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Most of the studies on air pollution focus on emissions from fossil fuel burning in urban centers. However, approximately half of the world's population is exposed to air pollution caused by biomass burning emissions. In the Brazilian Amazon population, over 10 million people are directly exposed to high levels of pollutants resulting from deforestation and agricultural fires. This work is the first study to present an integrated view of the effects of inhalable particles present in emissions of biomass burning. Exposing human lung cells to particulate matter smaller than 10 µm (PM 10 ), significantly increased the level of reactive oxygen species (ROS), inflammatory cytokines, autophagy, and DNA damage. Continued PM 10 exposure activated apoptosis and necrosis. Interestingly, retene, a polycyclic aromatic hydrocarbon present in PM 10 , is a potential compound for the effects of PM 10 , causing DNA damage and cell death. The PM 10 concentrations observed during Amazon biomass burning were sufficient to induce severe adverse effects in human lung cells. Our study provides new data that will help elucidate the mechanism of PM 10 -mediated lung cancer development. In addition, the results of this study support the establishment of new guidelines for human health protection in regions strongly impacted by biomass burning.

Various environmental contaminants are known to impair the growth trajectories of major organs, indirectly (gestational exposure) or directly (postnatal exposure). Evidence associates pre-gestational and gestational exposure to air pollutants with adverse birth outcomes (e.g., low birth weight, prematurity) and with a wide range of diseases in childhood and later in life. In this review, we explore the way that pre-gestational and gestational exposure to air pollution affects lung development. We present results in topics underlining epidemiological and toxicological evidence. We also provide a summary of the biological mechanisms by which air pollution exposure possibly leads to adverse respiratory outcomes. We conclude that gestational and early life exposure to air pollutants are linked to alterations in lung development and function and to other negative respiratory conditions in childhood (wheezing, asthma) that may last into adulthood. Plausible mechanisms encompass changes in maternal physiology (e.g., hypoxia, oxidative stress and inflammation) and DNA alterations in the fetus. Evidence for pre-gestational and gestational effects on the lung is scarce compared with that on early life exposure and further studies are needed. However, the suggested mechanisms are credible and the evidence of pre-gestational and gestational air pollution exposure is robust for adverse birth outcomes. Air pollutants might change lung developmental trajectories of the unborn child predisposing it to diseases later in life highlighting the urgent need for controls on urban air pollution levels worldwide.

Epidemiological studies have associated air particulate matter (PM) inhalation with a decline in lung function and increased morbo-mortality due to cardiorespiratory diseases, particularly in susceptible populations. Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by cellular infiltration in exocrine glands and extraglandular tissue, being the respiratory tract an important target. We evaluated the effect of PM on the airways of NOD mice, which develop SS and BALB/c mice. BALB/c or NOD mice (2-3 months) were randomized in two groups and exposed to intranasal instillation either with saline (control) or ROFA solution (1mg/kg body weight). After 24h, mice were euthanized in order to perform lung histology, or measure total cell number (TCN), differential cell count (DCC) and superoxide anion generation in the bronchoalveolar lavage (BAL) fluid. BALB/c mice showed normal histoarchitecture, while NOD mice showed lymphocytic peribronchial infiltrates. ROFA exposure affected the respiratory tract from both BALB/c and NOD mice, with a significant increase in the TCN (p<0.05) and generation of O2(-) (p<0.05), as well as an imbalance in the DCC (p<0.05). All histological observations correlated with the cellular parameters evaluated. Lesions in NOD mice were more severe than those of BALB/c, showing cellular infiltration in the alveoli and leading to a greater decrease in the alveolar space. We have proved that in this experimental Sjögren's Syndrome animal model (NOD mice); airborne pollution exacerbates pre-existing pulmonary lesions. These findings show experimental evidence on the harmful effects of airborne pollution on the airways of patients with Sjögren's Syndrome., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of São Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 μL of saline (CTRL) or PM2.5 at 5 or 15 μg in 30 μL of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical impedance and inflammation than CTRL, but lower inflammation and oxidative stress than P15. In conclusion, acute exposure to low doses of fine PM induced lung inflammation, oxidative stress and worsened lung impedance and histology in a dose-dependent pattern in mice.

