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The Global Initiative for Asthma report emphasises the use of spirometry in diagnosing and monitoring asthma in children from 6 years of age onwards [1]. Spirometry requires good cooperation and younger children are sometimes unable to perform repeated forced expiratory blows [2]. Alternative pulmonary function measurements, such as the forced oscillation technique (FOT), are increasingly available for children at preschool age [3]. FOT measures lung function by imposing small soundwaves over tidal breathing through a mouthpiece, where pressure and flow changes in the airways are measured to derive respiratory system properties [4, 5]. The first study on bronchodilator responses by FOT in preschool-aged children was published already two decades ago [6]. Guidelines endorse the use of respiratory oscillometry in diagnosing and following up asthma in young children [3, 7], and it has shown potential in predicting loss of asthma control in older children and adolescents [8]. However, little is known of how FOT indices correlate with flow–volume indices when this technique is used in adjunct with conventional spirometry., Evaluation of airway obstruction with forced oscillation technique can be an adjunct to spirometry or even used as a primary method in those children unable to perform spirometry https://bit.ly/34rE6x2

Introduction: Currently there is a lack of sensitive and specific tools which can objectively identify exacerbations and assess their progress or treatment response. FEV1 is often reported as a study outcome, but this forced manoeuvre has significant limitations. Studies have suggested that small airways measures might provide physiological biomarkers during exacerbations. Aims and Objectives: to assess which physiological tests of small airways function have been used in the acute setting during exacerbations of COPD and the evidence to support their use. Methods: Following PRISMA guidelines, a systematic review was conducted using several databases for relevant published studies of >10 participants which compared at least one small airway test with FEV1 at both exacerbation and a follow-up measurement up to and including two months after exacerbation onset to assess response to treatment. Results: From 1436 screened articles, seven studies were found to be eligible for inclusion. There was heterogeneity in which tests of small airways were used. Four different measures were reported (Impulse oscillometry (IOS), Maximal mid-expiratory flow (MMEF), Forced oscillation technique (FOT) and airway resistance (Raw) by body plethysmography). Studies were small (including 20 to 87 subjects). Six articles reported improvements in small airway measurements during the recovery from exacerbation which correlated with FEV1. Conclusion: There is some evidence to support the use of small airway tests in exacerbations of COPD; however, studies have been small with different tests being utilized. Further pilot studies to determine the usefulness of each test may be of interest

The Forced Oscillation Technique (FOT) measures the respiratory impedance at different frequencies by applying sinusoidal oscillation on spontaneous breathing. Previously, we introduced an extension of the Forced Oscillation Technique in which the patients breathe slowly from residual volume to total lung capacity. The result of the measurement is a volume-dependent respiratory impedance Z(V,f). The nonlinear volume-dependent extended RIC model consists of two nonlinear volume-dependent resistances (central and peripheral), an inertia, and a bronchial compliance. Applying the nonlinear Least Squares parameter estimation and comparing to the original extended RIC model, the volume-dependent RIC model yields the best fit to the experimental data comparing to classical lung models such as the extended RIC model, the Mead-model, and the constant-phase model. The volume-dependency of the respiratory impedance can be approximated adequately with the non-linear model. The volume-dependent FOT measurement and the nonlinear extended RIC model provide a new tool for pulmonary testing with focus on the volume-dependency of the respiratory parameters. It has a high potential for the detection of obstructive lung diseases in early stages.

Background: Expiratory flow limitation (EFL) is an hallmark of COPD. However has not implemented in the baseline routine functional assessment yet. Aim: to evaluate if the measurement of EFL by FOT could contribute to highlight pathophysiological mechanisms of improvement after PR. Method: in 75 stable moderate to very severe COPD patients, before and after PR, EFL as the within-breath change in reactance (DXrs), pulmonary function tests and rehabilitation outcomes were evaluated. Results: In the patients as a whole, after PR, DXrs decreased significantly (p 2.81 [cmH2O/(L/s)], patients were divided into two groups: flow-limited (FL, 36 patients, DXrs 5.14±2.6) and not flow-limited (NFL, 39 patients, DXrs 1.04±0.9) patients. Before PR FL patients were more severely obstructed (FEV1% 34.6±9.6 vs 52.0±20.6, p Conclusions: FOT measures provide new supplementary information to pulmonary functional evaluation in COPD patients enrolled in PR. These preliminary data show that the change in EFL could contribute to the effect of PR in severe patients.

Introduction: Commercial Forced oscillation technique (FOT) devices use patented data acquisition protocols to measure respiratory impedance. ERS guideline recommended that short term intra-individual variability of repeated measurements of FOT indices as expressed as coefficient of variation (CV) should be Methods: FOT were carried out in triplicate and within twenty minutes intervals by using “15 accepted breaths” protocol of Resmon Pro Full device ((Restech Srl, Italy). CV of R5 in 71 healthy adults, 16 COPD, and 20 adult asthmatic patients were analyzed. Results: The median CV of R5 was 10.6% (6.5-17.7) in healthy, 7.6% (5.6-10.3) in COPD, and 14.5% (6.9-22.9) in bronchial asthma respectively. Acceptable CV ( Conclusions: Short term CV of

Background: Obstructive sleep apnea (OSA) is related to narrowing upper airway. The forced oscillation technique (FOT) is a noninvasive method to evaluate resistance and reactance in airway system. Aims and Objectives: The aim of this study was to assess the relation between the airway resistance during awakening by FOT and the severity of OSA. Methods: We examined the respiratory impedance of 35 patients with OSA during awakening in the sitting, supine, and left lateral recumbent positions using the MostGraph-01® (CHEST M.I., Tokyo, Japan) FOT instrument. Results: Significant correlations between the apnea-hypopnea index (AHI) and respiratory resistance at 5 Hz (R5), as well as respiratory resistance at 20 Hz (R20), were observed in the supine position. In addition, AHI in the supine position were significantly correlated with R5 and R20 in each the sitting, supine, and left lateral recumbent positions. Conclusions: FOT might be a useful technique to estimate the pathophysiology and severity of OSA.

