27 results on '"Meghan E. McGarry"'
Search Results
2. Food insecurity and mental health during the COVID‐19 pandemic in cystic fibrosis households
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Janet T. Lim, Ngoc P. Ly, Shaina M. Willen, Kensho Iwanaga, Elizabeth R. Gibb, Marilynn Chan, Gwynne D. Church, Fatima Neemuchwala, and Meghan E. McGarry
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Adult ,Pulmonary and Respiratory Medicine ,Food Insecurity ,Cross-Sectional Studies ,Mental Health ,Cystic Fibrosis ,Pediatrics, Perinatology and Child Health ,COVID-19 ,Humans ,Child ,Pandemics ,Food Supply - Abstract
The COVID-19 pandemic impacted many households due to shelter-in-place orders and economic hardship. People with cystic fibrosis (CF) experienced increased food insecurity compared to the general population before the pandemic, even though adequate food access is needed to maintain nutrition goals associated with improved health-related outcomes. Little is known about the impact the pandemic had on the food insecurity of people with CF and their families.To investigate how the COVID-19 pandemic impacted food insecurity, mental health, and self-care in people with CF.Adults with CF and parents/guardians of children with CF were recruited via social media to complete online questionnaires from May 2020 to February 2021. Questionnaires in English and Spanish included USDA 2-question food insecurity screening, Patient Health Questionnaire-4 for mental health screening, and directed questions on the impact of the pandemic.Of 372 respondents, 21.8% of the households experienced food insecurity during the pandemic compared to 18.8% prepandemic (p .001). More food insecure patients with CF reported weight loss (32.1% vs. 13.1%, p .001), worse airway clearance adherence (13.6% vs. 5.8%, p .01), and worse medication adherence (12.4% vs. 1.7%, p .01) compared to food secure patients. Food insecure subjects were more likely to have an abnormal mental health screen compared to food secure subjects (53.1% vs. 16.2%, p .001).Food insecurity increased in the CF population during the COVID-19 pandemic. Food insecure subjects reported worse mental health and self-care during the pandemic compared to food secure subjects.
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- 2022
3. Changes in the Use of Invasive and Noninvasive Mechanical Ventilation in Pediatric Asthma: 2009-2019
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Michael A. Smith, Doantrang Dinh, Ngoc P. Ly, Shan L. Ward, Meghan E. McGarry, and Matt S. Zinter
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Pulmonary and Respiratory Medicine - Abstract
Despite lower overall hospitalization rates for asthma in recent years, there has been an increase in the number of pediatric patients receiving intensive care management in the United States.To investigate how the use of invasive and noninvasive mechanical ventilation for asthma has changed in the context of an evolving cohort of critically ill pediatric asthma patients.We analyzed children admitted to intensive care units for asthma from 2009 through 2019 in the Virtual Pediatric Systems database. Regression analyses were used to evaluate how respiratory support interventions, mortality, and patient characteristics have changed over time. Odds ratios were calculated to determine how patient characteristics were associated with respiratory support needs. Stratified analyses were performed to determine how changing practice patterns may have differed between patient subgroups.There were 67,614 admissions for 56,727 patients analyzed. Intubation occurred in 4.6% of admissions and decreased from 6.9% to 3.4% over time (p0.001), whereas noninvasive ventilation as the maximal respiratory support increased from 8.9% to 20.0% (p0.001). Over time, the cohort shifted to include more 2-6 year olds and patients of Asian/Pacific Islander or Hispanic race/ethnicity. Although intubation decreased and noninvasive ventilation increased in all subgroups, the changes were most pronounced in the youngest patients and slightly less pronounced for obese patients.In pediatric asthma, use of intubation has halved while use of noninvasive ventilation has more than doubled. This change in practice appears partially related to a younger patient cohort, although other factors merit exploration.
