Maternal and Infant Dietary Patterns Are Not Related to Food Allergy Risk in Singapore Children: GUSTO Cohort Study.

BACKGROUND: We previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. OBJECTIVES: We examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. METHODS: Among 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother-infant dyads, the infant's diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. RESULTS: Food allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant's diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). CONCLUSIONS: Apart from maternal diet quality showing a modest association, infant's allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.

Evaluation of Stool Short Chain Fatty Acids Profiles in the First Year of Life With Childhood Atopy-Related Outcomes.

Introduction: Short chain fatty acids (SCFAs) are the main intestinal intermediate and end products of metabolism of dietary fibers/polyphenols by the gut microbiota. The aim of this study was to evaluate the biological implication of stool SCFA profiles determined in the first year of life on the clinical presentation of allergic outcomes in childhood. Methods: From the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort, a sub-cohort of 75 participants was recruited. Scheduled questionnaire data was collected for cumulative prevalence of physician-diagnosed eczema, wheezing with the use of nebuliser, and allergen sensitization till the age of 8 years. Stool samples collected at week 3 and months 3, 6 and 12 were quantitated for 9 SCFAs using LC/MS/MS. SCFA data were grouped into lower (below the 25th) and higher (above the 75th percentiles) categories. Generalized Linear Mixed Models was employed to analyse longitudinal association between SCFAs and atopy-related outcomes. Results: Children with lower stool butyric acid levels (≤25th percentile) over the first 3 time points had higher odds ratio (OR) for wheezing (adjOR = 14.6), eczema (adjOR = 13.2), food sensitization (adjOR = 12.3) and combined outcomes of both wheezing and eczema (adjOR = 22.6) till age 8 years, compared to those with higher levels (≥75 percentile). Additionally, lower longitudinal levels of propionic acid (≤25th percentile) over 4 time points in first year of life was associated with recurrent wheezing (≥2 episodes) till 8 years (adjOR = 7.4) (adj p < 0.05). Conclusion: Our results suggest that relatively low levels of gut SCFAs in early life are associated with increased susceptibility to atopic-related outcomes in childhood.

Trajectories of early-onset rhinitis in the Singapore GUSTO mother-offspring cohort.

BACKGROUND: The natural history of childhood rhinitis is not well described. OBJECTIVE: This study aimed to identify different rhinitis trajectories in early childhood and their predictors and allergic associations. METHODS: Rhinitis symptoms were ascertained prospectively from birth until 6 years using standardized questionnaires in 772 participants. Rhinitis was defined as one or more episodes of sneezing, runny and/or blocked nose >2 weeks duration. Latent trajectories were identified using group-based modelling, and their predictive risk factors and allergic associations were examined. RESULTS: Three rhinitis trajectory groups were identified: 7.6% (n = 59) were termed early transient rhinitis, 8.6% (n = 66) late transient rhinitis, and 6.6% (n = 51) persistent rhinitis. The remaining 77.2% (n = 596) were classified as non-rhinitis/reference group. Early transient rhinitis subjects were more likely of Indian ethnicity, had siblings, reported childcare attendance, early wheezing and eczema in the first 3 years of life. Late transient rhinitis was associated with antenatal exposure to smoking, higher maternal education levels, and wheezing at age 36-72 months. Persistent rhinitis was associated with male gender, paternal and maternal history of atopy, eczema, and house dust mite sensitization. CONCLUSIONS & CLINICAL RELEVANCE: Risk factors for early transient rhinitis involve a combination of genetic and early environmental exposures, whereas late transient rhinitis may relate to maternal factors and early respiratory infections independent of atopy. In contrast, persistent rhinitis is strongly associated with atopic risk and likely represents the typical trajectory associated with allergic disorders. Allergic rhinitis symptoms may commence as early as the first year of life and may inform development of early interventive strategies.

A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema.

Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk. We measured the functionality of the gut microbiome and metabolome of 63 infants between ages 3 weeks and 12 months with well-defined eczema cases and controls in a sub-cohort from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. At 3 weeks, the microbiome and metabolome of allergen-sensitized atopic eczema infants were characterized by an enrichment of Escherichia coli and Klebsiella pneumoniae, associated with increased stool D-glucose concentration and increased gene expression of associated virulence factors. A delayed colonization by beneficial Bacteroides fragilis and subsequent delayed accumulation of butyrate and propionate producers after 3 months was also observed. Here, we describe an aberrant developmental trajectory of the gut microbiome and stool metabolome in allergen sensitized atopic eczema infants. The infographic describes an impaired developmental trajectory of the gut microbiome and metabolome in allergen-sensitized atopic eczema (AE) infants and infer its contribution in modulating allergy risk in the Singaporean mother-offspring GUSTO cohort. The key microbial signature of AE is characterized by (1) an enrichment of Escherichia coli and Klebsiella pneumoniae which are associated with accumulation of pre-glycolysis intermediates (D-glucose) via the trehalose metabolic pathway, increased gene expression of associated virulence factors (invasin, adhesin, flagellin and lipopolysaccharides) by utilizing ATP from oxidative phosphorylation and delayed production of butyrate and propionate, (2) depletion of Bacteroides fragilis which resulted in lower expression of immunostimulatory bacterial cell envelope structure and folate (vitamin B9) biosynthesis pathway, and (3) accompanied depletion of bacterial groups with the ability to derive butyrate and propionate through direct or indirect pathways which collectively resulted in reduced glycolysis, butyrate and propionate biosynthesis.

Epicutaneous sensitization to food allergens in atopic dermatitis: What do we know?

Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly affecting children, which has no definitive curative therapy apart from natural outgrowing. AD is persistent in 30%-40% of children. Epithelial barrier dysfunction in AD is a significant risk factor for the development of epicutaneous food sensitization, food allergy, and other allergic disorders. There is evidence that prophylactic emollient applications from birth may be useful for primary prevention of AD, but biomarkers are needed to guide cost-effective targeted therapy for high-risk individuals. In established early-onset AD, secondary preventive strategies are needed to attenuate progression to other allergic disorders such as food allergy, asthma, and allergic rhinitis (the atopic march). This review aims to describe the mechanisms underpinning the development of epicutaneous sensitization to food allergens and progression to clinical food allergy; summarize current evidence for interventions to halt the progression from AD to food sensitization and clinical food allergy; and highlight unmet needs and directions for future research.

Dynamics of helper CD4 T cells during acute and stable allergic asthma.

Asthma comprises heterogeneous clinical subtypes driven by diverse pathophysiological mechanisms. We characterized the modulation of the inflammatory environment with the phenotype, gene expression, and function of helper CD4 T cells among acutely exacerbated and stable asthma patients. Systemic Th2 immune deviation (IgE and Th2 cytokines) and inflammation (IL-6, CRP) were associated with increased Th17 cells during acute asthma. Th2/Th17 cell differentiation during acute asthma was regulated by the enhanced expression of transcription factors (c-MAF, IRF-4). The development of pathogenic Th2 cells during acute asthma was characterized by the secretion of inflammatory cytokines coupled with Th2 molecules and PPARγ expression. The acquisition of CD15S, CD39, CD101, and CCR4 contributed to the increased heterogeneity of Regulatory T cells during asthma. Two clusters were derived from above cytokines, CD4 T cell phenotypes, and clinical data. Cluster 1, characterized by high eosinophils, Th2 and ILC2 frequencies, and higher exacerbation rates, may represent Th2-high subtype. Cluster 2 represents a more complex subtype; it is constituted by higher neutrophils or Th17 frequencies, higher inhaled corticosteroids dose and poor asthma control. In conclusion, we characterized systematically and longitudinally Th2-high and non-Th2 asthma subtypes and the heterogeneity of CD4 T cells in stable and acute asthma.

Establishment of the nasal microbiota in the first 18 months of life: Correlation with early-onset rhinitis and wheezing.

BACKGROUND: Dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and susceptibility to childhood respiratory disorders. OBJECTIVE: The aim of this case-control study was to monitor, evaluate, and compare development of the nasal microbiota of infants with rhinitis and wheeze in the first 18 months of life with those of healthy control subjects. METHODS: Anterior nasal swabs of 122 subjects belonging to the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were collected longitudinally over 7 time points in the first 18 months of life. Nasal microbiota signatures were analyzed by using 16S rRNA multiplexed pair-end sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2) patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control subjects (n = 60). RESULTS: Maturation of the nasal microbiome followed distinctive patterns in infants from both rhinitis groups compared with control subjects. Bacterial diversity increased over the period of 18 months of life in control infants, whereas infants with rhinitis showed a decreasing trend (P < .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family (Actinobacteria phylum) and early colonization with the Staphylococcaceae family (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects (adjusted P < .05). The only difference between the rhinitis and control groups was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05). Determinants of nasal microbiota succession included sex, mode of delivery, presence of siblings, and infant care attendance. CONCLUSION: Our results support the hypothesis that the nasal microbiome is involved in development of early-onset rhinitis and wheeze in infants.

