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Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.

Exposure to complex mixtures of air pollutants produces infl ammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemica l expression of nuclear factor-kappa beta (NF- κB) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF- κB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequent damage included alterations of the blood—brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques , and neurofi brillary tangles. Persistent pulmonary infl ammation and deteriorating olfactory and respiratory barriers may play a role in the neuropathology observed in the brains of these highly exposed canines. Neurodegenerative disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

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 signifi cant 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 signifi cant statistical difference in the upper and lower respiratory symptomatology and ENT fi ndings 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 infi ltrates, 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 signifi cance 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 encourag e a balanced diet with an important component of fresh fruits and vegetables.

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.

Air pollution is a serious health problem in major cities in Mexico. The concentrations of monitored criteria pollutants have been above the US National Ambient Air Quality Standards for the last decade. To determine whether the number of primary malignant nasal and paranasal neoplasms has increased, we surveyed 256 such cases admitted to a major adult oncology hospital located in metropolitan Mexico City (MMC) for the period from 1976-1997 and to a tertiary hospital in Monterrey, an industrial city, for the period from 1993-1998. The clinical histories and histopathologic material were reviewed, and a brief clinical summary was written for each case. In the MMC hospital the number of newly diagnosed nasal and paranasal neoplasms per year for the period from 1976-1986 averaged 5.1, whereas for the next 11 years it increased to 12.5. The maximal increase was observed in 1995-1997, with an average of 20.3 new cases per year (P = 0.0006). The predominant neoplasms in these series were non-Hodgkin's lymphoma, squamous cell carcinoma, melanoma, adenocarcinoma, Schneiderian carcinoma, and nasopharyngeal carcinoma. In the Monterrey hospital a 2-fold increase in the numbers of newly diagnosed nasal and paranasal neoplasms was recorded between 1993 and 1998. The predominant MMC neoplasm in this series, namely nasal T-cell/natural killer cell non-Hodgkin's lymphoma, is potentially Epstein-Barr virus related. Nasal and paranasal malignant neoplasms are generally rare. Environmental causative factors include exposure in industries such as nickel refining, leather, and wood furniture manufacturing. Although epidemiologic studies have not addressed the relationship between outdoor air pollution and sinonasal malignant neoplasms, there is strong evidence for the nasal and paranasal carcinogenic effect of occupational aerosol complex chemical mixtures. General practitioners and ear, nose, and throat physicians working in highly polluted cities should be aware of the clinical presentations of these patients. Identification of this apparent increase in sinonasal malignant neoplasms in two urban Mexican polluted cities warrants further mechanistic and epidemiologic studies.

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.

The nasal passages are a common portal of entry and are a prime site for toxicant-induced pathology. Sustained increases in regenerative cell proliferation can be a significant driving force in chemical carcinogenesis. The atmosphere in Mexico City contains a complex mixture of air pollutants and its residents are exposed chronically and sequentially to numerous toxicants and potential carcinogens. We were concerned that exposure to Mexico City's atmosphere might induce cytotoxicity and increase nasal respiratory epithelial cell proliferation. Nasal biopsies were obtained for DNA cell cycle analysis from 195 volunteers. The control population consisted of 16 adults and 27 children that were residents in a Caribbean island with low pollution. The exposed Mexico City population consisted of 109 adults and 43 children. Sixty-one of the adult subjects were newly arrived in Mexico City and were followed for 25 days from their arrival. Control children, control adult and exposed Mexico City children all had similar percentages of cells in the replicative DNA synthesis phase (S phase) of the cell cycle (%S). A significant increase in %S in nasal epithelial cells was seen in exposed adult residents in Mexico City biopsied at three different dates compared with control adults. Newly arrived adults exhibited a control level of cell turnover at day 2 after coming to the city. However, at days 7, 14 and 25 they exhibited significant increases in %S. These data demonstrate an increased and sustained nasal cell turnover rate in the adult population observable in as little as 1 week of residence in Mexico City. This increase in cell proliferation is in agreement with other reports of induced pathological changes in the nasal passages of Mexico City dwellers. These observations suggest an increased potential risk factor of developing nasal neoplasms for residents of large cities with heavy pollution.

The nasal cavity is the most common portal of entry to the human body and a well-known target site for a wide range of air pollutants and chemically induced toxicity and carcinogenicity. DNA single-strand breaks (SSB) can be used as a biomarker of oxidant exposure and as an indicator of the carcinogenicity and mutagenicity of a substance. We examined the utility of using the alkaline single cell gel electrophoresis assay (SCGE) for measuring DNA damage in children's nasal epithelium exposed to air pollutants. We studied 148 children, ages 6–12, including 19 control children from a low polluted Pacific port and 129 children from Southwest Metropolitan Mexico City, an urban polluted area with high ozone concentrations year-round. Three sets of two nasal biopsies were taken in a 3-month period. All exposed children had upper respiratory symptoms and DNA damage in their nasal cells. Eleven- and twelve-year-olds had the most DNA damage, and more than 30% of children aged 9–12 exhibited patchy areas of squamous metaplasia over high-flow nasal regions. These areas had the greatest numbers of damaged DNA cells (P ≤ 0.001) and a large number of DNA tails > 80 μm (P < 0.001) when compared to the contralateral macroscopically normal site in the same child. The youngest children with significantly less outdoor exposure displayed patchy areas of goblet cell hyperplasia and had the least DNA damage. These findings suggest that SCGE can be used to monitor DNA damage in children's nasal epithelium and, further, the identification of DNA damage in nasal proliferative epithelium could be regarded as a sentinel lesion, most likely due to severe and sustained cell injury. Environ. Mol. Mutagen. 30:11–20, 1997 © 1997 Wiley-Liss, Inc.

