Correction to: Vilnius Declaration on chronic respiratory diseases: multisectoral care pathways embedding guided self-management, mHealth and air pollution in chronic respiratory diseases.

An amendment to this paper has been published and can be accessed via the original article.

CLOSTRIDIUM DIFFICILE INFECTION IN CHILDREN WITH EXPOSURE TO ANTIBIOTICS.

Clostridium difficile represents an example of healthcare-associated pathogen causing disease in community and hospital setting. The number of clinical studies determining risk factors for Clostridium difficile infection in children is limited as compared to adult patients. The aim of this study was to determine the association between antibiotic exposure in hospital setting and risk of Clostridium difficile infection in children. Systematic review of the electronic databases was used to update the literature, collect secondary data, critically appraise research studies, and synthesize study result from our institutions with available literature. Paper aimed to provide a complete, exhaustive summary of current literature relevant to our research question. A systematic review of the literature using databases PubMed (1935-2018) was conducted to compare our study results with available literature and determine significant differences and similarities that might impact clinical decisions in the country Georgia. The study of the association of several factors with the development of Clostridium difficile infection showed that the age more than 4 years old represented independent risk-factors of the development of Clostridium difficile infection, while the gender and ethnicity was not associated with the infection. Antibiotic exposure within the month preceding the onset of diarrhea was statistically significantly associated with an increased risk of Clostridium difficile infection. The risk was greatest with cephalosporins, followed by penicillins, carbapenems and macrolides. Antibiotic exposure in children is associated with increased risk of Clostridium difficile infections in hospital setting.

Vilnius Declaration on chronic respiratory diseases: multisectoral care pathways embedding guided self-management, mHealth and air pollution in chronic respiratory diseases.

BACKGROUND: Over 1 billion people suffer from chronic respiratory diseases such as asthma, COPD, rhinitis and rhinosinusitis. They cause an enormous burden and are considered as major non-communicable diseases. Many patients are still uncontrolled and the cost of inaction is unacceptable. A meeting was held in Vilnius, Lithuania (March 23, 2018) under the patronage of the Ministry of Health and several scientific societies to propose multisectoral care pathways embedding guided self-management, mHealth and air pollution in selected chronic respiratory diseases (rhinitis, chronic rhinosinusitis, asthma and COPD). The meeting resulted in the Vilnius Declaration that was developed by the participants of the EU Summit on chronic respiratory diseases under the leadership of Euforea. CONCLUSION: The Vilnius Declaration represents an important step for the fight against air pollution in chronic respiratory diseases globally and has a clear strategic relevance with regard to the EU Health Strategy as it will bring added value to the existing public health knowledge.

EVALUATION OF DEVELOPMENTAL OUTCOMES WITH BAYLEY III TEST IN PRETERM INFANTS WITH RESPIRATORY DISTRESS SYNDROME.

Aim of our study was assessment of developmental outcome of neonates with respiratory distress syndrome, evaluation of the impact of RDS on child's health, growth and neurodevelopment at 2 years of age. Case control study included 138 children, from those, 74 preterm (gestational age 32-36 weeks), who were divided into 2 study groups: I groups - involved 38 preterm with RDS and II group - 36 preterm patients without RDS and other neonatal problems. Control group included 42 patients born term with uncomplicated history. To assess the impact of RDS without other co-factors, we excluded from the study children with congenital malformations, genetic and metabolic disorders; intracranial hemorrhage, neuromuscular diseases, severe hyperbilirubinemia, sepsis, congenital infections as well as family with drug or alcohol addiction, severe mental disorder, parents younger than 17 years of age at the time of the baby's birth. The study and control group were homogenous based on family social-economic status, parents education, mean parental age, mother health status, to minimize the bias. We assessed the health status, physical growth and development of children at mean age (corrected age) of 24+4 months. Physical growth was assessed based on the WHO Standard Deviation growth charts, health status based on detailed history and clinical examination, child development was assessed using Bayley Scales of Infant and toddler development III. We calculate composite scores for each sphere and compare mean composite scores of each group to each other. Statistical analyses were based on SPSS 17. The assessment of the health shows that children with RDS as well as prematurely born children without RDS have more respiratory infections during first years of life and more hospitalization than control group. The p-value is >0,5 comparing children with RDS and children with prematurity without RDS, but p < 0,05 if we compare the both group of premature with control group of term infants. Our study does not show that RDS affects significantly the prevalence of acute respiratory infections. The main causes of hospitalization in studied as well as in control group are respiratory tract infections and diarrhea. Growth assessment does not show significant difference in child's height and head circumference, while the percentage of children with underweight according corrected age was more evident in I and II group than in control (p=0,0401). The motor composite scores are lower in premature infants with RDS, but it does not show the significant difference (p=0.7755) compared to second group of premature infants without RDS, at the same time comparing both groups to controls show significant difference (P =0.0021). Mostly were affected fine motor abilities. Assessment of the cognitive scores does not show difference between study and control groups, while the language developmental scores in first and second group were significantly lower than in control (P < 0.0001), but there was no difference between I and groups. We found that premature children at 2 years of age despite RDS have lower scores comparing to term newborns in fine motor and language development. Prematurity increases risk for neurodevelopmental impairments that is important to identify and start early intervention to improve the outcomes. It is shown that neonatal complications (Jaundice, infections, asphyxia and etc.) affect development more than prematurity itself, it is very important to conduct big cohort studies on neonates with RDS to identify the risks associated with RDS and its severity.

