Category: U.S. National Library of Medicine (NIH)

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Math-free guides for glycerin and allergens at variable subcutaneous injection volumes: How’s my dosing? Update.

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Math-free guides for glycerin and allergens at variable subcutaneous injection volumes: How’s my dosing? Update.

Ann Allergy Asthma Immunol. 2016 Mar 24;

Authors: Grier TJ, Converse LM, Rekkerth DJ, Renahan KE

Abstract
BACKGROUND: Current summaries of effective maintenance dose ranges for subcutaneous immunotherapy (SCIT) are based on administration of 0.5-mL volumes. Extract formulations delivering equivalent dose ranges for practices using different injection volumes have not been reported, and calculation of the final glycerin concentrations in these solutions remains an inconvenient and repetitive process.
OBJECTIVES: To create math-free guides for allergen doses and glycerin concentrations that identify the extract concentrate volumes required to deliver doses within the ranges cited in the 2011 immunotherapy practice parameters for clinicians using 5.0-mL maintenance vials and injection volumes ranging from 0.2 to 1.0 mL.
METHODS: Algebraic calculations were performed to determine the specific combinations of extract concentrate strengths, volumes of these products in patient vaccines, and injection volumes needed for administration of target allergen doses spanning the current SCIT practice parameter recommendations.
RESULTS: For each product or group (nonstandardized extracts), tables were constructed to define the allergen doses provided by various combinations of extract concentrate volumes and injection volumes. The values within the effective dose ranges for each product were highlighted to facilitate comparisons of specific conditions relevant to allergy specialists. Glycerin tables were also created to permit convenient assessments of the final concentrations of this stabilizer in patient prescriptions.
CONCLUSIONS: SCIT dosing and glycerin tables are useful tools to assist allergists with practice decisions that involve variable patient formulas and injection volumes and can help identify suitable conditions for treatment of patients presenting with diverse allergen sensitivities and specificity profiles.

PMID: 27017565 [PubMed – as supplied by publisher]

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TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease.

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TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease.

J Immunol. 2016 Mar 25;

Authors: Kourepini E, Paschalidis N, Simoes DC, Aggelakopoulou M, Grogan JL, Panoutsakopoulou V

Abstract
T cell Ig and ITIM domain receptor (TIGIT), expressed on T, NK, and regulatory T cells, is known as an inhibitory molecule that limits autoimmunity, antiviral and antitumor immunity. In this report, we demonstrate that TIGIT enhances Th2 immunity. TIGIT expression was upregulated in activated Th2 cells from mice with experimental allergic disease and in Th2 polarization cultures. In addition, its high-affinity ligand CD155 was upregulated in mediastinal lymph node dendritic cells from allergic mice. In an in vitro setting, we observed thatTigitexpression in Th2 cells and its interaction with CD155 expressed in dendritic cells were important during the development of Th2 responses. In addition, blockade of TIGIT inhibited Th2, but had no effect on either Th1 or Th17 polarization. In vivo blockade of TIGIT suppressed hallmarks of allergic airway disease, such as lung eosinophilia, goblet cell hyperplasia, Ag-specific Th2 responses, and IgE production, and reduced numbers of T follicular helper and effector Th2 cells. Thus, TIGIT is critical for Th2 immunity and can be used as a therapeutic target, especially in light of recent findings showing TIGIT locus hypomethylation in T cells from pediatric patients with allergic asthma.

PMID: 27016609 [PubMed – as supplied by publisher]

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Evaluation of the immunogenicity of the 13-valent conjugated pneumococcal vaccine in rheumatoid arthritis patients treated with etanercept.

Evaluation of the immunogenicity of the 13-valent conjugated pneumococcal vaccine in rheumatoid arthritis patients treated with etanercept.

Joint Bone Spine. 2016 Mar 16;

Authors: Rákóczi É, Perge B, Végh E, Csomor P, Pusztai A, Szamosi S, Bodnár N, Szántó S, Szücs G, Szekanecz Z

