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1 Portex Anaesthesia, Intensive Therapy and Respiratory Medicine Unit, Institute of Child Health, London, UK. 2 Hadassah University Hospital, Mount Scopus, Kiryat Hadassah, Jerusalem, Israel. 3 Dept of Child Health, Clinical Sciences Building, Leicester Royal Infirmary, Leicester, UK. 4 Pulmonary Function Laboratories, Hadassah University Hospital, Jerusalem, Israel. 5 Section of Pulmonary Medicine, Children's Hospital, Colombus, OH, USA
CORRESPONDENCE: J. Stocks, Portex Anaesthesia, Intensive Therapy and Respiratory Medicine Unit, Institute of Child Health, London, UK. Fax: 44 2078298634
Keywords: airways resistance, functional residual capacity, infant, methodology, respiratory function tests, standardization
Received: March 28, 2000
Accepted June 14, 2000
This
work was supported by a grant from the European Respiratory Society, and by
donations from GlaxoWellcome (UK) and GlaxoWellcome AB (Sweden).
Abstract
Functional residual capacity (FRC) is the only static lung volume
that can be measured routinely in infants. It is important for interpreting
volume-dependent pulmonary mechanics such as airway resistance or forced
expiratory flows, and for defining normal lung growth. Despite requiring complex
equipment, the plethysmographic method for measuring FRC is very simple to
apply and, unlike the gas dilution techniques, enables repeat measures of
lung volume to be obtained within a few minutes. This method has the further
advantage that with suitable adaptations to the equipment, simultaneous measurements
of airway resistance can also be obtained.
The aim of this paper is to provide recommendations pertaining to equipment
requirements, study procedures and reporting of data for plethysmographic
measurements in infants. Implementation of these recommendations should help
to ensure that such measurements are as accurate as possible and that meaningful
comparisons can be made between data collected in different centres or with
different equipment. These guidelines cover numerous aspects including terminology
and definitions, equipment, data acquisition and analysis and reporting of
results and also highlight areas where further research is needed before consensus
can be reached.
The recommendations presented here do not invalidate previously published data collected with less automated systems but provide guidance for current and future applications. It is recognized that this paper will need regular updating in response to advances in technology and understanding. In the meantime, every attempt has been made to avoid being too prescriptive to allow for future developments, while offering guidance on minimum standards for those developing equipment and performing the tests.
Recommendations regarding measurement of airway resistance have been restricted to those obtained under BTPS (Body temperature and pressure, saturated) conditions, using a heated rebreathing bag. This is the only approach that has been thoroughly assessed in infants and with the exception of the earliest trials in the 1960s, all published results of airway resistance in infants have been obtained using this approach. New methods such as those utilizing electronic/mathematical algorithms to compensate for thermal artefacts 1, 2 may eventually prove to be advantageous, and will certainly be simpler to operate. These will, however, need to be compared with the "gold standard" BTPS method before being adopted for routine use.
The theoretical background and practical details of how to apply this technique and interpret results have been described previously in a book published by the task force, which collates much of the relevant information and discusses background issues that may influence measurements 3. Further details regarding equipment and software specifications are described elsewhere 4, 5. It is anticipated that acceptance and application of these recommendations will be of particular value when attempting to compare data between centres, develop or use reference data, or participate in multicentre trials which use parameters of infant plethysmography as outcome measures.
Terminology and definitions
The infant whole body plethysmograph is a valuable tool for obtaining simultaneous measurements of lung volume and airways resistance 3. This technique aims to measure functional residual capacity (FRCp or FRCpleth) and airway resistance (Raw). From these, other key parameters such as airway conductance (Gaw=the reciprocal of Raw), specific resistance (sRaw=resistancexFRC), and specific conductance (sGaw=Gaw/FRC) can be calculated. In practice, the baby lies inside the plethysmograph, a rigid, closed container, and breathes through a pneumotachometer (PNT), which records changes in tidal flow and volume. While the infant is breathing quietly, the airway opening is occluded briefly using a remotely controlled shutter. The infant makes respiratory efforts against this obstruction, thereby compressing and rarefying the thoracic gas. It is assumed that during periods of no airflow, pressure at the airway opening reflects changes in alveolar pressure. By relating these changes to changes in alveolar volume, which are reflected by changes in the plethysmographic signal, the total volume of gas within the thorax at the moment of occlusion can be calculated. Similarly, providing the respired gas can be kept at BTPS conditions, changes in plethysmographic pressure during spontaneous breathing are inversely proportional to changes in alveolar pressure. By relating changes in box (alveolar) pressure to simultaneous changes in flow at the airway opening, airway resistance (Raw) can be calculated.
