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Background Current techniques for measuring absolute lung volumes rely on bulky and expensive equipment and are complicated to use for the operator and the patient. A novel method for measurement of absolute lung volumes, the MiniBox method, is presented. Research Question Across a population of patients and healthy participants, do values for total lung capacity (TLC) determined by the novel compact device (MiniBox, PulmOne Advanced Medical Devices, Ltd.) compare favorably with measurements determined by traditional whole body plethysmography? Study Design and Methods A total of 266 participants (130 men) and respiratory patients were recruited from five global centers (three in Europe and two in the United States). The study population comprised individuals with obstructive (n = 197) and restrictive (n = 33) disorders as well as healthy participants (n = 36). TLC measured by conventional plethysmography (TLCPleth) was compared with TLC measured by the MiniBox (TLCMB). Results TLC values ranged between 2.7 and 10.9 L. The normalized root mean square difference (NSD) between TLCPleth and TLCMB was 7.0% in healthy participants. In obstructed patients, the NSD was 7.9% in mild obstruction and 9.1% in severe obstruction. In restricted patients, the NSD was 7.8% in mild restriction and 13.9% in moderate and severe restriction. No significant differences were found between TLC values obtained by the two measurement techniques. Also no significant differences were found in results obtained among the five centers. Interpretation TLC as measured by the novel MiniBox system is not significantly different from TLC measured by conventional whole body plethysmography, thus validating the MiniBox method as a reliable method to measure absolute lung volumes.

Home monitoring of patients with chronic obstructive pulmonary disease can increase quality of life and decrease health care costs. Despite the existence of an important relationship between lung hyperinflation (LH) and patient outcomes, LH is often ignored in home monitoring as it difficult to assess at home. A smart shirt containing respiratory inductance plethysmography (RIP, which measures thoracic and abdominal cross-sectional area changes) is a promising tool for home monitoring of LH. This study investigates the feasibility of a smart shirt to monitor LH. We aimed to describe the relationship between temperature and the output, and between the circumference and output of the smart shirt and to correct for temperature dependency. To do so, the smart shirt was applied to a custom-made torso model. Ambient temperature was increased and decreased in 15 tests, while maintaining a constant torso circumference to derive a temperature correction. Additionally, sensor output was monitored with varying circumference. The results revealed a linear relation between temperature and RIP output. Nine of the twelve shirts showed a linear output to changes in circumference. A median temperature drift of -34.7 mL/°C was observed and corrected to a minimum drift of -0.5 mL/°C. In conclusion, RIP is a promising method for measuring LH in home monitoring. Patients will not be falsely diagnosed with LH due to temperature changes. Sensor output can easily be corrected for temperature. Furthermore, the relationship between circumference and output is linear, confirming the ease of implementing the calibration procedure for obtaining lung volumes.

OBJECTIVE: To assess the effects of a 3-week community-based exercise program on 30-day postoperative complications in high-risk patients scheduled for elective colorectal resection for (pre)malignancy.SUMMARY BACKGROUND DATA: Patients with a low preoperative aerobic fitness undergoing colorectal surgery have an increased risk of postoperative complications. It remains, however, to be demonstrated whether prehabilitation in these patients reduces postoperative complications.METHODS: This 2-center, prospective, single-blinded randomized clinical trial was carried out in 2 large teaching hospitals in the Netherlands. Patients (≥60 years) with colorectal (pre)malignancy scheduled for elective colorectal resection and with a score ≤7 metabolic equivalents on the veterans-specific activity questionnaire were randomly assigned to the prehabilitation group or the usual care group by using block-stratified randomization. An oxygen uptake at the ventilatory anaerobic threshold RESULTS: Between February 2014 and December 2018, 57 patients [30 males and 27 females; mean age 73.6 years (standard deviation 6.1), range 61-88 years] were randomized to either prehabilitation (n = 28) or usual care (n = 29). The rate of postoperative complications was lower in the prehabilitation group (n = 12, 42.9%) than in the usual care group (n = 21, 72.4%, relative risk 0.59, 95% confidence interval 0.37-0.96, P = 0.024).CONCLUSIONS: Exercise prehabilitation reduced postoperative complications in high-risk patients scheduled to undergo elective colon resection for (pre)malignancy. Prehabilitation should be considered as usual care in high-risk patients scheduled for elective colon, and probably also rectal, surgery.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance.This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond.Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals.The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.

Background The Hexoskin is a smart shirt that can take continuous and objective measurements and could be part of a potential telemonitoring system. Objective The aim of this study was to determine the accuracy of the calibrated Hexoskin in measuring tidal volumes (TVs) in comparison to spirometry during various tasks. Methods In a cross-sectional study, the TV of 15 healthy subjects was measured while performing seven tasks using spirometry and the Hexoskin. These tasks were performed during two sessions; between sessions, all equipment was removed. A one-time spirometer-based calibration per task was determined in session 1 and applied to the corresponding task in both sessions. Bland-Altman analysis was used to determine the agreement between TV that was measured with the Hexoskin and that measured with spirometry. A priori, we determined that the bias had to be less than ±5%, with limits of agreement (LOA) of less than ±15%. Lung volumes were measured and had to have LOA of less than ±0.150 L. Results In the first session, all tasks had a median bias within the criteria (±0.6%). In the second session, biases were ±8.9%; only two tasks met the criteria. In both sessions, LOA were within the criteria in six out of seven tasks (±14.7%). LOA of lung volumes were greater than 0.150 L. Conclusions The Hexoskin was able to correctly measure TV in healthy subjects during various tasks. However, after reapplication of the equipment, calibration factors were not able to be reused to obtain results within the determined boundaries. Trial Registration Netherlands Trial Register NL6934; https://www.trialregister.nl/trial/6934

