Introduction: Besides dyspnoea and cough, patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis may experience distressing non-respiratory symptoms, such as fatigue or muscle weakness. However, whether and to what extent symptom burden differs between patients with IPF or sarcoidosis and individuals without respiratory disease remains currently unknown. Objectives: To study the respiratory and non-respiratory burden of multiple symptoms in patients with IPF or sarcoidosis and to compare the symptom burden with individuals without impaired spirometric values, FVC and FEV1 (controls). Methods: Demographics and symptoms were assessed in 59 patients with IPF, 60 patients with sarcoidosis and 118 controls (age ≥18 years). Patients with either condition were matched to controls by sex and age. Severity of 14 symptoms was assessed using a Visual Analogue Scale. Results: 44 patients with IPF (77.3% male; age 70.6±5.5 years) and 44 matched controls, and 45 patients with sarcoidosis (48.9% male; age 58.1±8.6 year) and 45 matched controls were analyzed. Patients with IPF scored higher on 11 symptoms compared to controls (p<0.05), with the largest differences for dyspnoea, cough, fatigue, muscle weakness and insomnia. Patients with sarcoidosis scored higher on all 14 symptoms (p<0.05), with the largest differences for dyspnoea, fatigue, cough, muscle weakness, insomnia, pain, itch, thirst, micturition (night, day). Conclusions: Generally, respiratory and non-respiratory symptom burden is significantly higher in patients with IPF or sarcoidosis compared to controls. This emphasizes the importance of awareness for respiratory and non-respiratory symptom burden in IPF or sarcoidosis and the need for additional research to study the underlying mechanisms and subsequent interventions.
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INTRODUCTION: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.METHODS: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.FINDINGS: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2).INTERPRETATION: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality.
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The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NMon ILCs and other components of the serosal immune systemare scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NMmay lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NMon the serosal immune system.
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Validity and Reproducibility of a New Treadmill Protocol: The Fitkids Treadmill Test. Med. Sci. Sports Exerc., Vol. 47, No. 10, pp. 2241–2247, 2015. Purpose: This study aimed to investigate the validity and reproducibility of a new treadmill protocol in healthy children and adolescents: the Fitkids Treadmill Test (FTT). Methods: Sixty-eight healthy children and adolescents (6–18 yr) were randomly divided into a validity group (14 boys and 20 girls; mean T SD age, 12.9 T 3.6 yr) that performed the FTT and Bruce protocol, both with respiratory gas analysis within 2 wk, and a reproducibility group (19 boys and 15 girls; mean T SD age, 13.5 T 3.5 yr) that performed the FTT twice within 2 wk. A subgroup of 21 participants within the reproducibility group performed both FTT with respiratory gas analysis. Time to exhaustion (TTE) was the main outcome of the FTT. Results: V˙ O2peak measured during the FTT showed excellent correlation with V˙ O2peak measured during the Bruce protocol (r = 0.90; P G 0.01). Backward multiple regression analysis provided the following prediction equations for V˙ O2peak (LIminj1) for boys and girls, respectively: V˙ O2peak FTT ¼ j0:748 þ ð0:117 TTEFTTÞ þ ð0:032 bodymassÞ þ 0:263, and V˙ O2peak FTT ¼ j0:748 þ ð0:117 TTEFTTÞ þ ð0:032 bodymassÞ [R2 ¼ 0:935; SEE ¼ 0:256LI min j1]. Cross-validation of the regression model showed an R2 value of 0.76. Reliability statistics for the FTT showed an intraclass correlation coefficient of 0.985 (95% confidence interval, 0.971–0.993; P G 0.001) for TTE. Bland–Altman analysis showed a mean bias of j0.07 min, with limits of agreement between +1.30 and j1.43 min. Conclusions: Results suggest that the FTT is a useful treadmill protocol with good validity and reproducibility in healthy children and adolescents. Exercise performance on the FTT and body mass can be used to adequately predict V˙ O2peak when respiratory gas analysis is not available.
