The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants.

Clinical manifestations of respiratory syncytial virus (RSV) infection vary from minimal disease to severe acute bronchiolitis. The structural complex of TLR4/CD14 participates in the virus recognition as a component of natural immune response. Genetic variations of TLR4/CD14 may explain great variations in disease severity. The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis. Our study included two groups of Greek infants and young children (A and B). Group A consisted of 50 infants ≤2 years of age hospitalised with bronchiolitis and group B of 99 previously healthy children aged 4-14 years (control group) with a free past medical history. RSV was identified by PCR of genetic material that was extracted from nasopharyngeal samples collected from all patients. Blood samples were used to extract DNA and by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the development of acute bronchiolitis. For CD14 polymorphisms, a positive association was found between the C-159T and the development of bronchiolitis (p=0.05) but not for the other loci. There were no differences detected in the frequencies of the four polymorphisms studied among infants with RSV and non-RSV bronchiolitis. It is concluded that protein CD14 may have a functional role in the viral conjunction to the structural complex TLR4/CD14. The association between the polymorphism C-159T and the manifestation of disease found in our study points out that the severity in the development of acute bronchiolitis is not specified exclusively by the pathogen, but the immune response of the host also plays a significant role. More extensive multicentric studies need to take place, in order to lead to safer conclusions.

Association of the RANTES gene promoter polymorphisms -28C/G and -403G/A with pneumonia in Greek children.

Pneumonia is an inflammation of the lung caused by microbial or viral infection. It is an important factor of morbidity for children in the developed world, as well as a frequent cause of death of children in the developing world. Chemokines are a very important part of the immune system. The purpose of this study was to investigate the role of polymorphisms of chemokine RANTES (-28C/G and-403G/A) in the development of pneumonia in children. The study included two groups of children, the patient group and the control group. The patient group consisted of 60 children, who were hospitalized with the diagnosis of pneumonia from November 2009 until May 2010. The control group consisted of 135 healthy children who had no previous history of lower respiratory tract infections. According to the results, polymorphism of chemokine RANTES -28C/G was associated to the development of pneumonia in the studied population. Polymorphism of chemokine RANTES -403G/A was not associated to the development of pneumonia in the same population. Serum levels of chemokine RANTES were lower in children who were carriers of the polymorphism -28C/G compared to children who had the normal gene type. Also, serum levels of chemokine RANTES were higher in children with pneumococcal pneumonia compared to children with pneumonia caused by other pathogens.

Measles and mumps immunity in Northern Greece, 2004-2007.

A cross-sectional study was conducted in order to determine the prevalence of mumps and measles antibodies in a representative sample of the general population in Northern Greece between January 2004 and May 2007. Overall, 900 healthy individuals participated in the study. The great majority were found to be protected against measles. The total protection rate against mumps was significantly less (87% versus 72%, respectively; p<0.01). Compared to all other age groups, statistically significantly lower protection rates were found in children younger than 1.5 years (p<0.01). The lowest rates of all adult groups were found in the age group of 21 to 30 years (86% and 68% for measles and mumps, accordingly). In conclusion, protection rates against both measles and mumps seem to be lower than expected in certain age groups, such as infants and young adults.

Respiratory syncytial virus infection in hospitalized children older than 2 years with community-acquired pneumonia.

BACKGROUND/AIM: Respiratory syncytial virus (RSV) is one of the main causes of bronchiolitis and pneumonia in infants and young children. The aims of the present study were to evaluate the role of RSV in children >2 years old hospitalized with community-acquired pneumonia (CAP) and to type the circulating RSV strains. MATERIALS AND METHODS: Serum and throat swab samples were taken upon admission from Greek children aged > 2 years, hospitalized with atypical CAP, and when possible, a second serum sample was also taken. RSV IgG and IgM antibodies were determined by Enzyme Linked Immunosorbent Assay (ELISA), while throat swab samples were tested by nested RT-PCR. Additional serological testing was performed to find out probable co-infections. RESULTS: A total of 101 children with atypical CAP were included in the study, aged 2.5-14 years (median 8.25). RSV IgM antibodies were detected in 21 (20.7%) cases, either in the first or/and in the second serum sample, while RSV genome was detected in 11 out of 15 (73%) IgM-positive patients, which were further tested by PCR. PCR-positive results were obtained up to the 7(th) day of illness. Among the 11 cases, one was of type B, and all the rest were of type A. The median age of the RSV-positive children was 4 years (range 3-13 years). Although RSV was detected in all seasons, the majority of cases (31%) were detected in winter. Co-infection was detected in 3 cases (two with Mycoplasma pneumoniae and one with adenovirus). CONCLUSIONS: Apart from the known role of RSV as the most important pathogen causing acute respiratory disease in infants and young children, it is also a significant viral pathogen in older children hospitalized because of CAP. Genetic typing provides further insight into the epidemiology of the disease.

