Relationship between domestic smoking and metals and rare earth elements concentration in indoor PM2.5.

Cigarette smoke is the main source of indoor chemical and toxic elements. Cadmium (Cd), Thallium (Tl), Lead (Pb) and Antimony (Sb) are important contributors to smoke-related health risks. Data on the association between Rare Earth Elements (REE) Cerium (Ce) and Lanthanum (La) and domestic smoking are scanty. To evaluate the relationship between cigarette smoke, indoor levels of PM2.5 and heavy metals, 73 children were investigated by parental questionnaire and skin prick tests. The houses of residence of 41 "cases" and 32 "controls" (children with and without respiratory symptoms, respectively) were evaluated by 48-h PM2.5 indoor/outdoor monitoring. PM2.5 mass concentration was determined by gravimetry; the extracted and mineralized fractions of elements (As, Cd, Ce, La, Mn, Pb, Sb, Sr, Tl) were evaluated by ICP-MS. PM2.5 and Ce, La, Cd, and Tl indoor concentrations were higher in smoker dwellings. When corrected for confounding factors, PM2.5, Ce, La, Cd, and Tl were associated with more likely presence of respiratory symptoms in adolescents. We found that: i) indoor smoking is associated with increased levels of PM2.5, Ce, La, Cd, and Tl and ii) the latter with increased presence of respiratory symptoms in children.

Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis, modulates responses of the human immune system.

The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses. The derived amino acidic sequence in silico analysis showed specific binding to human Major Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci8 short peptide was investigated in a more evolved immune system using human Peripheral Blood Mononuclear Cells (PBMCs) as in vitro model. The biological activities of this molecule include the activation of 70kDa TCR ζ chain Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vß oligo clonal selection on CD4+ T lymphocytes as well as increased proliferation and IFN-γ secretion. Furthermore Ci8 short affects CD4+/CD25high induced regulatory T cells (iTreg) subset selection which co-expressed the functional markers TGF-ß1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new molecule that modulates important responses of the human adaptive immune system.

Hydroxytyrosol modulates Par j 1-induced IL-10 production by PBMCs in healthy subjects.

Several papers have demonstrated the importance of substances from natural sources which can exert powerful anti-inflammatory effects. In this respect, hydroxytyrosol, one of the major elements of the phenolic components of olive oil, has been extensively studied for its anti-inflammatory activities and safety profile. In this report, we demonstrate that the co-stimulation of human PBMCs from healthy subjects with the Par j 1 allergen and hydroxytyrosol induced a statistically significant increase in the amount of Par j 1-induced IL-10, demonstrating that hydroxytyrosol can modulate an allergen-specific immune response potentiating a suppressive immune response towards an allergen. Our work opens the way to further studies to elaborate the possibility of using hydroxytyrosol as a nutrient for allergy prevention.

Effect of indoor nitrogen dioxide on lung function in urban environment.

BACKGROUND: High levels of indoor NO2 are associated with increased asthma symptoms and decreased expiratory peak flows in children. We investigated the association of exposure to domestic indoor NO2, objectively measured in winter and spring, with respiratory symptoms and lung function in a sample of adolescents from a southern Mediterranean area. METHODS: From a large school population sample (n=2150) participating in an epidemiological survey in the urban area of the City of Palermo (southern Italy), a sub-sample of 303 adolescents was selected which furnished an enriched sample for cases of current asthma. All subjects were evaluated by a health questionnaire, skin prick tests and spirometry. One-week indoor NO2 monitoring of their homes was performed by diffusive sampling during spring and again during winter. RESULTS: We found that about 25% of subjects were exposed to indoor NO2 levels higher than the 40µg/m(3) World Health Organization limit, during both spring and winter. Moreover, subjects exposed to the highest indoor NO2 concentrations had increased frequency of current asthma (p=0.005), wheeze episodes in the last 12 months (p<0.001), chronic phlegm (p=0.013), and rhinoconjunctivitis (p=0.008). Finally, subjects with a personal history of wheeze ever had poorer respiratory function (FEF25-75%, p=0.01) when exposed to higher indoor NO2 concentrations. CONCLUSIONS: Home exposure to high indoor NO2 levels frequently occurs in adolescents living in a southern Mediterranean urban area and is significantly associated with the risks for increased frequency of both respiratory symptoms and reduced lung function.

