Patricia Minton - Academia.edu (original) (raw)
Papers by Patricia Minton
Clinical and Translational Science, Sep 1, 2008
Genetic variants in the beta(2)-adrenergic receptor (ADRB2) coding block have been associated wit... more Genetic variants in the beta(2)-adrenergic receptor (ADRB2) coding block have been associated with different parameters of asthma severity, but there is no consensus on which variants are most important. Our objective was to determine whether the genetic variants in the 5'- or 3'-flanking regions of ADRB2 impact the response to therapy. DNA was obtained initially from 72 adults hospitalized for an asthma exacerbation. We sequenced a 5,000 bp region of the ADRB2 gene that spanned the flanking regions and identified 31 single nucleotide polymorphisms (SNPs). Nonresponders to asthma therapy were defined as patients whose forced expiratory volume in 1 second (FEV(1)) worsened by >10% at 24 hours after admission. We then evaluated the relationship between the 19 common SNPs and response to asthma-specific therapy during acute disease exacerbations. Our results showed a significant association between nonresponders and a haplotype of five promoter SNPs in a nearly complete linkage disequilibrium. An analysis of the promoter and coding block polymorphisms in an extended cohort of 99 patients confirmed that promoter haplotype was the genetic component most strongly associated with asthmatic nonresponders, which was statistically significant among whites (p < 0.05). An identification of this promoter haplotype may provide an alternate explanation for the variation in the asthma responses observed with ADRB2 coding block polymorphisms.
BMC Medical Genetics, 2015
Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthm... more Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy.
Pediatric Allergy, Immunology, and Pulmonology, 2015
Background: A respiratory severity score (RSS) describing acute respiratory illness (ARI) severit... more Background: A respiratory severity score (RSS) describing acute respiratory illness (ARI) severity would be useful for research and clinical purposes. Methods: A total of 630 term infants presenting with ARI had their RSS measured. Results: RSS was higher in those with lower respiratory tract infection (LRTI) compared with those with upper respiratory infection (URI; LRTI 6.5 [4-8.5]; URI 1 [0-2], p<0.001) and in hospitalized infants compared with outpatients (hospitalized 6.5 [4-9]; outpatient 1 [0-3], p<0.001). Conclusions: RSS is higher in LRTI compared with URI and in hospitalized compared with nonhospitalized infants.
D40. INNOVATIVE APPROACHES AND NEW DEVELOPMENTS IN LUNG HEALTH RESEARCH, 2010
Page 1. / Thematic Poster Session / D40 INNOVATIVE APPROACHES AND NEW DEVELOPMENTS IN LUNG HEALTH... more Page 1. / Thematic Poster Session / D40 INNOVATIVE APPROACHES AND NEW DEVELOPMENTS IN LUNG HEALTH RESEARCH Wednesday, May 19/8:15 AM-4:00 PM / Area C, Hall G (First Level), Morial Convention Center ...
BMC Pulmonary Medicine, 2015
Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infa... more Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics.
Clinical cancer research : an official journal of the American Association for Cancer Research, 1997
CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fi... more CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines ...
Annals of Allergy, Asthma & Immunology, 2015
Pediatric Allergy, Immunology, and Pulmonology, 2014
It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronch... more It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings.
A55. CHILDHOOD ASTHMA EPIDEMIOLOGY, 2010
/ Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, Hall G (First A55 CHILDHOOD ... more / Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, Hall G (First A55 CHILDHOOD ASTHMA EPIDEMIOLOGY ... Measurement Of Vitamin D Levels Utilizing Laboratory And Dietary Recall Information From The Tennessee Children's Respiratory Initiative
Respirology, 2010
Background and Objective-The "attack rate" of asthma following viral LRTI is about 3 to 4 fold hi... more Background and Objective-The "attack rate" of asthma following viral LRTI is about 3 to 4 fold higher than that of the general population, however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age. Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma. The Tennessee Children's Respiratory Initiative (TCRI) has been established as a longitudinal prospective investigation of infants and their biological mothers. The primary goals are to investigate both the acute and the long-term health consequences of varying severity and etiology of clinically significant viral respiratory tract infections on early childhood outcomes.
PLoS ONE, 2011
Background: The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can s... more Background: The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can simplify sample collection versus samples obtained by venipuncture, particularly in populations in whom it is difficult to draw blood. We sought to validate the use of blood spot samples for the measurement of 25OHD compared to serum or whole blood samples and correlate the measured levels with intake estimated from dietary recall.
The Pediatric Infectious Disease Journal, 2014
In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was as... more In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was associated with decreased relative odds of a lower versus upper respiratory tract infection (adjusted odds ratio: 0.64; 95% confidence interval: 0.42-0.99). There was not a significant association between breast-feeding and bronchiolitis severity score or length of hospital stay.
