RESUMEN
Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 µg/m3) under placebo, and PM2.5 (250 µg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4+ T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (Pinteraction = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM2.5 effects, with possible significant public health benefit in areas with frequent PM2.5 peaks.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Epigénesis Genética/efectos de los fármacos , Ácido Fólico/administración & dosificación , Material Particulado/toxicidad , Vitamina B 12/administración & dosificación , Vitamina B 6/administración & dosificación , Adolescente , Adulto , Contaminación del Aire , Estudios Cruzados , Metilación de ADN/efectos de los fármacos , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Epigenómica , Femenino , Humanos , Masculino , Proyectos Piloto , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Exposures to ambient particulate matter (PM) are associated with increased morbidity and mortality. PM2.5 (<2.5 µm) and ozone exposures have been shown to associate with carotid intima media thickness in humans. Animal studies support a causal relationship between air pollution and atherosclerosis and identified adverse PM effects on HDL functionality. We aimed to determine whether brief exposures to PM2.5 and/or ozone could induce effects on HDL anti-oxidant and anti-inflammatory capacity in humans. METHODS: Subjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 µg/m(3), ozone targeted at 240 µg/m(3) (120 ppb), PM2.5 plus ozone targeted at similar concentrations, and filtered air (FA) for 2 h, on 4 different occasions, at least two weeks apart, in a randomized, crossover study. Blood was obtained before exposures (baseline), 1 h after and 20 h after exposures. Plasma HDL anti-oxidant/anti-inflammatory capacity and paraoxonase activity were determined. HDL anti-oxidant/anti-inflammatory capacity was assessed by a cell-free fluorescent assay and expressed in units of a HDL oxidant index (HOI). Changes in HOI (ΔHOI) were calculated as the difference in HOI from baseline to 1 h after or 20 h after exposures. RESULTS: There was a trend towards bigger ΔHOI between PM2.5 and FA 1 h after exposures (p = 0.18) but not 20 h after. This trend became significant (p <0.05) when baseline HOI was lower (<1.5 or <2.0), indicating decreased HDL anti-oxidant/anti-inflammatory capacity shortly after the exposures. There were no significant effects of ozone alone or in combination with PM2.5 on the change in HOI at both time points. The change in HOI due to PM2.5 showed a positive trend with particle mass concentration (p = 0.078) and significantly associated with the slope of systolic blood pressure during exposures (p = 0.005). CONCLUSIONS: Brief exposures to concentrated PM2.5 elicited swift effects on HDL anti-oxidant/anti-inflammatory functionality, which could indicate a potential mechanism for how particulate air pollution induces harmful cardiovascular effects.
Asunto(s)
Contaminación del Aire/efectos adversos , Enfermedades Cardiovasculares/etiología , Lipoproteínas HDL/sangre , Modelos Biológicos , Ozono/toxicidad , Material Particulado/toxicidad , Salud Urbana , Adulto , Contaminantes Atmosféricos/química , Contaminantes Atmosféricos/toxicidad , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inmunología , Estudios de Cohortes , Estudios Cruzados , Femenino , Humanos , Exposición por Inhalación/efectos adversos , Masculino , Oxidantes/química , Oxidantes/toxicidad , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Material Particulado/química , Riesgo , Método Simple Ciego , Adulto JovenRESUMEN
BACKGROUND: Knowledge of the inhalable particulate matter components responsible for health effects is important for developing targeted regulation. OBJECTIVES: In a double-blind randomised cross-over trial of controlled human exposures to concentrated ambient particles (CAPs) and their endotoxin and (1â3)-ß-D-glucan components, we evaluated acute inflammatory responses. METHODS: 35 healthy adults were exposed to five 130-min exposures at rest: (1) fine CAPs (~250 µg/m(3)); (2) coarse CAPs (200 µg/m(3)); (3) second coarse CAPs (~200 µg/m(3)); (4) filtered air; and (5) medical air. Induced sputum cell counts were measured at screening and 24 h postexposure. Venous blood total leucocytes, neutrophils, interleukin-6 and high-sensitivity C reactive protein (CRP) were measured pre-exposure, 3 and 24 h postexposure. RESULTS: Relative to filtered air, an increase in blood