Made available in DSpace on 2014-08-20T13:57:59Z (GMT). No. of bitstreams: 1 Dissertacao_Paula_Oliveira.pdf: 1081819 bytes, checksum: 9e319c71a8b01c131e6f3917156db97d (MD5) Previous issue date: 2012-12-14 / Objective: to evaluate the characteristics of the users of metered-dose inhalers and its prevalence, among those who reported a diagnosis of asthma, bronchitis and/or emphysema. Methods: a population-based study in Pelotas, RS, Brazil, including 3,670 subjects aged 10 years or older. Results: About 10% of the sample referred at least one respiratory disease. Among these, 59% referred symptoms in the last year and of those, only half have used inhalers, showing difference between the quintiles of socioeconomic status (39% poorest quintile vs. 61% richest quintile p=0,01). There was no difference in the use of inhalers by age and sex. Regarding the pharmacological group, the emphysematous used a combination of bronchodilator (BD) plus corticosteroids in greater proportion than just BD. Only among those who reported a medical diagnosis of asthma and with actual symptoms, the proportion of use of inhalers was higher than 50%. Conclusion: metered-dose inhalers are underused among those who relate these diagnoses and the type of medicine used by the ones who referred emphysema is not in accordance with the recommendations in the consensus about these diseases. / Objetivo: avaliar as características dos usuários de inaladores dosimetrados e sua prevalência de uso, entre aqueles que referem diagnóstico de asma, bronquite e/ou enfisema. Métodos: estudo de base populacional realizado em Pelotas, RS, incluindo 3670 indivíduos, com 10 anos de idade ou mais. Resultados: Cerca de 10% da amostra referiu pelo menos uma das doenças respiratórias investigadas. Entre eles, 59% apresentaram sintomas no último ano e, destes, apenas metade usou inaladores, havendo diferença entre os quintis de nível socioeconômico (39% quintil mais pobre vs. 61% no quintil mais rico p=0,01). Não houve diferença no uso de inaladores por sexo e idade. Quanto ao grupo farmacológico, os enfisematosos utilizaram a combinação broncodilatador (BD) + corticoide em maior proporção do que apenas BD. Somente dentre os que referiram diagnóstico médico de asma e sintomas atuais, a proporção de uso de inalador foi maior que 50%. Conclusão: os inaladores dosimetrados são subutilizados entre os que referem estes diagnósticos e que o tipo de medicamento usado por aqueles que referiram enfisema não está de acordo com o preconizado nos consensos sobre estas doenças.

Cette thèse présente nos travaux sur la prévention, le dépistage, le diagnostic précoce, et traitement du cancer broncho-pulmonaire (CBP) chez les personnes vivant avec le VIH (PVVIH). La finalité de cette synthèse est d’améliorer la prise en charge des PVVIH atteint de ce cancer, mais aussi de développer des axes de recherche après une évaluation rigoureuse de la bibliographie. Nos recherches soulignent tout d’abord que la prise en charge thérapeutique des PVVIH atteintes d’un CBP doit être identique à celle de la population générale, l’infection par le VIH ne constituant finalement qu’une comorbidité supplémentaire. Toutefois, une spécificité de la prise en charge de ce cancer chez les PVVIH est la survenue de complications potentiellement létales secondaires aux interactions et effets toxiques additifs entre les antirétroviraux et les médicaments cytotoxiques. Ce danger nécessite une bonne coordination des équipes oncologiques et infectiologiques, probablement par le biais de réunions de concertation pluridisciplinaires spécifiques, ainsi qu’une bonne connaissance des pharmacocinétiques et pharmacodynamies des produits administrés.Notre étude ANRS EP48 HIV CHEST, qui était une étude transversale multicentrique, a inclus 442 PVVIH à risque de développer un CBP, en raison (principalement) d’un tabagisme > 20 paquets-années, un âge > 40 ans, ainsi qu’un nadir en lymphocytes TCD4 < 350 cellules/ µl. Cette étude a rempli son objectif principal, qui était de démontrer la faisabilité du dépistage du CBP chez les PVVIH en France par TDM thoracique. Le diagnostic d’un nombre important de CBP de stades localisés, et donc guérissables, apporte probablement un bénéfice essentiel aux patients inclus. Le fait qu’aucune complication grave n’ait été engendrée par les explorations diagnostiques, et que la prévalence de nodules significatifs soit dans l’intervalle des résultats d’études en population générale, sont des éléments rassurants. Nos travaux, ainsi que d’autres données de la littérature de prévalence de ce cancer en fonction des âges, font apparaître que l’âge limite de dépistage par TDM faible dose pourrait être de 45 ans chez les PVVIH. Comme en population générale, l’apport du TDM thoracique ne se limite pas au diagnostic de CBP. Il permet d’augmenter l’efficacité du diagnostic précoce de comorbidités ayant un impact sur la qualité de vie et/ou la