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NO₂ levels as a contributing factor to COVID-19 deaths: The first empirical estimate of threshold values.

ABSTRACT: This study represents the first empirical estimation of threshold values between nitrogen dioxide (NO₂) concentrations and COVID-19-related deaths in France. The concentration of NO₂ linked to COVID-19-related deaths in three major French cities were determined using Artificial Neural Networks experiments and a Causal Direction from Dependency (D2C) algorithm. The aim of the study was to evaluate the potential effects of NO₂ in spreading the epidemic. The underlying hypothesis is that NO₂, as a precursor to secondary particulate matter formation, can foster COVID-19 and make the respiratory system more susceptible to this infection. Three different neural networks for the cities of Paris, Lyon and Marseille were built in this work, followed by the application of an innovative tool of cutting the signal from the inputs to the selected target. The results show that the threshold levels of NO₂ connected to COVID-19 range between 15.8 ?g/m³ for Lyon, 21.8 ?g/m³ for Marseille and 22.9 ?g/m³ for Paris, which were significantly lower than the average annual concentration limit of 40 ?g/m³ imposed by Directive 2008/50/EC of the European Parliament.

SUBMITTER: Mele M

PROVIDER: S-EPMC7783466 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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NO2 levels as a contributing factor to COVID-19 deaths: The first empirical estimate of threshold values.

Mele Marco M Magazzino Cosimo C Schneider Nicolas N Strezov Vladimir V

Environmental research 20210105

This study represents the first empirical estimation of threshold values between nitrogen dioxide (NO2) concentrations and COVID-19-related deaths in France. The concentration of NO2 linked to COVID-19-related deaths in three major French cities were determined using Artificial Neural Networks experiments and a Causal Direction from Dependency (D2C) algorithm. The aim of the study was to evaluate the potential effects of NO2 in spreading the epidemic. The underly ...[more]

PMID: 33417906

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Project description:Benzimidazoles act by disrupting microtubule polymerisation and are capable of inducing the formation of micronuclei. Considering the similarities in their mechanisms of action (inhibition of microtubule assembly by binding to the colchicine-binding site on tubulin monomers), combination effects according to the principles of concentration addition might occur. If so, it is to be expected that several benzimidazoles contribute to micronucleus formation even when each single one is present at or below threshold levels. This would have profound implications for risk assessment, but the idea has never been tested rigorously. To fill this gap, we analysed micronucleus frequencies for seven benzimidazoles, including the fungicide benomyl, its metabolite carbendazim, the anthelmintics albendazole, albendazole oxide, flubendazole, mebendazole and oxibendazole. Thiabendazole was also tested but was inactive. We used the cytochalasin-blocked micronucleus assay with CHO-K1 cells according to OECD guidelines, and employed an automated micronucleus scoring system based on image analysis to establish quantitative concentration-response relationships for the seven active benzimidazoles. Based on this information, we predicted additive combination effects for a mixture of the seven benzimidazoles by using the concepts of concentration addition and independent action. The observed effects of the mixture agreed very well with those predicted by concentration addition. Independent action underestimated the observed combined effects by a large margin. With a mixture that combined all benzimidazoles at their estimated threshold concentrations for micronucleus induction, micronucleus frequencies of ~15.5% were observed, correctly anticipated by concentration addition. On the basis of independent action, this mixture was expected to produce no effects. Our data provide convincing evidence that concentration addition is applicable to combinations of benzimidazoles that form micronuclei by disrupting microtubule polymerisation. They present a rationale for grouping these chemicals together for the purpose of cumulative risk assessment.

Project description:ImportanceIntracranial pressure (ICP) elevation is a compartment syndrome that impairs blood flow to the brain. Despite the importance of ICP values in neurocritical care, normal ICP values and the precise ICP threshold at which treatment should be initiated remain uncertain.ObjectiveTo refine our understanding of normal ICP values and determine the ICP threshold most strongly associated with outcome.Design, setting, and participantsProspective observational study (2004-2010), with outcomes determined at hospital discharge. The study included neurocritical care patients from a single level I trauma center, San Francisco General Hospital. Three hundred eighty-three patients had a traumatic brain injury with or without craniectomy; 140 patients had another indication for ICP monitoring. Consecutive patients were studied. Data analyses were completed between March 2015 and December 2019.ExposuresFive hundred twenty-three ICP-monitored patients.Main outcomes and measuresA computer system prospectively and automatically collected 1-minute physiologic data from patients in the intensive care unit during a 6-year period. Mean ICP was calculated, as was the proportion of ICP values greater than thresholds from 1 to 80 mm Hg in 1-mm Hg increments. The association between these measures and outcome was explored for various epochs up to 30 days from the time of injury. A principal component analysis was used to explore physiologic changes at various ICP thresholds, and elastic net regression was used to identify ICP thresholds most strongly associated with Glasgow Outcome Scale score at discharge.ResultsOf the 523 studied patients, 70.7% of studied patients were men (n = 370) and 72.1% had a traumatic brain injury (n = 377). A total of 4 090 964 1-minute ICP measurements were recorded for the included patients (7.78 years of recordings). Intracranial pressure values of 8 to 9 mm Hg were most commonly recorded and could possibly reflect normal values. The principal component analysis suggested state shifts in the physiome occurred at ICPs greater than 19 mm Hg and 24 mm Hg. Elastic net regression identified an ICP threshold of 19 mm Hg as most robustly associated with outcome when considering all neurocritical care patients, patients with TBI, and patients with TBI who underwent craniectomy. Intracranial pressure values greater than 19 mm Hg were associated with mortality, while lower values were associated with outcome in surviving patients.Conclusions and relevanceThis study provides insight into what normal ICP values could be. An ICP threshold of 19 mm Hg was robustly associated with outcome in studied patients, although lower ICP values were associated with outcome in surviving patients.

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NO₂ levels as a contributing factor to COVID-19 deaths: The first empirical estimate of threshold values.

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NO<sub>2</sub> levels as a contributing factor to COVID-19 deaths: The first empirical estimate of threshold values.

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