Received: 11 April 2016 | Revised: 12 November 2016 | Accepted: 28 December 2016

DOI 10.1002/ppul.23670

ORIGINAL ARTICLE

Chest physiotherapy can affect the lung clearance index in

cystic fibrosis patients

Joerg Grosse-Onnebrink MD1 | Uwe Mellies MD2 | Margarete Olivier MD2 |

Claudius Werner MD1 | Florian Stehling MD2
1 Department of General Pediatrics, Pediatric
Respiratory Medicine Unit, University Children's
Hospital Muenster, Muenster, Germany
2 Department of Pediatric Pulmonology,
University of Duisburg-Essen, Children's
Hospital, Essen, Germany
Correspondence
Joerg Grosse-Onnebrink, MD, Department of
General Pediatrics, University Children's
Hospital Muenster, Pediatric Respiratory
Medicine Unit, Albert-Schweitzer-Campus 1,
Building A, D-48149 Muenster, Germany.
Email: joerg.grosse-onnebrink@ukmuenster.de
Funding information
WTZ Research Support Service (supported in
part by the Deutsche Krebshilfe Comprehensive
Cancer Centre financing)
Abstract
OBJECTIVES: The lung clearance index (LCI) is determined by multiple-breath washout lung
function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP)
is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term
treatment effects of CP has not been sufficiently investigated. We assessed the short-term
influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the
LCI in CF patients.
METHODS: In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34
years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single
treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no
treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance
of possible treatment effects.
RESULTS: HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range −0.45; 3.47;
P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the
decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five
patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the
control group patients.
CONCLUSIONS: HFCWO can have a short-term decreasing effect on the LCI, but the treatment
response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation
to MBW should be considered a possible bias.

KEYWORDS
chest physiotherapy, coefficient of repeatability, high-frequency chest wall oscillation, lung
clearance index, multiple breath washout

1 | INTRODUCTION most established method to investigate factors that influence

Lung disease is the major reason for reduced life expectancy in the
majority of patients with cystic fibrosis (CF). While spirometry is the
Abbreviations: BMI, body mass index; CF, cystic fibrosis; CG, control group;
CR, coefficient of repeatability; DM, diabetes mellitus; FEV1, forced expira-
tory volume in one second; FEV1% pr, percent predicted forced expiratory
volume in 1 sec; FRC, functional residual capacity; FVC, forced vital capacity;
FVC% pr, percent predicted forced vital capacity; HFCWO, high-frequency
chest wall oscillation; ICC, intraclass correlation coefficient; IG, intervention
group; IQR, interquartile range; L, liter; LCI, lung clearance index; MBW,
multiple-breath washout lung function; PA, Chronic pulmonary infection with
Pseudomonas aeruginosa; SF6, sulfur hexafluoride.
progression of lung disease, other lung function methods have been
introduced. The most established parameter is the lung clearance
index (LCI), which is determined by multiple-breath washout lung
function (MBW). The LCI is a measure of global pulmonary ventilation
inhomogeneity. In contrast to parameters derived from spirometry, it
is feasible in all age groups and is largely independent of age, sex,
height, and weight in pediatric patients older than 6 years.1 There is
increasing evidence that the LCI is a clinically useful parameter. In CF
the LCI is correlated with forced expiratory volume in 1 s (FEV1), with
chest computed tomography scores reflecting structural lung
disease2–4 and it is a good predictor of disease progression in CF
patients.5 The LCI is increased after pulmonary infective