survie par : 1) le diagnostic des tassements vertébraux, pour la majorité asymptomatique, en rapport avec une prévalence élevée de l’ostéoporose fracturaire dans cette population, 2) l’évaluation de l’emphysème et de la bronchiolite du fumeur, 3) une estimation des calcifications coronaires, qui est associée aux événements cardio-vasculaires. Ce travail a également pour intérêt d’illustrer l’épidémiologie des complications actuelles des PVVIH sous traitement antirétroviral efficace et exposées à une intoxication tabagique. La BPCO, l’emphysème, le CBP, l’athérosclérose coronaire ont une prévalence élevée dans cette population et sont des enjeux importants de santé. Cette épidémiologie rapproche la population des PVVIH de la population générale mais avec des particularités liées, aux antécédents de déficit immunitaire et de traitements antirétroviraux toxiques, et à la prévalence plus élevée des comportements à risque. Pour certaines complications cependant (emphysème, bronchiolite, score calcique), l’absence d’association avec les variables immuno-virologiques souligne la primauté des facteurs comportementaux dans la survenue de ces complications. Ainsi, l’ensemble de ces travaux qui s’articulent principalement autour de l’étude ANRS EP48 HIV CHEST souligne que la réduction des risques liée aux facteurs d’exposition (tabagisme surtout, et probablement cannabis) est une priorité chez les PVVIH à l’ère des combinaisons antirétrovirales. / This thesis is an analysis of our on-going or published works on the theme of prevention, early diagnosis, screening, and treatment of subjects living with HIV with lung cancer. The ultimate objective of this work is to improve care and prevention of lung cancer in people living with HIV (PLWHIV), and to promote research in lung cancer in this population. Our work underscores that lung cancer treatment in PLWHIV should be identical to treatments administered for lung cancer in the general population. HIV is an additional comorbidity to be taken into account, but never a contraindication for optimal therapy. However, there exist specificities in management of PLWHIV with lung cancer, including the propensity for drug-to-drug interactions and additive toxicity between cytotoxic compounds for chemotherapy and antiretroviral therapy, with potentially lethal effects. Managing these toxicities implies optimal cooperation between oncologists and specialists in HIV, as well as good knowledge of pharmacokinetics and pharmacodynamics of these different compounds.The ANRS EP48 HIV CHEST Study in a cross-sectional, multicentre study, which included 442 subjects at lung cancer risk, primarily due to their age (> 40 years), smoking hazard (> 20 pack-years), as well as a CD4 cell nadir count < 350 cells/µl. This study showed feasibility of lung cancer screening with chest Computed Tomography (CT) in PLWHIV. The early diagnosis of localized lung cancers, potentially curable, suggests clinical benefits for most participants with cancer. Also, the facts that no serious adverse events occurred with invasive diagnostic procedures and that the prevalence of positive nodules was in the range of those found in lung cancer screening studies in the general population are reassuring. Also, our work, combined with data from previous epidemiological studies, support a lower age limit for screening lung cancer with chest CT in PLWHIV at risk than in the general population, starting as early as 45 years. As in the general population, the impact of lung cancer screening with chest CT is not limited to the diagnosis of early stage lung cancers. The diagnosis of other morbidities, such as vertebral fractures, generally asymptomatic, emphysema, bronchiolitis, and coronary calcifications, have a probable positive impact on quality of life and a benefit in survival if managed adequately. Our works also illustrate the epidemiology of complications in PLWHIV under antiretroviral therapy and exposed to smoking hazards. Chronic obstructive pulmonary diseases, emphysema, lung cancer, coronary atherosclerosis have high prevalence in this subpopulation of PLWHIV. The epidemiology of these emerging morbidities is close to the epidemiology in the smoking general population, but specificities exist, due to the presence of chronic immunodeficiency, antiretroviral toxicities, and an increased prevalence of behavioural risks in PLWHIV in comparison with the general population. However, some complications are not associated with HIV-related and immunological factors, such as prevalence of emphysema, coronary calcifications, and bronchiolitis, underscoring the major impact of behavioural hazards in the occurrence of these complications.Taken together, our work highlights the importance of reducing health hazards in PLWHIV, primarily smoking and probably cannabis, to reduce the emergence of these new life-threatening morbidities in the era of highly active antiretroviral therapy.

