Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab

Background

Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix.

Objective

We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.

Methods

Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.

Results

Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.

Conclusion and Clinical Relevance

Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.     

Examining Impacts of Allergic Diseases on Psychological Problems and Tobacco Use in Korean Adolescents: The 2008–2011 Korean National Health and Nutrition Examination Survey

Purpose

Asthma during adolescence can induce social, psychological, and behavioral problems. We examined the impact of asthma and other allergic diseases on psychological symptoms and health risk behaviors among South Korean adolescents.

Methods

In this population-based cross-sectional study, 3192 adolescents (10–18 years of age) participating in the 2008–2011 Korean National Health and Nutrition Examination Survey were enrolled. Psychological problems associated with clinically diagnosed asthma, allergic rhinitis, and atopic dermatitis were assessed using questionnaires and surveys. Data was analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, sex, body mass index, smoking experience, and alcohol use.

Results

Asthma and atopic dermatitis were associated with a higher prevalence of depression (17.2% and 13%, respectively). After adjusting for the covariates, asthma patients were approximately two times as likely to have depression as non-allergic participants (odds ratio, 1.81; 95% confidence interval, 1.22–2.68). Psychosocial stress significantly increased in the following order: no allergy, any allergy without asthma, asthma only, and asthma with any allergy (p for linear trend = 0.01). The asthma without other allergies group showed the highest prevalence of cigarette smoking (p = 0.007).

Conclusions

In this study, asthma with or without other allergies was significantly related to increases in depression, psychosocial stress, and smoking experience. Thus, care should be taken to adjust treatment to account for the psychological symptoms and health risk behaviors common among asthmatic adolescents.     

Leukocyte Populations in Human Preterm and Term Breast Milk Identified by Multicolour Flow Cytometry

Background

Extremely preterm infants are highly susceptible to bacterial infections but breast milk provides some protection. It is unknown if leukocyte numbers and subsets in milk differ between term and preterm breast milk. This study serially characterised leukocyte populations in breast milk of mothers of preterm and term infants using multicolour flow cytometry methods for extended differential leukocyte counts in blood.

Methods

Sixty mothers of extremely preterm (<28 weeks gestational age), very preterm (28–31 wk), and moderately preterm (32–36 wk), as well as term (37–41 wk) infants were recruited. Colostrum (d2–5), transitional (d8–12) and mature milk (d26–30) samples were collected, cells isolated, and leukocyte subsets analysed using flow cytometry.

Results

The major CD45+ leukocyte populations circulating in blood were also detectable in breast milk but at different frequencies. Progression of lactation was associated with decreasing CD45+ leukocyte concentration, as well as increases in the relative frequencies of neutrophils and immature granulocytes, and decreases in the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16- monocytes. No differences were observed between preterm and term breast milk in leukocyte concentration, though minor differences between preterm groups in some leukocyte frequencies were observed.

Conclusions

Flow cytometry is a useful tool to identify and quantify leukocyte subsets in breast milk. The stage of lactation is associated with major changes in milk leukocyte composition in this population. Fresh preterm breast milk is not deficient in leukocytes, but shorter gestation may be associated with minor differences in leukocyte subset frequencies in preterm compared to term breast milk.     

Got Milk? Breastfeeding and Milk Analysis of a Mother on Chronic Hemodialysis

Purpose

Women on dialysis rarely become pregnant. However, the overall rate of successful pregnancies is increasing in this patient population and breastfeeding becomes an option for mothers on dialysis. In this study we performed a systematic breast milk composition analysis of a mother on chronic hemodialysis (HD).

Methods

Specimens of breast milk and blood were collected in regular intervals before and after HD from a 39-year old woman starting on day 10 postpartum. Samples were analyzed for electrolytes, retention solutes, nutrients and other laboratory measurements. Breast milk samples from low-risk mothers matched for postpartum age were used as controls.