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- 2022
4. Detection of disease-causing CFTR variants in state newborn screening programs
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Meghan E. McGarry, Clement L. Ren, Runyu Wu, Philip M. Farrell, and Susanna A. McColley
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Pulmonary and Respiratory Medicine ,Pediatrics, Perinatology and Child Health - Abstract
Newborn screening (NBS) algorithms for cystic fibrosis (CF) vary in the United State of America and include different cystic fibrosis transmembrane conductance regulator (CFTR) variants. CFTR variant distribution varies among racial and ethnic groups.Our objectives were to identify differences in detection rate by race and ethnicity for CFTR variant panels, identify each US state detection rate for CFTR variant panels, and describe the rate of false-negative NBS and delayed diagnoses by race and ethnicity.This is a cross-sectional analysis of the detection rate of at least 1 CFTR variant for seven panels by race and ethnicity in genotyped people with CF (PwCF) or CFTR-related metabolic syndrome (CRMS)/CFTR-related disorders in CF Foundation Patient Registry (CFFPR) in 2020. We estimated the case detection rate of CFTR variant panels by applying the detection rate to Census data. Using data from CFFPR, we compared the rate of delayed diagnosis or false-negative NBS by race and ethnicity.For all panels, detection of at least 1 CFTR variant was highest in non-Hispanic White PwCF (87.5%-97.0%), and lowest in Black, Asian, and Hispanic PwCF (41.9%-93.1%). Detection of at least 1 CFTR variant was lowest in Black and Asian people with CRMS/CFTR-related disorders (48.4%-64.8%). States with increased racial and ethnic diversity have lower detection rates for all panels. Overall, 3.8% PwCF had a false-negative NBS and 11.8% had a delayed diagnosis; Black, Hispanic, and mixed-race PwCF were overrepresented.CFTR variant panels have lower detection rates in minoritized racial and ethnic groups leading to false-negative NBS, delayed diagnosis, and likely health disparities.
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- 2022
5. How (and why) does iconicity effect lexical access: An electrophysiological study of American sign language
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Meghan E. McGarry, Katherine J. Midgley, Phillip J. Holcomb, and Karen Emmorey
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Behavioral Neuroscience ,Cognitive Neuroscience ,Experimental and Cognitive Psychology - Published
- 2023
6. Early acquisition and conversion of Pseudomonas aeruginosa in Hispanic youth with cystic fibrosis in the United States
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Chiung Yu Huang, Meghan E. McGarry, Dennis W. Nielson, and Ngoc P. Ly
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Longitudinal study ,Younger age ,Adolescent ,Cystic Fibrosis ,Clinical Sciences ,Respiratory System ,medicine.disease_cause ,Cystic fibrosis ,Article ,Congenital ,Young Adult ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Clinical Research ,Internal medicine ,Humans ,Medicine ,Pseudomonas Infections ,Longitudinal Studies ,Registries ,Preschool ,Child ,Lung ,Survival analysis ,Pediatric ,Patient registry ,business.industry ,Pseudomonas aeruginosa ,Hazard ratio ,Infant, Newborn ,Infant ,Hispanic or Latino ,Newborn ,medicine.disease ,United States ,030104 developmental biology ,Increased risk ,030228 respiratory system ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Health disparities ,business - Abstract
BackgroundFor unknown reasons, Hispanic patients with cystic fibrosis (CF) have more severe pulmonary disease than non-Hispanic white patients. In CF, the pulmonary pathogen Pseudomonas aeruginosa is associated with worse outcomes. We sought to determine if Hispanic patients with CF are at an increased risk of acquiring P. aeruginosa or acquire it earlier than non-Hispanic white patients.MethodsThis is a longitudinal study comparing the timing and risk of acquisition of different forms of P. aeruginosa between Hispanic and non-Hispanic white patients aged 0-21 years old with CF in the CF Foundation Patient Registry (CFFPR) in 2008-2013. The age at the initial acquisition of P. aeruginosa (initial acquisition, mucoid, chronic, multidrug-resistant) was summarized using Kaplan-Meier survival curves and analyzed using Cox proportional hazards regression models.ResultsOf 10,464 patients, 788 (7.5%) were Hispanic and 9,676 (92.5%) were non-Hispanic white. Hispanic patients acquired all forms of P. aeruginosa at a younger age than non-Hispanic white patients. Hispanic patients had a higher risk of acquiring P. aeruginosa than non-Hispanic white patients: the hazard ratio (HR) was 1.26 (95% CI 1.16-1.38, p
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- 2021
7. Left behind: The potential impact of CFTR modulators on racial and ethnic disparities in cystic fibrosis
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Meghan E. McGarry, Elizabeth R. Gibb, Gabriela R. Oates, and Michael S. Schechter
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Pulmonary and Respiratory Medicine ,Race ,Cystic Fibrosis ,Respiratory System ,Cystic Fibrosis Transmembrane Conductance Regulator ,Cardiorespiratory Medicine and Haematology ,CFTR modulators ,Article ,Congenital ,Rare Diseases ,Orphan Drug ,Good Health and Well Being ,Clinical Research ,5.1 Pharmaceuticals ,Pediatrics, Perinatology and Child Health ,Mutation ,Ethnicity ,Humans ,Development of treatments and therapeutic interventions ,Lung ,Minority Groups - Abstract
The advent of CFTR modulators, a genomic specific medication, revolutionized the treatment of CF for many patients. However, given that these therapeutics were only developed for specific CFTR mutations, not all people with CF have access to such disease-modifying drugs. Racial and ethnic minority groups are less likely to have CFTR mutations that are approved for CFTR modulators. This exclusion has the potential to widen existing health disparities.