Background: Doxapram is a treatment option for severe apnea of prematurity (AOP). However, the effect of doxapram on the diaphragm, the main respiratory muscle, is not known. Objectives: To investigate the effect of doxapram on diaphragmatic activity measured with transcutaneous electromyography of the diaphragm (dEMG). Methods: A pilot study was conducted in a tertiary neonatal intensive care unit. Diaphragmatic activity was measured from 30 min before up to 3 h after the start of doxapram treatment. dEMG parameters were compared to baseline (5 min before doxapram treatment) and at 15, 60, 120 and 180 min after the start of doxapram infusion. Results: Eleven preterm infants were included with a mean gestational age of 25.5 ± 1.2 weeks and birth weight of 831 ± 129 g. The amplitudedEMG, peakdEMG and tonicdEMG values did not change in the 3 h after the start of doxapram infusion compared to baseline. Clinically, the number of apnea episodes in the 24 h after doxapram treatment decreased significantly. Conclusion: Doxapram infusion does not alter diaphragmatic activity measured with transcutaneous dEMG in preterm infants with AOP, indicating that its working mechanism is primarily on respiratory drive and not on respiratory muscle activity.

Molecular profiling of exhaled breath by electronic nose (eNose) might be suitable as a noninvasive tool that can help in monitoring of clinically unstable COPD patients. However, supporting data are still lacking. Therefore, as a first step, this study aimed to determine the accuracy of exhaled breath analysis by eNose to identify COPD patients who recently exacerbated, defined as an exacerbation in the previous 3 months. Data for this exploratory, cross-sectional study were extracted from the multicentre BreathCloud cohort. Patients with a physician-reported diagnosis of COPD (n=364) on maintenance treatment were included in the analysis. Exacerbations were defined as a worsening of respiratory symptoms requiring treatment with oral corticosteroids, antibiotics or both. Data analysis involved eNose signal processing, ambient air correction and statistics based on principal component (PC) analysis followed by linear discriminant analysis (LDA). Before analysis, patients were randomly divided into a training (n=254) and validation (n=110) set. In the training set, LDA based on PCs 1–4 discriminated between patients with a recent exacerbation or no exacerbation with high accuracy (receiver operating characteristic (ROC)–area under the curve (AUC)=0.98, 95% CI 0.97–1.00). This high accuracy was confirmed in the validation set (AUC=0.98, 95% CI 0.94–1.00). Smoking, health status score, use of inhaled corticosteroids or vital capacity did not influence these results. Exhaled breath analysis by eNose can discriminate with high accuracy between COPD patients who experienced an exacerbation within 3 months prior to measurement and those who did not. This suggests that COPD patients who recently exacerbated have their own exhaled molecular fingerprint that could be valuable for monitoring purposes., Exhaled breath analysis by eNose can identify COPD patients who recently exacerbated with high accuracy. This suggests that these patients have their own exhaled molecular fingerprint that could be valuable for monitoring purposes. https://bit.ly/34vTyrH

Introduction: Whole-body plethysmograpyh is the measurement of intrathoracic gasvolume and volume change. It is an important diagnostic tool in the definition of restrictive lung diseases and of abnormally increased lung volumes in obstructive lung diseases. The usefulness of any diagnostic tool depends on the combination of accuracy, reproducibility and stability. We conducted a validation study of the Cosmed Q-box system including both in-vitro and in-vivo testing. Methods: Three equal Q-box systems were used in this study. All measurements were done without any added volume, with 20 L and 50 L added volume. Weight was adjusted in software to compensate for added volume. In-vitro Simulated TGV tests were performed using an Erlenmeyer Flask as described in ERS/ATS Workshop Report, with 5 measurements per device. In-vivo 15 healthy subjects (3 F/12 M, age 42.5±9.2) performed standard measurements in each of the 3 boxes, in random order. Results:In-vitro ANOVA testing did not show any significant differences between the 3 devices. Relative difference to the flask volume was -0.49% (±1.23%). Adding extra volume did not differ the results. In-vivo ANOVA testing did not show any significant differences between the 3 devices, while Intra class correlation showed very good consistency between the 3 devices (ICC of 0.982 for FRC, 0.997 for VC and 0.967 for TLC (all p Discussion: We found good accuracy, inter-device reproducibility and no significant difference between devices. Devices are interchangeable in clinical or research setting.

Telemonitoring becomes more important in pulmonary research. It can be used to decrease the pressure on the health care system, to lower the costs of health care and to increase quality of life of patients. Previous studies show contradictory results regarding the effectiveness of telemonitoring. According to multiple researchers, inefficiency can be a result of poor study design, low data quality and usability issues. To counteract these issues, this review proves for an in-depth explanation of four (potential) telemonitoring systems in terms of work principle, accuracy, disturbing factors and usability. The evaluated systems are portable spirometry/breath-by-breath analyzers, respiratory inductance and magnetic plethysmography and electrical impedance tomography. These insights can be used to select the optimal technique for a specific purpose in future studies.

