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Vivek N. Iyer, MD, MPH; Kaiser G. Lim, MD, FCCP
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From the Division of Pulmonary and Critical Care Medicine, Mayo Clinic.

CORRESPONDENCE TO: Vivek N. Iyer, MD, MPH, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: iyer.vivek@mayo.edu


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(2):e74-e75. doi:10.1378/chest.14-2456
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To the Editor:

“res ipsa loquitur” - the thing speaks for itself

We welcome the opportunity to engage in an open and transparent discussion with Dr Castro and colleagues regarding our recent article in CHEST1 and the scientific merits of thermoplasty in asthma. They imply that critical appraisal of a peer-reviewed published paper requires multicenter corroboration for accuracy. We stand by our commentary on the Asthma Intervention Research (AIR)-2 trial and would like to reiterate several important facts.

The Methods section of the AIR2 trial is very clear in stating that “The primary outcome was the difference between study groups in the AQLQ (Asthma Quality of Life Questionnaire) change from baseline to the average of the 6, 9 and 12 month scores (integrated AQLQ).”2 This stated primary end point of the AIR2 trial did not achieve statistical significance (posterior probability of superiority of 96.0% vs the prespecified cutoff value of 96.4%).

The proportion of patients in each group that achieved a ≥ 0.5 increase in AQLQ was not the primary outcome of interest. This should be considered an exploratory analysis that has little bearing on the discussion regarding efficacy of thermoplasty. Moreover, important secondary end points (percentage of symptom-free days, total symptom score, FEV1, peak expiratory flow, rescue medication use) showed absolutely no difference between the two groups.

Long-term follow-up of patients in each arm of a clinical trial is essential (and very relevant) when studying chronic diseases such as asthma, heart disease, diabetes, and so forth.3,4 The long-term efficacy of an intervention such as thermoplasty can be judged only when follow-up outcomes in the control group (sham thermoplasty) are also available. Patients in the sham thermoplasty group showed robust clinical improvement in the AIR2 trial and it behooves us to know whether they maintained their improvement without undergoing actual thermoplasty.

The AIR2 trial was not designed or powered to assess “other end points” such as emergency room visits or hospitalizations. In fact, patients with ≥ 3 hospitalizations, steroid pulses, or lower respiratory infections/year were specifically excluded from the study. Furthermore, the small number of events (about 13 ED visits in the bronchial thermoplasty group vs about 42 in the sham group) could have been influenced by one or more outliers, as is illustrated vividly in the hospitalization data. Release of the entire data set into the public domain will allow for further analysis of such outliers. Furthermore, relative risk reduction overstates the benefit (or harm) with small event numbers and should be interpreted very cautiously.

The US Food and Drug Administration-approved thermoplasty was based on only one double-blind randomized controlled trial.1 The other three thermoplasty trials were all unblinded studies that should not be grouped together with the AIR2 trial, given our understanding of asthma5 and the strong placebo effect of invasive procedures.6

Bronchial thermoplasty is not the first procedure that has been tried in patients with asthma,7 and it will surely not be the last. We should be satisfied by nothing but the very best in evidence and efficacy for our patients with asthma.

References

Iyer VN, Lim KG. Bronchial thermoplasty: reappraising the evidence (or lack thereof). Chest. 2014;146(1):17-21. [CrossRef] [PubMed]
 
Castro M, Cox G. Asthma outcomes from bronchial thermoplasty in the AIR2 trial. Am J Respir Crit Care Med. 2011;184(6):743-744. [CrossRef] [PubMed]
 
Patel A, MacMahon S, Chalmers J, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. [CrossRef] [PubMed]
 
Zoungas S, Chalmers J, Neal B, et al; ADVANCE-ON Collaborative Group. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371(15):1392-1406. [CrossRef] [PubMed]
 
Wechsler ME, Kelley JM, Boyd IO, et al. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med. 2011;365(2):119-126. [CrossRef] [PubMed]
 
Sihvonen R, Paavola M, Malmivaara A, et al; Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med. 2013;369(26):2515-2524. [CrossRef] [PubMed]
 
Overholt RH. Glomectomy for asthma. Dis Chest. 1961;40:605-610. [CrossRef] [PubMed]
 

Figures

Tables

References

Iyer VN, Lim KG. Bronchial thermoplasty: reappraising the evidence (or lack thereof). Chest. 2014;146(1):17-21. [CrossRef] [PubMed]
 
Castro M, Cox G. Asthma outcomes from bronchial thermoplasty in the AIR2 trial. Am J Respir Crit Care Med. 2011;184(6):743-744. [CrossRef] [PubMed]
 
Patel A, MacMahon S, Chalmers J, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. [CrossRef] [PubMed]
 
Zoungas S, Chalmers J, Neal B, et al; ADVANCE-ON Collaborative Group. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371(15):1392-1406. [CrossRef] [PubMed]
 
Wechsler ME, Kelley JM, Boyd IO, et al. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med. 2011;365(2):119-126. [CrossRef] [PubMed]
 
Sihvonen R, Paavola M, Malmivaara A, et al; Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med. 2013;369(26):2515-2524. [CrossRef] [PubMed]
 
Overholt RH. Glomectomy for asthma. Dis Chest. 1961;40:605-610. [CrossRef] [PubMed]
 
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