RESUMO
Southwest Metropolitan Mexico City (SWMMC) atmosphere is a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Children in SWMMC are exposed chronically and sequentially to numerous toxicants, and they exhibit significant nasal damage. The objective of this study was to assess p53 accumulation by immunohistochemistry in nasal biopsies of SWMMC children. We evaluated 111 biopsies from 107 children (83 exposed SWMMC children and 24 control children residents in a pollutant-compliant Caribbean island). Complete clinical histories and physical examinations, including an ear-nose-throat (ENT) exam were done. There was a significant statistical difference in the upper and lower respiratory symptomatology and ENT findings between control and exposed children (p < 0.001). Control children gave no respiratory symptomatology in the 3 months prior to the study; their biopsies exhibited normal ciliated respiratory epithelium and were p53-negative. SWMMC children complained of epistaxis, nasal obstruction. and crusting. Irregular areas of whitish-gray recessed mucosa over the inferior and middle turbinates were seen in 25% of SWMMC children, and their nasal biopsies displayed basal cell hyperplasia, decreased numbers of ciliated and goblet cells, neutrophilic epithelial infiltrates, squamous metaplasia. and mild dysplasia. Four of 21 SWMMC children with grossly abnormal mucosal changes exhibited strong transmural nuclear p53 staining in their nasal biopsies (p 0.005, odds ratio 26). In the context of lifetime exposures to toxic and potentially carcinogenic air pollutants, p53 nasal induction in children could potentially represent. a) a checkpoint response to toxic exposures, setting up a selective condition for p53 mutation, or b) a p53 mutation has already occurred as a result of such selection. Because the biological significance of p53 nuclear accumulation in the nasal biopsies of these children is not clear at this point, we strongly suggest that children with macroscopic nasal mucosal abnormalities should be closely monitored by the ENT physician. Parents should be advised to decrease the children's number of outdoor exposure hours and encourage a balanced diet with an important component of fresh fruits and vegetables.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição por Inalação/efeitos adversos , Mucosa Nasal/efeitos dos fármacos , Biópsia , Criança , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , México , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
A complex mixture of air pollutants is present in the ambient air in urban areas. People, animals, and vegetation are chronically and sequentially exposed to outdoor pollutants. The objective of this first of 2 studies is to evaluate by light and electron microscopy the lungs of Mexico City dogs and compare the results to those of 3 less polluted cities in MEXICO: One hundred fifty-two clinically healthy stray mongrel dogs (91 males/61 females), including 43 dogs from 3 less polluted cities, and 109 from southwest and northeast metropolitian Mexico City (SWMMC, NEMMC) were studied. Lungs of dogs living in Mexico City and Cuernavaca exhibited patchy chronic mononuclear cell infiltrates along with macrophages loaded with particulate matter (PM) surrounding the bronchiolar walls and extending into adjacent vascular structures; bronchiolar epithelial and smooth muscle hyperplasia, peribronchiolar fibrosis, microthrombi, and capillary and venule polymorphonuclear leukocytes (PMN) margination. Ultrafine PM was seen in alveolar type I and II cells, endothelial cells, interstitial macrophages (Mtheta), and intravascular Mtheta-like cells. Bronchoalveolar lavage showed significant numbers of alveolar macrophages undergoing proliferation. Exposure to complex mixtures of pollutants-predominantly particulate matter and ozone-is causing lung structural changes induced by the sustained inflammatory process and resulting in airway and vascular remodeling and altered repair. Cytokines released from both, circulating inflammatory and resident lung cells in response to endothelial and epithelial injury may be playing a role in the pathology described here. Deep concern exists for the potential of an increasing rise in lung diseases in child populations exposed to Mexico City's environment.
