The role of the skin in the atopic march.

Atopic diseases, including atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR) are closely related to inflammatory diseases involving different body sites (i.e. the skin, airway, and digestive tract) with characteristic features including specific IgE to allergens (so-called 'atopy') and Th2 cell-mediated inflammation. It has been recognized that AD often precedes the development of other atopic diseases. The progression from AD during infancy to FA or asthma/AR in later childhood is referred as the 'atopic march' (AM). Clinical, genetic and experimental studies have provided evidence that allergen sensitization occurring through AD skin could be the origin of the AM. Here, we provide an updated review focusing on the role of the skin in the AM, from genetic mutations and environmental factors associated with epidermal barrier dysfunction in AD and the AM, to immunological mechanisms for skin sensitization, particularly recent progress on the function of key cytokines produced by epidermal keratinocytes or by immune cells infiltrating the skin during AD. We also highlight the importance of developing strategies that target AD skin to prevent and attenuate the AM.

Dog Allergy in Children: A Single-Centered Study.

INTRODUCTION: Dogs are among the most commonly allergenic pets for children. Data on risk factors for the development of dog allergy are scarce. This study aimed to evaluate the characteristics of children with dog allergy and identify predictors of symptom development with dog exposure. METHODS: The study included children with dog allergen sensitization demonstrated by skin prick test (SPT) between September 1, 2019, and December 1, 2022. Demographic, clinical, and laboratory data were collected from the patients' records and interviews with parents. RESULTS: Dog allergen sensitization was detected by SPT in 548 (5.5%) of 9,907 patients. Of these, 507 patients had complete data and were included in the analysis. The patients' median age was 11 (IQR: 8-15) years, 55.8% were male, 97.6% exhibited polysensitization (pollen 75.1%, cat 69.6%), 83.6% had allergic rhinitis, and 46.2% had asthma. Acute dog exposure caused symptoms in 164 patients (32.3%), most commonly sneezing (n = 97) and nasal symptoms (n = 80). Predictors of acute symptoms in dog-sensitized children were male sex (OR: 0.584 [CI: 0.38-0.87]), dog exposure before 1 year of age (OR: 2.35 [CI: 1.18-4.66]), close contact with a dog owner (OR: 2.93 [CI: 1.78-4.8]), and cat allergy (OR: 2.75 [CI: 1.82-4.1]). CONCLUSION: Approximately one-third of children with dog sensitization developed symptoms after exposure to the dog. Male sex, direct dog exposure before the age of one, close contact with a dog owner, and cat allergy were identified as predictors of dog allergy.

Higher maternal bread and thiamine intakes are associated with increased infant allergic disease.

BACKGROUND: A mother's diet during pregnancy may influence her infant's immune development. However, as potential interactions between components of our dietary intakes can make any nutritional analysis complex, here we took a multi-component dietary analysis approach. METHODS: Nutritional intake data was collected from 639 pregnant women using a validated semi-quantitative food frequency questionnaire to reflect their dietary intakes during 32-36 weeks of gestation. To investigate their dietary intake pattern, we calculated Dietary Inflammatory Index scores. Maternal consumption of 12 food groups, 20 individual whole foods, and 18 specific nutrient intakes, along with any vitamin and mineral supplementation, were determined. Infant outcomes included eczema, allergen sensitization, and IgE-mediated food allergy. Regression-based analyses with covariates adjustment were applied. RESULTS: Women with higher white bread consumption were more likely to have an infant with doctor-diagnosed eczema (adjusted relative risk [aRR] 1.16; 95% CI 1.08, 1.24; p < .001) and IgE-mediated food allergy (aRR 1.14; 95% CI 1.02, 1.28; p = .02). Higher maternal intakes of fiber-rich bread (aRR 1.14; 95% CI 1.04, 1.25; p = .01) and legumes (aRR 1.11; 95% CI 1.02, 1.21; p = .02) were also associated with infant doctor-diagnosed eczema. Higher maternal thiamine intakes were associated with increased parent-reported infant eczema (aRR 1.08; 95% CI 1.03, 1.12; p < .001). CONCLUSION: In Australia, where bread flour is fortified with thiamine, we identified consistent links between higher maternal thiamine-rich diets and increased risk of infant eczema and food allergy. Our results highlight a need for further investigation of potential effects of high thiamine exposures on immune development, especially in-utero.