Background: Biomass smoke is associated with adverse health effects on the respiratory system, including increased asthma morbidity and worsening of symptoms leading to emergency room visits. Aims and Objectives: The aim of this study was to investigate whether controlled exposure to wood smoke generated from incomplete soot-rich combustion would increase small airway resistance and reactance. Methods: Fifteen healthy subjects (20-45 ys) underwent controlled chamber exposure on two occasions to filtered air and to sooty wood smoke (PM1 ~ 450 μg/m3), generated by a common Swedish wood stove firing birch logs. The study was performed in a double-blind, randomized cross-over fashion and the subjects alternated between exercise (VE=20 L/min/m2) and rest at 15-minute intervals for 2 hours. Forced Oscillation Technique (FOT) (tremoFlo®, THORASYS) was used to determine airway resistance and reactance before and after exposure to wood smoke as well as before and after exposure to filtered air. Results: Both airway reactance (P Conclusions: Short term exposure to sooty wood smoke did not affect small airways resistance or reactance as determined using FOT in healthy subjects. Further research should study the effects in asthmatic populations, and also whether repeated exposures are needed to cause the small airways effects indicated by population-based studies.

Background: Chronic obstructive pulmonary disease (COPD) is a growing health problem, and detecting it early enough to improve prognosis remains a challenge. This study aimed to assess the ability of the forced oscillation technique (FOT) to detect COPD at an early stage. Materials and Methods: The study involved 2,297 COPD patients older than 40 yr as well as 4,416 non-COPD controls. The ability of FOT to detect COPD in different stages of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale as well as to detect airflow limitation in small airways was evaluated. Results: The combination of five FOT parameters (Z5, Fres, R5-R20, Rp, X5) performed best at detecting COPD (selectivity, 64.90%; specificity, 79.30%; positive predictive value, 61.83%; negative predictive value, 81.20%), detecting airflow limitation in small airways (selectivity, 62.80%; specificity, 70.70%; positive predictive value, 82.47%; negative predictive value, 51.27%) and distinguishing patients with COPD in GOLD stage 1 from non-COPD controls (selectivity, 56.80%; specificity, 71.60%; positive predictive value, 19.65%; negative predictive value, 97.43%). Conclusions: These results suggest that FOT can detect early-stage COPD and small airway limitation, which may make it a useful alternative to spirometry.

Surfactant improves lung mechanics and the success of non-invasive respiratory support in preterm infants. The lack of non-invasive bedside tools for monitoring lung mechanics makes current guidelines for surfactant therapy based on O2 requirements, which may be not specific for this application. Objective: To assess feasibility and role of early, non-invasive evaluation of respiratory mechanics by FOT in non-intubated preterm infants for stratifying the severity of respiratory disease. Eligibility: 28-34wk gestation, no need of early intubation after birth. FOT at 10Hz was applied by a modified ventilator (Fabian, Acutronic) and a face-mask during CPAP=5cmH2O. Measurements were performed at 2 and 24h of life. FiO2 was titrated and surfactant given as in Sweet (2016). 4 groups (n=45) were considered: Patients not requiring respiratory support (SB); receiving CPAP for less than (CPAP-S) or more than 28d (CPAP-L) but who never received surfactant and patients who received surfactant (Surf). Xrs in Surf and CPAP-L was significantly lower at 2h compared to SB and CPAP-S (fig 1). After receiving surfactant patients improved, leaving CPAP-L only showing significantly lower Xrs at 24h. Xrs stratifies patients according to the degree of respiratory disease. CPAP-L infants presented poor Xrs at 2h, did not match clinical criteria for surfactant but had a long respiratory support dependence.

Background: Chronic loss of lung function was described in SCD patients (pts), even if not fully characterized in children. Aim: to explore lung function in children with SCD, through the assessment of resistance measurements and ventilation patterns. Methods: spirometry, FOT, IOS and N2MBW were performed in 15 stable pediatric pts with SCD, F 46.67%, Caucasian 13.33%, aged 12 ±3.8 years, mean HbS 66.36 ±17.44, ICS/LABA therapy in 20%, ICS therapy in 13.33%. Results: A mild restrictive pattern was found (FEV1 86.96 ±15.91 %pred, FVC 75.47 ±26.62%pred, MMEF75-25 86.76 ±21%pred). Lung Clearance Index (LCI) 2.5% was elevated (7.91 ±2.26, 120%pred), as well as normalized acinar slope index Sacin (0.12 ±0.14, 220%pred). IOS measured an increase in resistance (R) at 5 Hz (119.37 [101.68-137.79] %pred) while FOT showed an increase in R at 8 Hz (118.05 [101.87-140.29] %pred) and decrease in reactance(X) at 8 Hz. Expiratory R inversely correlated with MMEF75-25 (r -0.6, p 0.03). Pts Conclusions: IOS and FOT may help to depict and monitor early lung function changes in children with SCD. N2MBW did not correlate here with spirometry, FOT or IOS, thus it may be considered to add a novel and complementary insight in functional status of children with SCD, through the representation of ventilation inhomogeneity.

Rationale: This study used an unreleased, modified noninvasive ventilator (BiPAP A40, Philips/Respironics, Monroeville, PA) using Forced Oscillation Technique (FOT) and the method of Dellaca et al (2004) to dynamically measure ∆Xrs and display an Expiratory Flow Limitation (EFL) index and optionally, adjust PEEP (PEEPopt) to abolish EFL. This information could be used to guide a physician’s plan of care and aid in determining if a Noninvasive Ventilator (NIV) is appropriate for the patient. Methods: Twelve naive NIV participants diagnosed with COPD were fitted with an oral-nasal facemask and instructed to breathe normally in the seated position, then in the supine position. The ventilator was set to non-therapy EFL screening mode that delivered 3 cmH20 CPAP pressure. Sessions lasted 5 minutes. If the ventilator displayed the presence of EFL, the participant remained supine to complete a third session where the ventilator titrated PEEPopt starting at 4 cmH20 with a fixed PS at 6 cmH2O. Results: Demographic and physiologic variables are presented in Table 1. All participants showed an increase in their ∆Xrs value from the seated to supine position. Conclusion: A simple process of identifying patients with EFL can be incorporated into a noninvasive ventilator in order to guide clinicians towards different therapeutic strategies, as well as, the option to provide automated therapy to abolish expiratory flow limitation.