Results

Significantly higher levels of creatinine and urea were found in pre-HD breast milk when compared to post-HD. A similar post-dialytic decrease was only found for uric acid but not for any other investigated parameter. Conversely, sodium and chloride were significantly increased in post-HD samples. Compared to controls creatinine and urea were significantly higher in pre-HD samples while the difference remained only significant for post-HD creatinine. Phosphate was significantly lower in pre- and post-HD breast milk when compared to controls, whereas calcium showed no significant differences. In terms of nutrient components glucose levels showed a strong trend for a decrease, whereas protein, triglycerides and cholesterol did not differ. Similarly, no significant differences were found in iron, potassium and magnesium content.

Conclusion

To the best of our knowledge this is the first report on a breastfeeding mother on chronic dialysis. Although we found differences in creatinine, urea, sodium, chloride and phosphate, our general analysis showed high similarity of our patient’s breast milk to samples from low-risk control mothers. Significant variations in breast milk composition between pre- and post-HD samples suggest that breastfeeding might be preferably performed after dialysis treatment. In summary, our findings indicate that breastfeeding can be considered a viable option for newborns of mothers on dialysis.     

Role of Maternal Dietary Peanut Exposure in Development of Food Allergy and Oral Tolerance

Background

The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring’s risk for peanut allergy is under debate.

Objective

To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring’s allergy risk.

Methods

Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings’ responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in the presence or absence of immune murine milk; Peyer’s patches were harvested for immunostaining.

Results

Preconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. When offspring were fed peanut directly, dose-dependent tolerance induction, unaltered by maternal feeding of peanut, was seen. Although peanut uptake into the gut-associated lymphoid tissues was enhanced by immune milk as compared to naïve milk, tolerance induction was not affected by the co-administration of immune milk either pre- or post-weaning.

Conclusion

Maternal peanut exposure during pregnancy and lactation has no impact on the development of peanut allergy in the offspring. Tolerance to peanut can be induced early, even pre-weaning, by giving moderate amounts of peanut directly to the infant, and this is neither enhanced nor impaired by concurrent exposure to immune milk.     

Uncoordinated production of Laminin-5 chains in airways epithelium of allergic asthmatics

Background

Laminins are a group of proteins largely responsible for the anchorage of cells to basement membranes. We hypothesized that altered Laminin chain production in the bronchial mucosa might explain the phenomenon of epithelial cell shedding in asthma. The aim was to characterize the presence of Laminin chains in the SEBM and epithelium in allergic and non-allergic asthmatics.

Patients and methods

Biopsies were taken from the bronchi of 11 patients with allergic and 9 patients with non-allergic asthma and from 7 controls and stained with antibodies against the Laminin (ln) chains alpha1-alpha5, beta1-beta2 and gamma1-gamma2.

Results

Lns-2,-5 and -10 were the main Laminins of SEBM. The layer of ln-10 was thicker in the two asthmatic groups while an increased thickness of lns-2 and -5 was only seen in allergic asthmatics. The ln gamma2-chain, which is only found in ln 5, was exclusively expressed in epithelial cells in association with epithelial injury and in the columnar epithelium of allergic asthmatics.

Conclusion

The uncoordinated production of chains of ln-5 in allergic asthma could have a bearing on the poor epithelial cell anchorage in these patients.     

Improvement of Expressed Breast Milk in Mothers of Preterm Infants by Recording Breast Milk Pumping Diaries in a Neonatal Center in China

Objectives

Because inadequate expression of human milk (EBM) in mothers of hospitalized infants were noticed in a neonatal center of our hospital, family education program was carried out to increase the EBM.

Methods

A breast milk pumping diary was introduced to the mothers with preterm infant(s) admitted in the NICU. The ratios of EBM (days of EBM to NICU/hospitalized days), breast milk feeding (BMF) (days of infants fed with exclusive human milk/hospitalized days), mixed feeding (MF) (days of infants fed with partial breast milk and partial formula/hospitalized days), and formula feeding (FF) (days of infants fed with preterm formula/hospitalized days) were evaluated.

Results

During January to April, 2014, the ratios of EBM to the NICU, BMF, MF and FF were 28.11%, 6.6%, 32.8% and 60.6%, respectively. After the introduction of breast milk pumping diary to the mothers from May 2014, the ratio of EBM to the NICU increased significantly to 53.3% (p<0.01) within the following eight months. Both the ratios of BMF and MF also rose to 23.8% and MF 55.3%, respectively. Consequently, the ratio of FF was reduced to 20.9%. Exclusive breast milk feeding also significantly reduce the duration of nil per oral (NPO) of the very low birth weight infants during hospital stay as compared to those fed with mixed feeding and formula feeding.