Relationship between dust allergen sensitization and cardiac autonomic function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Cardiac autonomic function predicts cardiovascular disease risk. The aim of this study was to investigate the relationship between sensitization to dust allergens and cardiac autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD), and to provide new ideas for the prevention of cardiovascular complications in these patients. METHODS: Immunoassays for sensitization to cats/dogs, cockroaches and dust mites were performed in 840 patients with COPD. Indicators of heart rate variability in these patients were used to assess cardiac autonomic function, including standard deviation of normal-to-normal intervals (SDNN), root-mean square of successive differences between normal-to-normal intervals (RMSSD), low-frequency power (LF), high-frequency power (HF), and LF/HF ratios, which were obtained based on ambulatory electrocardiographic monitoring data. The relationship between sensitization to these dust allergens and heart rate variability was explored using multivariate logistic regression. FINDINGS: The multivariate analyses showed that sensitization to total allergens was associated with reduced levels of SDNN, RMSSD, LF and HF and with increased levels of the LF/HF ratio in the patients with COPD (p < .05). CONCLUSION: Dust allergen sensitization may be associated with cardiac autonomic dysfunction in patients with COPD. Whether desensitization can prevent cardiovascular complications in these patients should be further explored.

Home Dust Allergen Exposure Is Associated with Outcomes among Sensitized Individuals with Chronic Obstructive Pulmonary Disease.

Rationale: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. Objectives: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. Methods: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. Measurements and Main Results: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV1 of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (ß, -8.29; 95% confidence interval [CI], -14.80 to -1.77), higher St. George's Respiratory Questionnaire Total Score (ß, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. Conclusions: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD outcomes.

Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is among the most common chronic inflammatory skin diseases, usually occurring early in life, and often preceding other atopic diseases such as asthma. TH2 has been believed to play a crucial role in cellular and humoral response in AD, but accumulating evidence has shown that follicular helper T cell (TFH), a critical player in humoral immunity, is associated with disease severity and plays an important role in AD pathogenesis. OBJECTIVES: This study aimed at investigating how TFHs are generated during the pathogenesis of AD, particularly what is the role of keratinocyte-derived cytokine TSLP and Langerhans cells (LCs). METHODS: Two experimental AD mouse models were employed: (1) triggered by the overproduction of TSLP through topical application of MC903, and (2) induced by epicutaneous allergen ovalbumin (OVA) sensitization. RESULTS: This study demonstrated that the development of TFHs and germinal center (GC) response were crucially dependent on TSLP in both the MC903 model and the OVA sensitization model. Moreover, we found that LCs promoted TFH differentiation and GC response in the MC903 model, and the depletion of Langerin+ dendritic cells (DCs) or selective depletion of LCs diminished the TFH/GC response. By contrast, in the model with OVA sensitization, LCs inhibited TFH/GC response and suppressed TH2 skin inflammation and the subsequent asthma. Transcriptomic analysis of Langerin+ and Langerin- migratory DCs revealed that Langerin+ DCs became activated in the MC903 model, whereas these cells remained inactivated in OVA sensitization model. CONCLUSIONS: Together, these studies revealed a dual functionality of LCs in TSLP-promoted TFH and TH2 differentiation in AD pathogenesis.

The nasal microbiome, nasal transcriptome, and pet sensitization.

BACKGROUND: Pet allergies are common in children with asthma. Microbiota and host responses may mediate allergen sensitization. OBJECTIVE: We sought to uncover host-microbe relationships in pet allergen sensitization via joint examination of the nasal microbiome and nasal transcriptome. METHODS: We collected nasal samples from 132 children with asthma for parallel 16S rRNA and RNA sequencing. Specific IgE levels for cat and dog dander were measured. Analyses of the nasal microbiome, nasal transcriptome, and their correlations were performed with respect to pet sensitization status. RESULTS: Among the 132 children, 91 (68.9%) were cat sensitized and 96 (72.7%) were dog sensitized. Cat sensitization was associated with lower nasal microbial diversity by Shannon index (P = .021) and differential nasal bacterial composition by weighted UniFrac distance (permutational multivariate ANOVA P = .035). Corynebacterium sp and Staphylococcus epidermidis were significantly less abundant, and the metabolic process "fatty acid elongation in mitochondria" was lower in pet-sensitized versus unsensitized children. Correlation networks revealed that the nasal expression levels of 47 genes representing inflammatory processes were negatively correlated with the relative abundances of Corynebacterium sp and S epidermidis. Thus, these species were directly associated not only with the absence of pet sensitization but also with the underexpression of host gene expression of inflammatory processes that contribute to allergen sensitization. Causal mediation analyses revealed that the associations between these nasal species and pet sensitization were mediated by nasal gene expression. CONCLUSIONS: Higher abundances of nasal Corynebacterium sp and S epidermidis are associated with absence of pet sensitization and correlate with lower expression of inflammatory genes.

