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Biomedical subjects

N G Papadopoulos

Publications and source records attributed to N G Papadopoulos.

At least 19 recordsLinked to original sources

Impact of influenza infection in healthy children examined as outpatients and their families.

Decisions regarding the introduction of influenza immunization in healthy children require an accurate evaluation of influenza disease burden not only in the inpatient but also in the outpatient setting. We prospectively examined the impact of virologically confirmed influenza in 1462 outpatient children (> or = 6 months to < 14 years) and their families, during two consecutive influenza seasons. Influenza was documented in 573/1462 (39%) outpatients with febrile respiratory illness and accounted for 13.5% of all outpatient visits during the 14 weeks of each season. Acute otitis media (AOM) was the most common complication (18.5%) and about 40% of influenza positive patients received antibiotics. AOM and antibiotic use were more common in children younger than 5 years of age who accounted for 58% of all patients. For each child sick with influenza a mean of 1.34 workdays were lost by the parents. Family members of influenza positive children were more likely to develop a secondary respiratory illness and to require medical visits and antibiotic prescriptions. Influenza is associated with a heavy morbidity burden in the community that may be reduced considerably with the implementation of immunization in children younger than 5 years of age.

Adolescent↗

Synergistic effects of fluticasone propionate and salmeterol on inhibiting rhinovirus-induced epithelial production of remodelling-associated growth factors.

BACKGROUND: Rhinoviruses (RV), the major trigger of acute asthma exacerbations, are able to infect bronchial epithelium and induce production of pro-inflammatory, but also angiogenic and pro-fibrotic mediators. Fluticasone propionate (FP) and salmeterol (S) are clinically effective and act synergistically in controlling persistent asthma; however, their effect on virus-associated asthma is less clear. AIM: The aim of this study was to assess the individual and combined effects of FP and S on RV-induced epithelial production of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). METHODS: Bronchial epithelial cells (BEAS-2B) were exposed in vitro to RV and were subsequently treated with FP and S, at physiologically relevant concentrations, alone or in combination. VEGF and FGF-2 were measured in the supernatants of these cultures using ELISA. RESULTS: FP was able to reduce RV-induced VEGF production in a dose-dependent manner. S also induced a smaller reduction; addition of both factors inhibited VEGF synergistically. FGF-2 production was not inhibited by either FP or S alone, but was significantly reduced when both substances were present in the culture. CONCLUSION: This study demonstrates that FP and S may synergistically inhibit the production of angiogenic and/or pro-fibrotic factors that are induced after RV infection of BEAS-2B and are implicated in airway remodelling, suggesting that this combination may represent an important therapeutic option on virus-induced asthma.

Albuterol↗

IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion.

BACKGROUND AND AIMS: Epidemiological evidence examining the role of atopy and/or allergy in the pathogenesis of otitis media with effusion (OME) is inconclusive. The aim of this study was to assess any increased risk for OME attributable to allergy-related factors, in a well-characterized population using a case-control design and multivariate analysis. SUBJECTS AND METHODS: Eighty-eight 1-7-year-old children with OME, diagnosed by clinical and tympanometric evaluation and 80 matched controls were enrolled. A standardized questionnaire was completed, in order to assess factors related to OME and allergy-related symptoms and diagnoses using strict clinical definitions. Specific IgE was measured by skin-prick tests and/or CAP-FEIA. RESULTS: The patient and control groups were well matched. Factors conferring increased risk for OME in the univariate analysis included IgE sensitization, dyspnea, wheezing, asthma, paroxysmal sneezing, rhinitis, eczema, 'any allergic disease,' family history of otitis media, and family history of allergy. After multivariate analysis IgE sensitization, wheezing, nasal obstruction, family history of otitis, and child-care attendance remained as independent risk factors for development of OME. CONCLUSION: IgE sensitization and respiratory allergy symptoms are independent risk factors for the development of OME, suggesting that both immunological and mechanical pathways may contribute to the development of the disease. Otitis heritability provides additional risk, as well as frequent exposure to viral upper respiratory tract infections in children attending daycare. Treatment and/or prevention of OME using anti-allergic medications should be further examined.

Age Distribution↗

Human rhinoviruses in otitis media with effusion.