Introduction: Much of the work supporting NIV for COPD has advocated the use of large pressure support (PS) with low fixed EPAP pressures. However, such high-intensity ventilation requires significant front-end resources, and may negatively impact patient adherence. The application success of higher EPAP with traditional PS settings to abolish EFL remain unclear. Aims: Evaluate a modified unreleased ventilator (BiPAP A40, Philips Respironics, Monroeville, PA) utilizing FOT to continuously monitor EFL, measured via the Dellaca et al (2004) method (ΔXRS > 2.8 cmH2O*s/L), and auto-titrate EPAP with fixed pressure support to abolish EFL. Methods: Overnight trial with 8 sessions across 6 NIV naive COPD patients, aged 64-78. Ventilator settings: EPAP auto-titration range: 4-20 cmH2O, PS: 6 cmH2O in S/T Mode. Results: All sessions showed a similar pattern: at onset, ΔXRS indicated EFL (mean [SD]: 3.9 [0.8] cmH2O*s/L) causing EPAP to increase (max: 16 [4.9] cmH2O). Once initial EFL was abolished EPAP titrated to a stable level (8 [3.3] cmH2O @ ΔXRS = 2.1 [0.5] cmH2O*s/L). This cycle occasionally repeated with EPAP titrating up (max 13 [4.6] cmH2O @ ΔXRS = 5 [2.2] cmH2O*s/L) before stabilizing again. The mean time between stabilizations was 15.7 [7.1] minutes. Conclusions: The method holds the potential to optimize automated settings to abolish EFL during NIV in COPD patients.

Background: Ventilated preterm infants may have respiratory morbidities early in life and later at school age and adulthood (Clemm HH, 2014). Modeling with large animals is needed to identify mechanisms Aim: Use a new former preterm (FPT) lamb model to evaluate lung mechanics, airway reactivity, and airway smooth muscle (ASM) thickness. Methods: 6 preterm lambs (128d; term ~150d; ~28w gestation in humans) were resuscitated and supported by mechanical ventilation for 3-6d before weaning from respiratory support (FPT lambs). They lived for ~6m (~5m corrected postnatal age; ≈6y in humans). Control lambs (n=20), born at term, lived 5m. We measured respiratory mechanics monthly by forced oscillation technique (FOT; 11Hz) and airway reactivity by changes in FOT variables after increased doses of nebulized methacholine (MCh; 0.06-4.00 mg; ATS guideline, 1999). We used quantitative histology to measure ASM thickness in terminal bronchioles. Results: FPT lambs had increased airway reactivity during the first 2m of life (figure). ASM thickness was significantly greater in FPT lambs (6.7±1.1vs 3.1±0.5 mm control lambs). Conclusions: The new FPT lamb model recapitulates altered lung mechanics and airway reactivity in FPT humans. Interestingly, airway muscularization persists at 5m when lung mechanics and airway reactivity are no longer impaired. This model provides opportunity to identify pathogenic mechanisms.

Aims: Forced oscillation technique (FOT) may provide a different aspect of lung mechanics compared to spirometry. We aimed to clarify discrepancies in bronchodilator responsiveness (BDR) results between FOT and spirometry in a clinical audit. Methods: Data were available for analysis in 54 subsequent FOT and spirometry BDR measurements in sequentially recruited 3-17 years old asthmatic children. Results BDR tests were in agreement in 87% (47/54): two cases (3.7%) were negative in spirometry but positive in FOT, and 5 (9.3%) positive in spirometry but negative in FOT (Figure 1). There was no statistical difference in age, sex, ethnicity, height, weight or BMI between cases with test agreement and disagreement. Use of bronchodilator (tiotropium+/-SABA/LABA) before the BDR testing was present in 71% (5/7) of the outliers vs. 17% (8/47) in those with test agreement (p=0.002). Conclusion: We found a good agreement of BDR between the two techniques. In case of test-to-test discrepancy, bronchodilator use before BDR testing may be a confounding factor in children with asthma. Figure 1 Scatterplot of baseline to post-bronchodilator spirometry FEV1 (%-baseline) against FOT Rrs8 (%-pred).

Background: Bronchial thermoplasty (BT) is a device based treatment for severe asthma targeting airway smooth muscle (ASM). Patient responder profile is still under debate. Forced oscillation technique (FOT) is an effort-independent technique using sinusoidal waveforms to assess respiratory resistance (Rrs) during tidal breathing. Aim: Assess the effect of BT on lung function parameters and evaluate whether BT treatment response could be predicted by lung function. Methods: Severe asthma patients from the TASMA trial underwent pre- and post-bronchodilation (BD) spirometry, bodybox and FOT before and 6 months after BT. Response was based on clinical improvement >0.5 on asthma questionnaires (ACQ/AQLQ). Results: 18 patients were evaluated. Pre and post-BD FEV1(%), sRaw(%) and FOT measurements did not change after BT. However when comparing results based on BT treatment response a significant higher Rrs (FOT at 5Hz) was found in non-responders (n=8) versus responders (n=10). This difference was already present at baseline (Fig 1). Moreover, sRaw post-BD(%) was significantly increased in non-responders (77% pre-BT vs 114% post-BT, p Conclusion: Lung function parameters were unchanged after BT, however a higher airway resistance in non-responders was observed which was already present at baseline, suggesting that a high resistance at baseline could be a negative predictor for BT response.

Changes in lung mechanics are in the centre of interest in rat models of respiratory diseases; however, they are frequently inferred from total respiratory system indices that are biased by chest wall properties. Thus, we assessed the separate contribution of the lung and chest wall compartments to the total respiratory system mechanics in rats, and we also evaluated the influence of altered lung volume on these estimates. The forced oscillation technique was applied in anesthetized, mechanically ventilated rats (n=14) to obtain mechanical impedance of the total respiratory system (Zrs) at 0, 3 and 6 cmH2O positive end-expiratory pressure (PEEP) levels. Oesophageal pressure was measured by a self-made balloon to separate Zrs into pulmonary (ZL) and chest wall (Zw) components. A model containing a frequency-independent Newtonian resistance (R), inertance (I) and a constant-phase tissue damping (G) and elastance (H), was fitted to Zrs, ZL, and Zw spectra. The contribution of Zw to the total respiratory R and I was negligible (3.8±5.6[SD]% and 5.5±23%) at all PEEP levels. However, the participation of Zw in G and H was significant at PEEP0 (17±10% and 12±6%, p These findings demonstrate that airway parameters can be accurately assessed from respiratory system mechanical assessments. However, the contribution of the chest wall to the viscoelastic parameters of the total respiratory tissues should be taken into account when these indices are used to estimate lung parenchymal mechanics, particularly at high PEEP levels. Grant support: NKFIH K115253 and GINOP-2.3.2-15-2016-00006