leucocytes 24 h (but not 3 h) postexposure was significantly associated with coarse (estimate=0.44×10(9) cells/L (95% CI 0.01 to 0.88); n=132) and fine CAPs (0.68×10(9) cells /L (95% CI 0.19 to 1.17); n=132), but not medical air. Similar associations were found with neutrophil responses. An interquartile increase in endotoxin (5.4 ng/m(3)) was significantly associated with increased blood leucocytes 3 h postexposure (0.27×10(9) cells/L (95% CI 0.03 to 0.51); n=98) and 24 h postexposure (0.37×10(9) cells/L (95% CI 0.12 to 0.63); n=98). This endotoxin effect did not differ by particle size. There were no associations with glucan concentrations or interleukin-6, CRP or sputum responses. CONCLUSIONS: In healthy adults, controlled coarse and fine ambient particle exposures independently induced acute systemic inflammatory responses. Endotoxin contributes to the inflammatory role of particle air pollution.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Endotoxinas/efectos adversos , Inflamación/inducido químicamente , Exposición por Inhalación/efectos adversos , Leucocitos/metabolismo , Tamaño de la Partícula , Material Particulado/efectos adversos , Adolescente , Adulto , Contaminantes Atmosféricos/química , Contaminantes Atmosféricos/inmunología , Método Doble Ciego , Endotoxinas/inmunología , Femenino , Humanos , Masculino , Neutrófilos/metabolismo , Material Particulado/química , Material Particulado/inmunología , Adulto JovenRESUMEN
CONTEXT: Strong epidemiological evidence exists linking particulate matter (PM) exposures with hospital admissions of individuals for cardiopulmonary symptoms. The PM size is important in influencing the extent of infiltration into the respiratory tract and systemic circulation and directs the differential physiological impacts. OBJECTIVE: To investigate the differential effects of the quasi-ultrafine (PM(0.2)), fine (PM(0.15-2.5)), and coarse PM (PM(2.5-10)) size fractions on pulmonary and cardiac function. METHODS: Female BALB/c mice were exposed to HEPA-filtered laboratory air or concentrated coarse, fine, or quasi-ultrafine PM using Harvard Ambient Particle Concentrators in conjunction with our nose-only exposure system. These exposures were conducted as part of the "Health Effects of Aerosols in Toronto (HEAT)" campaign. Following a 4 h exposure, mice underwent assessment of respiratory function and recording of electrocardiograms using the flexiVent® system. RESULTS: Exposure to coarse and fine PM resulted in a significant reduction in quasistatic compliance of the lung. Baseline total respiratory resistance and maximum responsiveness to methacholine were augmented after coarse PM exposures but were not affected by quasi-ultrafine PM exposures. In contrast, quasi-ultrafine PM alone had a significant effect on heart rate and in reducing heart rate variability. CONCLUSION: These findings indicate that coarse and fine PM influence lung function and airways responsiveness, while ultrafine PM can perturb cardiac function. This study supports the hypothesis that coarse and fine PM exerts its predominant physiologic effects at the site of deposition in the airways, whereas ultrafine PM likely crosses the alveolar epithelial barrier into the systemic circulation to affect cardiovascular function.
Asunto(s)
Resistencia de las Vías Respiratorias/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Material Particulado/toxicidad , Respiración/efectos de los fármacos , Animales , Líquido del Lavado Bronquioalveolar/citología , Electrocardiografía/efectos de los fármacos , Femenino , Cloruro de Metacolina/farmacología , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. METHODS: To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA) and challenged with nebulized PBS (OVA/PBS) or OVA (OVA/OVA) for three consecutive days (sub-acute model) or 12 weeks (chronic model), which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3), or HEPA-filtered air (FA), for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC) or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. RESULTS: Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. CONCLUSIONS: This study demonstrates that arginase is upregulated following environmental exposures in murine models of asthma, and contributes to the pollution-induced exacerbation of airways responsiveness. Thus arginase may be a therapeutic target to protect susceptible populations against the adverse health effects of air pollution, such as fine particles and ozone, which are two of the major contributors to smog.
