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Inhaled corticosteroid therapy in mild to moderate asthma

Question:

12/14/2017
Recently my partners and I got in a discussion about management of mild intermittent asthma. The discussion centered around whether continued ICS usage should be based on symptoms or FEV1. I have a few questions. Is there data on long term usage of ICS in mild intermittent asthmatics with a slightly low FEV1, who show improvement after initiation of ICS, and the reduction of asthma exacerbations? Second, does long term usage of steroids durably prevent a decline in FVC and FEV1 in both children and adults? Or in other words, if a mild intermittent asthmatic was on an ICS for 10 years would the FEV1 and FVC be significantly higher than if they hadn’t been on an ICS. If so, would that effect last even after cessation of the ICS?

Answer:

There is a great deal of data on the use of inhaled corticosteroids (ICS) in mild to moderate intermittent asthma (Pauwels; Boushey). The results demonstrate that quality of life and exacerbations are reduced with ICS therapy. FEV1 improves as well but there is limited evidence of a persistent effect on lung function if ICS therapy is discontinued. Use of ICS with minimal symptoms is effective, arguing that ICS should not be delayed until more frequent symptoms occur (Reddel). Also, variable, symptom based dosing of ICS is probably more effective than fixed dosing (Beasley; Wang; O’Byrne; Boushey; Strunk).

The evidence of ICS improving lung function over time is much less convincing. The Childhood Asthma Management Program (CAMP) is one of the best prospective studies addressing this question in children (Childhood Management Program Research Group; Strunk). The conclusion was that daily ICS improved quality of life and reduced exacerbations and systemic corticosteroid therapy but did not improve lung function. There is data on the study population as adults and the lung function of the group who received daily ICS is no better than those who received intermittent therapy. There is some information that early, long-term use of ICS improves lung function but it is not convincing in my opinion. Any benefit in lung function that occurs with ICS therapy typically is lost following discontinuation.

1. Reddel, Helen K., et al. "Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study." The Lancet 389.10065 (2017): 157-166.
2. Turpeinen, Markku, et al. "Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study)." Archives of disease in childhood 93.8 (2008): 654-659.
3. Beasley, Richard, et al. "Description of a randomised controlled trial of inhaled corticosteroid/fast-onset LABA reliever therapy in mild asthma." European Respiratory Journal (2016): ERJ-01692.
4. Pauwels, Romain A., et al. "Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial." The Lancet 361.9363 (2003): 1071-1076.
5. Wang, Gang, et al. "Corticosteroid plus β 2-agonist in a single inhaler as reliever therapy in intermittent and mild asthma: a proof-of-concept systematic review and meta-analysis." Respiratory research 18.1 (2017): 203.
6. O’Byrne, Paul M., et al. "The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given ‘as needed’in mild asthma: study protocols for two randomised controlled trials." Trials 18.1 (2017): 12.
7. Martinez, Fernando D., et al. "Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial." The Lancet 377.9766 (2011): 650-657.
8. Boushey, Homer A., et al. "Daily versus as-needed corticosteroids for mild persistent asthma." New England Journal of Medicine 352.15 (2005): 1519-1528.
9. Strunk, Robert C., et al. "Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents." The Journal of pediatrics 154.5 (2009): 682-687.
10. Childhood Asthma Management Program Research Group. "Long-term effects of budesonide or nedocromil in children with asthma." N Engl j Med 2000.343 (2000): 1054-1063.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI