Family history and cord blood eosinophil count as predictors for atopic manifestations.

OBJECTIVES: The aim of our study was to investigate the correlation between several clinical parameters and the appearance of atopic manifestations (atopic eczema, food allergy, wheezing bronchitis, allergic rhinoconjunctivitis) in the first four years of life. METHODS: A total of 139 unselected full-term newborns were included in a prospective follow up from birth to age 4. Cord blood total immunoglobulin E (cIgE) and cord blood absolute eosinophil count (cEo), positive family history of allergy, maternal smoking during pregnancy, mode of delivery, and duration of exclusive and overall breastfeeding were evaluated as predictors for appearance of atopic manifestations. RESULTS: We found that children with a positive family history of both mother and father are 19.03 times more likely to develop atopic manifestations and those with a positive family history of only mothers are 12.55 times more likely to develop atopy compared with children with a negative family history. Neonates with cord blood eosinophilia had 5.30 times higher chances for developing atopic manifestations. No statistically significant associations were found between cIgE (p = 0.099), mode of delivery (p = 0.379), maternal smoking (p = 0.661), exclusive (p = 0.867) and overall breastfeeding duration (p = 0.675) and the presence of atopic manifestations up to age 4. CONCLUSIONS: A positive medical history, especially of mothers and cEo, seem to be predictive in screening for the onset of allergic diseases.

Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations.

BACKGROUND: We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic endotoxin exposure in relation to asthma presence, and amongst children with asthma, we explored the association of these genetic variants and endotoxin exposure with hospital admissions due to asthma exacerbations. METHODS: In a case-control study, we analysed data from 824 children (417 asthmatics, 407 controls; age 5-18 yr). Amongst asthmatics, we extracted data on hospitalization for asthma exacerbation from medical records. Endotoxin exposure was measured in dust samples collected from homes. We included 26 single-nucleotide polymorphisms (SNPs) in the final analysis (5 CD14, 7LY96 and 14 TLR4). RESULTS: Two variants remained significantly associated with hospital admissions with asthma exacerbations after correction for multiple testing: for CD14 SNP rs5744455, carriers of T allele had decreased risk of repeated hospital admissions compared with homozygotes for C allele [OR (95% CI), 0.42 (0.25-0.88), p = 0.01, False Discovery Rate (FDR) p = 0.02]; for LY96 SNP rs17226566, C-allele carriers were at a lower risk of hospital admissions compared with T-allele homozygotes [0.59 (0.38-0.90), p = 0.01, FDR p = 0.04]. We observed two interactions between SNPs in CD14 and LY96 with environmental endotoxin exposure in relation to hospital admissions due to asthma exacerbation which remained significant after correction for multiple testing (CD14 SNPs rs2915863 and LY96 SNP rs17226566). CONCLUSION: Amongst children with asthma, genetic variants in CD14 and LY96 may increase the risk of hospital admissions with acute exacerbations. Polymorphisms in endotoxin pathway interact with domestic endotoxin exposure in further modification of the risk of hospitalization.

[Guidelines for the diagnosis and treatment of hereditary angioedema]. / Smjernice za dijagnostiku i lijecenje hereditarnog angioedema.

