Catherine Olden

Elizabeth Symes

Paul Christopher Seddon
email: paul.seddon@bsuh.nhs.uk

Olden C Rscn

Seddon P MB Symes E Rscn

Kjell Øygarden

Measuring tidal breathing parameters using a volumetric vest in neonates with and without lung disease

Keywords: infant, respiratory function, tidal breathing, chest wall Infant, respiratory function, tidal breathing, chest wall

Lung function measurement is difficult in unsedated infants; tidal breathing parameters are a useful non-invasive surrogate, but even these measurements cause disturbance from applying a facemask. We investigated a novel volumetric vest system (FloRight), which measures volume changes of the respiratory system from changes in the magnetic fields induced by current-carrying coils around the entire chest and abdomen.

Using a facemask and ultrasonic flowmeter as comparator, we assessed the validity and repeatability of tidal breathing parameters measured by FloRight in 10 healthy newborn infants during natural sleep. We also assessed the effect of a facemask on tidal volume and tidal expiratory flow parameters. To assess the ability of the FloRight system to detect disease, we compared the healthy infants with 11 infants suffering from bronchopulmonary dysplasia.

Tidal parameters with the FloRight vest corresponded closely with facemask measurements.

Mean difference, mask minus vest, for tidal volume was 0.096mL (p<0.05), with limits of agreement +4.5 to -4.3mL. Coefficient of repeatability was similar for mask and vest measurements. Tidal volume measured by FloRight with mask in place (20.6mL) was significantly higher than without mask (16.1mL), but tidal expiratory flow parameters were not altered. FloRight measurements of tidal parameters were markedly different between the two groups of infants, with tidal volume per Kg sigificantly higher and tidal expiratory flow parameters significantly lower.

Our findings suggest that the FloRight system is able to measure tidal breathing parameters accurately, in healthy newborn infants, without prior calibration on the infant. It appears to have at least sufficient sensitivity to detect severe respiratory disease.

Introduction

Assessing lung function in infants is difficult and time-consuming, and in certain situations virtually impossible with current techniques. Methods such as rapid thoracic compression and its raised volume refinement have advanced our understanding of infant lung disease 1 .

Because of the need for sedation, however, they are only practicable in stable infants without severe or acute lung disease. The need for sedation and the time taken for measurements also limits their clinical applicability. Measurement of tidal breathing parameters [2][3][4] is an attractive alternative, giving an indirect but non-invasive indication of lung function. They can be measured and repeated rapidly, and sedation is not always needed. However, the application of a facemask to capture respiratory airflow is problematic: it often causes disturbance or arousal, and there are suggestions 3;5;6 that both the trigeminal stimulation and the deadspace of a mask may alter the pattern of tidal breathing.

To avoid these problems, attempts have been made to measure tidal breathing parameters at the chest wall using respiratory inductive plethysmography (RIP) [START_REF] Adams | Respiratory Inductive Plethysmography[END_REF] . However, this requires prior calibration with airflow measured at a facemask if absolute volumes are to be measured [START_REF] Sackner | Calibration of respiratory inductive plethysmography during natural breathing[END_REF] , which negates most of the advantage of the technique. Using uncalibrated RIP has been advocated [START_REF] Stick | Validation of respiratory inductance plethysmography ("Respitrace") for the measurement of tidal breathing parameters in newborns[END_REF] , but the accuracy of tidal parameters measured in this way has been questioned [START_REF] Jackson | A critical assessment of uncalibrated respiratory inductance plethysmography (Respitrace) for the measurement of tidal breathing parameters in newborns and infants[END_REF] . Even when RIP is calibrated before use, changes in band position or in the pattern of breathing can invalidate the calibration. A method of measuring respiratory airflow accurately at the chest wall without mask calibration would be highly desirable. The FloRight system (Volusense, Kongsvinger, Oslo, Norway) consists of two continuous wire coils sewn into a vest worn over the entire chest and abdomen, the upper coil covering the chest, the lower the abdomen. A weak (100mA) alternating current is passed through the coils, resulting in a magnetic field around the child's torso which is detected by an external magnetic field sensor. With breathing movements, the volume contained within the coils expands and contracts, causing proportional changes in the magnetic field that is generated.

The device can therefore directly measure changes in the volume of the respiratory system, and these volume changes can be differentiated digitally to yield a flow signal -and hence measure tidal breathing parameters.

Basic laboratory studies (Unpublished observations, Volusense) have suggested that the measurement of volume change is accurate and requires only electrical calibration with a cylindrical volume reference coil. The primary aim of this study was to validate the measurement system in healthy newborn infants -ie to demonstrate that it gives accurate measurements of tidal breathing parameters without needing calibration on the infant against airflow measured from a mask at the airway opening. Our primary hypothesis is that in spontaneously breathing healthy term newborns, the FloRight vest gives estimates of tidal volume which are similar to estimates measured from flow at the airway opening.

Secondary aims were to quantify and compare the repeatability of tidal breathing measurements using the two methods -chest wall (vest) and airway opening (mask) measurements -and to compare tidal breathing parameters (measured at the chest wall) with and without a mask in place. A further aim was to assess whether it was possible, using tidal parameters measured with the system, to distinguish between healthy newborn infants and infants with bronchopulmonary dysplasia (BPD).

Patients and Methods

The study protocol was approved by the East Sussex Research Ethics Committee and all parents gave written informed consent. In the first part of the study (validation), healthy newborn infants were studied simultaneously using the Floright system and a system measuring airflow via a mask using an ultrasonic flowmeter (Exhalyzer D, EcoMedics AG, Duernten, Switzerland). Ten infants under a week of age and over 37 weeks gestation, without a history of respiratory symptoms or congenital abnormalities were studied on the postnatal ward of the Royal Sussex County Hospital, Brighton, UK.