Atopic dermatitis, inhalant allergy and food allergy: A paediatric approach.

Food and inhalant allergens have also been identified as potential trigger factors of atopic dermatitis symptoms. Here we aimed to investigate relationships between atopic dermatitis and inhalant-food allergen sensitization in Turkish children with atopic dermatitis. We included 70 patients (42 male, 28 female) with atopic dermatitis and 45 controls (30 male, 15 female) with no atopy, no atopy familial history, no atopy clinical findings no atopic dermatitis. We noted patients' and controls' age, gender, passive smoking exposure, atopy, xerosis, bath water temperature, shower gel type, clothes detergent type, blood hemoglobin, blood eosinophil count, blood eosinophil percent, values of serum immunoglobulin E, serum immunoglobulin A, serum immunoglobulin G, serum immunoglobulin M, results of inhalant allergen, and food allergen testing. We found that nine cases had inhalant allergen sensitization and 21 cases had food allergen sensitization. There were significant relationships between cases and controls in terms of count of eosinophil and percent of eosinophil (P = .008, P = .009, respectively). Humoral and cellular allergen-specific immune responses to food and inhalant allergens can be detected in patients with atopic dermatitis. Accordingly, we believe that blood eosinophil count and percent are more valuable laboratory parameters than serum total IgE for following patients with atopic dermatitis.

Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype.

BACKGROUND: Anti-interleukin-5 (IL-5) monoclonal antibodies can be used as add-on biological therapies in allergic and non-allergic patients with severe eosinophilic asthma. However, within such a therapeutic context real-life investigations are lacking. OBJECTIVE: Therefore, the aim of the present observational study was to evaluate the effects of mepolizumab in allergic and non-allergic subjects with severe eosinophilic asthma. METHODS: Relevant clinical, functional, laboratory, and pharmacotherapeutic parameters were assessed in the above patient subgroups. RESULTS: After one year of add-on biological treatment with mepolizumab, our 88 patients experienced a remarkable improvement of their severe asthma, documented by a better symptom control, expressed by a significant improvement in asthma control test (ACT) score. Indeed, the mean value (±standard deviation) of ACT score increased from 12.55 (±3.724) to 21.08 (±3.358). Moreover, significant improvements were also detected with regard to the median values (interquartile range) of forced expiratory volume in one second (FEV1 ), blood eosinophil numbers, annual rate of disease exacerbations, and daily intake of oral corticosteroids (OCS). In particular, FEV1 enhanced from 1640 mL (1110-2275) to 1920 mL (1525-2615), blood eosinophil count dropped from 711.0 cells/µL (500.0-1022) to 90.00 cells/µL (50.00-117.5), the annual rate of asthma exacerbations decreased from 3.000 (2.000-6.000) to 0.000 (0.000-1.000), and the daily prednisone intake fell from 6.250 mg (0.000-25.00) to 0.000 mg (0.000-0.000). After one year of mepolizumab treatment, the improvements in clinical, functional, and haematological parameters were quite similar in patient subgroups characterized by skin prick test (SPT) negativity or positivity, respectively. A significant correlation was observed between serum IgE levels and OCS intake decrease (r = -0.2257; P < .05). CONCLUSION AND CLINICAL RELEVANCE: Hence, our real-life data suggest that mepolizumab can represent a valid add-on therapeutic option for patients with severe eosinophilic asthma, irrespective of IgE serum concentrations, and allergic sensitization.

Predicting inadequate treatment response in children with chronic spontaneous urticaria.