Assuntos
Poluentes Atmosféricos/toxicidade , Cães/fisiologia , Exposição Ambiental/efeitos adversos , Pulmão/efeitos dos fármacos , Ozônio/toxicidade , Sistema Respiratório/efeitos dos fármacos , Distribuição por Idade , Análise de Variância , Animais , Líquido da Lavagem Broncoalveolar/citologia , Ciclo Celular , Sobrevivência Celular , Feminino , Hiperplasia/patologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/ultraestrutura , Masculino , México , Modelos Animais , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Neutrófilos/ultraestrutura , Tamanho da Partícula , Pneumonia/patologia , Sistema Respiratório/patologia , Sistema Respiratório/ultraestrutura , Tomógrafos ComputadorizadosRESUMO
The principal objective of this study is to evaluate by light and electron microscopy (LM, EM) the heart tissues in stray southwest and northeast metropolitan Mexico City (SWMMC, NEMMC) dogs and compare their findings to those from 3 less polluted cities (Cuernavaca, Tlaxcala, and Tuxpam). Clinically healthy mongrel dogs, including 109 from highly polluted SWMMC and NEMMC, and 43 dogs from less polluted cities were studied. Dogs residing in cities with lower levels of pollutants showed little or no cardiac abnormalities. Mexico City and Cuernavaca dogs exhibited LM myocardial alterations including apoptotic myocytes, endothelial and immune effector cells, degranulated mast cells associated with scattered foci of mononuclear cells in left and right ventricles and interventricular septum, and clusters of adipocytes interspersed with mononuclear cells. Vascular changes included scattered polymorphonuclear leukocytes (PMN) margination and microthrombi in capillaries, and small venous and arteriolar blood vessels. Small veins exhibited smooth muscle cell hyperplasia, and arteriolar blood vessels showed deposition of particulate matter (PM) in the media and adventitia. Unmyelinated nerve fibers showed endoneural and epineural degranulated mast cells. EM examination of myocardial mast cells showed distended and abundant rough endoplasmic reticulum with few secretory granules. Myocardial capillaries exhibited fibrin deposition and their endothelial cells displayed increased luminal and abluminal pinocytic activity and the formation of anemone-like protrusions of the endothelium into the lumen. A close association between myocardial findings, lung epithelial and endothelial pathology, and chronic inflammatory lung changes was noted. The myocardial changes described in dogs exposed to ambient air pollutants may form the basis for developing hypothesis-driven mechanistic studies that might explain the epidemiological data of increased cardiovascular morbidity and mortality in people exposed to air pollutants.
Assuntos
Poluentes Atmosféricos/toxicidade , Cães/fisiologia , Coração/efeitos dos fármacos , Modelos Animais , Miocárdio/patologia , Ozônio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Interações Medicamentosas , Exposição Ambiental/efeitos adversos , Feminino , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Mastócitos/ultraestrutura , México , Miocárdio/ultraestrutura , Tamanho da PartículaRESUMO
Southwest Metropolitan Mexico City (SWMMC) children are repeatedly exposed to a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Nasal biopsies taken from these children exhibit a wide range of histopathologic alterations: marked changes in ciliated and goblet cell populations, basal cell hyperplasia, squamous metaplasia, and mild dysplasias. We studied the ultrastructural features of 15 nasal biopsies obtained from clinically healthy children 4 to 15 yr of age, growing up in SWMMC. The results were compared with nasal biopsies from 11 children growing up in Veracruz and exposed to low pollutant levels. Ultrathin sections of nasal biopsies revealed an unremarkable mucociliary epithelium in control children, whereas SWMMC children showed an epithelium comprised of variable numbers of basal, ciliated, goblet, and squamous metaplastic as well as intermediate cells. Nascent ciliated cells, as evidenced by the presence of migratory kinetosomes, were common, as were ciliary abnormalities, including absent central microtubules, supernumerary central and peripheral tubules, ciliary microtubular discontinuities, and compound cilia. Dyskinesia associated with these abnormal cilia was suggested by the altered orientation of the central microtubules in closely adjacent cilia. A transudate was evident between epithelial cells, suggesting potential deficiencies in epithelial junction integrity. Particulate matter was present in heterolysosomal bodies in epithelial cells and it was also deposited in intercellular spaces. The severe structural alteration of the nasal epithelium together with the prominent acquired ciliary defects are likely the result of chronic airway injury in which ozone, particulate matter, and aldehydes are thought to play a crucial role. The nasal epithelium in SWMMC children is fundamentally disordered, and their mucociliary defense mechanisms are no longer intact. A compromised nasal epithelium has less ability to protect the lower respiratory tract and may potentially leave the distal acinar airways more vulnerable to reactive gases. Impairment of mucociliary clearance has the potential to increase the contact time between deposited mutagenic particulate matter and the epithelial surface, thus increasing the risk for nasal carcinogenesis. Chronic exposures to air pollutants affect the whole respiratory tract; the nasal epithelium is an accessible and valuable sentinel to monitor exposures to toxic or carcinogenic substances.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Mucosa Nasal/ultraestrutura , Adolescente , Biópsia , Criança , Feminino , Humanos , Masculino , México , Mucosa Nasal/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/ultraestruturaRESUMO
