Respiratory oscillometry in individuals with fibrodysplasia ossificans progressiva

Respiratory oscillometry in individuals with fibrodysplasia ossificans progressiva | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Respiratory oscillometry in individuals with fibrodysplasia ossificans progressiva Anastasiia Vasileva, Joyce K. Y. Wu, Melissa Valaee, Ethan Ortiz, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5753372/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Orphanet Journal of Rare Diseases → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic bone disease that is characterized by progressive heterotopic ossification of the thoracic cavity. Prognosis is poor with cardiopulmonary complications being the main cause of death. Spirometry is a well-established metric of functional exercise capacity and prognosis in lung diseases but its use is limited in this population. Accuracy and validity of spirometry is dependent on forced expiratory maneuvers which are difficult to perform for individuals with FOP. Oscillometry is an effort-independent pulmonary function test that is highly sensitive to changes in respiratory mechanics. Little is known about oscillometry in individuals with FOP. The purpose of this paper is to characterize FOP using oscillometry. Results: Eight participants with FOP were recruited for oscillometry prior to spirometry. Cumulative Analogue Joint Involvement Scale (CAJIS) scores were used to evaluate total body and regional FOP burden. Spirometry showed a uniform pattern of restrictive physiology in all eight participants with no significant difference amongst the group. Oscillometry revealed significant diversity in respiratory mechanics and chest wall involvement from normal, airway obstruction and ventilatory inhomogeneity to extra-thoracic airflow obstruction. We compared individuals with normal and abnormal oscillometry and found no statistically significant differences in functional status and clinical parameters. However, there is a tendency for lower CAJIS scores and fewer recent flare-ups in those with more normal respiratory mechanics. The tidal volumes were significantly higher in the group with more normal respiratory mechanics. Two wheelchair-dependent participants exhibited a pattern of high respiratory resistance that increased during both inspiration and expiration, to suggest presence of a fixed extra-thoracic defect. Conclusions: Oscillometry provides additional, more detailed information beyond spirometry in individuals with FOP. It is far easier than spirometry to complete and may be useful to help track disease progression and response to therapies in individuals with FOP. Fibrodysplasia Ossificans Progressiva pulmonary function respiratory oscillometry Figures Figure 1 Figure 2 Background Fibrodysplasia ossificans progressiva (FOP) is a severe progressive disabling, ultra-rare genetic bone disorder that affects approximately 1/2,000,000 people world-wide 1 . Death results primarily from cardiorespiratory failure 2 due to progressive immobilization of thorax with cumulative heterotopic ossification (HO) of the chest cavity 3 , 4 . With disease progression, individuals become totally dependent on diaphragmatic breathing as the diaphragm is spared 5 . Flare-ups are painful episodes of connective tissue inflammation that result in transformation of ligaments, tendons and skeletal muscles into heterotopic bone. Episodes of flare-ups start in early childhood, around age of five 6 . Progressive accumulation of HO decreases mobility, causing most individuals to become wheelchair bound by age of 30 4,7 . Life expectancy is 40–50 years. Identification of the specific ALK2/ACVR1 gene variation in individuals with FOP 8 has contributed to discovery of therapeutic targets. Palovarotene, a selective retinoic acid receptor gamma agonist, has been approved for treatment of FOP since 2022. Other compounds are currently being evaluated in clinical trials with the hope that disease progression can be modified 9 – 12 . However, assessing the effectiveness of novel therapies is limited by the lack of easily available and reliable biomarkers to monitor clinical response and disease progression. Pulmonary function tests (PFT) provide well established metrics of respiratory disease severity. These metrics correlate well with functional exercise capacity and are commonly used to evaluate progression and prognosis in lung diseases. Their use in individuals with FOP has been limited, as the forced expiratory maneuvers required for spirometry are difficult for this population. Limited mobility which worsens with disease progression renders moving in and out of the body box for plethysmography highly untenable. The few published studies in FOP have identified a restrictive pulmonary function defect and normal diffusing capacity for carbon monoxide (DLCO) 5 , 13 – 15 . Oscillometry is a different modality of PFT that is performed during normal breathing. It measures the mechanical impedance of the respiratory system with external oscillations superimposed on normal quiet breathing. Oscillometry is highly sensitive to changes in respiratory mechanics 16 and has been shown to provide information that can facilitate earlier diagnosis of different lung diseases. It has been shown to detect exacerbations of asthma 17 – 20 and chronic obstructive lung disease 21 – 25 with greater sensitivity than spirometry and has been found to be highly correlated with severity of idiopathic pulmonary fibrosis 26 . Oscillometry also offers additional pragmatic advantages over spirometry, as it is completed in less than 10 min in any clinical setting where patients can breathe quietly while wearing a nose-clip. There are no published data of oscillometry in people with FOP. The aim of this study is to characterize oscillometry and assess its relationship with FOP disease severity with regard to airway and thoracic involvement. Methods This study was approved by the University Health Network (UHN) Research Ethics Board (#19-5582 and 17-5652). Participants were recruited from the UHN-FOP clinic whose catchment includes all individuals with FOP in Canada. All individuals with FOP were eligible. From July 2022 to September 2024, we enrolled 8 participants and 18 healthy volunteers for oscillometry prior to conventional PFT at Toronto General Pulmonary Function Laboratory. Spectral oscillometry using multi-frequency signals from 5–37 Hz was performed first, followed by 10 Hz mono-frequency oscillometry. Oscillometry was performed using the tremoflo ® C-100 device (Thorasys, Canada) following published technical standards and quality control guidelines 27 – 31 . Conventional PFTs (spirometry and DLCO) were performed using the Medisoft HypAir PFS (Sorinnes, Belgium) conducted in accordance with the American Thoracic Society (ATS)/European Respiratory Society guidelines 32 , 33 . DLCO was measured using the rapid gas analyzer system. Reference values for oscillometry were derived from the Oostveen and Nowowiejska equations 34 , 35 and spirometry from the Global Lung Initiative 36 . Oscillometry parameters of interest are shown (Fig. 1). Spectral oscillometry (Fig. 1A) provides the mean values of impedance at different frequencies over an entire breath and include: R5, resistance at 5 Hz, a measure of total respiratory resistance; R5-19, difference in resistance between 5 and 19 Hz, a measure of small airway obstruction and inhomogeneity of ventilation; X5, reactance at 5 Hz which reflects the stiffness or elastance of the pulmonary and chest wall tissues; and AX, the integrative index of reactance between X5 and Fres (frequency of resonance). AX is considered a more robust metric of elastance and peripheral ventilation inhomogeneity compared to X5 as it is less subject to interference from the subject’s breathing rate 28 , 37 . Obstructive respiratory physiology is characterized by higher resistance at all frequencies, high R5-19, low X5 and high AX 38 . Restrictive physiology is characterized by a rightward shift of the reactance curve, leading to low X5 and high AX, while resistance is normal across the frequencies and R5-19 is low 26 . Intrabreath oscillometry tracks changes in respiratory mechanics within the breathing cycle, using a single sinusoidal signal. The key intrabreath oscillometry metrics are the measurements of resistance (R) and reactance (X) during zero flow, that is at end expiration (ReE and XeE) and end inspiration (ReI and XeI). Analysis of the intrabreath resistance and reactance loops during a tidal breath (Fig. 1B and C) provides more granular details that can help differentiate the site of airflow obstruction and parenchymal vs chest wall restriction 39 , 26 . Conventional PFT parameters of interest are the forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC ratio, DLCO, alveolar volume (VA) and DLCO/VA ratio. The cumulative analogue joint involvement scale (CAJIS) scores were used to evaluate total body and regional FOP burden 40 , 41 . The CAJIS scores, ambulatory status and number of flare-up episodes within the last two years were assessed by a physician as part of routine care during the participant’s clinical visit at TGH. Imaging data (including computed tomography and plain radiographs) were reviewed and included, if available in the participant’s electronic medical records. Exploratory statistical analysis was performed using the R Studio version 4.1.1 (R Foundation). Group comparisons were conducted using t-test for normally distributed continuous variables, Wilcoxon test for non-normal continuous variables, and Pearson’s chi-square test for categorical variables. Results The mean age of the group was 26 years (range 14–39) with a mean BMI of 25.1 (range 17.7–37.4) and a total body CAJIS score (mean = 11.9, range 7–23). All participants had the classic ACVR1 R206H variation except one who had a ACVR2A variation. All participants demonstrated clinical characteristic of FOP with progressive formation of HO observed on CT images and plain radiographs. The CAJIS thoraco-lumbar spine score was similar in all participants but one who had a lower score of 1. A score of 0 means no restriction, 1 some restriction, and 2 totally ankylosed and fixed. The mean number of flare-ups in the preceding 2 years was 5.9 (range 0–12). Of the 8 participants, only 2 were fully independent, and 2 were wheelchair dependent (Table 1 ). Table 1 Participants' characteristics at time of enrolment. ID Sex Age, years BMI, kg/m 2 CAJIS thoraco-lumbar spine score CAJIS total body score Flare-ups within last 2 years Functional status Treatment 1 M 14 37.4 2 7 6 Independent NSAID, pain medications; prednisone for flare up - last August 2024 2 M 35 24.9 2 23 5 Can walk, wheelchair for long distance Palovarotene; NSAID, antihistamine, pain medications; prednisone for flareup – last in May 2024 3 M 39 19.4 2 13 2 Independent Pain medications; In randomized clinical trial; prednisone for flare up - last January 2023 