1,720,993 research outputs found
Perception of Bronchodilation Assessed by Visual Analog Scale in Asthmatics: A Real-life Study
No full textLong term adjustment of stable asthma treatment with fractional exhaled nitric oxide and sputum eosinophils
No full textCurrent approaches to control asthma do not involve direct assessment of airway inflammation. The aim of this study is to assess whether the therapeutic adjustments of steroid treatment according to a stepwise algorithm based on sputum Eosinophils (sEos) and fractioned exhaled Nitric Oxide (FeNO) were effective in maintaining the stability of a group of stable asthmatic patients during a twelve-month follow-up. Fourteen asthmatic patients, treated for asthma according to a previously published protocol, were enrolled in the study. The patients underwent clinical evaluation, pulmonary function tests, measuring of airway hyperresponsiveness to methacholine, and determination of FeNO and sEos at visit 1. These procedures were repeated after 6 and 12 months (Visits 2 and 3, respectively). Symptoms score gradually improved during the study (p=0.008), no changes were observed in the frequency of clinical asthma exacerbations or in airway hyperresponsiveness to methacholine. At the end of the study both sEos and FeNO were significantly improved (p=0.011 and p=0.003, respectively) and at visit 3 the median steroid dose was reduced (p=0.039) in accordance with the improving of symptoms score, FeNO and sEos values. A direct relationship was observed between the difference of FeNO values and the difference of sEos registered between visits 1 and 2 (r2=609, p<0.001) and between visits 2 and 3 (r2=646, p<0.001). In conclusion, long-term titration of asthma inhaled steroid treatment based on sEos and FeNO values was able to provide long-term clinical stability and improvement to the asthmatic patients studied, without significant increases in the steroid dose
Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overview
No full textIn the last decade, the analysis of bronchial biopsies and lung parenchyma obtained from chronic obstructive pulmonary disease (COPD) patients compared with those from smokers with normal lung function and non-smokers has provided new insights on the role of the different inflammatory and structural cells, their signalling pathways and mediators, contributing to a better knowledge of the pathogenesis of COPD. This review summarizes and discusses the lung pathology of COPD patients with emphasis on inflammatory cell phenotypes that predominate in different clinical conditions. In bronchial biopsies, a cascade of events takes place during progression from mild-to-severe disease. T lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lung of healthy smokers and patients with mild COPD, while total and activated neutrophils predominate in severe COPD. The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-kappaB), STAT-4 and IFN-gamma proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease. In contrast, activated neutrophils (MPO+ cells) and increased nitrotyrosine immunoreactivity develops in severe COPD. In bronchial biopsies obtained during COPD exacerbations, some studies have shown an increased T cell and granulocyte infiltration. Regular treatment with high doses of inhaled glucocorticoids does not significantly change the number of inflammatory cells in bronchial biopsies from patients with moderate COPD. The profile in lung parenchyma is similar to bronchial biopsies. 'Healthy' smokers and mild/moderate diseased patients show increased T lymphocyte infiltration in the peripheral airways. Pulmonary emphysema is associated with a general increase of inflammatory cells in the alveolar septa. The molecular mechanisms driving the lymphocyte and neutrophilic prevalence in mild and severe disease, respectively, needs to be extensively studied. Up-regulation of pro-inflammatory transcription factors NF-kappaB and STAT-4 in mild, activated epithelial and endothelial cells in the more severe disease may contribute to this differential prevalence of infiltrating cells
Increased nitrotyrosine immunoreactivity in bronchial biopsies from patients with severe COPD
No full textPlatelet activation and cardiovascular co-morbidities in patients with chronic obstructive pulmonary disease.
No full textObjective: Platelet activation in COPD patients is associated with an increased risk of cardiovascular events. Aim of the study: to assess the mean platelet volume (MPV), as an index of platelet activation, in patients with COPD both when stable or during exacerbation.
Research design and methods: 478 patients with COPD (75 with exacerbation) and 72 age-matched healthy controls were enrolled. Medical history, co-morbidities, medications, pulmonary function tests, MPV and blood cell count, erythrocyte sedimentation rate (ERS) and C reactive protein (CRP) were recorded.
