Fixed breathing protocols in multiple-breath-washout testing: truly an option in children?

To the Editor:

We read with much interest the study by Verbanck et al. [1], which showed that multiple breath washout (MBW) protocols with fixed tidal volume (V_T) ranges tend to decrease acinar and conductive airway ventilation heterogeneity (S_acin and S_cond) variability, improve V_T normalisation methods and shorten test duration in healthy adults. However, we question whether direct extrapolation of the results of Verbanck et al. [1] to children and subjects with lung disease, as suggested by the authors, is appropriate.

We agree with Verbanck et al. [1] that the mean V_T of 9 mL·kg⁻¹ in natural breathing and 16 mL·kg⁻¹ in 1 L fixed breathing protocol, as seen in their study, overlaps with the recommended range of 10–15 mL·kg⁻¹ in children [1, 2]. However, depending on their age and thus their natural V_T, adopting 1 L fixed breathing protocols in children forces them to breathe beyond their natural V_T range. In 1 L fixed breathing protocol, a 5-year-old boy of 20 kg needs to maintain a V_T of 50 mL·kg⁻¹. This is nearly five times the natural V_T. Even a 14-year-old adolescent of 40 kg needs to maintain a V_T of 25 mL·kg⁻¹, which is clearly higher than the upper end of the recommended V_T range in children [2–5]. Thus, by nature, the 1 L fixed breathing protocol demands higher V_T per kilogramme ratios in children than in adults and it will force children to breathe in a non-physiological V_T range. In longitudinal studies throughout childhood, the natural V_T range will change with growth and might further complicate comparison over time when applying 1 L fixed breathing protocol.

This leads to the question whether MBW with 1 L fixed breathing protocol reflects ventilation distribution in children and lung disease adequately. Yammine et al. [4] showed that application of the 1 L fixed breathing protocol induced heterogeneous changes of the lung clearance index (LCI) with an overall increase of LCI in healthy children and children with cystic fibrosis compared to natural V_T. In this study population, 1 L fixed breathing protocol led to a clear overestimation of ventilation inhomogeneity. Thereby, the changes seen in the natural breathing pattern induced by the 1 L fixed breathing protocol were highly complex, which was reflected by very heterogeneous changes [3, 5]. In lung disease, additional pathophysiological factors may further add to the complexity. Factors such as hyperinflation or non-ventilated lung areas influence natural tidal breathing and the individual's possibility to adapt the breathing pattern to the 1 L fixed breathing protocol. Thus, the effect on MBW results in lung disease are even more unpredictable.

While one of the goals of the 1 L fixed breathing protocol in adults is to decrease breathing variability, in children variability of tidal breathing has shown to be an expression of the normal physiological capacity of the lung and its adaption to external stimuli [6]. This further raises the question how representative MBW measurements with suppressed natural breathing variability really are to assess ventilation inhomogeneity, especially in younger children.

In conclusion, we believe one should be cautious to apply breathing pattern recommendations derived from a study in healthy adults to children and patients with lung disease.

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