Asunto(s)
Arginasa/metabolismo , Asma/etiología , Hiperreactividad Bronquial/etiología , Broncoconstricción , Pulmón/efectos de los fármacos , Ozono/toxicidad , Material Particulado/toxicidad , Animales , Arginasa/antagonistas & inhibidores , Asma/enzimología , Asma/inmunología , Asma/fisiopatología , Western Blotting , Ácidos Borónicos/farmacología , Hiperreactividad Bronquial/enzimología , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/fisiopatología , Hiperreactividad Bronquial/prevención & control , Pruebas de Provocación Bronquial , Broncoconstricción/efectos de los fármacos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Femenino , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Exposición por Inhalación , Pulmón/enzimología , Pulmón/inmunología , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Estrés Oxidativo/efectos de los fármacos , Regulación hacia ArribaRESUMEN
RATIONALE: A well-known clinical paradox is that severe bacterial infections persist in the lungs of patients with cystic fibrosis (CF) despite the abundance of polymorphonuclear neutrophils (PMN) and the presence of a high concentration of human neutrophil peptides (HNP), both of which are expected to kill the bacteria but fail to do so. The mechanisms remain unknown. OBJECTIVES: This study examined several possible mechanisms to understand this paradox. METHODS: PMN were isolated from sputum and blood of subjects with and without CF or non-CF bronchiectasis for phagocytic assays. HNP isolated from patients with CF were used to stimulate healthy PMN followed by phagocytic tests. MEASUREMENTS AND MAIN RESULTS: PMN isolated from the sputum of the bronchiectatic patients display defective phagocytosis that correlated with high concentrations of HNP in the lung. When healthy PMN were incubated with HNP, decreased phagocytic capacity was observed in association with depressed surface Fc gamma RIII, actin-filament remodeling, enhanced intracellular Ca(2+), and degranulation. Treatment of PMN with an intracellular Ca(2+) blocker or alpha1-proteinase inhibitor to attenuate the activity of HNP largely prevented the HNP-induced phagocytic deficiency. Intratracheal instillation of HNP in Pallid mice (genetically deficient in alpha1-proteinase inhibitor) resulted in a greater PMN lung infiltration and phagocytic deficiency compared with wild-type mice. CONCLUSIONS: HNP or PMN alone exert antimicrobial ability, which was lost as a result of their interaction. These effects of HNP may help explain the clinical paradox seen in patients with inflammatory lung diseases, suggesting HNP as a novel target for clinical therapy.
Asunto(s)
Bronquiectasia/metabolismo , Bronquiectasia/patología , Fibrosis Quística/patología , Neutrófilos/fisiología , Fagocitosis/fisiología , alfa-Defensinas/metabolismo , Adolescente , Adulto , Animales , Bronquiectasia/complicaciones , Estudios de Casos y Controles , Técnicas de Cultivo de Célula , Fibrosis Quística/complicaciones , Fibrosis Quística/metabolismo , Femenino , Humanos , Elastasa de Leucocito/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Infiltración Neutrófila/fisiología , Receptores de IgG/metabolismo , Adulto JovenRESUMEN
Epidemiological studies have established significant associations between ambient pollutants, including fine particulate matter (PM(2.5)) and ozone (O(3)), and cardiopulmonary morbidity and mortality. One mechanism that has been proposed is a pulmonary/systemic inflammatory response. Although controlled human exposure studies have examined the independent inflammatory responses of PM(2.5) and O(3), no studies have previously examined their joint effects. The study objective was to examine the independent and combined associations between ambient PM(2.5) and O(3) and acute respiratory/inflammatory responses. Using their concentrated ambient particle (CAP) facility for PM(2.5), the authors studied 10 mild asthmatic and 13 nonasthmatic individuals. The 2-h exposures included CAP (range 48-199 microg/m(3)) and filtered air (FA), with/without O(3) (120 ppb), in a randomized block design. Response measures included pulmonary function and inflammatory indices in induced sputum (interleukin [IL]-6, cytology) and blood (IL-6, tumor necrosis factor [TNF]-alpha) measured before and after exposures. Three hours post exposure, there was an increase in blood levels of IL-6, but only after CAP alone exposures; the IL-6 increase was associated with increasing PM(2.5) mass concentration (p = .005). Some individuals switched to shallow breathing during CAP+O(3), possibly accounting for an attenuation of the resultant blood IL-6 response. Asthmatic and nonasthmatic responses were similar. There were no adverse changes in pulmonary function or other inflammatory measures. The study demonstrated an acute IL-6 response to PM(2.5), providing evidence to support the epidemiological findings of associations between ambient levels of particles and cardiopulmonary morbidity and mortality.
