Maintenance therapy with budesonide and formoterol in chronicobstructive pulmonary disease

Abstract

Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown.COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received formoterol (9 mg b.i.d.) and oral prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised to b.i.d. inhaled budesonide/formoterol 320/9 mg, budesonide 400 mg, formoterol 9 mg or placebo for 12 months.Postmedication FEV1 improved by 0.21 L and health-related quality of life using the St George9s Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/formoterol withdrew from the study than those receiving budesonide, formoterol or placebo. Budesonide/formoterol patients had a prolonged time to first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus 87% of baseline), both primary variables versus placebo. They had fewer exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQ versus placebo (-7.5 units). Budesonide/formoterol was more effective than either monocomponent in both primary variables.Budesonide/formoterol in a single inhaler (Symbicort1) [4]. Only two studies have followed the effects of treatment with long-acting, inhaled b 2 -agonists over 1 yr [5,6]. The results confirmed the effect on spirometry, but the change in HRQL was smaller than expected.The role of inhaled corticosteroids (ICS) in COPD is more controversial. Corticosteroids do not appear to affect the rate of decline of forced expiratory volume in one second (FEV1) [7][8][9][10]. However, ICS increased postbronchodilator FEV1 in two studies [8,9], and reduced the severity [11] and frequency of exacerbations when this end-point could be reliably assessed [9]. These observations have led to ICS being recommended for COPD patients with FEV1 v50% predicted who show a spirometric response [12]. In two 1-yr studies, the clinical effect of ICS on exacerbations requiring oral steroids was confirmed [5,6]; the reduction in exacerbation frequency was less evident for patients taking ICS alone in the study by SZAFRANSKI et al. [5]. These results may suggest that sicker patients require more than just ICS in their treatment for COPD.Combining a long-acting b 2 -agonist and an ICS as maintenance therapy has been very successful in managing bronchial asthma [13,14], but less is known about this treatment strategy in COPD. Lung function (prebronchodilator FEV1) is improved when these drugs are combined, compared with monotherapy [15], and recent studies have found that combining therapies is also associated with fewer exacerbations and improved HRQL, compared with placebo treatment [5,6].Patients with more severe COPD (Global Initiative for Obstructive Lung Disease (GOLD) stages III and IV) frequently exper...

A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD

“…In effect, some papers have documented the advantage for COPD patients in combining long-acting anticholinergic and long-acting ß2-adrenergic agents [3][4][5][6]. Other papers [4][5][6][7][8][9][10][11][12][13][14][15] have clearly shown that both longacting ß2-agonists and inhaled corticosteroids have an important role in COPD, which increases when the two drugs are combined in the same therapeutic regimen.…”

Effective management of COPD in primary care — the role of long-acting beta agonist/inhaled corticosteroid combination therapy

“…Some studies showed clinical benefits with ICS use in moderate to severe but not in mild COPD [33][34][35][36]. ICS use is associated with reductions in the number and severity of exacerbations experienced by patients with severe COPD [34,[36][37][38][39]. In addition, in a pooled analysis of seven randomised studies involving 5085 patients, inhaled corticosteroids reduced all-cause mortality by ∼25% relative to placebo in patients with stable COPD [40].…”

“…These recommendations have been based on a number of long-term (≥6 months) randomised, double-blind, placebocontrolled, parallel group trials assessing the efficacy and safety of combining a LABA with an ICS in a single inhaler [29,[37][38][39][41][42][43]. Outcome measures in these trials included lung function, symptom scores, exacerbation rates, quality of life, and safety and tolerability.…”

“…LABA/ICS combination treatment is associated with improvements in lung function, compared with monotherapy, in severe COPD [29,[37][38][39]41]. Studies show pre-dose FEV 1 is improved by 13-17% over baseline by LABA/ICS treatment and can significantly increase pre-dose and post-dose FEV 1 compared with ICS monotherapy (Table 1) [29,[37][38][39]41].…”

“…Studies show pre-dose FEV 1 is improved by 13-17% over baseline by LABA/ICS treatment and can significantly increase pre-dose and post-dose FEV 1 compared with ICS monotherapy (Table 1) [29,[37][38][39]41]. In patients taking LABA/ICS combination therapy, the withdrawal of ICS therapy is associated with a significant, acute, and persistent deterioration in lung function [44].…”