Inhaled corticosteroids have proven effective in the treatment of asthma, suppressing airway inflammation and reducing bronchial hyper-responsiveness. Beneficial clinical outcomes include fewer asthmatic symptoms, increased lung function, improved asthma-specific quality of life, and fewer asthmatic exacerbations, including severe attacks resulting in hospitalization or death. ICS are commonly used when asthmatic episodes are too frequent or too severe to be controlled solely by short acting beta agonists. ICS have few adverse effects at low to medium doses, which are mainly local effects such as hoarseness and oral thrush. On the other hand, high doses of ICS are associated with systemic effects such as increased risk of skin bruising, cataracts, elevated intraocular pressure and accelerated loss of bone mass. While there is less evidence pointing towards systemic effects of low to medium doses of ICS, several studies have suggested that such an effect exists. One study demonstrated changes in the hypothalamic-pituitary-adrenal (HPA) axis with ICS administration at doses as low as 88 μg of fluticasone per day. Moreover, a study in children showed ICS did not influence basal cortisol levels but significantly reduced peak cortisol and adrenocorticotropic hormone levels.
Hence, the extent of the systemic effect of ICS at high doses and especially at low to medium doses is not fully understood. This is partly due to the nature of most of the systemic side-effects which necessitate long term follow-up of a large population of patients, but also because of technical difficulties in assessing systemic cortisol levels over a prolonged period of time.
A similar clinical conundrum exists with intranasal glucocorticoids (INGC), regarding their systemic effect. INGCs are considered the first-line of medical therapy for allergic rhinitis and are more effective than systemic antihistamines. The most common adverse effects stem from local irritation of the nasal mucosa, while systemic effects are much rarer. The effect of INGC on the HPA axis and growth has been evaluated extensively in children. Most studies, especially those with the second generation agents and recommended doses, showed no or limited HPA suppression. Despite these reassuring data, the adverse effects of INGC can be additive with those of other glucocorticoid preparations for comorbid conditions, and thus caution should be exercised. A handful of studies have demonstrated detrimental effects of INGC therapy on bone mineral density and intraocular pressure. These studies have small sample sizes and have not clearly proven whether these effects result in clinically relevant long term outcomes, such as fractures. As a result, these studies are not reflected in current practice guidelines.
Cortisol levels are routinely determined from blood, salivary or urinary samples However, these methods do not provide information on long term cortisol secretion, accounting for the variability of HPA axis activity. There is a growing pool of evidence that shows that Hair Cortisol Concentration (HCC) examination provides a reliable retrospective estimation of integrated cortisol secretion over a period of several months. Hair grows at a rate of about 1 cm/month, thus 3 cm of hair would give an indication of the cortisol levels over the previous 3 months. HCC correlates with 24h urinary cortisol levels, but not with salivary or serum cortisol, supporting use of HCC as an indicator of cortisol levels over time rather than a point measurement. HCC has been evaluated in several clinical settings in which activity of the HPA axis and cortisol levels over a period of time are of interest. Studies have demonstrated increased levels of hair cortisol in patients with stress as well as in conditions associated with stress such as pregnancy, unemployment, PTSD, alcohol withdrawal, chronic pain and myocardial infarction. Elevated levels of hair cortisol were also shown in Cushing's syndrome, with reduced levels after correction of the disorder.
No study to date has examined the correlation between the use of inhaled or intranasal corticosteroids and levels of cortisol in hair. If such a correlation exists, it would indicate systemic absorption of these topical steroids which in turn would suggest a potential for systemic side effects. In addition, and pending further studies, HCC may serve as a validated test to determine which patients are more prone to systemic side effects, as well as help in assessing compliance.
