Infant Nasopharyngeal Microbiota Subphenotypes and Early Childhood Lung Function: Evidence from a Rural Ghanaian Pregnancy Cohort.
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ABSTRACT:
SUBMITTER: Dubowski K
PROVIDER: S-EPMC8305530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe exposure-response association between prenatal and postnatal household air pollution (HAP) and infant growth trajectories is unknown.ObjectivesTo evaluate associations between prenatal and postnatal HAP exposure and stove interventions on growth trajectories over the first year of life.MethodsThe Ghana Randomized Air Pollution and Health Study enrolled n=1,414 pregnant women at ≤24wk gestation from Kintampo, Ghana, and randomized them to liquefied petroleum gas (LPG), improved biomass, or open fire (control) stoves. We quantified HAP exposure by repeated, personal prenatal and postnatal carbon monoxide (CO) and, in a subset, fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)] assessments. Length, weight, mid-upper arm circumference (MUAC) and head circumference (HC) were measured at birth, 3, 6, 9, and 12 months; weight-for-age, length-for-age (LAZ), and weight-for-length z (WLZ)-scores were calculated. For each anthropometric measure, we employed latent class growth analysis to generate growth trajectories over the first year of life and assigned each child to a trajectory group. We then employed ordinal logistic regression to determine associations between HAP exposures and growth trajectory assignments. Associations with stove intervention arm were also considered.ResultsOf the 1,306 live births, 1,144 had valid CO data and anthropometric variables measured at least once. Prenatal HAP exposure increased risk for lower length [CO odds ratio (OR)= 1.17, 95% CI: 1.01, 1.35 per 1-ppm increase; PM2.5 OR= 1.07, 95% CI: 1.02, 1.13 per 10-μg/m3 increase], lower LAZ z-score (CO OR= 1.15, 95% CI: 1.01, 1.32 per 1-ppm increase) and stunting (CO OR= 1.25, 95% CI: 1.08, 1.45) trajectories. Postnatal HAP exposure increased risk for smaller HC (CO OR= 1.09, 95% CI: 1.04, 1.13 per 1-ppm increase), smaller MUAC and lower WLZ-score (PM2.5 OR= 1.07, 95% CI: 1.00, 1.14 and OR= 1.09, 95% CI: 1.01, 1.19 per 10-μg/m3 increase, respectively) trajectories. Infants in the LPG arm had decreased odds of having smaller HC and MUAC trajectories as compared with those in the open fire stove arm (OR= 0.58, 95% CI: 0.37, 0.92 and OR= 0.45, 95% CI: 0.22, 0.90, respectively).DiscussionHigher early life HAP exposure (during pregnancy and through the first year of life) was associated with poorer infant growth trajectories among children in rural Ghana. A cleaner-burning stove intervention may have improved some growth trajectories. https://doi.org/10.1289/EHP8109.
| S-EPMC8629028 | biostudies-literature
Project description:ObjectivesNearly 40% of African children under 5 are stunted. We leveraged the Ghana randomized air pollution and health study (GRAPHS) cohort to examine whether poorer growth was associated with worse childhood lung function.Study designGRAPHS measured infant weight and length at birth and 3, 6, 9,12 months, and 4 years of age. At age 4 years, n = 567 children performed impulse oscillometry. We employed multivariable linear regression to estimate associations between birth and age 4 years anthropometry and lung function. Next, we employed latent class growth analysis (LCGA) to generate growth trajectories through age 4 years. We employed linear regression to examine associations between growth trajectory assignment and lung function.ResultsBirth weight and age 4 weight-for-age and height-for-age z-scores were inversely associated with airway resistance (e.g., R5 , or total airway resistance: birth weight β = -0.90 cmH2O/L/s, 95% confidence interval [CI]: -1.64, -0.16 per 1 kg increase; and R20 , or large airway resistance: age 4 height-for-age β = -0.40 cmH2O/L/s, 95% CI: -0.57, -0.22 per 1 unit z-score increase). Impaired growth trajectories identified through LCGA were associated with higher airway resistance, even after adjusting for age 4 body mass index. For example, children assigned to a persistently stunted trajectory had higher R5 (β = 2.71 cmH2O/L/s, 95% CI: 1.07, 4.34) and R20 (β = 1.43 cmH2O/L/s, 95% CI: 0.51, 2.36) as compared to normal.ConclusionChildren with poorer anthropometrics through to age 4 years had higher airway resistance in early childhood. These findings have implications for lifelong lung health, including pneumonia risk in childhood and reduced maximally attainable lung function in adulthood.
