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Symptom-driven Steroid Combination Inhalers for Mild Persistent Asthma
Abstract & Commentary
By Mary Elina Ferris, MD, Clinical Associate Professor, University of Southern California. Dr. Ferris reports no financial relationship to this field of study.
Synopsis: Use of a symptom-driven dose of a combined steroid and albuterol inhaler was equally effective for mild persistent asthma compared to a twice daily steroid inhaler, and resulted in a smaller cumulative dose of inhaled steroids in the six month study period.
Source: Papi A, et al. N Engl J Med. 2007;356:2040-2052.
Four combinations of inhaled treatments were tested in a double blind, randomized controlled trial of 455 subjects between ages 18-65 years in 25 worldwide centers. Mild persistent asthma was identified as a prebronchodilator FEV1 75% or more of predicted, with a 12% increase of predicted value after 200 micrograms inhaled albuterol or a positive metacholine challenge. Participants recorded medication use, symptom scores and measured peak flows in morning and evening. Before being assigned to one of the four study arms, participants had 4 weeks of standard care (twice daily inhaled beclomethasone dipropionate 250 micrograms and rescue albuterol inhaler), and were excluded if asthma was not controlled on this regimen.
Current standard care was compared to two groups given placebo inhalers twice daily, with rescue inhalers either a combination of beclomethasone dipropionate 250 micrograms with albuterol 100 micrograms, or albuterol 100 micrograms alone. The fourth group used the combination inhaler twice daily. Approximately 100 subjects in each of the 4 groups completed the study, and were similar in demographic and clinical characteristics.
The group receiving rescue albuterol alone had the most severe exacerbations (10 out of 17 total), and the most nocturnal awakenings. The three other groups had similar numbers of exacerbations and all with similar improvements in lung function. The group receiving standard care with twice daily beclomethasone used less rescue medications, but all groups except the albuterol alone had improved numbers of symptom-free days and nights. The cumulative inhaled total over the 6 month study for beclomethasone was 19 mg for the symptom-driven combination group, compared to 77 mg for the twice daily groups.
This article supports less frequent use of inhaled steroids for mild persistent asthma, either as-needed or once daily in combination with inhaled albuterol. The authors state that acute asthma is a combination of bronchoconstriction and airway inflammation, and they used a higher inhaled beclomethasone dose at 250 micrograms for more immediate effect than the commercially available twice-daily inhaler at 40 or 80 micrograms. Smaller doses may also be effective, but this has not been studied, nor has the long-term effects on the course of the disease.
It was published alongside a similar study from the American Lung Association1, which also gave support for reducing medication use in controlled mild persistent asthma. The Lung Association study used inhaled fluticasone 100 micrograms instead of beclomethasone, and showed feasible options for substitution with once daily inhaled fluticasone combined with the long-acting beta2 agonist salmeterol 50 micrograms, or with a daily oral leukotriene-receptor antagonist using inhaled albuterol only for rescue. The latter option avoids steroids altogether but results in less asthma control (30% less control compared to 20%), but did give 79% symptom-free days compared to 83-86% for the other options.
All of these alternatives for step-down therapy reduce the cumulative amount of inhaled corticosteroids, which in large amounts has been suggested to increase the rate of fracture after 25 years along with other complications.2 The benefits of inhaled steroids used as-needed have been shown to be feasible in a previous study of budesonide,3 challenging past assumptions that steroids needed to be given regularly for maximal benefit. All of this evidence suggests that an individualized approach to minimize medications for mild persistent asthma will result in smaller doses with acceptable asthma control.
1. The American Lung Association Asthma Clinical Research Centers. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med. 2007;356:2027-2039.
2. Israel E, et al. N Engl J Med. 2001;345:941-947.
3. Boushey HA, et al. N Engl J Med. 2005;352:1519-1528.