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Lung function tests for pre-school children
PAEDIATRIC RESPIRATORY REVIEWS (2001) 2, 37–45 doi: 10.1053/prrv.2000.0100, available online at http://www.idealibrary.com on
SERIES: LUNG FUNCTION TESTING
Lung function tests for pre-school children S. A. McKenzie, P. D. Bridge and C. S. Pao Department of Paediatric Respiratory Medicine, Royal London Hospital, London, UK KEYWORDS lung function tests, interrupter technique, forced oscillation
Summary There are a few devices for measuring lung function in pre-school children. Neither the interrupter technique nor the forced oscillation techniques have been standardised.We highlight some of the issues around the measurement of airway resistance using the interrupter technique and emphasise that, as with other lung function measurements, operators should have a proper understanding of the methods before they can be applied. Both methods for measuring airway resistance have potential for clinical and research application. © 2001 Harcourt Publishers Ltd
INTRODUCTION Until recently, there were no lung function tests suitable for the majority of pre-school children. Only a few children are able to perform the forced expiratory manoeuvres necessary to measure peak flow accurately or perform spirometry reliably. What lung function testing in this age group needs, at the very least, is passive co-operation without the need for co-ordination. Four tests are potentially useful in this age-group: the measurement of peak flow using a whistle, incentive display spirometry, and the measurement of airway resistance by the interrupter (Rint ) and oscillation techniques (forced or impulse). These tests have moved out of the research laboratory and into routine use in some lung function laboratories. The peak flow whistle (PFW) is a simple device providing an audio incentive to encourage optimal results with a peak flow (PF) manoeuvre. Incentive display spirometry (IDS) uses an animated display to encourage optimum forced blows. Both these techniques are simply improvements on established techniques that should enable wellunderstood parameters to be obtained within a larger percentage of the pre-school population with increased reliability. Interruption and oscillation techniques measure airway resistance. They depend on a high level of sophistication from the equipment. Additionally, there is much discussion about what the “resistance” values obtained represent. Standardisation of both techniques is being considered. They require only passive co-operation, a considerable advantage in pre-school children. The majority of this review will feature the Rint technique. The size, cost and simplicity of use of the 1526–0550/01/010037 + 09 $35.00/0
equipment and the requirement of only passive cooperation suggests that this technique is suitable for young children in the ambulatory setting. Our own results demonstrate its feasibility1 and there is a good sensitivityspecificity profile for detecting bronchodilator responsiveness in children with previous wheeze.2
OTHER SPECIAL TECHNIQUES Another method investigated in 2–5-year-olds is whole body plethysmography with an accompanying adult.3 This method is not suitable for use outside a specialised lung function testing centre due to the cost, size and complexity of the equipment. Techniques such as assessment of lung volumes by helium dilution and assessment of inflammation by induced sputum and exhaled nitric oxide are generally considered to be unsuitable for the majority of children under 7 years. Also, they require larger, more expensive and complex equipment and would not be suitable for the ambulatory environment. Whilst not really a conventional lung function test, change in transcutaneous oxygen has been measured by several investigators and has been shown to be a sensitive indictor of bronchoconstriction during challenge testing. This measurement was preferred to chest auscultation for wheeze which developed in some children after they had become hypoxic.4 It has been shown in infants that, using the high speed interrupter technique,5 it is possible to obtain non-invasive information on both airway geometry and airway wall mechanics, which is useful in understanding airflow limitation phenomena. However, this technique is likely to remain a research tool for the foreseeable future. © 2001 Harcourt Publishers Ltd
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Peak flow whistle (PFW) Some very young children can manage peak flow without an incentive.6 The peak flow whistle (PFW) was developed to try to improve PF results, by encouraging children to blow harder and harder to produce a higher and higher tone, but PFWs do not appear to be widely used, perhaps because of the reservations about PF measurement in children.7 The PFW should help pre-school children but there is no evaluation of it in this age-group.
Animated incentive display spirometry (IDS) Young children can find it difficult to comprehend what is required for good spirometry. Some modern computerised spirometers, such as Jaeger’s Masterscreen Pneumo, have software animated incentive devices to motivate both adults and children to blow hard, down to residual volume (RV). Unless a forced blow is continued down to RV it is not possible to measure mid-expiratory flow (FEF50), FEV1/VC ratios or to obtain a clear picture of the degree of curvature on the flow-volume curve. Also, for the severely obstructed, it may take several seconds to reach RV. Incentive displays should help with both comprehension and motivation in young children. A study of spirometry measurements using an incentive device during forced expirations demonstrated an improved performance in children 4–10 years old.8 Readings were more reproducible. Higher values in relation to height were obtained with the spirometer with the incentive device compared to a spirometer without one and so normal values have been readjusted in the 4–7year-olds to reflect this. The relationship of FEV1 to height across this age-range has been shown to be non-linear.
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The animation used in IDS is important. The best at the moment appears to be a curly party-whistle or candles on a birthday cake (Fig. 1). Incentive spirometry (IS) to improve inspiration is used as a therapeutic tool to try to decrease atelectasis in patients who have had thoracotomies and upper abdominal surgery, and in children with sickle cell disease. An adapter to the spirometer can be fitted to tracheostomies. It is also helpful in following postoperative lung function, as IS correlates well with vital capacity. However, there do not appear to be any readily available commercial spirometers that incorporate inspiratory incentive displays. Young children frequently find it difficult to comprehend the concept of inspiring to total lung capacity (TLC), resulting in sub-maximum and inconsistent forced expiratory parameters. It seems important to develop an incentive device to encourage small children to inspire at a reasonable rate up to TLC – for instance, using a glass containing a drink. This may help prevent closure of the glottis which can occur during a rapid inspiration. It remains to be seen whether the availability of incentive devices will increase the number of pre-school children with respiratory symptoms who can have forced expiratory volumes and flows measured. Even with the use of incentive displays, it is important to appreciate that many pre-school children will find it difficult to undertake lung function tests successfully at a first attempt unless sufficient time is allowed for training and encouragement. This would appear to be especially true in the case of forced blows.9
The interrupter technique (Rint) for measurement of airway resistance This technique is not new, but interest in its development waned when values were found to differ from ‘gold standard’ plethysmography values of airway resistance. In the 1980s interest was revived when the physiology of the measurement was considered in both animals and man and technical aspects of the technique were refined.10
What does Rint measure?
Figure 1 The curly party-whistle incentive device for the Masterscreen Pneumo (Jaeger).