Alveolar LCI vs. standard LCI in detecting early CF lung disease.

Multiple breath washout (MBW) is a sensitive technique that detects early airways disease. However in very young children, large equipment and physiological dead space relative to lung volumes may result in a higher Lung Clearance Index (LCI). We investigated whether alveolar LCI (aLCI) is a more sensitive index than standard LCI in children. MBW data-sets from children aged 0.1-10.7 years [97 healthy controls and 93 with cystic fibrosis (CF)] were analysed. LCI is traditionally calculated by dividing the cumulative expired volume (CEV) by functional residual capacity (FRC) after correcting for equipment dead space. aLCI was calculated similarly, but after correcting the CEV and FRC for Langley's physiological dead space. There was a significant correlation between LCI and aLCI in health (r(2): 0.993; p<0.0001) and disease (r(2): 0.984; p<0.0001). Sensitivity of both LCI and aLCI in detecting abnormal lung function in CF was 39% during infancy, which increased to 77% and 83% respectively in older children. However, the difference in sensitivity (aLCI vs. LCI) was not significant (p=0.36). We conclude that LCI is minimally affected by airway deadspace, or relative equipment deadspace, and is an appropriate measure of lung function in infancy.

Reactive thrombocytosis in children with viral respiratory tract infections.

AIM: Secondary thrombocytosis occurs commonly in children and is associated with a variety of lower respiratory tract infections, bacterial most often than viral. Aim of the study was to have an insight into the incidence and the clinical significance of thrombocytosis in children with lower respiratory tract infection caused by viral pathogens. METHODS: Clinical data of 92 children, aged 10 days to 8 years, hospitalized with viral lower respiratory tract infection were studied retrospectively for presence of thrombocytosis (platelet count >500×109/l). RESULTS: Thrombocytosis was detected in 59.78% of patients. When children with and without thrombocytosis were compared a significant difference was found for age (P=0.002). We have found no differences among the two groups in sex, SaO2, clinical severity score and CRP levels at admission. Patients with RSV infection presented with significantly higher platelet counts (P=0.003). Extreme thrombocytosis (platelet count >1000×109/L) was noticed in eight patients (8.7%), seven of them were infants with RSV bronchiolitis. All children recovered uneventfully without requiring prophylaxis with anticoagulants or platelet aggregation inhibitors. CONCLUSION: Reactive thrombocytosis is a common finding in the acute care population of children hospitalized with viral lower respiratory tract infection. It represents a reactive phenomenon and does not indicate infection of bacterial cause or severe clinical course. Routine prophylactic antiplatelet treatment or further investigations are not necessary.

The effectiveness of local corticosteroids therapy in the management of mild to moderate viral croup.

AIM: The purpose of this study was to determine whether local anti-inflammatory therapy with inhaled beclomethasone dipropionate is effective in the outpatient management of acute viral croup. METHODS: Children six months to five years of age, presenting to the Emergency Department (ED) with a croup score of at least 2 participated in the study. All children were assigned in a randomised double-blind fashion to receive either nebulized L-epinephrine (LE), a single intramuscular injection of dexamethasone (D) 0.6 mg/kg, or inhaled beclomethasone dipropionate (BD) 200 mg, via aerochamber. Croup score (CS), heart rate (HR), blood pressure, respiratory rate (RR) and oxygen saturation were recorded at study entry and at 15, 30, 60, 90 and 120 minutes after treatment. RESULTS: Sixty-four patients were enrolled into the study. Significant improvement of the croup score was noticed at the end of observation time in all groups. The LE group showed significant improvements of CS, HR and RR in comparison to the other two groups. Inhaled BD was as effective as intramuscular D in the treatment of mild to moderate croup in the ED. CONCLUSION: The use of inhaled beclomethasone in the outpatient management of croup was associated with a significant reduction in the severity of illness within 24 h after treatment.