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1 Section of Pediatric Pulmonary Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA, 2 Dept of Paediatrics, Central Hospital, Skövde, Sweden, 3 Section of Pediatric Pulmonology, Indiana University Medical Centre, James Whitcomb Riley Memorial Hospital for Children, Indianapolis, IN, USA, 4 University Children's Hospital, Dept of Paediatric Pulmonology and Neonatology, Medizinische Hochschule Hannover, D-30623, Hannover, Germany and 5 Portex Anaesthesia, Intensive Therapy and Respiratory Medicine Unit, Institute of Child Health, London, UK
CORRESPONDENCE: M.G. Morris, University of Arkansas for Medical Sciences, Section of Pediatric Pulmonary Medicine, Arkansas Children's Hospital, 800 Marshall Street, Little Rock, AR 72202, USA. Fax: 1501 3203930
Keywords: functional residual capacity, gas dilution, infant, lung volume, nitrogen washout, respiratory function tests
Received: August 17, 2000
Accepted October 15, 2000
This
work was supported by a grant from the European Respiratory Society, and by
donations from Glaxo-Wellcome (UK) and Glaxo-Wellcome AB (Sweden).
M.G. Morris was supported by a Clinical Research Grant (CG-008-N)
co-funded by the American Lung Association (ALA) and the
Arkansas Chapter of ALA.
Abstract
The functional residual capacity (FRC) is the most commonly measured
static lung volume in infants. It is important for interpreting volume-dependent
pulmonary mechanics, e.g. airway resistance, and defining normal
lung growth. The bias flow nitrogen washout technique is widely used for measuring
FRC because the dead space and circuit resistance are low, making it suitable
for small or sick infants. Moreover, data acquisition and calculation are
easily programmed for a personal computer.
The aim of this paper is to provide recommendations pertaining to equipment
requirements, study procedures and reporting of data for functional residual
capacity measurements. While measuring the functional residual capacity is
regarded as physiologically and clinically important, the accuracy of the
measurement is undoubtedly equally important. Hence, the paper also emphasizes
factors influencing the accuracy of functional residual capacity measurements
independent of equipment requirements. These recommendations represent the "State
of the Art" in 2000.
FRC has been the only static lung volume routinely measured in infants 1, 2. FRC is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Longitudinal measurements of FRC are useful in infants with suspected impairment of alveolar growth such as in premature infants or pulmonary hypoplasia. Atelectasis, decreased lung or increased chest compliance also decreases FRC. Increased FRC commonly occurs in relation to gas trapping associated with airway obstruction. Measuring FRC has been clinically useful in the evaluation of infants with lung diseases, such as bronchiolitis, bronchopulmonary dysplasia, cystic fibrosis, and respiratory distress syndrome, as well as the evaluation of treatment efficacy 1–3.
FRC can be measured by body plethysmography (FRCpleth) or by multiple breath inert gas (x) washout/dilution technique (FRCgasx). The latter includes the closed circuit (e.g. closed circuit helium dilution) and the open washout systems. The latter in turn can be divided into bias flow and breath-by-breath washout systems. Different inert gas tracers can be used such as N2, helium (He), argon (Ar), and sulphur hexafluoride (SF6). The gases can be measured with various devices such as a helium catharometer, N2 emission spectrophotometer (known as the N2 analyser), mass spectrometer, main stream or side stream infrared (JR) detector. Breath-by-breath systems provide information on gas distribution and ventilatory efficiency that are not provided by the bias flow washout systems. N2 washout employs 100% oxygen (O2), but room air can be used when other inert gas tracers are washed out. N2 washout can also be performed using 21% O2/79% Ar mixture when using a mass spectrometer. The bias flow N2 washout technique has been the most commonly used approach. It is relatively simple and inexpensive to set up in the laboratory 1–14.
Definitions and terminology
The technique referred to in the present paper is for measuring the FRC in spontaneously breathing infants by the bias flow N2 washout technique. The FRC is the volume of air contained in the lung and airways at end-tidal expiration 1–3. The FRC measured is referred to as FRCN2 to differentiate it from measurements made with other tracer gases or plethysmography. For measurements of FRCN2 in ventilated infants the reader is referred to recent publications 6, 10, 15–19.
Equipment
See previous publications in this series 20, 21 for further details and justification of the recommendations presented.
