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Highlights • Rheumatoid arthritis (RA)-related pulmonary disorders are important. • Changes in respiratory impedance (Zrs) assessed by FOT were evaluated. • Zrs results were affected by complications of adverse respiratory events. • Zrs measurements combined with spirometry may be beneficial. Abstract The aim of this study was to examine long-term changes in pulmonary function and respiratory impedance (Zrs) as assessed by forced oscillation technique (FOT) of rheumatoid arthritis (RA)-related pulmonary disorders. Data of 42 RA patients who underwent pulmonary function tests and Zrs measurements at least twice at a >900-day interval were retrospectively reviewed. Zrs, respiratory resistance (Rrs) and reactance (Xrs), were measured as a function of oscillatory frequency from 4 to 36 Hz. The Rrs and difference between inspiratory and expiratory phases of Xrs were significantly decreased. Annual changes in Xrs parameters significantly correlated with those of spirometric parameters. Zrs parameters were significantly different between the low (the lower 75 percentile of incidence) and high (the top quartile) frequency of adverse respiratory event groups. The Zrs combined with spirometry may be beneficial to evaluate alterations in respiratory functions of RA. [ABSTRACT FROM AUTHOR]

Highlights • Particulate matter air pollution is common in military deployment environments of Iraq and Afghanistan. • Respiratory symptoms are frequently reported post-deployment, yet spirometry is frequently preserved. • Using the forced oscillation technique (FOT), 75% of veterans with preserved spirometry had distal airway dysfunction. • Veterans with distal airway dysfunction may represent at an at-risk population requiring closer surveillance. Abstract Purpose To evaluate the utility of the forced oscillation technique (FOT) among military veterans with preserved spirometry and chronic unexplained respiratory symptoms. Methods 178 veterans referred for evaluation of unexplained respiratory symptoms completed pulmonary function testing and FOT. Preserved spirometry was defined as FEV 1 /FVC, FEV 1 and FVC ≥ 5th percentile. Frequency dependence of resistance (R4-R20) and reactance area (AX) were assessed via FOT, and R4-R20 ≥ 20% and AX ≥ 95th percentile were considered abnormal. Results Spirometry was preserved in 71.3%, of whom 124 had acceptable FOT data. 93 of 124 (75.0%) veterans with preserved spirometry had one or more abnormal findings on FOT. Veterans with abnormal R4-R20 and/or AX had reduced FVC, FEV 1 , FEF 25-75 , and diffusing capacity (% predicted) in comparison to those with Normal FOT (p = 0.030 to p < 0.001). Conclusions In our referral sample, distal airway dysfunction in the presence of preserved spirometry appears common and may represent an at-risk group requiring closer surveillance. [ABSTRACT FROM AUTHOR]

Oscillometry has been around for almost 70 years, but there are still many unknowns. The test is performed during tidal breathing and is therefore free from patient-dependent factors that could influence the results. The Forced Oscillation Technique (FOT), which requires minimal patient cooperation, is gaining ground, particularly with elderly patients and children. In pulmonology, it is a valuable tool for assessing obstructive conditions (with a distinction between central and peripheral obstruction) and restrictive disorders (intrapulmonary and extrapulmonary). Its sensitivity allows the assessment of bronchodilator and bronchoconstrictor responses. Different lung diseases show different patterns of changes in FOT, especially studied in asthma and chronic obstructive pulmonary disease. Because of these differences, many studies have analysed the usefulness of this technique in different areas of medicine. In this paper, the authors would like to present the basics of oscillometry with the areas of its most recent clinical applications. • The Forced Oscillation Technique (FOT), performed during tidal breathing, is free from patient-dependent factors that may influence the results. • Different lung diseases show different patterns of change in FOT. • In some areas, this technique has shown advantages over traditional lung function tests, particularly in small airways disease. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to assess responses to a bronchodilator by forced oscillation technique (FOT) and to relate the results of respiratory impedance (Zrs) to spirometric parameters in patients with chronic obstructive pulmonary disease (COPD). Zrs was measured as a function of frequency from 4 to 36 Hz before and after inhalation of procaterol, a short-acting β 2 -agonist (n = 60). Respiratory resistance (Rrs) and reactance (Xrs) were significantly frequency-dependent, and inspiratory and expiratory phases were different both before and after procaterol inhalation. The Rrs at 4 Hz and Xrs at 4–20 Hz during a whole breath were significantly improved after procaterol inhalation. The response to procaterol inhalation varied among patients, and changes in Xrs at 4 Hz significantly correlated with% change in forced expiratory volume in one second and changes in forced vital capacity. Taken together, Zrs, and specifically Xrs parameters, are sensitive to acute physiological responses to a bronchodilator in COPD. [ABSTRACT FROM AUTHOR]