Asunto(s)
Interleucina-6/biosíntesis , Oxidantes Fotoquímicos/toxicidad , Ozono/toxicidad , Material Particulado/toxicidad , Adolescente , Adulto , Femenino , Filtración , Humanos , Exposición por Inhalación , Masculino , Oxidantes Fotoquímicos/administración & dosificación , Ozono/administración & dosificación , Tamaño de la Partícula , Material Particulado/administración & dosificación , Pruebas de Función Respiratoria , Mecánica Respiratoria/efectos de los fármacos , Esputo/citología , Factor de Necrosis Tumoral alfa/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: To investigate whether implanted cardioverter defibrillator (ICD) patients exercising indoors on higher air pollution (AP) days had reduced adverse cardiovascular effects compared with those exercising outdoors. METHODS: Eighteen participants were randomly divided into control or intervention groups. Blood pressure (BP), pulse rate (PR), and oxygen saturation (O2SAT) were measured daily before and after participants walked outdoors for 30âminutes. On days with higher forecast AP the intervention group exercised indoors. RESULTS: AP was significantly associated with increased BP and PR, and reduced O2SAT. After adjustment for exercise levels, AP was associated with increased diastolic BP and PR in controls only. Significant improvements in cardiovascular measures over time were observed in both groups. CONCLUSION: In ICD patients, reducing AP exposure may reduce adverse cardiovascular effects, while daily mild exercise may benefit cardiovascular function.
Asunto(s)
Contaminación del Aire/estadística & datos numéricos , Desfibriladores , Ejercicio Físico , Exposición por Inhalación/estadística & datos numéricos , Contaminación del Aire/efectos adversos , Contaminación del Aire Interior , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , Exposición por Inhalación/efectos adversos , Masculino , Persona de Mediana Edad , Material ParticuladoRESUMEN
BACKGROUND: Oxidative stress and inflammation are considered to be important pathways leading to particulate matter (PM)-associated disease. In this exploratory study, we examined the effects of metals and oxidative potential (OP) in urban PM on biomarkers of systemic inflammation, oxidative stress and neural function. METHODS: Fifty-three healthy non-smoking volunteers (mean age 28â¯years, twenty-eight females) were exposed to coarse (2.5-10⯵m, mean 213⯵g/m3), fine (0.15-2.5⯵m, 238⯵g/m3), and/or ultrafine concentrated ambient PM (<0.3⯵m, 136⯵g/m3). Exposures lasted 130â¯min, separated by ≥2â¯weeks. Metal concentrations and OP (measured by ascorbate and glutathione depletion in synthetic airway fluid) in PM were analyzed. Blood and urine samples were collected pre-exposure, and 1-h and 21-h post exposure for assessment of biomarkers. We used mixed-regression models to analyze associations adjusting for PM size and mass concentration. RESULTS: Results for metals were expressed as change (%) from daily pre-exposure biomarker levels after exposure to a metal at a level equivalent to the mean concentration. Exposure to various metals (silver, aluminum, barium, copper, iron, potassium, lithium, nickel, tin, and/or vanadium) was significantly associated with increased levels of various blood or urinary biomarkers. For example, the blood inflammatory marker vascular endothelia growth factor (VEGF) increased 5.3% (95% confidence interval: 0.3%, 10.2%) 1-h post exposure to nickel; the traumatic brain injury marker ubiquitin C-terminal hydrolase L1 (UCHL1) increased 11% (1.2%, 21%) and 14% (0.3%, 29%) 1-h and 21-h post exposure to barium, respectively; and the systemic stress marker cortisol increased 1.5% (0%, 2.9%) and 1.5% (0.5%, 2.8%) 1-h and 21-h post exposure to silver, respectively. Urinary DNA oxidation marker 8hydroxydeoxyguanosine increased 14% (6.4%, 21%) 1-h post exposure to copper; urinary neural marker vanillylmandelic acid increased 29% (3%, 54%) 1-h post exposure to aluminum; and urinary cortisol increased 88% (0.9%, 176%) 1-h post exposure to vanadium. Results for OP were expressed as change (%) from daily pre-exposure biomarker levels after exposure to ascorbate-related OP at a level equivalent to the mean concentration, or for exposure to glutathione-related OP at a level above the limit of detection. Exposure to ascorbate- or glutathione-related OP was significantly associated with increased inflammatory and neural biomarkers including interleukin-6, VEGF, UCHL1, and S100 calcium-binding protein B in blood, and malondialdehyde and 8-hydroxy-deoxy-guanosine in urine. For example, UCHL1 increased 9.4% (1.8%, 17%) in blood 21-h post exposure to ascorbate-related OP, while urinary malondialdehyde increased 19% (3.6%, 35%) and 8-hydroxy-deoxy-guanosine increased 24% (2.9%, 48%) 21-h post exposure to ascorbate- and glutathione-related OP, respectively. CONCLUSION: Our results from this exploratory study suggest that metal constituents and OP in ambient PM may influence biomarker levels associated with systemic inflammation, oxidative stress, perturbations of neural function, and systemic physiological stress.