Background: Cough variant asthma (CVA) is a form of asthma that presents mainly with cough. Last year in the ERS congress, we reported that about 43% of patients with CVA showed abnormalities in fractional exhaled nitric oxide (FeNO) or forced oscillation technique (FOT) using MostGraph. Since then, we have newly established reference ranges of inhaled and exhaled value of MostGraph, and have applied to classify and diagnose patients with CVA. Objective: The aim of study is to find out whether inhaled and exhaled value of FOT (MostGraph) is useful for the classification and diagnosis of CVA. Methods: The patients with CVA without comorbid infection or other diseases were recruited. Hierarchical cluster analysis (HCA) of the 458 participants was performed. The clinical diagnostic criteria for CVA were established. Results: Four clusters were identified (Fig.1): High value of FeNO, Low value of exhaled R5-R20, Abnormal exhaled reactance, and Abnormal resistance and reactance. The sensitivity of the criteria (Table 1) was 84% and specificity was 95% (Table 2). Conclusion: Exhaled value of FOT is useful for the CVA medical care. Figure 1 Cluster analysis

Background: The Resmon Pro system uses the forced oscillation technique (FOT) with sound waves at 5, 11 and 19 Hz, to avoid self-resonating waves. It separates inspiratory and expiratory resistance (Rinsp, Rexp) and reactance (Xinsp, Xexp), aiming to reflect obstruction, since expiration is affected by airway closure. Impulse oscillometry (IOS) use waves at 5-35 Hz, and does not separate the inspiratory phase from the expiratory. Aim: To validate the Resmon Pro system against IOS by Jaeger, and to define the uses of inspiratory and expiratory measurements in obstructive diseases. Methods: A total of 31 subjects (16 healthy, 9 COPD, 5 asthma) were included and performed FOT (Resmon Pro), IOS and spirometry in the given order. Results: Total resistance (R5) and central resistance (R20 or R19) correlated between IOS and FOT. FOT could detect increased total resistance in COPD, while IOS could not. The use of separating Rinsp from Rexp was most prominent in COPD, where R5exp was higher than R5insp. Peripheral resistance (R5-R20 or R5-R19) showed correlation between IOS and FOT, and only IOS detected differences between healthy and COPD. The elastic properties of the lungs (reactance; X5) also correlated between IOS and FOT, and both methods detected differences between healthy and COPD patients. When separated into insp and exp, Xinsp showed a smaller Confidence Interval, but did not detect any differences between COPD and healthy. Conclusion: Both systems showed similar results, but with different abilities to detect airway obstruction. Although less variation, the use of inspiratory resistance and reactance needs to be further investigated.

Background: The usefulness of the forced oscillation technique (FOT) in diagnosing cough variant asthma (CVA) has not been demonstrated. Aims: This retrospective study aimed to evaluate diagnostic accuracy of the changes in respiratory system resistance (Rrs) and reactance (Xrs) as possible predictors of CVA. Methods: Twenty-six patients with CVA and 20 with non-CVA (gastroesophageal reflux disease, rhinosinusitis, and post-infectious cough) were enrolled. FOT (MostGraph-01) and spirometry were performed in airway reversibility testing. Fractional exhaled nitric oxide (FeNO) was also measured before the testing. A diagnosis of CVA was based on an isolated cough lasting for at least 8 weeks without wheezing, which was relieved by β2 agonists. Receiver operator characteristic (ROC) curves were constructed to assess which parameters would predict CVA diagnosis. Results: CVA patients showed a significant improvement in Rrs at 5 Hz (R5), Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (AX), but not in spirometric indices. ROC curve analyses revealed that the changes in R5, X5, Fres, and AX were superior to the change in FEV1 or the FeNO value to diagnose CVA. The best area under the curve was 0.72 for AX with the optimal cutoff point of 0.41 cmH2O/L (sensitivity, 0.98; and specificity, 0.62). Conclusion: The FOT is superior to spirometry or FeNO measurements in predicting CVA.

Tidal Expiratory Flow Limitation (EFLT) promotes intrinsic PEEP (PEEPi) which increases work of breathing and patient-ventilator interaction. The application of an external PEEP adjusted to counterbalance PEEPi improves these variables. Forced oscillation technique can monitor EFLT by measuring within-breath changes in reactance at 5Hz (ΔXRS) (Dellaca et al ERJ 2004). This technique has been incorporated in a prototype of NIV ventilator (Synchrony, Philips/Respironics, Pittsburgh, USA) able to continuously adjust PEEP to the minimum pressure needed to abolish EFLT (AutoAdjusted, AA). Eight hyercapnic COPD patients (FEV1%pred=41.3±14.6; FEV1/FVC%pred=49.3±18.6) were studied during two nights, one with their prescribed PEEP (P) and the other with AA, in random sequence. Transcutaneous CO2 (TcCO2) and standard PSG were recorded over the night. The number of ineffective efforts (IE) per hour was manually assessed and the percentage of the night spent with TcCO2 > 45 mmHg was computed from tracings. Data is reported as median(IQR). The optimised PEEP delivered in the AA night was lower than P during 42(33)% of the night. Sleep efficacy index as computed by PSG was similar for both nights (76.8(13.3)% for AA, 73.6(11.5)% for P, p=0.58). The number of IE was reduced by 25(43)%, (p=0.02) and the percentage of night time spent in hypercapnia was reduced by 25(75)% (p=0.04) during AA night. Automatic adjustment of PEEP targeted to abolish EFLT during night improves patient-ventilator interaction and reduces hypercapnia in COPD.

Tidal expiratory flow limitation (EFLT) promotes Intrinsic PEEP (PEEPi) which has detrimental effects on respiratory mechanics. FOT can monitor EFLT by measuring within-breath changes in reactance at 5Hz (ΔXRS) (Dellaca et al ERJ 2004), a breath is considered as EFL if ΔXRS >2.8 cmH2Os/L. This technique has been incorporated in a prototype of NIV ventilator (Synchrony, Philips/Respironics, Pittsburgh, USA) and used to assess EFLT breath by breath over one night. Five COPD patients (FEV1%pred=39.4±13.5%; FEV1/FVC%pred=50.4±19.9%) on NIV were studied over one night while receiving their prescribed ventilatory settings. ΔXRS was assessed continuously and evaluated according to posture and sleep stages: awake, rapid eye movement (REM) and non-REM (NREM). Patients spent 81.3(31.4)% of the night in supine position, 18.7(31.4)% on the side, 6.6(31.2)% in REM, 70.6(38.1)% in NREM and 22.8(24.1)% awake (data reported as median(IQR)). The correspondent averaged values of ΔXRS, expressed in cmH2Os/L, are reported in the table: Supine posture in REM stages shows the highest ΔXRS and, on average, supine posture worsens EFL (ΔXRS 3.1(0.8) vs 1.8(0.3) cmH2Os/L). The value of ΔXRS is highly variable within the night and depends on both posture changes and sleep stages.

