Relationship between air quality and asthma-related emergency hospital admissions in Mexico City 2017-2019.

BACKGROUND: Previous studies found exposure to air pollution leads to exacerbations of asthma in paediatric and adult patients and increases asthma-related emergency hospital admissions (AREHA). METHODS: AREHAs and levels of air pollutants (PM10, PM2.5 and NO2) were obtained from Mexico City for the period 2017-2019. A time-series approach was used to explore the relationship between air pollutants and AREHA. Relative risks of AREHA were estimated using a negative binomial regression in young children (less than 5 years) and adults (greater than 18 years). RESULTS: There was a positive association between AREHA and PM10, PM2.5 and NO2 in adults, which remained after mutual adjustment for these pollutants. The relative risk (RR) of admission in adults increased by 3% (95% CI 1% to 4%) for a 10 µg/m3 increase in PM10, 1% (0.03% to 3%) for a 5 µg/m3 increase in PM2.5 and by 1% (0.06% to 2%) for a 5 µg/m3 increase in NO2. In contrast, in young children, AREHAs were negatively associated with PM10 after adjustment for NO2 (RR 0.97 (0.95 to 0.99) for a 10 µg/m3 and with NO2 after adjustment for PM10 and PM2.5 (RR 0.98 (0.96 to 0.99) and 0.97 (0.96 to 0.99), respectively, for a 5 µg/m3 increase in NO2). AREHAs in children were not associated with PM2.5 after adjustment for NO2. CONCLUSIONS: Ambient air pollution, within the previous week, was associated with emergency hospital admissions for asthma to public hospitals in adults in Mexico City. The relationship in children was less consistent. Further work is needed to explore why differences between adults and children exist to inform appropriate interventions to benefit public health.

A phase 1/2a safety, pharmacokinetics, and efficacy study of the novel nucleoside analog FF-10502-01 for the treatment of advanced solid tumors.

BACKGROUND: The nucleoside FF-10502-01, structurally similar to but with different biologic effects than gemcitabine, shows promising activity both alone and combined with cisplatin in preclinical gemcitabine-resistant tumor models. We conducted an open-label, single-arm, 3 + 3 first-in-human trial to explore the safety, tolerability, and antitumor activity of FF-10502-01 in patients with solid tumors. METHODS: Patients with inoperable metastatic tumors refractory to standard therapies were enrolled. Escalating intravenous FF-10502-01 doses (8-135 mg/m2 ) were administered weekly for 3 weeks in 28-day cycles until progressive disease or unacceptable toxicity was observed. Three expansion cohorts were subsequently evaluated. RESULTS: A phase 2 dose of 90 mg/m2 was determined after evaluating 40 patients. Dose-limiting toxicities included hypotension and nausea. Phase 2a enrolled patients with cholangiocarcinoma (36), gallbladder cancer (10), and pancreatic/other tumors (20). Common adverse events were grade 1-2 rash, pruritus, fever, and fatigue. Grade 3 or 4 hematologic toxicities were observed at low incidences, including thrombocytopenia (5.1%) and neutropenia (2%). Confirmed partial responses (PRs) occurred in five patients with gemcitabine-refractory tumors, including three with cholangiocarcinoma and one each with gallbladder and urothelial cancer. Median progression-free and overall survival rates in patients with cholangiocarcinoma were 24.7 and 39.1 weeks, respectively. Prolonged progression-free survival in patients with cholangiocarcinoma was associated with BAP1 and PBRM1 mutations. CONCLUSION: FF-10502-01 was well tolerated with manageable side effects and limited hematologic toxicity. Durable PRs and disease stabilizations were observed in heavily pretreated biliary tract patients who had received prior gemcitabine. FF-10502-01 is distinct from gemcitabine and may represent an effective therapy.

Predictive modeling of indoor dust lead concentrations: Sources, risks, and benefits of intervention.