EPIDEMIOLOGY OF CLOSTRIDIUM DIFFICILE INFECTION IN HOSPITALISED PEDIATRIC PATIENTS IN GEORGIA.

Clostridium difficile, a Gram-positive spore-forming bacillus, is the most common identifiable etiologic agent of antibiotic-associated diarrhea. The incidence of Clostridium difficile infections among hospitalized children has been increasing across the world. The aim of our study was to evaluate occurrence of Clostridium difficile and some other gastrointestinal pathogens among hospitalized pediatric patients in Georgia, as far as currently statistical data on the topic is very limited in the country. One of the objectives of the study was to test and pilot the real-time Polymerase Chain Reaction diagnostic systems for rapid and simultaneous identification of number of pathogens with a particular emphasis on diarrheal disease diagnostics as these are one of the primary public health priorities in Georgia and worldwide. Cross-Sectional study has been performed on 211 samples collected from 192 pediatric patients. Two pediatric hospitals were involved in the study: M. Iashvili Children's Central Hospital and Tbilisi Children's Clinical Hospital for Infectious Diseases. Laboratory investigations were done in the Clinic NeoLab, Tbilisi, Georgia. Study materials collected for testing were stool samples. Samples were tested by EIA kits (CerTest biotec, Zaragoza, Spain) for presence of A/B toxin according to the manufacturer's instructions. EIA test positive samples were analyzed by home-made multiplex real-time polymerase chain reaction (NeoPCR Diagnostics, NeoLab, Tbilisi, Gerogia) for confirmation of the infection and for simultaneous identification of additional gastrointestinal pathogens including Entamoeba histolitica, Giardia lamblia, Cryptsporidium parvum, Adenovirus, Rotavirus, Norovirus and Astrovirus. All samples were also tested for the presence of the above listed pathogenic agents using the same type EIA kits as for Clostridium difficile described above (CerTestbiotec, Zaragoza, Spain) for presence of the corresponding pathogen. The average age of the study participants was 3.5 years, 56.7% were male and 43.3% were female patients. Presence of Clostridium difficile have been documented in 21 samples out of 211 (10%). Besides the Clostridium difficile, other enteric pathogens have been revealed with the following frequencies: Rotavirus in 12 cases (5.7%), Adenovirus in 11 (5.2%), Giardia lamblia in 10 (4.7%), Astrovirus in 3 (1.4%), Cryptsporidium parvum in 3 (1.4%), Entamoeba histolitica in 2 (0.9%), Norovirus in 2 (0.9%). 49 samples were from out-patient cases (2 samples were positive for Clostridium difficile) and 162 samples were from in-patient cases (19 samples were positive for Clostridium difficile). Clostridium difficile is the frequent pathogenic agent causing diarrheal disease among hospitalized pediatric patients. Development of Clostridium difficile related diarrhea is associated with the antibiotic treatment of pediatric patients hospitalized due to different clinical diagnosis. Targeted early detection of these pathogens is important for the optimal management of diarrheal infection in pediatric patient which will lead to the better clinical outcome and reduction of morbidity rate among hospitalized pediatric patients.

CYTOKINES PROFILE AND ITS CONNECTION WITH DISEASE SEVERITY IN COMMUNITY-ACQUIRED PEDIATRIC PNEUMONIA.