The term "airway" resistance should be reserved for techniques such as plethysmography, which relate changes in alveolar pressure to airflow. It should not be used to describe pulmonary (lung tissue plus airway) resistance as calculated from changes in transpulmonary (oesophageal) pressure, or respiratory (airway plus tissue plus chest wall) resistance as measured from changes in pressure at the airway opening. Other documents in this series describe alternative methods of assessing FRC 6 and resistance 7. A full list of definitions, recommended abbreviations and units are included in the Appendix.
Equipment
Further details and justification of the recommendations presented have been published in previous documents in this series 4, 5, 8, 9.
Plethysmograph
Recommendations when using the plethysmograph: 1) The dimensions of
the plethysmographic chamber should generally be sufficient to accommodate
infants up to 
15 kg or 85 cm length. For such infants,
a box of 70–100 L is usually adequate. Centres wishing to
assess preschool children may require a somewhat larger box, whereas those
assessing preterm or new-born infants may require a smaller chamber to
achieve adequate resolution. 2) Particular attention is required to ensure
sufficient room for manipulation of the mask and breathing apparatus when
the infant is in situ, whilst maintaining a streamlined design to
facilitate rapid and complete pressure equilibration within the chamber. 3)
Clear vision and rapid access (<2 s) to the child is essential
at all times. 4) The compensation chamber should have identical thermal
and mechanical characteristics as the plethysmographic chamber, although a
smaller capacity (25–50%) is usually satisfactory.
5) The box should be constructed of suitable materials to ensure adequate
heat exchange and should not be excessively insulated. Net loss through the
walls should equal net gain from infant and equipment to ensure rapid thermal
equilibration. 6) The use of air conditioning and/or fans within
the box should be avoided except for the use of a small isolated fan within
the rebreathing bag during Raw measurement. 7) Compressible
objects within the box (e.g. avoid foam mattresses) should
be minimized. 8) Frequency response (amplitude and phase) should
be satisfactory to 10 Hz 4, 5. 9) The combined time constant should
be 10–14 s (63% decay) or a half life of
6–9 s 9. 10)
There should be a linear response of the box signal to known inputs over a
range of appropriate breathing frequencies (e.g. 20–100
breaths per minute (bpm)). If this is not achieved the box
calibration factor will need to be adjusted according to the infant's
precise respiratory pattern, which may vary considerably throughout the testing
period 3. 11) It is essential
to check the linearity of the plethysmographic output over a suitable range
of inputs. This should take into account the fact that changes in plethysmographic
volume or pressure may be as small as 1–2 mL or Pa respectively
during FRC measurements and even smaller during airway resistance measurement,
especially in healthy infants. Such assessments will generally require specialized
equipment 9. 12) A standard
lung model should be used to check the accuracy with which FRC can be measured.
Ideally this should cover a range of volumes 30–500 mL, at frequencies
20–100 bpm. A narrower range of volumes and frequencies may be
applicable according to the age range and clinical status of infants studied
within a particular laboratory 4, 9. Ideally such validation should be performed
prior to release of any commercially available equipment. 13) Clear specifications
must be provided by the manufacturers regarding the range of lung volumes
that can be reliably measured by the system, particularly with respect to
the lower range, since standard infant plethysmographs may not be suitable
for assessing lung volumes in neonates or preterm infants.
Breathing apparatus
Recommendations for the breathing apparatus: 1) The PNT must be linear
over the range of flows encountered, bearing in mind that relatively high
flows may be recorded if there is any stimulation of breathing while the infant
is switched into the heated rebreathing bag during assessments of Raw. The PNT must remain linear when heated 4. 2) The combined dead space of the PNT and occlusion shutter
should ideally be <2 mL·kg–1 together with
the smallest possible mask to minimize dead space. This means that at least
two sets of breathing apparatus will probably be required according to infant
size to attain minimum dead space and maximum resolution. Spare sets should
be available in case there are technical problems due to shutter failure,
leaking connections and so forth. 3) The resistance of the combined apparatus
should be <20% of the infant's intrinsic resistance at the
highest flow likely to be encountered, i.e. in term neonates, <0.7 kPa·L–1·s at 166 mL·s–1, whereas
for a 1-yr-old, it should not exceed 0.5 kPa·L–1·s at 500 mL·s–l. 4)
A low dead space, low resistive shutter is required. This shutter should not
influence the linearity of PNT adversely. If lung volumes alone are being
measured this can be a simple occlusion device. For airway resistance measurements,
a two-valve system is required (see later), designed to optimize
dead space, linearity and resistance. 5) Automated and remote control
of the shutter is essential, as is the need for default to the open position
in the event of any equipment or software failure. 6) Automated closure
should be feasible at end inspiration (EI), end expiration (EE),
or other points through the breath as specified by the user. 7) Speed
of valve opening and closing (excluding any lag time) should be <75 ms.
