Chest ACCP Career Connection
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bisgaard, H.
Right arrow Articles by Nielsen, K. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bisgaard, H.
Right arrow Articles by Nielsen, K. G.
(Chest. 2005;128:355-362.)
© 2005 American College of Chest Physicians

Plethysmographic Measurements of Specific Airway Resistance in Young Children*

Hans Bisgaard, MD, DMSci and Kim G. Nielsen, MD

* From the COPSAC Clinical Research Unit (Dr. Bisgaard), Department of Pediatrics, Copenhagen University Hospital, Gentofte; and Pulmonary Service (Dr. Nielsen), Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Correspondence to: Hans Bisgaard, MD, DMSci, Professor of Pediatrics, Copenhagen University Hospital, Gentofte, DK-2900 Copenhagen, Denmark; e-mail: Bisgaard{at}copsac.dk


    Abstract
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Validated methods for lung function measurements in young children are lacking. Plethysmographic measurement of specific airway resistance (sRaw) provides such a method applicable from 2 years of age. sRaw gauges airway resistance from the measurements of the pressure changes driving the airflow during tidal breathing. These measurements require no active cooperation and are therefore feasible in children from 2 years of age. The within-observer and between-observer variability of sRaw in young children compare favorably with alternative methods. Reference values are available for sRaw and have allowed discrimination of young children with respiratory disease. Bronchial hyperresponsiveness can be determined with acceptable short-term and long-term repeatability and provides good discrimination between asthmatics and healthy young children. The effects of the major antiasthmatic therapies have also been documented by this technique, and sRaw has recently been used in longitudinal studies of young children with chronic pulmonary diseases. Future developments should provide improved algorithms for thermal correction of the respired volumes and adapt the equipment to the special needs of young children. This article reviews the method, and proposes a protocol and criteria for quality assurance for assessment of sRaw in preschool children from 2 years of age. sRaw measurements offers a method for clinical monitoring and research during this critical period of growth and development early in life.

Key Words: airway resistance • child • method • preschool • specific airway resistance


    Introduction
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Longitudinal cohort studies12 suggest that outcomes in older children and adults with asthma may be determined primarily in early childhood. Measurement of lung function such as spirometry plays a key role in the management of children with chronic lung diseases such as asthma and cystic fibrosis, while such objective parameters are difficult in the age group < 6 years old. There are some measurements of lung function available for infants, while methods for measurements in the period between infancy and school children are sparsely reported. Whole-body plethysmography has been documented for measurements of airway resistance (Raw) in young children from 2 years of age.

Plethysmography was introduced by DuBois et al3 in 1956 for the assessment of Raw. The measurement of Raw requires a two-step procedure, with initial appraisal of the specific Raw (sRaw) through simultaneous recording of air flow and plethysmographic volume (Vpleth) swing during tidal breathing, and subsequent measurements of the thoracic gas volume (TGV) through recording of Vpleth swing and the corresponding mouth pressure swing while the subject performs tidal inspiratory and expiratory breathing (panting) against a closed shutter. Raw is then calculated as the ratio of sRaw/TGV. The procedure for measurement of TGV is poorly tolerated by young children, who often refuse or who perform the breathing maneuver against the closed shutter unsatisfactorily. Omitting this latter step provides measurements of sRaw and greatly facilitates the procedure allowing its use even in young children as suggested in 1976 by Dab and Alexander,45 but was not assessed until the recent decade.

Plethysmographic measurements of sRaw have lately been successfully adapted and approved for use in children from 2 years of age.67891011121314151617181920212223 Appropriate use of an adapted facemask, and an adult accompanying the child in the box has increased acceptance of this method.8 The approach to measurements of flow and pressure swing in a plethysmograph during tidal breathing is noninvasive and acceptable for use in awake young children from 2 years of age. The technique allows measurements during normal tidal breathing and requires only the passive cooperation of the child, independent of the child’s ability to follow verbal instructions.