Frequent viral upper respiratory tract infections (URTI) are considered to be risk factors for otitis media with effusion (OME). Atopy has also been associated with both OME and viral infections. The aim of this study was to evaluate the presence of viruses in middle ear effusions (MEE) in children 2-7 yr old with OME, and to determine risk factors for virus detection in the MEE. MEE samples, collected at the time of myringotomy from 37 children with OME were assessed. Physical examination, skin prick tests and a standardized questionnaire on OME and allergy were also performed. Viral RNA was detected by the use of reverse transcription PCR (RT-PCR). Fifteen samples (40.5%) were positive for rhinovirus (RV). One enterovirus and no other respiratory viruses were detected. Two out of five (40%), 3/7 (43%) and 10/25 (40%) were positive for RV in acute, subacute and chronic cases, respectively. Children with frequent episodes of OM, with early onset of OM (<2 yr old), and a positive family history of allergy had a statistically increased risk of RV detection. The two groups were comparable with respect to all other parameters examined. RV is the predominant virus recovered by RT-PCR in the middle ear cavity of children with asymptomatic OME, especially those with a history of longstanding OME or repeated episodes, or children with a family history of allergy. Interactions between allergy and RV infections are likely to predispose to middle ear disease.

Child↗

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗

Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections.

BACKGROUND: Community-acquired pneumonia (CAP) in young children is most commonly associated with viral infections; however, the role of viruses in CAP of school-age children is still inconclusive. METHODS: Seventy-five school-age children hospitalized with CAP were prospectively evaluated for the presence of viral and bacterial pathogens. Nasopharyngeal washes were examined by polymerase chain reaction for viruses and atypical bacteria. Antibody assays to detect bacterial pathogens in acute-phase and convalescent-phase serum samples were also performed. RESULTS: A viral infection was identified in 65% of cases. Rhinovirus RNA was detected in 45% of patients; infection with another virus occurred in 31%. The most common bacterial pathogen was Mycoplasma pneumoniae, which was diagnosed in 35% of cases. Chlamydia pneumoniae DNA was not detected in any patient; results of serological tests were positive in only 2 patients (3%). Mixed infections were documented in 35% of patients, and the majority were a viral-bacterial combination. CONCLUSIONS: The high prevalence of viral and mixed viral-bacterial infections supports the notion that the presence of a virus, acting either as a direct or an indirect pathogen, may be the rule rather than the exception in the development of CAP in school-age children requiring hospitalization.

Adolescent↗

Expression of costimulatory molecules in peripheral blood mononuclear cells of atopic asthmatic children during virus-induced asthma exacerbations.

BACKGROUND: Respiratory viruses are the most frequent triggers of acute asthma exacerbations. Herein we investigate costimulatory molecule expression on peripheral blood mononuclear cells (PBMC) during such exacerbations. METHODS: Eleven children with atopic asthma were followed prospectively and respiratory symptoms were recorded on diary cards. A blood sample and nasopharyngeal wash (NPW) were obtained at baseline and subsequently during an exacerbation. PBMC were immunophenotyped using flow cytometry. NPW samples were examined for the presence of respiratory viruses by RT-PCR. RESULTS: A virus was detected in 73% of exacerbations and none at baseline. A drop of NK cells and a marginal increase of monocytes were the only changes of cell count during the exacerbation. A significant downregulation of B7-2 on NK cells and of B7-1 on monocytes was also observed during exacerbations. CONCLUSIONS: The above observations are in contrast to in vitro findings showing an upregulation of costimulatory molecules after exposure of blood cells to viruses or allergens. It is possible that activated immune cells leave the blood stream to migrate to the inflammation site during acute asthma exacerbations.

Adolescent↗

Epidemiology of ankylosing spondylitis in Northwest Greece, 1983-2002.

