Normal values for respiratory oscillometry in pediatrics: The importance of a local control populationKeywords: pulmonary function testing, reference equations, predicted values, respiratory oscillometry, respiratory system resistance, respiratory system reactanceTo the Editor: Respiratory oscillometry is a test performed during normal tidal breathing, making it an ideal test of lung function for children too young to co-ordinate the maneuvers required for spirometry (1). The arrival of commercial devices has seen increasing interest in oscillometry as a test of respiratory system function; however, its integration into routine clinical care has been slow. There are several potential explanations for this reluctance to fully embrace oscillometry in clinical pulmonary function laboratories. Clinicians are more familiar with the spirometric and plethysmographic values of forced expiratory volume in one second, vital capacity and resistance than certain parameters reflecting respiratory system high frequency oscillation mechanics such as reactance at greater than 5 hz, or resonant frequency. The latter occurs at frequencies much higher than normal, or even abnormal, breathing frequences, making its clinical relevance seem remote. In addition, the mathematics of oscillation mechanics can be daunting, as it relies on “complex numbers” with a real (resistive) and imaginary (reactive, encompassing both elastic and inertial properties) component. A recent publication attempts to present these concepts in a more intuitive way (2).Another potential barrier to clinical implementation of oscillometry has been the lack of robust reference equations that generate normal predicted values accounting for growth from childhood to adulthood. How to best report results compared to normal, as percent predicted values versus z-scores, can also differ between pulmonary function laboratories. In addition, there are a number of different devices used in clinical care and research; these generate differing oscillatory signals, which may affect the results obtained.The recent publication of equipment specific reference equations by Ducharme et al for one such commercial device, the Tremoflo C-100, which was derived from a large cohort of children aged 3-17 years of age at a single center in Montreal, Canada (3), represented an important step forward, as the first equipment-specific pediatric equations for that device. However, the generalizability of these reference equations to other pediatric cohorts remains unclear. Generalizability of predicted equations to different local populations has been discussed extensively in the context of the Global Lung Function (GLI) initiative for spirometry (4). We therefore explored the applicability of the Montreal reference equations to a local healthy control population of 80 subjects, aged 4-18 years tested at the Children’s Hospital of Philadelphia in Philadelphia, USA.As part of a study investigating differences in impedance values obtained on different devices (5), oscillometry was performed using the same model Tremoflo device as was used in the Ducharme study. Approval was obtained by the Children’s Hospital of Philadelphia Institutional Review Board (IRB 20-018357_PERC). Parents or guardians provided written informed consent, and children aged 8 years and older provided assent for study participation.Airwave oscillometry was performed using the Tremoflo C-100 (Thorasys Thoracic Medical Systems, Inc., Montreal, QC, Canada), according to European Respiratory Society (ERS) guidelines (6). Before testing each subject, device calibration check was performed according to manufacturer’s guidelines. During testing, subjects sat upright and comfortably, wearing nose clips, with their chins in “sniffing” position and with their cheeks supported. A minimum of three to five 30-second trials were performed until at least three trials were obtained with visually observed and recorded regular respiratory pattern, with no evidence of artifact (air leak, mouthpiece occlusion by tongue, coughing or other glottic closure). Test results were reviewed to ensure satisfaction of ERS guidelines with a coefficient of variation < 10% in children over 10 years old, and < 15% in children < 10 years (6). Primary oscillometry outcomes were resistance and reactance at 5 and 11 Hz (R5, R11, X5, and X11, respectively), resonant frequency (Fres), and the area under the reactance curve (AX).Children without history of prematurity, chronic medical conditions, cardiopulmonary history, or recent viral or respiratory illness within 4 weeks prior to the study were recruited. Mean age was 9.8 years, and 38 subjects (47.5%) were female. Additional characteristics and demographics are included in Table 1 alongside reported characteristics of Ducharme’s Montreal population.One sample, 2-tailed t-tests were performed to determine if the means of the Philadelphia individual z-scores for each measured outcome compared to the Ducharme predicted were significantly different than zero. Representative results for respiratory system resistance and reactance at 11 Hz compared to Ducharme are presented in the Figure. We found the expected decreases