Occurrence and Risk Assessment of Personal PM2.5-Bound Phthalates Exposure for Adults in Hong Kong.

We performed personal PM2.5 monitoring involving 56 adult residents in Hong Kong. Additionally, paired personal and residential indoor fine particle (PM2.5) samples were collected from 26 homes and from 3 fixed monitoring locations (i.e., outdoor samples). Six PM2.5-bound phthalate esters (PAEs)-including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP)-were measured using a thermal desorption-gas chromatography/mass spectrometer method. Average ∑6PAEs (i.e., summation of six PAE congeners) concentrations in personal PM2.5 exposure (699.4 ng/m3) were comparable with those in residential indoors (646.9 ng/m3), and both were slightly lower than the outdoor levels. DEHP was the most abundant PAE congener (80.3%-85.0%) and found at the highest levels in different exposure categories, followed by BBP, DnBP, and DnOP. Strong correlations were observed between DEHP with DnBP (rs: 0.81-0.90; p < 0.01), BBP (rs: 0.81-0.90; p < 0.01), and DnOP (rs: 0.87-0.93; p < 0.01) in each exposure category. However, no apparent intercorrelations were shown for PAE congeners. Higher indoor concentrations and a stronger correlation between DMP and DEP were found compared with outdoor concentrations. Principal component analysis affirmed heterogeneous distribution and notable variations in PAE sources across different exposure categories. The average daily intakes of ∑6PAEs and DEHP via inhalation were 0.14-0.17 and 0.12-0.16 µg/kg-day for adults in Hong Kong. A time-weighted model was used to estimate PAE exposures incorporating residential indoor and outdoor exposure and time activities. The inhalation cancer risks attributable to measured and estimated personal exposure to DEHP exceeded the U.S. EPA's benchmark (1 × 10-6). The results provide critical information for mitigation strategies, suggesting that PAEs from both ambient and indoor sources should be considered when exploring the inhalation health risks of PAEs exposure.

Validity of using ambient concentrations as surrogate exposures at the individual level for fine particle and black carbon: A systematic review and meta-analysis.

Exposure measurement error is an important source of bias in epidemiological studies. We assessed the validity of employing ambient (outdoor) measurements as proxies of personal exposures at individual levels focusing on fine particles (PM2.5) and black carbon (BC)/elemental carbon (EC) on a global scale. We conducted a systematic review and meta-analysis and searched databases (ISI Web of Science, Scopus, PubMed, Ovid MEDLINE®, Ovid Embase, and Ovid BIOSIS) to retrieve observational studies in English language published from 1 January 2006 until 5 May 2021. Correlation coefficients (r) between paired ambient (outdoor) concentration and personal exposure for PM2.5 or BC/EC were standardized as effect size. We used random-effects meta-analyses to pool the correlation coefficients and investigated the causes of heterogeneity and publication bias. Furthermore, we employed subgroup and meta-regression analyses to evaluate the modification of pooled estimates by potential mediators. This systematic review identified thirty-two observational studies involving 1744 subjects from ten countries, with 28 studies for PM2.5 and 11 studies for BC/EC. Personal PM2.5 exposure is more strongly correlated with ambient (outdoor) concentrations (0.63, 95% confidence interval [CI]: 0.57-0.68) than personal BC/EC exposure (0.49, 95% CI: 0.38-0.59), with significant differences in r (0.14, 95% CI: 0.03-0.25; p < 0.05). The results demonstrated that the health status of participants was a significant modifier of pooled correlations. In addition, the personal to ambient (P/A) ratio for PM2.5 and average ambient BC/EC levels were potential effect moderators of the pooled r. The funnel plots and Egger's regression test indicated inevident publication bias. The pooled estimates were robust through sensitivity analyses. The results support the growing consensus that the validity coefficient of proxy measures should be addressed when interpreting results from epidemiological studies to better understand how strong health outcomes are affected by different levels of PM2.5 and their components.

Characteristics and health risks of personal exposure to particle-bound PAHs for Hong Kong adult residents: From ambient pollution to indoor exposure.