Firstly, a FloRight vest of suitable size -fitting snugly but without constriction -was put on over a single thin layer of clothing. The correct size of vest was gauged by measuring the chest circumference at nipple level, and the vest was placed covering the infant from armpit to groin. In this position the junction between the upper and lower coils of the vest is approximately at the lower border of the ribcage. The FloRight system was calibrated with the magnetic field detector in place and the volume reference cylinder at the side of the infant. For measurement the magnetic field detector was positioned so that the vest was aligned with the two fins and equidistant between them, with the baby lying on a surface 40 cm below the fins. The EcoMedics system was calibrated with a 100 ml Hans Rudolph volumetric syringe (Hans Rudolph Inc, Shawnee, Kansas, US). Once the baby was in quiet natural sleep, a firm face mask with inflatable cushion rim was placed over the baby's nose and mouth, then collection of two minutes of tidal breathing data was commenced simultaneously with the two systems. These recordings will be designated V1 (FloRight vest) and M1 (EcoMedics mask). The mask was then removed, and a two minute epoch of tidal breathing was recorded using FloRight alone, with no mask in place -designated V1A .

Finally, a further two-minute epoch was recorded using both systems for repeatability measurements -designated V2 and M2. Figure 1 shows the mask and vest in place simultaneously during data collection. The data sampling frequency was 200 Hz for the EcoMedics mask recording and 100 Hz for the FloRight vest system.

For calculation of the tidal breathing parameters, the traces were first inspected visually to select a 10-breath segment of stable tidal breathing with the following characteristics: no obvious artefacts, no sighs, no obvious changes in depth of breathing or baseline.

Simultaneous 10-breath segments from M1/V1, M2/V2, and from V1A were then analysed in detail to calculate the following parameters, measured breath-by-breath then averaged over the 10-breath segment:

1. Tidal volume (V T ) in ml, and per Kg body weight (V T /Kg) 2. Time to peak tidal expiratory flow as a ratio of expiratory time (T PTEF /T E ) For the vest recordings only, the following additional tidal parameters were calculated from the traces: The parameters were compared, using paired t-test and Bland-Altman analysis, between pairs of recordings as follows.

M1 and V1 were compared to assess the validity of the FloRight vest measurements.

M1 was compared with M2, and V1 with V2, to assess repeatability of both the mask and vest measurements.

V1 was compared with V1A to assess the effect of a facemask on tidal breathing parameters.

For the second part of the study, 11 oxygen-dependent infants with bronchopulmonary dysplasia (BPD, defined as persistent supplemental oxygen need beyond 36 weeks gestation, following neonatal respiratory failure) were measured, using the same protocol as above as far as possible. Mask measurements were not possible because of the nasal cannula oxygen (the oxygen flow caused a large baseline drift), so only V1 and V2 were recorded. The coefficient of repeatability of the vest measurements of tidal breathing parameters was calculated. In addition, the tidal measurements were compared with the 10 healthy term infants using two-sample t-tests. The characteristics of the infants studied are summarised in Table 1. Although the weight and length of the two groups is similar, the BPD infants, as would be expected, were short and light for age even when corrected for prematurity.

Results

Validity

Figure 2 shows Bland-Altman plots of M1 vs V1 for V T and for T PTEF /T E , with mean difference and limits of agreement shown. There was no significant difference in either parameter, and there was close correspondence between the paired measurements as shown by the small mean differences (Mask minus Vest V T +0.096 ml, T PTEF /T E -0.01) and narrow limits of agreement (V T +4.5 ml to -4.3 ml, T PTEF /T E +0.32 to -0.35).

Repeatability

Repeatability was expressed as the coefficient of repeatability (CR), defined as twice the standard deviation of the differences between measurements [START_REF] Bland | Statistical methods for assessing agreement between two methods of clinical measurement[END_REF] . We have also expressed it as a percentage of the mean value (CR%). Table 2 shows CR and CR% for: M1 vs M2 in healthy infants, V1 vs V2 in healthy infants, and V1 vs V2 in BPD infants.

Effect of facemask

Table 3 shows mean difference, 95% confidence intervals of mean difference, and limits of agreement for the tidal parameters, comparing V1 with V1A in the healthy infants. Tidal volume is significantly higher with the mask in place, as would be expected because of the additional deadspace. However, there was no significant difference in any of the tidal expiratory flow parameters. a healthy infant and a BPD infant: a clear difference can be seen in the pattern of expiratory flow ("sinusoidal" versus "quadrilateral" as originally described by Morris and Lane 12 ). Table 4 shows mean difference and 95% confidence intervals of mean difference, comparing V1 in healthy infants with V1 in BPD infants. There were significant differences in tidal volume (corrected for body weight) and all tidal expiratory flow parameters. V T per Kg was significantly higher in BPD infants (as expected due to increased physiological deadspace), while all the tidal expiratory flow parameters were significantly lower. Ratio of inspiratory to expiratory time (T I / T E ) showed only a non-significant trend to be lower.

Discussion

We have demonstrated that a novel volumetric vest system is able to measure both tidal volume and tidal expiratory flow parameters in unsedated infants, without prior calibration on the infant, and to yield values in healthy infants which are very close to those measured directly from airflow at the airway opening. The measurements using the vest are as repeatable as those measured at the airway opening. Furthermore, we have shown that tidal measurements made using this system are able to differentiate infants with bronchopulmonary dysplasia from healthy term infants.

Previous work using RIP has yielded conflicting results. Stick et al [START_REF] Stick | Validation of respiratory inductance plethysmography ("Respitrace") for the measurement of tidal breathing parameters in newborns[END_REF] , using uncalibrated RIP, showed close agreement between T PTEF /T E values from RIP with those from mask and pneumotachograph in unsedated healthy newborn infants. However, Jackson et al [START_REF] Jackson | A critical assessment of uncalibrated respiratory inductance plethysmography (Respitrace) for the measurement of tidal breathing parameters in newborns and infants[END_REF] a different uncalibrated RIP system in unsedated newborns and sedated older infants were unable to replicate this. In their study, RIP-measured T PTEF /T E was consistently lower, with wide limits of agreement. Neither study was designed to measure tidal volume.

Our values for tidal parameters in the healthy infants, measured both by mask and by vest, are very similar to published values in healthy term neonates measured by mask [START_REF] Stocks | Analysis of tidal breathing parameters in infancy: how variable is T PTEF :T E ?[END_REF][START_REF] Carlsen | Lung function in awake healthy infants: the first five days of life[END_REF][START_REF] Stick | Measurements during tidal breathing[END_REF] . This, as well as our finding that tidal expiratory flow parameters (unlike tidal volume) were not altered by the presence of a mask, suggests that existing normative values are appropriate in interpreting measurements made using this vest system. Our figures for repeatability of T PTEF /T E , both with mask (CR 41%) and vest (CR 37%), are also similar to published values [START_REF] Stocks | Analysis of tidal breathing parameters in infancy: how variable is T PTEF :T E ?[END_REF] , and demonstrate how variable this parameter is in newborn infants. This is a significant limitation of T PTEF /T E , however measured, and suggests that the parameters with better repeatability such as FVg may be worth exploring .