Hereditary angioedema (HAE) is a rare but potentially fatal genetic disorder with nonpitting, nonerythematous, and not pruritic swelling which can affect the hands, feet, face, genitals and visceral mucosa. The type, frequency, and severity of the attacks vary between patients, and over the lifetime of an individual patient. Efforts in Croatian counties have identified approximately 100 patients (but there must be more undiagnosed patients). The first global guideline for the management of HAE was developed by the World Allergy Organization HAE International Alliance and published in 2012. Based on that document the Working group of Croatian experts was assigned to propose guideline for HAE management in Croatia. HAE is is most often related to decreased or dysfunctional C1 inh with autoactivation of C1 and bradykinin accumulation leading to localized dilatation and increased permeability of blood vessels resulting in tissue swelling. A diagnosis of HAE can be confirmed by measuring complement and C1 inh quantitative and functional levels.Three HAE types could be differentiated: HAE type 1 (C1 inh level is low), HAE type 2 (C1 inh level is normal but dysfunctional), and HAE type 3 (normal level and function of C1 inh). All patients suspected to have HAE-1/2 should be assessed for blood levels of C4, C1 inh protein, and C1 inh function. All attacks that result in debilitation/dysfunction and/or involve the face, the neck, or the abdomen should be considered for on-demand treatment. It is recommended that attacks are treated as early as possible. HAE attacks are treated with C1 inh, ecallantide, or icatibant.If these drugs are not available, attacks should be treated with solvent detergent-treated plasma (SDP). If SDP is not available, then attacks should be treated with frozen plasma.Intubation or tracheotomy should be considered early in progressive upper airway edema. Patients with attacks could receive adjuvant therapy when indicated (pain management, intravenous fluids). All patients should have on-demand treatment for two attacks and carry their on-demand treatment at all times. The administration of short-term prophylaxis should be considered before surgeries (dental/intraoral surgery, where endotracheal intubation is required), where upper airway or pharynx is manipulated, and before bronchoscopy or endoscopy. Long-term prophylaxis should be considered in all severely symptomatic HAE-1/2 patients. C1 inh concentrate or androgens can be used. Screening children for HAE-1/2 should be deferred until the age of 12 months, and all offspring of an affected parent should be tested.

Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure.

BACKGROUND: We investigated the association between genetic variation in chromosomal region 20p13-p12 (ADAM33 and flanking genes ATRN, GFRA4, SIGLEC1 and HSPA12B) and asthma. Amongst asthmatics, we then investigated the association between genetic variants and asthma severity. We evaluated the effect of environmental tobacco smoke (ETS) exposure in the context of genetic variants. METHODS: In a case-control study, we recruited 423 asthmatic children and 414 non-asthmatic controls (age 5-18 yr). Amongst asthmatics, we measured lung function and extracted data on hospitalisation for asthma exacerbation from medical records. Early-life ETS exposure was assessed by questionnaire. We included 85 single-nucleotide polymorphisms (SNPs) in the analysis. RESULTS: Seventeen SNPs were significantly associated with asthma; one (rs41534847 in ADAM33) remained significant after correction for multiple testing. Thirty-six SNPs were significantly associated with lung function, of which 15 (six ARTN, three ADAM33, five SIGLEC1 and one HSPA12B) remained significant after correction. We observed a significant interaction between 23 SNPs and early-life ETS exposure in relation to lung function measures. For example, for rs512625 in ADAM33, there was significant interaction with ETS exposure in relation to hospitalisations (p(int)  = 0.02) and lung function (p(int)  = 0.03); G-allele homozygotes had a 9.15-fold [95% CI 2.28-36.89] higher risk of being hospitalized and had significantly poorer lung function if exposed to ETS, with no effect of ETS exposure amongst A-allele carriers. CONCLUSION: We demonstrated several novel significant interactions between polymorphisms in 20p13-p12 and early-life ETS exposure with asthma presence and, amongst asthmatics, a significant association with the severity of their disease.

17q12-21 and asthma: interactions with early-life environmental exposures.

BACKGROUND: 17q12-21 polymorphisms are associated with asthma presence and severity across different populations. OBJECTIVE: To extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures. METHODS: We included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry. RESULTS: We found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation. CONCLUSION: Our results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies.

Genetic variation in vascular endothelial growth factor-a and lung function.