4 F 21 24.0 1 7 6 Can walk with walker, wheelchair for long distance NSAID, antihistamine, pain medications; In randomized clinical trial; prednisone for flareup – last in February 2023 5 F 29 17.7 2 17 4 Wheelchair dependent Palovarotene until May 2024; NSAID, antihistamine, pain medications; In randomized clinical trial; prednisone for flareup – last dose April 2024 6 F 19 23.8 2 11 12 Wheelchair dependent NSAID, antihistamine medications; In randomized clinical trial; prednisone for flareup - last June 2024 7 F 34 33.3 2 9 0 Can walk, wheelchair for long distance NSAID, antihistamine, pain medications; In randomized clinical trial; prednisone for flareup – last in July 2024 8 F 18 20.1 2 8 12 Can walk, wheelchair for long distance NSAID, pain medications; In randomized clinical trial; prednisone for flare up - last July 2024 Spirometry showed a pattern of restriction in all participants with proportionate reduction in FEV 1 and FVC (mean = 56.7% and 52.1% predicted, respectively) and normal FEV 1 /FVC (mean = 92.4%; Table 2 ). Four of the 5 participants who attempted DLCO were able to complete testing. The findings were normal in all 4 participants with DLCO > 80% predicted and DLCO/VA ratio ranging from 5.98 to 7.13. Plethysmography was not possible due to the limited mobility from FOP and inability to get into the body box. In the overall group, oscillometry was abnormal, with the most significant abnormal being the X5 z-score and XeI when compared to healthy controls (Table 2 ). Table 2 Respiratory oscillometry in participants with FOP and healthy controls. FOP (n = 8) Healthy controls (n = 18) P-value Age (years) 26.12 (9.30) 30.67 (10.50) 0.303 Sex , F (%) 5 (62.5) 13 (72.2) 0.972 BMI (kg/m 2 ) 25.08 (6.90) 23.40 (6.31) 0.549 FEV 1 (L) 2.26 (0.48) 3.65 (0.57) < 0.001 %FEV 1 56.71 (5.28) 92.31 (8.71) < 0.001 FVC (L) 2.45 (0.56) 4.32 (0.70) < 0.001 %FVC 52.12 (6.30) 95.20 (13.06) < 0.001 FEV 1 /FVC 92.42 (5.62) 84.24 (2.05) < 0.001 DLCO # 18.18 - - %DLCO 88.78 - - VA (L) 2.83 - - %VA 46.06 - - DLCO/VA 6.38 - - R5 * 5.08 [3.80, 6.40] 3.02 [2.73, 3.75] 0.017 %R5 171.76 [148.35, 205.36] 110.16 [93.52, 129.96] 0.002 R5 z-score 1.98 (1.26) 0.31 (0.98) 0.001 R19 * 4.29 [2.60, 5.10] 2.97 [2.65, 3.37] 0.267 %R19 144.31 [116.10, 161.11] 103.16 [91.35, 112.48] 0.015 R19 z-score 1.19 (1.26) 0.17 (0.84) 0.021 X5 * -2.44 [-2.70, -1.65] -0.95 [-1.13, -0.81] 0.002 %X5 273.18 [233.89, 311.67] 95.69 [84.61, 113.14] 0.002 X5 z-score -2.98 (1.74) 0.16 (0.99) < 0.001 R5-19 * 0.79 [0.47, 1.45] 0.01 [-0.14, 0.14] 0.001 AX (cmH 2 O/L) 11.11 [6.13, 15.43] 2.60 [1.93, 3.82] 0.001 Vt (L) 0.80 [0.65, 0.86] 0.71 [0.58, 0.85] 0.697 Fres (Hz) 16.87 [13.90, 18.69] 10.17 [9.30, 12.99] 0.002 ReE * 3.72 [3.20, 4.32] 2.38 [2.17, 2.84] 0.012 ReI * 3.32 [2.50, 3.74] 1.92 [1.72, 2.46] 0.015 XeE * -0.39 [-0.59, -0.07] 0.31 [0.06, 0.48] 0.003 XeI * -0.48 [-0.72, -0.28] 0.24 [-0.11, 0.36] < 0.001 BMI: body mass index; FEV 1 : forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; VA: alveolar volume; X5: reactance at 5 Hz; R5: resistance at 5 Hz; R5-19: difference in resistance between 5 and 19 Hz; Fres: resonance frequency; AX: reactance area between 5 Hz and Fres; Vt: tidal volume; ReE: resistance at end-expiration; ReI: resistance at end-inspiration; XeE: reactance at end-expiration; XeI: reactance at end-inspiration. Units of measure: # ml/min/mmHg; * cmH 2 O∙s/L. Spirometry presented as mean (SD), oscillometry as median [IQR]. However, oscillometry was highly variable amongst the 8 participants (Table 3 , Fig. 2). Two participants (#1 and #4) had completely normal oscillometry with normal AX and R5-19 along with Z-scores -1.64 for X5. While participant #1 was fully independent, participant #4 was ambulatory but needed wheelchair assistance for longer outings. The oscillometry patterns of the remaining 3 ambulatory participants (#2, #7, #8) had ventilatory inhomogeneities, as reflected by elevated R5-19 (> 1.0 cm H 2 O.s/L), low X5 (z-scores 10 cm H 2 O/L). The particularly high R5-19 and AX values in participant #7 (BMI 33.3) likely reflect the impact of obesity-related changes in respiratory mechanics as this pattern of peripheral airway obstruction has been described in obese patients 38 . Participant #3 was fully independent and had oscillometry that was remarkable for low X5 (z-score − 3.02). The two wheelchair-dependent participants (#5 and #6) had different abnormal spectral oscillometry. While both participants exhibited high resistance values (R5 z-score: 4.13 and 2.87, respectively) which are indicative of overall narrowing of the airways and increased total respiratory resistance, participant 5 had normal R5-19 and AX, reflecting homogenous ventilation. In contrast, participant #6 exhibited high R5-19 and AX which are indicative of airflow obstruction with ventilatory inhomogeneity. Table 3 Spirometry and oscillometry at time of enrolment. ID 1 2 3 4 5 α 6 α 7 8 Sex M M M F F F F F Age (years) 14 35 39 21 29 19 34 18 BMI (kg/m 2 ) 37.4 24.9 19.4 24 17.7 23.8 33.3 20.1 FEV 1 (L) 2.89 2.64 2.57 2.64 2.05 1.68 1.79 1.79 %FEV 1 59.8 56.4 57.7 64.3 57.9 47.4 59.2 51.0 FVC (L) 3.43 2.65 2.67 2.91 2.08 1.81 1.96 2.09 %FVC 60.2 45.3 47.6 60.5 50.3 44.6 56.1 52.4 FEV 1 /FVC 84.2 99.6 96.3 90.7 98.6 93.0 91.2 85.8 DLCO # - 23.8 25.1 - 15.8 11.9 - 14.3 %DLCO - 95 97.4 - 83.7 (65.9) β - 101.9 VA (L) - 3.34 3.95 - 2.63 1.85 - 2.39 %VA - 43.9 53.3 - 47.6 35.9 - 49.6 DLCO/VA 7.13 6.35 6.01 6.43 5.98 R5 * 5.14 4.12 2.67 2.87 7.06 6.25 6.86 5.01 %R5 149.35 177.47 145.36 104.93 299.52 214.14 166.06 202.43 R5 z-score 0.72 2.05 1.33 0.18 4.13 2.87 1.91 2.65 R19 * 5.00 2.68 2.37 2.33 6.51 4.61 5.37 3.98 %R19 189.86 112.81 117.19 82.4 247.78 151.53 141.94 146.68 R19 z-score 1.02 0.46 0.61 -0.78 3.64 1.67 1.4 1.54 X5 * -0.81 -2.66 -1.8 -1.23 -2.35 -2.82 -4.29 -2.53 X5 z-score 0.33 -4.57 -3.02 -1.08 -3.48 -3.59 -4.65 -3.79 %X5 81.89 354.16 282.48 157.21 306.83 263.88 259.45 326.17 R5-19 * 0.13 1.43 0.3 0.53 0.55 1.64 1.49 1.03 AX (cmH 2 0/L) 3.22 16.12 6.15 6.08 8.25 15.2 35.81 13.96 Vt (L) 0.82 0.69 0.95 0.78 0.99 0.53 0.82 0.48 Fres (Hz) 14.08 18.66 11.96 15.77 13.32 18.77 27.05 17.97 ReE * 3.51 3.45 2.08 2.44 4.54 4.25 5.44 3.94 ReI * 3.40 2.64 1.36 2.08 4.25 4.41 3.57 3.24 XeE * 0.41 -0.55 -0.03 -0.29 -0.08 -0.50 -1.17 -0.73 XeI * -0.11 -0.65 -0.30 -0.35 -0.23 -0.94 -1.85 -0.62 BMI: body mass index; FEV 1 : forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; VA: alveolar volume; X5: reactance at 5 Hz; R5: resistance at 5 Hz; R5-19: difference in resistance between 5 and 19 Hz; Fres: resonance frequency; AX: reactance area between 5 Hz and Fres; Vt: tidal volume; ReE: resistance at end-expiration; ReI: resistance at end-inspiration; XeE: reactance at end-expiration; XeI: reactance at end-inspiration. Units of measure: # ml/min/mmHg; * cmH 2 O∙s/L. α Patient who were wheelchair dependent. β Patient unable to complete DLCO testing and results should be interpreted with caution. DLCO was not corrected for Hb. Analysis of the intrabreath oscillometry revealed normal dynamic patterns in all the ambulatory participants with minimal changes in the resistance and reactance loops during breathing (Fig. 2A and B, middle and right panels). The only exception was participant #7. The increase in ReE (denoted as *) compared ReI (denoted as #) and increased resistance vs flow loop area (denoted as §) are indicative of airflow obstruction. The two wheelchair-dependent participants and one of the fully independent individuals (#1) exhibited similar and abnormal intrabreath resistance loops showing increased resistance during both inspiration and expiration, a pattern suggestive of upper airway flow nonlinearities (Fig. 2C). Given the different patterns of oscillometry in the 8 participants, we next explored whether those with worse respiratory mechanics had different clinical characteristics. Participants were grouped according to low AX ( 12 cmH 2 O/L, n = 4). No significant differences were observed in the clinical or spirometry patterns although there was tendency to higher CAJIS scores and more flareup in the previous 2 years in those with high AX (Table 4 ). Table 4 Comparison of the participants with low vs high AX values. Low AX (n = 4) High AX (n = 4) P-value Age (years) 25.75 (10.75) 26.50 (9.26) 0.919 Sex , F (%) 2 (50) 3 (75) 1.000 BMI (kg/m 2 ) 24.62 (8.92) 25.52 (5.58) 0.870 CAJIS thoraco-lumbar spine 1.75 (0.50) 2.00 (0.00) 0.356 CAJIS total body score 11.00 (4.90) 12.75 (6.95) 0.695 Flare-ups within last 2 years 4.50 (1.91) 7.25 (5.85) 0.406 Wheelchair dependent (%) 1 (25) 1 (25) 1.000 FEV 1 (L) 2.54 (0.35) 1.98 (0.45) 0.095 %FEV 1 59.92 (3.07) 53.50 (5.30) 0.081 FVC (L) 2.77 (0.56) 2.13 (0.37) 0.102 %FVC 54.65 (6.67) 49.60 (5.59) 0.290 FEV 1 /FVC 92.45 (6.42) 92.40 (5.69) 0.991 DLCO # 20.45 (6.58) 16.67 (6.29) 0.563 %DLCO 90.55 (9.69) 87.60 (19.11) 0.858 VA (L) 3.29 (0.93) 2.53 (0.75) 0.382 %VA 50.45 (4.03) 43.13 (6.88) 0.279 DLCO/VA 6.18 (0.24) 6.51 (0.58) 0.513 R5 * 4.01 [2.82, 5.63] 5.63 [4.79, 6.40] 0.564 %R5 147.35 [135.25, 186.89] 189.95 [174.62, 205.36] 0.248 R5 z-score 1.59 (1.76) 2.37 (0.46) 0.425 R19 * 3.69 [2.36, 5.39] 4.29 [3.66, 4.80] 0.773 %R19 153.53 [108.49, 204.34] 144.31 [134.66, 147.89] 0.773 R19 z-score 1.12 (1.84) 1.27 (0.55) 0.885 X5 * -1.51 [-1.93, -1.13] -2.74 [-3.18, -2.63] 0.021 %X5 219.85 [138.38, 288.57] 295.03 [262.78, 333.17] 0.248 X5 z-score -1.81 (1.77) -4.15 (0.54) 0.045 R5-19 * 0.41 [0.26, 0.54] 1.46 [1.33, 1.53] 0.021 AX (cmH 2 0/L) 6.12 [5.37, 6.68] 15.66 [14.89, 21.04] 0.021 Vt (L) 0.89 [0.82, 0.96] 0.61 [0.52, 0.72] 0.043 Fres (Hz) 13.70 [12.98, 14.51] 18.72 [18.49, 20.84] 0.021 ReE * 2.97 [2.35, 3.76] 4.09 [3.82, 4.54] 0.248 ReI * 2.74 [1.90, 3.61] 3.40 [3.09, 3.78] 0.386 XeE * -0.06 [-0.13, 0.08] -0.64 [-0.84, -0.53] 0.021 XeI * -0.26 [-0.31, -0.20] -0.79 [-1.17, -0.64] 0.021 BMI: body mass index; FEV 1 : forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; VA: alveolar volume; X5: reactance at 5 Hz; ex: during expiration; in: during inspiration; R5: resistance at 5 Hz; R5-19: difference in resistance between 5 and 19 Hz; Fres: resonance frequency; AX: reactance area between 5 Hz and Fres; Vt: tidal volume; ReE: resistance at end-expiration; ReI: resistance at end-inspiration; XeE: reactance at end-expiration; XeI: reactance at end-inspiration. Units of measure: # ml/min/mmHg; * cmH2O∙s/L. Spirometry presented as mean (SD), oscillometry as median [IQR]. Discussion In the current study, 8 of the 20 known individuals with FOP (of whom 4 are children) living in Canada were evaluated with spirometry and oscillometry. To our knowledge, this is the first study to characterize oscillometry in the FOP population. As a pulmonary function test, oscillometry offers significant advantages to the traditional tests with spirometry and plethysmography as it is conducted during normal quiet breathing and can be performed in any setting because the devices are portable. Patients prefer oscillometry over spirometry 29 , 42 . Moreover, oscillometry is possible for patients who cannot perform the forced expiratory maneuvers needed for spirometry or whose mobility limits their ability to sit in the plethysmograph box. Similar to previous studies, all participants exhibited a restrictive physiology pattern on spirometry and normal DLCO 5 , 13 – 15 . Surprisingly, we found diverse oscillometry patterns of respiratory mechanics in the 8 participants. They varied from normal to central airway narrowing with increased R5 to small airway obstruction with ventilatory inhomogeneity (increased R5-19 and increased AX) and extrathoracic airflow obstruction (increased resistance during both inspiration and expiration in intrabreath analysis). Intrabreath reactance measurements were found to be normal in some participants (#1, #3, and #4), suggesting that both the lung parenchyma and the chest wall tissues were unaffected. Conversely, low XeI values were observed in others (#6 and #7), which may indicate excessive stretch of the respiratory tissues. Additionally, the resistive defect observed on spirometry may also result from the chest wall. The assessment of the contribution of chest wall impedance (Zcw) to Zrs through esophageal pressure measurement was not feasible in the present investigation. Earlier studies addressing different frequency ranges 43 – 45 have demonstrated that, in healthy subjects, Zcw is comparable to that of the lungs. To the best of our knowledge, no study has hitherto investigated oscillation mechanics and its components in FOP. Van Noord et al. 46 measured Zrs in patients with ankylosing spondylitis and kyphoscoliosis, and observed decreases in Xrs in both groups; however, kyphoscoliosis was also associated with a significant elevation in Rrs. Consequently, it can be inferred that, akin to the aforementioned study by Van Noord et al., the increased viscous and elastic losses observed in patients with elevated Rrs and lowered Xrs are attributable to the modified chest wall mechanics. In a related investigation, oscillometry measurements were made in a small group of patients suffering from osteogenesis imperfecta 47 . However, since the primary focus of this study was bronchial obstruction and bronchodilator response, the potential effect of altered chest wall structure on Zrs remains unclear. Given the small sample size, meaningful comparisons could not be made about correlation of the respiratory mechanics and the CAJIS scores, particularly the thoraco-lumbar spine scores. The strong flow dependence of the intrabreath resistance in three participants suggests extrathoracic airflow obstruction. The underlying mechanism is not known. Airway and vocal cord calcification have not been reported in individuals with FOP, and were not seen in the low-dose whole body CT scans of these three participants. Calcification of oropharyngeal muscles and soft tissues or calcification impinging on the trachea or larynx could potentially lead to a fixed airway aperture but was also not seen in the CT scans of these two participants. One participant did have an unusual cord of mineralization from the hyoid anteriorly to the mandible, but it is unlikely for this cord to cause airflow obstruction. Since upper airway flow nonlinearities can be due to many causes, further studies are needed to better understand the underlying mechanism of extrathoracic airflow obstruction in affected individuals. Conclusions Oscillometry is particularly advantageous in FOP as accurate measurements can still be made in people with severe functional limitations for whom the maneuvers needed for spirometry and DLCO are challenging. Our data show that oscillometry provides additional information beyond spirometry regarding the respiratory status of individuals with FOP. In particular, our data reveal that participants had a range of normal to abnormal respiratory mechanics despite similar severity of restriction observed on spirometry. These findings are congruent with data in different patient populations and in several large population surveys where oscillometry was found to detect disease earlier and to be associated with burden of respiratory symptoms 17 – 25 . Given the ease of application, our data support the addition of oscillometry for monitoring individuals with FOP as it may be useful for tracking disease progression and response to therapies. Declarations Ethics approval and consent to participate: This study was approved by the University Health Network (UHN) Research Ethics Board (#19-5582 and 17-5652). The participants provided their written informed consent to participate in this study Consent for publication: Not applicable. Availability of data and materials: The datasets generated during and/or analysed during the current study are available on reasonable request. Following publication of the manuscript, deidentified data will be made available on request following review, approval and completion of data sharing agreements between University Health Network and the requesting institution(s). Competing interests: AMC: consultant fees Ipsen, grants to UHN from Ipsen and Incyte for the clinical trials in FOP; CWC: speaker honoraria from AstraZeneca Canada and Covis Pharma, investigator-initiated research grant from Thorasys Thoracic Medical Devices Corp. (held at UHN); JW: speaker honoraria from Covis Pharma; consultant fees from Thorasys Thoracic Medical Devices Corp; ZH: consultant fees from Thorasys Thoracic Medical Devices Corp and Piston Medical Ltd. Funding : The study was funded by the University of Toronto Pettit Block Term Grant. ZH was supported by Hungarian Scientific Research Fund grant 128701. Authors’ contributions: AV conducted the research, performed the data analysis, drafted the manuscript. JW maintained the research ethics protocol, developed the standard operating procedures and quality control of the oscillometry tests, and quality assurance of the data. MV and EO conducted the intrabreath analysis. ZH developed the intrabreath technique, oversaw the intrabreath analysis and edited the manuscript. LT edited the manuscript. ccCWC developed the concept, study protocol and oversaw all aspects of the project. Acknowledgements: The authors thank all participants involved in the study. The authors thank the Registered Pulmonary Technologists at Toronto General Hospital for helping to conduct the study and C-WC’s research group members for collecting the oscillometry data. References Liljesthröm M, Pignolo RJ, Kaplan FS. Epidemiology of the Global Fibrodysplasia Ossificans Progressiva (FOP) Community. J Rare Dis Res Treat. 2020;5(2):31–6. Kaplan FS, Zasloff MA, Kitterman JA, Shore EM, Hong CC, Rocke DM. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. 2010;92(3):686–91. Kaplan FS, Pignolo RJ, Al Mukaddam M, Shore EM. Genetic disorders of heterotopic ossification: fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In: Bilezikian J, editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism – Ninth Edition. Washington, D.C.: The American Society for Bone and Mineral Research; 2019. pp. 865–70. Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol reviews: PER. 2013;10(Suppl 2):437–48. Connor JM, Evans CC, Evans DA. Cardiopulmonary function in fibrodysplasia ossificans progressiva. Thorax. 1981;36(6):419–23. Pignolo RJ, Bedford-Gay C, Liljesthrom M, et al. The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment. J bone mineral research: official J Am Soc Bone Mineral Res. 2016;31(3):650–6. Pignolo RJ, Cheung K, Kile S, et al. Self-reported baseline phenotypes from the International Fibrodysplasia Ossificans Progressiva (FOP) Association Global Registry. Bone. 2020;134:115274. Shen Q, Little SC, Xu M, et al. The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J Clin Investig. 2009;119(11):3462–72. Pignolo RJ, Baujat G, Hsiao EC, Keen R, Wilson A, Packman J, Kaplan FS. Palovarotene for fibrodysplasia ossificans progressiva (FOP): results of a randomized, placebo-controlled, double‐blind phase 2 trial. J Bone Miner Res. 2020;37(10):1891–902. Pignolo RJ, Hsiao EC, Mukaddam A, Baujat M, Berglund G, Brown SK, Kaplan MA. Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res. 2023;38(3):381–94. Nikishina IP, Arsenyeva SV, Matkava VG, Arefieva AN, Kaleda MI, Smirnov AV, Blank LM, Kostik MM. Successful experience of tofacitinib treatment in patients with Fibrodysplasia Ossificans Progressiva. Pediatr Rheumatol Online J. 2023;21(1):92. Di Rocco M, Forleo-Neto E, Pignolo RJ, Keen R, Orcel P, Funck-Brentano T, Kaplan F. Garetosmab in fibrodysplasia ossificans progressiva: A randomized, double-blind, placebo-controlled phase 2 trial. Nat Med. 2023;29(10):2615–24. Kussmaul WG, Esmail AN, Sagar Y, Ross J, Gregory S, Kaplan FS. Pulmonary and cardiac function in advanced fibrodysplasia ossificans progressiva. Clin Orthop Relat Res 1998(346):104–9. Buhain WJ, Rammohan G, Berger HW. Pulmonary function in myositis ossificans progressiva. Am Rev Respir Dis. 1974;110(3):333–7. Botman E, Smilde BJ, Hoebink M, et al. Deterioration of pulmonary function: An early complication in Fibrodysplasia Ossificans Progressiva. Bone Rep. 2021;14:100758. Bates JH, Irvin CG, Farre R, Hantos Z. Oscillation mechanics of the respiratory system. Compr Physiol. 2011;1(3):1233–72. Shi Y, Aledia AS, Tatavoosian AV, Vijayalakshmi S, Galant SP, George SC. Relating small airways to asthma control by using impulse oscillometry in children. J Allergy Clin Immunol. 2012;129(3):671–8. Kuo CR, Lipworth B. (2020). Airwave oscillometry and patient-reported outcomes in persistent asthma. Ann Allergy Asthma Immunol, 124 (3). Foy BH, Soares M, Bordas R, et al. Lung Computational Models and the Role of the Small Airways in Asthma. Am J Respir Crit Care Med. 2019;200(8):982–91. Tang FSM, Rutting S, Farrow CE et al. Ventilation heterogeneity and oscillometry predict asthma control improvement following step-up inhaled therapy in uncontrolled asthma. Respirology 2020. Frantz S, Nihlen U, Dencker M, Engstrom G, Lofdahl CG, Wollmer P. Impulse oscillometry may be of value in detecting early manifestations of COPD. Respir Med. 2012;106(8):1116–23. Aarli BB, Calverley PMA, Jensen RL, Eagan TML, Bakke PS, Hardie JA. Variability of within- breath reactance in COPD patients and its association with dyspnoea. Eur Respir J. 2015;45(3):625–34. Dean J, Kolsum U, Hitchen P, Gupta V, Singh D. Clinical characteristics of COPD patients with tidal expiratory flow limitation. Int J Chronic Obstr Pulm Dis. 2017;12:1503–6. Young H, Guo F, Eddy R, Maksym G, Parraga G. Oscillometry and pulmonary MRI measurements of ventilation heterogeneity in obstructive lung disease: relationship to quality of life and disease control. J Appl Physiol. 2018;125:73–85. 10.1152/japplphysiol.01031.2017 . Eddy RL, Westcott A, Maksym GN, Parraga G, Dandurand RJ. Oscillometry and pulmonary magnetic resonance imaging in asthma and COPD. Physiol Rep. 2019;7(1):e13955. Wu JK, Ma J, Nguyen L, Dehaas EL, Vasileva A, Chang E, Liang J, Huang QW, Cassano A, Binnie M, Shapera S. Correlation of respiratory oscillometry with CT image analysis in a prospective cohort of idiopathic pulmonary fibrosis. BMJ Open Respiratory Res. 2022;9(1):e001163. Oostveen E, MacLeod D, Lorino H, et al. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003;22(6):1026–41. King GG, Bates J, Berger KI, Calverley P, de Melo PL, Dellacà RL, et al. Technical standards for respiratory oscillometry. Eur Respir J. 2020;55:1900753. Wu JK, DeHaas E, Nadj R, Cheung AB, Dandurand RJ, Hantos Z, et al. Development of quality assurance and quality control guidelines for respiratory oscillometry in clinic studies. Respir Care. 2020;65:1687–93. 10.4187/respcare.07412 . Chang E, Vasileva A, Nohra C, Ryan CM, Chow CW, Wu JKY. (2022). Conducting respiratory oscillometry in an outpatient setting. JoVE (Journal Visualized Experiments), (182), e63243. Hantos Z, Wu JK, Dandurand RJ, Chow CW. (2023). Quality control in respiratory oscillometry: reproducibility measures ignoring reactance? ERJ Open Res, 9 (3). Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of spirometry 2019 Update. An official American thoracic society and European respiratory society technical statement. Am J Respir Crit Care Med. 2019;200:e70–88. 10.1164/rccm.201908-1590ST . Graham BL, Brusasco V, Burgos F, Cooper BG, Jensen R, Kendrick A, MacIntyre NR, Thompson BR, Wanger J. (2017). 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J, 49 (1). Oostveen E, Boda K, van der Grinten CP, et al. Respiratory impedance in healthy subjects: baseline values and bronchodilator response. Eur Respir J. 2013;42(6):1513–23. Nowowiejska B, Tomalak W, Radliński J, Siergiejko G, Latawiec W, Kaczmarski M. Transient reference values for impulse oscillometry for children aged 3–18 years. Pediatr Pulmonol. 2008;43(12):1193–7. Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40(6):1324–43. 10.1183/09031936.00080312 . (In eng). Kaminsky DA, Simpson SJ, Berger KI, Calverley P, De Melo PL, Dandurand R, Dellacà RL, Farah CS, Farré R, Hall GL, Ioan I. 2022. Clinical significance and applications of oscillometry. European respiratory review , 31(163). Bates JHT, Maksym GN. Mechanical Determinants of Airways Hyperresponsiveness. Crit ReviewsTM Biomedical Eng. 2011;39(4). https://doi.org/10.1615/CritRevBiomedEng.v39.i4.30 . Hantos Z. Intra-breath oscillometry for assessing respiratory outcomes. Curr Opin Physiol. 2021;22:100441. Kaplan FS, Mukaddam A, M., Pignolo RJ. A cumulative analogue joint involvement scale (CAJIS) for fibrodysplasia ossificans progressiva (FOP). Bone. 2017;101:123–8. Pignolo RJ, Kaplan FS. Clinical staging of fibrodysplasia ossificans progressiva (FOP). Bone. 2018;109:111–4. Wu JKY, Xu JJ, Vasileva A, Nohra C, Binnie M, Shapera S, Fisher JH, Ryan CM, McInnis M, Hantos Z, Chow CW. Respiratory oscillometry with CT image analysis in idiopathic pulmonary fibrosis following single lung transplant. Respir Med Case Rep. 2024;49:102016. Ferris BG Jr, Mead J, Opie LH. Partitioning of respiratory flow resistance in man. J Appl Physiol. 1964;19(4):653–8. Nagels J, Landser FJ, Van der Linden L, Clement J, Van de Woestijne KP. Mechanical properties of lungs and chest wall during spontaneous breathing. J Appl Physiol. 1980;49(3):408–16. Hantos Z, Daroczy B, Suki B, Galgoczy G, Csendes T. Forced oscillatory impedance of the respiratory system at low frequencies. J Appl Physiol. 1986;60(1):123–32. Van Noord JA, Cauberghs M, Van de Woestijne KP, Demedts M. Total respiratory resistance and reactance in ankylosing spondylitis and kyphoscoliosis. Eur Respir J. 1991;4(8):945–51. Storoni S, Verdonk SJ, Micha D, Jak PM, Bugiani M, Eekhoff EM, van den Aardweg JG. Bronchial obstruction in osteogenesis imperfecta can be detected by forced oscillation technique. Front Med. 2023;10:1301873. Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Orphanet Journal of Rare Diseases → Version 1 posted Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 24 Apr, 2025 Editor assigned by journal 23 Apr, 2025 First submitted to journal 22 Apr, 2025 Editorial decision: Minor revision 23 Feb, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5753372","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":447564183,"identity":"3b99a96b-5480-46c8-88b8-168c4eebe8a6","order_by":0,"name":"Anastasiia Vasileva","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-5915-9265","institution":"University Health Network","correspondingAuthor":true,"prefix":"","firstName":"Anastasiia","middleName":"","lastName":"Vasileva","suffix":""},{"id":447564184,"identity":"46f1df36-664c-40d8-9db1-c23b2003ddb7","order_by":1,"name":"Joyce K. Y. Wu","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Joyce","middleName":"K. Y.","lastName":"Wu","suffix":""},{"id":447564185,"identity":"f904d0e5-82c1-4853-b857-7a3e30d830f7","order_by":2,"name":"Melissa Valaee","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Melissa","middleName":"","lastName":"Valaee","suffix":""},{"id":447564186,"identity":"05a405ce-669d-4929-80bb-e0d599897d82","order_by":3,"name":"Ethan Ortiz","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Ethan","middleName":"","lastName":"Ortiz","suffix":""},{"id":447564187,"identity":"c52b71d5-b2bd-445b-b940-5a95c5b9c946","order_by":4,"name":"Zoltán Hantos","email":"","orcid":"","institution":"Semmelweis University","correspondingAuthor":false,"prefix":"","firstName":"Zoltán","middleName":"","lastName":"Hantos","suffix":""},{"id":447564188,"identity":"442a9b32-d8eb-4143-b8ba-39d1b8681d31","order_by":5,"name":"Lianne Tile","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Lianne","middleName":"","lastName":"Tile","suffix":""},{"id":447564189,"identity":"a3cc8758-98d9-4558-9a37-d44c9fd09474","order_by":6,"name":"Irene Ho","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Irene","middleName":"","lastName":"Ho","suffix":""},{"id":447564190,"identity":"2f3440e1-3a30-4e5c-8d3e-c7825c19afb3","order_by":7,"name":"Angela M. Cheung","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Angela","middleName":"M.","lastName":"Cheung","suffix":""},{"id":447564191,"identity":"fed816aa-c1d3-414b-ae01-3185b24d7cde","order_by":8,"name":"Chung-Wai Chow","email":"","orcid":"https://orcid.org/0000-0001-9344-8522","institution":"University Health Network","correspondingAuthor":false,"prefix":"","firstName":"Chung-Wai","middleName":"","lastName":"Chow","suffix":""}],"badges":[],"createdAt":"2025-01-02 17:22:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5753372/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5753372/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13023-025-03846-6","type":"published","date":"2025-07-01T15:58:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82071042,"identity":"c840ae36-c031-45a2-946f-fdcb034af213","added_by":"auto","created_at":"2025-05-06 13:19:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":90138,"visible":true,"origin":"","legend":"\u003cp\u003eKey metrics in spectral (A) and mono-frequency intrabreath (B, C) oscillometry\u003c/p\u003e\n\u003cp\u003eSpectral oscillometry provides the mean values of resistance (Rrs) and reactance (Xrs) over an entire breath. The key metrics in a spectral oscillogram (A) are shows: R5, resistance at 5 Hz, a measure of total respiratory resistance; R5-19, difference in resistance between 5 and 19 Hz, a measure of small airway obstruction and inhomogeneity of ventilation; X5, reactance at 5 Hz which reflects the stiffness or elastance of the pulmonary and chest wall tissues; and AX, the integrative index of reactance between X5 and Fres (frequency of resonance).\u003c/p\u003e\n\u003cp\u003eIntrabreath oscillometry tracks the changes in Rrs and Xrs at a single frequency(10 Hz) during breathing and is plotted againsttidal volume (B) or flow (C). The resistance (R) and reactance (X) during zero flow at end expiration (eE) and end inspiration (eI) are shown. The solid arrow indicates beginning of inspiration. The dotted arrow indicated beginning of expiration.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753372/v1/d8c66ae4d3b57d49e610bfd1.jpg"},{"id":82071049,"identity":"79015cc2-b599-4ee7-be1e-3a36fc25ca44","added_by":"auto","created_at":"2025-05-06 13:19:49","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":233696,"visible":true,"origin":"","legend":"\u003cp\u003eSpectral and mono-frequency intrabreath oscillometry at time of enrolment.\u003c/p\u003e\n\u003cp\u003eRespiratory impedance plots from a Fully independent (A), Ambulatory (B) and Wheelchair-dependent (C) participants.\u003c/p\u003e\n\u003cp\u003eMean impedance data vs. frequency (left), intrabreath impedance data vs. volume (middle) and flow (right).\u003c/p\u003e\n\u003cp\u003eResistance and reactance data are plotted in solid/ black and dotted/ red, respectively.\u003c/p\u003e\n\u003cp\u003e* ReE (resistance at end expiration); # ReI (resistance at end inspiration); § increased resistance vs flow loop area.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753372/v1/3f32a584ae2dee92e29d41da.jpg"},{"id":86179862,"identity":"6359733e-af54-442b-b3b2-8d6dd8ae314e","added_by":"auto","created_at":"2025-07-07 16:19:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1590790,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5753372/v1/20e5a59f-a64c-4df6-91ea-fc3ea66a7e79.pdf"}],"financialInterests":"","formattedTitle":"Respiratory oscillometry in individuals with fibrodysplasia ossificans progressiva","fulltext":[{"header":"Background","content":"\u003cp\u003eFibrodysplasia ossificans progressiva (FOP) is a severe progressive disabling, ultra-rare genetic bone disorder that affects approximately 1/2,000,000 people world-wide\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Death results primarily from cardiorespiratory failure\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e due to progressive immobilization of thorax with cumulative heterotopic ossification (HO) of the chest cavity\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. With disease progression, individuals become totally dependent on diaphragmatic breathing as the diaphragm is spared\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Flare-ups are painful episodes of connective tissue inflammation that result in transformation of ligaments, tendons and skeletal muscles into heterotopic bone. Episodes of flare-ups start in early childhood, around age of five\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Progressive accumulation of HO decreases mobility, causing most individuals to become wheelchair bound by age of 30\u003csup\u003e4,7\u003c/sup\u003e. Life expectancy is 40\u0026ndash;50 years.\u003c/p\u003e \u003cp\u003eIdentification of the specific ALK2/ACVR1 gene variation in individuals with FOP\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e has contributed to discovery of therapeutic targets. Palovarotene, a selective retinoic acid receptor gamma agonist, has been approved for treatment of FOP since 2022. Other compounds are currently being evaluated in clinical trials with the hope that disease progression can be modified\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. However, assessing the effectiveness of novel therapies is limited by the lack of easily available and reliable biomarkers to monitor clinical response and disease progression.\u003c/p\u003e \u003cp\u003ePulmonary function tests (PFT) provide well established metrics of respiratory disease severity. These metrics correlate well with functional exercise capacity and are commonly used to evaluate progression and prognosis in lung diseases. Their use in individuals with FOP has been limited, as the forced expiratory maneuvers required for spirometry are difficult for this population. Limited mobility which worsens with disease progression renders moving in and out of the body box for plethysmography highly untenable. The few published studies in FOP have identified a restrictive pulmonary function defect and normal diffusing capacity for carbon monoxide (DLCO)\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOscillometry is a different modality of PFT that is performed during normal breathing. It measures the mechanical impedance of the respiratory system with external oscillations superimposed on normal quiet breathing. Oscillometry is highly sensitive to changes in respiratory mechanics\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and has been shown to provide information that can facilitate earlier diagnosis of different lung diseases. It has been shown to detect exacerbations of asthma\u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e and chronic obstructive lung disease\u003csup\u003e\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e with greater sensitivity than spirometry and has been found to be highly correlated with severity of idiopathic pulmonary fibrosis\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Oscillometry also offers additional pragmatic advantages over spirometry, as it is completed in less than 10 min in any clinical setting where patients can breathe quietly while wearing a nose-clip.\u003c/p\u003e \u003cp\u003eThere are no published data of oscillometry in people with FOP. The aim of this study is to characterize oscillometry and assess its relationship with FOP disease severity with regard to airway and thoracic involvement.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was approved by the University Health Network (UHN) Research Ethics Board (#19-5582 and 17-5652). Participants were recruited from the UHN-FOP clinic whose catchment includes all individuals with FOP in Canada. All individuals with FOP were eligible. From July 2022 to September 2024, we enrolled 8 participants and 18 healthy volunteers for oscillometry prior to conventional PFT at Toronto General Pulmonary Function Laboratory. Spectral oscillometry using multi-frequency signals from 5\u0026ndash;37 Hz was performed first, followed by 10 Hz mono-frequency oscillometry. Oscillometry was performed using the tremoflo\u003csup\u003e\u0026reg;\u003c/sup\u003e C-100 device (Thorasys, Canada) following published technical standards and quality control guidelines\u003csup\u003e\u003cspan additionalcitationids=\"CR28 CR29 CR30\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Conventional PFTs (spirometry and DLCO) were performed using the Medisoft HypAir PFS (Sorinnes, Belgium) conducted in accordance with the American Thoracic Society (ATS)/European Respiratory Society guidelines\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. DLCO was measured using the rapid gas analyzer system. Reference values for oscillometry were derived from the Oostveen and Nowowiejska equations\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e and spirometry from the Global Lung Initiative\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOscillometry parameters of interest are shown (Fig.\u0026nbsp;1). Spectral oscillometry (Fig.\u0026nbsp;1A) provides the mean values of impedance at different frequencies over an entire breath and include: R5, resistance at 5 Hz, a measure of total respiratory resistance; R5-19, difference in resistance between 5 and 19 Hz, a measure of small airway obstruction and inhomogeneity of ventilation; X5, reactance at 5 Hz which reflects the stiffness or elastance of the pulmonary and chest wall tissues; and AX, the integrative index of reactance between X5 and Fres (frequency of resonance). AX is considered a more robust metric of elastance and peripheral ventilation inhomogeneity compared to X5 as it is less subject to interference from the subject\u0026rsquo;s breathing rate\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. Obstructive respiratory physiology is characterized by higher resistance at all frequencies, high R5-19, low X5 and high AX\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Restrictive physiology is characterized by a rightward shift of the reactance curve, leading to low X5 and high AX, while resistance is normal across the frequencies and R5-19 is low\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIntrabreath oscillometry tracks changes in respiratory mechanics \u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003ewithin\u003c/span\u003e the breathing cycle, using a single sinusoidal signal. The key intrabreath oscillometry metrics are the measurements of resistance (R) and reactance (X) during zero flow, that is at end expiration (ReE and XeE) and end inspiration (ReI and XeI). Analysis of the intrabreath resistance and reactance loops during a tidal breath (Fig.\u0026nbsp;1B and C) provides more granular details that can help differentiate the site of airflow obstruction and parenchymal vs chest wall restriction\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eConventional PFT parameters of interest are the forced expiratory volume in one second (FEV\u003csub\u003e1\u003c/sub\u003e), forced vital capacity (FVC), FEV\u003csub\u003e1\u003c/sub\u003e/FVC ratio, DLCO, alveolar volume (VA) and DLCO/VA ratio.\u003c/p\u003e \u003cp\u003eThe cumulative analogue joint involvement scale (CAJIS) scores were used to evaluate total body and regional FOP burden\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. The CAJIS scores, ambulatory status and number of flare-up episodes within the last two years were assessed by a physician as part of routine care during the participant\u0026rsquo;s clinical visit at TGH. Imaging data (including computed tomography and plain radiographs) were reviewed and included, if available in the participant\u0026rsquo;s electronic medical records.\u003c/p\u003e \u003cp\u003eExploratory statistical analysis was performed using the R Studio version 4.1.1 (R Foundation). Group comparisons were conducted using t-test for normally distributed continuous variables, Wilcoxon test for non-normal continuous variables, and Pearson\u0026rsquo;s chi-square test for categorical variables.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of the group was 26 years (range 14\u0026ndash;39) with a mean BMI of 25.1 (range 17.7\u0026ndash;37.4) and a total body CAJIS score (mean\u0026thinsp;=\u0026thinsp;11.9, range 7\u0026ndash;23). All participants had the classic ACVR1 R206H variation except one who had a ACVR2A variation. All participants demonstrated clinical characteristic of FOP with progressive formation of HO observed on CT images and plain radiographs. The CAJIS thoraco-lumbar spine score was similar in all participants but one who had a lower score of 1. A score of 0 means no restriction, 1 some restriction, and 2 totally ankylosed and fixed. The mean number of flare-ups in the preceding 2 years was 5.9 (range 0\u0026ndash;12). Of the 8 participants, only 2 were fully independent, and 2 were wheelchair dependent (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParticipants' characteristics at time of enrolment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge,\u003c/p\u003e \u003cp\u003eyears\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBMI,\u003c/p\u003e \u003cp\u003ekg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCAJIS\u003c/p\u003e \u003cp\u003ethoraco-lumbar spine score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCAJIS total body score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFlare-ups within last 2 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFunctional status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e37.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNSAID, pain medications; prednisone for flare up - last August 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCan walk, wheelchair for long distance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePalovarotene; NSAID, antihistamine, pain medications; prednisone for flareup \u0026ndash; last in May 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePain medications; In randomized clinical trial; prednisone for flare up - last January 2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCan walk with walker, wheelchair for long distance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNSAID, antihistamine, pain medications; In randomized clinical trial; prednisone for flareup \u0026ndash; last in February 2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eWheelchair dependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePalovarotene until May 2024; NSAID, antihistamine, pain medications; In randomized clinical trial; prednisone for flareup \u0026ndash; last dose April 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eWheelchair dependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNSAID, antihistamine medications; In randomized clinical trial; prednisone for flareup - last June 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCan walk, wheelchair for long distance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNSAID, antihistamine, pain medications; In randomized clinical trial; prednisone for flareup \u0026ndash; last in July 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCan walk, wheelchair for long distance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNSAID, pain medications; In randomized clinical trial; prednisone for flare up - last July 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSpirometry showed a pattern of restriction in all participants with proportionate reduction in FEV\u003csub\u003e1\u003c/sub\u003e and FVC (mean\u0026thinsp;=\u0026thinsp;56.7% and 52.1% predicted, respectively) and normal FEV\u003csub\u003e1\u003c/sub\u003e/FVC (mean\u0026thinsp;=\u0026thinsp;92.4%; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Four of the 5 participants who attempted DLCO were able to complete testing. The findings were normal in all 4 participants with DLCO\u0026thinsp;\u0026gt;\u0026thinsp;80% predicted and DLCO/VA ratio ranging from 5.98 to 7.13. Plethysmography was not possible due to the limited mobility from FOP and inability to get into the body box. In the overall group, oscillometry was abnormal, with the most significant abnormal being the X5 z-score and XeI when compared to healthy controls (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRespiratory oscillometry in participants with FOP and healthy controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFOP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHealthy controls (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.12 (9.