It is worth noting that there is always considerable interindividual variability in the susceptibility to adrenal suppression. Unfortunately, the presented data from Szefler et al16 have not included a scatterplot to illustrate the individual cortisol responses. This is relevant because from a real-life clinical perspective, one deals with an individual rather than average patient. As Dr. Szefler correctly points out, the relatively small degree of suppression in their study probably reflects the reduced lung absorption of fluticasone in severe asthmatics with impaired caliber, as reflected by the low FEV1 of 60.6%. Indeed, in another study,19of patients with severe asthma and a mean FEV1 of 47%, also receiving 1,760 μg of fluticasone per day (via a spacer), there was no suppression of the cortisol response to 100-μg human corticotrophin releasing factor (hCRF) stimulation, compared to 42.2% mean suppression in healthy volunteers receiving the same dose. Interestingly, in patients with severe COPD with (mean FEV1 43%) or without emphysema (mean FEV1 51%) receiving 1,760 μg of fluticasone, there was 40.1% vs 41.0% suppression, respectively, of overnight urinary cortisol.20 One might predict that peripheral absorption would be impaired in COPD, especially in the presence of alveolar destruction due to emphysema, perhaps inferring that at least for fluticasone, absorption may be occurring more proximally. This observation suggests that patients with severe asthma but not COPD may be serendipitously protected from systemic adverse effects with fluticasone, although the mechanism for this discrepancy is unclear.