OBJECTIVE: To investigate the incidence and the prevalence of ankylosing spondylitis (AS) in a defined area of northwest Greece with a total population of about 500,000 inhabitants. METHODS: AS cases were recorded from (i) in- and out-patients referred to the rheumatology clinics of the Ioannina university hospital and the Ioannina general hospital, and (ii) patients referred to private rheumatologists practising in the study area. An incident case was defined as any patient with AS, diagnosed during the period between 1 January 1983 and 31 December 2002 who were resident in the study area for at least 1 yr before the diagnosis. A prevalent case was defined as any patient with AS who was a resident of the study area on 31 December 2002. Diagnosis was based on the modified New York criteria for AS. Population data were based on the 1981, 1991 and 2001 National Censuses. RESULTS: A total of 113 cases were diagnosed among the population of the area studied during the period 1983-2002. Men constituted a 4.65-fold higher number of patients than women, and had a significantly higher mean age at diagnosis. All patients presented bilateral sacroiliitis, 40 patients (35.9%) had peripheral joint involvement and 15 patients presented extra-articular manifestations (13.27%). HLA-B27 antigen was found in 80.5% of our patients. The age-adjusted mean annual incidence rate for the population aged > or =16 yr was 1.5 cases per 10(5) inhabitants [95% confidence interval (CI) 0.4-2.5], and the age-adjusted prevalence rate on 31 December 2002 was 29.5 cases per 10(5) inhabitants (95% CI 25.9-33.1). The incidence rates were higher in the age group 35-44 yr for men and in the age group 25-34 yr for women. CONCLUSION: The incidence and prevalence of AS in the area studied were significantly lower than in other white populations and higher than in the Japanese population.

Adolescent↗

Rhinovirus-induced alterations on peripheral blood mononuclear cell phenotype and costimulatory molecule expression in normal and atopic asthmatic subjects.

BACKGROUND: Rhinovirus (RV) infection is the commonest trigger of acute asthma exacerbations; however, the immune response to these viruses and any potential implications in the mechanisms leading to asthma exacerbations are not well understood. OBJECTIVE: To assess the effects of in vitro RV infection on the phenotype and expression of costimulatory molecules on peripheral blood mononuclear cells (PBMC) from normal and atopic asthmatic subjects, as a model for RV antigen presentation. METHODS: PBMC from seven normal and seven asthmatic subjects were exposed to one infectious unit/cell of RV16 for 48 h. Surface expression of CD25, CD28, CD40, CD54, CD80, CD86 and CTLA-4 was evaluated on CD3, CD4, CD8, CD14 and CD19 PBMC subpopulations by three-colour flow cytometry. RESULTS: No changes in the percentage of CD3, CD4, CD8 or CD19 were observed. CD14 was significantly reduced by the infection and this was more pronounced in normal subjects. On Th cells CTLA-4 was increased after RV infection only in the asthmatic group. Levels of CD80 and CD86 in the control cultures were lower in the asthmatic group. RV infection induced a significant increase of CD80 on monocytes and of CD86 on B cells, which occurred in both groups but were less marked in atopic asthmatic subjects. CONCLUSION: Exposure of PBMC to RV is able to activate the antigen presentation machinery. Differences between normal and atopic asthmatic individuals are compatible with the hypothesis that an aberrant immune response to RV may be involved in the development of acute exacerbations in atopic asthmatic subjects.

Adult↗

A defective type 1 response to rhinovirus in atopic asthma.

BACKGROUND: Rhinoviruses (RVs) are the most frequent precipitants of the common cold and asthma exacerbations, but little is known about the immune response to these viruses and its potential implications in the pathogenesis of asthma. METHODS: Peripheral blood mononuclear cells (PBMC) from patients with atopic asthma and normal subjects were exposed to live or inactivated RV preparations. Levels of interferon (IFN)gamma and interleukins IL-12, IL-10, IL-4, IL-5 and IL-13 were evaluated in the culture supernatants with specific immunoassays. RESULTS: Exposure of PBMC to RVs induced the production of IFNgamma, IL-12, IL-10, and IL-13. Cells from asthmatic subjects produced significantly lower levels of IFNgamma and IL-12 and higher levels of IL-10 than normal subjects. IL-4 was induced only in the asthmatic group, while the IFNgamma/IL-4 ratio was more than three times lower in the asthmatic group. CONCLUSIONS: This evidence suggests that the immune response to RVs is not uniquely of a type 1 phenotype, as previously suggested. The type 1 response is defective in atopic asthmatic individuals, with a shift towards a type 2 phenotype in a way similar, but not identical, to their aberrant response to allergens. A defective type 1 immune response to RVs may be implicated in the pathogenesis of virus induced exacerbations of asthma.

Adult↗

Circulating cytokines in patients with cat scratch disease.

Levels of circulating interleukin (IL)-2, IL-6, and IL-10, measured by enzyme-linked immunosorbent assay, were significantly higher in patients with cat scratch disease (CSD) than in healthy control subjects; no induction of IL-12 was observed, and levels of interferon-gamma and IL-4 were generally not detectable. This is the first report showing increased circulating cytokine levels in patients with CSD. The induction of these mediators can partly explain some clinical and pathological features of the disease.