It is the aim of this article to further a wider dissemination of measurements of sRaw in young children in research as well as in clinical practice. With this aim, this article explains the simple principles of sRaw measurements, reviews the data on the validity of the method in young children, proposes a protocol for assessing sRaw, and suggests areas for future research.


    Physics
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
sRaw is a measure of airway caliber-comprising effects of lung size. sRaw reflects the overall dimensions of the airway, including the effect of lung expansion on the caliber of the airway. Since sRaw is the product of Raw and TGV, it cannot distinguish if improvements are due to either of its two components. Breathing at different levels of lung volume might give the same sRaw, although the relationship between Raw and TGV differs. Likewise, other principles of lung function measurements do not distinguish the effect of lung volume on the flow or resistance.

Any increase, however, of Raw or increase of TGV or both results in an elevated sRaw. Similarly, sRaw will decrease if either Raw or TGV or both are minimized, and a normal sRaw would indicate that both Raw and TGV must be in a normal range. That is why sRaw is the more dynamic parameter, as supported in empiric data comparing sRaw and Raw in asthmatics and healthy children.24 In summary, sRaw is always reflecting the complete respiratory tract, consisting of both resistive and volume properties.


    Measurements of sRaw
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
The child breathes though a flowmeter (pneumotachograph) recording the flow () while seated inside a sealed, volume-constant box equipped with a pressure transducer that records changes of pressure inside the plethysmograph (Fig 1 ). This enables the measurement of the variations of the pressure in the plethysmograph due to the compression of the lung gas volume during expiration and decompression during inspiration through the breathing cycle, ie, the effort driving the flow is reflected as the pressure swing within the box. Calculating the Raw from pressure difference and flow is analogous with Ohms law of resistance in an electric circuit.



View larger version (174K):
[in this window]
[in a new window]
[Download PPT slide]
 
Figure 1. A 3-year-old child in the whole-body plethysmograph. {Delta}V indicates the volume (pressure) swing caused by the child’s thoracic excursions during tidal breathing as measured by pressure transducers in the box. indicates the respiratory flow during tidal breathing as measured by the pneumotachograph. sRaw is assessed from the ratio {Delta}V/.

 
Volume and pressure in the plethysmograph is calibrated before measurements, whereby the change in Vpleth ({Delta}Vpleth) is measured through the change in box pressure. The simultaneous recordings of and {Delta}Vpleth are depicted as the specific resistance loop and the inserted straight parameter line from which sRaw is calculated (Fig 2 ):

where ({Delta}Vpleth/{Delta}) corresponds to 1/tan ß as shown in Figure 2, Pamb is ambient pressure, PH2O is the pressure of water vapor at body temperature, and Pamb – PH2O is the approximate thoracic gas pressure.



View larger version (33K):
[in this window]
[in a new window]
[Download PPT slide]
 
Figure 2. An illustration of how different estimates of sRaw may be calculated from the specific resistance loop depending on how various parameter lines are applied on the loop and the slope of such lines.

 

    Equipment
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
The constant-volume, whole-body plethysmograph is in principle a sealed cabin. The flow may be measured by a pneumotachograph or other flowmeters. Commercially available plethysmographs are built for adults and are typically approximately 800 L. The price of the equipment is approximately $50,000 (US dollars). Commercially available ple-thysmographs are available in most secondary and tertiary care units, which allows a widely disseminated use of this method, although their size and price precludes their use in field studies and in most primary care facilities.


    Practical Aspects
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Standard commercial equipment and software is basically sufficient. However, some adaptations to standard, whole-body plethysmography may be required, including entertainment (video) to attract the child’s interest during the test and to distract him/her from potential discomfort from the closed box, the seat, and the adapted facemask.6 Also, a dedicated, trained, and committed pulmonary function technician is important.

Seating of the Child
The child is seated upright in the box with the neck slightly extended and with avoidance of flexion or rotation, since measurement of Raw is influenced by the position of the neck that may compress the airways. To ensure slight neck extension as well as to improve cooperation of the patient, a monitor showing video cartoons may be placed in front and above the patient during all measurements. Communication via microphone and loudspeaker ensures instruction of the child and adult during testing. The walls of the box should not be touched during measurement, since this confounds the pressure (volume) signal.

