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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 S cond , S acin 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 (FRC M ), dead space volume (V D ), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of S acin (S acin-M ). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRC M  < 5.2%, V D  < 5.4%, [Formula: see text] < 9.0%, and S acin-M  < 45.6% for controlled breathing, and FRC M  < 4.6%, V D  < 5.3%, [Formula: see text] < 13.2%, and S acin-M  < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with S cond  < 73.6% and S acin  < 49.2% for controlled breathing and S cond  < 35.0% and S acin  < 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 S cond ., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The lack of comparability in indices of ventilation heterogeneity between free- and controlled-breathing MBNW protocols is confirmed in asthma https://bit.ly/3lmri4A., Competing Interests: Provenance: Submitted article, peer reviewed. Conflicts of interest: B.M. Handley has nothing to disclose. Conflicts of interest: J. Bozier has nothing to disclose. Conflicts of interest: E. Jeagal has nothing to disclose. Conflicts of interest: S. Rutting has nothing to disclose. Conflicts of interest: R.E. Schoeffel has nothing to disclose. Conflicts of interest: P.D. Robinson has nothing to disclose. Conflicts of interest: G.G. King reports fees for consultancy services, conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini, MundiPharma. G.G. King also reports NHMRC research grants and fellowships. Conflicts of interest: S. Milne has nothing to disclose. Conflicts of interest: C. Thamrin reports supply of equipment for an unrelated study from Restech SRL. C. Thamrin also reports funded research collaboration for an unrelated project., (Copyright ©The authors 2021.)

Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: "controlled breathing", with targeted tidal volume ( V T ) and respiratory rate (RR); and "free breathing", with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity (FRC), lung clearance index (LCI), S cond , S acin ) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences and to determine the between-session variabilities of each protocol. We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently proposed correction for V T to S cond and S acin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months. While FRC was comparable between controlled versus free breathing (3.17 (0.98) versus 3.18 (0.94) L, p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for S cond (r=0.18, p=0.36) and significant bias for S acin (0.057 (0.021) L -1 versus 0.085 (0.038) L -1 , p=0.0004). Between-protocol differences in S acin were related to differences in the breathing pattern, i.e. V T (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but S cond and S acin from free breathing showed poor repeatability with wide limits of agreement. These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that S cond and S acin from free breathing, despite V T correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of S cond during free breathing may limit its clinical utility., Competing Interests: Conflict of interest: B.M. Handley has nothing to disclose. Conflict of interest: E. Jeagal has nothing to disclose. Conflict of interest: R.E. Schoeffel has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: C.E. Farrow has nothing to disclose. Conflict of interest: G.G. King reports fees for consultancy services (which include lectures and advisory board services), conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants and fellowships from the National Health & Medical Research Council and the Asthma Foundation, outside the submitted work. Conflict of interest: P.D. Robinson has nothing to disclose. Conflict of interest: S. Milne reports personal fees from Novartis and Boehringer Ingelheim outside the submitted work, and is supported by the MITACS Accelerate programme. Conflict of interest: C. Thamrin has nothing to disclose., (Copyright ©ERS 2021.)

The forced oscillation technique (FOT) is gaining clinical acceptance, facilitated by more commercial devices and clinical data. However, the effects of variations in testing protocols used in FOT data acquisition are unknown. We describe the effect of duration of data acquisition on FOT results in subjects with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. FOT data were acquired from 20 healthy, 22 asthmatic and 18 COPD subjects for 60 s in triplicate. The first 16, 30 and 60 s of each measurement were analysed to obtain total, inspiratory and expiratory resistance of respiratory system ( R rs ) and respiratory system reactance ( X rs ) at 5 and 19 Hz. With increasing duration, there was a decrease in total and expiratory R rs for healthy controls, total and inspiratory R rs for asthmatic subjects and magnitude of total and inspiratory X rs for COPD subjects at 5 Hz. These decreases were small compared to the differences between clinical groups. Measuring for 16, 30 and 60 s provided ≥3 acceptable breaths in at least 90, 95 and 100% of subjects, respectively. The coefficient of variation for total R rs and X rs also decreased with duration. Similar results were found for R rs and X rs at 19 Hz. FOT results are statistically, but likely minimally, impacted by acquisition duration in healthy, asthmatic or COPD subjects., Competing Interests: can be found alongside this article at openres.ersjournals.com

Inert gas washout methods have been shown to detect pathological changes in the small airways that occur in the early stages of obstructive lung diseases such as asthma and COPD. Numerical lung models support the analysis of characteristic washout curves, but are limited in their ability to simulate the complexity of lung anatomy over an appropriate time period. Therefore, the interpretation of patient-specific washout data remains a challenge. A new numerical lung model is presented in which electrical components describe the anatomical and physiological characteristics of the lung as well as gas-specific properties. To verify that the model is able to reproduce characteristic washout curves, the phase 3 slopes (S 3 ) of helium washouts are simulated using simple asymmetric lung anatomies consisting of two parallel connected lung units with volume ratios of 1.25 0.75 , 1.50 0.50 , and 1.75 0.25 and a total volume flow of 250 ml/s which are evaluated for asymmetries in both the convection- and diffusion-dominated zone of the lung. The results show that the model is able to reproduce the S 3 for helium and thus the processes underlying the washout methods, so that electrical components can be used to model these methods. This approach could form the basis of a hardware-based real-time simulator., (© 2024. The Author(s).)

