Rebuttal Comments from Dr. Dunn and Dr. Wechsler

Response to Iyer and Lim⁷:

As with any novel therapy, we believe that critical review of clinical trials is vital to advancing science and thus we appreciate the comments of Dr. Iyer and Lim who have thoroughly reviewed the literature on bronchial thermoplasty. However, we are concerned that misinterpretation of data can lead to incorrect conclusions and potentially result in misuse or nonuse of beneficial therapies such as bronchial thermoplasty.

For example, Drs. Iyer and Lim deemphasize the beneficial effects of BT on hospitalizations, emergency room visits, and exacerbations, and neglect to report on the long term benefits on these outcomes lasting up to 5 years and they incorrectly note that the AIR2 study excluded individuals with these outcomes. Indeed, while patients with greater than four asthma exacerbations/year, three or more asthma-related hospitalizations or an FEV1 less than 60% were excluded for safety concerns, over 85% patients in both treatment and sham arm met American Thoracic Society criteria for severe refractory asthma. Further, while they suggest that an outlier with several exacerbations may have skewed the data, analyses without that subject did not significantly change study findings.

In addition, Drs. Iyer and Lim are critical of the AIR2 study's primary end point, but fail to recognize that the minimally clinically significant important difference (MCID) is a measure relevant to an individual and is used to show a significant change in an individual's asthma QOL at different time points. Thus, the conclusion that a mean change of 0.19 does not reflect a clinically significant change in a group is invalid. It is very relevant that there were both a statistically significant change in mean AQLQ scores in the group and a significantly higher number of subjects in the treatment group who, individually, achieved an MCID of 0.5. Statistically, the change in AQLQ scores was significant as the adjusted posterior probability (PPS) of superiority cut-off was 95.2% and the improvement in AQLQ PPS was 96%.

BT has performed well in multiple published studies to date, and thus we disagree with their conclusion that ”BT does not meet the burden of proof required to incorporate this procedure into routine clinical practice.” Indeed, while we agree that BT requires further study so that we can identify specific responders and better understand the mechanisms by which BT works, we are supportive of recommendations to include BT as part of treatment strategies recommended by the Global Initiative for Asthma, the American College of Chest Physicians, and the British Thoracic Society. We feel that the demonstrated efficacy and safety of BT, coupled with the significant unmet needs in this patient population, warrant increased use of this exciting and novel therapy.