Sex-based Differences in the Use of Best Practices in Mechanically Ventilated Adults in the Intensive Care Unit: An Analysis of the Toronto Multi-center iCORE Database.

Rationale Patients who are critically ill and require admission to an Intensive Care Unit (ICU) should receive the same quality of care regardless of their sex. Objectives To determine, using population data from a multicenter database in Ontario, Canada, whether sex is associated with differences in the use of 8 best practices and other interventions during the ICU care of mechanically ventilated women and men. Methods Using a cohort of patients receiving mechanical ventilation in 8 intensive care units, our co-primary outcomes were differences in compliance with 8 evidence-based practices between women and men (opioid administration, use of continuous sedation or opioids, sedation minimization; spontaneous breathing trials; stress ulcer prophylaxis; deep venous thrombosis prophylaxis; physical restraint; and mobilization). All analyses were adjusted for confounders using logistic regression and restricted to patients eligible for each best practice. Measurements and Main Results We included 19070 (11910 men, 7160 women) patients who were mechanically ventilated for more than 4 hours. Men and women had similar opioid administration, sedation minimization, stress ulcer prophylaxis, DVT prophylaxis, and mobilization. Women were less likely to receive continuous infusions of sedation or opioids than men (adjusted OR 0.86, 95% CI 0.78, 0.95), and less likely to be physically restrained (adjusted OR 0.82, 95% CI 0.74, 0.89). Conclusions: In this cohort of mechanically ventilated patients, the use of evidence-based practices was similar between women and men, except for a higher utilization of continuous sedative or opioid infusions and physical restraints in men.

Chronic respiratory disease observatory for Africa (CHEST-Africa): study protocol for the prevalence, determinants and economic impacts of asthma and COPD in Africa.

INTRODUCTION: Contemporary data on the burden of chronic respiratory diseases in sub-Saharan Africa is limited. More so, their economic burden is not well described. This study aims to establish a chronic respiratory disease observatory for Africa. Specific study aims are (1) to describe the prevalence and determinants of asthma with a target to screen up to 4000 children and adolescents across four African cities; (2) to determine the prevalence and determinants of chronic obstructive pulmonary disease (COPD) with a target to screen up to 3000 adults (≥18 years) across five African cities; (3) to describe the disease burden by assessing the frequency and severity of symptoms and exacerbations, medication use, emergency healthcare utilisation and hospitalisation; and (4) to assess the economic burden and affordability of the medicines for these diseases. METHODS AND ANALYSIS: Surveys will be conducted in schools to identify children and adolescents with asthma using the Global Asthma Network screening questionnaire in Ghana, Nigeria, the Democratic Republic of Congo, and Uganda. Community surveys will be conducted among adults using an adapted version of the Burden of Obstructive Lung Disease Questionnaire to identify persons with COPD symptoms in Nigeria, Burkina Faso, Mozambique, Rwanda, and Sierra Leone. Fractional exhaled nitric oxide and pre-bronchodilator and post-bronchodilator spirometry will be done for children with asthma or asthma symptoms and for all adult participants. Children and adults with respiratory symptoms or diagnoses will complete the health economic questionnaires. Statistical analysis will involve descriptive and analytical statistics to determine outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from participating institutions. This study's results will inform deliberations at the United Nations General Assembly high-level meeting on non-communicable diseases in 2025. The results will be shared through academic conferences and journals and communicated to the schools and the communities.

Mortality risk associated with occupational exposures in people with small airways obstruction.

BACKGROUND: Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO. METHODS: We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes-VGDF; solvents; pesticides; metals), adjusting for potential confounders. RESULTS: The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04-1.78) for low levels and 1.41 (95%CI: 1.11-1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures. CONCLUSION: Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control.

Armoured Lepidopteran Caterpillars Preserved in Non-Fossil Resins and What They Tell Us about the Fossil Preservation of Caterpillars.