The nitrogen washout circuit
Further details of the theoretical background and basic methodology have
been described by Tepper et al. 3.
Concept
The open circuit N2 washout method for assessment of FRCN2 entails measuring the volume of nitrogen expired after
end-tidal expiratory switching of the inspired gas from room air to 100%
O2. At a constant bias flow that exceeds the infant's inspiratory
peak flow during tidal breathing, the integrated mixed expired FN2 (area
under the curve of the N2 concentration (F=fractional
concentration) versus time (t)) is multiplied
by the constant flow of O2 (V'), to obtain
the volume of expired N2 (VN2) 3, 5, 6:
|
| (001) |
A two-point calibration is performed with known air volumes. With the
amount of N2 washed out measured and the initial fractional alveolar
N2 concentration (FAi,N2) known (FAi,N2: room air=0.79), then the lung volume at
which the washout was initiated can be calculated:
|
| (002) |
0.0065 in the chamber, which corresponds to the end-tidal FN2 of 0.02. This dilution effect will depend upon the flow of gas through
the N2 mixing chamber and the size of the chamber. The end-tidal
FN2 cut-off of 0.02 reduces the overestimation of FRC, since
previous tissue N2 elimination studies during pure O2
breathing in adults and animals suggested that FRCN2
includes tissue-N2 dissolved into the lung during prolonged
washout 4, 22–24. Corrections are made for the dead space of the mask and apparatus, the switching error above FRC and body temperature, pressure and saturation (BTPS) (see later).
Equipment required
The equipment required is outlined in fig. 1
and includes a: clear face mask; three-way switching
valve with two inlet/outlet ports and a mask port; T-piece; pneumotachometer (PNT);
O2 supply with a precision flowmeter (0–15 L·min–1); N2 analyser and mixing chamber; calibrating
syringe; collapsible breathing bag and a T-connection (recommended;
see later) 11, 12.
|
Three-way switching valve
The three-way switching valve allows the infant to breathe either room
air through the PNT or 100% O2 through a T-piece.
Computer-controlled electronic switching of the three-way valve via a computer keyboard stroke is preferred. The PNT is connected to
one of the two-inlet/outlet ports of the three-way valve (fig. 1
). The other inlet/outlet port
is attached to the T-piece which carries the constant O2
bias flow from the flowmeter, through the T-piece, tubing and N2 mixing chamber. The infant breathes room air through the face mask,
mask port of the three-way valve and PNT. When switched into pure O2 during the washout, the infant no longer breathes through the PNT (fig. 1) 7, 12. Connecting
the PNT to the inlet/outlet port of the three-way valve is the preferred
placement because this decreases the dead space and resistance during the
washout. The PNT may be placed within the washout circuit by connecting it
to the mask port, which is useful in preterm infants with unstable breathing
patterns. However, variations in gas temperature, composition and viscosity
need to be accounted for as well as the phase shift between the flow and N2 concentration signals 3.
The operator should be able to choose one of two switching modes: 1) automatic, whereby the software programme monitors stability of the tidal volume (VT) and expiatory time (tE) so that when the user triggers the activation of the slide valve, it occurs at the end of the next expiration provided that VT and tE of that breath are within a set percentage (e.g. 10%) of the previous mean of 5–10 breaths. This may be difficult to achieve in small babies with rapid or irregular breathing, and it may therefore, be necessary to allow user adjustment of the selected percentage. Nevertheless, this mode has the advantage of being simple to use and minimizing inter-observer variability. For a detailed discussion regarding the use of automatic breath identification, see Bates et al. 26. 2) Manual, whereby the operator waits until a stable tidal breathing (end-expiratory level) pattern is observed in real time on the computer monitor and activates the slide valve as close as possible to end-expiration in a chosen breath 3, 7, 12. This mode requires an experienced operator but is useful if the infant has irregular breathing.
Nitrogen analyser
N2 concentration is usually measured using emission spectrophotometry
in a low-pressure ionization chamber under conditions of constant flow,
although a mass spectrometer can also be used. An adjustable needle valve
mounted on the mixing chamber is connected to a vacuum pump in order to provide
the optimum negative pressure and constant flow for the ionization of nitrogen.
The analyser should have: a linear output with a range 0–100%
N2; an accuracy of 1% full range; a resolution of 0.01%;
a drift <0.2% N2·h–1 (stability
close to zero N2 concentration is particularly important);
a range of gas sampling rate 9–50 mL·min–1; a recorder output of 0–10 Volts Direct Current (VDC)
full scale; a response time (10–90% full scale) of <100 ms.
