Are daily inhaled steroids appropriate for mild persistent asthma?
Studies have shown that the regular use of inhaled corticosteroids significantly improves multiple outcomes in patients with mild persistent asthma (MPA), including asthma control, airway hyper-responsiveness and inflammation, and lung function.
We even have some evidence that regular inhaled corticosteroids (ICS) in MPA may reduce exacerbations and prevent decline in lung function.
The OPTIMA study found that regular ICS use in MPA, even in ICS-naive patients, could significantly reduce severe exacerbations, improve asthma control, and improve multiple other outcomes (Am. J. Resp. Crit. Care Med. 2001;164:1392-7).
The START study enrolled more than 7,000 MPA adults and children within 2 years of their asthma diagnosis. During this 3-year placebo-controlled trial, patients randomized to regular ICS had significantly fewer severe asthma exacerbations, more symptom-free days, and decreased need for rescue oral corticosteroids. They also had significant improvements in both pre- and postbronchodilator forced expiratory volume in 1 second (FEV1), suggesting that early intervention with regular ICS can forestall decreases in lung function (Lancet 2003;361:1071-6).
The IMPACT trial, which was published in 2005, studied 225 adults with MPA who were treated with intermittent short-course corticosteroids guided by a symptom-based action plan, either alone or with daily ICS (budesonide) or zafirlukast (N. Engl. J. Med. 2005;352:1519-28). After 1 year, the budesonide group had significantly better prebronchodilator FEV1, better asthma control scores, more symptom-free days, and less airway hyperresponsiveness.
The authors suggested that it is possible to treat MPA with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen because they did not find a difference between groups in morning peak flow expiratory flows, postbronchodilator FEV1, or exacerbations. However, morning peak expiratory flow likely is not a very useful end point in patients whose lung function is near normal to begin with.
IMPACT also had a substantially lower incidence of exacerbations in patients than did START or OPTIMA, likely too low to draw any conclusions. And it only included adult patients with a long history of asthma (17-21 years), a population in whom regular ICS may be less likely to preserve lung function.
Although further studies are needed, regular ICS treatment in MPA could also have an important beneficial impact on the economics of asthma, particularly if reduced exacerbations translate into less time off work and school and fewer hospital visits. An economic subset analysis of the START data concluded that even in children aged 5-10 years, regular ICS resulted in societal savings of $192 over 3 years, partly because caregivers had to take less time off from work (Pediatr. Allergy Immunol. 2006;17[suppl. 17]:21-7).
Overall, the low doses of ICS needed to control mild persistent asthma are very safe. START did show a mild reduction in growth velocity for children receiving regular ICS, although it is unlikely that final adult height will be significantly affected.
Symptom-based intermittent corticosteroid treatment for MPA would require a very thorough, continuing assessment of asthma severity and control. In actual practice, both physicians and patients tend to underestimate asthma severity. Consequently, symptom-based intermittent treatment for MPA likely would lead to undertreatment of many patients whose asthma is actually more severe.
In conclusion, there is insufficient evidence to alter the well-grounded recommendation to treat MPA with regular ICS.
DR. DYKEWICZ is director of the allergy and immunology program at St. Louis University School of Medicine.
BY MARK DYKEWICZ, M.D.
ICS therapy on an as-needed basis is just as effective.
For patients with mild persistent asthma, inhaled corticosteroids taken on an as-needed basis are just as effective as daily therapy, much less expensive, and more in line with the way our patients are actually taking the drug.
And although the jury is still out on whether as-needed inhaled corticosteroids (ICS) positively affect airway remodeling, there is likewise little firm evidence that daily use is any more effective.
We treat mild persistent asthma (MPA) with regular ICS simply because our 1997 National Asthma Education and Prevention Program guidelines suggested that daily treatment might preserve lung function as well as relieve symptoms and prevent exacerbation. But this guideline change was based on few studies, all of which were performed before the division of mild asthma into the two groups we now recognize: persistent and intermittent.
Let's examine some more recent data. IMPACT is often cited as evidence that regular ICS improves many outcomes for patients with MPA. But this study showed no significant differences in morning peak flow. There were no differences in asthma exacerbation rates, and no differences in the need for the addition of prednisone. Those on regular ICS had more symptom-free days, but the difference was only about 26 days per year. And there were no differences on the asthma control questionnaire or in exacerbation rates.
Nor was there a difference in postbronchodilator forced expiratory volume, demonstrating that regular ICS did not significantly affect airway remodeling. Daily ICS seemed to have a positive effect on airway inflammation, with that group having fewer sputum eosinophils and lower exhaled nitrous oxide.
The START trial did show that patients with new-onset MPA could benefit from daily ICS therapy--but not very much. The difference in FE[V.sub.1] after 3 years of budesonide or placebo was only 1%--a finding that the investigator himself said could be attributed to the high rate of concomitant ICS use in the placebo group, which was allowed by study design (Chest 2006;129:1478-85).
The CAMP study examined daily low-dose budesonide in children with MPA. Patients in the budesonide group had better asthma control than did those taking nedocromil or placebo, but there was still no significant change in FE[V.sub.1], suggesting once more that the daily ICS does not have an effect on airway remodeling (N. Engl. J. Med. 2000;343:1054-63).
The CARE study looked at daily fluticasone compared with placebo in children at risk of developing asthma. The results of this 3-year trial were less than impressive for daily ICS, with just 1 less episode-free day (96 vs. 97), no change in hospitalizations or lung function, and no benefit on airway remodeling (N. Engl. J. Med. 2006;354:1985-97).
If our main thrust in daily ICS therapy is to prevent airway remodeling and preserve lung function, we are clearly missing the target--possibly because only higher doses of ICS could bring about these kinds of changes. And high-dose ICS is not something we're ready to discuss. But ICS administered according to symptoms does fulfil our other asthma management goals, increasing control and quality of life, decreasing symptoms and mortality just as well as daily ICS, with some notable benefits.
In summary, as-needed treatment is less expensive than is daily treatment with ICS. It is associated with fewer side effects. And with as-needed therapy, you don't have the compliance worries that come with daily treatment.
Of concern is that the patient will require an asthma action plan, will require medications available at home if an exacerbation occurs, will need to be trained on proper technique, and must understand the importance of intervening with therapy early when symptoms occur.
DR. CRAIG is the training program director of the allergy section and director of clinical allergy and respiratory research at Pennsylvania State University, Hershey Medical Center, Hershey, Pa.
BY TIMOTHY CRAIG, D.O.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||POINT/COUNTERPOINT; inhaled corticosteroids|
|Author:||Dykewicz, Mark; Craig, Timothy|
|Publication:||Internal Medicine News|
|Article Type:||Clinical report|
|Date:||Mar 15, 2007|
|Previous Article:||Where is subspecialty care going?|
|Next Article:||Evidence shows big tobacco funding.|
|Inhaled corticosteroids and fetal growth.|
|Steroid rage: using aerosolized steroids for asthma treatment.|
|Clinical application of nonsteroidal agents.|