Accompanying Adult in the Box
If the child refuses to enter the whole-body plethysmograph alone or otherwise is uncooperative, sRaw measurements may be attempted with an adult person accompanying the child inside the plethysmograph.8 sRaw measured by this procedure shows good agreement with values obtained from the child alone.8 It is recommended for the adult to perform a constant slow expiratory maneuver for a period of 20 s, which allows sufficient time for measurement of sRaw of the child. Such a maneuver gives rise to a slight continuous drift of the signal measuring {Delta}Vpleth, which is corrected for by the data-processing software together with the drift from temperature buildup, and is easily separated from the more rapid pressure swing of the child’s breathing. Most commercial software compensates such slow drift expected from temperature buildup and will therefore adapt to the accompanying adult. Breath-hold has also been successfully attempted2025 but introduces a risk of thoracic or abdominal excursions, causing disturbance less likely to occur during a continuous expiratory maneuver.

Mouthpiece/Facemask
Measurement of lung function normally requires the subject to wear a nose clip and keep the lips sealed around a mouthpiece. In young children, such requirements detract from acceptance. With a standard facemask, the child is likely to breathe through the nose. To overcome these difficulties, we recommend a facemask with a large cushion, which ensures a good seal and stabilizes the cheeks and chin.6 To avoid nasal breathing, a built-in flexible tube ensures that the mouth remains open (ie, a mouth opener and not an actual mouthpiece since the seal is secured by the facemask).

Respiratory Breathing Frequency
sRaw measurements performed with commercially available electronic body temperature and pressure, saturated (BTPS) compensation exhibit positive frequency dependency.826 When electronic BTPS compensation is used, measurements should be made at breathing frequencies of 30 to 45 breaths/min, which will also reduce the risk of disturbance caused by irregular breathing. Most children of 2 years and 3 years of age breathe at the required frequency either spontaneously or as a result of the use of facemask, but coaching of children > 3 years old may be required.

Collection of Measurements
The child should be seated in the closed box for at least 1 min prior to lung function testing to stabilize temperature buildup in the box. Once testing is started, spirometry traces will be monitored; when a stable breathing pattern, defined from a regular tidal volume-time curve, and a breathing rate within the target range have been established, five separate, specific resistance loops will be collected.

Blinding of Measurements
Treatment with placebo provided significant bronchodilation in a double-blind study.17 This suggests an observer bias in the conduct of the measurements despite a carefully described protocol. Likewise, a placebo effect was seen with the interrupter technique and impulse oscillometry.17 Such observer bias is probably inherent to any lung function measurement. Therefore, it is recommended that whenever possible the operator should be kept unaware of the history of the patient tested.


    Quality Control of Measurements
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Data Analysis
On-line display of the flow-pressure loops allows deletion of artifacts such as abnormal patterns caused by swallowing, vocalization, breath-hold, coughing, or leakage around the facemask. The decision whether to accept or reject a measurement should be made on-line during measurements, not allowing subsequent censoring of the data.

Pressure builds up in the box while the door is closed due to rising temperature. This constant drift in the box pressure is compensated for in most commercially available data-processing software.

sRaw Estimates
sRaw is calculated as the median value of five technically satisfactory specific resistance loops. Figure 2 illustrates how different estimates of sRaw may be calculated from the specific resistance loop depending on how various parameter lines are applied on the loop and the slope of such lines. The method used for calculation of sRaw should always be stated: sRawTOT is the parameter line connecting the flow points at maximum change in Vpleth (pressure); sRawmax is the parameter line connecting the maximum flow points; sRaw0.5 or sRaw0.2 are the parameter lines connecting the points where the flow reaches fixed values such as 0.5 L/s or 0.2 L/s, respectively; sRaw50% is the parameter line connecting the points where the flow is 50% of the maximal flow reached (not shown, but resembles sRaw0.5 or sRaw0.2); sRawMID is the parameter line through the relevant midpoints of the lines formed by the intersections of the loop at the flow values ± 0.5 L/s.

sRawTOT seems to be more sensitive or as sensitive as other methods of estimating the total resistance, although this estimate may have a higher variability as compared with sRaw0.2 and sRaw50%.12 However, detailed comparisons of such different algorithms need to be further studied.

