Daño pulmonar asociado al uso de cigarrillos electrónicos-vapeadores / Pulmonary damage associated with the use of electronic cigarettes or vapers

Ha habido mucha discusión sobre los efectos dañinos para la salud producidos por los cigarrillos electrónicos o vapeadores y su utilidad como ayuda para dejar de fumar. Cada vez aparecen más publicaciones con efectos deletéreos sobre la salud. Esta discusión se ha acentuado en los últimos años, por el importante aumento del uso de los vapeadores en todo el mundo, especialmente entre los adolescentes y adultos jóvenes. En septiembre de 2019 el Centro de Control y Prevención de Enfermedades (CDC) de los EE. UU. alertó sobre un importante número de casos de enfermedad pulmonar asociada al uso de cigarrillo electrónico (EVALI: e-cigarette or vaping associated lung injury). Epidemiológicamente se consideró un brote que al 17 de enero, 2020 ha presentado 2.668 pacientes hospitalizados, con 57 fallecidos. Durante la semana del 15 de septiembre 2019 ocurrió el 'peak' de hospitalizaciones por EVALI. La mayoría eran varones jóvenes. El 82% usó productos con Tetrahidrocanabinoides (THC) y el 14% productos con nicotina. En el lavado bronquio-alveolar de 51 casos de EVALI se encontró la presencia de acetato de Vitamina E, producto utilizado como espesante para la elaboración de productos de 'vapeo' que contienen THC, lo que lo hace un posible factor causal, pero no se puede descartar el papel de otros compuestos tóxicos. Las principales sociedades científicas del mundo y la OMS han advertido de los riesgos a largo plazo del uso de los cigarrillos electrónicos y recomiendan su control y regulación.

There has been a lot of discussion about the harmful health effects caused by electronic cigarettes or vapers and their usefulness as a smoking cessation aid. More and more publications appear with deleterious effects on health. This discussion has been straightened in recent years, due to the significant increase in the use of vapers worldwide, especially among adolescents and young adults. In September 2019, the US Center for Disease Control and Prevention warned of a significant number of cases of lung disease associated with the use of electronic cigarettes (EVALI: e-cigarette or vaping associated lung injury). Epidemiologically it was considered an outbreak that as of January 17, 2020 presented 2668 hospitalized patients, with 57 deaths. During the week of September 15, 2019 the peak of hospitalizations for EVALI occurred. The majority were young men. 82% of them used products with Tetrahydrocanabinoids (THC) and 14% products with nicotine. In the bronchoalveolar lavage of 51 cases of EVALI, the presence of Vitamin E acetate was found, a product used as a thickener for the elaboration of vaping products containing THC, which makes it a possible causal factor, but it cannot be ruled out the contribution of other toxic compounds. The world's leading scientific societies and World Health Organization have warned of the long-term risks of using electronic cigarettes and recommend their control and regulation.

Inflammatory lung injury in rabbits: effects of high-frequency oscillatory ventilation in the prone position / Lesão inflamatória pulmonar em coelhos: efeitos da ventilação oscilatória de alta frequência em posição prona

ABSTRACT Objective: To compare the effects that prone and supine positioning during high-frequency oscillatory ventilation (HFOV) have on oxygenation and lung inflammation, histological injury, and oxidative stress in a rabbit model of acute lung injury (ALI). Methods: Thirty male Norfolk white rabbits were induced to ALI by tracheal saline lavage (30 mL/kg, 38°C). The injury was induced during conventional mechanical ventilation, and ALI was considered confirmed when a PaO2/FiO2 ratio < 100 mmHg was reached. Rabbits were randomly divided into two groups: HFOV in the supine position (SP group, n = 15); and HFOV with prone positioning (PP group, n = 15). For HFOV, the mean airway pressure was initially set at 16 cmH2O. At 30, 60, and 90 min after the start of the HFOV protocol, the mean airway pressure was reduced to 14, 12, and 10 cmH2O, respectively. At 120 min, the animals were returned to or remained in the supine position for an extra 30 min. We evaluated oxygenation indices and histological lung injury scores, as well as TNF-α levels in BAL fluid and lung tissue. Results: After ALI induction, all of the animals showed significant hypoxemia, decreased respiratory system compliance, decreased oxygenation, and increased mean airway pressure in comparison with the baseline values. There were no statistically significant differences between the two groups, at any of the time points evaluated, in terms of the PaO2 or oxygenation index. However, TNF-α levels in BAL fluid were significantly lower in the PP group than in the SP group, as were histological lung injury scores. Conclusions: Prone positioning appears to attenuate inflammatory and histological lung injury during HFOV in rabbits with ALI.

