Immunological Effects of Diesel Particles in a Murine Model of Healthy Mice.

Introduction: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of respiratory disease exacerbation. However, the possible effects of these particles on the general population remain poorly understood. The present study aimed to assess the immunomodulatory and inflammatory effects of the inhalation of DEP in a model of healthy mice undergoing short-, mid- and long-term exposure. Materials and Methods: BALB/c ByJ mice were randomly divided into five experimental groups. The control group received three intranasal instillations of saline over 8 days while the other four groups received intranasal instillations of 150 µg of DEP 3 days per week for 8, 17, 26, and 53 days. Lung function assessment and flow cytometry were performed. Results: In lung tissue, intranasal exposure to DEP decreased total monocytes (p < 0.015 in all groups). At 26 days, a reduction in inflammatory monocytes and an increase in resident monocytes were observed, p = 0.001 and 0.0001, respectively. Eosinophils and neutrophils decreased at 26 days (p = 0.017 and p = 0.041, respectively). The intranasal challenges of DEP increased the total population of dendritic cells (DC) at 26 and 53 days (p = 0.017 and p = 0.022, respectively) and decreased the total and alveolar populations of macrophages (p < 0.003 for all groups compared to control), while interstitial macrophage populations increased over the time period (p = 0.0001 for all groups compared to control). Conclusions: Continuous DEP exposure triggers immune mechanisms that predispose healthy individuals to a pro-inflammatory and hyper-reactive microenvironment. This mouse model provides evidence of the capacity of DEP to increase DC, interstitial macrophages, and resident monocytes.

Increased TGFß1, VEGF and IFN-γ in the Sputum of Severe Asthma Patients With Bronchiectasis.

BACKGROUND: Bronchiectasis is one of the most common comorbidities in severe asthma. However, the mechanisms by which asthma promotes the development and progress of this condition are not well defined. This study aimed to analyze the inflammatory phenotypes and quantify the expression of proinflammatory and remodeling cytokines in asthma patients with and without bronchiectasis. METHODS: The study sample comprised individuals with severe asthma and bronchiectasis (group AB, n=55) and a control population of individuals with severe asthma without bronchiectasis (group AC, n=45). Induced sputum samples were obtained and cell types determined by differential cell count. Proinflammatory and bronchial remodeling cytokines (IL-8, neutrophilic elastase, TGFß1, VEGF, IFN-γ, TNF-α, and GM-CSF) were analyzed by immunoassay in sputum supernatant. RESULTS: Neutrophilic inflammation was the primary phenotype in both asthma groups. Higher levels of TGFß1, VEGF and IFN-γ were observed in asthma patients with bronchiectasis (group AB) than in controls (group AC) (15 vs 24pg/ml, p=0.014; 183 vs 272pg/ml, p=0.048; 0.85 vs 19pg/ml, p<0.001, respectively). Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly lower in the AB group than in the AC group (1.2 vs 4.4pg/ml, p<0.001). IL-8, neutrophil elastase and TNF-α did not present significant differences between the groups. CONCLUSIONS: Raised levels of TGFß1 and VEGF cytokines may indicate airway remodeling activation in asthma patients with bronchiectasis. The type of inflammation in asthma patients did not differ according to the presence or absence of bronchiectasis.

The Impact of the Reduction in Environmental Pollution during COVID-19 Lockdown on Healthy Individuals.

The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to determine and compare the oxidative stress biomarkers Th1/Th2 and inflammatory-related cytokines in healthy individuals first during lockdown and then six months after the easing of the restrictions on mobility. A prospective study of a representative sample of 58 healthy, non-smoking adults was carried out. During lockdown and six months post-easing of restrictions, blood samples were drawn to measure the percentage of eosinophils, levels of Th1/Th2 and inflammatory-related cytokines assessed by a multiplex assay (BioRad Laboratories S.A., Marnes-la-Coquette, France), and levels of 8-isoprostane, glutathione peroxidase activity, and myeloperoxidase (Cayman Chemical Co., Ann Arbor, MI, USA), to assess their value as biomarkers of oxidative stress. Six months after easing mobility restrictions, increases in the levels of 8-isoprostane (p < 0.0001), IL-1ß (p = 0.0013), IL-1ra (p = 0.0110), IL-4 (p < 0.0001), IL-13 (p < 0.0001), G-CSF (p = 0.0007), and CCL3 (p < 0.0001) were recorded, along with reductions in glutathione peroxidase (p < 0.0001), IFN-γ (p = 0.0145), TNFα (p < 0.0001), IP-10 (p < 0.0001), IL-2 (p < 0.0001), IL-7 (p < 0.0001), basic FGF (p < 0.0001), CCL4 (p < 0.0001), and CCL5 (p < 0.0001). No significant differences were observed in the rest of the biomarkers analyzed. The reduction in environmental pollution during the COVID-19 lockdown significantly lowered the levels of oxidative stress, systemic inflammation, and Th2-related cytokines in healthy people.

