Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria.

The reports on atopic diseases and microbiota in early childhood remain contradictory, and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r = -0.54, P = 0.002) and with the abundance of butyrate-producing bacteria (r = -0.52, P = 0.005). During the 3-month follow-up, microbiota diversity increased (P < 0.001) and scoring atopic dermatitis values decreased (P < 0.001) in all infants. This decrease coincided with the increase in bacteria related to butyrate-producing Coprococcus eutactus (r = -0.59, P = 0.02). In conclusion, the high diversity of microbiota and high abundance of butyrate-producing bacteria were associated with milder eczema, thus suggesting they have a role in alleviating symptoms of atopic eczema.

Costs of allergic diseases from birth to two years in Finland.

OBJECTIVES: Costing studies are needed to identify the resources used for treatment and inform payers of the costs incurred. The objectives were to determine the costs of diagnosing and treating atopic dermatitis, food allergy and asthma, and to compare the share of costs to society and to the family during the first two years of life. STUDY DESIGN: The data were obtained from an ongoing mother-infant nutrition study. The sample comprised 60 infants who developed allergic disease by the age of 24 months and 56 healthy infants with no allergic disease. METHODS: The costs included diagnosis and treatment of the allergy, disability allowances, travel expenses and time spent by parents. RESULTS: The median costs per infant were €275 (range 94-1306) for atopic dermatitis, €1408 (163-5408) for asthma, €3182 (628-11195) for food allergy, and €10 (0-619) for the healthy infants due to the suspicion of allergic disease. The highest costs in atopic dermatitis were caused by primary care visits, topical treatments, travel costs and parents' time, and those for food allergy by hospital out-patient care, infant formulae for cow's milk allergy, disability allowances and travel costs. The families paid 43% of the costs arising from atopic dermatitis, 13.6% of those from food allergy and 16.5% of those from asthma. CONCLUSIONS: Cow's milk allergy emerged as the most expensive allergic disease, especially for the society, and concurrent asthma in particular further increased the costs.

Quality of life in infants with atopic dermatitis and healthy infants: a follow-up from birth to 24 months.

AIM: To evaluate quality of life (QOL) in infants with atopic dermatitis (AD) by comparison with healthy infants to find treatment modalities contributing most to QOL in these patients. METHODS: The population (N=134) was recruited in the context of an on-going prospective mother-infant study. QOL was measured using the Infant Dermatitis Quality of Life Index for the infants with AD and a modification of this for the healthy infants. RESULTS: The index scores of infants with AD were 4.15 (SD 2.96), 3.89 (SD 3.62) and 3.23 (SD 2.71) at 6, 12 and 24 months, respectively, the QOL being significantly poorer at 6 (p<0.001) and 12 (p=0.01) months compared to healthy infants. The principal impairments were itching, scratching and sleep disturbances at 6 and 12 months and treatment difficulties at 6 months. Problems with getting to sleep were reported at all stages irrespective of AD. CONCLUSIONS: Simple treatment regimens targeting itching in particular are likely to contribute most to the QOL of infants with AD; however, sleeping problems may remain as an age-related phenomenon. Early detection of symptoms and effective parent guidance contributed to the well-being of the child.

Interaction of orally administered Lactobacillus rhamnosus GG with skin and gut microbiota and humoral immunity in infants with atopic dermatitis.

BACKGROUND: The intestinal mucosa functions as a defence barrier against gut intraluminar antigens. The maturational events in the gut parallel its step-wise colonization. Atopic dermatitis (AD) is associated with aberrant barrier functions of the skin epithelium and, in a subgroup of patients, of the gut mucosa. OBJECTIVE: To investigate the interaction of Lactobacillus rhamnosus GG (LGG) with skin and gut microbiota and humoral immunity in infants with AD. METHODS: Thirty-nine infants with AD were randomized for a 3-month period in a double-blind design to receive extensively hydrolysed casein formula supplemented with (n=19) or without (n=20) LGG (ATCC 53103) 5.0 × 107 CFU/g to achieve a daily intake of 3.4 × 109 CFU. Sampling (blood and fecal samples, cotton swab from the skin) was carried out at entry, 1 and 3 months thereafter. Ig-secreting cells were determined by enzyme-linked immunospot and the proportions of CD19(+)CD27(+) B cells among peripheral blood leucocytes by flow cytometry. The major groups of gut and skin bacteria were characterized using PCR. RESULTS: The proportions of IgA- and IgM-secreting cells decreased significantly in the treated group; the baseline-adjusted ratios for treated vs. untreated at 1 month were 0.59 (95%CI 0.36-0.99, P=0.044) for IgA- and 0.53 (95%CI 0.29-0.96, P=0.036) for IgM-secreting cells. The proportions of CD19(+)CD27(+) B cells increased in the probiotic-treated infants but not in the untreated. There were no significant differences in bifidobacterial species composition of the gut between the study groups. On the skin, the bacterial counts of Bifidobacterium genus vs. Clostridium coccoides in the treated and untreated infants were similar. CONCLUSION AND CLINICAL RELEVANCE: Specific probiotics may enhance gut barrier function and aid in the development of immune responses. Thus, specific probiotics may afford protection against offending macromolecules in the gut and provide control for future infections by accelerated immunological maturation (ClinicalTrials.gov ID NCT01148667).

