Is mold sensitization associated with severe asthma exacerbation in children?

BACKGROUND: Mold sensitization has been reported as a factor associated with severe asthma exacerbation (SAE). OBJECTIVE: To identify the factors associated with SAE in asthmatic children, particularly mold sensitization. METHODS: The asthmatic children recruited into this case-control study were classified into an SAE and an outpatient (OPD) group, based on their histories of asthma exacerbation with hospitalization in the preceding year. A skin prick test to common aeroallergens was performed. Possible SAE risk factors were analyzed. RESULTS: A total of 102 patients were enrolled. The 51 patients in the SAE group were significantly younger than the 51 in the OPD group (mean ages of 6.8 ± 3.3 vs 8.7 ±3.2 years, p = 0.005). Higher proportions of patients with partly controlled or uncontrolled asthma were found in the SAE group (41.2% vs 17.6%, p = 0.009). The incidences of a paternal history of atopy, an emergency department visit, and a history of systemic corticosteroid administration in the preceding year were significantly higher for the SAE group (35.3% vs 15.7%, p = 0.023; 100% vs 43.5%, p < 0.001; and 100% vs 31.4%, p < 0.001; respectively). The multivariate logistic regression analysis showed that risk factors for SAE were Alternaria sensitization (adjusted odds ratio [AOR] 3.00; 95% CI 1.09-8.3; p = 0.033), patients who were younger than 6 years (AOR 3.28; 95% CI 1.17-9.18; p = 0.024), and a paternal history of atopy (AOR 2.94; 95% CI 1.05-8.25; p = 0.040). CONCLUSIONS: Alternaria sensitization, an age younger than 6 years, and a paternal history of atopy were associated with SAE in asthmatic children.

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis.

Atopic dermatitis (AD) is one of the most common skin conditions in humans. AD affects up to 20% of children worldwide and results in morbidity for both patients and their caregivers. The basis of AD is an interplay between genetics and the environment characterized by immune dysregulation. A myriad of mutations that compromise the skin barrier and/or immune function have been linked to AD. Of these, filaggrin gene (FLG) mutations are the most evidenced. Many other mutations have been implicated in isolated studies that are often unreplicated, creating an archive of genes with potential but unconfirmed relevance to AD. Harnessing big data, polygenic risk scores (PRSs) and genome-wide association studies (GWAS) may provide a more practical strategy for identifying the genetic signatures of AD. Epigenetics may also play a role. Staphylococcus aureus is the most evidenced microbial contributor to AD. Cutaneous dysbiosis may result in over-colonization by pathogenic strains and aberrant skin immunity and inflammation. Aeroallergens, air pollution, and climate are other key environmental contributors to AD. The right climate and/or commensals may improve AD for some patients.

Food sensitization and food allergy in allergic Thai patients from a tertiary care center in Thailand.

BACKGROUND: A skin prick test (SPT) and food challenge test (OFC) are useful in identification of food sensitization and food allergy. OBJECTIVE: To evaluate food allergen sensitization by SPT and food allergy by OFC in allergic Thai patients. METHODS: SPTs for common food allergens were performed on allergic patients at Siriraj Hospital, Bangkok, Thailand, from 2011 to 2015. An OFC was performed in positive food SPT patients with informed consent. RESULTS: SPTs to food were positive in 539 (20%) out of 2,678 allergic patients (73.8% were < 10 years old). Crab was the most common sensitized food in each year of the study period. In patients aged < 1 year, the most common sensitized foods were egg white (23.8%) and wheat (22.2%), while shrimp was for patients aged > 10 years (25%). A positive OFC was found in 29 (26.1%) out of the 111 OFCs performed (9.1% in patients with asthma, 28.6% in allergic rhinitis and 26.3% in food allergy). Positive OFCs were found for 60% of the crab, 35.7% of the egg yolk, and 31% of the cow's milk OFCs. Compared to OFC, SPT showed high specificity (71%-100%) but low sensitivity (0%-40%). The percentage of sensitization to egg white, egg yolk, wheat, soy, and peanut significantly increased (p < 0.05) from 2011 to 2015. CONCLUSION: The sensitization to egg white, egg yolk, wheat, soy, and peanut significantly increased and crab was the most common sensitized food. Food allergy in patients with allergic rhinitis was as common as in patients diagnosed food allergy.

Prick and intradermal skin tests in patients with severe hymenoptera sting allergy using commercial versus in-house allergen extracts.

