Elnara M. Negri

Biological effects of air pollution in Sao Paulo and Cubatao

Rats were used as biological indicators of air quality in two heavily polluted Brazilian towns: São Paulo and Cubatão. They were exposed for 6 months to ambient air in areas where the pollution was known to be severe. The following parameters were studied and compared to those of control animals: respiratory mechanics, mucociliary transport, morphometry of respiratory epithelium and distal air spaces, and general morphological alterations. The results showed lesions of the distal and upper airways in rats exposed in Cubatão, whereas the animals from São Paulo showed only alterations of the upper airways but of greater intensity than those observed in the Cubatão group. There are both qualitative and quantitative differences in the pollutants of these places: in São Paulo automobile exhaust gases dominate and in Cubatão the pollution is due mainly to particulates of industrial sources. The correlation of the pathological findings with the pollutants is discussed and it is concluded that biological indicators are useful to monitor air pollutions which reached dangerous levels in São Paulo and Cubatão.

Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Objective:Corticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. Design:Prospective, randomized, controlled experimental study. Setting:University research laboratory. Subjects:One hundred twenty-eight BALB/c mice (20–25 g). Interventions:Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 &mgr;g, ALIp) or intraperitoneally (125 &mgr;g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). Measurements and Main Results:At 24 hrs, lung static elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interleukin-6, and transforming growth factor (TGF)-&bgr; levels in bronchoalveolar lavage fluid, as well as tumor necrosis factor (TNF)-&agr;, migration inhibitory factor (MIF), interferon (IFN)-&ggr;, TGF-&bgr;1 and TGF-&bgr;2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-&agr;, MIF, IFN&ggr;, and TGF-&bgr;2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. Conclusions:Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Flow and volume dependence of respiratory system mechanics during constant flow ventilation in normal subjects and in adult respiratory distress syndrome

Seven control subjects and seven patients with adult respiratory distress syndrome (ARDS) were artificially ventilated and flow, volume, and tracheal pressure were monitored. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. In both groups Ers did not vary with different inspiratory flows and volumes, but was significantly higher in ARDS. With increasing volume (isoflow maneuvers), Rrs,max and Rrs,u increased but Rrs,min remained unaltered in ARDS. In control patients, however, resistances did not vary but Rrs,max and Rrs,u were smaller and Rrs,min equaled their corresponding values in ARDS. Hence, stress relaxation seems to be increased in ARDS. During isovolume maneuvers Rrs,max and Rrs,u decreased with increasing flows (both groups), although they were significantly higher in ARDS. Rrs,min was not modified by different flows and was similar in both groups. Thus, pendelluft is also increased in ARDS. In conclusion, the mechanical profile of ARDS is characterized by increased Ers and Rrs,max, the latter being secondary to augmented mechanical unevenness within the system.

Time course of respiratory mechanics and pulmonary structural remodelling in acute lung injury

The aim of this study was to evaluate the time course of in vivo and in vitro respiratory mechanics and examine whether these parameters could reflect the temporal changes in lung parenchyma remodelling in paraquat (PQ)-induced lung injury. Measurements were done 1, 3 and 8 weeks after the intraperitoneal (i.p.) injection of saline (control) or paraquat (7mgkg(-1)) in rats. Airway and tissue resistances increased from control in PQ1 and PQ3 and returned to control values in PQ8, in accordance with the magnitude of bronchoconstriction. Viscoelastic/inhomogeneous pressure, tissue elastance, the number of polymorphonuclear cells, and collagen fibre content in lung parenchyma increased in PQ1 and remained elevated in PQ3 and PQ8. Static elastance increased in PQ1, returned to control values after 3 weeks, and was correlated with the volume fraction of collapsed alveoli. In conclusion, there is a restoration of normal alveolar-capillary lung units with a gradual improvement in airway and tissue resistances and static elastance. However, the on-going fibrotic process kept elevated tissue elastance and viscoelastic/inhomogeneous pressure.

Respiratory system mechanics in guinea pigs after acute hemorrhage: role of adrenergic stimulation.