Clearly caution is needed in applying our conclusions on the validity of the system. We were not able to make mask measurements in our BPD infants because of the administration of nasal cannula oxygen, and therefore were not able to show whether the Floright system makes valid measurements in the presence of chest distortion. All our measurements were made during spontaneous tidal breathing in infants lying supine, so that we cannot comment on the validity of measurements in prone or side-lying infants, in older children measured in a sitting position, or in artificially ventilated infants. All our healthy neonates were above 2Kg weight: it is not yet clear whether the system will be accurate in small preterm infants.

At the beginning of the study we encountered difficulty in calibrating the equipment in an electrically "noisy" environment (eg near television screens): a software change was required to resolve this problem. Interference from nearby devices producing a high frequency changing magnetic field may still cause problems, in some settings, but would be likely to produce a "noisy" trace, rather than inaccurate measurements. The equipment is currently large and cumbersome, making its use in acute or intensive care settings difficult: we understand that design changes to modify this problem are planned. Despite these caveats, our findings suggest that this is an accurate technique for measuring tidal breathing without the need for a face mask. This technique has the potential to measure tidal flow parameters in situations where a mask is not tolerated (eg tachypnoea, awake infants) or mask measurements are problematic (eg oxygen therapy, continuous positive airway pressure, non-invasive ventilation). The volume changes can also be partitioned into chest and abdominal components, giving the potential to measure thoracoabdominal asynchrony in the context of acute respiratory disease or sleepdisordered breathing. Further work is needed to validate the technique in these settings. Because of the need for sedation, however, they are only practicable in stable infants without severe or acute lung disease. The need for sedation and the time taken for measurements also limits their clinical applicability. Measurement of tidal breathing parameters [2][3][4] is an attractive alternative, giving an indirect but non-invasive indication of lung function. They can be measured and repeated rapidly, and sedation is not always needed. However, the application of a facemask to capture respiratory airflow is problematic: it often causes disturbance or arousal, and there are suggestions 3;5;6 that both the trigeminal stimulation and the deadspace of a mask may alter the pattern of tidal breathing.

F

To avoid these problems, attempts have been made to measure tidal breathing parameters at the chest wall using respiratory inductive plethysmography (RIP) [START_REF] Adams | Respiratory Inductive Plethysmography[END_REF] . However, this requires prior calibration with airflow measured at a facemask if absolute volumes are to be measured [START_REF] Sackner | Calibration of respiratory inductive plethysmography during natural breathing[END_REF] , which negates most of the advantage of the technique. Using uncalibrated RIP has been advocated [START_REF] Stick | Validation of respiratory inductance plethysmography ("Respitrace") for the measurement of tidal breathing parameters in newborns[END_REF] , but the accuracy of tidal parameters measured in this way has been questioned [START_REF] Jackson | A critical assessment of uncalibrated respiratory inductance plethysmography (Respitrace) for the measurement of tidal breathing parameters in newborns and infants[END_REF] . Even when RIP is calibrated before use, changes in band position or in the pattern of breathing can invalidate the calibration. A method of measuring respiratory airflow accurately at the chest wall without mask calibration would be highly desirable. The FloRight system (Volusense, Kongsvinger, Oslo, Norway) consists of two continuous wire coils sewn into a vest worn over the entire chest and abdomen, the upper coil covering the chest, the lower the abdomen. A weak (100mA) alternating current is passed through the coils, resulting in a magnetic field around the child's torso which is detected by an external magnetic field sensor. With breathing movements, the volume contained within the coils expands and contracts, causing proportional changes in the magnetic field that is generated.

The device can therefore directly measure changes in the volume of the respiratory system, and these volume changes can be differentiated digitally to yield a flow signal -and hence measure tidal breathing parameters.

Basic laboratory studies (Unpublished observations, Volusense) have suggested that the measurement of volume change is accurate and requires only electrical calibration with a cylindrical volume reference coil. The primary aim of this study was to validate the measurement system in healthy newborn infants -ie to demonstrate that it gives accurate measurements of tidal breathing parameters without needing calibration on the infant against airflow measured from a mask at the airway opening. Our primary hypothesis is that in spontaneously breathing healthy term newborns, the FloRight vest gives estimates of tidal volume which are similar to estimates measured from flow at the airway opening.

Secondary aims were to quantify and compare the repeatability of tidal breathing measurements using the two methods -chest wall (vest) and airway opening (mask) measurements -and to compare tidal breathing parameters (measured at the chest wall)

with and without a mask in place. A further aim was to assess whether it was possible, using tidal parameters measured with the system, to distinguish between healthy newborn infants and infants with bronchopulmonary dysplasia (BPD).

Patients and Methods

The study protocol was approved by the East Sussex Research Ethics Committee and all parents gave written informed consent. In the first part of the study (validation), healthy newborn infants were studied simultaneously using the Floright system and a system measuring airflow via a mask using an ultrasonic flowmeter (Exhalyzer D, EcoMedics AG, Duernten, Switzerland). Ten infants under a week of age and over 37 weeks gestation, without a history of respiratory symptoms or congenital abnormalities were studied on the postnatal ward of the Royal Sussex County Hospital, Brighton, UK.

Firstly, a FloRight vest of suitable size -fitting snugly but without constriction -was put on over a single thin layer of clothing. The correct size of vest was gauged by measuring the chest circumference at nipple level, and the vest was placed covering the infant from armpit to groin. In this position the junction between the upper and lower coils of the vest is approximately at the lower border of the ribcage. The FloRight system was calibrated with the magnetic field detector in place and the volume reference cylinder at the side of the infant. For measurement the magnetic field detector was positioned so that the vest was aligned with the two fins and equidistant between them, with the baby lying on a surface 40 cm below the fins. The EcoMedics system was calibrated with a 100 ml Hans Rudolph volumetric syringe (Hans Rudolph Inc, Shawnee, Kansas, US). Once the baby was in quiet natural sleep, a firm face mask with inflatable cushion rim was placed over the baby's nose and mouth, then collection of two minutes of tidal breathing data was commenced simultaneously with the two systems. These recordings will be designated V1 (FloRight vest) and M1 (EcoMedics mask). The mask was then removed, and a two minute epoch of tidal breathing was recorded using FloRight alone, with no mask in place -designated V1A .

