Comparison of the utility of multiple breath inert gas washout parameters in cystic fibrosis.

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doi: 10.1136/thx.2009.121590
2010 65: 659Thorax

P D Robinson, A Lindblad and P M Gustafsson
inert gas washout parameters in cystic fibrosis
Comparison of the utility of multiple breath

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LETTERS
Comparison of the utility of
multiple breath inert gas washout
parameters in cystic fibrosis
Ventilation inhomogeneity, measured using
multiple breath washout (MBW), reflects
small airway function and has emerged as
a valuable tool in cystic fibrosis (CF).
Improved sensitivity to detect early lung
damage has been suggested from preschool
children through to adults and confirmed in
high-resolution CT (HRCT) studies.1Longi-
tudinal utility is now emerging.2A large
number of parameters reflecting overall
ventilationinhomogeneity
proposed, but consensus is lacking about the
optimal parameter to report.
The two most commonly reported are
lung clearance index (LCI) and moment
ratios (MR). LCI, the easier to calculate and
understandconceptually,
number of lung turnovers (or functional
residual capacities, FRC) required to reduce
the end tidal inert gas concentration to 1/
40th of its starting value. The calculation of
MR adds more weight to the latter portion
of the washout curve and, while more
complicated intheir
improved robustness to variations in tidal
volume (VT)3
and potentially improved
sensitivity.4 5Truncation of MR to facilitate
comparison between subjects is recom-
mended.6In practice, however, the large VT
fluctuations used by Saidel et al3are beyond
that seen during routine MBW tests, which
encourage regular tidal breathing. The deri-
vation of these parameters is described in
more detail in the online supplement.
MBW tests from two cohorts, a CF
(n¼56) and a healthy control (n¼32),
containing preschool children through to
adults were retrospectively studied. Testing,
performed in triplicate with results averaged,
took place at the West-Swedish CF Centre,
Göteborg, Sweden using equipment previ-
ously described.7In children a regular spon-
taneous breathing pattern was targeted,
while an adult protocol was used in older
subjects.8
Spirometry
according to ATS criteria and z-scores were
generated from appropriate Swedish refer-
ence values. LCI and MR results from the
healthy cohort generated upper limits of
normality. Prism Version 4.0 (GraphPad
Software, San Diego, USA) was used for
statistical analyses: t tests were used for
parametric continuous variables, the Mann-
Whitney test for non-parametric continuous
variables and multivariate logistic regression
analyses to investigate factors influencing
the within-subject coefficient of variation
(CV) of MBW indices from the triplicate
tests. Data were pooled from previous
studies with ethics approval, and some of
the LCI CF data have been previously
reported.9
have been
representsthe
derivation,offer
wasperformed
The demographic characteristics of the
two groups are summarised in table 1 of the
online supplement.
significantly raised
compared with controls: LCI 9.03 (2.51) vs
6.28 (0.58); µ1/µ0 2.01 (0.55) vs 1.45 (0.12);
and
µ2/µ0 6.59 (3.76e30.4)
(2.96e5.43), all p<0.001 (see table 2 in the
online supplement). Comparable sensitivity
was seen between parameters and was not
affected by truncation of MR. No significant
difference in CV was seen between LCI and
µ1/µ0 in either cohort, but was significantly
greater for µ2/µ0 in both (p<0.001). Trun-
cation of MR improved the CV in the CF
cohort (table 3 in online supplement). Vari-
ation in breathing parameters (respiratory
rate (mean, CV), VT (CV), or VT/FRC) did
not explain the variation in CV seen
between the indices. Correlation was strong
between LCI and both MR parameters in the
CF cohort but negatively affected by trun-
cation at higher LCI values (figure 1) (see also
figure 1 in online supplement).
While MR truncation improved stability
and did not affect sensitivity, a negative
effect on the relationship with LCI was seen
at higher LCI values, potentially affecting
sensitivity and utility in more severe disease.
Given the frequency of higher LCI values
reported in established CF lung disease2and
its comparable sensitivity and stability to
µ1/µ0, this easily derived and simple to
understand index should be the preferred
longitudinal assessment outcome parameter
of ventilation inhomogeneity reported in
future CF studies.
MBW
in
indices
CF
were
cohort the
vs3.85
P D Robinson,1,2,3A Lindblad,4,5P M Gustafsson5,6
1Department of Respiratory Medicine, Childrens’ Hospital
at Westmead, Sydney, Australia;2The Children’s
Hospital at Westmead Clinical School, Discipline of
Paediatrics and Child Health, Faculty of Medicine,
University of Sydney, Australia;3Woolcock Institute of
Medical Research, Sydney, Australia;4Department of
Paediatrics, Queen Silvia’s Children Hospital,
Gothenburg, Sweden;5The Sahlgrenska Academy at the
University of Gothenburg, Gothenburg, Sweden;
6Department of Paediatrics, Central Hospital, Sko ¨vde,
Sweden
Correspondence to Dr P D Robinson, The Children’s
Hospital at Westmead, Locked Bag 4001, Westmead,
NSW, 2145 Australia; paulr3@chw.edu.au
<Additional details are published online only. To view
these files please visit the journal online (http://thorax.
bmj.com).
Competing interests None.
Contributors PDR was responsible for conception and
design of this study, analysis and interpretation of data
and the writing of the manuscript. PMG was responsible
for performing the original recordings, analysis and
interpretation of the study results and contributed to the
writing of the manuscript. AL was responsible for original
recruitment of subjects and setting up of the laboratory
and contributed to the writing of the manuscript.
Provenance and Peer review Not commissioned; not
externally peer reviewed.
Accepted 18 August 2009
Thorax 2009;65:659.
doi:10.1136/thx.2009.121590
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Association of PHF11
polymorphisms with asthma
and allergy
Two recent reports in Thorax failed to show
an associationbetween
within PHF11 and asthma phenotypes.1 2
Against this, there is evidence for an associa-
tion between PHF11 and one or more
phenotypes of total immunoglobulin E (IgE),
atopic eczema and asthma in six independent
cohorts.3e5Here, we argue in support of the
continued investigation into the biological
role of PHF11 in the unravelling of the path-
ogenesis of atopic disease and asthma.
In the report by McClenaghan et al, posi-
tive associations were identified but lost
polymorphisms
Figure 1
index (LCI) and the first moment ratio in its
untruncated (µ1/µ0) and truncated forms
(µ1/µ0e8). *p<0.001.
Correlation between lung clearance
Thorax July 2010 Vol 65 No 7 659
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