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Biomedical subjects

G A Rossi

Publications and source records attributed to G A Rossi.

At least 19 recordsLinked to original sources
PubMed2006

High serum levels of tumour necrosis factor-alpha and interleukin-8 in severe asthma: markers of systemic inflammation?

BACKGROUND: 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.

Adult↗
PubMed2005

Cytokine-activated bronchial epithelial cell pro-inflammatory functions are effectively downregulated in vitro by ciclesonide.

Ciclesonide, a new inhaled corticosteroid, is administered as a parent compound and converted in the airway mucosa into the active metabolite, desisobutyryl-(des-)ciclesonide. A study was designed to evaluate the ability of ciclesonide to modulate pro-inflammatory functions of human bronchial epithelial cell (HBEC) primary cultures being converted into des-ciclesonide. HBECs were stimulated with interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha (20 ng/mL) in the presence of ciclesonide and intercellular adhesion molecule (ICAM)-1 expression, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-8 release evaluated respectively by FACS and ELISA. Ciclesonide (3 microM) significantly inhibited ICAM-1 expression by stimulated HBECs, already after 3h and still after 48 h culture (p < 0.01). At all the concentrations tested ciclesonide inhibited ICAM-1 expression (p < 0.05). GM-CSF and IL-8 release by stimulated HBECs was also downregulated by ciclesonide (p < 0.05). All the ciclesonide activities tested appeared to be mainly due to a partial inhibition of the 'IL-4 + TNF-alpha-induced' and little or no involvement of the 'constitutive' cell functions. Des-ciclesonide was detected in 24 h culture HBEC supernatants using high-performance liquid chromatography, while no parental compound ciclesonide was present. These results show at cellular level the fast and prolonged activity of ciclesonide on pro-inflammatory functions of HBECs, a selective target of asthma therapy, involved in the activation of this new inhaled corticosteroid.

Adrenal Cortex Hormones↗
PubMed2005

Incidence of respiratory syncytial virus positivity in young Italian children referred to the emergency departments for lower respiratory tract infection over two consecutive epidemic seasons.

BACKGROUND: The rate and severity of respiratory syncytial virus (RSV) infections within the same nation may vary from one year to another. PATIENTS AND METHODS: The "Osservatorio VRS" study collected epidemiological data on RSV infection among Italian children aged < or = 4 years referred to emergency departments of 14 centers, for suspected lower respiratory tract infections (LRTI) in two consecutive RSV seasons (October 2000-April 2001 and October 2001-April 2002). Medical history and physical examination were recorded and an immunoenzymatic RSV test was performed on nasal secretions. Study variables were collected and evaluated separately, then compared. RESULTS: In all, 272 and 756 children were included in the two seasons, respectively, of which 31.6% and 19.2% were RSV positive (+). Children of the first season had lower gestational and chronological age, higher rates of chronic lung disease (CLD), very low birth weight (< 1,500 g), larger use of corticosteroids or bronchodilators. Main risk factors for RSV infection were a young age (< 1 year) and a low birth weight (< 1,500 g). RSV infection reached its peak in February (first season) or March (second season), with an earlier appearance in the northern and central as compared to the southern regions. Rate of hospitalization and LRTI was higher in RSV+ children, especially if young. CONCLUSION: Although rhythms of the RSV seasons and patient characteristics may vary from one year to another, the severity of RSV disease in nonprophylaxed infants and young children remains high.

Child, Preschool↗
PubMed2005

Early decrease in nasal eosinophil proportion after nasal allergen challenge correlates with baseline bronchial reactivity to methacholine in children sensitized to house dust mites.

BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after allergen exposure of the membranes lining the nose which, in predisposed individuals, may constitute a risk factor for the occurrence of asthma. OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure, 11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr) were studied. METHODS: The following parameters were evaluated: i) pulmonary function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh; iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal allergen challenge (NAC). On NBs, the following markers of inflammation were evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed after NAC (p=0.002) was associated with a significant decrease in the 'intact to degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM, experimental allergen exposure is followed by an early depletion of nasal eosinophils. The correlation between allergen-induced changes in nasal eosinophilia and bronchial reactivity to MCh further supports the concept of a tight link between upper and lower respiratory tract involvement in respiratory allergy.

Allergens↗
PubMed2004

Necessity for surgery in children with gastrooesophageal reflux and supraoesophageal symptoms.

BACKGROUND/PURPOSE: The majority of gastrooesophageal reflux (GER) manifestations in children are supraoesophageal, and "spitting/posseting" is "the tip of the iceberg" because most reflux episodes are not regurgitated. Aim of the present study was to prospectively evaluate the incidence of gastrooesophageal reflux and the incidence of antireflux surgery in patients with difficult-to-treat respiratory symptoms. PATIENTS AND METHODS: Five hundred and ninety-five children with difficult-to-treat respiratory symptoms were prospectively enrolled in a blind study looking for the correlation between clinical presentation (asthma or non-asthma), oesophageal pH monitoring, X-ray barium meal, broncho-alveolar lavage, necessity for surgery, and outcome. RESULTS: pH monitoring was anomalous in 47% of patients with asthma (group A) and in 43% of those who did not have asthma as main symptom (group B). Overall, 48 patients finally underwent anti-reflux surgery (8%) as anti-reflux medical treatment did not ensure stable benefits. No major surgical complications were experienced. Postoperatively, respiratory symptoms improved strongly (Visick 1) in 69% of cases, moderately (Visick 2) in 27%, while clinical worsening (Visick 4) was observed in 4%. CONCLUSIONS: The results of this study stress the importance of symptoms, clinical response to anti-reflux medical treatment and broncho-alveolar lavage compared to classical pH parameters in the decision-making process for patients with difficult-to-treat supraoesophageal symptoms. To date no single tool alone has proved to be diagnostic in these patients. Fundoplication is recommended only when a relationship between supraoesophageal symptoms and gastrooesophageal reflux is strongly suspected.