O enfisema pulmonar é caracterizado pela destruição das paredes alveolares, sendo a fumaça de cigarro o principal agente etiológico. Pretendeu-se, neste estudo, comparar os efeitos terapêuticos do transplante de células mononucleares da medula óssea (BMMC) e células mesenquimais (CTM) em animais com enfisema pulmonar induzido por exposição à fumaça de cigarro. Camundongos fêmeas da linhagem C57Bl6/J foram expostos à fumaça de cigarro durante 90 dias e, 21 dias após o término do período de exposição, receberam BMMC ou CTM derivadas da medula óssea de camundongos machos da linhagem C57Bl6/J, expressando a proteína GFP. As análises morfométricas mostraram que os tratamentos com BMMC e CTM foram eficientes na recuperação do parênquima pulmonar dos animais expostos à fumaça de cigarro. Testes de fluorescência direta e PCR mostraram a migração de BMMC e CTM para o pulmão. Desta forma, pode-se concluir que, morfologicamente, a terapia celular com BMMC ou CTM é eficaz no tratamento do enfisema pulmonar resultante da exposição à fumaça de cigarro em modelo animal. / Pulmonary emphysema is characterized by destruction of alveolar walls, and the cigarette smoking is the main etiologic agent. It was intended in this study to compare the therapeutic effects of the transplantation of bone marrow mononuclear cells (BMMC) and mesenchymal stem cells (MSC) in animals with pulmonary emphysema induced by exposure to cigarette smoke. C57Bl6/J female mice were exposed to cigarette smoke for 90 days and 21 days after the end of the exposure time, received BMMC or MSC derived from bone marrow of C57Bl6/J male mice expressing the GFP protein. The morphometric analysis showed that treatments with BMMC and MSC were efficient in recovering the lung of animals exposed to cigarette smoke. Fluorescence and PCR tests showed the migration of BMMC and MSC to the lung. Thus, it is concluded the cell therapy with BMMC or CTM is morphologically effective in the treatment of pulmonary emphysema resulting from exposure to cigarette smoke in an animal model.

We present a case of farmer’s lung (FL) with the primary presenting feature of a large bulla in the lung. A 70-year-old nonsmoking woman with dyspnea on exercise was referred for surgical resection of a large bulla in the lung. The postoperative evaluation of the lung tissue revealed a follicular lymphocytic alveolitis and loosely formed granulomas suspicious for hypersensitivity pneumonitis (HP). The patient had worked in farming since her youth. Dyspnea on exercise was the only symptom, but it was related to the large bulla. No other radiologic features of HP were shown in a high-resolution CT of the lung. Specific IgG antibodies against typical antigens of FL were detected, bronchoalveolar lavage demonstrated no lymphocytic alveolitis but an inhalative challenge with own hay was positive. A diagnosis of chronic FL was made. Despite lung emphysema being a possible reaction in FL, giant bullae as primary and single manifestation of this disease have not been reported before.

Vascular corrosion casting has been used for about 40 years to produce replicas of normal and abnormal vasculature and microvasculature of various tissues and organs that could be viewed at the ultrastructural level. In combination with scanning electron microscopy (SEM), the primary application of corrosion casting has been to describe the morphology and anatomical distribution of blood vessels in these tissues. However, such replicas should also contain quantitative information about that vasculature. This report summarizes some simple quantitative applications of vascular corrosion casting. Casts were prepared by infusing Mercox resin or diluted Mercox resin into the vasculature. Surrounding tissues were removed with KOH, hot water, and formic acid, and the resulting dried casts were observed with routine SEM. The orientation, size, and frequency of vascular endothelial cells were determined from endothelial nuclear imprints on various cast surfaces. Vascular volumes of heart, lung, and avian salt gland were calculated using tissue and resin densities, and weights. Changes in vascular volume and functional capillary density in an experimentally induced emphysema model were estimated from confocal images of casts. Clearly, corrosion casts lend themselves to quantitative analysis. However, because blood vessels differ in their compliances, in their responses to the toxicity of casting resins, and in their response to varying conditions of corrosion casting procedures, it is prudent to use care in interpreting this quantitative data. Some of the applications and limitations of quantitative methodology with corrosion casts are reviewed here.

Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death in the US, and idiopathic pulmonary fibrosis (IPF), a type of Interstitial Lung Disease (ILD), is a fast acting, irreversible disease that leads to mortality within 3-5 years. RNA-sequencing provides the opportunity to quantitatively examine the sequences of millions mRNAs, and offers the potential to gain unprecedented insights into the structure of chronic non-malignant lung disease transcriptome. By identifying changes in splicing and novel loci expression associated with disease, we may be able to gain a better understanding of their pathogenesis, identify novel disease-specific biomarkers, and find better targets for therapy. Using RNA-seq data that our group generated on 281 human lung tissue samples (47=Control, 131=COPD, 103=ILD), I initially defined the transcriptomic landscape of lung tissue by identifying which genes were expressed in each tissue sample. I used a mixture model to separate genes into reliable and not reliable expression. Next, I employed reads that overlapped splice junctions in a linear model interaction term to identify disease-specific differential splicing. I identified alternatively spliced genes between control and disease tissues and validated three (PDGFA, NUMB, SCEL) of these genes with qPCR and nanostring (a hybridization-based barcoding technique used to quantify transcripts). Finally, I implemented and improved a pipeline to perform transcriptome assembly using Cufflinks that led to the identification of 1,855 novel loci that did not overlap with UCSC, Vega, and Ensembl annotations. The loci were classified into potential coding and non-coding loci (191 and 1,664, respectively). Expression analysis revealed that there were 120 IPF-associated and 10 emphysema-associated differentially expressed (q < 0.01) novel loci. RNA-seq provides a high-resolution transcript-level view of the pulmonary transcriptome and its modification in lung disease. It has enabled a new understanding of the lung transcriptome structure because it measures not only the transcripts we know but also the ones we do not know. The approaches and improvements I have employed have identified these novel targets and make possible further downstream functional analysis that could identify better targets for therapy and lead to an even better understanding of chronic lung disease pathogenesis. / 2031-01-01T00:00:00Z

Chronic obstructive pulmonary disease is the fourth largest cause of death worldwide and the prevalence is predicted to increase even further to make it the third largest cause of death by 2020. The main cause of the disease is exposure to tobacco smoke. COPD is a complex disease and there is a strong need of better understanding of the pathogenetic mechanisms in order to come up with novel therapeutic interventions and preventive strategies. The golden standard to image the lungs today is to use computed tomography (CT) which is an imaging modality that involves ionizing radiation and could thus harm the patient, especially with repeated exposure. New techniques in the image acquisition of magnetic resonance imaging (MRI), an imaging modality that does not involve ionizing radiation, has emerged that allows for lung imaging. The work included segmentation of the lungs, image registration and partitioning of the lungs inorder to perform regional analysis. The results indicate that the mean value of the T1-parameter in the left and right lung is not affected to the same degree, where the left lung showed a greater decrease. The results also showed that the anterior parts of the lungs are not showing any statistically significant changes but the changes were instead seen in the center and posterior parts. Both lungs also showed results that indicate that the mean T1-value is recovered at the end of the longitudinal study, a phenomenon that couldn’t be explained and further studies have to be performed.

