Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review.

The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.

Serum 25-hydroxyvitamin D levels in children with recurrent wheezing and relation to the phenotypes and frequency of wheezing.

SUMMARY: Background. Recurrent wheezing may be related to various reasons. There is a lack of knowledge about the effect of vitamin D status in the children with recurrent wheezing. The aim of this study is to compare the level of vitamin D between recurrent wheezing children and healthy controls, and to investigate the relationship between vitamin D status and the clinical parameters of recurrent wheezing in preschool children. Methods. One hundred-ten children followed up in our hospital with recurrent wheezing were included in the study. The control group included fifty children without wheezing episodes. The serum 25-hydroxyvitamin D (25OHD) level was measured. The patients with recurrent wheezing were grouped according to their vitamin D status as "deficient group" and "non-deficient group (Vitamin D level is insufficient and normal)". We investigated the relationship between vitamin D status and the clinical and laboratory parameters of children with recurrent wheezing. Results. Mean 25OHD level was 21.66 ± 8.13 ng/mL (5.6-53) in the study group and 25.36 ± 10.17 ng/mL (6-59) in the control group. The difference was statistically significant (p = 0.015). When the patients with recurrent wheezing were compared according to their vitamin D status, number of hospitalizations, number of positive sensitivity, percentage of eosinophil, serum IgE levels, Asthma Predictive Index positivity and wheezing phenotypes were not found to be different between groups. However, the duration of wheezing, the number of wheezing episodes and systemic glucocorticoid need in the previous year, and the total number of wheezing episodes were significantly higher in the deficient group (p < 0.05). The serum 25OHD level was negatively correlated with the duration of wheezing (r: -0.238; p: 0.012), total number of wheezing episodes (r: -0.436; p: 0.001), number of wheezing episodes in the previous year (r: -0.395; p: 0.001), and systemic glucocorticoid need in the previous year (r: -0.324; p: 0.001). Conclusions. Mean 25OHD levels were lower in patients with recurrent wheezing than in healthy controls. The duration of illness and number of wheezing episodes were correlated with vitamin D levels. An evaluation of the serum levels of vitamin D and supplementation if needed should be recommended in patients with recurrent wheezing, especially in those with long-term and frequent wheezing episodes.

Clinical trial/experimental study (consort compliant): Optimal time period to achieve the effects on synbiotic-controlled wheezing and respiratory infections in young children.

INTRODUCTION: Urban life is often followed by immune dysfunction and loss of immune tolerance in the youngest children. OBJECTIVE: The study aimed to determine optimal time efficiency of a synbiotic (5 x 109 Lactobacillus acidophilus Rosell-52, Bifidobacterium infantis Rosell-33, Bifidobacterium bifidum Rosell-71) in controlling respiratory infections and wheezing disease. METHODS: We randomly selected a group of children younger than five years, hospitalized earlier, and classified them into three groups. RESULTS: The incidence of respiratory infection before the study was once a month, while after a three-month supplementation with the synbiotic children rarely suffered from respiratory infections, and the state was maintained after six-month and nine-month supplementations with the synbiotic. The decreased incidence of respiratory infections was followed by a falling incidence of concomitant wheezing. A significant increase in tIgA serum was observed in all groups for only three months, the increase being the highest in children with recurrent respiratory infections accompanied by wheezing. After a nine-month administration of the synbiotic, total IgE serum was lower in all groups of patients. CONCLUSION: The optimal duration of administration of the synbiotic containing three probiotic cultures to provide effective control of the frequency of respiratory infections was three months, and six months were required to establish control of the frequency of wheezing. This synbiotic is useful for immunomodulation in children and is well-tolerated in young children.

Is vitamin D deficiency correlated with childhood wheezing and asthma?

There is increasing evidence that vitamin D regulates immune responses. There is also epidemiological evidence of a relationship between vitamin D deficiency and development of asthma. In addition, several epidemiological studies suggest that low levels of vitamin D during pregnancy and early life are inversely associated with the risk of developing respiratory infections and wheezing in childhood. Vitamin D also seems to reduce asthma exacerbation and increase the response to glucocorticoids. These findings have led to considering a possible link between the occurrence of allergic respiratory diseases and low levels of vitamin D. However, the precise role of vitamin D in the pathogenesis of asthma still remains unclear, emphasizing the need for well-designed trials on vitamin D supplementation to decipher its role in preventing and/or managing the disease. This review examines the relationship that exists between vitamin D deficiency and childhood wheezing and asthma.

Urban tree canopy and asthma, wheeze, rhinitis, and allergic sensitization to tree pollen in a New York City birth cohort.