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626 | GROSSE-ONNEBRINK
exacerbations6 and it predicts pulmonary infective exacerbations in
CF.7 The LCI better reflects early lung disease than FEV1 and is more
sensitive in detecting small airway disease in CF patients.3,8 Treatment
effects of LCI have been reported in interventional trials and
observational studies with antibiotics,9 with nebulized hypertonic
saline,2,10 with nebulized dornase alfa11 and with ivacaftor.12 Chest
physiotherapy is a mainstay of CF care but short-term effects of chest
physiotherapy on parameters of MBW have shown conflicting
results.13–15 In previous studies, that addressed the short-term
influence of chest physiotherapy on the LCI, chest physiotherapy
was poorly standardized and the study protocol scheduled a forced
breathing maneuver for spirometry in between the pre- and post-
intervention MBW testing. As both factors possibly bias short-term
treatment effects on the LCI, we used a test-protocol with highly
standardized chest physiotherapy, and we opted against performing
spirometry prior to a MBW test. Our aim was to test the short-term
influence of highly standardized chest physiotherapy on the LCI in a
heterogeneous group of CF patients. We included only patients
suffering from infective exacerbation because we hypothesized that
during infective exacerbation more secretion is present in the airways,
which may result in a more distinct effect of physiotherapy on the LCI.
We, therefore, tested whether highly standardized chest physiother-
apy could reduce the LCI in a short-term setting.
2 | M ATERIA LS AN D METH ODS
2.1 | Study population and study design
This randomized controlled study was carried out between November
2009 and December 2010 at the CF Center of the University
Children's Hospital Essen, Germany. The local ethics committee
approved the study protocol and all patients and/or their parents gave
informed consent. The study was performed in accordance of the
declarations of Helsinki. All patients had a confirmed diagnosis of CF.
Exclusion criteria were: airway infection with Burkholderia cepacia
complex or oxacillin-resistant strains of Staphylococcus aureus in the
past year, lung transplantation, oxygen supplementation, or a history
of pneumothorax. Patients were hospitalized due to infective
pulmonary exacerbation and had a wet cough. Pulmonary infective
exacerbation was physician diagnosed following Fuchs criteria.16 All
patients underwent the study protocol on day 2 or 3 after onset of
intravenous antibiotic treatment and received neither chest physio-
therapy nor mucolytics or bronchodilators on the test day. Patients
were randomly assigned (by sealed envelopes) to intervention and
non-intervention groups. On the test day, every subject performed
two technically acceptable MBW tests (baseline MBW run). Patients in
the intervention group underwent 30 min of chest physiotherapy with
a high-frequency chest wall oscillation (HFCWO) device and were
advised to cough. Patients in the non-intervention group waited
30 min without receiving chest physiotherapy before being advised to
cough. Blinding of the intervention was not feasible, as the vibrations
caused by the HFCWO device were clearly perceivable from both the
study participant and the observer. Subsequently, both groups
ET AL.
repeated two technically acceptable MBW tests (second MBW run),
followed by spirometry. We opted against performing three techni-
cally acceptable MBW tests for each MBW run, because the cough
frequency of patients, who already suffered from pulmonary infective
exacerbation, was increased. Hence, MBW tests had to be frequently
repeated, and we decided to shorten the overall test duration to only
two technically acceptable MBW tests. In our test protocol, the
spirometry was performed after the completion of all MBW tests
because forced breathing maneuvers possibly influence secretions in
the airways and possibly bias the LCI.17
2.2 | Equipment and assessment of outcomes
2.2.1 | High-frequency chest wall oscillation
Standardized chest physiotherapy with HFCWO was carried out in
the intervention group patients in order to prevent bias by applying
different techniques of conventional chest physiotherapy. The
Vest® (Model 104, Hill-Rom) was used for HFCWO. The system
consists of an inflatable vest that is fitted to the patient's thorax
and a pulse generator that applies vibrations with predefined pulse-
pressure and oscillation frequency onto the thorax. The oscillation
frequency was set to 13 Hz and the pulse pressure was set to
3 mbar. To our knowledge, no specific setting has been proven to
be superior to another, so we chose HFCWO settings after review
of literature18 and the clinical experience in our center. The
HFCWO setting used for the study was comfortable to most of our
patients who were treated with this protocol. The interval between
MBW tests and chest physiotherapy was in the range of a few
minutes; two trained medical assistants conducted the lung
function tests and HFCWO.
2.2.2 | Spirometry and body plethysmography
Forced vital capacity (FVC), functional residual capacity (FRC), and
FEV1 were measured with the JAEGER® MasterScreen® Body
(CareFusion, Hoechberg, Germany) according to American Thorax
Society guidelines19; the predicted values and z-scores were
calculated from published reference values.20,21
2.2.3 | Multiple-breath washout
A previously described and validated system (Spiroson, ndd Medical
Technologies, Zurich, Switzerland) was used to test MBW.22 The
tracer gas contained 4% sulfur hexafluoride (SF6), 21% oxygen and
balance nitrogen and was delivered in premixed gas cylinders (BOC,
Manchester, UK). All measurements were conducted according to
American Thorax Society guidelines23,24 and performed with the
patient in a sitting position, wearing a nose clip and breathing through a
mouthpiece while watching a video. Measurements for each test were
performed until two tests reached quality control criteria; we carefully
checked each MBW test for air leaks as previously suggested
(Robinson et al24). We used previously described methods to analyze
FRCMBW and LCI.25,26 Wbreath software (version 3.22.0.0) was used
for data acquisition, storage, and analysis (ndd Medical Technologies,
Zurich, Switzerland).
GROSSE-ONNEBRINK ET AL.
| 627