The measurement of Rint is based on the premise that when the airway is suddenly occluded, there is a pressure change at the mouth, which equates to the resistive pressure drop across the airway. The ratio of the pressure drop to the airflow immediately before the occlusion provides an estimate of resistance. This premise is simplistic because the method is influenced by the compliance of the upper airway and retarded equilibration between mouth and alveolar pressure in the presence of airway disease because of mechanical non-heterogeneity of the lungs. Bates and colleagues have shown in dog experiments that there are two components to the pressure trace
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Oscilatory Phase
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Figure 2 An acceptable mouth pressure curve (Pmo ) obtained after flow interruption using MicroRint in an asymptomatic child with intermittent wheeze.The initial rapid pressure rise (Pfast ) is followed by a series of oscillations and the secondary pressure change (Pslow ) consists of a slower increase in pressure. Pfast reflects airway resistance; Pslow approximates tissue and chest wall resistance.
after interruption (Fig. 2). In open-chested dogs, the first represents the pressure drop across the airways alone11 and the second pressure rise reflects the stress-recovery of the lung tissues and the effect of gas redistribution, which in histamine-challenged lungs can last for some time after interruption.12 Experiments on closed-chested dogs to examine the effect of the chest wall13 suggested that it introduced a significant additional component to the first pressure change. In humans the contribution of the chest wall to the first pressure change is less important as the airways have much more importance since they are smaller. The contribution of the effect of gas redistribution, especially important in disease, and chest wall resistance to the second component is not known. Whilst it is simple to measure flow, it is not possible to measure alveolar pressure non-invasively. Therefore, pressure is measured at the mouth, Pmo , during rapid flow interruption, typically over a 100 ms period. The measurements of pressure and flow are not simultaneous. Flow is measured before occlusion and pressure afterwards (Fig. 3a). It is the method of estimating the alveolar pressure, and hence resistive pressure drop across the airway, which is most controversial. There may never be agreement about what exactly this measures in humans. What can be said is that it reflects airway resistance and as
long as change can be measured with sensitivity, it should be a useful clinical and research tool. The main issues to resolve are the best method for measuring pressure and the “timing” of the occlusion within the tidal breath.
How should the pressure drop be estimated? The best method of estimating the pressure has yet to be determined. This dilemma is confounded by: (a) the time needed to close the valve, which according to Bates et al. should be within 10 ms10; and (b) incomplete equilibration of mouth and alveolar pressure within the time that the valve is closed, typically 100 ms. Equilibration between mouth and alveoli is almost instantaneous in the healthy lung. However, even in the case of moderate disease, equilibration is unlikely to have occurred within the duration of occlusion (Fig. 3a and b). Therefore, the pressure at the mouth does not equal alveolar pressure, the secondary phase rises slowly and the estimate of the resistive pressure drop across the airway may be falsely low. In order to address this, a two point back-extrapolation to the time of interruption was recommended by Phagoo.14 MicroMedical interrupter devices use T30 and T70 extrapolated back to T15 (MicroLab 4000) or To (Micro Rint ), so if equilibration is
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Flow (measured immediately prior to interruption)=292 ml/sec Rint=2.19 kPa.L–1.sec
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Figure 3 (a) A mouth pressure curve (Pmot) obtained after flow interruption using MicroRint in a child wheezy at the time of test at baseline. Note the curvature that is seen following the oscillations. Measurement is obtained before a plateau is reached. T0 = Time of interruption (T0 is defined as the point at which the pressure signal reaches 25% of the difference between the maximum value of the first clearly defined peak of pressure oscillations and the baseline value); T30 = 30 ms after interruption; T70 = 70 ms after interruption. (---) Interruption; (---..--..) calculation of pressure change using 2-point back extrapolation using T30 and T70; (——) calculation of pressure change at valve opening. (b) A mouth pressure curve (Pmot) obtained after flow interruption using MicroRint in the same child 20 min after inhalation of 400 µg salbutamol. The child is breathing at a slightly higher flow, the pressure change is less than pre-salbutamol and the calculated resistance Rint is lower. (---) Interruption; (---..--..) calculation of pressure change using 2-point back extrapolation using T30 and T70 T0; (——) pressure at valve opening.
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delayed beyond this, pressure change and thus resistance will be underestimated (Fig. 3a). Jaeger have selected the point at end-interruption for the measurement of pressure with flow measured immediately after opening. It remains to be seen which of these methods is ‘best’, i.e. most sensitive, for measuring change in Rint.
and attention span of the child. The mean or median of these readings (values) is the measurement.
Timing of the occlusion: peak of tidal flow or fixed flow or volume? There are three points at which occlusion can occur. Occlusion can be set to begin close to the peak of tidal flow either in inspiration (I) or in expiration (E), after a fixed volume has passed the transducer, or when a fixed flow has been reached. All three options have been implemented in commercially available devices. Triggering as close as possible to the peak of tidal flow (either E or I) during quiet breathing is the method used by MicroMedical. Measurements in our laboratory using a MicroRint, which displays flow against time, indicate that interruption occurs at the start of expiration and at the start of inspiration. If these timings correspond to high and low lung volumes, respectively, then RintE would be expected to be lower than RintI, the opposite of our findings and those of others (see below). This suggests that volume over the tidal range has little effect in the measurement of Rint. To achieve a near peak tidal flow occlusion, typically the device is set to detect a peak at a flow greater than 80% of the peak of the previous tidal flow.
How many interruptions (readings) are required for a valid measurement? Six acceptable readings will generally result in a coefficient of variation of <20%. There is no significant improvement with more than six. In pre-school children, at a first attempt, we have found the number of interruptions needed for six acceptable values is <10, median 6. This is important as, especially in the pre-school group in the ambulatory setting, it can be difficult to retain the cooperation
Mean or median? We have shown (in press) that there is no important difference between median and mean, <1% in pre-school children. The median of the six or so values should be used as the measurement, as this is less affected than the mean by outlying values. Such values cannot be avoided with fully automated equipment in which transients cannot easily be examined for acceptability. Some commercial devices collect values which are considered by the machine’s software to be acceptable. Inexperienced operators may overlook outlying values which could have resulted from poor technique, such as moving the head or blowing the cheeks out. We have shown that mean and median values in our data differed by very little, so that studies which have used the mean are still valid.1,2,15–17
What about the upper airway? Measurements made without supporting the cheeks give significantly lower readings.18,19 The nose should be clipped, the cheeks supported (Fig. 4) and transients inspected for acceptability (Fig. 2). Unacceptable traces are shown in Figures 5A and 5B. Some workers routinely make measurements using a tightly fitting17 mask but it is not known how well mask and mouthpiece measurements compare. Some manufactures include software to automatically reject mouth-pressure time transients (Pmo(t)) that appear to include artefacts but it is the responsibility of the technician to inspect all transients for acceptability according to published criteria14. This would suggest that fully automated devices are not to be recommended until the technology has moved a stage further.
Should interruption occur in inspiration or in expiration?
Figure 4
Making a measurement in a 4-year-old.
Unlike the oscillation techniques which sample data over several complete breathing cycles, interrupter devices are generally set to trigger in E or I. In the ambulatory environment of a busy clinical support laboratory, there would rarely be time to obtain a set on readings in both phases of breathing. Some believe that with interruption during E a signal with minimum interference from muscular activity can be obtained.20 Others have used inspiration16,17 because of concern about variations in glottic opening which are more likely to have an effect on the measurement during expiration.21 Klug and Bisgaard (unpublished pilot study, personal communication) observed that, during expiration, children sometimes blow in anticipation of the trigger. Our own work has suggested that when interruption occurs at 80% of peak
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Figure 5 (A) An unacceptable mouth pressure curve (Pmo) obtained after flow interruption using MicroRint in a child with recurrent cough. There is no definite Pfast the oscillations are coarse and Pslow is broken by further oscillations instead of rising gradually. (B) An unacceptable mouth pressure curve (Pmo) obtained after flow interruption using MicroRint showing no identifiable Pfast following interruption, persistent oscillations and no Pslow.
flow, there is only 4% difference between measurements in inspiration or in expiration.22 Only two other studies, in older children, have systematically investigated Rint E and RintI19,23 and have shown RintE to be greater than RintI.