The burden of rhinitis and rhinoconjunctivitis in adolescents.

PURPOSE: Rhinitis and conjunctivitis are common diseases worldwide that are frequently associated. Nevertheless, the risk factors for rhinoconjunctivitis are not well-described and the impact of conjunctivitis on rhinitis and asthma in children remains unknown. This study explored the different risk factors and evaluated the burden of rhinoconjunctivitis among adolescents. METHODS: This was a cross-sectional study conducted on a random sample of schoolchildren, aged 10-17 years, using skin prick tests and a self-administered questionnaire on respiratory health investigating the impact of rhinitis and rhinoconjunctivitis on daily activities. RESULTS: A complete evaluation was obtained for 2,150 children. The prevalence of rhinitis alone was 18.2% and rhinitis associated with conjunctivitis was 20.5%. Rhinoconjunctivitis was more frequently associated with females, a parental history of atopy, domestic exposure to mold/dampness, passive smoke exposure, and reported truck traffic in residential streets. Moreover, rhinoconjunctivitis was associated with a higher level of allergic sensitization. The prevalence of current asthma was 1.7% in subjects without rhinitis or rhinoconjunctivitis, 5.1% in rhinitis and 10.7% in rhinoconjunctivitis. In a logistic model, rhinoconjunctivitis yielded a 2-fold risk for current asthma with respect to rhinitis. Subjects with rhinoconjunctivitis had poorer quality of life (QoL); there was an impact on daily activities in 4.6% of rhinitis and 10.7% of rhinoconjunctivitis. CONCLUSIONS: Ocular symptoms increase the role of rhinitis as a risk factor for asthma and its impact on daily activities in children.

Rhinitis as a risk factor for depressive mood in pre-adolescents: a new approach to this relationship.

BACKGROUND: Respiratory allergic symptoms impact on social life and school activities, influencing the patient's mood states. We evaluated the relationships between allergic respiratory diseases and depressive/anxious mood in a large sample of Italian middle school students, using the partial directed acyclic graph (P-DAG). METHODS: We studied 1283 subjects aged 10-13. A health respiratory questionnaire including questions relevant to socioeconomic status (HCI) and a test for depression and anxiety were administered. All subjects performed spirometry and skin prick tests. RESULTS: A causal role of rhinitis on depression was found: the likelihood of being depressed increased from 11.2 to 17.7%, when rhinitis was present. Moreover, a direct effect of low HCI on depressive mood was shown (p < 0.0001) as well as the correlation between anxiety and depression (p < 0.0001). Gender was not a direct causal factor for depressive mood, but their relation was mediated through anxious mood. Anxiety appeared to have a stronger association with depression than gender. Allergic sensitization was significantly related to both asthma and rhinitis (p < 0.0001, respectively). Asthma and rhinitis were also directly associated (p < 0.0001). Conversely, asthma was not directly associated with depressive mood, but their relation was mediated through rhinitis. Body mass index (BMI) and impaired lung function (IPF) were not associated with the other variables. CONCLUSIONS: The use of this novel approach to analyzing the dynamic relationships allowed us to find a causal role of rhinitis on depressive state. Moreover, anxious condition and low socioeconomic status contributed to induce depressive mood.

Proportional Venn diagram and determinants of allergic respiratory diseases in Italian adolescents.

Large variations in prevalence of atopy and allergic diseases are reported worldwide in children, but in epidemiological studies the use of skin prick tests (SPT) and spirometry along with questionnaires is not common in the Mediterranean Area. The present work was aimed at evaluating the prevalence of current asthma (CA), rhinoconjunctivitis (RC), and eczema (E), with atopy and respiratory function, and the role of risk factors for allergic respiratory diseases. A total of 2150 Italian schoolchildren were cross-sectionally investigated through respiratory questionnaire, SPT, and spirometry. A proportional Venn diagram quantified the distribution of CA, RC, and E, stratifying for allergic sensitization to show differences in prevalence of allergic diseases among subjects with and without positive SPT. CA prevalence was 4.2%, RC 17.9%, and E 5.3%. CA and RC increased, while E decreased, with respect to previous local studies. Allergic sensitization prevalence (evaluated as positive response to at least one SPT) was 39.2%. A double Venn diagram identified 15 categories. Atopic CA was threefold more frequent than non-atopic CA. Atopic vs non-atopic RC and E were 9.6% vs 10.3% and 2.0% vs 3.3%, respectively. Atopic vs non-atopic RC associated with CA were 1.6% vs 0.5%; the same figures for RC associated with E were 0.8% vs 1.3%. Asymptomatic atopic subjects were 27.0%. Atopy, RC, parental asthma, and environmental risk factors were associated with CA. Atopy and environmental factors were risk factors also for RC. Asthma and traffic exposure were linked to reduced lung function. Respiratory allergic diseases are still increasing and largely concomitant in Italian adolescents. Atopy is more important for CA than RC. Avoiding exposures to measured environmental risk factors would prevent 41% of current asthma and 34% of rhinoconjunctivitis.