Results: MPV was higher in COPD patients than in controls (8.7 ± 1.1 fL and 8.4 ± 0.8 fL respectively, p = 0.025) and increased across the severity of the diseases as assessed by the GOLD post bronchodilator FEV1 categorized I to IV (p>0.05). MPV was higher in COPD patients during acute exacerbation as compared with stable condition (8.7 ± 1.0 fL and 8.9 ± 1.0 fL, p = 0.021).
MPV ≥ 10.5 fL correlated with the presence of at least one co-existing cardiovascular disease (p = 0.008) . No correlation was observed between MPV and CRP or ERS in patients or in controls. An inverse significant correlation was found between platelets count and MPV in COPD patients.
Conclusions: Elevated MPV is associated with lower platelet count and with cardiovascular co-morbidity in COPD patients. MPV value is higher in more severe COPD and during acute exacerbation. Present findings warrant future studies to confirm a possible clinically relevant role for platelet activation and cardiovascular risk in the population of COPD
Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease
Full text linkBackground: Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons. Objective: To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners. Methods: In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, − 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, − 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation “in vitro”. Results: The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm2 correlated positively with scored total IgA in lamina propria of all patients. “In vitro” stimulation of 16HBE cells with LPS (10 μg/ml) and IL-8 (10 ng/ml) induced a significant increase while H2O2 (100 μM) significantly decreased pIgR epithelial expression. Conclusion: These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognostic stratification and treatment of COPD
High serum levels of tumour necrosis factor-alpha and interleukin-8 in severe asthma: markers of systemic inflammation?
No full textBackground Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. Objective To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. Methods We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)((%pred)): 89 +/- 3] and 14 severe asthmatics [FEV1(%pred): 49 +/- 2]. Results IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P < 0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P < 0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P < 0.05), but inferior than in mild-moderate asthmatics (P < 0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. Conclusion sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma
Increased neutrophil (Neu) adhesion in bronchial biopsies from patients with severe COPD
No full textIncreased Neu presence has been reported in COPD, particularly in sputum and BAL from mild/moderate patients and in bronchial biopsies from severe diseased patients. CXC and CC chemokines and their receptors are thought to play a role in Neu chemoattraction and activation. Furthermore, increased tissutal neutrophilia may be related also to increased adhesion to submucosal collagens in the submucosa.
We investigated the expression of CXCL7, CCL5, CD44 and CD11b in bronchial biopsies from subjects with severe COPD (n=13), mild/moderate COPD (n=12), and from control smokers (Ctr-S) (n=12) and control non smokers (Ctr-NS) (n=11). Immunopositivity was quantified as number of cells+/mm2 in the submucosa.
Severe COPD and mild/moderate COPD had higher CXCL7+ in the submucosa (38(0–83) and 74(0–129)) compared to Ctr-NS (14(0–32)) but did not differ from Ctr-S (24(0–136). Severe COPD also had higher CCL5+ in the submucosa (281(75–839) compared to Ctr-NS (77(26–203)). No differences were observed in the total cell count of CD44 and CD11b receptors in the four groups examined. Double staining of Neu coexpressing CD44 and CD11b showed increased percentages of CD44+Neu+ and CD11b+Neu+ cells in severe COPD (48(39–54) and 47(38–52)) compared to Ctr-S (13(9–20) and 17(10–21)). These data show that increased presence of chemotactic factors for Neu and increased Neu adhesiveness may play a role in sustaining neutrophilia in patients with severe COPD
INCREASED NITROTYROSINE PLASMA LEVELS IN RELATION TO SYSTEMIC MARKERS OF INFLAMMATION AND MYELOPEROXIDASE IN CHRONIC HEART FAILURE.
No full textThe presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure
(CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients.
ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H2O2, total NO, nitrite (NO2
−), myeloperoxidase
(MPO), Tumor Necrosis Factor-alpha (TNFα) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II,
23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (pb0.05),
NYHA I (pb0.03) and controls (pb0.02), whereas NO2
− and total NO were higher in NYHA III compared to I (pb0.05 and pb0.04,
respectively) and controls (pb0.004 and 0.002) and in NYHA II compared to controls (pb0.04 and pb0.009). NT levels correlated
significantly with MPO (r=0.37, pb0.003), TNFα (r=0.32, pb0.01) and proBNP (r=0.32, pb0.01). These data demonstrate an increased
NT plasma level in patients with moderate/severe CHF which is associated to increased levels of markers of systemic inflammation
Epithelial overexpression of Interleukin-8 in bronchial biopsies from patients with COPD
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