Differences are of the order of 20% in both, much higher than we have demonstrated. We cannot explain this, other than noting that age and health status of subjects and methods are different.
LUNG FUNCTION TESTS IN PRE-SCHOOL CHILDREN
Repeatability The repeatability of the measurement at 30 s and at 15 min (the time of a test of bronchodilator responsiveness) is about 15–20% (two standard deviations (SDs) of the mean difference between two measurements).1 The repeatability from day to day is not known.
Making the measurement The measurement of respiratory resistance in young subjects by the interrupter technique (Rint) has been evaluated by several laboratories since the 1980s.1,19,20,23,24 The simplicity of use for the patient and smaller size of the device make it attractive for children aged 2–5 years in the ambulatory setting. Even acutely ill or tired children should be able to undertake the test successfully. There is no evidence that either bronchoconstriction or bronchodilation result when extra attempts are required to obtain valid data. The main possible disadvantage of an ambulatory setting, which is where it could be of clinical value, is that quiet, tidal breathing could be difficult for very young children. Neck position, upper airway compliance, variations in flow and volume during tidal breathing and the contribution of the glottis are impossible to standardise or correct for, and so the coefficient of variation of a set of values is high.20 However, the technique essentially provides a valid estimate of airway resistance provided upper airway compliance is minimised by supporting the cheeks and pharynx.18
Reference data There are a number of publications which report reference data19,24–26 for Rint measurements. Good practice for the choice of reference data is discussed by Quanjar.27 Our own data (unpublished) for a British inner city group of children of mixed ethnic background suggest that age and height predict measurement equally. Since age is easier to measure than height, this is particularly helpful for epidemiology studies. Bangladeshi children, although shorter as a group, had similar measurements to the other mixed group and the group as a whole had measurements very similar to a group of Dutch children of very different ethnic background (Merkus, unpublished). Our data compare well with very old data measuring total respiratory resistance.28 The higher measurements of Klug and Bisgaard compared to the others probably reflect their method of calculating resistance using the pressure just before valve opening (Fig. 3).17
Comparison with other methods The pressure change between the mouth and the alveoli can be measured in the plethysmograph. This measurement is made during rapid shallow breathing and is unaffected by stress relaxation in the tissues and chest wall
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resistance. Using the interrupter technique and measuring pressure change during interruption as a measure of pressure change across the airway, there is good agreement between measurement of airway resistance (Raw) in the plethysmograph and using the interrupter technique in normal lungs.24,30 If pressure measurements include part of the secondary phase then Rint will be higher than Raw.23,30,31 In diseased lungs (in children with asthma and cystic fibrosis), Rint has been shown to be lower than specific Raw (sRaw ) measured by plethysmography probably because mouth pressure has not equilibrated with alveolar pressure.32 Comparison in young children between sRaw resistance, measured using the forced oscillation technique, and Rint suggested that there was little difference between sRaw and Rint but measurements using FOT were very much higher.24
Clinical applicability Absolute measurements. In a group of asthmatics on different treatments, measurement was above the reference range in 44%.33 In another group of pre-school children, subjects with observed wheeze in the previous 6 weeks but not wheezy at the time of the test demonstrated significantly higher measurements than controls with no history of respiratory symptoms.2 However, there was a large overlap and measurements of above 1.45 kPa/I/s were 80% specific but only 60% sensitive for previous wheeze. This suggests that, in common with most other measurements of baseline lung function, measurement of Rint on its own will not help diagnose previously wheezy children. Measurement of bronchial hyper-responsiveness. Because of concern that Rint is underestimated during bronchoconstriction, bronchial provocation testing has been considered to be possibly dangerous. This anxiety has not been fully evaluated. Chan (personal communication) has shown in 6–9-year-old asthmatics that a response to increasing dosage of histamine could be measured by PEF when it could no longer be measured by Rint, tending to confirm the anxiety that measurements are falsely low at increased resistance. In a group of children 4–6 years old with suspected asthma there was a clear dose-response to methacholine challenge, although this appeared less than the change in sRaw.16 Measurement of bronchodilator responsiveness. The USA guidelines suggest that bronchodilator responsiveness (BDR) should be measured during the workup of asthma. However, the guidelines do not refer to how sensitive or specific is the technique. BDR is usually measured by the change in forced expiratory volume in 1s 15 min following bronchodilator. Pre-school children cannot undertake this test with spirometry and only 60% schoolchildren can complete it at the first visit.9 BDR using Rint is much more successful.
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If reversibility is considered as a change greater than repeatability (see above) then BDR measured by Rint is more sensitive than spirometry.34 The sensitivity and specificity of the technique compared to BDR testing with spirometry in this age-group is unknown. However, in pre-school children BDR is 80% specific for previous wheeze with a sensitivity of 76%.2
Standardisation A sub-group of the European Task Force on the measurement of respiratory impedance is considering standardisation of Rint measurement in children. One of the most important aspects of this will be the determination of the most suitable method of measuring pressure change during interruption. Hopefully there should be a statement during 2001.
Oscillation techniques – forced and impulse Submitting a physical system to oscillations is a very general approach to investigation of its structure and properties. There are two main variations – the forced oscillation technique (FOT) and the impulse oscillation system (IOS). The basic principle of FOT and IOS is measurement of the relationship between well-defined pressure waves applied externally to the respiratory system and the resulting respiratory air flow. The ratio of the amplitude of the input pressure wave to the amplitude of the resulting flow wave constitutes the impedance of the respiratory system (Zrs), which in turn can be characterised by the magnitude and phase angle between pressure and flow. Unlike the interrupter technique, which provides only one index of airway calibre, oscillation techniques generate two main indices. the total respiratory resistance (Rrs) and the reactance (Xrs). In FOT systems, sinusoidal pressure variations are applied to the respiratory system via an external generator – typically a loudspeaker under computer control. By choosing the frequency range of the oscillating loudspeaker, it is possible to selectively study different aspects of respiratory mechanics due to the varying frequency responses of the respiratory system. In IOS, a loudspeaker generates brief square wave pulses, typically at 0.2-second intervals, which are superimposed on the spontaneous mouth breathing of the patient.
Clinical applicability A study of methacholine (MCh) responsiveness in 5year-old children, measured using FOT4, concluded that FOT was unreliable due to the measurements being technically unsatisfactory and inconsistent after challenge. However, in this study it was necessary for the child to breath quietly for 12–16 s before the system was able to
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derive a measurement. More modern systems are probably able to obtain the necessary data in a shorter time period. More recently it has been possible to reliably evaluate bronchial obstruction and its reversibility in asthmatic children over 3 years old.37 Using IOS, 20 of 23 young children successfully undertook MCh challenge and the technique reliably reflected short-term changes in respiratory function.24 In general, oscillation systems are larger and require a greater level of technical expertise than interrupter systems. Oscillation techniques are not standardised and an ERS task force is looking into this.