Lead (Pb) contamination continues to contribute to world-wide morbidity in all countries, particularly low- and middle-income countries. Despite its continued widespread adverse effects on global populations, particularly children, accurate prediction of elevated household dust Pb and the potential implications of simple, low-cost household interventions at national and global scales have been lacking. A global dataset (∼40 countries, n = 1951) of community sourced household dust samples were used to predict whether indoor dust was elevated in Pb, expanding on recent work in the United States (U.S.). Binned housing age category alone was a significant (p < 0.01) predictor of elevated dust Pb, but only generated effective predictive accuracy for England and Australia (sensitivity of ∼80%), similar to previous results in the U.S. This likely reflects comparable Pb pollution legacies between these three countries, particularly with residential Pb paint. The heterogeneity associated with Pb pollution at a global scale complicates the predictive accuracy of our model, which is lower for countries outside England, the U.S., and Australia. This is likely due to differing environmental Pb regulations, sources, and the paucity of dust samples available outside of these three countries. In England, the U.S., and Australia, simple, low-cost household intervention strategies such as vacuuming and wet mopping could conservatively save 70 billion USD within a four-year period based on our model. Globally, up to 1.68 trillion USD could be saved with improved predictive modeling and primary intervention to reduce harmful exposure to Pb dust sources.

Driving factors behind the continuous increase of long-term PM2.5-attributable health burden in India using the high-resolution global datasets from 2001 to 2020.

Air pollution is the fourth leading global risk factor, whereas in India air pollution is reported as the highest risk factor with millions of premature deaths every year. Despite implementation of several air pollution control plans, PM2.5 levels over India have not noticeably reduced. PM2.5-associated health burdens in India have increased significantly in past decades. A fine resolution (0·01° × 0·01°) analysis of PM2.5-attribulable premature deaths (rather than the coarse-level analysis) may elucidate the reason for this increase and inform and effective start-of-the-art state-level and national emission control strategies. This study quantified the spatiotemporal dynamics of PM2.5-attributable premature deaths from 2001 to 2020 and applied a decomposition analysis to dissect the contribution of various associated parameters, such as PM2.5 concentration, population distribution and disease-specific baseline death rate. Results show significant spatiotemporal variations of PM2.5 and associated health burden in India. During the study period, population weighted PM2.5 value increased from 46.0 to 59.5 µg/m3 and associated non-communicable death increased around 87.6 %, from 1050 [95 % (CI): 880-1210] thousand to 1970 (95 % CI: 1658-2259) thousand. The states of Uttar Pradesh, Bihar, West Bengal, Maharashtra, Rajasthan, and Madhya Pradesh had the highest PM2.5-attributable deaths. In these states, non-accidental deaths increased from 232.1, 112.7, 81.4, 79.1, 66.3 and 58.5 thousand in 2001 to 424.1, 226.7, 156.2, 154.5, 123.3 and 119.7 thousand in 2020. In per capita population (/105 population), the highest PM2.5-attributable deaths were observed in Delhi, Uttar Pradesh, Bihar, Haryana and Punjab. Throughout the study period, demographic changes outweighed the health burden and were responsible for ~62.8 % increase of PM2.5-related non-accidental deaths across India, whereas the change in PM2.5 concentration influenced only 18.7 %. The change in baseline mortality rate impacts differently for the estimation of disease-specific mortality changes. Our findings suggest more dynamic and comprehensive policies at state-specific level, especially for North India is very indispensable for the overall decrease of PM2.5-related deaths in India.

Determinants of blood and saliva lead concentrations in adult gardeners on urban agricultural sites.