Asunto(s)
Contaminantes Atmosféricos , Inflamación/inducido químicamente , Exposición por Inhalación/efectos adversos , Metales , Oxidantes , Material Particulado/efectos adversos , Adulto , Contaminantes Atmosféricos/sangre , Contaminantes Atmosféricos/orina , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Humanos , Masculino , Metales/sangre , Metales/orina , Persona de Mediana Edad , Fenómenos Fisiológicos del Sistema Nervioso/efectos de los fármacos , Ontario , Oxidantes/sangre , Oxidantes/orina , Estrés Oxidativo , Adulto JovenRESUMEN
BACKGROUND: The longer the duration of symptoms of occupational asthma (OA) before diagnosis, the poorer the outcome. Physicians can play a key role in the early recognition of occupational lung diseases (OLDs), including OA. Our objective was to document and compare the practice patterns, barriers, and needs for early diagnosis of OA among pulmonologists and family physicians. METHODS: Based on information from the literature and interviews with pulmonologists and family physicians, a survey was developed to obtain information on practice patterns. The survey was sent to all pulmonologists and a random sample of 600 family physicians in Ontario. RESULTS: Eight percent of pulmonologists and 7% of family physicians report seeing >20 patients a year with OLD. The majority report taking a workplace exposure history. The most commonly stated barrier to obtaining a workplace exposure history was time constraints. Main reasons for referral to specialists for diagnosis include personal lack of expertise, testing facilities, and knowledge about workers' compensation, while lack of timely access to specialists is a barrier for referral. While most physicians identified a need for further education, those who did not identify a need for further occupational respiratory education cited low volume of patients, access to specialists, and time constraints as reasons for not wanting further education. CONCLUSIONS: Opportunities are identified to improve health services delivery and educational initiatives for OA, with approaches tailored to each particular physician group.
Asunto(s)
Asma/diagnóstico , Medicina Familiar y Comunitaria , Enfermedades Profesionales/diagnóstico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neumología , Derivación y Consulta/estadística & datos numéricos , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of this study was to compare psychological status, quality of life (QoL), work limitation, and socioeconomic status between patients with occupational asthma (OA) and work-exacerbated asthma (WEA). METHODS: The following questionnaires were administered to participants: Beck anxiety and depression (II) inventories, Marks' Asthma Quality of Life Questionnaire, and Work Limitations Questionnaire. Cross-sectional analyses between OA and WEA subgroups were completed. RESULTS: There were 77 participants. WEA subjects had a trend to higher anxiety scores (OAâ=â9.2â±â8.0, WEAâ=â12.8â±â8.3, Pâ=â0.07, Cohen dâ=â0.4). Depression scores trended higher for those with WEA (OAâ=â9.6â±â10.3, WEAâ=â13.4â±â13.5, Pâ=â0.2, Cohen dâ=â0.3). QoL was comparable between groups. WEA subjects had fewer work limitations (Nâ=â50, OAâ=â25.1â±â27.3, WEAâ=â20.6â±â24.4, Pâ=â0.56, Cohen dâ=â0.3) and OA subjects were more likely to have reduced income. CONCLUSION: In a tertiary clinic, there were some modest differences for specific variables between OA and WEA subjects that may help inform management.