Introduction Exhaled-breath analysis of volatile organic compounds could detect lung cancer earlier, possibly leading to improved outcomes. Combining exhaled-breath data with clinical parameters may improve lung cancer diagnosis. Methods Based on data from a previous multi-centre study, this article reports additional analyses. 138 subjects with non-small cell lung cancer (NSCLC) and 143 controls without NSCLC breathed into the Aeonose. The diagnostic accuracy, presented as area under the receiver operating characteristic curve (AUC-ROC), of the Aeonose itself was compared with 1) performing a multivariate logistic regression analysis of the distinct clinical parameters obtained, and 2) using this clinical information beforehand in the training process of the artificial neural network (ANN) for the breath analysis. Results NSCLC patients (mean±sd age 67.1±9.1 years, 58% male) were compared with controls (62.1±7.0 years, 40.6% male). The AUC-ROC of the classification value of the Aeonose itself was 0.75 (95% CI 0.69–0.81). Adding age, number of pack-years and presence of COPD to this value in a multivariate regression analysis resulted in an improved performance with an AUC-ROC of 0.86 (95% CI 0.81–0.90). Adding these clinical variables beforehand to the ANN for classifying the breath print also led to an improved performance with an AUC-ROC of 0.84 (95% CI 0.79–0.89). Conclusions Adding readily available clinical information to the classification value of exhaled-breath analysis with the Aeonose, either post hoc in a multivariate regression analysis or a priori to the ANN, significantly improves the diagnostic accuracy to detect the presence or absence of lung cancer., Adding readily available clinical information to the classification value of exhaled-breath analysis with the Aeonose significantly improves the diagnostic accuracy to detect the presence or absence of lung cancer http://bit.ly/38ps6fH

ObjectiveTo describe the incidence of patient-ventilator asynchrony and different types of asynchrony in preterm infants treated with non-synchronised nasal intermittent positive pressure ventilation (nIPPV).DesignAn observational study was conducted including preterm infants born with a gestational age (GA) less than 32 weeks treated with non-synchronised nIPPV. During 1 hour, spontaneous breathing was measured with transcutaneous electromyography of the diaphragm simultaneous with ventilator inflations. An asynchrony index (AI), a percentage of asynchronous breaths, was calculated and the incidence of different types of inspiratory and expiratory asynchrony were reported.ResultsTwenty-one preterm infants with a mean GA of 26.0±1.2 weeks were included in the study. The mean inspiratory AI was 68.3%±4.7% and the mean expiratory AI was 67.1%±7.3%. Out of 5044 comparisons of spontaneous inspirations and mechanical inflations, 45.3% of the mechanical inflations occurred late, 23.3% of the mechanical inflations were early and 31.4% of the mechanical inflation were synchronous. 40.3% of 5127 expiratory comparisons showed an early termination of ventilator inflations, 26.7% of the mechanical inflations terminated late and 33.0% mechanical inflations terminated in synchrony with a spontaneous expiration. In addition, 1380 spontaneous breaths were unsupported and 611 extra mechanical inflations were delivered.ConclusionNon-synchronised nIPPV results in high patient-ventilator asynchrony in preterm infants during both the inspiratory and expiratory phase of the breathing cycle. New synchronisation techniques are urgently needed and should address both inspiratory and expiratory asynchrony.

In this study, the hypercapnic ventilatory response (HCVR) was measured, defined as the ventilation response to carbon dioxide tension (PCO2). We investigated which method, rebreathing or steady-state, is most suitable for measurement of the HCVR in healthy subjects, primarily based on reproducibility. Secondary outcome parameters were subject experience and duration. 20 healthy adults performed a rebreathing and steady-state HCVR measurement on two separate days. Subject experience was assessed using numeric rating scales (NRS). The intraclass correlation coefficient (ICCs) of the sensitivity to carbon dioxide above the ventilatory recruitment threshold and the projected apnoea threshold were calculated to determine the reproducibility of both methods. The ICCs of sensitivity were 0.89 (rebreathing) and 0.56 (steady-state). The ICCs of the projected apnoea threshold were 0.84 (rebreathing) and 0.25 (steady-state). The steady-state measurement was preferred by 16 out of 20 subjects; the differences in NRS scores were small. The hypercapnic ventilatory response measured using the rebreathing setup provided reproducible results, while the steady-state method did not. This may be explained by high variability in end-tidal PCO2. Differences in subject experience between the methods are small., The hypercapnic ventilatory response measured by a rebreathing setup is reproducible, as opposed to a steady-state setup http://ow.ly/yGDg30hStIB

Introduction: Lung cancer is a leading cause of cancer mortality. Exhaled-breath analysis of volatile organic compounds (VOC’s) may detect lung cancer at an early stage, possibly leading to better outcomes. Artificial neural networks (ANN) have proven to be accurate tools to diagnose lung cancer by distinguishing between breath profiles of healthy and sick individuals. Adding readily available clinical information to the ANN may improve the diagnostic accuracy. Methods: Subjects with non-small cell lung cancer (NSCLC) and healthy controls breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Diagnostic accuracy, presented as Area under the Curve (AUC) was studied in a prospective, multi-center study in 282 individuals of whom 140 had confirmed NSCLC. We compared a 6-element breath-vector (Aeonose-only) with a 10-element vector (Aeonose plus age, pack years, COPD-presence, and gender). Results: Confirmed NSCLC patients (67.1 (9.0) years; 57.6% male) were compared with non-NSCLC controls (62.1 (7.1) years; 40.4% male). The AUC based on the Aeonose-only classification was 0.75 (95% CI: 0.69-0.81). Adding age, number of pack years, presence of COPD, and gender to the ANN resulted in an improved performance with an AUC of 0.84 (95% CI: 0.79-0.88). By choosing an appropriate threshold value in the ROC-diagram of the multivariate model, we observed a sensitivity of 92.9%, a specificity of 53.3%, and a positive and negative predictive value of 66.3% and 88.4%, respectively. Conclusion: The diagnostic accuracy to predict presence or absence of lung cancer can be improved significantly by adding readily available clinical information to the ANN.