Many types of lung disease lead to constriction of airways within the conducting zone, causing increases in airway resistance and ventilation heterogeneity (VH). The multiple-breath washout (MBW) and forced oscillation technique (FOT) are two clinical measures of small airway bronchoconstriction. Within this study computational modelling of the MBW and FOT was applied to the analysis of thousands of bronchoconstriction scenarios in the conducting zone of the lungs. The simulations show that MBW indices primarily respond to the severity of constriction, while FOT indices may be able to distinguish between constrictions at differing airway depths. Following this, we show the potential utility in the joint interpretation of indices from the two tests, providing motivations for future clinical investigations. [ABSTRACT FROM AUTHOR]

Introduction The aim was to elucidate the relationship between the annual changes in respiratory system impedance, measured by FOT, and lung function tests in patients with asthma. Methods Between March 2011 and March 2012, asthma outpatients who attended Kobe City Medical Center West Hospital were recruited. Lung function tests, FOT were conducted every 6 months until March 2016. The relationships between annual parameter changes were evaluated. Results and conclusion Sixty-four patients were completed this study. The median follow-up period was 55 months. At enrollment, although resistance showed no relationship with forced expiratory volume in one second (%FEV 1 ), the reactance was moderately correlated with X5 (r = 0.524, r 2 = 0.275, <0.001), Fres (r = −0.498, r 2 = 0.248, <0.001) and ALX (r = −0.416, r 2 = 0.173, p = < 0.001). By contrast, the annual resistance change at 5 Hz (R5) was highly and significantly associated with%FEV 1 change (r = −0.564, r 2 = 0.318, p < 0.001). Longitudinal changes in airway resistance and reactance measured by FOT might be useful for the assessment of lung function in patients with asthma. [ABSTRACT FROM AUTHOR]

The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting β2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1. The responders to the treatment regimen exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at 5 Hz (R5), as well as a difference between R5 and R20 (R5–R20) at baseline compared to the nonresponders. In the multivariate logistic regression analyses, a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced oscillatory parameter and predicts an improvement in FEV1 following treatment. [ABSTRACT FROM AUTHOR]

Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. The negative expiratory pressure (NEP) technique has been the gold standard to detect EFL, while the forced oscillation technique (FOT) has also been reported to detect it. However, the association of FOT with NEP is not fully understood. We assessed whether broadband frequency FOT would predict the presence of EFL measured by NEP. FOT, NEP, and spirometry were performed in 51 patients with COPD. The extent of emphysema was measured by high-resolution computed tomography and scored. Fifteen patients were classified into the EFL-positive group and 36 into the EFL-negative group. In multivariate logistic regression analysis, EFL was independently predicted by emphysema score, forced vital capacity, and whole-breath respiratory system reactance at 5 Hz (X5). The receiver operator characteristic curve analysis revealed that inspiratory X5 best predicted EFL-positivity. X5-related forced oscillatory parameters are useful for detecting EFL in the management of COPD. [ABSTRACT FROM AUTHOR]