PRACTICE POINTS
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It is now possible to measure lung function in pre-school children outside a research laboratory. The measurements should be undertaken by trained personnel who are familiar with the pitfalls and difficulties of measurement and interpretation. Reference values should be tested in a sample of healthy children from the locality which each laboratory serves. This should ensure, as far as possible, that local measurements are similar to published reference values. The interrupter technique for measuring airway resistance and the forced oscillation technique have not been standardised.
RESEARCH DIRECTIONS
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Standardisation of the methods is needed so that different laboratories’ results can be compared. Ideally, the repeatability over days should be known in healthy controls. Clear guidelines are needed for the potential of each test, e.g. Rint may not be the best for testing bronchial hyperreactivity but may be acceptable for bronchodilator responsiveness.
REFERENCES 1. Bridge PD, Ranganathan S, McKenzie SA. The measurement of airway resistance using the interrupter technique (Rint) in pre-school children in the ambulatory setting. Eur Respir J 1999; 13: 792–796. 2. McKenzie SA, Bridge PD, Healy MJR. Airways resistance in preschool children with wheeze and cough. Eur Respir J 1999; 15: 533–538.
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3. 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. 4. Wilson NM, Bridge P, Phagoo SB, Silverman M. The measurement of methacholine responsiveness in 5 year old children: three methods compared. Eur Respir J 1995; 8: 364–370. 5. Frey U, Silverman M, Kraemer R, Jackson AC. High- frequency respiratory input impedance measurements in infants assessed by the high speed interrupter technique. Eur Respir J 1998; 12: 148–158. 6. Truong M, Iniguez JL, Chouhou D, Dessange JF, Gendrel D, Chaussain M. Measurement of peak expiratory flow in young children: comparison of four portable equipments. Arch Pediatr 1995; 2: 324–327. 7. Sly PD. Peak flow monitoring in children. Monaldi Arch Chest Dis 1993; 48: 662–667. 8. Skinner K, Connett G. The effects of animated incentive devices on measurements of forced lung volumes during childhood. Arch Dis Child 2000; 82: A42. 9. Bridge PD, McKenzie SA. Feasibility of spirometry and in children 5–10 years for the measurement of bronchodilator responsiveness. Arch Dis Child 2000; 82(Suppl 1): A42. 10. Bates JHT, Milic-Emili J. The flow Interruption technique for measuring respiratory resistance. J Crit Care 1991; 6: 227–238. 11. Bates JHT, Ludwig MS, Sly PD, Brown K, Martin JG, Fredberg JJ. Interrupter resistance elucidated by alveolar pressure measurement in open-chested normal dogs. J App Physiol 1988; 65: 408–414. 12. Ludwig MS, Romero PV, Sly PD, Fredberg JJ, Bates JH. Interpretation of interrupter resistance after histamine-induced constriction in the dog. J Appl Physiol 1990; 68: 1651–1656. 13. Bates JH, Abe T, Romero PV, Sato J. Measurement of alveolar pressure in closed-chest dogs during flow interruption. J Appi Physiol 1989; 67: 488–492. 14. Phagoo SB, Watson RA, Pride NB, Silverman M. Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects. Eur Respir J 1993; 6: 996–1003. 15. Phagoo SB, Wilson NM, Silverman M. Evaluation of the interrupter technique for measuring change in airway resistance in 5-year-old asthmatic children. Pediatr Pumonol 1995; 20: 387–395. 16. Bisgaard H, Kiug B. Lung function measurement in awake young children. Eur Respir J 1995; 8: 2067–2075. 17. 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. 18. Bates JH, Sly PD, Kochi T, Martin JG. The effect of a proximal compliance on interrupter measurements of resistance. Respir Physiol 1987; 70: 301–312. 19. Oswald-Mammosser M, Llerena C, Speich JP, Donata L, Lonsdorfer. J Measurements of respiratory system resistance by the interrupter technique in healthy and asthmatic children. Pediatr Pulmonol 1997; 24: 78–85.
20. Phagoo SB, Wilson NM, Silverman M. Evaluation of a new interrupter device for measuring bronchial responsiveness and the response to bronchodilator in 3 year old children. Eur Respir J 1996; 9: 1374–1380. 21. Stanescu DC, Clement J, Pattijn J, Woestijne KP. Glottis opening and airway resistance. J Appl Physiol 1972; 32: 460–466. 22. Bridge PD, McKenzie SA. Airway resistance measured by the interrupter technique (Rint) in pre-school children in inspiration and expiration. Eur Respir J 1999; 14: 44s. 23. Carter ER, Stecenko AA, Pollock BH, Jaeger MJ. Evaluation of the interrupter technique for the use of assessing airway obstruction in children. Pediatr Pulmonol 1994; 17: 211–217. 24. 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. 25. Son BK, Lim DH, Kim JH. Normal predicted values of airway resistance by flow interrupter technique in Korean primary school-aged children. Korean Paed Allergy and Resp Dis 1998; 8: 198–204. 26. Eiser N, Phillips P, Wooler P, Hanna S. Normal values of interrupter resistance in children. Eur Respir J 2000; 16(Suppl. 31): 81S. 27. Quanjer PhH, Stocks J, Polgar G, Wise M, Karlberg J, Borsboom G. Compilation of reference values for lung function in children. Eur Respir J 1989; 2(Suppl. 4): 184s–261s. 28. Helliesen PJ, Cook CD, Friedlander L, Agathon S. Studies of respiratory physiology in children. I. Mechanics of respiration and lung volumes in 85 normals children 5 to 15 years of age. Pediatrics 1958; 22: 80–93. 29. Jackson AC, Milhorn HTJ, Norman JR. A reevaluation of the interrupter technique for airway resistance measurement. J Appl Physio 1974; 36: 264–268. 30. Fichter J, Wierich W, Hartung W. Resistance measurement in normal and obstructed excised human lungs by means of the interrupter method. Respiration 1989; 56: 34–42. 31. Chowienczyk PJ, Lawson CP, Lane S et al. A flow interruption device for measurement of airway resistance. Eur Respir J 1991; 4: 623–628. 32. Oswald-Mammosser M, Charloux A, Donato L et al. Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis. Pediatr Pulmonol 2000; 29: 213–220. 33. Klug B, Bisgaard H. Lung function and short-term outcome in young asthmatic children. Eur Respir J 1999; 14: 1185–1189. 34. Bridge PD, Mylonopoulou M, McKenzie SA. Comparison of bronchodilator responsiveness measured by the interrupter technique and spirometry in 5<10 year olds in an ambulatory environment. Eur Respir J 2000; 16(Suppl. 31): 385S. 35. Pride NB. Forced oscillation techniques for measuring mechanical properties of the respiratory system. Thorax 1992; 47: 317–320. 36. Vogel J, Smidt U. Impulse Oscillometry. Frankfurt am Main: PMI Verlagsgruppe, 1994; 1–106. 37. Delacourt C, Lorino H, Herve-Guillot M, Reinert P, Harf A, Housset B. Use of the forced oscillation technique to assess airway obstruction and reversibility in children. Am J Respir Crit Care Med 2000; 161: 730–736.