Soil Pb concentrations at urban agriculture sites (UAS) commonly exceed recommended safe levels. There is a lack of evidence regarding uptake of Pb by gardeners using such sites for food crops. Our study aimed to elucidate whether gardening in soil with raised Pb levels results in Pb body burdens of concern to health, and to assess confounding factors influencing Pb body burden. Our cross-sectional case study measured Pb in saliva and blood of UAS gardeners (n = 43), soil and produce samples from their UAS, and home tap water. Blood and saliva Pb concentrations were compared with those from non-UAS gardener controls (n = 29). A health risk threshold of 5 µg dL-1 blood Pb level (BLL) was selected in keeping with international guidance. Detailed surveys investigated individuals' anthropometrics and potential Pb exposures from diet, and historic and everyday activities. Saliva was not found to be a suitable biomarker of adult Pb exposure in this context. Predictors of higher BLLs were being older, being male and eating more root vegetables and shrub fruit. Eating more green vegetables predicted a lower BLL, suggesting a protective effect against Pb uptake. UAS gardeners' BLLs (geometric mean 1.53; range 0.6-4.1 µg dL-1) were not significantly higher (p = 0.39) than the control group (geometric mean 1.43; range 0.7-2.9 µg dL-1). All BLLs were below 5 µg dL-1 except one resulting from occupational exposure. Having paired the UAS gardeners with closely matched controls, we found Pb in UAS soils (with range 62-1300 mg kg-1from common urban sources) unlikely to pose an additional risk to adult health compared to their neighbours who did not access UAS. As such, other Pb sources may be the dominant factor controlling BLL.

An apple a day? Assessing gardeners' lead exposure in urban agriculture sites to improve the derivation of soil assessment criteria.

Globally, many of our urban agriculture sites (UAS) contain high levels of lead (Pb), a contaminant of toxicological concern to humans. To improve the derivation of soil assessment criteria at UAS, and avoid inappropriate closure of these valuable community spaces, we sampled nearly 280 paired soil and crop samples across 31 UAS gardens. This sampling was coupled with an exposure and food frequency questionnaire and participants blood Pb levels (BLL), (43 gardeners and 29 non-gardening neighbours). In 98% of the sampled soils, Pb concentrations were above the current UK soil guideline for UAS (80 mg/kg), however despite the high soil Pb (geometric mean: 324 mg/kg), and high soil bioaccessible Pb (geometric mean: 58.7%), all participants BLL were <4.1 µg/dL (range: 0.6-4.1 µg/dL). Indeed, there was no statistically significant difference between the BLL of the UAS gardeners and those of their non-gardening neighbours (p = 0.569). Pb uptake, however, varied with crop type and our study highlights the suitability of certain crops for growing at UAS with elevated Pb (e.g. tubers, shrub and tree fruit), whilst limiting the consumption of others (selected root vegetables, such as rhubarb, beetroot, parsnips and carrots, with observed Pb concentrations > 0.1 mg/kg FW). The importance of defining the exposure scenario of a specific sub-population (i.e. UAS gardeners) is highlighted. Our preferred models predict site specific assessment criteria (SSAC) of 722-1634 mg/kg. We found fruit and vegetable consumption rates by all participants, and not just the UAS gardeners, to be considerably higher than those currently used to derive the UK's category 4 screening levels (C4SLs). Furthermore, the soil to plant concentration factors (SPCFs) used to derive the UAS C4SL significantly over predict Pb uptake. Our study indicates it may be appropriate to develop a distinct exposure dataset for UAS. In particular we recommend the derivation of SPCFs that are reflective of urban soils, both in terms of the range of soil Pb concentrations typically observed, but also the sources (and hence human oral bioaccessibility and plant-availability) of this Pb.

UK dietary exposure to PCDD/Fs, PCBs, PBDD/Fs, PBBs and PBDEs: comparison of results from 24-h duplicate diets and total diet studies.

