From the Authors:
We welcome the opportunity to respond to the letter from Serisier and Bowler.
The title of the article clearly states that the study is a randomized controlled trial and it is frankly stated in the Methods section that this was a single-blind randomized study (1). Furthermore, it is clearly stated that the clinical research fellow (Dr. Murray) was the sole individual to conduct all the patient assessments for both the routine study visits and exacerbations. It is clearly stated that the clinical research fellow was blinded to patient treatment allocation.
This was not a placebo-controlled study. The article clearly describes a study evaluating two treatments and consistently refers to two treatment arms: one arm receiving nebulized 0.9% saline and one arm receiving gentamicin reconstituted in 0.9% saline for nebulization.
The primary aim of the study was a microbiology endpoint. Such an endpoint cannot be influenced by blinding in the study. The gentamicin treatment group had significant benefits with reduced microbial burden and reduced neutrophilic airways inflammation, both endpoints that cannot be influenced by blinding in the study. The incremental walking test was conducted by the blinded clinical research fellow with the patients fully aware that they were in one of two treatment groups: treatment with nebulized saline or treatment with nebulized gentamicin. We agree that the mechanism for the improvement in exercise capacity needs further study, but spirometry alone would measure only one physiological mechanism for the proposed change.
We believe that the improvement in both the primary microbiological endpoint as well as the improvements seen in the secondary endpoints (neutrophilic airways inflammation, sputum purulence, exercise capacity, exacerbation frequency, and health-related quality of life) prove efficacy for regular long-term nebulized gentamicin in non–cystic fibrosis bronchiectasis. Further multicenter studies are welcome.
|Murray MP, Govan JRW, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT. A randomized controlled trial of nebulized gentamicin in non–cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2011;183:491–499.