Asunto(s)
Asma Ocupacional/psicología , Salud Mental , Exposición Profesional/efectos adversos , Calidad de Vida , Adulto , Anciano , Ansiedad/etiología , Asma Ocupacional/etiología , Asma Ocupacional/fisiopatología , Estudios Transversales , Depresión/etiología , Femenino , Volumen Espiratorio Forzado , Humanos , Renta , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios , Capacidad Vital , Evaluación de Capacidad de TrabajoRESUMEN
BACKGROUND: Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear. OBJECTIVES: We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles. METHODS: Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10µm, mean 213µg/m3) and fine (0.15-2.5µm, mean 238µg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (mean size 59.6nm, range 47.0-69.8nm), mean (136µg/m3) and filtered medical air. Exposures lasted 130min, separated by ≥2weeks, and the biological constituents endotoxin and ß-1,3-d-glucan of each particle size fraction were measured. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post-exposure to determine neural biomarker levels. Mixed-model regressions assessed associations between exposures and changes in biomarker levels. RESULTS: Results were expressed as percent change from daily pre-exposure biomarker levels. Exposure to coarse CAP was significantly associated with increased urinary levels of the stress-related biomarkers vanillylmandelic acid (VMA) and cortisol when compared with exposure to filtered medical air [20% (95% confidence interval: 1.0%, 38%) and 64% (0.2%, 127%), respectively] 21hours post-exposure. However exposure to coarse CAP was significantly associated with decreases in blood cortisol [-26.0% (-42.4%, -9.6%) and -22.4% (-43.7%, -1.1%) at 1h and 21h post-exposure, respectively]. Biological molecules present in coarse CAP were significantly associated with blood biomarkers indicative of blood brain barrier integrity. Endotoxin content was significantly associated with increased blood ubiquitin C-terminal hydrolase L1 [UCHL1, 11% (5.3%, 16%) per ln(ng/m3+1)] 1-hour post-exposure, while ß-1,3-d-glucan was significantly associated with increased blood S100B [6.3% (3.2%, 9.4%) per ln(ng/m3+1)], as well as UCHL1 [3.1% (0.4%, 5.9%) per ln(ng/m3+1)], one-hour post-exposure. Fine CAP was marginally associated with increased blood UCHL1 when compared with exposure to filtered medical air [17.7% (-1.7%, 37.2%), p=0.07] 21hours post-exposure. Ultrafine CAP was not significantly associated with changes in any blood and urinary neural biomarkers examined. CONCLUSION: Ambient coarse particulate matter and its biological constituents may influence neural biomarker levels that reflect perturbations of blood-brain barrier integrity and systemic stress response.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Biomarcadores/sangre , Material Particulado/toxicidad , beta-Glucanos/análisis , Adolescente , Adulto , Contaminación del Aire/análisis , Biomarcadores/orina , Barrera Hematoencefálica , Estudios Cruzados , Exposición a Riesgos Ambientales , Femenino , Filtración , Humanos , Masculino , Persona de Mediana Edad , Ontario , Proteoglicanos , Población Rural , Ubiquitina Tiolesterasa/sangre , Ubiquitina Tiolesterasa/orina , Adulto JovenRESUMEN
Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 µg/m3) under placebo, and PM2.5 (250 µg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.
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Sistema Nervioso Autónomo/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Inflamación/prevención & control , Material Particulado/efectos adversos , Complejo Vitamínico B/administración & dosificación , Adulto , Estudios Cruzados , Electrocardiografía , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/farmacología , Humanos , Inflamación/inducido químicamente , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Proyectos Piloto , Método Simple Ciego , Vitamina B 12/administración & dosificación , Vitamina B 12/farmacología , Vitamina B 6/administración & dosificación , Vitamina B 6/farmacología , Complejo Vitamínico B/farmacología , Adulto JovenRESUMEN
BACKGROUND: The objective was to determine the repeatability and stability of capnography interfaced with human exposure facility. METHODS: Capnographic wave signals were obtained from five healthy volunteers exposed to particle-free, filtered air during two consecutive 5 min intervals, 10 min apart, within the open and then the sealed and operational human exposure facility (HEF). Using a customized setup comprised of the Oridion Microcap portable capnograph, DA converter and AD card, the signal was acquired and saved as an ASCII file for subsequent processing. The minute ventilation (VE), respiratory rate (RR) and expiratory tidal volume (VTE) were recorded before and after capnographic recording and then averaged. Each capnographic tracing was analyzed for acceptable waves. From each recorded interval, 8 to 19 acceptable waves were selected and measured. The following wave parameters were obtained: total length and length of phase II and III, slope of phase II and III, area under the curve and area under phase III. In addition, we recorded signal measures including the mean, standard deviation, mode, minimum, maximum--which equals end-tidal CO2 (EtCO2), zero-corrected maximum and true RMS. RESULTS: Statistical analysis using a paired t-test for means showed no statistically significant changes of any wave parameters and wave signal measures, corrected for RR and VTE, comparing the measures when the HEF was open vs. sealed and operational. The coefficients of variation of the zero-corrected and uncorrected EtCO2, phase II absolute difference, signal mean, standard deviation and RMS were less than 10% despite a sub-atmospheric barometric pressure, and slightly higher temperature and relative humidity within the HEF when operational. CONCLUSION: We showed that a customized setup for the acquisition and processing of the capnographic wave signal, interfaced with HEF was stable and repeatable. Thus, we expect that analysis of capnographic waves in controlled human air pollution exposure studies is a feasible tool for characterization of cardio-pulmonary effects of such exposures.
