At treating asthma, patients may be as good as their doctors (BASALT trial)
Consensus guidelines advise that patients with regular symptoms of asthma should take inhaled corticosteroids every day, and when they're having poor asthma control, they should tell their doctor, who can increase the steroid dose or add other "step-up" therapies.
But asthma symptoms vary daily and can worsen at any time. And it can be hard to get in to see a doctor, or even to get her on the phone. Further, some research suggests that daily inhaled steroids may not really be necessary for all patients. So William Calhoun, Bill Ameredes, Homer Boushey, et al (for NHLBI's Asthma Clinical Research Network) asked, what if we were to chuck the guidelines? What if we encouraged some patients to self-diagnose and treat their own asthma attacks with increased doses of inhaled corticosteroids on an as-needed basis, without a doctor visit, and with no therapy at all on days without symptoms?
What They Did
Investigators enrolled 342 patients with a clinical diagnosis of asthma who also had a 12% bronchodilator response in FEV1 and/or a positive methacholine bronchoprovocation test. Patients were entered into the trial after they demonstrated they had well- or partially-controlled asthma (after a run-in period with b.i.d. beclomethasone), and were able to comply at least 75% with the cumbersome trial protocol (requiring them to use 4 separate inhalers on days with symptoms). They were then randomized to one of three asthma treatment strategies:
Physician-directed adjustments of b.i.d. inhaled corticosteroids, based on physician assessments during clinic visits every 6 weeks, using spirometry, history, and exam based on NHLBI guidelines;
Physician-directed changes in inhaled b.i.d. steroid based on changes in exhaled nitric oxide concentration at clinic visits every 6 weeks;
Symptom-directed inhaled steroid therapy, controlled by the patient. For every puff of albuterol, she also took a puff of inhaled corticosteroid, with no inhaled steroid use on days when albuterol was not used. (These patients had placebo in their "daily" inhalers, so only took inhaled corticosteroid when they also used rescue albuterol.)
All arms were placebo-controlled and blinded (in a complex, multi-dummy "shell game" approach in which each patient used 2 placebo inhalers, a third containing beclomethasone 40 μg/puff, and an albuterol MDI).
The primary outcome was time to first treatment failure, defined as an asthma exacerbation requiring an unscheduled doctor visit with an increase in therapy; a significant and sustained drop in peak flows or spirometry at home or in clinic; patient dissatisfaction with asthma control, the need to add montelukast, or new, excessive albuterol use (e.g., an extra 8 puffs a day) for 2 days in a row.
Patients were followed for 9 months, with numerous secondary outcomes (spirometry, asthma control scores, sputum eosinophils etc) also recorded.
What They Found
Self-treating patients had the the longest average time to treatment failure, the fewest exacerbations, and the fewest lost days from school or work, although these outcomes were not statistically different between groups:
15% of patients who self-treated, with inhaled corticosteroid use only during symptom periods, had a treatment failure in 9 months.
22% of patients whose asthma therapy was adjusted based on physician assessment had treatment failure within 9 months.
20% of patients with physician-adjusted treatment based on exhaled nitric oxide had 9-month treatment failure.
The self-treating patients also had fewer asthma exacerbations (0.12 events per person per year, vs ~0.22 for the other 2 groups), and fewer days lost from work or school (0.11 days per person per year, vs. 0.25 for physician-assessed or 0.46 for exhaled-nitric-assessed patients), although this difference was not statistically significant. There was no difference in other outcomes like spirometry and asthma symptoms on validated questionnaires.
Not only did they appear to have equivalent outcomes, but the symptom-driven self-treating patients actually used only half the inhaled corticosteroid dosage of the other two groups (832 μg monthly vs. ~1615 μg).
Physician-assessment-driven asthma therapy appeared to be a clearly inferior strategy to the other 2 arms in the fall and winter months, especially in Autumn, with a 10-11% rate of treatment failure compared to 3-5% with the other strategies. Hispanic and African-American patients had higher rates of treatment failure, and in Hispanic patients, a physican-assessment-directed treatment changes seemed to reduce this excess risk.
The trial was not powered to prove equivalence, only superiority (an 87% power to detect a 60% relative difference in treatment failure rate between groups), which it did not do.
What It Means
Daily inhaled corticosteroid (ICS) therapy has been a pillar of asthma management for anyone with persistent asthma (daily symptoms more than twice a week at the time of diagnosis), and is canonized in the NHLBI's 2007 Expert Panel Report 3's "Step-Up / Step-Down" algorithm. But these guidelines are based on consensus, not on any data from prospective trials comparing asthma treatment strategies. What if daily inhaled steroids are actually not necessary, or even helpful, for most people with asthma?
It may sound controversial, but it's not a new idea. In the IMPACT trial, 10 days of inhaled steroids triggered by symptoms (and no ICS in between) was equivalent to daily ICS therapy in controlling persistent asthma. In the BEST trial, outcomes with as-needed beclomethasone + albuterol were comparable to patients taking daily beclomethasone. And in Europe, a combination long-acting beta agonist (LABA) + ICS is commonly used as both the maintenance and rescue therapy (but in the U.S. our black-box warning on LABAs discourages this).
Given our humbling lack of deep understanding about asthma, and its amazing heterogeneous manifestations between patients, we don't have much reason to lecture patients who forget to use their steroid inhalers during times they're feeling well -- maybe they've always been onto something we didn't yet know. This study suggests that many patients might be just as good as their doctors at deciding when to "step-up" their treatment.
Calhoun WJ et al, for the ACRN Network. Comparison of Physician-, Biomarker-, and Symptom-Based Strategies for Adjustment of Inhaled Corticosteroid Therapy in Adults With Asthma. The BASALT Randomized Controlled Trial. JAMA 2012; 308 (10): 987-997.