Marina Bianchi

Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells

Exposure to hypoxia (PO2 = 9 +/- 1 torr) increased human peripheral blood mononuclear cell production and secretion of interleukin-1 (IL-1)alpha, IL-1 beta, and tumor necrosis factor (TNF) percent of control = 190% for IL-1 alpha, p = 0.014; 219% for IL-1 beta, p = 0.014; and 243% for TNF, p = 0.037) following treatment with endotoxin (1 ng/ml). Hypoxia potentiated the increased production of these inflammatory cytokines at subthreshold levels of endotoxin with potentiation increasing at lower O2 concentrations. Hypoxia also increased cytokine production induced by the tumor promoter phorbol myristate acetate, suggesting a generalized biologic response. We conclude that hypoxia increases IL-1 and TNF production and speculate that this mechanism aggravates a variety of pathologic conditions involving endotoxin such as adult respiratory distress syndrome (ARDS), multiple organ failure, and septic shock.

Cytokines in acute myocardial infarction: selective increase in circulating tumor necrosis factor, its soluble receptor, and interleukin-1 receptor antagonist.

Summary Cytokines play a pathogenetic role in a variety of infective and inflammatory diseases. In the present study, we had two objectives: (a) to define the kinetics of tumor necrosis factor (TNF) in plasma after acute myocardial infarction (AMI) in patients treated with early thrombolysis, and (b) to measure other cytokines, interleukin-1 (IL-1) and TNF receptor antagonists, in plasma. TNF-α, but not IL-1β or IL-8, was present in plasma of 6 of 7 patients with severe AMI (Killip class 3 or 4). No TNF (<50 pg/ml) was detected in a group of 11 patients with uncomplicated myocardial infarction (Killip class 1) or in control patients without AMI. Soluble TNF receptor type I and IL-1 receptor antagonist (IL-1Ra) were also significantly increased in the group with severe AMI compared with those with uncomplicated AMI. Circulating TNF is increased only in AMI complicated by heart failure at hospital admission. This finding may have diagnostic and therapeutic relevance.

Inter-country variations in anti-asthmatic drug prescriptions for children. Systematic review of studies published during the 2000?2009 period

ObjectiveThe objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents.MethodsA literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed.ResultsTwelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population ≤19xa0years, with Italy having a prescription prevalence of 19.0%, Canada, 18.0%, USA, 14.6%, Denmark, 13.9%, Norway, 9.1% and the Netherlands, 6.2%. The overall prevalence was 13.3%. The analysis of qualitative inter-country differences revealed that, except for Italy, inhalatory short-acting β-agonists were the most prescribed, followed by inhalatory corticosteroids.ConclusionsThis first overall analysis of anti-asthmatic utilization studies in out-of-hospital children indicates a wide variability in anti-asthmatic prescription prevalence. It also reveals that epidemiological evaluations should be improved by using homogeneous indicators and, in order to validate the use of anti-asthmatic prescription as a proxy of disease, the diagnosis of asthma should accompany the data of prescriptions within the same population.

Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells

We have studied the effect of Ambroxol on the production of Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) in human mononuclear cells (MNC). For this purpose MNC were cultured for 24 h in the presence of endotoxin and different doses of Ambroxol. The results indicate that Ambroxol markedly inhibited IL-1 and TNF production at doses of 10–100 μg/ml, without any apparent toxicity.

Anti-asthmatic drug prescriptions to an Italian paedriatic population

To estimate the prevalence and evaluate the appropriateness of anti‐asthmatic drug prescriptions in an Italian paediatric population, drug prescriptions involving 24,407 children <18u2003years old, dispensed during 2003 by the retail pharmacies of the local health unit in Lecco, Italy, were analysed. Children ≥6u2003years old receiving anti‐asthmatics were categorized into three subgroups based on the number of boxes prescribed: occasional (one box), low (two and three boxes) and high (≥four boxes) users. A logistic regression analysis was performed to estimate the relationship between the drug use patterns and formulations, antibiotic co‐prescriptions, systemic steroid prescriptions and rate of hospitalization. Anti‐asthmatic drugs were prescribed to 6594 (12%) children and adolescents; 58% of whom received only one box of the drug. Prevalence varied according to age, with the highest values at 1 and 4u2003years (24% and 21% respectively), and decreased to 6% in 17‐year‐old adolescents. Inhaled steroids were the most prescribed drugs (83%). The most common of these was beclomethasone. Occasional, low and high users represented 58%, 29%, and 13%, respectively, of the treated population ≥6u2003years old. High users were found to be at increased risk of systemic steroid prescriptions (OR 8.6) and hospital admission for asthma (OR 6.8). This study confirms that in Italy the prevalence of anti‐asthmatic prescription is much higher than prevalence of disease, indicating that anti‐asthmatics are over‐prescribed. Moreover, steroids, especially nebulized, are mainly prescribed only once in a year, supporting the idea that are prescribed not for asthma, which as chronic disease requires a chronic therapy. The approach to create subgroups on the basis of number of boxes prescribed seems to be effective in estimating asthma severity and appropriateness of the therapies.