Low Food Allergy Prevalence Despite Delayed Introduction of Allergenic Foods-Data from the GUSTO Cohort.

BACKGROUND: There is mounting evidence that early introduction of allergenic food decreases the risk of food allergy development, especially in high-risk infants with eczema. However, there is a lack of data to suggest whether this association holds true in Asian populations. OBJECTIVE: To investigate the relationship between the timing of introduction of allergenic foods and food allergy outcomes in infants in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. METHODS: The GUSTO cohort recruited 1152 mothers of Chinese, Malay, and Indian ethnicity who had singleton, naturally conceived pregnancies and followed their offspring prospectively. Information on demographic characteristics, child health, infant feeding practices, and a convincing history of IgE-mediated food allergy was obtained from interviewer-administered questionnaires at multiple time points. Corroborative skin prick tests to food allergens were performed at 18 and 36 months. RESULTS: Most of the infants were introduced to egg (49.6%), peanut (88.7%), and shellfish (90.2%) after age 10 months. Food allergy prevalence was, however, very low between age 12 and 48 months: egg, 0.35% to 1.8%; peanut allergy, 0.1% to 0.3%; and shellfish, 0.2% to 0.9%. There were no significant associations between the timing of introduction of allergenic foods and the development of food allergy, adjusted for confounders including breast-feeding and eczema. CONCLUSIONS: Food allergy rates in Singapore are low despite delayed introduction of allergenic foods. Early introduction of allergenic foods may thus not be necessary in populations in which overall food allergy prevalence is low, and thus infant feeding recommendations should be carefully tailored to individual populations.

Neuropeptide Y associated with asthma in young adults.

OBJECTIVE: Neuropeptide Y, a widely circulating neurotransmitter, plays a pivotal role in energy balance, immunomodulation and asthma, and several NPY polymorphisms are promising genetic risk factors for asthma and obesity. We explored the associations of candidate NPY gene polymorphisms with prevalent asthma and its relationship with obesity in young adult asthma patients free of other chronic medical morbidity. METHODS: Five common gene variants of NPY (rs16147 (-399T/C), rs17149106 (-602G/T), rs16140 (+1000C/G), rs5573 (+1201A/G), rs5574 (+5327C/T)) previously validated to account for most of the NPY expression in vitro and in vivo were investigated in 126 physician-diagnosed asthma patients without other chronic medical morbidity and 182 healthy controls (21-35years). Plasma levels of NPY, adiponectin, and CRP were determined using ELISA, and IL-6 was measured by Luminex in a subgroup of 70 patients and 69 age- and sex-matched healthy controls. RESULTS: In logistic regression models controlling for gender and obesity, the CT genotype of rs5574 (OR=0.54, 95%CI: 0.30-0.89) and the GT genotype of rs17149106 (OR=5.58, 95%CI: 1.09-28.54) were significantly associated with asthma. No significant interaction between NPY SNP polymorphisms and obesity were detected. Plasma NPY level was correlated with adiponectin levels (p<0.05). Compared with the healthy controls, patients with asthma had higher BMI (p<0.001), adiponectin (p<0.05), IL-6 (p=0.001) and CRP (p<0.001), and lower NPY levels (p<0.01). CONCLUSIONS: The CT genotype of rs5574 and the GT genotype of rs17149106 are significantly associated with prevalent asthma.

OPINION: Primary prevention of allergy - Will it soon become a reality?

It is generally accepted that allergic diseases are not curable and not preventable, but mainly controllable using pharmacotherapy (i.e. symptomatic medication). Recent research, however, demonstrated that a number of specific interventions can lead to (partial) primary prevention of allergy, especially of atopic dermatitis (AD) and food allergy (FA). Three types of primary prevention strategies have been successfully studied: early administration of bacterial products (most studies are on probiotics), early moisturizing in infants at risk for AD and early exposure to allergenic foods (peanut and egg). Results of these studies indicate that the stage might have been set. Surely, much more research needs to be carried out before advice can be given in clinical practice. This opinion article discusses the three types of beneficial interventions and gives ideas for future research, which might show the way for better strategies in primary prevention of allergic diseases.