Oxidative stress plays a major role in the pathogenesis of particle-dependent lung injury. Ambient particle levels from vehicles have not been previously shown to cause oxidative stress to the lungs. The present study was conducted to a) determine whether short-term exposure to ambient levels of particulate air pollution from vehicles elicits inflammatory responses and lipid peroxidation in rat lungs, and b) determine if intermittent short-term exposures (every 4 days) induce some degree of tolerance. Three-month-old male Wistar rats were exposed to ambient particulate matter (PM) from vehicles (N = 30) for 6 or 20 continuous hours, or for intermittent (5 h) periods during 20 h for 4 consecutive days or to filtered air (PM <10 microm; N = 30). Rats continuously breathing polluted air for 20 h (P-20) showed a significant increase in the total number of leukocytes in bronchoalveolar lavage compared to control (C-20: 2.61 x 105 +/- 0.51;P-20: 5.01 x 105 +/- 0.81; P < 0.05) and in lipid peroxidation ([MDA] nmol/mg protein: C-20: 0.148 +/- 0.01; P-20: 0.226 +/- 0.02; P < 0.05). Shorter exposure (6 h) and intermittent 5-h exposures over a period of 4 days did not cause significant changes in leukocytes. Lipid damage resulting from 20-h exposure to particulate air pollution did not cause a significant increase in lung water content. These data suggest oxidative stress as one of the mechanisms responsible for the acute adverse respiratory effects of particles, and suggest that short-term inhalation of ambient particulate air pollution from street with high automobile traffic represents a biological hazard.

Studies of cooking-generated NO2 effects are rare in occupational epidemiology. In the present study, we evaluated the lung function of professional cooks exposed to NO2 in hospital kitchens. We performed spirometry in 37 cooks working in four hospital kitchens and estimated the predicted FVC, FEV1 and FEF(25-75), based on age, sex, race, weight, and height, according to Knudson standards. NO2 measurements were obtained for 4 consecutive days during 4 different periods at 20-day intervals in each kitchen. Measurements were performed inside and outside the kitchens, simultaneously using Palm diffusion tubes. A time/exposure indicator was defined as representative of the cumulative exposure of each cook. No statistically significant effect of NO2 exposure on FVC was found. Each year of work as a cook corresponded to a decrease in predicted FEV1 of 2.5% (P = 0.046) for the group as a whole. When smoking status and asthma were included in the analysis the effect of time/exposure decreased about 10% and lost statistical significance. On predicted FEF(25-75), a decrease of 3.5% (P = 0.035) was observed for the same group and the inclusion of controllers for smoking status and asthma did not affect the effects of time/exposure on pulmonary function parameter. After a 10-year period of work as cooks the participants of the study may present decreases in both predicted FEV1 and FEF(25-75) that can reach 20 and 30%, respectively. The present study showed small but statistically significant adverse effects of gas stove exposure on the lung function of professional cooks.

Rationale and Hypothesis: Previous studies evaluating the histoarchitecture of distal airspaces have been shown to be limited by the difficulty in adequately differentiating alveoli and alveolar ducts. This limitation has been specially noticed in studies addressing lung recruitment and in situations of diffuse alveolar damage (DAD), where generic nominations for distal airspaces had to be created, such as "peripheral airspaces" (PAS) and "large-volume gas-exchanging airspaces" (LVGEA). Elastic stains have been largely used to describe normal lung structures. Weigert's resorcin-fuchsin staining (WRF) demarcates the thickened free portions of the ductal septum facilitating its recognition. We hypothesized that this staining could help in differentiating alveoli from alveolar ducts in distorted lung parenchyma., Material and Methods: Samples of control lungs and of DAD lungs induced by mechanical ventilation (VILI) were stained with hematoxylin-eosin (HE) and with WRF. Using morphometry we assessed the volume proportion of alveoli, alveolar ducts and LVGEA in control and VILI lungs., Results: WRF stained VILI lungs showed a significant decrease in the volume proportion of LVGEA and alveoli and a significant increase in the volume proportion of alveolar ducts when compared to HE stained samples., Conclusion: We conclude that WRF staining is useful to distinguish alveolar ducts from alveoli in a DAD model, and suggest that it should be routinely used when morphometric studies of lung parenchyma are performed.

Several epidemiological studies have consistently demonstrated significant associations between ambient levels of particulate matter and lung injury and cardiovascular events with increased morbidity and mortality. Particle surrogates (PS), such as residual oil fly ash (ROFA), have been widely used in experimental studies aimed at characterizing the mechanisms of particle toxicity. Since PS composition varies depending on its source, studies with different types of PS may provide clues about the relative toxicity of the components generated by high-temperature combustion process. In this work, we have studied the effects of nasal instillation of increasing doses of different PS in mice: saline, carbon, and two types of particle surrogates. PS type A (PSA) was the ROFA collected from the waste incinerator of our university hospital; PS type B (PSB) was collected from the electrostatic precipitator of a large steel company and thus had an elevated metal content. After 24h, we analyzed hematological parameters, fibrinogen, bronchoalveolar lavage, bone marrow, and pulmonary histology. Nasal instillation of the two types of PS-induced leucopenia. PSB elicited a greater elevation of plasma fibrinogen levels. Bone marrow and pulmonary inflammatory changes were more intense for PSA. We concluded that the PS composition modulates acute inflammatory changes more significantly than the mass for these two types of PS.

Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lung injury induced by oleic acid (OA) to compare the effects of mannitol to those of another diuretic, furosemide (FUR), and to assess if mannitol effects remained after correction of the volume depletion induced by this agent. Acute lung injury was induced in Wistar rats by intravenous administration of 100 mg/kg of OA. Mannitol (1 mL of a 20% solution) was infused either 15 min before or 2 h after OA infusion. FUR was infused intravenously in a dose (1 mg/kg) that induced a similar amount of diuresis compared to mannitol. We also studied rats that received NaCl 0.9% infusion to correct for volume losses induced by mannitol. The severity of the acute lung injury was evaluated by morphometric studies of the lungs 4 h after OA infusion. The amount of intraalveolar fluid accumulation and the intensity of alveolar distention and collapse were evaluated. Mannitol infusion either 15 min before or 2 h after OA administration resulted in a significant decrease in the amount of intraalveolar edema and alveolar distention and collapse (P < 0.001). FUR administration before OA infusion had an effect similar to mannitol. We did not observe any significant effect of mannitol when the rats received saline infusion to correct for diuresis induced by mannitol. We conclude that mannitol decreases the severity of pulmonary injury induced by OA in rats. This effect is mainly due to its diuretic properties.

Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary bypass. The purpose of the present study was to develop an experimental model of acute pulmonary injury induced by cardiopulmonary bypass in Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non-pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass group and n = 7 for control rats). We measured tracheal pressure, airflow, and lung volume changes and obtained pulmonary resistance and dynamic elastance. After the cardiopulmonary bypass, lungs were submitted to a quick-freezing protocol and morphometric analysis was performed. There was a time-dependent increase in dynamic elastance, but not pulmonary resistance, only in the rats submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025) and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to control rats. In our experimental model, rats submitted to cardiopulmonary bypass developed acute pulmonary changes similar to the early phase of acute pulmonary distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary elastance without changes in resistance. This experimental model is suitable for studies concerning the mechanisms of acute lung injury induced by cardiopulmonary bypass.

The present study was undertaken in order to describe the morphological differences between pulmonary lesions in acute respiratory distress syndrome originating from direct pulmonary injury (ARDSp) and those originating from extrapulmonary injury (ARDSexp). We investigated a total of 38 ARDS-patients (27 males) ranging in age from 19 to 75 years, classified according to underlying disease in pulmonary (ARDSp) and extrapulmonary disease (ARDSexp). The extent of acute diffuse alveolar damage was assessed morphometrically on histologic gross sections in the upper and lower lobes of one lung. The lesions showed quantitative differences in extent and distribution according to underlying disease (primary pulmonary or secondary involvement). In pulmonary ARDS, a predominance of alveolar collapse (16.6%+/-12.3% versus 10.3%+/-11.9%, p = 0,03), fibrinous exudate (1.7%+/-3.2% versus 0.4%+/-1.1%, p = 0.01) and alveolar wall edema (11.2%+/-7.4% versus 6.6%+/-4.4%, p = 0,05) were found compared to extrapulmonary ARDS. We conclude that the morphology of acute diffuse alveolar damage (DAD) is mainly determined by underlying disease (pulmonary ARDS or extrapulmonary ARDS) differing in quantitative terms within the lung. Physiological, radiographic and respiratory system mechanics differences described in ARDSp and ARDSexp may therefore be due to morphometric differences in pulmonary lesions.

In this study, instrumental neutron activation analysis was applied to the determination of Sc, La, Ce, Nd, Sm, Eu, Tb, Yb, Lu, Hf, Th, and U in lung samples from miners working in coal mines located in the state of Santa Catarina, Brazil. These results were compared to those from a control group constituted of healthy individuals. The results showed that the elements determined exhibit considerable intersubject variability within a single group of individuals and the mean values of concentrations in miners' lungs were higher than those of normal individuals. Lung samples presented U concentrations varying from 11 to 890 micrograms/kg. Therefore, for some samples, the contribution of the uranium fission products in the analysis of La, Ce, Nd, and Sm was considered by determining the interference correction factors. The accuracy of the results was evaluated by analyzing certified reference materials.