2.2.4 | Data evaluation and statistical analysis
Analysis was performed using SPSS, version 19 (SPSS Inc., Chicago, IL).
Data are presented as mean and SD or median, min, max and interquartile
range (IQR), if appropriate. Wilcoxon sign rank test was used to assess the
differences between the prior and post intervention/non-intervention
time points. Chi-square test and t test were used to assess the differences
regarding age, gender distribution, weight, height, body mass index,
in the control group failed to meet the quality control criteria despite
repeated MBW tests. Thus a total of 41 patients completed the
study. Baseline characteristics and results of baseline lung function
tests of the study population are shown in Tables 1 and 2. The two
groups did not differ with regard to the following: FEV1 z-score, FVC
z-score, baseline LCI, physical characteristics (age, sex, weight,
height, and body mass index), status of P. aeruginosa colonization or

presence of chronic airway infection with Pseudomonas aeruginosa (defined the presence of cystic fibrosis-related diabetes mellitus. The mean
as two or more positive cultures in the previous year and/or currently on FEV1 z-score was −4.19 ± 1.14 (SD) (−5.55; −2.1, range) in the
inhaled antipseudomonal treatment), and presence of diabetes mellitus intervention group and −3.55 ± 1.64 (SD) (−6.18; 0.12, range) in the

between the intervention and the control group; P < 0.05 was considered
significant. We calculated the intraclass correlation coefficient (ICC) from
baseline MBW lung function tests to assess intra-test repeatability. The
ICC calculates the ratio of between-subject to total variation: the maximum
value of the ICC of one means perfect repeatability, an ICC of 0.8 is
27
considered to represent good repeatability. We calculated the coefficient
of repeatability (CR) from MBW lung function tests according to Bland and
control group. Data for LCI were not normally distributed. The
median LCI in both the intervention and control group was 11.8
(Table 2). The intra-test repeatability was good or excellent with an
ICC of 0.94 for LCI (0.98 for FRCMBW) in the intervention group and
0.81 for LCI (0.99 for FRCMBW) in the control group (Table 3). At the
group level, a single treatment with HFCWO resulted in a
statistically significant decrease of LCI by a median of 0.9 (range

