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Cheryl M Salome - One of the best experts on this subject based on the ideXlab platform.

  • changes in oscillatory impedance and Nitrogen Washout with combination fluticasone salmeterol therapy in copd
    Respiratory Medicine, 2014
    Co-Authors: Sophie Timmins, Cheryl M Salome, Robin E Schoeffel, Chantale Diba, Gregory G King
    Abstract:

    Summary Introduction Combination inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) therapy reduces the exacerbation rate and improves spirometry and quality of life in COPD. We hypothesized that ICS/LABA therapy also improves small airway function measured by FOT. Methods 14 subjects with COPD were commenced on combination fluticasone propionate/salmeterol therapy for 3 months. At baseline, subjects completed the St George Respiratory Questionnaire (SGRQ) and underwent standard pulmonary function tests as well as forced oscillation technique (FOT) and single and multiple breath Nitrogen Washouts. All tests were repeated at the completion of 3 months of therapy. Results Subjects were of mean (SD) age 65.9 years (8.4), BMI 30.0 (5.6), pack years 51.4 (21.1), post-bronchodilator FEV 1 % predicted 62.7 (20). At baseline, mean SGRQ total was 39.0 (17.7) and FRC% predicted 125.4 (31.3). From FOT, Rrs-total was 5.69 (1.29) cmH 2 O/L/s, Xrs-total −3.48 (2.16) cmH 2 O/L/s, EFL Index 3.51 (2.45) cmH 2 O/L/s. After 3 months of therapy, there were significant improvements in SGRQ score (−13.81, p 1 (+40 mL, p  = 0.14). From FOT, total resistance (−0.63 cmH 2 O/L/s, p  = 0.0004), reactance (+1.2 cmH 2 O/L/s, p  = 0.013), and expiratory flow limitation (−1.21 cmH 2 O/L/s, p  = 0.02) also improved. There were no significant changes in ventilation heterogeneity indices. Conclusion Combination therapy is associated with improvements in small airways function in COPD, despite an absence of change in FEV 1 . FOT may be a clinically useful marker of small airway function in COPD that is responsive to treatment.

  • effect of methacholine on peripheral lung mechanics and ventilation heterogeneity in asthma
    Journal of Applied Physiology, 2013
    Co-Authors: Sylvia Verbanck, Cheryl M Salome, Bruce Thompson, Sue R Downie, Norbert Berend
    Abstract:

    The forced oscillation technique (FOT) and multiple-breath Nitrogen Washout (MBNW) are noninvasive tests that are potentially sensitive to peripheral airways, with MBNW indexes being especially sen...

  • effects of methacholine on small airway function measured by forced oscillation technique and multiple breath Nitrogen Washout in normal subjects
    Respiratory Physiology & Neurobiology, 2005
    Co-Authors: Gregory G King, Norbert Berend, William C Thorpe, Cheryl M Salome, Sylvia Verbanck, Stephen R Downie
    Abstract:

    The multiple breath Nitrogen Washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5 Hz (sGrs 5 =Grs 5 /FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R 2 = 0.68, p = 0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R 2 = 0.79, p<0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs 5 in a multivariate model (R 2 = 0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and sGrs 5 before and after methacholine challenge. In conclusion, Scond and sGrs 5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in termina] airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions.

  • a comparison of two methods for measuring airway distensibility Nitrogen Washout and the forced oscillation technique
    Physiological Measurement, 2004
    Co-Authors: Norbert Berend, William C Thorpe, Sylvia Verbanck, Bruce Thompson, Nathan J Brown, Sue R Downie, Cheryl M Salome
    Abstract:

    The measurement of airway stiffness is an important tool for studying airway remodelling in asthma. The relationship between airway calibre and lung volume (airway distensibility) was measured by forced oscillation technique (FOT) and compared with that measured by single-breath Nitrogen Washout (SBNW). In four non-asthmatic healthy subjects and three asthmatics, anatomical dead space (VDF) was measured by SBNW and respiratory system conductance (Grs) was measured by FOT at 6 Hz. During SBNW testing, 0.51 oxygen boluses were inhaled from three different lung volumes: functional residual capacity (FRC), 11 above FRC and near total lung capacity (TLC). Following inhalation of the oxygen bolus subjects exhaled to residual volume and then inhaled to TLC. During FOT, subjects breathed 0.5-1.01 tidal volumes but with gradually increasing end-expiratory lung volume until close to TLC, then returned to normal breathing before inhaling to TLC. This was also repeated but with reducing lung volume from TLC. Absolute lung volumes were measured by body plethysmography and related to volumes during FOT and SBNW by reference to TLC obtained at the end of each SBNW or FOT test manoeuvre. Distensibility was calculated as the linear regression slopes of VDF or Grs versus lung volume. Distensibility measured by VDF ranged 16-37 ml 1(-1) lung volume and by Grs it ranged 0.06-0.19 1 s(-1) cmH2O(-1) 1(-1) lung volume. Both distensibility measurements were correlated (Pearson's R2 = 0.91, p = 0.001). The SBNW and FOT are comparable methods for measuring airway distensibility and may have similar clinical usefulness. However, further studies are required to make any specific inferences about the relationship between airway distensibility by FOT and airway remodelling.

Gregory G King - One of the best experts on this subject based on the ideXlab platform.

  • controlled versus free breathing for multiple breath Nitrogen Washout in healthy adults
    ERJ Open Research, 2021
    Co-Authors: Blake M Handley, Edward Jeagal, Robin E Schoeffel, Tanya Badal, David G Chapman, Catherine E Farrow, Gregory G King
    Abstract:

    Multiple breath Nitrogen Washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: “controlled breathing”, with targeted tidal volume (VT) and respiratory rate (RR); and “free breathing”, with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity [FRC], lung clearance index [LCI], Scond, Sacin) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences, and to determine the between-session variabilities of each protocol. We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently-proposed correction for VT to Scond and Sacin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months. While FRC was comparable between controlled versus free breathing (3.17(0.98) versus 3.18(0.94) L,p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for Scond (r=0.18,p=0.36) and significant bias for Sacin (0.057(0.021)L−1versus 0.085(0.038)L−1,p=0.0004). Between-protocol differences in Sacin were related to differences in the breathing pattern, i.e. VT (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but Scond and Sacin from free breathing showed poor repeatability with wide limits of agreement. These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that Scond and Sacin from free breathing, despite VT correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of Scond during free breathing may limit its clinical utility.

  • in vivo and in vitro functional residual capacity comparisons between multiple breath Nitrogen Washout devices
    European Respiratory Journal, 2016
    Co-Authors: Gregory G King, Katrina O Tonga, Paul Robinson, C S Farah, Cindy Thamrin
    Abstract:

    Background and Aim: Multiple-breath Nitrogen Washout (MBNW) system validation is based on accurate functional residual capacity (FRC) measurement. Our aim was to perform in-vitro and in-vivo FRC comparisons between 2 commercial devices (EasyOne Pro® LAB, ndd Medical Technologies, analysed using both clinical (“nddClinical”) and updated research software (“nddWBreath” Version 3.41.4.1); Exhalyzer® D, Eco Medics AG, “EM”) and an in-house device (“WIMR”). Methods:In-vitro FRC (FRCin-vitro) was measured using an optimised syringe lung model (FRC 2.11 L, ATPD conditions). In-vivo FRC (FRCin-vivo) was measured in 18 healthy and 9 asthmatic subjects (10 male;mean±SD age 37±13 years). MBNW measurements were performed in triplicate on each device, in random order on the same day, followed by body plethysmography (Pleth). FRC differences between devices were examined by repeated measures ANOVA and posthoc tests. Results: FRCin-vitro measurements were within 10% of 2.11 L on all devices except on nddClinical. FRCin-vivo measurements on all devices were significantly different from each other (p Conclusion: FRC can be standardised across MBNW devices in-vitro but accuracy varies in-vivo. Better understanding of the reasons behind these differences is vital for MBNW standardisation efforts. A syringe lung model provides useful information as a MBNW development and calibration.

  • changes in oscillatory impedance and Nitrogen Washout with combination fluticasone salmeterol therapy in copd
    Respiratory Medicine, 2014
    Co-Authors: Sophie Timmins, Cheryl M Salome, Robin E Schoeffel, Chantale Diba, Gregory G King
    Abstract:

    Summary Introduction Combination inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) therapy reduces the exacerbation rate and improves spirometry and quality of life in COPD. We hypothesized that ICS/LABA therapy also improves small airway function measured by FOT. Methods 14 subjects with COPD were commenced on combination fluticasone propionate/salmeterol therapy for 3 months. At baseline, subjects completed the St George Respiratory Questionnaire (SGRQ) and underwent standard pulmonary function tests as well as forced oscillation technique (FOT) and single and multiple breath Nitrogen Washouts. All tests were repeated at the completion of 3 months of therapy. Results Subjects were of mean (SD) age 65.9 years (8.4), BMI 30.0 (5.6), pack years 51.4 (21.1), post-bronchodilator FEV 1 % predicted 62.7 (20). At baseline, mean SGRQ total was 39.0 (17.7) and FRC% predicted 125.4 (31.3). From FOT, Rrs-total was 5.69 (1.29) cmH 2 O/L/s, Xrs-total −3.48 (2.16) cmH 2 O/L/s, EFL Index 3.51 (2.45) cmH 2 O/L/s. After 3 months of therapy, there were significant improvements in SGRQ score (−13.81, p 1 (+40 mL, p  = 0.14). From FOT, total resistance (−0.63 cmH 2 O/L/s, p  = 0.0004), reactance (+1.2 cmH 2 O/L/s, p  = 0.013), and expiratory flow limitation (−1.21 cmH 2 O/L/s, p  = 0.02) also improved. There were no significant changes in ventilation heterogeneity indices. Conclusion Combination therapy is associated with improvements in small airways function in COPD, despite an absence of change in FEV 1 . FOT may be a clinically useful marker of small airway function in COPD that is responsive to treatment.

  • effects of methacholine on small airway function measured by forced oscillation technique and multiple breath Nitrogen Washout in normal subjects
    Respiratory Physiology & Neurobiology, 2005
    Co-Authors: Gregory G King, Norbert Berend, William C Thorpe, Cheryl M Salome, Sylvia Verbanck, Stephen R Downie
    Abstract:

    The multiple breath Nitrogen Washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5 Hz (sGrs 5 =Grs 5 /FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R 2 = 0.68, p = 0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R 2 = 0.79, p<0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs 5 in a multivariate model (R 2 = 0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and sGrs 5 before and after methacholine challenge. In conclusion, Scond and sGrs 5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in termina] airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions.

Paul Robinson - One of the best experts on this subject based on the ideXlab platform.

  • controlled versus free breathing for multiple breath Nitrogen Washout in asthma
    ERJ Open Research, 2021
    Co-Authors: Blake M Handley, Edward Jeagal, Robin E Schoeffel, Jack Bozier, Sandra Rutting, Paul Robinson
    Abstract:

    Multiple Breath Nitrogen Washout (MBNW) is an emerging clinical test for assessing ventilation heterogeneity [1], often characteristically increased in asthma. MBNW indices both indicate and predict response to asthma treatment [2–4], and therefore may be an important tool for guiding treatment decisions [2]. Two established breathing protocols are currently in use: 1-litre tidal volume-controlled breathing (CB) [5, 6] and unrestricted free breathing (FB) [7]. The CB protocol requires targeted tidal volume (VT) and respiratory rate (RR), whereas the FB protocol encourages relaxed tidal breathing, making it more suitable for paediatrics [8]. Two recently-published studies in healthy adults showed that indices of conductive and acinar ventilation heterogeneity (Scond and Sacin, respectively), and to a lesser extent, lung clearance index (LCI), were not comparable between breathing protocols [9, 10]. Importantly, differences between the protocols were dependent on the magnitude of ventilation heterogeneity. Thus, the assumption is that these effects would be amplified in disease, where ventilation heterogeneity is greater and clinical utility is most relevant. However, this has not been confirmed to date. We hypothesised that people with asthma, where ventilation heterogeneity is greater, would exhibit greater differences between the two protocols, than the differences seen in healthy adults. Footnotes This manuscript has recently been accepted for publication in the ERJ Open Research . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article. Conflict of interest: Mr. Handley has nothing to disclose. Conflict of interest: Dr. Bozier has nothing to disclose. Conflict of interest: Edward Jeagal has nothing to disclose. Conflict of interest: Dr. Rutting has nothing to disclose. Conflict of interest: Robin Schoeffel has nothing to disclose. Conflict of interest: Dr. Robinson has nothing to disclose. Conflict of interest: Dr. King reports grants, personal fees, non-financial support and other from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini, MundiPharma, grants from National Health & Medical Research Council, Asthma Foundation, outside the submitted work. Conflict of interest: Dr. Milne has nothing to disclose. Conflict of interest: Dr. Thamrin reports non-financial support from Restech SRL, Milan, Italy, grants from AstraZeneca, UK, outside the submitted work.