BACKGROUND: Fire ant, honey bee, and wasp allergen extracts are useful in the diagnosis and treatment of severe Hymenoptera allergic patients. OBJECTIVE: To evaluate the result of skin prick test (SPT) and intradermal test (ID) compared between local and commercial insect allergen extracts in patients with severe Hymenoptera sting allergy. METHODS: SPT and ID using local and commercial insect allergen extracts were performed. Specific IgE (sIgE) to honey bee, wasp, and fire ant; component-resolved diagnosis (CRD); (rApi m1, rApi m2, rApi m3, rApi m5, rApi m10, rVes v5, rPol d5, and rVes v1); and, cross-reactive carbohydrate determinant (CCD) were performed. RESULTS: Twenty-seven patients were included. Twenty-five had anaphylaxis, and 2 had severe systemic skin reaction. Positive skin test (SPT and/or ID) result from local and commercial allergen extracts was 74% vs. 67% for fire ant, 48% vs. 59% for honey bee, and 52% vs. 74% for yellowjacket. Local and commercial allergen extracts showed substantial agreement for fire ant (k = 0.647, p = 0.001) and honey bee (k = 0.632, p = 0.001), and moderate agreement for wasp (k = 0.547, p = 0.001). When compared with sIgE subtracted with CCD and/or CRD, skin test results of local fire ant allergen extract showed higher sensitivity (87% vs. 67%), specificity (42% vs. 33%), and accuracy (67% vs. 52%) than commercial extract. Commercial honey bee and wasp showed higher sensitivity (62% vs. 50%, 85% vs. 65%) and accuracy (63% vs. 52%, 78% vs. 70%), respectively. CONCLUSIONS: SPT and ID with local or commercial insect venoms could help in confirming and/or identifying the causative insects.

Clinical Characteristics of Allergy to Hymenoptera Stings.

OBJECTIVE: The purpose of this study was to evaluate the clinical characteristics of allergy to stings from the Hymenoptera order of insects in a hospital in Thailand. METHODS: A descriptive retrospective analytical study was carried out in inpatients and outpatients suffering from Hymenoptera stings from 2009 to 2013 in Siriraj Hospital. RESULTS: Medical records of 386 patients with an allergy to Hymenoptera stings were evaluated. Anaphylaxis was more common in patients younger than 15 years, who comprised 22.3% of patients in this study. The most common sting type was from wasps (58.3%). Eighty-five percent of patients sought medical treatment less than 24 hours after being stung. A systemic reaction and anaphylaxis were found in 9.9% and 4.4% of subjects, respectively. In 17 patients with anaphylaxis, only 11 patients (64.7%) received an epinephrine (adrenaline) injection as treatment, and only 8 (47.1%) received epinephrine autoinjectors or epinephrine-prefilled syringes to prevent a possible subsequent severe reaction. Significantly more patients younger than 15 years received epinephrine for prevention of an allergic reaction than did those older than 15 years (87.5% vs 11.7%, P < 0.001). Antibiotics were given to 43.0% of patients. CONCLUSIONS: Anaphylaxis from Hymenoptera stings was more common in children than in adults. Only half of the patients visited the emergency room within 1 hour of being stung. Overuse of antibiotics and underuse of epinephrine were found. More information about Hymenoptera stings should be provided to the public, and the use of epinephrine should be encouraged in the case of severe reactions and anaphylaxis.

Immune Mechanisms Involved in Schistosoma mansoni-Cathepsin B Vaccine Induced Protection in Mice.

A vaccine against schistosomiasis would contribute to a long-lasting decrease in disease spectrum and transmission. Our previous protection studies in mice using Schistosoma mansoni Cathepsin B (Sm-Cathepsin B) resulted in 59 and 60% worm burden reduction with CpG oligodeoxynucleotides and Montanide ISA720 VG as adjuvants, respectively. While both formulations resulted in significant protection in a mouse model of schistosomiasis, the elicited immune responses differed. Therefore, in this study, we aimed to decipher the mechanisms involved in Sm-Cathepsin B vaccine-mediated protection. We performed in vitro killing assays using schistosomula stage parasites as targets for lung-derived leukocytes and serum obtained from mice immunized with Sm-Cathepsin B adjuvanted with either Montanide ISA 720 VG or CpG and from non-vaccinated controls. Lung cells and immune sera from the Sm-Cathepsin B + Montanide group induced the highest killing (63%) suggesting the importance of antibodies in cell-mediated parasite killing. By contrast, incubation with lung cells from Sm-Cathepsin B + CpG immunized animals induced significant parasite killing (53%) independent of the addition of immune serum. Significant parasite killing was also observed in the animals immunized with Sm-Cathepsin B alone (41%). For the Sm-Cathepsin B + Montanide group, the high level killing effect was lost after the depletion of CD4+ T cells or natural killer (NK) cells from the lung cell preparation. For the Sm-Cathepsin B + CpG group, high parasite killing was lost after CD8+ T cell depletion, and a reduction to 39% was observed upon depletion of NK cells. Finally, the parasite killing in the Sm-Cathepsin B alone group was lost after the depletion of CD4+ T cells. Our results demonstrate how the different Sm-Cathepsin B formulations influence the immune mechanisms involved in parasite killing and protection against schistosomiasis.