BACKGROUND: We aimed to investigate the treatment response and associated factors for loss of control in children with chronic spontaneous urticaria (CSU). METHODS: A total of 240 CSU patients (aged 0-17 years) were enrolled in a single-center study in Korea from May 2014 to May 2019. We retrospectively reviewed the medical records and compared the duration of treatment and step of medications using the urticaria control test (UCT, range 0-16 points). Serum total immunoglobulin levels, eosinophil count, allergic sensitization, autologous serum skin test, antinuclear antibody, thyroid function test, erythrocyte sedimentation rate, and C-reactive protein were measured. The patients were divided into well-controlled (sustained UCT ≥12), partly controlled (fluctuating UCT around 12), and poorly controlled (sustained UCT <12) groups. RESULTS: Of the 240 children, 150 (62.5%) achieved well-controlled status; 74 (30.8%), partly controlled; and 16 (6.7%), poorly controlled. Longer duration (adjusted odds ratio: 1.09, 95% confidence interval: 1.05-1.13, P < .001) and higher treatment steps (5.61, 2.82-11.14, P < .001) for reaching the initial 12 points or more of UCT score, initial urticaria activity score (UAS) score (1.06, 1.03-1.09, P < .001), and food sensitization (1.88, 1.03-3.46, P = .041) were associated with inadequate treatment response. The mean duration to symptom free for 1 month without medication was 14.6 months in the well-controlled group and 22.1 months in the partly controlled group (P = .002). CONCLUSION: Children with CSU have a good treatment response. Longer duration and higher treatment step until the initial disease control, higher initial UAS7 score, and food sensitization can predict inadequate treatment response.

Recurrent wheezing during the first 3 years of life in a birth cohort of moderate-to-late preterm infants.

BACKGROUND: Data addressing short- and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. METHODS: Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0  weeks' gestation and followed for 3 years to assess the incidence of physician-diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed-effects models to identify risk factors associated with recurrent wheezing. RESULTS: A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5 ) were significantly lower in children who developed recurrent wheezing. CONCLUSIONS: In moderate-to-late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3 years of life and were associated with abnormal pulmonary function tests. Only anti-RSV prophylaxis exerted a protective effect in the development of recurrent wheezing.

Detection of profilin in SPT extracts that are supposed to contain it.

INTRODUCTION AND OBJECTIVES: Profilin is a panallergen contained in pollen, plant foods and latex. Although cross-reactivity is expected while performing skin prick tests (SPT) with allergens that contain profilin, this is not always noticed. The purpose of this study was to detect if profilin is contained in the commercial SPT extracts of pollen and plant foods which, in their fresh form, contain determined epitopes of profilin. MATERIAL AND METHODS: Commercial SPT extracts of different pharmaceuticals were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The study included purified palm date profilin, peach (whole, pulp and peel extracts), hazelnut, Olea europea, Parietaria judaica and Phleum pratense. RESULTS: Profilin was detected in all, but peach extracts; it was neither contained in the whole peach extract nor in the ones of peel or pulp. CONCLUSION: The only accurate way to detect sensitization to profilin, while performing SPT, is the use of purified profilin extract. Even if a plant food or pollen contain an identified molecule of profilin, the relevant SPT commercial extract may not.

Platelets Play a Central Role in Sensitization to Allergen.

Platelet activation occurs in patients with allergic inflammation, and platelets can be activated directly by allergen via an IgE-dependent process. Platelets have been shown to activate APCs such as CD11c+ dendritic cells in vitro. Although CD11c+ dendritic cells are a requisite for allergen sensitization, the role of platelets in this process is unknown. In this study, we investigated whether platelets were necessary for allergen sensitization. Balb/c mice sensitized to ovalbumin were exposed to subsequent aerosolized allergen (ovalbumin challenge). We analyzed lung CD11c+ cell activation, colocalization with platelets, and some other indices of inflammation. The role of platelets at the time of allergen sensitization was assessed through platelet depletion experiments restricted to the period of sensitization. Platelets colocalized with airway CD11c+ cells, and this association increased after allergen sensitization as well as after subsequent allergen exposure. Temporary platelet depletion (>95%) at the time of allergen sensitization led to a suppression of IgE and IL-4 synthesis and to a decrease in the pulmonary recruitment of eosinophils, macrophages, and lymphocytes after subsequent allergen exposure. Furthermore, in mice previously depleted of platelets at the time of sensitization, the recovered platelet population was shown to have reduced expression of FcεRI. Pulmonary CD11c+ cell recruitment was suppressed in these mice after allergen challenge, suggesting that the migration of CD11c+ cells in vivo may be dependent on direct platelet recognition of allergen. We conclude that platelets are necessary for efficient host sensitization to allergen. This propagates the subsequent inflammatory response during secondary allergen exposure and increases platelet association with airway CD11c+ cells.