Rationale: A variety of techniques to measure molecular profiles in exhaled breath are available. The methods used for breath sampling (e.g. tidal breathing and vital capacity (VC)) vary between different devices. To provide a fundament for standardization, the influence of various sampling techniques on breathprints needs to be examined. Aim: To determine the diagnostic accuracy of breath analysis by electronic nose (eNose), using tidal breaths or a VC manoeuvre, for the diagnosis of asthma, COPD, lung cancer and healthy controls. Methods: This was a multi-center observational study in controls and asthma, COPD and lung cancer patients. As part of spirometry, breathprints were collected in duplicate by eNose (SpiroNose) [De Vries ERJ 2018]. Subjects performed 5 tidal breaths followed by an inspiratory capacity maneuver, a 5 second breath hold and a slow expiratory VC. Data-analysis involved signal processing, ambient air correction and statistics based on principal component (PC), linear discriminant and ROC analysis. Results: Breath data of 2161 subjects, asthma (n=702), COPD (n=540), lung cancer (n=256) and controls (n=663) were available. The results are presented in figure 1. Conclusion: SpiroNose data obtained by tidal breaths and VC manoeuvres are not interchangeable. VC manoeuvres provide the highest accuracies in the cross comparison of controls and asthma, COPD and lung cancer patients.

Background: Little is known about the spontaneous recovery of unilateral diaphragm dysfunction (UDD). The aim of the study is to evaluate the recovery rate of UDD and to determine predictors for recovery time. Methods: A retrospective study was conducted in patients with UDD. Spontaneous recovery was measured during follow-up, with a maximum of five years, and was defined as an increase in VC > 400ml. Cox proportional hazard regression analyses were performed to determine predictors for time to spontaneous recovery. Furthermore, the number of respiratory related hospital admissions and pneumonias were obtained. Results: 69 patients (72.5% male, 60 ± 13 years, BMI 29.5 ± 4.2) were included between 1992 and 2018. Spontaneous recovery occurred after 6, 12, 24 and 60 months in respectively 9.0% (95% CI 3.1-14.9), 26.0% (95% CI 16.2-35.8), 35.0% (95% CI 23.2-46.8) and 64.0% (95% CI 48.3-79.7) of the patients. Patients with a traumatic etiology had approximately a 4 till 5 times greater chance of recovery compared to patients with respectively idiopathic (HR 4.08; 95% CI 1.18-14.14) or other causes of UDD (HR 5.47; 95% CI 2.47-12.13). Age, gender, BMI, comorbidities and the severity of UDD did not affect recovery time. Pneumonias and respiratory related hospital admissions were observed in respectively 24.3% and 29.7% of the patients. Conclusion: This study indicates that spontaneous recovery may occur years after onset of UDD. Recovery time depends strongly on underlying etiology. Complications as pneumonia and hospital admissions are common features in these patients.

Background: Wearables are of increasing relevance in the pulmonary field. The validity and reproducibility of tidal volumes (TV) measured during daily tasks is investigated, comparing a smart shirt to mobile spirometry. Methods: Fifteen healthy subjects (age 34.1±13.7) were included. TV measured with QDC-calibrated respiratory inductance plethysmography (RIP) sensors in a smart shirt (Hexoskin) with a custom developed app (Medwear) was compared to Oxycon Mobile (OM) (Vyaire Medical) in seven tasks of daily living. All tasks were performed twice in two sessions (s1 and s2), in between the shirt was removed. Calibration was determined per task in s1, and was applied to the repeated task in s2. TV from RIP and OM were compared within a task within a subject with a Bland-Altman analysis. The mean of these subject-task biases and limits of agreement (loa) were calculated to determine the overall validity of RIP. Results: TV ranges between 0.64±0.13 L (bend sitting) and 1.63±0.49 L (stair climbing). Conclusion: The smart shirt is valid to measure TV in healthy subjects, and calibration determined in a task can be applied to the same repeated task with reproducible results. In the near future the same method will be used to investigate the ability of the shirt to measure lung volumes in patients with chronic obstructive pulmonary disease.

Introduction: Lung cancer remains a leading cause of cancer mortality. Exhaled-breath analysis of volatile organic compounds (VOC’s), reflecting pathological processes, might detect lung cancer at an early stage, possibly leading to improved outcomes. Combining breath patterns with clinical parameters may improve the accuracy to diagnose lung cancer. Methods: In a multi-center study 144 subjects diagnosed with non-small cell lung cancer (NSCLC) and 146 healthy subjects breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). The diagnostic accuracy, presented as Area under the Curve (AUC) of the Aeonose™ sec was compared with the diagnostic accuracy when combined with clinical parameters in a multivariate logistic regression analysis. Results: Confirmed NSCLC patients (67.1 (9.0) years; 57.6% male) were compared with controls without NSCLC (62.1 (7.1) years; 40.4% male). The AUC of the absolute Aeonose™ value obtained by a trained neural network was 0.76 (95% CI: 0.71-0.82). Adding age, number of pack years, and presence of COPD to this absolute value of the Aeonose™ from the neural network resulted in an improved performance with an AUC of 0.86 (95% CI: 0.81-0.90). By choosing an appropriate threshold value in the ROC-diagram of the multivariate model, we observed a sensitivity of 95.7%, a specificity of 59.7%, and a positive and negative predictive value of 69.5% and 92.5%, respectively. Conclusion: Adding readily available clinical information to the absolute obtained value of exhaled-breath analysis with the Aeonose™ improves the diagnostic accuracy to detect the presence or absence of lung cancer.