BACKGROUND: Urban landscape elements, particularly trees, have the potential to affect airflow, air quality, and production of aeroallergens. Several large-scale urban tree planting projects have sought to promote respiratory health, yet evidence linking tree cover to human health is limited. OBJECTIVES: We sought to investigate the association of tree canopy cover with subsequent development of childhood asthma, wheeze, rhinitis, and allergic sensitization. METHODS: Birth cohort study data were linked to detailed geographic information systems data characterizing 2001 tree canopy coverage based on LiDAR (light detection and ranging) and multispectral imagery within 0.25 km of the prenatal address. A total of 549 Dominican or African-American children born in 1998-2006 had outcome data assessed by validated questionnaire or based on IgE antibody response to specific allergens, including a tree pollen mix. RESULTS: Tree canopy coverage did not significantly predict outcomes at 5 years of age, but was positively associated with asthma and allergic sensitization at 7 years. Adjusted risk ratios (RRs) per standard deviation of tree canopy coverage were 1.17 for asthma (95% CI: 1.02, 1.33), 1.20 for any specific allergic sensitization (95% CI: 1.05, 1.37), and 1.43 for tree pollen allergic sensitization (95% CI: 1.19, 1.72). CONCLUSIONS: Results did not support the hypothesized protective association of urban tree canopy coverage with asthma or allergy-related outcomes. Tree canopy cover near the prenatal address was associated with higher prevalence of allergic sensitization to tree pollen. Information was not available on sensitization to specific tree species or individual pollen exposures, and results may not be generalizable to other populations or geographic areas.

Onions, myths, beliefs, fashion and reality in asthma.

Some myths and unsupported beliefs about asthma are very popular and enjoy general public acceptance and fairly strong support on the Internet. Onions for cough; dairy products avoidance for asthma; and some other popular myths are reviewed, along with some other medical and mixed (popular and medical) myths comparing their popular and scientific support. Classifying medical statements as realities or unsupported beliefs is a hard and serious work nowadays addressed by Evidence Based Medicine methods, which are not devoid of the influence of medical fashion: the medical community is more prone to accept fashionable statements compared to non-fashionable or old-fashioned statements.

A clinical study of Japanese cedar (Cryptomeria japonica) pollen-induced asthma.

BACKGROUND: Grass and birch pollens are known to induce asthma. However there are few reports about other pollen-induced asthma. Japanese cedar is the most common allergen in rhinitis in Japan but is controversial on whether it can provoke asthma. METHODS: To clarify Japanese cedar pollen-induced asthma, we studied adult patients who were sensitized only to the Japanese cedar (CAP-RAST > = 2) and had symptoms of asthma during the cedar season. We defined cedar asthma as a patient who satisfied the 2 criteria mentioned above. RESULTS: We found 6 adult asthma patients who fulfilled the two criteria. Five patients suffered from cedar pollinosis in addition to asthma, and 1 patient had no pollinosis. The cedar pollinosis preceded asthma in 3 cases and occurred at almost the same time in the other 2 cases. Pulmonary function was normal in these cases (FEV 1%, mean +/- SD, 76.5 +/- 10%), with a high threshold value in the non-specific airway hypersensitivity test (Ach-PC20, 2,696 to 20,000 microg/ml, 9294 +/- 2) and low total IgE (101 +/- 86 IU/ml). In the allergen provocation test, 3 subjects showed both an immediate and late asthmatic reaction. CONCLUSIONS: We concluded that Japanese cedar pollen could provoke not only pollinosis but also asthma in adults.

Transforming growth factor-beta and interleukin-10 in breast milk and development of atopic diseases in infants.

BACKGROUND: Precise relationship between breastfeeding and infant allergy is poorly understood. Objective Aim was to quantify TGF-beta(1) and IL-10 in colostrum and mature milk from allergic and non-allergic mothers and to verify relationship with allergic disease development. METHODS: Mothers (13 allergics, nine controls) of 22 newborns participated to prospective study on development of children atopy. Colostrum and mature milk were assayed for TGF-beta(1) and IL-10 by ELISA. Children underwent paediatrician evaluation at 6 months of life. RESULTS: Data are presented as median values and range. A significant difference in concentration of TGF-beta(1) between colostrum (330, range 0-3400 pg/mL) and mature milk (215, range 0-2400 pg/mL) was observed in samples from allergic mothers (P=0.015). In mature milk TGF-beta(1) was significantly lower in allergic (215, range 0-2400 pg/mL) than in non-allergic mothers (1059, range 0-6250 pg/mL) (P=0.015). IL-10 was weakly expressed without significant differences between allergic (4.8, range 0-42 and 9.5, range 0-42 pg/mL in colostrum and in mature milk) and non-allergic mothers (0, range 0-42 pg/mL in colostrum and 0, range 0-42 pg/mL in mature milk). After 6 months 46% infants from allergic mothers, but none from controls, presented atopic dermatitis. CONCLUSION: TGF-beta(1) was significantly less secreted in mature milk of allergic mothers, while no difference in IL-10 was found. Particular cytokine patterns in milk could influence development of atopic diseases. Further immunological studies in this field are necessary.