Finally, a further two-minute epoch was recorded using both systems for repeatability measurements -designated V2 and M2. Figure 1 shows the mask and vest in place simultaneously during data collection. The data sampling frequency was 200 Hz for the EcoMedics mask recording and 100 Hz for the FloRight vest system.

For calculation of the tidal breathing parameters, the traces were first inspected visually to select a 10-breath segment of stable tidal breathing with the following characteristics: no obvious artefacts, no sighs, no obvious changes in depth of breathing or baseline.

Simultaneous 10-breath segments from M1/V1, M2/V2, and from V1A were then analysed in detail to calculate the following parameters, measured breath-by-breath then averaged over the 10-breath segment:

1. Tidal volume (V T ) in ml, and per Kg body weight (V T /Kg) 2. Time to peak tidal expiratory flow as a ratio of expiratory time (T PTEF /T E )

For the vest recordings only, the following additional tidal parameters were calculated from the traces: The parameters were compared, using paired t-test and Bland-Altman analysis, between pairs of recordings as follows.

M1 and V1 were compared to assess the validity of the FloRight vest measurements.

M1 was compared with M2, and V1 with V2, to assess repeatability of both the mask and vest measurements.

V1 was compared with V1A to assess the effect of a facemask on tidal breathing parameters.

For the second part of the study, 11 oxygen-dependent infants with bronchopulmonary dysplasia (BPD, defined as persistent supplemental oxygen need beyond 36 weeks gestation, following neonatal respiratory failure) were measured, using the same protocol as above as far as possible. Mask measurements were not possible because of the nasal cannula oxygen (the oxygen flow caused a large baseline drift), so only V1 and V2 were recorded. The coefficient of repeatability of the vest measurements of tidal breathing parameters was calculated. In addition, the tidal measurements were compared with the 10 healthy term infants using two-sample t-tests. The characteristics of the infants studied are summarised in Table 1. Although the weight and length of the two groups is similar, the BPD infants, as would be expected, were short and light for age even when corrected for prematurity.

Results

Validity

Figure 2 shows Bland-Altman plots of M1 vs V1 for V T and for T PTEF /T E , with mean difference and limits of agreement shown. There was no significant difference in either parameter, and there was close correspondence between the paired measurements as shown by the small mean differences (Mask minus Vest V T +0.096 ml, T PTEF /T E -0.01) and narrow limits of agreement (V T +4.5 ml to -4.3 ml, T PTEF /T E +0.32 to -0.35).

Repeatability

Repeatability was expressed as the coefficient of repeatability (CR), defined as twice the standard deviation of the differences between measurements [START_REF] Bland | Statistical methods for assessing agreement between two methods of clinical measurement[END_REF] . We have also expressed it as a percentage of the mean value (CR%). Table 2 shows CR and CR% for: M1 vs M2 in healthy infants, V1 vs V2 in healthy infants, and V1 vs V2 in BPD infants.

Effect of facemask

Table 3 shows mean difference, 95% confidence intervals of mean difference, and limits of agreement for the tidal parameters, comparing V1 with V1A in the healthy infants. Tidal volume is significantly higher with the mask in place, as would be expected because of the additional deadspace. However, there was no significant difference in any of the tidal expiratory flow parameters. a healthy infant and a BPD infant: a clear difference can be seen in the pattern of expiratory flow ("sinusoidal" versus "quadrilateral" as originally described by Morris and Lane 12 ). Table 4 shows mean difference and 95% confidence intervals of mean difference, comparing V1 in healthy infants with V1 in BPD infants. There were significant differences in tidal volume (corrected for body weight) and all tidal expiratory flow parameters. V T per Kg was significantly higher in BPD infants (as expected due to increased physiological deadspace), while all the tidal expiratory flow parameters were significantly lower. Ratio of inspiratory to expiratory time (T I / T E ) showed only a non-significant trend to be lower.

Discussion

We have demonstrated that a novel volumetric vest system is able to measure both tidal volume and tidal expiratory flow parameters in unsedated infants, without prior calibration on the infant, and to yield values in healthy infants which are very close to those measured directly from airflow at the airway opening. The measurements using the vest are as repeatable as those measured at the airway opening. Furthermore, we have shown that tidal measurements made using this system are able to differentiate infants with bronchopulmonary dysplasia from healthy term infants.

Previous work using RIP has yielded conflicting results. a different uncalibrated RIP system in unsedated newborns and sedated older infants were unable to replicate this. In their study, RIP-measured T PTEF /T E was consistently lower, with wide limits of agreement. Neither study was designed to measure tidal volume.

Our values for tidal parameters in the healthy infants, measured both by mask and by vest, are very similar to published values in healthy term neonates measured by mask [START_REF] Stocks | Analysis of tidal breathing parameters in infancy: how variable is T PTEF :T E ?[END_REF][START_REF] Carlsen | Lung function in awake healthy infants: the first five days of life[END_REF][START_REF] Stick | Measurements during tidal breathing[END_REF] . This, as well as our finding that tidal expiratory flow parameters (unlike tidal volume) were not altered by the presence of a mask, suggests that existing normative values are appropriate in interpreting measurements made using this vest system. Our figures for repeatability of T PTEF /T E , both with mask (CR 41%) and vest (CR 37%), are also similar to published values [START_REF] Stocks | Analysis of tidal breathing parameters in infancy: how variable is T PTEF :T E ?[END_REF] , and demonstrate how variable this parameter is in newborn infants. This is a significant limitation of T PTEF /T E , however measured, and suggests that the parameters with better repeatability such as FVg may be worth exploring .

Clearly caution is needed in applying our conclusions on the validity of the system. We were not able to make mask measurements in our BPD infants because of the administration of nasal cannula oxygen, and therefore were not able to show whether the Floright system makes valid measurements in the presence of chest distortion. All our measurements were made during spontaneous tidal breathing in infants lying supine, so that we cannot comment on the validity of measurements in prone or side-lying infants, in older children measured in a sitting position, or in artificially ventilated infants. All our healthy neonates were above 2Kg weight: it is not yet clear whether the system will be accurate in small preterm infants.