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Contaminantes Atmosféricos/farmacocinética , Algoritmos , Capnografía/métodos , Diagnóstico por Computador/métodos , Pulmón/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Environmental microbes have been associated with both protective and adverse health effects in children and adults. Epidemiological studies often rely on broad biomarkers of microbial exposure (i.e. endotoxin, 1 â 3-beta-d-glucan), but fail to identify the taxonomic composition of the microbial community. Our aim was to characterize the bacterial and fungal microbiome in different types of environmental samples collected in studies of human health effects. We determined the composition of microbial communities present in home, school and outdoor air samples by amplifying and sequencing regions of rRNA genes from bacteria (16S) and fungi (18S and ITS). Samples for this pilot study included indoor settled dust (from both a Boston area birth cohort study on Home Allergens and Asthma (HAA) (n = 12) and a study of school exposures and asthma symptoms (SICAS) (n = 1)), as well as fine and coarse concentrated outdoor ambient particulate (CAP) samples (n = 9). Sequencing of amplified 16S, 18S, and ITS regions was performed on the Roche-454 Life Sciences Titanium pyrosequencing platform. Indoor dust samples were dominated by Gram-positive bacteria (Firmicutes and Actinobacteria); the most abundant bacterial genera were those related to human flora (Streptococcus, Staphylococcus, Corynebacterium and Lactobacillus). Outdoor CAPs were dominated by Gram-negative Proteobacteria from water and soil sources, in particular the genera Acidovorax, and Brevundimonas (which were present at very low levels or entirely absent in indoor dust). Phylum-level fungal distributions identified by 18S or ITS regions showed very similar findings: a predominance of Ascomycota in indoor dust and Basidiomycota in outdoor CAPs. ITS sequencing of fungal genera in indoor dust showed significant proportions of Aureobasidium and Leptosphaerulina along with some contribution from Cryptococcus, Epicoccum, Aspergillus and the human commensal Malassezia. ITS sequencing detected more than 70 fungal genera in indoor dust not observed by culture. Microbiome sequencing is feasible for different types of archived environmental samples (indoor dust, and low biomass air particulate samples), and offers the potential to study how whole communities of microbes (including unculturable taxa) influence human health.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Polvo/análisis , Monitoreo del Ambiente/métodos , Microbiota , Contaminación del Aire Interior/análisis , Micobioma , Proyectos PilotoRESUMEN
BACKGROUND: Fine particulate air pollution and ozone are associated with increased cardiovascular events. To help explain the mechanism behind these observations, we investigated the effect of air pollution exposure on vascular function. METHODS AND RESULTS: Twenty-five healthy adults underwent a randomized, double-blind, crossover study comparing the vascular response to the 2-hour inhalation of approximately 150 microg/m(3) of concentrated ambient fine particles (CAP) plus ozone (120 ppb) versus the response to the inhalation of filtered air. High-resolution vascular ultrasonography was used to measure alterations in brachial artery diameter, endothelial-dependent flow-mediated dilatation (FMD) and endothelial-independent nitroglycerin-mediated dilatation (NMD). Exposure to CAP plus ozone caused a significant brachial artery vasoconstriction compared with filtered air inhalation (-0.09+/-0.15 mm versus +0.01+/-0.18 mm, P=0.03). There were no significant differences in FMD (+0.29+/-4.11% versus -0.03+/-6.63%, P=0.88), NMD (+3.87+/-5.43% versus +3.46+/-7.92%, P=0.83), or blood pressure responses between exposures. CONCLUSIONS: Short-term inhalation of fine particulate air pollution and ozone at concentrations that occur in the urban environment causes acute conduit artery vasoconstriction.