| S-EPMC9398957 | biostudies-literature
Project description:BackgroundAccruing epidemiological evidence suggests that prenatal exposure to emissions from cooking fuel is associated with increased risks of adverse maternal and perinatal outcomes including hypertensive disorders of pregnancy, low birth weight, stillbirth and infant mortality. We aimed to investigate the relationship between cooking fuel use and various pregnancy related outcomes in a cohort of urban women from the Accra region of Ghana.MethodsSelf-reported cooking fuel use was divided into "polluting" (wood, charcoal, crop residue and kerosene) and "clean" fuels (liquid petroleum gas and electricity) to examine 12 obstetric outcomes in a prospective cohort of pregnant women (N = 1010) recruited at < 17 weeks of gestation from Accra, Ghana. Logistic and multivariate linear regression analyses adjusted for BMI, maternal age, maternal education and socio-economic status asset index was conducted.Results34% (n = 279) of 819 women with outcome data available for analysis used polluting fuel as their main cooking fuel. Using polluting cooking fuels was associated with perinatal mortality (aOR: 7.6, 95%CI: 1.67-36.0) and an adverse Apgar score (< 7) at 5 min (aOR:3.83, 95%CI: (1.44-10.11). The other outcomes (miscarriage, post-partum hemorrhage, pre-term birth, low birthweight, caesarian section, hypertensive disorders of pregnancy, small for gestational age, and Apgar score at 1 min) had non-statistically significant findings.ConclusionsWe report an increased likelihood of perinatal mortality, and adverse 5-min Apgar scores in association with polluting fuel use. Further research including details on extent of household fuel use exposure is recommended to better quantify the consequences of household fuel use.Study registrationGhana Service Ethical Review Committee (GHS-ERC #: 07-9-11).
| S-EPMC7036189 | biostudies-literature
Project description:Associations between prenatal household air pollution exposure (HAP), newborn telomere length and early childhood blood pressure are unknown. Methods: Pregnant women were randomized to liquefied petroleum gas (LPG) stove, improved biomass stove or control (traditional, open fire cook stove). HAP was measured by personal carbon monoxide (CO) (n = 97) and fine particulate matter (PM2.5) (n = 60). At birth, cord blood mononuclear cells (CBMCs) were collected for telomere length (TL) analyses. At child age four years, we measured resting blood pressure (BP) (n = 97). We employed multivariable linear regression to determine associations between prenatal HAP and cookstove arm and assessed CBMC relative to TL separately. We then examined associations between CBMC TL and resting BP. Results: Higher prenatal PM2.5 exposure was associated with reduced TL (β = -4.9% (95% CI -8.6, -0.4), p = 0.03, per 10 ug/m3 increase in PM2.5). Infants born to mothers randomized to the LPG cookstove had longer TL (β = 55.3% (95% CI 16.2, 109.6), p < 0.01)) compared with control. In all children, shorter TL was associated with higher systolic BP (SBP) (β = 0.35 mmHg (95% CI 0.001, 0.71), p = 0.05, per 10% decrease in TL). Increased prenatal HAP exposure is associated with shorter TL at birth. Shorter TL at birth is associated with higher age four BP, suggesting that TL at birth may be a biomarker of HAP-associated disease risk.
