Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: A nationwide birth cohort study in South Korea.

BACKGROUND: There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. METHODS: Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. RESULTS: During the follow-up period (median 6.92 years [IQR, 4.72-9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04-1.09] and postnatal [HR, 1.05; 95% CI, 1.01-1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. CONCLUSION: This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

Total airway mechanics and fractional exhaled nitric oxide levels of children living in banjihas (semi-basements).

BACKGROUND: The ISAAC phase III study in Korea found a higher incidence of wheezing illnesses among residents in basements or semi-basements. OBJECTIVE: This study investigates the link between living in banjihas (semi-basements) and airway resistance and Th2 airway inflammation in Korean children, compared to those on higher floors. METHODS: We assessed 575 fifth- and sixth-grade students (aged 10-12) in an inner-city area of South Korea. The study utilized impulse oscillometry to measure small and total airway resistance (Rrs20-5 and Rrs0, respectively) and Fractional Exhaled Nitric Oxide (FeNO) measurements to evaluate airway inflammation. We also considered a range of biological and environmental factors, including allergen sensitization, serum 25-hydroxyvitamin D levels, and urinary metabolites like VOCs, bisphenol, and triclosan. Participants were categorized by living floors: banjihas, first-fifth floors, and sixth floors or higher. RESULTS: Twenty-five children (4.3%) lived in banjihas, 311 (54.1%) on the first to fifth floor, and 239 (41.6%) on the sixth floor or above. Despite similar levels of allergen sensitization and urinary pollutant metabolite levels across all groups, banjiha dwellers showed significantly higher total airway resistance (adjusted &1: 0.633, 95%CI: 0.156, 1.109; P = 0.009) and a greater prevalence of elevated FeNO levels (> 35 ppb) (P = 0.033). These findings persisted after adjusting for critical factors like height, gender, BMI z-score, and birth conditions. CONCLUSION: Children in banjihas exhibit elevated airway resistance and FeNO levels independently of allergen sensitization or pollution exposure, underscoring the necessity for enhanced focus on their respiratory health in such living conditions.

Investigating the occurrence of autoimmune diseases among children and adolescents hospitalized for Mycoplasma pneumoniae infections.

Background: Mycoplasma pneumoniae infection is common in the general population and may be followed by immune dysfunction, but links with subsequent autoimmune disease remain inconclusive. Objective: To estimate the association of M. pneumoniae infection with the risk of subsequent autoimmune disease. Methods: This retrospective cohort study examined the medical records of South Korean children from 01/01/2002 to 31/12/2017. The exposed cohort was identified as patients hospitalized for M. pneumoniae infection. Each exposed patient was matched with unexposed controls based on birth year and sex at a 1:10 ratio using incidence density sampling calculations. The outcome was subsequent diagnosis of autoimmune disease, and hazard ratios (HRs) were estimated with control for confounders. Further estimation was performed using hospital-based databases which were converted to a common data model (CDM) to allow comparisons of the different databases. Results: The exposed cohort consisted of 49,937 children and the matched unexposed of 499,370 children. The median age at diagnosis of M. pneumoniae infection was 4 years (interquartile range, 2.5-6.5 years). During a mean follow-up time of 9.0 ± 3.8 years, the incidence rate of autoimmune diseases was 66.5 per 10,000 person-years (95% CI: 64.3-68.8) in the exposed cohort and 52.3 per 10,000 person-years (95% CI: 51.7-52.9) in the unexposed cohort, corresponding to an absolute rate of difference of 14.3 per 10,000 person-years (95% CI: 11.9-16.6). Children in the exposed cohort had an increased risk of autoimmune disease (HR: 1.26; 95% CI: 1.21-1.31), and this association was similar in the separate analysis of hospital databases (HR: 1.25; 95% CI 1.06-1.49). Conclusion: M. pneumoniae infection requiring hospitalization may be associated with an increase in subsequent diagnoses of autoimmune diseases.

Prenatal mold exposure is associated with development of atopic dermatitis in infants through allergic inflammation / Exposição pré-natal a mofo está associada ao desenvolvimento de dermatite atópicaem neonatos por reação alérgica

Abstract Objective Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. Method The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n = 1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. Results Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p = 0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r = 0.613, p < 0.001). Conclusion Indoor mold exposure during the fetal period is associated with development of atopic dermatitis via IgE-mediated allergic inflammation. Avoidance of mold exposure during this critical period might prevent the development of atopic dermatitis.

Resumo Objetivo A exposição ao mofo no início da vida pode estar associada ao desenvolvimento de dermatite atópica; contudo, os estudos sobre esse vínculo são inconclusivos e faltam evidências dos mecanismos subjacentes. Identificamos a associação entre o momento da exposição ao mofo e o desenvolvimento de dermatite atópica e investigamos os mecanismos subjacentes. Método A associação entre dermatite atópica e exposição a mofo foi examinada em um estudo de coorte de nascimento da Origem da Asma e de Doenças Alérgicas em Crianças (COCOA) (n = 1446). A dermatite atópica foi diagnosticada em pacientes com um ano de vida por pediatras alergistas. A exposição ao mofo foi avaliada por um questionário. A plataforma Illumina MiSeq foi utilizada para examinar o microbioma ambiental em 20 neonatos saudáveis escolhidos aleatoriamente e 20 com dermatite atópica a 36 semanas de gestação. Resultados A exposição pré-natal, porém não pós-natal, ao mofo foi significativamente associada à dermatite atópica (razão de chances ajustada, 1,36; intervalo de confiança de 95%, 1,01-1,83). Os níveis séricos totais de Imunoglobulina E (IgE) no primeiro ano de vida foram maiores em neonatos com dermatite atópica expostos a mofo durante a gravidez do que em neonatos não expostos a mofo durante a gravidez (p = 0,021). A abundância relativa de Ascomycota não cultivado foi maior em neonatos com dermatite atópica do que em neonatos saudáveis. A abundância relativa de Ascomycota não cultivado correlacionou-se com os níveis séricos totais de IgE no primeiro ano de vida (r = 0,613, p < 0,001). Conclusão A exposição ao mofo no ambiente domiciliar durante a gravidez está associada ao desenvolvimento de dermatite atópica por meio de reação alérgica mediada por IgE. A prevenção à exposição ao mofo durante o período crítico da gravidez pode prevenir o desenvolvimento de dermatite atópica.