Pollen exposure is associated with risk of respiratory symptoms during the first year of life

BACKGROUND: Pollen exposure is associated with respiratory symptoms in children and adults. However, the association of pollen exposure with respiratory symptoms during infancy, a particularly vulnerable period, remains unclear. We examined whether pollen exposure is associated with respiratory symptoms in infants and whether maternal atopy, infant's sex or air pollution modifies this association. METHODS: We investigated 14,874 observations from 401 healthy infants of a prospective birth cohort. The association between pollen exposure and respiratory symptoms, assessed in weekly telephone interviews, was evaluated using generalized additive mixed models (GAMMs). Effect modification by maternal atopy, infant's sex, and air pollution (NO$_{2}$ , PM$_{2.5}$ ) was assessed with interaction terms. RESULTS: Per infant, 37 ± 2 (mean ± SD) respiratory symptom scores were assessed during the analysis period (January through September). Pollen exposure was associated with increased respiratory symptoms during the daytime (RR [95% CI] per 10% pollen/m$^{3}$ : combined 1.006 [1.002, 1.009]; tree 1.005 [1.002, 1.008]; grass 1.009 [1.000, 1.23]) and nighttime (combined 1.003 [0.999, 1.007]; tree 1.003 [0.999, 1.007]; grass 1.014 [1.004, 1.024]). While there was no effect modification by maternal atopy and infant's sex, a complex crossover interaction between combined pollen and PM$_{2.5}$ was found (p-value 0.003). CONCLUSION: Even as early as during the first year of life, pollen exposure was associated with an increased risk of respiratory symptoms, independent of maternal atopy and infant's sex. Because infancy is a particularly vulnerable period for lung development, the identified adverse effect of pollen exposure may be relevant for the evolvement of chronic childhood asthma

Exposure to moderate air pollution and associations with lung function at school-age: A birth cohort study

Adverse effects of higher air pollution levels before and after birth on subsequent lung function are often reported in the literature. We assessed whether low-to-moderate levels of air pollution during preschool-age impact upon lung function at school-age.; In a prospective birth cohort of 304 healthy term-born infants, 232 (79%) completed lung function at follow-up at six years. Using spatial-temporal models, levels of individual air pollution (nitrogen dioxide (NO; 2; ) and ozone (O; 3; ), particulate matter with a diameter <10 μm (PM; 10; )) were estimated for the time windows pregnancy, first up to the sixth year of life separately, and birth until follow-up at six years. Time window means were compared to World Health Organization (WHO) guideline limits. Associations of exposure windows with spirometry and body plethysmography indices were analyzed using regression models, adjusting for potential confounders. For subgroup analysis, air pollution exposure was categorized into quartiles (four groups of 52 children).; Mean NO; 2; level from birth until follow-up was [mean (range)] [11.8 (4.9 to 35.9 μg/m; 3; )], which is almost 4-times lower than the WHO suggested limit of 40 μg/m; 3; . In the whole population, increased air pollution levels from birth until follow-up were associated with reduced lung function at six years. In the subgroup analysis, the 52 children exposed to NO; 2; levels from the highest quartile during pregnancy, the first and second years of life and from birth until follow-up, had a significant decrease in forced expiratory volume in 1 s (FEV; 1; ). Per interquartile range increase of NO; 2; , FEV; 1; decreased by [z-score change (95% confidence interval)] [-1.07 (-1.67 to -0.47)], [-1.02 (-1.66 to -0.39)], [-0.51 (-0.86 to -0.17)] and [-0.80 (-1.33 to -0.27)], respectively. Air pollution exposure during pregnancy and childhood resulted in a non-significant decrease in lung volume at six years, as assessed by functional residual capacity measured by body plethysmography (FRC; pleth; ).; Our results suggest that exposure to higher NO; 2; levels, which are still much lower than WHO guideline limits, especially during the sensitive period of early lung development, may be associated with reduced lung function at school-age. These findings support the concept of age and dose-dependent pollution effects on lung function in healthy school-aged children and underline the importance of pollution reduction measures

Differences in autophagy marker levels at birth in preterm vs. term infants.

