Diaphragm paralysis after nephrectomy.
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Biomedical subjects
Publications and source records attributed to D Olivieri.
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BACKGROUND: There is increasing in vitro evidence to support a role for vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, as a mediator of fibrosis associated with neovascularization. OBJECTIVE: We tested the hypothesis that VEGF is involved both in increased airway mucosal vascularity and in the subepithelial fibrosis of asthmatic patients. METHODS: Bronchial biopsies were performed in 24 asthmatic patients and eight healthy controls. Immunostaining, using computerized image analysis, was performed using monoclonal antibodies against VEGF(+) cells, type IV collagen, to outline the basement membrane thickness, and tryptase and EG2, to identify mast cells and eosinophils, respectively. RESULTS: The counts of VEGF(+) cells (P<0.05), mast cells and EG2(+) cells (both P<0.01) were higher in asthmatics than in controls. The number of vessels, the vascular area in the lamina propria, and the basement membrane thickness were significantly higher in asthmatics than in healthy volunteers (P<0.01). Moreover, in asthmatic patients, the number of VEGF(+) cells was significantly related to the number of vessels (P<0.01), to mast cells (P<0.01) and to basement membrane thickness (P<0.01). A colocalization study also revealed that mast cells were a relevant cellular source of VEGF. High doses of inhaled fluticasone propionate significantly reduced VEGF(+) cells (P<0.05), vessel number (P<0.05), vascular area (P<0.05) and basement membrane thickness (P<0.05) in a subgroup of asthmatic patients. CONCLUSIONS: This study shows that VEGF, in addition to being involved in the vascular component of airway remodelling, may play a role in the thickening of the basement membrane in asthma.
This report describes the quality control programme used within the Bronchitis Randomized on N-acetylcysteine (NAC) Cost-Utility Study, a trial designed to assess the decline in lung function, exacerbation rate, health status, and cost-effectiveness with NAC or a placebo in 523 patients with chronic obstructive pulmonary disease over a 3-yr period. Spirometry was scored from 0 (worst quality) to 6 (best quality). The mean score of 314 spirometries from 243 patients evaluated during the trial was 5.63+/-0.83. Linear regression analysis of the scores of 47 participating centres plotted against the time at which spirometries were performed yielded an intercept of 5.7+/-0.5 and a slope of -0.0001+/-0.001, which suggests that the initial high quality was maintained over time. Retrospective examination of a further 345 postbronchodilator spirometries from 208 patients with a forced expiratory volume at one second exceeding the mean individual value recorded over the study in excess of 20% revealed a slightly lower quality of the start-of-test manoeuvre compared with the 314 spirometries. In conclusion, these findings would suggest that the quality control programme is likely to have helped achieve and maintain long-term spirometry performance in the Bronchitis Randomized on N-acetylcysteine (NAC) Cost-Utility Study trial. Special care should be paid to the spirometries whose forced expiratory volume in one second values exceed the mean value.
Cough flows and pressures were measured during cough augmentation in healthy subjects and patients with bulbar and nonbulbar amyotrophic lateral sclerosis. Manual assistance increased flow 11% in bulbar (p < 0.01) and 13% in nonbulbar (p < 0.001) patients. Mechanical insufflation-exsufflation increased flow 17% in healthy subjects (p < 0.05), 26% (p < 0.001) in bulbar, and 28% (p < 0.001) in nonbulbar patients. The greatest improvements were in patients with the weakest coughs. Patient group and level of weakness influenced the effect of augmentation.
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We compare the efficacy including spirometry, peak expiratory flow (PEFR) and quality of life and safety of an 8-week treatment with inhaled oxitropium, theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease (COPD). We conducted a multicentre, double-blind, double-dummy randomized, parallel-group study at 29 Italian outpatients clinics. A group of 236 patients with mild-to-severe COPD (baseline FEV1 < or = 70% of predicted value) were recruited. Treatments were as follows: Inhaled oxitropium bromide 200 microg (N=75), sustained-release oral theophylline 300 mg (N=81) or their combination (N=80), taken twice daily. Spirometry (FEV1 and FVC) was evaluated every 4 weeks, and morning and evening PEFR (before and 2-4 h after drug intake) was measured daily. Symptoms, cough and dysponea, were recorded daily. Health status was evaluated at baseline and week 8 using the disease specific St George' Respiratory Questionnaire (SGRQ). Any adverse event occurring during the treatment period was recorded on a diary card. FEV1 and FVC improved in all the groups at 4 and 8 weeks, but the difference between treatment groups did not reach statistically significant levels. Differences between groups in pre-dosing morning and evening PEFR were not significant. Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs. However, differences between groups was significant only for evening values (P=0.008). The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed. SGRQ total scores decreased in all treatment groups after 8 weeks, particularly in the oxitropium and combination groups. Clinically significant change (> or = 4 units) was only observed in patients treated with oxitropium bromide whether with or without theophylline. Adverse events related to treatments were higher in the group treated with theophylline alone (P < 0.02). We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1, PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs. Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR. Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophylline alone.