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- 2022
8. Matching Pictures and Signs: An ERP Study of the Effects of Iconic Structural Alignment in American Sign Language
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Meghan E. McGarry, Natasja Massa, Katherine J. Midgley, Karen Emmorey, Phillip J. Holcomb, and Megan Mott
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Male ,Matching (statistics) ,American Sign Language ,Cognitive Neuroscience ,Experimental and Cognitive Psychology ,Sign language ,Deafness ,Article ,Behavioral Neuroscience ,Sign Language ,Humans ,Evoked Potentials ,Language ,Electroencephalography ,N400 ,language.human_language ,United States ,Semantics ,Comprehension ,language ,Depiction ,Female ,Psychology ,Iconicity ,Cognitive psychology ,Sign (mathematics) - Abstract
Event-related potentials (ERPs) were used to explore the effects of iconicity and structural visual alignment between a picture-prime and a sign-target in a picture-sign matching task in American Sign Language (ASL). Half the targets were iconic signs and were presented after a) a matching visually-aligned picture (e.g., the shape and location of the hands in the sign COW align with the depiction of a cow with visible horns), b) a matching visually-nonaligned picture (e.g., the cow's horns were not clearly shown), and c) a non-matching picture (e.g., a picture of a swing instead of a cow). The other half of the targets were filler signs. Trials in the matching condition were responded to faster than those in the non-matching condition and were associated with smaller N400 amplitudes in deaf ASL signers. These effects were also observed for hearing non-signers performing the same task with spoken-English targets. Trials where the picture-prime was aligned with the sign target were responded to faster than non-aligned trials and were associated with a reduced P3 amplitude rather than a reduced N400, suggesting that picture-sign alignment facilitated the decision process, rather than lexical access. These ERP and behavioral effects of alignment were found only for the ASL signers. The results indicate that iconicity effects on sign comprehension may reflect a task-dependent strategic use of iconicity, rather than facilitation of lexical access.
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- 2021
9. Regional variations in longitudinal pulmonary function: A comparison of Hispanic and non‐Hispanic subjects with cystic fibrosis in the United States
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Meghan E. McGarry, Ngoc P. Ly, John Neuhaus, and Dennis W. Nielson
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Vital capacity ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,Respiratory System ,Vital Capacity ,Ethnic group ,Cystic fibrosis ,Article ,White People ,Pulmonary function testing ,Paediatrics and Reproductive Medicine ,Young Adult ,03 medical and health sciences ,FEV1/FVC ratio ,Rare Diseases ,0302 clinical medicine ,Clinical Research ,Forced Expiratory Volume ,030225 pediatrics ,Epidemiology ,medicine ,Humans ,Child ,Lung ,Retrospective Studies ,pulmonary function testing ,Patient registry ,business.industry ,Retrospective cohort study ,Hispanic or Latino ,respiratory system ,medicine.disease ,social dimensions of pulmonary medicine ,United States ,Respiratory Function Tests ,Good Health and Well Being ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Linear Models ,epidemiology ,Female ,business ,Demography - Abstract
Background Hispanic subjects with cystic fibrosis (CF) have increased morbidity and mortality than non-Hispanic white subjects. The ethnic disparity in mortality varies by region. Factors influencing pulmonary function vary by both ethnicity and region. Objective To determine if the ethnic difference in pulmonary function varies by region. Methods This retrospective cohort study compared differences in longitudinal pulmonary function (percent-predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1 ], forced expiratory flow at 25% to 75% [FEF25-75 ], FEV1 /FVC, and FEV1 decline) between Hispanic and non-Hispanic white subjects with CF by Census region of the United States (West, South, Midwest, and Northeast). Subjects were of ages 6 to 25 years and in the CF Foundation Patient Registry from 2008 to 2013. We used linear mixed effects models with subject-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. Results Of 14 932 subjects, 1433 (9.6%) were Hispanic and 13 499 (90.4%) were non-Hispanic white. Hispanic subjects' FEV1 was 9.0% (8.3%-9.8%) lower than non-Hispanic white subjects in the West, while Hispanic subjects' FEV1 was only 4.0% (3.0%-5.0%) lower in the Midwest, 4.4% (3.1%-5.7%) lower in the Northeast, and 4.4% (3.2%-5.5%) lower in the South. Similarly, FVC and FEF25-75 were lower among Hispanic subjects compared to non-Hispanic white subjects in all US regions, with the biggest differences in the West. Only in the West was FEV1 /FVC significantly lower in Hispanic subjects (-0.019; -0.022 to -0.015). FEV1 decline was not significantly different between ethnicities in any region. Conclusions In CF, Hispanic subjects have lower pulmonary function than non-Hispanic white subjects in all geographic regions with the largest difference in occurring in the West.