BACKGROUND Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants. METHODS In the prospective Basel-Bern Infant Lung Development (BILD) birth cohort we compared cord blood levels of macroautophagy (Beclin-1, LC3B), selective autophagy (p62) and regulation of autophagy (SIRT1) in 64 preterm and 453 term infants. RESULTS Beclin-1 and LC3B did not differ between preterm and term infants. However, p62 was higher (0.37, 95% confidence interval (CI) 0.05;0.69 in log2-transformed level, p = 0.025, padj = 0.050) and SIRT1 lower in preterm infants (-0.55, 95% CI -0.78;-0.31 in log2-transformed level, padj < 0.001). Furthermore, p62 decreased (padj-value for smoothing function was 0.018) and SIRT1 increased (0.10, 95% CI 0.07;0.13 in log2-transformed level, padj < 0.001) with increasing gestational age. CONCLUSION Our findings suggest differential levels of key autophagy markers between preterm and term infants. This adds to the knowledge of the sparsely studied field of autophagy mechanisms in preterm infants and might be linked to impaired oxidative stress response, preterm birth, impaired lung development and higher susceptibility to respiratory morbidity in preterm infants. IMPACT To the best of our knowledge, this is the first study to investigate autophagy marker levels between human preterm and term infants in a large population-based sample in cord blood plasma This study demonstrates differential levels of key autophagy markers in preterm compared to term infants and an association with gestational age This may be linked to impaired oxidative stress response or developmental aspects and provide bases for future studies investigating the association with respiratory morbidity

Response of cord blood cells to environmental, hereditary and perinatal factors : a prospective birth cohort study

Many studies investigating the impact of individual risk factors on cord blood immune cell counts may be biased given that cord blood composition is influenced by a multitude of factors. The aim of this study was to comprehensively investigate the relative impact of environmental, hereditary and perinatal factors on cord blood cells.; In 295 neonates from the prospective Basel-Bern Infant Lung Development Cohort, we performed complete blood counts and fluorescence-activated cell sorting scans of umbilical cord blood. The associations between risk factors and cord blood cells were assessed using multivariable linear regressions.; The multivariable regression analysis showed that an increase per 10μg/m3 of the average nitrogen dioxide 14 days before birth was associated with a decrease in leukocyte (6.7%, 95% CI:-12.1,-1.0) and monocyte counts (11.6%, 95% CI:-19.6,-2.8). Maternal smoking during pregnancy was associated with significantly lower cord blood cell counts in multiple cell populations. Moreover, we observed sex differences regarding eosinophilic granulocytes and plasmacytoid dendritic cells. Finally, significantly increased numbers of cord blood cells were observed in infants exposed to perinatal stress. Cesarean section seems to play a significant role in Th1/Th2 balance.; Our results suggest that all three: environmental, hereditary and perinatal factors play a significant role in the composition of cord blood cells at birth, and it is important to adjust for all of these factors in cord blood studies. In particular, perinatal circumstances seem to influence immune balance, which could have far reaching consequences in the development of immune mediated diseases

Dynamics of respiratory symptoms during infancy and associations with wheezing at school age

Children with frequent respiratory symptoms in infancy have an increased risk for later wheezing, but the association with symptom dynamics is unknown. We developed an observer-independent method to characterise symptom dynamics and tested their association with subsequent respiratory morbidity. In this birth-cohort of healthy neonates, we prospectively assessed weekly respiratory symptoms during infancy, resulting in a time series of 52 symptom scores. For each infant, we calculated the transition probability between two consecutive symptom scores. We used these transition probabilities to construct a Markov matrix, which characterised symptom dynamics quantitatively using an entropy parameter. Using this parameter, we determined phenotypes by hierarchical clustering. We then studied the association between phenotypes and wheezing at 6 years. In 322 children with complete data for symptom scores during infancy (16 864 observations), we identified three dynamic phenotypes. Compared to the low-risk phenotype, the high-risk phenotype, defined by the highest entropy parameter, was associated with an increased risk of wheezing (odds ratio (OR) 3.01, 95% CI 1.15-7.88) at 6 years. In this phenotype, infants were more often male (64%) and had been exposed to environmental tobacco smoke (31%). In addition, more infants had siblings (67%) and attended childcare (38%). We describe a novel method to objectively characterise dynamics of respiratory symptoms in infancy, which helps identify abnormal clinical susceptibility and recovery patterns of infant airways associated with persistent wheezing