RESUMO Objetivo: Comparar os efeitos das posições prona e supina durante ventilação oscilatória de alta frequência (VOAF) sobre oxigenação e inflamação pulmonar, lesão histológica e estresse oxidativo em um modelo de lesão pulmonar aguda (LPA) em coelhos. Métodos: Trinta coelhos Norfolk machos brancos foram submetidos à LPA por meio de lavagem traqueal com salina (30 ml/kg, 38°C). A lesão foi induzida durante a ventilação mecânica convencional, e a LPA foi considerada confirmada na presença de relação PaO2/FiO2 < 100 mmHg. Os coelhos foram aleatoriamente divididos em dois grupos: VOAF em posição supina (grupo PS, n = 15); e VOAF em posição prona (grupo PP, n = 15). Para a VOAF, a pressão média das vias aéreas foi inicialmente estabelecida em 16 cmH2O. No 30º, 60º e 90º min após o início do protocolo de VOAF, a pressão média das vias aéreas foi reduzida para 14, 12 e 10 cmH2O, respectivamente. No 120º min, os animais foram recolocados ou permaneceram na posição supina por mais 30 min. Foram avaliados os índices de oxigenação e escores histológicos de lesão pulmonar, bem como os níveis de TNF-α em lavado broncoalveolar e tecido pulmonar. Resultados: Após a indução da LPA, todos os animais apresentaram hipoxemia significativa, diminuição da complacência do sistema respiratório, diminuição da oxigenação e aumento da pressão média das vias aéreas em comparação aos valores basais. Não houve diferenças estatisticamente significativas entre os dois grupos, em nenhum dos momentos avaliados, quanto a PaO2 e índice de oxigenação. Entretanto, os níveis de TNF-α no lavado broncoalveolar foram significativamente menores no grupo PP que no grupo PS, assim como os escores histológicos de lesão pulmonar. Conclusões: A posição prona parece atenuar a lesão pulmonar inflamatória e histológica durante a VOAF em coelhos com LPA.

Hypercapnia attenuates ventilator-induced lung injury through vagus nerve activation

Abstract Purpose: To investigate the role of vagus nerve activation in the protective effects of hypercapnia in ventilator-induced lung injury (VILI) rats. Methods: Male Sprague-Dawley rats were randomized to either high-tidal volume or low-tidal volume ventilation (control) and monitored for 4h. The high-tidal volume group was further divided into either a vagotomy or sham-operated group and each surgery group was further divided into two subgroups: normocapnia and hypercapnia. Injuries were assessed hourly through hemodynamics, respiratory mechanics and gas exchange. Protein concentration, cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight and pathological changes were examined. Vagus nerve activity was recorded for 1h. Results: Compared to the control group, injurious ventilation resulted in a decrease in PaO2/FiO2 and greater lung static compliance, MPO activity, enhanced BALF cytokines, protein concentration, cell count, and histology injury score. Conversely, hypercapnia significantly improved VILI by decreasing the above injury parameters. However, vagotomy abolished the protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced efferent vagus nerve activity compared to normocapnia. Conclusion: These results indicate that the vagus nerve plays an important role in mediating the anti-inflammatory effect of hypercapnia on VILI.