Obesity, asthma prevalence and IL-4: Roles of inflammatory cytokines, adiponectin and neuropeptide Y.

BACKGROUND: Obesity is associated with asthma risk and severity, but the underlying biological mechanisms are poorly understood. We hypothesized that cytokine markers of systemic inflammation, and adiponectin and neuropeptide Y (NPY) markers of immuno-modulating and neurohormonal regulation are involved in the obesity-asthma association. METHODS: We explored the relationships between body mass index (BMI), C-reactive protein (CRP), IL-6, TNF-α, adiponectin and NPY with asthma prevalence and IL-4 levels in 70 youth with asthma and 69 age- and gender-matched healthy controls using cross-sectional and longitudinal data. RESULTS: Mean BMI level was higher among patients with asthma than healthy controls (p < 0.001). In logistic regression models controlling for potential confounders, independent associations with asthma prevalence were found for obesity (p = 0.001), increasing tertiles of CRP (linear trend p < 0.001), IL-6 (linear trend p < 0.001) and lowest and highest tertiles of TNF-α (quadratic trend p < 0.05), increasing adiponectin (linear p = 0.022) and decreasing tertiles of NPY (linear trend p = 0.001). Among patients with asthma, NPY level was positively correlated with adiponectin (p < 0.05) and TNF-α (p < 0.05), and levels of NPY and IL-6 were significantly associated with IL-4 level at baseline and 1-year follow-up. CONCLUSIONS: The obesity-asthma association was not explained by systemic inflammation. Specifically, CRP, TNF-a, IL-6, NPY and adiponectin were independently associated with asthma prevalence. NPY and IL-6 were associated with IL-4 marker of allergic airway inflammation in asthma and should be further investigated as prognostic markers of asthma outcomes.

Atopic Dermatitis in Early Life: Evidence for at Least Three Phenotypes? Results from the GUSTO Study.

BACKGROUND: Atopic dermatitis (AD) has been highlighted as a likely first step in the 'atopic march', emphasizing the need to define predisposing factors. METHODS: We evaluated AD risk factors and phenotypes in an Asian mother-offspring cohort . We defined three phenotypes of doctor-diagnosed AD based on the time of onset of the disease: early AD occurring within the first 6 months of life, AD occurring between 6 and 12 months and late-onset AD starting after the age of 12 months. RESULTS: Maternal allergic history was associated with an increased risk of developing early-onset AD (adjusted odds ratio (aOR) 20.46, 95% confidence interval (CI) 2.73-153.15, p < 0.01). Maternal allergic history and attendance at a daycare centre increased the odds of the development of AD between 6 and 12 months (aOR 4.19, 95% CI 1.01-17.45, p = 0.049 and aOR 11.42, 95% CI 1.49-87.50, p = 0.02, respectively). Risk factors associated with increased odds of late-onset AD from 12 months were the consumption of probiotics between the age of 9 and 12 months and antibiotic treatment in the first 6 months of life (aOR 4.32, 95% CI 1.07-17.45, p = 0.04 and aOR 3.11, 95% CI 1.10-8.76, p = 0.03, respectively). Early-onset AD was associated with an increased risk of developing allergic sensitization (aOR 46.51, 95% CI 3.44-628.81, p < 0.01). CONCLUSION: We found that early-onset AD was mainly associated with familial factors, while late-onset AD was associated with the consumption of antibiotics or probiotics. The findings support the concept that different phenotypes of AD exist in young children.

Maternal PUFA status and offspring allergic diseases up to the age of 18 months.

Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother-offspring cohort were assayed at 26-28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.

Rhinitis in the first 18 months of life: exploring the role of respiratory viruses.