in resistance and absolute value of reactance with height. However, the mean z-scores of the Philadelphia population calculated from the Montreal population data were significantly different than zero for both resistance and reactance, as well as Fres and AX (Table 2).The reasons for the significant differences seen in oscillometric outcomes between children in Philadelphia compared to those in Montreal are unclear. The instruments used to perform the measurements were the same model made by the same manufacturer. Selection bias may have played a role, although both centers used rigorous questionnaires to screen for prematurity and underlying cardiopulmonary disease. There was only a mean 0.2-year difference in age and a mean 2 cm difference in height between the Montreal and Philadelphia cohorts (Table 1); however, since z-scores are adjusted for height, even the small differences in height between the two centers are unlikely to provide an explanation for the differing z-scores. Ducharme’s screening criteria eliminated children who were obese (BMI > 97%ile) from their study while ours did not; our Philadelphia cohort did have a higher mean weight and BMI and wider ranges as compared to the Montreal cohort (Table 1), and 12 subjects (15%) had BMI > 97%ile. However, we think that if anything, this should have caused higher resistance and more negative reactance in the Philadelphia cohort; we found the opposite. Socioeconomic, or race and ethnicity differences between the two cities provide a possible explanation. However, while height was shown to be a significant predictor in Ducharme’s oscillometry predicted equations, race and ethnicity were not. There may also be possible between- device differences in Tremoflo C100 equipment.Whatever the explanation, these findings point to the importance of centers comparing their oscillomety results to a local control population, ideally tested at the same center, to determine the applicability of published reference values to the local population. The differences noted between healthy cohorts reinforces the value of current efforts to collate international datasets to produce robust generalizable GLI reference data for oscillometry.REFERENCESKaminsky DA, Simpson SJ, Berger KI, et al. Clinical significance and applications of oscillometry. Eur Respir Rev 2022; 31 (163): 210208 DOI: 10.1183/16000617.0208-2021.Vamos L, Allen J. The use of stringed instruments as an analogy to explain oscillation mechanics of the developing normal and diseased respiratory system. Pediatr Pulmonol. 2024; 59(4):1110-1113. DOI: 10.1002/ppul.26846Ducharme FM, Smyrnova A, Lawson CC, Miles LM. Reference values for respiratory sinusoidal oscillometry in children aged 3 to 17 years. Pediatric Pulmonology. 2022; 57:2092‐2102. doi:10.1002/ppul.25984Weber Santos B, Scalco JC, Parazzi PLF, Schivinski CIS. Compatibility of the global lung function 2012 spirometry reference values in children, adolescents and young adults: a systematic review. Expert Review of Respiratory Medicine. 18:883-892, 2024.Boas H, Tsukahara K, McDonough J, Travaglini L, Scully T, Qiu C , DeMauro SB, Ren CL, Allen JL. Airwave and Impulse Oscillometry in Healthy Children: Is All Respiratory Oscillometry the Same? Am J Respir Crit Care Med. 2023; 207: A2940.King, G.G., Bates J, Berger KI et al. Technical standards for respiratory oscillometry. Eur Respir J, 2020. 55. 1900753; ISSN 0903-1936 - 55:2(2020), 1900753 https://doi.org/10.1183/13993003.00753-2019Authors:Heather Boas, MD1, 2, Joseph McDonough, MS1, 2, Adam Lane, PhD3, 4, Sara B. DeMauro, MD2, 5, Clement L. Ren, MD1, 2, Maureen Josephson, DO1, 2, Samuel B. Goldfarb, MD6, Paul D. Robinson, PhD7, 8, Julian L. Allen, MD1, 21 Division of Pulmonary and Sleep Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA2 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA3 Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA4 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA5 Department of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA6 Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Minnesota, Masonic Children’s Hospital, Minneapolis, MN, USA7 Department of Respiratory Medicine, Queensland Children’s Hospital, Brisbane, QLD, Australia8 Children’s Health and Environment Program, Child Health Research Centre, University of Queensland, Brisbane, QLD, AustraliaAcknowledgements: The authors thank study coordinators Kris Ziolkowski and Laurie TravagliniFunding: HB reports grant funding from the Cystic Fibrosis Foundation (BOAS23D0). SBD reports grant funding from the National Institute of Health (UG3HL137872). SBG reports grant funding from the National Heart, Lung, and Blood Institute (NCT04098445). JLA received funding from National Heart, Lung, and Blood Institute (NCT04098445), the Morse Foundation, and the Capek Foundation.Conflicts of Interest: The authors have no conflicts of interest to disclose.FIGURE: A) Resistance and B) reactance at 11 Hz vs height. The dark circles represent normal predicted values vs. height using the published reference equations by Ducharme et al (3). The light circles are data obtained from the cohort of healthy children in Philadelphia.
