Respiratory infections have been implicated in the origin and exacerbation of asthma in a variety of ways; however, systemisation of this knowledge in a way helpful for disease management remains suboptimal. Several conceptual issues need to be taken into account: the fact that the effects of an infection may vary according to genetic background, the current immune status of the host, and parallel environmental stimuli, in addition to the particular infectious agent itself. Moreover, childhood is a very special period because of the continuous processes taking place, such as neural, immune and respiratory maturation. Epidemiological studies have convincingly demonstrated that the majority of asthma exacerbations, in both adults and children, follow viral upper respiratory tract infections. Asthma exacerbations are still often unresponsive to current asthma treatment, and new therapeutic approaches are required. This review presents current knowledge on the associations between infection and exacerbation of established asthma with respect to definitions, epidemiology, mechanisms and treatment.

{Exhaled breath temperature (EBT) has been suggested as a non-invasive surrogate marker of airway inflammation in asthma. The aim of the study was to evaluate differences in EBT between periods of controlled disease and during exacerbations in children with virus-induced asthma.|Twenty-nine children (aged 6-14 years) with a history of intermittent, virus-induced asthma were included in this case-control study. Cases presented with a common cold and/or mild exacerbation of asthma, while controls were free of asthmatic or common cold symptoms during the previous 6 weeks. A baseline questionnaire was obtained. Atopy assessment, central temperature and a spirometric measurement were recorded. EBT was measured with a new device (Delmedica, Singapore). A nasal wash (for identification of common respiratory viruses) was obtained.|Twenty-four children (12 from each group) completed the study. Groups were homogeneous with respect to baseline characteristics. PCR revealed the presence of a virus in 3 out of 17 controls and 10 out of 12 cases (17.6 and 83.3%, respectively

The performance of QuantiFERON-tuberculosis (TB) Gold-In-Tube assay was compared with the tuberculin skin test for the diagnosis of TB among children. It was shown that among non-Bacille Calmette Guèrin immunized children, agreement between tests was excellent both in those with TB disease and in TB contacts. Among Bacille Calmette Guèrin-immunized children, agreement was fair in those with active disease and poor among TB contacts. It is concluded that QuantiFERON-TB Gold-In-Tube compares with the tuberculin skin test in the diagnosis of TB disease and latent tuberculosis infection in TB contacts among children and has enhanced specificity.

Fish allergens represent one of the most common causes of adverse reactions to food worldwide. Double-blind placebo-controlled food challenges (DBPCFC) are the gold standard for food allergy diagnosis. However, no standardised recipes are available for common food allergens such as fish, and a well trained dietitian is essential for creating and standardising them. The present study aimed to create and standardise recipes for use in DBPCFCs to fish.|Three recipes were prepared. Employing a standardised procedure, a total of 35 panelists evaluated the different matrices using an evaluation form. A paired comparison test was used to estimate total evaluation's outcome. Fish allergic patients were challenged with different fish species blinded with the selected matrix and evaluated the recipe using the same form.|From a base recipe and step-by-step modifications, a low fat recipe was selected among other recipes tested, which proved to be appropriate for fish blinding, in terms of taste, odour, appearance and blinding. Patients challenged with the final matrix found it acceptable, no matter which fish type was used.|In this pilot study, a recipe with satisfactory organoleptic characteristics was developed and validated for DBPCFC to fish.

Inquiries into the relationships between viral respiratory tract illnesses and the inception and exacerbation of asthma are being facilitated by recent advances in research approaches and technology. In this article we identify important knowledge gaps and future research questions, and we discuss how new investigational tools, including improved respiratory tract virus detection techniques, will permit current and future researchers to define these relationships and the host, virus, developmental, and environmental mechanisms that regulate them. A better understanding of these processes should facilitate the development of improved strategies for the prevention and treatment of virus-induced wheezing illnesses and asthma exacerbations and, possibly, the ultimate goal of discovering effective approaches for the primary prevention of asthma.

Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active-passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg(+)) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg(+)/HBeAg(-) mothers. Blood was collected from 46 HBsAg(+) mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg(+) mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon (IFN)-γ concentrations were determined by ELISA. HBsAg-induced production of IL-2, IL-5, IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination. All neonates were HBsAg(-) and responded to vaccination. Increased IFN-γ production following HBcAg stimulation was seen in 30.4% of neonates born to HBsAg(+)/HBeAg(-) mothers. Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation, whereas IL-5, IL-6 and IL-10 cytokine responses were not significantly different. Almost one-third of uninfected neonates developed viral antigen-induced IFN-γ production, suggesting that they had been exposed to virions or viral derivatives. This encounter, however, did not impair their T-cell responses to vaccination.

Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-alpha) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-alpha production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-alpha production until the age of 6 months and inhibits IFN-alpha responses triggered by the TLR7 pathway.

alpha-Lactalbumin (alpha-La) is a major cow's milk (CM) allergen responsible for allergic reactions in infants.|We performed molecular, structural, and immunologic characterization of alpha-La.|Recombinant alpha-lactalbumin (ralpha-La) was expressed in Escherichia coli, purified to homogeneity, and characterized by means of mass spectrometry and circular dichroism, and its allergenic activity was studied by using microarray technology, as well as in a basophil histamine release assay. IgE epitope mapping was performed with synthetic peptides.|According to circular dichroism analysis, ralpha-La represented a folded protein with a high thermal stability and refolding capacity. ralpha-La reacted with IgE antibodies from 57.6% of patients with CM allergy (n = 66) and induced the strongest basophil degranulation with sera from patients with CM allergy who had exhibited gastrointestinal symptoms or severe systemic reactions on CM exposure. ralpha-La contained sequential and conformational IgE epitopes. Superposition of IgE-reactive peptides onto the 3-dimensional structure of alpha-La revealed a close vicinity of the N- and C-terminal peptides within a surface-exposed patch.|ralpha-La can be used for the diagnosis of patients with severe allergic reactions to CM and serves as a paradigmatic tool for the development of therapeutic strategies for CM allergy.

Mean diameter or longest diameter are the 2 most frequently used parameters for wheal response assessment after skin prick testing (SPT). We aimed to compare these 2 parameters taking as gold standard the surface of the wheal skin response.|Patients suspected of having an allergic reaction against inhalant allergens have been skin prick tested using the Pan-European GA(2)LEN SPT panel. Fifteen minutes later, macroscopically evident wheal and flare reactions were marked with a pen and transferred to paper with a transparent scotch tape. Each paper-transferred wheal was scanned with an ordinary scanner, and its surface-corresponding maximum perpendicular diameters and longest diameters were measured using a computer software application for image recognition, developed for this purpose. Correlation coefficients (Spearman's rho) between surfaces and respective mean (rho(mean)) or longest (rho(longest)) diameters were calculated and subsequently compared.|1,554 SPTs were performed in 74 patients. In 264, a macroscopically evident wheal and flare response was observed. Both mean and longest diameters correlated significantly with the wheal surfaces. However, rho(longest) was statistically significantly larger than rho(mean) when the surface of the wheal was >17 mm(2) (rho(longest) > 0.860 vs. rho(mean) < 0.660; p < 0.05).Such a surface corresponds to a maximum diameter of approximately 7 mm and a mean diameter of approximately 6 mm. Thus, the larger the surface of the wheal, the more appropriate the usage of the longest diameter.|The longest wheal diameter alone seems to be a better surrogate marker of the wheal surface in comparison with the mean diameter. In addition, it is easier and faster to measure. Therefore, we propose this as the optimal methodology to evaluate SPTs.