Airway bacterial carriage and childhood respiratory health: A population-based prospective cohort study

Background Airway bacterial carriage might play a role in respiratory disease. We hypothesize that nasal carriage with Staphylococcus aureus or nasopharyngeal carriage with Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae predisposes individuals to adverse respiratory health. Objective To examine the association of early‐life airway bacterial carriage with respiratory tract infections and vice versa, and of early‐life airway bacterial carriage with wheezing, lung function, and asthma in later childhood. Methods We collected upper airway swabs for bacterial culturing for S aureus, H influenzae, M catarrhalis, and H influenzae at six timepoints between the ages of 6 weeks and 6 years among 945 children participating in a population‐based prospective cohort study. Information on respiratory tract infections and wheezing until age 6 years, and asthma at age 10 years was obtained by questionnaires. Lung function at age 10 years was measured by spirometry. We tested possible bidirectional associations between airway bacterial carriage and respiratory tract infections by cross‐lagged models, and associations of repeatedly measured airway bacterial carriage with wheezing, lung function, and asthma by generalized estimating equations models and regression models. Results Cross‐lagged modeling showed that early‐life airway bacterial carriage was not consistently associated with upper and lower respiratory tract infections or vice versa. Nasopharyngeal carriage with any bacteria in infancy was associated with an increased risk of wheezing (OR [95% CI]: 1.66 [1.31, 2.10]). Airway bacterial carriage was not consistently associated with school‐age lung function or asthma. Conclusion Nasopharyngeal carriage with any bacteria is associated with wheezing, but not respiratory tract infections, asthma, or lung function

Association between nasal and nasopharyngeal bacterial colonization in early life and eczema phenotypes

Background: An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and associations with other bacterial species are unclear.Objective: To examine the associations of early life nasal and nasopharyngeal bacterial carriage with eczema phenotypes, and the direction of any associations identified.Methods: Among 996 subjects of a population-based prospective cohort study, nasal swabs for Staphylococcus aureus, and nasopharyngeal swabs for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected and cultured from age 6 weeks to 6 years. Never, early, mid-, late transient and persistent eczema phenotypes were identified from parental-reported physician-diagnosed eczema from age 6 months until 10 years. Multinomial regression models and cross-lagged models were applied.Results: Staphylococcus aureus nasal carriage at 6 months was associated with an increased risk of early transient and persistent eczema (OR (95% CI): 2.69 (1.34, 5.39) and 4.17 (1.12, 15.51)). The associations between Staphylococcus aureus nasal carriage and eczema were mostly cross-sectional, and not longitudinal. No associations of Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal bacterial carriage with eczema and eczema phenotypes were observed (OR range (95% CI): 0.71 (0.35, 1.44) to 1.77 (0.84, 3.73)).Conclusions: Early life Staphylococcus aureus nasal carriage, but not Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal carriage, was associated with early transient and persistent eczema. Staphylococcus aureus nasal carriage and eczema were mostly cross-sectionally associated, and not longitudinally, making a causal relationship in either direction unlikely.Public Health and primary carePrevention, Population and Disease management (PrePoD

Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: the Generation R Study

Background Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets.Methods This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27(+) and CD27(-) memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires.Results FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets.Conclusions School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population.Prevention, Population and Disease management (PrePoD)Public Health and primary car

The role of vitamin D on circulating memory T cells in children: The Generation R study

Genome Instability and Cance

Childhood Adiposity Associated With Expanded Effector Memory CD8(+) and V delta 2(+)V gamma 9(+)T Cells

