Aim of the study was to compare efficacy of 2 commonly used therapies for asthma control in children with asthma.
Methods:
This was a 1-year, prospective cohort study at a tertiary care children's hospital. Patients were referred by their primary care physicians (PCPs) for asthma control. All patients were on low-dose inhaled corticosteroids (ICSs) at baseline. They were either switched to medium-dose ICS (ICS group) or medium-dose ICS and long-acting beta agonist (ICS+LABA group). Results were compared over time and between both groups.
Results:
Our cohort included 163 children (ages 2–18 years) with mean age of 5.62 ± 3.61 years. Mean Asthma Control Test (ACT) score at baseline was 15.9 ± 5.4. Mean ACT and percent predicted forced expiratory volume in one second improved (P < 0.0001 for both) in both groups. Median emergency department visits, short courses of oral steroids, and unscheduled PCP visits for acute asthma significantly decreased (P < 0.001 for all) in both groups. Similarly, days/month with wheezing, nighttime cough, and missed school days significantly decreased in both groups (P < 0.001 for all). Patients in ICS group were more likely to fail to achieve asthma control compared to patients in ICS+LABA group.
Conclusion:
Our study suggests that in children with uncontrolled asthma on low-dose ICS, switching to either medium-dose ICS or medium-dose ICS+LABA resulted in better symptom control, ACT improvement, and less asthma exacerbations over time. ICS+LABA had the additional benefit of less risk of treatment failure when compared to medium-dose ICS.
Ni ChroininM, GreenstoneI, LassersonTJ, DucharmeFM. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children. Cochrane Database System Rev, 2009:CD005307.
5.
O'ByrnePM, FitzGeraldJM, BatemanED, et al.Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med, 2018; 378:1865–1876.
6.
BatemanED, ReddelHK, O'ByrnePM, et al.as-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med, 2018; 378:1877–1887.
7.
BeasleyR, HollidayM, ReddelHK, et al.Novel START study team. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med, 2019; 380:2020–2030.
8.
MartinezFD, ChinchilliVM, MorganWJ, et al.Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomized, double-blind, placebo-controlled trial. Lancet, 2011; 377:650–657.
9.
BisgaardH, Le RouxP, BjåmerD, et al.Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest, 2006; 130:1733–1743.
Ni ChroininM, LassersonTJ, GreenstoneI, DucharmeFM. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev, 2009:CD007949.
12.
Vaessen-VerberneAA, van den BergNJ, van NieropJC, et al.Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am J Respir Crit Care Med, 2010; 182:1221–1227.
13.
BisgaardH. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children. Pediatr Pulmonol, 2003; 36:391–398.
14.
VerberneAA, FrostC, DuivermanEJ, et al.Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group. Am J Respir Crit Care Med, 1998; 158:213–219.
15.
DucharmeFM, Ni ChroininM, GreenstoneI, et al.Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev, 2010:CD005533.
16.
ChauhanBF, DucharmeFM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev, 2012; 2012:CD002314.
17.
AdamsNP, BestallJC, JonesP, et al.Fluticasone at different doses for chronic asthma in adults and children. Cochrane Database Syst Rev, 2008; 2008:CD003534.
18.
ChauhanBF, DucharmeFM. Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev, 2014:CD003137.
19.
ErnstP, HabbickB, SuissaS, et al.Is the association between inhaled beta-agonist use and life-threatening asthma because of confounding by severity?. Am Rev Respir Dis, 1993; 148:75–79.
20.
SpitzerWO, SuissaS, ErnstP, et al.The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med, 1992; 326:501–506.
21.
SuissaS, ErnstP, BoivinJF, et al.A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med, 1994; 149:604–610.
22.
CatesCJ, CatesMJ. Regular treatment with salmeterol for chronic asthma: serious adverse events. Cochrane Database Syst Rev, 2008; 3:CD006363.
23.
CastleW, FullerR, HallJ, PalmerJ. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ, 1993; 306:1034–1037.
24.
NelsonHS, WeissST, BleeckerER, et al.The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest, 2006; 129:15–26.
25.
LevensonM. Long-acting beta-agonists and adverse asthma events meta-analysis. Statistical briefing package for Joint Meeting of the Pulmonary-Allergy Drugs Advisory Committee, Drug Safety and Risk Management Advisory Committee and Pediatric Advisory Committee on December 2008. Available at http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4398b1-01-FDA.pdf (accessed October2016).
26.
WeatherallM, WijesingheM, PerrinK, et al.Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy. Thorax, 2010; 65:39–43.
27.
StempelDA, RaphiouIH, KralKM, et al.Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. N Engl J Med, 2016; 374:1822–1830.
28.
FitzGeraldJM, BouletLP, McIvorRA, et al.Asthma control in Canada remains suboptimal: The Reality of Asthma Control (TRAC) study. Can Respir J, 2006; 13:253–259.
29.
WoolcockA, LundbackB, RingdalN, JacquesLA. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med, 1996; 153:1481–1488.
30.
PauwelsRA, LöfdahlCG, PostmaDS, et al.Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med, 1997; 337:1405–1411.
31.
RussellG, WilliamsDA, WellerP, PriceJF. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol, 1995; 75:423–428.
32.
ZimmermanB, D'UrzoA, BerubeD. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Pediatr Pulmonol, 2004; 37:122–127.
33.
Vaessen-VerberneAA, van den BergNJ, van NieropJC, et al.Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am J Respir Crit Care Med, 2010; 182:1221–1227.
34.
LemanskeRF Jr, MaugerDT, SorknessCA, et al.Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med, 2010; 362:975–985.
35.
ChauhanBF, ChartrandC, Ni ChroininM, et al.Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev, 2015; CD007949.