  • in vitro and in vivo functional residual capacity comparisons between multiple breath Nitrogen Washout devices
    ERJ Open Research, 2017
    Co-Authors: Katrina O Tonga, Paul Robinson, C S Farah, Greg King
    Abstract:

    Functional residual capacity (FRC) accuracy is essential for deriving multiple-breath Nitrogen Washout (MBNW) indices, and is the basis for device validation. Few studies have compared existing MBNW devices. We evaluated in vitro and in vivo FRC using two commercial MBNW devices, the Exhalyzer D (EM) and the EasyOne Pro LAB (ndd), and an in-house device (Woolcock in-house device, WIMR). FRC measurements were performed using a novel syringe-based lung model and in adults (20 healthy and nine with asthma), followed by plethysmography (FRC pleth ). The data were analysed using device-specific software. Following the results seen with ndd, we also compared its standard clinical software (ndd v.2.00) with a recent upgrade (ndd v.2.01). WIMR and EM fulfilled formal in vitro FRC validation recommendations (>95% of FRC within 5% of known volume). Ndd v.2.00 underestimated in vitro FRC by >20%. Reanalysis using ndd v.2.01 reduced this to 11%, with 36% of measurements ≤5%. In vivo differences from FRC pleth (mean±sd) were 4.4±13.1%, 3.3±11.8%, −20.6±11% (p Direct device comparison highlighted important differences in measurement accuracy. FRC discrepancies between devices were larger in vivo , compared to in vitro results; however, the pattern of difference was similar. These results represent progress in ongoing standardisation efforts.

  • is twice the duration of Washout sufficient time between multiple breath Nitrogen Washout tests
    European Respiratory Journal, 2017
    Co-Authors: Kate Hardaker, Per Gustafsson, Peter Cooper, Dominic A Fitzgerald, Hiran Selvadurai, Paul Robinson
    Abstract:

    Multiple breath Washout (MBW) assesses both lung volume (functional residual capacity (FRC)) and ventilation inhomogeneity (lung clearance index (LCI)). The latter's insight into underlying lung pathology and response to intervention has triggered a recent MBW resurgence [1–4]. Validated commercial equipment has become available [5], increasing suitability for widespread use, and a European Respiratory Society/American Thoracic Society endorsed MBW consensus statement has been published to guide manufacturers and operators [6]. This document highlights the need for further evidence across several recommendation areas. In the May 2015 issue of this journal Salamon et al. [7] tackled one such important issue: what duration should be employed between two MBW tests within a testing session? Previous recommendations of gaps of ≥15 min in healthy and ≤60 min in obstructed patients [8] were shown to be too conservative . Using a gap of the previous Washout duration led to 10% lower FRC values (p<0.001) but no effect was observed if this was doubled, in line with the recent consensus-based recommendation. [9]. The results presented here address two important limitations to the data presented by Salamon et al. [7], as acknowledged by the authors themselves, to further strengthen the recommendation's evidence base. First, in their paediatric cohort, an alternate, fixed-gap duration protocol was used (5 and 15 min), which translated to an excessive duration between tests (mean 2.6×). Secondly, LCI data was not reported, which may have compromised the ability to detect any detrimental effects. A wait time between MBNW tests of twice the Washout duration has no detrimental effect on LCI and FRC outcomes

  • in vivo and in vitro functional residual capacity comparisons between multiple breath Nitrogen Washout devices
    European Respiratory Journal, 2016
    Co-Authors: Gregory G King, Katrina O Tonga, Paul Robinson, C S Farah, Cindy Thamrin
    Abstract:

    Background and Aim: Multiple-breath Nitrogen Washout (MBNW) system validation is based on accurate functional residual capacity (FRC) measurement. Our aim was to perform in-vitro and in-vivo FRC comparisons between 2 commercial devices (EasyOne Pro® LAB, ndd Medical Technologies, analysed using both clinical (“nddClinical”) and updated research software (“nddWBreath” Version 3.41.4.1); Exhalyzer® D, Eco Medics AG, “EM”) and an in-house device (“WIMR”). Methods:In-vitro FRC (FRCin-vitro) was measured using an optimised syringe lung model (FRC 2.11 L, ATPD conditions). In-vivo FRC (FRCin-vivo) was measured in 18 healthy and 9 asthmatic subjects (10 male;mean±SD age 37±13 years). MBNW measurements were performed in triplicate on each device, in random order on the same day, followed by body plethysmography (Pleth). FRC differences between devices were examined by repeated measures ANOVA and posthoc tests. Results: FRCin-vitro measurements were within 10% of 2.11 L on all devices except on nddClinical. FRCin-vivo measurements on all devices were significantly different from each other (p Conclusion: FRC can be standardised across MBNW devices in-vitro but accuracy varies in-vivo. Better understanding of the reasons behind these differences is vital for MBNW standardisation efforts. A syringe lung model provides useful information as a MBNW development and calibration.

