This review describes the recent literature on microbial exposures and protective effects for asthma and atopy. Certain microorganism-associated molecular patterns have been identified as agents that might influence the development of the immune system, which in turn leads to protective effects for asthma and atopy. Endotoxins from gram-negative bacteria were the first agents associated with a reduced risk for asthma and atopy. In later studies, β(1→3)glucans, extracellular polysaccharides, and muramic acid from, respectively, molds and gram-positive bacteria were associated with a reduced risk of allergy and asthma separately in rural and urban populations. These results already suggested that not just one but several independent microbial signals from gram-negative and gram-positive bacteria, as well as molds, might play a role in explaining the protective effects. Recently, the diversity of microbial exposure has been associated with such a reduced risk in farmers’ children. Surprisingly, the diversity of both fungal and bacterial exposure seemed to have protective effects. These results open new areas of research and create complex challenges. Methodological issues, such as environmental exposure characterization and assessment and elucidation of potential underlying mechanisms, are discussed because these aspects have a major influence on how microbial diversity can be studied in future studies in relation to protective effects for asthma and atopy.

Background: Environmental factors can affect the development of atopic dermatitis, and this was described to be already effective during pregnancy and in early life. An important early postnatal exposure is nutrition, although its association with allergic disease remains unclear.Objective: We sought to determine prospectively whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality.Methods: One thousand forty-one children who participated in the Protection Against Allergy–Study in Rural Environments birth cohort study were included in the current study. Atopic dermatitis was defined by a doctor's diagnosis reported by the parents of children up to 4 years of age, by questionnaires, and/or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life. Feeding practices were reported by parents in monthly diaries between the 3rd and 12th months of life.Results: The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life (adjusted odds ratio for atopic dermatitis with each additional major food item introduced, 0.76; 95% CI, 0.65-0.88). The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis (adjusted odds ratio, 0.41; 95% CI, 0.23-0.73).Conclusion: As early-life exposure, the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis.

Background: The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD).Objective: We sought to determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time.Methods: Children aged 5 to 12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled corticosteroids and oral corticosteroids (OCSs) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial, and serial dual-energy x-ray absorptiometry scans of the lumbar spine were performed. Annual BMA rates were defined as follows: [(BMD at 4 years’ follow-up − BMD at baseline)/4 years].Results: BMA was calculated for 780 subjects. In boys baseline vitamin D levels significantly modified the relationship between OCSs and BMA (vitamin D × OCS interaction, P = .023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCSs in vitamin D–insufficient boys only (P < .001). Compared with vitamin D–sufficient boys, vitamin D–insufficient boys exposed to more than 2 courses of OCSs per year had twice the decrease in BMA rate (relative to boys who were OCS unexposed).Conclusions: Vitamin D levels significantly modified the effect of OCSs on BMA in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma might confer benefits to bone health.

Background: Although the extreme condition of typical profound T-cell dysfunction (TD), severe combined immunodeficiency (SCID), has been carefully defined, we are currently in the process of better defining less typical T-cell deficiencies, which tend to present with autologous circulating T-cell combined immunodeficiency (CID). Because autologous cells might interfere with the outcome of bone marrow transplantation, protocols usually include conditioning regimens. Therefore it is important to define the numbers of autologous cells usually detected in patients with CID versus those with SCID.Objectives: We sought to determine the number of circulating T cells in patients with SCID as opposed to those with CID, to study their function, and to evaluate their possible detection during newborn screening using T-cell receptor excision circle (TREC) analysis.Methods: Numbers of circulating CD3+ T cells (as determined by means of flow cytometry), in vitro responses to PHA, and TREC levels, all measured at presentation, were compiled from the research charts of the entire cohort of patients followed prospectively for T-cell immunodeficiency at the Hospital for Sick Children. Clinical data were ascertained retrospectively from the patient's hospital charts.Results: One hundred three patients had CD3+ determinations, and 80 of them had a genetic diagnosis. All patients considered to have typical SCID had CD3+ T-cell counts of fewer than 500 cells/μL. Some variability was observed among different genotypes. In vitro responses to PHA were recorded in 88 patients, of whom 68 had a genetic diagnosis. All patients with low CD3+ T-cell numbers (<500 cells/μL) also had markedly decreased responses to PHA (typical SCIDs). However, responses ranged widely in the groups of patients with TD who had more than 500 CD3+ autologous circulating T cells per microliter. Although patients with Omenn syndrome and ζ chain–associated protein, 70 kDa (ZAP70), and purine nucleoside phosphorylase (PNP) deficiencies had low responses, patients with the p.R222C mutation in the IL-2 receptor γ (IL2RG) gene as well as IL-10 receptor and CD40 ligand deficiencies had normal or near-normal mitogen responses. Finally, 51 patients had TREC levels measured. All patients with typical SCID, Omenn syndrome, and ZAP70 deficiency had low TREC levels. In contrast, patients with mutations in forkhead box protein 3 (FOXP3), CD40 ligand (CD40L), and IL-10 receptor α (IL10RA), as well as patients with the p.R222C mutation in the IL2RG gene, had normal TREC levels.Conclusion: Patients with typical SCID can be defined as having fewer than 500 circulating CD3+ T cells. Most patients with autologous T cells still have profound TD, as defined by reduced in vitro function and thymus output. Some patients with conditions including TD have normal TREC levels and will therefore not be detected in a TREC-based newborn screening program.