BACKGROUND: Eosinophils and T lymphocytes represent constant features in the airways of subjects with exacerbated chronic bronchitis. Eotaxin is the most potent and selective eosinophil chemoattractant which can also attracts lymphocytes. The aim of the study was to evaluate the expression of eotaxin and its receptor, CCR3, in bronchial airways during exacerbation of chronic bronchitis. METHODS: By immunohistochemistry we studied eotaxin and CCR3 expression in the lamina propria of 14 subjects with acute exacerbation of chronic bronchitis. 20 asthmatics, and 8 healthy subjects. We determined the cell types expressing the CCR3 receptor by colocalization experiments. We finally studied the relationship between eotaxin and CCR3 and eosinophils and T lymphocytes. RESULTS: The number of eotaxin+ and CCR3+ cells was significantly higher in exacerbated chronic bronchitis (P<0.003 and P<0.002) and asthma (P<0.002 and P<0.0001) when compared to healthy subjects. CCR3 was mainly expressed by eosinophils and to a lesser extent by CD4+ and CD8+ lymphocytes. In exacerbated chronic bronchitis the number of CCR3+ cells was strongly correlated to the number of eosinophils (P<0.0002. r=0.85) and to the number of CD4+ lymphocytes (P<0.05, r=0.57). CONCLUSION: Our study suggests that eotaxin and CCR3 are up-regulated and could be involved in the eosinophil and CD4+ lymphocyte recruitment into the airways which occur during acute exacerbations of chronic bronchitis.
Bronchial asthma is one of the most common chronic diseases in the world and can affect people of all ages. In the last few years there has been a considerable improvement in the etiopathogenetic knowledge of the disease and extremely effective anti-asthmatic drugs are available. However, asthma-related morbidity and mortality are increased, especially in Western countries. In an attempt to reverse this negative trend, for a number of years national and international guidelines on asthma have been published all over the world. These guidelines have the aim of improving asthma diagnosis and treatment and of conveying a fundamental educational message both to health workers and to patients and their families. From the data in the literature it can be clearly seen that only through the application of valid educational programs is it possible for asthmatics to improve their knowledge of the disease and to understand how they can look after themselves by a careful evaluation of their own symptoms and respiratory function. They should also be aware of the drugs available for the treatment of both acute asthmatic crises and chronic asthma, but especially of the fact that this chronic inflammatory affection can be fully treated. In particular, an educational program organized with groups of maximum 10-12 people attending 2 lessons and with helpful training tools, can increase significantly asthma knowledge, treatment compliance and patient self-management. The aim of this review is to highlight the importance of educational programs and those obscure areas which slow down their large scale application and universal acceptance.
Cigarette smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD). However, only 10-15% of smokers develop the disease and early changes within the airways are poorly defined. We aimed to compare cell profiles in induced sputum (IS) from asymptomatic smokers to that from healthy subjects, and to ascertain whether or not inflammatory cells in IS are related to lung function and smoking habit. We recruited 34 heavy, non-allergic asymptomatic smokers with normal lung function and 15 healthy volunteers, who performed lung function tests and IS by hypertonic saline (3%) solution. In smokers, significantcorrelation between pack-years and FEF25-75 (rs = -0.43, P < 0.02) was found. In IS, smokers had higher counts of macrophages (P < 0.01) and eosinophils (P < 0.02), when compared to those of healthy subjects. Additionally, eosinophils were found in IS of 14 out of 34 smokers, with eosinophils had a higher pack-years (31 +/- 25 vs. 13 +/- 10, P = 0.02) and lower FEF 25-75% value (78% +/- 34 vs. 100% +/- 23. P < 0.04). when compared to smokers without eosinophils. Additionally, on the basis of regression equations by stepwise multiple regression analysis, eosinophils were predicted by pack-years (r2 = 0.41). Our results showed that asymptomatic smokers have evidence of inflammatory cells in IS samples. In addition, we found thatthe degree of eosinophilic inflammation is related to early changes of lung function and can be predicted by smoking habit.
