In preterm-born children with prematurity-associated lung disease, combined treatment with inhaled corticosteroids (ICSs) and long-acting β2 agonists (LABAs) results in significantly improved lung spirometry. A double-blind, randomized, placebo-controlled trial was conducted to evaluate this combination therapy compared with placebo. Results of the analysis were published in JAMA Pediatrics.
The investigators sought to compare 12 weeks of combined ICS/LABA treatment vs inhaled placebo therapy for improving lung function and exercise capacity in school-aged, preterm-born children whose percent predicted forced expiratory volume in 1 second (%FEV1) is 85% or less. The participating children were between 7 and 12 years of age, with a gestational age of 34 weeks or less at birth. The children did not have any clinically significant congenital, cardiopulmonary, or neurodevelopmental abnormalities. All participants underwent spirometry, exercise testing, and measurement of fractional exhaled nitric oxide (FENO) prior to and after treatment.
The study identified a total of 144 preterm-born children between July 1, 2017, and August 31, 2019, all of whom had been born at Children’s Hospital for Wales in Cardiff, United Kingdom. The participants were randomized to 1 of 3 study cohorts: (1) fluiticasone propionate 50 µg, (2) fluiticasone propionate 50 µg plus salmeterol 25 µg, or (3) placebo inhalers. All of the medications were administered as 2 puffs twice daily for 12 weeks. The primary study outcome was between-group differences evaluated by pretreatment and posttreatment differences in %FEV1 after 12 weeks of inhaler therapy in the 3 arms.
Of the 144 preterm-born children with a %FEV1 of 85% or less, a total of 53 were randomized to treatment — 20 in the ICS group, 19 in the ICS/LABA group, and 14 in the placebo group. The mean participant age was 10.8±1.2 years; 55% of the children were female. The mean %FEV1 among the 53 children was 75.3% (range, 53.0% to 85.0%). Adjustments were made in the posttreatment %FEV1 for sex, gestation, bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, and pretreatment values.
The %FEV1 increased from 75.1% to 81.1% and the forced midexpiratory flow increased from 48.1% to 57.6% following ICS treatment. After ICS/LABA treatment, the %FEV1 increased from 77.9% to 86.2%. The %FEV1/forced vital capacity ratio increased and the FENO levels decreased in both the ICS treatment arm and the ICS/LABA arm, but not in the placebo arm.
Per analysis of covariance, posttreatment adjusted means for %FEV1 were 7.7% (95% CI, –0.27% to 15.72%; P =.16) higher in the ICS arm and 14.1% (95% CI, 7.3%-21.0%; P =.002) higher in the ICS/LABA arm than in the placebo arm. Although the use of active treatment was associated with a decrease in FENO levels and an improvement in postexercise bronchodilator response, it did not enhance exercise capacity.
The investigators concluded that future analyses are warranted, in which the current study findings are replicated in multicenter studies to ensure that the results are relevant to all populations of preterm-born children with lung deficits.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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. Published online December 13, 2021. doi:10.1001/jamapediatrics.2021.5111