Most modern valves suitable for plethysmography close considerably faster
than this. 8) At least two complete respiratory efforts against the occlusion
are generally required for satisfactory assessments of FRCp. It
may therefore, be necessary to hold the occlusion for at least 10 s,
although a default set to 8 s is generally satisfactory. 9) An
alarm should sound if the occlusion exceeds 15 s or that designated
by the user. 10) The shutter must be able to withstand pressures of ±3 kPa
without any leaks or compressive effects. 11) A "shutter test"
should be incorporated within the software and calibration protocol, so that
the shutter can be checked prior to each study occasion. 12) The shutter
must be easy to clean and reassemble. It should be light, with a suitable
means of support and easy manipulation within the box. 13) Activation
of the shutter should result in minimal volume change within the box and be
as quiet as possible to avoid disturbing the infant or altering sleep state.
Mask
Factors to consider for successful employment of the mask: 1) Dead
space of the mask should be measured by water displacement and 50%
of this value subtracted to take into account the space occupied by the infant's
face and the putty seal 4, 10. 2) A very firm mask is essential
to prevent errors due to compressive changes during occlusions when pressure
swings of ±1–2 kPa may occur. 3) The use of therapeutic
putty to achieve a good, airtight seal is recommended.
Additional equipment for airway resistance measurements under BTPS conditions
Additional equipment that is required for airway resistance measurements:
1) The apparatus will require two ports through which the infant can
breathe. The first opens to the box, and the second connects to a heated rebreathing
bag (HRB). Both ports should be controlled by remotely operating
shutters so that the infant can be switched to breathe through the desired
port. 2) Both the apparatus and the HRB should incorporate servo-controlled
heating elements. 3) The HRB should be completely contained within the
box, be of approximately 1 L capacity, and be made of highly compliant
but nonelastic material. It is essential that no pressure changes occur within
the bag itself while the infant is rebreathing. 4) An easily accessible
port through which the HRB can be emptied (a vacuum source) and
refilled with heated humidified air/O2 is required. Adequate
humidification is essential for accurate measurements. 5) A small fan
to circulate the air within the bag has been found to improve temperature
control.
Transducers
Ideal transducer parameters include (see also previous publications
on equipment specifications 4):
1) A requirement for 3 perfectly matched transducers. 2) The range
of signals encountered to cover: box pressure: range ±0.1 kPa (i.e. 1 cmH2O); airway opening pressure ±2 kPa (20 cmH2O) (±5 kPa transducer will suffice); flow:
during Raw measurements, peak flows vary according to
infant age and weight from <100 mL·s–1 in
neonates to as high as 400 mL·s–1 at around
1 yr 11. Care should be taken
to avoid excessive rebreathing (and increased end-tidal partial
pressure of carbon dioxide (Pet,CO2))
which may result in significantly elevated flows. 3) Any transducer tubing
should be noncompliant (stiff), perfectly matched on both sides
of the transducers and of minimal length. Many modern systems now use solid
state transducers. 4) All transducers should be checked for similar frequency
response to at least 10 Hz while set up as for use during lung function
tests, with all connections in situ 9.
Data acquisition and signal processing
Data acquisition requirements are dealt with elsewhere in this series 5. Points of particular relevance to plethysmographic measurements are discussed in the present paper.
Recommended sampling rate
The recommended sampling rate is 200 Hz since this will be adequate
for measurements of both Raw and FRCp. If only
lung volumes are being measured, a lower sampling rate of 100 Hz would
generally suffice.
