La NIV nel paziente con insufficienza respiratoria cronica, la gestione domiciliare - Competenza specialistica nelle patologie pneumologiche pure

Questo capitolo ha lo scopo di revisionare la letteratura in merito ai meccanismi dell’insufficienza respiratoria cronica e gli effetti fisiologici e l’efficacia della ventilazione meccanica non invasiva nei pazienti affetti da BPCO in fase di stabilità clinica, cercando di dare indicazioni sulla selezione dei pazienti che potrebbero maggiormente beneficiare di questo trattamento

Acute exacerbations of chronic obstructive pulmonary disease provide a unique opportunity to take care of patients

Exacerbation of chronic obstructive pulmonary disease (ECOPD) identifies the acute phase of COPD. The COPD patient is often frail and elderly with concomitant chronic diseases. This requires the physician not only looks at specific symptoms or organs, but to consider the patient in all his or her complexity. \ua9Copyright B. Begh\ue9 et al., 2013 Licensee PAGEPress

We Have to Learn to Do Without Knowing Enough: Anti-Eosinophilic Treatments for Severe Asthma

Interleukin.5 (IL.5) is the main eosinophilic cytokine that promotes the differentiation, survival, and activation of eosinophils, which are the key inflammatory cells in severe eosinophilic asthma .Thus, it is no surprise that anti.IL.5 pathways have been explored for several years for their ability to reduce eosinophilic inflammation and thus to improve the treatment of this disease

BPCO e altre malattie polmonari croniche

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a relatively irreversible airflow limitation caused by chronic inflammation, in most cases tobacco-related. The impact of COPD on morbidity and mortality at the single-patient level depends upon the severity of COPD symptoms and the existence of other types of systemic and/or pulmonary disease, also known as co-morbid conditions. Materials and methods: This review examines the pulmonary diseases commonly associated with COPD, in terms of their prevalence, clinical features, pathogenic mechanisms, prognoses, and implications for management of COPD. Results: The incidence and prevalence of various pulmonary diseases are significantly increased in patients with COPD. These conditions include symptomatic bronchiectasis, combined pulmonary fibrosis and emphysema, lung cancer, sleep-related respiratory disorders, and pulmonary embolism. Some of these concomitant respiratory diseases have an independent negative impact on the prognosis of COPD patients, and their presence has important implications for treatment of these patients. Conclusions: Physicians treating patients with COPD need to be aware of these coexisting pulmonary diseases. All patients with COPD should be carefully evaluated to identify pulmonary comorbidities, since they not only influence the prognosis but also have an impact on disease management. The treatment of COPD is no longer restricted exclusively to inhaled therapy. The therapeutic approach to this disease is becoming increasingly multidimensional in view of the fact that successful management of comorbidities might positively affect the course of COPD itself. \ua9 2011 Elsevier Srl. All rights reserved

Baseline exercise tolerance and perceived dyspnea to identify the ideal candidate to pulmonary rehabilitation: a risk chart in COPD patients.

Background The appropriate criteria for patient selection are still a key issue in the clinical management of patients referred to pulmonary rehabilitation (PR). Methods We retrospectively analyzed the records of a wide population of 1470 outpatient or inpatients with chronic obstructive pulmonary disease (COPD) referred to standard PR at two specialized Italian centers. Two models of multivariate logistic regression were developed to test the predictive powers of baseline exercise tolerance, namely the distance walked in 6 minutes (6MWD), and of baseline dyspnea on exertion, measured by the modified Medical Research Council scale (mMRC), versus the minimal clinically important difference (MCID) for the same outcomes. Results- (p<0.001) of predicting a MCID change. Compared to the category of individuals with mMRC 0-1point, all the other categories (2, 3, and 4) also showed a higher probability (p<0.001) of predicting a MCID change. The incorporation of baseline categories of 6MWD and mMRC in a risk chart showed that the percentage of patients reaching MCID in both variables increased as the baseline level of 6MWD decreased and of mMRC increased. Conclusion- This study demonstrates that lower levels of exercise tolerance and greater perceived dyspnea on exertion predict achieving clinically meaningful changes for both these treatment outcomes following PR. A specific risk chart that integrates these two variables may help clinicians to select ideal candidates and best responders to PR

Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease.