Advances in asthma in 2016: Designing individualized approaches to management.

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management.

[SENSITIZATION PATTERN FOR INHALED AND FOOD ALLERGENS IN JAPANESE RECURRENT WHEEZERS UNDER 60 MONTHS OF AGE].

BACKGROUND: Allergen sensitization differs according to countries and regions. Understanding the characteristics of allergen sensitization in one's own country is useful for the treatment of patients with allergic diseases. Recently, Japanese cedar pollen (JCP) sensitization is increasing in young Japanese children. Therefore, we evaluated allergen sensitization patterns in under 60-month-old Japanese recurrent wheezers using multiple allergen tests. METHODS: Allergen tests for 204 Japanese recurrent wheezers between April 2010 and April 2016 were reviewed. Children were divided into 10 groups by age, in 6-month intervals, from 0 months and analyzed by age group. RESULTS: Seventy five percent of children were diagnosed as bronchial asthma. Children under 12-months showed sensitization to food allergens, such as egg white (13.3%) and cow's milk (3.3%), and no sensitization to inhaled allergens. However, house dust mite (HDM) and JCP sensitization increased significantly in children 1 to 2 year of age (HDM; 7.7-32.1%, JCP; 3.9-17.9%) and both sensitization increased to most frequent in children over 36 months of age. JCP sensitization was also frequently detected in children with HDM sensitization (47.1%). CONCLUSION: Sensitization to inhaled allergens was significantly increased in Japanese recurrent wheezers over 12 months of age and sensitization to HDM and JCP increased to most frequent over 36 months of age. JCP sensitization was established from early childhood and detected frequently in Japanese recurrent wheezers under 60 months of age. These characteristics are the same with HDM sensitization.

Influence of Intrinsic and Lifestyle Factors on the Development of IgE Sensitization.

BACKGROUND: IgE sensitization is a prerequisite for the development of allergic symptoms. The investigation of factors influencing the development of IgE is therefore crucial for understanding the onset of allergic diseases. METHODS: This epidemiological study investigated personal, intrinsic, and lifestyle factors in a nonselected cohort of 501 Austrian adolescents (aged 12-21 years). IgE levels to 112 allergen molecules were analyzed in the serum of participants using the ImmunoCAP ISAC®. Allergic sensitization, IgE levels to single allergens, and ISAC score sums were correlated with results obtained from a questionnaire. RESULTS: In this adolescent cohort, male participants showed a higher sensitization frequency (56.8%) compared to females (50.9%) and significantly increased IgE levels to profilins. Underweight subjects demonstrated a stronger IgE sensitization. Family size inversely correlated with IgE levels to PR-10 allergens, and predominately paternal allergies were a predictive factor for IgE sensitization in the children. Vaccination, breastfeeding, and delivery mode showed no influence, while a highly protective effect was observed for growing up on a farm. Of all of the investigated lifestyle factors, only smoking significantly influenced the risk for IgE development. Participants with moderate frequencies of colds showed increased sensitization levels. CONCLUSION: A hereditary predisposition and lifestyle factors such as a farming environment, smoking, family size, body weight, or frequency of colds significantly influenced the development of allergen-specific IgE in this cohort of adolescents.

Fruit intake reduces the onset of respiratory allergic symptoms in schoolchildren.