The composite physiologic index (CPI), which is derived from FEV1, FVC, and diffusing capacity, has been developed to predict the extent of fibrosis on high-resolution computed tomography (HRCT). However, the relevance to the forced oscillation technique (FOT) is not fully understood. We hypothesized that FOT would independently predict the CPI in interstitial lung disease (ILD). In this cross-sectional study we assessed the relationship between pulmonary function tests, forced oscillatory parameters, and the degree of fibrosis in ILD. Spirometry, evaluation of diffusing capacity for carbon monoxide, and the broadband frequency FOT were performed in 93 patients with a clinical/HRCT diagnosis of ILD. The CPI was calculated and fibrosis extent was measured by HRCT and scored. Univariate analyses revealed that, of the forced oscillatory parameters, inspiratory resonant frequency best correlated with FVC, FEV1, diffusing capacity, CPI, and fibrosis score. In multiple regression analyses, CPI was independently predicted by inspiratory resonant frequency and fibrosis score (model R 2 = 0.405, p < 0.0001). [ABSTRACT FROM AUTHOR]

Highlights: [•] Halothane is amore potent bronchodilator of the small airways than isoflurane. [•] We evaluated if intranasal challenge under halothane vs. isoflurane anesthesia would lead to an enhanced allergic response. [•] Peripheral lung inflammation was significantly increased in halothane compared to isoflurane OA-challenged mice. [•] Airway challenge under halothane induces a higher level of airway hyperresponsiveness than under isoflurane anesthesia. [•] Intranasal challenges under different anesthesia support the importance of the small airways in asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Short-term high V T-low PEEP ventilation is not deleterious in infant rats. [•] Changes in lung function can be attributed to loss of lung volume. [•] BALF interleukin-6 concentration is increased in all ventilated infant rats. [•] Age-specific animal models are needed to investigate paediatric VILI. [ABSTRACT FROM AUTHOR]

Highlights: [•] The N2 single-breath washout (SBW) is a measure of ventilation inhomogeneity. [•] The phase III slope (delta N2) is derived from N2 SBW. [•] We assessed the relationship between delta N2 and other parameters in COPD. [•] Resonant frequency of forced oscillation technique was an independent predictor. [•] Forced vital capacity and degree of emphysema were also independent predictors. [ABSTRACT FROM AUTHOR]

Highlights: [•] Obesity is associated with reduced operating lung volume. [•] Breathing at low operating lung volume leads to airway closure during tidal breathing. [•] Airway closure does not begin earlier in exhalation in the obese. [•] Low lung volume and tidal airway closure affects airway function. [•] After accounting for lung volume, abnormalities in ventilation heterogeneity in very peripheral airways and in airway caliber persist. [Copyright &y& Elsevier]

Abstract: Both obesity and sleep reduce lung volume and limit deep breaths, possibly contributing to asthma. We hypothesize that increasing lung volume dynamically during sleep would reduce airway resistance in asthma. Asthma (n =10) and control (n =10) subjects were studied during sleep at baseline and with increased lung volume via bi-level positive airway pressure (BPAP). Using forced oscillations, respiratory system resistance (R rs) and reactance (X rs) were measured during sleep and R rs was partitioned to upper and lower airway resistance (R up, R low) using an epiglottic pressure catheter. R rs and R up increased with sleep (p <0.01) and X rs was decreased in REM (p =0.02) as compared to wake. R rs, R up, and R low, were larger (p <0.01) and X rs was decreased (p <0.02) in asthma. On BPAP, R rs and R up were decreased (p <0.001) and X rs increased (p <0.01), but R low was unchanged. High R up was observed in asthma, which reduced with BPAP. We conclude that the upper airway is a major component of R rs and larger lung volume changes may be required to alter R low. [Copyright &y& Elsevier]

Abstract: The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance () at 5, 11 and 19Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz () were related to changes in lung volume () to estimate airway distensibility. at FRC showed a slight but significant increase at all forcing frequencies by approximately 12–16%. TLC decreased after HSCT whereas the ratio became higher after than before HSCT and was positively correlated (R 2 =0.87) with lung tissue density determined by quantitative CT scanning. We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT. [Copyright &y& Elsevier]

