Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future.

  • Chung K
  • Caramori G
  • Adcock I
  • 26

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Abstract

Inhaled corticosteroid (ICS) therapy in combination with long-acting beta-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting beta-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 mug daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 mug daily, and addition of the LABA formoterol to budesonide (800 mug) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV(1) and the rate of exacerbations. A reduction in the rate of decline in FEV(1) of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases.

Author-supplied keywords

  • Administration
  • Adrenal Cortex Hormones
  • Adrenal Cortex Hormones: administration & dosage
  • Adrenal Cortex Hormones: adverse effects
  • Adrenal Cortex Hormones: pharmacology
  • Adrenal Cortex Hormones: therapeutic use
  • Adrenergic beta-Agonists
  • Adrenergic beta-Agonists: administration & dosage
  • Adrenergic beta-Agonists: adverse effects
  • Adrenergic beta-Agonists: pharmacology
  • Adrenergic beta-Agonists: therapeutic use
  • Anti-Asthmatic Agents
  • Anti-Asthmatic Agents: administration & dosage
  • Anti-Asthmatic Agents: adverse effects
  • Anti-Asthmatic Agents: pharmacology
  • Anti-Asthmatic Agents: therapeutic use
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents: pharmacology
  • Anti-Inflammatory Agents: therapeutic use
  • Asthma
  • Asthma: drug therapy
  • Biological Availability
  • Bone
  • Bone and Bones
  • Bone and Bones: drug effects
  • Bone: chemically induced
  • Chronic Obstructive
  • Chronic Obstructive: drug thera
  • Combination
  • Dose-Response Relationship
  • Drug
  • Drug Administration Schedule
  • Drug Therapy
  • Drug Tolerance
  • Fractures
  • Humans
  • Inhalation
  • Pulmonary Disease
  • Recurrence
  • Severity of Illness Index

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Authors

  • Kian Fan Chung

  • Gaetano Caramori

  • Ian M Adcock

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