Cigarette-related cadmium and environmental pollution exposure are reflected in airway ultrafine particle content.
ABSTRACT: Introduction:Particulate matter (PM) and cigarette-related cadmium exposure increases inflammation and smokers' susceptibility to developing lung diseases. The majority of inhaled metals are attached to the surface of ultrafine particles (UFPs). A low inhaled UFP content in exhaled breath condensate (EBC) reflects a high inflammatory status of airways. Methods:EBC was collected from 58 COPD patients and 40 healthy smokers and nonsmokers. Participants underwent spirometry, diffusion capacity, EBC and blood sampling. Environmental pollution data were collected from monitoring stations. UFPs were measured in EBC and serum, and cadmium content was quantified. Results:Subjects with low UFP concentrations in EBC (<0.18×108·mL-1) had been exposed to higher long-term PM2.5 levels versus subjects with high UFP concentrations in EBC (>0.18×108·mL-1) (21.9 µg·m-3 versus 17.4 µg·m-3, p?0.001). Long-term PM2.5 exposure levels correlated negatively with UFP concentrations in EBC and positively with UFP concentrations in serum (r=-0.54, p?0.001 and r=0.23, p=0.04, respectively). Healthy smokers had higher cadmium levels in EBC versus healthy nonsmokers and COPD patients (25.2 ppm versus 23.7 ppm and 23.3 ppm, p=0.02 and p=0.002, respectively). Subjects with low UFP concentrations in EBC also had low cadmium levels in EBC versus subjects with high UFP levels (22.8 ppm versus 24.2 ppm, p=0.004). Conclusions:Low UFP concentration in EBC is an indicator of high-level PM exposure. High cadmium levels in EBC among smokers and the association between cadmium and UFP content in EBC among COPD patients indicate cadmium lung toxicity.
Project description:Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels). UFPs were separated in two fractions: (1) sub-10?nm particles, named nano organic carbon (NOC) particles and (2) primarily soot particles of 20-40?nm and their agglomerates (200?nm). We found that both NOC and soot UFPs induced the release of IL-18 and IL-33 from unstable/exacerbated COPD-derived PBMCs. This effect was associated with higher levels of mitochondrial dysfunction and derived reactive oxygen species, which were higher in PBMCs from unstable COPD patients after combustion-generated UFP exposure. Moreover, lower mRNA expression of the repairing enzyme OGG1 was associated with the higher levels of 8-OH-dG compared with non-smoker and smokers. It was interesting that IL-18 and IL-33 release from PBMCs of unstable COPD patients was not NOD-like receptor 3/caspase-1 or caspase-8-dependent, but rather correlated to caspase-4 release. This effect was not evident in stable COPD-derived PBMCs. Our data suggest that combustion-generated UFPs induce the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects, shedding new light into the biology of this key complex in COPD.
Project description:BACKGROUND:Exposure to ultrafine particles (UFP, particles with aerodynamic diameter?<?100?nm) is associated with reduced lung function and airway inflammation in individuals with asthma. Recently, elevated UFP number concentrations (PN) from aircraft landing and takeoff activity were identified downwind of the Los Angeles International Airport (LAX) but little is known about the health impacts of airport-related UFP exposure. METHODS:We conducted a randomized crossover study of 22 non-smoking adults with mild to moderate asthma in Nov-Dec 2014 and May-Jul 2015 to investigate short-term effects of exposure to LAX airport-related UFPs. Participants conducted scripted, mild walking activity on two occasions in public parks inside (exposure) and outside (control) of the high UFP zone. Spirometry, multiple flow exhaled nitric oxide, and circulating inflammatory cytokines were measured before and after exposure. Personal UFP PN and lung deposited surface area (LDSA) and stationary UFP PN, black carbon (BC), particle-bound PAHs (PB-PAH), ozone (O3), carbon dioxide (CO2) and particulate matter (PM2.5) mass were measured. Source apportionment analysis was conducted to distinguish aircraft from roadway traffic related UFP sources. Health models investigated within-subject changes in outcomes as a function of pollutants and source factors. RESULTS:A high two-hour walking period average contrast of ~34,000?particles·cm-3 was achieved with mean (std) PN concentrations of 53,342 (25,529) and 19,557 (11,131)?particles·cm-3 and mean (std) particle size of 28.7 (9.5) and 33.2 (11.5) at the exposure and control site, respectively. Principal components analysis differentiated airport UFPs (PN), roadway traffic (BC, PB-PAH), PM mass (PM2.5, PM10), and secondary photochemistry (O3) sources. A standard deviation increase in the 'Airport UFPs' factor was significantly associated with IL-6, a circulating marker of inflammation (single-pollutant model: 0.21, 95% CI?=?0.08-0.34; multi-pollutant model: 0.18, 0.04-0.32). The 'Traffic' factor was significantly associated with lower Forced Expiratory Volume in 1?s (FEV1) (single-pollutant model: -1.52, -2.28 to -0.77) and elevated sTNFrII (single-pollutant model: 36.47; 6.03-66.91; multi-pollutant model: 64.38; 6.30-122.46). No consistent associations were observed with exhaled nitric oxide. CONCLUSIONS:To our knowledge, our study is the first to demonstrate increased acute systemic inflammation following exposure to airport-related UFPs. Health effects associated with roadway traffic exposure were distinct. This study emphasizes the importance of multi-pollutant measurements and modeling techniques to disentangle sources of UFPs contributing to the complex urban air pollution mixture and to evaluate population health risks.