Effectual components of Polygonum ciliinerve protects against Staphylococcus aureus infection with immunomodulatory functions in C57BL/6 mice

Abstract Purpose: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. Methods: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. Results: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. Conclusion: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.

Effects of hypothermia on lung inflammation in a rat model of meconium aspiration syndrome

Abstract Purpose: To evaluate the effects of hypothermia treatment on meconium-induced inflammation. Methods: Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. Results: The BAL fluid TNF-α, IL-1β, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). Conclusion: Meconium-induced inflammatory cytokine production is affected by the body temperature control.

Treatment with 1,25(OH)2D3 induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.

Proteomic differences with and without ozone-exposure in a smoking-induced emphysema lung model

BACKGROUND/AIMS: Acute exacerbations in chronic obstructive pulmonary disease may be related to air pollution, of which ozone is an important constituent. In this study, we investigated the protein profiles associated with ozone-induced exacerbations in a smoking-induced emphysema model. METHODS: Mice were divided into the following groups: group I, no smoking and no ozone (NS + NO); group II, no smoking and ozone (NS + O); group III, smoking and no ozone (S + NO); and group IV, smoking and ozone (S + O). Bronchoalveolar lavage, the mean linear intercept (MLI) on hematoxylin and eosin staining, nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS), and Western blotting analyses were performed. RESULTS: The MLIs of groups III (S + NO) and IV (S + O) (45 +/- 2 and 44 +/- 3 microm, respectively) were significantly higher than those of groups I (NS + NO) and II (NS + O) (26 +/- 2 and 23 +/- 2 microm, respectively; p < 0.05). Fourteen spots that showed significantly different intensities on image analyses of two-dimensional (2D) protein electrophoresis in group I (NS + NO) were identified by LC-MS/MS. The levels of six proteins were higher in group IV (S + O). The levels of vimentin, lactate dehydrogenase A, and triose phosphate isomerase were decreased by both smoking and ozone treatment in Western blotting and proteomic analyses. In contrast, TBC1 domain family 5 (TBC1D5) and lamin A were increased by both smoking and ozone treatment. CONCLUSIONS: TBC1D5 could be a biomarker of ozone-induced lung injury in emphysema.

Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

Detección temprana de cáncer de mama y cervicouterino en localidades con concentración de población indígena en Morelos / Early detection of breast and cervical cancer among indigenous communities in Morelos, Mexico

Objetivo. Analizar la percepción de mujeres y proveedores de salud sobre cuándo y cómo realizar acciones para la detección temprana del cáncer de mama y cervicouterino en localidades de Morelos con presencia de población indígena. Material y métodos. Se entrevistó a 10 proveedores de salud y 58 usuarias en unidades médicas del primer nivel de atención de cinco localidades; luego se analizó la información con base en el paradigma de la teoría fundamentada. Resultados. El personal de salud está deficientemente familiarizado con los lineamientos oficiales para la detección de cáncer cervicouterino y de mama. Pocos practican sus labores bajo una perspectiva de sensibilización intercultural. Las usuarias tienen nociones imprecisas o equivocadas de las acciones de detección. Conclusiones. La necesidad de capacitación con apego a las normas es evidente. Urge asumir un abordaje con pertinencia cultural que permita la comunicación eficiente y alfabetización en salud para la detección oportuna de estos dos cánceres.

Objective. To analyze the perception in relation to when and how to perform actions for the early detection of breast and cervical cancer among women and health care providers in communities with a high percentage of indigenous population in Morelos, Mexico. Materials and methods. Ten health providers and 58 women users of health services were interviewed which have a first level of attention in five communities. The analysis was developed under the approach of the Grounded Theory. Results. Providers are poorly informed about current regulations and specific clinical indications for the detection of cervical and breast cancer. Few propitiate health literacy under intercultural sensitization. The users have imprecise or wrong notions of the early detection. Conclusions. The need for training in adherence to norms is evident. It is urgent to assume a culturally relevant approach to enable efficient communication and promote health literacy for early detection of these two cancers.

