Comparing LABA plus inhaled corticosteroids to inhaled corticosteroids only for treating prematurity-associated lung disease

For infants born preterm, there’s a risk of having increased respiratory symptoms and deficits in lung function, particularly in infants with bronchopulmonary dysplasia. However, the management of decreased lung function currently lacks much evidence-based guidance. A new study looks at whether just inhaled corticosteroids or long-acting β2 agonists with inhaled corticosteroids can improve percent predicted forced expiratory volume in 1 second (%FEV1) when compared to a placebo.¹

The double-blind randomized, placebo-controlled trial was performed at the Children’s Hospital for Wales in Cardiff, United Kingdom. Children who were born preterm (gestation ≤34 weeks at birth) and did not have significant congenital, cardiopulmonary, or neurodevelopmental abnormalities were recruited from July 2017 to August 2019, when they were aged 7 to 12 years, to undergo a number of tests including spirometry, exercise testing, and measurement of fractional exhaled nitric oxide before and after treatment. The children were randomized into 3 cohorts: fluticasone propionate, 50 μg, with placebo; fluticasone propionate, 50 μg, with salmeterol, 25 μg; or placebo inhalers, all given as 2 puffs twice daily for 12 weeks. If as child was already using a preexisting inhaled corticosteroid treatment, he or she went through a washout period before being randomized.

From a potential pool of 144 preterm-born children with a %FEV1 less than or equal to 85%, 53 were randomized: 20 received inhaled corticosteroids (including 5 with a preexisting treatment); 19 received long-acting β2 agonists with inhaled corticosteroids (including 4 with a preexisting corticosteroid treatment); and 14 were given a placebo. Posttreatment %FEV1 was adjusted for bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, sex, gestation, and pretreatment values. Posttreatment adjusted averages for %FEV1 were 7.7% (95% CI, −0.27% to 15.72%; P = .16) higher in the inhaled corticosteroids subcohort and 14.1% (95% CI, 7.3% to 21.0%; P = .002) higher in the long-acting β2 agonists with inhaled corticosteroids subcohort than in the placebo group. Treatment did not improve exercise capacity, but improvement in postexercise bronchodilator response and a decrease in fractional exhaled nitric oxide were both noted. When starting inhaler treatment, one participant developed a cough and no other adverse events that could be attributed to inhaler treatment were noted.

The investigators concluded that the use of combined inhaled corticosteroids and long-acting β2 agonists was beneficial for children who had lung disease linked to prematurity. Furthermore, this therapy was more effective than the use of inhaled corticosteroids alone.

Reference

1. Goulden N, Cousins M, Hart K, et al. Inhaled Corticosteroids alone and in combination with long-acting β2 receptor agonists to treat reduced lung function in preterm-born children : a randomized clinical trial. JAMA Pediatr. Epub ahead of print. December 13, 2021. doi:10.1001/jamapediatrics.2021.5111