Community-acquired pneumonia is (CAP) associated with serious complications and is the leading cause of death in children. Severity of CAP is depend on an impairment of host defenses. Persistent and toxic inflammation directs to an excessively pro-inflammatory cytokine production, neutrophil hyper-responsiveness, and dysregulation of lung neutrophil apoptosis, which results in lung injury and poor patient outcomes. However, the correlation between increased cytokine levels and clinical outcome in children remains unclear. The main aim of present work was evaluation the potential association serum cytokine levels with complications and severity of pneumonia and identification marker for earlier diagnosis of pneumonia complications. For this purposes, 62 children admitted to Iashvili Central Children Hospital during 2013-2014, Tbilisi, Georgia, were investigated. The study was approved by the Ethics Committee of the Tbilisi State Medical University and written informed consent was obtained from the parents/legal guardians of all study participants. Control group consisted of 10 healthy age matched individuals. All samples (serum, urine, sputum, nasopharyngeal swabs) were analyzed for the presence of respiratory viruses and/or bacterial pathogens. The serum cytokines (IFN-gamma, TNF-alfa, IL-8, IL-10) levels were determined by enzyme-linked immunosorbent assay (ELISA) on the first and fifth day of hospitalization. The patients with community-acquired pneumonia on the first and fifth day of the treatment had significantly higher cytokine concentrations (IFN-g, TNF-a, IL-8, IL-10) than age matched individuals (p<0.01). Moreover, IL-10 and TNF-a (p<0.05) levels were statistical differ between groups with high and low saturation, However, patients with pleural effusion have significantly lower circulating IL- 8, than without effusion. Based on our results, circulatory cytokines (IL-10, TNF, IL-8) were elevated in CAP patient and can be used as markers of pneumonia severity signs (saturation, pleural effusion etc). However more studies are needed for before using cytokines as indicator of disease prognosis.

CYTOKINES AS THE PREDICTORS OF SEVERE MYCOPLASMA PNEUMONIAE PNEUMONIA IN CHILDREN (REVIEW).

In spite of many attempts to differentiate bacterial from viral disease and predict severity and outcome, the etiologic diagnosis of paediatric community acquired pneumonia and the estimation of potential outcomes remain unsolved problems in most cases. Mycoplasma pneumoniae is one of the major pathogens causing CAP in children. Although MP infection was traditionally thought to be a self-limited process, more and more severe cases even fatal cases of MP infections were reported in recent years. So it is essential for pediatricians to recognize severe or refractory or severe MP early, treat it promptly and prevent the progress of the disease. In recent years, several new biomarkers have been tested in children with CAP. Some of the biomarkers used for etiologic diagnosis in children with CAP and they also have been used the MP infection severity. Among traditional biomarkers, several cytokines appears to be effective both in selection of bacterial cases and in evaluation of severity. However, a precise cut-off level able to separate bacterial from viral cases and mild from severe cases has not been defined. Further studies enrolled with a large number of children with Mycoplasma pneumoniae is needed to be carried out to identify the potential utility of different cytokines as the good predictors.

ACUTE VIRAL BRONCHIOLITIS IN INFANTS (REVIEW).

Bronchiolitis is a common condition in children less than 2 years of age and is a leading cause of infant hospitalization. Acute bronchiolitis is characterized by acute wheezing in infants or children and is associated with signs or symptoms of respiratory infection; the most common etiologic agent is respiratory syncytial virus. There is a lack of consensus regarding the clinical definition of acute viral bronchiolitis in children and hence the management varies across the globe. Usually it does not require investigation, treatment is merely supportive and a conservative approach seems adequate in the majority of children, especially for the youngest ones. Managing bronchiolitis, both in the outpatient and inpatient setting remains a challenge to the treating pediatrician. Several recent evidence-based reviews have suggested that bronchodilators or corticosteroids lack efficacy in bronchiolitis and should not be routinely used. The cornerstones of the management of viral bronchiolitis are the administration of oxygen and appropriate fluid therapy, and overall a "minimal handling approach" is recommended. Inhaled adrenaline is commonly used in some countries, but the evidences are sparse. Recently, inhalation with hypertonic saline has been suggested as an optional treatment. When medical treatment fails to stabilize the infants, non-invasive and invasive ventilation may be necessary to prevent respiratory failure. The key to reducing the morbidity and mortality in children with RSV bronchiolitis is through prevention of infection through immunoprophylaxis especially in high-risk children. This review focuses on the epidemiological, clinical, radiographic, and pathologic characteristics, as well as the recent advances in management of acute bronchiolitis.

