Assessing the calculation of conductive and acinar ventilatory heterogeneity indices Scond and Sacin from multiple-breath washout data.

Sensor errors resulting in elevated values of N2 concentration [N2] in commercial multiple-breath washout (MBW) devices have been shown to prolong the washout and result in erroneously high functional residual capacity (FRC) and lung clearance index (LCI) values. The errors also affect the indices of conductive and acinar ventilatory heterogeneity (Scond and Sacin) although the mechanism by which this change in values occurs remains unclear. Exploring these effects also provides a timely opportunity to examine the appropriateness of the algorithm used to calculate these indices. Using a two-compartment model with differing specific ventilation (SV) such that the lower SV unit empties late, noise-free MBW were simulated both corrected and uncorrected for the recent sensor error. Scond was calculated using regression of normalized phase III slope (SnIII) against lung turnover (TO) from a TO range starting at 1.5 and ending at an upper turnover (TOupper) between 4 and 8 (default 6) over a range of simulated values. The principal effect of the sensor error was that as the MBW proceeded the phase III slope of successive breaths was normalized by an increasingly overestimated [N2], resulting in SnIII values that fell precipitously at high TO, greatly reducing Scond. Reanalysis of previously published data and of simulated data showed a large proportional bias in Scond, whereas Sacin was only minimally affected. In adult subject data, reducing TOupper below 5.5 was associated with a large drop of up to ∼60% in Scond calculated from data corrected for sensor error. Raising the upper TO limit elevated Scond by ∼20% but with a large concomitant increase in variability. In contrast to Scond, Sacin was relatively unaffected by changes in TOupper with changes of <3%. This work serves to emphasize that the upper limit of TO of 6 represents an appropriate upper limit for the calculation of Scond.NEW & NOTEWORTHY Sensor errors that elevated values of N2 concentration in commercial multiple-breath washout (MBW) devices resulted in errors in calculated parameters including Scond and Sacin. We examined the mechanism of the change in values produced by these errors and explored the appropriateness of the calculation of Scond and Sacin. This work serves to emphasize that the current algorithm in use is appropriate for the calculation of Scond and Sacin.

Model analysis of multiple breath nitrogen washout data: robustness to variations in breathing pattern.

We recently developed a model-based method for analyzing multiple breath nitrogen washout data that does not require identification of Phase-III. In the present study, we assessed the effect of irregular breathing patterns on the intra-subject variabilities of the model parameters. Nitrogen fraction at the mouth was measured in 18 healthy and 20 asthmatic subjects during triplicate performances of multiple breath nitrogen washout, during controlled (target tidal volume 1 L at 8-12 breaths per minute) and free (unrestricted) breathing. The parameters Scond, Sacin and functional residual capacity (FRC) were obtained by conventional analysis of the slope of Phase-III. Fitting the model to the washout data provided functional residual capacity (FRCM), dead space volume (VD), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of Sacin (Sacin-M). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRCM < 5.2%, VD < 5.4%, [Formula: see text] < 9.0%, and Sacin-M < 45.6% for controlled breathing, and FRCM < 4.6%, VD < 5.3%, [Formula: see text] < 13.2%, and Sacin-M < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with Scond < 73.6% and Sacin < 49.2% for controlled breathing and Scond < 35.0% and Sacin < 74.4% for free breathing. The model-fitting approach to multiple breath nitrogen washout analysis provides a measure of regional ventilation heterogeneity in [Formula: see text] that is less affected by irregularities in the breathing pattern than its corresponding Phase-III slope analysis parameter Scond.

The effect of oxygen and carbon dioxide cross-sensitivity sensor error in the Eco Medics Exhalyzer D device on measures of conductive and acinar airway function.