Enhanced Methods for Needle Biopsy and Cryopreservation of Skeletal Muscle in Older Adults.

Human muscle biopsies are increasingly important for diagnosis, research, and to monitor therapeutic trials. We examined the use of a self-contained, vacuum-assisted biopsy system and a novel muscle freezing technique to improve, simplify, and standardize human muscle biopsy collection and cryopreservation in older adults. The VACORA vacuum-assisted biopsy system was deployed in muscle biopsies of 12 individuals ranging in age from 57 to 80 years. This office-based approach was well tolerated as it is minimally invasive, uses only local anesthetic, and has a quick recovery. To maximize biopsy sample quality and reproducibility, we developed a novel muscle sample freezing protocol. Fresh muscle biopsy samples were placed into readily available tissue cassettes followed by direct freezing in liquid nitrogen. After this modified snap freezing protocol, frozen muscle samples were enrobed in embedding medium for cryosectioning. We examined the effect of this freezing approach in histological sections of rodent and human muscle samples. The VACORA Biopsy System provided as many as four skeletal muscle core samples from a single biopsy site. Biopsy samples from 12 older adults weighed an average of 147.5 ± 11 mg each and had a consistent size and shape. There were no complications, and the residual scar is less than 10 mm. The freezing method using standard tissue cassettes with direct freezing in liquid nitrogen yielded high quality cryopreserved muscle tissue suitable for histological analysis without the need for isopentane and with little to no freeze-thaw damage. These enhancements have streamlined and improved the consistency of our muscle biopsy protocol and provide sufficient high-quality sample for multi-dimensional downstream studies of human muscle in aging and disease.

Effects of Home-Based Exercise Training Systems, Combined with Diet, on Cardiometabolic Health.

The efficacy of exercise training systems designed to be used in the home on cardiometabolic outcomes remains largely unknown. This investigation included two studies. Study 1 tested the effects a multi-exercise pulley system (NordicTrack Fusion CST with video trainer) and Study 2 an incline trainer (NordicTrack X22i with video trainer), both combined with daily food provision, for 12-weeks on indices of cardiometabolic health. Study 1 enrolled 27 adults (11 men, 16 women, 33.8±4.4 years of age) and Study 2 enrolled 29 adults (11 men, 18 women, 40.8±12.5 years of age). Pre- and post-intervention measurements were performed for body weight, fat mass, lean tissue mass, and visceral fat by dual energy x-ray absorptiometry, blood pressure, aerobic fitness and body circumferences. For Study 1, there were significant decreases in body weight, fat mass, visceral fat, diastolic blood pressure (DBP), resting heart rate (RHR), and all circumference sites, while there was an increase in aerobic fitness (all p<0.001). Both males and females exhibited significant improvement in all these outcomes. For Study 2, there were significant decreases in body weight, fat mass, visceral fat, DBP, RHR, all circumference sites (all p<0.001), and lean tissue mass (LTM) (p=0.006), and an increase in aerobic fitness (p<0.001). Both males and females exhibited significant changes in all these outcomes, except LTM which did not change in females. Both studies exhibited high exercise session attendance and high dietary adherence. Overall these data indicate the potential efficacy of home-based training systems, when combined with diet, on selected cardiometabolic outcomes.

Consistency of Continuous Ambulatory Interstitial Glucose Monitoring Sensors.

AIMS: The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. METHODS: Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m²) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. RESULTS: There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points (p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left (p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. CONCLUSIONS: CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods.

Setting and Method of Measurement Affect Blood Pressure Readings in Older Veterans.

The present study demonstrated that standardized measurements of blood pressure were lower than the routine method used in most office settings.