RATIONALE: Given the role of vascular endothelial growth factor (VEGF) in lung development, we hypothesized that polymorphisms in VEGF-A may be associated with lung function. OBJECTIVES: The current study was designed to assess the role of genetic variants in VEGF-A as determinants of airway function from infancy through early adulthood. METHODS: Association between five single-nucleotide polymorphisms (SNPs) in VEGF-A and lung function were assessed longitudinally in two unselected birth cohorts and cross-sectionally among infants. Replication with two SNPs was conducted in adults and children with asthma. We investigated the functionality of the SNP most consistently associated with lung function (rs3025028) using Western blotting to measure the ratio of plasma VEGF-A(165b)/panVEGF-A(165) among homozygotes. MEASUREMENTS AND MAIN RESULTS: In two populations in infancy, C-allele homozygotes of rs3025028 had significantly higher VmaxFRC, forced expiratory flow(50), and forced expiratory flow(25-75) compared with other genotype groups. Among preschool children (age 3 yr), C allele of rs3025028 was associated with significantly higher specific airway conductance, with similar findings observed for lung function in school-age children. For FEV(1)/FVC ratio similar findings were observed among adolescents and young adults (birth cohort), and then replicated in adults and schoolchildren with asthma (cross-sectional studies). For rs3025038, plasma VEGF-A(165b)/panVEGF-A(165) was significantly higher among CC versus GG homozygotes (P ≤ 0.02) at birth, in school-age children, and in adults. CONCLUSIONS: We report significant associations between VEGF-A SNP rs3025028 and parameters of airway function measured throughout childhood, with the effect persisting into adulthood. We propose that the mechanism may be mediated through the ratios of active and inhibitory isoforms of VEGF-A(165), which may be determined by alternative splicing.

Croatian children's views towards importance of health care information.

The aim of research was to investigate: the need for health care information of Croatian adolescents aged from 13 to 18 years; the difference in evaluation of the frequency of receiving information between hospitalized and healthy children; if the hospitalized children expectations about the frequency of receiving health care information differed significantly from information they have actually received; whose information was most comprehensible to the hospitalized children (doctors, parents, other health care givers). The children were either hospitalized in the pediatrics departments or were high schools pupils (healthy children). The hospitalized children "Completely agreed" (92.7%) with the statement "When I am sick, I should receive information about my health" in comparison to the healthy children (85.1%). In comparison to healthy children, the hospitalized children assessed that doctors, other health care givers and parents should give them information more frequently. The experience of hospitalized children indicate that they received less information then they have actually excepted. The information received from doctors was mostly in correlation with the understanding of this information. We concluded that the children want to be informed about their health, especially hospitalized children. Health care professionals should offer understandable health care information according to the children's expectation.

Decreased Toll-like receptor 8 expression and lower TNF-α synthesis in infants with acute RSV infection.

BACKGROUND: Toll-like receptors (TLRs) are part of the innate immune system, able to recognize pathogen-associated molecular patterns and activate immune system upon pathogen challenge. Respiratory syncytial virus (RSV) is a RNA virus particularly detrimental in infancy. It could cause severe lower respiratory tract disease and recurrent infections related to inadequate development of anti-viral immunity. The reason could be inadequate multiple TLRs engagement, including TLR8 in recognition of single-stranded viral RNA and diminished synthesis of inflammatory mediators due to a lower expression. METHODS: Intracellular TLR8 expression in peripheral blood monocytes from RSV-infected infants was profiled and compared to healthy adults and age matched controls. Whether the observed difference in TLR8 expression is a transitory effect, infants in convalescent phase (4-6 weeks later) were retested. Specific TLR8-mediated TNF-α production in monocytes during an acute and convalescent phase was analyzed. RESULTS: RSV-infected and healthy infants had lower percentage of TLR8-expressing monocytes than healthy adults whereas decreased of TLR8 protein levels were detected only for RSV-infected infant group. Lower protein levels of TLR8 in monocytes from RSV-infected infants, compared to healthy infants, negatively correlated with respiratory frequency and resulted in lower TNF-α synthesis upon a specific TLR8 stimulation. In the convalescent phase, levels of TLR8 increased, accompanied by increased TNF-α synthesis compared to acute infection. CONCLUSIONS: Lower TLR8 expression observed in monocytes, during an acute RSV infection, might have a dampening impact on early anti-viral cytokine production necessary to control RSV replication, and subsequently initiate an adaptive Th1 type immune response leading to severe disease in infected infants.