Research on individual level polycyclic aromatic hydrocarbons (PAHs) exposure is scarce. Moreover, the independent contribution of ambient- and indoor-origin PAHs to personal exposure remains poorly studied. We performed simultaneous ambient, residential indoor, and personal exposure measurements in a panel of healthy adults to investigate particle-bound PAHs, focusing on their carcinogenic congeners (cPAHs). Average PAH concentrations were much higher in ambient and residential indoor than personal exposure, with distinct seasonal variations. We employed chrysene as a tracer to investigate residential indoor and personal PAHs exposure by origin. Personal cPAH exposure was largely attributable to ambient-origin exposures (95.8%), whereas a considerable proportion of residential indoor PAHs was likely attributable to indoor emissions (33.8%). Benzo[a]pyrene equivalent (BaPeq) concentrations of cPAH accounted for 95.2%-95.6% of total carcinogenic potential. Uncertainties in estimated PAHs (and BaPeq) exposure and cancer risks for adults were calculated using the Monte Carlo simulation. Cancer risks attributable to ambient, residential indoor, and personal cPAH inhalation exposures ranged from 4.0 × 10-6 to 1.0 × 10-5 . A time-activity weighted model was employed for personal PAH exposure estimations. Estimated cPAH exposures demonstrate high cancer risks for adults in Hong Kong, suggesting that exposure to indoor-generated PAHs should be of great concern to the general population.

Conceptualising illness and disease: reflections on Sharpe and Greco (2019).

In a recent paper, Sharpe and Greco suggest that chronic fatigue syndrome/myalgic encephalomyelitis (MECFS) can be viewed as an instance of "illness without disease", and consequently, treatment should be directed towards altering the patient's experience of, and response to, their symptoms. We discuss two broad issues that arise from Sharpe and Greco's article, one relating to the assumptions they make about MECFS and its treatment specifically, and the other relating to their conceptualisation of the illness/disease dichotomy. We argue that the term "illness without disease", in the sense that Sharpe and Greco use it, is problematic because it can lead to unwarranted causal assumptions. Following these critical comments, we present a new framework for conceptualising the relationship between explanatory disease models and the experience of illness.

ERS/ATS workshop report on respiratory health effects of household air pollution.

Exposure to household air pollution (HAP) from solid fuel combustion affects almost half of the world population. Adverse respiratory outcomes such as respiratory infections, impaired lung growth and chronic obstructive pulmonary disease have been linked to HAP exposure. Solid fuel smoke is a heterogeneous mixture of various gases and particulates. Cell culture and animal studies with controlled exposure conditions and genetic homogeneity provide important insights into HAP mechanisms. Impaired bacterial phagocytosis in exposed human alveolar macrophages possibly mediates several HAP-related health effects. Lung pathological findings in HAP-exposed individuals demonstrate greater small airways fibrosis and less emphysema compared with cigarette smokers. Field studies using questionnaires, air pollution monitoring and/or biomarkers are needed to better establish human risks. Some, but not all, studies suggest that improving cookstove efficiency or venting emissions may be associated with reduced respiratory symptoms, lung function decline in women and severe pneumonia in children. Current studies focus on fuel switching, stove technology replacements or upgrades and air filter devices. Several governments have initiated major programmes to accelerate the upgrade from solid fuels to clean fuels, particularly liquid petroleum gas, which provides research opportunities for the respiratory health community.

Deterministic Lateral Displacement: The Next-Generation CAR T-Cell Processing?

Reliable cell recovery and expansion are fundamental to the successful scale-up of chimeric antigen receptor (CAR) T cells or any therapeutic cell-manufacturing process. Here, we extend our previous work in whole blood by manufacturing a highly parallel deterministic lateral displacement (DLD) device incorporating diamond microposts and moving into processing, for the first time, apheresis blood products. This study demonstrates key metrics of cell recovery (80%) and platelet depletion (87%), and it shows that DLD T-cell preparations have high conversion to the T-central memory phenotype and expand well in culture, resulting in twofold greater central memory cells compared to Ficoll-Hypaque (Ficoll) and direct magnetic approaches. In addition, all samples processed by DLD converted to a majority T-central memory phenotype and did so with less variation, in stark contrast to Ficoll and direct magnetic prepared samples, which had partial conversion among all donors (<50%). This initial comparison of T-cell function infers that cells prepared via DLD may have a desirable bias, generating significant potential benefits for downstream cell processing. DLD processing provides a path to develop a simple closed system that can be automated while simultaneously addressing multiple steps when there is potential for human error, microbial contamination, and other current technical challenges associated with the manufacture of therapeutic cells.