Background: The loss of enzymatic activity in lysosomal storage diseases (LSD) results in progressive cellular accumulation of macromolecules. In these patients, respiratory dysfunction is usually a leading cause of morbidity and mortality. Thus, clinical assessments and objective measures of lung function, are crucial for prompt diagnosis and management. However, the use of spirometry is limited to patients who can perform forced expiration. Nevertheless, the forced oscillation technique (FOT) is performed during tidal breathing; thus, it is amenable to most patients who fail spirometry test. This study describes the feasibility of FOT in patients with LSD Methods: Patients with LSD at Tawam Hospital (Al Ain, UAE) were enrolled in the study in 2016 and 2017 (n=29); the mean ± SD age was 10±6 y. Their airway resistance was assessed using FOT at 5 Hz (Rrs5) and expressed as Rrs5 z-scores Results: Fifteen patients with mucopolysaccharidoses (MPS) were studied. Despite several attempts; the FOT study was successful in six patients (two patients with MPS-I, three with and MPS-IVA and one with MPS-VI). The mean Rrs5 z-scores for these patients was 1.99. The remaining ten patients with MPS-III failed to do the test Among the 13 patients with other LSD, nine patients completed FOT study. Three of them had abnormally high Rrs5 (a patient with Gaucher disease type I had Rrs5 z-score of 2.19, a patient with Niemann-Pick disease type C had Rrs5 z-score of 3.87 and a patient with mucolipidosis type III had Rrs5 z-score of 2.13) Conclusions: Most patients with MPS failed to complete FOT study. Nevertheless, this uncovered a remarkably increased Rrs5 patients with LSD

Exercise induced bronchoconstriction (EIB) is assessed in the laboratory with an exercise challenge (EC). A ≥10% decline in FEV1 post EC is considered positive. The forced oscillation technique (FOT) is suggested to produce equivalent and more sensitive measures of airway calibre post EC than maximal expiratory manoeuvres. The rate of recovery and effect of raised minute ventilation (VE) post EC is uncertain. We investigated changes in airway mechanics measured with FOT post EC in people with asthma. Method: Inspiratory resistance (R5in) and reactance (X5) at 5Hz were measured prior to FEV1, before and up to 20min after an EC. BHR to the hyperosmolar mannitol test was measured in the asthmatic subjects within one week of the EC. Baseline and sequential FEV1, R5in, X5 and VE post EC were compared using ANOVA and Pearson’s correlation. Results: Subjects with current asthma (n=19, mean[SD] age 28[6] yr) and controls (n=10, 31[5] yr) were studied. Baseline FEV1, R5in, X5 and VE were similar between groups (P>0.09). BHR was present in 12/19 of asthmatic subjects. The %change in R5in (13[10] vs 105[106]% p=0.01) and X5 (16[14] vs 178[188]%, p=0.01) were different to controls in EC-positive but not EC-negative asthmatic subjects. Following EC, max %change FEV1 correlated with R5in and X5 (R>0.8, p 0.3). Conclusion: FOT parameters tracked well with forced manoeuvres following EC and were not influenced by the raised VE. FOT could be used as an end-point in EC in identifying EIB from those with BHR.

Background: The assessment of lung mechanics in preterm infants is of potential value for the early evaluation of lung disease and pulmonary outcomes. We aimed (i) to identify early predictors of respiratory outcome from lung mechanics obtained in week 1 of life in preterm infants below 32 weeks gestational age (GA) and (ii) to evaluate which clinical factors are associated with lung mechanics at 36 weeks postmenstrual age (PMA). Methods: Lung mechanics were assessed by the Forced Oscillation Technique using a mechanical ventilator (Fabian HFOi, Acutronic, Hirzel, Switzerland) that superimposed small amplitude oscillations (10 Hz) on a continuous positive pressure during spontaneous tidal breathing in unsedated infants. Reactance (Xrs), representing the elasticity of the respiratory system, was computed from flow and pressure data. Measurements were performed on days 2, 4, and 7 of life and at 36 PMA. Results: 61 infants (GA 29.2±1.9 w , weight 1225±376 g, respiratory support 24±21 d, supplemental O2 6 ± 15 d) were studied. There was a significant negative association between the duration of respiratory support and Xrs measured on days 2 and 7. A multilevel model including Xrs on days 2 and 7 and GA explained 54% of the variability in duration of respiratory support vs 38% explained by a model including only GA. Xrs at 36 weeks PMA was not significantly associated with either GA, birth weight, days of respiratory support or O2 requirement. Conclusion: Early assessment of Xrs has the potential to improve prediction of pulmonary outcome.

The use of the forced oscillation technique (FOT) to assess within-breath respiratory mechanics has lead to new insights into airway obstruction (Czovek et al., Thorax, 2016), flow limitation and lung inhomogeneity (Lorx et al., ERJ2017) in adults and older children. Aim: To test within-breath respiratory mechanics in a South African birth cohort (Drakenstein study) for predicting lower respiratory tract illness (LRTI) during the first 6 months of life. Methods: The within-breath changes of respiratory resistance (R) and reactance (X) were measured at 16 Hz with a modified FOT during natural sleep in healthy infants at 6-10 weeks. The mean total R and X values, and the changes between end-expiration and end-inspiration (ΔR and ΔX) were calculated. LRTI surveillance was performed and any episode was confirmed by study staff. Results: Acceptable assessments of respiratory mechanics were available in 666 infants (50.1% male, median[IQR] gestational age: 39[37;40] w, length z-score: -0.76[-1.67;0.11]) of which 113 infants had 177 LRTI episodes in the first 6 months of life. From the impedance variables, ΔX and ΔR were significantly different between the two groups (p Conclusion: This study is the first to show that within-breath measures of respiratory mechanics in infants may predict susceptibility to LRTI. The altered ΔX in healthy infants suggests that lung inhomogeneity may be a predisposing factor for lung disease in early life. Wellcome Trust;Gates Foundation;HRF

Background: forced oscillation technique (FOT) is a non–invasive method used to assess respiratory mechanics. The main parameters, resistance (R) and reactance (X); inspiratory (Rinsp), expiratory (Rexp) and total (Rtot); can be obtained at different frequencies and with a minimal cooperation. This makes FOT fit for epidemiological studies. Aim: to investigate reproducibility and acceptability of FOT in assessing the respiratory function in school-aged children and adolescents. Methods: 159 subjects have been studied by FOT, 100 from primary and 59 from high school. The measurements were considered of high quality (HQ) if the standard deviations (SD) of Rinsp, Rexp and Rtot were less than 0,7 and the ratio between SD and each R parameter was less than 0,3. If just one condition was met, the measurement was considered acceptable (AQ). Results: HQ and AQ measurements were obtained respectively from 81% and 98% of subjects. Learning and age effect on the variance was considered. The best reproducibility was achieved at 5 Hz in 151 children. The distribution of the results is reported in the table. Conclusions: measurements obtained by FOT have proved to have high acceptability and good reproducibility. This confirms that FOT can be efficiently used in epidemiological studies, particularly in school age.