BTPS Correction
{Delta}Vpleth caused by changes in temperature and humidity of the air inspired by the subject during the measurements needs to be adjusted to BTPS, particularly at low breathing frequency.2627 Most commercially available plethysmographs perform an electronic compensation to simulate conditioning of the inspired and expired air. This affects the accuracy of sRaw measurements and has been reported to cause significant overestimation.826 Using a heated rebreathing system, Buhr et al24 found a negative breathing-frequency dependence of sRaw, which tends to counteract the positive frequency dependence found with electronic compensation.

Equipment-Specific Adjustments
Correction must be made for the dead space of the apparatus. Correction must be made for the resistance of the pneumotachograph (Rscreen)28:

Since TGV is not measured, the predicted values of TGV according to body height are used for the above correction. Correction must be made to allow for the volume displacement caused by the adult person if one accompanies the child in the box:

where Vsubject is the volume of the accompanying adult as approximated from weight.


    Acceptance
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
The acceptability of measurements of sRaw is good. Since no active cooperation is required, sRaw measurements should be feasible at a younger age than methods requiring active cooperation. Clearly, acceptance increases with age, but many children from 2 years of age can perform acceptable measurements. Particularly, children familiar with the use of facemasks are successful from an early age.

At the age of 2 years, 57% of untrained healthy children (n = 28) completed the measurement.10 At the age of 3 years, 65% of untrained healthy children (n = 31) completed measurements.10 Likewise, in a large birth cohort study of 766 children, 66% completed measurements at 3 years of age.20

The main reason for failure to obtain measurements was that the child was unfamiliar with the facemask.10 A short period of training can improve the acceptance, since the majority of very young children will accept the facemask if they are allowed to spend some time playing with it. In conclusion, sRaw allows measurements from 2 years of age.


    Reference Values
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
sRaw is independent of height and gender,52930 facilitating the interpretation of measurements carried out longitudinally in individual children. We reported measurements of sRaw in 121 healthy 2- to 7-year-old white children (61 boys and 60 girls), with approximately 20 youngsters at each year of age. The participants in this study had no history of recurrent lower respiratory symptoms, no history of eczema and no atopic first-degree relatives, no significant exposure to tobacco smoke, and no history of respiratory symptoms during 1 month prior to the examination of lung function. The reference value for sRawTOT was 1.3 kPa/s and 1.1 kPa/s for sRawmax. Neither measurement of sRaw showed any significant correlation with gender, age, weight, or height.10 Other studies52930 have reported values of sRawmax ranging from 0.45 to 1.0 kPa/s. The difference is probably due to the use of electronic BTPS compensation in the former study and heated rebreathing system in the latter.

Such substantial differences between the absolute values in currently available reference materials emphasize the need for standardization. Relating sRaw measurements to the available reference data assumes the use of similar method. The relation to reference values should preferably be expressed as z-scores (deviation in multiplex of the SD of the reference material).


    Reliability
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Within-Observer Repeatability
Short-term Repeatability (Within-Day):
Repeatability is slightly dependent on the chosen estimate for sRaw. The total SD for sRaw is in the range of 0.20 to 0.21 kPa/s, with its constituents the within-subject SD (SDw) and between-subject SD (SDb) ranging from 0.086 to 0.109 kPa/s and 0.19 to 0.20 kPa/s, respectively. Correcting SDb for the SDw gives SDb in the range from 0.172 to 0.176 kPa/s. The within-subject coefficient of variation is in the range of 8 to 11%, and the short-term intraclass correlation coefficient (ICC) within occasion is 0.86.4810 Repeatability is independent of age,10 and measurements of sRaw with and without an accompanying adult do not significantly change repeatability.8