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- 2019
10. An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos
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Dan L. Nicolae, Pedro C. Avila, Badri Padhukasahasram, Eugene R. Bleecker, W. James Gauderman, Carole Ober, Lindsey A. Roth, Cheryl A. Winkler, Luisa N. Borrell, Meghan E. McGarry, Sam S. Oh, Neeta Thakur, Esteban G. Burchard, Blanca Estela Del Río-Navarro, Jose R. Rodriguez-Santana, Isabelle Romieu, Emerita Brigino-Buenaventura, David V. Conti, Joshua Galanter, Benjamin A. Raby, Frank D. Gilliland, Albert M. Levin, Carlos Bustamante, Maria Pino-Yanes, Dara G. Torgerson, Kathleen C. Barnes, William Rodriguez-Cintron, Scott T. Weiss, Christopher R. Gignoux, Ryan D. Hernandez, Andrés Moreno-Estrada, Stephanie J. London, Scott Huntsman, Elizabeth A. Nguyen, Weiniu Gan, Fernando J. Martinez, Max A. Seibold, Lawrence H. Uricchio, Shannon Thyne, Saunak Sen, Celeste Eng, Harold J. Farber, L. Keoki Williams, Karla Sandoval, Juan José Luis Sienra-Monge, Deborah A. Meyers, Donglei Hu, Kelley Meade, Michael A. LeNoir, Bonnie R. Joubert, Rasika A. Mathias, Denise Serebrisky, and Rajesh Kumar
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0301 basic medicine ,Linkage disequilibrium ,Allergy ,Genome-wide association study ,Smad2 Protein ,SMAD2 ,0302 clinical medicine ,2.1 Biological and endogenous factors ,Immunology and Allergy ,Aetiology ,Lung ,Chromosome Mapping ,Single Nucleotide ,Hispanic or Latino ,Transmission disequilibrium test ,admixture mapping ,asthma exacerbations ,Respiratory ,Human ,medicine.medical_specialty ,rare variation ,Immunology ,Genetic admixture ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,Chromosomes ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Latinos ,Polymorphism ,targeted sequencing ,Asthma ,Pair 18 ,business.industry ,Human Genome ,Odds ratio ,medicine.disease ,meta-analysis ,030104 developmental biology ,030228 respiratory system ,Expression quantitative trait loci ,gene expression ,Chromosomes, Human, Pair 18 ,business - Abstract
BackgroundAsthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.ObjectiveWe sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.MethodsWe leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.ResultsWe identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P=6.8×10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P=.002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P=.008). Our findings were replicated in an independent childhood asthma study in Latinos (P=5.3×10-3, combined P=2.6×10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P 
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- 2019
11. Cystic fibrosis patients of minority race and ethnicity less likely eligible for CFTR modulators based on CFTR genotype
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Meghan E. McGarry and Susanna A. McColley
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Cystic Fibrosis ,Genotype ,Ethnic group ,Cystic Fibrosis Transmembrane Conductance Regulator ,Cystic fibrosis ,Article ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Internal medicine ,Epidemiology ,Ethnicity ,Medicine ,Humans ,Minority Groups ,biology ,business.industry ,respiratory system ,medicine.disease ,Cystic fibrosis transmembrane conductance regulator ,Health equity ,digestive system diseases ,respiratory tract diseases ,Cross-Sectional Studies ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Cohort ,Mutation ,biology.protein ,business - Abstract
Background Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are disease-modifying medications for cystic fibrosis (CF) and are shown to be efficacious for only specific CFTR mutations. CFTR mutation frequency varies by ancestry, which is different from but related to demographic racial and ethnic group. Eligibility for CFTR modulator therapy has not been previously reported by race and ethnicity. Methods We conducted a cross-sectional study of patients in the 2018 CF Foundation Patient Registry. We analyzed the percentage of patients in each US Census defined racial and ethnic group eligible for CFTR modulators based on CFTR mutations approved by the US FDA and then based on both mutations and FDA approval by age. We compared lung function based on CFTR modulator eligibility and prescription. Findings Based on CFTR mutations alone, 92.4% of non-Hispanic White patients, 69.7% of Black/African American patients, 75.6% of Hispanic patients, and 80.5% of