BACKGROUND: Rhinitis is common in early childhood, but allergic rhinitis is considered a later manifestation of the atopic march. This study aimed to evaluate rhinitis (allergic and non-allergic) in the first 18 months of life, its link with other atopic manifestations and the role of respiratory viruses. METHODS: Subjects (n = 1237) of the Singapore GUSTO birth cohort were followed up quarterly until 18 months of age with questionnaires to screen for rhinitis symptoms lasting at least 2 wk and with monthly calls to positive subjects to detect prolonged/recurrent rhinitis symptoms (total duration ≥ 4 wk). Anterior nasal swabbing for molecular-based virus detection was conducted during these visits and near (within a month) rhinitis episodes. Skin prick testing to common environmental and food allergens was conducted at the 18 month visit. RESULTS: Prolonged/recurrent rhinitis was significantly associated with history of parental atopy (mother: aOR = 2.17; father: aOR = 1.82) and atopic comorbidities of eczema (aOR = 2.53) and wheeze (aOR = 4.63) (p < 0.05), though not with allergen sensitization. Although the frequency of nasal respiratory virus detection during scheduled quarterly visits did not differ between prolonged/recurrent rhinitis and matched controls (p > 0.05), virus detection was higher in swabs obtained within a month following rhinitis episodes in prolonged/recurrent rhinitis subjects compared with scheduled visits (adjusted p = 0.04). CONCLUSIONS: Based on the duration of rhinitis symptoms, this study defined a subset of early childhood rhinitis which was associated with atopic predisposition and comorbidities. Persistent respiratory viral shedding may contribute to the symptomatology. Whether this entity is a precursor of subsequent childhood allergic rhinitis will require longer follow-up.

Knowledge of anaphylaxis among Emergency Department staff.

BACKGROUND: Anaphylaxis is an emergency condition that requires immediate, accurate diagnosis and appropriate management. However, little is known about the level of knowledge of doctors and nurses treating these patients in the Emergency Department. OBJECTIVE: To determine the knowledge of doctors and nurses in the Emergency Department on the recent definition and treatment recommendations of anaphylaxis. METHODS: We surveyed doctors and nurses of all grades in a tertiary Hospital Emergency Department using a standardized anonymous questionnaire. RESULTS: We had a total of 190 respondents-47 doctors and 143 nurses. The response rate was 79.7% for doctors and 75.3% for nurses. Ninety-seven point eight percent of the doctors and 83.7% of the nurses chose the accepted definition of anaphylaxis. High proportions of doctors (89-94%) and nurses (65-72%) diagnose anaphylaxis in the three scenarios demonstrating anaphylaxis and anaphylactic shock. Forty-two point six percent of the doctors and 76.9% of the nurses incorrectly diagnosed single organ involvement without hypotension as anaphylaxis. As for treatment, 89.4% of the doctors indicated adrenaline as the drug of choice and 85.1% chose intramuscular route for adrenaline administration. Among the nurses, 40.3% indicated adrenaline as the drug of choice and 47.4% chose the intramuscular route for adrenaline. CONCLUSION: High proportion of doctors and nurses are able to recognize the signs and symptoms of anaphylaxis, although there is a trend towards over diagnosis. There is good knowledge on drug of choice and the accepted route of adrenaline among the doctors. However, knowledge of treatment of anaphylaxis among nurses was moderate and can be improved.

Psychiatric comorbidities in Asian adolescent asthma patients and the contributions of neuroticism and perceived stress.

PURPOSE: Psychiatric comorbidity is reported to be common among adolescents with asthma, but little is known about its underlying psychological factors. OBJECTIVE: This study explored the profile of anxiety and depressive comorbidities among adolescents with well-controlled and poorly controlled asthma and the contribution of neuroticism and perceived stress. METHODS: The Revised Child Anxiety and Depression Scale, Neuroticism subscale of Big Five Inventory, Perceived Stress Scale, and Asthma Control Test were administered to 198 adolescents (aged 12-19 years) with well-controlled (n = 137) and poorly controlled asthma (n = 61) as well as 171 healthy neighborhood controls. RESULTS: Adolescents with poorly controlled asthma, compared with well-controlled asthma patients and healthy controls, had higher scores of depression (p = .006), panic attacks (p = .002), total anxiety (p = .038), and total internalizing symptoms (p = .017), after adjusting for gender, age, ethnicity, smoking status, and family housing type. Adolescents with asthma had higher neuroticism (p = .025), perceived stress (p = .022), and body mass index (p = .006) and lower self-rated health (p < .001) than healthy controls. No significant differences in psychiatric comorbidity scores were observed after accounting for differences in underlying psychological and physical factors. Among asthma patients, increased asthma control was associated with decreased scores of psychiatric comorbidity (p < .01), but the association was not significant after allowing for decreased neuroticism and perceived stress. CONCLUSIONS: The diagnosis of asthma and poor asthma control in adolescents is associated with excess psychiatric comorbidity, which is likely due to increased neuroticism and perceived stress.