Divergent effects of Nitric oxide on airway epithelial cell activation

Nitric oxide (NO*) is a gaseous mediator synthesized by Nitric oxide sinthases. NO* is involved in the modulation of inflammation, but its role in airway inflammation remains controversial. We investigated the role of NO* in the synthesis of the chemok Nes Interleukin-8 and Monocyte Chemotactic Protein-1, and of Intercellular Adhesion Molecule-1 by human airway epithelial cells. normal human bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used. Neterleukin-8 (IL-8) and Monocyte Chemotactic Protein-1 (MCP-1) secretion and Intercellular Adhesion Molecule-1 (ICAM-1) expression were measured by ELISA. mRNA was assessed by semiquantitative RTI-PCR. Neterleukin-8 secretion was significantly reduced after 24h incubation with the NO* donor, sodium nitroprusside. The effect was dose-dependent. Similar results were obta Ned with S-Nitroso-N-D,L-penicillam Ne and S-Nitroso-L-glutathione. Inhibition of endogenous NO* with the Nitric oxide synthase inhibitor N-Nitro-L-arg N Ne-methyl-esther caused an increase in IL-8 secretion by lypopolisaccharide- and cytok Ne-stimulated BEAS-2B cells. Sodium nitroprusside also caused a reduction in Monocyte Chemotactic Protein-1 secretion by both cell types. In contrast, Intercellular Adhesion Molecule-1 expression was upregulated by sodium NItroprusside. RTI-PCR results indícate that the modulation of protein levels was paralleled by modification in mRNA levels. NO* has divergent effects on the synthesis of different inflammatory mediators in human bronchial epithelial cells

Comparison between Airway Responses to High versus Low Molecular Weight Compounds in Occupational Asthma

Occupational asthma (OA) is a heterogeneous disease, and the characteristics of the sensitizer responsible for OA may induce different clinical, functional, and biological manifestations. We examined the characteristics of 74 patients with OA induced by low molecular weight compounds (LMWC) or by high molecular weight compounds (HMWC) and diagnosed by specific inhalation challenge (SIC). Patients with OA induced by LMWC had a longer occupational exposure before the beginning of symptoms, a lower sputum eosinophilia, and a higher prevalence of late airway response (LAR), in comparison with patients with OA induced by HMWC. Pulmonary function tended to be poorer and atopy tended to be less frequent in LMWC-induced OA than in HMWC-induced OA. These data confirm and extend previous observations showing that the characteristics of the specific sensitizer inducing OA may determine different clinical, functional, and biological features, probably related to the difference pathogenetic mechanisms underlying these different types of OA

Malondialdehyde in Exhaled Breath Condensate as a Marker of Oxidative Stress in Different Pulmonary Diseases

Background. Oxidative stress plays a role in the pathogenesis of many chronic inflammatory lung diseases. Exhaled breath condensate (EBC) collection is a noninvasive method to investigate pulmonary oxidative stress biomarkers such as malondialdehyde (MDA). Subjects and Methods. We measured MDA levels in EBC in a large number of patients (N = 194) with respiratory diseases: asthma (N = 64), bronchiectasis (BE, N = 19), chronic obstructive pulmonary disease (COPD, N = 73), idiopathic pulmonary fibrosis (IPF, N = 38). Fourteen healthy nonsmoking subjects were included as controls. Results. Excluding IPF subjects, MDA levels were significantly higher in all disease groups than in control group. MDA was significantly higher in COPD than asthmatic and BE subjects. Among asthmatics, corticosteroids-treated subjects had lower MDA levels than untreated subjects. COPD subjects showed an inverse correlation between MDA concentrations and FEV1% (rho:  −0.24, P < .05). Conclusions. EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV1 reduction

Effects of systemic glucocorticosteroids on peripheral neutrophil functions in asthmatic subjects: an ex vivo study

