Markers of oxidative stress are increased in exhaled breath condensates of children with atopic dermatitis.

BACKGROUND: Airway inflammation may be present in subjects affected by atopic dermatitis (AD) but still without asthma symptoms. Exhaled breath condensate (EBC) reflects the composition of bronchoalveolar extracellular lining fluid that contains a large number of mediators of airway inflammation and oxidative damage. OBJECTIVES: We assessed inflammatory markers in the EBC of patients with AD. Fifty-six children (34 girls and 22 boys) were enrolled: 33 affected by AD and 23 healthy controls. METHODS: EBC was collected using a condenser device. We measured EBC pH and concentrations of leukotriene B4 (LTB4), 8-isoprostane, H(2) O(2) , malondialdehyde and 4-hydroxynoneal. Respiratory resistance was also evaluated. RESULTS: EBC pH in patients with AD was significantly lower than in healthy children, median (range) being 8·02 (7·94-8·12) in AD vs. 8·11 (8·05-8·16) (P = 0·02). The values of exhaled 8-isoprostane and LTB4 were significantly increased in subjects with AD compared with normal controls (P < 0·01 and P < 0·001, respectively). There was increased 4-hydroxynoneal in patients with AD but this did not reach statistical significance. Evaluating respiratory resistance, no bronchoreversibility was demonstrated in the children with AD. CONCLUSIONS: pH, LTB4 and 8-isoprostane in EBC could be sensitive markers of airway inflammation in children with AD. Prospective studies would be of interest to evaluate if airway inflammation, not yet clinically evident, could predict the development of asthma later in life in children with AD.

Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia.

No study has evaluated the correlation between different expression of nitric oxide synthase (NOS) isoforms in nasal epithelial cells and nasal NO (nNO) level in primary ciliary dyskinesia (PCD). Gene expression of endothelial (NOS3) and inducible NOS (NOS2) and their correlation with nNO level, ciliary function and morphology were studied in patients with PCD or secondary ciliary dyskinesia (SCD). NOS3 gene polymorphisms were studied in blood leukocytes. A total of 212 subjects were studied (48 with PCD, 161 with SCD and three normal subjects). nNO level correlated with mean ciliary beat frequency (p = 0.044; r = 0.174). The lower the nNO level the higher was the percentage of immotile cilia (p<0.001; r = -0.375). A significant positive correlation between NOS2 gene expression and nNO levels was demonstrated in all children (p = 0.001; r = 0.428), and this correlation was confirmed in patients with PCD (p = 0.019; r = 0.484). NOS2 gene expression was lower in PCD than in SCD (p = 0.04). The NOS3 isoform correlated with missing central microtubules (p = 0.048; r = 0.447). nNO levels were higher in PCD subjects with the NOS3 thymidine 894 mutation, and this was associated with a higher ciliary beat frequency (p = 0.045). These results demonstrate a relationship between nNO level, NOS mRNA expression and ciliary beat frequency.

A Multi-Variate framework to assess reliability and discrimination power of Bayesian estimation of Intravoxel Incoherent Motion parameters.

PURPOSE: To propose a multivariate multi-step framework for a systematic assessment of the estimation reliability and discriminability of Intravoxel Incoherent Motion (IVIM) model parameters. METHODS: Monte-Carlo simulations were generated on a range of SNRs and in different IVIM combinations considering: i) a dense discretization with 24 b-values; ii) a discretization with 9 b-values. A state-of-the-art Bayesian fitting method was adopted. The framework assessed: i) the best model between mono- and bi-exponential, through the BIC index; ii) the fitting accuracy; iii) the power in discriminating two different IVIM parameters distributions of estimated coefficients, using a multivariate test. Exemplificative oncologic cases were also presented. RESULTS: The bi-exponential fitting was reliable for perfusion fraction higher than 5%, with high accuracy in D estimation, acceptable error for f, but high uncertainty in D*. The discrimination of two distributions is generally feasible if differences in D values (at least 0.3 x10-3 mm2/s) are present; in the case of similar D values, a minimal difference of 5% in f can be discriminated just in case of balanced sample size and dense b-values discretization, whereas the impact of D* is quite negligible. These results were also supported by clinical examples. CONCLUSIONS: IVIM model is generally accurate in estimating diffusion, but uncertainties related to perfusion estimation are not negligible and compromise the discrimination power when different populations should be differentiated. The proposed framework should be adopted as interpretative guidelines to better understand when IVIM model applied on real data can provide reliable findings.

Nasal nitric oxide levels in healthy pre-school children.

