Chest
Volume 135, Issue 6, June 2009, Pages 1628-1633
Journal home page for Chest

Clinical Commentary
Rescue Treatment in Asthma: More Than As-Needed Bronchodilation

https://doi.org/10.1378/chest.08-2536Get rights and content

International guidelines recommend the use of rapid-onset inhaled β2-agonists alone for symptom relief in all asthmatic patients. However, recent clinical trials have shown that the “as-required,” or PRN, use of inhaled combinations of a corticosteroid and a rapid-onset β2-agonist provides clinical advantages over the traditional PRN inhaled rapid-onset β2-agonists alone in patients with different degrees of asthma severity.

Asthma symptoms are associated not only with bronchoconstriction but also with increased airway inflammation. Inhaled β2-agonists have a rapid onset of bronchodilator action that is mainly mediated by a relaxing effect on airway smooth muscle. Inhaled corticosteroids also have rapid clinical effects that can suppress lower airway inflammation, and there is a rapid synergistic potentiation of the antiinflammatory effect of corticosteroids and of the bronchodilatory action of β2-agonists when the two drugs are given simultaneously. On the basis of this emerging evidence, we propose that the current rescue use of rapid-onset inhaled β2-agonists alone should now be replaced by an inhaled rapid-acting β2-agonist combined with a corticosteroid as preferred PRN strategy. We conclude with a call for clinical trials aimed to test the superiority of this approach in all degrees of asthma severity in a real-world setting in addition to any of the regular treatments recommended by international guidelines. In the future it might even be possible to control asthma entirely with PRN combination inhalers without maintenance therapy, at least in patients with less severe disease.

Section snippets

Clinical Evidence and Rationale

Several studies have shown the efficacy of ICS in acute conditions, in mild to moderate exacerbations, where high-dose ICS resulted in comparable efficacy to systemic steroids.10, 11, 12, 13, 14

The use of intermittent treatment with inhaled corticosteroid, guided on a symptom-based written action plan in the absence of any regular treatment, has been recently tested in adults with mild asthma.15 Compared to twice-daily regular treatment with ICS, intermittent treatment is not associated with an

Pathophysiology and Underlying Molecular Mechanisms

Asthma symptoms are associated not only with bronchoconstriction but also with enhanced lower airway inflammation,3, 4, 5, 6, 7 and both β2-agonists and ICS rapidly exert their bronchodilator or antiinflammatory effects on the lower airways.

The fast bronchodilator effect of rapid-onset inhaled β2-agonists bronchodilators is mediated mainly by a relaxing effect on contracted lower airway smooth muscle. In addition to their direct bronchodilator effect, inhaled β2-agonists may also have important

Rapid Pharmacologic Interactions Between Inhaled Corticosteroids and β2-Agonists

Not only can ICS and β2-agonists act rapidly, but they can interact in a two-way fashion when simultaneously present at the pharmacologic cell target, with each drug enhancing the effect of the other. This interaction is likely to be relevant in the use of their combination as a rescue medication for symptom relief.

Conventional wisdom had been that corticosteroids and β2-agonists act through separate and distinct pathways. Corticosteroids diffuse into the target cells (in the lower airways,

Future Research

Taken together, this evidence clarifies the potentiating effect of corticosteroids and β2-agonists interactions that occurs rapidly and could explain the clinical efficacy of the use of this combination as rescue treatment. Given the clinical advantages and the established molecular mechanisms, with virtually absent side effects, we suggest that this approach should now be regarded as optimal PRN strategy at any degree of asthma severity: it needs no technical explanation, it is easy to learn

References (46)

  • M Roth et al.

    Interaction between glucocorticoids and beta2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling

    Lancet

    (2002)
  • G Horvath et al.

    The effect of corticosteroids on the disposal of long-acting beta2-agonists by airway smooth muscle cells

    J Allergy Clin Immunol

    (2007)
  • National Asthma Educational and Prevention Program NH, Lung, and Blood Institute, Expert Panel Report 3. Guidelines for...
  • ED Bateman et al.

    Global strategy for asthma management and prevention: GINA executive summary

    Eur Respir J

    (2008)
  • M Romagnoli et al.

    Eosinophilic inflammation in sputum of poorly controlled asthmatics

    Eur Respir J

    (2002)
  • J Bousquet et al.

    Eosinophilic inflammation in asthma

    N Engl J Med

    (1990)
  • R Djukanovic et al.

    Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma

    Am Rev Respir Dis

    (1992)
  • PG Gibson et al.

    A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid

    Clin Exp Allergy

    (1992)
  • A Jatakanon et al.

    Changes in sputum eosinophils predict loss of asthma control

    Am J Respir Crit Care Med

    (2000)
  • PG Gibson et al.

    Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial

    Am J Respir Crit Care Med

    (2001)
  • G Rodrigo et al.

    Inhaled flunisolide for acute severe asthma

    Am J Respir Crit Care Med

    (1998)
  • GJ Rodrigo

    Comparison of inhaled fluticasone with intravenous hydrocortisone in the treatment of adult acute asthma

    Am J Respir Crit Care Med

    (2005)
  • HA Boushey et al.

    Daily versus as-needed corticosteroids for mild persistent asthma

    N Engl J Med

    (2005)
  • Cited by (0)

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

    1

    Dr. Papi received research funding from and has been on scientific advisory boards for AstraZeneca, Chiesi, GlaxoSmithKline, and UCB;

    2

    Dr. Caramori has received lecture fees from GSK and Chiesi Farmaceutici;

    3

    Dr. Adcock received research funding from and has been on scientific advisory boards for GlaxoSmithKline, Chiesi, and AstraZeneca;

    4

    Dr. Barnes received research funding from and has been on scientific advisory boards for AstraZeneca, Chiesi, Cipla, GlaxoSmithKline, and UCB.

    View full text