Introduction: Resistive breathing (RB) is the hallmark of diseases of airway obstruction, such as chronic obstructive pulmonary disease (COPD), especially during exacerbations. RB results in increased mechanical stress and inflammation in the lung of previously healthy mice. Cigarette smoke (CS) exposure, the main cause of COPD, also induces pulmonary inflammation. Aim: To investigate the potential synergistic effect of the combination of RB with CS exposure model. Methods: Mice were exposed to CS of 5 reference cigarettes, 4 times daily, 5 days per week for one month. Control mice were exposed to room air. By the end of the month mice were subjected to RB for 24 hours by tracheal banding or were sham operated. Tracheal banding was induced by placing the mice under a surgical microscope, the trachea was exposed and a nylon band was placed around the trachea and firmly sutured to provide a surface area 50% of the initial. Following 24 hours, respiratory system mechanics were assessed by the forced oscillation technique. Bronchoalveolar lavage (BAL) was performed and total and differential cell count and total protein level were measured in BAL fluid. Results: CS exposure was associated with increased BAL cellularity (10-fold to ctr, p Conclusions: Combining resistive breathing with cigarette smoke exposure results into augmented inflammatory responses.

Supine position may promote EFL T in COPD leading to intrinsic PEEP. The application of PEEP during NIV is used to counterbalance its effects. Forced oscillation technique (FOT) allows a real-time automatic optimization of PEEP (APEEP) by adjusting it continuously to abolish EFLT (Dellaca’ et al, ERJ 2004). The aim of this study is to evaluate the effect of posture on APEEP in COPD. 23 COPD patients (FEV 1 %pred= 40.1±16.6, FVC%pred=65.4±12.1 %) were studied seated (Se) first and then supine(Su) for 15 mins. PEEP was automatically adjusted continuously by a prototype of NIV ventilator (Synchrony, Philips, USA) incorporating FOT at 5Hz to abolish EFL T . APEEP, breathing pattern (tidal volume, V T , and minute ventilation, V E ) and inspiratory reactance (X RSi ) were recorded in the last 2 min of each condition. Data reported as median/IQR. When moving from the seated to the supine position APEEP, Vt, Ve and X RSi changed significantly (* p

Tidal expiratory flow limitation (EFL T ) promotes Intrinsic PEEP (PEEPi). Applying an external PEEP matching PEEPi reduces WoB and patient-ventilator asynchronies. FOT can monitor EFL T by measuring within-breath changes in reactance at 5Hz (ΔX RS ) (Dellaca et al ERJ 2004). FOT has been incorporated in a prototype of NIV ventilator (Synchrony, Philips/Respironics, Pittsburgh, USA) and used to automatically adjust PEEP to the minimum pressure able to abolish EFL T . The aim is to evaluate the effect of automatic adjustment of PEEP to minimize EFL during sleep. Six COPD patients were studied during two nights. In one night they received their prescribed PEEP (PPEEP), in the other night PEEP was continuously adjusted to abolish EFL T (APEEP). Measured parameters were PEEP delivered through the night, pulse oximetry (SpO 2 ), transcutaneous CO2 (TcCO 2 ) and heart rate variability (HRV). In average, PEEP, SpO 2 and TcCO 2 were similar in the two nights (table, median/IQR). In 3 patients, APEEP was lower than PPEEP for more than 50% of the night, 85.1/21.6%, and both SpO 2 and TcCO 2 improved in the APEEP night by 0.86/2.57% and 7.55/8.04 mmHg, respectively. The other patients received APEEP>PPEEP for more than 50% of the night 71.4/9.3%, SpO2 didn’t change (delta=0.21/1.91%) and TcCO2 improved by 9.78/9.56 mmHg. Conclusions: Automatic adjustment of PEEP to minimize EFLT prevents the delivery of unnecessary high PEEP, maintaining or improving blood gasses and promoting HRV.

Background: Frequency dependence of resistance derived from forced oscillation technique is a potential small airways dysfunction/early airways obstruction tool. However the structural basis of this measurement has not been fully elucidated. Methods: We sought to evaluate the central airway contribution to frequency dependence of resistance, measured with Impulse Oscillometry (IOS: R5-R20) and Sinusoidal Forced Oscillations (TremoFlo C-100: R5-R19). We derived a patient specific 3D printed airway model of the central airways (Clear Flex (r) 50 water clear urethane rubber, Smooth-On Inc), from a CT segementation in a mild asthmatic (age=64, FEV1/FVC=71%, FEV1%=95%). Systematic obstruction of the model outlets was achieved by heterogeneous occlusion (sequence generated by a Matlab algorithm), whilst IOS and FOT was applied to the model in triplicate for each occlusion. Additionally a computer simulation was applied to the same model under the same conditions. Results: Sequential occlusion of the printed model was not associated with frequency dependence of resistance, which was further validated by the computational model (Figure 1). In contrast there was a non-linear and exponential increase in R20/R19 and R5. Conclusions: We have demonstrated that central airway obstruction alone will not generate frequency dependence of resistance using patient specific printed and computational airway models.

Rationale: Forced oscillation technique (FOT) is a very feasible and reliable technique for young children. A new equipment has recently been released on the market, which is based on intrabreath analysis of respiratory impedance. Aim of this study was to verify the applicability of previously published FOT reference values to the new equipment. Methods: Children were recruited in randomly selected kindergartens using a standardized questionnaire (modified ISAAC), translated into Italian. Preemies ( 30 days were excluded. Other exclusion criteria were history of asthma diagnosed by a physician and wheezing during the previous 12 months or >3 episodes of wheezing ever. FOT was performed with a Resmon Pro Full device (Restech Srl, Milan, Italy). To allow the comparison with previously published reference values (Calogero, C. et al. Pediatr Pulmonol 2010;45:1086-94) measured with the “i2m” device (Cosmed, Rome, Italy), total resistance (R8tot) and reactance (X8tot) at 8 Hz were calculated as the mean of at least 3 acceptable measurements, as recommended (Beydon, N. et al. Am J Respir Crit Care Med 2007;175:1304-45). Results: A total of 38 healthy children (18 male, 20 female; age 3.2-6.3 yr) were tested. Mean (SD) respiratory impedance indices are reported in the table. Conclusions: Although the difference was minimal for R8, impedance values measured in a small sample size of healthy prechoolers using intrabreath analysis were statistically different from those previously published.

