Pity The Fool Who Extubates Too Soon: Does T-Piece Weaning Have Better Outcomes Compared With Standard Pressure Support Weaning?

and lower lung function.1 The approach of combining an inhaled corticosteroid (ICS) with a beta-agonist is not new, having been shown in 2007 that a SABA/ICS combination as needed was superior to SABA as needed in preventing exacerbations in mild asthma.2 In 2018, there were 2 trials exploring the role of budesonide-formoterol as needed for mild asthma.3,4 In these randomized controlled trials, the safety and efficacy of budesonide-formoterol as needed was demonstrated. Budesonide-formoterol as needed resulted in lower risk of exacerbation than SABA as needed and was similar to budesonide daily plus SABA as needed. The authors of the study to be reviewed here argued that, given these were placebo-controlled trials, participants all took inhalers twice a day plus a rescue inhaler, which removed the advantage of a one-inhaler-as-needed approach. In addition, these trials had run-in periods and stricter inclusion criteria inconsistent with clinical practice. In order to expand the external validity of these findings, an open-label clinical trial was performed to further investigate the budesonide-formoterol as needed strategy in mild asthma. “Controlled Trial of Budesonide-Formoterol as Needed for Mild Asthma” is a multinational, multicenter, randomized, openlabel, parallel-group controlled trial. Patients were randomized into 3 treatment groups: albuterol (100 μg 2 inhalations from a pressurized metered-dose inhaler as needed) (albuterol group), budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol (budesonide maintenance group), or budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed) (budesonide-formoterol group). The inclusion criteria were 18 to 75-year-old patients with physician-diagnosed asthma using SABA as needed as the sole treatment. SABA had to be used at least twice in the last 3 months and no more than twice per day. If there was a severe exacerbation in the last year, there was no minimum SABA use. Exclusion criteria were hospitalization in the last year, a 20-pack-year or more smoking history, or onset of respiratory symptoms after the age of 40 with either a 10-pack-year history of smoking or currently smoking. A total of 675 patients were randomized in a 1:1:1 manner between the 3 groups. The definition of exacerbation was an urgent medical visit, steroid use, or 16 albuterol puffs or 8 budesonide-formoterol puffs in 24 hours. Severe exacerbation was defined as requiring systemic steroids for at least 3 days or hospitalization or an emergency department visit leading to systemic steroids. Patients were withdrawn from the study for severe exacerbation, 3 exacerbations separated by 7 days, or unstable asthma symptoms. The primary outcome was exacerbations per patient per year. Secondary outcomes were number of exacerbations, time to first exacerbation, severe exacerbation, Asthma Control Questionnaire-5 (ACQ-5) score, forced expiratory volume in 1 second, fractional exhaled nitric oxide, daily budesonide dose, daily prednisone dose, number of beta 2-agonist actuation per day, and adverse events. All patients who underwent 7 trial visits during the 52-week period were provided with asthma action plans and had electronic inhaler usage monitors. Primary outcome results showed that the budesonideformoterol group had lower exacerbation rates than the albuterol group, but did not differ significantly from the budesonide maintenance group. Absolute rates per patient per year were 0.195, 0.400, and 0.175 for the budesonide-formoterol, albuterol, and budesonide maintenance group, respectively. Relative rates were similar after sensitivity analysis that included covariates to account for potential predictors of response, such as baseline SABA use and the number of severe exacerbations. Secondary outcomes showed that the ACQ-5 score was lower in the budesonide maintenance group compared with the budesonide-formoterol group (mean difference, −0.15), but was higher in the albuterol group compared with the budesonideformoterol group (mean difference, 0.14). Severe exacerbations were less frequent in the budesonide-formoterol group compared with the budesonide maintenance group and the albuterol group (relative risk, 0.4; 95% confidence interval, 0.18-0.86 and 0.44; 95% confidence interval, 0.20-0.96, respectively). Forced expiratory volume in 1 did not differ significantly in any of the groups. The mean budesonide dose was 107±109 μg/d in the budesonide-formoterol group and 222±113 μg/day in the budesonide maintenance group. Overall adherence to twice-daily budesonide was 56%. On the basis of this study, the authors concluded that the openlabel designed study more accurately reflects clinical practice and revealed that budesonide-formoterol used as needed was superior to albuterol used as needed to prevent exacerbations in adults with mild asthma. This study does have several limitations: open labeling, partial support from a grant from AstraZeneca, more frequent clinic visits for mild asthmatic patients and better use of asthma action plans than in clinical practice and, as the authors note, the secondary outcomes were not adjusted for multiplicity of analysis. Moreover, this study and those with similar results from 2018 used formoterol as the long-acting beta-agonist (LABA), and this drug is known for having a fast onset of action. It is unclear whether these results would be seen with the use of other LABAs. Despite these study limitations, the overall conclusion of the authors is supported in this study and in the previous literature. As a result of this accumulating evidence, the 2019 Global Initiative for Asthma (GINA) recommendations no longer list SABA alone as a recommended treatment.1 For mild asthma, as-needed low-dose ICS-formoterol is now a preferred reliever strategy. If the combination is not available, then the recommendation is to use an ICS whenever SABA as needed is taken. The GINA 2019 recommendations list ICS-formoterol as a reliever option at each step of therapy, which begs the question —is this the end of albuterol?