PREVALENCE OF ATOPIC DERMATITIS SYMPTOMS IN CHILDREN WITH DEVELOPMENTAL AND BEHAVIORAL PROBLEMS.

A link between atopic dermatitis (AD,eczema) and emotional and behavioral dysfunction is more or less well recognized but concern still exists. Children with a chronic health condition have long been considered at excess risk for psychosocial morbidity. But psychosocial morbidity is less linked and studied in connection with other disease, especially AD. As mentioned before, AD is the most prevalent chronic disease in young children. The aim of the study was assessment of incidence of atopic dermatitis in children of 5-6 years with developmental and behavioral problems. The cross sectional study was conducted. Children with developmental and behavioral problems according to medical records and aged five to six years were recruited consecutively from a preventive care register in M. Iashvili Childrens Hospital Child Developmental Center in 2010-2014 years. Recruitment was done according developmental and behavioral assessment performed on the basis of team approach by pediatrician and psychologist. Parents evaluation of development status: developmental milestones (PEDS:DM) and Pictorial Checklist ( PIK -17) was used for assessment. 639 children with language delays, problems of externalization and internalization were enrolled in study. Children were examined by pediatricians based on the presence of at least three major and three minor criteria of Hanifin and Rajka's diagnostic criteria(H&R) and by semi structured, one-to-one interview with the parents. According our study: 1. Significant amount of children with developmental and behavioral problems and symptoms are developing AD(36%). 2. Children with language delay were more frequently developing AD symptoms than children with behavioral problems.3.There was not significant difference in children with language delay and behavioral problems in terms of impact on QL. In both cases everyday activities, sleep and recreational actives were affected and there more affected then in children with developmental and behavioral problems and symptoms with AD comparable to children without AD, especially sleep.4. Date represents that boys are more likely to develop AD than girls, this information is in correlation with known facts about dermatitis. Both boys and girls were similarly affected by QL problems in case of AD and developmental and behavioral problems and symptoms. Chronic diseases and development and behavior of children in further dilemma for researchers. Our study gives us further impulse for more deep insight in factors affecting children with delays and behavioral problems and prospective studies in group with developmental and behavioral problems and symptoms and AD.

INCIDENCE OF ALLERGIC RHINITIS AND RESPIRATORY INFECTIONS IN FIRST GRADE SCHOOL CHILDREN IN GEORGIA.

The aim of the study was assessment of incidence of allergic rhinitis and respiratory infections and evaluation of quality of life of first grade school age children with allergic rhinitis. The cross sectional study in randomly selected regions and schools was conducted using specially developed parent questionnaire and mini rhino conjunctivitis quality of life questionnaire (MiniRQLQ). On the first was used special questionnaire, and on the second phase MiniRQLQ was used in cases with allergic rhinitis. Total of 1530 parent of 6-8 years children were interviewed, 1499 first phase questionnaires and 174MiniRQLQ were analyzed by SPSS 19 program. From 1499 children 799 (53.3%) were girls and 700 (46.7%) - boys. The 810 (54%) live in urban, 524 (35%) in rural area and 165 (11%) in high mountains. The study revealed that 2.3% of children have respiratory infections 7-8 times per year, 19.9% 3-5 times, 53.4% 1-2 times and 24.2% became ill very rarely. There was statistically significant difference between the frequency of respiratory infection in rural and urban area (p<0,001).The frequency of chronic diseases reported by parents is 18.3% (n=274), from those 201 (73.3%) are allergic disorders (asthma, rhinitis, atopic dermatitis), that is 13.4% of total respondents. The incidence of allergic rhinitis was 11.6%, most frequent symptom was rhinorrhea 168 (11.2%), recurrent sneezing episodes during last year was seen in 153 (10.2%), nasal pruritus was reported in 137 (9.1%), nasal obstruction in 117 (7.8%). The eye symptoms were reported in 62 (4.2%). The symptoms of allergic rhinitis is significantly higher in urban population then in rural area (P<0.02), as well as in boys (P<0.05). The 109 (62.6%) of respondents answer that symptoms and mostly nasal obstruction affected their quality of life, especially on recreational activities and sleep. In 91 (52.9%) patients with already diagnosed allergic rhinitis treatment was prescribed according international guidelines. In group with symptoms but non-diagnosed allergic rhinitis frequently was used I generation antihistamines 52 (62.6%) and decongestants 57 (68.5%). Incidence of allergic rhinitis in first grade school population is high and it is comparable to indices of developed countries. Allergic rhinitis affects quality of life of children especially outdoor activities and sleep. ARI does not show an impact on severity of allergic rhinitis symptoms.