BTPS conditions
During adult plethysmography, temperature measurements close to the PNT
screen have indicated that considerable warming of inspired air may occur
by the time inspired air reaches the subject (J. Reinstaedtler, Erich
Jaeger GmBH, Hochberg, Germany, personal communication). By contrast,
considerable deconditioning of the gas may occur during expiration such that
some adaptation to the conventional BTPS correction may be advisable. Since
equivalent data are not available in infants, it is currently recommended
that the conventional approach whereby inspiratory air is corrected to BTPS
whereas expired gas is assumed to be at BTPS be adopted. This approach may
however, result in an upward drift of tidal volume if inspiratory volumes
are consistently over corrected and expiratory volumes under corrected with
respect to true conditions at the PNT at the moment of measurement. It is
therefore, suggested that the magnitude of tidal volume drift is routinely
recorded to assist in further investigation of this problem. Recommendations
are as follows: 1) For calculation of FRCp: when occlusions
are performed above the end expiratory level (EEL), the volume inspired
above the EEL must be converted to BTPS conditions prior to subtraction from
the total occluded gas volume (TOGV) 8. Since plethysmographic FRC is measured under BTPS conditions,
additional correction of the measured lung volumes is not required. 2)
During airway resistance measurements: in systems where there is automatic
BTPS correction of tidal breathing data, with intermittent use of a heated
rebreathing bag for Raw measurements, care must be taken
to ensure that flows and volumes collected under BTPS conditions are not further
corrected! 3) Ambient temperature: the temperature used for BTPS corrections
should ideally be that within the box, but room temperature on the day of
study will suffice since this is generally within a few degrees of that of
the box with the baby in situ. 4) Ambient relative humidity:
ideally, the value measured in the laboratory on the day of study should be
used in BTPS corrections. If this is not available, an approximation of 50%
humidity is generally substituted. 5) Barometric pressure: the barometric
pressure should be obtained from a room barometer or the local meteorological
office on the day of study. 6) Gas mixtures other than air: options should
be available within the software to enter the gas mixture used on the day
of study if this is other than air. Thus if infants are receiving supplemental
oxygen, an automated correction for differences in density and viscosity should
be applied by the software 8.
Drift correction of box signal
The box volume signal tends to drift during tidal breathing, due to slight
increases in temperature, and in the opposite direction during the occlusion,
when transfer of thermal energy into the box from respiration ceases. It is
important to ensure that thermal equilibrium has occurred, with minimal drift,
prior to performing the occlusion. It is important to observe the magnitude
of this drift during the monitoring and data collection period to assess when
equilibration has occurred. However, drift correction of the box signal prior
to displaying recorded signals is essential to assess the phase relationships
between the box signal and either flow (Raw)
or airway opening pressure (FRCp). Various algorithms
have been proposed, as discussed later.
Identification of end expiratory level
There are a number of factors to consider when identifying the EEL: 1)
It is vital to establish a representative baseline EEL for accurate estimations
of FRCp irrespective of whether EE or EI occlusions are performed.
The calculated EEL must be displayed clearly on the time-based trace so
that the operator can evaluate whether a representative level has been selected.
2) The tidal volume signal must be stable to estimate EEL accurately.
The various factors that may contribute to a drift of the tidal volume signal
and the way in which this can be corrected have been discussed in detail elsewhere 8. The drift correction algorithm uses the
EE points from each epoch of breathing to assess the drift. The more breaths
that are available, the more accurate this correction is likely to be. It
is also important to apply this drift correction to the postocclusion tidal
volume data. 3) It is important to check for any shift in EEL postocclusion.
This can indicate a leak around the mask 12. 4) The facility to rezero flow to correct for any flow
offset should be available during both data collection and analysis.
Calibration
To ensure adequate equipment calibration (see previous documents in
this series for additional details regarding equipment calibration 4, 8):
1) All channels should be calibrated, or a calibration check performed,
prior to every infant study according to the manufacturer's recommendations.
2) It is vital that calibration tools are checked regularly. 3)
Ideally, calibration of the plethysmograph should be performed using an automated
sinusoidal pump with a variable frequency and volume. The use of automated
calibration procedures is recommended, but must be intermittently checked
manually. 4) Calibration must be performed under identical conditions
as during measurements, for example with the PNT attached to the shutter block.
5) If the inspired gas differs from room air, e.g. during measurements
of Raw, deviations in gas viscosity must be taken into
account 8. 6) Calibration
factors/checks should be displayed, recorded and saved with infant details
on each occasion for subsequent quality control checks.
Monitor display
Modern software generally allows several displays simultaneously, thereby,
greatly facilitating the monitoring of breathing patterns and quality control
during data collection and analysis. The following displays are recommended
during plethysmographic measurements: 1) For monitoring the infant: continuous
display of tidal volume or flow and pressure at the airway opening (Pao) whenever the mask and apparatus are connected, not
just during data collection. 2) For lung volume measurements: time based
displays of flow, volume, Pao and Vpleth before, during and after the occlusion; X-Y plots of Pao versus Vpleth during airway occlusions
for FRCp; tabulation and/or cumulative plot of all relevant
manoeuvres, to inform the operator how many acceptable measures of FRCp have been obtained. 3) For resistance measurements: real time
displays of flow, volume, Pao and Vpleth both while breathing room air from the box and while rebreathing from
the heated rebreathing bag; simultaneous X-Y plots of flow versus Vpleth; tabulation and/or cumulative plot of
all relevant manoeuvres, to inform the operator how many acceptable measures
of Raw have been obtained; composite flow versus Vpleth plot; composite Raw-VT plot.
Procedure
Measurement conditions
The measurement conditions have been previously discussed 13, 14.