BACKGROUND: Previous studies have shown that dietary pattern is associated with allergy prevention. METHODS: We conducted a prospective cohort study on all primary schools in Omihachiman City, Shiga Prefecture, Japan. Questionnaires regarding allergic symptoms and diet were distributed to the parents of all 759 7-year-old schoolchildren for 4 consecutive years, from 2011 to 2014. Specific immunoglobulin E to inhalant allergens was measured at 10 years of age. Participants were then categorized as low, medium, or high intake during the study period for four food groups (fruits, vegetables, fish, and beans). Logistic regression analysis was performed to estimate odds ratios and 95% confidence intervals. RESULTS: A total of 520 children (68.5%) whose parents responded to the questionnaires all 4 years were included in the analysis. The prevalence of asthma, rhinitis, and any allergic symptoms at age 10 was significantly decreased with increases in fruit intake. In addition, the onset of any allergic symptoms during the study period was significantly decreased with increases in fruit intake (33.3%, 28.3%, and 14.3% in children with low, medium, and high fruit intake, respectively; P for trend =.01). The sensitization rate to ragweed at age 10 was significantly decreased with increases in fruit intake (P for trend =.046). No significant effect was observed for the other three food groups, except for the association between fish intake and new-onset asthma symptoms. CONCLUSIONS: These findings suggest that higher intake of fruit can help prevent respiratory allergic symptoms in schoolchildren.

Effects of infant weight gain on subsequent allergic outcomes in the first 3 years of life.

BACKGROUND: The association between early weight gain and later allergic outcomes has not been well studied. We examined the relation between weight gain and the subsequent development of allergic outcomes in the first 36 months of life in a Singapore birth cohort. METHODS: In repeated visits in the first 15 months, we measured infant weight and administered questionnaires ascertaining allergic outcomes. At ages 18 and 36 months, we administered skin prick tests (SPTs) to inhalant and food allergens. RESULTS: At 18 months, 13.5% had a positive SPT, 3.5% had wheeze and a positive SPT, 3.9% had rhinitis and a positive SPT, and 6.1% had eczema and a positive SPT. Higher weight gain from 6 to 9 months, 9 to 12 months and 12 to 15 months were independently associated with a reduced risk of developing a positive SPT at 18 months (p-trend ≤0.03). At 36 months, 23.5% had a positive SPT, 11.9% had wheeze and a positive SPT, 12.2% rhinitis and a positive SPT, and 11.5% eczema and a positive SPT. Higher weight gain from 12 to 15 months was associated with a reduced risk of developing a positive SPT at 36 months (p-trend <0.01). No significant associations were observed between weight gain in any period and wheeze, rhinitis or eczema combined with a positive SPT at 18 or 36 months. CONCLUSION: Higher weight gain in the first 15 months of life was associated with a reduced risk of allergen sensitization, but not with combinations of allergic symptoms. TRIAL REGISTRATION: NCT01174875 Registered 1 July 2010, retrospectively registered.

Asthma phenotypes in inner-city children.

BACKGROUND: Children with asthma in low-income urban areas have high morbidity. Phenotypic analysis in these children is lacking, but may identify characteristics to inform successful tailored management approaches. OBJECTIVE: We sought to identify distinct asthma phenotypes among inner-city children receiving guidelines-based management. METHODS: Nine inner-city asthma consortium centers enrolled 717 children aged 6 to 17 years. Data were collected at baseline and prospectively every 2 months for 1 year. Participants' asthma and rhinitis were optimally managed by study physicians on the basis of guidelines. Cluster analysis using 50 baseline and 12 longitudinal variables was performed in 616 participants completing 4 or more follow-up visits. RESULTS: Five clusters (designated A through E) were distinguished by indicators of asthma and rhinitis severity, pulmonary physiology, allergy (sensitization and total serum IgE), and allergic inflammation. In comparison to other clusters, cluster A was distinguished by lower allergy/inflammation, minimally symptomatic asthma and rhinitis, and normal pulmonary physiology. Cluster B had highly symptomatic asthma despite high step-level treatment, lower allergy and inflammation, and mildly altered pulmonary physiology. Cluster C had minimally symptomatic asthma and rhinitis, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Clusters D and E exhibited progressively higher asthma and rhinitis symptoms and allergy/inflammation. Cluster E had the most symptomatic asthma while receiving high step-level treatment and had the highest total serum IgE level (median, 733 kU/L), blood eosinophil count (median, 400 cells/mm3), and allergen sensitizations (15 of 22 tested). CONCLUSIONS: Allergy distinguishes asthma phenotypes in urban children. Severe asthma often coclusters with highly allergic children. However, a symptomatic phenotype with little allergy or allergic inflammation was identified.