Resin is a plastic-like product of trees. Older occurrences of such resin are referred to as amber and are considered fossil resin. Younger resins are termed copals. Even younger ones have been dubbed defaunation resins. Non-fossil resins remain in a terminological limbo, often referred to as "sub-fossils". We report two lepidopteran caterpillars preserved in non-fossil resin: one from Madagascar, one from Brazil. Prominent hairs (=setae) and spines (=spine-like setae) of the specimens make it likely that they represent larvae of Erebidae (e.g., tussock moths and others). So far, most known caterpillars preserved in resins are either "naked" or bear protective cases; only few are armoured with spines or hairs. In particular, long-haired caterpillars such as the ones reported here are so far almost absent. Only one specimen with comparable setae has been reported from 15-million-year-old Dominican amber, but no significant details of this specimen are accessible. We briefly also review the record of caterpillars known from the Holocene, recognising that it is very sparse. The new specimens demonstrate that very hairy caterpillars can readily be preserved in resins in fine detail. Furthermore, the specimens increase the known size range of caterpillars preserved in resins, with one measuring more than 12 mm.

Small Airways Obstruction and Mortality: Findings From the UK Biobank.

BACKGROUND: Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown. RESEARCH QUESTION: Is spirometry-defined SAO associated with increased mortality? METHODS: Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV1/forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential confounders such as sex, BMI, smoking status, smoking pack-years, assessment center, Townsend deprivation index, and ethnicity. RESULTS: A total of 59,744 participants with SAO were identified, of whom 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (hazard ratio [HR], 1.31; 95% CI, 1.26-1.36), cardiovascular (HR, 1.39; 95% CI, 1.29-1.51), respiratory (HR, 2.20; 95% CI, 1.92-2.51), and neoplasm (HR, 1.23; 95% CI, 1.17-1.29) mortality risk. These associations were not modified by sex. However, in those who never smoked, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR, 1.14; 95% CI, 1.07-1.20). INTERPRETATION: Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease.

Rheological and Biological Properties of Adhesive Skin Secretions from Eupsophus vertebralis (Anura: Alsodidae).

Skin secretions from Patagonian ground frogs, Eupsophus vertebralis, have previously been reported as a potent proteinaceous adhesive with potential biomedical applications. Here, we conducted a rheological analysis indicating the mechanical robustness of these secretions, with a storage modulus ranging from 1 to 10 Pa. In addition, antimicrobial and cytotoxicity assays were performed, revealing no antimicrobial activity against both the Gram-positive and Gram-negative bacteria. The cytotoxicity results were intriguing, as three samples showed no harm, and one exhibited a severe cytotoxic effect on the human cell line MG63. These properties, as indicated by these preliminary results, reinforce their potential for practical applications in the industrial and medical sectors.

Expanding the Mesozoic Record of Early Brachyceran Fly Larvae, including New Larval Forms with Chimera-Type Morphologies.

Diptera are one of the four megadiverse groups of holometabolan insects. Flies perform numerous ecological functions, especially in their larval stages. We can assume that this was already the case in the past; however, fly larvae remain rare in most deposits. Here we report new dipteran larvae preserved in Cretaceous (about 99 Ma) Kachin amber from Myanmar and, even older, Jurassic (about 165 Ma) compression fossils from China. Through light microscopy and micro-CT scanning we explore their peculiar morphology and discuss their possible phylogenetic affinities. Several larvae seem to represent the lineage of Stratiomyomorpha. A few others present characters unique to Xylophagidae (awl-flies), as well as to Athericidae (water sniper-flies), resulting in a chimeric morphology. Understanding the exact relationships of most of these specimens with a particular lineage remains challenging, since they differ considerably from any other known dipteran larvae and present some unique traits. Additionally, we report new specimens of Qiyia jurassica Chen et al., 2014, supposedly parasitic larvae, most likely representatives of Athericidae. These new findings offer valuable insights into the evolution of the early diversification of the brachyceran flies and underscore the importance of immature stages in understanding the evolutionary history and ecology of flies.

Occupational exposure to particulate matter and staff sickness absence on the London underground.

The London Underground (LU) employs over 19,000 staff, some of whom are exposed to elevated concentrations of particulate matter (PM) within the network. This study quantified the occupational exposure of LU staff to subway PM and investigated the possible association with sickness absence (SA). A job exposure matrix to quantify subway PM2.5 staff exposure was developed by undertaking measurement campaigns across the LU network. The association between exposure and SA was evaluated using zero-inflated mixed-effects negative binomial models. Staff PM2.5 exposure varied by job grade and tasks undertaken. Drivers had the highest exposure over a work shift (mean: 261 µg/m3), but concentrations varied significantly by LU line and time the train spent subway. Office staff work in office buildings separate to the LU network and are unexposed to occupational subway PM2.5. They were found to have lower rates of all-cause and respiratory infection SA compared to non-office staff, those who work across the LU network and are occupational exposed to subway PM2.5. Train drivers on five out of eight lines showed higher rates of all-cause SA, but no dose-response relationship was seen. Only drivers from one line showed higher rates of SAs from respiratory infections (incidence rate ratio: 1.24, 95% confidence interval 1.10-1.39). Lower-grade customer service (CS) staff showed higher rates of all-cause and respiratory infection SA compared to higher grade CS staff. Doctor-certified chronic respiratory and cardiovascular SAs were associated with occupational PM2.5 exposure in CS staff and drivers. While some groups with higher occupational exposure to subway PM reported higher rates of SA, no evidence suggests that subway PM is the main contributing factor to SA. This is the largest subway study on health effects of occupational PM2.5 exposure and may have wider implications for subway workers, contributing to safer working environments.

A Canadian survey of perceptions and practices related to ordering of blood tests in the intensive care unit.

PURPOSE: The ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients. METHODS: We conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate. RESULTS: Over seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from Ontario. Respondents had a mean (SD) clinical experience of 12 (9) years, and 61% worked in academic centres. When asked about their perceptions of how frequently unnecessary blood tests are ordered, 61% responded "sometimes" and 23% responded "almost always." Fifty-seven percent favoured ordering complete blood counts one day in advance. Only 24% of respondents believed that advanced blood test ordering frequently led to changes in management. The most common factors perceived to influence blood test ordering in the ICU were physician preferences, institutional patterns, and order sets. CONCLUSION: Most respondents to this survey perceived that unnecessary blood testing occurs in the ICU. The survey identified possible strategies to decrease the number of blood tests.

RéSUMé: OBJECTIF: La prescription à l'avance de tests sanguins de routine est courante dans les unités de soins intensifs (USI), avec une prise en compte limitée de la probabilité de découverte d'anomalies avant le test. Cette pratique contribue à l'anémie, aux résultats faussement positifs et aux coûts des soins de santé. Nous avons cherché à comprendre les pratiques et les attitudes des intensivistes pour adultes au Canada en ce qui concerne la prescription d'analyses sanguines chez la patientèle gravement malade. MéTHODE: Nous avons mené un sondage transversal à l'échelle nationale au Canada en posant 15 questions évaluant trois domaines (perceptions globales, commande de tests, pratique quotidienne), ainsi que 11 questions démographiques. L'échantillon cible était composé d'un·e intensiviste par unité de soins intensifs pour adultes au Canada. Nous avons résumé les réponses à l'aide de statistiques descriptives et présenté les données sous forme de moyennes avec écarts type (ET) ou de dénombrements avec pourcentages, selon le cas. RéSULTATS: Sur une période de sept mois, 80 médecins sur 131 (61%) ont répondu dans 77 unités de soins intensifs, dont 50% en Ontario. Les répondant·es avaient une expérience clinique moyenne (ET) de 12 (9) ans, et 61% travaillaient dans des centres universitaires. Lorsqu'on leur a demandé ce qu'ils ou elles pensaient de la fréquence à laquelle des tests sanguins inutiles étaient prescrits, 61% ont répondu « parfois ¼ et 23% ont répondu « presque toujours ¼. Cinquante-sept pour cent étaient en faveur de la réalisation d'une formule sanguine complète un jour à l'avance. Seulement 24% des personnes interrogées estimaient que la prescription de tests sanguins à l'avance entraînait fréquemment des changements dans la prise en charge. Les facteurs les plus souvent perçus comme influençant la prescription d'analyses sanguines à l'unité de soins intensifs étaient les préférences des médecins, les habitudes institutionnelles et les ensembles d'ordonnances. CONCLUSION: La plupart des répondant·es à ce sondage ont l'impression que des tests sanguins inutiles sont prescrits aux soins intensifs. L'enquête a permis d'identifier des stratégies possibles pour réduire le nombre de tests sanguins.

Extended excess hazard models for spatially dependent survival data.

Relative survival represents the preferred framework for the analysis of population cancer survival data. The aim is to model the survival probability associated with cancer in the absence of information about the cause of death. Recent data linkage developments have allowed for incorporating the place of residence into the population cancer databases; however, modeling this spatial information has received little attention in the relative survival setting. We propose a flexible parametric class of spatial excess hazard models (along with inference tools), named "Relative Survival Spatial General Hazard," that allows for the inclusion of fixed and spatial effects in both time-level and hazard-level components. We illustrate the performance of the proposed model using an extensive simulation study, and provide guidelines about the interplay of sample size, censoring, and model misspecification. We present a case study using real data from colon cancer patients in England. This case study illustrates how a spatial model can be used to identify geographical areas with low cancer survival, as well as how to summarize such a model through marginal survival quantities and spatial effects.

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Chitosan nanoparticles encapsulating farnesol evaluated in vivo against Candida albicans.

Farnesol is a natural essential oil with antimicrobial properties. Complexation of farnesol in chitosan nanoparticles can be useful to improve its bioavailability and potentiate its antifungal capabilities such as inhibition of hyphal and biofilm formation. The aim of this study was to develop and characterize chitosan nanoparticles with farnesol (NF) and evaluate their toxicity and antifungal action on C. albicans in vivo. The NF were prepared by the ionic gelation method and showed physicochemical characteristics such as diameter less than 200 nm, monodisperse distribution, positive zeta potential, spherical morphology, and stability after 120 days of storage. In the evaluation of toxicity in Galleria mellonella, NF did not reduce the survival rate, indicating that there was no toxicity in vivo at the doses tested. In the assays with G. mellonella infected by C. albicans, the larvae treated with NF had a high survival rate after 48 h, with a significant reduction of the fungal load and inhibition of the formation of biofilms and hyphae. In the murine model of vulvovaginal candidiasis (VVC), histopathological analysis showed a reduction in inflammatory parameters, fungal burden, and hyphal inhibition in mice treated with NF. The produced nanoparticles can be a promising alternative to inhibit C. albicans infection.

High prevalence of TB multimorbidity among adults of a tertiary hospital in Sierra Leone: a cross-sectional study.

OBJECTIVE: Tuberculosis (TB) is a leading cause of death globally, with approximately 1.5 million deaths in 2020. TB often coexists with chronic communicable and non-communicable diseases, but data to determine the extent of comorbid diseases are limited. In this study, we aimed to assess the prevalence of TB multimorbidity and its risk factors in a tertiary hospital in Sierra Leone. This is a cross-sectional study of 240 adults with microbiologically-confirmed TB at Connaught Hospital in Freetown, between March and May 2022. Logistic regression analysis was used to identify factors associated with TB multimorbidity. RESULTS: The mean age of the patients was 37 years. More than two-thirds were males and about the same number had two or more chronic diseases. The most common were hypertension (47.9%) and diabetes (24.2%). Patients under 35 years of age were less likely to have TB multimorbidity (< 25 years: adjusted OR 0.07, 95%CI 0.01-0.6; 25-34 years: adjusted OR 0.2, 95%CI 0.01-0.9). We report a high prevalence of comorbid diseases among TB patients in the largest treatment center in Sierra Leone, with hypertension and diabetes being the most common. These findings support the current call for addressing comorbid non-communicable diseases in TB patients through integrated care.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

Isolated small airways obstruction predicts future chronic airflow obstruction: a multinational longitudinal study.

BACKGROUND: Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life. METHODS: We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25-75) if a result was less than the lower limit of normal (

3D Filaments Based on Polyhydroxy Butyrate-Micronized Bacterial Cellulose for Tissue Engineering Applications.

In this work, scaffolds based on poly(hydroxybutyrate) (PHB) and micronized bacterial cellulose (BC) were produced through 3D printing. Filaments for the printing were obtained by varying the percentage of micronized BC (0.25, 0.50, 1.00, and 2.00%) inserted in relation to the PHB matrix. Despite the varying concentrations of BC, the biocomposite filaments predominantly contained PHB functional groups, as Fourier transform infrared spectroscopy (FTIR) demonstrated. Thermogravimetric analyses (i.e., TG and DTG) of the filaments showed that the peak temperature (Tpeak) of PHB degradation decreased as the concentration of BC increased, with the lowest being 248 °C, referring to the biocomposite filament PHB/2.0% BC, which has the highest concentration of BC. Although there was a variation in the thermal behavior of the filaments, it was not significant enough to make printing impossible, considering that the PHB melting temperature was 170 °C. Biological assays indicated the non-cytotoxicity of scaffolds and the provision of cell anchorage sites. The results obtained in this research open up new paths for the application of this innovation in tissue engineering.

Biomarkers of the L-Arginine/Dimethylarginine/Nitric Oxide Pathway in People with Chronic Airflow Obstruction and Obstructive Sleep Apnoea.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are common chronic diseases that are associated with chronic and intermittent hypoxemia, respectively. Patients affected by the overlap of COPD and OSA have a particularly unfavourable prognosis. The L-arginine/nitric oxide (NO) pathway plays an important role in regulating pulmonary vascular function. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) interfere with NO production. METHODS: We analysed the serum concentrations of ADMA, SDMA, L-arginine, L-citrulline, and L-ornithine in a large sample of the Icelandic general population together with chronic airflow obstruction (CAO), a key physiological marker of COPD that was assessed by post-bronchodilator spirometry (FEV1/FVC < LLN). OSA risk was determined by the multivariable apnoea prediction (MAP) index. RESULTS: 713 individuals were analysed, of whom 78 (10.9%) showed CAO and 215 (30%) had MAP > 0.5. SDMA was significantly higher in individuals with CAO (0.518 [0.461-0.616] vs. 0.494 [0.441-0.565] µmol/L; p = 0.005), but ADMA was not. However, ADMA was significantly associated with decreasing FEV1 percent predicted among those with CAO (p = 0.002). ADMA was 0.50 (0.44-0.56) µmol/L in MAP ≤ 0.5 versus 0.52 (0.46-0.58) µmol/L in MAP > 0.5 (p = 0.008). SDMA was 0.49 (0.44-0.56) µmol/L versus 0.51 (0.46-0.60) µmol/L, respectively (p = 0.004). The highest values for ADMA and SDMA were observed in individuals with overlap of CAO and MAP > 0.5, which was accompanied by lower L-citrulline levels. CONCLUSIONS: The plasma concentrations of ADMA and SDMA are elevated in COPD patients with concomitant intermittent hypoxaemia. This may account for impaired pulmonary NO production, enhanced pulmonary vasoconstriction, and disease progression.

Variability of the Human Serum Metabolome over 3 Months in the EXPOsOMICS Personal Exposure Monitoring Study.

Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and untargeted metabolomics are increasingly used in exposome studies to study the interactions between nongenetic factors and the blood metabolome. To reliably and efficiently link detected compounds to exposures and health phenotypes in such studies, it is important to understand the variability in metabolome measures. We assessed the within- and between-subject variability of untargeted LC-HRMS measurements in 298 nonfasting human serum samples collected on two occasions from 157 subjects. Samples were collected ca. 107 (IQR: 34) days apart as part of the multicenter EXPOsOMICS Personal Exposure Monitoring study. In total, 4294 metabolic features were detected, and 184 unique compounds could be identified with high confidence. The median intraclass correlation coefficient (ICC) across all metabolic features was 0.51 (IQR: 0.29) and 0.64 (IQR: 0.25) for the 184 uniquely identified compounds. For this group, the median ICC marginally changed (0.63) when we included common confounders (age, sex, and body mass index) in the regression model. When grouping compounds by compound class, the ICC was largest among glycerophospholipids (median ICC 0.70) and steroids (0.67), and lowest for amino acids (0.61) and the O-acylcarnitine class (0.44). ICCs varied substantially within chemical classes. Our results suggest that the metabolome as measured with untargeted LC-HRMS is fairly stable (ICC > 0.5) over 100 days for more than half of the features monitored in our study, to reflect average levels across this time period. Variance across the metabolome will result in differential measurement error across the metabolome, which needs to be considered in the interpretation of metabolome results.