Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: sub-sample analysis from a RCT.

Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.

Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

BACKGROUND: Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. METHODS AND PATIENTS: We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. RESULTS: A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. CONCLUSIONS: Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick and intradermal tests should be used. There is evidence of cross-reactivity between steroids, so a panel is recommended. False-positive and false-negative reactions do occur; however, the frequency is unknown. Challenge remains the only definitive way to demonstrate a safe alternative to use. CLINICAL RELEVANCE: As the largest case series described, this article provides new evidence for the interpretation of skin tests when investigating possible immediate hypersensitivity to corticosteroids.

Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization?

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clear; efficacy may depend on the timing, dose, duration, and specific probiotic used. Using a double-blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high-risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema at 2 and 4 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no significant effect. OBJECTIVE: To determine whether differences in effects of HN001 and HN019 on eczema persist to age 6 years, and to investigate effects on sensitization. METHODS: Standard procedures were used to assess eczema (The UK Working Party's Criteria), eczema severity (SCORAD), atopic sensitization [skin prick tests (SPT), total and specific IgE] and standard questions used for asthma, wheeze, and rhinoconjunctivitis. RESULTS: HN001 was associated with significantly lower cumulative prevalence of eczema (HR = 0.56, 95% CI 0.39-0.80), SCORAD ≥ 10 (HR = 0.69, 0.49-0.98) and SPT sensitization (HR = 0.69, 95% CI 0.48-0.99). The point prevalence of eczema (RR = 0.66, 95% CI 0.44-1.00), SCORAD ≥ 10 (RR = 0.62, 95% CI 0.38-1.01) and SPT sensitization (RR = 0.72, 95% CI 0.53-1.00) were also reduced among children taking HN001. HN019 had no significant effect on any outcome. CONCLUSION AND CLINICAL RELEVANCE: This study provides evidence for the efficacy of the probiotic L. rhamnosus HN001 in preventing the development of eczema and possibly also atopic sensitization in high risk infants to age 6 years. The absence of a similar effect for HN019 indicates that benefits may be species specific.

A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years.

BACKGROUND: Using a double blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema by age 2 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no effect. OBJECTIVE: The aim of this study was to investigate the associations of HN001 and HN019 with allergic disease and atopic sensitization among these children at age 4 years, 2 years after stopping probiotic supplementation. METHODS: The presence (UK Working Party's Diagnostic Criteria) and severity SCORing Atopic Dermatitis (SCORAD) of eczema and atopy (skin prick tests) and parent-reported symptoms of asthma and rhinoconjunctivitis were assessed using standard protocols and questions. RESULTS: Four-hundred and seventy-four infants were eligible at birth of whom 425 (90%) participated in this follow-up. The cumulative prevalence of eczema by 4 years (Hazard ratio (HR) 0.57 (95% CI 0.39-0.83)) and prevalence of rhinoconjunctivitis at 4 years (Relative risk 0.38 (95% CI 0.18-0.83)) were significantly reduced in the children taking HN001; there were also nonsignificant reductions in the cumulative prevalence of SCORAD ≥ 10 (HR 0.74 (95% CI 0.52-1.05), wheeze (HR 0.79 (95% CI 0.59-1.07)) and atopic sensitization (HR = 0.72 (95% CI 0.48-1.06)). HN019 did not affect the prevalence of any outcome. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that the protective effect of HN001 against eczema, when given for the first 2 years of life only, extended to at least 4 years of age. This, together with our findings for a protective effect against rhinoconjunctivitis, suggests that this probiotic might be an appropriate preventative intervention for high risk infants.

Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon-gamma and breast milk transforming growth factor-beta and immunoglobin A detection.