Abstract
OBJECTIVES: To prospectively evaluate the immunogenicity of a 13-valent conjugated pneumococcal vaccine (PCV13) in rheumatoid arthritis (RA) patients undergoing etanercept therapy.
METHODS: Twenty-two RA patients treated with etanercept (ETA) in combination with methotrexate (MTX) (n=15) or monotherapy (n=7) for at least one year were included. Altogether 24 osteoarthritis patients not receiving biological or MTX therapy, treating only NSAIDs or analgesics served as controls. All subjects were vaccinated with a single dose (0.5ml) of the PCV13. Pneumococcal antibody levels at baseline, 4 and 8weeks were assessed by a VaccZyme™ Anti-PCP IgG Enzyme Immunoassay Kit. Based on recommendations of the American Academy of Allergy, Asthma & Immunology, an at least two-fold increase in antibody level, as the protective antibody response (pAR) was an indicator of responsiveness (i.e., ratio of postvaccination and prevaccination antibody levels). The antibody levels and their ratios were analysed in a variety of different ways, vaccine safety parameters (fever, infections, changes in regular antirheumatic treatments) were assessed at baseline, 4 and 8weeks after vaccination.
RESULTS: Four weeks after vaccination, the anti-pneumococcal antibody levels significantly increased in both groups. At week 8, antibody levels somewhat decreased in both groups, however, still remained significantly higher compared to baseline. Compared with postvaccination levels at 4 and 8weeks between two groups, the mean protective antibody levels were higher in control group (1st month P=0.016; 2nd month: P=0.039). Possible predictors of pAR were analysed by logistic regression model. In RA, increases of antibody levels at week 8 compared to baseline exerted a negative correlation with age, (Spearman’s R=-0,431; P=0.045). There were no clinically significant side effects or reaction after administration of vaccine observed in any of these patients after the 2-month follow-up period, all patients medical condition were stable.
CONCLUSIONS: In RA patients treated with ETA, vaccination with PCV13 is effective and safe, resulting in pAR one and two months after vaccination. Higher age at vaccination was identified as predictors of impaired pAR. The efficacy of vaccination may be more pronounced in younger RA patients. The vaccine is safe in RA patients on ETA.

PMID: 26995488 [PubMed – as supplied by publisher]

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Vitamin D and Lung Function Decline in Adults With Asthma: The HUNT Study.

Vitamin D and Lung Function Decline in Adults With Asthma: The HUNT Study.

Am J Epidemiol. 2016 Mar 18;

Authors: Brumpton BM, Langhammer A, Henriksen AH, Camargo CA, Chen Y, Romundstad PR, Mai XM

Abstract
We investigated whether low 25-hydroxyvitamin D (25(OH)D) levels were associated with more lung function decline in adults with asthma and whether this association was modified by smoking status or inhaled corticosteroid (ICS) use. We analyzed data on 395 adults with asthma from the Nord-Trøndelag Health Study (1995-2008), Norway. Plasma 25(OH)D and lung function were measured at baseline, and lung function measurements were repeated at follow-up, approximately 11 years later. Linear regression was used to estimate lung function decline. Participants with low 25(OH)D (<50 nmol/L) had more decline in lung function measurements for forced expiratory volume in 1 second (FEV1) (388 mL), forced vital capacity (298 mL), and the FEV1/forced vital capacity ratio (3.7%) over the follow-up, compared with those with high 25(OH)D (?50 nmol/L) who declined 314 mL, 246 mL, and 3.0%, respectively (P = 0.08, 0.30, and 0.23, respectively). The associations were stronger in never smokers and non-ICS users. In never smokers, low 25(OH)D levels were associated with more decline in FEV1 (445 vs. 222 mL) (P = 0.01). In non-ICS users, low 25(OH)D levels were associated with more decline in FEV1 (467 vs. 320 mL) (P = 0.02). Low serum 25(OH)D levels were weakly associated with more lung function decline in adults with asthma, and stronger associations were observed in never smokers and non-ICS users.

PMID: 26994061 [PubMed – as supplied by publisher]

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[Prevalence of asthma consultations in general practice].

[Prevalence of asthma consultations in general practice].

Rev Mal Respir. 2016 Mar 9;

Authors: Schuers M, Chopinaud PA, Guihard H, Mercier A

Abstract
INTRODUCTION: Few data from primary care settings are available about asthma prevalence. The aim of this study was to evaluate the prevalence of asthma consultations in general practice, and to describe their characteristics.
METHODS: This was a multicenter, cross-sectional national study, conducted in general practice. Investigators were 54 interns from 27 medical schools. Between December 2011 and April 2012, they collected and entered variables specific to each consultation over a period of 20 days from a structured electronic health record using the International classification of primary care (ICPC-2) together with data about their trainer(s).
RESULTS: Data were recorded for 20,613 consultations with 45,582 consultation outcomes described. Asthma represented 348 (1.69%) of consultations. The presence of an asthma code was associated with fewer reasons for the consultation, but with more processes of care. Forty-two percent of other consultation results associated with asthma in the same consultation concerned chronic diseases.
CONCLUSION: Our findings suggest that asthma remains underdiagnosed in general practice in France. In order to address this problem, the development of validated diagnostic tools that can be used in general practice settings, and a better access to spirometry, may be directions to explore in future research.

PMID: 26971076 [PubMed – as supplied by publisher]

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The severity of acute bronchiolitis in infants was associated with quality of life nine months later.

