Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial

The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.

https://science.sciencemag.org/content/sci/296/5567/490.full.pdf

Allergy, Parasites, and the Hygiene Hypothesis

Allergic Diseases and Their Treatment Allergic Rhinitis Allergic rhinitis is characterized by episodes of sneezing, itching, rhinorrhea, and nasal obstruction. Perennial allergic rhinitis should be distinguished from nonallergic, noninfectious forms of rhinitis, such as idiopathic (“vasomotor”) rhinitis, nonallergic rhinitis with eosinophilia syndrome, hormonal rhinitis, drug-induced rhinitis, and food-induced rhinitis. The treatment of allergic rhinitis (and other allergic diseases) consists of allergen avoidance (whenever possible and practical), antiallergic medication, and immunotherapy for specific allergens, which is also called hyposensitization or desensitization. Currently, the drugs usually used to treat allergic rhinitis are antihistamines and anticholinergic agents (for the relief of symptoms) and . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM200101043440106?listPDF=true

Allergy and allergic diseases.

Background. Declining family size is one factor that has been proposed to contribute to increasing asthma and hay fever prevalence, but its relative importance has not been quantified. Objective. Our purpose was to determine the change in asthma and hay fever prevalence that would be expected from the reduction in family size that has occurred in England/Wales and New Zealand over recent decades. Methods. The relative change in family size between 1961 and 1991 in England/Wales and New Zealand was determined from census data for these years. Summary weighted odds ratios were calculated for the associations among birth order, family size, and asthma and hay fever prevalence. The expected increase in the prevalence of asthma and hay fever between 1961 and 1991 resulting from changes in family size was then calculated. Results. The expected relative increase in the prevalence of asthma between 1961 and 1991 as a result of the smaller family size was 1% and 5% for England/ Wales and New Zealand, respectively; smaller family size would be expected to increase the prevalence of hay fever prevalence in England/Wales by 4%. Conclusions. Changes in family size over the last 30 years do not appear to explain much of the reported increase in asthma or hay fever prevalence. The contribution that other risk factors have made to these increases could be assessed with use of a similar approach. (J Allergy Clin Immunol 1999;104:554–8)

https://thorax.bmj.com/content/thoraxjnl/55/suppl_1/S2.full.pdf

Family size, infection and atopy: the first decade of the "hygiene hypothesis".

Background: The intestinal microflora is a likely source for the induction of immune deviation in infancy. Objective: The purpose of this study was to prospectively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases. Methods: Newborn infants were followed prospectively through the first 2 years of life in Estonia (n = 24) and Sweden (n = 20). By that age, 9 Estonian and 9 Swedish infants had developed atopic dermatitis and/or positive skin prick test results. Stool samples were obtained at 5 to 6 days and at 1, 3, 6, and 12 months, and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of standard methods. Results: In comparison with healthy infants, babies who developed allergy were less often colonized with enterococci during the first month of life (72% vs 96%; P < .05) and with bifidobacteria during the first year of life (17% to 39% vs 42% to 69%; P < .05). Furthermore, allergic infants had higher counts of clostridia at 3 months (median value, 10.3 vs 7.2 log10; P < .05). The prevalence of colonization with Staphylococcus aureus was also higher at 6 months (61% vs 23%; P < .05), whereas the counts of Bacteroides were lower at 12 months (9.9 vs 10.6 log10; P < .05). Conclusion: Differences in the composition of the gut flora between infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy. Because the observations were made in 2 countries with different standards of living, we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy. (J Allergy Clin Immunol 2001;108:516-20.)

https://www.jacionline.org/article/S0091-6749(01)96140-8/pdf

Allergy development and the intestinal microflora during the first year of life

The intestinal microflora of 1-y-old healthy Estonian (n = 27) and Swedish infants (n = 29) was studied by quantitative culture of faecal samples. The major differences were high counts of lactobacilli and eubacteria in the former and increased numbers of clostridia in the latter babies. Bifidobacteria and anaerobic cocci prevailed equally in both groups, while eubacteria and enterococci were the major microorganisms in many Estonian infants and bacteroides and clostridia in many Swedish infants. The microflora of the Estonian infants was in many aspects similar to the flora prevailing in infants of western Europe in the 1960s. The results suggest a shift in the intestinal microflora among infants in western industrialized countries.