other race patients eligible for CFTR modulators. For each CFTR modulator, Black/African American patients were least likely to have eligible mutations, and non-Hispanic White patients were most likely. There was no difference in the disparity between racial and/or ethnic groups with the addition of current FDA approval by age. The lowest pulmonary function in the cohort was seen in non-Hispanic White, Black/African American, and Hispanic patients not eligible for CFTR modulators. Interpretation Patients with CF from minority groups are less likely to be eligible for CFTR modulators. Because people with CF who are racial and ethnic minorities have increased disease severity and earlier mortality, this will further contribute to health disparities.
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- 2020
12. Delayed Diagnosis of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Vein in a Term Infant
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Ngoc P. Ly, Meghan E. McGarry, J.T. Lim, Kensho Iwanaga, and M. Chan
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Alveolar capillary dysplasia ,medicine.medical_specialty ,Term Infant ,business.industry ,Internal medicine ,Cardiology ,medicine ,Delayed diagnosis ,business ,medicine.disease ,Pulmonary vein - Published
- 2020
13. Outcomes of Children With Cystic Fibrosis Admitted to PICUs
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Michael A. Smith, Ngoc P. Ly, Meghan E. McGarry, and Matt S. Zinter
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Gastrointestinal bleeding ,medicine.medical_specialty ,pediatrics ,Cystic Fibrosis ,intensive care units ,medicine.medical_treatment ,artificial ,Nursing ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Intensive Care Units, Pediatric ,Cystic fibrosis ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,0302 clinical medicine ,Rare Diseases ,7.1 Individual care needs ,Clinical Research ,medicine ,Humans ,Child ,Lung ,Retrospective Studies ,Mechanical ventilation ,Pediatric ,business.industry ,Mortality rate ,Respiration ,Infant ,030208 emergency & critical care medicine ,Odds ratio ,medicine.disease ,Respiration, Artificial ,Hospitalization ,Good Health and Well Being ,Pneumothorax ,Pediatrics, Perinatology and Child Health ,Cohort ,Emergency medicine ,Zero Hunger ,pulmonary medicine ,Management of diseases and conditions ,business ,critical care outcomes ,Cohort study - Abstract
Objectives Data on outcomes of children with cystic fibrosis admitted to PICUs are limited and outdated. Prior studies cite PICU mortality rates ranging from 37.5% to 100%. Given the advances made in cystic fibrosis care, we expect outcomes for these patients to have changed significantly since last studied. We provide an updated report on PICU mortality and the factors associated with death among critically ill children with cystic fibrosis. Design Retrospective multicenter cohort analysis utilizing data from the Virtual Pediatric Systems database. Setting Data were collected from 135 PICUs from January 1, 2009, to June 20, 2018. Patients One-thousand six-hundred thirty-three children with cystic fibrosis accounting for 2,893 PICU admissions were studied. Interventions None. Measurements and main results The primary outcome was mortality during PICU admission. Predictors included demographics, anthropometrics, diagnoses, clinical characteristics, and critical care interventions. Odds ratios of mortality were calculated in univariate and multivariable analyses to assess differences in mortality associated with predictor variables. Generalized estimating equation models were used to account for multiple admissions per patient. The overall PICU mortality rate was 6.6%. Factors associated with increased odds of mortality included hemoptysis/pulmonary hemorrhage, pneumothorax, gastrointestinal bleeding, bacterial/fungal infections, lower body mass index/malnutrition, and need for noninvasive or invasive respiratory support. Intubation/mechanical ventilation occurred in 26.4% of the 2,893 admissions and was associated with a 19.1% mortality rate. Of the nonsurvivors, 20.7% died without receiving mechanical ventilation. Conclusions The mortality rate during PICU admissions for patients with cystic fibrosis is lower than has been reported in prior studies, both in the overall cohort and in the subset requiring invasive mechanical ventilation. These data provide updated insight into the prognosis for cystic fibrosis patients requiring critical care.