Background: Current ERS recommendations suggest recording 3-5 acceptable FOT tests to measure a subject’s resistance (Rrs) and reactance (Xrs). A different approach that evaluates Rrs and Xrs during 10-15 breaths from a single test, excludes breaths with artefacts and calculates Rrs and Xrs as the mean value of the accepted breaths has been introduced. However, no data is available to support the equivalence between the methods. Aim: To assess the impact of using an increasing number of complete breaths without artefacts for calculating Rrs and Xrs as compared with the method recommended by ERS in healthy children. Methods: 155 subjects (8.3±2.1 years old) without a history of asthma, wheezing or systemic diseases were recruited in primary schools. 3 FOT tests of 10-15 breaths each were performed using the Resmon PRO FULL (Restech, Italy). Rrs and Xrs were computed at 5Hz for each test using the cross-spectrum method and results were averaged as per ERS recommendations. For the first test, Rrs and Xrs were also computed as the average of the first 3, 4, 5, 7 and 10 full free-from-artefacts breaths. Differences were tested by ANOVA for repeated measurements. Results: Significant differences between the methods were found only for Xrs (Figure) and associated with a higher within-breath variation of this parameter. Conclusions: Rrs can be reliably calculated by the within-breath method from a single FOT test.

To improve children’s comfort during FOT measurement, use of full face masks has been suggested as an alternative to mouthpieces. However, mask’s additional internal dead space and the presence of both nose and mouth breathing paths may influence the breathing pattern (BP) and FOT measurements. Different mask designs allowing or excluding nasal breathing are commercially available. The aim of this study was to evaluate the effect of mask design on measured FOT and BP parameters. Twenty-four children (14/10 males/females; 3.9±1.0 years) were recruited between those attending the pulmonary function test lab. Within-breath FOT at 8 Hz and BP parameters were measured during 10-15 quiet breaths using a commercial device (RESMON PRO FULL, RESTECH Italy) using in random order: 1) a mouthpiece with a nose clip; 2) a full face mask A allowing nasal and mouth breathing and 3) a full face mask B allowing only mouth breathing. Differences in variables were tested by ANOVA for repeated measurements. Compared to mouthpiece, full face mask A generated an underestimation of both resistance and reactance but not in BP parameters. Use of mask B provided similar results to mouthpiece and no differences were observed in any of the FOT and BP parameters. Mask design had an impact on FOT measurements. Only masks impeding nasal breathing provided comparable results to conventional mouthpieces.

Rationale: The standard methacholine provocation test repeatedly measures forced expiratory volume in 1 second (FEV 1 ) as index of bronchoconstriction to assess airway (hyper)responsiveness. Since this is labor intensive for the patient, the forced oscillation technique (FOT) could be an alternative. The FOT uses optimized pseudo-random noise to detect changes in respiratory resistance during normal breathing. Objective: We hypothesized that the FOT is an accurate alternative to FEV 1 during methacholine provocation test. Methods: This cross-sectional study included 78 new out-patient referrals for asthma diagnostics. The FOT and FEV 1 were measured in this order after each inhaled dose of methacholine. Provocation concentrations (PC) at given changes in resistance (R) and FEV 1 were used as outcome. Analysis was done by correlation and ROC analysis. Results: The PC values of resistance at 5 hertz (R 5 ) showed moderate and significant correlation with PC 20 FEV 1 (R 5 PC 30 : r=0.44, p= 5 PC 40 : r=0.41, p=0.0004; R 5 PC 50 : r=0.43, p=0.0001; R 5 PC 100 : r=0.40, p=0.0009). Comparisons of accuracies at different threshold values of R 5 with PC 20 FEV 1 showed 47% accuracy for PC 30 R 5 with negative predictive value (NPV) of 71% and positive predictive value (PPV) of 41%; PC 100 R 5 showed 86% accuracy, NPV of 87% and PPV of 85%. The mean (log)PC values were: PC 20 FEV 1 = 0.85 mg/ml; PC 30 R 5 = 0.27 mg/ml; PC 30 R 5-19 = 0.02 mg/ml. Conclusion: The FOT is an accurate alternative for FEV 1 in measuring bronchial responsiveness during methacholine provocation test. Using the FOT, lower concentrations of methacholine were needed for a positive test. Therefore, the FOT can help facilitate the diagnostic assessment of asthma.

Introduction: In silico airway models of asthma have incorporated airway abnormalities related to MRI ventilation defects to predict airway impedance (1) but this work did not include a direct comparison with experimental forced oscillation technique (FOT) measurements of airway reactance (X rs ), which is sensitive to peripheral airway narrowing. Objective: We investigated the relationship between FOT measurements in moderate-severe asthmatics with simulated measurements of airway impedance derived using an asymmetric branching airway tree model that was modified for individual patients using their MRI ventilation defect map. We hypothesized that X rs measured using FOT would be strongly related to airway tree model predictions. Methods: Participants underwent pulmonary function tests and hyperpolarized 3 He MRI to generate ventilation defect percent (VDP). MRI ventilation maps were co-registered to the airway tree model and small airways proximal to ventilation defects were constricted; model predictions of X rs at 5Hz were generated for each participant as previously described (1). On the same visit as MRI, X rs was measured using FOT and compared with model-predicted values. Results: We evaluated 35 moderate-severe asthmatics (15M/20F, 47±12 years, R AW =178±84% pred , FEV 1 =69±25% pred , FEV 1 /FVC=65±15%, VDP=10±9%). FOT-measured X rs was significantly correlated with VDP (ρ=-0.46, p=0.003) and model-predicted X rs (ρ=0.45, p=0.003). Conclusion: Ventilation MRI and airway tree models may be used to better understand reactance measurements in asthma. Our results provide strong support for the clinical use of FOT and MRI in asthmatics. REFERENCES: 1. Leary, D., et al. Physiol Rep, 2016. 4(7).

