Quality Control of Nitrogen Multiple Breath Washout in a Multicenter Pediatric Asthma Study

Abstract

Background Nitrogen multiple breath washout (N2MBW) is a lung function test increasingly used in small airway diseases. Quality criteria have not yet been globally implemented and time-consuming retrospective overreading is necessary. Little data has been published on children with recurrent wheeze or asthma from multicentered studies.

Methods Children with wheeze or asthma and healthy controls were included in the longitudinal All Age Asthma Cohort (ALLIANCE). To assess ventilation inhomogeneity, N2MBW tests were performed in five centers from 2013 until 2020. All N2MBW tests were centrally overread by one center. Multiple washout procedures (trials) at the visit concluded to one test occasion. Tests were accepted if trials were technically sound (started correctly, terminated correctly, no leak, regular breathing pattern) and repeatable within one test occasion. Signal misalignment was retrospectively corrected. Factors that may impact test quality were analyzed, such as experience level.

Results N2MBW tests of n=561 participants were analyzed leading to n=949 (68.3%) valid tests of n=1,390 in total. Inter-center test acceptability ranged from 27.6% to 77.8%. End-of-test criterion and leak were identified to be the most common reasons for rejection. Data loss and uncorrectable signal misalignment led to rejection of 58% of trials in one center. In preschool children, significant improvement of test acceptability was found longitudinally (χ2(8)=18.6; p=0.02).

Conclusion N2MBW is feasible in a multicenter asthma study in children. However, the quality of this time-consuming procedure is dependent on experience level of staff in preschool children and still requires retrospective overreading for all age groups.

Zusammenfassung

Hintergrund Nitrogen Multiple Breath Washout (N2MBW) ist ein Lungenfunktionstest, der zur frühen Diagnostik von Erkrankungen der kleinen Atemwege eingesetzt wird. Qualitätskriterien werden aktuell nicht einheitlich angewendet und bisher wurden aus multizentrischen Studien nur wenige N2MBW Daten von Kindern mit asthmatischen Erkrankungen veröffentlicht.

Methoden Kinder mit asthmatischen Erkrankungen sowie gesunde Kontrollpersonen wurden in die All Age Asthma Kohorte (ALLIANCE) eingeschlossen. Für die Messung der Ventilationsinhomogenität wurden N2MBW Tests von 2013 bis 2020 von fünf Zentren durchgeführt. In der retrospektiven zentralen Qualitätskontrolle wurde geprüft, ob die Messungen technisch verwertbar und wiederholbar waren. Mögliche Einflussfaktoren wie das Erfahrungsniveau wurden untersucht. Fehlerhaft kalibrierte Messsignale wurde nachträglich korrigiert.

Ergebnisse N2MBW Tests von n=561 Teilnehmern wurden analysiert. Dies ergab n=949 (86.3%) gültige von insgesamt n=1390 Tests. Die Testakzeptanz in den Zentren reichte von 27.6% bis 77.8%. Vorzeitiges Beenden und Leckagen waren die häufigsten Ablehnungsgründe. Datenverlust führte zudem in einem Zentrum zur Ablehnung von 58% der Tests. Für Vorschulkinder ließ sich longitudinal eine steigende Qualität feststellen (χ2(8)=18,6; p=0,02).

Schlussfolgerung N2MBW ist von Kindern mit asthmatischen Erkrankungen multizentrisch durchführbar. Die Qualität dieses zeitaufwändigen Verfahrens hängt von dem Erfahrungsstand des Personals bei Vorschulkindern ab und erfordert standardisierte Qualitätskontrolle.

Key words

N2MBW - MBW - lung function - ventilation inhomogeneity - LCI - Turn Over

Schlüsselwörter

Auswaschverfahren - Ventilationsinhomogenität - N2MBW - MBW - Lungenfunktionsprüfung

Publication History

Article published online:
19 January 2023

• References

• 1 Arianto L, Hallas H, Stokholm J. et al. Multiple Breath Washout for Diagnosing Asthma and Persistent Wheeze in Young Children. Ann Am Thorac Soc 2019; 16: 599-605 DOI: 10.1513/AnnalsATS.201807-503OC.
• 2 Downing B, Irving S, Bingham Y. et al. Feasibility of lung clearance index in a clinical setting in pre-school children. Eur Respir J 2016; 48: 1074-1080 DOI: 10.1183/13993003.00374-2016.
• 3 ECO MEDICS AG. Operator’s Manual Pulmonary Function Testing Device. Exhalyzer D. EXH405 V32. 60. Duernten; 2020
• 4 Frauchiger BS, Carlens J, Herger A. et al. Multiple breath washout quality control in the clinical setting. Pediatr Pulmonol 2021; 56: 105-112 DOI: 10.1002/ppul.25119.
• 5 Gaillard EA, Kuehni CE, Turner S. et al. European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5–16 years. Eur Respir J 2021; 58: 2004173 DOI: 10.1183/13993003.04173-2020.
• 6 GINA 2021. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021. www.ginasthma.org (01.12.21)
• 7 Jensen R, Stanojevic S, Klingel M. et al. A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality. PLoS One 2016; 11: e0157523 DOI: 10.1371/journal.pone.0157523.
• 8 O’Neill K, Elborn JS, Tunney MM. et al. Training in multiple breath washout testing for respiratory physiotherapists. Physiotherapy 2018; 104: 61-66 DOI: 10.1016/j.physio.2017.04.003.
• 9 O’Neill K, Lakshmipathy GR, Ferguson K. et al. Quality control for multiple breath washout tests in multicentre bronchiectasis studies: Experiences from the BRONCH-UK clinimetrics study. Respir Med 2018; 145: 206-211 DOI: 10.1016/j.rmed.2018.10.030.
• 10 Robinson PD, Latzin P, Ramsey KA. et al. Preschool Multiple-Breath Washout Testing. An Official American Thoracic Society Technical Statement. Am J Respir Crit Care Med 2018; 197: e1-e19 DOI: 10.1164/rccm.201801-0074ST.
• 11 Robinson PD, Latzin P, Verbanck S. et al. Consensus statement for inert gas washout measurement using multiple- and single- breath tests. Eur Respir J 2013; 41: 507-522 DOI: 10.1183/09031936.00069712.
• 12 Saunders C, Jensen R, Robinson PD. et al. Integrating the multiple breath washout test into international multicentre trials. J Cyst Fibros 2020; 19: 602-607 DOI: 10.1016/j.jcf.2019.11.006.
• 13 Stahl M, Joachim C, Kirsch I. et al. Multicentre feasibility of multiple-breath washout in preschool children with cystic fibrosis and other lung diseases. ERJ Open Res 2020; 6: 00408-02020 DOI: 10.1183/23120541.00408-2020.
• 14 Summermatter S, Singer F, Latzin P. et al. Impact of Software Settings on Multiple-Breath Washout Outcomes. PLoS One 2015; 10: e0132250 DOI: 10.1371/journal.pone.0132250.
• 15 Fuchs O, Bahmer T, Weckmann M, et al. The all age asthma cohort (ALLIANCE) - from early beginnings to chronic disease: a longitudinal cohort study. BMC Pulm Med 2018; 18: 140, doi:10.1186/s12890-018-0705-6