Air pollution produces adverse health effects. The consequences of lifelong daily exposures to atmospheric pollutants upon the respiratory apparatus of healthy children are of considerable clinical importance. We investigated the association between exposure to a highly polluted urban environment with a complex mixture of air pollutants-ozone and particulate matter the predominant ones-and chest x-ray abnormalities in 59 healthy Mexican children who are lifelong residents of Southwest Metropolitan Mexico City (SWMMC), with a negative history of tobacco exposure and respiratory illnesses. Their clinical results and x-ray findings were compared to those of 19 Mexican control children, residents of a low-pollution area, with a similar negative history of tobacco exposure and respiratory illnesses. Ozone concentrations in SWMMC exceeded the U.S. Environmental Protection Agency (U.S. EPA) National Ambient Air Quality Standard (NAAQS) for O(3): 0.08 ppm as 1-h maximal concentration, not to be exceeded more than 4 times a year, on 71% of days in 1986 and 95% in 1997, with values as high as 0.48 ppm. Ozone maximal peaks are usually recorded between 2 and 5 pm coinciding with children's outdoor physical activities. Children in the control group reported no upper or lower respiratory symptomatology. Every SWMMC child complained of upper and/or lower respiratory symptoms, including epistaxis, nasal dryness and crusting, cough, shortness of breath, and chest discomfort. Children aged 7-13 yr had the most symptomatology, while 5- to 6-year olds and adolescents with the lowest number of statistically significant outdoor exposure hours had less respiratory symptoms. Bilateral symmetric mild lung hyperinflation was significantly associated with exposure to the SWMMC atmosphere (p = .0004). Chronic and sustained inhalation of a complex mixture of air pollutants, including ozone and particulate matter (PM), is associated with lung hyperinflation, suggestive of small airway disease, in a population of clinically healthy children and adolescents. Small airways are a target of air pollutants in SWMMC children, with ozone and PM being most likely responsible, based on experimental animal, controlled-chamber, and epidemiological data available. Our main concern is the potential likelihood for the development of chronic lung disease in this highly exposed population.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição por Inalação , Pneumopatias/induzido quimicamente , Adolescente , Criança , Pré-Escolar , Monitoramento Ambiental , Feminino , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Masculino , Concentração Máxima Permitida , México , Ozônio/análise , Projetos Piloto , Radiografia Torácica , Estados Unidos , United States Environmental Protection Agency , Saúde da População UrbanaRESUMO
Chronic exposure of children to a complex mixture of air pollutants leads to recurrent episodes of upper and lower respiratory tract injury. An altered nasal mucociliary apparatus leaves the distal acinar airways more vulnerable to reactive gases and particulate matter (PM). The heterogeneity of structure in the human lung can impart significant variability in the distribution of ozone dose and particle deposition; this, in turn, influences the extent of epithelial injury and repair in chronically exposed children. Cytokines are low-molecular-weight proteins that act as intercellular mediators of inflammatory reactions, including lung injury of various etiologies. Cytokines are involved in generating inflammatory responses that contribute to injury at the lung epithelial and endothelial barriers. Mexico City is a 20-million-person megacity with severe air pollution problems. Southwest Metropolitan Mexico City (SWMMC) atmosphere is characterized by a complex mixture of air pollutants, including ozone, PM, and aldehydes. There is radiological evidence that significant lower respiratory tract damage is taking place in clinically healthy children chronically and sequentially exposed to air pollutants while growing up in SWMMC. We hypothesize that there is an imbalanced and dysregulated cytokine network in SWMMC children with overproduction of proinflammatory cytokines and cytokines involved in lung tissue repair and fibrosis. The nature of the sustained imbalance among the different cytokines ultimately determines the final lung histopathology, which would include subchronic inflammation, emphysema, and fibrosis. Cytokines likely would reach the systemic circulation and produce systemic effects. Individuals with an underlying respiratory or cardiovascular disease are less able to maintain equilibrium of the precarious cytokine networks.