Altman as 1.96 times the SD of LCI differences between the two baseline −0.45; 3.47; P = 0.002). No significant change in LCI was observed in
MBW tests (first MBW run). 28
The CR assesses the intra-test repeatability the control group (P = 0.639) (Table 3). The treatment response was
and reflects the short-term variability between tests; it can be explained by heterogeneous. In the intervention group, we observed a decrease in

technical or physiological factors, which generally affect physiological LCI in 15 patients and an increase in LCI in five patients. In the
29,30
tests. The clinical relevance of changes in LCI between the tests can be control group, the LCI decreased in 11 patients and increased in 10
estimated by assessing the CR: if the change in LCI exceeds the CR, the patients (Table 3, Fig. 2). We assessed the CR of the two baseline

intervention is considered clinically relevant. 30

Bland and Altman plots
were generated using Graph Pad Prism Software Version 5.0 (2010) (Fig. 1).
26
The power calculation was based on previously published data in a cohort
using the same MBW equipment that we used for this study. We estimated
that 38 individuals are sufficient to detect a difference of LCI >1.0 between
prior and post HFCWO measurements in a parallel group design, with a
power of >90% at a two-sided 5% significance level. We estimated a
MBW tests in each group to estimate the range of short-term
variability for MBW tests in the study cohort (Fig. 1). The CR for LCI
(FRCMBW) was 2.15 (0.43) in the intervention group and 2.24 (0.31)
in the control group. The decrease in LCI after the intervention was
clinically relevant (change in LCI > CR) in five patients (25%) from the
intervention group but in no patients from the control group. The
increase in LCI (in 5 patients in the intervention group and in 10

dropout rate of 10%. patients in the control group) was not clinically relevant (Table 3).

3 | RE SULTS 4 | DISCUSSION

We initiated the study with 22 patients in both the intervention and In our study cohort we observed that a single treatment with HFCWO
control groups. Two patients in the treatment group and one patient resulted in a statistically significant decrease in LCI (with a median

F I G UR E 1 Bland Altman plots for the two tests of the baseline multiple-breath washout (MBW) run in intervention group and control group
individuals. The differences of the lung clearance index (LCI) of the 1st and 2nd MBW test (of the baseline MBW run) are plotted against the
mean of the two tests (in the intervention group and in the control group). The dashed line shows the bias, which is the mean of LCI
differences for the 1st and 2nd test. The dotted lines represent the upper and lower limits of agreement. The limits of agreement are
calculated as 1.96 times the SD of differences between pairs of the 1st and 2nd MBW test (of the baseline MBW run) ± the bias and they are
directly related to the coefficient of repeatability (CR). 95% confidence intervals for the bias and for the upper and lower limits of agreement
are gray-shaded
628 | GROSSE-ONNEBRINK ET AL.

TABLE 1 Characteristics of the study population

Intervention group (n = 20) Control group (n = 21) Δ/P-value (95%CI)
Male (%) 15 (75%) 13 (62%) P = 0.6
Age (years) 19 ± 7.9 (7; 34) 23.6 ± 11.8 (7; 51) Δ = −4.6 (−11.0; 1.82)
Weight (kg) 51.1 ± 15.8 (23; 89) 52.7 ± 18.1 (23; 89) Δ = −1.6 (−12.4; 9.2)
Height (cm) 163.9 ± 16.2 (126; 183) 164.0 ± 17.4 (126; 191) Δ = −0.1 (−10.8; 10.5)
BMI (kg/m ) 2
18.6 ± 3.4 (13.8; 29.2) 18.8 ± 3.2 (13.8; 24.7) Δ = −0.2 (−2.4; 1.8)
PA (%) 11 (55%) 18 (86%) P = 0.1
DM (%) 3 (15%) 5 (24%) P = 0.8

Results are presented as mean ± SD (range). Differences are calculated as intervention group—control group. Δ, mean difference; BMI, body mass index; PA,
Chronic pulmonary infection with Pseudomonas aeruginosa; DM, diabetes mellitus.