Secundum atrial septal defects (ASDs) are one of the most common congenital heart diseases and cause left-to-right shunting through the interatrial septum. The major indication for closure is a haemodynamically significant shunt, defined as a pulmonary-to-systemic flow ratio ≥1.5 with pulmonary vascular resistance, Atrial septal defects are characterised by a low DLNO/DLCOc ratio in diffusion testing. Successful percutaneous closure shows an increase in DLNO/DLCOc ratio and vital capacity through correction of a hyperdynamic pulmonary circulation. http://ow.ly/Rqkc30o5yMM

Introduction: Obstructive sleep apnea (OSA) is common, and diagnosis requires expensive and laborious testing to assess the apnea hypopnea index (AHI). We performed an analysis to explore the relationship between the oxygen desaturation index (ODI) as measured with pulse oximetry and the AHI in our large portable monitoring (PM) database to find an optimal cutoff value for the ODI in order to be able to exclude AHI ≥ 5 on PM. Methods: Three thousand four hundred thirteen PM recordings were randomly divided into a training set (N = 2281) and a test set (N = 1132). The optimal cutoff for the ODI to exclude an AHI ≥ 5 on PM was determined in the training set and subsequently validated in the test set. Results: Area under the curve of the ODI to exclude an AHI ≥ 5 on PM was 0.997 in the training set and 0.996 in the test set. In the training set, the optimal cutoff to predict an AHI < 5 was an ODI < 5. Using this cutoff in the test set provided a sensitivity of 97.7%, a specificity of 97.0%, a positive predictive value of 99.2%, and a negative predictive value of 91.4%. Conclusion: An ODI < 5 predicts an AHI < 5 with high sensitivity and specificity when measured simultaneously using the same oximeter during PM recording.

To assess the changes in (regional) lung volume and gas exchange during minimally invasive surfactant therapy (MIST) in preterm infants with respiratory distress syndrome. In this prospective observational study, infants requiring a fraction of inspired oxygen (FiO2) ≥ 0.30 during nasal continuous positive airway pressure of 6 cmH2O were eligible for MIST. Surfactant (160-240 mg/kg) was administered in supine position in 1-3 minutes via an umbilical catheter placed 2 cm below the vocal cords. Changes in end-expiratory lung volume (EELV), tidal volume, and its distribution were recorded continuously with electrical impedance tomography before and up to 60 minutes after MIST. Changes in transcutaneous oxygen saturation (SpO2) and partial carbon dioxide pressure, FiO2, respiratory rate, and minute ventilation were recorded. A total of 16 preterm infants were included. One patient did not finish study protocol because of severe apnea 10 minutes after MIST. In the remaining infants (gestational age 29.8 ± 2.8 weeks, body weight 1545 ± 481 g) EELV showed a rapid and sustained increase, starting in the dependent lung regions, followed by the nondependent regions approximately 5 minutes later. Oxygenation, expressed as the SpO2/FiO2 ratio, increased from 233 (IQR 206-257) to 418 (IQR 356-446) after 60 minutes (P < .001). This change was significantly correlated with the change in EELV (ρ = 0.70, P < .01). Tidal volume and minute volume decreased significantly after MIST, but transcutaneous partial carbon dioxide pressure was comparable with pre-MIST values. Ventilation distribution remained unchanged. MIST results in a rapid and homogeneous increase in EELV, which is associated with an improvement in oxygenation

Rationale: Patients with COPD are at high risk of developing lung cancer [Biswas Curr Opin Pulm Med 2018], but no biomarkers have been reported to identify these patients. Molecular profiling of exhaled air by electronic nose (eNose) technology may qualify for early detection of lung cancer in COPD patients. Aim: To determine the diagnostic accuracy of exhaled breath analysis for the prediction of early stages of lung cancer in COPD patients. Methods: BreathCloud is an ongoing multicentre cross-sectional observational study using diagnostic and monitoring visits in day-to-day clinical care of patients with a standardized diagnosis of asthma, COPD or lung cancer. Exhaled breathprints were collected in duplicate by eNose (SpiroNose) [De Vries ERJ 2018]. All patients with COPD were managed according to standard care and the incidence of clinically diagnosed lung cancer was prospectively monitored for 1 year. Data-analysis involved signal processing, ambient correction and statistics based on principal component analysis followed by discriminant analysis. Results: Exhaled breath data of 639 COPD patients were available. 35 COPD patients (5%) developed clinically manifest lung cancer within 1 year after inclusion. Principal component 1 showed a significant difference (p Conclusion: Exhaled breath analysis by SpiroNose is able to discriminate at baseline between COPD patients in whom lung cancer manifested within 1 year after inclusion. These results show that eNose assessment may detect early stages of lung cancer and may therfore be of value in the screening of patients with COPD.

