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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. [ABSTRACT FROM AUTHOR]

Presents a study which evaluated an alternative approach to the feasibility of partitioning respiratory impedance into its airway and tissular components. Reliability of body plethysmography to partition respiratory impedence; Comparison of technical variants for partitioning respiratory impedence; Materials and methods used in the study.

Enhanced intrapulmonary gas transport enables oscillatory ventilation modalities to support gas exchange using extremely low tidal volumes at high frequencies. However, it is unknown whether gas transport rates can be improved by combining multiple frequencies of oscillation simultaneously. The goal of this study was to investigate distributed gas transport in vivo during multi-frequency oscillatory ventilation (MFOV) as compared with conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). We hypothesized that MFOV would result in more uniform rates of gas transport compared to HFOV, measured using contrast-enhanced CT imaging during wash-in of xenon gas. In 13 pigs, xenon wash-in equilibration rates were comparable between CMV and MFOV, but 21 to 39% slower for HFOV. By contrast, the root-mean-square delivered volume was lowest for MFOV, increased by 70% during HFOV and 365% during CMV. Overall gas transport heterogeneity was similar across all modalities, but gravitational gradients and regional patchiness of specific ventilation contributed to regional ventilation heterogeneity, depending on ventilator modality. We conclude that MFOV combines benefits of low lung stretch, similar to HFOV, but with fast rates of gas transport, similar to CMV. [ABSTRACT FROM AUTHOR]

Background. In patients with multiple sclerosis (MS), there is a decline in muscle strength and physical capacity due to demyelination and axonal loss in the central nervous system. In patients with advanced MS or in a later stage of the disease, also respiratory impairment may occur. The degree of pulmonary dysfunction in the earlier stages of MS has not been thoroughly described. Therefore, the primary aims of this study are to describe pulmonary function and respiratory muscle strength in patients with a moderate disease course and to identify associations between respiratory muscle strength and functional capacity. Methods. A sample of 48 patients with a diagnosis of MS and mean age 56 ± 11 years was studied using a descriptive cross-sectional design. The patients had a disease duration of 24 ± 11 years and a median Expanded Disability Status Scale (EDSS) score of 4.5 (interquartile range 4.0-6.5). Pulmonary function assessed by spirometry, respiratory muscle strength, peak cough flow and peripheral oxygen saturation, subjective breathing and coughing ability, and physical capacity measured using the 6MWT were evaluated. Results. The patients had normal pulmonary function with no significant abnormalities in dynamic spirometry (vital capacity 103 ± 16 % predicted, forced expiratory volume in 1 second 95 ± 15 % predicted). Peak expiratory flow rate 89 ± 17 % predicted was in the lower limit of normal. Respiratory muscle strength, determined by maximal inspiratory (MIP) and expiratory (MEP) static pressures, was normal but with large differences between individuals. MIP ranged from 26 to 143 cmH2O (98 ± 31 % predicted); the MEP values ranged from 43 to 166 cmH2O (104 ± 29 % predicted), with two patients having values below the lower limit of normal. Significant positive associations between MIP as well as MEP were found in several pulmonary function variables. A significant negative association was found between EDSS score and MEP (r = − 0.312 , p = 0.031). Mean peak cough flow was 389 ± 70 L/min, which is comparable with the values reported for healthy adults. The patients did not experience a severely decreased ability to take deep breaths or cough. There was a moderate correlation between MEP and physical capacity, as assessed by the 6MWT (r = 0.399 , p = 0.010) and between peak expiratory flow (PEF) and the 6MWT (r = 0.311 , p = 0.048). Conclusion. Respiratory muscle strength, pulmonary function assessed by spirometry, and peak cough flow were normal in patients with mild to moderate MS; however, there were large individual differences demonstrating low respiratory muscle strength in some patients. Significant associations between MEP and functional capacity and between MEP and disease severity were found, indicating that patients with impaired respiratory muscle strength have lower functional capacity and more severe disease. [ABSTRACT FROM AUTHOR]

Capnography, the measurement of the concentration of carbon dioxide in exhaled air has the potential to provide insight into the diagnosis of many cardiopulmonary diseases. Our objective is to develop an effective deep learning algorithm to analyze capnograph and thereby diagnose Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF). In this paper, we propose a novel 1D Deformable Convolutional Neural Network for the quantitative analysis of the capnograph. A learnable and deformable convolution layer and pooling layer are incorporated in 1D Convolutional Neural Network (CNN) to form a 1D Deformable CNN. The feature extraction and classification which are the main two steps in quantitative analysis of capnograph are fused into a single learning system in the proposed architecture. The learnable parameters are extracted by backpropagating the error. The proposed system classifies the capnographic signals extracted using a speed of sound-based sensor and the signal from a reference database into three classes namely, Healthy, COPD and CHF. The experimental results were clinically validated. Performance analysis yields an average classification accuracy of 92.9% and 92.16% for the signal from the reference database and the signal acquired using the sensor respectively. The performance depicts the feasibility of the proposed 1D Deformable CNN to replace existing methods for diagnosis using capnograph. The analysis shows that better learning is achieved in 1D Deformable CNN compared to state-of-the-art techniques. Moreover, no prior knowledge is required to use the system because the proposed method performs feature extraction and classification automatically. [ABSTRACT FROM AUTHOR]

Auscultation is the most efficient way to diagnose cardiovascular and respiratory diseases. To reach accurate diagnoses, a device must be able to recognize heart and lung sounds from various clinical situations. However, the recorded chest sounds are mixed by heart and lung sounds. Thus, effectively separating these two sounds is critical in the pre-processing stage. Recent advances in machine learning have progressed on monaural source separations, but most of the well-known techniques require paired mixed sounds and individual pure sounds for model training. As the preparation of pure heart and lung sounds is difficult, special designs must be considered to derive effective heart and lung sound separation techniques. In this study, we proposed a novel periodicity-coded deep auto-encoder (PC-DAE) approach to separate mixed heart-lung sounds in an unsupervised manner via the assumption of different periodicities between heart rate and respiration rate. The PC-DAE benefits from deep-learning-based models by extracting representative features and considers the periodicity of heart and lung sounds to carry out the separation. We evaluated PC-DAE on two datasets. The first one includes sounds from the Student Auscultation Manikin (SAM), and the second is prepared by recording chest sounds in real-world conditions. Experimental results indicate that PC-DAE outperforms several well-known separation works in terms of standardized evaluation metrics. Moreover, waveforms and spectrograms demonstrate the effectiveness of PC-DAE compared to existing approaches. It is also confirmed that by using the proposed PC-DAE as a pre-processing stage, the heart sound recognition accuracies can be notably boosted. The experimental results confirmed the effectiveness of PC-DAE and its potential to be used in clinical applications. [ABSTRACT FROM AUTHOR]

The development of attosecond pump–probe experiments at high repetition rate requires the development of novel attosecond sources maintaining a sufficient number of photons per pulse. We use 7 fs, 800 nm pulses from a non-collinear optical parametric chirped pulse amplification laser system to generate few-pulse attosecond pulse trains (APTs) with a flux of >106 photons per shot in the extreme ultraviolet at a repetition rate of 100 kHz. The pulse trains have been fully characterised by recording frequency-resolved optical gating for complete reconstruction of attosecond bursts (FROG-CRAB) traces with a velocity map imaging spectrometer. For the pulse retrieval from the FROG-CRAB trace a new ensemble retrieval algorithm has been employed that enables the reconstruction of the shape of the APTs in the presence of carrier envelope phase fluctuations of the few-cycle laser system. [ABSTRACT FROM AUTHOR]

Background: Massively obese subjects frequently undergo pulmonary function tests nowadays. Obesity-associated decreases in key operating lung volumes (reduced inspiratory capacity and reduced vital capacity) are particularly concerning because they may shorten the "room" for tidal volume expansion with negative physiologic and sensory consequences.Research Question: Is massive obesity associated with reduced operating lung volumes? If so, is this effect more pronounced in men than women?Study Design and Methods: We performed an observational, retrospective study in a tertiary, hospital-based laboratory. Pulmonary function test results from 248 super-obese (SO; BMI, 50 to 59.9 kg/m2) and 83 super-super obese (SSO; BMI, ≥60 kg/m2) men and women were analyzed. Electronic medical records were screened to ensure that subjects were free of any disease that potentially could interfere with lung volumes.Results: The prevalence of a low total lung capacity (restriction) was 26.9%, which increased to 38.6% in SSO. Despite the absence of between-sex differences in BMI and spirometric variables derived from the forced maneuver in both SO and SSO, men presented with higher prevalence of restriction (46.7%) than women (19.4%) (P < .05). Between-sex differences in residual volume differed according to the BMI group; SO men presented with higher values than SO women; the opposite was found in the SSO group. The prevalence of restriction with low operating lung volumes was approximately twice (SSO) and approximately thrice (SSO) as high in men compared with women (P < .01). Linear prediction equations as a function of sex, demographic, and anthropometric attributes markedly reduced the prevalence of these abnormalities across the population.Interpretation: Obesity-related restriction leading to low operating lung volumes is highly prevalent in the massively obese subject, particularly in men. These alterations that are associated with massive obesity should be taken into consideration for an accurate interpretation of pulmonary function tests in this growing population. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies revealed substantially varying therapy efficacy of automatic continuous positive airway pressure (APAP) devices in the treatment of obstructive sleep apnea (OSA). We evaluated the efficacy of a new APAP device using the forced oscillation technique (FOT) to evaluate upper airway obstruction during apneas and flow contour analyses during hypopneas. Methods: Forty-six initially diagnosed OSA patients were included and the pressure range was set from 5 to 20 hPa. Therapy efficacy was assessed based on the reduction of apnea-hypopnea index (AHI), improvement of objective sleep quality parameters, and the appropriateness of the device's pressure regulation. Results: AHI and arousal index significantly decreased during APAP therapy (median [interquartile range]: AHI 36 [23–55] vs. 2 [1–6]/h, arousal index 30 [22–45] vs. 15 [10–19]/h, both p < 0.001). The amount of slow wave sleep (SWS) and rapid-eye-movement (REM) sleep significantly increased (SWS 20 [14–29] vs. 29 [19–34]%, REM 16 [11–21] vs. 24 [14–30]%, both p < 0.01). Most residual respiratory events during therapy were of central etiology and attributable to five patients, who presented with treatment-emergent central sleep apnea. The device's pressure regulation abolished most obstructive respiratory events (n = 6.7 residual obstructive events per patient). Of central respiratory events, 534/646 (83%) did not lead to pressure increases. Conclusion: This pilot study provides a proof of concept that the APAP device combining FOT and evaluation of flow contour allows for the suppression of obstructive events without relevant false reactions. [ABSTRACT FROM AUTHOR]

We present an automated point-of-care testing (POCT) system for rapid detection of species- and resistance markers in methicillin-resistant Staphylococcus aureus (MRSA) at the level of single cells, directly from nasal swab samples. Our novel system allows clear differentiation between MRSA, methicillin-sensitive S. aureus (MSSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS), which is not the case for currently used real-time quantitative PCR based systems. On top, the novel approach outcompetes the culture-based methods in terms of its short time-to-result (1 h vs. up to 60 h) and reduces manual labor. The walk-away test is fully automated on the centrifugal microfluidic LabDisk platform. The LabDisk cartridge comprises the unit operations swab-uptake, reagent pre-storage, distribution of the sample into 20 000 droplets, specific enzymatic lysis of Staphylococcus spp. and recombinase polymerase amplification (RPA) of species (vicK) – and resistance (mecA) -markers. LabDisk actuation, incubation and multi-channel fluorescence detection is demonstrated with a clinical isolate and spiked nasal swab samples down to a limit of detection (LOD) of 3 ± 0.3 CFU μl−1 for MRSA. The novel approach of the digital single cell detection is suggested to improve hospital admission screening, timely decision making, and goal-oriented antibiotic therapy. The implementation of a higher degree of multiplexing is required to translate the results into clinical practice. [ABSTRACT FROM AUTHOR]

