Zoe Daniil

The role of leptin in the respiratory system: an overview

Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptins involvement in the most common disorders of the respiratory system.

Discrimination of exudative pleural effusions based on multiple biological parameters

Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers. Adenosine deaminase (ADA), interferon-γ, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-α and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups. The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of >45 U·L−1 and a CRP concentration of <4 mg·dL−1 was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of <40 U·L−1 and a CRP concentration of >6 mg·dL−1 was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of <4 mg·dL−1 to the malignant pleural effusion group. The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.

Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial

Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.

Polymorphisms and haplotypes in TLR9 and MYD88 are associated with the development of Hodgkin's lymphoma: a candidate-gene association study

Toll-like receptors (TLRs) and myeloid differentiation primary response protein 88 (MYD88) gene polymorphisms may be involved in the pathogenesis of Hodgkins lymphoma (HL) through altered immunoregulatory and inflammatory responses. A candidate–gene association study was conducted to investigate the association between TLR9 −1237T>C, TLR9 2848A>G, MYD88 −938C>A and MYD88 1944C>G gene polymorphisms and the risk for HL. The impact of haplotypes was also examined. The study showed that carriership for −1237C and 2848A was associated with an increased risk for HL (odds ratio (OR)=2.53 (1.36–4.71) and OR=6.20 (1.3–28.8)). The MYD88 polymorphisms produced nonsignificant results. The estimated frequencies of the TLR9/1237C-2848A and MYD88/938C-1944G haplotypes were also significantly different between HL and controls (P<0.01). In addition, a significant difference between HL and controls was observed for the TLR9/1237C-TLR9/2848A-MYD88/938C-MYD88/1944C haplotypes (P<0.01). In conclusion, our study showed that TLR polymorphisms, and TLR9 and MYD88 haplotypes are related to the development of HL.

CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

BackgroundSeveral studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea.MethodsSurgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale.ResultsElastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD68+ cells for the 16.6% ± 2, CD3+ TLs for the 28.8% ± 7, CD4+ TLs for the 14.5 ± 4 and CD8+ TLs for the 13.8 ± 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (rs = -0.80, p = 0.002) and FEV1 % predicted (rs = -0.68, p = 0.01).ConclusionIn UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.

Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

BackgroundThe association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.MethodsSerum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.ResultsSerum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure.ConclusionSerum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.

Combined pulmonary fibrosis and emphysema in patients exposed to agrochemical compounds

To the Editors: In the very interesting article concerning the clinical syndrome resulting from combined pulmonary fibrosis and emphysema (CPFE) published in the European Respiratory Journal , Cottin et al . 1 speculated that both emphysema and fibrosis might be related to a common environmental trigger and/or genetic factor, with tobacco exposure playing a central role. Here, we report our clinical experience of the same syndrome in order to emphasise the possible role of environmental …

Leptin, adiponectin, and ghrelin levels in female patients with asthma during stable and exacerbation periods.

Objective. The mechanisms underlying the relationship between obesity and asthma have not been fully established. Data in the literature suggest that adipose tissue-derived hormones may be implicated. However, no definite conclusions regarding the role of leptin and adiponectin with asthma are available. No studies have examined the role of ghrelin in asthma. Methods. We assessed the circulating concentrations of leptin, adiponectin, and ghrelin in 32 postmenopausal stable asthma patients, 37 female asthmatics during exacerbations and 8 weeks later, and 22 controls. We examined the relationship between the three peptides and indexes of pulmonary function, airway inflammation, and atopy. Results. Stable asthma patients exhibited higher leptin and lower ghrelin concentrations compared with controls. Patients with severe asthma had higher leptin and lower adiponectin levels versus patients with mild to moderate asthma. Both leptin concentrations and leptin/adiponectin ratio served as markers for discriminating asthma patients from controls on the one hand, and severe from mild to moderate asthmatics on the other. Leptin levels were inversely correlated with both FEV1/FVC and FEF25–75 in patients with mild to moderate asthma. Atopic asthma patients had higher leptin concentrations than nonatopic asthma patients. There was a positive correlation between serum leptin and total IgE levels in atopic asthmatics. Finally, serum leptin levels and leptin/adiponectin ratio were significantly increased during asthma exacerbations, while adiponectin and ghrelin levels were significantly decreased. Conclusion. Our findings suggest that leptin, adiponectin, and ghrelin may play a significant role in the pathogenesis of asthma during both stable state and asthma exacerbation, independent of obesity.

Relationship of BAL and Lung Tissue CD4+ and CD8+ T Lymphocytes, and Their Ratio in Idiopathic Pulmonary Fibrosis

BACKGROUND Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma. STUDY OBJECTIVE To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid. PATIENTS AND METHODS Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry. RESULTS In lung tissue, CD3+ TLs accounted for a mean (+/- SEM) of 28.8 +/- 7% of total cells, CD4+ TLs accounted for 14.5 +/- 4% of total cells (50.1 +/- 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 +/- 4% of total cells (47.4 +/- 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 +/- 2.5% of total cells, CD4+ TLs accounted for 51.8 +/- 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 +/- 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAL fluid (r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 +/- 0.21 and 1.5 +/- 0.27, respectively; r = 0.832; p = 0.01). CONCLUSION The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.

Endothelial Progenitor Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis: An Evolving Concept

Background Idiopathic pulmonary fibrosis (IPF) has been associated with abnormal vascular remodeling. Bone marrow derived endothelial progenitor cells (EPCs) are considered to possess lung tissue repair and vascular remodeling properties. Objectives The study aimed to assess early EPCs levels and EPCs endogenous vascular endothelial growth factor (VEGF) expression in IPF. In order to examine alterations in the mobilization of EPCs from the bone marrow we measured plasma VEGF. Main Results Twenty-three patients with IPF and fifteen healthy subjects were included. The number of early EPCs colonies was markedly reduced in IPF patients vs controls (6.00±6.49 vs 49.68±16.73, respectively, p<0.001). EPCs were further decreased in patients presenting systolic pulmonary arterial pressure (sPAP)≥35 mmHg. The number of colonies per well correlated negatively with P(A-a)O2 (r =  −0.750, p<0.001). Additionally, VEGF mRNA levels were significantly increased in IPF patients. There were no differences observed in VEGF plasma levels in IPF patients when compared to controls. Conclusions The current data suggest that inadequate levels of early EPCs may potentially contribute to suppressed repair and recovery of the damaged pulmonary endothelium and thereby may drive the sequence of events in profibrogenic direction. Increased VEGFmRNA levels in the clinical context of IPF may represent a compensatory mechanism to overcome reduced EPCs levels.