The evaluation of nasal nitric oxide (nNO) has been proposed as a screening tool in children with clinically suspectable primary ciliary dyskinesia. Nevertheless, normal values have been reported for school-aged children. This study was designed to identify normal nNO levels in pre-school children. nNO was assessed in 300 healthy children aged between 1.5 and 7.2. Two hundred and fifty of them were unable to fulfill the guideline requirements for nNO measurement and were assessed by sampling the nasal air continuously with a constant trans-nasal aspiration flow for 30 s during tidal breathing. For those children who were able to cooperate, the average nNO concentration was calculated according to guidelines. A statistically significant relationship between nNO level and age was demonstrated in this study group of pre-school children (p < 0.001). An increase in nNO of about 100 ppb was observed in children older than 6 yr vs. those aged < 3. This study presents a description of normal nNO values in pre-school children. The effect of the age and the eventual presence of rhinitis and snoring need to be considered whenever nNO is evaluated in the clinical practice, in particular in non-cooperative children.

Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C-ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function. METHODS: A total of 200 asthmatic children were included in the study: 47 children with newly diagnosed asthma ('New') and without any regular controller therapy; and 153 children with previously diagnosed asthma, treated according to GINA guidelines, and evaluated during a scheduled follow-up visit ('Follow-up'). Childhood Asthma Control Test, FeNO and lung function [forced expiratory volume 1 (FEV1) and forced vital capacity (FVC)] were evaluated. RESULTS: In New vs Follow-up participants, C-ACT score (P < 0.001), FVC (P < 0.005) and FEV1 (P < 0.05) were significantly lower, and FeNO (P = 0.011) were significantly higher. In New, but not in Follow-up participants, significant correlations were observed between C-ACT score and FeNO (r = -0.51; P < 0.001), FEV1 (r = 0.34; P = 0.022) and FEV1/FVC (r = 0.32; P = 0.03). This lack of correlation in Follow-up visits seemed attributable to dissociation between inadequately controlled asthma by C-ACT ratings with normalization of other measures such as FeNO levels. CONCLUSIONS: This study confirms and expands the concept that C-ACT is complementary to, but not a substitute for, other markers of disease control in asthmatic children, especially in the context of follow-up visits.

Azithromycin may reduce cholestasis in primary sclerosing cholangitis: a case report and serendipitous observation.

The newer macrolides have been shown to exert additional anti-inflammatory effects. We report the possible effect of azithromycin on primary sclerosing cholangitis in a patient treated with the drug for severe asthma. A 45-year-old woman with Crohn?s disease and primary sclerosing cholangitis, also suffering from severe asthma, was treated with azithromycin 500 mg OD for 3 consecutive days a week because of the clinical suspicion of bronchiectasis and the severity of her asthma. When the therapy was discontinued, her urine again became darker, pruritus reappeared with the usual severity and laboratory parameters, evaluated after 6 weeks without azithromycin, also worsened. For these reasons macrolide treatment was re-established. Cholestasis-related symptoms and the dark colour of the urine were again reduced 6 weeks later and laboratory parameters were again reversed. We are therefore tempted to speculate that azithromycin may have an effect on primary sclerosing cholangitis on the basis of its anti-inflammatory properties.

IL-8 and pH values in exhaled condensate after antibiotics in cystic fibrosis children.

Interleukin (IL)-8 is a major factor in inflammatory response and the IL-8 levels in exhaled breath condensate (EBC) may be used as a marker of airway inflammation. Airway acidification is implicated in the pathophysiology of obstructive airway diseases and pH EBC values have been used as a marker of airway acidification. The aim of our study is to investigate whether IL-8 and pH levels in EBC of cystic fibrosis (CF) children with respiratory exacerbations change after antibiotic treatment. Lung function, IL-8 and pH EBC values were measured in fifteen CF children (mean age 11 years) with acute exacerbation before (T0) and after two weeks (T1) of antibiotic treatment. IL-8 and pH values were compared by paired t-test. A p less than 0.05 was considered significant. IL-8 EBC levels decreased after antibiotic treatment (T0 0.36+/-0.03pg/ml vs T1 0.28+/-0.03pg/ml; p=0.03) and pH values increased (T0 7.36+/-0.09 vs T1 7.61+/-0.08; p=0.04). Results suggest possible application of EBC as a non-invasive tool to monitor efficacy of antibiotic treatment in CF patients.

Serum and exhaled breath condensate leptin levels in asthmatic and obesity children: a pilot study.