Mycoplasma Pneumoniae and Chlamydophila pneumoniae in hospitalized children with bronchiolitis.

Bronchiolitis is an acute lower respiratory tract infection in early childhood caused mainly by different viruses. Etiology of bronchiolitis have been studied in different environments and populations. Respiratory syncytial virus (RSV), human Metapneumovirus (hMPV), human Bocavirus (hBoV), human Rhinoviruses (hRV) have consistently been shown to predominate. Few studies however have attempted to determine whether other pathogens, particularly Mycoplasma Pneumoniae (MP) and Chlamydophila pneumoniae (CP), are associated with bronchiolitis in children under 2 years of age. The aim of this study was to determine the prevalence and clinical features of MP and CP in children under the age of 2 years presenting to the Iashvili Central Children Hospital in Tbilisi with various severities and clinical manifestations of bronchiolitis. Acute and convalescent serum samples were tested by ELISA for IgM and IgG antibodies to RSV, CP and MP.37 children under two years of age were studied. In 19 patients out of 37 (51.35%) etiological diagnosis were established and in 18 patients (48.65%) no pathogens were found. 11 patients (29.72%) had either CP or MP and 8 patients (21.62%) had RSV. Children infected with CP and MP had less severe bronchiolitis than those infected with RSV. Co-infection was not associated with disease severity. There were no statistically significant differences between groups with respect to length of hospital stay. Our study underlines the importance of atypical bacterial pathogens in acute bronchiolitis in children under 2 years and highlights the complex epidemiology and clinical features of these pathogens in this age group.

Infants' complementary feeding and factors influencing its timing.

The aim of our study was to detect factors that influence timing and adequacy of complementary feeding (CF) practices in Georgian families. The study was conducted at M. Iashvili Central Children's Hospital Child Developmental Center in 2013-2014 year. The data was collected from 389 mothers of infants' age ranging from six months to one year. Results of the study show that CF was started in time only in 30,2%, In 18,1% it was CF was introduced too early (<4 month), in 27,3 early (4-6 month) and in 11% - late. 13.4% of children haven't started CF at all. Most of mothers received information about CF and semi-solid and solid food used for CF from pediatricians and family-doctors. Timing of complementary feeding was related to maternal age, young mothers started CF too early, early or late. In urban areas early CF was significantly high (51.1%) than in rural (29.7%) areas (P<0,05). Proportionally employed mothers and students also started CF earlier (51.4%) than housewives (33%) (P<0.01). Mothers who had 2 and more child introduced CF timely compared to those who had the first child (P<0.01). Our research study showed that educated women started complementary feeding of their infants at appropriate ages as compared to those who were uneducated (P<0.001) among women who introduced CF in time most were educated (91%). The data from the study shows that many infants are beginning complementary feeding earlier than WHO recommends (6 month). Findings from our study revealed that maternal knowledge, age, education level was directly related with timing of CF. Promotion of strong community based education and support to ensure optimal infant and young child feeding is recommended.

Chronic respiratory diseases at primary health care level in Georgia: the results of the pilot study.

BACKGROUND AND AIM: Millions of people suffer from chronic respiratory diseases (CRD). To address this serious global health problem WHO formed the Global Alliance against Chronic Respiratory Diseases (GARD). Chronic obstructive pulmonary disease (COPD) is a major priority of GARD due to high chronic morbidity and mortality; however, there is still little prevalence data available. The prevalence of COPD in Georgia, as well as other CRD, is suspected to be high. METHODS: GARD Pilot Survey (GAPS) in Georgia had been carried out by the Georgian Respiratory Association. The survey was conducted in the Sagarejo and Mtskheta districts with total population of about 70.000. All subjects provided information on asthma, bronchitis, respiratory symptoms, smoking, allergic conditions, CRD comorbidity and lifestyle via an interviewer-administered questionnaire. A total of 3,646 questionnaires were analysed. RESULTS: It was discovered that official data concerning allergic rhinitis, TB and asthma are almost equal, but readings in relation to CRD are about five times lower according to official data of the Ministry of Health of Georgia. The data results: for allergic rhinitis - 218 in GAPS vs. 177 in the official statistics (for 100.000 population); for TB -105 in GAPS vs. 147 in the official statistics; for asthma -250 in GAPS vs. 374 in the official statistics; the data about CRD according to our survey is almost five times higher - 365 in GAPS vs. 84 in the official statistics (for 100.000 population). CONCLUSIONS: It is necessary to expand the survey to the entire country population. Country results are likely to be useful and interesting for local doctors and managers, as well as for officials.