Introduction: The multiple breath nitrogen washout (MBNW) test provides important clinical information in obstructive airways diseases. Recently, a significant cross-sensitivity error in the O2 and CO2 sensors of a widely used commercial MBNW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) was detected, which leads to overestimation of N2 concentrations. Significant errors in functional residual capacity (FRC) and lung clearance index (LCI) have been reported in infants and children. This study investigated the impact in adults, and on additional important indices reflecting conductive (S cond) and acinar (S acin) ventilation heterogeneity, in health and disease. Methods: Existing MBNW measurements of 27 healthy volunteers, 20 participants with asthma and 16 smokers were reanalysed using SPIROWARE V 3.3.1, which incorporates an error correction algorithm. Uncorrected and corrected indices were compared using paired t-tests and Bland-Altman plots. Results: Correction of the sensor error significantly lowered FRC (mean difference 9%) and LCI (8-10%) across all three groups. S cond was higher following correction (11%, 14% and 36% in health, asthma and smokers, respectively) with significant proportional bias. S acin was significantly lower following correction in the asthma and smoker groups, but the effect was small (2-5%) and with no proportional bias. Discussion: The O2 and CO2 cross-sensitivity sensor error significantly overestimated FRC and LCI in adults, consistent with data in infants and children. There was a high degree of underestimation of S cond but minimal impact on S acin. The presence of significant proportional bias indicates that previous studies will require reanalysis to confirm previous findings and to allow comparability with future studies.

Ultrafine particle exposure and biomarkers of effect on small airways in children.

The small size and large surface area of ultrafine particles (UFP) enhance their ability to deposit in the lung periphery and their reactivity. The Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH) cross-sectional study was conducted in 8-11-year-old schoolchildren attending 25 primary (elementary) schools, randomly selected from the Brisbane Metropolitan Area, Queensland, Australia. Main study findings outlined indirect evidence of distal airway deposition (raised C reactive protein) but as yet, there is no direct evidence in the literature of effects of UFP exposure on peripheral airway function. We present further UPTECH study data from two sensitive peripheral airway function tests, Oscillometry and Multiple Breath Nitrogen Washout (MBNW), performed in 577 and 627 children (88% and 96% of UPTECH study cohort) respectively: mean(SD) age 10.1(0.9) years, 46% male, with 50% atopy and 14% current asthma. Bayesian generalised linear mixed effects regression models were used to estimate the effect of UFP particle number count (PNC) exposure on key oscillometry (airway resistance, (Rrs), and reactance, (Xrs)) and MBNW (lung clearance index, (LCI) and functional residual capacity, (FRC)) indices. We adjusted for age, sex, and height, and potential confounders including socio-economic disadvantage, PM2.5 and NO2 exposure. All models contained an interaction term between UFP PNC exposure and atopy, allowing estimation of the effect of exposure on non-atopic and atopic students. Increasing UFP PNC was associated with greater lung stiffness as evidenced by a decrease in Xrs [mean (95% credible interval) -1.63 (-3.36 to -0.05)%] per 1000#.cm-3]. It was also associated with greater lung stiffness (decrease in Xrs) in atopic subjects across all models [mean change ranging from -2.06 to -2.40% per 1000#.cm-3]. A paradoxical positive effect was observed for Rrs across all models [mean change ranging from -1.55 to -1.70% per 1000#.cm-3] (decreases in Rrs indicating an increase in airway calibre), which was present for both atopic and non-atopic subjects. No effects on MBNW indices were observed. In conclusion, a modest detrimental effect of UFP on peripheral airway function among atopic subjects, as assessed by respiratory system reactance, was observed extending the main UPTECH study findings which reported a positive association with a biomarker for systemic inflammation, C-reactive protein (CRP). Further studies are warranted to explore the pathophysiological mechanisms underlying increased respiratory stiffness, and whether it persists through to adolescence and adulthood.

Relationship between concavity of the flow-volume loop and small airway measures in smokers with normal spirometry.

BACKGROUND: There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements. METHODS: Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity. RESULTS: We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in "normal" smokers. Concavity measures were not related to either MBNW or IOS measurements. CONCLUSION: Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Fixed Airflow Obstruction in Asthma: A Problem of the Whole Lung Not of Just the Airways.

Asthma with irreversible or fixed airflow obstruction (FAO) is a severe clinical phenotype that is difficult to treat and is associated with an accelerated decline in lung function and excess morbidity. There are no current treatments to reverse or prevent this excessive decline in lung function in these patients, due to a lack of understanding of the underlying pathophysiology. The current paradigm is that FAO in asthma is due to airway remodeling driven by chronic inflammation. However, emerging evidence indicates significant and critical structural and functional changes to the lung parenchyma and its lung elastic properties in asthma with FAO, suggesting that FAO is a 'whole lung' problem and not just of the airways. In this Perspective we draw upon what is known thus far on the pathophysiological mechanisms contributing to FAO in asthma, and focus on recent advances and future directions. We propose the view that structural and functional changes in parenchymal tissue, are just as (if not more) important than airway remodeling in causing persistent lung function decline in asthma. We believe this paradigm of FAO should be considered when developing novel treatments.