Chemicals in food are monitored to check for compliance with regulatory limits and to evaluate trends in dietary exposures, among other reasons. This study compared two different methods for estimating human dietary exposure to lipophilic persistent organic pollutants (POPs) during 2011/12: (1) the 2012 Total Diet Study (TDS) conducted by the UK Food Standards Agency (FSA) and (2) a 24-h duplicate diet (DD) study of 20 adults from the North East of England. The equivalence of the two approaches was assessed; anything less than an order of magnitude could be considered reasonable and within three-fold (equivalent to 0.5 log) as good. Adult dietary exposure estimates derived from the DD study for both average and high-level (97.5th percentile) consumers compared well with those from the TDS. Estimates from the DD study when compared with those from the TDS were within 10% for P97.5 for total PCDD/F/PCB with divergence increasing to a factor of 3.4 for average BDE-209. Most estimates derived from the TDS were slightly higher than those derived from the DD. Comparison with earlier UK TDS data over the last 30 years or so confirmed a gradual decline in levels of PCDD/F/PCBs in food. Such comparisons also indicated peaks in dietary exposure to ∑PBDE (excluding BDE-209) between 2000 and 2005. Exposure estimates for all measured compounds using both TDS and DD data were found to be within recommended tolerable daily intakes where available or within acceptable margins of exposure.

Associations between human exposure to polybrominated diphenyl ether flame retardants via diet and indoor dust, and internal dose: A systematic review.

The aim of this review was to identify and appraise the current international evidence of associations between concentrations of polybrominated diphenyl ethers (PBDEs) in humans and their indoor dusts and food. We systematically searched Medline, Embase, Web of Science and Scopus (up to Jan 2015), using a comprehensive list of keywords, for English-language studies published in peer-reviewed journals. We extracted information on study design, quality, participants, sample collection methods, adjustments for potential confounders and correlations between PBDE concentrations in internal and external matrices. Of 131 potential articles, 17 studies met the inclusion criteria and were included in the narrative synthesis. We concluded that three key factors influenced correlations between external and internal PBDE exposure; half-life of individual congeners in the human body; proximity and interaction between PBDE source and study subject; and time of study relative to phase out of PBDE technical products. Internal dose of Penta-BDE technical mix congeners generally correlated strongly with dust. The exception was BDE-153 which is known to have higher persistence in human tissues. Despite the low bioaccessibility and short half-life of BDE-209, its high loading in dusts gave strong correlations with body burden where measured. Correlations between PBDE concentrations in duplicate diet and body burden were not apparent from the included studies. Whether dust or diet is the primary exposure source for an individual is tied to the loading of PBDE in dust or food items and the amounts ingested. Simple recommendations such as more frequent hand washing may reduce PBDE body burden.

PBDEs and PBBs in human serum and breast milk from cohabiting UK couples.

Concentrations of PBDEs and PBBs were measured in matched blood and breast milk samples from 10 UK couples collected in 2011-12. These data are the first measurements in human serum from the UK since the 2004 EU ban on all uses of the penta-and octa-BDE formulations and the 2008 ban on the use of the deca-BDE formulation in some applications. Serum ∑PBDE tri-hepta concentrations ranging from 1.0 to 16 ng g(-1) lipid weight, with median 4.0 ng g(-1) lw were measured. Breast milk ∑PBDE tri-hepta concentrations ranged from 1.3 to 21 ng g(-1) lw, with median 5.7 ng g(-1) lw. Couples had similar serum congener concentrations unless one of them frequently stayed away from home for work (different diet and dust exposures) or one had occupational exposure to foams and furnishings or electronics. BB-153 were measured above LOD in 40% of sera and 100% of breast milks samples, with median concentrations of 0.04 and 0.06, and maximums of 0.91 and 0.79 ng g(-1) lw respectively. Concentrations in this study indicated a modest decrease from pre-ban levels reported for the UK. BDE-209 was detected above the limit of detection (LOD) in 15% of sera and 83% of breast milks, with ranges <1.2-20 and <0.2-1.0 ng g(-1) lw respectively. Average daily infant intakes were estimated at 17, 5, 5 and 3 ng kg(-1) bw for BDE-47,-99,-153 and -209 respectively, all well below relevant US-EPA threshold reference dose values (RfDs).