Reply to Svenningsen et al.: Eosinophilia and Response to Bronchial Thermoplasty

Goorsenberg and colleagues reported, in their 35 patients with severe asthma who underwent bronchial thermoplasty (BT), that higher baseline blood eosinophil count was associated with greater improvement in Asthma-related Quality of Life Questionnaire (AQLQ) (r=0.48, P=0.004) and Asthma Control Questionnaire (ACQ) scores (r=20.46, P=0.006) following BT treatment (1). Our clinical experience has been just the opposite (2, 3). In an analysis of 14 patients who underwent BT, we had previously reported a greater improvement in AQLQ score (mean6 SD, 2.26 1.2 vs. 0.86 0.9, P=0.04), ACQ score (22.36 1.3 vs. 20.56 1.1, P=0.02), and airway hyperresponsiveness quantified by the provocative concentration of methacholine that results in a 20% drop in FEV1 (PC20) (3.96 1.2 vs. 0.66 0.8 doubling-doses, P=0.008) in those whose sputum cell counts were normalized before BT compared with those who were treated based on standard clinical optimization (3). The improvement in ACQ and AQLQ scores reported by patients with asthma in whom airway inflammation was absent or controlled prior to BT was.4 times the minimum clinically important difference, being the largest improvement when compared with published trials (4–6) and approximately 3 times that reported by Goorsenberg and colleagues. In contrast to their observations, lower baseline blood eosinophil count was associated with greater improvement in AQLQ score (r=20.62, P=0.02) but not ACQ score (r=0.44, P=0.11). Additionally, PC20 improved by 3.96 1.2 doubling-doses (P=0.06) in patients with asthma in whom airway inflammation was absent or controlled prior to BT. This observation is in agreement with the mechanism of action of BT, at least in part, being a reduction in airway smooth muscle mass confirmed in this report by Goorsenberg and colleagues (1). We are not quite sure why the results are contradictory. Both studies are limited by small sample sizes and could therefore be underpowered for responder analyses to draw definite conclusions. It should also be emphasized that the reported P value cutoff after Bonferroni correction for multiple comparisons in Goorsenberg’s responder analysis is P, 0.006. Using this corrected cutoff, the associations of higher baseline blood eosinophil count with greater improvement in AQLQ and ACQ scores reported by Goorsenberg are rendered statistically insignificant. It is also conceivable that in Goorsenberg’s analysis, the predictive benefits attributed to baseline eosinophilia (unclear when this was assessed), which is a marker of steroid responsiveness, may have been confounded by the 150 mg prednisone (over 3 d) administered before each session of BT. In conclusion, there is considerable variability in patient outcomes following BT in clinical practice. Therefore, we share the enthusiasm of the authors to identify baseline characteristics of optimal candidates for BT treatment. However, we caution overinterpretation of the BT responder analysis reported by Goorsenberg and colleagues. In agreement with the authors, the current literature has shaped a debatable BT responder profile, necessitating a large multicenter cohort study that is sufficiently powered for BT responder analysis. n