Abstract
This first RCT of hypertonic saline use in pediatric non-CF
bronchiectasis patients uses a cross over design and demonstrates an
improvement in predicted FEV1 and FVC. Limitations include lack of
blinding and risk of information bias, as well as reduced precision due
to absence of within subject comparisons.
Dear Editor,
I congratulate the authors of “Effectiveness of hypertonic saline
nebulization in airway clearance in children with non-cystic fibrosis
(non-CF) bronchiectasis: a randomized control trial” on performing the
first randomized control trial of its kind in the pediatric population.
Through a crossover design, the authors demonstrate that nebulized 3%
saline significantly improved mean predicted forced expiratory volume in
1 second and predicted forced vital capacity.
Unfortunately, the absence of a placebo introduces significant bias to
the authors’ intended comparison of conventional airway clearance
therapy (ACT) to conventional ACT with hypertonic saline. Isotonic
saline (+/- amiloride to mask taste) has been used as a placebo in
cystic fibrosis studies with no significant therapeutic
effect1. Although a bronchiolitis and chronic
obstructive pulmonary disease study suggest that isotonic saline may not
be benign, consideration of a placebo would still be reasonable in this
context2,3. With this non-blinded
design in a population of patients who demonstrated adherence prior to
participation, knowledge of the intervention status may have influenced
participant behaviour. Differential adherence to conventional ACT would
lead to information bias.
Furthermore, the 2010 British Thoracic Society bronchiectasis definition
includes subjective elements: perception of increased cough, sputum, and
fatigue. Non-blinded participants and investigators were at risk for
differential misclassification of exacerbations.
The method of analysing the intervention and control arms for each phase
of the study allows the two phases to be easily compared by the reader
but does not take advantage of the cross over design. Performing within
subject comparisons would have decreased variability within the data and
enabled a more precise treatment effect.
The European Respiratory Society regards non-CF bronchiectasis as “one
of the most neglected diseases in respiratory
medicine”4. There is disproportionately even less
research in children than adults. This article is much appreciated, and
will hopefully result in larger, potentially multisite studies that
incorporate blinding and are powered to enable stratification by
bronchiectasis type.