The comparison of anthropometrical parameters of the four-year-old children in the urban and rural Slavonia, Croatia, 1985 and 2005.

The aim of the study is to identify the secular trends in the anthropometrical parameters of the 4-year-old children in Slavonski Brod, Slavonia, Croatia, and the nearby rural area by comparing data of height, weight, and mid-arm circumferences from 2005 with the historical control data published in 1985. The cross-sectional study of 342 children, aged 4 years, from Slavonski Brod and the nearby villages was taken in 2005. The body height, weight, and mid-arm circumferences were measured and compared with the historical control data from the study performed in 1985 in the same area using the same methods. The data were compared according to sex and the place of residence. Results show that there were no significant differences in the body height, weight, mid-arm circumference and body mass index (BMI) between the urban and rural children in 2005. The Children in 2005 were significantly shorter (103.7 +/- 8.3 cm vs. 108.3 cm in 1985, P < 0.001, one-sample T test) and had lower weight (17.4 +/- 2.7 kg vs. 17.9 kg, P = 0.001, one-sample T test) compared with their counterparts in 1985. In 2005 there was no significant difference in the body mass index (kg/m2) between girls and boys in total (15.9 +/- 2.12, vs. 16.1 +/- 1.8, p = 0.262, Independent samples t-test). Differences between the urban and rural parameters have disappeared over the last 20 years, which could be assigned to life-style changes in the rural areas.

Allergic Diseases and Atopy Among Schoolchildren in Eastern Croatia.

A cross-sectional study was carried out in Brod-Posavina County, Croatia, to assess the prevalence of allergic diseases and atopy, as well as to investigate the possible etiologic factors for asthma, allergic rhinitis and eczema in childhood. The study included 1687 schoolchildren aged 10-11 years. Data were collected using standardized International Study of Asthma and Allergies in Childhood (ISAAC) Phase II written questionnaire. Skin prick tests were performed to provide an objective measure of atopy, defined as skin reactivity to one or more allergens. Lifetime prevalence of wheezing was 22.7%, rhinitis symptoms 22.5%, and eczema symptoms 17.9%. Period prevalence in the past 12 months was 7.9% for attacks of wheezing, 9.9% for rhinoconjunctivitis symptoms, and 10.1% for eczema symptoms. Of the children in which skin prick test was performed, 20.2% were positive for at least one of the allergens used, with house dust mite sensitization being the most frequent one. Risk factors for allergic disease include allergic disease in family, atopy, sensitization to indoor and outdoor allergens, and environmental tobacco smoke exposure at home. International comparison with the results of other ISAAC Phase II studies showed the Brod-Posavina County to be an area with moderate prevalence of atopy and current asthma symptoms.

Emotional and physical abuse in family: survey among high school adolescents.

AIM: To determine the prevalence of different forms of child abuse among high school pupils in Slavonski Brod, Croatia. METHOD: The study included 2140 first and fourth-grade pupils aged between 14 and 18 years from all 10 high schools in Slavonski Brod and the area (4 grammar and 6 vocational schools). The pupils were asked to complete an anonymous structured questionnaire during a 45-minute class. The questionnaire, developed for the needs of this study, collected basic demographic data on family life and experience of emotional or physical abuse. RESULTS: First-grade pupils were more satisfied with their family life than fourth-grade pupils (96.9% vs 91.3%, P<0.001, chi(2) test). The feeling of being insufficiently loved or unloved was reported by 17.5% of the first-grade and 24.6% of the fourth-grade pupils and a greater percentage of pupils whose parents were divorced or who had a step-parent. Almost 80% of pupils had been verbally or nonverbally punished for disobedience. Emotional abuse was significantly associated with female sex (Nagelkerke R(2)=0.87, beta=0.474, P=0.028), younger age (beta=1.263, P<0.001), and alcoholism in the family (beta=2.037, P<0.001. Physical punishment for disobedience was reported significantly more often by first-grade than fourth-grade pupils (15.6% vs 12.9% P=0.021, chi(2) test). Physical abuse was significantly associated (Nagelkerke R2=0.69) with younger age (Beta=0.379, P<0.012), emotional abuse (Beta=0.665, P<0.002), alcoholism in the family (Beta=1.791, P<0.001) and the lack of parental love (Beta=-0.645, P<0.001). Possible sexual molestation was admitted by 6.0% boys and 3.3% girls. CONCLUSION: Most high school pupils in Slavonski Brod were satisfied with their life at home. Disobedience was usually punished verbally or by aggressive behavior of the parents. Physical punishment was less common and usually did not result in serious injuries.