Conclusion

The introduction of a breast milk pumping diary was associated with a significant increase in the intake of EBM of the hospitalized preterm newborns.     

MiRNA Analysis by Quantitative PCR in Preterm Human Breast Milk Reveals Daily Fluctuations of hsa-miR-16-5p

Background and Aims

Human breast milk is an extremely dynamic fluid containing many biologically-active components which change throughout the feeding period and throughout the day. We designed a miRNA assay on minimized amounts of raw milk obtained from mothers of preterm infants. We investigated changes in miRNA expression within month 2 of lactation and then over the course of 24 hours.

Materials and Methods

Analyses were performed on pooled breast milk, made by combining samples collected at different clock times from the same mother donor, along with time series collected over 24 hours from four unsynchronized mothers. Whole milk, lipids or skim milk fractions were processed and analyzed by qPCR. We measured hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-146-5p, and hsa-let-7a, d and g (all -5p). Stability of miRNA endogenous controls was evaluated using RefFinder, a web tool integrating geNorm, Normfinder, BestKeeper and the comparative ΔΔCt method.

Results

MiR-21 and miR-16 were stably expressed in whole milk collected within month 2 of lactation from four mothers. Analysis of lipids and skim milk revealed that miR-146b and let-7d were better references in both fractions. Time series (5H-23H) allowed the identification of a set of three endogenous reference genes (hsa-let-7d, hsa-let-7g and miR-146b) to normalize raw quantification cycle (Cq) data. We identified a daily oscillation of miR-16-5p.

Perspectives

Our assay allows exploring miRNA levels of breast milk from mother with preterm baby collected in time series over 48–72 hours.     

Documenting Penicillin Allergy: The Impact of Inconsistency

Background

Allergy documentation is frequently inconsistent and incomplete. The impact of this variability on subsequent treatment is not well described.

Objective

To determine how allergy documentation affects subsequent antibiotic choice.

Design

Retrospective, cohort study.

Participants

232,616 adult patients seen by 199 primary care providers (PCPs) between January 1, 2009 and January 1, 2014 at an academic medical system.

Main Measures

Inter-physician variation in beta-lactam allergy documentation; antibiotic treatment following beta-lactam allergy documentation.

Key Results

15.6% of patients had a reported beta-lactam allergy. Of those patients, 39.8% had a specific allergen identified and 22.7% had allergic reaction characteristics documented. Variation between PCPs was greater than would be expected by chance (all p<0.001) in the percentage of their patients with a documented beta-lactam allergy (7.9% to 24.8%), identification of a specific allergen (e.g. amoxicillin as opposed to “penicillins”) (24.0% to 58.2%) and documentation of the reaction characteristics (5.4% to 51.9%). After beta-lactam allergy documentation, patients were less likely to receive penicillins (Relative Risk [RR] 0.16 [95% Confidence Interval: 0.15–0.17]) and cephalosporins (RR 0.28 [95% CI 0.27–0.30]) and more likely to receive fluoroquinolones (RR 1.5 [95% CI 1.5–1.6]), clindamycin (RR 3.8 [95% CI 3.6–4.0]) and vancomycin (RR 5.0 [95% CI 4.3–5.8]). Among patients with beta-lactam allergy, rechallenge was more likely when a specific allergen was identified (RR 1.6 [95% CI 1.5–1.8]) and when reaction characteristics were documented (RR 2.0 [95% CI 1.8–2.2]).

Conclusions

Provider documentation of beta-lactam allergy is highly variable, and details of the allergy are infrequently documented. Classification of a patient as beta-lactam allergic and incomplete documentation regarding the details of the allergy lead to beta-lactam avoidance and use of other antimicrobial agents, behaviors that may adversely impact care quality and cost.     