IL-4 and IL-5 Secretions Predominate in the Airways of Wistar Rats Exposed to Toluene Diisocyanate Vapor / 예방의학회지

OBJECTIVES: We established a Wistar rat model of asthma caused by toluene diisocyanate (TDI) exposure, and investigated the relationship between TDI exposure concentrations and respiratory hypersensitivity, airway inflammation, and cytokine secretions in animals, to better understand the mechanism of TDI induced occupational asthma. METHODS: Wistar rats were exposed to two different concentrations of TDI vapor four hours a day for five consecutive days. Bronchoalveolar lavage (BAL) was performed, and differential leucocytes from the BAL fluid were analyzed. Lung histopathological examination was carried out to investigate the inflammatory status in the airways. Production of cytokines interleukin (IL)-4 and IL-5 productions in the BAL fluid in vivo was determined with enzyme-linked immunosorbent assay kits. RESULTS: The TDI-exposed rats exhibited greater airway hypersensitivity symptoms than the control rats. The BAL differential cell count and lung histopathological examination demonstrated that inflammation reactions were present in both the central and peripheral airways, characterized with marked infiltration of eosinophils in the TDI-exposed rats. The cytokine assay showed that IL-4 and IL-5 were predominantly produced in the BAL fluid in vivo. CONCLUSIONS: These findings imply that TDI exposure concentrations may greatly affect the occurrence and extent of inflammatory events and that Th2 type cytokines may play an important role in the immunopathogenesis of TDI-induced occupational respiratory hypersensitivity.

A comparative study of pentoxifylline effects in adult and aged rats submitted to lung dysfunction by thermal injury

PURPOSE: To investigate the protective effects of pentoxifylline against lung injury observed after dorsal scald in aged animals. METHODS: Adult (eight months old) and aged (20 months old) rats were subjected to thermal injury or sham procedure. The six hours post-trauma animals received pentoxifylline and after 24 hours were euthanatized and lung tissue samples collectedted. The bronchoalveolar lavage fluid was evaluated for total protein content and tumor necrosis factor-alpha cytokine. Malondialdehyde and myeloperoxidase activety in the lung homogenate were measured and a histological lung examination was undertaken. RESULTS: Burn injury induced oxidative stress in lung homogenate was higher in elderly-burned rats compared to adult-burned rats (p<0.001). Total protein and cytokine in bronchoalveolar lavage increased in the elderly-burned group when compared to the adult-burned group (p<0.001). All parameters decreased in bolth groups treated with pentoxifylline (p<0.05). CONCLUSIONS: The injury was augmented in elderly rats when compared to adult rats. Damage was reduced with the use of pentoxifylline, however further studies are needed to evaluate the dose-response of the drug.

Lesão pulmonar aguda induzida pela administração endovenosa de extrato da fumaça do cigarro / Acute lung injury induced by the intravenous administration of cigarette smoke extract