We evaluated the effects of acute blood loss on the respiratory mechanics of guinea pigs. We measured respiratory system elastance (Ers) and resistance (Rrsmax) using the end-inflation occlusion method. Rrsmax was partitioned into its homogeneous component (Rrsmin) and that due to the unevenness within the respiratory system (Rrsu). Respiratory mechanics were studied both before and immediately after bleeding in eight animals. Another eight guinea pigs had received propranolol previously and were also submitted to hemorrhage. Propranolol-treated animals showed higher control values of Rrsmax (p less than .02) and Rrsmin (p less than .0001). Animals not treated with propranolol exhibited a decrease (p less than 0.001) in Rrsmax after hemorrhagic hypovolemia (from 0.375 +/- 0.051 to 0.323 +/- 0.042 cm H2O/ml.sec), due to a decrease (p less than 0.005) in Rrsmin (from 0.140 +/- 0.031 to 0.094 +/- 0.032 cm H2O/ml.sec), whereas Ers and Rrsu did not change. Propranolol-treated animals showed an increase (p less than .001) in Rrsmax (from 0.512 +/- 0.133 to 0.664 +/- 0.144 cm H2O/ml.sec), Rrsu (p less than 0.01) from 0.252 +/- 0.09 to 0.345 +/- 0.139 cm H2O/ml.sec, and Ers (p less than 0.001) (from 4.565 +/- 0.933 to 5.402 +/- 1.24 cm H2O/ml) after bleeding. The results indicate that the immediate effects of acute bleeding on respiratory mechanics are significantly influenced by catecholamines.

Wet M1a non-small cell lung cancer: is it possible to predict recurrence of pleural effusion?

BackgroundnThe propose was to recognize risk factors of malignant pleural effusion (MPE) recurrence in patients with symptomatic M1a non-small cell lung cancer (NSCLC).nnnMethodsnAll patients with NSCLC and MPE submitted to pleural palliative procedures were enrolled in a prospective study. Group I contained patients who had pleural recurrence, and Group II with no pleural recurrence. Prognostic factors for pleural recurrence were identified by univariable analysis, using Fishers exact test for categorical variables and Students t test for quantitative variables. Afterwards the significant variables were entered into a multivariable logistic regression analysis (with P<0.05 considered significant). Receiver operating characteristics (ROC) analysis determined the cutoff points for continuous variables.nnnResultsnA total of 82 patients were included in the analysis. There were 15 patients (18.3%) in Group I and 67 patients (81.7%) in Group II. Univariable analysis regarding factors affecting postoperative recurrence was: adenosine deaminase concentration in pleural fluid <16 mg/dL (P=0.04), albumin concentration in pleural fluid <2.4 mg/dL (P=0.03), administration of second-line palliative chemotherapy (P=0.018) and type of procedure [therapeutic pleural aspiration (TPA)] (P=0.023). At the multivariable analysis, only the type of procedure (TPA) (P=0.031) was identified as independent predictor of recurrence.nnnConclusionsnThe identification of this factor may assist the choice of the optimal palliative technique; at the first episode of MPE in NSCLC patients and definitive procedure as pleurodesis or indwelling pleural catheter are recommended.

Effects of amiodarone on lung tissue mechanics and parenchyma remodeling

We studied the results of chronic oral administration of amiodarone on in vitro lung tissue mechanics, light and electron microscopy. Fifteen Wistar male rats were divided into three groups. In control (CTRL) group animals received saline (0.5 mL/day). In amiodarone (AMIO) groups, amiodarone was administered by gavage at a dose of 175 mg/kg 5 days per week for 6 (6AMIO) or 12 weeks (12AMIO). Lung tissue strips were analyzed 24h after the last drug administration. Tissue resistance and elastance were higher in 6AMIO and 12AMIO than in CTRL, while hysteresivity was similar in all groups. Total amount of collagen fibers in lung parenchyma increased progressively with the time course of the lesion. However, at 6 weeks there was an increase in the amount of type III collagen fibers, while in 12AMIO mainly type I collagen fibers were found. In our study amiodarone increased lung tissue impedance that was accompanied by matrix remodeling and lesion of type II pneumocytes.