| S-EPMC8309911 | biostudies-literature
Project description:BackgroundPneumonia, a leading cause of childhood mortality, is associated with household air pollution (HAP) exposure. Mechanisms between HAP and pneumonia are poorly understood, but studies suggest that HAP may increase the likelihood of bacterial, instead of viral, pneumonia. We assessed the relationship between HAP and infant microbial nasal carriage among 260 infants participating in the Ghana Randomized Air Pollution and Health Study (GRAPHS).MethodsData are from GRAPHS, a cluster-randomized controlled trial of cookstove interventions (improved biomass or LPG) versus the 3-stone (baseline) cookstove. Infants were surveyed for pneumonia during the first year of life and had routine personal exposure assessments. Nasopharyngeal swabs collected from pneumonia cases (n = 130) and healthy controls (n = 130) were analyzed for presence of 22 common respiratory microbes by MassTag polymerase chain reaction. Data analyses included intention-to-treat (ITT) comparisons of microbial species presence by study arm, and exposure-response relationships.ResultsIn ITT analyses, 3-stone arm participants had a higher mean number of microbial species than the LPG (LPG: 2.71, 3-stone: 3.34, p < 0.0001, n = 260). This difference was driven by increased bacterial (p < 0.0001) rather than viral species presence (non-significant). Results were pronounced in pneumonia cases and attenuated in healthy controls. Higher prevalence bacterial species were Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Exposure-response relationships did not yield significant associations between measured CO and nasal microbial carriage.ConclusionsOur intention-to-treat findings are consistent with a link between HAP and bacterial nasal carriage. No relationships were found for viral carriage. Given the null results in exposure-response analysis, it is likely that a pollutant besides CO is driving these differences.
| S-EPMC6868532 | biostudies-literature
Project description:Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.
| S-EPMC10978544 | biostudies-literature
Project description:BackgroundRecent research suggests that the microbiota affects susceptibility to both respiratory tract infections (RTIs) and gastrointestinal infections (GIIs). In order to optimize global treatment options, it is important to characterize microbiota profiles across different niches and geographic/socioeconomic areas where RTI and GII prevalences are high.MethodsWe performed 16S sequencing of nasopharyngeal swabs from 209 Venezuelan Amerindian children aged 6 weeks-59 months who were participating in a 13-valent pneumococcal conjugate vaccine (PCV13) study. Using random forest models, differential abundance testing, and regression analysis, we determined whether specific bacteria were associated with RTIs or GIIs and variation in PCV13 response.ResultsMicrobiota compositions differed between children with or without RTIs (P = .018) or GIIs (P = .001). Several species were associated with the absence of infections. Some of these health-associated bacteria are also observed in developed regions, such as Corynebacterium (log2(fold change [FC]) = 3.30 for RTIs and log2(FC) = 1.71 for GIIs), while others are not commonly observed in developed regions, such as Acinetobacter (log2(FC) = 2.82 and log2(FC) = 5.06, respectively). Klebsiella spp. presence was associated with both RTIs (log2(FC) = 5.48) and GIIs (log2(FC) = 7.20).ConclusionsThe nasopharyngeal microbiota of rural Venezuelan children included several bacteria that thrive in tropical humid climates. Interestingly, nasopharyngeal microbiota composition not only differed in children with an RTI but also in those with a GII, which suggests a reciprocal interplay between the 2 environments. Knowledge of region-specific microbiota patterns enables tailoring of preventive and therapeutic approaches.
| S-EPMC7840112 | biostudies-literature
Project description:BACKGROUND:Childhood asthma is a syndrome composed of heterogeneous phenotypes; furthermore, intrinsic biologic variation among racial/ethnic populations suggests possible genetic ancestry variation in childhood asthma. The objective of the study is to identify clinically homogeneous asthma subphenotypes in a diverse sample of asthmatic children and to assess subphenotype-specific genetic ancestry in African-American asthmatic children. METHODS:A total of 1211 asthmatic children including 813 in the Childhood Asthma Management Program and 398 in the Childhood Asthma Research and Education program were studied. Unsupervised cluster analysis on clinical phenotypes was conducted to identify homogeneous subphenotypes. Subphenotype-specific genetic ancestry was estimated for 167 African-American asthmatic children. Genetic ancestry association with subphenotypes/clinical phenotypes were determined. RESULTS:Three distinct subphenotypes were identified: a moderate atopic dermatitis (AD) group with negative skin prick test (SPT) and preserved lung function; a high AD group with positive SPT and airway hyperresponsiveness; and a low AD group with positive SPT and lower lung function. African ancestry at asthma genome-wide association study (GWAS) SNPs differed between subphenotypes (64, 89, and 94% for the three subphenotypes, respectively) and was inversely correlated with AD; each additional 10% increase in African ancestry was associated with 1.5 fold higher in IgE and 6.3 higher odds of positive SPT (all p-values <?0.0001). CONCLUSIONS:By conducting phenotype-based cluster analysis and assessing subphenotype-specific genetic ancestry, we were able to identify homogeneous subphenotypes for childhood asthma that showed significant variation in genetic ancestry of African-American asthmatic children. This finding demonstrates the utility of these complementary approaches to understand and refine childhood asthma subphenotypes and enable more targeted therapy.