Impacts of air cleaners on indoor air quality in residences impacted by wood smoke.

Residential wood combustion is an important source of ambient air pollution, accounting for over 25% of fine particulate matter (PM2.5) emissions in Canada. In addition to these ambient contributions, wood smoke pollutants can enter the indoor environment directly when loading or stoking stoves, resulting in a high potential for human exposure. A study of the effectiveness of air cleaners at reducing wood smoke-associated PM2.5 of indoor and outdoor origin was conducted in 31 homes during winter 2009-10. Day 1, the residents' wood burning appliance operated as usual with no air cleaner. Days 2 and 3, the wood burning appliance was not operational and the air cleaner was randomly chosen to operate in "filtration" or "placebo filtration" mode. When the air cleaner was operating, total indoor PM2.5 levels were significantly lower than on placebo filtration days (p = 0.0001) resulting in a median reduction of 52%. There was also a reduction in the median PM2.5 infiltration factor from 0.56 to 0.26 between these 2 days, suggesting the air cleaner was responsible for increased PM2.5 deposition on filtration days. Our findings suggest that the use of an air cleaner reduces exposure to indoor PM2.5 resulting from both indoor and ambient wood smoke sources.

Comparison of how ambient PMc and PM2.5 influence the inflammatory potential.

Airborne particulate matter (PM) is one of the six criteria air pollutants currently regulated by the U.S. Environmental Protection Agency (EPA), with existing ambient standards for PM2.5 and PM10. Currently there are no health-based regulations for the size fraction between 2.5 and 10 µm, commonly known as the coarse fraction (PMc). The present study investigates current gaps in knowledge for PMc including exposure toxicity and PM ratios (PMc:PM2.5) in PM10. Throughout the world, all the three PM size fractions have been shown to be associated with adverse impacts. Recent studies have shown that PMc can be more detrimental to susceptible populations when directly compared to PM2.5, and that the PMc fraction in PM10 can account for the majority of the inflammatory response from PM10 exposure. In our studies we utilized a bone marrow-derived mouse macrophage in vitro system to compare the inflammatory potential of PMc, PM2.5 and mixtures of the two. The result was a linear increase in interleukin(IL) -1ß with increasing levels of exposure to winter and summer PMc, as compared to PM2.5, which exhibited logarithmic growth. Also, exposure to PM10 as a function of PM2.5 and PMc mass ratios showed that IL-1ß and TNF-α levels increased synergistically with a greater burden of PMc. Endotoxin content in the PM did not correlate with these results, suggesting that other activators in PMc are likely responsible for activating the NF-κB pathway and the inflammasome.

Adverse effects of wood smoke PM(2.5) exposure on macrophage functions.

Epidemiological studies have shown a correlation between chronic biomass smoke exposure and increased respiratory infection. Pulmonary macrophages are instrumental in both the innate and the adaptive immune responses to respiratory infection. In the present study, in vitro systems were utilized where alveolar macrophages (AM) and bone marrow-derived macrophages (BMdM) were exposed to concentrated wood smoke-derived particulate matter (WS-PM) and mice were exposed in vivo to either concentrated WS-PM or inhaled WS. In vivo studies demonstrated that WS-exposed mice inoculated with Streptococcus pneumoniae had a higher bacterial load 24 h post-exposure, and corresponding AM were found to have decreased lymphocyte activation activity. Additionally, while classic markers of inflammation (cellular infiltration, total protein, neutrophils) were not affected, there were changes in pulmonary macrophages populations, including significant decreases in macrophages expressing markers of activation in WS-exposed mice. The lymphocyte activation activity of WS-PM-exposed AM was significantly suppressed, but the phagocytic activity appeared unchanged. In an effort to determine a pathway for WS-induced suppression, RelB activation, assessed by nuclear translocation, was observed in AM exposed to either inhaled WS or instilled WS-PM. Finally, an analysis of WS-PM fractions determined the presence of 4-5 polycyclic aromatic hydrocarbons (PAHs), and preliminary work suggests a potential role for these PAHs to alter macrophage functions. These studies show a decreased ability of WS-exposed pulmonary macrophages to effectively mount a defense against infection, the effect lasts at least a week post-exposure, and appears to be mediated via RelB activation.