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.67 (10.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e, F (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (72.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.08 (6.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.40 (6.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.26 (0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.65 (0.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%FEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56.71 (5.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.31 (8.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFVC\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.45 (0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.32 (0.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%FVC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52.12 (6.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.20 (13.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e/FVC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92.42 (5.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.24 (2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDLCO\u003c/b\u003e \u003csup\u003e\u003cb\u003e#\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%DLCO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVA\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%VA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDLCO/VA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.08 [3.80, 6.40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.02 [2.73, 3.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%R5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e171.76 [148.35, 205.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110.16 [93.52, 129.96]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.98 (1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31 (0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR19 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.29 [2.60, 5.10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.97 [2.65, 3.37]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%R19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e144.31 [116.10, 161.11]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103.16 [91.35, 112.48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR19 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.19 (1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17 (0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eX5 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.44 [-2.70, -1.65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.95 [-1.13, -0.81]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%X5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e273.18 [233.89, 311.67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.69 [84.61, 113.14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eX5 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.98 (1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.16 (0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5-19 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.79 [0.47, 1.45]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 [-0.14, 0.14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAX\u003c/b\u003e (cmH\u003csub\u003e2\u003c/sub\u003eO/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.11 [6.13, 15.43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.60 [1.93, 3.82]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVt\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.80 [0.65, 0.86]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.71 [0.58, 0.85]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFres\u003c/b\u003e (Hz)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.87 [13.90, 18.69]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.17 [9.30, 12.99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReE *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.72 [3.20, 4.32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.38 [2.17, 2.84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReI *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.32 [2.50, 3.74]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.92 [1.72, 2.46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eXeE *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.39 [-0.59, -0.07]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31 [0.06, 0.48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eXeI *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.48 [-0.72, -0.28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24 [-0.11, 0.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI: body mass index; FEV\u003csub\u003e1\u003c/sub\u003e: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; VA: alveolar volume; X5: reactance at 5 Hz; R5: resistance at 5 Hz; R5-19: difference in resistance between 5 and 19 Hz; Fres: resonance frequency; AX: reactance area between 5 Hz and Fres; Vt: tidal volume; ReE: resistance at end-expiration; ReI: resistance at end-inspiration; XeE: reactance at end-expiration; XeI: reactance at end-inspiration. Units of measure: # ml/min/mmHg; * cmH\u003csub\u003e2\u003c/sub\u003eO∙s/L. Spirometry presented as mean (SD), oscillometry as median [IQR].\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHowever, oscillometry was highly variable amongst the 8 participants (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;2). Two participants (#1 and #4) had completely normal oscillometry with normal AX and R5-19 along with Z-scores\u0026thinsp;\u0026lt;\u0026thinsp;1.64 for R5 and R19, and \u0026gt;-1.64 for X5. While participant #1 was fully independent, participant #4 was ambulatory but needed wheelchair assistance for longer outings. The oscillometry patterns of the remaining 3 ambulatory participants (#2, #7, #8) had ventilatory inhomogeneities, as reflected by elevated R5-19 (\u0026gt;\u0026thinsp;1.0 cm H\u003csub\u003e2\u003c/sub\u003eO.s/L), low X5 (z-scores\u0026thinsp;\u0026lt;\u0026thinsp;1.64) and high AX (\u0026gt;\u0026thinsp;10 cm H\u003csub\u003e2\u003c/sub\u003eO/L). The particularly high R5-19 and AX values in participant #7 (BMI 33.3) likely reflect the impact of obesity-related changes in respiratory mechanics as this pattern of peripheral airway obstruction has been described in obese patients\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Participant #3 was fully independent and had oscillometry that was remarkable for low X5 (z-score \u0026minus;\u0026thinsp;3.02). The two wheelchair-dependent participants (#5 and #6) had different abnormal spectral oscillometry. While both participants exhibited high resistance values (R5 z-score: 4.13 and 2.87, respectively) which are indicative of overall narrowing of the airways and increased total respiratory resistance, participant 5 had normal R5-19 and AX, reflecting homogenous ventilation. In contrast, participant #6 exhibited high R5-19 and AX which are indicative of airflow obstruction with ventilatory inhomogeneity.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSpirometry and oscillometry at time of enrolment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%FEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e47.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e51.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFVC\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%FVC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e52.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e/FVC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e93.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e91.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e85.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e 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colname=\"c3\"\u003e \u003cp\u003e43.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e35.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e49.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDLCO/VA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e 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align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%R5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e149.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e145.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e104.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e299.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e214.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e166.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e202.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR19 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%R19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e189.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e247.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e151.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e141.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e146.68\u003c/p\u003e \u003c/td\u003e 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align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-3.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-3.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-4.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-3.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%X5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e354.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e282.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e157.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e306.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e263.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e259.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e326.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5-19 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAX\u003c/b\u003e (cmH\u003csub\u003e2\u003c/sub\u003e0/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e35.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVt\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFres\u003c/b\u003e (Hz)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e27.