Variation of in Vitro Glucocorticoid Response in Asthma
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Monica B. Reddy, MD, Donald Y.M. Leung, MD PhD FAAAAI, Joseph D. Spahn, MD, Douglas Curran-Everett, PhD, Vijaya Knight, MD, PhD, Ronina A. Covar, MD FAAAAI
Rationale: Asthmatic patients show variable responses to glucocorticoids (GC).   The GC lymphocyte stimulation (GCLS) assay has been used to assess GC response in vitro.  There is limited information on the variability of this assay and how well it correlates with clinical response.

Methods: GCLS results from 169 patients with asthma having evidence of expiratory airflow limitation and variability were analyzed.  Log IC50values (the amount of GC required to inhibit lymphocyte activation by 50%) for prednisolone, dexamethasone, budesonide and fluticasone were calculated; highest quartile values for each GC were considered as insensitive.

Results: Mean (SD) log IC50 values for prednisolone, dexamethasone, budesonide, and fluticasone propionate were 1.59 (0.63), 0.68 (0.67), 0.06 (0.61), and -0.07 (0.66), respectively.  57% were pansensitive; 11% were insensitive to all GCs. 65% of patients were sensitive to fluticasone and budesonide; 15% were insensitive to both. 66% of patients were sensitive to prednisolone and dexamethasone; 16% were insensitive to both.  Patients who were insensitive to all GCs were older [50.4 (19.4) vs. 34.4 (23.8) years, p=0.007], more obese [BMI 30.4 (8.0) vs. 26.1 (8.4) kg/m2, p=0.04], and had worse airflow limitation [FEV1/FVC 64 (22) vs. 73 (13), p= 0.02] compared to those who were pansensitive.

Conclusions: Variation in in vitro responses to GC exists. The association of steroid insensitivity and older age, obesity, and worse airflow limitation needs further investigation, as this may imply a need for increased doses of GC to overcome inflammation or airflow limitation in patients who are already susceptible to develop adverse effects.