Forced Oscillation Technique: a surrogate measure of lung function in
neuromuscular disease patients?
Esther S. Veldhoen, MRCPCH1, Johan H. Roos,
Msc1, Rolien Bekkema, MSc2, W. Ludo
van der Pol, PhD3 , Marcel H.B. Tinnevelt,
MSc1, Laura P. Verweij-van den Oudenrijn,
MSc1, Roelie M. Wösten-van Asperen,
PhD4, Erik H.J. Hulzebos, PhD5,
Camiel A. Wijngaarde, PhD3, C. Kors van der Ent,
PhD2
1 Pediatric Intensive Care Unit and Center of Home
Mechanical Ventilation, Wilhelmina Children’s Hospital, University
Medical Center Utrecht, Utrecht University, The Netherlands
2 Department of Pediatric Pulmonology, Wilhelmina
Children’s Hospital, University Medical Center Utrecht University, The
Netherlands
3 Department of Neurology, Brain Centre Rudolf Magnus,
University Medical Center Utrecht, Utrecht University, The Netherlands
4 Pediatric Intensive Care Unit, Wilhelmina Children’s
Hospital, University Medical Center Utrecht.
5 Child Development and Exercise Center, Wilhelmina
Children’s Hospital, University Medical Center Utrecht University, The
Netherlands
Corresponding Author: E.S. Veldhoen Wilhelmina Children’s Hospital,
University Medical Center Utrecht, PO box 85090, 3508 AB Utrecht The
Netherlands Tel +31 887554702
E.S.Veldhoen@umcutrecht.nl
No financial support.
Not presented at scientific meeting
Keywords: Neuromuscular diseases, Child, Lung function,
Abbreviated title: Forced Oscillation Technique in neuromuscular
patients
Abstract
Introduction
Spirometry plays an important role in the assessment of possible
respiratory failure in children with neuromuscular disorders (NMDs).
However, obtaining reliable spirometry results is a major challenge. We
studied the relation between Forced Oscillation Technique (FOT) and
spirometry results. FOT is an easy, non-invasive method to measure
respiratory mechanics, i.e. respiratory resistance R and respiratory
reactance X. We hypothesized an increased resistance R and reduced
reactance X in patients with more reduced lung function.
Methods
In this prospective single center study we included all children with
NMDs able to perform spirometry. We consecutively measured respiratory
resistance R and reactance X at 5, 11 and 19 Hz and (Forced) Vital
Capacity, Peak Expiratory Flow. Spearman correlation coefficients were
calculated and regression curves were estimated.
Results
We included 148 patients, with a median age of 13 years (IQR 8-16). All
correlation coefficients were statistically significant with p = 0.000.
A negative correlation was found between resistance R and spirometry
outcomes (spearman correlation coefficient (ρ) between -0.5 and -0.6). A
positive correlation was found between reactance X (i.e. less negative
outcomes) and spirometry outcomes (ρ between 0.4 and 0.6). Highest
correlation was found at lower frequencies. Regression analysis showed a
non-linear relation between FOT and spirometry results.
Conclusion
We found a non-linear relation between FOT and spirometry results with
increased resistance R and reduced reactance X in patients with more
restrictive lung function decline. Given the difficulties with
performing spirometry, FOT may be a promising surrogate measure of lung
function.
Introduction
Children with neuromuscular diseases (NMDs) may develop progressive
respiratory failure due to respiratory muscle weakness. This leads to a
decline in lung function, which is often further aggravated by a
scoliosis and recurrent respiratory tract infections. Timing of
respiratory failure varies in different NMDs 1.
Guidelines suggest to measure vital capacity (VC) in all patients with
NMDs who are capable of performing spirometry as part of the respiratory
assessment 2.
In children with NMDs spirometry results may steer clinical decision
making with regards to respiratory care, support counseling about timing
of pending chronic respiratory failure, and may assist in the evaluation
of effects of NMD-specific treatments (such as the recently introduced
survival motor neuron protein augmenting therapies in spinal muscular
atrophy (SMA)) 1–4. In healthy children reproducible
spirometry is generally achievable from 6 years of age. In children of
all ages who are weak, obtaining reliable spirometry results may be
challenging, especially forced maneuvers 2.
Respiratory function in children with NMDs is often impaired by the age
at which spirometry is feasible 5. For this reason,
there is an urgent need for alternative noninvasive lung function tests
in children unable to perform spirometry 1. Forced
Oscillation Technique (FOT) may serve as a surrogate test in children
unable to perform spirometry. FOT is a noninvasive, versatile method to
measure respiratory mechanics. FOT can be performed in less than half a
minute 6. Small-amplitude pressure oscillations are
superimposed on the normal breathing, thereby avoiding the need for any
special breathing maneuver or any noticeable interference with
respiration 7. FOT measures respiratory resistance R
and respiratory reactance X. Resistance R describes the dissipative
mechanical properties of the respiratory system, and mainly measures
viscous resistance in large airways and to a lesser extent the tissue
resistance. Reactance X measures the relationship between pressure and
volume (the elastic properties) at low oscillation frequencies and the
relationship between pressure and volume acceleration (the inertive
properties) which become progressively more important at increasing
frequencies 5,7. Previous studies have shown that FOT
is feasible in children with SMA as young as 3 years5,8. Here, we aimed to assess the relation between
results of FOT and spirometry in children with NMDs and hypothesized the
presence of a correlation between these tests. We hypothesized an
increased resistance R and reduced reactance X and in patients with more
restrictive lung function decline, due to reduced compliance of the
chest wall and reduced lung volumes 5.