Ideally, 2–3 min of baseline tidal volume recordings should precede
the measurements of Raw and FRC to monitor breathing pattern
and provide a broad assessment of sleep state. These can be obtained while
the box is equilibrating. If a rebreathing bag is being used measurements
of lung volume should precede those of airway resistance, unless care is taken
to minimize the period of rebreathing. The baseline measures of FRCp should also be made with minimal dead space and with no additional
equipment such as "squeeze" jackets in situ 15. Posture measurements should be performed
in the supine position with the head in the midline and the neck slightly
extended. Any deviations from this posture should be documented. Measurements
should be restricted to periods when the infant is well settled, breathing
regularly, with no eye or body movements.
Data collection
Points to consider for data collection (for further details see previous
publications 3) when measuring
FRCp include: checking for facemask leaks 3, 12;
leaving the box to equilibrate for 2–3 min after closing, or
until the box signal has begun to stabilize with minimal drift; once the infant
is breathing regularly with a well-established EEL, occlude at EI; holding
occlusion for at least two complete respiratory efforts to allow for accurate
drift correction; releasing occlusion and checking postocclusion EEL; checking
phase relationship of Pao versus Vpleth; repeating until up to 5 (minimum 3) technically satisfactory
EI occlusions have been obtained; and if desired, repeating at EE.
When making airway resistance measurements: fill the heated rebreathing bag (HRB) with moist warm air/O2 from the humidifier and allow it to reach BTPS conditions before switching the infant to breathe this mixture; during this period of adaptation, the box pressure is likely to drift and the box should therefore, remain vented or be vented frequently; the optimal temperature of gas in the HRB will depend somewhat on circuitry. The bag and apparatus need precise servo-control; adequate humidification is essential as are stringent safety measures to ensure that the infant is never exposed to inspired gases above 40°C; ensure that the bag does not touch the sides of the plethysmograph once the lid is closed and is not over-inflated; when the box signal is stable and the infant is breathing regularly switch the infant into the HRB at EE for no longer than 30 s to avoid excess buildup of CO2; once stable pressure/flow loops are observed, switch the infant back to breathing air from the box; flush the bag thoroughly and repeat until at least three technically satisfactory epochs are obtained; CO2 and O2 concentrations in the HRB should be measured intermittently.
Data analysis
Calculation of lung volume
TOGV is determined from the ratio of 
Vpleth:Pao during respiratory efforts against the closed shutter.
The tidal volume should be converted to BTPS conditions and any drift correction
applied. To calculate EEL prior to occlusion, the mean of at least 6 EE points
after drift correction should be taken. The occluded volume above the EEL (Vocc) at BTPS conditions for subsequent subtraction from
TOGV should be calculated. Some disturbance of the box signal inevitably occurs
immediately after shutter closure. This is exacerbated by the fact that an
expiratory pause usually occurs following EI occlusion. Since there is minimal
true change in the Vpleth signal during this period, it
is recommended that this portion of the trace should be excluded from the
analysis. Evaluation of both the Vpleth drift and the Vpleth/Pao relationship should therefore,
not commence until the onset of the first inspiratory effort following EI
occlusion or the second inspiratory tug if an EEO has been performed.
The box signal generally drifts during airway occlusions 3. Drift correction is performed by identifying Vpleth at the transition points where the Pao=0, where by definition Vpleth should also be zero. The change in Vpleth as a function of time between these points is then subtracted from the recorded value using a linear drift correction in time. As the baby only performs short efforts against the occluded shutter while relaxing in between, it is desirable to evaluate the signals only during the rapid changes in Pao in order to improve the signal:noise ratio. To do this the signal trace is separated into single respiratory efforts, each consisting of a paired inspiratory (decreasing Pao) and "expiratory" effort (increasing Pao) against the occlusion. The slopes should be calculated by regression of Vpleth versus Pao through all the data points that lie between the 5% limits, thereby truncating the peaks and troughs where noise is greatest. The 5% limit is calculated from the peak-to-trough Pao per slope rather than the absolute maximum or minimum value during the whole occlusion. These limits should be user adjustable and be recorded with the results. Each inspiratory and the subsequent expiratory slope are combined to form a single "respiratory effort" slope by calculating the average angle of the two. The TOGV for each respiratory effort is calculated from the averaged slopes. It should be noted that some previous studies have been performed using calculations based on the inspiratory limb only. This practice is now discouraged.
Each individual effort should be displayed with the facility to exclude,
if necessary, due to noise such as glottic closure. The mean value of the
selected slopes within each occlusion are averaged to give a single result
for that trial:
|
| (001) |
Vpleth/Pao must be corrected as shown.