The Pediatric Infectious Disease Journal, 2013
Methods-This prospective cohort enrolled previously healthy term infants during inpatient or outp... more Methods-This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute upper respiratory illness (URI) or bronchiolitis during September -May 2004-2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time RT-PCR.
The Journal of Pediatrics, 2013
Objective To examine healthcare resource utilization for acute respiratory illness in Latino infa... more Objective To examine healthcare resource utilization for acute respiratory illness in Latino infants compared with other racial/ethnic groups.
The Journal of Infectious Diseases, 2005
We determined the prevalence of human metapneumovirus (hMPV) infection in adults with asthma who ... more We determined the prevalence of human metapneumovirus (hMPV) infection in adults with asthma who were prospectively enrolled after hospitalization for an acute asthma exacerbation. Nasal wash specimens collected at admission and 3 months after discharge were tested for hMPV by real-time reverse-transcription polymerase chain reaction assays. hMPV was detected in 7 (6.9%) of 101 subjects at hospitalization and in 1 (1.3%) of 75 subjects at follow-up (odds ratio, 7 [95% confidence interval, 0.9-312]; P =.03). None of the patients with hMPV infection at hospitalization tested positive at follow-up, strongly suggesting that hMPV plays a direct etiologic role in acute asthma exacerbations.
The Journal of Infectious Diseases, 2006
Although rhinovirus (RV) respiratory infections trigger asthma exacerbations, the etiologic assoc... more Although rhinovirus (RV) respiratory infections trigger asthma exacerbations, the etiologic association between this virus and severe exacerbations, as well as the clinical characteristics of adults at risk for RV-associated asthma that necessitates hospitalization, have not been established. During 1999-2003, we conducted a cohort study of 101 adults prospectively enrolled at hospital admission for an asthma exacerbation. Patient characteristics and frequencies of RV in nasal specimens were analyzed, by reverse-transcription polymerase chain reaction (RT-PCR), at asthma-related hospital admission and at a 3-month convalescent follow-up visit. RV was detected by RT-PCR in 21% of hospitalized patients over a 4-year period and in 1.3% of patients who returned for a 3-month follow-up visit. RV detection was strongly associated with hospitalization for asthma (adjusted odds ratio [OR], 15.1 [95% confidence interval {CI}, 1.88-121.4]). After adjustment for baseline asthma severity, RV-positive patients were more likely than RV-negative patients to be current smokers and nonusers of inhaled corticosteroids (ICSs) (adjusted OR, 11.18 [95% CI, 2.37-52.81]; P=.002). RV respiratory infection is an etiologic agent in severe asthma exacerbations necessitating hospitalization in adults. Compared with hospitalized patients with asthma who were RV negative, RV-positive patients were significantly more likely to be smokers and nonusers of ICSs.
Journal of Allergy and Clinical Immunology, 2009
Journal of Allergy and Clinical Immunology, 2009
RATIONALE: Cigarette smoke induces profound disturbances in epithelial cell biology, such as infl... more RATIONALE: Cigarette smoke induces profound disturbances in epithelial cell biology, such as inflammation and metaplasia. Our goal was to assess the effects of smoke on epithelial antiviral interferon defense and cell-cycle. METHODS: Primary cultures of bronchial epithelial cells were exposed to cigarette smoke extract (CSE-5%) and rhinovirus (RV)16 (MOI 5 2). qPCR was used to quantify interferon type I & III response, viral load, telomerase expression (hTERT gene). Cell cycle was assessed by flow cytometry. RESULTS: Exposure of epithelial cells to cigarette smoke extract impaired by 80% the expression of type III IFN induced by RV infection. CSE increased telomerase in epithelial cells as measured by the upregulation of hTERT transcription. A synergistic effect of CSE and RV16 was observed for the upregulation of ICAM-1 gene transcription (increased 25% with either CSE, or RV16 alone, and 3 fold with the combination). CSE also induced a 3 fold increase in gene expression of B7H2. Exposure to CSE led to cell cycle arrest with accumulation in G2/M phase (12.5 6 3.2% vs. 43 6 7% before and after the treatment respectively, p < 0.05). RV infection decreased cells in G2/M (12.5 6 3.2% vs. 6.1 6 2.7%, p < 0.05). No significant increase in viral load was observed in CSE treated cultures. CONCLUSIONS: Cigarette smoke impairs epithelial production of type III IFN after rhinovirus infection, and increases expression of ICAM-1 and B7H2, which may increase susceptibility to RV infection and enhance inflammatory response. CSE also arrests epithelial cell cycle in the G2/M phase and upregulates telomerase expression.
Journal of Allergy and Clinical Immunology, 2011
Objectives-To examine the role of HRV in infant respiratory illness, and assess viral and host ri... more Objectives-To examine the role of HRV in infant respiratory illness, and assess viral and host risk factors for HRV disease severity.
