Susceptibility and exposure biomarkers in people exposed to PAHs from diesel exhaust.

Xenobiotic metabolizing enzymes, especially CYP1A1 and GSTM1, are involved in the activation and conjugation of PAHs and are controlled by polymorphic genes. PAHs released from diesel emissions in many cities of the world, especially in developing countries, contribute significantly to the toxic effects of airborne inhalable particles. We have evaluated the gene-environment interaction in Santiago of Chile, studying the contribution of CYP1A1 and GSTM1 polymorphisms on 1-OH-P urinary levels used as the PAHs exposure biomarker. The study was performed on 59 diesel exposed (38 diesel revision workers and 21 subjects working in an urban area as established street vendors) and 44 non-exposed subjects living in a rural area. The 1-OH-P urinary levels of the urban (P=0.043) and rural (P=0.040) populations showed, without considering the genotypes, significant differences between smokers and non-smokers, but no significant differences were found between smokers and non-smokers among the diesel plant workers (P=0.33). Non-smoking subjects of the diesel plants and the urban area showed similar 1-OHP levels (P=0.466) which were significantly higher than those of the subjects living in the rural area (P<0.05). When 1-OH-P levels were related with genotypes, an association was observed for the CYP1A1*2A genotype, so that the diesel-exposed workers carrying the CYP1A1*2A allele showed significantly higher 1-OH-P levels than the subjects from the rural area with the same genotype (P=0.008). On the other hand, there was no significant correlation between urinary 1-OH-P levels and GSTM1 null genotype, although higher levels of the urinary metabolite were found in individuals carrying the combined CYP1A1*2A and GSTM1 null genotype (P=0.055). These results may suggest an association between levels of the exposure biomarker 1-OH-P and presence of the CYP1A1*2A genotype, a potential genetic susceptibility biomarker which might be useful in identifying individuals at higher risk among people exposed to high PAH levels in diesel exhaust.

[Indoor air pollution in a zone of extreme poverty of La Pintana, Santiago-Chile]. / Contaminación intradomiciliaria en un sector de extrema pobreza de la comuna de la pintana.

BACKGROUND: Indoor pollution can be an important risk factor for human health, considering that people spend more than 60% of their time in their houses. AIM: To investigate indoor pollution in a zone of extreme poverty in Metropolitan Santiago. MATERIAL AND METHODS: During 24 h, carbon monoxide (CO), sulfur dioxide (SO2), respirable particulate matter (PM10), polycyclic aromatic hydrocarbons absorbed in PM5, temperature and humidity, were measured in the interior of 24 houses in a La Pintana, Santiago. RESULTS: The higher pollutant concentrations were observed during hours when heating was used, in houses that used coal (mean PM10 250 micrograms/m3, CO 42 ppm, SO2 192 pph) or firewood (mean PM10 489 micrograms/m3, CO 57 ppm, SO2 295 pph). In all houses, polycyclic aromatic hydrocarbons were detected and they came from the interior of the house and not from external filtered air. Coal, firewood and cigarette smoke were important sources of carcinogenic and kerosene and gas were sources of non carcinogenic polycyclic aromatic hydrocarbons. CONCLUSIONS: In the houses studied, the population was exposed to an accumulation of highly toxic pollutants, caused by a lack of ventilation. A high relative humidity also contributed to the growth of biological pollutants.

[Importance of pre-analytical variables in the quality of arterial blood gas determination]. / Importancia de las variables pre-analíticas en la calidad de la medición de los gases arteriales.

BACKGROUND: Several frequent errors in the measurement of arterial blood gases, shed doubts on their real usefulness. AIM: To identify sampling, manipulation and transport errors in the measurement of arterial blood gases. MATERIALS AND METHODS: Three hundred and nine consecutive arterial blood samples received at the central laboratory of a public hospital were analyzed. Patient data in the order form, reception conditions at the laboratory, transport media, time of arrival and analysis of each sample were recorded. RESULTS: Five percent of orders informed the hour of sampling, 0.6% the patient's temperature and 18.1% the inspired oxygen fraction. Bubbles or clots were present in 12.9% and 3.2% of samples respectively, 87.3% of samples were well sealed and the amount of blood withdrawn in relation to the syringe capacity was optimal in 47.2% of cases. Ninety three percent of syringes were transported with ice cubes that did no cover the syringe and 5.8% of samples were received at room temperature. The delay in analysis, since the time of reception at the laboratory, ranged from 0 to 55 min (mean 12.9 min). CONCLUSIONS: Several deficiencies in pre analytical variables in blood gas analysis were identified, most caused by neglect and susceptible of correction. Quality controls for this determination should be performed frequently.

[Respiratory symptoms and pulmonary function in O' Higgins antarctic base residents]. / Síntomas respiratorios y función pulmonar en residentes de la base antártica O'Higgins.