Forced expiration is the most commonly applied lung function tests. Despite the problem of spirometry modeling was solved a few decades ago, a relatively small amount of work has been devoted to indirect measurements of lung properties from spirometry data. Just recently, a new method, based on the reduced model for forced expiration and two-stage estimation (global with the feed-forward neural network approximating the inverse mapping (InvNN) and then local with the Levenberg–Marquardt algorithm, starting with the rough estimates yielded by the InvNN) was proposed. The aim of this work was to evaluate the accuracy of the above approach to the indirect measurement of lung properties. To this end, 16,000 synthetic spirometry results were generated, and then used to optimize, train, and validate the InvNN, and to test the entire method. The total estimation errors of model parameters were from 3.7% to 16.6% in relation to their variability ranges. Those original estimates were then recalculated to clinically interpretable airway resistances and compliances, assessed with the relative errors of 7%–35% and 5%–12%, respectively. These outcomes encourage the future use of the method to analyze the results of bronchial challenge or dilation tests. [ABSTRACT FROM AUTHOR]

Chronic respiratory symptoms are frequently reported after Southwest Asia deployment in support of combat operations. The full spectrum of clinical lung diseases related to these deployments is not well characterized. Military personnel with chronic symptoms, primarily exertional dyspnea, underwent a standardized cardiopulmonary evaluation at two tertiary medical centers. Pulmonary function testing consisted of spirometry, lung volume, diffusing capacity, impulse oscillometry, and bronchodilator testing. Further testing included methacholine challenge, exercise laryngoscopy, high-resolution CT scan, ECG, and transthoracic echocardiography. A total of 380 participants with a mean age of 38.5 ± 8.4 years completed testing. Asthma was the most common diagnosis in 87 patients (22.9%) based on obstructive spirometry/impulse oscillometry and evidence of airway hyperreactivity, whereas another 57 patients (15.0%) had reactivity with normal spirometry. Airway disorders included 25 (6.6%) with laryngeal disorders and 16 (4.2%) with excessive dynamic airway collapse. Interstitial lung disease was identified in six patients (1.6%), whereas 11 patients (2.9%) had fixed obstructive lung disorders. Forty patients (10.5%) had isolated pulmonary function abnormalities and 16 (4.2%) had miscellaneous disorders. The remaining 122 patients (32.1%) with normal studies were classified as undiagnosed exertional dyspnea. Significant comorbidities identified included elevated BMI > 30 kg/m2 (34.2%), smoking (36.4%), positive allergy testing (43.7%), sleep apnea (38.5%), and esophageal reflux (13.6%). Mental health disorders and posttraumatic stress disorder were likewise common. Postdeployment pulmonary evaluation should focus on common diseases, such as asthma and airway hyperreactivity, and include testing for upper airway disorders. Diffuse lung diseases were rarely diagnosed, whereas numerous comorbidities were common. [ABSTRACT FROM AUTHOR]

Objective: Several commercial and custom-made forced oscillation technique (FOT) devices are used to assess respiratory system impedance. The impulse oscillometry system (IOS) is a widespread device, which yields similar but not identical results to those provided by other FOT systems. Differences may be related to the forcing waveform, the device hardware, or the data processing algorithms. We evaluated the agreement between resistance (Rrs) and reactance (Xrs) measurements while alternating between different forcing waveforms and data processing algorithms. Approach: We performed pre- and post-bronchodilator measurements in 20 patients with respiratory complaints. We generated pulse waveforms using an IOS, and sinusoidal oscillations by replacing the IOS loudspeaker with customized loudspeaker providing a 5 Hz sinusoidal pressure signal. Pressure and flow were measured using the IOS sensors and breathing circuit. We developed a data processing algorithm compatible to both forcing signals. We also applied commercial IOS software during pulse waveform and a least mean square (lms) algorithm during sinusoidal waveform. Main results: The median (5th, 95th percentile) differences between Rrs and Xrs were (1) −0.35 (−2.49, 1.23) and 0.16 (−1.63, 3.07 cmH2O*s l−1, when the same algorithm was used during pulse vs sinusoidal stimulus; (2) 0.34 (−2.33, 5.98) and 0.57 (−2.64, 6.09) cmH2O*s l−1, when our algorithm and the IOS software were used during pulse waveform; and (3) 0.33 (−1.20, 6.05) and 0.25 (−4.94, 4.28) cmH2O*s l−1 when the IOS software was used during pulse and the lms algorithm during sinusoidal waveforms. Significance: Both forcing signal and data processing contribute to differences in impedance values measured by different FOT devices. [ABSTRACT FROM AUTHOR]

Background: Clinical characteristics of the international population with severe asthma are unknown. Intercountry comparisons are hindered by variable data collection within regional and national severe asthma registries. We aimed to describe demographic and clinical characteristics of patients treated in severe asthma services in the United States, Europe, and the Asia-Pacific region.Methods: The International Severe Asthma Registry retrospectively and prospectively collected data in patients with severe asthma (≥ 18 years old), receiving Global Initiative for Asthma (GINA) Step 5 treatment or with severe asthma remaining uncontrolled at GINA Step 4. Baseline demographic and clinical data were collected from the United States, United Kingdom, South Korea, Italy, and the Severe Asthma Web-based Database registry (including Australia, Singapore, and New Zealand) from December 2014 to December 2017.Results: We included 4,990 patients. Mean (SD) age was 55.0 (15.9) years, and mean (SD) age at asthma onset was 30.7 (17.7) years. Patients were predominantly female (59.3%) and white (72.6%), had never smoked (60.5%), and were overweight or obese (70.4%); 34.9% were at GINA Step 5; and 57.2% had poorly controlled disease. A total of 51.1% of patients were receiving regular intermittent oral corticosteroids, and 25.4% were receiving biologics (72.6% for those at GINA Step 5). Mean (SD) exacerbation rate was 1.7 (2.7) per year. Intercountry variation was observed in clinical characteristics, prescribed treatments, and biomarker profiles.Conclusions: Using a common data set and definitions, this study describes severe asthma characteristics of a large patient cohort included in multiple severe asthma registries and identifies country differences. Whether these are related to underlying epidemiological factors, environmental factors, phenotypes, asthma management systems, treatment access, and/or cultural factors requires further study. [ABSTRACT FROM AUTHOR]