BACKGROUND: Recent studies have highlighted the possible involvement of leptin in inflammation. The leptin receptor is also expressed by alveolar macrophages, T lymphocytes and bronchial epitelial cells, suggesting a possible role in the cascade of airway inflammation. OBJECTIVES: The aim of the study was to evaluate the levels of leptin in exhaled breath condensate (EBC) from asthmatic, normal- and overweight children, in relationship with airway inflammation. METHODS: 15 asthmatic non-obese children, 15 healthy non-asthmatic non-obese children, 11 obese children with asthma (OA) and 20 obese children without asthma (ONA) were enrolled. Body impedance of body weight, EBC collection, FeNO, spirometry and a blood sampling for serum leptin were assessed. RESULTS: Leptin EBC levels were significantly higher (3.9 ng ml-1 ± 1.3) in overweight children than those obese with asthma (3.6 ng ml-1 ± 1.6; p = 0.97), non-owerweight asthmatics (2.2 ng ml-1 ± 1.2; p < 0.0001) and in healthy children (0.9 ng ml-1 ± 0.6; p < 0.001). Leptin EBC levels in asthmatic children were significantly higher than in healthy children (p = 0.05). Leptin serum levels were significantly higher in the overweight children compared with the asthmatics (12.7 ng ml-1 ± 13.2; p < 0.001) and the healthy group (11.1 ng ml-1 ± 11.2; p < 0.001). We observed a significant correlation between EBC-leptin levels and the serum-leptin levels (p = 0.001). No correlations were found between EBC-leptin levels, FeNO and lung function. CONCLUSIONS: This study shows that leptin is measurable in EBC in children and that EBC-leptin levels are significantly higher in the obese subjects and in asthmatic ones compared with healthy subjects. Leptin may therefore represent a non-invasive marker of non-specific airway inflammation in children.

Exhaled nitric oxide levels in childhood asthma: a more reliable indicator of asthma severity than lung function measurement?

The level of exhaled nitric oxide (NO) has been demonstrated to reflect the degree of airway inflammation in patients with asthma and to be related to the severity of asthma, as well as to the efficacy of treatment. In contrast, lung function tests provide information about airway volumes and flows reflecting the level of airway obstruction, but do not allow any direct information about the degree of airway inflammation. Several studies have evaluated the relationships between the level of airway inflammation assessed by exhaled NO and the levels of airway obstruction and/or bronchial hyperresponsiveness in asthmatic adults and children. These studies highlight the complex pathophysiology of asthma and suggest that exhaled NO may have a promising role in addition to lung function measurement in the evaluation of asthma severity in children.

Exhaled nitric oxide is reduced after sputum induction in asthmatic children.

Exhaled nitric oxide (ENO) and eosinophil sputum markers are considered noninvasive markers of airway inflammation in asthma. The aim of this study was to evaluate whether the procedure of sputum induction can affect the level of ENO. We measured ENO before and after sputum induction by inhalation of hypertonic saline solution in 22 asthmatic children and 9 healthy controls. The ENO mean (+/- S. E.M.) value in the group of asthmatic children was reduced from a baseline value of 20.8 (+/- 3.0) ppb to 17.4 (+/- 2.4) ppb after sputum induction (P = 0.0012). In the healthy controls, the mean baseline value of ENO was 9.1 (+/- 2.1) ppb and it was reduced to 4. 8 (+/- 1.1) ppb after induction of sputum (P < 0.01). We suggest that measurements of ENO should be performed after the induction of sputum in asthmatic patients whenever both tests are done in sequence.

What is the role of predation on stability of natural communities? A theoretical investigation.

A basic question in ecology concerns the role of species interaction on dynamics of natural communities. In this framework, ecologists have considered predation, competition, mutualism, the three most important interactions, highlighting their specific effects on distribution and abundance of species, providing knowledge about phenomena like coexistence and extinction. This paper seeks to identify the effects of predation on stability of natural communities by mathematical models. Simple multispecies community models, organized in trophic levels, are analyzed by means of a qualitative technique, loop analysis, combined with a computer calculation procedure. Results do not support the hypothesis of predation as a stabilizing factor. Rather, the outcomes of the analysis suggest that predation may or may not stabilize a community. This depends on the predator's behaviour and on the network of the community.

The qualitative approach in investigating the role of species interactions on stability of natural communities.