Lung functional development and asthma trajectories

Early life environmental risk factors are associated with chronic respiratory morbidity in child- and adulthood. A possible mechanism for this sustained effect is their influence on early life lung functional growth and development, a susceptible phase of rapid lung growth with increased plasticity. We summarize evidence of hereditary and environmental ante-, peri-, and early postnatal factors on lung functional development, such as air pollution, tobacco exposure, nutrition, intrauterine growth retardation, prematurity, early life infections, microbiome, and allergies and their effect on lung functional trajectories. While some of the factors (e.g., prematurity) directly impair lung growth, the influence of many environmental factors is mediated through inflammatory processes (e.g., recurrent infections or oxidative stress). The timing and nature of these influences and their impact result in degrees of impaired maximal lung functional capacity in early adulthood; and they potentially impact future long-term respiratory morbidity such as chronic asthma or chronic obstructive airway disease (COPD). We discuss possibilities to prevent or modify such early abnormal lung functional growth trajectories and the need for future studies and prevention programs

Lung functional development and asthma trajectories

Early life environmental risk factors are associated with chronic respiratory morbidity in child- and adulthood. A possible mechanism for this sustained effect is their influence on early life lung functional growth and development, a susceptible phase of rapid lung growth with increased plasticity. We summarize evidence of hereditary and environmental ante-, peri-, and early postnatal factors on lung functional development, such as air pollution, tobacco exposure, nutrition, intrauterine growth retardation, prematurity, early life infections, microbiome, and allergies and their effect on lung functional trajectories. While some of the factors (e.g., prematurity) directly impair lung growth, the influence of many environmental factors is mediated through inflammatory processes (e.g., recurrent infections or oxidative stress). The timing and nature of these influences and their impact result in degrees of impaired maximal lung functional capacity in early adulthood; and they potentially impact future long-term respiratory morbidity such as chronic asthma or chronic obstructive airway disease (COPD). We discuss possibilities to prevent or modify such early abnormal lung functional growth trajectories and the need for future studies and prevention programs

Effects of breastfeeding on respiratory symptoms in infancy

To assess the impact of potential risk factors on the development of respiratory symptoms and their specific modification by breastfeeding in infants in the first year of life.; We prospectively studied 436 healthy term infants from the Bern-Basel Infant Lung Development cohort. The breastfeeding status, and incidence and severity of respiratory symptoms (score) were assessed weekly by telephone interview during the first year of life. Risk factors (eg, pre- and postnatal smoking exposure, mode of delivery, gestational age, maternal atopy, and number of older siblings) were obtained using standardized questionnaires. Weekly measurements of particulate matter &lt;10 μg were provided by local monitoring stations. The associations were investigated using generalized additive mixed model with quasi Poisson distribution.; Breastfeeding reduced the incidence and severity of the respiratory symptom score mainly in the first 27 weeks of life (risk ratio 0.70; 95% CI 0.55-0.88). We found a protective effect of breastfeeding in girls but not in boys. During the first 27 weeks of life, breastfeeding attenuated the effects of maternal smoking during pregnancy, gestational age, and cesarean delivery on respiratory symptoms. There was no evidence for an interaction between breastfeeding and maternal atopy, number of older siblings, child care attendance, or particulate matter &lt;10 μg.; This study shows the risk-specific effect of breastfeeding on respiratory symptoms in early life using the comprehensive time-series approach

Associations of air pollution and greenness with the nasal microbiota of healthy infants: A longitudinal study.