Journal of Allergy and Clinical Immunology, 2011
Clinical and Translational Science, Sep 1, 2008
Genetic variants in the beta(2)-adrenergic receptor (ADRB2) coding block have been associated wit... more Genetic variants in the beta(2)-adrenergic receptor (ADRB2) coding block have been associated with different parameters of asthma severity, but there is no consensus on which variants are most important. Our objective was to determine whether the genetic variants in the 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;- or 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-flanking regions of ADRB2 impact the response to therapy. DNA was obtained initially from 72 adults hospitalized for an asthma exacerbation. We sequenced a 5,000 bp region of the ADRB2 gene that spanned the flanking regions and identified 31 single nucleotide polymorphisms (SNPs). Nonresponders to asthma therapy were defined as patients whose forced expiratory volume in 1 second (FEV(1)) worsened by &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10% at 24 hours after admission. We then evaluated the relationship between the 19 common SNPs and response to asthma-specific therapy during acute disease exacerbations. Our results showed a significant association between nonresponders and a haplotype of five promoter SNPs in a nearly complete linkage disequilibrium. An analysis of the promoter and coding block polymorphisms in an extended cohort of 99 patients confirmed that promoter haplotype was the genetic component most strongly associated with asthmatic nonresponders, which was statistically significant among whites (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). An identification of this promoter haplotype may provide an alternate explanation for the variation in the asthma responses observed with ADRB2 coding block polymorphisms.
BMC Medical Genetics, 2015
Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthm... more Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy.
Pediatric Allergy, Immunology, and Pulmonology, 2015
Background: A respiratory severity score (RSS) describing acute respiratory illness (ARI) severit... more Background: A respiratory severity score (RSS) describing acute respiratory illness (ARI) severity would be useful for research and clinical purposes. Methods: A total of 630 term infants presenting with ARI had their RSS measured. Results: RSS was higher in those with lower respiratory tract infection (LRTI) compared with those with upper respiratory infection (URI; LRTI 6.5 [4-8.5]; URI 1 [0-2], p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and in hospitalized infants compared with outpatients (hospitalized 6.5 [4-9]; outpatient 1 [0-3], p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Conclusions: RSS is higher in LRTI compared with URI and in hospitalized compared with nonhospitalized infants.
D40. INNOVATIVE APPROACHES AND NEW DEVELOPMENTS IN LUNG HEALTH RESEARCH, 2010
Page 1. / Thematic Poster Session / D40 INNOVATIVE APPROACHES AND NEW DEVELOPMENTS IN LUNG HEALTH... more Page 1. / Thematic Poster Session / D40 INNOVATIVE APPROACHES AND NEW DEVELOPMENTS IN LUNG HEALTH RESEARCH Wednesday, May 19/8:15 AM-4:00 PM / Area C, Hall G (First Level), Morial Convention Center ...
BMC Pulmonary Medicine, 2015
Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infa... more Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics.
Clinical cancer research : an official journal of the American Association for Cancer Research, 1997
CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fi... more CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines ...
Annals of Allergy, Asthma & Immunology, 2015
Pediatric Allergy, Immunology, and Pulmonology, 2014
It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronch... more It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings.
A55. CHILDHOOD ASTHMA EPIDEMIOLOGY, 2010
/ Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, Hall G (First A55 CHILDHOOD ... more / Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, Hall G (First A55 CHILDHOOD ASTHMA EPIDEMIOLOGY ... Measurement Of Vitamin D Levels Utilizing Laboratory And Dietary Recall Information From The Tennessee Children's Respiratory Initiative
Respirology, 2010
Background and Objective-The "attack rate" of asthma following viral LRTI is about 3 to 4 fold hi... more Background and Objective-The "attack rate" of asthma following viral LRTI is about 3 to 4 fold higher than that of the general population, however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age. Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma. The Tennessee Children's Respiratory Initiative (TCRI) has been established as a longitudinal prospective investigation of infants and their biological mothers. The primary goals are to investigate both the acute and the long-term health consequences of varying severity and etiology of clinically significant viral respiratory tract infections on early childhood outcomes.
PLoS ONE, 2011
Background: The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can s... more Background: The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can simplify sample collection versus samples obtained by venipuncture, particularly in populations in whom it is difficult to draw blood. We sought to validate the use of blood spot samples for the measurement of 25OHD compared to serum or whole blood samples and correlate the measured levels with intake estimated from dietary recall.
The Pediatric Infectious Disease Journal, 2014
In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was as... more In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was associated with decreased relative odds of a lower versus upper respiratory tract infection (adjusted odds ratio: 0.64; 95% confidence interval: 0.42-0.99). There was not a significant association between breast-feeding and bronchiolitis severity score or length of hospital stay.