Abstract BACKGROUND: Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. METHODS: 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 micrograms three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. RESULTS: There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (-27%) and total cells (-42%) with respect to baseline, while the control group did not (neutrophils +9%, total cells +7%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52% in the treated group and 73.3% in the control group (95% confidence interval (CI) -27.2 to -15.4). The mean final value of sputum macrophages was 35.8% in treated group and 19.3% in control group (95% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (-21.3%), macrophages (+16.5%), and total cells (-65%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. CONCLUSIONS: A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation

Comparison of two methods of processing induced sputum: selected versus entire sputum.

Abstract Sputum analysis is increasingly used to assess airway inflammation in asthma. The analysis of sputum is currently performed with two techniques, i.e., analysis of selected sputum (plugs) and analysis of entire sputum. To investigate the diagnostic value of these two methods, we compared total and differential cell counts and supernatant eosinophil cationic protein (ECP) in selected and entire sputum collected on two occasions in a group of healthy and asthmatic subjects. We induced sputum with hypertonic saline in 18 asthmatics and in eight healthy subjects. On one occasion we analyzed selected sputum, and on another occasion we analyzed entire sputum. In each sample we measured total and differential cell counts and ECP concentration in supernatant. We found a higher percentage of eosinophils (15.3 versus 8.3%; p < 0.01), more viable nonsquamous cells (80.6 versus 71.8%; p < 0.01), and higher levels of ECP (548 versus 105 microg/L; p < 0.001) in selected sputum as compared with entire sputum, whereas the percentage of neutrophils was higher in the entire sputum (42.7 versus 33.3%; p < 0.05). The percentage of eosinophils and ECP concentration were significantly and similarly increased in both selected and entire sputum of asthmatic subjects, i.e., independent of the method of sputum analysis. In conclusion, the selected sputum method may indeed provide more viable cells, more eosinophils, and a higher concentration of ECP. However, both the selected sputum and the entire sputum method have the same diagnostic value in distinguishing asthmatics from healthy subjects

Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops

Hypoxia is a common feature of solid tumors and is associated with poor patient prognosis, therapy resistance and metastasis. Radiobiological hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response and the unfolded protein response. Recently, we found that hypoxia also leads to the robust accumulation of R-loops, which led us to question here both the mechanism and consequence of hypoxia-induced R-loops. Interestingly, we found that the mechanism of R-loop accumulation in hypoxia is dependent on non-DNA damaging levels of reactive oxygen species. We show that hypoxia-induced R-loops play a critical role in the transcriptional stress response, evidenced by the repression of ribosomal RNA synthesis and the translocation of nucleolin from the nucleolus into the nucleoplasm. Upon depletion of R-loops, we observed a rescue of both rRNA transcription and nucleolin translocation in hypoxia. Mechanistically, R-loops accumulate on the rDNA in hypoxia and promote the deposition of heterochromatic H3K9me2 which leads to the inhibition of Pol I-mediated transcription of rRNA. These data highlight a novel mechanistic insight into the hypoxia-induced transcriptional stress response through the ROS–R-loop–H3K9me2 axis. Overall, this study highlights the contribution of transcriptional stress to hypoxia-mediated tumorigenesis

Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema.

BACKGROUND: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-beta1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p < or = 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p < or = 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 +/- 2.2 vs 1.7 +/- 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p < or = 0.05). TGF-beta1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p < or = 0.05). A positive correlation between TGF-betaRII and AI was observed only in the control group (p < or = 0.005, r2 = 0.8). A negative correlation was found between the TGF-beta pathway (particularly TGF-betaRII) and T lymphocytes infiltrate in smoking-related cases (p < or = 0.05, r2 = 0.99) CONCLUSION: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFbeta-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-beta1 may differently orchestrate cell fate in AAT and smoking-related emphysema types