Background: MostGraph is one of the forced oscillation technique devices mainly used in Japan. However, the reference values in healthy Japanese adults have not been not established. Objective: The aim of this study was to establish predictive equations and reference ranges of MostGraph measures for healthy Japanese adults. Methods: Healthy subjects were recruited from the visitors for a medical checkup at the health examination center of Yokohama City Minato Red Cross Hospital and from healthy volunteers at Tokyo Medical and Dental University. They underwent forced oscillation technique using MostGraph-01, exhaled nitric oxide fraction (FeNO) measurement, and pulmonary function tests (PFTs). Subjects with elevated FeNO or abnormal PFTs were excluded. Finally, 79 subjects (41 men, ages 18-72 years; 38 women, ages 21-73 years) were analyzed. The parameters were transformed into normal distribution using a Box-Cox transformation. We created predictive equations for R5, R20, X5, Fres, and ALX of the MostGraph parameters using age, height, and weight as explanatory variables. Results: The logarithm of male R5 and R20 revealed nomal distributions. The square root of ALX revealed nomal distributions in both male and female. The predictive equations ± standard deviation × 2 are shown in the table below. Conclusion: We established predictive equations and reference ranges of MostGraph measures for healthy Japanese adults.

The airway clearance techniques (ACT) are essential to reduce the recurrence of bronchial infections that affect morbidity/mortality in COPD patients. Despite the widespread application of bronchial ACT in pulmonary rehabilitation (PR), the attempts to quantify their efficacy through usual pulmonary function tests lead to conficting results. The Forced Oscillation Technique (FOT) is a non-invasive method, superimposed on tidal volume that measures the airways resistance (Rrs) and reactance (Xrs) at different levels of the bronchial tree. Since the ACT can have an effect on the airways caliber, we believe that FOT canhighlight these effects in terms of Rrs and Xrs and the latter being related to obstruction perception following the ACT. We studied 17 stable hypersecretive COPD patients with moderate to severe obstruction, enrolled in a PR program. For 5 days, before and one hour later the airway clearance morning session (ELTGOL technique), obstruction/dyspnea perception score (VAS), a FOT test and mucus volume were measured. We observed i) a significant reduction (%pv) of Rrs (p FOT is able to quantify the physiological effects of ACT and these effects are related to clinical improvement induced by ACT application.

Background: diagnosis of asthma is based on respiratory symptoms and airflow obstruction, both characterized by variability over time, assessed by questionnaires and expiratory peak flow (PEF) monitoring (GINA report 2015). Pathophysiology of asthma is characterized by airway hyperresponsiveness, which may be assessed by metacholine (MCh) challenge and more recently by measuring variability of inspiratory resistance at 5 Hz (R insp5 ) by FOT (Gulotta et al. AJRCCM 2012;185: 1330-1331). Aim: to investigate the variability of R insp5 measured by FOT compared to PEF variability in assessing patients reporting asthma symptoms. Methods: 21 healthy, 28 mild asthmatics and 16 subjects with asthma symptoms but negative MCh challenge test (MChNeg) were monitored for 14 consecutive days by FOT and PEF measured twice a day (morning and evening). Results: R insp5 variability, expressed as standard deviation (SD 14Rinsp ) and PEF variability were equally significantly higher in asthmatics compared to MChNeg subjects, while only R insp5 variability was significantly higher in MChNeg vs healthy subjects. Conclusions: day-to-day inspiratory resistance variability on a temporal window of 14 days measured by FOT could be employed at home in remote mode in order to assess subjects with asthma like symptoms but negative MCh challenge. The clinical and pathophysiological characteristics of these subjects need to be furtherly investigated.

Introduction: ELVR improves static lung function and quality of life in carefully selected patients with COPD. The FOT is increasingly used to study lung mechanics during tidal breathing. The effect of ELVR on FOT parameters has not previously been described. Methods: Patients with severe COPD undergoing ELVR completed the St Georges9 Respiratory Questionnaire (SGRQ) and had resistance at 5Hz (R5) and reactance at 5Hz (X5) measured by FOT, spirometry, plethysmography and a six minute walk distance (6MWD) measured at baseline and 3 months post-ELVR. Paired t-test and correlation statistics were derived for changes in parameters. Results: In 9 subjects (age range 63-75 yrs), FEV1, R5 and X5 were unchanged, while residual volume (RV) trended from 203±21 %pred to 191±20 %pred (p=0.13). SGRQ scores improved from 63.41±5.90 to 46.75±3.81 units (p=0.02). The change in R5 correlated with the change in RV (r = -0.71, p=0.03) and there was a trend with the change in FVC (r = -0.61, p=0.08). The change in X5 correlated with the change in 6MWD (r = 0.83, p=0.04) but not with RV. Changes in 6MWD or SGRQ did not relate to changes in FEV1, FVC, or lung volumes. In the 4 patients with complete lobar collapse, FEV1 improved (39±4 %pred to 48±3 %pred; p Conclusions: Change in respiratory system resistance during tidal breathing correlates with volume changes induced by ELVR. Respiratory system reactance was minimally changed in this small cohort. The improvement in SGRQ post-ELVR is not explained solely by changes in lung mechanics.

Introduction: The forced oscillation technique (FOT) is ideal for assessing airway hyperresponsiveness, as it does not require maximal breathing manoeuvres that may affect airway tone. Previous studies have examined FOT responses to methacholine, however new commercial FOT devices mean new cut-points are needed. Aim: Compare FEV 1 vs FOT responses to a methacholine challenge using a commercial FOT device, and propose potential cut-points that define a positive response. Methods: We recruited patients referred for a methacholine challenge to the Respiratory Laboratory, Concord Hospital. At each dose, FOT measurements (tremoFlo C-100, Thorasys Medical Systems, Canada) were made prior to spirometry. The challenge was terminated when FEV 1 fell by 20% of baseline (positive response) or a cumulative dose of 8 µmoles was reached (negative response). We calculated the dose response slope (DRS) for FEV 1 and for resistance (Rrs) and reactance (Xrs) at 5 Hz. Relationships between logDRS FEV 1 vs logDRS Rrs and Xrs were examined using Spearman correlations. Accuracy in detecting a positive response was assessed using receiver operating characteristics (ROC) curves. Results: Out of 29 patients, 9 were positive responders. DRS FEV 1 correlated with DRS Rrs (r=0.68, p 2 O s L -1 decrease in Xrs yielded optimal sensitivity and specificity for a positive response. Conclusions: Changes in FOT correlated well with spirometry during methacholine challenge. FOT has potential as a substitute for spirometry for assessing AHR. Cut-points will need to be validated in a larger study.