What is the rationale for using corticosteroids (CS) for asthma management?

From the Guidelines

Corticosteroids are the most effective long-term control medication for asthma, reducing airway hyperresponsiveness, inhibiting inflammatory cell migration and activation, and blocking late-phase reaction to allergen, as evidenced by the expert panel report 3 (EPR-3) guidelines 1. The rationale for using corticosteroids in asthma management is based on their powerful anti-inflammatory effects on the airways. They work by suppressing multiple inflammatory pathways in the lungs, reducing airway hyperresponsiveness, decreasing mucus production, and preventing airway remodeling.

• Inhaled corticosteroids (ICS) are the preferred treatment for maintenance therapy, as they deliver medication directly to the airways while minimizing systemic side effects.
• For acute exacerbations, systemic corticosteroids such as prednisone (40-60 mg daily for 5-7 days) or methylprednisolone (60-125 mg IV) are used to quickly reduce inflammation, as recommended by the American Heart Association guidelines 1. The effectiveness of corticosteroids stems from their ability to bind to cytoplasmic glucocorticoid receptors, which then translocate to the nucleus and suppress pro-inflammatory gene transcription while enhancing anti-inflammatory gene expression.
• This mechanism reduces the production of inflammatory cytokines, inhibits inflammatory cell recruitment, and decreases vascular permeability in the airways. Regular use of inhaled corticosteroids has been shown to decrease asthma symptoms, improve lung function, reduce exacerbation frequency, and decrease asthma-related mortality, making them essential in asthma management, as supported by the medical therapy for asthma updates from the NAEPP guidelines 1.

From the Research

Rationale for Corticosteroids in Asthma

• Corticosteroids are the most effective controllers of asthma, suppressing inflammation by switching off multiple activated inflammatory genes 2.
• Inhaled corticosteroids (ICS) reduce airway hyperresponsiveness and control asthma symptoms, making them the first-line therapy for all patients with persistent asthma 2, 3.
• ICS are effective in most patients with asthma, irrespective of age or asthma severity, and not only control asthma symptoms and improve lung function but also prevent exacerbations and may reduce asthma mortality 3.

Mechanism of Action

• ICS work by recruiting histone deacetylase 2 (HDAC2), which reverses histone acetylation and suppresses inflammation in asthmatic airways 2.
• The addition of long-acting beta-adrenergic agonists (LABAs) to ICS can potentiate the anti-inflammatory effects of ICS and improve asthma control 4.

Combination Therapy

• Combination inhalers containing ICS and LABAs improve compliance and control asthma at lower doses of corticosteroids 2.
• The combination of ICS and LABAs is more effective than ICS alone in reducing severe exacerbations and improving lung function 4, 5.
• Different combinations of ICS and LABAs, such as fluticasone/salmeterol and budesonide/formoterol, have similar efficacy and safety profiles 5.

Safety and Efficacy

• ICS have negligible systemic side effects at the doses most patients require, although high doses can increase the risk of developing pneumonia 2.
• The use of LABAs alone in patients with asthma increases the risk of asthma-related events, including deaths, but this risk is reduced when LABAs are used in combination with ICS 4.