O propósito da presente investigação foi avaliar o papel da atividade física no desenvolvimento de enfisema induzido por papaína em ratos. Para tanto, ratos Wistar foram randomicamente divididos em quatro grupos (n = 10 para cada grupo) que receberam, respectivamente, infusão intra-traqueal de papaína (6 mg em 1 mL de NaCl 0,9%) ou veículo e foram submetidos ou não ao protocolo de exercício em uma esteira ergométrica. Os ratos exercitaram-se a 13,3 m/min, 6 dias por semana, durante 9 semanas (o tempo de exercício foi aumentado gradualmente, de 10 a 35 min). Foram medidas a elastância e a resistência do sistema respiratório (Ers e Rrs, respectivamente), o peso e tamanho do coração, volume das câmaras cardíacas, diâmetro médio das fibras cardíacas e diâmetro alveolar médio. Após 9 semanas de atividade física não houve diferença para os valores de Ers e Rrs entre os quatro grupos experimentais. Houve um aumento estatisticamente significativo do peso do coração preenchido por solução de formaldeído nos grupos de animais submetidos à atividade física comparados aos grupos de animais sedentários (P = 0,007). Não houve diferenças significativas entre os dois grupos que fizeram exercício físico (tendo ou não recebido papaína) ou entre os dois grupos sedentários. O volume das câmaras cardíacas direita e esquerda não foram diferentes entre os diferentes grupos. O diâmetro médio das fibras do ventrículo esquerdo foi significativamente maior nos grupos submetidos à atividade física quando comparados aos grupos sedentários (P = 0,006). O diâmetro alveolar médio foi significativamente maior em ratos que receberam papaína quando comparados aos ratos que receberam salina intratraqueal (P = 0,025). Entretanto o diâmetro alveolar médio foi significativamente maior nos animais que receberam instilação intratraqueal de papaína e que foram submetidos à atividade física, quando comparados aos animais que foram instilados com papaína, mas não foram submetidos ao condicionamento físico. Concluímos que a atividade física pode aumentar à lesão alveolar induzida pela infusão de papaína / The purpose of the present study was to evaluate the role of exercise training on the development of papain-induced emphysema in rats. Wistar rats were randomly assigned to four groups (n = 10 for each group) that received, respectively, intratracheal infusion of papain (6 mg in 1 mL NaCl 0.9%) or vehicle and were submitted or not to a protocol of exercise on a treadmill. Rats exercised at 13.3 m/min, 6 days per week, for 9 weeks (increasing exercise time, from 10 to 35 min). We measured respiratory system elastance (Ers) and resistance (Rrs), the size and weight of the heart and mean alveolar diameter (Lm). After 9 weeks of exercise training, there were no differences in Rrs and Ers values among the four experimental groups. There was a significant increase in the heart weight filled with formaldehyde solute in animals submitted to exercise training compared to the sedentary groups (P = 0.007). There were no differences between the two groups submitted to exercise training (receiving or not papaine) or between the sedentary groups. There were no differences in cardiac chambers volume between all groups. The left ventricule fibers mean diameter was significantly greater in rats submitted to exercise training compared to sedentary rats (P = 0.006). Lm was significantly greater in rats that received papain compared to saline-infused rats (P = 0.025). However, Lm was significantly greater in papain + exercise rats compared to rats that received papain and were not submitted to exercise. We conclude that exercise training can increase alveolar damage induced by papain infusion

O propósito da presente investigação foi avaliar o papel da atividade física no desenvolvimento de enfisema induzido por papaína em ratos. Para tanto, ratos Wistar foram randomicamente divididos em quatro grupos (n = 10 para cada grupo) que receberam, respectivamente, infusão intra-traqueal de papaína (6 mg em 1 mL de NaCl 0,9%) ou veículo e foram submetidos ou não ao protocolo de exercício em uma esteira ergométrica. Os ratos exercitaram-se a 13,3 m/min, 6 dias por semana, durante 9 semanas (o tempo de exercício foi aumentado gradualmente, de 10 a 35 min). Foram medidas a elastância e a resistência do sistema respiratório (Ers e Rrs, respectivamente), o peso e tamanho do coração, volume das câmaras cardíacas, diâmetro médio das fibras cardíacas e diâmetro alveolar médio. Após 9 semanas de atividade física não houve diferença para os valores de Ers e Rrs entre os quatro grupos experimentais. Houve um aumento estatisticamente significativo do peso do coração preenchido por solução de formaldeído nos grupos de animais submetidos à atividade física comparados aos grupos de animais sedentários (P = 0,007). Não houve diferenças significativas entre os dois grupos que fizeram exercício físico (tendo ou não recebido papaína) ou entre os dois grupos sedentários. O volume das câmaras cardíacas direita e esquerda não foram diferentes entre os diferentes grupos. O diâmetro médio das fibras do ventrículo esquerdo foi significativamente maior nos grupos submetidos à atividade física quando comparados aos grupos sedentários (P = 0,006). O diâmetro alveolar médio foi significativamente maior em ratos