Mechanical ventilation in children with severe asthma.

Hospital admissions for childhood asthma have increased during the past few decades. The aim of this study was to describe the need for mechanical ventilation for severe asthma exacerbation in children in Finland from 1976 to 1995. We reviewed medical records and collected data retrospectively from all 5 university hospitals in Finland, thus covering the entire population of about 5 million. The endpoints selected were the number of admissions and readmissions leading to mechanical ventilation, duration of stay in the hospital, and mortality. Moreover, asthma medications prescribed prior to admission and administered in the intensive care unit (ICU), as well as the etiology of the exacerbation associated with mechanical ventilation were examined. Mechanical ventilation was required in 66 ICU admissions (59 patients). This constituted approximately 10% of all 632 admissions for acute asthma to an ICU. The number of admissions decreased from 1976 to 1995: 41 admissions between 1976 and 1985 vs. 25 admissions during the next 10-year period. The mean age at admission to the ICU was 3.6 years, and 46% of the patients were boys. Prior to the index admission, 70% of the patients had used asthma medication such as oral bronchodilator (50%), inhaled bronchodilator (20%), theophylline (38%), inhaled glucocorticoid (18%), oral glucocorticoid (5%), and cromoglycate (7%). Respiratory infection was by far the most common cause of all the exacerbations (61%), followed by food allergy (8%) and gastroesophageal reflux (3%). In 28% of cases the cause of the severe asthma exacerbation could not be identified. In the mechanically ventilated patients readmissions occurred 38 times between 1976 and 1985 vs. 5 times between 1986 and 1995. Five of the patients who received mechanical ventilation died, and in 3 of these patients asthma was the event causing death. In conclusion, there has been decrease in the number of first and repeat ICU admission for asthma requiring mechanical ventilation between 1970 and 1995. This trend occurred despite a simultaneous 5% yearly increase in hospital admissions for childhood asthma during these 2 decades.

Acute childhood asthma in Finland: a retrospective review of hospital admissions from 1976 to 1995.

The prevalence of childhood asthma has increased markedly in many Western societies during recent decades. We wanted to study whether the incidence and severity of childhood asthma in Finland had changed during the time-period 1976-95. Hospital admission rates from 1976 to 1995 were obtained from the National Hospital Discharge Register and the individual intensive care unit (ICU) registers of the five university hospitals in Finland. The number and length of treatment periods for childhood asthma in all Finnish hospitals and at the ICUs of the five university hospitals were analyzed. The number of children receiving special reimbursement for asthma medication costs was obtained from the central register of the Social Insurance Institution. The data showed that during the time-period investigated, hospital admissions as a result of asthma had increased by 2.8-fold, but the mean length of hospital stay had more than halved (from 7.3 to 2.6 days). The increase in hospital admissions showed greatest significance in the 0-4-year age-group among both sexes (p <0.001). In contrast, a significant reduction in hospital admissions was found among the 10-14-year age-group (p <0.001). No discernible change in admission to ICUs was seen. During the same time-period, the number of children receiving special reimbursement for asthma medication costs increased 7.5-fold. Hence, a major increase has occurred in the number of children diagnosed with asthma that has not been paralleled by a proportionate increase in the number of hospital admissions. While the prevalence of mild and moderate asthma has increased, the occurrence of severe asthma has remained essentially unchanged.

Cross-reacting IgE and IgG antibodies to Pityrosporum ovale mannan and other yeasts in atopic dermatitis.

