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Adrenal insufficiency in asthma is due to combined steroid burden

Published: June 10, 2022

Patients with asthma receive regular glucocorticoid exposure in the form of inhaled corticosteroids (ICS) or with intermittent courses of oral corticosteroids (OCS), both of which are associated with adrenal insufficiency (AI). The available literature detailing the prevalence of AI in patients with asthma is limited by retrospective study design, which makes it subject to selection bias, and it fails to account for treatment adherence, something that is known to be variable amongst the population. Factors such as inhaler adherence and technique influence the amount of ICS that the patient receives. As a result, the current data assessing the relationship between ICS and adrenal function is likely to overestimate the ICS dose received by the patient, underestimating the contribution of ICS towards the development of AI.

In a recent article published in The Journal of Allergy and Clinical Immunology: In Practice, Brennan, Martin-Grace and colleagues prospectively evaluated the relationship between steroid exposure and risk of AI in a population of patients with severe asthma. The study covered an 8-month period in which detailed cumulative OCS and ICS exposure were recorded. OCS exposure was recorded with the use of pharmacy records, and ICS exposure was documented with the use of the INCA device, an electronic inhaler monitoring device. This device records, not just the day and time the inhaler is used, but also identifies common errors in inhaler technique that may reduce the amount of drug received, allowing the authors to more accurately document each patient’s ICS exposure. The risk of AI was defined using published data on morning cortisol ranges, classifying patients as being at low, indeterminate, or high risk of AI.

In the entire study population, 1 in 4 patients (n=20) with severe asthma had a morning cortisol level consistent with undiagnosed AI. Patients who were prescribed regular maintenance OCS treatment had the highest risk of AI at 60% (n=6) as expected but 17% of patients who were not taking maintenance OCS and had not received  OCS in the previous 2 weeks were also found to have morning cortisol values consistent with AI . Intermittent OCS courses in patients treated with high-dose ICS were associated with a significant risk of AI (OR 1.41 per treatment course). Logistic regression analysis showed that higher doses of ICS were significantly associated with the risk of AI and that this effect was independent of OCS exposure. This relationship was found to be even more significant when the cumulative steroid exposure was adjusted for the patient’s weight [OR 2.17 of having AI per 1mg/kg increase in fluticasone propionate exposure, (CI 1.06-4.42), p=0.033]. Patients with AI reported worse asthma control although there were no significant differences in measures of lung function or inflammation when compared to those with intact adrenal function.
Whilst being prescribed maintenance OCS therapy appears to convey the greatest influence on risk of AI, this study shows  the importance of considering the cumulative corticosteroid exposure, including ICS and pulse courses of OCS, when assessing a patient’s risk for potential AI.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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