ORCID Profile
0000-0003-0422-5875
Current Organisations
Golisano Children's Hospital
,
University of Rochester Medical Center
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2008
Publisher: Springer Science and Business Media LLC
Date: 15-02-2011
Publisher: Massachusetts Medical Society
Date: 29-09-2011
Publisher: Elsevier BV
Date: 07-2007
Publisher: American Thoracic Society
Date: 10-2008
Publisher: Springer Science and Business Media LLC
Date: 22-09-2008
Abstract: A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results. To examine the relationship between the bacterial ersity of the gut and the development of eczema in early life by methods other than stool culture. Fecal s les were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool s les, we compared the microbial ersity of cases and controls using the number of electrophoretic bands and the Shannon index of ersity ( H' ) as indicators. Control subjects had significantly greater fecal microbial ersity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in ersity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32). Our findings suggest that reduced microbial ersity is associated with the development of eczema in early life.
Publisher: Wiley
Date: 12-2005
DOI: 10.1111/J.1541-0420.2005.00364.X
Abstract: The case-cohort design for longitudinal data consists of a subcohort s led at the beginning of the study that is followed repeatedly over time, and a case s le that is ascertained through the course of the study. Although some members in the subcohort may experience events over the study period, we refer to it as the "control-cohort." The case s le is a random s le of subjects not in the control-cohort, who have experienced at least one event during the study period. Different correlations among repeated observations on the same in idual are accommodated by a two-level random-effects model. This design allows consistent estimation of all parameters estimable in a cohort design and is a cost-effective way to study the effects of covariates on repeated observations of relatively rare binary outcomes when exposure assessment is expensive. It is an extension of the case-cohort design (Prentice, 1986, Biometrika73, 1-11) and the bidirectional case-crossover design (Navidi, 1998, Biometrics54, 596-605). A simulation study compares the efficiency of the longitudinal case-cohort design to a full cohort analysis, and we find that in certain situations up to 90% efficiency can be obtained with half the s le size required for a full cohort analysis. A bootstrap method is presented that permits testing for intra-subject homogeneity in the presence of unidentifiable nuisance parameters in the two-level random-effects model. As an illustration we apply the design to data from an ongoing study of childhood asthma.
Publisher: Elsevier BV
Date: 09-2002
Publisher: Elsevier BV
Date: 11-2002
Abstract: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52 95 % CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend =.005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 26-09-2006
Abstract: The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora). CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-γ, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. Cesarean section was associated with increased levels of IL-13 and IFN-γ. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-γ. Cesarean section is associated with increased levels of IL-13 and IFN-γ, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.JACI.2004.12.1138
Abstract: Asthma is common in minority and disadvantaged populations, whereas atopic disorders other than asthma appear to be less prevalent. It is unclear whether the same holds true for objective markers of sensitization. To determine the association of asthma, atopic disorders, and specific sensitization with race and socioeconomic factors. We analyzed total and specific IgE among 882 women (577 white, 169 black, and 136 Hispanic) who delivered a child at a large tertiary hospital in Boston, Mass, and who were screened for participation in a family and birth cohort study. Race/ethnicity and other characteristics were obtained from screening questionnaires. Addresses were geocoded, and 3 census-based geographic area socioeconomic variables were derived from block group information from the 1990 US Census. Black and Hispanic women were more likely to come from areas with low socioeconomic indicators and were more likely to have asthma than white women. However, these women were less likely to have hay fever and eczema than their white counterparts. Compared with white women, black women had higher mean total IgE levels had greater proportions of sensitization to indoor, outdoor, and fungal allergens and were more than twice as likely to be sensitized to > or =3 aeroallergens. The racial/ethnic disparities in atopic disorders may represent either underdiagnosis or underreporting and suggest that allergy testing may be underused in some populations. Differences in total IgE levels and specific allergen sensitization are likely a result of the complex interplay between exposures associated with socioeconomic disadvantage.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2005
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.JACI.2007.09.005
Abstract: Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma, they may result in elevated IgE levels, which are associated with exacerbations. To determine whether variation in the low-affinity IgE receptor gene, FCER2, is associated with severe exacerbations defined as emergency department visits and/or hospitalizations in patients with asthma on ICSs. We resequenced, then genotyped 10 FCER2 single nucleotide polymorphisms (SNPs) in 311 children randomized to inhaled budesonide as part of the Childhood Asthma Management Program. We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial. We also evaluated differences in cellular expression of the novel FCER2 SNP, T2206C. In white subjects, 3 FCER2 SNPs were significantly associated (P < .05) with elevated 4-year IgE level each was also associated with increased severe exacerbations. Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children (hazard ratio, 3.95 95% CI, 1.64-9.51 and hazard ratio, 3.08 95% CI, 1.00-9.47), despite ICS use. Interaction models supported a true gene-environment effect in white subjects (interaction P = .004). T2206C was also associated with decreased FCER2 expression (P = .02). FCER2 predicts the likelihood of treatment protocol success in asthma. The associations of T2206C with IgE level, severe exacerbations, and FCER2 expression may provide a mechanistic basis for the observed findings. Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma.