Acute myocardial infarction (AMI) may yield several respiratory changes. Nevertheless, no comprehensive pulmonary morphological/physiological correlation has been performed under this condition. The aims of the present investigation were: 1) to determine the respiratory parameters in an experimental model of coronary artery occlusion, 2) to relate these results to findings from lung histopathology, and 3) to evaluate the effects of propranolol used prior to AMI. Twenty-eight rats were anaesthetized and mechanically ventilated. In the control group (C), a suture line was passed around the left anterior descending coronary artery (LADCA). The infarct group (I) was similarly prepared but the LADCA was ligated and infarct resulted. In the control/propranolol (CP) and infarct/propranolol (IP) groups, propranolol was intravenously injected 5 min before surgery as performed in groups C and I, respectively. Lung static (EL,st) and dynamic (EL,dyn) elastances, airway resistance (RL,int), and viscoelastic/inhomogeneous pressure (deltaP2L) were determined before and 30, 60 and 120 min after surgery. In group I, EL,st, EL,dyn, RL,int and deltaP2L increased progressively throughout the experiment, and were higher than those found in groups C, CP and IP. All respiratory parameters but EL,st remained unaltered in group IP. Lung histopathological examination demonstrated alveolar, interstitial and intrabronchial oedema in group I. Group IP showed only interstitial oedema. Acute myocardial infarction yields lung resistive, elastic and viscoelastic changes. The last two results from alveolar and interstitial oedema, respectively. The previous use of propranolol diminishes respiratory changes.

Study Objectives: To evaluate the potential associations between long-term exposure to air pollution and histopathologic evidence of damage to the lungs in humans., Design: Lung tissue samples were collected during necropsies of individuals who died due to violent causes, selected on the basis of their exposure background., Patients: The exposed group was composed of individuals who lived in Guarulhos, an area with high mean levels of inhalable particles. The control group was composed of individuals who lived in two cities with economies based on agricultural activities: Ribeirão Preto and Ourinhos., Interventions: Information about cigarette smoking and occupational exposure was obtained from family members., Measurements and Results: Morphometric evaluation of the main bronchus was conducted to determine the volume ratio of submucosal glands. Histopathologic alterations of the bronchioli were evaluated by scoring the presence of inflammatory reaction, wall thickening, and secretory hyperplasia. The number of spots of carbon deposition was counted along the regions of lymphatic drainage (visceral pleura and axial connective tissue around bronchi and blood vessels). Statistical analysis was done by means of regression models controlled for age, smoking, and occupational exposure. Lungs collected from the high pollution area presented evidence of more histopathologic damage in comparison to those from the clean environments. These effects were observed even after controlling for individual differences in age, sex, and cigarette smoking levels., Conclusions: These results suggest that long-term exposure to air pollution may contribute to the pathogenesis of airway disease, and that urban levels of air pollution have adverse effects on the respiratory tract.

The elastic system fibers were studied at the light microscopic level by using Weigert's resorcin-fuchsin method after oxidation. This study was designed to describe the distribution of these fibers in intrapulmonary guinea-pig airways and to characterize their conformational changes during bronchoconstriction induced by methacholine aerosol. Airways present a palisade of elastic system fibers just beneath the epithelial basement membrane; these fibers are also present in the adventitial connective tissue. Thin fibers link the fibers located in the palisade among themselves and also connect them to those fibers located in the bronchial adventitial tissue, by traversing the airway smooth muscle. During bronchoconstriction, the fibers located beneath the epithelial basement membrane are divided into two components: one follows the epithelial invaginations towards airway lumen, while the other population remains attached through airway smooth muscle to the fibers located in the adventitial connective tissue. At the ultrastructural level, the findings corroborated those of the light microscopy and in addition, disclosed that typical mature elastic fibers and also elaunin fibers attach directly to the basal lamina, a feature that has not been reported previously in other tissues studied. This configuration is compatible with the idea that fibers of the elastic system restrict the mucosal folding during bronchoconstriction, and may also provide energy to restore airway configuration to its normal status after contraction.

Pulmonary dysfunction represents the most important cause of death in patients with paracoccidioidomycosis (PBM). In order to investigate the functional changes of the lungs in the early stages of PBM, a model of benign disease was developed by intratracheal challenge of 12-week old isogenic Wistar rats with 1 x 10(6) yeast forms of Paracoccidioides brasiliensis. Animals were studied 30 and 60 days after infection, when fully developed granulomas were demonstrable in the lungs. Measurements of airway resistance, lung elastance and tissue hysteresis were made during sinusoidal deformations (100 breaths/min, tidal volume = 2 ml) with direct measurement of alveolar pressure using the alveolar capsule technique. Infection caused a significant increase in hysteresis (infected: 1.69, N = 13; control: 1.13, N = 12, P = 0.024, ANOVA), with no alterations in airway resistance or lung elastance. Histopathological analysis revealed the presence of fully developed granulomas located in the axial compartment of the lung interstitial space. These results suggest that alterations of tissue mechanics represent an early event in experimental PBM.