The manufacturer should provide details regarding the necessary warming time for the equipment 11.
It is anticipated that these requirements will need to be amended for use with newer generations of equipment or alternative ways of measuring FRCN2, such as those based on CO2 and O2 subtraction techniques, which have not yet been validated or sufficiently tried in infant testing. Time characteristics of these systems may have to be assessed using Fast Fourier Transform (FFT) analysis of the N2 signal using a rapid N2 analyser.
Nitrogen mixing chamber
The mixing chamber should contain at least three serial channels with baffles
to recirculate and mix the gas prior to exiting the chamber. A long (
2.0 m),
low resistance tubing is attached to the outlet port of the mixing chamber
to prevent ambient air from diffusing back into the mixing chamber. A chamber
volume of about 500 mL would be adequate, even in toddlers, particularly
if a collapsible breathing bag is incorporated in the circuit (see later) 11, 12.
Collapsible breathing bag
A collapsible breathing bag (0.5 L) can be incorporated
into the washout circuit via a second T-connection. It should
be placed between the infant and the O2 source but closer to the
former. This has been reported to enhance the reproducibility of measurements
by acting as a buffer reservoir. This minimizes flow swings within the N2 mixing chamber during the breathing cycle as well as the retrograde
movement of mixed O2 and N2 gas after it passes beyond
the N2 sampling needle port. In addition, the bag can be used to
monitor the infant's breathing pattern both during the washout and when
determining the "end of test" (see later) 11, 12.
Bias flow of oxygen
The bias flow of O2 should be standardized to facilitate comparison
of washout times between laboratories: 10 L·min–1 and 5 L·min–1 are suitable for infants
weighing 
5.0 kg, respectively 3, 12. Nevertheless,
the volume of the washout circuit may influence the circuit time constant.
Flowmeter
This has been described elsewhere 20, 26, 27.
Calibration syringe
The exact dead space of the calibration syringe should be known. The combined
volume of the syringe once connected to the mask port is generally less than
the sum of their individual volumes as determined by water replacement. If
both have been made by the same manufacturer, the latter can provide these
data, but further confirmation by the investigator using water displacement
with the equipment assembled as for use in vivo is recommended 11.
Measurements in infants who require an oxygen supplement
In infants who require an O2 supplement, FRC can be measured
in one of two ways: calibration is performed with gas volumes of the same
FN2 as the infant is breathing, and FRC is calculated as described
earlier; calibration is performed with room air, with the calculated volume
subsequently being multiplied by a correction factor that accounts for the
difference in FN2 between calibration and alveolar gas 3.
The bias flow N2 washout technique becomes inaccurate when the fractional concentration of inspired oxygen is >0.7 3.
Helium/O2 (80/20%) has been used in premature infants to prevent exposure to high O2 concentration 28 but may not be used interchangeably 29. In addition, the effect of a helium/oxygen mixture on gas mixing, equilibration time and lung volume have yet to be evaluated 3. While pure O2 has been suggested to decrease tidal breathing significantly 30, 31, there are no data indicating that any potentially harmful effects could result from such short exposures to pure O2 as during FRC measurement.
Data acquisition
Data acquisition requirements are dealt with elsewhere in this series 21, 26, 27, 32. Particular points of relevance to lung
volume measurements are: 1) a sampling rate of 100 Hz is normally
adequate for the acquisition of FRCN2 data. However,
200 Hz may be required for rapidly breathing infants or the washout
volume/time measurements (see later). 2) Prior to data
acquisition, the operator should be prompted to enter whether a subject is
being tested or anin vitro assessment performed, so that any body
temperature, pressure and saturation (BTPS) corrections can be switched
on or off, respectively. The type of measurement should be indicated in the
report 11, 12. 3) Prior to the FRC measurements, tidal flow
and hencevolume should be corrected to BTPS conditions, assuming that inspired
air is at ambient temperature, pressure and saturation conditions (ATPS)
and expired air at BTPS conditions 26.
4) Volume drift, any drift of the tidal volume signal prior to switching
the infant into O2 during FRC measurement should be minimized.