Human Breast Milk miRNA,Maternal Probiotic Supplementation and Atopic Dermatitis in Offspring

Background

Perinatal probiotic ingestion has been shown to prevent atopic dermatitis (AD) in infancy in a number of randomised trials. The Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT) trial involved a probiotic supplementation regime given solely to mothers in the perinatal period and demonstrated a ~40% relative risk reduction in the cumulative incidence of AD at 2 years of age. However, the mechanisms behind this effect are incompletely understood. Micro-RNAs (miRNA) are abundant in mammalian milk and may influence the developing gastrointestinal and immune systems of newborn infants. The objectives of this study were to describe the miRNA profile of human breast milk, and to investigate breast milk miRNAs as possible mediators of the observed preventative effect of probiotics.

Methods

Small RNA sequencing was conducted on samples collected 3 months postpartum from 54 women participating in the ProPACT trial. Differential expression of miRNA was assessed for the probiotic vs placebo and AD vs non-AD groups. The results were further analysed using functional prediction techniques.

Results

Human breast milk samples contain a relatively stable core group of highly expressed miRNAs, including miR-148a-3p, miR-22-3p, miR-30d-5p, let-7b-5p and miR-200a-3p. Functional analysis of these miRNAs revealed enrichment in a broad range of biological processes and molecular functions. Although several miRNAs were found to be differentially expressed on comparison of the probiotic vs placebo and AD vs non-AD groups, none had an acceptable false discovery rate and their biological significance in the development of AD is not immediately apparent from their predicted functional consequences.

Conclusion

Whilst breast milk miRNAs have the potential to be active in a diverse range of tissues and biological process, individual miRNAs in breast milk 3 months postpartum are unlikely to play a major role in the prevention of atopic dermatitis in infancy by probiotics ingestion in the perinatal period.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00159523","term_id":"NCT00159523"}}NCT00159523     

Search for Allergens from the Pollen Proteome of Sunflower (Helianthus annuus L.): A Major Sensitizer for Respiratory Allergy Patients

Background

Respiratory allergy triggered by pollen allergens is increasing at an alarming rate worldwide. Sunflower pollen is thought to be an important source of inhalant allergens. Present study aims to identify the prevalence of sunflower pollinosis among the Indian allergic population and characterizes the pollen allergens using immuno-proteomic tools.

Methodology

Clinico-immunological tests were performed to understand the prevalence of sensitivity towards sunflower pollen among the atopic population. Sera from selected sunflower positive patients were used as probe to detect the IgE-reactive proteins from the one and two dimensional electrophoretic separated proteome of sunflower pollen. The antigenic nature of the sugar moiety of the glycoallergens was studied by meta-periodate modification of IgE-immunoblot. Finally, these allergens were identified by mass-spectrometry.

Results

Prevalence of sunflower pollen sensitization was observed among 21% of the pollen allergic population and associated with elevated level of specific IgE and histamine in the sera of these patients. Immunoscreening of sunflower pollen proteome with patient sera detected seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical clustering of 2D-immunoblot data highlighted three allergens characterized by a more frequent immuno-reactivity and increased levels of IgE antibodies in the sera of susceptible patients. These allergens were considered as the major allergens of sunflower pollen and were found to have their glycan moiety critical for inducing IgE response. Homology driven search of MS/MS data of these IgE-reactive proteins identified seven previously unreported allergens from sunflower pollen. Three major allergenic proteins were identified as two pectate lyases and a cysteine protease.

Conclusion

Novelty of the present report is the identification of a panel of seven sunflower pollen allergens for the first time at immuno-biochemical and proteomic level, which substantiated the clinical evidence of sunflower allergy. Further purification and recombinant expression of these allergens will improve component-resolved diagnosis and therapy of pollen allergy.     

Food allergy enhances allergic asthma in mice

Background

Atopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.

Objectives

To develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.

Methods

Food allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.

Results

OVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.

Conclusion

Gut sensitization to OVA amplifies Der f-induced asthma in mice.     

Updated Prevalences of Asthma,Allergy, and Airway Symptoms,and a Systematic Review of Trends over Time for Childhood Asthma in Shanghai,China

Background

The prevalence of asthma among Shanghai children has increased over time. This increase might be associated with changes in environmental exposures. Investigation of the time-trend of asthma and current prevalences is essential to understanding the causes.