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Surgery aims to improve a patient’s medical condition. However, surgery is a major life event with the risk of negative consequences, like peri- and postoperative complications, prolonged hospitalization and delayed recovery of physical functioning. One of the major common side effects, functional decline, before (in the “waiting” period), during and after hospitalization is impressive, especially in frail people. Preoperative screening aims to identify frail, highrisk patients at an early stage, and advice these high-risk patients to start supervised preoperative home-based exercise training (prehabilitation) as soon as possible. Depending on the health status of the patient and his/her outcomes during the screening and the type of surgery, prehabilitation should focus on respiratory, cardiovascular and/or musculoskeletal parameters to prepare the patient for surgery. By improving preoperative physical fitness, a patient is able to better with stand the impact of major surgery and this will lead to a both reduced risk of negative side effects and better short term outcomes as a result. Besides prehabilitation hospital culture and infrastructure should be inherently activating so that patients stay as active as can be, socially, mentally and physically. In the first part of this chapter the concept of prehabilitation and different parameters that should be trained will be described. The second part focuses on the “Better in, Better out” (BiBo™) strategy, which aims to optimize patient’s pre-, peri- and postoperative physical fitness. Prehabilitation should comprise “shared decisions” between patient and physical therapist regarding experience and evidence based best options for rehabilitation goals, needs, and potential of the individual patient and his/her (in) formal support-system. Next, a case will describe the preoperative care pathway. This chapter will close with conclusions about how moving people before and after surgery will improve their outcomes.
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Praktische aanbevelingen op basis van bevindingen uit systematisch literatuuronderzoek bij de Covid-19 en vergelijkbare virusuitbraken en interviews met experts en ervaringsdeskundigen.
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From the publisher: "Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs." Authors: Jolanda H. M. van BilsenEmail author, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx and Erwin L. Roggen
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Background: Particulate matter (PM) exposure is an important health risk, both in daily life and in the workplace. It causes respiratory and cardiovascular diseases and results in 800,000 premature deaths per year worldwide. In earlier research, we assessed workers’ information needs regarding workplace PM exposure, the properties and effects of PM, and the rationale behind various means of protection. We also concluded that workers do not always receive appropriate risk communication tools with regards to PM, and that their PM knowledge appears to be fragmented and incomplete. Methods: We considered several concepts for use as an educational material based on evaluation criteria: ease of use, costs, appropriateness for target audiences and goals, interactivity, implementation issues, novelty, and speed. We decided to develop an educational folder, which can be used to inform employees about the properties, effects and prevention methods concerning PM. Furthermore, we decided on a test setup of a more interactive way of visualisation of exposure to PM by means of exposimeters. For the development of the folder, we based the information needs on our earlier mental models-based research. We adjusted the folder based on the results of ten semi-structured interviews evaluating its usability. Results: The semi-structured interviews yielded commentaries and suggestions for further improvement, which resulted in a number of alterations to the folder. However, in most cases the folder was deemed satisfactory. Conclusion: Based on this study, the folder we developed is suitable for a larger-scale experiment and a practical test. Further research is needed to investigate the efficacy of the folder and the application of the exposimeter in a PM risk communication system.
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IntroductionThe driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing.AimTo compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS.MethodsSingle-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation.ResultsThirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0–10.0] vs. 10.0 [8.0–11.0] cmH2O, mean difference − 2.5 [95% CI − 2.6 to − 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients.ConclusionsIn this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation.Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1.
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Objective: Despite the common occurrence of lower levels of physical activity and physical fitness in youth with spina bifida (SB) who use a wheelchair, there are very few tests available to measure and assess these levels. The purpose of this study was to determine reliability and the physiologic response of the 6-minute push test (6MPT) in youth with SB who self-propel a wheelchair. Methods: In this reliability and observational study, a sample of 53 youth with SB (5-19 years old; mean age = 13 years 7 months; 32 boys and 21 girls) who used a wheelchair performed 2 exercise tests: the 6MPT and shuttle ride test. Heart rate, minute ventilation, respiratory exchange ratio, and oxygen consumption were measured using a calibrated mobile gas analysis system and a heart rate monitor. For reliability, intraclass correlation coefficients (ICCs), SE of measurement, smallest detectable change for total covered distance, minute work, and heart rate were calculated. Physiologic response during the 6MPT was expressed as percentage of maximal values achieved during the shuttle ride test. Results: The ICCs for total distance and minute work were excellent (0.95 and 0.97, respectively), and the ICC for heart rate was good (0.81). The physiologic response during the 6MPT was 85% to 89% of maximal values, except for minute ventilation (70.6%). Conclusions: For most youth with SB who use a wheelchair for mobility or sports participation, the 6MPT is a reliable, functional performance test on a vigorous level of exercise. Impact: This is the first study to investigate physiologic response during the 6MPT in youth (with SB) who are wheelchair using. Clinicians can use the 6MPT to evaluate functional performance and help design effective exercise programs for youth with SB who are wheelchair using. Keywords: 6-minute push test; adolescent; disabled children; spinal diseases; wheelchairs.
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