/Formoterol in COPD Exacerbations

Systemic corticosteroids and additional short-acting ββ2-agonists are commonly used in exacerbations of chronic obstructive pulmonary disease (COPD). In this double-blind study, the combination of a high-dose inhaled corticosteroid with a rapid-onset long-acting ββ2-agonist was evaluated in the treatment of out-patient COPD exacerbations. The primary aim was to compare 14-day treatment effects of budesonide/formoterol to placebo on sputum eosinophils and, secondarily, on other indices of inflammation, forced expiratory flow in one second (FEV1), symptoms, health status, and adverse events. Forty-five patients not using steroids (37 male, 21/24 current/ex smoker, median packyears 38, age 65 years, FEV1 61% predicted), experiencing a COPD exacerbation, were treated at home with budesonide/formoterol (320/9 μg 4 times daily), prednisolone (30 mg daily), or placebo for 14 days. Sputum eosinophils were significantly reduced by budesonide/formoterol (−57%) compared to placebo (+24%) (p = 0.01). Budesonide/formoterol reduced total symptom scores significantly (p = 0.01) compared to placebo. The increase in FEV1 by 2 weeks of treatment with budesonide/formoterol (125 ml) was not significantly different from that of placebo (43 ml) (p = 0.07). Budesonide/ formoterol treatment did not suppress morning serum cortisol compared to placebo (−16 %; p = 0.50). In conclusion, budesonide/formoterol reduces sputum eosinophils and improves symptoms in the treatment of out-patient COPD exacerbations.

[1]  D. Postma,et al.  Safety of sputum induction during exacerbations of COPD. , 2007, Chest.

[2]  T. Molen,et al.  Health status measurement in COPD: the minimal clinically important difference of the clinical COPD questionnaire , 2006, Respiratory research.

[3]  I. Pavord,et al.  Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease. , 2006, American journal of respiratory and critical care medicine.

[4]  G. Donaldson,et al.  MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation , 2005, Respiratory research.

[5]  K. Kubo,et al.  Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease , 2005, European Respiratory Journal.

[6]  I. Pavord,et al.  Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease , 2005, Thorax.

[7]  D. Sin,et al.  Bmc Pulmonary Medicine Effects of Inhaled Corticosteroids on Sputum Cell Counts in Stable Chronic Obstructive Pulmonary Disease: a Systematic Review and a Meta-analysis , 2022 .

[8]  H. Bisgaard,et al.  Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. , 2005, American journal of respiratory and critical care medicine.

[9]  J. Walters,et al.  Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. , 2005, The Cochrane database of systematic reviews.

[10]  W. Pierzchała,et al.  Decreased levels of myeloperoxidase in induced sputum of patients with COPD after treatment with oral glucocorticoids. , 2004, Chest.

[11]  Dirkje S Postma,et al.  Health and Quality of Life Outcomes , 2003 .

[12]  R. Pauwels,et al.  Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial , 2003, The Lancet.

[13]  R. Sansores,et al.  Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease , 2003, European Respiratory Journal.

[14]  P. Shah,et al.  Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. , 2003, American journal of respiratory and critical care medicine.

[15]  N. Leidy,et al.  Evaluating symptoms in chronic obstructive pulmonary disease: validation of the Breathlessness, Cough and Sputum Scale. , 2003, Respiratory medicine.

[16]  P. Jeffery,et al.  The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. , 2002, American journal of respiratory and critical care medicine.

[17]  F. Maltais,et al.  Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. , 2002, American journal of respiratory and critical care medicine.

[18]  T. Sandström,et al.  Effects of budesonide and formoterol on NF-kappaB, adhesion molecules, and cytokines in asthma. , 2001, American journal of respiratory and critical care medicine.

[19]  I. Pavord,et al.  Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial , 2000, The Lancet.

[20]  B. Balbi,et al.  Inhaled corticosteroids in stable COPD patients: do they have effects on cells and molecular mediators of airway inflammation? , 2000, Chest.

[21]  G. Koëter,et al.  Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. , 2000, The European respiratory journal.

[22]  D. Postma,et al.  Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma , 1999, Thorax.

[23]  L. Davies,et al.  Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial , 1999, The Lancet.

[24]  D. Niewoehner,et al.  Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. , 1999, The New England journal of medicine.

[25]  K. Kubo,et al.  Eosinophilic inflammation in the airway is related to glucocorticoid reversibility in patients with pulmonary emphysema. , 1999, Chest.

[26]  P. Howarth,et al.  The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma. , 1999, American journal of respiratory and critical care medicine.

[27]  F. Hargreave,et al.  Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. , 1998, American journal of respiratory and critical care medicine.

[28]  B. Beghé,et al.  Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease , 1998, Thorax.

[29]  D. Postma,et al.  Prostaglandin E2 differentially modulates IL-5 gene expression in activated human T lymphocytes depending on the costimulatory signal. , 1998, The Journal of allergy and clinical immunology.

[30]  F. Hargreave,et al.  Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment. , 1997, American journal of respiratory and critical care medicine.

[31]  A. Morice,et al.  A comparison of nebulized budesonide with oral prednisolone in the treatment of exacerbations of obstructive pulmonary disease , 1996, Clinical pharmacology and therapeutics.

[32]  J. Crowley,et al.  Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. , 1996, American journal of respiratory and critical care medicine.

[33]  R. Stockley,et al.  Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema. , 1996, American journal of respiratory and critical care medicine.

[34]  L. Fabbri,et al.  Airway eosinophilia in chronic bronchitis during exacerbations. , 1994, American journal of respiratory and critical care medicine.

[35]  J E Cotes,et al.  Lung volumes and forced ventilatory flows , 1993, European Respiratory Journal.

[36]  J E Cotes,et al.  Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[37]  K. Takatsu.  Interleukin 5 (IL‐5) and Its Receptor , 1991, Microbiology and immunology.

[38]  A. Connors,et al.  A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD. , 1989, Chest.

[39]  R. Albert,et al.  Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. , 1980, Annals of internal medicine.