Objective

To estimate the current prevalences of asthma, allergies and other respiratory symptoms among Shanghai preschool children, and to investigate the time-trend of childhood asthma prevalence of from 1990 to 2011.

Methods

From April 2011 to April 2012, the CCHH (China, Children, Homes, Health) cross-sectional study was conducted in Shanghai. Questionnaires were distributed to 17,898 parents or guardians of preschool children from 72 kindergartens in 5 districts. Previous similar studies were also summarized by a systematic literature review.

Results

From a total of 14,884 questionnaires for 3–7 year old children, prevalences of the following diseases and symptoms were calculated: asthma 10.2%, wheeze (ever) 28.1%, pneumonia (ever) 33.5%, otitis media 11.0%, rhinitis (ever) 54.1%, hay fever 12.2%, eczema (ever) 22.7%, and food allergy 15.7%. Urban children had higher prevalences of most symptoms than suburban children. The prevalence of asthma has increased significantly, almost five-fold, from 2.1% in 1990 to 10.2% in the present study. The prevalence of asthma in boys was higher than in girls in the present study and in all reviewed studies.

Conclusions

Asthma, allergy and airway symptoms are common among preschool children in Shanghai. The prevalence of childhood asthma in Shanghai has increased rapidly from 1990 to 2011.     

N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer

Objective

The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality.

Methods

Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality.

Results

We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality.

Discussion

These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.     

Prevalence of Asthma and Allergic Rhinitis among Adults in Yaounde,Cameroon

Background

Population-based estimates of asthma and allergic rhinitis in sub-Saharan African adults are lacking. We assessed the prevalence and determinants of asthma and allergic rhinitis in urban adult Cameroonians.

Methods

A community-based survey was conducted from December 2013 to April 2014 among adults aged 19 years and above (N = 2,304, 57.3% women), selected through multilevel stratified random sampling across all districts of Yaounde (Capital city). Internationally validated questionnaires were used to investigate the presence of allergic diseases. Logistic regressions were employed to investigate the determinants of allergic conditions.

Results

Prevalence rates were 2.7% (95% CI: 2.1-3.4) for asthma-ever, 6.9% (5.9-7.9) for lifetime wheezing, 2.9% (92.2-3.6) for current wheezing and 11.4% (10.1-12.7) for self-reported lifetime allergic rhinitis; while 240 (10.4%) participants reported current symptoms of allergic rhinitis, and 125 (5.4%) had allergic rhino-conjunctivitis. The prevalence of current asthma medication use and self-reported asthma attack was 0.8 (0.4-1.2) and 1 (0.6-1.4) respectively. Multivariable adjusted determinants of current wheezing were signs of atopic eczema [2.91 (1.09-7.74)] and signs of allergic rhinitis [3.24 (1.83-5.71)]. Age group 31-40 years [0.27(0.09-0.78), p = 0.016] was an independent protective factor for wheezing. Determinants of current rhinitis symptoms were active smoking [2.20 (1.37-3.54), p<0.001], signs of atopic eczema [2.84 (1.48-5.46)] and current wheezing [3.02 (1.70-5.39)].

Conclusion

Prevalence rates for asthma and allergic rhinitis among adults in this population were at the lower tails of those reported in other regions of the world. Beside the classical interrelation between allergic diseases found in this study, active smoking was an independent determinant of allergic rhinitis symptoms. Nationwide surveys are needed to investigate regional variations.     

High Prevalence of Nickel Allergy in an Overweight Female Population: A Pilot Observational Analysis

Context

In our Allergy Unit, we incidentally observed that a low Nickel diet, prescribed for delayed allergy to Nickel sulfate, reduced body mass index (BMI) and waist circumference in overweight patients.

Objectives

This pilot cross-sectional analysis was undertaken to compare the prevalence of Nickel allergy of overweight individuals versus the general population. We also had the chance to report the efficacy of a low Nickel diet on BMI and waist circumference in Nickel-sensitive overweight subjects.

Methods

Eighty-seven overweight subjects, with a BMI >26 Kg/m², were consecutively enrolled in a health prevention program, and screened for the presence of Nickel allergy. The enrolled population was mostly females (72/87) (82.8%). Forty-three overweight women and two men showed a Nickel allergy and started a low Nickel diet. After 6-months of dieting, 24 overweight allergic women could be traced and changes in BMI and waist circumference were calculated.