At the beginning of the study we encountered difficulty in calibrating the equipment in an electrically "noisy" environment (eg near television screens): a software change was required to resolve this problem. Interference from nearby devices producing a high frequency changing magnetic field may still cause problems, in some settings, but would be likely to produce a "noisy" trace, rather than inaccurate measurements. The equipment is currently large and cumbersome, making its use in acute or intensive care settings difficult:

we understand that design changes to modify this problem are planned.

Despite these caveats, our findings suggest that this is an accurate technique for measuring tidal breathing without the need for a face mask. This technique has the potential to measure tidal flow parameters in situations where a mask is not tolerated (eg tachypnoea, awake infants) or mask measurements are problematic (eg oxygen therapy, continuous positive airway pressure, non-invasive ventilation). The volume changes can also be partitioned into chest and abdominal components, giving the potential to measure thoracoabdominal asynchrony in the context of acute respiratory disease or sleepdisordered breathing. Further work is needed to validate the technique in these settings.

3 . 2 5. 6 .

 326 Ratio of expiratory time to inspiratory time (T E /T I )4. Expiratory flow at 50% of tidal volume as a ratio of peak tidal expiratory flow (TEF 50 /PTEF) Expiratory flow at 25% of tidal volume as a ratio of peak tidal expiratory flow (TEF 25 /PTEF)2 Centre of gravity along the volume axis for the tidal expiratory flow-volume curve (FVg). This is the dimensionless value along the volume axis (taking 0 as the start of expiration and 1 as the end of expiration) such that the areas under the curves to right and left of this point are equal. A symmetrical curve with peak flow occurring at mid-tidal volume would have FVg=0.5; any shift of peak tidal expiratory flow towards the start of inspiration will give values below 0.5.

Figure 3

 3 Figure 3 shows typical flow-time and flow-volume traces recorded by the FloRight device in

Figure 1 :Figure 2 :Figure 3 :

 123 Figure 1: Study setup, showing both FloRight vest and mask with ultrasonic flowmeter in place. 194x153mm (96 x 96 DPI)

  in infants is difficult and time-consuming, and in certain situations virtually impossible with current techniques. Methods such as rapid thoracic compression and its raised volume refinement have advanced our understanding of infant lung disease 1 .

3 . 4 . 2 5. 6 .

 3426 Ratio of expiratory time to inspiratory time (T E /T I ) Expiratory flow at 50% of tidal volume as a ratio of peak tidal expiratory flow (TEF 50 /PTEF) Expiratory flow at 25% of tidal volume as a ratio of peak tidal expiratory flow (TEF 25 /PTEF)2 Centre of gravity along the volume axis for the tidal expiratory flow-volume curve (FVg). This is the dimensionless value along the volume axis (taking 0 as the start of expiration and 1 as the end of expiration) such that the areas under the curves to right and left of this point are equal. A symmetrical curve with peak flow occurring at mid-tidal volume would have FVg=0.5; any shift of peak tidal expiratory flow towards the start of inspiration will give values below 0.5.

Figure 3

 3 Figure 3 shows typical flow-time and flow-volume traces recorded by the FloRight device in

Figure 1a :

 1a Figure 1a: Study setup, showing both FloRight vest and mask with ultrasonic flowmeter in place. The two fins of the magnetic field detector are shown suspended above the infant. 105x72mm (150 x 150 DPI)

Table 1 :

 1 Adams JA. Respiratory Inductive Plethysmography. In: Stocks J, Sly PD, Tepper RS, Morgan WJ, editors. Infant Respiratory Function Testing. New York: Wiley-Liss; 1996. 139-164. Characteristics of infants studied, showing mean (SD). Z scores for weight and length are calculated as the number of SD above or below the predicted mean from growth charts; for the BPD infants, age is corrected for prematurity.

	(6) Dolfin T, Duffty P, Wilkes D, England S, Bryan H. Effects of a face mask and
	pneumotachograph on breathing in sleeping infants. Am Rev Respir Dis 1983; 128(6):977-
	979.
	(7) (8) Sackner MA, Watson H, Belsito AE, Finerman D, Saurez M, Gonzalez G et al. Calibration of
	respiratory inductive plethysmography during natural breathing. J Appl Physiol 1989;
	66:410-420.
	(9) Stick SM, Ellis E, LeSouëf PN, Sly PD. Validation of respiratory inductance plethysmography
	("Respitrace") for the measurement of tidal breathing parameters in newborns. Pediatr
	Pulmonol 1992; 14:187-191.
	(10) Jackson E, Stocks J, Pilgrim L, Dundas I, Dezateux C. A critical assessment of uncalibrated
	respiratory inductance plethysmography (Respitrace) for the measurement of tidal
	r o breathing parameters in newborns and infants. Pediatr Pulmonol 1995; 20(2):119-124.
	P
	e
	e r
	R
	e
	v i e
	w

(11)

Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; i:307-310. (12) Morris MJ, Lane DJ. Tidal expiratory flow patterns in airflow obstruction. Thorax 1981; 36:135-142. (13) Stocks J, Dezateux CA, Jackson EA, Hoo A-F, Costeloe KL, Wade AM. Analysis of tidal breathing parameters in infancy: how variable is T PTEF :T E ? Am J Resp Crit Care Med 1994; 150:1347-1354. (14) Lodrup Carlsen KC, Carlsen K-H. Lung function in awake healthy infants: the first five days of life. Eur Respir J 1993; 6:1496-1500. (15) Stick SM. Measurements during tidal breathing. In: Stocks J, Sly PD, Tepper RS, Morgan WJ, editors. Infant Respiratory Function Testing. New York: Wiley-Liss; 1996. 117-138.

Table 2 .

 2 Tidal breathing parameters, showing mean values, repeatability coefficient (CR) and CR as percent of mean value (CR%), for mask and vest measurements in healthy infants, and for mask measurements in BPD infants.