Antibodies, Bacterial↗

The role of viruses in the induction and progression of asthma.

Viral respiratory infections have been related to asthma in several ways. It is well established that viral common colds precipitate exacerbations of asthma. Severe bronchiolitis in early life is related to subsequent wheezing and therefore may represent a marker of susceptibility to asthma; alternatively, it could be involved in the initiation of the disease. Finally, it is possible that some infections may protect from the development of asthma and allergies by promoting a type-1 host response. However, whether respiratory or other viruses could mediate such a protective effect is debated. The design and implementation of novel anti- or proviral strategies targeting asthma depends on the resolution of these questions. This review presents current evidence on the epidemiologic correlations and proposed mechanisms for the involvement of viral infections in the development and progression of asthma.

Animals↗

Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells.

BACKGROUND: Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention. OBJECTIVE: To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in-vitro. METHODS: BEAS-2B cells were infected with major and minor RVs and the mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin, eotaxin-2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus-specificity of the observed reactions, cells were also exposed to inactivated RVs. RESULTS: RV infection was able to up-regulate mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin and eotaxin-2, did not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL-8, RANTES and eotaxin, but not for MIP-1alpha. When RVs were inactivated cytokine up-regulation was almost completely lost. CONCLUSION: Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus-induced asthma exacerbations.

Bronchi↗

Effect of desloratadine and loratadine on rhinovirus-induced intercellular adhesion molecule 1 upregulation and promoter activation in respiratory epithelial cells.

BACKGROUND: Rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM-1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of rhinoviruses. Rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H(1)-receptor blockers. Anti-inflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined. OBJECTIVE: We have investigated the effects of desloratadine and loratadine on rhinovirus-induced ICAM-1 expression, mRNA upregulation, and promoter activation. METHODS: Cultured primary bronchial or transformed (A549) respiratory epithelial cells were pretreated with desloratadine and loratadine for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated with flow cytometry, and ICAM-1 mRNA was evaluated with specific RT-PCR. In A549 cells promoter activation was evaluated with a chloramphenicol acetyltransferase assay, and binding activity of nuclear factor kappa B in nuclear extracts was evaluated with an electrophoretic mobility shift assay. RESULTS: Desloratadine and loratadine (0.1-10 micromol/L) inhibited rhinovirus-induced ICAM-1 upregulation in both primary bronchial or transformed (A549) respiratory epithelial cells. In A549 cells the 2 compounds showed a dose-dependent inhibition with similar efficacy (inhibitory concentration of 50%, 1 micromol/L). Desloratadine and loratadine also inhibited ICAM-1 mRNA induction caused by rhinovirus infection in a dose-dependent manner, and they completely inhibited rhinovirus-induced ICAM-1 promoter activation. Desloratadine also inhibited rhinovirus-induced nuclear factor kappa B activation. Desloratadine and loratadine had no direct effect on rhinovirus infectivity and replication in cultured epithelial cells. CONCLUSION: These effects are unlikely to be mediated by H(1)-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.

Asthma↗

Unsuspected extralymphocutaneous dissemination in febrile cat scratch disease.

Cat scratch disease (CSD) commonly manifests as regional self-limited lymphadenitis. However, dissemination of the infection to distant multiple sites may occur even in immunocompetent patients. We report a series of 11 children with fever and extralymphocutaneous manifestations of CSD, in order to highlight potential multiorgan involvement in patients with febrile CSD. To be eligible for enrollment, patients had to present with involvement of sites other than regional lymph nodes. The diagnosis was based on suggestive clinical criteria, histological findings and positive serology. The utilization of ultrasound imaging revealed hepatic lesions in 3 children and splenic lesions in 8 children, whereas osteolytic lesions were observed in 4 children by bone scan. Hepatic or splenic involvement was not suggested by clinical signs or biochemical investigation in 2/3 and 6/8 children, respectively. Bone involvement was supported either by relative symptoms or signs. Our findings indicate that, in the presence of fever, extralymphocutaneous manifestations have to be anticipated in patients with clinically suspected CSD. The systematic use of imaging modalities in patients with serologically documented Bartonella henselae infection could contribute to a better understanding of the clinical spectrum of CSD.