BACKGROUND: This study explored the effects of maternal probiotic supplementation on immune markers in cord blood (CB) and breast milk. METHODS: CB plasma and breast milk samples were collected from a cohort of women who had received daily supplements of either 6 x 10(9) CFU/day Lactobacillus rhamnosus HN001 (n=34), 9 x 10(9) CFU/day Bifidobacterium lactis HN019 (n=35) or a placebo (n=36) beginning 2-5 weeks before delivery and continuing for 6 months in lactating women. CB plasma and breast milk (collected at 3-7 days, 3 months and 6 months postpartum) were assayed for cytokines (IL-13, IFN-gamma, IL-6, TNF-alpha, IL-10, TGF-beta1) and sCD14. Breast milk samples were also assayed for total IgA. RESULTS: Neonates of mothers who received a probiotic had higher CB IFN-gamma levels (P=0.026), and a higher proportion had detectable blood IFN-gamma levels, compared with the placebo group (P=0.034), although levels were undetectable in many infants. While this pattern was evident for both probiotics, when examined separately only the L. rhamnosus HN001 group showed statistically significant higher IFN-gamma levels (P=0.030) compared with the placebo group. TGF-beta1 levels were higher in early breast milk (week 1) from the probiotic groups (P=0.028). This was evident for the B. lactis HN019 group (P=0.041) with a parallel trend in the L. rhamnosus HN001 group (P=0.075). Similar patterns were seen for breast milk IgA, which was more readily detected in breast milk from both the B. lactis HN019 (P=0.008) and the L. rhamnosus HN001 group (P=0.011). Neonatal plasma sCD14 levels were lower in the B. lactis HN019 group compared with the placebo group (P=0.041). CONCLUSION: The findings suggest that supplementation with probiotics in pregnancy has the potential to influence fetal immune parameters as well as immunomodulatory factors in breast milk.

Is the effect of probiotics on atopic dermatitis confined to food sensitized children?

BACKGROUND: Probiotics have previously been shown to reduce the severity of atopic dermatitis (AD) in infants and children. OBJECTIVE: To examine the effect of two probiotics (Lactobacillus rhamnosus and Bifidobacteria lactis) on established AD in children. SUBJECTS AND METHODS: Atopic children with current dermatitis received 2 x 10(10) colony forming units/g of probiotic (n=29) or placebo (n=30). Both were given daily as a powder mixed with food or water. SCORing Atopic Dermatitis (SCORAD; developed by the European Task Force on Atopic Dermatitis) a measure of the extent and severity of AD, was assessed at baseline, 2 and 12 weeks after starting treatment and 4 weeks after treatment was discontinued. RESULTS: SCORAD geometric mean score at baseline was 26.0 (21.9-30.8) in the probiotic group and 35.1 (28.9-42.8) in the placebo group (P=0.02). After adjustment for these between-group baseline differences there was no significant improvement in AD at 12 weeks, SCORAD geometric mean ratio: 0.80 (95% confidence level (CI) 0.62-1.04, P=0.10). Among the food sensitized children, there was an improvement in those treated with probiotics, SCORAD geometric mean ratio: 0.73 (95% CI 0.54-1.00, P=0.047). CONCLUSION: In this study a combination of Lactobacillus rhamnosus and Bifidobacteria lactis improved AD only in food sensitized children.

House dust-mite allergen and cat allergen variability within carpeted living room floors in domestic dwellings.

Exposure to allergens from house dust-mites (Der p 1) and domestic cats (Fel d 1) is associated with symptom severity in atopic subjects with asthma and rhinitis. Assessment of allergen exposure in the domestic environment is normally determined by measurement from a single floor site. We determined the variability of these allergens and protein throughout the whole living room floor area. Dust samples were collected from 1 m2 areas from 16 carpeted living room floors in Wellington, New Zealand, and analyzed for concentrations of Der p 1 and Fel d 1. Mean coefficients of variation for Der p 1 and Fel d 1 were 53.1% (range: 28.5-136.8) and 65.6% (range: 28.5-131), respectively. This study has demonstrated a large variation of house dust-mite and cat allergens within living room floors and thus a single sampling site may not be representative for assessment of an individual's exposure risk. House dust-mite and cat allergen levels from the center of the room, in front of a couch or chair, or from a corner of the room are similar to mean levels from the whole room, these sites may thus be representative of the whole living room floor in large-scale epidemiological studies.