| S-EPMC5984446 | biostudies-literature
Project description:BackgroundBronchial airway expression profiling has identified inflammatory subphenotypes of asthma, but the invasiveness of this technique has limited its application to childhood asthma.ObjectivesWe sought to determine whether the nasal transcriptome can proxy expression changes in the lung airway transcriptome in asthmatic patients. We also sought to determine whether the nasal transcriptome can distinguish subphenotypes of asthma.MethodsWhole-transcriptome RNA sequencing was performed on nasal airway brushings from 10 control subjects and 10 asthmatic subjects, which were compared with established bronchial and small-airway transcriptomes. Targeted RNA sequencing nasal expression analysis was used to profile 105 genes in 50 asthmatic subjects and 50 control subjects for differential expression and clustering analyses.ResultsWe found 90.2% overlap in expressed genes and strong correlation in gene expression (ρ = .87) between the nasal and bronchial transcriptomes. Previously observed asthmatic bronchial differential expression was strongly correlated with asthmatic nasal differential expression (ρ = 0.77, P = 5.6 × 10(-9)). Clustering analysis identified TH2-high and TH2-low subjects differentiated by expression of 70 genes, including IL13, IL5, periostin (POSTN), calcium-activated chloride channel regulator 1 (CLCA1), and serpin peptidase inhibitor, clade B (SERPINB2). TH2-high subjects were more likely to have atopy (odds ratio, 10.3; P = 3.5 × 10(-6)), atopic asthma (odds ratio, 32.6; P = 6.9 × 10(-7)), high blood eosinophil counts (odds ratio, 9.1; P = 2.6 × 10(-6)), and rhinitis (odds ratio, 8.3; P = 4.1 × 10(-6)) compared with TH2-low subjects. Nasal IL13 expression levels were 3.9-fold higher in asthmatic participants who experienced an asthma exacerbation in the past year (P = .01). Several differentially expressed nasal genes were specific to asthma and independent of atopic status.ConclusionNasal airway gene expression profiles largely recapitulate expression profiles in the lung airways. Nasal expression profiling can be used to identify subjects with IL13-driven asthma and a TH2-skewed systemic immune response.
| S-EPMC4043390 | biostudies-literature
Project description:Rodents serve as reservoirs and/or vectors for several human infections of high morbidity and mortality in the tropics. Population growth and demographic shifts over the years have increased contact with these mammals, thereby increasing opportunities for disease transmission. In Africa, the burden of rodent-borne diseases is not well described. To investigate human seroprevalence of selected rodent-borne pathogens, sera from 657 healthy adults in ten rural communities in Ghana were analyzed. An in-house enzyme-linked immunosorbent assay (ELISA), for immunoglobulin G (IgG) antibodies to Lassa virus was positive in 34 (5%) of the human samples. Using commercial kits, antibodies to hantavirus serotypes, Puumala and Dobrava, and Leptospira bacteria were detected in 11%, 12% and 21% of the human samples, respectively. Forty percent of residents in rural farming communities in Ghana have measurable antibodies to at least one of the rodent-borne pathogens tested, including antibodies to viral hemorrhagic fever viruses. The high seroprevalence found in rural Ghana to rodent-borne pathogens associated with both sporadic cases and larger disease outbreaks will help define disease threats and inform public health policy to reduce disease burden in underserved populations and deter larger outbreaks.
| S-EPMC6481813 | biostudies-literature