Pleural mesothelial cells express both BLT2 and PPARalpha and mount an integrated response to pleural leukotriene B4.

Leukotriene B(4) (LTB(4)) plays a crucial role in the recruitment of neutrophils into the pleural space. We identified for the first time the mechanisms by which LTB(4) interacts with mesothelial cells and recruits neutrophils in the pleural compartment. Primary pleural mesothelial cells express both the proinflammatory receptor for LTB(4) BLT2, and the anti-inflammatory receptor for LTB(4), PPARalpha. Parapneumonic pleural effusions highly increase BLT2 expression and, via BLT2 activation, increase the adhesion between mesothelial cells and neutrophils and the expression of ICAM-1 on mesothelial cells. The block of PPARalpha further increases both cell adhesion and ICAM-1 expression. BLT2 activation promotes the activation, on mesothelial cells, of STAT-1 but not the activation of NF-kappaB transcription factor. The increase of ICAM-1 expression is achieved via increased tyrosine phosphorylation activity since herbimycin, a tyrosine kinase inhibitor, reduces and since Na orthovanadate, a tyrosine phosphatase inhibitor, further increases ICAM-1 expression. This study demonstrates that pleural mesothelial cells, expressing both proinflammatory and anti-inflammatory LTB(4) receptors, are able to mount an integrated response to LTB(4) with a prevalence of BLT2 activities in the presence of an inflammatory milieu within the pleura.

Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia.

BACKGROUND: Prostaglandin E2 (PGE2) is known to be produced within human airways, but it is not clear whether in airway diseases it can play a deleterious or a beneficial role. Recently it has been reported that PGE2 can enhance eosinophil survival in vitro. OBJECTIVE: To evaluate whether the concentrations of PGE2 in asthmatic airways correlate with the number of eosinophils and can be responsible for eosinophil-enhanced survival and to identify the cyclooxygenase isoform contributing to the synthesis of PGE2 by cells present in asthmatic airways. METHODS: Reversed-phase high-performance liquid chromatography and/or specific radioimmunoassay was used to measure PGE2 concentrations in induced sputum supernatants from 14 control and 30 asthmatic subjects. Correlations between concentrations of PGE2 and the number of eosinophils in induced sputum were evaluated. Expression of cyclooxygenase-2 (COX-2) in induced sputum cells was determined by immunocytochemistry, and the effect of COX-2 inhibition on PGE2 production was evaluated with the use of radiolabeled arachidonic acid. The effects on eosinophil apoptosis by PGE2 or induced sputum supernatants were studied by using peripheral blood eosinophils obtained by negative immunomagnetic selection. RESULTS: PGE2 concentrations resulted in elevated samples from asthmatic subjects and directly correlated with the percentage of eosinophils and the concentrations of eosinophilic cationic protein. Immunostaining for COX-2 showed enhanced expression in macrophages of asthmatic subjects when compared with control subjects, and the use of a specific COX-2 inhibitor provided evidence that PGE2 synthesis was the result of COX-2 enzymatic activity in asthma-induced sputum cells. Supernatant from induced sputum of asthmatic subjects with high eosinophil counts caused a decreased apoptosis of peripheral blood eosinophils when compared with control subjects, and immunoprecipitation of PGE2 significantly reverted this phenomenon, suggesting that PGE2 was present in biologically relevant concentrations in induced sputum. CONCLUSIONS: The results obtained suggest that COX-2 expression in alveolar macrophages from asthmatic subjects may contribute to enhanced eosinophil survival through an increased PGE2 production.