The six-minute walking test (6MWT) has been widely utilized to evaluate global exercise capacity in patients with cystic fibrosis. The aim of this study was to assess the exercise capacity by 6MWT, measuring four outcome measures: walk distance, oxygensaturation and pulse rate during the walk, and breathlessness perception after the walk, in a group of cystic fibrosis adults with mild to moderate lung disease, and in healthy volunteers, as the control group. Moreover, the study examined the relationship between 6MWT outcome measures and pulmonary function in patients. Twenty-five adults (15 females, age range 18-39 years) with cystic fibrosis and 22 healthy volunteers (14 females, age range 20-45 years) performed a 6MWT following a standard protocol. Walk distance, oxygen saturation (SpO2) and pulse rate at rest and during walk, and breathlessness perception after walk assessed by visual analogue scale (VAS) were measured. Cystic fibrosis patients did notdiffer from healthy volunteers in walk distance (626 +/- 49 m vs. 652 +/- 46 m) and pulse rate. Patients significantly differed from healthy volunteers in SPO2 during the walk (mean SpO2) (P < 0.0001) and VAS (P < 0.0001). In patients, SPO2 during the walk significantly correlated with forced expiratory volume in 1 sec (FEV1) (P < 0.0001), residual volume (RV) (P < 0.001), resting SPO2 (base SpO2) (P < 0.001), and inspiratory capacity (IC) (P < 0.01). In addition, VAS significantly correlated with resting SPO2 (P < 0.01) and IC (P < 0.01). On the basis of regression equations by stepwise multiple regression analysis, SpO2 during walk was predicted by FEV1 (r2 = 0.60) and VAS by IC (r2 = 0.31), whereas walk distance was not reliably predicted by any assessed variables. This study showed that cystic fibrosis adults with mild to moderate lung disease covered a normal walk distance with unimpaired cardiac adaptation, but experienced a significant fall in oxygen saturation and an increased breathlessness perception during exercise. Resting pulmonary function was related to oxygen saturation and breathlessness perception during walk, but contributed significantly only tothe prediction of oxygen saturation. We suggest that 6MWT could be valuable for identifying patients who might experience oxygen desaturation and dyspnoea during demanding daily activities.
Chronic obstructive pulmonary disease (COPD) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second (FEV1). At present, no treatment except quitting smoking appears to affect the progression of the disease. Oxidative stress has been implicated in its pathogenesis. The Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) is a phase III, randomized, double-blind, placebo-controlled, parallel group, multicentre study designed to assess the effectiveness of the antioxidant agent N-acetylcysteine (NAC) in altering the decline in FEV1, exacerbation rate, and quality of life in patients with moderate to severe COPD. In addition, cost-utility of the treatment will be estimated. Patients will be followed for 3 yrs and evaluated every 3 months. The necessary sample size to demonstrate an effect on the decline in FEV1 of 20 mL x yr(-1) was estimated to be 478 patients. Five hundred and twenty-three patients with moderate to severe COPD were recruited from 10 European countries from June 1, 1997-December 31, 1999. They were 63+/-8 yrs old and consisted of 243 (46%) current smokers and 280 (54%) exsmokers. Patients had on the average 4.9+/-1.6 exacerbations during the last 2 yrs. Postbronchodilator FEVI averaged 57+/-9% and the reversibility after 400 microg of Salbutamol averaged 4+/-4% predicted. The final results of the trial will be available in about 2 yrs. The study will provide objective data on the effects of N-acetylcysteine on outcome variables in chronic obstructive pulmonary disease.