Intestinal microflora of Estonian and Swedish infants.

In a prospective study, 251 infants were followed from birth up to 12 months of age, recording manifestations of allergy by questionnaires at 3, 6, 9 and 12 months and by clinical examinations at 6 and/or 12 months. Blood samples were obtained at birth and at 6 and 12 months and analysed for serum IgE levels. The children were skin-prick tested with foods at 6 and 12 months of age and with inhalant allergens at 12 months. Blood samples from SPT-positive individuals and controls were analysed for the presence of IgE antibodies to common inhalant allergens and their cord sera for the presence of IgE antibodies to cow's milk and egg. Twelve infants (7%) were sensitized against foods [3 to cow's milk (CM) and 9 to egg white (EW)] at 6 months and 11 (5%) (2 to CM and 9 to EW) at 12 months. Seventeen infants (7%) had IgE antibodies against inhalant allergens at 6 and/or 12 months, as determined by either SPT and/or the demonstration of circulating IgE antibodies. Out of 30 children with positive SPT and/or circulating IgE antibodies against foods and inhalant allergens at any age, 6 had atopic dermatitis, 4 gastrointestinal food allergy, 1 urticaria and 4 probable allergy, while 15 had no clinical manifestation of allergy. Immunoglobulin E antibodies against Ascaris were detected in 17% of the infants with S-IgE levels > 20 kU/l. The study indicates that the incidence of sensitization and manifestations of allergic disease is similar among Estonian and Scandinavian infants during the first year of life. Given earlier findings indicating a significantly higher prevalence of atopic disease in Scandinavian school-children relative to their counterparts in Eastern Europe, the present study suggests that the key events which determine disease expression do not occur exclusively during the first year of life.

The development of atopic sensitization in Estonian infants

There is a lack of established criteria to identify asthma and bronchial hyperreactivity (BHR) in epidemiological studies, although both conditions appear to bear some relationship to atopy, at least in children. Recent studies indicate a low prevalence of atopy in former Socialist countries in Europe, yet the prevalence of BHR has been reported to be high. We have analysed the relationship between the outcome of various lung function tests, atopy and clinical symptoms of bronchial asthma in an epidemiological survey of Estonian 10-12 year old schoolchildren. Metacholine provocation test (four steps with the cumulative doses 100, 300, 700 and 1100 micrograms), exercise challenge test and PEF-variability over two weeks were done in 806 children in Tallinn (coastal, industrialised city) and 774 children in Tartu (inland, university town). A positive response to the metacholine challenge test was recorded in 19% in Tallinn and in 32% in Tartu (p < 0.001). A similar tendency was observed for a more than 15% decrease of FEV1 in the exercise challenge test, i.e. 6% in Tallinn and 18% in Tartu. There was only a weak relationship between BHR, as defined by either a positive metacholine challenge and/or exercise test, diagnosed asthma and reported wheezing. Thus, 47% of the wheezing children and 30% of the children with asthma had negative test results. Only 17% of the children with a positive metacholine challenge were atopic, as defined by at least one positive skin prick test. In conclusion, none of the methods employed to assess bronchial hyperresponsiveness were very useful for the identification of wheezing and asthmatic children in this epidemiological study. In contrast to the results of studies in Western Europe, most children with bronchial hyperreactivity in Estonia are not atopic.

K Julge

Papers

Intestinal microflora of Estonian and Swedish infants.

The development of atopic sensitization in Estonian infants

Prevalence of bronchial hyperreactivity as determined by several methods among Estonian schoolchildren.