Older age at Fontan completion is associated with reduced lung volumes and increased lung reactance.

BACKGROUND: Fontan patients have abnormal lung function, in particular restrictive lung disease and low diffusing capacity of carbon monoxide (DLCO). We sought to further characterise these abnormalities with detailed pulmonary function testing and examine associations with clinical parameters. METHODS: 132 Fontan patients across Australia and New Zealand underwent spirometry, with 126 subjects included in final analyses. Measurement of diffusion capacity (DLCO) including its components (alveolar volume (VA) and rate of uptake of CO (KCO)) and oscillometry (reactance (X5) and resistance (R5)) were assessed in a subset of Fontan patients (n = 44) and healthy controls (n = 12). Double diffusion (to assess diffusing capacity of nitric oxide (DLNO), capillary blood volume (Vc), alveolar capillary membrane function (DmCO)) was performed in Fontan patients (n = 18) and healthy controls (n = 12). RESULTS: FEV1 and FVC z-scores were low in Fontan subjects (mean - 1.67 ± 1.24 and - 1.61 ± 1.29, respectively) and correlated with exercise capacity. Compared to controls, z-scores for X5, DLCO, KCO, VA and DLNO were significantly lower in Fontan patients. R5, Vc and DmCO z-scores were preserved. X5 was associated with VA (r = 0.41,p = 0.009) and DmCO (r = 0.61,p = 0.008). Older age at Fontan completion was associated with lower z-scores for FEV1 (r = -0.46,p = 0.002), FVC (r = -0.47,p = 0.002), X5 (r = -0.32,p = 0.033) and VA (r = -0.36,p = 0.022). CONCLUSION: Fontan patients have a reduced DLCO which is largely driven by low VA. Lung stiffness (X5) is increased which is associated with VA and DmCO. These parameters negatively correlate with older age of Fontan completion suggesting that earlier Fontan completion may have a beneficial effect on lung function.

Quality assessment pathway for respiratory oscillometry.

A flow-chart-driven procedure is presented to facilitate respiratory oscillometry operator competency and measurement quality. A novel feature is a quality grading system, in line with other standards of lung function. https://bit.ly/3G4r0X1.

Clinical significance and applications of oscillometry.

Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.

Oscillometry and Asthma Control in Patients With and Without Fixed Airflow Obstruction.

BACKGROUND: Asthma is defined by the presence of reversible airflow limitation, yet persistently abnormal spirometry may develop despite appropriate asthma treatment. Fixed airflow obstruction (FAO) describes abnormal postbronchodilator spirometry that is associated with greater symptom burden and disease severity. Respiratory oscillometry measures the mechanics of the entire airway tree, including peripheral airway changes that have been shown to influence asthma symptoms. OBJECTIVE: To evaluate the relationship between abnormal oscillometry following bronchodilator and symptom control in adults with asthma. METHODS: A prospective cohort of patients with asthma attending an airways clinic completed oscillometry (resistance and reactance), spirometry, and the Asthma Control Test. Postbronchodilator lung function below the lower limit of normal was considered abnormal. Spirometric FAO was defined as FEV1/forced vital capacity below the lower limit of normal. Spearman's rank coefficient and multiple linear regression were performed to assess associations of lung function parameters with Asthma Control Test. The discriminative ability of abnormal lung function to identify poor asthma control was determined using Cohen's kappa. RESULTS: Ninety patients with asthma were included; 48% had spirometric FAO. Only reactance parameters, not spirometry, significantly related to (rs ≥ 0.315; P < .05) and identified asthma control (r2 = 0.236; P < .001). Lung function was more strongly associated with asthma control in patients with FAO compared with those without. Abnormal oscillometry identified an additional 24% of patients with poor asthma control as compared with spirometric FAO. CONCLUSIONS: Reactance related to asthma control, independently of spirometric FAO. Abnormal postbronchodilator reactance identified more patients with poor asthma control compared with spirometry. These findings confirm that oscillometry is a relevant lung function test in the clinical assessment of asthma.

Novel Methods of Measuring Adherence Patterns Reveal Adherence Phenotypes with Distinct Asthma Outcomes.