Atopic dermatitis (AD) patients often demonstrate positive skin prick test results and serum IgE antibodies to a range of different yeasts. This has been thought to be due to cross-reactivity. In this study, the cross-reactivity of IgE and IgG antibodies between mannan and crude antigens of Pityrosporum ovale, Candida albicans, and Saccharomyces cerevisiae and crude antigens of Cryptococcus albidus and Rhodotorula rubra was examined by RAST and ELISA inhibition with two serum pools of AD patients. We found cross-reacting IgE and IgG antibodies. In the IgE response, the main cross-reacting pattern was the mannan region, although inhibition could be achieved also with crude antigens of C. albicans, S. cerevisiae, and, to some extent, C. albidus. P. ovale was the most potent inhibitor of IgE-binding components, and against it the highest IgE antibody levels were detected in AD serum pools. In contrast, C. albicans was found to be the most important inducer of IgG antibodies, since the IgG level against P. ovale mannan in both AD serum pools was very low. Cross-reacting antibodies were also seen in ELISA inhibition with both crude and mannan antigens, but since the IgG antibody level of P. ovale mannan in AD serum pools was low, further studies are needed to confirm the IgG results.

IgE, IgA, and IgG responses to common yeasts in atopic patients.

This study was undertaken to analyze the differences in exposure and sensitization to five common environmental yeasts. The responses of IgG, IgA, and IgE to Candida albicans, C. utilis, Cryptococcus albidus, Rhodotorula rubra, and Saccharomyces cerevisiae and purified S. cerevisiae enolase were analyzed by immunoblotting (IgE-IB), and the cross-reactivity of their IgE-binding components by IgE-IB inhibition. Twenty atopic subjects, with asthma, allergic rhinitis, or atopic dermatitis were included. In skin prick tests (SPT), 12 of the patients showed simultaneous reactivity to at least two of the five yeasts, four reacted to one of the yeasts, and four had no responses. Antigens run in SDS-PAGE and transferred to nitrocellulose were probed with enzyme-labeled IgA-, IgG-, and IgE-specific antibodies. The IgE immunoblotting revealed most IgE-binding bands in C. albicans (11 bands) followed by C. utilis (eight bands), S. cerevisiae (five bands), R. rubra (five bands), and Cr. albidus (four bands). Six of the IgE-binding bands of C. albicans and C. utilis shared molecular weight, and only two bands shared molecular weight with other yeasts. These were the 46-kDa band, shared by all five yeasts, and a 13-kDa band shared by four yeasts. Prominent IgE binding was seen to a 46-kDa band of C. albicans (seven patients), C. utilis (five patients), and S. cerevisiae (one patient) and to corresponding weak bands of Cr. albidus and R. rubra (one patient). The possible cross-reactivity of the 46-kDa band was analyzed by IgE-IB inhibition and densitometry, revealing clear C. albicans inhibition of C. utilis (80%) and enolase (98%) (autoinhibition 100%). The strongest IgG responses were seen against S. cerevisiae and C. albicans. The responses were mainly against mannans of C. albicans and S. cerevisiae, suggesting that most of the exposure is to these yeasts. Yeasts with different types of exposure, from saprophytic growth on human mucous membranes to exposure by air and food, were shown to cross-react at the allergenic level. Atopic patients primarily sensitized by C. albicans and S. cerevisiae may develop allergic symptoms by exposure to other environmental yeasts due to cross-reacting IgE antibodies.

IgE antibody response against Aspergillus umbrosus in farmer's lung disease.

IgG and IgA antibodies against fungus Aspergillus umbrosus have been found in the sera of patients with farmer's lung (FL) disease and healthy exposed farmers in Finland. To determine the IgE response to antigens of A. umbrosus and Candida albicans, sera from 20 patients with FL, 20 healthy farmers and 20 nonfarming controls were tested by nitrocellulose radioallergosorbent test (RAST). The values of RAST indices were low in each group and the only statistically significant difference was found between the groups of FL patients and nonfarming controls against A. umbrosus polysaccharide antigen. Individual IgE responses to polysaccharide antigens of A. umbrosus and C. albicans correlated among FL patients, however, no cross-reacting IgE antibodies could be shown. To conclude, the IgE antibody levels of A. umbrosus polysaccharide and crude antigens were low in FL patients, healthy exposed farmers and nonfarming controls. Neither polysaccharide nor crude antigen-specific IgE antibodies of A. umbrosus have any diagnostic value in FL disease.

Enhanced IgE response to Candida albicans in postoperative invasive candidiasis.