Long-term Repeatability (Weeks):
No long-term data on repeatability in healthy young children exist. However, repeatability 1 month apart in young children with asthma showed an ICC of 0.87 between occasions,9 similar to the within-occasion ICC in healthy subjects.10

Between-Observer Repeatability
SDw of measurements obtained by two trained observers according to a predefined protocol is greater than the within-observer variability. This between-observer variability of sRaw appeared to be reduced when sRaw was calculated as sRaw0.2 or sRaw50% instead of the sRawTOT.12

Accuracy
Accuracy of sRaw has been evaluated against measurements under BTPS conditions, which showed that the available electronic BTPS compensation causes significant overestimation in children.826

Sensitivity
The sensitivity to pharmacologically induced changes of airway patency (eg, by inhalation of bronchoconstrictor or bronchodilator agents) as well as during acute severe asthma was comparable for sRaw, transcutaneous oxygen, and impulse oscillometry measurements in young children from 2 years of age. Their sensitivity was better than that of spirometry and interrupter airway resistance.67


    Response to Bronchodilators
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Two provisos should be made when evaluating the response to ß-agonist as an indication of asthma. First, there is no standard for estimating the response to a ß-agonist. It may be calculated as the absolute change, the percentage change from baseline, the number of SDw units, or the percentage change of the predicted value.1731 The latter expresses an estimate of the absolute ß-agonist response independent of baseline lung function, age, and height, and may therefore be recommended.1731

Secondly, healthy young children have an inherent bronchomotor tone as seen from a 16% decrease in sRaw after inhaled ß2-agonist.17 Asthmatics bronchodilate significantly more than healthy children, attesting to their increased bronchomotor tone.17 Receiver operating curve analysis has suggested three SDw units (corresponds to a change of 25%) as the optimal cut-off level for discriminating healthy and asthmatic preschool children, providing a sensitivity of 66%, a specificity of 81%, and predictive value of a positive test result of 84%.17 The discrimination by sRaw was found to be better than that obtained by the interrupter and impulse oscillometry techniques. In conclusion, it is recommended to use a 25% decrease in sRaw relative to the predicted value as the cut-off to screen for asthma in young children.


    Challenge Tests
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Bronchial responsiveness to direct stimuli such as methacholine and histamine can be estimated safely and reliably in young children from 2 years of age by measurement of sRaw.92532 Dosimetry is recommended to reduce the variability of the dose of the drug to the lung. The day-to-day repeatability studied in eight young children showed a mean repeatability of 0.7 (SD, 0.6) doubling doses, comparable to that reported in school children and adults.9 Another study32 showed good correlation between bronchial responsiveness measured on 2 consecutive days. However, the test is time-consuming due to the multiple-step protocols defining the dose-response curves. Such repeated lung function tests detract from acceptance in young children.

Cold dry air hyperventilation challenge is an alternative stimulus for the test of bronchial hyperresponsiveness. It can be performed as a single-step test with a good acceptability. Software that visually prompts the child to hyperventilate is available and will be provided as shareware (www.copsac.dk). Cold dry air hyperventilation with sRaw as outcome provides a good separation between asthmatic and nonasthmatic young children with a sensitivity of 68%, specificity of 93%, and predictive values of positive and negative test results of 93% and 69%, respectively, which is superior to the use of interrupter airway resistance and impulse oscillometry in such challenge. The long-term repeatability is good, with a correlation coefficient of 0.96 between sRaw responses to cold dry air hyperventilation challenge repeated within 8 weeks.14 Hyperventilation with dry air at room temperature may be an even simpler and less expensive test similar in mechanism to that of cold dry air hyperventilation challenge. However, responsiveness to cold dry air hyperventilation exceeded responsiveness to dry air challenge and cold dry air hyperventilation seemed to induce refractoriness in contrast to dry air challenge, probably because of the additional stimulus from airway cooling.19 This suggests cold dry air hyperventilation as the preferred method.