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The severity of acute bronchiolitis in infants was associated with quality of life nine months later.

Acta Paediatr. 2016 Mar 11;

Authors: Rolfsjord LB, Skjerven HO, Carlsen KH, Mowinckel P, Bains KE, Bakkeheim E, Lødrup Carlsen KC

Abstract
AIM: Acute bronchiolitis in infancy increases the risk of later asthma and reduced health-related quality of life (QoL). We aimed to see if the severity of acute bronchiolitis in the first year of life was associated with QoL nine months later.
METHODS: The parents of 209 out of 404 of children hospitalised for acute bronchiolitis in eight paediatric departments in South-East Norway at a mean four months of age (range 0-12 months) completed the Infant Toddler Quality of Life Questionnaire sent by mail nine months after the acute illness. Disease severity was measured by length of stay and the need for supportive treatment. Interactions with gender, inclusion age, prematurity, maternal ethnicity and maternal education were examined.
RESULTS: Reduced QoL in four domains was associated with increased length of stay and need for ventilatory support. Physical abilities and general health were associated with both severity markers, whereas bodily pain and discomfort and change in health were associated with length of stay. Ventilatory support was more negatively associated with QoL than atopic eczema and also associated with reduced parental emotions and parental time.
CONCLUSION: The severity of acute bronchiolitis in infants was associated with reduced QoL nine months later. This article is protected by copyright. All rights reserved.

PMID: 26970427 [PubMed – as supplied by publisher]

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Anaphylaxis in children.

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Anaphylaxis in children.

Curr Opin Pediatr. 2016 Mar 8;

Authors: Farbman KS, Michelson KA

Abstract
PURPOSE OF REVIEW: Anaphylaxis is a serious allergic reaction that can be life threatening. We will review the most recent evidence regarding the diagnosis, treatment, monitoring, and prevention of anaphylaxis in children.
RECENT FINDINGS: Histamine and tryptase are not sufficiently accurate for the routine diagnosis of anaphylaxis, so providers should continue to rely on clinical signs. Platelet-activating factor shows some promise in the diagnosis of anaphylaxis. Intramuscular is the best route for epinephrine administration for children of all weights. Glucocorticoids may reduce prolonged hospitalizations for anaphylaxis. Children with anaphylaxis who have resolving symptoms and no history of asthma or previous biphasic reactions may be observed for as few as 3-4?h before emergency department discharge. Early peanut introduction reduces the risk of peanut allergy.
SUMMARY: Epinephrine remains the mainstay of anaphylaxis treatment, and adjuvant medications should not be used in its place. All patients with anaphylaxis should be prescribed and trained to use an epinephrine autoinjector. Clinically important biphasic reactions are rare. Observation in the emergency department for most anaphylaxis patients is recommended, with the duration determined by risk factors. Admission is reserved for patients with unimproved or worsening symptoms, or prior biphasic reaction.

PMID: 26963947 [PubMed – as supplied by publisher]

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Risk of Migraine in Patients With Asthma: A Nationwide Cohort Study.

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Risk of Migraine in Patients With Asthma: A Nationwide Cohort Study.

Medicine (Baltimore). 2016 Mar;95(9):e2911

Authors: Peng YH, Chen KF, Kao CH, Chen HJ, Hsia TC, Chen CH, Liao WC

Abstract
Asthma has been described as an “acephalic migraine” and “pulmonary migraine.” However, no study has investigated the temporal frequency of migraine development in patients with asthma, and the results of previous studies may be difficult to generalize.We investigated the effect of asthma on the subsequent development of migraine by using a population-based data set in Taiwan.We retrieved our study sample from the National Health Insurance Research Database. Specifically, 25,560 patients aged 12 years and older with newly diagnosed asthma were identified as the asthma group, and 102,238 sex and age-matched patients without asthma were identified as the nonasthma group. Cox proportional-hazards regression models were employed to measure the risk of migraine for the asthmatic group compared with that for the nonasthmatic group.The risk of migraine in the asthmatic group was 1.45-fold higher (95% confidence interval 1.33-1.59) than that in the nonasthmatic group after adjustment for sex, age, the Charlson comorbidity index, common medications prescribed for patients with asthma, and annual outpatient department visits. An additional stratified analysis revealed that the risk of migraine remained significantly higher in both sexes and all age groups older than 20 years.Asthma could be an independent predisposing risk factor for migraine development in adults.

PMID: 26945388 [PubMed – in process]

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Identifying Mutations of the Tetratricopeptide Repeat Domain 37 (TTC37) Gene in Infants With Intractable Diarrhea and a Comparison of Asian and Non-Asian Phenotype and Genotype: A Global Case-report Study of a Well-Defined Syndrome With Immunodeficiency.