Little is known about the association between physical activity and lung function in childhood. We conducted a survey including parental reports of the child's participation in physical activity and measurements of lung function. The associations between physical activity and lung function were estimated by linear regression analysis adjusting for potential confounders in 2,537 children (9 to 10 years). Using the linear model in exploring the effect of physical activity on lung function with those who were physical active less than once a week as the reference category, showed that forced expiratory volume in 1 s (FEV1) was highest among those who were physical active ≥ 4 times a week also when adjusting for potential confounders (p = .02). FEV1 increased with 70 ml. A similar pattern was present for forced vital capacity (FVC; p = .002). The present study suggested that lung function was highest in highly physical active children age 9 to 10 years. The implications are that exercise may influence lung function, but these findings need to be confirmed using a longitudinal study design. [ABSTRACT FROM AUTHOR]

Pulmonary function was measured in 48 air divers (age range: 8-38 yr) and 56 control participants (age range: 8-34 yr). Static lung volumes, dynamic lung volumes and flows, and the pulmonary diffusing capacity for carbon monoxide were measured twice, 29 months apart. At both times the adult divers (>18 years) had higher forced vital capacity, forced expiratory volume in 1 s and maximal expiratory flow rate at 50%, as well as lower pulmonary diffusing capacity for carbon monoxide, than did the adult controls. Whatever the age, mean annual changes in these parameters did not differ between groups. Our results indicate that there were no significant changes in pulmonary function in the young (8-12 years), adolescent, or adult divers compared with healthy controls over the 29-month period. The mean annual changes in forced expiratory flow and volume, however, were negatively correlated with number of years of diving experience in adult divers and with maximal diving depth in adolescent (13-18 yr) divers (p < .05 and p < .001, respectively). Deep diving during the teenage years coupled with years of recreational diving might increase the risk of airway obstruction. [ABSTRACT FROM AUTHOR]

Frequency dependence of respiratory mechanics is a well-established behavior of the respiratory system and is known to be an indicator of severity of obstructive disease, attributed to both tissue viscoelasticity and heterogeneity of airflow in the lung. Despite the fact that respiratory parameters are known to vary in time, often amplified in disease, all analysis methods assume stationarity or short-time stationarity in the parameters used to describe the respiratory system, and the effects of this assumption have not yet been examined in any detail. Here, using a generalized approach, we developed a theory for time-varying respiratory mechanics in time-frequency domain for analysis of linear time-varying systems, then, we analyzed the same respiratory system model with time-varying parameters in the time domain. Both time-frequency domain and time-domain derivations revealed a striking correlation between time-varying behavior of the respiratory system and frequency dependence of resistance. Remarkably, this phenomenon arose from the amplitude of time variations of the elastance. This links two mechanisms that are known to increase in obstructive disease: apparent low frequency increases in resistance and the time variations of reactance. [ABSTRACT FROM AUTHOR]

Background: Heroin smoking is associated with deprivation, early onset severe emphysema, premature morbidity and mortality, and high use of health care, but individuals engage poorly with traditional health services.Methods: In this cross-sectional study, we screened a population of heroin smokers, prescribed opiate substitution therapy by community drug services, for airway disease. We assessed drug exposure, respiratory symptoms, health status, and COPD prevalence. Subjects completed spirometry, completed Medical Research Council (MRC) Dyspnea Scale, COPD Assessment Tool (CAT) questionnaire, recorded drug exposure, and provided feedback.Results: A total of 753 people (73% of those approached) completed screening, with 260 participants (35%) having COPD using FEV1/FVC < 0.7 and 293 (39%) participants having COPD using the lower limit of normal. A further 112 participants (15%) had asthma-COPD overlap (ACO) with features of COPD and asthma. Compared with those with normal spirometry, participants with COPD were more breathless (MRC score 3.1 vs 1.9; P < .001) and had worse health status (CAT score 22.9 vs 13.4; P < .001), respectively. Individuals with COPD had smoked cigarettes (P < .001), heroin (P < .001), and crack (P = .03) for longer and were more likely to still be smoking heroin (P < .01). Feedback was strongly positive, with 92% of respondents happy for other health-care appointments to be colocated with drug key worker appointments.Conclusions: Most heroin smokers had COPD or ACO, most commonly mild to moderate disease. In high-risk areas, screening this population provides an opportunity to reduce symptoms and risk. Anchoring respiratory health screening to drug center appointments delivers high completion and satisfaction and is an appropriate model for screening other hard-to-reach populations. [ABSTRACT FROM AUTHOR]

Purpose: This study supports the use of thin-film micro-electro-mechanical system (MEMS) airflow sensors in the forced oscillation technique. Materials and methods: The study employed static testing using air flow standards and computer-controlled sound attenuations at 8 Hz. Human feasibility studies were conducted with a testing apparatus consisting of a pneumotach and thin-film MEMS air flow sensors in series. Short-time Fourier transform spectra were obtained using SIGVIEW software. Results: Three tests were performed, and excellent correlations were observed between the probes. The thin-film MEMS probe showed superior sensitivity to higher frequencies up to 200 Hz. Conclusion: The results suggest that lower-cost thin-film MEMS can be used for forced oscillation technique applications (including home care devices) that will benefit patients suffering from pulmonary diseases such as asthma, COPD, and cystic fibrosis. [ABSTRACT FROM AUTHOR]

Expiratory flow limitation (EFL) is present when the flow cannot rise despite an increase in the expiratory driving pressure. The mechanisms of EFL are debated but are believed to be related to the collapsibility of small airways. In patients who are mechanically ventilated, EFL can exist during tidal ventilation, representing an extreme situation in which lung volume cannot decrease, regardless of the expiratory driving forces. It is a key factor for the generation of auto- or intrinsic positive end-expiratory pressure (PEEP) and requires specific management such as positioning and adjustment of external PEEP. EFL can be responsible for causing dyspnea and patient-ventilator dyssynchrony, and it is influenced by the fluid status of the patient. EFL frequently affects patients with COPD, obesity, and heart failure, as well as patients with ARDS, especially at low PEEP. EFL is, however, most often unrecognized in the clinical setting despite being associated with complications of mechanical ventilation and poor outcomes such as postoperative pulmonary complications, extubation failure, and possibly airway injury in ARDS. Therefore, prompt recognition might help the management of patients being mechanically ventilated who have EFL and could potentially influence outcome. EFL can be suspected by using different means, and this review summarizes the methods to specifically detect EFL during mechanical ventilation. [ABSTRACT FROM AUTHOR]