The aim was to study pulmonary function and physical capacity and their relation to respiratory symptoms among military personnel before and after one year of permanence in an Antarctic base. In 21 men aged 38 +/- 5.5 years, enquiries about smoking habits and respiratory symptoms, spirometry, bronchial provocation test and measures of aerobic capacity and peak expiratory flow were performed. After 75 days of permanence in the base, there was a significant increase in weight, exertional dyspnea appeared in 8 subjects and there was an 8.4% decrease in aerobic capacity. The bronchial provocation test was positive outdoors in 7 of the 21 staff members; when performed indoors, no subject had a positive test and in Santiago only one subject had a positive test (Chi sq p < 0.025). After 7.5 and 11 months of permanence, forced vital capacity decreased in 13% and no diurnal differences of peak expiratory flow were observed. In conclusion, the permanence in Antarctica may slightly affect the respiratory system with the appearance of exertional dyspnea and outdoor airway hyper reactivity in some residents.

Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions.

We have measured the total and differential cell counts, histamine, leukotriene (LT) B4 and LTC4, immunoglobulins, complement (C3), eosinophil-derived basic proteins, and monocyte complement rosettes in bronchoalveolar lavage (BAL) 6 h after challenge with either antigen or diluent control in seven patients with antigen-induced single early reactions, and seven with dual (early and late phase) reactions. In both groups, the total cell counts in BAL were similar, irrespective of whether they were challenged with antigen or diluent. However, in the late-phase responders (LPR), there were significant increases in lymphocytes, neutrophils, and eosinophils (p less than 0.05), and significant decreases in the percentage of lung mast cells (p less than 0.05). The eosinophil major basic protein and eosinophil-derived neurotoxin increased in four of five subjects with dual responses and in the majority of single early responders (SER). BAL histamine concentrations increased in five of seven patients with dual responses. There were no consistent changes in LTB4 concentrations in either the LPR or the SER between diluent and antigen days, but a small but significant increase in LTC4 was observed in the LPR. Concentrations of IgG, IgA, IgM, IgE, C3, and albumin did not differ significantly. The percentage of monocyte complement rosettes also increased significantly (p less than 0.05) in LPR, but not in SER. These findings support the hypothesis that eosinophils and their products play a role in tissue injury in LPR and that eosinophil infiltration may be associated with macrophage activation.

Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cells in asthma. Relative increases in OKT8 cells in single early responders compared with those in late-phase responders.

We measured the numbers of helper (OKT4) and suppressor (OKT8) T-cells in blood and bronchoalveolar lavage (BAL) in 6 patients who developed single early reactions after allergen inhalational challenge and in 6 subjects who developed dual (early- and late-phase) responses. The asthmatics were lavaged twice. On the first occasion, they inhaled the diluent control (Dil) solution, and after an interval of at least 7 days, allergen (Ag) inhalational challenge was undertaken. Significant differences were observed in the single early responders (SER) only. For instance, when the results obtained on the Dil day were compared with those obtained on the Ag day, there was a significant (p less than 0.05) increase in the percentage of OKT4 cells in the blood of SER. Also in the BAL of SER there was a significant (p less than 0.05) decrease in the percentage of OKT4 and an increase (p less than 0.05) in the percentage and absolute numbers of OKT8 cells. Furthermore, the percentage of OKT4 was highly significantly (p less than 0.005) lower on the Ag day in the SER than on the Ag day in the late-phase responders (LPR). The OKT4/OKT8 ratio was significantly (p less than 0.05) lower on the Ag day than on the Dil day in BAL from SER and highly significantly decreased (p less than 0.001) when results on the Ag day in the SER were compared with those on the Ag day in the LPR. These findings raise the possibility that mobilization of suppressor T-cells into the lung after allergen-induced single early reactions in asthma might be associated with the prevention of a subsequent late-phase response.

Pulmonary function changes after bronchoalveolar lavage in asthmatic patients.

Pulmonary function changes were studied following bronchoalveolar lavage (BAL) in a group of mild to moderate asthmatic patients and in control subjects. After BAL significant decreases in FEV1 and FVC which were not inhibited by atropine and a consistent decline in PaO2 were seen in both groups. The magnitude of changes in these asthmatics was similar to that in control subjects.

Airways responses to oral ethanol in normal subjects and in patients with asthma.

The effect of oral ethanol on airflow was studied in 5 normal subjects and 5 patients with asthma. On 4 different study days, each subject was asked to drink 40 ml of either water or 20%, 40% or 60% ethanol, and measurements were made of specific airways conductance (sGaw), blood ethanol levels, pulse rate and blood pressure. In some subjects in both groups there was a significant immediate fall in sGaw after drinking ethanol (below 5% confidence limits). Once absorbed, ethanol had a slight bronchodilator effect in 2 normal subjects and in 3 patients with asthma (5% level). Sixty per cent ethanol, when drunk slowly, showed significant bronchodilatation in 4 out of 5 patients with asthma and in one normal subject (5% level) with no acute fall in sGaw. Pulse rate and blood pressure did not change after water, 20% and 40% ethanol in either group, but immediately after 60% ethanol normal subjects showed a significant rise in pulse rate (P less than 0.01) which was not seen in patients with asthma. The immediate changes in sGaw and pulse rate may be due to stimulation of irritant receptors in the upper airways. Ethanol may act directly on bronchial smooth muscle to produce bronchodilatation and may be useful as a bronchodilator when given intravenously.