Abstract: Sensory (physiological) and affective (psychological) dimensions of dyspnea have been described but the usefulness of measuring psychological status in addition to ventilatory capacity (spirometry, lung volumes) in the assessment of exertional dyspnea remains controversial. We hypothesized that activity-related dyspnea would not be modified by psychological status. Principal component analysis (PCA) was used to reduce the number of parameters (psychological or functional) to fewer independent dimensions in 328 patients with altered ventilatory capacity: severe obesity (BMI≥35, n =122), COPD (n =128) or interstitial lung disease (n =78). PCA demonstrated that psychological status (Hospital Anxiety-Depression, Fatigue Impact scales) and dyspnea (Medical Research Council [MRC] scale) were independent dimensions. Ventilatory capacity was described by three main dimensions by PCA related to airways, volumes, and their combination (specific airway resistance, FEV1/FVC), which were weakly correlated with dyspnea. In conclusion, in patients with COPD, interstitial lung disease or severe obesity, psychological status does not modify activity-related dyspnea rating as evaluated by the MRC scale. [Copyright &y& Elsevier]

Few studies have examined whether baseline spirometry and the forced oscillation technique (FOT) would predict The COPD Assessment Test (CAT) score improvement after treatment of untreated COPD patients. The study subjects included 65 untreated COPD patients. They underwent the CAT, spirometry, and FOT (MostGraph) before and after treatment for more than 2 months. In addition, recursive partitioning analysis was performed using spirometry and the FOT parameters to identify the predictors of CAT improvement (CAT score ≥2). CAT scores and lung function significantly improved after treatment. Recursive partitioning analysis identified 3 improved classes, defined by Rrs at 20 Hz (R20), Xrs at 5 Hz (X5), and ΔX5, but not by spirometry. The accuracy of predicting CAT improvement was as follows: odds ratio, 25.3; 95 % confidence interval, 6.1 to 104.1; sensitivity, 91.2 %; specificity, 71.0 %; positive likelihood ratio, 3.14; and negative likelihood ratio, 0.12. FOT helps predict improved health status in untreated COPD patients. [ABSTRACT FROM AUTHOR]

• Bronchial wall thickening made respiratory reactance more negative in bronchiectasis. • Bronchial wall thickening deteriorated the severity of airflow obstruction. • Abnormal respiratory reactance might affect airflow obstruction in bronchiectasis. The association between airflow obstruction and bronchial dilation has been researched in bronchiectasis. However, the impact of bronchial wall thickening on airflow obstruction has not been thoroughly investigated. This study assessed the underlying mechanism of airflow obstruction in bronchiectasis due to abnormal bronchial wall thickening using oscillometry. A total of 98 patients with bronchiectasis were retrospectively reviewed. At the time of diagnosis, spirometric and oscillometric parameters, high-resolution computed tomography scores, and clinical characteristics were collected. The bronchial diameter, bronchial wall thickness, and extent of emphysema were evaluated semi-quantitatively. Correlations between patient data and characteristics were analyzed. Thirty-three patients with airflow obstruction showed higher respiratory resistance, more negative respiratory reactance (Xrs) at 5 Hz (X5), and higher bronchial wall thickness score than those without airflow obstruction. The bronchial wall thickness score negatively affected forced expiration volume in 1 s /forced vital capacity and X5. Abnormal bronchial wall thickening might make Xrs more negative and progress airflow obstruction in bronchiectasis. [ABSTRACT FROM AUTHOR]

• Few studies have examined the influence of water immersion on the airway impedance. • Forced oscillation technique can measure the airway impedance non-invasively. • The spirometric value during clavicle water immersion was lower than on land. • The airway impedance with immersion above the xiphoid level was higher than land. Few studies have examined the influence of different water depths on the airway impedance measured by forced oscillation technique in healthy adults. Eleven healthy men (23.2 ± 1.5 years old) participated in this study. We measured the respiratory impedance assessed with the resistance at frequency of 5 Hz and 20 Hz, the reactance at frequency of 5 Hz, and frequency of resonance. To compare the influence of water depths, we carried out one dryland (DL) and two water level conditions: clavicle level (CL) and xiphoid appendix level (XA). The respiratory resistance at frequency of 5 Hz was higher in CL and XA than DL, and at 20 Hz was significantly higher in CL than DL. The respiratory reactance at 5 Hz was lower in CL and XA than DL, and frequency of resonance was higher in CL and XA than DL. These results suggested that water immersion above xiphoid appendix level increase airway resistance. [ABSTRACT FROM AUTHOR]