  • time between multiple breath Nitrogen Washout mbnw tests is duration of Washout enough across childhood
    European Respiratory Journal, 2015
    Co-Authors: Kate Hardaker, Peter Cooper, Dominic A Fitzgerald, Hiran Selvadurai, Geshani Jayasuriya, Per A Gustafsson, Paul Robinson
    Abstract:

    Background: Recommendations state that up to twice the Washout time may be required between multiple breath Washout (MBW) tests to avoid detrimental effects on FRC and LCI. Current commercial Nitrogen MBW (MBNW) equipment employ a “lockout” period between tests, whilst stabilisation of breathing prior to starting the next Washout portion further lengthens duration of Nitrogen re-accumulation between tests. Aims and Objectives: To investigate for evidence of insufficient wash-in (FRC or LCI decline) occurs if a “lockout” period equal to previous Washout period duration is used from preschool age range onwards. Methods: Retrospective analysis of clinical MBW tests at a single tertiary paediatric centre using commercial MBNW equipment (Ecomedics Exhalyser D, Switzerland). Lockout period set to duration of Washout on previous test. Consecutive pairs of technically acceptable MBNW tests analysed for FRC or LCI difference using paired t-test and Bland Altman analysis. If three successive tests available, test 1-3 difference also analysed. Secondary analysis of effect across preschool (2-6 yrs), school age (7-12 yrs) and adolescence (13-18 yrs). Results: Data from 80 children (30 preschool, 30 school age, 20 adolescent subjects) included to date, mean (SD) FRC 1523 (827) mL and LCI 8.08 (2.38), generating 137 test pairs and 55 triplets. No significant differences observed between FRC or LCI test pairs or across tests 1-3 for entire cohort or in each age group examined. Conclusion: No evidence of insufficient wash-in was observed. Clinical application of a lockout period of previous Washout duration can be recommended across the paediatric age range in commercial MBNW equipment.

Mohy G Morris - One of the best experts on this subject based on the ideXlab platform.

  • a novel physiological investigation of the functional residual capacity by the bias flow Nitrogen Washout technique in infants
    Pediatric Pulmonology, 2009
    Co-Authors: Mohy G Morris
    Abstract:

    The dynamic functional residual capacity (FRCdyn), the lung volume most routinely measured in infants, is an unreliable volume landmark. In addition to the FRCdyn, we measured the (passive) static FRC (FRCst) by inducing a brief post-hyperventilation apnea (PHA) in 33 healthy infants aged 7.4–127.2 weeks. A commercial system for Nitrogen (N2) Washout to measure FRC, and a custom made system to monitor and record flow and airway opening pressure signals in real-time were used in unison. Infants were manually hyperventilated to induce a PHA. After the last passive expiration, FRCst was estimated by measuring the volume of N2 expired after end-passive expiratory switching of the inspired gas from room air to 100% oxygen during the post-expiratory apneic pause. Repeatable intrasubject FRCst and FRCdyn measurements overlapped in most infants including the younger ones (P = 0.2839). Mean (95% confidence interval [CI]) FRCst was 21.1 (20.0–22.3), and error-corrected FRCdyn was 21.4 (20.4–22.4) ml/kg. Mean (Washout time [t]) tFRCst was longer than tFRCdyn 60 sec (95% CI 55–65) versus 47 sec (95% CI 43–51) (P < 0.0001). The FRC and Washout time were dependent on body length, weight and age. We conclude that the FRCst is not different from the FRCdyn in infants. The FRCst is a reliable volume landmark because the PHA stabilizes the end-expiratory level by potentially abolishing the sedated infant's breathing strategies. The FRCst lacks potential sources of errors and disadvantages associated with measuring the FRCdyn. The findings cast significant doubt on the traditional physiology of air trapping in healthy infants' lungs. Pediatr Pulmonol. 2009; 44:683–692. © 2009 Wiley-Liss, Inc.