Sources of infection in childhood tuberculosis in a region of east Croatia.

Possible sources of tuberculosis (TBC) infection in children have been assessed in a retrospective epidemiological study covering a north-east region of Croatia in which the incidence of childhood tuberculosis has been increasing since the war in 1991-1995. During the past decade (1993-2003), 271 children up to 18 years of age have been referred for hospital care because of known contacts with tuberculosis (142 children, group A) or because of indicative clinical signs and symptoms (129 children, group B). Possible sources of infection were identified on the basis of medical documentation and field investigations. Frequencies of source identification for different age groups were compared. In group A, the exposure took place most often within the family (parents, grandparents, siblings, 129 of 142 children, 90.87%). Relatives, neighbors, friends and schoolmates accounted for 9.2%. In group B, possible sources of infection were identified for 44 of 129 children (34.1%) and were within the family for 16 of those 44 (36.4%). Evidenced contact with tuberculosis was more usual among younger children (0-9 years of age, 65.5%) in group A than among the older ones (10-18 years of age, 34.5%). In group B, contacts with tuberculosis were equally distributed (50.0%) among younger and older children. High proportion of unrecognized contacts in children having clinical signs and symptoms indicative of tuberculosis (group B, 85 of 129, 65.9%) opens the possibility that extra-familial exposure to tuberculosis occurs more often than expected regardless of the age of children.

Circulating levels of hormones, lipids, and immune mediators in post-traumatic stress disorder - a 3-month follow-up study.

A number of peripheral blood analytes have been proposed as potential biomarkers of post-traumatic stress disorder (PTSD). Few studies have investigated whether observed changes in biomarkers persist over time. The aim of this study was to investigate the association of combat-related chronic PTSD with a wide array of putative PTSD biomarkers and to determine reliability of the measurements, i.e., correlations over time. Croatian combat veterans with chronic PTSD (n = 69) and age-matched healthy controls (n = 32), all men, were assessed at two time points separated by 3 months. Serum levels of lipids, cortisol, dehydroepiandrosterone-sulfate (DHEA-S), prolactin, and C-reactive protein were determined. Multiplex assay was used for the simultaneous assessment of 13 analytes in sera: cytokines [interferon-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-6, TNF-α], adhesion molecules (sPECAM-1, sICAM-1), chemokines (IL-8 and MIP-1α), sCD40L, nerve growth factor, and leptin. Group differences and changes over time were tested by parametric or non-parametric tests, including repeated measures analysis of covariance. Reliability estimates [intraclass correlation coefficient (ICC) and kappa] were also calculated. Robust associations of PTSD with higher levels of DHEA-S [F(1,75) = 8.14, p = 0.006)] and lower levels of prolactin [F(1,75) = 5.40, p = 0.023] were found. Measurements showed good to excellent reproducibility (DHEA-S, ICC = 0.50; prolactin, ICC = 0.79). Serum lipids did not differ between groups but significant increase of LDL-C after 3 months was observed in the PTSD group (t = 6.87, p < 0.001). IL-8 was lower in the PTSD group (t = 4.37, p < 0.001) but assessments showed poor reproducibility (ICC = -0.08). Stable DHEA-S and prolactin changes highlight their potential to be reliable markers of PTSD. Change in lipid profiles after 3 months suggests that PTSD patients may be more prone to hyperlipidemia. High intra-individual variability in some variables emphasizes the importance of longitudinal studies in investigations of PTSD biomarkers.

Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells.

BACKGROUND: Regulatory T cells (Tregs) play a key role in immune homeostasis in vivo. Tregs have a critical role in preventing the development of autoimmune diseases and defects in Treg function are implicated in various autoimmune disorders. Individuals with posttraumatic stress disorder (PTSD) have higher prevalence of autoimmune disorders than the general population. We hypothesized that war veterans with PTSD would exhibit a decreased number and/or altered phenotype of Tregs. METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) of patients with PTSD (N = 21) (mean age = 45.9) and age-matched healthy controls (N = 23) (mean age = 45.7) to determine the proportion of Tregs and their phenotype according to the expression of CD127 and HLA-DR markers which describe the differentiation stages of Tregs. In addition, we analyzed the expression of membrane ectoenzyme CD39 on Tregs of the study groups, an important component of the suppressive machinery of Tregs. RESULTS: We found no differences in the proportion of Tregs between PTSD patients and controls, but PTSD patients had a higher percentage of CD127(-)HLA-DR(-) Tregs and a lower percentage of CD127(lo)HLA-DR(+) Tregs compared to controls. There was no difference in expression of CD39 on Tregs of the study groups. CONCLUSIONS: Although the proportions of Tregs in PTSD patients were unchanged, we found that they exhibit a different phenotype of Tregs that might be less suppressive. Impaired differentiation and function of Tregs is likely involved in disruption of immune homeostasis in PTSD.

The increased type-1 and type-2 chemokine levels in children with acute RSV infection alter the development of adaptive immune responses.

Severe RSV infections and frequent recurrence could be related to the altered polarization of type-2/type-1 T cells. This increases the importance of determining distinctive chemokines and chemokine receptor profiles on memory T cells. We analyzed systemic adaptive T cell response in the acute (n=17) and convalescent phase (n=7) of RSV-infected children, in the acute (n=11) and convalescent phase (n=6) of children with other viral respiratory infections (adenovirus and influenza virus), and in healthy children (n=18). Expression of CCR4 and CXCR3 on effector-memory (TEM) and central-memory (TCM) T cells was compared between tested groups. Serum concentrations of specific chemokines were determined. High CXCL10 levels were detected in acutely infected children regardless of virus pathogen, whereas increased CCL17 production was RSV-specific. Higher percentages of CCR4+ CD4 TEM cells in acute RSV infection were accompanied with higher percentages of CXCR3+ CD8 TEM cells, whereas the development of long-lived memory CXCR3+ CD4 and CD8 TCM cells seems to be compromised, as only children with other viral infections had higher percentages in the convalescent phase. Presence of type-2 and type-1 adaptive antiviral immune response, together with insufficient development of long-lived type-1 T cell memory, could play an important role in RSV pathogenesis and reinfection.

Interferon-γ release assay for the diagnosis of latent tuberculosis in children younger than 5 years of age.

BACKGROUND: There are limited data available on interferon-γ release assay (IGRA) performance in children up to 5 years of age, with documented exposure to active tuberculosis (TB). The aim of this study was to evaluate (1) the influence of infectivity of adult source cases on test results, (2) the impact of age, and (3) the level of agreement, between IGRA and tuberculin skin test (TST) results. METHODS: A total of 142 Bacille Calmette-Guerin-vaccinated children up to 5 years of age were investigated because of a history of exposure to active TB. QuantiFERON-TB Gold In-Tube IGRA (QFT) and TST assays were performed. RESULTS: Test results were significantly influenced by positive finding of cavitary lesions (QFT, odds ratio [OR] = 6.15; TST, OR = 7.48) and positive acid-fast bacilli (QFT, OR = 4.01; TST, OR = 4.47) in active TB contacts. QFT resulted in 1 indeterminate response (0.7%), attributable to low mitogen. There was no evidence for age having any effect on QFT performance. The 2 tests showed a moderate overall concordance (89%; κ = 0.591) at a TST cutoff value of ≥ 10 mm. CONCLUSIONS: Association of positive QFT and TST results with risk factors for infection in child contacts (presence of cavitary lesions and acid-fast bacilli smear positivity in index cases) suggests that both the tests have good diagnostic accuracy. However, there was significant discord between results of the 2 tests that could not be definitively resolved. Thus, in a high-risk population of children up to 5 years of age, both tests (QFT and TST) should be performed and the child should be considered infected if either or both tests are positive.