SERIES: LUNG FUNCTION TESTING
Lung function tests for pre-school children S. A. McKenzie, P. D. Bridge and C. S. Pao Department of Paediatric Respiratory Medicine, Royal London Hospital, London, UK KEYWORDS lung function tests, interrupter technique, forced oscillation
Summary There are a few devices for measuring lung function in pre-school children. Neither the interrupter technique nor the forced oscillation techniques have been standardised.We highlight some of the issues around the measurement of airway resistance using the interrupter technique and emphasise that, as with other lung function measurements, operators should have a proper understanding of the methods before they can be applied. Both methods for measuring airway resistance have potential for clinical and research application. © 2001 Harcourt Publishers Ltd
INTRODUCTION Until recently, there were no lung function tests suitable for the majority of pre-school children. Only a few children are able to perform the forced expiratory manoeuvres necessary to measure peak flow accurately or perform spirometry reliably. What lung function testing in this age group needs, at the very least, is passive co-operation without the need for co-ordination. Four tests are potentially useful in this age-group: the measurement of peak flow using a whistle, incentive display spirometry, and the measurement of airway resistance by the interrupter (Rint ) and oscillation techniques (forced or impulse). These tests have moved out of the research laboratory and into routine use in some lung function laboratories. The peak flow whistle (PFW) is a simple device providing an audio incentive to encourage optimal results with a peak flow (PF) manoeuvre. Incentive display spirometry (IDS) uses an animated display to encourage optimum forced blows. Both these techniques are simply improvements on established techniques that should enable wellunderstood parameters to be obtained within a larger percentage of the pre-school population with increased reliability. Interruption and oscillation techniques measure airway resistance. They depend on a high level of sophistication from the equipment. Additionally, there is much discussion about what the “resistance” values obtained represent. Standardisation of both techniques is being considered. They require only passive co-operation, a considerable advantage in pre-school children. The majority of this review will feature the Rint technique. The size, cost and simplicity of use of the 1526–0550/01/010037 + 09 $35.00/0
equipment and the requirement of only passive cooperation suggests that this technique is suitable for young children in the ambulatory setting. Our own results demonstrate its feasibility1 and there is a good sensitivityspecificity profile for detecting bronchodilator responsiveness in children with previous wheeze.2
OTHER SPECIAL TECHNIQUES Another method investigated in 2–5-year-olds is whole body plethysmography with an accompanying adult.3 This method is not suitable for use outside a specialised lung function testing centre due to the cost, size and complexity of the equipment. Techniques such as assessment of lung volumes by helium dilution and assessment of inflammation by induced sputum and exhaled nitric oxide are generally considered to be unsuitable for the majority of children under 7 years. Also, they require larger, more expensive and complex equipment and would not be suitable for the ambulatory environment. Whilst not really a conventional lung function test, change in transcutaneous oxygen has been measured by several investigators and has been shown to be a sensitive indictor of bronchoconstriction during challenge testing. This measurement was preferred to chest auscultation for wheeze which developed in some children after they had become hypoxic.4 It has been shown in infants that, using the high speed interrupter technique,5 it is possible to obtain non-invasive information on both airway geometry and airway wall mechanics, which is useful in understanding airflow limitation phenomena. However, this technique is likely to remain a research tool for the foreseeable future. © 2001 Harcourt Publishers Ltd
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Peak flow whistle (PFW) Some very young children can manage peak flow without an incentive.6 The peak flow whistle (PFW) was developed to try to improve PF results, by encouraging children to blow harder and harder to produce a higher and higher tone, but PFWs do not appear to be widely used, perhaps because of the reservations about PF measurement in children.7 The PFW should help pre-school children but there is no evaluation of it in this age-group.
Animated incentive display spirometry (IDS) Young children can find it difficult to comprehend what is required for good spirometry. Some modern computerised spirometers, such as Jaeger’s Masterscreen Pneumo, have software animated incentive devices to motivate both adults and children to blow hard, down to residual volume (RV). Unless a forced blow is continued down to RV it is not possible to measure mid-expiratory flow (FEF50), FEV1/VC ratios or to obtain a clear picture of the degree of curvature on the flow-volume curve. Also, for the severely obstructed, it may take several seconds to reach RV. Incentive displays should help with both comprehension and motivation in young children. A study of spirometry measurements using an incentive device during forced expirations demonstrated an improved performance in children 4–10 years old.8 Readings were more reproducible. Higher values in relation to height were obtained with the spirometer with the incentive device compared to a spirometer without one and so normal values have been readjusted in the 4–7year-olds to reflect this. The relationship of FEV1 to height across this age-range has been shown to be non-linear.
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The animation used in IDS is important. The best at the moment appears to be a curly party-whistle or candles on a birthday cake (Fig. 1). Incentive spirometry (IS) to improve inspiration is used as a therapeutic tool to try to decrease atelectasis in patients who have had thoracotomies and upper abdominal surgery, and in children with sickle cell disease. An adapter to the spirometer can be fitted to tracheostomies. It is also helpful in following postoperative lung function, as IS correlates well with vital capacity. However, there do not appear to be any readily available commercial spirometers that incorporate inspiratory incentive displays. Young children frequently find it difficult to comprehend the concept of inspiring to total lung capacity (TLC), resulting in sub-maximum and inconsistent forced expiratory parameters. It seems important to develop an incentive device to encourage small children to inspire at a reasonable rate up to TLC – for instance, using a glass containing a drink. This may help prevent closure of the glottis which can occur during a rapid inspiration. It remains to be seen whether the availability of incentive devices will increase the number of pre-school children with respiratory symptoms who can have forced expiratory volumes and flows measured. Even with the use of incentive displays, it is important to appreciate that many pre-school children will find it difficult to undertake lung function tests successfully at a first attempt unless sufficient time is allowed for training and encouragement. This would appear to be especially true in the case of forced blows.9
The interrupter technique (Rint) for measurement of airway resistance This technique is not new, but interest in its development waned when values were found to differ from ‘gold standard’ plethysmography values of airway resistance. In the 1980s interest was revived when the physiology of the measurement was considered in both animals and man and technical aspects of the technique were refined.10
What does Rint measure?
Figure 1 The curly party-whistle incentive device for the Masterscreen Pneumo (Jaeger).