Community models with competition and mutualism are qualitatively analyzed using the methodology of loop analysis combined with computer stochastic simulation. The concept of "moving equilibrium" in the growth rate of the species is discussed in 14 "tables of predictions", presented as analytical tools that can help to shed light on controversial ecological issues such as direct versus indirect interaction and positive feedback effects on stability. While the stochastic simulation shows that only little or no difference exists in probability of stability between models with competition and models with mutualism, the related tables of predictions show that the networks among links are able to activate indirect interactions, with both negative and positive effects, between any pair of species. This phenomenon makes it difficult to determine how much stability is related to the direct interactions.

A Multimethodological Approach for the Sustainable Management of Perifluvial Wetlands of the Po River (Italy).

/ Marginal aquatic systems (wetlands) of the Po River (Italy) have become the target of a renewed interest because of their value for recreation, natural reserves, and deposits of sand. To preserve these sites, wise management must be the objective of local administrations. In this paper a strategy for the sustainable use of 11 wetlands is presented. It uses simple economic analysis and multiple criteria techniques and provides suggestions to promote sustainability in terms of conservation of natural resources, economic self-sufficiency, and minimization of potential conflicts about the use of the wetlands. In the understanding that sustainability is framed in a long-term perspective, stability analysis is also considered and performed by means of loop analysis, a qualitative technique. Conditions for stability are then discussed about management opportunities.

[Visual reaction times in a group of patients with single cerebrovascular lesions in rehabilitation]. / Studio dei tempi di reazione visivi in un gruppo di pazienti con lesione cerebrovascolare singola in fase riabilitativa.

UNLABELLED: Approximately fifty percent of stroke survivors have neurological deficits. The evaluation of reaction times permits a study of psychomotor performance, which could be very important for a good rehabilitation outcome. AIM: The aim of the study was the evaluation of visual reaction times in a group of patients with cerebrovascular lesions, during inpatient hospitalisation in a rehabilitation centre. MATERIALS AND METHODS: 46 right-handed patients (34M, 12F) with unilateral cerebrovascular lesion, confirmed by CT or MRI, were enrolled in the study. In each patients visual Simple Reaction Times (SRT) and Multiple Choice Reaction Times (MCRT) were studied. The patients were asked to react by using the hand ipsilateral to the side of the cerebral lesion. Functional impairment of walking, upper limb and hand were measured by a tailored clinical scale with score ranging from 1 to 12. Depression was measured by a modified version of Hamilton scale, tailored for this kind of patient. RESULTS: 13 of 46 patients (28.2%) showed a pathologic reaction time. There was a lack of correlation between reaction times and age, aphasia, lesion size, time from stroke, functional impairment. Patients with hemorrhagic lesions had significantly lower SRT and MCRT. The subgroup of patients with pathologic reaction times were significantly more depressed than patients with normal reaction times. CONCLUSION: Judging from the present set of results: a) patients with hemorrhagic lesions have lower reaction times; b) the prolongation of reaction times and post-stroke depression appear to be related in stroke patients. This relationship seems to suggest that post stroke depression can negatively affect functional recovery also by means of an impairment of psychomotor performance.

Inhibition of somatosensory evoked potentials during spinal cord stimulation and its possible role in the comprehension of antalgic mechanisms of neurostimulation for neuropathic pain.

BACKGROUND: Spinal cord stimulation (SCS) has been widely used for pain relief of patients with neuropathic chronic pain, frequently with only partial efficacy. Further advancements probably need a better understanding of SCS mechanisms, yet largely unknown. Aims of this paper were to answer the question if the lumbar SCS inhibits the tibial nerve somatosensory evoked potentials (SEPs) and to discuss the role of lemniscal afferents modulation in the antalgic mechanism of SCS. METHODS: Ten consecutive patients successfully treated with implanted SCS devices for chronic pain in the lower limbs (four males, six females, age range 42-72 years) were enrolled. All the patients had an implanted system with an epidural lead connected to a pulse generator. The vertebral level ranged from T9 to T12. The cortical SEPs complex P39-N50-P60 was recorded at the basal (T0) evaluation, during the stimulation (T1) and immediately after the stimulation (T2). RESULTS: In two of ten patients (20%) the complex P39-N50-P60 became unrelievable at the T1 control (stimulator on). In the remaining eight patients statistical analysis showed a significant reduction of the P39/N50 amplitude at T1 recording. In all patients considered, T0 and T2 recordings were not significantly different, suggesting a fast recovery of the SCS effect on SEPs. CONCLUSION: The results obtained in the present study show an inhibitory effect of SCS on SEPs and support the hypothesis that in some forms of neuropathic pain the antalgic effect of SCS could be attributed to the collision of action potentials travelling in opposite direction on peripheral large diameter fibres.