We studied the morphological elements associated with airway and pulmonary tissue responses to capsaicin in mechanically ventilated guinea pigs. Lungs were excised and frozen in liquid nitrogen 3 and 20 min after capsaicin infusion (1 or 100 micrograms/kg i.v.). Using image analysis, we obtained contraction index (CI) and peribronchial edema area (CUFF) for both central (C) and peripheral airways (P). We also assessed alveolar size (mean linear intercepts, Lm) and tissue distortion (standard deviation of the number of intercepts, SDI). Multiple regression analysis showed significant associations between pulmonary tissue resistance (Rti) and CUFFP (p < 0.001); pulmonary dynamic elastance and SDI (p = 0.002); and airway resistance and CUFFC (p < 0.0001). Our results suggest that increases in Rti observed in guinea pigs after capsaicin infusion are primarily dependent on changes in the small airways, mainly peribronchiolar edema; the increase in lung elastance is related to distortion of parenchymal tissues; and large airway edema contributes significantly to airway resistance.

The role of NK-1 and NK-2 receptors on the pulmonary response to capsaicin in guinea pigs was evaluated using intravenous infusion of selective nonpeptide antagonists of NK 1 (CP 96345, 300 nmol/kg, and SR 140333, 300 nmol/kg) and NK-2 (SR 48968, 100 nmol/kg) neurokinin receptors. Maximal values of pulmonary dynamic elastance (Edyn) and pulmonary resistance (RL) after capsaicin infusion were significantly lower in the presence of SR 48968 (p < .005). Morphometric analysis of lungs obtained by quick-freezing showed significant attenuation of airway contraction and peribronchiolar edema formation in the presence of NK-2 antagonist (p < .001). When compared to guinea pigs that received only capsaicin, animals that received SR 140333 or CP 96345 showed lower values of Edyn, RL, airway contraction, and peribronchiolar edema, but only the difference in Edyn values was significant. The combination of NK-1 and NK-2 antagonists was not more effective than NK-2 antagonist alone in attenuating capsaicin effects. The results suggest that airway effects of capsaicin are mainly mediated by activation of NK-2 receptors although NK-1 receptors may also play a role.

Patients who receive amiodarone may develop interstitial pulmonary disease. The objective of the present study was to develop an experimental model of interstitial pulmonary disease in rats based on the chronic oral administration of amiodarone diluted in water ad libitum. A total of 97 three-month old male Wistar rats weighing 133-167 g (control and intoxicated) were studied after daily administration of amiodarone (about 50 mg/kg) for 3 weeks and 3, 6, and 13 months. We carried out conventional histopathologic evaluation, morphometric studies of the alveolar wall, transmission electron microscopy, measurement of pulmonary volumes and forced expiratory flows, and computed respiratory system resistance and elastance during spontaneous breath cycles. Chronic ingestion of amiodarone by rats produced pulmonary disease that started as a phospholipidosis, as early as 3 weeks after the use of the drug. After 6, and mainly after 13 months, a focal inflammatory reaction with reactive alveolar epithelium was observed. Signals of a concomitant repair process were also present, but fibrosis was visible only by electron microscopy. The physiologic dysfunction could be identified after 13 months; expiratory flow (ml/sec) limitation and an increased respiratory system elastance (cmH2O/ml) were the main functional changes, respectively 10.8 (forced expiratory mean flow between 0-25% of forced vital capacity) and 5.36 in treated animals vs 13.3 and 3.65 in controls, reported as mean +/- SD for 6 animals in each group. A body of evidence suggests that amiodarone may cause changes in lung phospholipid metabolism that may be responsible for a part of the functional derangement observed in this study.