Systemic inflammatory responses in patients with acute otitis media and the impact of treatment with sinupret.

The systemic inflammatory responses and the impact of sinupret therapy have been investigated in 14 patients with acute otitis media, AOM. The age of inspected individuals covered a range of 29.0+/-12.3 years. The blood samples were taken at the admission and after ten days treatment with sinupret. The dosage of sinupret application was two tablets or 50 drops three times per day. Utilizing the technique of enzymelinked immunoassays, the concentrations of two cytokines, TNF-alpha and IL-6, were measured in the blood serum. The minimum detectable amount of cytokines was less then 2.5 pg/ml. Age-matched five healthy subjects without significant medical history served for controls. The study proved an existence of systemic inflammatory responses under the AOM. In AOM patients as compared with healthy individuals the concentrations of both cytokines were elevated, although the difference reached the statistically significant level with respect to TNF-alpha but not to IL-6. After treatment with sinupret, the TNF-alpha level dropped noticeably, proving a recovery from the pathology. IL-6 displayed a similar pattern, although the difference between pre- and post-treatment samples was statistically nonsignificant. Assessment of varies cytokines and proper establishment of their profiles could detect more specific marker(s) of AOM of both bacterial or viral etiology and could promote thus a precise prediction of the outcome of the pathology. Generally, the estimation of cytokines under AOM could offer a powerful tool for the objective evaluation of efficacy of treatment and for the avoidance of the ineffective drug therapy.

Serodiagnosis of acute respiratory infections in children in Georgia.

OBJECTIVE: To investigate the etiology of acute respiratory infections in hospitalized children. METHODS: A total of 808 children were studied. Investigation of RSV, Adenovirus, Parainfluenza, Influenza A and B, C.trachomatis, C.pneumoniae, M. pneumonia and Legionella were performed with an ELISA for IgM, IgG and IgA antibodies detection. RESULTS: There were 496 males and 312 females giving a male: female ratio of 1.6:1. Ages range from 1 month to 15 years. The overall detection rate was 57.9%. The most frequently detected were: parainfluenza 12.6%, adenovirus 11.2%, influenza A 7.3%, RSV 6%, M. pneumoniae 5.4%, C.trachomatis 3.5% and mixed-infections 9.2%. Pneumonia was associated most frequently with adenovirus and mixed-infections; wheezing bronchitis--with adenovirus, RSV and M. pneumoniae; bronchitis--with parainfluenza and adenovirus, diseases of upper respiratory tract--with parainfluenza and adenovirus. Peak of the virus activity was during winter (influenza, parainfluenza, adenovirus, RSV) and autumn (parainfluenza, RSV). CONCLUSION: Viruses are the main causes of ARI in Georgian children. A better understanding of the etiology of ARI in all of the regions of the world may be helpful for timely decision of specific therapy, which can help pediatricians to estimate and manage children with ARI.

Non-viral wheezing in preschool children: the effect of inhaled fluticasone on symptoms and lung function.

Aims of this study were: to evaluate changes in lung function in wheezing children with detected MP and CP infection according to treatment; to measure the response to inhaled corticosteroids in children with significant wheezing who were selected as having a high risk of progressing into childhood asthma. 54 children were randomly assigned 2:1 into 2 groups-the main group (36 patients), in which inhaled corticosteroids were administered, and the control group (18 patients), without inhaled corticosteroids. Serum IgE levels were determined using the ELISA (reagents: IBL-Hamburg). Serologic studies were performed by the ELISA for IgM and IgG antibodies to MP and for IgG and IgA antibodies to CP (reagents: ImmunoLISA, Orgenics, Israel) on the Hiperion MRIII (USA). Pulmonary function testing was done with SpiroLab II (DEGO GmbH, Medizin-Elektronik, Germany). The patients of both groups were administered macrolides: azitromycin during five days. Patients of the first group received inhaled fluticasone propionate 125 mg twice daily. The parents were asked to record symptoms. Each symptom (wheezing, cough, and shortness of breath) were scored on a scale of 0 to 3--daily symptom score (DSS). Scores were calculated every 4 weeks for a total treatment period 16 weeks. The days within each period on which the DSS equalled zero were pointed as symptom free days (SFD). It had been shown an significant improvement in DSS, an increase in SFD and significant improvement of the lung functions following the treatment with inhaled fluticasone and macrolide in children with wheezing and documented MP or CP infection, compared to control group treated only with antibiotics. In conclusion, the use of ICS should be seriously considered in children with wheezing and the risk of persisting symptoms.