Expiratory muscle strength is a determinant of cough function. Mouth pressures during a maximal static expiratory effort (PE,max) are dependent on patient motivation and technique and low values are therefore difficult to interpret. This study hypothesized that a short, sharp and maximal expiration through a narrow aperture, a "whistle", might provide a complementary test of expiratory muscle strength. To obtain a maximal whistle, subjects (27 healthy volunteers and 10 patients with amyotrophic lateral sclerosis) were asked to perform a short, sharp blow as hard as possible, from total lung capacity, through a reversed paediatric inhaler whistle, connected to a flange-type mouthpiece. In both healthy subjects and patients, whistle mouth pressure (Pmo,W) was closely related to the pressure measured in the oesophagus and stomach during the same manoeuvre. In healthy subjects, Pmo,W and PE,max correlated with wide limits of agreement, although Pmo,W values were significantly higher than PE,max (131+/-31 cmH2O versus 101+/-27 cmH2O, p<0.0001). In patients, it was also found that Pmo,w and PE,max values were strongly related (r=0.937, p<0.0001). In healthy subjects, the intraclass correlation coefficient and the variation coefficient for Pmo,W repeated measurements were respectively 0.88 and 7.0%. However Pmo,W and PE,max were always smaller than the gastric pressure generated by a maximal cough. It is concluded that mouth whistle pressure, a noninvasive, reproducible and simple test, provides a reliable measure of expiratory muscle strength in healthy subjects that is acceptable to patients and can be used in a complementary fashion to maximal static expiratory effort.
BACKGROUND AND AIM OF THE WORK: In patients with interstitial lung disease (ILD), the six-minute walk test (6MWT) has been rarely used, and up till now, the relationship between outcome measures of the test and baseline lung function has not yet been examined. Therefore, we assessed walk distance, oxygen desaturation, and breathlessness perception during 6MWT, and their relationships to baseline lung function in patients with ILD. METHODS: Forty ILD patients with history of breathlessness during physical exertion performed a 6MWT following a standard protocol. Breathlessness perception during walk was assessed by visual analogue scale (VAS, in mm). RESULTS: The mean walk distance was 487 meters (range 271-689). Mean baseline oxygen saturation (Base SpO2, %) was 94% and was reduced during walk, either as mean oxygen saturation (Mean SpO2, 89%, p < 0.001) or as mean fall in oxygen saturation during walk (Fall SpO2, 5%). Furthermore, VAS significantly increased after walk (5 mm to 44 mm, p < 0.001). A close relationship of TLco and TLC to walk distance and Fall SpO2 was found (r = 0.45 and 0.42 and r = -0.75 and -0.64, respectively; p < 0.001, each). On the basis of regression equations by stepwise multiple regression analysis, walk distance was predicted by age and FVC (r2 = 0.50), Mean SpO2 by TLco and Base SpO2 (r2 = 0.80), and Fall SpO2 only by TLco (r2 = 0.57). Breathlessness perception was not reliably predicted by any assessed variables. CONCLUSIONS: We confirmed that 6MWT provides a global evaluation of sub-maximal exercise capacity in ILD patients. We also found that walk distance and oxygen desaturation, but not breathlessness perception during walk, are strictly related to baseline lung function.
BACKGROUND: Lymphocyte function associate-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late activation antigen-4 (VLA-4) are involved in the infiltration of leukocytes into the tissues. Experimental models of allergic inflammation suggest that VLA-4 could determine the selective recruitment of eosinophils into the inflamed airways. OBJECTIVE: Our purpose was to evaluate the involvement of integrins in eosinophil recruitment in asthma. METHODS: We evaluated by immunocytochemistry the expression of VLA-4, LFA-1, and Mac-1 and their relationship with inflammatory cells and severity of disease in the induced sputum of 20 mild to moderate atopic asthmatic subjects and in 8 healthy subjects. RESULTS: The number of VLA-4+ cells is increased in asthmatic patients and VLA-4 is mainly localized on eosinophils. Furthermore, VLA-4+ cells are significantly related to eosinophils. In contrast, LFA-1 and Mac-1 cellular expressions do not differ between asthmatic and control subjects and are not related to any specific cell type. Eosinophils and VLA-4+ cells are significantly higher in moderately compared with mildly asthmatic patients (P <.01, P <.05) and with healthy control subjects (P <.0005, P <.001). Eosinophils and VLA-4+ cells are also higher in mildly asthmatic patients compared with control subjects (P <.001, P <.005). CONCLUSION: This is the first report demonstrating, by a noninvasive method in humans, that VLA-4+ cells are increased and correlate with the eosinophils in the induced sputum of atopic patients with mild to moderate asthma and that VLA-4 expression is related to the severity of disease.
