Reply to "As-needed budesonide-formoterol for adolescents with mild asthma: importance of lung function"

To the Editor: We thank Shanthikumar and Robinson for their comments about our paper on as-needed budesonide-formoterol compared with as-needed short-acting beta2-agonist (SABA) alone, or with maintenance budesonide plus as-needed SABA, in adolescents with mild asthma,1 in which they questioned the potential long-term consequences of as-needed budesonide-formoterol on lung growth, adult lung function decline, and all-cause mortality in adulthood.2 The authors' concern relates to the reported 2.3% difference over 12 months in change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) % predicted with as-needed budesonide-formoterol compared with maintenance inhaled corticosteroids (ICS), which was statistically significant in Symbicort Given as Needed in Mild Asthma (SYGMA) 1 (highly controlled, frequent visits, twice-daily adherence reminders, diary, and lung function) and in the pooled data from SYGMA 1 and 2, but not observed in SYGMA 2 (more pragmatic, no diary/reminders, only 2 midstudy visits).1 We agree that these findings require further evaluation, preferably in longer-term studies. Pre-bronchodilator FEV1 has sometimes been used as a marker of lung growth3,4 and, as the correspondents observe, has been linked with some long-term sequelae.5 However, in epidemiological studies of obstructive lung disease, post-bronchodilator FVC is preferred,6 and has a different trajectory to FEV1 during lung growth that is affected by the presence of asthma.4 In most papers cited in this correspondence,2 the associations with adverse outcomes during adulthood were with FVC rather than FEV1, although sometimes with both.5 In asthma populations, pre-bronchodilator FEV1 is more variable and susceptible to changes in day-to-day asthma control that may explain differences in comparisons of pre-bronchodilator FEV1 and post-bronchodilator FVC in ours and other studies.1,5 The common assumption that regular ICS are needed to prevent impaired lung growth and/or accelerated decline in lung function in asthma is not supported by the findings of long-term studies. In long-term follow-up of the Childhood Asthma Management Program (CAMP) study, there was no difference in lung function trajectories according to whether or not patients received ICS.3 Instead, predictors of reduced lung growth included prednisone courses and other measures of severe persistent symptomatic asthma.3 A recent systematic review found that, whereas ICS improved pre-bronchodilator FEV1, th