  • a novel physiological investigation of the functional residual capacity by the bias flow Nitrogen Washout technique in infants
    Pediatric Pulmonology, 2009
    Co-Authors: Mohy G Morris
    Abstract:

    The dynamic functional residual capacity (FRCdyn), the lung volume most routinely measured in infants, is an unreliable volume landmark. In addition to the FRCdyn, we measured the (passive) static FRC (FRCst) by inducing a brief post-hyperventilation apnea (PHA) in 33 healthy infants aged 7.4–127.2 weeks. A commercial system for Nitrogen (N2) Washout to measure FRC, and a custom made system to monitor and record flow and airwayopening pressure signals in real-time were used in unison. Infants were manually hyperventilated to induce a PHA. After the last passive expiration, FRCst was estimated by measuring the volume of N2 expired after end-passive expiratory switching of the inspired gas from room air to 100% oxygen during the post-expiratory apneic pause. Repeatable intrasubject FRCst and FRCdyn measurements overlapped in most infants including the younger ones (P = 0.2839). Mean (95% confidence interval [CI]) FRCst was 21.1 (20.0–22.3), and error-corrected FRCdyn was 21.4 (20.4–22.4) ml/kg. Mean (Washout time [t]) tFRCst was longer than tFRCdyn 60 sec (95% CI 55–65) versus 47 sec (95% CI 43–51) (P<0.0001). The FRC and Washout time were dependent on body length, weight and age. We conclude that the FRCst is not different from the FRCdyn in infants. The FRCst is a reliable volume landmark because the PHA stabilizes the end-expiratory level by potentially abolishing the sedated infant’s breathing strategies. The FRCst lacks potential sources of errors and disadvantages associated with measuring the FRCdyn. The findings cast significant doubt on the traditional physiology of air trapping in healthy infants’ lungs.

  • a novel non invasive technique for measuring the residual lung volume by Nitrogen Washout with rapid thoracoabdominal compression in infants
    Thorax, 1999
    Co-Authors: Mohy G Morris
    Abstract:

    BACKGROUND—The functional residual capacity (FRC), the only lung volume to be routinely measured in infants, is an unreliable volume landmark. In addition to FRC, the residual volume (RV) was measured by Nitrogen Washout using rapid thoracoabdominal compression (RTC) in nine infants with cystic fibrosis aged 5-31 months. METHODS—A commercial system for Nitrogen Washout to measure lung volumes and a custom made system to perform RTC were used. Lung volume was raised to an airway opening pressure of 30 cm H2O (V30). RTC was performed from V30. The jacket pressure (Pj; 65-92 cm H2O) which generated the highest forced expiratory volume (mean 40.2 ml/kg; 95% confidence interval (CI) 33.03 to 47.33) was used during the RV manoeuvre. The infants were manually hyperventilated to inhibit the respiratory drive briefly. RTC was initiated during the last passive expiration. RV was estimated by measuring the volume of Nitrogen expired after end forced expiratory switching of the inspired gas from room air to 100% oxygen while jacket inflation was maintained at the time of switching into oxygen during the post-expiratory pause. RESULTS—In each infant RV and FRC measurements were reproducible and did not overlap; the difference between mean values, which is the expiratory reserve volume, was statistically significant (p<0.05). Mean RV was 21.3 (95% CI 18.7 to 24.0), FRC was 25.5 (95% CI 22.8to 28.1), and TLC30 (total lung capacity at V30) was 61.5 (95% CI 54.4 to 68.7) ml/kg. These values were dependent on body length, weight and age. When measuring RV the period between switching to oxygen and the end of the Pj plateau was 0.301 (95% CI 0.211to 0.391) s. The Washout duration was longer for RV than for FRC measurement (80.9 s (95% CI 71.3 to 90.4) versus 72.4 s (95% CI 64.9 to 79.8)) (p<0.001). CONCLUSIONS—A new non-invasive and reliable technique for routine measurement of RV in infants is presented.

