Multiple Breath Washout
The multiple breath washout (MBW) technique can be used to assess ventilation inhomogeneity, which can be seen in a variety of pediatric lung diseases, most notably cystic fibrosis (CF) [6]. MBW can be performed either by washing in a tracer gas, such as sulfur hexafluoride, and then washing the tracer gas out with ambient air or washing out the resident nitrogen (N2) in the lungs with 100% oxygen. The lung clearance index (LCI) is the most commonly used measure derived from N2 MBW, and it represents the number of lung turnovers required to washout resident N2from the lungs down to 2.5% of the original concentration; a higher LCI indicates increased ventilation inhomogeneity. In addition to LCI, other measures derived from MBW include LCI5.0, where N2 is washed out to 5% of the original concentration, slope of phase III indices, and moment ratio analysis.
Parisi, et al performed MBW and spirometry in a group of childhood cancer survivors and matched healthy controls [7]. They found that LCI was higher in these children compared to healthy controls, but this difference was not statistically significant; and there was no difference in spirometry measurements. There was a significant correlation between years following chemotherapy and increased LCI. Their results suggest that the chemotherapy used to treat childhood tumors may have less pulmonary toxicity than previously expected, at least during childhood. The increase in LCI over time suggests that LCI could be used to non-invasively assess pulmonary fibrosis but larger prospective studies are needed.
Gambazza, et al evaluated the association of LCI with exercise capacity in patients with CF [8]. LCI was significantly higher in patients with exercise intolerance, but it was also higher in some patients with normal exercise tolerance and normal to moderate airflow obstruction. No association was found between predicted peak work and LCI, but there was a significant association between peak work and nutritional status, airflow obstruction, and chronic Pseudomonas aeruginosainfection. Based on these findings, providers should not assume that patients with normal exercise tolerance do not have early lung disease.
Irving, et al compared MBW results between children with severe treatment resistant asthma (STRA), difficult asthma (DA) and healthy controls [9]. LCI was significantly higher in the patients with STRA compared to those with DA and controls but there was no difference between DA and controls. FeNO and LCI showed significant improvement following parenteral steroids. These results suggest that distal airways disease is worse in patients with STRA and can sometimes be improved with parenteral steroids. The improvement in FeNO and LCI suggests these patients with STRA may have distal airway eosinophilic inflammation that may not respond to inhaled corticosteroids. These results suggest that FeNO and LCI may be useful in monitoring treatment response in patients with STRA.
Other studies of MBW focused on use of outcome measures other than LCI and comparison of difference MBW devices. Arigliani, et al compared the conduction-dependent contribution to ventilation inhomogeneity (Scond), the diffusion-convection interaction-dependent inhomogeneity (Sacin), LCI, spirometry, and transfer capacity of the lung to carbon monoxide (TLCO) in children born at <28 weeks gestational age (GA) [10]. Scondwas abnormal in about one third of children while LCI and FEV1 were only abnormal in 18% and 14% respectively. They did not identify any significant difference in Scomd between infants born prematurely with BPD compared to those without BPD. No significant difference was observed in Sacin between the premature infants and the control group and no significant difference was found when comparing those with BPD to those without BPD. Finally, extremely preterm children had lower TLCO compared to controls,Although moment ratios correlated with pulmonary symptoms, high variability limits its utility in the clinical setting. These results suggest that LCI5.0 can be used to track disease progression in young children with CF. Compartment analysis (CA) allows partitioning of MBW data into slower and faster ventilating units. Skov, et al applied CA to MBW testing in children with CF [12]. Because CA requires an extremely regular breathing pattern, it could only be successfully performed in 53% of children with CF. However, CA did correlate with other MBW measurements, such as LCI. Further research is needed to determine the clinical value of CA. Isaac, et al used a lung model to compare functional residual capacity (FRC) and LCI measured with 2 different MBW devices and body plethysmography [13]. Not only were there differences in these measurements using these 3 different methods, but for one device LCI decreased with age. These results indicate that MBW data obtained on one device cannot be directly compared to data from other devices.