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReE *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReI *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eXeE *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eXeI *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eBMI: body mass index; FEV\u003csub\u003e1\u003c/sub\u003e: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; VA: alveolar volume; X5: reactance at 5 Hz; R5: resistance at 5 Hz; R5-19: difference in resistance between 5 and 19 Hz; Fres: resonance frequency; AX: reactance area between 5 Hz and Fres; Vt: tidal volume; ReE: resistance at end-expiration; ReI: resistance at end-inspiration; XeE: reactance at end-expiration; XeI: reactance at end-inspiration. Units of measure: # ml/min/mmHg; * cmH\u003csub\u003e2\u003c/sub\u003eO∙s/L. \u003csup\u003eα\u003c/sup\u003e Patient who were wheelchair dependent. \u003csup\u003eβ\u003c/sup\u003e Patient unable to complete DLCO testing and results should be interpreted with caution. DLCO was not corrected for Hb.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAnalysis of the intrabreath oscillometry revealed normal dynamic patterns in all the ambulatory participants with minimal changes in the resistance and reactance loops during breathing (Fig.\u0026nbsp;2A and B, middle and right panels). The only exception was participant #7. The increase in ReE (denoted as *) compared ReI (denoted as #) and increased resistance vs flow loop area (denoted as \u0026sect;) are indicative of airflow obstruction. The two wheelchair-dependent participants and one of the fully independent individuals (#1) exhibited similar and abnormal intrabreath resistance loops showing increased resistance during both inspiration and expiration, a pattern suggestive of upper airway flow nonlinearities (Fig.\u0026nbsp;2C).\u003c/p\u003e \u003cp\u003e Given the different patterns of oscillometry in the 8 participants, we next explored whether those with worse respiratory mechanics had different clinical characteristics. Participants were grouped according to low AX (\u0026lt;\u0026thinsp;12 cmH\u003csub\u003e2\u003c/sub\u003eO/L, n\u0026thinsp;=\u0026thinsp;4) or high AX (\u0026gt;\u0026thinsp;12 cmH\u003csub\u003e2\u003c/sub\u003eO/L, n\u0026thinsp;=\u0026thinsp;4). No significant differences were observed in the clinical or spirometry patterns although there was tendency to higher CAJIS scores and more flareup in the previous 2 years in those with high AX (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the participants with low vs high AX values.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow AX\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh AX\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.75 (10.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.50 (9.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.919\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e, F (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.62 (8.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.52 (5.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.870\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCAJIS thoraco-lumbar spine\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.75 (0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.356\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCAJIS total body score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.00 (4.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.75 (6.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.695\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFlare-ups within last 2 years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.50 (1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.25 (5.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWheelchair dependent\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.54 (0.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.98 (0.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%FEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.92 (3.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.50 (5.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFVC\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.77 (0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.13 (0.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%FVC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.65 (6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.60 (5.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV\u003c/b\u003e\u003csub\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e/FVC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92.45 (6.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.40 (5.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.991\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDLCO\u003c/b\u003e \u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.45 (6.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.67 (6.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.563\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%DLCO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.55 (9.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.60 (19.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.858\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVA\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.29 (0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.53 (0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%VA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.45 (4.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.13 (6.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.279\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDLCO/VA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.18 (0.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.51 (0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.01 [2.82, 5.63]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.63 [4.79, 6.40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%R5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e147.35 [135.25, 186.89]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e189.95 [174.62, 205.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.59 (1.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.37 (0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR19 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.69 [2.36, 5.39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.29 [3.66, 4.80]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.773\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%R19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153.53 [108.49, 204.34]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144.31 [134.66, 147.89]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.773\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR19 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.12 (1.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.27 (0.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.885\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eX5 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.51 [-1.93, -1.13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.74 [-3.18, -2.63]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e%X5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e219.85 [138.38, 288.57]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e295.03 [262.78, 333.17]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eX5 z-score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.81 (1.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4.15 (0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.045\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR5-19 *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.41 [0.26, 0.54]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.46 [1.33, 1.53]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAX\u003c/b\u003e (cmH\u003csub\u003e2\u003c/sub\u003e0/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.12 [5.37, 6.68]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.66 [14.89, 21.04]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVt\u003c/b\u003e (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.89 [0.82, 0.96]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61 [0.52, 0.72]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFres\u003c/b\u003e (Hz)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.70 [12.98, 14.51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.72 [18.49, 20.84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReE *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.97 [2.35, 3.76]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.09 [3.82, 4.54]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReI *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.74 [1.90, 3.61]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.40 [3.09, 3.78]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.386\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eXeE *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.06 [-0.13, 0.08]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.64 [-0.84, -0.53]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eXeI *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.26 [-0.31, -0.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.79 [-1.17, -0.64]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI: body mass index; FEV\u003csub\u003e1\u003c/sub\u003e: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; VA: alveolar volume; X5: reactance at 5 Hz; ex: during expiration; in: during inspiration; R5: resistance at 5 Hz; R5-19: difference in resistance between 5 and 19 Hz; Fres: resonance frequency; AX: reactance area between 5 Hz and Fres; Vt: tidal volume; ReE: resistance at end-expiration; ReI: resistance at end-inspiration; XeE: reactance at end-expiration; XeI: reactance at end-inspiration. Units of measure: # ml/min/mmHg; * cmH2O∙s/L. Spirometry presented as mean (SD), oscillometry as median [IQR].\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the current study, 8 of the 20 known individuals with FOP (of whom 4 are children) living in Canada were evaluated with spirometry and oscillometry. To our knowledge, this is the first study to characterize oscillometry in the FOP population. As a pulmonary function test, oscillometry offers significant advantages to the traditional tests with spirometry and plethysmography as it is conducted during normal quiet breathing and can be performed in any setting because the devices are portable. Patients prefer oscillometry over spirometry\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Moreover, oscillometry is possible for patients who cannot perform the forced expiratory maneuvers needed for spirometry or whose mobility limits their ability to sit in the plethysmograph box.