Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

Background: Many patients with asthma have type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide levels. Objective: To assess disease burden in relation to type-2 inflammatory biomarker status (history of allergy, blood EOS count, and fractional exhaled nitric oxide level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). Methods: Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test score (uncontrolled <20, controlled ≥20) and/or 1 or more severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and fractional exhaled nitric oxide level), symptom burden (Asthma Control Test score, modified Medical Research Council dyspnea scale), health status (St George's Respiratory Questionnaire score), exacerbations, and health care resource utilization were assessed. Results: Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among those with uncontrolled asthma, 196 (44%) had 2 or more positive biomarkers, 187 (42%) had 1 positive biomarker, 325 (73%) had low blood EOS, and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (Asthma Control Test score 14.9-16.6), impaired health status (St George's Respiratory Questionnaire total score 46.7-49.4), clinically important breathlessness (modified Medical Research Council grade ≥2 in 47.3%-57.1%), and 1 or more severe exacerbation (70.6%-76.2%). Conclusions: Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed

Cluster Analyses From the Real-World NOVELTY Study: Six Clusters Across the Asthma-COPD Spectrum

Background: Asthma and chronic obstructive pulmonary disease (COPD) are complex diseases, the definitions of which overlap. Objective: To investigate clustering of clinical/physiological features and readily available biomarkers in patients with physician-assigned diagnoses of asthma and/or COPD in the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329). Methods: Two approaches were taken to variable selection using baseline data: approach A was data-driven, hypothesis-free and used the Pearson dissimilarity matrix; approach B used an unsupervised Random Forest guided by clinical input. Cluster analyses were conducted across 100 random resamples using partitioning around medoids, followed by consensus clustering. Results: Approach A included 3796 individuals (mean age, 59.5 years; 54% female); approach B included 2934 patients (mean age, 60.7 years; 53% female). Each identified 6 mathematically stable clusters, which had overlapping characteristics. Overall, 67% to 75% of patients with asthma were in 3 clusters, and approximately 90% of patients with COPD were in 3 clusters. Although traditional features such as allergies and current/ex-smoking (respectively) were higher in these clusters, there were differences between clusters and approaches in features such as sex, ethnicity, breathlessness, frequent productive cough, and blood cell counts. The strongest predictors of the approach A cluster membership were age, weight, childhood onset, prebronchodilator FEV1, duration of dust/fume exposure, and number of daily medications. Conclusions: Cluster analyses in patients from NOVELTY with asthma and/or COPD yielded identifiable clusters, with several discriminatory features that differed from conventional diagnostic characteristics. The overlap between clusters suggests that they do not reflect discrete underlying mechanisms and points to the need for identification of molecular endotypes and potential treatment targets across asthma and/or COPD

Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

Background: Many patients with asthma have type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide levels. Objective: To assess disease burden in relation to type-2 inflammatory biomarker status (history of allergy, blood EOS count, and fractional exhaled nitric oxide level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). Methods: Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test score (uncontrolled = 20) and/or 1 or more severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and fractional exhaled nitric oxide level), symptom burden (Asthma Control Test score, modified Medical Research Council dyspnea scale), health status (St George's Respiratory Questionnaire score), exacerbations, and health care resource utilization were assessed. Results: Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among those with uncontrolled asthma, 196 (44%) had 2 or more positive biomarkers, 187 (42%) had 1 positive biomarker, 325 (73%) had low blood EOS, and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (Asthma Control Test score 14.9-16.6), impaired health status (St George's Respiratory Questionnaire total score 46.7-49.4), clinically important breathlessness (modified Medical Research Council grade >= 2 in 47.3%-57.1%), and 1 or more severe exacerbation (70.6%-76.2%). Conclusions: Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed

Arsenic Speciation Analysis Elucidates the Risk Assesment of Food Supplements with Ingredients of Marine Origin. 9th Nordic Conference on plasma spectrochemistry

&lt;p&gt;Many potential health benefits are related to the consumption of marine organisms due to the presence of high amounts of beneficial bioactive compounds (e.g. polyunsaturated fatty acids, various peptides, minerals …). Therefore, these organisms are frequently used as base for several food supplements (FS). On the other hand, marine organisms are also known to contain high levels of arsenic (As), resulting in elevated As concentrations in FS with ingredients of marine origin, such as fish oil, krill oil or algae. Since human health risks are not related to the total As concentration but are species dependent, analysis of the relevant toxic As species in FS is mandatory for a correct risk assessment.&lt;/p&gt; &lt;p&gt;The aim of the present study was to make an exposure and risk assessment of As (species) resulting from the consumption of these types of FS, based on 60 samples collected in a Belgian market study. In this context, the determination of the most toxic fraction, inorganic arsenic (As&lt;sub&gt;i&lt;/sub&gt;) and the non-toxic fraction arsenobetaine (AB) is particularly important. In addition, we considered the ‘potentially toxic As fraction’ i.e. ‘As&lt;sub&gt;tot&lt;/sub&gt;-AB’, consisting of not only As&lt;sub&gt;i&lt;/sub&gt;, but also As species with unknown toxicity, such as arsenosugars and arsenolipids which can occur in marine matrices, in particular in algae.&lt;/p&gt; &lt;p&gt;Analysis of As&lt;sub&gt;i&lt;/sub&gt; in algae by HPLC-ICP-MS is complicated by the presence of arsenosugars in these organisms. Routine methods for As&lt;sub&gt;i&lt;/sub&gt; analysis in terrestrial matrices do not automatically guarantee a separation of As&lt;sup&gt;V&lt;/sup&gt; and arsenosugars. The objective of this study was to optimize and validate a method to ensure a correct quantification of methylarsonate (MA), dimethylarsinate (DMA), AB and As&lt;sub&gt;i&lt;/sub&gt; in marine matrices. Arsenobetaine could not be determined on the same anionic column as the other species, therefore a method using a cationic column was needed to separate AB from other uncharged or cationic species.&lt;/p&gt; &lt;p&gt;Exposure to As&lt;sub&gt;i&lt;/sub&gt;, MA, DMA and ‘As&lt;sub&gt;tot&lt;/sub&gt;-AB’ was calculated for each sample by multiplying the concentration of these compounds with the maximal recommended dose of the FS. Risks related to the intake of arsenic species in the food supplements were evaluated by comparing the calculated exposure to selected acute and (sub)chronic reference values. For As&lt;sub&gt;i&lt;/sub&gt;, a distinction was made between the general Belgian population and a sensitive population group, i.e. persons with an increased cancer risk. For the latter group a more severe reference value was applied. The risk evaluation for the chronic intake of As&lt;sub&gt;i&lt;/sub&gt; and the potentially toxic As fraction was carried out by calculating a margin of exposure (MOE), whereby MOE values &amp;gt; 100 were considered as ‘of concern’. Regarding MA and DMA no (sub)chronic risk was present, and no risk for acute toxicity of As&lt;sub&gt;i&lt;/sub&gt; was detected either. The intake of As&lt;sub&gt;i&lt;/sub&gt; was only of concern for sensitive groups in the case of chronic consumption of 24% of the tested FS based on algae. The intake of the potentially toxic As fraction was of concern in the case of chronic consumption of 19% of the tested food supplements based on algae, 6% of the tested food supplements based on fish oil and 67% of the tested food supplements based on krill oil.&lt;/p&gt; &lt;p&gt;These findings illustrate the need for more information regarding the toxicity of the potentially toxic arsenic species (mainly arsenosugars and arsenolipids), starting with a correct characterization of these species.&lt;/p&gt;</p

Does arsenic pose a health concern after consumption of clay products?

Clay products for oral use form a particular group of food supplements in relation to potential arsenic (As) toxicity, because&#8239;—&thinsp;certainly in case of pure clay- all arsenic in these supplements is expected to be present in the most toxic inorganic form (As). In terms of risk, the most important questions to answer relate to the bioaccessibility and bioavailability of the inorganic arsenic present, rather than to the As species distribution, which often receives most attention in standard foodstuffs. In the present study, clay products for oral use were bought on the Belgian market and analysed for total arsenic (As), arsenic species (As, arsenobetaine, dimethylarsenate and monomethylarsenate)) and bioaccessible arsenic, in order to perform an exposure assessment and risk characterisation. Total As concentrations differed considerably between the samples and ranged from 0.20 to 6.4 mg As/kg. Bioaccessibility of As, determined via the Unified Barge Method (extraction making use of digestive enzymes) varied between 8% and 51%. The As concentration determined via HPLC-ICP-MS after extraction with diluted HNO +HO (as in the CEN method for foodstuffs) was only a poor predictor of the bioaccessible As fraction, despite the significant relationship (R&nbsp;=&nbsp;0.36; &lt;&nbsp;.05). The risk characterisation did not reveal acute risks related to As exposure. However, a potential concern with regard to chronic As intake was identified for the general population in 42% of the analysed food supplements, and for sensitive population groups in 67% of the samples, even after taking into account the bioaccessible fraction. The data presented illustrate that consumption of some of these clay products may contribute significantly to dietary As intake and that these should not be taken&nbsp;chronically.</p