How do Inhaled Corticosteroids (ICS) affect the body systemically?

From the Guidelines

Inhaled corticosteroids (ICS) can have systemic effects after absorption into the bloodstream, including suppression of the hypothalamic-pituitary-adrenal axis, impact on bone metabolism, and effects on glucose metabolism, among others. After inhalation, a portion of the medication deposits in the lungs while some is swallowed and absorbed through the gastrointestinal tract. Once in the bloodstream, ICS bind to glucocorticoid receptors throughout the body, potentially affecting multiple organ systems. Systemically, ICS can suppress the hypothalamic-pituitary-adrenal axis, leading to reduced cortisol production, as demonstrated in the DICE study 1, which established a rank order of side effect potency for different ICS formulations. They may also affect bone metabolism by decreasing calcium absorption and inhibiting osteoblast function, potentially causing osteoporosis with long-term use. ICS can impact glucose metabolism, occasionally raising blood sugar levels in susceptible individuals. Other potential systemic effects include skin thinning, easy bruising, cataracts, glaucoma, and growth suppression in children.

According to the NAEPP guidelines 1, inhaled corticosteroids are the most potent and consistently effective long-term control medication for asthma, and their systemic effects are typically not clinically important, except with long-term use. The guidelines also recommend considering alternative diagnoses and treatment options if lack of control persists, and stepping down therapy once asthma is well controlled for at least 3 months. The Expert Panel Report 3 (EPR-3) guidelines 1 provide additional guidance on the potential adverse effects of systemic corticosteroids and the importance of regular follow-up contact to maintain control of asthma.

Some key points to consider when evaluating the systemic effects of ICS include:

• The dose and potency of the ICS formulation, as demonstrated in the DICE study 1
• The individual patient's sensitivity and responsiveness to ICS therapy, as noted in the NAEPP guidelines 1
• The potential for systemic effects to vary depending on the specific ICS formulation and delivery method, as discussed in the EPR-3 guidelines 1
• The importance of monitoring for systemic effects and adjusting therapy as needed to minimize risks and maintain therapeutic efficacy.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Systemic Effects of Inhaled Corticosteroids (ICS)

• ICS can have systemic effects, particularly at high doses, which may lead to adverse events such as osteoporosis, cataracts, glaucoma, and fractures 2.
• The risk of systemic adverse effects increases with higher doses of ICS, with medium to high daily doses associated with an increased risk of major adverse cardiac events, arrhythmia, pulmonary embolism, and pneumonia 3.
• However, low doses of ICS are generally considered safe and effective for the treatment of asthma, with minimal systemic effects 4, 3.

Dose-Response Relationship of ICS

• The dose-response relationship of ICS in adult asthma suggests that the majority of the therapeutic benefit is achieved at low to medium doses, with higher doses providing minimal additional benefit but increasing the risk of systemic adverse effects 5, 3.
• The Global Initiative for Asthma guidelines recommend using the lowest effective dose of ICS to minimize the risk of systemic adverse effects while maintaining adequate asthma control 5.
• A systematic review of clinical studies found that fluticasone and formoterol provided improved therapeutic benefits compared to budesonide and salmeterol, respectively, with combination therapies appearing to be more effective than monotherapies 6.

Safety of ICS in Specific Populations

• ICS use in children has been associated with a decrease in growth velocity, although long-term studies suggest that this effect is transient and does not affect final adult height 4.
• Pregnant women with asthma can safely use inhaled budesonide, with no increased risk of adverse perinatal outcomes 4.
• Older adults and individuals with certain comorbidities may be more prone to systemic adverse effects from ICS use, highlighting the need for careful dose selection and monitoring 2.