que receberam papaína quando comparados aos ratos que receberam salina intratraqueal (P = 0,025). Entretanto o diâmetro alveolar médio foi significativamente maior nos animais que receberam instilação intratraqueal de papaína e que foram submetidos à atividade física, quando comparados aos animais que foram instilados com papaína, mas não foram submetidos ao condicionamento físico. Concluímos que a atividade física pode aumentar à lesão alveolar induzida pela infusão de papaína / The purpose of the present study was to evaluate the role of exercise training on the development of papain-induced emphysema in rats. Wistar rats were randomly assigned to four groups (n = 10 for each group) that received, respectively, intratracheal infusion of papain (6 mg in 1 mL NaCl 0.9%) or vehicle and were submitted or not to a protocol of exercise on a treadmill. Rats exercised at 13.3 m/min, 6 days per week, for 9 weeks (increasing exercise time, from 10 to 35 min). We measured respiratory system elastance (Ers) and resistance (Rrs), the size and weight of the heart and mean alveolar diameter (Lm). After 9 weeks of exercise training, there were no differences in Rrs and Ers values among the four experimental groups. There was a significant increase in the heart weight filled with formaldehyde solute in animals submitted to exercise training compared to the sedentary groups (P = 0.007). There were no differences between the two groups submitted to exercise training (receiving or not papaine) or between the sedentary groups. There were no differences in cardiac chambers volume between all groups. The left ventricule fibers mean diameter was significantly greater in rats submitted to exercise training compared to sedentary rats (P = 0.006). Lm was significantly greater in rats that received papain compared to saline-infused rats (P = 0.025). However, Lm was significantly greater in papain + exercise rats compared to rats that received papain and were not submitted to exercise. We conclude that exercise training can increase alveolar damage induced by papain infusion

A new pathobiologic hypothesis has recently emerged that the alveolar structural destruction and loss in emphysema are caused by the deficiency of vascular endothelial growth factor (VEGF). Therefore, this project hypothesized that such pathobiologic VEGF deficiency of emphysematous lungs can be recovered with a natural caffeic acid tetramer, salvianolic acid B (SalB), through activation of signal transducer and activator of transcription 3 (STAT3), so that emphysema can be reversed as a result of inhibition of induced cell death, stimulation of cell proliferation and migration, and promotion of stem cell recruitment to the lungs. SalB was first shown to be potently anti-oxidative (IC50 = 3.7 μM), but devoid of anti-elastase activity. SalB was then administered to the lungs of healthy rats at 0.2 mg/kg for two weeks, verifying ~1.7-fold increased lung tissue expressions of phosphorylated STAT3 (pSTAT3; an activated form of STAT3) and VEGF. Subsequently, SalB was examined in the anti-cell death assay, cell proliferation and migration assays, and trans- endothelial stem cell recruitment assay in the in vitro lung epithelial (A549) and endothelial (HMVEC-L) cell systems. SalB at 25 μM exerted significant 48-88 % inhibitory activities against cell death induced with oxidative stress and VEGF receptor blockade (with SU5416) in both cell systems, measured by the trypan blue exclusion and propidium iodide-based flow cytometry assays. SalB at 25 μM also stimulated A549 and HMVEC-L cell proliferation by ~1.4-fold and promoted cell migration by ~1.6-fold, while recovering stem cell recruitment impaired with SU5416 by 60 %. The anti-cell death, and proliferation and migration stimulatory activities of SalB were significantly opposed by pharmacological inhibitors of JAK2 (Janus kinase 2; an upper signal of STAT3), STAT3 and VEGF. SalB was then examined for its in vivo reversal activities in emphysema induced with porcine pancreatic elastase (PPE) and cigarette smoke extract (CSE) in rats. Upon establishment of emphysema on day 21, SalB was administered to the lungs three times weekly over three weeks. SalB at 0.2 mg/kg significantly recovered ~85 %-impaired treadmill exercise endurance by 57-82 %; and reduced abnormal airspace enlargement by 59-75 %. In the PPE-induced emphysematous rats, SalB also reduced the 4-fold greater alveolar destruction index by 61 %. The lung tissue protein expression by Western blot analysis found that cleaved caspase 3 (cell apoptotic marker) was induced by 13-fold, and VEGF was reduced by 60 % in the PPE -induced emphysematous rats. However, pulmonary treatment with SalB at 0.2 mg/kg normalized these proteins, and also significantly increased the expression of a cell proliferation marker, proliferative cell nuclear antigen (PCNA) by 2.6-fold. Note however that SalB treatment did not reduce the neutrophilic myeloperoxidase activity in the lungs induced in the PPE-induced rats. Taken all together, this study has demonstrated that SalB potently inhibited lung cell death, stimulates lung cell proliferation and migration, and restores stem cell migration with its mechanism of STAT3 activation and VEGF elevation and reversed established emphysema in rat models.