[Neopterine and ige during respiratory-syncytial virus infection in infants].

The number of studies confirms the correlation between IgE and neopterine levels. One of the forms of revelation of the immune answer of T-cells is the activation of T-cell system, that in its turn results in secretion of IL-2 and INF-gamma by Th-1 subtype cells. Activation of macrophages by INF-gamma the human organism. The target of our research was the evaluation of the role of the marker of macrophage activation -- neopterine in children with recurrent wheezing developed during onset of RSV infection and possible connection with IgE level. In the study 52 children of age from 1 to 12 months having RS-virus infection were included. Two groups were determined as controls -- group of healthy children and children with wheezing of non RSV etiology. Determination of neopterine was performed by enzyme immunoassay method (ELISA). During the RS-virus induced acute respiratory infection the rate of neopterine in the blood serum was significantly decreased in the group of patients with recurrent wheezing in comparison with the I group (first episode of wheezing). At the same time the significant difference between the group with wheezing of non -- RSV etiology and the control group was not observed. Decreasing of neopterin was significant in the II and III groups. IgE levels were elevated significantly in the second group of patients with recurrent wheezing. In this group negative correlation between neopterin and IgE was found.

[IFN-gamma in non atopic children with recurrent obstructive bronchitis].

Recurrent respiratory infection cause an imbalance of Th1/Th2 immune response with decreased level of IFN-gamma. Result of several studies have provided evidence linking Mycoplasma infection with recurrent wheezing in atopic children. The aim of the present study was to investigate the influence of Mycoplasma infection on IFN-gamma level in non-atopic children with recurrent obstructive bronchitis. Serum IFN-gamma was measured in two groups: the study group included 30 non-atopic children 1-4 years of age with recurrent obstructive bronchitis caused by Mycoplasma pneumoniae, the control group included 15 children with the same disease with negative Mycoplasma pneumoniae result. There were no differences in age, sex and family history of atopy. This result shows reduced Th 1 immune response that causes reduced antiviral activity and high morbidity in non-atopic wheezy children.

Wobenzym in treatment of recurrent obstructive bronchitis in children.

A total of 27 patients with recurrent obstructive bronchitis (at least 3 episodes of obstructive bronchitis per year) of 5-15 years of age were studied. Serum IgE level (by ELISA method) and pulmonary function indices were determined together with the full clinical examination. The systemic enzyme preparation Wobenzym was administered with a dosage of 1 tablet for 6 kg weight. Wobenzym was administered for 3 months. Effectiveness of the treatment was assessed by special questionnaire, in which existence of the main symptoms were recorded. Analysis of the data, obtained after treatment, demonstrated decrease of the Daily Symptom Score and an increase of Symptom Free Days, as well as an improvement in spirometric indices (FVC, FEV, PEF). According to these data, it was concluded, that systemic enzyme preparation Wobenzym should be used as a supporting measure in combination treatment of recurrent obstructive bronchitis.

[Effectiveness of treatment of bronchoobstruction in children with acute respiratory infections using home-made spacer].

A metered-dose inhaler (MDI) with spacer is the best way to deliver bronchodilator therapy for treatment of bronchoobstructive syndrome, especially in children. In developing countries, commercially produced spacers are generally unavailable or are too costly. Hence, a home-made spacer modified from a 500 ml plastic bottle, was compared with imported spacer (AeroChamber) in 80 children with spastic bronchitis. Clinical score, PEF and oximetry were recorded at baseline and 15 min after treatment. A beta-2- agonist (Ventolin) was given via MDI and two spacers (home-made and conventional spacers). PEF and oxygen saturation were significantly increased at 15 min after administration of the ventolin in both groups. No significant difference was observed between Aerochamber and the home-made spacer. In conclusion, ventolin delivered by MDI with AeroChamber was as effective in bronchodilatation as MDI with home-made spacer. The home-made spacer therefore offers a simple, inexpensive and effective method for delivering aerosol drug.