BACKGROUND Air pollution and greenness are associated with short- and long-term respiratory health in children but the underlying mechanisms are only scarcely investigated. The nasal microbiota during the first year of life has been shown to be associated with respiratory tract infections and asthma development. Thus, an interplay between greenness, air pollution and the early nasal microbiota may contribute to short- and long-term respiratory health. We aimed to examine associations between fine particulate matter (PM2.5), nitrogen dioxide (NO2) and greenness with the nasal microbiota of healthy infants during the first year of life in a European context with low-to-moderate air pollution levels. METHODS Microbiota characterization was performed using 16 S rRNA pyrosequencing of 846 nasal swabs collected fortnightly from 47 healthy infants of the prospective Basel-Bern Infant Lung Development (BILD) cohort. We investigated the association of satellite-based greenness and an 8-day-average exposure to air pollution (PM2.5, NO2) with the nasal microbiota during the first year of life. Exposures were individually estimated with novel spatial-temporal models incorporating satellite data. Generalized additive mixed models adjusted for known confounders and considering the autoregressive correlation structure of the data were used for analysis. RESULTS Mean (SD) PM2.5 level was 17.1 (3.8 μg/m3) and mean (SD) NO2 level was 19.7 (7.9 μg/m3). Increased PM2.5 and increased NO2 were associated with reduced within-subject Ružička dissimilarity (PM2.5: per 1 μg/m3 -0.004, 95% CI -0.008, -0.001; NO2: per 1 μg/m3 -0.004, 95% CI -0.007, -0.001). Whole microbial community comparison with nonmetric multidimensional scaling revealed distinct microbiota profiles for different PM2.5 exposure levels. Increased NO2 was additionally associated with reduced abundance of Corynebacteriaceae (per 1 μg/m3: -0.027, 95% CI -0.053, -0.001). No associations were found between greenness and the nasal microbiota. CONCLUSION Air pollution was associated with Ružička dissimilarity and relative abundance of Corynebacteriaceae. This suggests that even low-to-moderate exposure to air pollution may impact the nasal microbiota during the first year of life. Our results will be useful for future studies assessing the clinical relevance of air-pollution-induced alterations of the nasal microbiota with subsequent respiratory disease development

CHI3L1 polymorphisms, cord blood YKL-40 levels and later asthma development.

BACKGROUND Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1), the gene encoding YKL-40, and increased serum YKL-40 levels are associated with severe forms of asthma. It has never been addressed whether SNPs in CHI3L1 and cord blood YKL-40 levels could already serve as potential biomarkers for milder forms of asthma. We assessed in an unselected population whether SNPs in CHI3L1 and cord blood YKL-40 levels at birth are associated with respiratory symptoms, lung function changes, asthma, and atopy. METHODS In a prospective birth cohort of healthy term-born neonates (n = 260), we studied CHI3L1 polymorphisms, and measured cord blood YKL-40 levels by ELISA in (n = 170) infants. Lung function was performed at 5 weeks and 6 years. Respiratory health during the first year of life was assessed weekly by telephone interviews. Diagnosis of asthma and allergic sensitisation was assessed at 6 years (n = 142). RESULTS The SNP rs10399805 was significantly associated with asthma at 6 years. The odds ratio for asthma was 4.5 (95 % CI 1.59-12.94) per T-allele. This finding was unchanged when adjusting for cord blood YKL-40 levels. There was no significant association for cord blood YKL-40 levels and asthma. SNPs in CHI3L1 and cord blood YKL-40 were not associated with lung function measurements at 5 weeks and 6 years, respiratory symptoms in the first year, and allergic sensitisation at 6 years. CONCLUSION Genetic variation in CHI3L1 might be related to the development of milder forms of asthma. Larger studies are warranted to establish the role of YKL-40 in that pathway