		With Mask	Without Mask	Mean Difference
		Mean (SD)	Mean (SD)	(95%Confidence Interval)
	Tidal Volume (ml) 20.56	16.096	4.67	*
		(4.10)	(3.79)	(+1.64 to +7.29)
	T PTEF /T E	0.51	0.53	0.01
		(0.14)	(0.15)	(-0.09 to +0.06)
	TEF 50 /PTEF	0.918	0.849	0.069
		(0.043)	(0.095)	(-0.010 to +0.148)
	TEF 25 /PTEF	0.776	0.772	0.004
		(0.102)	(0.137)	(-0.038 to +0.047)
	FVg	0.498	0.502	-0.005
		(0.020)	(0.028)	(-0.02 to +0.01)
		F o r
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Table 3 .

 3 Tidal breathing parameters in healthy newborn infants measured by volumetric vest, comparing values with and without face mask in place. * = p < 0.05

		Normal	BPD	p value
		(n=10)	(n=11)
	V T / Kg	5.40	7.01	0.009
	(ml/Kg)	(1.23)	(1.32)
	T PTEF /T E	0.506	0.217	0.00004
		(0.150)	(0.094)
	T E / T I	1.04	1.30	0.08
		(0.18)	(0.42)
	TEF 50 /PTEF	0.920	0.744	0.009
		(0.068)	(0.125)
	TEF 25 /PTEF	0.787	0.457	0.00002
		(0.116)	(0.148)
	FVg	0.501	0.430	0.00009
		(0.028)	(0.037)
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Table 4 .

 4 Tidal breathing parameters measured by volumetric vest in healthy and BPD infants, showing mean (SD) values and p value for comparison (two-sample t-test).

Page 19 of 32 John

	Pediatric Pulmonology
	Measuring tidal breathing parameters using a volumetric vest in Summary
	neonates with and without lung disease Lung function measurement is difficult in unsedated infants; tidal breathing parameters are
	a useful non-invasive surrogate, but even these measurements cause disturbance from
	Olden C RSCN, Symes E RSCN, Seddon P MB ChB. applying a facemask. We investigated a novel volumetric vest system (FloRight), which
	Respiratory Research Unit, Royal Alexandra Children's Hospital, Brighton BN2 5BE, UK measures volume changes of the respiratory system from changes in the magnetic fields
	induced by current-carrying coils around the entire chest and abdomen.
	Using a facemask and ultrasonic flowmeter as comparator, we assessed the validity and
	F o r repeatability of tidal breathing parameters measured by FloRight in 10 healthy newborn F o r infants during natural sleep. We also assessed the effect of a facemask on tidal volume and
	P e tidal expiratory flow parameters. To assess the ability of the FloRight system to detect P e disease, we compared the healthy infants with 11 infants suffering from bronchopulmonary
	e r e r Tidal parameters with the FloRight vest corresponded closely with facemask measurements. dysplasia.
	R e v i e Respiratory Care, Royal Alexandra Children's Hospital, Brighton BN2 5BE, UK Correspondence to Dr Paul Seddon: Tel: +44 1273 696955 paul.seddon@bsuh.nhs.uk R Mean difference, mask minus vest, for tidal volume was 0.096mL (p<0.05), with limits of e agreement +4.5 to -4.3mL. Coefficient of repeatability was similar for mask and vest v i e measurements. Tidal volume measured by FloRight with mask in place (20.6mL) was
	w w significantly higher than without mask (16.1mL), but tidal expiratory flow parameters were
	not altered. FloRight measurements of tidal parameters were markedly different between
	the two groups of infants, with tidal volume per Kg sigificantly higher and tidal expiratory
	flow parameters significantly lower.
	Our findings suggest that the FloRight system is able to measure tidal breathing parameters
	accurately, in healthy newborn infants, without prior calibration on the infant. It appears to
	have at least sufficient sensitivity to detect severe respiratory disease.
	Running head: Measuring tidal breathing with a volumetric vest

Wiley & Sons, Inc. C Olden and E Symes receive salary support from the Research for Patient Benefit scheme of the National Institute for Health Research, UK. The authors gratefully acknowledge technical assistance from Roy Norum of OKB Medical Ltd, UK, and from Kjell Øygarden and Morten Eriksen of Volusense, Norway. Keywords: Infant, respiratory function, tidal breathing, chest wall.

  Stick et al[START_REF] Stick | Validation of respiratory inductance plethysmography ("Respitrace") for the measurement of tidal breathing parameters in newborns[END_REF] , using uncalibrated RIP, showed close agreement between T PTEF /T E values from RIP with those from mask and pneumotachograph in unsedated healthy newborn infants. However, Jackson et al10 , using

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John Wiley & Sons, Inc.Pediatric Pulmonology


Professor Hilary Humphreys
email: hhumphreys@rcsi.ie

Elisabeth Nagy

Gunnar Kahlmeter

Andreas Voss
email: vossandreas@gmail.com

Elisabeth Ridgway
email: elisabeth.ridgway@sth.nhs.uk

Gjhm Ruijs

The Need for European Professional Standards and the Challenges Facing Clinical Microbiology

Keywords: clinical microbiology, professional standards, curriculum, centralization, outsourcing, integration clinical microbiology, professional standards, curriculum, centralization, outsourcing, integration

Microorganisms spread across national boundaries and the professional activities of clinical (medical) microbiologists are critical in minimising their impact. Clinical microbiologists participate in many activities, e.g. diagnosis, antibiotic therapy and there is a need for a set of professional standards for Europe with a common curriculum, to build upon the current strengths of the specialty and to facilitate the free movement of specialists within the European Union. Such standards will also better highlight the important contribution of clinical microbiologists to healthcare. There is a move to larger centralised microbiology laboratories often located off-site from an acute hospital, driven by the concentration of resources, amalgamation of services, outsourcing of diagnostics, automation, an explosion in the range of staff competencies and accreditation. Large off-site centralised microbiology laboratories are often distant to the patient and may not facilitate the early detection of microbial spread. Ultimately, the needs of patients and the public are paramount in deciding on the future direction of clinical microbiology. Potential conflicts between integration on an acute hospital site and centralization can be resolved by a common set of professional standards and a team-based approach that puts patients first.

The ease with which we move across continents alters our perception of distance and we are increasingly part of a global community. This applies to us and to our microorganisms such as H1N1 influenza virus, methicillin-resistant Staphylococcus aureus (MRSA), human immunodeficiency virus (HIV), tuberculosis and hyper virulent strains of Clostridium difficile 027. Their success in causing epidemics is influenced by the effectiveness of early detection, therapy and control.