reduction of 0.9 lung volume turnovers) on the group level. To assess
whether the suspected effect of HFCWO on the LCI is also clinically
relevant we calculated the CR of the LCI and the FRCMBW for the two
consecutive baseline tests (first MBW run): in physiological tests the
CR reflects the 95% range of technical and physiological variability. If
the treatment effect exceeds the CR, the treatment effect is
28,30
considered clinically relevant. In our study the majority of cases
(15 of 20) in the intervention-group did not show a clinically relevant
treatment effect. In 5 of 20 patients the difference in LCI (post
intervention LCI—baseline LCI) exceeded the CR (2.15), what indicates
a clinically relevant treatment response in these cases only (Table 3,
Fig. 2). We did not observe a statistically significant or clinically
relevant effect in the control group patients. Our findings suggest that
a single treatment with HFCWO can result in a decrease of the LCI in
CF patients. To address the question if the supposed effect of HFCWO
on the LCI indicates a real treatment effect, mechanisms how chest
physiotherapy may alter the LCI should be considered.
The following factors can contribute to an LCI decrease after chest
physiotherapy: if chest physiotherapy removes secretions from the
airways, this likely enhances gas washout, which leads to a decrease of
the LCI. The type of chest physiotherapy possibly impacts changes of
the LCI: physiotherapy with oscillating techniques like HFCWO
31,32
reduces sputum viscoelasticity in CF patients and increases
mucociliary clearance in the peripheral airways.18 This can result in
improved peripheral mucociliary clearance and thus improve ventila-
tion inhomogeneity, which is reflected by a decreased LCI. To our
knowledge these effects are not described in classical chest
physiotherapy.
At the individual level, the treatment response in our study was
heterogeneous as 15 patients showed a decrease in LCI and five
patients showed an increase in LCI. The heterogeneous treatment
response may be explained by several factors that alter direction and
degree of change in LCI in individuals: airway mucus plugging can lead
to non-ventilated areas in the lung. These areas do not contribute to
the baseline LCI; if physiotherapy causes mucus movements, non-
ventilated areas may get re-ventilated. The inherent ventilation
inhomogeneity of the re-ventilated areas is added to the overall
ventilation inhomogeneity and thus increases the LCI.33 Bannier et al34
have shown that chest physiotherapy has regional varying effects on
ventilation inhomogeneity in hyperpolarized helium three magnetic
resonance imaging of the lung. As the LCI is a parameter of overall
ventilation inhomogeneity, the locally varying effects of chest
physiotherapy on ventilation inhomogeneity may offset each other.
Chest physiotherapy with HFCWO possibly decreases the end-
expiratory lung volume (FRC) due to repetitive compressions of the
thorax.35 Because the LCI is calculated by dividing the lung volume
turnovers by the FRC, a reduction of the FRC conceivably leads to an
increase in LCI. In two cases from the intervention group, a reduction
of FRC was associated with an increase in LCI, while in eight cases a
reduction of FRC was associated with a decrease in LCI (Table 4).
Although we did not observe a significant change in FRCMBW after the
intervention (Table 3), these mechanisms possibly contribute to

TABLE 2 Results of baseline lung function tests

Intervention group (n = 20) Control group (n = 21) Mean difference (95%CI) P-value
FVC (l) 2.85 ± 1.1 (1.21; 5.34) 3.08 ± 1.3 (0.96; 5.38) −0.2 (−1.0; 0.5) P = 0.53
FVC% pr 69.2 ± 15.1 (41; 95) 74.3 ± 22.3 (35; 134) −5.2 (−17.3; 6.9) P = 0.39
FVC z-score −2.72 ± 1.38 (−5.0; −0.56) −2.31 ± 1.81 (−6.1; 1.75) 0.4 (−0.6; 1.5) P = 0.41
FEV1 (l) 1.69 ± 0.8 (0.64; 3.66) 2.02 ± 1.1 (0.6; 4.3) −0.3 (−0.9; 0.3) P = 0.27
FEV1% pr 50.87 ± 15.7 (29; 81) 57.36 ± 19.9 (25; 105) −6.5 (−17.8; 4.9) P = 0.25
FEV1 z-score −4.19 ± 1.14 (−5.55; −2.1) −3.55 ± 1.64 (−6.18; 0.12) 0.7 (−0.3; 1.7) P = 0.14
LCIbaseline 11.8 (8.81; 19.28) 11.8 (7.06; 15.04) 0.0 P = 0.87