The measurement of Rint is based on the premise that when the airway is suddenly occluded, there is a pressure change at the mouth, which equates to the resistive pressure drop across the airway. The ratio of the pressure drop to the airflow immediately before the occlusion provides an estimate of resistance. This premise is simplistic because the method is influenced by the compliance of the upper airway and retarded equilibration between mouth and alveolar pressure in the presence of airway disease because of mechanical non-heterogeneity of the lungs. Bates and colleagues have shown in dog experiments that there are two components to the pressure trace
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Figure 2 An acceptable mouth pressure curve (Pmo ) obtained after flow interruption using MicroRint in an asymptomatic child with intermittent wheeze.The initial rapid pressure rise (Pfast ) is followed by a series of oscillations and the secondary pressure change (Pslow ) consists of a slower increase in pressure. Pfast reflects airway resistance; Pslow approximates tissue and chest wall resistance.
after interruption (Fig. 2). In open-chested dogs, the first represents the pressure drop across the airways alone11 and the second pressure rise reflects the stress-recovery of the lung tissues and the effect of gas redistribution, which in histamine-challenged lungs can last for some time after interruption.12 Experiments on closed-chested dogs to examine the effect of the chest wall13 suggested that it introduced a significant additional component to the first pressure change. In humans the contribution of the chest wall to the first pressure change is less important as the airways have much more importance since they are smaller. The contribution of the effect of gas redistribution, especially important in disease, and chest wall resistance to the second component is not known. Whilst it is simple to measure flow, it is not possible to measure alveolar pressure non-invasively. Therefore, pressure is measured at the mouth, Pmo , during rapid flow interruption, typically over a 100 ms period. The measurements of pressure and flow are not simultaneous. Flow is measured before occlusion and pressure afterwards (Fig. 3a). It is the method of estimating the alveolar pressure, and hence resistive pressure drop across the airway, which is most controversial. There may never be agreement about what exactly this measures in humans. What can be said is that it reflects airway resistance and as
long as change can be measured with sensitivity, it should be a useful clinical and research tool. The main issues to resolve are the best method for measuring pressure and the “timing” of the occlusion within the tidal breath.
How should the pressure drop be estimated? The best method of estimating the pressure has yet to be determined. This dilemma is confounded by: (a) the time needed to close the valve, which according to Bates et al. should be within 10 ms10; and (b) incomplete equilibration of mouth and alveolar pressure within the time that the valve is closed, typically 100 ms. Equilibration between mouth and alveoli is almost instantaneous in the healthy lung. However, even in the case of moderate disease, equilibration is unlikely to have occurred within the duration of occlusion (Fig. 3a and b). Therefore, the pressure at the mouth does not equal alveolar pressure, the secondary phase rises slowly and the estimate of the resistive pressure drop across the airway may be falsely low. In order to address this, a two point back-extrapolation to the time of interruption was recommended by Phagoo.14 MicroMedical interrupter devices use T30 and T70 extrapolated back to T15 (MicroLab 4000) or To (Micro Rint ), so if equilibration is
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Flow (measured immediately prior to interruption)=292 ml/sec Rint=2.19 kPa.L–1.sec
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Figure 3 (a) A mouth pressure curve (Pmot) obtained after flow interruption using MicroRint in a child wheezy at the time of test at baseline. Note the curvature that is seen following the oscillations. Measurement is obtained before a plateau is reached. T0 = Time of interruption (T0 is defined as the point at which the pressure signal reaches 25% of the difference between the maximum value of the first clearly defined peak of pressure oscillations and the baseline value); T30 = 30 ms after interruption; T70 = 70 ms after interruption. (---) Interruption; (---..--..) calculation of pressure change using 2-point back extrapolation using T30 and T70; (——) calculation of pressure change at valve opening. (b) A mouth pressure curve (Pmot) obtained after flow interruption using MicroRint in the same child 20 min after inhalation of 400 µg salbutamol. The child is breathing at a slightly higher flow, the pressure change is less than pre-salbutamol and the calculated resistance Rint is lower. (---) Interruption; (---..--..) calculation of pressure change using 2-point back extrapolation using T30 and T70 T0; (——) pressure at valve opening.
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delayed beyond this, pressure change and thus resistance will be underestimated (Fig. 3a). Jaeger have selected the point at end-interruption for the measurement of pressure with flow measured immediately after opening. It remains to be seen which of these methods is ‘best’, i.e. most sensitive, for measuring change in Rint.
and attention span of the child. The mean or median of these readings (values) is the measurement.
Timing of the occlusion: peak of tidal flow or fixed flow or volume? There are three points at which occlusion can occur. Occlusion can be set to begin close to the peak of tidal flow either in inspiration (I) or in expiration (E), after a fixed volume has passed the transducer, or when a fixed flow has been reached. All three options have been implemented in commercially available devices. Triggering as close as possible to the peak of tidal flow (either E or I) during quiet breathing is the method used by MicroMedical. Measurements in our laboratory using a MicroRint, which displays flow against time, indicate that interruption occurs at the start of expiration and at the start of inspiration. If these timings correspond to high and low lung volumes, respectively, then RintE would be expected to be lower than RintI, the opposite of our findings and those of others (see below). This suggests that volume over the tidal range has little effect in the measurement of Rint. To achieve a near peak tidal flow occlusion, typically the device is set to detect a peak at a flow greater than 80% of the peak of the previous tidal flow.
How many interruptions (readings) are required for a valid measurement? Six acceptable readings will generally result in a coefficient of variation of <20%. There is no significant improvement with more than six. In pre-school children, at a first attempt, we have found the number of interruptions needed for six acceptable values is <10, median 6. This is important as, especially in the pre-school group in the ambulatory setting, it can be difficult to retain the cooperation
Mean or median? We have shown (in press) that there is no important difference between median and mean, <1% in pre-school children. The median of the six or so values should be used as the measurement, as this is less affected than the mean by outlying values. Such values cannot be avoided with fully automated equipment in which transients cannot easily be examined for acceptability. Some commercial devices collect values which are considered by the machine’s software to be acceptable. Inexperienced operators may overlook outlying values which could have resulted from poor technique, such as moving the head or blowing the cheeks out. We have shown that mean and median values in our data differed by very little, so that studies which have used the mean are still valid.1,2,15–17
What about the upper airway? Measurements made without supporting the cheeks give significantly lower readings.18,19 The nose should be clipped, the cheeks supported (Fig. 4) and transients inspected for acceptability (Fig. 2). Unacceptable traces are shown in Figures 5A and 5B. Some workers routinely make measurements using a tightly fitting17 mask but it is not known how well mask and mouthpiece measurements compare. Some manufactures include software to automatically reject mouth-pressure time transients (Pmo(t)) that appear to include artefacts but it is the responsibility of the technician to inspect all transients for acceptability according to published criteria14. This would suggest that fully automated devices are not to be recommended until the technology has moved a stage further.
Should interruption occur in inspiration or in expiration?
Figure 4
Making a measurement in a 4-year-old.
