Allergen sensitizations in southern Italy: a 5-year retrospective study in allergic respiratory patients.

The assessment of the distribution of allergen skin test sensitizations is highly recommended for the optimal management of allergic respiratory conditions. We aimed at evaluating the distribution of allergen sensitizations in individuals with asthma and/or rhinitis in the Southern region of ltaly, and at exploring whether changes in the frequency of allergen sensitizations occurred after a 5-year period. Demographic data and skin prick test sensitizations to allergens from asthmatics and/or rhinitis attending the Division of Respiratory Diseases, University of Palermo, Italy in 2005 (Phase 1) and in 2010 (Phase 2) were extrapolated and retained for analysis. A total of 2033 allergic respiratory patients were included (1002 in Phase 1 and 1031 in Phase 2). In both investigations, the most prevalent allergen sensitization was towards Parietaria; however, a significant reduction in the rate of prevalence after 5 years was recorded (from 60% to 48% of skin test positive patients, p < 0.0001). Up to one out of two subjects showed sensitization to dust mites in both Phases. Interestingly, Cypress pollen sensitization almost doubled from Phase 1 (17%) to Phase 2 (29%; p < 0.0001). Overall, the mean number of skin test sensitizations for each patient increased from 2.7 +/- 1.6 in Phase 1 to 3.1 + 1.8 in Phase 2 (p < 0.0001). The present findings confirm the prevalent role of Parietaria sensitization in the allergic population of the Mediterranean area of Southern Italy, and document the increase of Cypress sensitization. These observations could contribute to a proper management of chronic allergic respiratory conditions in this region.

Diagnostic role of internal mammary lymph node involvement in tuberculous pleurisy: a multicenter study.

BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma.

BACKGROUND: Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. AIM: To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. METHODS: After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. RESULTS: Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters. CONCLUSION: The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.

Validation of FEV6 in the elderly: correlates of performance and repeatability.

BACKGROUND: Forced expiratory volume in 6 s (FEV6) has been proposed as a more easily measurable parameter than forced vital capacity (FVC) to diagnose airway disease using spirometry. A study was undertaken to estimate FEV6 repeatability, to identify correlates of a good quality FEV6 measurement and of volumetric differences between FEV6 and FVC in elderly patients. METHODS: 1531 subjects aged 65-100 years enrolled in the SA.R.A project (a cross-sectional multicentre non-interventional study) were examined. FEV6 was measured on volume-time curves that achieved satisfactory start-of-test and end-of-test criteria. Correlates of FEV6 achievement were assessed by logistic regression. RESULTS: Valid FEV6 and FVC measurements were obtained in 82.9% and 56.9%, respectively, of spirometric tests with an acceptable start-of-test criterion. Female sex, older age, lower educational level, depression, cognitive impairment and lung restriction independently affected the achievement of FEV6 measurement. Good repeatability (difference between the best two values <150 ml) was found in 91.9% of tests for FEV6 and in 86% for FVC; the corresponding figures in patients with airway obstruction were 94% and 78.4%. Both FEV6 and FVC repeatability were affected by male sex and lower education. Male sex, airway obstruction and smoking habit were independently associated with greater volumetric differences between FEV6 and FVC. CONCLUSIONS: In elderly patients, FEV6 measurements are more easily achievable and more reproducible than FVC although 1/6 patients in this population were unable to achieve them.

Emphysema: coiling up the lungs, trick or treat?

Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

Emphysema: coiling up the lungs, trick or treat?

Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53.

The tumor suppressor p53 is mainly involved in the transcriptional regulation of a large number of growth-arrest- and apoptosis-related genes. However, a clear understanding of which factor/s influences the choice between these two opposing p53-dependent outcomes remains largely elusive. We have previously described that in response to DNA damage, the RNA polymerase II-binding protein Che-1/AATF transcriptionally activates p53. Here, we show that Che-1 binds directly to p53. This interaction essentially occurs in the first hours of DNA damage, whereas it is lost when cells undergo apoptosis in response to posttranscriptional modifications. Moreover, Che-1 sits in a ternary complex with p53 and the oncosuppressor Brca1. Accordingly, our analysis of genome-wide chromatin occupancy by p53 revealed that p53/Che1 interaction results in preferential transactivation of growth arrest p53 target genes over its pro-apoptotic target genes. Notably, exposure of Che-1(+/-) mice to ionizing radiations resulted in enhanced apoptosis of thymocytes, compared with WT mice. These results confirm Che-1 as an important regulator of p53 activity and suggest Che-1 to be a promising yet attractive drug target for cancer therapy.