House dust-mite allergen and cat allergen variability within carpeted living room floors in domestic dwellings.

Exposure to allergens from house dust-mites (Der p 1) and domestic cats (Fel d 1) is associated with symptom severity in atopic subjects with asthma and rhinitis. Assessment of allergen exposure in the domestic environment is normally determined by measurement from a single floor site. We determined the variability of these allergens and protein throughout the whole living room floor area. Dust samples were collected from 1 m2 areas from 16 carpeted living room floors in Wellington, New Zealand, and analyzed for concentrations of Der p 1 and Fel d 1. Mean coefficients of variation for Der p 1 and Fel d 1 were 53.1% (range: 28.5-136.8) and 65.6% (range: 28.5-131.0), respectively. This study has demonstrated a large variation of house dust-mite and cat allergens within living room floors and thus assessment of a single sampling site may not be representative of an individual's exposure risk. House dust-mite and cat allergen levels from the center of the room, in front of a couch or chair, or from a corner of the room are similar to mean levels from the whole room. These sites may thus be representative of the whole living room floor in large-scale epidemiological studies.

Determinants of endotoxin levels in carpets in New Zealand homes.

Endotoxin in house dust has been shown to be associated with asthma severity. Little is known about the influence of housing characteristics on endotoxin distribution. Using standardized methods, dust was sampled from a 1m(2) site and the whole accessible carpet area in selected Wellington, New Zealand homes (n = 77). Endotoxin was measured using a Limulus Amoebocyte Lysate assay. Relative humidity and temperature were recorded using sensors placed in carpet bases. Questionnaires were used to collect information on housing characteristics. All analyses were performed for endotoxin units (EU)/mg and EU/m2 for each site. Geometric mean endotoxin levels were 22.7 EU/mg [geometric standard deviation (GSD) = 2.4] or 30,544 EU/m2 (GSD = 3.2) from the 1m(2) site, and 28.4 EU/mg (GSD = 3.4) or 5653 EU/m2 (GSD = 6.4) from the whole room. After controlling for confounding, endotoxin was positively associated with dogs inside [geometric mean ratio (GMR): 0.9-2.0], total household occupants (GMR: 1.7-2.0, for 1 m2 sample only), vacuum cleaners <1-year old (GMR: 2.3-2.7), reusing vacuum dust collection bags (GMR: 1.4-3.1), steamcleaning or shampooing the carpet (GMR: 1.4-2.2) and high relative humidity (GMR: 1.4-1.6). Lower endotoxin was associated with floor insulation (GMR: 0.4-0.8), and north-facing living rooms (GMR: 0.4-0.8). This study has identified home characteristics that could be modified to reduce endotoxin exposure.

Farm residence and exposures and the risk of allergic diseases in New Zealand children.

BACKGROUND: Studies in Europe have reported a reduced prevalence of allergy in farmers' children. We aimed to determine if there is a similar reduction in allergy among New Zealand farm children. METHODS: Two hundred and ninety-three children participated (60%) aged 7-10 years, from selected schools in small towns and the surrounding rural area. Skin prick tests (SPT) to eight common allergens were performed. Parents completed questionnaires about allergic and infectious diseases, place of residence, exposure to animals, and diet, and they provided dust from the living-room floor. Endotoxin was measured using an Limulus amoebocyte lysate (LAL) assay and Der p 1 using enzyme-linked immunoassay (ELISA). RESULTS: Current farm abode was found to increase the risk of having symptoms associated with allergy, but not SPT positivity. Independent inverse associations were found for early-life exposures: at least weekly consumption of yoghurt with hayfever (odds ratio (OR) = 0.3, 95% confidence intervals (CI) 0.1-0.7) and allergic rhinitis (OR = 0.3, 95% CI 0.2-0.7); any unpasteurized milk consumption with atopic eczema/dermatitis syndrome (AEDS) (OR = 0.2, 95% CI 0.1-0.8); cats inside or outside with hayfever (OR = 0.4, 95% CI 0.1-1.0) and AEDS (OR = 0.4, 95% CI 0.2-0.8); dogs inside or outside with asthma (OR = 0.4, 95% CI 0.2-0.8); and pigs with SPT positivity (OR = 0.2, 95% CI 0.1-0.9). CONCLUSIONS: Despite finding a protective effect of early-life animal exposures, we found a greater prevalence of allergic disease on farms.