Validation of questions on asthma and wheeze in farming and anthroposophic children.

BACKGROUND: In most epidemiological surveys the estimated prevalence of asthma is based on questionnaire responses, which may depend on the individual's perception as well as medical consulting habits in a given population. Therefore, measurement of bronchial hyper-responsiveness as a key feature of asthma has been suggested as an objective parameter for asthma. OBJECTIVE: The aim of the present study was to validate questionnaire responses on asthma and wheeze against bronchial response to hypertonic saline (HS) (4.5%) in populations previously shown to have a lower prevalence of asthma and allergies: farmers' children and children from anthroposophic families. METHODS: Children whose parents had completed a written questionnaire in the cross-sectional PARSIFAL-study were drawn from the following four subgroups: 'farm children' (n=183), 'farm reference children' (n=173), 'Steiner schoolchildren' (n=243) and 'Steiner reference children' (n=179). Overall, 319 children with wheeze in the last 12 months and 459 children without wheeze in the last 12 months performed an HS challenge. RESULTS: Odds ratios, sensitivity, specificity, likelihood ratios and measures of association did not differ significantly between the four subgroups. The correlation between the bronchial response to HS and wheeze and asthma questions was moderate and similar for farm children, farm reference children, Steiner schoolchildren and Steiner reference children (kappa for 'wheeze': 0.25, 0.33, 0.31, 0.35, respectively, P=0.754, kappa for 'doctor's diagnosis of asthma': 0.33, 0.19, 0.33, 032, respectively, P=0.499). CONCLUSION: The findings from this study suggest that the reliabilitiy of questionnaire responses on asthma and wheeze is comparable between farmers' children, children raised in families with anthroposophic lifestyle and their respective peers.

Skin sensitization to common allergens in Turkish wheezy children less than 3 years of age.

Infants and small children with asthma are not commonly skin tested, as allergy is not considered to be a major cause of infantile asthma. The aim of this study was to determine the frequency of skin test positivity to various allergens in wheezy children less than 3 years of age. We evaluated 161 patients with infantile asthma (median age 20 months) and 100 healthy controls (median age 18 months). Infantile asthma was defined as three or more episodes of wheezing in a child less than 3 years of age, whose symptoms improved on treatment with beta-agonist and anti-inflammatory agents. All children were skin tested to house dust mites (HDM), pollens, molds, and cow milk extracts using prick technique. One hundred and eighteen (73.3%) children In the patient group tested positive to HDM, 84 (52.1%) to pollens, 37 (22.9%) to molds, and 16 (10%) to cow milk. Sensitization rates to HDM were significantly higher in the patient group than In the healthy controls. Sensitization rates to pollens were not statistically different between the two groups. There was no association between family history of atopy and frequency of sensitization to allergens in the wheezy and control groups. We concluded that skin sensitization to allergens was common In wheezy infants. The prevalence of sensitization to indoor allergens was higher than to outdoor or food allergens.

Development of seasonal allergic rhinitis during the first 7 years of life.

BACKGROUND: Against the background of the controversial discussion about an increase in allergic rhinitis in recent years, intraindividual longitudinal data is lacking for IgE-mediated seasonal allergic rhinitis (SAR). Little is known about the development of SAR in terms of prevalence and incidence rates from birth to school age. OBJECTIVE: In a prospective birth cohort, we investigated the development of sensitization and symptoms of SAR. SAR should be defined with high specificity, and associated risk factors should be determined. METHODS: Annual longitudinal data about seasonal allergic symptoms and sensitization was available for 587 children from birth to their seventh birthday. The definition of SAR was based on a combination of exposure-related symptoms and sensitization. RESULTS: Up to 7 years of age, SAR developed in 15% of the children. Incidence and prevalence of symptoms and sensitization were low during early childhood (<2%) and increased steadily with age. Children in which SAR had already developed in the second year all were born in spring or early summer, resulting in at least two seasons of pollen exposure before manifestation of SAR. Risk factors assessed by multiple logistic regression analysis were male sex (odds ratio [OR] = 2.4), atopic mothers (OR = 2.6) and fathers (OR = 3.6) having allergic rhinitis themselves, first-born child (OR = 2.0), early sensitization to food (OR = 3.3), and atopic dermatitis (OR = 2.5), whereas early wheezing was not associated with SAR. CONCLUSION: The development of SAR is characterized by a marked increase in prevalence and incidence after the second year of life. Our longitudinal data further indicate that in combination with the risk of allergic predisposition, at least 2 seasons of pollen allergen exposure are needed before allergic rhinitis becomes clinically manifest.