Rationale: Poor adherence with asthma controller medication contributes to worse symptom control and increased exacerbation risk. Adherence is often expressed as the mean proportion of prescribed doses taken over a period of 6-12 months. New metrics may capture individual day-to-day variability patterns linked with distinct clinical outcomes. Objectives: To test the hypotheses that novel time- and dose-based adherence variability metrics offer independent value to mean adherence in identifying distinct adherence patterns that are associated with symptom control (Asthma Control Test [ACT] score) and exacerbation risk, using electronically recorded medication data from a 6-month cluster randomized trial examining the effect of inhaler reminders on adherence. Methods: Adherence metrics were calculated from the first 2 months (Months 0-2) of the study period. In addition to mean adherence (percentage prescribed puffs/day taken), we examined novel metrics, including time adherence area under the curve (T-AUC), reflecting cumulative gaps in adherence over time; entropy, reflecting disorder in the ways in which a patient changed their medication dose adherence from day to day; and standard deviation of the percentage prescribed puffs/day taken. Dominant metrics identified from factor analysis were included in hierarchical clustering analysis. We compared the resultant clusters in terms of outcomes over Months 2-6 and exacerbation risk over the entire study period. Results: Two factors explained >65% of the total variance in adherence, primarily driven by T-AUC and entropy. Two main patient clusters based on their adherence metrics were identified: cluster 1 (high time adherence, n = 75) had better T-AUC (i.e., fewer gaps between medication-taking days) than cluster 2 (low time adherence, n = 23). Though both clusters had similar symptom control at 2 months, cluster 1 showed less subsequent decline in ACT over Months 2-6 (median [interquartile range] change in ACT score: 1 [-1 to 4] vs. -2 [-3.75 to 0.75]; P = 0.012), and had better symptom control at 6 months (ACT score: 20 [17-23] vs. 17 [15-20]; P = 0.034). There were no significant differences between the clusters in terms of proportion of exacerbators or time to exacerbation. Conclusions: Novel metrics showed that low time adherence was associated with greater risk of decline in asthma symptom control. Adherence patterns may exhibit "memory" relevant to future clinical status, warranting validation in a larger dataset.

Controlled versus free breathing for multiple-breath nitrogen washout in asthma.

The lack of comparability in indices of ventilation heterogeneity between free- and controlled-breathing MBNW protocols is confirmed in asthma https://bit.ly/3lmri4A.

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

INTRODUCTION: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. METHODS: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 µg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. RESULTS: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. DISCUSSION: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.

Within-session variability as quality control for oscillometry in health and disease.

Oscillometry is increasingly adopted in respiratory clinics, but many recommendations regarding measurement settings and quality control remain subjective. The aim of this study was to investigate the optimal number of measurements and acceptable within-session coefficient of variation (CoV) in health, asthma and COPD. 15 healthy, 15 asthma and 15 COPD adult participants were recruited. Eight consecutive 30-s measurements were made using an oscillometry device, from which resistance at 5 Hz (R rs5 ) was examined. The effect of progressively including a greater number of measurements on R rs5 and its within-session CoV was investigated. Data were analysed using one-way repeated-measures ANOVA with Bonferroni post hoc test. The CoV(R rs5 ) of the first three measurements was 6.7±4.7%, 9.7±5.7% and 12.6±11.2% in healthy, asthma and COPD participants, respectively. Both mean R rs5 and CoV(R rs5 ) were not statistically different when progressively including four to eight measurements. Selecting the three closest R rs5 values over an increasing number of measurements progressively decreased the CoV(R rs5 ). In order for ≥95% of participants to fall within a target CoV(R rs5 ) of 10%, four or more, five and six measurements were needed in health, asthma and COPD, respectively. Within-session variability of oscillometry is increased in disease. Furthermore, the higher number of measurements required to achieve a set target for asthma and COPD patients may not be practical in a clinical setting. Provided technical acceptability of measurements is established, i.e. by removing artefacts and outliers, then a CoV of 10% is a marker of quality in most patients, but we suggest higher CoVs up to 15-20% should still be reportable.

Dynamics of inhaled corticosteroid use are associated with asthma attacks.