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Contaminación del Aire/efectos adversos , Arterias/fisiología , Ozono/efectos adversos , Vasoconstricción , Adulto , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/química , Arterias/diagnóstico por imagen , Arteria Braquial/fisiología , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Exposición por Inhalación , Masculino , Ozono/administración & dosificación , Tamaño de la Partícula , Ultrasonografía , VasodilataciónRESUMEN
Exposure to air pollution has been shown to cause arterial vasoconstriction and alter autonomic balance. Because these biologic responses may influence systemic hemodynamics, we investigated the effect of air pollution on blood pressure (BP). Responses during 2-hr exposures to concentrated ambient fine particles (particulate matter < 2.5 microm in aerodynamic diameter; PM2.5) plus ozone (CAP+O3) were compared with those of particle-free air (PFA) in 23 normotensive, nonsmoking healthy adults. Mean concentrations of PM2.5 were 147 +/- 27 versus 2 +/- 2 microg/m3, respectively, and those of O3 were 121 +/- 3 versus 8 +/- 5 ppb, respectively (p < 0.0001 for both). A significant increase in diastolic BP (DBP) was observed at 2 hr of CAP+O3 [median change, 6 mm Hg (9.3%); binomial 95% confidence interval (CI), 0 to 11; p = 0.013, Wilcoxon signed rank test] above the 0-hr value. This increase was significantly different (p = 0.017, unadjusted for basal BP) from the small 2-hr change during PFA (median change, 1 mm Hg; 95% CI, -2 to 4; p = 0.24). This prompted further investigation of the CAP+O3 response, which showed a strong association between the 2-hr change in DBP (and mean arterial pressure) and the concentration of the organic carbon fraction of PM2.5 (r = 0.53, p < 0.01; r = 0.56, p < 0.01, respectively) but not with total PM2.5 mass (r < or = 0.25, p > or = 0.27). These findings suggest that exposure to environmentally relevant concentrations of PM2.5 and O3 rapidly increases DBP. The magnitude of BP change is associated with the PM2.5 carbon content. Exposure to vehicular traffic may provide a common link between our observations and previous studies in which traffic exposure was identified as a potential risk factor for cardiovascular disease.
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Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Presión Sanguínea/efectos de los fármacos , Oxidantes Fotoquímicos/toxicidad , Ozono/toxicidad , Adulto , Contaminantes Atmosféricos/análisis , Carbono/análisis , Monóxido de Carbono/análisis , Monóxido de Carbono/toxicidad , Polvo/análisis , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Exposición por Inhalación , Masculino , Persona de Mediana Edad , Óxidos de Nitrógeno/análisis , Óxidos de Nitrógeno/toxicidad , Oxidantes Fotoquímicos/análisis , Ozono/análisis , Tamaño de la Partícula , Dióxido de Azufre/análisis , Dióxido de Azufre/toxicidad , Emisiones de VehículosRESUMEN
BACKGROUND: Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers. OBJECTIVES: We examined changes of blood and urinary biomarkers following exposures to three particle sizes. METHODS: Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5-10 µm; mean, 213 µg/m3) and fine (0.15-2.5 µm; mean, 238 µg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 µm; mean, 136 µg/m3) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences. RESULTS: One hour postexposure, for every 100-µg/m3 increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs. CONCLUSIONS: Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress.
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Contaminantes Atmosféricos/toxicidad , Inflamación/inducido químicamente , Exposición por Inhalación/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Material Particulado/toxicidad , Enfermedades Vasculares/inducido químicamente , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Método Simple Ciego , Factores de Tiempo , Enfermedades Vasculares/sangre , Enfermedades Vasculares/orina , Adulto JovenRESUMEN
Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) in epidemiological studies. Understanding the impact of specific PM components on BP is essential in developing effective risk-reduction strategies. We investigated the association between endotoxin and ß-1,3-d-Glucan-two major biological PM components-and BP. We also examined whether vascular endothelial growth factor, a vasodilatory inflammatory marker, modified these associations. We conducted a single-blind, randomized, crossover trial of controlled human exposure to concentrated ambient particles with 50 healthy adults. Particle-associated-endotoxin and ß-1,3-d-Glucan were sampled using polycarbonate-membrane-filters. Supine resting systolic BP and diastolic BP were measured pre-, 0.5-hour post-, and 20-hour postexposure. Urine vascular endothelial growth factor concentration was determined using enzyme-linked immunosorbant assay and creatinine-corrected. Exposures to endotoxin and ß-1,3-d-Glucan for 130 minutes were associated with increases in BPs: at 0.5-hour postexposure, every doubling in endotoxin concentration was associated with 1.73 mm Hg higher systolic BP (95% confidence interval, 0.28, 3.18; P=0.02) and 2.07 mm Hg higher diastolic BP (95% confidence interval, 0.74, 3.39; P=0.003); every doubling in ß-1,3-d-Glucan concentration was associated with 0.80 mm Hg higher systolic BP (95% confidence interval, -0.07, 1.67; P=0.07) and 0.88 mm Hg higher diastolic BP (95% confidence interval, 0.09, 1.66; P=0.03). Vascular endothelial growth factor rose after concentrated ambient particle endotoxin exposure and attenuated the association between endotoxin and 0.5-hour postexposure diastolic BP (Pinteraction=0.02). In healthy adults, short-term endotoxin and ß-1,3-d-Glucan exposures were associated with increased BP. Our findings suggest that the biological PM components contribute to PM-related cardiovascular outcomes, and postexposure vascular endothelial growth factor elevation might be an adaptive response that attenuates these effects.