Unlike the oscillation techniques which sample data over several complete breathing cycles, interrupter devices are generally set to trigger in E or I. In the ambulatory environment of a busy clinical support laboratory, there would rarely be time to obtain a set on readings in both phases of breathing. Some believe that with interruption during E a signal with minimum interference from muscular activity can be obtained.20 Others have used inspiration16,17 because of concern about variations in glottic opening which are more likely to have an effect on the measurement during expiration.21 Klug and Bisgaard (unpublished pilot study, personal communication) observed that, during expiration, children sometimes blow in anticipation of the trigger. Our own work has suggested that when interruption occurs at 80% of peak
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Figure 5 (A) An unacceptable mouth pressure curve (Pmo) obtained after flow interruption using MicroRint in a child with recurrent cough. There is no definite Pfast the oscillations are coarse and Pslow is broken by further oscillations instead of rising gradually. (B) An unacceptable mouth pressure curve (Pmo) obtained after flow interruption using MicroRint showing no identifiable Pfast following interruption, persistent oscillations and no Pslow.
flow, there is only 4% difference between measurements in inspiration or in expiration.22 Only two other studies, in older children, have systematically investigated Rint E and RintI19,23 and have shown RintE to be greater than RintI.
Differences are of the order of 20% in both, much higher than we have demonstrated. We cannot explain this, other than noting that age and health status of subjects and methods are different.
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Repeatability The repeatability of the measurement at 30 s and at 15 min (the time of a test of bronchodilator responsiveness) is about 15–20% (two standard deviations (SDs) of the mean difference between two measurements).1 The repeatability from day to day is not known.
Making the measurement The measurement of respiratory resistance in young subjects by the interrupter technique (Rint) has been evaluated by several laboratories since the 1980s.1,19,20,23,24 The simplicity of use for the patient and smaller size of the device make it attractive for children aged 2–5 years in the ambulatory setting. Even acutely ill or tired children should be able to undertake the test successfully. There is no evidence that either bronchoconstriction or bronchodilation result when extra attempts are required to obtain valid data. The main possible disadvantage of an ambulatory setting, which is where it could be of clinical value, is that quiet, tidal breathing could be difficult for very young children. Neck position, upper airway compliance, variations in flow and volume during tidal breathing and the contribution of the glottis are impossible to standardise or correct for, and so the coefficient of variation of a set of values is high.20 However, the technique essentially provides a valid estimate of airway resistance provided upper airway compliance is minimised by supporting the cheeks and pharynx.18
Reference data There are a number of publications which report reference data19,24–26 for Rint measurements. Good practice for the choice of reference data is discussed by Quanjar.27 Our own data (unpublished) for a British inner city group of children of mixed ethnic background suggest that age and height predict measurement equally. Since age is easier to measure than height, this is particularly helpful for epidemiology studies. Bangladeshi children, although shorter as a group, had similar measurements to the other mixed group and the group as a whole had measurements very similar to a group of Dutch children of very different ethnic background (Merkus, unpublished). Our data compare well with very old data measuring total respiratory resistance.28 The higher measurements of Klug and Bisgaard compared to the others probably reflect their method of calculating resistance using the pressure just before valve opening (Fig. 3).17
Comparison with other methods The pressure change between the mouth and the alveoli can be measured in the plethysmograph. This measurement is made during rapid shallow breathing and is unaffected by stress relaxation in the tissues and chest wall
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resistance. Using the interrupter technique and measuring pressure change during interruption as a measure of pressure change across the airway, there is good agreement between measurement of airway resistance (Raw) in the plethysmograph and using the interrupter technique in normal lungs.24,30 If pressure measurements include part of the secondary phase then Rint will be higher than Raw.23,30,31 In diseased lungs (in children with asthma and cystic fibrosis), Rint has been shown to be lower than specific Raw (sRaw ) measured by plethysmography probably because mouth pressure has not equilibrated with alveolar pressure.32 Comparison in young children between sRaw resistance, measured using the forced oscillation technique, and Rint suggested that there was little difference between sRaw and Rint but measurements using FOT were very much higher.24
Clinical applicability Absolute measurements. In a group of asthmatics on different treatments, measurement was above the reference range in 44%.33 In another group of pre-school children, subjects with observed wheeze in the previous 6 weeks but not wheezy at the time of the test demonstrated significantly higher measurements than controls with no history of respiratory symptoms.2 However, there was a large overlap and measurements of above 1.45 kPa/I/s were 80% specific but only 60% sensitive for previous wheeze. This suggests that, in common with most other measurements of baseline lung function, measurement of Rint on its own will not help diagnose previously wheezy children. Measurement of bronchial hyper-responsiveness. Because of concern that Rint is underestimated during bronchoconstriction, bronchial provocation testing has been considered to be possibly dangerous. This anxiety has not been fully evaluated. Chan (personal communication) has shown in 6–9-year-old asthmatics that a response to increasing dosage of histamine could be measured by PEF when it could no longer be measured by Rint, tending to confirm the anxiety that measurements are falsely low at increased resistance. In a group of children 4–6 years old with suspected asthma there was a clear dose-response to methacholine challenge, although this appeared less than the change in sRaw.16 Measurement of bronchodilator responsiveness. The USA guidelines suggest that bronchodilator responsiveness (BDR) should be measured during the workup of asthma. However, the guidelines do not refer to how sensitive or specific is the technique. BDR is usually measured by the change in forced expiratory volume in 1s 15 min following bronchodilator. Pre-school children cannot undertake this test with spirometry and only 60% schoolchildren can complete it at the first visit.9 BDR using Rint is much more successful.
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If reversibility is considered as a change greater than repeatability (see above) then BDR measured by Rint is more sensitive than spirometry.34 The sensitivity and specificity of the technique compared to BDR testing with spirometry in this age-group is unknown. However, in pre-school children BDR is 80% specific for previous wheeze with a sensitivity of 76%.2
Standardisation A sub-group of the European Task Force on the measurement of respiratory impedance is considering standardisation of Rint measurement in children. One of the most important aspects of this will be the determination of the most suitable method of measuring pressure change during interruption. Hopefully there should be a statement during 2001.
Oscillation techniques – forced and impulse Submitting a physical system to oscillations is a very general approach to investigation of its structure and properties. There are two main variations – the forced oscillation technique (FOT) and the impulse oscillation system (IOS). The basic principle of FOT and IOS is measurement of the relationship between well-defined pressure waves applied externally to the respiratory system and the resulting respiratory air flow. The ratio of the amplitude of the input pressure wave to the amplitude of the resulting flow wave constitutes the impedance of the respiratory system (Zrs), which in turn can be characterised by the magnitude and phase angle between pressure and flow. Unlike the interrupter technique, which provides only one index of airway calibre, oscillation techniques generate two main indices. the total respiratory resistance (Rrs) and the reactance (Xrs). In FOT systems, sinusoidal pressure variations are applied to the respiratory system via an external generator – typically a loudspeaker under computer control. By choosing the frequency range of the oscillating loudspeaker, it is possible to selectively study different aspects of respiratory mechanics due to the varying frequency responses of the respiratory system. In IOS, a loudspeaker generates brief square wave pulses, typically at 0.2-second intervals, which are superimposed on the spontaneous mouth breathing of the patient.
Clinical applicability A study of methacholine (MCh) responsiveness in 5year-old children, measured using FOT4, concluded that FOT was unreliable due to the measurements being technically unsatisfactory and inconsistent after challenge. However, in this study it was necessary for the child to breath quietly for 12–16 s before the system was able to
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derive a measurement. More modern systems are probably able to obtain the necessary data in a shorter time period. More recently it has been possible to reliably evaluate bronchial obstruction and its reversibility in asthmatic children over 3 years old.37 Using IOS, 20 of 23 young children successfully undertook MCh challenge and the technique reliably reflected short-term changes in respiratory function.24 In general, oscillation systems are larger and require a greater level of technical expertise than interrupter systems. Oscillation techniques are not standardised and an ERS task force is looking into this.