The role of neurokinins in the acute pulmonary response to antigen was studied in guinea pigs that received ovalbumin (50 mg/kg ip) on days 1 and 3 and capsaicin (50 mg/kg sc) on day 21 (OAC); ovalbumin on days 1 and 3 (OA1); capsaicin on day 1 and OA on days 8 and 10 (COA); and ovalbumin on days 8 and 10 (OA2). On day 28, guinea pigs were submitted to ovalbumin aerosol challenge. Maximal values of pulmonary dynamic elastance (Edyn) and pulmonary resistance (RL) were significantly lower in OAC and COA groups compared with OA1 and OA2 groups (P < 0.001). There was no difference between maximal Edyn and RL values obtained in OAC and COA groups. Morphometric analysis of lungs showed significantly (P < 0.05) lower values of contraction index of airways, peribronchial edema, and alveoli over inflation in guinea pigs that received capsaicin compared with intact guinea pigs. Capsaicin treatment did not influence the formation of specific IgG1 anaphylactic antibodies. We conclude that neurokinin depletion results in a decrease in the pulmonary mechanical and inflammatory responses to antigen challenge in sensitized guinea pigs. These effects are observed when capsaicin is given either before or after sensitization.

Lung samples from smokers, nonsmokers, and one stillborn were analyzed by an instrumental neutron activation analysis (INAA) method. Pulmonary tissue and hilum lymph node samples were obtained separately from autopsies, and then submitted to cryogenic homogenization, lyophilization, and sterilization. Short and long irradiations were performed in an IEA-R1 nuclear reactor, and gamma-ray activities were measured using a Ge(Li) or hyperpure Ge detector. Precision of results was evaluated by analyzing one lung tissue in replicates and their accuracy by analyzing reference materials. Comparisons were carried out between results obtained in pulmonary tissues and lymph nodes, as well as those obtained in samples from different groups of individuals.

We studied the effects of selective depletion of neurokinins in sensory nerve fibers by capsaicin treatment on the airway and pulmonary tissue responses to methacholine. Dose-response curves to aerosolized methacholine were performed on anesthetized and mechanically ventilated Wistar rats. Capsaicin (50 mg/kg sc) was administered to 2-day-old rats, and the animals were studied after 12 wk. The response to each dose of methacholine was determined by measuring changes in airway resistance (R(aw)), dynamic pulmonary elastance (Edyn), and pulmonary tissue resistance (Rtis). We calculated sensitivity (Kx) as the concentration of methacholine required for a one-half maximal response and reactivity as the relationship between the maximum response and Kx. Capsaicin treatment resulted in significantly greater values of Kx and lower values of reactivity for R(aw), Edyn, and Rtis compared with control rats. Morphometric analysis of airways showed similar values of the area occupied by smooth muscle but a significantly lower (P < 0.02) area of airway epithelium in capsaicin-treated rats. Our results suggest that methacholine requires capsaicin-sensitive nerves for part of its airway and lung tissue effects.

The induction of pancreatitis by injecting the taurocholate acid 2.5% solution into the rat's hepatic duct. Ten rats formed the normal control group, nine rats the two hours pancreatitis group and eight rats the eight hours pancreatitis group. The comparison of the groups has shown a significant increase in the numbers of macrophages, neutrophils and lymphocytes in the broncho-alveolar lavage of pancreatitis group (p < 0.05) indicating an acute inflammatory pneumopathy.

We studied the effects of capsaicin on airway and lung tissue mechanics in anesthetized and tracheostomized guinea pigs that were mechanically ventilated at constant tidal volume (8 ml/kg) and breathing frequency (60 breaths/min). Dose-response curves to intravenously infused capsaicin (1, 10, and 100 micrograms/kg) were performed (five animals for each dose, one dose per animal). We measured airflow, volume (by integration of the flow signal), tracheal pressure, and alveolar pressure with an alveolar capsule. Capsaicin induced a dose-dependent increase in airway resistance, tissue resistance, and dynamic elastance. The relationship between airway pressure and flow was fitted by a quadratic (Rohrer) equation. Airflow became more turbulent after infusion of capsaicin. After infusion of 100 micrograms/kg capsaicin, airway pressure (at flow rates of 10 ml.s-1) increased from 3.03 +/- 0.40 (mean +/- SEM) to 9.58 +/- 1.88 cm H2O, whereas the pressure corresponding to viscoelastic properties of lung tissue increased from 0.92 +/- 0.14 to 8.58 +/- 1.12 cm H2O. We conclude that infusion of capsaicin results in mechanical effects in both airways and pulmonary tissue.

The current study was designed to assess the methacholine dose-response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155-250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg-1 i.p.) and mechanically ventilated. Measurements of tracheal (ptr) and alveolar (pA) pressures and the pressure change across the airway (p(aw)) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml-1) through the breathing circuit. Baseline p(aw) and pA mean (+/- SD) values (6.44 +/- 2.06 and 8.25 +/- 3.44 cmH2O, respectively) were not statistically different (P = 0.220). The increases in ptr and pA were significant during the dose-response study (P = 0.001), whereas p(aw) was not increased. The increase in pA was significantly higher than that of p(aw) (P less than 0.001). The relationship between the mean (+/- SE) values of ptr and pA could be well described by a straight line (r = 0.990, P less than 0.001). There were also significant correlations based on regression equations between ptr and p(aw) (r = 0.947, P less than 0.001) and pA and p(aw) (r = 0.913, P = 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge protocols in rats.