Adolescent↗

Rhinoviruses infect the lower airways.

Rhinoviruses are the major cause of the common cold and a trigger of acute asthma exacerbations. Whether these exacerbations result from direct infection of the lower airway or from indirect mechanisms consequent on infection of the upper airway alone is currently unknown. Lower respiratory infection was investigated in vitro by exposing primary human bronchial epithelial cells to rhinoviruses and in vivo after experimental upper respiratory infection of human volunteers. Bronchial infection was confirmed by both approaches. Furthermore, rhinoviruses induced production of interleukin-6, -8, and -16 and RANTES and were cytotoxic to cultured respiratory epithelium. This evidence strongly supports a direct lower respiratory epithelial reaction as the initial event in the induction of rhinovirus-mediated asthma exacerbations. The frequency of infection and the nature of the inflammatory response observed are similar to those of the upper respiratory tract, suggesting that rhinovirus infections may be one of the most important causes of lower in addition to upper respiratory disease.

Bronchi↗

Rhinovirus infection induces major histocompatibility complex class I and costimulatory molecule upregulation on respiratory epithelial cells.

Human respiratory epithelial cells may act as antigen-presenting cells during respiratory viral infections. In addition to major histocompatibility complex (MHC) molecules, antigen presentation requires participation of costimulatory molecules. Here the authors investigated class I and class II antigens and B7-1 and B7-2 costimulatory molecule expression in human A549 pulmonary epithelial cells and primary bronchial epithelial cells (HBECs) at baseline and after rhinovirus infection. Constitutive expression of MHC class I and B7-1 molecules was observed on both cell types. MHC class I molecules were up-regulated by rhinovirus infection, while B7-1 was up-regulated only on A549 cells. B7-2 molecules were constitutively expressed at a low level and were up-regulated by rhinovirus only on HBECs. Rhinovirus induction of antigen-presenting molecule expression on A549 cells was accompanied by cellular activation in terms of induction of release of the chemokines RANTES and Groalpha. These data show that respiratory epithelium expresses full antigen-presentation machinery and that rhinovirus infection up-regulates this expression.

Bronchi↗

Corticosteroids inhibit rhinovirus-induced intercellular adhesion molecule-1 up-regulation and promoter activation on respiratory epithelial cells.

BACKGROUND: Rhinoviruses are associated with the majority of asthma exacerbations. To date, the pathogenesis of virus-induced asthma exacerbations is still unclear, and no safe effective therapy is available. Intercellular adhesion molecule-1 (ICAM-1) has a central role in inflammatory cell recruitment to the airways in asthma and is the receptor for 90% of rhinoviruses. We have previously shown that rhinovirus infection of lower airway epithelium induces ICAM-1 expression by a transcriptional mechanism that is critically nuclear factor-kappaB-dependent. OBJECTIVE: The purpose of this study was to investigate the effect of systemic (hydrocortisone [HC], dexamethasone [DM]) and topical (mometasone furoate [MF]) corticosteroids on rhinovirus-induced ICAM-1 up-regulation. METHODS: Cultured primary bronchial or transformed (A549) respiratory epithelial cells were pretreated with corticosteroids for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated by flow cytometry. In A549 cells ICAM-1 messenger RNA was evaluated by specific reverse transcription-PCR and promoter activation by chloramphenicol acetyltransferase assay. RESULTS: We observed inhibition of rhinovirus-induced ICAM-1 up-regulation with corticosteroid pretreatment in both primary bronchial epithelial and A549 cells. In A549 cells systemic and topical corticosteroids demonstrated a dose-dependent inhibition with similar efficacy (inhibitory concentration 50% 10(-10) mol/L, 10(-11) mol/L, and 10(-11) mol/L for HC, DM, and MF respectively). MF also inhibited ICAM-1 messenger RNA induction by rhinovirus infection in a dose-dependent manner. MF completely inhibited rhinovirus-induced ICAM-1 promoter activation. HC, DM, and MF had no direct effect on rhinovirus infectivity and replication in cultured cells. CONCLUSION: Corticosteroids decrease rhinovirus-induced ICAM-1 up-regulation in respiratory epithelial cells and modulate pretranscriptional mechanisms. This effect may be important for the therapeutic control of virus-induced asthma exacerbations.

Adrenal Cortex Hormones↗