Inhaled corticosteroids (ICS) suppress eosinophilic airway inflammation in asthma, but patients may not adhere to prescribed use. Mean adherence-averaging total doses taken over prescribed-fails to capture many aspects of adherence. Patients with difficult-to-treat asthma underwent electronic monitoring of ICS, with data collected over 50 days. These were used to calculate entropy (H) a measure of irregular inhaler use over this period, defined in terms of transitional probabilities between different levels of adherence, further partitioned into increasing (Hinc) or decreasing (Hdec) adherence. Mean adherence, time between actuations (Gapmax), and cumulative time- and dose-based variability (area-under-the-curve) were measured. Associations between adherence metrics and 6-month asthma status and attacks were assessed. Only H and Hdec were associated with poor baseline status and 6-month outcomes: H and Hdec correlated negatively with baseline quality of life (H:Spearman rS = - 0·330, p = 0·019, Hdec:rS = - 0·385, p = 0·006) and symptom control (H:rS = - 0·288, p = 0·041, Hdec: rS = - 0·351, p = 0·012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic = - 2.34, p = 0·019), and Hdec with subsequent asthma attacks of other severities. Significant associations were maintained in multivariable analyses, except when adjusted for blood eosinophils. Entropy analysis may provide insight into adherence behavior, and guide assessment and improvement of adherence in uncontrolled asthma.

Effect of combination inhaled therapy on ventilation distribution measured by SPECT/CT imaging in uncontrolled asthma.

Asthma is characterized by heterogeneous ventilation as measured by three-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) treatment response is variable in asthma, and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma. Twenty-two symptomatic participants with asthma underwent single-photon emission computed tomography (SPECT)/CT imaging with Technegas, before and after 8-wk fluticasone/formoterol (1,000/40 µg/day) treatment. Lung regions that were nonventilated, low ventilated, or well ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airways function (Sacin and Scond, respectively). Forced oscillation technique (FOT) was used to measure respiratory system resistance and reactance. At baseline and posttreatment, Scond z-score was related to percentage of nonventilated lung, whereas Sacin z-score was related to percentage of low-ventilated lung. Although symptoms, spirometry, FOT, and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide range of changes in SPECT ventilation such that greater percentage of nonventilated lung, older age, and higher Scond predicted a reduction in nonventilated lung after treatment. SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable, with improvement occurring when small airways dysfunction and ventilation defects are more severe. Persistent ventilation defects that correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodeling underlie these defects.NEW & NOTEWORTHY This study provides insights into the mechanisms of high-dose ICS treatment in uncontrolled asthma. Ventilation defects as measured by SPECT/CT imaging respond heterogeneously to increased ICS/LABA treatment, with improvement occurring when ventilation defects and impairment of convection-dependent small airways function are more severe. Persistent correlations between ventilation defects and measures of small airways function suggest the potential presence of ICS nonresponsive inflammation and/or remodeling.

Longitudinal monitoring of asthma in the clinic using respiratory oscillometry.

BACKGROUND AND OBJECTIVE: Asthma guidelines emphasize the importance of assessing lung function and symptoms. The forced oscillation technique (FOT) and its longitudinal relationship with spirometry and symptoms are unresolved. We examined concordance between longitudinal spirometry, FOT and symptom control, and determined FOT limits of agreement in stable asthma. METHODS: Over a 3-year period, adults with asthma attending a tertiary clinic completed the asthma control test (ACT), fraction of exhaled nitric oxide (FeNO), FOT and spirometry. Analysis included between-visit concordance for significant change using Cohen's kappa (κ) and stable asthma FOT limits of agreement. RESULTS: Data (n = 186) from 855 visits (mean ± SD 4.6 ± 3.0 visits), 114 ± 95 days apart, were analysed. Between-visit concordance was moderate between reactance at 5 Hz (X5) and forced expiratory volume in 1 s (FEV1 ) (κ = 0.34, p = 0.001), and weak between ACT and FEV1 (κ = 0.18, p = 0.001). Change in FeNO did not correlate with lung function or ACT (κ < 0.05, p > 0.1). Stable asthma between visits (n = 75; 132 visits) had reduced lung function variability, but comparable concordance to the entire cohort. Limits of agreement for FEV1 (0.42 L), resistance at 5 Hz (2.06 cm H2 O s L-1 ) and X5 (2.75 cm H2 O s L-1 ) in stable asthma were at least twofold greater than published values in health. CONCLUSION: In adults with asthma, there is moderate concordance between longitudinal change in FOT and spirometry. Both tests relate poorly to changes in asthma control, highlighting the need for multi-modal assessment in asthma rather than symptoms alone. The derivation of longitudinal FOT limits of agreement will assist in its clinical interpretation.