The Pediatric Infectious Disease Journal, 2013
Methods-This prospective cohort enrolled previously healthy term infants during inpatient or outp... more Methods-This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute upper respiratory illness (URI) or bronchiolitis during September -May 2004-2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time RT-PCR.
The Journal of Pediatrics, 2013
Objective To examine healthcare resource utilization for acute respiratory illness in Latino infa... more Objective To examine healthcare resource utilization for acute respiratory illness in Latino infants compared with other racial/ethnic groups.
The Journal of Infectious Diseases, 2005
We determined the prevalence of human metapneumovirus (hMPV) infection in adults with asthma who ... more We determined the prevalence of human metapneumovirus (hMPV) infection in adults with asthma who were prospectively enrolled after hospitalization for an acute asthma exacerbation. Nasal wash specimens collected at admission and 3 months after discharge were tested for hMPV by real-time reverse-transcription polymerase chain reaction assays. hMPV was detected in 7 (6.9%) of 101 subjects at hospitalization and in 1 (1.3%) of 75 subjects at follow-up (odds ratio, 7 [95% confidence interval, 0.9-312]; P =.03). None of the patients with hMPV infection at hospitalization tested positive at follow-up, strongly suggesting that hMPV plays a direct etiologic role in acute asthma exacerbations.
The Journal of Infectious Diseases, 2006
Although rhinovirus (RV) respiratory infections trigger asthma exacerbations, the etiologic assoc... more Although rhinovirus (RV) respiratory infections trigger asthma exacerbations, the etiologic association between this virus and severe exacerbations, as well as the clinical characteristics of adults at risk for RV-associated asthma that necessitates hospitalization, have not been established. During 1999-2003, we conducted a cohort study of 101 adults prospectively enrolled at hospital admission for an asthma exacerbation. Patient characteristics and frequencies of RV in nasal specimens were analyzed, by reverse-transcription polymerase chain reaction (RT-PCR), at asthma-related hospital admission and at a 3-month convalescent follow-up visit. RV was detected by RT-PCR in 21% of hospitalized patients over a 4-year period and in 1.3% of patients who returned for a 3-month follow-up visit. RV detection was strongly associated with hospitalization for asthma (adjusted odds ratio [OR], 15.1 [95% confidence interval {CI}, 1.88-121.4]). After adjustment for baseline asthma severity, RV-positive patients were more likely than RV-negative patients to be current smokers and nonusers of inhaled corticosteroids (ICSs) (adjusted OR, 11.18 [95% CI, 2.37-52.81]; P=.002). RV respiratory infection is an etiologic agent in severe asthma exacerbations necessitating hospitalization in adults. Compared with hospitalized patients with asthma who were RV negative, RV-positive patients were significantly more likely to be smokers and nonusers of ICSs.
Journal of Allergy and Clinical Immunology, 2009
Journal of Allergy and Clinical Immunology, 2009
RATIONALE: Cigarette smoke induces profound disturbances in epithelial cell biology, such as infl... more RATIONALE: Cigarette smoke induces profound disturbances in epithelial cell biology, such as inflammation and metaplasia. Our goal was to assess the effects of smoke on epithelial antiviral interferon defense and cell-cycle. METHODS: Primary cultures of bronchial epithelial cells were exposed to cigarette smoke extract (CSE-5%) and rhinovirus (RV)16 (MOI 5 2). qPCR was used to quantify interferon type I & III response, viral load, telomerase expression (hTERT gene). Cell cycle was assessed by flow cytometry. RESULTS: Exposure of epithelial cells to cigarette smoke extract impaired by 80% the expression of type III IFN induced by RV infection. CSE increased telomerase in epithelial cells as measured by the upregulation of hTERT transcription. A synergistic effect of CSE and RV16 was observed for the upregulation of ICAM-1 gene transcription (increased 25% with either CSE, or RV16 alone, and 3 fold with the combination). CSE also induced a 3 fold increase in gene expression of B7H2. Exposure to CSE led to cell cycle arrest with accumulation in G2/M phase (12.5 6 3.2% vs. 43 6 7% before and after the treatment respectively, p < 0.05). RV infection decreased cells in G2/M (12.5 6 3.2% vs. 6.1 6 2.7%, p < 0.05). No significant increase in viral load was observed in CSE treated cultures. CONCLUSIONS: Cigarette smoke impairs epithelial production of type III IFN after rhinovirus infection, and increases expression of ICAM-1 and B7H2, which may increase susceptibility to RV infection and enhance inflammatory response. CSE also arrests epithelial cell cycle in the G2/M phase and upregulates telomerase expression.
Journal of Allergy and Clinical Immunology, 2011
Objectives-To examine the role of HRV in infant respiratory illness, and assess viral and host ri... more Objectives-To examine the role of HRV in infant respiratory illness, and assess viral and host risk factors for HRV disease severity.
Journal of Allergy and Clinical Immunology, 2011