\u003c/p\u003e \u003cp\u003eSimilar to previous studies, all participants exhibited a restrictive physiology pattern on spirometry and normal DLCO\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Surprisingly, we found diverse oscillometry patterns of respiratory mechanics in the 8 participants. They varied from normal to central airway narrowing with increased R5 to small airway obstruction with ventilatory inhomogeneity (increased R5-19 and increased AX) and extrathoracic airflow obstruction (increased resistance during both inspiration and expiration in intrabreath analysis). Intrabreath reactance measurements were found to be normal in some participants (#1, #3, and #4), suggesting that both the lung parenchyma and the chest wall tissues were unaffected. Conversely, low XeI values were observed in others (#6 and #7), which may indicate excessive stretch of the respiratory tissues. Additionally, the resistive defect observed on spirometry may also result from the chest wall. The assessment of the contribution of chest wall impedance (Zcw) to Zrs through esophageal pressure measurement was not feasible in the present investigation. Earlier studies addressing different frequency ranges\u003csup\u003e\u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e have demonstrated that, in healthy subjects, Zcw is comparable to that of the lungs.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, no study has hitherto investigated oscillation mechanics and its components in FOP. Van Noord et al.\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e measured Zrs in patients with ankylosing spondylitis and kyphoscoliosis, and observed decreases in Xrs in both groups; however, kyphoscoliosis was also associated with a significant elevation in Rrs. Consequently, it can be inferred that, akin to the aforementioned study by Van Noord et al., the increased viscous and elastic losses observed in patients with elevated Rrs and lowered Xrs are attributable to the modified chest wall mechanics. In a related investigation, oscillometry measurements were made in a small group of patients suffering from osteogenesis imperfecta\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. However, since the primary focus of this study was bronchial obstruction and bronchodilator response, the potential effect of altered chest wall structure on Zrs remains unclear.\u003c/p\u003e \u003cp\u003eGiven the small sample size, meaningful comparisons could not be made about correlation of the respiratory mechanics and the CAJIS scores, particularly the thoraco-lumbar spine scores. The strong flow dependence of the intrabreath resistance in three participants suggests extrathoracic airflow obstruction. The underlying mechanism is not known. Airway and vocal cord calcification have not been reported in individuals with FOP, and were not seen in the low-dose whole body CT scans of these three participants. Calcification of oropharyngeal muscles and soft tissues or calcification impinging on the trachea or larynx could potentially lead to a fixed airway aperture but was also not seen in the CT scans of these two participants. One participant did have an unusual cord of mineralization from the hyoid anteriorly to the mandible, but it is unlikely for this cord to cause airflow obstruction. Since upper airway flow nonlinearities can be due to many causes, further studies are needed to better understand the underlying mechanism of extrathoracic airflow obstruction in affected individuals.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOscillometry is particularly advantageous in FOP as accurate measurements can still be made in people with severe functional limitations for whom the maneuvers needed for spirometry and DLCO are challenging. Our data show that oscillometry provides additional information beyond spirometry regarding the respiratory status of individuals with FOP. In particular, our data reveal that participants had a range of normal to abnormal respiratory mechanics despite similar severity of restriction observed on spirometry. These findings are congruent with data in different patient populations and in several large population surveys where oscillometry was found to detect disease earlier and to be associated with burden of respiratory symptoms\u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22 CR23 CR24\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Given the ease of application, our data support the addition of oscillometry for monitoring individuals with FOP as it may be useful for tracking disease progression and response to therapies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e This study was approved by the University Health Network (UHN) Research Ethics Board (#19-5582 and 17-5652). The participants provided their written informed consent to participate in this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets generated during and/or analysed during the current study are available on reasonable request. Following publication of the manuscript, deidentified data will be made available on request following review, approval and completion of data sharing agreements between University Health Network and the requesting institution(s).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eAMC: consultant fees Ipsen, grants to UHN from Ipsen and Incyte for the clinical trials in FOP; CWC: speaker honoraria from AstraZeneca Canada and Covis Pharma, investigator-initiated research grant from Thorasys Thoracic Medical Devices Corp. (held at UHN); JW: speaker honoraria from Covis Pharma; consultant fees from Thorasys Thoracic Medical Devices Corp; ZH: consultant fees from Thorasys Thoracic Medical Devices Corp and Piston Medical Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e The study was funded by the University of Toronto Pettit Block Term Grant. ZH was supported by Hungarian Scientific Research Fund grant 128701.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions:\u003c/strong\u003e AV conducted the research, performed the data analysis, drafted the manuscript. JW maintained the research ethics protocol, developed the standard operating procedures and quality control of the oscillometry tests, and quality assurance of the data. MV and EO\u0026nbsp;conducted the intrabreath analysis. ZH developed the intrabreath technique, oversaw the intrabreath analysis and edited the manuscript. LT edited the manuscript. ccCWC developed the concept, study protocol and oversaw all aspects of the project.\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors thank all participants involved in the study. The authors thank the Registered Pulmonary Technologists at Toronto General Hospital for helping to conduct the study and C-WC’s research group members for collecting the oscillometry data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLiljesthr\u0026ouml;m M, Pignolo RJ, Kaplan FS. Epidemiology of the Global Fibrodysplasia Ossificans Progressiva (FOP) Community. J Rare Dis Res Treat. 2020;5(2):31\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaplan FS, Zasloff MA, Kitterman JA, Shore EM, Hong CC, Rocke DM. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. 2010;92(3):686\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaplan FS, Pignolo RJ, Al Mukaddam M, Shore EM. Genetic disorders of heterotopic ossification: fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. 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Front Med. 2023;10:1301873.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fibrodysplasia Ossificans Progressiva, pulmonary function, respiratory oscillometry","lastPublishedDoi":"10.21203/rs.3.rs-5753372/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5753372/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic bone disease that is characterized by progressive heterotopic ossification of the thoracic cavity. Prognosis is poor with cardiopulmonary complications being the main cause of death. Spirometry is a well-established metric of functional exercise capacity and prognosis in lung diseases but its use is limited in this population. Accuracy and validity of spirometry is dependent on forced expiratory maneuvers which are difficult to perform for individuals with FOP. Oscillometry is an effort-independent pulmonary function test that is highly sensitive to changes in respiratory mechanics. Little is known about oscillometry in individuals with FOP. The purpose of this paper is to characterize FOP using oscillometry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Eight participants with FOP were recruited for oscillometry prior to spirometry. Cumulative Analogue Joint Involvement Scale (CAJIS) scores were used to evaluate total body and regional FOP burden. Spirometry showed a uniform pattern of restrictive physiology in all eight participants with no significant difference amongst the group. Oscillometry revealed significant diversity in respiratory mechanics and chest wall involvement from normal, airway obstruction and ventilatory inhomogeneity to extra-thoracic airflow obstruction. We compared individuals with normal and abnormal oscillometry and found no statistically significant differences in functional status and clinical parameters. However, there is a tendency for lower CAJIS scores and fewer recent flare-ups in those with more normal respiratory mechanics. The tidal volumes were significantly higher in the group with more normal respiratory mechanics. Two wheelchair-dependent participants exhibited a pattern of high respiratory resistance that increased during both inspiration and expiration, to suggest presence of a fixed extra-thoracic defect.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eOscillometry provides additional, more detailed information beyond spirometry in individuals with FOP. It is far easier than spirometry to complete and may be useful to help track disease progression and response to therapies in individuals with FOP.\u003c/p\u003e","manuscriptTitle":"Respiratory oscillometry in individuals with fibrodysplasia ossificans progressiva","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 13:19:44","doi":"10.21203/rs.3.rs-5753372/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-04-24T20:39:49+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-24T15:18:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-23T11:37:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2025-04-22T08:30:42+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor revision","date":"2025-02-23T09:25:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc85b1b9-087d-425b-87bc-b41c2bf14db7","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:12:13+00:00","versionOfRecord":{"articleIdentity":"rs-5753372","link":"https://doi.org/10.1186/s13023-025-03846-6","journal":{"identity":"orphanet-journal-of-rare-diseases","isVorOnly":false,"title":"Orphanet Journal of Rare Diseases"},"publishedOn":"2025-07-01 15:58:18","publishedOnDateReadable":"July 1st, 2025"},"versionCreatedAt":"2025-05-06 13:19:44","video":"","vorDoi":"10.1186/s13023-025-03846-6","vorDoiUrl":"https://doi.org/10.1186/s13023-025-03846-6","workflowStages":[]},"version":"v1","identity":"rs-5753372","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5753372","identity":"rs-5753372","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}