OBJETIVO: Investigar os efeitos agudos da administração endovenosa de extrato da fumaça do cigarro (EFC) em parâmetros funcionais respiratórios, inflamatórios e histológicos em ratos e comparar esse potencial modelo de lesão pulmonar aguda (LPA) com aquele com o uso de ácido oleico (AO). MÉTODOS: Foram estudados 72 ratos Wistar machos divididos em quatro grupos: tratados somente com soro fisiológico (SF; grupo controle); tratados com EFC e SF (grupo EFC); tratados com SF e AO (grupo AO); e tratados com EFC e AO (grupo EFC/AO). RESULTADOS: As médias de complacência foram significantemente menores nos grupos AO e EFC/AO (2,12 ± 1,13 mL/cmH2O e 1,82 ± 0,77 mL/cmH2O, respectivamente) do que no controle (3,67 ± 1,38 mL/cmH2O). A proporção de neutrófilos e a atividade das metaloproteinases 2 e 9 em lavado broncoalveolar foram significantemente maiores nos grupos AO e EFC/AO que no controle. O acometimento pulmonar avaliado por morfometria foi significantemente maior nos grupos AO e EFC/AO (72,9 ± 13,8% e 77,6 ± 18,0%, respectivamente) do que nos grupos controle e EFC (8,7 ± 4,1% e 32,7 ± 13,1%, respectivamente), e esse acometimento foi significantemente maior no grupo EFC que no grupo controle. CONCLUSÕES: A administração endovenosa de EFC, nas doses e tempos deste estudo, associou-se à LPA mínima. O EFC não potencializou a LPA induzida por AO. Estudos adicionais são necessários para esclarecer o papel potencial desse modelo como método de estudo dos mecanismos de agressão pulmonar pelo tabaco.

OBJECTIVE: To investigate the acute effects of intravenous administration of cigarette smoke extract (CSE) on histological, inflammatory, and respiratory function parameters in rats, as well as to compare this potential acute lung injury (ALI) model with that with the use of oleic acid (OA). METHODS: We studied 72 Wistar rats, divided into four groups: control (those injected intravenously with saline); CSE (those injected intravenously with CSE and saline); OA (those injected intravenously with saline and OA); and CSE/OA (those injected intravenously with CSE and OA). RESULTS: Mean lung compliance was significantly lower in the OA and CSE/OA groups (2.12 ± 1.13 mL/cmH2O and 1.82 ± 0.77 mL/cmH2O, respectively) than in the control group (3.67 ± 1.38 mL/cmH2O). In bronchoalveolar lavage fluid, the proportion of neutrophils was significantly higher in the OA and CSE/OA groups than in the control group, as was the activity of metalloproteinases 2 and 9. Pulmonary involvement, as assessed by morphometry, was significantly more severe in the OA and CSE/OA groups (72.9 ± 13.8% and 77.6 ± 18.0%, respectively) than in the control and CSE groups (8.7 ± 4.1% and 32.7 ± 13.1%, respectively), and that involvement was significantly more severe in the CSE group than in the control group. CONCLUSIONS: The intravenous administration of CSE, at the doses and timing employed in this study, was associated with minimal ALI. The use of CSE did not potentiate OA-induced ALI. Additional studies are needed in order to clarify the potential role of this model as a method for studying the mechanisms of smoking-induced lung injury.

The effects of pycnogenol on antioxidant enzymes in a mouse model of ozone exposure

BACKGROUND/AIMS: Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone. METHODS: Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction. RESULTS: Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas gamma-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and gamma-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment. CONCLUSIONS: Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.

Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

PURPOSE: Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. MATERIALS AND METHODS: We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) beta, and tumor necrosis factor (TNF) alpha in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. RESULTS: Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. CONCLUSION: Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.

Avaliação dos níveis de citocinas e da função pulmonar de pacientes submetidos à cirurgia cardíaca com circulação extracorpórea / Evaluation of cytokine levels and pulmonary function in patients undergoing coronary artery bypass graft / Evaluación de los niveles de citocinas y de la función pulmonar de pacientes sometidos a la cirugía cardíaca con circulación extracorpórea

