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.