Introduction: Small cell lung cancer (SCLC) is an aggressive type of lung cancer and accounts for 15% of all lung cancer cases. Progress in the survival rate of SCLC is poor with a 5-year survival rate of only 5-10%, depending on tumour stage at presentation. Tumour detection earlier in the course of this disease is a potential tool to improve outcome. Exhaled-breath analysis of volatile organic compounds (VOC’s), reflecting pathological processes, have the potential to diagnose lung cancer in a sensitive, non-invasive way. We aimed to determine the diagnostic accuracy of breath analysis in SCLC using an electronic nose (Aeonose™). Methods: Subjects with confirmed SCLC and healthy subjects breathed into the Aeonose™ (The eNose Company, Zutphen, The Netherlands) for 5 minutes. Diagnostic performance was studied in a prospective multicentre study conducted in 4 hospitals in 93 subjects of which 18 had pathologically confirmed SCLC. The breath prints of the two groups were compared, using data compression and artificial neural networks for the statistical analysis of VOC data. Results: SCLC patients and healthy subjects had a mean age of 63.2±8.2 and 65.9±8.8 years, respectively. Choosing a proper point at the ROC curve to rule out SCLC resulted in a sensitivity of 88.9%, a specificity of 80.0%, a positive predictive value of 51.6%, a negative predictive value of 96.8%, and an area under the curve of 0.86. Conclusion: The data show that electronic nose technology with the Aeonose™ can play an important role in rapidly excluding SCLC due to the high negative predictive value that was obtained in this study. Patients showing positive breath tests should still be subjected to further diagnostic testing.

Rationale: Clinical/inflammatory phenotypes of chronic airway disease have been obtained by eNose, irrespective of the diagnostic label [De Vries ERJ 2018]. This requires prospective validation at the point-of-care. Aim: To determine the accuracy of the eNose for classifying newly presented patients with a differential diagnosis of asthma or COPD into diagnostic labels and clinical/inflammatory phenotypes. Methods: BreathCloud is a multicentre cross-sectional study in patients with e.g. asthma and COPD. Exhaled breathprints were collected in duplicate by eNose (SpiroNose). Four weeks after inclusion all clinical diagnoses based on current guidelines were available. Correct classification into eNose phenotypes (1. obese non-atopic; 2. eosinophilic predominant; 3. non-Caucasian; 4. inflammation atopic; 5. well-controlled) [De Vries ERJ 2018] was defined as a complete clinical/inflammatory match. Data analysis involved advanced signal processing and statistics based on principal component analysis and discriminant analysis. Results: Patients with a differential diagnosis of asthma or COPD (n=257) were classified by eNose into diagnostic labels with an overall accuracy of 81% (asthma:82%, COPD:79%) and a ROC-AUC of 0.83(CI:0.81-0.86). Classification into phenotypes reached an accuracy of 89% (phenotype 1:83%, 2:92%, 3:89%, 4:92%, 5:88%) with a ROC-AUC of 0.91(CI:0.87-0.95). Conclusion: Enose technology is able to classify newly presented patients with a differential diagnosis of asthma or COPD with high accuracy into their classic diagnostic labels and clinical/inflammatory phenotypes. These data validate breathomics for stratification of patients with chronic airway diseases in the doctor’s office.

Introduction: COPD is a heterogeneous disease with differences in response to treatment. Efforts are ongoing to find new biomarkers that are able to stratify patients at the point-of-care. Molecular profiling of exhaled breath by electronic nose (eNose) may qualify for this in patients using LAMA/LABA with or without ICS. Aim: To determine the accuracy of exhaled breath analysis to detect COPD patients that have a history of being unstable on treatment. Methods: This was a multi-center cross-sectional study in COPD patients using LAMA/LABA with or without ICS. Exhaled breathprints were collected in duplicate by eNose (SpiroNose) [De Vries ERJ 2018]. Instability was defined as the occurrence of ≥1 exacerbation within 3 months prior to inclusion. An exacerbation was defined as a worsening of respiratory symptoms which required treatment with OCS, antibiotics or both. Data analysis involved signal processing, ambient correction and statistics based on principal component (PC) analysis followed by discriminant analysis. Results: COPD patients (n=363) using LAMA/LABA with ICS (n=227; unstable:37) or LAMA/LABA (n=136, unstable:13) were included. PC 2-4 showed a significant difference (p Conclusion: Exhaled breath analysis by SpiroNose is able to accurately identify COPD patients that are clinically unstable during the previous 3 months. This indicates that clinical instability in COPD has its own exhaled molecular fingerprint that could be valuable in COPD monitoring.

Of all older patients that opt for elective colorectal surgery, approximately one-third has one or more postoperative complications, particularly those patients with a low cardiorespiratory fitness (ventilatory anaerobic threshold (VAT)

BACKGROUND: To explore the feasibility of transcutaneous electromyographic respiratory muscle recordings to automatically quantify the synchronicity of patient-ventilator interaction in the pediatric intensive care unit.METHODS: Prospective observational study in a tertiary paediatric intensive care unit in an university hospital. Spontaneous breathing mechanically ventilated children < 18 years of age were eligible for inclusion. Patients underwent a 5-min continuous recording of ventilator pressure waveforms and transcutaneous electromyographic signal of the diaphragm. To evaluate patient-ventilator interaction, the obtained neural inspiration and ventilator pressurization timings were used to calculate trigger and cycle-off errors of each breath. Calculated errors were displayed in the dEMG-phase scale.RESULTS: Data of 23 patients were used for analysis. Based on the dEMG-phase scale, the median rates of synchronous, dyssynchronous and asynchronous breaths as classified by the automated analysis were 12.2% (1.9-33.8), 47.5% (36.3-63.1), and 28.9% (6.6-49.0).CONCLUSIONS: The dEMG-phase scale quantifying patient-ventilator breath synchronicity was demonstrated to be feasible and a reliable scale for mechanically ventilated children, reflected by high intra-class correlation coefficients. As this non-invasive tool is not restricted to a type of ventilator, it could easily be clinical implemented in the ventilated pediatric population. However; correlation studies between the EMG signal measured by surface EMG and esophageal catheters have to be performed.

Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath.Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set.This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology. Data analysis involved signal processing and statistics based on principal component analysis followed by unsupervised cluster analysis and supervised linear regression.Clustering based on eNose resulted in five significant combined asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04), exhaled nitric oxide fraction (p2=0.581) and neutrophilic (R2=0.409) blood counts based on eNose. Similar clusters and regression results were obtained in the validation set.Phenotyping a combined sample of asthma and COPD patients using eNose provides validated clusters that are not determined by diagnosis, but rather by clinical/inflammatory characteristics. eNose identified systemic neutrophilia and/or eosinophilia in a dose-dependent manner.

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a “direct” airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

Aim Humidifying noninvasively ventilated preterm infants is critical to prevent dehydration of respiratory mucosa, but over-humidification can result in impaired airway patency and lung mechanics. This neonatal bench study investigated the humidity delivered using invasive and noninvasive humidification modes during nasal continuous positive airway pressure. Methods The study was conducted at the neonatal intensive care unit of Emma Children's Hospital, the Netherlands, in March 2014. A mannequin was connected to a CareFusion Infant Flow SiPAP system, combined with a Fisher & Paykel MR850 humidifier and a Carefusion Infant Flow LP Generator. We measured the temperature, relative humidity and absolute humidity at the humidification chamber's expiratory port and at the patient's mask. Results The absolute humidity at the mask was 35-40 mg H2 O/L at 38-39°C (relative humidity 74-80%) for the invasive mode of the humidifier and 23-27 mg H2 O/L at 34-35°C (relative humidity 63-70%) for the noninvasive mode. The absolute humidities exceeded the recommended values for the invasive mode of the humidifier, but not the noninvasive mode, and could be associated with increased condensation. Conclusion The absolute humidity delivered by the humidifier in invasive mode could be associated with increased condensation, which has been associated with airway impairment.

Background: Minimally invasive surfactant therapy (MIST) is increasingly used to treat preterm infants with respiratory distress syndrome (RDS). However, the effect of MIST on breathing effort is poorly studied. Objectives: To describe the effect of MIST on neural breathing effort assessed with transcutaneous electromyography of the diaphragm (dEMG) in preterm infants with RDS. Methods: Preterm infants with a gestational age < 37 weeks treated with MIST for RDS were included. dEMG measurements were done from 15 min before to 1 h after MIST. The percentage change in dEMG activity after MIST and the clinical response were analyzed. Results: Twenty preterm infants (mean gestational age 29.3 [SD 2.1] weeks; mean birth weight 1,230 [SD 391] g) were included. Seventeen infants did complete the 1-h measurement. Eleven (65%) infants had a decrease in their peakdEMG activity (median change –11.8% [IQR –26.8 to 5.8, p = 0.08]) 1 h after MIST. TonicdEMG activity decreased in 12 (71%) infants, with a median reduction of 6.3% (IQR –29.2 to 9.0, p = 0.07). FiO2 showed a rapid decrease following MIST (before, 0.47 [IQR 0.38–0.84]; 1 h after, 0.25 [IQR 0.21–0.30], p < 0.001). Conclusion: In addition to improved oxygenation, MIST results in a decrease in neural breathing effort measured by dEMG activity in the majority of preterm infants with RDS.

Introduction During routine nursing care, preterm infants are often placed in lateral position for several hours, but the effect of this­­­­ procedure on regional lung volume and ventilation is unknown. In our study we examined this effect during 3 hrs of lateral positioning in stable preterm infants. Methods Preterm infants on non-invasive respiratory support were eligible for the study. Infants were placed in supine position and subsequently transferred to right or left lateral position, according to their individual routine nursing schedule. Changes in end-expiratory lung volume (EELV), tidal volume (VT) and ventilation distribution were recorded using electrical impedance tomography (EIT), starting 10 min before and up to 180 min after the positional change. Additionally, oxygen requirement, transcutaneous oxygen saturation and respiratory rate were recorded. Results 15 infants were included (GA 28.9 ± 2.0 wk, BW 1167 ± 290 g). EELV increased significantly after changing to lateral position, stabilizing at a median value of 40.8 (IQR 29.0–99.3) AU/kg at 30 min. This increase could almost be exclusively attributed to the non-dependent lung regions. Tidal volume, oxygenation, and respiratory rate remained stable. Changing to the right, but not the left, lateral position resulted in a rapid but transient shift in ventilation to the dependent lung regions. After 180 min there were no differences in ventilation distribution between lateral and supine positioning. Conclusion This study shows that lateral position up to 3 hours, as part of normal nursing care of preterm infants, has no adverse effects on lung volumes and its regional distribution.