Quantitative versus qualitative modeling: a complementary approach in ecosystem study.

Natural disturbance or human perturbation act upon ecosystems by changing some dynamical parameters of one or more species. Foreseeing these modifications is necessary before embarking on an intervention: predictions may help to assess management options and define hypothesis for interventions. Models become valuable tools for studying and making predictions only when they capture types of interactions and their magnitude. Quantitative models are more precise and specific about a system, but require a large effort in model construction. Because of this very often ecological systems remain only partially specified and one possible approach to their description and analysis comes from qualitative modelling. Qualitative models yield predictions as directions of change in species abundance but in complex systems these predictions are often ambiguous, being the result of opposite actions exerted on the same species by way of multiple pathways of interactions. Again, to avoid such ambiguities one needs to know the intensity of all links in the system. One way to make link magnitude explicit in a way that can be used in qualitative analysis is described in this paper and takes advantage of another type of ecosystem representation: ecological flow networks. These flow diagrams contain the structure, the relative position and the connections between the components of a system, and the quantity of matter flowing along every connection. In this paper it is shown how these ecological flow networks can be used to produce a quantitative model similar to the qualitative counterpart. Analyzed through the apparatus of loop analysis this quantitative model yields predictions that are by no means ambiguous, solving in an elegant way the basic problem of qualitative analysis. The approach adopted in this work is still preliminary and we must be careful in its application.

Bioimpedance monitoring of airway inflammation in asthmatic allergic children.

BACKGROUND: Asthma in childhood is characterized by chronic inflammation. Measurement of bioimpedance (BI) is a non-invasive way of detecting airway inflammation. The aim was to compare BI with exhaled nitric oxide (eNO) and lung function evaluations in asthmatic allergic children while not exposed to offending allergens. METHODS: 22 asthmatic children allergic to house dust mites have been enrolled while residents at high altitude in an environment free of house dust mites. They were evaluated at T0 after allergen exposure at home, at T1 and at T2 after 1 and 4 months of allergen avoidance, respectively. RESULTS: eNO decreased from 32.21 +/- 5.70 ppb at T0 to 21.92 +/- 4.36 ppb at T1, after one month at high altitude (p = 0.038), without a further decrease at T2. Data in electrical activity showed a significant decrease in conductivity of lower airways between T0 (48.53 +/- 3.53 microA) and T1 (42.08 +/- 3.47 microA) (p = 0.023). deltaB parameter (difference between conductivity of lower respiratory tract and average yield) showed significant decrease from T0 (20.75 +/- 2.64 microA), and T1 (12.84 +/- 2.52 microA) (p < 0.01), but no further decrease at T2. No difference in lung function parameters was observed. CONCLUSION: Allergen avoidance regimen modifies inflammatory parameters in allergic asthmatics. Evaluation of extracellular bioelectrical conductivity seems to represent a promising non-invasive method to assess airway inflammation.

Prevalence and risk factors for atopic dermatitis in preschool children.

BACKGROUND: Atopic dermatitis (AD) is a common condition in infancy which usually disappears by 3 years of age in a significant proportion of children. The prognosis is mostly determined by severity and presence of atopic sensitization. OBJECTIVES: To investigate prevalence of AD, comorbidities and risk factors in a population of preschool children aged 3-5 years. METHODS: Children in kindergartens were evaluated. The International Study of Asthma and Allergies in Childhood written questionnaire (WQ) was used, with additional questions on risk factors. Atopy was investigated by skin prick tests. RESULTS: One thousand, four hundred and two valid WQs (92% response rate) were returned for evaluation. The prevalence of AD symptoms in the last 12 months in the whole population was 18.1% (254 cases). Seventy-two per cent of these children presented AD-specific localizations. The prevalence of eczema as a doctor's diagnosis in the total population was 15.4%. Positive atopic sensitization was present in 18.6% of the total and in 32.2% of the AD study population, respectively. Multiple sensitivities were observed in 58.2% of sensitized children. The prevalence of sensitization demonstrated that the most common sensitizing allergens in children with AD were mites and grass pollen. Rhinitis symptoms and wheezing were present in 32.2% and 24.2%, respectively, of children with AD. Allergic sensitization to egg, cat, grass pollen and mites, as well as the presence of symptoms of rhinitis, and a positive family history of atopy were all significant risk factors for AD. CONCLUSIONS: The study demonstrates a high prevalence of AD and a close relationship with rhinitis symptoms. Significant risk factors for AD were sensitization to food or inhalant allergens as well as parental history of atopy.