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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Inhalation therapy is essential for the management of respiratory conditions such as asthma and chronic obstructive pulmonary disease. However, current inhalation systems face limitations, including polydisperse aerosols that reduce drug delivery efficiency and complex treatment regimens that affect patient adherence. To improve drug targeting and efficacy, Gilbert Innovation B.V. is developing a next-generation soft-mist inhaler based on electrohydrodynamic atomization (EHDA), which produces uniform micrometer sized droplets. Effective drug delivery requires high flow rates and precise aerosol discharge to ensure deep lung deposition while minimizing losses to the device and oropharynx. To achieve this, the device employs a multi-nozzle system for increased flow and corona discharge needles for charge neutralization. However, ensuring uniform neutralization across multiple nozzles and maintaining stable electrospray operation remain key challenges. COSMIC aims to increase system robustness by optimizing neutralization efficiency, refining material selection, and controlling electrospray stability under varying conditions. The electrospray control system will incorporate advanced strategies leveraging computer vision, machine learning and big data analytics. These innovations will increase efficiency, accessibility and patient comfort in inhalation therapy.
Regular physical activity is considered to be an important component of a healthy lifestyle that decreases the risk of coronary heart disease, diabetes mellitus type 2, hypertension, colon and breast cancer, obesity and other debilitating conditions. Physical activity can also improve functional capacity and therefore also the quality of life in older adults. Despite all these favorable aspects, a substantial part of the Dutch older adult population is still underactive or even sedentary. To change this for the better, the Groningen Active Living Model (GALM) was developed.Aim of GALM is to stimulate recreational sports activities in sedentary and underactive older adults in the 55-65 age band. After a door-to-door visit as part of an intensive recruitment phase, a fitness test was conducted followed by the GALM recreational sports program. This program was based on principles from evolutionary-biological play theory and insights fromsocial cognitive theory. The program was versatile in nature (e.g. softball, dance, self-defense, swimming, athletics, etc.) in two main ways: a) to improve compliance with the program different sports were offered, which was reported to be more appealing for older adults; b) by aiming at more components of motor fitness (e.g. strength, flexibility, speed, endurance and coordination). Between 1997 and 2005 more than 552,000 persons were visited door-to-door, over 55,700 were tested, and 41,310 participated in the GALM recreational sports program. The aim of the present thesis is to determine the effects of participation in the GALM recreational sports program on physical activity, health and fitness outcomes.Chapter 2 describes the effectiveness of the GALM recruitment in selecting and recruiting sedentary and underactive older adults. Three municipalities in the Netherlands were selected, and in every municipality four neighborhoods were included. Two of each of the four neighborhoods were randomly assigned as intervention and the others as control neighborhoods. In total, 8,504 persons were mailed and received a home visit. During this home visit the GALM recruitment questionnaire was collected on which the selection between sedentary/underactive and physically active older adults was based. Ultimately we succeeded inincluding 12.3% (315 of the 2,551 qualifying) of the older adults, 79.4% of whom could be indeed considered sedentary or underactive. The cost of successfully recruiting an older adult was estimated at $84.To assess the effects of a physical activity intervention on health and fitness and explain the results, it is necessary to know program characteristics regarding frequency, intensity, time and content of the activities. With respect to the GALM recreational sports activity program, the only unknown characteristic was intensity. Chapter 3 describes the intensity of this program systematically. Using heart rate monitors, data of 97 persons (mean age 60.1 yr) were collected in three municipalities. The mean intensity of all 15 GALM sessions was 73.7% of the predicted maximal heart rate. Six percent of the monitored heart rate time could be classified as light, 33% as moderate and 61% as hard. In summary, the GALM recreational sports program meets the 1998 ACSM recommendations for intensity necessary to improve cardiorespiratory fitness.Chapters 4 and 5 describe the effects of 6 and 12 months of participation in the GALM recreational sports program, and 181 persons were followed over time. Results after 6 months revealed only few significant between-group differences favoring the intervention group (i.e. sleep, diastolic blood pressure, perceived fitness score and grip strength). Changes in energyexpenditure for leisure-time physical activities (EELTPA) showed an increase in both study groups. From 6 to 12 months a decrease in EELTPA occurred in the intervention group and an increase in the control group. The significant positive time effects for the health outcomes (diastolic blood pressure, BMI, percentage of body fat) that were found after 6 months were diminishedfrom 6 to 12 months. However, the energy expenditure for recreational sports activities (EERECSPORT) demonstrated a continuous increase over 12 months. Parallel to this, significant main effects for time were found in performance-based fitness outcomes (i.e. simple reaction time, leg strength, flexibility of hamstrings and lower back, and aerobic endurance). After 12 months only a significant between-group difference for flexibility of the hamstrings andlower back was found, favoring the control group. In conclusion, a short-term increase in EELTPA was found with accompanying improvements in health outcomes that more or less disappeared in 6 to 12 months. In the long term, results showed a continuous increase in EERECSPORT and performance-based fitness. This latter increase is probably a reflection of the significantimprovement over time in EERECSPORT and the fact that recreational sports activities are of a higher intensity.Aerobic endurance is regarded as the most important component of motor fitness that is relevant for older adults to function independently. In Chapter 6, the development in aerobic endurance after 18 months of participation in the GALM recreational sports program was assessed by means of changes in heart rate during fixed submaximal exercise. Since both groups were comparable regarding changes in energy expenditure for physical activity after 6 months and testing confirmed this, both groups were combined and considered as one group. Multilevel analyses were conducted and models for change were developed. A significant decrease in heart rate over time was found at all walking speeds (4, 5, 6 and 7 km/h). The average decrease in heart rate was 5.5, 6.0, 10.0 and 9.0 beats/min for the 4, 5, 6 and 7 km/h walking speeds, respectively. The relative decrease varied from 5.1 to 7.4% relative to average heart rates at baseline. These results illustrate that participation in the GALM recreational sports program has a positive significant effect on aerobic endurance, and that the participants are able to perform at submaximal intensity more easily.Based on the overall results it can be concluded that this study contributes to the field in how to effectively recruit sedentary and underactive older adults and stimulate them to become and stay active in recreational sports activities. As far as we know, this recruitment in combination with the recreational sport program is not only unique but also effective toward increasing performance-based fitness in the long term. Short-term effects were found in other leisure-time activities and health outcomes. To further stimulate other leisure-time and probably health outcomes besides the favorable effects that were already seen, additional interventions that pay more attention to behavioral change in terms of how to integrate other activities besides sports activities are recommended.