Amphibole asbestos in tree bark--a review of findings for this inhalational exposure source in Libby, Montana.

In June 2009, the U.S. Environmental Protection Agency (EPA) designated the town of Libby, Montana, a public health emergency--the first and only time the EPA has made such a determination under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). From about 1920 until 1990, the leading source of vermiculite ore for the United States and the world was from a mine near Libby. This vermiculite ore was contaminated with fibrous and asbestiform amphibole in veins throughout the deposit. Today, areas surrounding the abandoned vermiculite processing/mining facilities and much of the town of Libby are contaminated with these asbestos fibers, contributing to an outbreak of asbestos-related diseases in the Libby population. Trees in Libby and in forested areas surrounding the abandoned mine have accumulated amphibole asbestos fibers on their bark surface, providing for inhalational exposures. Several studies have been conducted to further understand this exposure pathway. To address exposures to the public, Libby amphibole (LA) was measured in personal breathing zone and Tyvek surface wipe samples collected during firewood harvesting simulations, as well as in the ash and emissions of woodstoves when amphibole-contaminated firewood was combusted. Occupational studies simulating wildland firefighting and routine U.S. Department of Agriculture (USDA) Forest Service activities have also been conducted in the forested areas surrounding the abandoned mine, demonstrating the potential for inhalational exposures during common regional workplace activities. We present a review of the findings of this emerging environmental health concern impacting not only the residents of Libby but applicable to other populations living near asbestos-contaminated areas.

An evaluation of potential occupational exposure to asbestiform amphiboles near a former vermiculite mine.

Amphibole asbestos (AA) has been detected on the surface of tree bark in forests neighboring an abandoned vermiculite mine near Libby, Montana. In the present study, simulations were performed to assess potential AA exposure associated with United States Department of Agriculture Forest Service (FS) occupational activities. Bark samples were collected prior, and personal breathing zone (PBZ) and Tyvek clothing wipe samples were collected during and immediately after trials that simulated FS activities. Transmission electron microscopy (TEM) analyses revealed AA bark concentrations up to 15 million structures per square centimeter (s/cm(2)). AA was detected in 25% of the PBZ TEM samples. AA was detected on wipe samples collected from all activities evaluated. This research demonstrates the potential for airborne exposure and transport of AA in the Kootenai National Forest. These findings are especially relevant to those that work in the area and to the general public who may conduct recreational activities.

Separation and characterization of respirable amphibole fibers from Libby, Montana.

The vermiculite mine in Libby, Montana, was in operation for over 70 yr and was contaminated with asbestos-like amphibole fibers. The mining, processing, and shipping of this vermiculite led to significant fiber inhalation exposure throughout the community, and residents of Libby have developed numerous pulmonary diseases such as lung cancer and mesothelioma. The present study describes the separation of Libby 6-mix into respirable and nonrespirable size fractions by means of aqueous elutriation. The elutriator, designed to separate fibers with aerodynamic diameters smaller than 2.5 microm (respirable) from larger fibers, used an upward flow rate of 3.4 x 10(- 4) cm s(-1). The resultant respirable fraction constituted only 13% of the raw Libby 6-mix mass, and less than 2% of the fibers in the elutriated fraction had aerodynamic diameters exceeding 2.5 microm. Surface area of the elutriated fibers was 5.3 m(- 2) g(-1), compared to 0.53 m(-2) g(-1) for the raw fibers. There were no detectable differences in chemical composition between the larger and smaller fibers. Such harvesting of respirable fractions will allow toxicological studies to be conducted within a controlled laboratory setting, utilizing fiber sizes that may more accurately simulate historical exposure of Libby residents' lungs. Importantly, this work describes a method that allows the use of material enriched in more uniform respirable material than raw Libby 6-mix, making comparisons with other known fiber preparations more valid on a mass basis.