The upper airway (UA) in humans is commonly modeled as a Starling resistor. However, negative effort dependence (NED) observed in some patients with obstructive sleep apnea (OSA) contradicts predictions based on the Starling resistor model in which inspiratory flow is independent of inspiratory driving pressure when flow is limited. In a respiratory bench model consisting of a collapsible tube and an active lung model (ASL5000), inspiratory flow characteristics were investigated in relation to upstream, downstream, and extra-luminal pressures (denoted as Pus, Pds, and Pout, respectively) by varying inspiratory effort (muscle pressure) from −1 to −20 cmH2O in the active lung. Pus was provided by a constant airway pressure device and varied from 4 to 20 cmH2O, and Pout was set at 10 and 15 cmH2O. Upstream resistance at onset of flow limitation and critical transmural pressure (Ptm) corresponding to opening of the UA were found to be independent of Pus, Pds, and Pout. With fixed Ptm, when Pds fell below a specific value (Pds′), inspiratory peak flow became constant and independent of Pds. NED plateau flow patterns at mid-inspiration (V̇n) were produced within the current bench setting when Pds fell below Pds′. V̇n was proportional to Pds, and the slope (ΔV̇n/ΔPds) increased linearly with Ptm. Ptm and Pds were the two final independent determinants of inspiratory flow. Our bench model closely mimics a flow-limited human UA, and the findings have implications for OSA treatment and research, especially for bench-testing auto-titrating devices in a more physiological way. NEW & NOTEWORTHY A respiratory model consisting of a collapsible tube was used to mimic a flow-limited human upper airway. Flow-limited breathing patterns including negative effort dependence were produced. Transmural and downstream pressures acting on the tube are the two independent determinants of the resulting inspiratory flow during flow limitation. The findings have implications for obstructive sleep apnea treatment and research, especially for bench-testing auto-titrating devices in a more physiological way. [ABSTRACT FROM AUTHOR]

Calcium carbonate nanomaterials (nano-CaCO3) are widely used in both manufacturing and consumer products, but their potential health hazards remain unclear. The objective of this study was to survey workplace exposure levels and health effects of workers exposed to nano-CaCO3. Personal and area sampling, as well as real-time and dust monitoring, were performed to characterize mass exposure, particle size distribution, and particle number exposure. A total of 56 workers (28 exposed workers and 28 unexposed controls) were studied in a cross-sectional study. They completed physical examinations, spirometry, and digital radiography. The results showed that the gravimetric nano-CaCO3 concentration was 5.264 ± 6.987 mg/m3 (0.037-22.192 mg/m3) at the workplace, and 3.577 ± 2.065 mg/m3 (2.042-8.161 mg/m3) in the breathing zone of the exposed workers. The particle number concentrations ranged from 8193 to 39 621 particles/cm3 with a size range of 30-150 nm. The process of packing had the highest gravimetric and particle number concentrations. The particle number concentration positively correlated with gravimetric concentrations of nano-CaCO3. The levels of hemoglobin, creatine phosphokinase (CK), lactate dehydrogenase, and high-density lipoprotein cholesterol (HDL-C) in the nano-CaCO3 exposure group increased significantly, but the white blood cell count (WBC), Complement 3 (C3), total protein (TP), uric acid, and creatinine (CREA) all decreased significantly. The prevalence rate of pulmonary hypofunction was significantly higher (p = 0.037), and the levels of vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, peak expiratory flow and forced expiratory flow 25% (FEF 25%), FEF 25-75% were negatively correlated with gravimetric concentrations of nano-CaCO3 (p < 0.05). Logistic analysis showed that nano-CaCO3 exposure level was associated with pulmonary hypofunction (p = 0.005). Meanwhile, a dose-effect relationship was found between the accumulated gravimetric concentrations of nano-CaCO3 and the prevalence rate of pulmonary hypofunction (p = 0.048). In conclusion, long-term and high-level nano-CaCO3 exposure can induce pulmonary hypofunction in workers. Thus, lung function examination is suggested for occupational populations with nano-CaCO3 exposure. Furthermore, future health protection efforts should focus on senior workers with accumulation effects of nano-CaCO3 exposure. [ABSTRACT FROM AUTHOR]

Particulate matter levels and physiological parameters of 150 school going children were monitored continually for 3 years (2013-2016) at three agriculturally active sites. Percent changes in physiological parameters like forced vital capacity, peak expiratory flow, etc. were estimated using mixed effect model with adjustment of covariates such as BMI. Results show that the increase in fine PM levels were much more in rice seasons than in wheat seasons. During the burning episodes, severe adverse effects on physiological parameters of the selected subjects were observed due to enhanced PM2.5 levels. Significant changes were observed in FVC (− 5.27 to − 7.53%) and PEF (− 4.89 to − 7.12%) in comparison to FEV1 and FEF25-75%. Respiratory health in terms of FVC and PEF corresponded very well with the body mass indices of the human subjects for different PM levels in the ambient air. The subjects having lower BMI level were affected more than those with normal and high BMI on exposure to same level of fine particulate matter. It has been concluded that the trends of fall in respiratory parameters were alarming especially for the subjects with lower and higher BMI during crop residue burning episodes. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this report was to illustrate how thoracic gas compression (TGC) artifact, and differences in air density, may together conflate the interpretation of changes in the forced expiratory flows (FEFs) at high altitude (>2400 m). Twenty‐four adults (10 women; 44 ± 15 year) with normal baseline pulmonary function (>90% predicted) completed a 12‐day sojourn at Mt. Kilimanjaro. Participants were assessed at Moshi (Day 0, 853 m) and at Barafu Camp (Day 9, 4837 m). Typical maximal expiratory flow‐volume (MEFV) curves were obtained in accordance with ATS/ERS guidelines, and were either: (1) left unadjusted; (2) adjusted for TGC by constructing a “maximal perimeter” MEFV curve; or (3) adjusted for both TGC and differences in air density between altitudes. Forced vital capacity (FVC) was lower at Barafu compared with Moshi camp (5.19 ± 1.29 L vs. 5.40 ± 1.45 L, P < 0.05). Unadjusted data indicated no difference in the mid‐expiratory flows (FEF25–75%) between altitudes (∆ + 0.03 ± 0.53 L sec−1; ∆ + 1.2 ± 11.9%). Conversely, TGC‐adjusted data revealed that FEF25–75% was significantly improved by sojourning at high altitude (∆ + 0.58 ± 0.78 L sec−1; ∆ + 12.9 ± 16.5%, P < 0.05). Finally, when data were adjusted for TGC and air density, FEFs were “less than expected” due to the lower air density at Barafu compared with Moshi camp (∆–0.54 ± 0.68 L sec−1; ∆–10.9 ± 13.0%, P < 0.05), indicating a mild obstructive defect had developed on ascent to high altitude. These findings clearly demonstrate the influence that TGC artifact, and differences in air density, bear on flow‐volume data; consequently, it is imperative that future investigators adjust for, or at least acknowledge, these confounding factors when comparing FEFs between altitudes. [ABSTRACT FROM AUTHOR]

