SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.
"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."
Dr. Ejaz Yousef
As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.
To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.
The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.
The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.
Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.
The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.
Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.
Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.
The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."
Dr. Yousef said that he had no relevant financial conflicts to disclose.