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- 2020
14. Picture-naming in American Sign Language: an electrophysiological study of the effects of iconicity and structured alignment
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Phillip J. Holcomb, Katherine J. Midgley, Karen Emmorey, Megan Mott, and Meghan E. McGarry
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Linguistics and Language ,American Sign Language ,picture-naming ,Cognitive Neuroscience ,Experimental and Cognitive Psychology ,Article ,050105 experimental psychology ,Language and Linguistics ,Task (project management) ,03 medical and health sciences ,0302 clinical medicine ,Psychology ,0501 psychology and cognitive sciences ,N400 ,05 social sciences ,Linguistics ,Experimental Psychology ,ERPs ,language.human_language ,language ,Iconicity ,Cognitive Sciences ,030217 neurology & neurosurgery ,Picture naming - Abstract
A picture-naming task and ERPs were used to investigate effects of iconicity and visual alignment between signs and pictures in American Sign Language (ASL). For iconic signs, half the pictures visually overlapped with phonological features of the sign (e.g. the fingers of CAT align with a picture of a cat with prominent whiskers), while half did not (whiskers are not shown). Iconic signs were produced numerically faster than non-iconic signs and were associated with larger N400 amplitudes, akin to concreteness effects. Pictures aligned with iconic signs were named faster than non-aligned pictures, and there was a reduction in N400 amplitude. No behavioural effects were observed for the control group (English speakers). We conclude that sensory-motoric semantic features are represented more robustly for iconic than non-iconic signs (eliciting a concreteness-like N400 effect) and visual overlap between pictures and the phonological form of iconic signs facilitates lexical retrieval (eliciting a reduced N400).
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- 2020
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15. A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma
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Rajesh Kumar, Meghan E. McGarry, Pedro C. Avila, Shannon Thyne, Ryan D. Hernandez, Max A. Seibold, Dara G. Torgerson, Jean G. Ford, Jose R. Rodriguez-Santana, Maria Pino-Yanes, Melissa L. Spear, Rocio Chapela, Donglei Hu, Neeta Thakur, Joshua Galanter, Angel C.Y. Mak, Adam Davis, Deborah A. Myers, Marquitta J. White, Celeste Eng, L. Keoki Williams, Emerita Brigino-Buenaventura, Albert M. Levin, Harold J. Farber, Eugene R. Bleecker, Stephen P. Peters, Andres Moreno Estrada, Denise Serebrisky, Scott Huntsman, Esteban G. Burchard, Sam S. Oh, Victor E. Ortega, Kelley Meade, William Rodriguez Cintron, Elizabeth J. Ampleford, Cheryl A. Winkler, Karla Sandoval, and Michael A. LeNoir
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0301 basic medicine ,Genetic genealogy ,Genetic admixture ,Single-nucleotide polymorphism ,Genome-wide association study ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Genetic variation ,Genetics ,Medicine ,Pharmacology & Pharmacy ,1000 Genomes Project ,Lung ,Asthma ,Pharmacology ,business.industry ,Human Genome ,Pharmacology and Pharmaceutical Sciences ,medicine.disease ,3. Good health ,030104 developmental biology ,Respiratory ,Molecular Medicine ,business ,Imputation (genetics) ,Demography - Abstract
Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.
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- 2018
16. The demographics of adverse outcomes in cystic fibrosis
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Meghan E. McGarry, Susanna A. McColley, and Wadsworth A. Williams
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Cystic Fibrosis ,Demographics ,Adverse outcomes ,MEDLINE ,Psychological intervention ,Cystic Fibrosis Transmembrane Conductance Regulator ,Gene mutation ,Cystic fibrosis ,Article ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Epidemiology ,Health care ,Ethnicity ,medicine ,Humans ,Intensive care medicine ,Demography ,business.industry ,medicine.disease ,United States ,030228 respiratory system ,Mutation ,Pediatrics, Perinatology and Child Health ,business - Abstract
Understanding variability in cystic fibrosis (CF) health outcomes requires an understanding of factors that go far beyond Cystic Fibrosis Transmembrane Receptor (CFTR) function caused by different gene mutations. Social and environmental factors that influence health have a significant influence on the trajectory of health in CF and in other chronic diseases. In this article, we review demographic factors associated with poorer health outcomes in CF, known and postulated biological mechanisms of these outcomes, and interventions that healthcare teams can implement that may reduce outcome disparities.