The measurement of lung function in mice and rats is crucial for understanding how well small animal models of pulmonary disease recapitulate human clinical pathology but brings with it the challenge of making accurate measurements in animals as small as a mouse. Overcoming these challenges can be achieved in a number of ways, each based on a model idealization of how the lung works as a mechanical system. Accordingly, it is important to understand the theoretical basis on which an assessment of lung function rests to interpret experimental measurements appropriately. It is also crucial to attend to a number of practical issues that determine the quality of the measurements. The most accurate measurements of lung function in small animals are provided by the forced oscillation technique that provides lung resistance and elastance and its multifrequency generalization known as impedance. Measurement quality is maximized when the greatest possible degree of control is exerted over the amplitude and frequency with which air is oscillated in and out of the lungs, the mean or end-expiratory transpulmonary pressure pertaining to when the oscillations are applied, and the immediate past volume history of the lungs. It is also crucial that no spontaneous breathing efforts occur during the measurement period. Finally, there is no substitute for the skill in animal handling and surgical preparation that comes with practice; such a skill should be in place before embarking on any important series of experiments. [ABSTRACT FROM AUTHOR]

This report summarizes the proceedings of the American Thoracic Society Workshop on the Noninvasive Identification of Inspiratory Flow Limitation in Sleep Studies held on May 16, 2015, in Denver, Colorado. The goal of the workshop was to discuss methods for standardizing the scoring of flow limitation from nasal cannula pressure tracings. The workshop began with presentations on the physiology underlying flow limitation, existing methods of scoring flow limitation, the effects of signal acquisition and filtering on flow shapes, and a review of the literature examining the adverse outcomes related to flow limitation. After these presentations, the results from online scoring exercises, which were crowdsourced to workshop participants in advance of the workshop, were reviewed and discussed. Break-out sessions were then held to discuss potential algorithms for scoring flow limitation. Based on these discussions, subsequent online scoring exercises, and webinars after the workshop, a consensus-based set of recommendations for a scoring algorithm for flow limitation was developed. Key conclusions from the workshop were: (1) a standardized and automated approach to scoring flow limitation is needed to provide a metric of nonepisodic elevated upper airway resistance, which can then be related to clinical outcomes in large cohorts and patient groups; (2) at this time, the most feasible method for standardization is by proposing a consensus-based framework, which includes scoring rules, developed by experts (3) hardware and software settings of acquisition devices, including filter settings, affect the shape of the flow curve, and should be clearly specified; and (4) a priority for future research is the generation of an open-source, expert-derived training set to encourage and support validation of automated flow limitation scoring algorithms. [ABSTRACT FROM AUTHOR]

While controlled ventilation is most frequently used during cardiopulmonary resuscitation (CPR), the application of continuous positive airway pressure (CPAP) and passive ventilation of the lung synchronously with chest compressions and decompressions might represent a promising alternative approach. One benefit of CPAP during CPR is the reduction of peak airway pressures and therefore a potential enhancement in haemodynamics. We therefore evaluated the tidal volumes and airway pressures achieved during CPAP-CPR. During CPR with the LUCAS™ 2 compression device, a manikin model was passively ventilated at CPAP levels of 5, 10, 20 and 30 hPa with the Boussignac tracheal tube and the ventilators Evita® V500, Medumat® Transport, Oxylator® EMX, Oxylog® 2000, Oxylog® 3000, Primus® and Servo®-i as well as the Wenoll® diver rescue system. Tidal volumes and airway pressures during CPAP-CPR were recorded and analyzed. Tidal volumes during CPAP-CPR were higher than during compression-only CPR without positive airway pressure. The passively generated tidal volumes increased with increasing CPAP levels and were significantly influenced by the ventilators used. During ventilation at 20 hPa CPAP via a tracheal tube, the mean tidal volumes ranged from 125 ml (Medumat®) to 309 ml (Wenoll®) and the peak airway pressures from 23 hPa (Primus®) to 49 hPa (Oxylog® 3000). Transport ventilators generated lower tidal volumes than intensive care ventilators or closed-circuit systems. Peak airway pressures during CPAP-CPR were lower than those during controlled ventilation CPR reported in literature. High peak airway pressures are known to limit the applicability of ventilation via facemask or via supraglottic airway devices and may adversely affect haemodynamics. Hence, the application of ventilators generating high tidal volumes with low peak airway pressures appears desirable during CPAP-CPR. The limited CPAP-CPR capabilities of transport ventilators in our study might be prerequisite for future developments of transport ventilators. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the pharmacokinetics and pharmacodynamics of CVT-301, an inhalation powder formulation of levodopa, as treatment of OFF episodes in patients with Parkinson's disease (PD). Also cited are the effects of CVT-301 in dogs, cough as the most common adverse event during preclinical trials, and the rapid absorption of inhaled CVT-301 in humans.