  • the open circuit Nitrogen Washout technique for measuring the lung volume in infants methodological aspects
    Thorax, 1999
    Co-Authors: Mohy G Morris
    Abstract:

    BACKGROUND—Lung volume measurement by Nitrogen Washout is widely used in infants, though a lack of accuracy and changes of calibration over time have been reported. The potential sources of error were explored in order to increase the accuracy and reliability of the technique. METHODS—A commercial system for Nitrogen Washout and a 0.5 litre calibrating syringe as a lung model were used to perform over 2000in vitro Washouts, including simulated rapid breathing, shallow breathing, periodic breathing, sighs, and brief apnoeas. A constant 10 l/min bias flow of oxygen and extended equipment warming times were employed. A collapsible breathing bag was incorporated into the Washout circuit. Following a single two point calibration, known air volumes from 42 ml to 492 ml were measured by Nitrogen Washout over a 14 hour period. The flow waveform in the Nitrogen mixing chamber during a Washout in vitro, with and without the breathing bag in the circuit, was also studied. RESULTS—The mean coefficient of variation of all volumes was 0.66%. The mean difference between measured and known volumes was 0.30ml (95% confidence interval (CI) -0.18 to 0.79). This difference was not statistically significant (p = 0.22). The mean percentage error was -0.1% (range -0.47% to 0.46%). Nitrogen calibration remained stable for 14 hours. Without the breathing bag flow transients were frequent in the mixing chamber during in vitro Washout. CONCLUSIONS—This technique increases the accuracy in vitro and the precision in vivo of volume measurement by Nitrogen Washout. Sources of potential errors including baseline drifting and inadequate equipment warming times were identified. The breathing bag acted as a buffer reservoir, preventing large swings in flows within the Nitrogen mixing chamber during Washouts, and should be an integral component of the Nitrogen Washout circuit.

Felix Ratjen - One of the best experts on this subject based on the ideXlab platform.

  • development of a quality assessment algorithm for multiple breath Nitrogen Washout
    European Respiratory Journal, 2019
    Co-Authors: Renee Jensen, Michelle Klingel, Sanja Stanojevic, Reginald Mcdonald, Felix Ratjen
    Abstract:

    Introduction: There is a need to integrate quality control (QC) into multiple breath Washout (MBW) tests to facilitate accurate interpretation of results. We aimed to develop an algorithm to automate application of QC criteria for MBW. Methods: We defined quantitative measures of quality into a series of algorithms [Jensen R. et al. PLoS ONE; 2016] and applied these to MBW data collected on the Exhalyzer® D (EcoMedics AG). The performance of the algorithm was compared to independent assessment by experienced reviewers. Results: Anonymized MBW data (15,070 trials; 2,866 tests) in healthy children, and subjects with Cystic Fibrosis, were retrospectively evaluated using the algorithm. Seventy percent of trials were categorized as accept/exclude, whereas 30% were flagged for manual review. The algorithm agreed with the reviewer’s decision for 88% of trials. The lung clearance index was similar between the algorithm and reviewers (Δ -0.01, limits of agreement -0.31, 0.29) and resulted in a similar proportion of acceptable test occasions (86.4% vs. 83.6%). An equal number of trials flagged for review were subsequently classified as accept/exclude by reviewers. Conclusion: QC criteria can successfully be applied to MBW data using an algorithm and only requires review in approximately 30% of trials. The agreement between the algorithm and manual review was similar to previously observed inter-reviewer agreement [Jensen R. et al. PLoS ONE; 2016]; disagreement may reflect subjective interpretation.

  • o2concentration based definition of wait times between multiple breath Nitrogen Washout trials
    European Respiratory Journal, 2016
    Co-Authors: Michelle Klingel, Sarah Isaac, Renee Jensen, Lena Raaijmakers, Sanja Stanojevic, Felix Ratjen
    Abstract:

    Introduction: The time required to perform Multiple Breath Nitrogen Washout (MBNW) testing is influenced by the time needed between trials to equilibrate intrapulmonary gas concentrations to baseline levels. Current convention is to define this time using either the length of the preceding Washout, or to monitor alveolar gas concentrations have returned to baseline values. The purpose of this study was to define wait time using an end-tidal oxygen concentration ([O 2 ]) limit based on the natural variability of end-tidal [O 2 ]. Methods: 12 healthy adults performed MBNW testing using the Exhalyzer D ® (Ecomedics AG, Switzerland). Prior to exposure to O 2 , an extended pre-Washout phase (50 breaths (range 30-74)) was collected to define the baseline variability of the end-tidal [O 2 ] . Subjects subsequently performed a modified MBNW testing protocol to capture the wash-in phase of [O 2 ] following each Washout. Results: The within-subject standard deviation (SD) of the [O 2 ] in healthy adults was 0.5 %, thus the upper limit was defined as baseline [O 2 ] + 1%. On average, healthy adults returned to baseline [O 2 ] levels for three consecutive breaths within 3 minutes (SD 1min) or 1 times (SD 0.3) the length of the preceding Washout. In 6 trials, subjects did not return to baseline [O 2 ] despite waiting a median of 1.8 (IQR 1.5, 2.7) times the Washout time. If we apply a standard of 1.5 times the previous Washout, the [O 2 ] based definition saves an average of 1.5 minutes (SD 1.1) per trial in healthy subjects. Conclusions: Defining wait time between MBNW trials based on [O 2 ] rather than Washout time may reduce total testing time. Evaluation of this approach in CF patients is ongoing.