1. Volume, airflow, tracheal, esophageal and transpulmonary pressures were measured in 6 mechanically ventilated, anesthetized and paralyzed guinea pigs. 2. The elastic and resistive properties of the respiratory system were partitioned into their lung and chest wall components a) following end-inflation occlusion of the airways subsequent to constant flow inspirations, and b) during relaxed expirations following release of occlusion. The values obtained by both methods were similar. 3. Mean respiratory system, lung and chest wall elastances were 3.518, 2.671, and 0.847 cm H2O/ml, respectively. 4. Mean respiratory system, pulmonary and chest wall resistances (at flows of 4.3 ml/s) were 0.302, 0.184, and 0.118 cm H2O ml-1 s, respectively. 5. Respiratory system, lung and chest wall resistances were partitioned into two components: 1) a homogeneous one whose values corresponded to 0.171, 0.095, and 0.076 cm H2O ml-1 s, for respiratory system, lung and chest wall, respectively, and 2) a component due to Pendelluft and stress relaxation and corresponding to 0.131, 0.089, and 0.042 cm H2O ml-1 s, respectively. 6. Resistive pressure vs flow relationships for the respiratory system, lung and chest wall were also determined during the entire tidal expiration. 7. We conclude that the chest wall participates significantly in respiratory system unevenness.

Two groups of 12 male Wistar rats received either 243 ppm of acetaldehyde or 5.7 ppm of formaldehyde for 8 h a day, 5 days a week during 5 weeks. These levels represent three times the threshold limit values (TLV) for these substances in Brazilian legislation. The animals were evaluated by pulmonary function tests before and after exposure to the pollutants. The data obtained from these rats were compared with those of 12 controls, housed in identical conditions for the same length of time but breathing normal air. The results showed an increase of the functional residual capacity, residual volume, total lung capacity and respiratory frequency in the rats exposed to acetaldehyde atmosphere. The animals exposed to formaldehyde did not present pulmonary function alterations when compared with the controls. The damage caused by acetaldehyde to the peripheral regions of the lung parenchyma, affecting small airways or altering pulmonary elastic properties, is discussed. It is suggested that the Brazilian TLV for acetaldehyde (78 ppm) is not as safe as that for formaldehyde (1.6 ppm).

1. This paper describes the pulmonary alterations that occur after cardiopulmonary bypass (CPB) when a bubble oxygenator is used. 2. Two groups of patients who underwent myocardial revascularization were studied before and after CPB. The first group (7 patients with a bypass time of 130 +/- 17 min), when examined by light and electron microscopy showed platelet/neutrophil accumulation in the pulmonary parenchyma, endothelial lesions and interstitial edema. In the second group (10 patients with a bypass time of 123 +/- 37 min), extravascular lung water (EVLW) was measured by the thermal and green-dye dilution technique, and showed a significant increase immediately after CPB which lasted through the 1st and 2nd post-operative days. 3. No statistical correlation was found between the increase in EVLW and the plasma colloid oncotic pressure/pulmonary artery wedge pressure gradient, CPB time or intra-operative fluid balance. 4. Our results indicate an increase in pulmonary endothelium permeability after CPB when a bubble oxygenator is used.

A simple technic for studying the pulmonary mechanics of rats by whole body plethysmography is presented. The parameters measured were: Tidal Volume (TV); Respiratory Frequency (RF); Transpulmonary Basal Pressure (TBP); Dynamic Compliance (Cdyn); Functional Residual Capacity (FRC); Transpulmonary Pressure/Volume curve (TP/V); Forced Expiratory Volume of 1/4 second (FEV 1/4); Expiratory Reserve Volume (ERV); Inspiratory Capacity (IC); Inspiratory Reserve Volume (IRV); Forced Vital Capacity (FVC); Residual Volume (RV); Forced Expiratory Mean Flow between 100-50% (FEMF 100-50), 50-25% (FEMF 50-25) and 25-0% (FEMF 25-0) of the FVC, and Total Lung Capacity (TLC). In order to verify the accuracy of the technic, common male adult Wistar rats, in which pulmonary obstructive disease is normally expected, were first submitted to these functional tests and then to pathological examination. According to the intensity of the morphological pulmonary lesion, the rats were divided in two groups: with and without suppurative pneumopathy. The analysis of the pulmonary function data showed significant decrease of the FEV 1/4 and FEMF 50-25 and increase of the FRC and RV in the groups with pulmonary suppuration. Thus, a discriminant function could be established to characterize the two groups with 100% efficiency. It was concluded that these pulmonary function tests are a valuable and reliable tool to detect lung diseases in rats.