Great flood and aeroallergen sensitization in children with asthma and/or allergic rhinitis.

BACKGROUND: Flooding may affect aeroallergen sensitization. OBJECTIVE: To evaluate aeroallergen sensitization in children with asthma and/or allergic rhinitis (AR) by skin prick test (SPT) before and after the great flood of 2011 in Bangkok, Thailand. METHODS: The study was performed retrospectively in asthma and/or AR children (aged 0-18 years) in Siriraj Hospital, Bangkok, Thailand from 2009 to 2013. All of the cases received SPT with common aeroallergens. RESULTS: SPTs were performed from 2009-2013 in a total of 2,010 asthma and/or AR children and 58.2% and 60.5% showed positive results, respectively. Poly-sensitization to aeroallergens was found in 67.5% of asthma and 67.0% of AR SPT-positive patients. In the study period, Dermatophagoides pteronyssinus (Dp) and Dermatophagoides ferinae (Df) were the most common causes of aeroallergen sensitization (82.4% and 76.5%, respectively), followed by American cockroach (43.5%). After the severe flood in Bangkok in 2011, the trend of sensitization to American cockroach, Bermuda grass, Johnson grass, and Cladosporium spp. significantly decreased. However, the trend of sensitization to dog and Alterneria allergens in 2010 studied cases, significantly increased. During the study period, mean wheal diameter (MWD) of dog SPT was significantly associated with asthma severity, while the MWD of Dp SPT was significantly associated with AR severity. CONCLUSIONS: The aeroallergen sensitizations patterns had changed from previous years compared to the year during or after the flood. Thus, the great flood may have had a major impact on types of sensitization and the clinical patterns of airway allergy. Further confirmed by a prospective study is warranted.

Durability and correlates of vaccine protection against Zika virus in rhesus monkeys.

An effective Zika virus (ZIKV) vaccine will require long-term durable protection. Several ZIKV vaccine candidates have demonstrated protective efficacy in nonhuman primates, but these studies have typically involved ZIKV challenge shortly after vaccination at peak immunity. We show that a single immunization with an adenovirus vector-based vaccine, as well as two immunizations with a purified inactivated virus vaccine, afforded robust protection against ZIKV challenge in rhesus monkeys at 1 year after vaccination. In contrast, two immunizations with an optimized DNA vaccine, which provided complete protection at peak immunity, resulted in reduced protective efficacy at 1 year that was associated with declining neutralizing antibody titers to subprotective levels. These data define a microneutralization log titer of 2.0 to 2.1 as the threshold required for durable protection against ZIKV challenge in this model. Moreover, our findings demonstrate that protection against ZIKV challenge in rhesus monkeys is possible for at least 1 year with a single-shot vaccine.

Comparison of different local and imported histamine concentrations used as a skin prick test positive control.

BACKGROUND: The skin prick test (SPT) is a valid and approved tool that is used to diagnose atopic diseases. The SPT is accurate, safe, simple and inexpensive. However, the histamine concentration used as a positive control in the SPT varies among centers. OBJECTIVE: To compare SPT results using different concentrations of locally-prepared and imported histamine solutions. METHOD: This prospective, randomized, double-blind, self-controlled study was performed in healthy adult volunteers. The SPT was performed using 4 concentrations of histamine solutions (imported, 1 mg/mL; locally-prepared, 1, 5 and 10 mg/mL). Locally-prepared histamine positive controls were prepared from histamine biphosphate monohydrate using sterile technique. RESULTS: Seventy-five adult volunteers (mean age, 36 years) were included in the study. Eight volunteers were male and 9 had a history of atopy. Mean wheal diameter (MWD) for imported histamine was 3.49 mm for a concentration of 1 mg/mL, and that of locally-prepared histamine was 2.94 mm, 5.05 mm and 5.52 mm for concentrations of 1, 5 and 10 mg/mL histamine, respectively. Negative SPT results (MWD <3 mm) were found in 11 subjects (14.7%) who received imported histamine and 26 subjects (34.7%) who received the locally-prepared histamine at concentration of 1 mg/mL. All subjects tested with locally-prepared histamine at concentrations of 5 and 10 mg/mL had a MWD > 3 mm. CONCLUSIONS: Locally-prepared histamine base at concentrations of 5 and 10 mg/mL yielded better positive results than both imported and locally-prepared histamine at a concentration of 1 mg/mL.

A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis.

BACKGROUND: Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual's quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. METHOD: Our group has chosen Schistosoma mansoni (Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels. RESULTS: The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60%, 6%, and 56%, respectively in immunized animals compared to controls (P = 0.0002, P < 0.0001, P = 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-γ, IL-12, and TNF-α, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls. CONCLUSION: The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.