It must be noted that this method of calculation ensures that TOGV and hence
FRCp are calculated as the mean of both the inspired and expired
efforts. Subtract Vocc from TOGV, together with the apparatus
dead space (DS,app)
|
| (002) |
Criteria for technically satisfactory data have been described elsewhere 3, 16 but include the fact that: there should be no airflow during
the occlusion, as shown by a zero flow signal (no flutter) and a
stable EE baseline for tidal volume before and after the occlusion; and during
the airway occlusion, changes in Pao and Vpleth should be inphase, without evidence of glottic closure
or leak.
Calculation of airways resistance
A full description of the derivation of equations for calculating sRaw and Raw has been published previously 3. The essential quality criteria for assessment
of plethysmographic Raw is that there is a good phase
relationship between the box signal and flow. Points to remember include:
1) Drift correction of the box signal during resistance measurements:
prior to any calculations, Vpleth, must be drift corrected.
This has to be performed on a breath-by-breath basis since changes in atmospheric
pressure may influence the magnitude and direction of box signal drift, despite
the presence of a compensatory chamber. Drift correction is performed by identifying
the data sample points of Vpleth at the beginning of inspiration
and end of the subsequent expiration, when alveolar pressure should be zero,
and then subtracting the change over time from the box signal, by using a
linear drift correction in time. The start and end of each breath is identified
from simultaneous zero crossings on the flow trace; breaths should not be
used for analysis if the drift is excessive. Signal to noise ratio may be
considerably worse in healthy infants with low resistance and hence small
changes in the plethysmographic signal. 2) Apparatus resistance (Rapp): Rapp should be calculated
continuously and on a breath-by-breath basis by relating Pao:flow so that this can subsequently be subtracted
from total measured resistance. 3) Calculation of specific airway resistance (Rapp): providing there are no artefacts due to changes
in the humidity and temperature of the respired gas, specific airway resistance
can be calculated directly from the relationship of Vpleth/flow prior to airway occlusion 1, 17–20 using the following equation:
|
| (003) |
|
| (004) |
Reporting results
See appendix for the full list of parameters that can be calculated for full quality control, assessment of breathing pattern, comparison within and between laboratories and so forth. For clinical reports it is probably only necessary to record mean±sd FRCp and various key parameters for airway resistance. An X-Y plot of Vpleth/Pao from a representative FRC manoeuvre and Vpleth/flow plot to show the shape of the specific resistance curve are also invaluable. Important points to remember when reporting results are: individual values of FRC should be stored, but the default set to report FRC as the mean±sd of results from the first three technically acceptable occlusions (where each individual value for FRC represents the mean of all data collected during one occlusion). Separate summaries of EI and EE occlusions can be presented if desired; Raw, designated with appropriate suffixes to denote how it was calculated (see appendix) should be reported as the weighted mean±sd of as many breaths as possible (minimum 5, which will hopefully be far more in the future), together with the number of breaths the result was obtained from; according to individual preference the weighted mean± sd for number of breaths for sRaw or sGaw can also be reported.
Reference data
The published "reference" data for plethysmographic parameters
in infants may not be applicable to the current studies and should be used
with great caution 3. FRCp should never be expressed as a ratio per unit of body length, the
proposed preliminary equation for predicting FRCpleth in healthy
infants up to 15 months is:
|
| (005) |
The 95% confidence intervals around predicted FRCpleth, from this equation are 76–132% respectively. This equation will need to be amended as further data become available. There is a relative lack of reference values for Raw during the first year of life, especially with respect to any data published in recent years. New standards will need to be developed as new analytical approaches are implemented.
Future directions/controversies
Considerable further work is required to evaluate the potential usefulness
of implementing some means of compensating for the thermal/humidification
artefacts during Raw measurements in infants without having
to use a heated rebreathing bag. While the latter is certainly feasible, it
requires carefully designed equipment and considerable skill on the part of
the operator, thereby limiting its use to specialized laboratories. Furthermore,
even when the period of rebreathing is restricted, some build up of CO2 is inevitable, which may influence the very parameters that are under
investigation.
There is currently no consensus regarding the best approach to analysing Raw in infants, and further experimental work is required
to provide the necessary objective evidence. However, it is generally recognized
that: 1) no single value can adequately describe Raw
in any infant, since this parameter is strongly influenced by so many factors,
including phase of respiration, lung volume and flow at time of measurements.