The pneumotoxicant paraquat induces IL-8 mRNA in human mononuclear cells and pulmonary epithelial cells

Paraquat (PQ) is a herbicide which is highly pneumotoxic by generating reactive oxygen intermediates (ROI). Pro-inflammatory cytokines, particularly IL-1 and TNF, have been implicated in some ROI-mediated pathologies, including bleomycin toxicity and ischaemia/reperfusion injury. We have studied the effect of PQ on the expression of the neutrophil chemotactic cytokine, IL-8, by human peripheral blood mononuclear cells (PBMC). While almost no IL-8 mRNA was detected in unstimulated cells, PQ (100 microM) induced high mRNA expression with a maximum at 24 h of incubation. While PQ did stimulate the appearance of IL-8 mRNA, no significant production of IL-8 protein was detected. However, PQ potentiated the production of IL-8 in the presence of 1 ng/ml of endotoxin (lipopolysaccharide, LPS). This was paralleled by an increased production of chemotactic activity for neutrophils, indicating that the IL-8 was actually bioactive. Stimulation of IL-8 mRNA by PQ was suppressed by IL-4 and by free radical scavengers (dimethylsulfoxide, mannitol). Increased IL-8 expression by PQ was also observed in the human pulmonary epithelial cell line A549 indicating that the effect of PQ was not specific for PBMC. These findings suggest that IL-8 might be involved in the pulmonary effects of PQ and that its production might be stimulated following an oxidative insult, and might clarify the pathogenetic mechanisms of adult respiratory distress syndrome (ARDS) or oxidant-induced pulmonary fibrosis.

The pneumotoxicant paraquat potentiates IL-1 and TNF production by human mononuclear cells

Interleukin 1 (IL-1) and tumor necrosis factor (TNF) have been implicated in the pathogenesis of bleomycin- and silica-induced lung damage. We have studied the effect of paraquat (PQ), a well-known pneumotoxicant, on IL-1 and TNF production by human peripheral blood mononuclear cells from different healthy donors stimulated with endotoxin. PQ (100 μM) potentiated IL-1 production (2–40 fold) and TNF production (2–18 fold). It is, therefore, possible that IL-1 and TNF are also involved in the pneumotoxic action of PQ.

Anti-asthma medication prescribing to children in the Lombardy Region of Italy: chronic versus new users

BackgroundAlthough anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices.MethodsThe analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italys Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as new onset or chronic cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments.ResultsDuring 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment.ConclusionsThis study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.

Spirometry testing in a population of Italian children: Age and gender differences

AIMnTo estimate how many asthmatic children underwent spirometry testing in one year in a large Italian region, and evaluate sociodemographic determinants.nnnMETHODSnData were retrieved from the administrative databases that store all pharmacological and diagnostic prescriptions issued to individuals living in the Lombardy Region. The analysis involved prescriptions dispensed to all 6-17 year olds (1,047,241 subjects) during 2008. Youths were identified as asthmatics by a previously validated strategy. Number of subjects having ≥1 spirometry claims was calculated, and factors associated with the probability of undergoing spirometry were evaluated by multivariate analysis.nnnRESULTSnA total of 40,528 (3.9%) asthmatic subjects were identified. Only 30% of them underwent ≥1 spirometry during 2008, with differences between local health units (range 22-45%) and degree of anti-asthmatic use (26-35%). Moreover, in a multivariate analysis, the chance of undergoing spirometry was greater in boys than in girls (OR=2.3).nnnCONCLUSIONSnA low percentage of asthmatic children, especially girls (who are more at risk of developing severe disease in adulthood), underwent spirometry during 1-year period. This highlights a low compliance with guidelines in the monitoring of childhood asthma. Educational intervention is needed in order to encourage use of spirometry in primary care settings.

Serological screening for celiac disease in a northern Italian child and adolescent population after the onset of type 1 diabetes: a retrospective longitudinal study of a 7-year period.

Aim To evaluate the temporal trend and extent of screening for celiac disease in an Italian pediatric population of incident type 1 diabetes in the period 2006–2011, providing information on adherence to guidelines in primary care. Methods Using the Lombardy region’s administrative database, 1–17-year-old children and adolescents diagnosed with type 1 diabetes during the 2006–2011 period were identified. Among these patients, the number screened for celiac disease was calculated on the basis of specific antibodies. Results Of the 1563 children and adolescents receiving a diagnosis of type 1 diabetes during the observational period, 53% were tested for celiac disease compared with 12% of individuals without diabetes. The extent to which screening was performed increased two-fold from the 2006–2008 to the 2009–2011 period (P<0.0001). Among the screened population, 1.8 of the non-type 1 diabetes population and 9.4% of the new cases of type 1 diabetes received a diagnosis of celiac disease (90% after type1 diabetes diagnosis and 10% before). Being female and less than 4 years old were factors associated with an increased risk of receiving both diagnoses. Conclusion In conclusion, to the best of our knowledge, this is the first report in which celiac disease screening is measured in a type 1 diabetes population from the time of diagnosis up to at least 12 months afterwards. The results provide evidence that, although the rate of screening increased over time, nearly half of children with type 1 diabetes were not screened after diagnosis during the observed period, suggesting scarce adherence to guidelines in primary care.