Project description:Little is known about the long-term health effects of ambient ultrafine particles (<0.1 ?m) (UFPs) including their association with respiratory disease incidence. In this study, we examined the relationship between long-term exposure to ambient UFPs and the incidence of lung cancer, adult-onset asthma, and chronic obstructive pulmonary disease (COPD).Our study cohort included approximately 1.1 million adults who resided in Toronto, Canada and who were followed for disease incidence between 1996 and 2012. UFP exposures were assigned to residential locations using a land use regression model. Random-effect Cox proportional hazard models were used to estimate hazard ratios (HRs) describing the association between ambient UFPs and respiratory disease incidence adjusting for ambient fine particulate air pollution (PM2.5), NO2, and other individual/neighbourhood-level covariates.In total, 74,543 incident cases of COPD, 87,141 cases of asthma, and 12,908 cases of lung cancer were observed during follow-up period. In single pollutant models, each interquartile increase in ambient UFPs was associated with incident COPD (HR = 1.06, 95% CI: 1.05, 1.09) but not asthma (HR = 1.00, 95% CI: 1.00, 1.01) or lung cancer (HR = 1.00, 95% CI: 0.97, 1.03). Additional adjustment for NO2 attenuated the association between UFPs and COPD and the HR was no longer elevated (HR = 1.01, 95% CI: 0.98, 1.03). PM2.5 and NO2 were each associated with increased incidence of all three outcomes but risk estimates for lung cancer were sensitive to indirect adjustment for smoking and body mass index.In general, we did not observe clear evidence of positive associations between long-term exposure to ambient UFPs and respiratory disease incidence independent of other air pollutants. Further replication is required as few studies have evaluated these relationships.
Project description:Marine traffic in harbors can be responsible for significant atmospheric concentrations of ultrafine particles (UFPs), which have widely recognized negative effects on human health. It is therefore essential to model and measure the time evolution of the number size distributions and chemical composition of UFPs in ship exhaust to assess the resulting exposure in the vicinity of shipping routes. In this study, a sequential modelling chain was developed and applied, in combination with the data measured and collected in major harbor areas in the cities of Helsinki and Turku in Finland, during winter and summer in 2010-2011. The models described ship emissions, atmospheric dispersion, and aerosol dynamics, complemented with a time-microenvironment-activity model to estimate the short-term UFP exposure. We estimated the dilution ratio during the initial fast expansion of the exhaust plume to be approximately equal to eight. This dispersion regime resulted in a fully formed nucleation mode (denoted as Nuc2). Different selected modelling assumptions about the chemical composition of Nuc2 did not have an effect on the formation of nucleation mode particles. Aerosol model simulations of the dispersing ship plume also revealed a partially formed nucleation mode (Nuc1; peaking at 1.5 nm), consisting of freshly nucleated sulfate particles and condensed organics that were produced within the first few seconds. However, subsequent growth of the new particles was limited, due to efficient scavenging by the larger particles originating from the ship exhaust. The transport of UFPs downwind of the ship track increased the hourly mean UFP concentrations in the neighboring residential areas by a factor of two or more up to a distance of 3600 m, compared with the corresponding UFP concentrations in the urban background. The substantially increased UFP concentrations due to ship traffic significantly affected the daily mean exposures in residential areas located in the vicinity of the harbors.