Methods
In this prospective cohort study, all children with NMDs attending the
outpatient department of the Center of Home Mechanical Ventilation, and
able to perform spirometry were included once between August 2019 and
May 2021. Patients with tracheostomy were excluded.
FOT (ResmonPro Restech®) and spirometry data (Geratherm
Spirostik®) were measured consecutively at the
department of pediatric pulmonology at our hospital. These lung function
tests were performed by a small team of professionals experienced in
conducting these tests in children.
To measure FOT, children were seated with the head in neutral position,
connected to the oscillation device via a mouthpiece and a noseclip in
place. Cheek and floor of mouth were supported by the lung function
technician. Measurements were obtained according to the American
Thoracic Society/European Respiratory Society guidelines9. FOT was measured at 5 Hz, 11 Hz, and 19 Hz. We
studied (Forced) Vital Capacity ((F)VC) and Peak Expiratory Flow (PEF).
Spirometry was measured and reported according to the European
Respiratory Society guidelines 10. All tests were
performed in sitting position, without corsets or braces.
We studied the relation between resistance R and reactance X during
inspiration (insp), expiration (exp) and total breath (tot) and (F)VC
and PEF. We did not study standardized FOT results, as standardized
values are not available at these frequencies in children.
The study was approved by the institutional medical ethical committee.
Statistical analysis
We used descriptive statistics to describe baseline characteristics.
Only measurements obtained during the first visit after inclusion were
used for analyses. We calculated the non-parametric two-tailed spearman
correlation coefficients (ρ ) to describe the relation between FOT
and spirometry results. Regression curve was estimated using IBM SPSS
26.0.
Results
We included 148 patients with a median age of 13 years. One third of the
patients were patients with spinal muscular atrophy (SMA), one quarter
of the patients were patients with Duchenne Muscular Atrophy (DMD).
Fifteen percent of the patients were supported by home mechanical
ventilation. Baseline characteristics are shown in Table 1.
FOT measurement was feasible in all children. Spearman correlation
coefficients of the relation between FOT and spirometry results are
shown in Table 2. All correlation coefficients were statistically
significant with p = 0.000. A negative correlation was found between
resistance R and spirometry outcomes (spearman correlation coefficient
(ρ) between -0.5 and -0.6). A positive correlation was found between
reactance X (i.e. less negative outcomes) and spirometry outcomes (ρ
between 0.4 and 0.6). Highest correlation was found at lower
frequencies. This confirmed our hypothesis: an increased resistance R
and reduced reactance X was observed in patients with lower (F)VC and
PEF.
Regression curves showing the relation between both respiratory
resistance R and reactance X measured at 5 Hz and spirometry results are
shown in respectively Figure 1 and Figure 2.
Discussion
In this study we have shown that FOT may be used as a surrogate measure
of lung function in children with NMDs, especially FOT measurements at
lower frequencies. An increased resistance R and reduced reactance X was
observed in patients with lower (F)VC and PEF.
Although obtaining reliable spirometry results are challenging in young
or severely affected patients with NMDs, spirometry results are
important outcomes in patients with NMDs. For example, in these patients
significantly lowered FVC values are associated with an increased risk
of REM- and NREM-related sleep disordered breathing2,11, and PEF has been shown to be a sensitive marker
to monitor respiratory muscle strength in patients with
DMD12. However, limited data are available on FOT in
patients with NMDs. Although FOT provides an objective measure, it does
not measure the same aspects of respiratory function as other tests5. Respiratory resistance R mainly measures viscous
resistance in large airways and, to a lesser extent, tissue resistance.
In patients with NMDs tissue compliance is reduced due to underinflation
and microatelectasis. As compliance reduces, it is expected that tissue
resistance and R values increase 5. In this study we
confirmed increased R values with decreased spirometry results. In
patients with NMDs the reactance X is expected to be reduced due to
reduced compliance of the chest wall and reduced lung volumes5. In this study we confirmed more reduced, i.e. more
negative, X values in patients with more reduced spirometry outcomes.
Two previous studies by the same group have shown that the use of FOT as
a surrogate outcome to measure lung function was feasible in children
with SMA. Gauld, et al. showed a linear relationship between respiratory
reactance X measured at 8Hz and FVC in 4 children with SMA5. Kapur, et al. showed that children with SMA
requiring non-invasive ventilation (NIV) (n=10) had an abnormal
respiratory resistance R measured at 8Hz compared to children not using
NIV (n=15) 8. Although not linear, we confirmed the
significant relation between spirometry and resistance R and reactance X
in this larger cohort.
Our study has several limitations. Firstly, in contrast to previous
studies 5,8 we did not study standardized values of
FOT. To our knowledge, no pediatric reference values are available of
the frequencies used in this study . Secondly, as this study was not
aimed at studying feasibility of FOT measurements in young or less
cooperative children, we only included patients able to perform
spirometry. It therefore remains unclear whether our results are
generalizable to much younger children with NMDs, although we expect
this to be the case as FOT has been shown to allow for evaluations of
respiratory mechanics in neonates and very young children. FOT is able
to distinguish between healthy neonates and neonates with respiratory
problems 6.
Although the number of included patients in this study are more than 10
times higher than in previous studies, we did not study follow up data
of these patients. Research is required to include repeated measures
over time, to study the ability to predict lung function decline by
using FOT.
Conclusion
We observed a non-linear relation between FOT measurements and
spirometry results in children with NMDs. We confirmed our hypothesis
and found an increased resistance R and reduced reactance X in patients
with more restrictive lung function decline. FOT may be promising as a
surrogate measure of lung function in these children.
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