A key medical specialty in this regard, is Clinical Microbiology (CM), referred to as Medical Microbiology in some countries, but is there a broad consensus within Europe of what CM involves? CM is a combination of many activities including amongst other things the synthesis and reporting of microbiology laboratory results and clinical consultation. Many of the components are interdependent and must be underpinned by agreed professional standards. Furthermore, deficiencies in one aspect, e.g. laboratory diagnosis can impair quality in another, e.g. clinical consultation.

CM has evolved over the last three decades from one that was largely laboratorybased and dominated by bacteriology to a complex mix of diagnostic, therapeutic, scientific, epidemiological and preventative activities. During that time, enormous changes have impacted on CM and infectious diseases (ID), including dramatically increased rates and novel complex mechanisms of antibiotic resistance rendering an increased number of bacteria virtually untreatable, more patients highly susceptible to infection, the application of molecular microbiology to rapid diagnosis and new infections, e.g. Legionella pneumophila, Borrelia burgdorferi, Clostridium difficile, Helicobacter pylori disease, HIV, Hepatitis C, SARS and West Nile virus, all described in the last 30-35 years.

Professional Standards

Given these changes, a set of European professional standards for the medical specialty of CM is needed for three main reasons. Although, professional standards for related disciplines such as ID are of course also important, they are not the subject of this article.

Firstly, it is necessary to discuss and define the professional standards required in delivering optimal microbiological support to colleagues and patients in all health care settings, thus providing a clear common professional identity. Presently there is no common European tradition with regards to the balance between laboratory-based diagnostic microbiology and bedside consultation and infection prevention and control. 1).

Members of the public often view any infection as a medical failure due to inadequacies in CM and related specialties, not realizing that some infections, especially in very vulnerable patients, are difficult to prevent and virtually inevitable.

This view can only be countered by the highest professional standards that are recognizable and acceptable to the public. Outsourcing refers to the sub-contracting of microbiology processes to a third party.

Challenges facing CM

This already partly occurs such as when specialist tests are referred to a regional or national reference laboratory. However, it is important to distinguish between the referring on of samples between professionals to enhance services and to provide appropriate expertise compared with outsourcing driven solely by cost savings and logistics. Outsourcing may separate the three main activities of CM; analysis on one side and synthesis and consultation on the other with a lack of input as to what is being done and why. Accreditation is driven by patient safety, political pressures and a desire for harmonization of services. It can enhance professional standards but often excessively focuses on technical aspects with delayed improvements in service development.

The range of competences among staff is rapidly increasing, e.g. staff exclusively involved in flow cytometry or antimicrobial susceptibility testing. Medically trained staff work with biomedical scientists, immunologists, physicists, biologists, molecular microbiologists, statisticians and others. The need for many competences drives concentration and amalgamation and may be seen by some as a substitute for medical staff rather than as complementary. Finally, despite advantages such as costeffectiveness, automation may lead to a loss of expertise, and overdependence on technology, at the expense of clinical acumen.

Rationalization and professional standards

The roles of the clinical microbiologist are linked and complementary. For example, the laboratory diagnosis of MRSA surgical site infection requires technical skills, clinical consultation, advice on antimicrobial therapy, infection prevention and control measures, and the findings may challenge the efficacy of antibiotic stewardship measures. All components must be included in any agreement or contract between the provider (public or private off-site laboratory) and user (acute hospital, primary care facility).

The multidisciplinary or large-scale microbiological laboratory on a green-field or non-hospital site is often characterized by the provision of services on a regional (or national) scale with large volumes of specimens collected from many different sources. Logistics become all-important, clinical liaison is difficult because of distances, with non-participation by CM in patient care and due to the scale of operation, the needs of the individual patient are lost.

The integrated CM service is usually part of a hospital and provides a comprehensive service including diagnostics (analysis and synthesis), clinical consultation and infection prevention and control to that hospital, and to the surrounding community, e.g. general practitioners and nursing homes. Consultants in CM work with and assist other medical specialists, most particularly ID, internal medicine, paediatrics, surgery and public health but must not be separated from the laboratory. Some small hospitalbased CM laboratories are finding it increasingly difficult to afford developments in modern CM because of the absence of large numbers of specimens or the need to invest upstream in the laboratory. For example PCR for MRSA before surgery leads to earlier decolonisation with greater efficiencies and potential cost savings for surgery, although sometimes difficult to quantify, but these are not repatriated to the microbiology laboratory.

The availability of critical but preliminary results can be communicated by staff as part of an integrated CM service to allow interim therapeutic or infection prevention and control action for which detailed knowledge of the local circumstances and facilities is essential. Hospitals located in the north and west of Europe were more likely to examine blood cultures more than once a day and just over 40% of laboratories conducted daily ward rounds by CMs or ID physicians to advise on therapy, more common in the north (58%) and west (49%) [START_REF] Mackenzie | The role of microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals[END_REF]. However, there was no analysis in terms of the size of the departments surveyed. Requests for telephone advice came most frequently from the medical specialties, neurosurgery and intensive care in an Irish hospital but those relating to infection prevention and control had increased in the later years [START_REF] Humphreys | Where do out-of-hours calls to a consultant microbiologist come from?[END_REF]. The clinical microbiologist also acts as a "gatekeeper" in the approval of requests for testing, contributing to cost-effective CM services.

Large centralised microbiology laboratories have the potential and expertise to assess new technologies and to combine basic with translational research because of the professional skill mix, e.g. medical doctors, doctoral scientists, immunologists, molecular biologists, etc. In a large regional French laboratory, ribosomal sequencing of brain abscess material identified 49 bacterial species compared with 14 by culture Large centralised microbiology laboratories can designate specific staff to prioritize quality assurance issues but quality per se may then not be embedded in all staff. A review of staff in the UK suggests that there may be an optimal number of staff, i.e. less than 30 which maximizes efficiency and staff satisfaction [START_REF] Pitt | Effect of staff attitudes on quality in clinical microbiology services[END_REF].