In conclusion, cold and/or dry air hyperventilation challenge is feasible in young children from 2 years of age. Whole-body plethysmography (sRaw) seems superior to other methods separating asthmatics from healthy control subjects. Change in sRaw in response to cold and/or dry air hyperventilation challenge may be used as a diagnostic test for asthma in young children.


    Discrimination Between Health and Disease
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Studies in children suggest that sRaw is as efficient as Raw and TGV in distinguishing between asthmatic and healthy children. In a study24 of children aged 5 to 8 years, the single-step sRaw measurement discriminated more accurately between healthy and asthmatic children than did the measurement of Raw.

sRaw was significantly increased compared to healthy control subjects in random11 and selected groups of 2- to 6-year-old asthmatics.1314151724 sRaw was reported in 110 consecutive 2- to 5-year-old children who had a history of three or more episodes of wheezing after the age of 1 year. sRaw was measured while the children were without clinical symptoms. Fourteen percent had sRaw values greater than the 97.5% range for healthy children,11 representing a significant proportion of subclinically impaired lung function in young asthmatics. Similarly, sRaw related significantly to history of recurrent wheeze in a longitudinal birth cohort study.20

Antiasthma treatments have been evaluated in young children, including the effects of inhaled corticosteroid,15 leukotriene receptor antagonist,13 and short-acting17 and long-acting ß2-agonists.16 Confirming the effects of these classic antiasthma treatments in young asthmatic children substantiate the relevance of the sRaw measurements and their ability to separate controlled from uncontrolled asthma.

sRaw has been shown to be a relevant objective parameter used in serial18 and cross-sectional23 measurements in preschool children with cystic fibrosis. In a 4-year prospective study18 with serial measurements of sRaw, a consistently abnormal, increased level of sRaw was demonstrated from preschool to school age, but not by measurements with impulse oscillometry or interrupter resistance.


    Future Directions
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
Improvements of equipment and software are needed for more reliable measurement of sRaw in young children. Improvements in the equipment should pay special attention to the seating and footrest. A facemask with a large cushion and a built-in noncompressible yet soft tube should be made available. Software improvements should specifically focus on the algorithms for thermal correction of the inspired volumes. The software should include an algorithm for automatic selection of acceptable and rejection of unacceptable loops.

Interactive software with visual prompts should serve as an instructional aide for the child to target the relaxed tidal breathing pattern and the breathing rate and provide biofeedback. Reference materials should be included in the software of the plethysmograph with allowance for the use of individual materials. Reporting of measurements should add the z-score.

The protocol proposed in this article on measurements of sRaw should be further explored. Optimal breathing frequency, number of loops collected, and criteria defining the line through the flow-pressure loop need to be further validated, and the best method to reduce the confounding effect of an accompanying adult should be studied (breath-hold vs slow exhalation).

Long-term repeatability should be determined, and more comprehensive multicenter reference values from healthy children of different ethnicity should be collected. Determination of intercenter reproducibility and variability of the technique has important relevance for its application to multicenter clinical trials. Further studies in chronic lung diseases such as cystic fibrosis, bronchopulmonary dysplasia, and congenital malformations in the airways are important and feasible with the sRaw method since knowledge of lung function in such diseases during preschool age is very limited.


    Conclusions
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 
sRaw measurements are feasible in children from 2 years of age. The reliability and feasibility compares favorably with alternative methods. sRaw allows clinical monitoring and research during this critical period of growth and development in early life. sRaw measurements promise to bridge the gap of lung function measurements between infancy and school age.