JUSTIFICATIVA E OBJETIVOS: A Síndrome da Resposta Inflamatória Sistêmica é uma ocorrência habitual em cirurgias cardíacas com circulação extracorpórea (CEC). O objetivo deste estudo foi avaliar os níveis sistêmicos e pulmonares de citocinas e a correlação com a função pulmonar em pacientes submetidos à revascularização miocárdica (RM) com CEC. MÉTODOS: O estudo foi aprovado pela Comissão de Ética institucional, com a avaliação de 13 pacientes submetidos à RM com CEC. Após a indução anestésica, ao término da CEC, realizaram-se dosagens plasmáticas e no lavado broncoalveolar de IL-1β, IL-6, IL-8, IL-10 e TNF-α. Foram avaliados o tempo de CEC e de cirurgia, a relação PaO2/FiO2, o gradiente alvéolo-arterial de oxigênio (GA-aO2), o shunt e a complacência pulmonares. Os resultados foram submetidos à análise de variância para medidas repetidas (*p < 0,05) e coeficiente de correlação de Spearman. RESULTADOS: Observaram-se aumento dos níveis de citocinas no plasma e no lavado broncoalveolar após a CEC e relação direta entre o aumento da IL-1β e a diminuição da complacência pulmonar (p = 0,0439), assim como relação inversa entre o aumento da IL-10 e a redução da complacência (p = 0,0325). O aumento da IL-6 teve relação direta com o tempo de CEC (p = 0,012), enquanto o aumento da IL-8 teve relação direta com o tempo de cirurgia (p < 0,0001). Os níveis de IL-1β, IL-8 e TNF-α foram maiores no LBA em relação ao plasma. CONCLUSÕES: Ocorre aumento dos níveis de citocinas no plasma e lavado broncoalveolar após a CEC e há correlação entre o aumento dos níveis de citocinas e o tempo de CEC e de cirurgia e as alterações na complacência pulmonar.

BACKGROUND AND OBJECTIVES: Systemic inflammatory response syndrome is commonly observed in coronary artery bypass grafts (CABG) with cardiopulmonary bypass (CB). The objective of this study was to evaluate the systemic and pulmonary levels of cytokines and their correlation with lung function in patients undergoing myocardial revascularization (MR) with CB. METHODS: This study was approved by the Institutional Ethics Committee, and 13 patients undergoing MR with CB were evaluated. After anesthetic induction and at the end of CB, plasma and bronchoalveolar lavage levels of IL-1β, IL-6, IL-8, IL-10, and TNF-α were determined. The dur ation of CB and surgery, PaO2/FiO2 ratio, alveolar-arterial oxygen gradient (A-a gradient), shunt, and lung compliance were evaluated. Results were submitted to analysis of variance for repeated measurements (*p < 0.05) and Spearman's correlation coefficient. RESULTS: We observed increased levels of cytokines in plasma and bronchoalveolar lavage after CB and a direct relationship between the increase in IL-1β and decrease in lung compliance (p = 0.0439), as well as the inverse relationship between the increase in IL-10 and a decrease in compliance (p = 0.0325). The increase in IL-6 was directly related to the duration of CB (p = 0.012), while the increase in IL-8 was directly related to the duration of surgery (p < 0.0001). Levels of interleukin-1β, IL-8, and TNF-α in bronchoalveolar lavage were higher than in plasma. CONCLUSIONS: There is an increase in cytokine levels in plasma and bronchoalveolar lavage after CB, as well as a correlation between increased cytokine levels and CB duration and surgery and changes in lung compliance.