For LCIbaseline the median (range) is given, all other results are presented as mean ± SD (range). Differences are calculated as intervention group—control
group; FVC, forced vital capacity; l, liter; FVC% pr, percent predicted forced vital capacity; FEV1, forced expiratory volume in 1 s; FEV1% pr, percent predicted
forced expiratory volume in 1 s; LCI, lung clearance index
GROSSE-ONNEBRINK ET AL.
| 629

TABLE 3 Multiple-breath washout response

Decrease/
Baseline Post Median diff. Δ > CR Increase n
(range/IQR) CR ICC (95%CI) (range/IQR) (range/IQR) P n (%) (%)
LCIIG 11.8 2.15 0.94 (0.84; 0.98) 11.1 0.93 0.002 5 (25%) 15 (75%)/
(8.81; 19.28/ (8.15; 17.80/ (−0.45; 3.47/ 5 (25%)
10.50; 16.35) 9.34; 14.54) −0.04; 2.36)
FRCMBW_IG (liters) 2.0 0.43 0.98 (0.95; 0.99) 1.8 0.01 0.881 1 (5%) 10 (50%)/
(0.84; 4.28/ (0.89; 4.20/ (−0.45; 0.44/ 10 (50%)
1.47; 2.40) 1.44; 2.40) −0.14; 0.13)
LCICG 11.8 2.24 0.81 (0.53; 0.92) 12.3 0.34 0.639 0 (0%) 11 (52%)/
(7.06; 15.04/ (7.59; 15.16/ (−2.14; 2.12/ 10 (48%)
10.38; 13.65) 9.63; 13.05) −0.81; 0.95)
FRCMBW_CG (liters) 2.1 0.31 0.99 (0.97; 1.00) 2.1 −0.02 0.476 1 (5%) 12 (57%)/
(0.85; 3.53/ (0.87; 3.75/ (−0.69; 0.27/ 9 (43%)
1.55; 2.48) 1.31; 2.35) −0.17; 0.10)

CR and ICC relate to the baseline MBW tests. IQR, interquartile range; CR, coefficient of repeatability; ICC, interclass correlation coefficient; LCI, lung
clearance index; FRCMBW, functional residual capacity assessed by multiple-breath washout; IG, intervention group; CG, control group; Δ > CR, number of
subjects, in whom the change between baseline and post values exceeds the CR.