Context: Adult obesity is associated with chronic low-grade inflammation and may give rise to future chronic disease. However, it is unclear whether adiposity-related inflammation is already apparent in childhood.Objective: To study associations between child adiposity measures with circulating monocytes and naive and memory subsets in CD4, CD8, and gamma delta T cell lineages.Methods: Ten-year-old children (n = 890) from the Generation R Cohort underwent dual-energy x-ray absorptiometry and magnetic resonance imaging for body composition (body mass index [BMI], fat mass index [FMI], android-to-gynoid fat mass ratio, visceral fat index, liver fat fraction). Blood samples were taken for detailed immunophenotyping of leukocytes by 11-color flow cytometry.Results: Several statistically significant associations were observed. A 1-SD increase in total FMI was associated with +8.4% (95% CI 2.0, 15.2) V delta 2(+)V gamma 9(+) and +7.4% (95% CI 2.4, 12.5) CD8(TEMRO)(+) cell numbers. A 1-SD increase in visceral fat index was associated with +10.7% (95% CI 3.3, 18.7) V delta 2(+)V gamma 9(+) and +8.3% (95% CI 2.6, 14.4) CD8(TEMRO)(+) cell numbers. Higher android-to-gynoid fat mass ratio was only associated with higher V delta 2(+)V gamma 9(+) T cells. Liver fat was associated with higher CD8(TEMRO)(+) cells but not with V delta 2(+)V gamma 9(+) T cells. Only liver fat was associated with lower Th17 cell numbers: a 1-SD increase was associated with -8.9% (95% CI -13.7, -3.7) Th17 cells. No associations for total CD8(+), CD4(+) T cells, or monocytes were observed. BMI was not associated with immune cells.Conclusion: Higher V delta 2(+)V gamma 9(+) and CD8(TEMRO)(+) cell numbers in children with higher visceral fat index could reflect presence of adiposity-related inflammation in children with adiposity of a general population.Public Health and primary carePrevention, Population and Disease management (PrePoD

Association between nasal and nasopharyngeal bacterial colonization in early life and eczema phenotypes

Background: An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and associations with other bacterial species are unclear.Objective: To examine the associations of early life nasal and nasopharyngeal bacterial carriage with eczema phenotypes, and the direction of any associations identified.Methods: Among 996 subjects of a population-based prospective cohort study, nasal swabs for Staphylococcus aureus, and nasopharyngeal swabs for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected and cultured from age 6 weeks to 6 years. Never, early, mid-, late transient and persistent eczema phenotypes were identified from parental-reported physician-diagnosed eczema from age 6 months until 10 years. Multinomial regression models and cross-lagged models were applied.Results: Staphylococcus aureus nasal carriage at 6 months was associated with an increased risk of early transient and persistent eczema (OR (95% CI): 2.69 (1.34, 5.39) and 4.17 (1.12, 15.51)). The associations between Staphylococcus aureus nasal carriage and eczema were mostly cross-sectional, and not longitudinal. No associations of Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal bacterial carriage with eczema and eczema phenotypes were observed (OR range (95% CI): 0.71 (0.35, 1.44) to 1.77 (0.84, 3.73)).Conclusions: Early life Staphylococcus aureus nasal carriage, but not Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal carriage, was associated with early transient and persistent eczema. Staphylococcus aureus nasal carriage and eczema were mostly cross-sectionally associated, and not longitudinally, making a causal relationship in either direction unlikely

T cell composition and polygenic multiple sclerosis risk

Background and purpose: Patients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population. Methods: We included genotyped participants from the population-based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS-PRSs on total T cell numbers (n = 1261), CD4+ and CD8+ lineages, and subsets therein (n= 675). In addition, T-cell-specific PRSs were constructed based on functional pathway data. Results: The MS-PRS negatively correlated with CD8+ T cell frequencies (p = 2.92 × 10−3), which resulted in a positive association with CD4+/CD8+ T cell ratios (p = 8.27 × 10−9). These associations were mainly driven by two of 195 genome-wide significant MS risk variants: the main genetic risk variant for MS, HLA-DRB1*15:01 and an HLA-B risk variant. We observed no significant associations for the T-cell-specific PRSs. Conclusions: Our results suggest that MS-associated genetic variants affect T cell composition during childhood in the general population.</p