Changes in Raw through the breath are likely to be most
marked in those with airway disease, and may provide important information
regarding the underlying pathology; 2) the breath-to-breath variability
of Raw is likely to be particularly high if the algorithms
relate the box signal to flow between specified single data
points such as zero flow to 50 or 66% peak flow as has been reported
in previous publications 3, 22, 23. 3) With modern computing facilities, a better approach
may be to calculate mean Raw throughout the breath, and
to look at relative changes in Raw at high and low volumes
throughout the tidal breath, together with the relationship between inspiratory
and expiratory resistance at similar lung volumes. One such approach has been
described previously 24–26, wherein Raw can
be calculated for each sampled point in order to acquire an array of values
as a function of VT throughout the breath. If the pressure/flow
relationship is perfectly linear, Raw versus VT will yield a constant, horizontal plot, whereas if resistance
rises towards EE, for example, this will be graphically evident. 4) Ideally
far more breaths should be analysed than has been common in the past. This
may require a new approach regarding breath selection etc. 5)
The use of specific resistance in infants needs to be investigated more thoroughly,
together with an examination of the relationship between these various parameters.
The relative reproducibility and potential clinical usefulness of the various
estimations of Raw also requires considerable further
study 1, 17, 18.
Potentially useful methods of analysing sRaw and hence Raw include: 1) specific effective airway resistance (average
sRaw throughout breath–sRaw,eff:
the specific effective airway resistance can be calculated by dividing the
integrated area of the specific work of breathing loop (tidal volume versus box signal) by the tidal flow/volume loop). Provided
such data points are equidistant this is equivalent to regressing through
all sampled data points of the specific resistance loop (Vpleth/flow throughout the breath). Slight
differences will occur when sample points are unequally distributed as may
occur, for example, when rapid changes in flow with minimal volume change
occur at the start of inspiration. This may result in relatively few data
points over this portion of the breath even when sampling at 200 Hz.
"Effective" airway resistance (Raw,eff)
is derived from specific effective resistance by using the average lung volume
during the breath. The latter is calculated as the mean FRCp from
all valid FRC measurements, plus half the VT of the breath
used to analyse Raw i.e.:
|
| (006) |
|
| (007) |
It should be stressed that all these approaches need considerable further evaluation before clear recommendations can be given.
Summary of recommendations
Equipment
The recommendations for the equipment include ensuring: the plethysmograph
is constructed of suitable materials to ensure adequate heat exchange and
also that it is not excessively insulated. The compensation chamber should
have identical thermal and mechanical characteristics as the plethysmographic
chamber; frequency response is satisfactory to 10 Hz; the PNT is linear
over the range of flows encountered; a low dead space, low resistive shutter
is used. The combined dead space of the PNT and occlusion shutter should ideally
be less than 2 mL·kg–1. The resistance of the
combined apparatus should be <20% of the infant's intrinsic
resistance; automated and remote control of the shutter, which is essential,
as is the need for it to default to the open position in the event of any
equipment or software failure; when measuring airways resistance the apparatus
and the HRB incorporates servo-controlled heating elements. The HRB should
be made of highly compliant but nonelastic material.
Data acquisition and signal processing
Recommendations include: a sampling rate of 200 Hz; drift correction
of the box signal, which is essential when assessing the relationships between
the box signal and either flow (Raw) or airway
opening pressure (FRCp); establishing a representative
baseline EEL before calculating FRCp.
Data collection of functional residual capacity
The data collection recommendations include: performing measurements in
the supine position while the infant is in quiet sleep; carrying out occlusion
at EI, once the infant is breathing regularly with a well-established
EEL; holding occlusion for at least two complete respiratory efforts to allow
for accurate drift correction; repeating measurements until up to 5 (minimum
3) technically satisfactory occlusions have been obtained.
Data collection for airway resistance
The airway resistance recommendations for data collection include: switching
the infant into a rebreathing bag filled with warm, humidified air/O2 (BTPS) at EE for up to 30 s when the box signal is
stable and the infant is breathing regularly; switching the infant back to
breathing air from the box, once stable pressure/flow loops are observed;
flushing the bag thoroughly and repeating until at least three technically
satisfactory epochs are obtained.
Calculation of the functional residual capacity
When calculating the functional residual capacity: care must be taken to
apply an appropriate drift correction to the box signal, to calculate the
mean slope of each respiratory effort against the occlusion (not simply
the inspiratory limb) and to exclude periods of noise immediately after
shutter closure and during the peaks and troughs of each respiratory tug;
the volume above FRC at time of occlusion must be subtracted from the TOGV.
This requires accurate evaluation of the EEL preceding airway occlusion; all
relevant dead space must be subtracted from TOGV, including that of the facemask
and any transducer tubing; technically satisfactory data are essential, ensuring
that only those in which box volume and airway opening pressure are inphase
and have no evidence of leak or glottic closure are accepted.
Calculation of specific resistance
When calculating Raw: prior to any calculations, the
box signal (Vpleth) must be drift corrected
on a breath-by-breath basis; apparatus resistance (Rapp) should be calculated continuously and subtracted from total
measured resistance; providing there are no artefacts due to changes in the
humidity and temperature of the respired gas, specific airway resistance can
be calculated directly from the relationship of Vpleth/flow prior to airway occlusion; corrections must be made
for the lung volume at which sRaw is measured; if technically
acceptable measurements of FRCp have been obtained, values of Raw, Gaw and specific airway conductance (sGaw) can subsequently be derived, whereby: Raw=sRaw/FRCRaw, Gaw=1/Raw and sGaw=1/sRaw.
Reporting results
The following are the recommendations for reporting the results: report
FRC as the mean±sd of the first three technically acceptable
occlusions (where each individual value for FRC represents the mean of
all data collected during one occlusion); Raw, designated
with appropriate suffixes to denote how it is calculated (see appendix)
should be reported as the weighted mean±sd of as many breaths
as possible (minimum 5, which should hopefully be far more in the future).
Reference data
Caution should be exercised when attempting to interpret results with respect
to published reference data, since this may be very specific to the population
studied and the equipment used.
Future work
A considerable amount of further work is required, to evaluate the validity of implementing some means of compensating for the thermal/humidification artefacts during airway resistance measurements, in infants, without having to use a heated rebreathing bag and to assess the relative usefulness of the wide variety of analytical approaches to calculating airway resistance.
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Calculation of the following parameters are recommended in any automated, commercially available system for plethysmographic assessments of FRCp and Raw in infants. Use of the suggested abbreviations is recommended in order to facilitate comparisons between systems and minimize confusion when reporting results. Some refer to quality control variables, which would not be reported for each individual test but which should be stored for verification purposes. All results should be displayed to at least 3 effective digits.
Acknowledgements
The authors would like to thank all the other members of the Task Force who contributed to developing these recommendations: J. Allan (Philadelphia, PA, USA), J.H.T. Bates (Montreal, Canada), J.B. Clough (Southampton, UK), A.L. Coates (Toronto, Canada), I. Dundas (London, UK), D. Filbrun (Colombus, OH, USA), U. Frey (Berne, Switzerland), P. Gustafsson (Skövde, Sweden), R. Gregson (Southampton, UK), Matthias Henschen (Freiburg, Germany), A.-F. Hoo (London, UK), A. Jackson (Boston, MA, USA), J. de Jongste (Rotterdam, the Netherlands), R. Kraemer (Berne, Switzerland), S. Lum (London, UK), P. Merkus (Rotterdam, the Netherlands), I.T. Merth (Leiden, the Netherlands), M. Morris. (Little Rock, AR, USA), B. Reinmann (Berne, Switzerland), G. Schmalisch (Berlin, Germany), P. Seddon (Brighton, UK), G. Sharma (Chicago, IL, USA), M. Silverman (Leicester, UK), P.D. Sly (West Perth, Western Australia), R. Tepper, (Indianapolis, IN, USA), D. Vilozni (Petach-Tikva, Israel), E. van der Wiel (Rotterdam, the Netherlands) and to members of the industry, who read the various drafts and provided invaluable feedback.
Footnotes
Previous articles in this series: No. 1: U. Frey,
J. Stocks, A. Coates, P.D. Sly, J. Bates, on behalf of the ERS/ATS Task
Force on Standards for Infant Respiratory Function Testing. Specifications
for equipment used for infant pulmonary function testing. Eur Respir J 2000; 16: 731–740. No. 2: P.D. Sly, R. Tepper, M.
Henschen, M. Gappa, J. Stocks, on behalf of the ERS/ATS Task Force on
Standards for Infant Respiratory Function Testing. Tidal Forced Expirations. Eur Respir J 2000; 16: 741–748. No. 3: U. Frey, J.
Stocks, P. Sly, J. Bates, on behalf of the ERS/ATS Task Force on Standards
for Infant Respiratory Function Testing. Specifications for signal processing
and data handling used for infant pulmonary function testing. Eur Respir
J 2000; 16: 1016–1022. No. 4: J.H.T. Bates, G. Schmalisch,
D. Filburn, J. Stocks, on behalf of the ERS/ATS Task Force on Standards
for Infant Respiratory Function Testing. Tidal breath analysis for infant
pulmonary function testing. Eur Respir J 2000; 16: 1180–1192. No. 5: M. Gappa, A.A. Colin, I. Goetz, J. Stocks, on behalf of
the ERS/ATS Task Force on Standards for Infant Respiratory Function Testing.
Passive respiratory mechanics: The occlusion techniques. Eur Respir J 2001; 17: 141–148. 
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|
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|
|
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|
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|
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|
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|
|
|
|
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|
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|
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|
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|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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