variable effects on direction and quantity of LCI changes. In summary,
HFCWO can have a decreasing effect on the LCI and we suggest that
this effect is reversed to a varying degree by physiological and
technical factors, resulting in a heterogeneous treatment response.
The treatment response cannot definitively be regarded as a short-
term treatment effect of chest physiotherapy on ventilation
inhomogeneity.
The CR in our study was higher compared to other studies (see
Singer et al: intra-test CR = 1.036), which limits the value of the LCI as a
surrogate to detect short-term treatment effects in our cohort. The
composition of the study cohort (subjects with advanced lung disease
suffering from infective exacerbation) may have contributed to the
increased CR.
Studies that report short-term treatment effects of chest
physiotherapy are rare and show conflicting results. Abbas et al14
showed a significant and clinically relevant treatment effect of a single
intervention with standard airway clearance techniques plus bron-
chodilator therapy in CF patients. In their study a tidal single breath
washout technique with a double tracer gas was applied and
parameters using slope III analyses were used as endpoints. Two
studies have reported no significant short-term treatment effect of
physiotherapy on LCI.13,15 Fuchs et al.13 investigated the short-term
treatment effect of classical chest physiotherapy on the LCI in a group
of 19 CF patients. The study of Pfleger et al15 included CF patients
with a wide range of age and lung disease severity in stable clinical
condition. Chest physiotherapy was performed with PEP mask after
inhalation of salbutamol and showed a heterogeneous effect on study
endpoints. The variations in patient cohorts, types of chest
physiotherapy and study protocols likely contributed to the different
short-term effects on parameters of MBW in these studies.
Our study has some limitations: despite the calculated power of
>90%, it included a relatively small number of patients (n = 41).
Furthermore, a cross over design might have been more appropriate
to compare short-term treatment effects: although both the interven-
tion group and the control group did not differ in baseline parameters,
we cannot exclude that differences in the groups may have affected the
results. We preferred a parallel group design because the patients had to
undergo a time consuming and strenuous test protocol with a minimum
of four MBW tests, each lasting up to 30 min as well as 30 min for chest
physiotherapy and additional time for spirometry. Furthermore, our
study was not designed to test the duration of the effect of HFCWO on
the LCI; thus, we cannot recommend a specific interval between chest
physiotherapy and MBW. A strength of our study relates to the inclusion
criteria that were selected to maximize the effect of a single

TABLE 4 FRC/LCI increase/decrease

Intervention group (n) Control group (n)

FRC↓ FRC FRC↓ FRC

LCI ↓ 8 7 8 3

LCI ↑ 2 3 4 6
F I G UR E 2 Lung clearance index (LCI) before and after treatment
with high-frequency chest wall oscillation (HFCWO)/non- LCI, lung clearance index; FRC, functional residual capacity measured by
intervention for each study participant multiple breath washout lung function.
630 | GROSSE-ONNEBRINK
physiotherapeutic treatment on airway secretion: patients were
hospitalized for infective exacerbation—they had wet cough and
advanced lung disease. While the amount of airway secretion is
increased in these patients, we supposed that a single physiotherapeutic
intervention more likely improves ventilation inhomogeneity of the lung
and consequently may have a more distinct effect on the LCI. We used
highly standardized chest physiotherapy with HFCWO (in contrast to
conventional low standardized chest physiotherapy) in order to
minimize bias by applying different physiotherapies; no spirometry
was performed in between the MBW tests in order to minimize bias by
forced breathing maneuvers.17
In conclusion, the results of our study show that a single chest
physiotherapy treatment with HFCWO can have a short-term effect
on the LCI in CF patients. Although HFCWO can lead to a statistically
significant decrease of the LCI in CF patients on the group level, the
supposed treatment effect is heterogeneous and not clinically relevant
for the majority of the patients in our cohort. The effect of HFCWO on
the LCI thus cannot inevitably be interpreted a “true” short-term
treatment effect of physiotherapy on ventilation inhomogeneity.
Results of our study have implications on the design of clinical trials in
which the LCI is an endpoint: the timing and type of chest
physiotherapy relative to MBW lung function testing should be
determined and recorded throughout the study, because chest
physiotherapy can bias MBW lung function results.
ACKNOWLEDGMENTS
The authors thank the WTZ Research Support Service (supported in
part by the Deutsche Krebshilfe Comprehensive Cancer Centre
financing) and Dr. Gerard W. Dougherty (Research Group, Professor
Heymut Omran, Muenster, Germany) for commenting on and editing
the manuscript. We thank Nadine Kordt and Manuela Groch-Seidler
for their excellent work regarding lung function testing and data
collection. We thank all patients that participated in this study.
POTENTIAL CONFLICTS OF INTEREST
Nothing to disclose.
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How to cite this article: Grosse-Onnebrink J, Mellies U,
Olivier M, Werner C, Stehling F. Chest physiotherapy can
affect the lung clearance index in cystic fibrosis patients.
Pediatric Pulmonology. 2017;52:625–631. https://doi.org/
10.1002/ppul.23670