Asthma↗
PubMed2003

Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol.

Summary beta2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express beta2-adrenoreceptors, were used to test the effects of different concentrations (0.1-100.0 nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-alpha or IL-4 plus TNF-alpha-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-alpha, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-alpha (P<0.05), but not by TNF-alpha alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0 nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2 +/- 9.3% and 32.9 +/- 9.6%, respectively; P>0.05), but higher for RANTES (88.4 +/- 4.4%), as compared to IL-8 (21.8 +/- 7.0%) or GM-CSF (30.1 +/- 6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.

Adult↗
PubMed2003

Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling.

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.

Airway Obstruction↗
PubMed2003

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms.

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.

Adolescent↗
PubMed2003

[Respiratory diseases in infants hospitalized during the 1st 2 years of life for viral lower respiratory tract infections: a one-year follow-up].

BACKGROUND: Epidemiologic data suggest strong links between hospitalisation with bronchiolitis in infancy and subsequent higher risk of developing lower respiratory tract infections (LRTI) and/or hyperreactive airway diseases. The aim of this study was to evaluate in an Italian population the natural history of respiratory diseases in children hospitalised for LRTI when they were <2 years. METHODS: An observational, perspective, longitudinal study was performed through telephone interviews. Nine pediatric tertiary care centres participated to the study evaluating a population of 187 children, hospitalised in the previous year (November 1999-April 2000) for bronchiolitis or pneumonia when they were <2 years of age and participated to a previous study on the prevalence of infant LRTI in Italy (RADAR). RESULTS: Twenty-three (12.3%) children had a gestational age <36 weeks. In the 12 months following the first hospitalisation, an elevated frequency of respiratory symptoms was found. Indeed, 152 (81.3%) children suffered from not-requiring-hospital-admission respiratory infections and 21 (11.2%) were hospitalized again for LRTI: 11.6% had bronchiolitis, 23.5% bronchitis and 35.2% pneumonia. In addition, 1.2% had gs;3 infectious episodes and 21.4% gs;6: 68 (36.4%) showed wheezy bronchitis and 17 (9.1%) were reported to have asthma; 132 children (71%) took antibiotics during the last year, 19.4% >3 times; 111 (59.4%) bronchodilators and 49 (26.2%) oral corticosteroids. One year after the first hospitalisation, 19 subjects (10.2%) were found to be positive to at least one class of allergens by prick test or RAST. CONCLUSIONS: Thus, the demonstration of a high morbidity rate for LRTI, wheezing and asthma in this study group during the first year follow-up after hospital admission further support the need for prophylactic interventions to reduce the morbidity and severity of sequelae of LRTI, in particularly in premature children and/or with additional risk factors.

Anti-Bacterial Agents↗
PubMed2002

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Acute Disease↗
PubMed2002

Recurrent unilateral bacterial pneumonias and interstitial fibrosis associated with pulmonary vein atresia: successful treatment with endovascular stent implantation.

A variety of pulmonary vascular disorders, such as hemangiomatosis, telangectasia, and veno-occlusive disease, may be involved in the pathogenesis of interstitial lung diseases. We describe the case of a girl with recurrent bacterial pneumonia and progressive interstitial fibrosis affecting the right lung. Morphologic evaluation of the lung biopsy showed structural changes of the vessel walls suggesting pulmonary hypertension. The echocardiogram showed the presence of centripetal blood flow in the right pulmonary artery from the periphery of the lung to the heart. A selective right angiography demonstrated the presence of pulmonary venous obstruction at the veno-atrial junction, successfully treated by endovascular stent implantation during cardiac catheterization.

Cardiac Catheterization↗
PubMed2002

In allergic asthma experimental exposure to allergens is associated with depletion of blood eosinophils overexpressing LFA-1.

BACKGROUND: In atopic individuals, exposure to allergens is followed by recruitment of blood eosinophils in the target tissue. We investigated whether allergen inhalation challenge could result in depletion of blood eosinophils overexpressing adhesion molecules involved in eosinophil migration. METHODS: Blood eosinophils were isolated from seven atopic asthmatic patients and seven control subjects and the "at baseline" expression of lymphocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and very late antigen-4 (VLA-4) was assessed by monoclonal antibody staining and flow cytometry analysis. Asthmatic patients underwent allergen challenge and the expression of LFA-1, Mac-1 and VLA-4 by blood eosinophils was again evaluated 3 h and 24 h after allergen challenge. RESULTS: As compared to controls, eosinophils from atopics showed at baseline enhanced LFA-1 expression (P=0.0012), but similar Mac-1 or VLA-4 expression (P > 0.1, each comparison). In atopics, the percentage and absolute number of blood eosinophils were significantly decreased 3 h after allergen challenge (P=0.001 and P=0.022, respectively) but returned to similar values to prechallenge values after an additional 21 h (P > 0.1). Allergen challenge was also followed by a significant decrease in LFA-1 expression by eosinophils, at 3 h (P=0.002) and at 24 h (P=0.038), while no changes in Mac-1 and VLA-4 were observed. A significant correlation between postchallenge decrease in LFA-1 expression and in blood eosinophilia, both expressed as percentage (r=0.88; P < 0.01) or absolute number (r=0.87; P < 0.01) was demonstrated at 3 h (r=0.88; P < 0.01) but not at 24 h (r=0.64, P > 0.05 and r=0.11; P > 0.05, respectively). CONCLUSION: In allergic asthma, an early recruitment of blood eosinophils overexpressing LFA-1 occurs in the first hours after allergen challenge.

Adolescent↗