    Footnotes
 
Abbreviations: BTPS = body temperature and pressure, saturated; ICC = intraclass correlation coefficient; Pamb = ambient pressure; PH2O = pressure of water vapor at body temperature; Raw = airway resistance; SDb = between-subject SD; SDw = within-subject SD; sRaw = specific airway resistance; sRawTOT = parameter line connecting the flow points at maximum change in plethysmographic volume (pressure); sRawmax = parameter line connecting the maximum flow points; sRaw0.2 = parameter line connecting the points where the flow reaches 0.2 L/s; sRaw0.5 = parameter line connecting the points where the flow reaches 0.5 L/s; sRaw50% = parameter line connecting the points where the flow is 50% of the maximal flow; TGV = thoracic gas volume; = air flow; Vpleth = plethysmographic volume; {Delta}Vpleth = change in plethysmographic volume

Received for publication September 9, 2004. Accepted for publication December 16, 2004.


    References
 TOP
 Abstract
 Introduction
 Physics
 Measurements of sRaw
 Equipment
 Practical Aspects
 Quality Control of Measurements
 Acceptance
 Reference Values
 Reliability
 Response to Bronchodilators
 Challenge Tests
 Discrimination Between Health...
 Future Directions
 Conclusions
 References
 

  1. Martinez, FD, Wright, AL, Taussig, LM, et al (1995) Asthma and wheezing in the first six years of life: The Group Health Medical Associates. N Engl J Med 332,133-138[Abstract/Free Full Text]
  2. Sears, MR, Greene, JM, Willan, AR, et al A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med 2003;349,1414-1422[Abstract/Free Full Text]
  3. DuBois, AB, Botelho, SY, Comroe, JH, Jr A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease. J Clin Invest 1956;35,327-335[ISI][Medline]
  4. Dab, I, Alexander, F A simplified approach to the measurement of specific airway resistance. Pediatr Res 1976;10,998-999[Medline]
  5. Dab, I, Alexander, F Lung function measured with a whole body plethysmograph: standard values for children and young adults. Acta Paediatr Belg 1979;32,259-267[ISI][Medline]
  6. Bisgaard, H, Klug, B Lung function measurement in awake young children. Eur Respir J 1995;8,2067-2075[Abstract]
  7. Klug, B, Bisgaard, H Measurement of lung function in awake 2–4-year-old asthmatic children during methacholine challenge and acute asthma: a comparison of the impulse oscillation technique, the interrupter technique, and transcutaneous measurement of oxygen versus whole-body plethysmography. Pediatr Pulmonol 1996;21,290-300[CrossRef][ISI][Medline]
  8. Klug, B, Bisgaard, H Measurement of the specific airway resistance by plethysmography in young children accompanied by an adult. Eur Respir J 1997;10,1599-1605[Abstract]
  9. Klug, B, Bisgaard, H Repeatability of methacholine challenges in 2- to 4-year-old children with asthma, using a new technique for quantitative delivery of aerosol. Pediatr Pulmonol 1997;23,278-286[CrossRef][ISI][Medline]
  10. Klug, B, Bisgaard, H Specific airway resistance, interrupter resistance, and respiratory impedance in healthy children aged 2–7 years. Pediatr Pulmonol 1998;25,322-331[CrossRef][ISI][Medline]
  11. Klug, B, Bisgaard, H Lung function and short-term outcome in young asthmatic children. Eur Respir J 1999;14,1185-1189[Abstract]
  12. Klug, B, Nielsen, KG, Bisgaard, H Observer variability of lung function measurements in 2–6-yr-old children. Eur Respir J 2000;16,472-475[Abstract]
  13. Bisgaard, H, Nielsen, KG Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children. Am J Respir Crit Care Med 2000;162,187-190[Abstract/Free Full Text]
  14. Nielsen, KG, Bisgaard, H Lung function response to cold air challenge in asthmatic and healthy children of 2–5 years of age. Am J Respir Crit Care Med 2000;161,1805-1809[Abstract/Free Full Text]