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- 2019
17. Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico
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Angel C.Y. Mak, Vivian Medina, Gonçalo R. Abecasis, Meghan E. McGarry, Hyun Min Kang, Sam S. Oh, Jose R. Rodriguez-Santana, Amy K. Liu, Thomas W. Blackwell, Esteban G. Burchard, Sandra Salazar, Deepti Jain, Max A. Seibold, Thomas J. Nuckton, Leandra Cordero Oñate, Celeste Eng, and Andrew M. Zeiger
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Latino ,Pulmonary and Respiratory Medicine ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Cystic Fibrosis ,CFTR variants ,Respiratory System ,Sweat chloride ,Puerto rican ,Black People ,Cystic Fibrosis Transmembrane Conductance Regulator ,Cystic fibrosis ,Article ,White People ,Paediatrics and Reproductive Medicine ,Congenital ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Clinical Research ,030225 pediatrics ,Genetics ,medicine ,Humans ,In patient ,Allele ,Lung ,health disparities ,whole genome sequencing ,Base Sequence ,business.industry ,Dominican Republic ,Puerto Rico ,Hispanic or Latino ,respiratory system ,medicine.disease ,digestive system diseases ,respiratory tract diseases ,Good Health and Well Being ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Female ,Detection rate ,business ,geographic locations - Abstract
BackgroundIn cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well-described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico.MethodsCFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF andgreater than 60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools.ResultsOur study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del andp.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del.ConclusionsIn this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.
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- 2019
18. Transparency and diversity in cystic fibrosis research
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Meghan E. McGarry
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business.industry ,Internet privacy ,Medicine ,General Medicine ,business ,Transparency (behavior) - Published
- 2020
19. Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children
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Katrina Kalantar, Charles Langelier, Meghan E. McGarry, Marie E. Steiner, Kristin A. Shimano, Alexis Melton, Lauren E Faricy, Gregory A. Yanik, Joseph L. DeRisi, Janet R. Hume, Ngoc P. Ly, Kensho Iwanaga, Christopher C. Dvorak, Gwynne D. Church, Emily D. Crawford, Matt S. Zinter, Courtney M. Rowan, Madeline Y. Mayday, Steve Miller, Eric D. Chow, and Anil Sapru
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0301 basic medicine ,Lung Diseases ,Male ,intensive care units ,Pilot Projects ,respiratory tract infections ,Disease ,medicine.disease_cause ,Medical and Health Sciences ,0302 clinical medicine ,Interquartile range ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,030212 general & internal medicine ,Aetiology ,Respiratory system ,Child ,Articles and Commentaries ,Lung ,0303 health sciences ,Respiratory tract infections ,biology ,Microbiota ,High-Throughput Nucleotide Sequencing ,Biological Sciences ,3. Good health ,medicine.anatomical_structure ,Infectious Diseases ,Child, Preschool ,030220 oncology & carcinogenesis ,Viruses ,Female ,Infection ,Microbiology (medical) ,Lung microbiome ,Adolescent ,030106 microbiology ,Microbiology ,DNA sequencing ,Vaccine Related ,Immunocompromised Host ,03 medical and health sciences ,Clinical Research ,Biodefense ,Genetics ,microbiota ,medicine ,Humans ,Microbiome ,Preschool ,Retrospective Studies ,030304 developmental biology ,metagenomics ,Bacteria ,Missed Diagnosis ,business.industry ,Prevention ,Human Genome ,Fungi ,Pathogenic bacteria ,biology.organism_classification ,DNA extraction ,Good Health and Well Being ,pediatric ,Metagenomics ,Metagenome ,business - Abstract
Author(s): Zinter, Matt S; Dvorak, Christopher C; Mayday, Madeline Y; Iwanaga, Kensho; Ly, Ngoc P; McGarry, Meghan E; Church, Gwynne D; Faricy, Lauren E; Rowan, Courtney M; Hume, Janet R; Steiner, Marie E; Crawford, Emily D; Langelier, Charles; Kalantar, Katrina; Chow, Eric D; Miller, Steve; Shimano, Kristen; Melton, Alexis; Yanik, Gregory A; Sapru, Anil; DeRisi, Joseph L | Abstract: BackgroundDespite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.MethodsWe collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.ResultsWe identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P l .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P l .001).ConclusionsAn optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.