Objective In an attempt to reduce the work of breathing (WOB) and the risk of respiratory failure, preterm infants are increasingly treated with nasal synchronised biphasic positive airway pressure (BPAP) via the Infant Flow SiPAP system. However, the relatively high resistance of the generator limits the pressure amplitude (PA) and pressure build-up (PB) of this system. This in vitro study investigates the impact of a new generator with improved fluid mechanics on the WOB, PA and PB during BPAP. Methods Using a low compliance lung model, WOB, PA and PB, were measured during BPAP using the old and the new Infant Flow generators. Airway resistance (tube sizes 2.5 mm, 3.0 mm and 3.5 mm), nasal interface sizes (small, medium and large) and four different ventilator settings were used to mimic different clinical conditions. Results Compared with the old generator, the new generator significantly reduced the WOB between 10% and 70%, depending on the measurement configuration. The maximum PA was higher when using the new (6–7 cm H 2 O) generator versus the old (3–4 cm H 2 O) generator. During the first 100 ms of inspiration, the new generator reached between 33% and 40% of the peak pressure compared with 11–20% for the old generator. Conclusions This in vitro study shows that a new generator of the Infant Flow SiPAP device results in a significant reduction in WOB and an increase in PA and PB during BPAP. The results of this study need to be confirmed under variable clinical conditions in preterm infants.

Introduction: Lung cancer occupies the first place in cancer-related deaths. 15% of lung cancer cases present timely with localized, potentially curable disease. Therefore, a sensitive, non-invasive tool to detect lung cancer earlier is desired. Exhaled breath analysis by electronic nose technology measures volatile organic compounds (VOC9s), which reflect pathological processes in the body. We aimed to determine the diagnostic accuracy of exhaled breath analysis by the Aeonose™ in non-small cell lung cancer (NSCLC). Methods: Subjects diagnosed with NSCLC and healthy subjects breathed into the Aeonose™ (The eNose Company, Zutphen, The Netherlands) during 5 minutes. 3 Aeonoses were used, producing repeatable and interchangeable results. The diagnostic accuracy was prospectively studied in a multicentre study in 107 subjects. 60 Had a histopathologically confirmed diagnosis of NSCLC. Their exhaled breath prints were compared with 47 subjects without lung cancer. Data compression and artificial neural networks were used for the analysis of VOC data. Results: The subjects had a mean age of 64.4±8.8 years and 53 (50%) were male. The optimal threshold to rule out NSCLC resulted in a sensitivity of 90% (54/60) with a specificity of 74% (35/47), positive predictive value of 82% (54/66), negative predictive value of 85% (35/41) and an area under the curve of 0.80. Conclusion: The data suggest that electronic nose technology with the Aeonose™ can have a substantial added value in the non-invasive diagnostic workup in NSCLC. Data collection is still ongoing. With more subjects added (N=350 expected), the model can in all likelihood be further improved to increase sensitivity and negative predictive value, so no patient is missed.

Introduction: detection and quantification of dynamic hyperinflation (DH) in COPD patients in real-life is an intriguing issue, but hard to perform. This study assessed a smart shirt, capable of measuring breathing parameters, as a new diagnostic tool compared to standard lung function equipment. Methods: 31 healthy controls and 11 COPD patients performed basic spirometry, metronome-paced tachypnea (MPT) and an exercise test (either a six-minute-walk or a cardio-pulmonary exercise test (CPET)) wearing the smart shirt (Hexoskin, Carre Technologies, Montreal, Canada) and breathing through a sensor measuring flow. Breathing waveforms produced by the shirt were compared with mobile spirometry (Oxycon Mobile, Care Fusion, San Diego, USA) for its ability to register breathing (e.g. FEV1, IVC and breathing frequency) and detect DH. Results: Moderate-high correlations between the two devices were observed during basic spirometry (median Spearman’s rho for FEV1 (0.81), IVC (0.90) and frequency (0.95)) and during the longer MPT and exercise measurements (range 0.80 - 0.95). The agreement between the shirt and the mobile spirometry with respect to the detection of DH was poor to fair (kappa 0.2-0.3). The smart shirt detected DH more often than the spirometer. Conclusion: the smart shirt is capable of registering breathing patterns and alterations in breathing over time and DH can be detected. Several disturbing factors (such as movement, skin temperature and smart shirt sizing) need to be addressed to improve the detection algorithm. Disclosure: the authors declare no conflict of interest with any company whose equipment has been used.

Introduction: Respipedia is a peer-reviewed medical wiki on respiratory medicine created by and for ERS members. Aims and objectives: To create a specialised knowledge base on respiratory medicine for clinical practice purposes. The project aims at encouraging ERS members to develop, update and benefit from valuable resources on diverse respiratory topics. Respipedia is also willing to act as an entry point for selected references and material, including ERS e-learning resources. Methods: Extended research was conducted on wikis and their utilisation in medical education. Consequently, the platform9s thematic structure and the workflow for article creation, reviewing and publishing were approved by the ERS Education Committee. Furthermore, topics were identified based on curriculum entries related to the Harmonised Education in Respiratory Medicine for European Specialists (HERMES). Quality control is ensured by a reviewing process. Results: Since its launch in July 2015, Respipedia has been enriched with a total of 30 articles on various areas of respiratory medicine. However, the number of contributions is still low. In order to reach its objectives, the wiki needs more engagement and contribution from ERS Members. As a means to increase contribution during this year, new strategies will be implemented: the use of Respipedia for ERS course materials; article creation in Respipedia as a requirement for fellowship application; and CME credits for article authoring and reviewing. Conclusion: Respipedia is now online. Articles are available to be viewed and edited by ERS members at: http://respipedia.ers-education.org/home.aspx