Bottom Line Up Top: In patients with mild to moderate asthma exacerbations that are stable for discharge home, there is evidence to support discharging patients from the ED with combination Inhaled Corticosteroid/Long-Acting Beta Agonist (ICS-LABA) maintenance therapy.
Clinical Scenario: A 21-year-old man with a history of asthma presents with difficulty breathing for the past two days. His vital signs are: HR 115, BP 113/67. Temp 98.9, O2 Sat 96% on RA, RR 24. Lung auscultation demonstrates bilateral expiratory wheezing and diminished breath sounds. After administration of three albuterol/atrovent nebs and prednisone, the patient is markedly improved and stable for discharge. As you are writing outpatient prescriptions, you contemplate whether you should send the patient an albuterol inhaler or an inhaled corticosteroid/long-acting beta agonist combo inhaler.
What Your Gut Says: Send the patient home with a rescue albuterol inhaler and their pulmonologist can decide if other inhalers are needed.
What The Evidence Says:
Most ED physicians discharge stable patients with mild to moderate asthma exacerbations with a short-acting beta agonist (SABA) rescue inhaler. This has been standard practice for decades. However, organizations like the Global Initiative for Asthma (GINA) now recommend symptom-driven treatment or daily corticosteroid-containing inhalers to reduce the risk of severe exacerbations (Reddel 2019).
Building on these guideline changes, recent studies have investigated alternative approaches to asthma management, including combined LABA/ICS therapies.Jiang found that combining Formoterol and Budesonide (Symbicort) offers a more patient-centered approach, functioning as both an acute reliever and a maintenance therapy (Jiang 2021). Though Formoterol is a LABA, it has immediate effects on bronchoconstriction like albuterol and can be used as rescue therapy as well. Large RCTs showed that low-dose ICS in mild asthma reduced severe exacerbations by ~50%, controlled symptoms, and improved quality of life (Reddel 2019). Another study confirmed that fixed-dose LABA/ICS PRN was as effective as regular ICS, reducing asthma-related hospital visits and daily ICS exposure without increasing adverse events (Crossingham 2021). Chew et al. also showed statistically significant quantitative improvements in SaO2, peak expiratory flow rate (PEFR), and a reduction in respiratory rates in patients post-treatment (Chew 2012).
Bottom Line: Current research suggests we should replace prescriptions for a SABA inhaler (i.e. albuterol) with a LABA-ICS combination inhaler as it can be used both for maintenance therapy and as a rescue inhaler. Furthermore, Budesonide + Formoterol is a safe patient-centered option that is at least as effective, if not better, than SABA alone. This change does not alter the recommendation of treating with a systemic steroid (ie dexamethasone, prednisone etc). The practice of discharging a patient with SABA inhalers alone should be ended.
Prescription: Budesonide/formoterol 80/4.5 μg/puff, 1-2 puffs once to twice daily for maintenance, and then 1-2 puffs every 2-4 hours as needed for asthma symptoms, with instructions to go to the ED if more than that is required.
Additional Reading:
Mayo Clinic: Asthma Medications: Know your Options
References
A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks Chew KS, Kamarudin H, Hashim CW. A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks. Int J Emerg Med. 2012;5:16. Published 2012 Apr 13. doi:10.1186/1865-1380-5-16 PMID: 22503137
Asthma-related hospitalizations after implementing SABA-free asthma management with a maintenance and anti-inflammatory reliever regimen Nannini LJ, Neumayer NS, Brandan N, et al. Eur Clin Respir J. 2022;9(1):2110706. doi: 10.1080/20018525.2022.2110706. PMID: 35959199
Beclometasone-formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med. 2013;1(1):23-31. doi:10.1016/S2213-2600(13)70012-2 Papi A, Corradi M, Pigeon-Francisco C, et al. PMID: 24321801
Budesonide/formoterol versus salmeterol/fluticasone for asthma in children: an effectiveness and safety analysis. Jiang P, Zhao L, Yao Z. Budesonide/formoterol versus salmeterol/fluticasone for asthma in children: an effectiveness and safety analysis. J Comp Eff Res. 2021;10(17):1283-1289. doi:10.2217/cer-2021-0142 PMID: 34668718
Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. Crossingham I, Turner S, Ramakrishnan S, et al. Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. BMJ Evid Based Med. 2022;27(3):178-184. doi:10.1136/bmjebm-2021-111764 PMID: 34282031
Comparative effectiveness of budesonide-formoterol combination and fluticasone-salmeterol combination for asthma management: a United States retrospective database analysis. Tunceli O, Williams SA, Kern DM, et al. Comparative effectiveness of budesonide-formoterol combination and fluticasone-salmeterol combination for asthma management: a United States retrospective database analysis. J Allergy Clin Immunol Pract. 2014;2(6):719-726. doi:10.1016/j.jaip.2014.07.016 PMID: 25439363
Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al. J Allergy Clin Immunol. 2020;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. PMID: 33280709 [published correction appears in J Allergy Clin Immunol. 2021 Apr;147(4):1528-1530]
Formoterol for acute asthma in the emergency department: a systematic review with meta-analysis. Rodrigo GJ, Neffen H, Colodenco FD, Castro-Rodriguez JA. Formoterol for acute asthma in the emergency department: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2010;104(3):247-252. doi:10.1016/j.anai.2009.11.064 PMID: 2037714
GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents Reddel HK, FitzGerald JM, Bateman ED, et al. Eur Respir J. 2019;53(6):1901046. doi: 10.1183/13993003.01046-2019. PMID: 31249014
Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme Nwaru BI, Ekström M, Hasvold P, et al. Eur Respir J. 2020;55(4):1901872. doi: 10.1183/13993003.01872-2019. PMID: 31949111
Real-world patterns and implications of short-acting β2-agonist use in patients with asthma in the United States Lugogo N, Gilbert I, Tkacz J, et al. Ann Allergy Asthma Immunol. 2021;126(6):681-689.e1. doi: 10.1016/j.anai.2021.01.024. PMID: 33515710
The cost-effectiveness of as-needed budesonide/formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in the UK
FitzGerald JM, Arnetorp S, Smare C, et al. The cost-effectiveness of as-needed budesonide/formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in the UK. Respir Med. 2020;171:106079. doi:10.1016/j.rmed.2020.106079 PMID: 32917353