All organisms have the ability to respond and adapt to a myriad of environmental insults. The human respiratory epithelium, when exposed to oxidant gases in photochemical smog, is at risk of DNA damage and requires efficient cellular adaptative responses to resist the environmentally induced cell damage. Ozone and its reaction products induce in vitro and in vivo DNA single strand breaks (SSBs) in respiratory epithelial cells and alveolar macrophages. To determine if exposure to a polluted atmosphere with ozone as the main criteria pollutant induces SSBs in nasal epithelium, we studied 139 volunteers, including a control population of 19 children and 13 adult males who lived in a low-polluted Pacific port, 69 males and 16 children who were permanent residents of Southwest Metropolitan Mexico City (SWMMC), and 22 young males newly arrived to SWMMC and followed for 12 weeks. Respiratory symptoms, nasal cytology and histopathology, cell viabilities, and single-cell gel electrophoresis were investigated. Atmospheric pollutant data were obtained from a fixed-site monitoring station. SWMMC volunteers spent >7 hr/day outdoors and all had upper respiratory symptoms. A significant difference in the numbers of DNA-damaged nasal cells was observed between control and chronically exposed subjects, both in children (p

Strategies to promote lifelong physical activity among children are needed to stem the adverse health consequences of inactivity. However, the health effects in growing children of long-term exposure to a polluted atmosphere are of deep concern. The atmosphere of south Mexico City (SMC) is characterized by a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Radiological evidence suggests that small-airway disease could be present in clinically healthy, tobacco unexposed SMC children. The aim of this study was to assess, by means of a self-reported questionnaire, the physical education class times, daily outdoor after-school exposure time, and tobacco exposure in students attending public elementary and middle schools in SMC. Additionally, the time each student spent viewing television was assessed, and the authors measured each student's weight and height to determine body mass index (BMI, weight in kg divided by height in m2). The survey included 1,159 students in grades 7-9. The authors identified 2 critical periods of outdoor exposure in SMC children that coincided with significant concentrations of both ozone and particulate matter with diameters less than 10 micrometers (PM10): during school time after 11:00 A.M. and in the after-school outdoor activity period, usually extending from 1:00 P.M. to 6:00 P.M. Thirty-two percent of elementary and 61% of middle school students have physical education classes after 11:00 A.M. Students in SMC spend an average of 19.6 hr/wk outdoors in the after-school period, during which time they are engaged in light to moderate physical activities. Half of the students are exposed to tobacco smoke at home, and 7% of middle school students smoke. On the basis of BMI, 60% of students were classified as undernourished, overweight, or obese. No correlations were found between BMI and time spent viewing TV, time outdoors (on weekdays and weekends), or exposure to environmental tobacco smoke. Children and adolescents in SMC are participating in physical activities that enhance multiple components of health-related fitness. However, their activities occur outdoors, where they are exposed to high concentrations of air pollutants throughout the year. The authors believe that SMC children and adolescents must be educated, through both the school and health systems, regarding ways to obtain the necessary exercise while protecting themselves from the high concentrations of pollutants. Individuals should instruct and encourage young people to be involved in lifetime fitness activities and to eat balanced diets, if the goal is to control health-care costs, reduce disease incidence, and improve the overall quality of life of the Mexico City population.

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.

A wide range of chemicals, particulate matter, and gaseous air pollutants are present in urban atmospheres and may pose a significant health risk for human populations. Nasal passages are the first site of contact of the respiratory tract with the environment and offer significant protection to the lower respiratory tract by conditioning the inspired air. This activity, which includes removal of certain pollutants, places the nose at risk of pathological changes, including cancer. Mexico City residents are exposed to a complex mixture of air pollutants. Based on predicted nasal air flow characteristics, four nasal biopsy sites were selected for study in adult male volunteers from a control low polluted town (n = 12) and southwest metropolitan Mexico City permanent residents (n = 54). Clinical data with emphasis on nasal symptoms and histopathological changes including basal and goblet cell hyperplasia, squamous metaplasia, epithelial dysplasia, and neovascularization were evaluated. Immunohistochemical staining was used to assess accumulation of p53 protein. Control individuals had no respiratory symptoms and their biopsies were unremarkable. Mexico City residents complained of epistaxis, rhinorrea, nasal crusting, dryness, and nasal obstruction. Their biopsies showed patchy shortening of cilia, deciliated areas, basal cell hyperplasia, and squamous metaplasia. Dysplastic lesions were predominantly located on antral squamous epithelium and in squamous metaplastic epithelium of the posterior inferior turbinates and they exhibited p53 nuclear accumulation. Individuals with > 10 h of daily outdoor exposure for 5 years or more had the highest rate of dysplasia. Subjects with epistaxis were more likely to have dysplasias and neovascularization. Results of this study suggest: (a) Nasal lesions in Mexico City residents are likely the result of many potentially toxic and/or carcinogenic pollutants, including ozone, aldehydes, particulate matter, and unmeasured pollutants; (b) the alteration of the nasal mucociliary defense mechanisms and the effects of reactive and/or water-soluble materials and particulates could be playing a major role in the nasal pathology; (c) the accumulation of p53 protein in dysplastic nasal lesions in the context of prolonged exposure to air pollutants raises the possibility that p53 mutations are already present and are providing the squamous cells with a selective advantage for clonal expansion; and (d) the nasal passages provide a valuable sentinel tissue for the detection of toxic air pollutants.