Abstract: The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8–256Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests. [Copyright &y& Elsevier]

Abstract: This review discusses the history and current state of the art of the forced oscillation technique (FOT) to measure respiratory impedance. We focus on how the FOT and its interaction with models have emerged as a powerful method to extract out not only clinically relevant information, but also to advance insight on the mechanisms and structures responsible for human lung diseases, especially asthma. We will first provide a short history of FOT for basic clinical assessment either directly from the data or in concert with lumped element models to extract out specific effective properties. We then spend several sections on the more exciting recent advances of FOT to probe the relative importance of tissue versus airway changes in disease, the impact of the disease on heterogeneous lung function, and the relative importance of small airways via synthesis of FOT with imaging. Most recently, the FOT approach has been able to directly probe airway caliber in humans and the distinct airway properties of asthmatics that seem to be required for airway hyperresponsiveness. We introduce and discuss the mechanism and clinical implications of this approach, which may be substantial for treatment assessment. Finally, we highlight important future directions for the FOT, particularly its use to probe specific lung components (e.g., isolated airways, isolated airway smooth muscle, etc.) and relate such data to the whole lung. The intent is to substantially advance an integrated understanding of structure–function relationships in the lung. [Copyright &y& Elsevier]

Abstract: The multiple breath nitrogen washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5Hz (sGrs5 =Grs5/FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R 2 =0.68, p =0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R 2 =0.79, p &#60;0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs5 in a multivariate model (R 2 =0.82, p =0.0002). Sacin was unrelated to VtrappedFRC and sGrs5 before and after methacholine challenge. In conclusion, Scond and sGrs5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in terminal airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions. [Copyright &y& Elsevier]

Abstract: The mechanical properties of the lung periphery are vital to the overall function of the whole organ, and play a key role in the symptomatology of many lung diseases. We first review the experimental methodologies that have been used to investigate peripheral lung mechanics, including the retrograde catheter, the alveolar capsule, the alveolar capsule oscillator, and the forced oscillation technique. We then discuss the interpretation of the data provided by these techniques in terms of inverse mathematical models of the lung, including the constant-phase model. Finally, we describe efforts to construct anatomically accurate forward models of the lung based on data from imaging modalities such as computed tomography and magnetic resonance imaging. Together, these various approaches have provided a great deal of information about the relative importance of the lung periphery in mechanical function in animal models of lung disease and in human patients. An increasing body of evidence indicates that constriction in this part of the lung is a crucial determinant of the severity of asthma. [Copyright &y& Elsevier]

• Pulmonary function test requires patients' effort in idiopathic pulmonary fibrosis • Forced oscillation technique can be noninvasively performed during normal breathing • Results of forced oscillation technique and pulmonary function test were correlated • Respiratory reactance predicted subsequent lung capacity deterioration • Respiratory reactance reflects disease severity in idiopathic pulmonary fibrosis Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease. Although pulmonary function test (PFT) is useful for evaluating the progression of IPF, obtaining adequate results in advanced cases can be challenging. Conversely, the forced oscillation technique (FOT) can be noninvasively performed, even in patients with severely deteriorated lung function. In this study, the usefulness of FOT for the evaluation of IPF disease status was investigated. We analyzed the PFT and FOT data of 97 patients with IPF. The respiratory reactance (Xrs) components of FOT, especially in the inspiratory phase, correlated with the PFT values. Patients with advanced disease had significantly lower reactance at 5 Hz (X5), higher resonant frequency (Fres) and low-frequency reactance area (ALX). The longitudinal deterioration of Xrs was also observed. Moreover, X5 in the inspiratory phase predicted subsequent lung capacity deterioration. The Xrs components of FOT, especially in the inspiratory phase, reflected restrictive ventilatory impairment and disease severity in patients with IPF. [ABSTRACT FROM AUTHOR]