Chest

Chest

Volume 126, Issue 1, July 2004, Pages 220-237
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Reviews
Inhaled Combination Therapy With Long-Acting β2-Agonists and Corticosteroids in Stable COPD

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Long-acting β2-agonists (LABAs) have been shown to be effective first-line bronchodilators in the treatment of COPD patients, and inhaled corticosteroids (ICSs) have been shown to reduce the frequency and/or severity of exacerbations in COPD patients. The concomitant use of a LABA and an ICS can influence both airway obstruction (ie, smooth muscle contraction, increased cholinergic tone, and loss of elastic recoil), and airway inflammation (ie, increased numbers of neutrophils, macrophages, and CD8+ lymphocytes, elevated interleukin-8 and tumor necrosis factor-α levels, and protease/antiprotease imbalance). They are also able to reduce the total number of bacteria adhering to the respiratory mucosa in a concentration-dependent manner without altering the bacterial tropism for mucosa, and to preserve ciliated cells. Several clinical trials support the concept of inhaled combination therapy with LABAs and corticosteroids in stable COPD patients. This type of therapy not only improves airflow obstruction but also provides clinical benefits, as manifested by sustained reduction in overall symptoms, improvements in health-related quality of life, and reductions in exacerbations. All of these effects are very important because, despite recent advances in our understanding of COPD and its treatment, therapy remains suboptimal for a considerable number of patients.

Section snippets

Use of Long-Acting β2-Agonists in COPD

Long-acting β2-agonists (LABAs) have been shown to be elective first-line bronchodilators in the treatment of patients with COPD.5,6 They safely attenuate airflow obstruction, decrease the frequency and severity of symptoms by reducing the amount of dynamic hyperinflation, and improve quality of life (QOL). Interestingly, several studies have documented that the LABAs formoterol7,8 and salmeterol9,10 are more effective than ipratropium bromide for the regular treatment of COPD. This finding is

Use of Corticosteroids in COPD

The role of corticosteroids in the management of COPD remains controversial. ICSs are commonly prescribed in high doses on the basis that COPD is like poorly responsive asthma, but evidence that they are beneficial in patients with pure COPD is still weak. In effect, although it is well-known that corticosteroids are effective at suppressing airway inflammation, their effect on the inflammation in COPD is still unclear.

Pharmacologic Rationale for Combining a LABA and an ICS in COPD

It must always be emphasized that the use of ICSs should not leave the use of a LABA out of consideration. The concomitant use of a LABA and an ICS can influence airway obstruction (eg, smooth muscle contraction, increased cholinergic tone, and, perhaps, bronchial hyperreactivity), mucociliary dysfunction (eg, reduced mucociliary transport and mucosal damage), and airway inflammation (eg, increased numbers of neutrophils, macrophages, and CD8+ lymphocytes, elevated levels of IL-8, TNF-α, and

Inhaled Combination Therapy With LABAs and Corticosteroids in Stable COPD Patients

Several clinical trials support the concept of inhaled combination therapy with LABAs and corticosteroids in stable COPD patients, although some reports have not been published yet. Nonetheless, the currently available information has recently induced the European Agency for the Evaluation of Medicinal Products to issue a positive opinion83 on the use of combination therapy with LABAs and ICSs in the maintenance treatment of patients with severe COPD and a history of exacerbations.

Systemic Adverse Effects Using Combination Therapy With LABAs and Corticosteroids

Consideration of the risk/benefit ratio is important when using inhaled combination therapy with LABAs and ICSs in patients with COPD, mainly because of the potential systemic adverse effects induced by ICSs.

Need for Further Studies

First of all, there is a need to assess the antiinflammatory effects of long-term inhaled combination therapy with LABAs and ICSs. There is little knowledge at present about the effects of regular treatment with LABAs and/or ICSs on airway inflammation in COPD patients. Studies99 using bronchial biopsy specimens obtained during fiberoptic bronchoscopy in patients with COPD have yielded valuable information about the inflammatory process in the large airways of patients with this disease.

Conclusions

There is an increasing volume of evidence showing that combination treatment with both salmeterol/fluticasone and formoterol/budesonide can provide an effective treatment option for COPD patients. However, it must always be considered that the trials that explored the effect of these therapies recruited a select group of patients with COPD, and the results may not be generalizable to patients with extremely advanced or mild forms of the disorder.106 Nevertheless, since the goals of COPD therapy

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    • Cited by (0)

    Dr. Cazzola has received fees for participating to Advisory Boards from Altana, AstraZeneca, and Novartis, for consulting from Chiesi Farmaceutici and GSK, and for speaking from AstraZeneca, Boehringer Ingelheim, GSK, Menarini Farmaceutici, Novartis, and Pfizer, and research-related grants from GSK. Dr. Dahl has received fees for participating in Advisory Boards from Altana, Boehringer-Ingelheim, and GSK, for speaking from Schering-Plough, MSD, and ALK-Abello, and research-related grants from Astra-Zeneca, GSK, ALK-Abello, Pfizer, Boehringer-Ingelheim, Novartis, Almirall, MSD, and UCB.

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    Copyright © 2004 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.