PRACTICE POINTS
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It is now possible to measure lung function in pre-school children outside a research laboratory. The measurements should be undertaken by trained personnel who are familiar with the pitfalls and difficulties of measurement and interpretation. Reference values should be tested in a sample of healthy children from the locality which each laboratory serves. This should ensure, as far as possible, that local measurements are similar to published reference values. The interrupter technique for measuring airway resistance and the forced oscillation technique have not been standardised.
RESEARCH DIRECTIONS
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Standardisation of the methods is needed so that different laboratories’ results can be compared. Ideally, the repeatability over days should be known in healthy controls. Clear guidelines are needed for the potential of each test, e.g. Rint may not be the best for testing bronchial hyperreactivity but may be acceptable for bronchodilator responsiveness.
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3. 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. 4. Wilson NM, Bridge P, Phagoo SB, Silverman M. The measurement of methacholine responsiveness in 5 year old children: three methods compared. Eur Respir J 1995; 8: 364–370. 5. Frey U, Silverman M, Kraemer R, Jackson AC. High- frequency respiratory input impedance measurements in infants assessed by the high speed interrupter technique. Eur Respir J 1998; 12: 148–158. 6. Truong M, Iniguez JL, Chouhou D, Dessange JF, Gendrel D, Chaussain M. Measurement of peak expiratory flow in young children: comparison of four portable equipments. Arch Pediatr 1995; 2: 324–327. 7. Sly PD. Peak flow monitoring in children. Monaldi Arch Chest Dis 1993; 48: 662–667. 8. Skinner K, Connett G. The effects of animated incentive devices on measurements of forced lung volumes during childhood. Arch Dis Child 2000; 82: A42. 9. Bridge PD, McKenzie SA. Feasibility of spirometry and in children 5–10 years for the measurement of bronchodilator responsiveness. Arch Dis Child 2000; 82(Suppl 1): A42. 10. Bates JHT, Milic-Emili J. The flow Interruption technique for measuring respiratory resistance. J Crit Care 1991; 6: 227–238. 11. Bates JHT, Ludwig MS, Sly PD, Brown K, Martin JG, Fredberg JJ. Interrupter resistance elucidated by alveolar pressure measurement in open-chested normal dogs. J App Physiol 1988; 65: 408–414. 12. Ludwig MS, Romero PV, Sly PD, Fredberg JJ, Bates JH. Interpretation of interrupter resistance after histamine-induced constriction in the dog. J Appl Physiol 1990; 68: 1651–1656. 13. Bates JH, Abe T, Romero PV, Sato J. Measurement of alveolar pressure in closed-chest dogs during flow interruption. J Appi Physiol 1989; 67: 488–492. 14. Phagoo SB, Watson RA, Pride NB, Silverman M. Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects. Eur Respir J 1993; 6: 996–1003. 15. Phagoo SB, Wilson NM, Silverman M. Evaluation of the interrupter technique for measuring change in airway resistance in 5-year-old asthmatic children. Pediatr Pumonol 1995; 20: 387–395. 16. Bisgaard H, Kiug B. Lung function measurement in awake young children. Eur Respir J 1995; 8: 2067–2075. 17. 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. 18. Bates JH, Sly PD, Kochi T, Martin JG. The effect of a proximal compliance on interrupter measurements of resistance. Respir Physiol 1987; 70: 301–312. 19. Oswald-Mammosser M, Llerena C, Speich JP, Donata L, Lonsdorfer. J Measurements of respiratory system resistance by the interrupter technique in healthy and asthmatic children. Pediatr Pulmonol 1997; 24: 78–85.
20. Phagoo SB, Wilson NM, Silverman M. Evaluation of a new interrupter device for measuring bronchial responsiveness and the response to bronchodilator in 3 year old children. Eur Respir J 1996; 9: 1374–1380. 21. Stanescu DC, Clement J, Pattijn J, Woestijne KP. Glottis opening and airway resistance. J Appl Physiol 1972; 32: 460–466. 22. Bridge PD, McKenzie SA. Airway resistance measured by the interrupter technique (Rint) in pre-school children in inspiration and expiration. Eur Respir J 1999; 14: 44s. 23. Carter ER, Stecenko AA, Pollock BH, Jaeger MJ. Evaluation of the interrupter technique for the use of assessing airway obstruction in children. Pediatr Pulmonol 1994; 17: 211–217. 24. 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. 25. Son BK, Lim DH, Kim JH. Normal predicted values of airway resistance by flow interrupter technique in Korean primary school-aged children. Korean Paed Allergy and Resp Dis 1998; 8: 198–204. 26. Eiser N, Phillips P, Wooler P, Hanna S. Normal values of interrupter resistance in children. Eur Respir J 2000; 16(Suppl. 31): 81S. 27. Quanjer PhH, Stocks J, Polgar G, Wise M, Karlberg J, Borsboom G. Compilation of reference values for lung function in children. Eur Respir J 1989; 2(Suppl. 4): 184s–261s. 28. Helliesen PJ, Cook CD, Friedlander L, Agathon S. Studies of respiratory physiology in children. I. Mechanics of respiration and lung volumes in 85 normals children 5 to 15 years of age. Pediatrics 1958; 22: 80–93. 29. Jackson AC, Milhorn HTJ, Norman JR. A reevaluation of the interrupter technique for airway resistance measurement. J Appl Physio 1974; 36: 264–268. 30. Fichter J, Wierich W, Hartung W. Resistance measurement in normal and obstructed excised human lungs by means of the interrupter method. Respiration 1989; 56: 34–42. 31. Chowienczyk PJ, Lawson CP, Lane S et al. A flow interruption device for measurement of airway resistance. Eur Respir J 1991; 4: 623–628. 32. Oswald-Mammosser M, Charloux A, Donato L et al. Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis. Pediatr Pulmonol 2000; 29: 213–220. 33. Klug B, Bisgaard H. Lung function and short-term outcome in young asthmatic children. Eur Respir J 1999; 14: 1185–1189. 34. Bridge PD, Mylonopoulou M, McKenzie SA. Comparison of bronchodilator responsiveness measured by the interrupter technique and spirometry in 5<10 year olds in an ambulatory environment. Eur Respir J 2000; 16(Suppl. 31): 385S. 35. Pride NB. Forced oscillation techniques for measuring mechanical properties of the respiratory system. Thorax 1992; 47: 317–320. 36. Vogel J, Smidt U. Impulse Oscillometry. Frankfurt am Main: PMI Verlagsgruppe, 1994; 1–106. 37. Delacourt C, Lorino H, Herve-Guillot M, Reinert P, Harf A, Housset B. Use of the forced oscillation technique to assess airway obstruction and reversibility in children. Am J Respir Crit Care Med 2000; 161: 730–736.