A comparative chronic inhalation exposure study was performed to investigate the potential health effects of gasoline and ethanol engine exhaust fumes. Test atmospheres of gasoline and ethanol exhaust were given to Wistar rats and Balb C mice housed in inhalation chambers for a period of 5 weeks. Gas concentration and physical parameters were continually monitored during the exposure period. Several biological parameters were assessed after the exposure including pulmonary function, mutagenicity, and hematological, biochemical, and morphological examinations. The results demonstrated that the chronic toxicity of the gasoline-fueled engine is significantly higher than that of the ethanol engine.

The level of cytosolic glucocorticoid receptors (GR) was measured in 12 open-chest lung biopsies of interstitial pulmonary diseases. The results showed an increase in the GR content in the diseased lungs correlated to the degree of septal cellularity in nine cases. Two pulmonary sarcoidosis and one end-stage idiopathic pulmonary fibrosis patients presented higher levels of GR than those predicted by the septal cellularity. It was concluded that the GR content of the lungs increases in the course of interstitial diseases, reflecting the number of cells that express cytosolic GR in pulmonary parenchyma.

The collagen content and its aggregational state was histochemically measured in interstitial lung diseases. Open chest biopsies of ten patients with adult respiratory distress syndrome, seven patients with sarcoidosis, and nine patients with fibrosis associated with connective tissue diseases and with idiopathic pulmonary fibrosis (IPF/CTD) were compared with eight samples of normal lungs. The collagen content of diseased lungs was significantly increased when compared to control lungs, but no difference was observed among the pathologic groups. The analysis of collagen aggregational state showed maximal aggregation in IPF/CTD, followed by sarcoidosis, ARDS, and control lungs, in decreasing order. The results suggest that measurement of collagen aggregation coupled with collagen content could be used in the evaluation of interstitial lung disease and encourage the use of new techniques in order to better explain the dramatic histologic and functional alterations observed in many disease-associated lung processes.

In five lung biopsies from patients who developed the clinical picture of Adult Respiratory Distress Syndrome (ARDS) after cardiopulmonary bypass the pulmonary alterations were studied morphologically and glucocorticoid receptors determined. The time between cardiac surgery and pulmonary biopsy was 4-7 days. The results showed severe pulmonary lesions, with marked endothelial damage and active collagen secretion in the pulmonary interstitium, along the capillary bed. The glucocorticoid receptor level of the lungs with ARDS was 4.7 +/- 7.04 fmol/mg protein (control 4.28 +/- 4.32 fmol/mg protein). The results indicate that the process of collagen secretion may begin in the early phase of ARDS and that the benefits of glucocorticoid therapy in the management of ARDS should be reassessed.

This paper describes the effects of repeated exposure to gasoline and ethanol exhaust fumes on the pulmonary mechanics of rats assessed by whole-body plethysmography. Two groups of 12 male Wistar albino rats each were tested before and after exposure to diluted gasoline or ethanol exhaust gases for 5 weeks, 8 h per day and 5 days per week. An additional group of 12 rats were exposed to clean air under the same experimental conditions. The variations of the functional parameters observed in the three groups before and after exposure were compared. Peak Expiratory Flow and Forced Expiratory Mean Flows in the ranges 0-25%, 25-50% and 50-75% of Forced Vital Capacity were significantly reduced in animals exposed to gasoline exhaust fumes, whereas the group exposed to ethanol exhaust fumes did not differ from the control group. This respiratory impairment is probably due to the presence of SO2 and the quality of the hydrocarbons in gasoline exhaust gases.

Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 µg of DEP/10 µl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation. [ABSTRACT FROM AUTHOR]

Aims : We report uncommon histopathological findings in fatal measles infection. Methods and results : We describe the autopsies of four patients who died during a measles outbreak in São Paulo, Brazil, in 1997. Two of the patients were children receiving chemotherapy for non-Hodgkin's lymphoma, one was an adult with acquired immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman. All patients had their deaths attributed to measles pneumonia. The autopsies revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles antigen was detected in lung tissue using a monoclonal anti-measles antibody. Conclusions : Pancreatitis, thyroiditis and sialoadenitis are not previously reported histopathological findings in measles infection. Pancreatitis is a potentially severe complication and should be considered when treating patients with atypical measles. [ABSTRACT FROM AUTHOR]