Objective: Some of the most common causes of chronic cough include cough variant asthma (CVA), bronchial asthma (BA), and asthma–COPD overlap (ACO). Although there is some overlap in the etiology of these diseases, it is clinically important to attempt an early differential diagnosis due to treatment strategies and prognoses. Methods: Spirometry and impulse oscillometry (IOS) before and after bronchodilator inhalation were analyzed for clinically diagnosed CVA (cCVA, n = 203), BA (cBA, n = 222), and ACO (cACO, n = 61). Results: A significant difference in ΔFEV1 was observed between cBA and cCVA (ΔFEV1 improvement of 122.5 mL/5.4% and 65.7 mL/2.2%, respectively), but no difference was observed in ΔPEF, ΔV50, or ΔV25. Except for R20 (resistance at 20 Hz), significant differences between the three groups were observed in IOS. In IOS, cCVA and cBA showed comparable peripheral airway response to bronchodilator which was thought to be commensurate with changes in V50 and V25. cACO improved ΔFEV1 improvement of 81.0 mL/6.2% and was distinguished by a downward respiratory system reactance (Xrs) waveform with a limited bronchodilator response. FEV1/FVC, %FEV1, and %V25 had relatively strong correlations with the three IOS parameters, X5 (reactance at 5 Hz), resonant frequency (Fres), and low-frequency reactance area (ALX), in the correlation between IOS and spirometers. Conclusion: Changes in IOS parameters were more sensitive in this study than changes in FEV1 or the flow-volume curve. Considering the benefits and relevance of the two different tests, simultaneous IOS and spirometry testing were useful in the diagnosis of asthmatic cough. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and objective: Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma. Methods: Non‐smoking asthmatic subjects aged >40 years, treated with 2 months of high‐dose inhaled corticosteroid/long‐acting beta‐agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5) and respiratory system reactance at 5 Hz (Xrs5) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure–volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), Rrs5 and Xrs5 were assessed. Results: Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z‐score) post‐bronchodilator FEV1: −2.2 ± 0.5, FVC: −0.7 ± 1.0, FEV1/FVC: −2.6 ± 0.7) and by increased Rrs5 (median (IQR) z‐score) 2.7 (1.9 to 3.2) and decreased Xrs5: −4.1(−2.4 to −7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1/FVC correlated negatively with K (rs = −0.60, P = 0.008) and Rrs5 correlated negatively with B/A (rs = −0.52, P = 0.026), independent of age. Xrs5 did not correlate with lung elasticity indices. Conclusion: Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non‐smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid‐resistant airflow obstruction.Clinical trial registration: ACTRN126150000985583 at anzctr.org.au (UTN: U1111‐1156‐2795) [ABSTRACT FROM AUTHOR]

Derecruitment of air spaces in the lung occurs when airways close during exhalation and is related to ventilation heterogeneity and symptoms in asthma. The forced oscillation technique has been used to identify surrogate measures of airway closure via the reactance (Xrs) versus lung volume relationship. This study used a new algorithm to identify derecruitment from the Xrs versus lung volume relationship from a slow vital capacity maneuver. We aimed to compare two derecruitment markers on the Xrs versus volume curve, the onset reduction of Xrs (DR1vol) and the onset of more rapid reduction of Xrs (DR2vol), between control and asthmatic subjects. We hypothesized that the onset of DR1vol and DR2vol occurred at higher lung volume in asthmatic subjects. DR1vol and DR2vol were measured in 18 subjects with asthma and 18 healthy controls, and their relationships with age and height were examined using linear regression. In the control group, DR1vol and DR2vol increased with age (r2 = 0.68, P < 0.001 and r2 = 0.71, P < 0.001, respectively). DR1vol and DR2vol in subjects with asthma [76.58% of total lung capacity (TLC) and 56.79%TLC, respectively] were at higher lung volume compared with control subjects (46.1 and 37.69%TLC, respectively) (P < 0.001). DR2vol correlated with predicted values of closing capacity (r = 0.94, P < 0.001). This study demonstrates that derecruitment occurs at two points along the Xrs-volume relationship. Both derecruitment points occurred at significantly higher lung volumes in subjects with asthma compared with healthy control subjects. This technique offers a novel way to measure the effects of changes in airways/lung mechanics. NEW & NOTEWORTHY This study demonstrates that the forced oscillation technique can be used to identify two lung volume points where lung derecruitment occurs: 1) where derecruitment is initiated and 2) where onset of rapid derecruitment commences. Measurements of derecruitment increase with age. The onset of rapid derecruitment was highly correlated with predicted closing capacity. Also, the initiation and rate of derecruitment are significantly altered in subjects with asthma. [ABSTRACT FROM AUTHOR]