Publisher: American Thoracic Society
Date: 10-2012
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.RMED.2005.03.023
Abstract: Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects. We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes Time1, the point when the definition of diabetes was met and Time2, the most recent follow-up exam. Cases had lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV1 or FVC change over time between cases and controls. Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.
Publisher: American Thoracic Society
Date: 07-2007
Publisher: American Thoracic Society
Date: 09-2010
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.JACI.2006.09.012
Abstract: The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood. We sought to examine the relationship between respiratory illnesses in early life and atopic diseases at school age. We performed a prospective birth cohort study of the relationship between respiratory illnesses in the first year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic rhinitis at school age in 440 children with a parental history of atopy. Logistic regression was used to examine the relationship between respiratory illnesses and asthma, atopy, and allergic rhinitis. The relationship between respiratory illnesses in early life and repeated measures of wheezing between the ages of 1 and 7 years was investigated by using a proportional hazards models. Physician-diagnosed croup (adjusted odds ratio [OR], 0.30 95% CI, 0.12-0.72) and having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58 95% CI, 0.35-0.98) in the first year of life were inversely associated with atopy at school age. Physician-diagnosed bronchiolitis before age 1 year was significantly associated with asthma at age 7 years (adjusted OR, 2.77 95% CI, 1.23-6.22). Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99 95% CI, 1.03-8.67). The relationship between early-life respiratory illnesses and asthma and atopy is complex and likely dependent on the type of infection and immune response it initiates. Certain respiratory illnesses in early life modify the risk of atopy and asthma at school age.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.JACI.2006.09.002
Abstract: Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels. Our objective was to identify predictors of cord blood IgE levels among infants at increased risk of atopy. Cord blood IgE levels were measured in 874 infants who were screened for participation in a birth cohort. Questionnaires were administered after birth of the infant, and maternal and cord blood was obtained for measurement of IgE levels. Logistic and tobit regression models were used to study the association between perinatal factors and cord blood IgE levels. In multivariable models infant male sex, increased maternal total IgE level, maternal allergen sensitization, Hispanic ethnicity, and residence in low-income areas were associated with detectable or increased cord blood IgE levels, whereas increasing maternal age was associated with undetectable or lower cord blood IgE levels. Although maternal smoking during pregnancy was positively associated with cord blood IgE levels in univariable models, the effect did not persist after adjusting for potential confounders. Maternal allergen sensitization, markers of socioeconomic disadvantage and race/ethnicity, maternal age, and infant sex might influence fetal production of IgE. We found no association of maternal parity, mode of delivery, gestational age, or season of birth with cord blood IgE levels. The identification of these definable familial and environmental factors that predict cord blood IgE levels might help in the early detection of infants at risk for atopic disorders.
Publisher: Wiley
Date: 24-09-2022
DOI: 10.1111/ALL.15516
Abstract: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. Our objective was to identify associations between features of the prenatal and early‐life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool s les collected from mothers during the third trimester of pregnancy ( n = 120) and offspring at ages 3–6 months ( n = 265), 1 ( n = 436) and 3 years ( n = 506) in a total of 657 mother–child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate‐adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p = .03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. Overall, our results suggest that the early‐life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years.
Publisher: American Thoracic Society
Date: 2006
Location: United States of America
No related grants have been discovered for Augusto Litonjua.