BACKGROUND: Eosinophilic inflammation is known to play an important role in the pathogenesis of allergic diseases. Apoptosis, a form of programmed cell death, is characterized by morphologic cell changes and leads to recognition and ingestion by macrophages. Apoptosis could be an important mechanism controlling the resolution of tissue eosinophilia. OBJECTIVE: This study was designed to investigate the presence of apoptotic eosinophils in induced sputum of patients with seasonal allergic rhinitis (SAR), when examined during natural pollen exposure and of patients with perennial asthma of different degrees of severity. METHODS: We recruited 11 patients with SAR to grass pollens, 26 patients with asymptomatic asthma (AA), and 18 patients with symptomatic asthma (SA). The severity of asthma was assessed by clinical scoring. Sputum was induced following a standard method and differential cell count was estimated. Eosinophils showing cell shrinkage and nuclear coalescence were classified as apoptotic. The number of apoptotic eosinophils was expressed as the percentage of total cells in sputum and as the proportion of apoptotic eosinophils relative to normal bilobed eosinophils ("apoptotic ratio"). RESULTS: We found the number of eosinophils in the SA group was significantly greater than that in the SAR and the AA groups (P < .001 and P < .0001 respectively). The number of apoptotic eosinophils in the AA group was significantly lower than that in the SAR group (P < .001) and in the SA group (P < .0001). The apoptotic ratio for eosinophils in the SAR group was significantly greater than in the AA group (P < .05) and in the SA group (P < .05). There was no difference in the apoptotic ratio between the AA and SA groups. CONCLUSIONS: This study confirms that apoptotic eosinophils are detectable in induced sputum of allergic patients. Further, the results of our study suggest that apoptosis could be an important mechanism in the control of acute eosinophilic inflammation in patients with SAR exposed to the sensitizing antigens. It appears that the apoptotic mechanism could be less effective in controlling tissue eosinophilia in asthmatic patients with chronic eosinophilic inflammation.
BACKGROUND: Airway dendritic cells are essential for stimulating naive T cells in response to inhaled antigen and for the development of allergic sensitization. IL-4 in vitro can distinguish dendritic cell lines from peripheral blood mononuclear cells. Our study had the following aims: 1) to compare the distribution of CD1a+ dendritic cells and IL-4+ cells, in the bronchial mucosa of asthmatics and controls 2) to determine the relationship between the numbers of CD1a+ dendritic cells and IL-4+ cells in the bronchial mucosa of asthmatics 3) to determine whether CD1a+ cells express the IL-4 receptor. METHODS: Twenty atopic asthmatic and eight normal subjects were studied. In each subject, bronchoscopy with bronchial biopsies was performed. CD1a, IL-4, and IL-4 receptor expressions were evaluated by immunohistochemistry. RESULTS: The number of CD1a+ and IL-4+ cells was significantly higher in asthmatics than controls. The number of CD1a+ cells was positively correlated to the number of IL-4 + cells. Bronchial biopsy serial section studies showed that CD1a+ cells express the receptor for IL-4. CONCLUSIONS: These results suggest that an increased amount of IL-4 may play a physiopathologic role in maintaining the dendritic cell pool in vivo. Therefore, because of possible IL-4 activity on antigen-presenting cells in T-cell immune responses to allergens, an important new role of IL-4 in asthma inflammation can be envisaged.
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Induced sputum by inhalation of hypertonic saline solution is a noninvasive technique used to collect cellular and soluble material from lung airways. During the past decade, this method has been widely used to assess airway inflammation in asthma and chronic obstructive pulmonary disease, since it produces reliable results and compares favorably to other invasive techniques, such as biopsy and bronchoalveolar lavage (BAL). Induced sputum has been recently used to study interstitial lung disease (ILD), more specifically pneumoconiosis, sarcoidosis, and nongranulomatous ILD. Moreover, results from induced sputum supplied information comparable to BAL findings for occupational lung disease and were able to distinguish sarcoidosis patients from healthy subjects and from patients with nongranulomatous ILD. Although induced sputum had previously provided promising results in assessing patients with ILD, its diagnostic role has not yet been well defined. Further studies of the evaluation by induced sputum of grading of severity, follow-up of disease, and effects of treatment are needed. Additionally, to date no specific studies have been undertaken to evaluate the safety and functional effects of sputum induction on patients with ILD. In conclusion, we think that induced sputum can be used as a complementary tool to BAL both in research and in clinical monitoring of patients with ILD.