  • in vitro and in vivo comparison of two multiple breath Nitrogen Washout devices
    European Respiratory Journal, 2015
    Co-Authors: Lena Raaijmakers, Renee Jensen, Sanja Stanojevic, Peter J F M Merkus, Felix Ratjen
    Abstract:

    Background: There are currently several commercially available Nitrogen (N 2 ) multiple breath Washout (MBW) devices. Individual devices have been tested in lung models and human subjects, but comparative studies including both in vitro and in vivo assessments of devices are lacking. Objective: The aim of this study was to compare the accuracy of two commercially available MBW N2 devices (Exhalyzer D (EcoMedics, AG, Duernten, Switzerland) (EM) and EasyOne Pro LAB (NDD, Zurich, Switzerland) (NDD)) with respect to lung volume measurements. Methods: In vitro measurements were performed using a Soloplex lung model, as described previously by Singer et al (PLoS One, 2012; 7(4):e36083). Functional residual capacity (FRC) was measured under BTPS conditions at 33 different volumes between 2 and 4.2 L by both EM and NDD MBW devices. FRC was also measured in ten healthy adults (median age 23 years (range 19 – 37)) by EM (FRC EM ), NDD (FRC ndd ) and by plethysmography (FRC pleth ) (Vmax Encore PFT system, CareFusion, San Diego, CA, US). Measurements were performed on the same day in randomized order. Results: In the lung model, differences to the actual FRC were relatively small for both devices, with a mean relative FRC EM difference of -4.2% (range -13.6 to 1.5%) and a mean relative FRC NDD difference of 1.1% (range -4.9 to 6.8%). In contrast, FRC measured in vivo differed substantially with a mean relative difference of 14.1% (range -7.3 to 33.3%) for FRC EM and -23.3% (range -35.7 to -8.7%) for FRC NDD compared with FRC pleth (P Conclusion: The lack of agreement between the in vitro and in vivo FRC results underscores the need to perform both in vitro and in vivo validation studies for MBW devices.

  • multiple breath Nitrogen Washout a feasible alternative to mass spectrometry
    PLOS ONE, 2013
    Co-Authors: Renee Jensen, Per Gustafsson, Sanja Stanojevic, Karyn Gibney, Juliana Salazar, Padmaja Subbarao, Felix Ratjen
    Abstract:

    Background The lung clearance index (LCI), measured by multiple breath Washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early cystic fibrosis (CF) lung disease. Current evidence is based on a customized mass spectrometry system that uses sulfur hexafluoride (SF6) as a tracer gas, which is not widely available. Nitrogen (N2) Washout may be better suited for clinical use and multi-center trials. Objective To compare the results obtained from a N2 Washout system to those generated by the SF6 based system in healthy children and children with CF. Methods Children with CF were recruited from outpatient clinics; healthy children were recruited from the Research4Kids online portal. Participants performed MBWSF6 (Amis 2000, Innovision, Denmark) and MBWN2 (ExhalyzerD, EcoMedics, Switzerland) in triplicate, in random order on the same day. Agreement between systems was assessed by Bland-Altman plot. Results Sixty-two healthy and 61 children with CF completed measurements on both systems. In health there was good agreement between systems (limits of agreement −0.7 to 1.9); on average N2 produced higher values of LCI (mean difference 0.58 (95% CI 0.42 to 0.74)). In CF the difference between systems was double that in health with a clear bias towards disproportionately higher LCIN2 compared to LCISF6 at higher mean values of LCI. Conclusion LCIN2 and LCISF6 have similar discriminative power and intra-session repeatability but are not interchangeable. MBWN2 offers a valid new tool to investigate early obstructive lung disease in CF, but requires independent normative values.