This paper presents a method for breath-by-breath noninvasive estimation of respiratory resistance and elastance in mechanically ventilated patients. For passive patients, well-established approaches exist. However, when patients are breathing spontaneously, taking into account the diaphragmatic effort in the estimation process is still an open challenge. Mechanical ventilators require maneuvers to obtain reliable estimates for respiratory mechanics parameters. Such maneuvers interfere with the desired ventilation pattern to be delivered to the patient. Alternatively, invasive procedures are needed. The method presented in this paper is a noninvasive way requiring only measurements of airway pressure and flow that are routinely available for ventilated patients. It is based on a first-order single-compartment model of the respiratory system, from which a cost function is constructed as the sum of squared errors between model-based airway pressure predictions and actual measurements. Physiological considerations are translated into mathematical constraints that restrict the space of feasible solutions and make the resulting optimization problem strictly convex. Existing quadratic programming techniques are used to efficiently find the minimizing solution, which yields an estimate of the respiratory system resistance and elastance. The method is illustrated via numerical examples and experimental data from animal tests. Results show that taking into account the patient effort consistently improves the estimation of respiratory mechanics. The method is suitable for real-time patient monitoring, providing clinicians with noninvasive measurements that could be used for diagnosis and therapy optimization. [ABSTRACT FROM AUTHOR]

The effect of exercise on ventilation heterogeneity has not been investigated. We hypothesized that a maximal exercise bout would increase ventilation heterogeneity. We also hypothesized that increased ventilation heterogeneity would be associated with exercise-induced arterial hypoxemia ( EIAH). Healthy trained adult males were prospectively assessed for ventilation heterogeneity using lung clearance index ( LCI), Scond, and Sacin at baseline, postexercise and at recovery, using the multiple breath nitrogen washout technique. The maximal exercise bout consisted of a maximal, incremental cardiopulmonary exercise test at 25 watt increments. Eighteen subjects were recruited with mean ± SD age of 35 ± 9 years. There were no significant changes in LCI, Scond, or Sacin following exercise or at recovery. While there was an overall reduction in SpO2 with exercise (99.3 ± 1 to 93.7 ± 3%, P < 0.0001), the reduction in SpO2 was not associated with changes in LCI, Scond or Sacin. Ventilation heterogeneity is not increased following a maximal exercise bout in healthy trained adults. Furthermore, EIAH is not associated with changes in ventilation heterogeneity in healthy trained adults. [ABSTRACT FROM AUTHOR]

This study presents a rule-based method for automated, real-time snoring detection using nasal pressure recordings during overnight sleep. Although nasal pressure recordings provide information regarding nocturnal breathing abnormalities in a polysomnography (PSG) study or continuous positive airway pressure (CPAP) system, an objective assessment of snoring detection using these nasal pressure recordings has not yet been reported in the literature. Nasal pressure recordings were obtained from 55 patients with obstructive sleep apnea. The PSG data were also recorded simultaneously to evaluate the proposed method. This rule-based method for automatic, real-time snoring detection employed preprocessing, short-time energy and the central difference method. Using this methodology, a sensitivity of 85.4% and a positive predictive value of 92.0% were achieved in all patients. Therefore, we concluded that the proposed method is a simple, portable and cost-effective tool for real-time snoring detection in PSG and CPAP systems that does not require acoustic analysis using a microphone. [ABSTRACT FROM AUTHOR]

Highland populations living permanently under hypobaric hypoxia have been subject of extensive research because of the relevance of their physiological adaptations for the understanding of human health and disease. In this context, what is considered high altitude is a matter of interpretation and while the adaptive processes at high altitude (above 3000 m) are well documented, the effects of moderate altitude (below 3000 m) on the phenotype are less well established. In this study, we compare physiological and anthropometric characteristics as well as genetic variations in two Andean populations: the Calchaquíes (2300 m) and neighboring Collas (3500 m). We compare their phenotype and genotype to the sea-level Wichí population. We measured physiological (heart rate, oxygen saturation, respiration rate, and lung function) as well as anthropometric traits (height, sitting height, weight, forearm, and tibia length). We conducted genome-wide genotyping on a subset of the sample ( n = 74) and performed various scans for positive selection. At the phenotypic level ( n = 179), increased lung capacity stood out in both Andean groups, whereas a growth reduction in distal limbs was only observed at high altitude. At the genome level, Calchaquíes revealed strong signals around PRKG1, suggesting that the nitric oxide pathway may be a target of selection. PRKG1 was highlighted by one of four selection tests among the top five genes using the population branch statistic. Selection tests results of Collas were reported previously. Overall, our study shows that some phenotypic and genetic differentiation occurs at intermediate altitude in response to moderate lifelong selection pressures. [ABSTRACT FROM AUTHOR]

We develop an approach to quantitative analysis of carbon dioxide concentration in exhaled breath, recorded as a function of time by capnography. The generated waveform—or capnogram—is currently used in clinical practice to establish the presence of respiration as well as determine respiratory rate and end-tidal CO 2 concentration. The capnogram shape also has diagnostic value, but is presently assessed qualitatively, by visual inspection. Prior approaches to quantitatively characterizing the capnogram shape have explored the correlation of various geometric parameters with pulmonary function tests. These studies attempted to characterize the capnogram in normal subjects and patients with cardiopulmonary disease, but no consistent progress was made, and no translation into clinical practice was achieved. We apply automated quantitative analysis to discriminate between chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF), and between COPD and normal. Capnograms were collected from 30 normal subjects, 56 COPD patients, and 53 CHF patients. We computationally extract four physiologically based capnogram features. Classification on a hold-out test set was performed by an ensemble of classifiers employing quadratic discriminant analysis, designed through cross validation on a labeled training set. Using 80 exhalations of each capnogram record in the test set, performance analysis with bootstrapping yields areas under the receiver operating characteristic (ROC) curve of 0.89 (95% CI: 0.72–0.96) for COPD/CHF classification, and 0.98 (95% CI: 0.82–1.0) for COPD/normal classification. This classification performance is obtained with a run time sufficiently fast for real-time monitoring. [ABSTRACT FROM PUBLISHER]

The use of sensors and sensing devices in breath analysis is a very recent achievement in medicine. In this study, a portable pre-industrial device capable of monitoring NO in lung exhaled in respect to the ATS/ERS guidelines was designed and manufactured. The proposed equipment, called NOESIS, involved the use of a conductive polymer doped with nanofibres of an electrospun metal oxide, and was characterised by high sensing features, low power consumption, cost-effectiveness and cheapness. The properties of the sensor and the strategies utilised to achieve such results in that device are here reported and discussed. [ABSTRACT FROM AUTHOR]

