Dario Nieri

Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis

Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P < 0.0001; rho = −0.428), weakly with Leicester Cough Questionnaire score (P = 0.068; rho = −0.58), and directly with duration of the disease (P = 0.004; rho = 0.3) and BSI severity score (P = 0.005; rho = 0.37), but not with FACED. Sputum neutrophilia was higher in colonized subjects, P. aeruginosa colonized subjects showing greater sputum neutrophilia and lower FEV1. Patients with ≥3 exacerbations in the last year showed a significantly greater EBC-MDA than the remaining patients. Conclusions. Sputum neutrophilic inflammation and biomarkers of oxidative stress in EBC can be considered good biomarkers of disease severity in NCFB patients, as confirmed by pulmonary function, disease duration, bacterial colonization, BSI score, and exacerbation rate.

Cell-derived microparticles and the lung

Cell-derived microparticles are small (0.1–1 μm) vesicles shed by most eukaryotic cells upon activation or during apoptosis. Microparticles carry on their surface, and enclose within their cytoplasm, molecules derived from the parental cell, including proteins, DNA, RNA, microRNA and phospholipids. Microparticles are now considered functional units that represent a disseminated storage pool of bioactive effectors and participate both in the maintenance of homeostasis and in the pathogenesis of diseases. The mechanisms involved in microparticle generation include intracellular calcium mobilisation, cytoskeleton rearrangement, kinase phosphorylation and activation of the nuclear factor-κB. The role of microparticles in blood coagulation and inflammation, including airway inflammation, is well established in in vitro and animal models. The role of microparticles in human pulmonary diseases, both as pathogenic determinants and biomarkers, is being actively investigated. Microparticles of endothelial origin, suggestive of apoptosis, have been demonstrated in the peripheral blood of patients with emphysema, lending support to the hypothesis that endothelial dysfunction and apoptosis are involved in the pathogenesis of the disease and represent a link with cardiovascular comorbidities. Microparticles also have potential roles in patients with asthma, diffuse parenchymal lung disease, thromboembolism, lung cancer and pulmonary arterial hypertension. Microparticles are potential biomarkers and targets for therapeutic interventions in respiratory medicine http://ow.ly/ZTCp6

An observation of prescription behaviors and adherence to guidelines in patients with COPD: real world data from October 2012 to September 2014

Abstract Introduction: GOLD guideline recommendations are currently the “gold standard” for the treatment of COPD patients. Objectives: The objective of this analysis was to evaluate compliance with GOLD guidelines in managing COPD patients’ treatment by general practitioners (GPs) and pulmonologists. Since inhaled corticosteroid (ICS) use is defined as inappropriate in mild and moderate COPD patients, special attention was paid to ICS therapy use in these classes. Methods: The study was based on the Italian GP database IMS Health Longitudinal Patient Database (IMS Health LPD) and on the Patient Analyzer specialist IMS Health database. The observed cohort included all patients with a diagnosis of COPD, aged 40 years or more, with at least one ATC R03 class prescription, visited by GPs and pulmonologists during four timeframes: October 2012 – March 2013 (cohort 1), April 2013 – September 2013 (cohort 2), October 2013 – March 2014 (cohort 3); April 2014 – September 2014 (cohort 4). Patients were classified into disease severity groups following 2008 GOLD guidelines, based on FEV1 value. Results: Cohorts were quite similar in size (about two thousand patients per cohort). Pulmonologists visited more severe patients than GPs. About 50% of GPs’ mild and moderate patients received treatments containing inhaled corticosteroids. Pulmonologists were more adherent to guidelines, with smaller percentages of mild patients treated with therapies containing ICS (ranging from 19.0% to 30.1%). An improvement in adherence was observed during the four time periods, with a decrease in the use of therapies containing ICS in mild and moderate patients. In absolute terms, it emerged that GPs more often prescribe ICS improperly to patients in the mild and moderate severity classes than pulmonologists. Conclusion: Real world data indicate that adherence to GOLD guidelines is only partially met by GPs in their general practice and shows higher prescription appropriateness by pulmonologists.

Acute administration of bronchodilators on exercise tolerance in treated COPD patients.

Exercise intolerance is a major feature in patients with Chronic Obstructive Pulmonary Disease (COPD). Bronchodilators increase endurance time (ET) and reduce dynamic hyperinflation (DH). We evaluated whether a single-dose of salbutamol/ipratropium + flunisolide (BD+ICS), added on top of the regular treatment, may improve ET in COPD patients. In a single-blind randomized crossover pilot trial, nebulised BD+ICS or placebo (PL) was administered 30 min before a constant load cardiopulmonary test, in 22 moderate-to-severe COPD patients (FEV₁: 53.9% pred). ET was the primary outcome measured. BD+ICS did not improve ET or VO₂ peak with respect to PL. BD+ICS increased pre-test FEV₁ and pre-test Inspiratory Capacity but did not modify DH. In a retrospective analysis, patients were divided in Improvers (N=11) and Non-Improvers (N=11) according to the difference in ET between BD+ICS and PL (> 25 s). Improvers had a worst BODE index, a higher static hyperinflation and poorer Vd/Vt ratio at peak of exercise with respect to Non-Improvers. Improvers only had a significant increase from BD+ICS on pre-test FEV₁ and IC. In conclusion, although a single-dose BD+ICS did not improve ET in COPD patients under regular treatment, a subgroup of more severe patients may have some benefit from that.

Sputum inflammatory cells in COPD patients classified according to GOLD 2011 guidelines.

Recently the definition of chronic obstructive pulmonary disease (COPD) severity, stated in 2001 by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and based on forced expiratory volume in 1 s (FEV1) evaluation, has been considered inadequate to recognise all the multifaceted aspects of the disease. To overcome this limitation, 2011 GOLD recommendations suggested a new approach, which stratified COPD patients in four groups of severity (A, B, C, D) according to the level of symptoms (as assessed by either the modified Medical Research Council (mMRC) score or the COPD Assessment Test), the degree of airflow limitation (expressed as percentage of predicted forced expiratory volume in 1 s (FEV1) value) and the number of exacerbations in the previous year [1]. It is still matter of debate if this new classification helps to better understand the disease and improve COPD treatment and prognosis. Studies on the existing database have been published comparing the old with the new GOLD classifications, showing that GOLD 2011 classification adds new details on the phenotyping and on the prognosis of COPD [2–5]. Despite the many post hoc analyses performed on the large databases of the most important recent observational studies (ECLIPSE, CCLS, COPDgene), the demonstration that these different groups of GOLD 2011 classification are different for physiological and biological features is controversial. The A, B, C and D groups of the new GOLD classification are at least partly related to different COPD phenotypes http://ow.ly/Xgr8q