Effect of house dust mite immunotherapy on transforming growth factor beta1-producing T cells in asthmatic children.

BACKGROUND: Recent evidence suggests that regulatory T cells (Treg cells) and immunosuppressive cytokines, such as transforming growth factor BETA1 (TGF-BETA1) and interleukin 10 (IL-10), may have a role in clinically effective allergen specific immunotherapy (SIT). OBJECTIVE: To evaluate the effect of SIT on the induction of Treg cells in house dust mite-allergic children and on the expression of specific Treg cell markers (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], IL-10, and TGF-BETA1). METHODS: In this uncontrolled open-label study, the percentage of peripheral blood CD4+ Treg cells (CD69 CD45RO+CTLA-4+ and CD3+CD4+CD25+FOXP3+) and the expression of molecules associated with their functions (CTLA-4, TGF-BETA1, and IL-10) were analyzed using flow cytometry in 16 children allergic to house dust mites before and at 3 and 12 months of subcutaneous SIT. Clinical variables, such as symptom score, medication requirements, forced expiratory volume in 1 second, peak expiratory flow rate, and serum IgE levels, were also determined. Ten healthy children were included as controls. RESULTS: All the clinical variables improved during immunotherapy. The percentage of CD4+CD25+CD69-CD45RO+ Treg cells remained unchanged. The percentage of CTLA-4+ -expressing Treg cells transiently increased after 3 months of immunotherapy, whereas the percentage of FOXP3+ Treg cells did not change after 1 year of immunotherapy. Levels of IL-10+ cells transiently decreased after 3 months of immunotherapy. Four children who required inhaled fluticasone propionate administration for significant symptom worsening had no statistically significant increase in TGF-BETA1-secreting T cells at 12 months of SIT, in contrast to 12 children without inhaled corticosteroid treatment. CONCLUSIONS: The increase in TGF-BETA1-positive T cells only in children without significant symptom worsening requiring inhaled corticosteroid treatment limits the usefulness of TGF-BETA1 in monitoring response to allergen immunotherapy.

Increasing rate of childhood tuberculosis in a region of east Croatia.

BACKGROUND: The incidence of childhood tuberculosis as well as the number of children being in contact with persons having tuberculosis has increased in the region of Slavonski Brod during the past decade (1993-2003). The region is located in east Croatia along the border with Bosnia and close to the besieged and destroyed town of Vukovar. The region was heavily involved in recent military activities and migrations in Croatia and Bosnia (1991-1995). Before the war, the population was reasonably well situated, educated and provided with health services. METHODS: Routine clinical and epidemiological methods for the diagnosis of tuberculosis were used. RESULTS: A total of 225 cases of tuberculosis were discovered among 271 suspected cases in a total number of 19 623 children below 18 years of age admitted during the last decade to the county hospital (1.38%). The number increased from three patients with tuberculosis in 1993 to 59 in 2003. Discharge diagnoses were: latent infection 40.1%, specific hilar lymphadenopathy 22.1%, primary lung tuberculosis 18.0%, postprimary tuberculosis 3.0%, and contact with infected person but otherwise normal findings 16.9%. The infection was usualy (53.1%) acquired within the family, more often so in younger patients. Bacteriological cultures were positive in 19 of 117 patients with tuberculosis (16.4%). Antituberculosis drug treatment was carried out to completion in all children. Resistance was not encountered. CONCLUSION: The authors attribute high incidence of childhood tuberculosis in the region of Slavonski Brod, the second highest incidence in Croatia, to the sequellae of migrations during military activities in Croatia and Bosnia (1991-1995) and to the post-war recession.