In 21 asthmatic subjects, several functions of isolated peripheral neutrophils (chemokinesis and chemotaxis toward 10% E. coli; superoxide anion generation after PMA; leukotriene B4 (LTB4) release from whole blood and isolated neutrophtls, before and after different stimuli) were evaluated during an acute exacerbation of asthma, and after 14 – 54 days of treatment with systemic glucocorticosteroids (GCS). During acute exacerbation, superoxide anion generation was higher in asthmatics than in eleven normal subjects (39.2 ± 14.1 vs. 25.2 ± 7.3 nmol, p < 0.05); there was a significant correlation between FEV1 (% of predicted) and neutrophil chemotaxis (r = −0.52, p = 0.04). After treatment, there was no significant change in all neutrophil functions, except for a decrease in neutrophil chemotaxis in subjects who showed an FEV1 increase > 20% after GCS treatment (from 131 ± 18 to 117 ± 21 μm, p = 0.005). Chemokinesis sicantly decreased in all subjects, and the changes significantly correlated with an arbitrary score of the total administered dose of GCS (r = 0.57, p < 0.05). These data suggest that neutrophil activation plays a minor role in asthma, and that treatment with GCS is not able to modify most functions of peripheral neutrophils in asthmatic subjects; chemotaxis seems to be related only to the severity of the asthma and it could reflect the improvement of the disease

Tiotropium: a new therapeutic option in asthma

Tiotropium: a new therapeutic option in asthma. F. Novelli, F. Costa, M. Latorre, L. Malagrinò, A. Celi, B. Vagaggini, P. Paggiaro. Although bronchial hyperresponsiveness to cholinergic agents is a main feature of asthma, the role of anticholinergic drugs in chronic asthma management has been largely underestimated. Several single-dose studies comparing acute bronchodilation induced by ipratropium bromide with salbutamol have shown that salbutamol is more effective than ipratropium in treating asthma. Recently, tiotropium has been studied in asthma, when added to low-medium dose inhaled corticosteroids (ICS) in unselected moderate asthmatics or in patients with uncontrolled asthma, or with COPD and history of asthma. Later, studies on patients with Arg/Arg beta2-receptor polymorphism demonstrated a similar efficacy of tiotropium in comparison with salmeterol, when both were added to ICS. More recently, pivotal long-term studies have been performed on severe asthmatics uncontrolled under ICS/LABA combination, showing the efficacy of tiotropium in improving lung function and in increasing the time until the first severe asthma exacerbation. These data support the use of tiotropium on top of ICS/LABA combination in moderate-severe asthmatic patients. New studies are going to be published on the use of tiotropium in mild and moderate asthmatics, when added to low or medium dose ICS, in comparison with ICS alone or with ICS/LABA combination. These data might extend the indication for using tiotropium in asthma. Therefore, tiotropium represents now a valid therapeutic option, in addition to the current therapy available for severe asthmatics, and in alternative to LABA in selected asthma populations. The specific asthma phenotype which may be appropriate for tiotropium treatment should still be defined

are italian pulmonologists aware of the guidelines for asthma management and do they know how to apply them

Background. Since 1995 GINA (Global Initiative on Asthma) guidelines for asthma management have been updated annually and published in order to promote better management of asthma in real life situations. The aim of our study was to assess the level of implementation of GINA Guidelines among Italian Pulmonary Specialists (PSs). Methods. A detailed questionnaire was sent to 296 Respiratory Units (RUs) in Italy in order to collect information about personnel involved in the management of asthma patients, availability and use of diagnostic tools, recommended treatment according to the degree of asthma severity, educational activity. Data were analysed by using the SPSS programme. Results. 74 (25%) questionnaires were returned and analysed. Most RUs (70%) do not have a dedicated asthma clinic; however, spirometry is available in more than 90% of RUs, although it is performed in no more than 50% of patients in most RUs. Asthma treatment concurs with GINA recommendations in most RUs. Educational activity is performed by almost all RUs, usually in informal manner, during clinical visits, whereas only few RUs arrange individual educational sessions or "asthma school". Conclusions. GINA guidelines for asthma management are applied by most Italian RUs included in this study in regard to educational activity and, to a lesser extent, to treatment. Surprisingly, many RUs perform spirometry in a relatively small number of patients despite its availability

Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial

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COVID-19 in Severe Asthma Network in Italy (SANI) patients: Clinical features, impact of comorbidities and treatments

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