  15. Nielsen, KG, Bisgaard, H The effect of inhaled budesonide on symptoms, lung function, and cold air and methacholine responsiveness in 2- to 5-year-old asthmatic children. Am J Respir Crit Care Med 2000;162,1500-1506[Abstract/Free Full Text]
  16. Nielsen, KG, Bisgaard, H Bronchodilation and bronchoprotection in asthmatic preschool children from formoterol administered by mechanically actuated dry-powder inhaler and spacer. Am J Respir Crit Care Med 2001;164,256-259[Abstract/Free Full Text]
  17. Nielsen, KG, Bisgaard, H Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years. Am J Respir Crit Care Med 2001;164,554-559[Abstract/Free Full Text]
  18. Nielsen, KG, Pressler, T, Klug, B, et al Serial lung function and responsiveness in cystic fibrosis during early childhood. Am J Respir Crit Care Med 2004;169,1209-1216[Abstract/Free Full Text]
  19. Nielsen, KG, Bisgaard, H Hyperventilation with cold versus dry air in 2 to 5 year old children with asthma. Am J Respir Crit Care Med 2005;171,238-241[Abstract/Free Full Text]
  20. Lowe, L, Murray, CS, Custovic, A, et al Specific airway resistance in 3-year-old children: a prospective cohort study. Lancet 2002;359,1904-1908[CrossRef][ISI][Medline]
  21. Lowe, LA, Simpson, A, Woodcock, A, et al Wheeze phenotypes and lung function in preschool children. Am J Respir Crit Care Med 2005;171,231-237[Abstract/Free Full Text]
  22. Woodcock, A, Lowe, LA, Murray, CS, et al Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years. Am J Respir Crit Care Med 2004;170,433-439[Abstract/Free Full Text]
  23. Aurora, P, Bush, A, Gustafsson, P, et al Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis. Am J Respir Crit Care Med 2005;171,249-256[Abstract/Free Full Text]
  24. Buhr, W, Jorres, R, Knapp, M, et al Diagnostic value of body plethysmographic parameters in healthy and asthmatic young children is not influenced by breathing frequency. Pediatr Pulmonol 1990;8,23-28[Medline]
  25. Badier, M, Guillot, C, Dubus, JC Bronchial challenge with carbachol in 3–6-year-old children: body plethysmography assessments. Pediatr Pulmonol 1999;27,117-123[CrossRef][Medline]
  26. Peslin, R, Duvivier, C, Malvestio, P, et al Frequency dependence of specific airway resistance in a commercialized plethysmograph. Eur Respir J 1996;9,1747-1750[Abstract]
  27. Peslin, R, Duvivier, C, Vassiliou, M, et al Thermal artifacts in plethysmographic airway resistance measurements. J Appl Physiol 1995;79,1958-1965[Abstract/Free Full Text]
  28. Haluszka, J, Willim, G, Cutrera, R, et al A correction formula for computing specific airway resistance from a single-step measurement. Pediatr Pulmonol 1989;6,118-121[Medline]
  29. Doershuk, CF, Fisher, BJ, Matthews, LW Specific airway resistance from the perinatal period into adulthood: alterations in childhood pulmonary disease. Am Rev Respir Dis 1974;109,452-457[ISI][Medline]
  30. Leben, M, von der Hardt, H Airway resistance, airway conductance, specific airway resistance, and specific airway conductance in children. Pediatr Res 1983;17,508-513[Medline]
  31. Waalkens, HJ, Merkus, PJ, Essen-Zandvliet, EE, et al Assessment of bronchodilator response in children with asthma: Dutch CNSLD Study Group. Eur Respir J 1993;6,645-651[Abstract]
  32. De Baets, F, Van Daele, S, Franckx, H, et al Inhaled steroids compared with disodium cromoglycate in preschool children with episodic viral wheeze. Pediatr Pulmonol 1998;25,361-366[Medline]



This article has been cited by other articles:


Home page
NEJMHome page
H. Bisgaard, M. N. Hermansen, L. Loland, L. B. Halkjaer, and F. Buchvald
Intermittent inhaled corticosteroids in infants with episodic wheezing.
N. Engl. J. Med., May 11, 2006; 354(19): 1998 - 2005.
[Abstract] [Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bisgaard, H.
Right arrow Articles by Nielsen, K. G.