High throughput and an extended working day are potentially easier in large centralised or off-site laboratories because the increased numbers of staff provide more flexibility. Nonetheless, there may be a failure to reflect individual patient needs, and a lack of urgency. A large complement of staff may facilitate a 24 hour service, resulting in quicker results and a more extensive range of tests but this may lead to unnecessary testing with the failure to prioritize tests because there is not full integration with a CM service. Some of the positive features of both models are highlighted in Table 2.

Conclusions

Ultimately, the needs of patients and the public are paramount in the future of CM.

Potential conflicts between integration and specialization can be resolved by a common set of professional standards and a team-based, flexible approach. However, the separation of CM from patient care risks undermining the diagnosis and management of infection in all patients, and the infrastructure that currently facilitates infection prevention and antibiotic stewardship must be preserved. A rational and safe option should include integrated comprehensive CM laboratories taking the lead in providing services for the individual patient, usually on a hospital site as the sickest patients are located there, assisted by specialized and regional laboratories, which may be off site. In the Netherlands, the National Health Care Inspectorate has concluded that the current structure for CM should be maintained in the interests of patient safety and that widespread outsourcing is not necessary or acceptable [START_REF] Bonten | Medisch-microbiologische laboratoria in Nederlandse ziekenhuizen: essentieel voor veilige patiëntenzorg (Medical microbiology laboratories in Dutch hospitals: essential for safe patient care)[END_REF].

Finally, the European professional societies, ESCMID and UEMS, must lead in defining the appropriate professional standards for CM and in addressing the challenges ahead while at the same time recognizing differences in regional and national approaches to service delivery.

Research and development

 leadership in larger institutions or contribution from smaller institutions to research programmes  evaluation of new diagnostic or other techniques  clinical trials of pathogenesis, antimicrobial chemotherapy, etc  liaison with academic institutions/universities

  CM must also adapt to new challenges which include changing professional practice, technological advances in the laboratory and information technology (IT). In CM there is much discussion on what can provide the better service -an on-site hospital clinical microbiology laboratory with close links between the clinical microbiologists and other specialists in consultation, or a large multidisciplinary laboratory located off-site at a distance from a hospital. This second option concentrates technical resources on a single site with diagnostic automation and IT, but with the risk of only processing microbiology specimens. There is no one correct option for all circumstances but CM must not become a bystander to a largely analytic service without clinical and consultative aspects. When assessing which model is appropriate, it is important to understand what professional standards in CM should support. These are - Delivering safe, rapid, efficient and effective care to all patients. Creating a microbiologically safe environment for patients and health care workers in hospitals and in other healthcare facilities. Assessing and counteracting the evolution of new and existing diseases, and the rapid increase in antimicrobial resistance.Current trends in CM include concentration of resources (the formation of larger microbiological units from the closing of smaller units), amalgamation of services (the formation of multidisciplinary laboratory facilities), outsourcing of microbiology laboratory diagnostics, automation of sample handling and diagnostics, accreditation of services and an explosion in microbiology laboratory staff competencies with greater sub-specialisation of skills and tasks.The formation of larger microbiology laboratories, through concentration and/or amalgamation, and the closure of smaller facilities may increase the range of diagnostics and staff competences, and increase flexibility in staffing, affordability of automation and perceived cost/effectiveness. However, contact with the individual patient and the consultative aspect of the services may be lost as much energy will be devoted to the logistics of services, e.g. transport of a sample and the automation of diagnostics. Consequently, we may lose control over the rapid spread of certain infections with preventative measures not being implemented. Epidemiological monitoring is a key component of publically funded CM services to quickly identify changing trends to facilitate early interventions but this support is not necessarily provided by private organisations or consortia.

[ 3 ]

 3 but the apparent failure to try and interpret the significance of the additional species in individual patients and how this extra information affected antimicrobial chemotherapy and clinical outcome, means the true role of this technology is not yet clear.

Table 1 .

 1 We are grateful to Dr Edmond G Smyth and Professor John Degener, chairman of the UEMS Section of Medical Microbiology, for helpful feedback during the preparation of this manuscript. Professional standards and the role of the clinical microbiologist  provision of information to patients and the public  undergraduate and postgraduate education and training to medical doctors, scientists, nurses, etc  conduct and dissemination of clinical and laboratory audit results

	Core function	Role of the clinical microbiologist
	Laboratory	 hospital and community infections
	diagnosis	 guidelines, e.g. appropriate specimens for which infections
		 screening for the appropriateness of specimens
		 patient focused, clinically relevant with standard operating
		procedures
		 interpretation of results
	Clinical	 patient focused
	consultation	 solicited and unsolicited advice
		 incidental and regular, e.g. intensive care unit ward rounds
	Laboratory	 strategic planning with scientific and other staff
	management	 prioritising resources with input to purchasing
		 human resources policy; from applications to the ageing workforce
		 staff health and safety
		 quality assurance and accreditation
	Multidisciplinary	 prevention, diagnosis and treatment of infection
	protocols and	 antimicrobial stewardship
	guidelines	 committee work, e.g. antimicrobial surveillance, antimicrobial
		stewardship, infection prevention and control in hospital and in the
		community
	Infection	 leadership within and outside hospitals with other professionals
	prevention and	 day-to-day advice
	control	 outbreak management
		 collection and interpretation of surveillance data for action
	Public health	 collaboration with local, regional and national agencies
		 notification of laboratory surveillance data
		 collection of national surveillance data
	Communication,
	education and
	training

Table

Table 2

 2 Positive aspects of on-site hospital microbiology laboratories and off-site multi-disciplinary laboratories

	On-site hospital microbiology laboratory	Off-site multi-disciplinary laboratory
	 Focus on the individual patient	 Focus on logistics and information
	 Clinically relevant diagnostics	technology
	 Close contact between laboratory and clinic	 Greater scope of services, e.g. 24h
	 Comprehensive service, i.e. diagnosis,	provision
	clinical liaison and infection prevention	 Greater range of staff competencies
	 Close collaboration between laboratory and	 Automation
	infection control teams	 Rationalisation and cost-
	 Integrated service with other disciplines, e.g.	effectiveness per test
	infectious diseases

Table

Transparency Declarations HH has received research funding or support from Pfizer, Steris Corporation, 3M, Inov8 Science and Cepheid in the last three years. He has also received lecture or consultancy fees from 3M, Novartis and Astellas.