Project description:Adenosine and related purines have established roles in inflammation, and elevated airway concentrations are predicted in patients with COPD. However, accurate airway surface purine measurements can be confounded by stimulation of purine release during collection of typical respiratory samples.Airway samples were collected noninvasively as exhaled breath condensate (EBC) from 36 healthy nonsmokers (NS group), 28 healthy smokers (S group), and 89 subjects with COPD (29 with GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage II, 29 with GOLD stage III, and 31 with GOLD stage IV) and analyzed with mass spectrometry for adenosine, adenosine monophosphate (AMP), and phenylalanine, plus urea as a dilution marker. Variable dilution of airway secretions in EBC was controlled using ratios to urea, and airway surface concentrations were calculated using EBC to serum urea-based dilution factors.EBC adenosine to urea ratios were similar in NS (0.20 ± 0.21) and S (0.22 ± 0.20) groups but elevated in those with COPD (0.32 ± 0.30, P < .01 vs NS). Adenosine to urea ratios were highest in the most severely affected cohort (GOLD IV, 0.35 ± 0.34, P < .01 vs NS) and negatively correlated with FEV(1) (r = -0.27, P < .01). Elevated AMP to urea ratios were also observed in the COPD group (0.58 ± 0.97 COPD, 0.29 ± 0.35 NS, P < .02), but phenylalanine to urea ratios were similar in all groups. Airway surface adenosine concentrations calculated in a subset of subjects were 3.2 ± 2.7 ?M in those with COPD (n = 28) relative to 1.7 ± 1.5 ?M in the NS group (n = 16, P < .05).Airway purines are present on airway surfaces at physiologically significant concentrations, are elevated in COPD, and correlate with markers of COPD severity. Purinergic signaling pathways are potential therapeutic targets in COPD, and EBC purines are potential noninvasive biomarkers.
Project description:BACKGROUND:Ambient ultrafine particles (UFPs, <0.1 µm) can reach the human brain, but to our knowledge, epidemiologic studies have yet to evaluate the relation between UFPs and incident brain tumors. METHODS:We conducted a cohort study of within-city spatial variations in ambient UFPs across Montreal and Toronto, Canada, among 1.9 million adults included in multiple cycles of the Canadian Census Health and Environment Cohorts (1991, 1996, 2001, and 2006). UFP exposures (3-year moving averages) were assigned to residential locations using land-use regression models with exposures updated to account for residential mobility within and between cities. We followed cohort members for malignant brain tumors (ICD-10 codes C71.0-C71.9) between 2001 and 2016; Cox proportional hazards models (stratified by age, sex, immigration status, and census cycle) were used to estimate hazard ratios (HRs) adjusting for fine particle mass concentrations (PM2.5), nitrogen dioxide (NO2), and various sociodemographic factors. RESULTS:In total, we identified 1,400 incident brain tumors during the follow-up period. Each 10,000/cm increase in UFPs was positively associated with brain tumor incidence (HR = 1.112, 95% CI = 1.042, 1.188) after adjusting for PM2.5, NO2, and sociodemographic factors. Applying an indirect adjustment for cigarette smoking and body mass index strengthened this relation (HR = 1.133, 95% CI = 1.032, 1.245). PM2.5 and NO2 were not associated with an increased incidence of brain tumors. CONCLUSIONS:Ambient UFPs may represent a previously unrecognized risk factor for incident brain tumors in adults. Future studies should aim to replicate these results given the high prevalence of UFP exposures in urban areas.