The importance of housing characteristics in determining Der p 1 levels in carpets in New Zealand homes.

BACKGROUND: A previous study of homes in Wellington, New Zealand showed that having carpets on floors was the most important determinant of floor Der p 1 levels, but there was much unexplained variability between houses in carpet levels. OBJECTIVE: To determine to what extent housing characteristics might explain this variability in Der p 1 levels between houses. METHODS: We returned to a selection of houses with carpets and sampled living room dust from 1 square metre for 1 min and from the whole floor at 5 m(2) per min. Der p 1 levels were estimated by double monoclonal antibody ELISA and are expressed as geometric mean microg/g and microg/m(2) (95% confidence intervals). Questionnaires were used to collect information on housing characteristics. RESULTS: Der p 1 levels were significantly higher in the 1 square metre sample (40.0, 31.9-50.2 microg/g; 53.4, 41.4-68.9 microg/m(2)) than in the whole room (25.8, 21.3-31.1 microg/g; 5.3, 3.8-7.4 microg/m(2)). However, results from the different sampling methods were correlated (r = 0.51, P = 0.001 for microg/g and r = 0.58, P = 0.001 for microg/m(2)). After controlling for possible confounders, houses with insulation or a room or garage below the living room had approximately half the Der p 1 concentration (P = 0.05 for both samples) and the amount of Der p 1 per m(2) (P = 0.004 for the 1 square meter sample, P = 0.06 for the whole room sample) than houses without these features. Having more than two children was associated with higher levels of Der p 1 in 1 square meter, significant (P = 0.05) for microg/m(2). Carpet underlay less than 8 mm thick was associated with an almost 3-fold increase in microg/m(2) Der p 1 (P = 0.03) and a 1.6-fold increase in microg/g Der p 1 (P = 0.08) in the whole room sample, when compared with thicker carpet underlays. CONCLUSION: The presence of insulation is the single most important housing characteristic explaining the between-house variability in Der p 1 levels on carpeted living room floors.

Association of beta2-adrenergic receptor polymorphisms with severe asthma.

BACKGROUND: There is considerable interest in the role of different candidate loci in the development of asthma. This study investigates the association between asthma severity and previously identified polymorphisms at two sites within the beta2-adrenergic receptor (beta2AR) gene: the Arg16-->Gly16 and Gln27-->Glu27 alleles. METHODS: Restriction enzyme analysis of amplified beta2AR gene products (PCR-RFLP) was used to analyse the frequency of the Arg16-->Gly16 and Gln27-->Glu27 polymorphisms within the beta2AR gene in 95 severe asthmatic patients (with a markedly increased risk of death from asthma), 59 mild asthmatic patients, and a control group of 92 nonasthmatic subjects. RESULTS: The Gly16 polymorphism was significantly associated with asthma severity with odds ratios (95% CI) for the Gly16 allele being 1.56 (1.02-2.40, P = 0.04) and 0. 98 (0.61-1.57, P = 0.92) for the severe and mild asthma groups, respectively. The corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82-4.41, P = 0.13) and 0.82 (0.35-1.92, P = 0.65) for the severe and mild asthma groups, respectively. There was no significant association between either polymorphism at amino acid 27 and asthma or asthma severity. CONCLUSIONS: We conclude that the polymorphisms of amino acids 16 and 27 of the beta2AR gene are not associated with the development of asthma per se, but that the Gly16 polymorphism may play a role in the pathogenesis of asthma severity.