5) A representative end expiratory level must be established (see
later). 6) In the absence of any injected air into the O2
circuit, there should be no drift in the baseline of the integrated nitrogen
signal (INS), that is the INS should read zero (arbitrary units),
after the three-way valve is activated. When testing patients with airway
obstruction, the period during which there is no drift must persist for at
least 90–120 seconds 11, 12. 7) End of test should be operator-controlled
rather than automatic. End of test is defined by a FN2 decreasing
to 0.0065 within the mixing chamber and N2 analyser, in the presence
of regular breathing. Before ending the washout, the operator must ensure
that this low N2 concentration has been recorded during regular
breathing. This can be confirmed by watching the movements of a collapsible
breathing bag provided this has been incorporated in the washout circuit (see
earlier) 11. In the absence
of such movements the test should continue, since the low N2 concentration
may simply be due to a brief apnoea. The infant's head may need to be
repositioned if there is any suggestion thatsuch an apnoea could be due to
a temporary upper airway obstruction rather than periodic breathing 11. 8) For calculation of FRCN2 see later. Measured FRC must be converted to BTPS conditions.
Calibration of the nitrogen analyser
Equipment calibration has a significant influence on the calculated results
and should be performed with utmost care and according to the manufacturer's
recommendations. It is essential that: adequate equipment warming times be
used according to the manufacturer's recommendation; calibration is performed
with the same equipment configuration as during measurements; the calibration
tools are checked periodically; qualified personnel, who understand boththe
procedure and data acquisition, perform thecalibration; manual calibration
is performed intermittently to check automatic calibration procedures.
After stabilization of the INS baseline, calibration with known low (LV) and a high (HV) room air volumes, below and above the infant's expected FRC, is performed. For a computerized system, integration of the mixed FN2 signal (INS) (arbitrary units) begins when the mixed FN2 value is >0.006. Washout is complete when FN2 falls <0.0065 in the mixing chamber 3.
The slope and intercept of the calibration line are calculated as follows 3:
|
| (003) |
|
| (004) |
|
| (005) |
With any BTPS correction switched off, calibration should be confirmed by using the same syringe volume on two consecutive occasions; the calculated washout volume should be within 1% of the known volume. After infant testing has been completed, calibration should again be confirmed with a known volume after installing a clean N2 circuit to avoid contamination of the calibrating syringe. This is important to check that there has been no drift of the N2 analyser during the testing period. The use of calibration volumes equivalent to the infant's measured FRC is recommended, as is the use of similar VT/FRC ratios and respiratory rates to those of the infant 7, 9, 11, 12.
Monitor display
See also Frey et al. 10.
Tidal breathing prior to FRC assessment
During data collection and/or replay, time-based displays of flow
and volume are required to observe breathing pattern and facilitate activation
of the slide valve at end-expiration.
During measurement of FRCN2
Once the slide valve is activated, a time-based display of the following
are required: the N2 concentration (FN2) curve
over time (s); the initial N2 concentration at the time
of switching the subject into O2 (should read 0.00);
the changes in the N2 concentration (displayed to two decimal
points) during washout; the integrated N2 signal (arbitrary
units).
After the washout is completed the operator needs to be able to: reject a curve before storage due to technical patterns, together with the ability to exclude (but not delete) selected trials during the analysis process; read off respective values of flow and volume during the tidal breathing recording prior to washout by, for example, moving a cursor through such data; examine/print any cumulative calculations/plots of volume by washout as a function of time, e.g. from time zero up to a certain point in time or over any specified time period.
In summary, it is essential that both graphics and tabulation be of sufficiently high standard to allow the user to decide when a washout is complete. Furthermore, printouts of washout curves should be of sufficient resolution for later quality assurance. It is essential that such curves are saved for later inspection.
Measurement protocol
Further practical details of how to apply this technique and interpret results have been described previously. The task force has published a book that collates much of the relevant information and discusses background issues that may influence the measurement 3.
Preparing the infant for measurements
The following are necessary when preparing the infant for measurements:
full resuscitation equipment, including suction, should be available at the
site of infant lung function testing; two individuals (other than parents)
should be present during testing, one of whom has the prime responsibility
for the infant's well being. The infant must never be left unattended;
the infant must be monitored continuously using at least a pulse oximeter;
the hospital-specific protocol for sedation must be adhered to; measurements
should be generally obtained with the sleeping infant laying supine. If other
postures are used, these should be clearly indicated; the neck and/or
shoulders should be supported in the midline in slight extension and position
stabilized by using a neck-roll or head ring; the face mask should be
transparent. It should cover the mouth and nose and be placed with minimal
pressure. An airtight seal can be maintained with a thin ring of silicone
putty; measurements should be restricted to periods of regular quiet breathing.
It is particularly important to avoid switching the infant into O2
during rapid eye movement sleep when FRC may be very unstable 33; if a squeeze jacket had been applied to perform
forced expiatory manoeuvrers, it must be unfastened before measuring FRC.
Preparation for collecting data for functional residual capacity
The following is necessary when preparing for data collecting of the functional
residual capacity: connecting the PNT-three way valve assembly to the
face mask and recording at least 30 s of tidal breathing prior to FRC
measurement; once a stable tidal breathing is observed on the monitor, switching
the infant into O2 as close to end-expiration as possible;
depending on the bias flow of O2 used and the length of the washout
tube carrying the mixed O2/N2 gas from the infant
to the N2 mixing chamber, the FRCN2 washout curve usually
rises above the baseline within one 11, 12 or more seconds. It reaches an initial
sharp peak followed by a stepwise decrease until the washout is complete.
When the nitrogen analyser reads an FN2 of 0.0065 within the N2 mixing chamber at the end of the washout period, the three-way
valve is activated switching the infant back into room air; the waiting period
in between tests should be at least twice the washout time. After a washout
has been completed and the infant is switched to room air, giving the infant
a few sigh breaths via a Y-adapter carrying a bias flow (12–15 L·min–1) of air and connected to the PNT can speed the restoration
of FAi,N2 11.
Potential sources of error when measuring FRCN2
In addition to equipment related errors, factors that may adversely affect
the accuracy of measurements 3, 7, 9, 11, 12, 25 include:
insufficient equipment warming times; inadequate equilibration of the calibrating
syringe with room air N2 after it had been used for calibration;
mask or circuit leaks; drift of the tidal volume signal and changes in the
end-expiratory level; baseline drifting of the N2 washout curve;
PNT calibration errors and effect of heating; errors in estimating mask/apparatus
dead space; retrograde movement of mixed O2 and N2 gas
after it has passed beyond the N2 sampling needle port; switching
errors above FRC; errors in BTPS correction; infant's apnoea during a
washout; inadequate interval between washouts; malfunction of the gas sampling
needle or the N2 analyser; incorrectly connecting the tube carrying
the washout mixed O2/N2 gas (fig. 1) to the outlet instead of the inlet
port of the N2 mixing chamber.
Calculations
Tidal breathing parameters
The tidal breathing parameters that need calculating include (see
also Bates et al. 26, 32): End
expiratory level (EEL); tidal volume; respiratory rate.
The end expiatory level (i.e. FRC) should be established over at least 5 breaths prior to switching the infant into O2, after correcting for any volume drift. For consistency, it is suggested that the EEL is calculated as the mean of all selected end expiratory points after drift correction, and that the selected level is clearly displayed on a time based trace for verification of accuracy by the operator. Some user flexibility may be required in those cases where EEL is particularly variable.
Calculation of FRCN2
As described earlier, the integrated mixed expired FN2 versus time (t) is multiplied by the constant flow
of O2 (V') to obtain the volume of expired
N2 (VN2):
|
| (006) |
|
| (007) |
|
| (008) |
The switching errors above FRC should be corrected for by subtracting any
volume above EEL (previously converted to BTPS conditions) from
the Veff-BTPS to obtain FRCN2 7, 12:
|
| (009) |
FRC should be calculated from at least two technically acceptable measurements that are within 10% or 10 mL of each other, whichever is the larger or, in the presence of increased variability, the mean of three technically satisfactory trials.
Quality control parameters
FRCN2 is the only "outcome measure" that
will be routinely reported from the nitrogen washout technique. Calibration
and raw data of FRC should be saved in ASCII or similar format. Data that
should be retrievable for validation purposes by the user, but not necessarily
visible, include the uncalibrated analogue-to-digital (A/D)
signal and all intermediate calculations leading to the final results. The
parameters that should be displayed/available for each individual trial
to assist in user or automated selection ofthe "best" data and
to provide overall quality assurance, are listed below. Since many of these
quality control features need to be summarized in publications describing
FRCN2 measurements in infants, it is essential that
such information can be automatically saved and, if required, exported to
a suitable spreadsheet.
The use of standard abbreviations as indicated would be of considerable benefit and is strongly recommended. The quality control and other parameters include: number of acceptable measurements (n); total number of measurements performed (n-tot); volume of apparatus dead space (Vds,app) (mL); type and size of mask e.g. Rendall Baker size; mean tidal volume prior to FRC measurement (VT (mL)); mean respiratory rate prior to FRC measurement (RR (min–1)); minute ventilation (expired minute ventilation) prior to FRC measurement, calculated as RRxVT (V'E; also referred to as MV); stability of EEL prior to switching the infant into O2, expressed as % variability of end expiratory points over "n" (five) breaths prior to each switching of the infant into O2 during FRC measurement (EEL%) 26, 27; stability of EEL prior to each switching into O2 during FRC measurement, expressed as the SD of the end expiratory points relative to the baseline over "n" (five) breaths prior to each manoeuvre (EEL-s, (mL)) 26, 27; volume above EEL reflecting the switching error above FRC (V>FRC (mL)); FRC washout time (tFRCN2 (s)); cumulative volume washed out at 50, 75, and 85% of the (total) washout time, FRC50N2, FRC75N2, FRC85N2 (the potential usefulness of such parameters have yet to be explored).
Reporting
Data should be reported according to the following: for FRC (mL)
the mean from three trials or a minimum of two if these are within 10%
or 10 mL of each other (see earlier); the coefficient of
variation (CV=100xSD/mean) of 3–5
technically satisfactory FRC measurements should be available as a measure
of the intra-subject variability; for quality control, a print out of
the FRCN2 nitrogen washout curve should also be provided;
a print out of the time-based flow and volume traces at the time of switching
into O2 is helpful; ideally, data should not be presented as "per
cent of predicted"; predicted values of FRCN2
beyond the neonatal period should be expressed as the regression of FRC on
crown-heel length along with the residual standard deviation (
RSD). Observed values of FRCN2 can then be
reported as the number of RSD removed from the predicted mean 34; FRCN2 may be
expressed per unit body weight during the first month of life as the regression
of FRC versus weight is fairly linear and passes close to zero. FRCN2 should never be expressed per unit body length, as neither
of the conditions discussed earlier are met 34; results can also be expressed in relation to the "normal
range" according to the infant's age and sex; a reference equation
from collated data of FRCHe 34 (table 1)
that can be used until sufficient reference data is obtained for FRCN2 is:
|
| (010) |
|
Each individual laboratory should attempt to study at least some healthy infants to check whether available reference data are appropriate for their population. Regular checks should also be made to ensure that the equipment produces appropriate values during in vitro assessment over the full range of lung volumes likely to be encountered during studies.
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), E. Bar-Yishay (Jerusalem,Israel), J.H.T. Bates (Montreal, Canada), C. Beardsmore (Leicester, UK), R. Castile (Columbus, OH, USA), J.B. Clough (Southampton, UK), A.L. Coates (Toronto, Canada), I. Dundas (London, UK), D. Filbrun (Colombus, OH, USA), U. Frey (Berne, Switzerland), S. Godfrey (Jerusalem, Israel), R. Gregson (Southampton, UK), M. 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), 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), D. Vilozni (Sharon, 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
infants 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. Filbrun, 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. No. 6: J. Stocks, S. Godfrey, C. Beardsmore, E. Bar-Yishay, R. Castile,
on behalf of the ERS/ATS Task Force on Standards for Infant Respiratory
Function Testing. Plethysmographic measurements of lung volume and airway
resistance. Eur Repir J 2001; 17: 302–31. 
References
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 M. R. Perez and D. J. Weiner Measurement of Forced Expiratory Flows and Lung Volumes NeoReviews, May 1, 2004; 5(5): e202 - e207. [Full Text] [PDF]
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G. Hulskamp, A.-f. Hoo, H. Ljungberg, S. Lum, J. J. Pillow, and J. Stocks Progressive Decline in Plethysmographic Lung Volumes in Infants: Physiology or Technology? Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 1003 - 1009. [Abstract] [Full Text] [PDF]
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 B. Reinmann, J. Stocks, and U. Frey Assessment of an infant whole-body plethysmograph using an infant lung function model Eur. Respir. J., April 1, 2001; 17(4): 765 - 772. [Abstract] [Full Text] [PDF]
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