Smoking cessation, anxiety, mood and quality of life: reassuring evidences.

A close and complex relationship between smoking and mental health problems was found. Different hypotheses have been proposed to explain these associations: 1) smoking and poor mental health may share common causes (genetic factors or environmental mechanisms); 2) for people with poor mental health smoking is a coping strategy to regulate psychiatric symptoms; 3) smokings worsen mental health. Moreover, smokers with psychiatric disorders may have more difficulty quitting and patients with mental diseases who received mental health treatment within the previous year were more likely to stop smoking than those not receiving treatment. Taylor et al. hypothesized that quitting smoking might improve rather than exacerbate mental health, because it allows to avoid multiple episodes of negative affect induced by withdrawal. With the aim to verify this hypothesis, they conducted a systematic review and meta-analysis on longitudinal studies (randomized controlled trials and cohort studies) in which the difference in change in mental health between subjects who stop smoking and subjects who continue to smoke has been explored. A total of 26 longitudinal studies evaluating anxiety, depression, mixed anxiety and depression, positive effect, psychological quality of life, and stress have been included. The study results provided enough evidence to assure that quitting smoking is associated with a reduction of depression, anxiety, and stress, with an improvement of psychological quality of life and positive affect compared with continuing to smoke. The strength of association was similar for both the general population and study enrolled populations, including those with mental health disorders. The results of this meta-analysis have direct clinical implications: the benefits for mental health could motivate physicians and patients to take into account the possibility of smoking cessation.

Spirometric criteria to diagnose airway obstruction in the elderly: fixed ratio vs lower limit of normal.

COPD is the most common chronic lung disease. It becomes more prevalent with increasing age but remains under-diagnosed in the elderly. A heated debate concerns the most suitable way to diagnose airway obstruction in this age group. Most COPD guidelines recommend to use a FEV1/FVC of 0.70 as threshold to define an obstructive ventilatory defect. While the use of a 0.70 ratio may be simple, it may result in under-diagnosis of airflow obstruction in young people and over-diagnosis in the elderly due to an age-related decline in pulmonary volumes, especially in FEV1. This might lead to unnecessary use of medications and increased risk of adverse effects. A proposed strategy for reducing the misclassification of airway obstruction include the use of the statistically derived lower limit of normal (LLN) for FEV1/FVC, calculated as the fifth percentile of the normal distribution in a healthy population. Some authors addressed the possibility to evaluate lung function through high-resolution CT. In contrast to spirometry, CT imaging may allow for regional assessment of the compartments involved (airways, parenchyma, vasculature), and may enable a phenotype-driven characterization of COPD. Bhatt et al. recently observed that a small proportion (7%) of subjects with CT-defined emphysema were identified by the 0.70 threshold for FEV1/FVC but not by the LLN. However, there is no evidence that CT-emphysema corresponds to a clinical entity that can benefit by inhaled therapy. Further studies are needed to assess the classificatory and prognostic value of the different proposed criteria to diagnose airway obstruction in the elderly.

HIPK2 sustains apoptotic response by phosphorylating Che-1/AATF and promoting its degradation.

Che-1/AATF is an RNA polymerase II-binding protein that is involved in the regulation of gene transcription, which undergoes stabilization and accumulation in response to DNA damage. We have previously demonstrated that following apoptotic induction, Che-1 protein levels are downregulated through its interaction with the E3 ligase HDM2, which leads to Che-1 degradation by ubiquitylation. This interaction is mediated by Pin1, which determines a phosphorylation-dependent conformational change. Here we demonstrate that HIPK2, a proapoptotic kinase, is involved in Che-1 degradation. HIPK2 interacts with Che-1 and, upon genotoxic stress, phosphorylates it at specific residues. This event strongly increases HDM2/Che-1 interaction and degradation of Che-1 protein via ubiquitin-dependent proteasomal system. In agreement with these findings, we found that HIPK2 depletion strongly decreases Che-1 ubiquitylation and degradation. Notably, Che-1 overexpression strongly counteracts HIPK2-induced apoptosis. Our results establish Che-1 as a new HIPK2 target and confirm its important role in the cellular response to DNA damage.