Project description:Interleukin(IL)-33 is an epithelial alarmin important for eosinophil maturation, activation and survival. The aim of this study was to examine the association between IL-33, its receptor expression and airway eosinophilic inflammation in non-atopic COPD.IL-33 concentrations were measured in exhaled breath condensate (EBC) collected from healthy non-smokers, asthmatics and non-atopic COPD subjects using ELISA. Serum and sputum samples were collected from healthy non-smokers, healthy smokers and non-atopic COPD patients. Based on sputum eosinophil count, COPD subjects were divided into subgroups with airway eosinophilic inflammation (sputum eosinophils >?3%) or without (sputum eosinophils ?3%). IL-33 and soluble form of IL-33 receptor (sST2) protein concentrations were measured in serum and sputum supernatants using ELISA. ST2 mRNA expression was measured in peripheral mononuclear cells and sputum cells by qPCR. Hemopoietic progenitor cells (HPC) expressing ST2 and intracellular IL-5 were enumerated in blood and induced sputum by means of flow cytometry.IL-33 levels in EBC were increased in COPD patients to a similar extent as in asthma and correlated with blood eosinophil count. Furthermore, serum and sputum IL-33 levels were higher in COPD subjects with sputum eosinophilia than in those with a sputum eosinophil count ?3% (p?<?0.001 for both). ST2 mRNA was overexpressed in sputum cells obtained from COPD patients with airway eosinophilic inflammation compared to those without sputum eosinophilia (p?<?0.01). Similarly, ST2?+?IL-5+ HPC numbers were increased in the sputum of COPD patients with airway eosinophilia (p?<?0.001).Our results indicate that IL-33 is involved in the development of eosinophilic airway inflammation in non-atopic COPD patients.
Project description:INTRODUCTION:Ambient air pollution is a known risk factor for adverse birth outcomes, but the role of ultrafine particles (UFPs) is not well understood. Aircraft-origin UFPs adversely affect air quality over large residential areas downwind of airports, but their reproductive health burden remains uninvestigated. OBJECTIVES:This analysis evaluated whether UFPs from jet aircraft emissions are associated with increased rates of preterm birth (PTB) among pregnant mothers living downwind of Los Angeles International Airport (LAX). METHODS:This population-based study used birth records, provided by the California Department of Public Health, to ascertain birth outcomes and a novel, validated geospatial UFP dispersion model approach to estimate in utero exposures. All mothers who gave birth from 2008 to 2016 while living within 15km of LAX were included in this analysis (N=174,186; including 15,134 PTBs). RESULTS:In utero exposure to aircraft-origin UFPs was positively associated with PTB. The odds ratio (OR) per interquartile range (IQR) increase [9,200 particles per cubic centimeter (cc)] relative UFP exposure was 1.04 [95% confidence interval (CI): 1.02, 1.06]. When comparing the fourth quartile of UFP exposure to the first quartile, the OR for PTB was 1.14 (95% CI: 1.08, 1.20), adjusting for maternal demographic characteristics, exposure to traffic-related air pollution, and airport-related noise. CONCLUSION:Our results suggest that emissions from aircraft play an etiologic role in PTBs, independent of noise and traffic-related air pollution exposures. These findings are of public health concern because UFP exposures downwind of airfields are common and may affect large, densely populated residential areas. https://doi.org/10.1289/EHP5732.
Project description:Exposure to ambient particulate matter (PM) is a risk factor for cardiovascular diseases. The redox-active ultrafine particles (UFPs) promote vascular oxidative stress and inflammatory responses. We hypothesized that UFPs modulated lipid metabolism and anti-oxidant capacity of high density lipoprotein (HDL) with an implication in atherosclerotic lesion size. Fat-fed low density lipoprotein receptor-null (LDLR?/? mice were exposed to filtered air (FA) or UFPs for 10 weeks with or without administering an apolipoprotein A-I mimetic peptide made of D-amino acids, D-4F. LDLR?/? mice exposed to UFPs developed a reduced plasma HDL level (P < 0.01), paraoxonase activity (P < 0.01), and HDL anti-oxidant capacity (P < 0.05); but increased LDL oxidation, free oxidized fatty acids, triglycerides, serum amyloid A (P < 0.05), and tumor necrosis factor ? (P < 0.05), accompanied by a 62% increase in the atherosclerotic lesion ratio of the en face aortic staining and a 220% increase in the cross-sectional lesion area of the aortic sinus (P < 0.001). D-4F administration significantly attenuated these changes. UFP exposure promoted pro-atherogenic lipid metabolism and reduced HDL anti-oxidant capacity in fat-fed LDLR?/? mice, associated with a greater atherosclerotic lesion size compared with FA-exposed animals. D-4F attenuated UFP-mediated pro-atherogenic effects, suggesting the role of lipid oxidation underlying UFP-mediated atherosclerosis.
Project description:Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health.