JUSTIFICATIVA Y OBJETIVOS: El Síndrome de la Respuesta Inflamatoria Sistémica es algo habitual en las cirugías cardíacas con circulación extracorpórea (CEC). El objetivo de este estudio fue evaluar los niveles sistémicos y pulmonares de citocinas y la correlación con la función pulmonar en los pacientes sometidos a la revascularización miocárdica (RM) con CEC. MÉTODOS: El estudio fue aprobado por la Comisión de Ética Institucional, con la evaluación de 13 pacientes sometidos a la RM con CEC. Después de la inducción anestésica al término de la CEC, se realizaron dosificaciones plasmáticas y también en el lavado broncoalveolar de IL-1β, IL-6, IL-8, IL-10 y TNF-α. Se evaluaron el tiempo de CEC y de cirugía, la relación PaO2/FiO2, el gradiente alvéolo-arterial de oxígeno (GA-aO2), el shunt y la complacencia pulmonares. Los resultados fueron sometidos al análisis de variancia para medidas repetidas (*p < 0,05) y al coeficiente de correlación de Spearman. RESULTADOS: Se observó un aumento en los niveles de citocinas en el plasma y en el lavado broncoalveolar después de la CEC y una relación directa entre el aumento de la IL-1β y la disminución de la complacencia pulmonar (p = 0,0439), como también una relación inversa entre el aumento de la IL-10 y la reducción de la complacencia (p = 0,0325). El aumento de la IL-6 tuvo una relación directa con el tiempo de CEC (p = 0,012), mientras que el aumento de la IL-8 tuvo una relación directa con el tiempo de cirugía (p < 0,0001). Los niveles de IL-1β, IL-8 y TNF-α fueron mayores en el LBA con relación al plasma. CONCLUSIONES: Ocurre un aumento de los niveles de citocinas en el plasma y en el lavado broncoalveolar después de la CEC, con una correlación entre el aumento de los niveles de citocinas y el tiempo de CEC y de cirugía, y las alteraciones en la complacencia pulmonar.

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1beta, IL-6 and TNF-alpha, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.

Biomarcadores en neumonías / Biomarkers in pneumonia

Las neumonías, tanto comunitarias como nosocomiales, constituyen una importante causa de morbimortalidad a nivel global y ocasionan además importantes costos sanitarios. Como en cualquier otro proceso infeccioso, una adecuada respuesta a la infección es un fenómeno complejo que requiere un apropiado y oportuno tratamiento antibiótico, así como una apropiada respuesta inflamatoria inicial para contener la proliferación y diseminación de los microorganismos, seguida por una respuesta antiinflamatoria compensatoria que restaure la homeostasis inicial. Recientes estudios han demostrado que una excesiva respuesta inflamatoria en sepsis y NAC severa puede asociarse con efectos deletéreos y peor pronóstico. Por otro lado, una exagerada respuesta antiinflamatoria puede tener efecto negativo en la resolución de la infección. Por lo tanto, una mejor comprensión de este delicado equilibrio proinflamatorio/antiinflamatorio y sus mediadores podrán ser de gran ayuda para valorar la presencia y gravedad de la neumonía así como su probable evolución. En estudios previos varios marcadores han sido ensayados: Proteína C reactiva (PCR), Procalcitonina (PCT), diversas interleuquinas (IL1, IL6, IL8 e IL10), factor de necrosis tumoral alfa (TNFalfa), etc., como marcadores de inflamación/infección, gravedad, fallo de tratamiento y pronóstico. La presente monografía tiene por objeto hacer una revisión sintética de la literatura reciente sobre el tema, tratando de explorar y objetivar fortalezas y debilidades de tales marcadores biológicos.

Community acquired and nosocomial pneumonia are considered a global health issue and a significant cause of morbility, mortality and important economic costs. As in other infectious diseases, an appropriate therapeutic response to the infection is a complex phenomenon that requires appropriate and timely antimicrobial treatment and acorrect initial inflammatory response to stop the microbial proliferation and dissemination, followed by an anti-inflammatory response to restore the initial homeostasis. Recently published studies have showed that exaggerated inflammatory response in sepsis and severe community acquired pneumonia may be associated with poorer outcomes. On the other hand, an exagerated inflammatory response may have a deleterious effect on the infection resolution. Consequently, a better understanding of the delicate balance inflammation/anti-inflammation and their mediators could be of great help to understand the presence and severity of pneumonia and even to predict its outcome. Several marker shave been used, including C-reactive protein (CRP), procalcitonin, several interleukines [IL1, IL6, IL8, IL10], tumor necrosis factor-alpha (TNF alfa), etc, as markers of inflammation /infection, severity, therapeutic failure, severity therapeutic failure and prognostic tool. This review was performed to summarize the observations of the more recent published data on this topic, trying to explore strengths and weaknesses of these markers.