The forced oscillation technique (FOT) is a lung function test used in clinical practice to evaluate the respiratory impedance. One of the main advantages of FOT over other lung function tests is that it does not require any special breathing maneuvers from the subject, making it one of the simplest tests to evaluate respiratory mechanics. This paper describes the nonlinear effects in the respiratory signals and related measurement instrumentation during the FOT tests. First, this paper discusses some improvements made on a prototype FOT device to allow the generation of multisines below 4 Hz. Second, two methods are evaluated to detect the nonlinear effects: a robust method and a fast method. These methods allow a comparison of the nonlinear distortions in a prototype FOT device and a commercial FOT device. The nonlinear effects are also quantified using a new index definition. FOT lung function tests are performed to obtain two distinct data sets: 1) one mixed group of patients diagnosed with asthma and cystic fibrosis and 2) one group of healthy volunteers. With the extracted nonlinear contributions, a significant difference has been observed between the two groups. This delivers the proof of concept that low-frequency measurements of the respiratory mechanics are useful to evaluate lung pathologies. [ABSTRACT FROM PUBLISHER]

Respiratory impedance measured by the forced oscillation technique (FOT) can be contaminated by artifacts such as coughing, vocalization, swallowing or leaks at the mouthpiece. We present a novel technique to detect these artifacts using multilevel discrete wavelet transforms. FOT was performed with artifacts introduced during separate 60 s recordings at known times in 10 healthy subjects. Brief glottal closures were generated phonetically and confirmed by nasopharyngoscopic imaging of the glottis. Artifacts were detected using Daubechies wavelets by applying a threshold to squared detail coefficients from the wavelet transforms of both pressure and flow signals. Sensitivity and specificity were compared over a range of thresholds for different level squared detail coefficients. Coughs could be identified using 1st level detail (cd1) coefficients of pressure achieving 96% sensitivity and 100% specificity while swallowing could be identified using cd2 thresholds of pressure with 95% sensitivity and 97% specificity. Male vocalizations could be identified using cd1 coefficients with 88% sensitivity and 100% specificity. For leaks at the mouthpiece, cd3 thresholds of flow could identify these events with 98% sensitivity and 99% specificity. Thus, this method provided an accurate, easy, and automated technique for detecting and removing artifacts from measurements of respiratory impedance using FOT. [ABSTRACT FROM AUTHOR]

Assessment of human airway lumen opening is important in diagnosing and understanding the mechanisms of airway dysfunctions such as the excessive airway narrowing in asthma and chronic obstructive pulmonary disease (COPD). Although there are indirect methods to evaluate the airway calibre, direct in vivo measurement of the airway calibre has not been commonly available. With recent advent of the flexible fiber optical nasopharyngoscope with video recording it has become possible to directly visualize the passages of upper and lower airways. However, quantitative analysis of the recorded video images has been technically challenging. Here, we describe an automatic image processing and analysis method that allows for batch analysis of the images recorded during the endoscopic procedure, thus facilitates image-based quantification of the airway opening. Video images of the airway lumen of volunteer subject were acquired using a fiber optical nasopharyngoscope, and subsequently processed using Gaussian smoothing filter, threshold segmentation, differentiation, and Canny image edge detection, respectively. Thus the area of the open airway lumen was identified and computed using a predetermined converter of the image scale to true dimension of the imaged object. With this method we measured the opening/narrowing of the glottis during tidal breathing with or without making "Hee" sound or cough. We also used this method to measure the opening/narrowing of the primary bronchus of either healthy or asthmatic subjects in response to histamine and/or albuterol treatment, which also provided an indicator of the airway contractility. Our results demonstrate that the image-based method accurately quantified the area change waveform of either the glottis or the bronchus as observed by using the optical nasopharygoscope. Importantly, the opening/narrowing of the airway lumen generally correlated with the airflow and resistance of the airways, and could differentiate the level of airway contractility between the healthy and asthmatic subjects. Thus, this quantitative assessment of airway opening may provide a useful tool to assist clinical diagnosis of airway dysfunctions and understanding the mechanisms of associated pathophysiologies. [ABSTRACT FROM AUTHOR]

Byline: M. Vassiliou (2), C. Saunier (1), C. Duvivier (1), P. Behrakis (3), R. Peslin (1) Keywords: Expiratory flow limitation Linear regression Volume dependence of resistance Respiratory impedance Respiratory elastance Respiratory resistance Mechanical ventilation Abstract: The volume dependence of respiratory resistance (Rrs), usually observed during normal breathing, is expected to be accentuated during expiratory flow limitation (EFL). In order to quantify this dependence we studied the pressure, flow, and volume data obtained from eight New Zealand rabbits, artificially ventilated at different levels of applied expiratory pressure (0--10 hPa), before and during histamine i.v. infusion. EFL was provoked by lowering the expiratory pressure and was detected by the application of an additional negative expiratory pressure and by forced oscillations. The analysis of respiratory system mechanics was performed by multiple regression, using the classical linear first-order model and also a nonlinear model, accounting for volume dependence of Rrs. Both models satisfactorily fitted the data in the absence of EFL. The nonlinear model proved to be more appropriate in the presence of EFL. The coefficient expressing the volume dependence of Rrs (Rvd) was significantly more negative during EFL. Rvd values were highly correlated with the fraction of the tidal volume left to be expired at the onset of EFL. A threshold Rvd value of --1,000 (hPa*s*l.sup.--2) detected EFL with high sensitivity and specificity. We conclude that a strongly negative volume dependence of Rrs is a reliable and noninvasive index of EFL during artificial ventilation. Author Affiliation: (1) Unite 14 de Physiopathologie Respiratoire, Institut National de la Sante et de la Recherche Medicale, Universite H. Poincare Nancy I, 54500 Vandoeuvre-les-Nancy, France (2) Distomou Str. 14121, N. Herakleio, Athens, Greece (3) Laboratory of Experimental Physiology, Medical School, University of Athens, Athens, Greece Article History: Received Date: 09/06/2000 Accepted Date: 12/02/2001 Article note: Final revision revised: 12 February 2001 Electronic Publication