BACKGROUND: Invasive candidiasis is a life-threatening complication problem in post-operative and immunocompromized patients, e.g. those treated by intensive care. Candida is frequently cultured from the mucous membranes of hospital patients and fungal cultures offer little diagnostic help. Other diagnostic methods, such as blood cultures, serology and diagnostic imaging techniques produce results too late and, if positive, low sensitivity. OBJECTIVE: To study the value of Candida-specific antibodies, especially those of IgE class, in diagnosing invasive Candida infection. METHODS: The immunoglobulins IgE, IgG and IgM responses to antigens of Candida albicans in the sera of 14 patients with culture, biopsy and/or autopsy proven postoperative invasive candidiasis and of 11 colonized and 19 non-colonized operated patients were studied by mannan radioallergosorbent test (RAST), mannan enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Detection of IgE antibodies to C. albicans polysaccharide (mannan) and protein antigens proved specific and sensitive in diagnostics of invasive candidiasis after major abdominal surgery. IgE rose early in the course of the infection and the method made a clear distinction between invasive infection and mucous colonization. Immunoblotting for protein antibodies was most sensitive while nitrocellulose-RAST for mannan antibodies was most specific. The combined use of immunoblotting and RAST increased the sensitivity and the specificity. Determinations of anti-Candida IgG and IgM antibodies had low sensitivity and specificity. CONCLUSION: Critically ill patients with invasive candidiasis develop IgE antibodies to Candida antigens probably because of disturbed TH1/TH2 responses. Determination of specific IgE antibodies can be used as a diagnostic aid in the early stage of invasive Candida infection.

A comparison of the development of antibody responses to the polysaccharide antigen (Candida albicans mannan) in atopic and healthy infants and children.

BACKGROUND: Defective antibody response against bacterial polysaccharide antigens is known to be associated with recurrent pyogenic infections. The role of childhood allergy as a risk factor for repeated infections with capsulated micro-organisms has been controversial. OBJECTIVE: To compare the development of polysaccharide specific antibody responses in atopic and healthy infants and children. METHODS: The antibody responses against a common polysaccharide antigen, Candida albicans mannan, were studied longitudinally in 18 atopic and 19 non-atopic children over the first 5 years of life. Determinations of IgA, IgG and IgM antibodies were carried out by enzyme-linked immunosorbent assay and IgE antibodies by nitrocellulose-based radioallergosorbent test. RESULTS: The polysaccharide specific antibody responses were similar in both groups, except that anti-mannan IgM levels were higher at 5 years in the atopic children (P < 0.05, student's t-test). CONCLUSION: Atopic children are not more susceptible to bacterial infections on the basis of poorer ability to produce antibodies against polysaccharide antigens.

Nitrocellulose-RAST analysis of allergenic cross-reactivity of Candida albicans and Saccharomyces cerevisiae mannans.

Two chemically purified mannan preparations and one affinity purified mannan preparation of Candida albicans and Saccharomyces cerevisiae were analyzed for allergenic cross-reactivity. Simultaneous IgE binding in radioallergosorbent test (RAST) was studied with all preparations and the chemically purified mannans were also used for RAST inhibitions. The yeast mannans were purified with the Peat method, using repeated ethanol precipitations and Fehling's precipitation in alkaline conditions, and the Cetavlon method, using hexadecyltrimethylammonium bromide and ethanol precipitations. Affinity purification of the mannans was performed with concanavalin A lectin bound to a Sepharose column. Mannan from Pityrosporum ovale was purified with the Cetavlon method for analysis of simultaneous RAST reactivity. Simultaneous IgE binding to all the studied yeast mannans was generally seen in all the studied sera of patients suffering from atopic dermatitis. The strongest responses were seen against C. albicans mannan, especially the Cetavlon mannan. In the RAST inhibition studies IgE binding to S. cerevisiae mannan was completely inhibited by C. albicans mannan preparations, whereas reciprocal inhibition was not complete. These results indicate that in atopic dermatitis simultaneous IgE response to yeast polysaccharides occurs and that the major sensitizer is C. albicans and IgE antibodies against S. cerevisiae mannan are cross-reacting.

Determination of IgE antibodies to Candida albicans mannan with nitrocellulose-RAST in patients with atopic diseases.

A nitrocellulose-based radioallergosorbent test (RAST) was developed and used for the determination of IgE antibodies to Candida albicans mannan in patients with atopic dermatitis, asthma and allergic rhinitis. The results were expressed as mannan-RAST index values (an inter- and intra-assay coefficient for variation of 8.0-10.2%). The normal range for mannan-RAST index values was determined in 102 non-atopic adults. Fifty-three of 78 (67.9%) patients with atopic dermatitis showed elevated mannan-RAST index values with a significant correlation to the severity of the dermatitis (r = 0.33, P < 0.01). Sixteen of 30 (53.3%) patients with asthma had a positive mannan-RAST index value; however, 12 of the 16 asthmatics (75%) who were positive also suffered from atopic dermatitis. Those who had allergic rhinitis but not atopic dermatitis showed a positive mannan-RAST index value in 12 of 32 (37.5%) cases. Nitrocellulose-RAST offered a sensitive method for the determination of polysaccharide-specific IgE antibodies in atopic diseases. The results show that high values are observed mainly in atopic dermatitis and less sensitization to C. albicans occurs in respiratory allergy.