Environmental tobacco smoke, woodstove heating and risk of asthma symptoms.

The effect of common indoor combustion heating sources on childhood asthma is not well described. The objective was to determine if the use of woodstoves in the home or other factors such as environmental tobacco smoke exposure were associated with the frequency of asthma-related symptoms among children in a rural community. Having a person in the household who smoked was associated with a more than doubling in risk for wheezing and other asthma-related symptoms. The use of woodstoves or other types of heating in the homes of children was not associated with reported wheezing during the winter.

Evaluation of asbestos exposures during firewood-harvesting simulations in Libby, MT, USA--preliminary data.

Research was conducted in order to assess potential exposure to asbestos while harvesting firewood from amphibole-contaminated trees near Libby, MT, USA. Three firewood-harvesting simulations took place in the summer and fall of 2006 in the Kootenai Forest inside the US Environmental Protection Agency (EPA) restricted zone surrounding the former W.R. Grace vermiculite mine. Another simulation was conducted near Missoula, MT, USA, which served as the control. The work practices following each simulation were consistent throughout each trial. Personal breathing zone (PBZ) asbestos concentrations were measured by phase contrast microscopy (PCM) and transmission electron microscopy (TEM). Surface wipe samples of personal protective clothing were measured by TEM. The mean (n = 12) PBZ PCM sample time-weighted average (TWA) concentration was 0.29 fibers per milliliter, standard deviation (SD = 0.54). A substantial portion (more than five fibers per sample) of non-asbestos fibers (cellulose) was reported on all PBZ samples (excluding field blanks) when analyzed by TEM. The mean (n = 12) PBZ TEM sample TWA concentration for amphibole fibers <5-microm long was 0.15 fibers per milliliter (SD = 0.21) and the mean (n = 12) PBZ TEM concentration for amphibole fibers >5-microm long was 0.07 fibers per milliliter (SD = 0.08). Substantial amphibole fiber concentrations were revealed on Tyvek clothing wipe samples. The mean concentration (n = 12) was 29 826 fibers per square centimeter (SD = 37 555), with 91% (27 192 fibers per square centimeter) comprised fibers <5-microm long. There were no significant differences in PBZ and wipe sample concentrations among the tasks performed by four investigators. Each of these three simulations were consistent in demonstrating that amphibole fibers are released from tree reservoirs during firewood-harvesting activities in asbestos-contaminated areas and that the potential for exposure exists during such activities.

Evidence and reconstruction of airborne asbestos from unconventional environmental samples.

The understanding of historical ambient asbestos concentrations is critical to exposure mapping and retrospective health impact studies involving asbestos related diseases. Two presentations at the University of Montana Center for Environmental Health Sciences Asbestos Conference (July 28, 2005) introduced novel methods for detecting evidence of past airborne asbestos contamination. In each of these studies, transmission electron microscopy was used to identify and measure asbestos fibers collected in samples from unconventional environmental sources. In the first study, paleolimnology, analytical transmission electron microscopy, particle-separation techniques, and empirical aerosol-sediment modeling were combined to provide the first measurements of airborne asbestos concentrations prior to the 1980s. In an upstate New York study area, airborne concentrations of chrysotile followed its 20th-century usage, with highest concentrations near mid-century (approximately 0.1 fibers/cm3), followed by a decrease in the last quarter century. Airborne concentrations of anthophyllite asbestos (a contaminant from nearby talc mines and mills) increased from <0.004 to 0.022 fibers/cm3 from 1847 to 1995. In the second study, tree bark and core samples were collected from areas near the asbestos-contaminated vermiculite mine in Libby, MT. We originally hypothesized that trees in the areas surrounding the mine could serve as reservoirs for ambient amphibole fibers. Though gravimetric reduction of a tree core sample did not indicate the presence of amphibole fibers, transmission electron microscopy analysis of bark samples yielded substantial amphibole fiber concentrations ranging from 14 to 260 million amphibole fibers/cm2. Based on these preliminary results, we conclude that trees in the Libby valley can serve as reservoirs for amphibole fibers, and that a continued potential for exposure exists for those who harvest contaminated wood.