Main Outcome Measurements

Prevalence of Nickel allergy in overweight.

Results

Prevalence of Nickel allergy in overweight female was 59.7%, compared with a prevalence rate of 12.5% in the general population. A significant reduction in BMI was observed in 24 out of 43 overweight females with Nickel allergy after 24 weeks of a low Nickel diet. Relative to baseline, mean BMI decrease was 4.2±0.5 (P <0.001) and the mean decline in waist circumference was 11.7±0.6 cm (P< 0.001).

Conclusions

This pilot observational analysis showed a substantially higher prevalence of Nickel allergy among overweight females, especially those with metabolic syndrome and fatty liver disease. A normocaloric low Nickel diet was effective in reducing BMI in this population. Further research is strongly needed to confirm these preliminary findings.     

Early colonization with a group of Lactobacilli decreases the risk for allergy at five years of age despite allergic heredity

Background

Microbial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age.

Methods and Findings

Fecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, Clostridium (C.) difficile, a group of Lactobacilli (Lactobacillus (L.) casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014). However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028). Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038). Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048).

Conclusion

In this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that early Lactobacilli (L. casei, L. paracasei, L. rhamnosus) colonization seems to decrease the risk for allergy at five years of age despite allergic heredity.     

Inter-Relationship between Rhinitis and Conjunctivitis in Allergic Rhinoconjunctivitis and Associated Risk Factors in Rural UK Children

Objective

Allergic conjunctivitis (AC) is a common condition, especially in childhood. The extent to which it occurs concurrently with or independently from allergic rhinitis (AR) has not been well described.

Aim

To examine the inter-relationship between rhinitis and conjunctivitis and the epidemiological risk factors for these conditions in a rural UK population.

Methods

Cross-sectional study of rural school children (aged 5–11 years). Parental questionnaires were used to diagnose allergic outcomes (including conjunctivitis, rhinitis and rhinoconjunctivitis), and to collect data on atopic history, demographic and environmental exposures. Odds ratios of allergic outcome by exposure were examined adjusted for age, sex, breastfeeding, family history of allergy, number of older and younger siblings.

Results

Prevalence of conjunctivitis was 17.5%, rhinitis 15.1% and rhinoconjunctivitis 13.0%. Seasonality of symptoms varied by condition: 64.7% of those with conjunctivitis had seasonal symptoms (April-Sept only), 46.7% of those with rhinitis and 92.2% of those with rhinoconjunctivitis. Living on a farm consistently reduced the risk of conjunctivitis (odds ratio 0.47, 95%CI 0.29–0.79, p = 0.004), rhinitis (OR 0.57, 95%CI 0.33–1.01, p = 0.05) and rhinoconjunctivitis (OR 0.57, 95%CI 0.32–1.03, p = 0.06). Exposure to farm animals (particularly in early life), current consumption of unpasteurised milk and playing in a barn or stable significantly reduced the risk of all three conditions.

Conclusion

More children had parent-reported conjunctivitis than rhinitis. The majority of children with either condition also reported symptoms with the other condition. Farmers’ children have less eye and/or nasal symptoms. A number of farming variables linked with the farm microbial environment are likely to be mediating the protective effect.     

Cost-Effectiveness of Bronchial Thermoplasty,Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma

Background

Bronchial thermoplasty (BT) is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy.

Objective

To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA.

Methods

A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]). A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs) and exacerbations as the outcomes.

Results

For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER) of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP) of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI) was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%.

Conclusions

Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes cost-effective relative to omalizumab and standard therapy at the WTP of $100,000/QALY in patients with moderate-to-severe allergic asthma. However, there is a substantial uncertainty in the underlying evidence, indicating the need for future research towards reducing such uncertainty.     

Nevirapine,Sodium Concentration and HIV-1 RNA in Breast Milk and Plasma among HIV-Infected Women Receiving Short-Course Antiretroviral Prophylaxis

Introduction

Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.

Objective

To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).

Methods

Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant.

Results

HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05).

Conclusion

After short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk.