Inhaled Corticosteroid Dose Adjustment in Mild Persistent Asthma

Abstract

REGULAR USE OF CONTROLLER MEDICATIONS, SUCH AS INhaledcorticosteroids(ICS), improvesoutcomesinpatientswithasthma.Theimportanceofdailyuseof ICS is emphasized in asthma management guidelines. However, ensuring that patients with asthma adhere to daily useof ICS,evenwhenasymptomatic, is achallenge.Therefore, cliniciansspendsubstantial timeandenergyeducatingpatients with asthma about the importance of daily use of ICS. The latter medications, however, do not lead to the immediate relief of asthmasymptomsassociatedwithshort-actingrescuebronchodilators, such as albuterol, so patients often neglect to take ICS due to the incorrect perception that they do not help. This frequently observed pattern of poor adherence to daily use of ICShasledtothehypothesisthattyinguseofICStotheas-needed use of a short-acting bronchodilator may lead to better asthma control forpatientswithrelativelymildasthma.Combininguse of ICS with as-needed short-acting bronchodilators may improve asthma control by increasing the patient’s motivation to take ICS and by focusing ICS therapy on periods when symptoms of asthma (which vary over time due to environmental factors) are more prounounced. This as-needed ICS strategy could also potentially reduce costs and patient inconvenience by avoiding use of ICS when asthma is not bothersome. In this issue of JAMA, Calhoun et al report the results of the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial comparing as-needed, symptom-based use of ICS, as well as a biomarker-based dosing strategy, with traditional everyday use of ICS with dosing determined by a physician. In this randomized controlled trial, conducted by the National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network (ACRN), the investigators randomly assigned adults with mild to moderate persistent asthma (defined as acceptable symptom control and lung function while receiving low-dose ICS therapy) to 1 of 3 strategies for dose adjustment of ICS: physician assessment–based adjustment (n=114 patients), in which the physician prescribes a regular twice-daily ICS dose, which is guided by the National Asthma Education and Prevention Program (NAEPP) guidelines, at clinic visits approximately every 6 weeks; symptombased adjustment (n=113 patients), in which patients are instructed to take 2 puffs of beclomethasone HFA (40 μg/puff) whenever taking 2 puffs of albuterol to relieve asthma symptoms; or biomarker-based adjustment (n=115 patients) in which ICS dosing is adjusted according to the concentration of exhaled nitric oxide, which was measured every 6 weeks. During the 36-week follow-up, the time to clinical worsening of asthma (the primary outcome measure of the trial) did not differ in the primary comparisons of symptombased adjustment vs physician assessment–based adjustment or of biomarker-based adjustment vs physician assessment–based adjustment. Nine-month rates of clinical failure estimated by Kaplan-Meier analysis were 22% for the physician assessment–based adjustment group, 15% for the symptom-based adjustment group, and 20% for the biomarker-based adjustment group. Participants in the symptom-based adjustment group took significantly less ICS per month than the other groups. This outcome was 1 of 18 secondary outcome measures, and most of these did not differ significantly among the treatment groups; thus, this finding should be interpreted with caution. This report adds to prior randomized trials that have compared the typical physician-prescribed dosing of ICS with intermittent dosing guided by symptoms for patients with relatively mild asthma. A prior ACRN study of adults with mild persistent asthma indicated that a strategy of initiating a course of inhaled or oral corticosteroid only when asthma symptoms became bothersome (according to a written action plan), led to a similar peak expiratory flow rate and asthma exacerbation rate as the everyday physician-prescribed dosing of controller medications (ICS or leukotriene antagonist), although some outcomes such as bronchial reactivity and symptom-free days were improved by regular twice-daily use of ICS. Like the BASALT trial, the prior ACRN study was designed to show superiority of one strategy over another, rather than to test equivalence, and the lack of superiority of any strategy over the others must be interpreted accordingly. Taking a different approach to intermittent ICS treatment, European investigators conducted an equivalence study comparing asneeded use of an inhaler containing both the short-acting bronchodilator albuterol and beclomethasone (a combination inhaler not available in the United States) with the traditional approach of regular twice daily beclomethasone and as-