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Identifying Mutations of the Tetratricopeptide Repeat Domain 37 (TTC37) Gene in Infants With Intractable Diarrhea and a Comparison of Asian and Non-Asian Phenotype and Genotype: A Global Case-report Study of a Well-Defined Syndrome With Immunodeficiency.

Medicine (Baltimore). 2016 Mar;95(9):e2918

Authors: Lee WI, Huang JL, Chen CC, Lin JL, Wu RC, Jaing TH, Ou LS

Abstract
Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare, autosomal recessive and severe bowel disorder mainly caused by mutations in the tetratricopeptide repeat domain 37 (TTC37) gene which act as heterotetrameric cofactors to enhance aberrant mRNAs decay. The phenotype and immune profiles of SD/THE overlap those of primary immunodeficiency diseases (PIDs).Neonates with intractable diarrhea underwent immunologic assessments including immunoglobulin levels, lymphocyte subsets, lymphocyte proliferation, superoxide production, and IL-10 signaling function. Candidate genes for PIDs predisposing to inflammatory bowel disease were sequencing in this study.Two neonates, born to nonconsanguineous parents, suffered from intractable diarrhea, recurrent infections, and massive hematemesis from esopharyngeal varices due to liver cirrhosis or accompanying Trichorrhexis nodosa that developed with age and thus guided the diagnosis of SD/THE compatible to TTC37 mutations (homozygous DelK1155H, Fs*2; heterozygous Y1169Ter and InsA1143, Fs*3). Their immunologic evaluation showed normal mitogen-stimulated lymphocyte proliferation, superoxide production, and IL-10 signaling, but low IgG levels, undetectable antibody to hepatitis B surface antigen and decreased antigen-stimulated lymphocyte proliferation. A PubMed search for bi-allelic TTC37 mutations and phenotypes were recorded in 14 Asian and 12 non-Asian cases. They had similar presentations of infantile onset refractory diarrhea, facial dysmorphism, hair anomalies, low IgG, low birth weight, and consanguinity. A higher incidence of heart anomalies (8/14 vs 2/12; P?=?0.0344, Chi-square), nonsense mutations (19 in 28 alleles), and hot-spot mutations (W936Ter, 2779-2G>A, and Y1169Ter) were found in the Asian compared with the non-Asian patients. Despite immunoglobulin therapy in 20 of the patients, 4 died from liver cirrhosis and 1 died from sepsis.Patients of all ethnicities with SD/THE with the characteristic triad of T nodosa, hepatic cirrhosis, and intractable enteropathy have low IgG, poor vaccine response and/or decreased antigen-stimulated lymphocyte proliferation. This is now better classified into the subgroup of “well-defined syndromes with immunodeficiency” (the update termed as “combined immunodeficiencies with associated or syndromic features”) than “predominantly antibody deficiencies” in the update PIDs classification, and requires optimal interventions.

PMID: 26945392 [PubMed – in process]

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Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.

Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.

BMC Med Genomics. 2016;9(1):9

Authors: Troy NM, Hollams EM, Holt PG, Bosco A

Abstract
BACKGROUND: Asthma is strongly associated with allergic sensitization, but the mechanisms that determine why only a subset of atopics develop asthma are not well understood. The aim of this study was to test the hypothesis that variations in allergen-driven CD4 T cell responses are associated with susceptibility to expression of asthma symptoms.
METHODS: The study population consisted of house dust mite (HDM) sensitized atopics with current asthma (n?=?22), HDM-sensitized atopics without current asthma (n?=?26), and HDM-nonsensitized controls (n?=?24). Peripheral blood mononuclear cells from these groups were cultured in the presence or absence of HDM extract for 24 h. CD4 T cells were then isolated by immunomagnetic separation, and gene expression patterns were profiled on microarrays.
RESULTS: Differential network analysis of HDM-induced CD4 T cell responses in sensitized atopics with or without asthma unveiled a cohort of asthma-associated genes that escaped detection by more conventional data analysis techniques. These asthma-associated genes were enriched for targets of STAT6 signaling, and they were nested within a larger coexpression module comprising 406 genes. Upstream regulator analysis suggested that this module was driven primarily by IL-2, IL-4, and TNF signaling; reconstruction of the wiring diagram of the module revealed a series of hub genes involved in inflammation (IL-1B, NFkB, STAT1, STAT3), apoptosis (BCL2, MYC), and regulatory T cells (IL-2Ra, FoxP3). Finally, we identified several negative regulators of asthmatic CD4 T cell responses to allergens (e.g. IL-10, type I interferons, microRNAs, drugs, metabolites), and these represent logical candidates for therapeutic intervention.
CONCLUSION: Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets.

PMID: 26922672 [PubMed – as supplied by publisher]

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