- Published
- 2018
20. Pulmonary Function Disparities Exist and Persist in Hispanic Patients With Cystic Fibrosis: A Longitudinal Analysis
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Dennis W. Nielson, Meghan E. McGarry, John Neuhaus, Ngoc P. Ly, and Esteban G. Burchard
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Pulmonary and Respiratory Medicine ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Heterozygote ,Adolescent ,Cystic Fibrosis ,hispanic latino ,Respiratory System ,Cystic Fibrosis Transmembrane Conductance Regulator ,Cystic fibrosis ,Article ,Pulmonary function testing ,Paediatrics and Reproductive Medicine ,Cohort Studies ,Congenital ,03 medical and health sciences ,Young Adult ,Rare Diseases ,0302 clinical medicine ,Clinical Research ,Forced Expiratory Volume ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Young adult ,Child ,Lung ,pulmonary function testing ,Patient registry ,business.industry ,Homozygote ,Hispanic or Latino ,medicine.disease ,healthcare disparities ,social dimensions of pulmonary medicine ,Good Health and Well Being ,medicine.anatomical_structure ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Life expectancy ,epidemiology ,Female ,business ,Cohort study - Abstract
BackgroundHispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF.MethodsThis cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV1 percent predicted and longitudinal change in FEV1 percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use.ResultsHispanic patients had lower FEV1 percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P 0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05).ConclusionsDisparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF.
- Published
- 2017
21. Breastfeeding associated with higher lung function in African American youths with asthma
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Randal Du, Emerita Brigino-Buenaventura, Jose R. Rodriguez-Santana, Celeste Eng, William Rodriguez-Cintron, Jean G. Ford, Shannon Thyne, Meghan E. McGarry, Kirsten Bibbins-Domingo, Sam S. Oh, Joshua Galanter, Andrew M. Zeiger, Donglei Hu, Rajesh Kumar, Michael A. LeNoir, Kelley Meade, Maria Pino-Yanes, Scott Huntsman, Denise Serebrisky, Pedro C. Avila, Neeta Thakur, Katherine K. Nishimura, Esteban G. Burchard, Keoki Williams, Saunak Sen, and Harold J. Farber
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Pulmonary and Respiratory Medicine ,Gerontology ,Male ,Allergy ,breastfeeding ,Hispanics ,Clinical Sciences ,Ethnic group ,Breastfeeding ,Genetic admixture ,Article ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,exacerbations ,Clinical Research ,Forced Expiratory Volume ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Lung ,Lung function ,Asthma ,Pediatric ,African Americans ,business.industry ,minority ,lung function ,Hispanic or Latino ,medicine.disease ,United States ,Black or African American ,Breast Feeding ,030228 respiratory system ,Socioeconomic Factors ,Pediatrics, Perinatology and Child Health ,Hypot ,Respiratory ,Public Health and Health Services ,Female ,business ,Body mass index ,Breast feeding ,genetic admixture ,geographic locations ,Demography - Abstract
ObjectiveIn the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1second (FEV1) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma.MethodsAs part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV1% predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations.ResultsPrevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p < 0.001). After adjusting for covariates, breastfeeding was associated with a 3.58% point increase in FEV1% predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only.ConclusionBreastfeeding was associated with higher FEV1% predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.
- Published
- 2017
22. A Genome-wide Association and Admixture Mapping Study of Bronchodilator Drug Response in African Americans with Asthma
- Author
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Melissa L. Spear, Donglei Hu, Maria Pino-Yanes, Scott Huntsman, Anton S. M. Sonnenberg, Celeste Eng, Albert M. Levin, Marquitta J. White, Meghan E. McGarry, Neeta Thakur, Joshua M. Galanter, Angel C. Y. Mak, Sam S. Oh, Adam Davis, Rajesh Kumar, Harold J. Farber, Kelly Meade, Pedro C. Avila, Denise Serebrisky, Michael A. Lenoir, Emerita A. Brigino-Buenaventura, William Rodriquez Cintron, Shannon M. Thyne, Jose R. Rodriguez-Santana, Jean G. Ford, Rocio Chapela, Andrés Moreno Estrada, Karla Sandoval, Max A. Seibold, L. Keoki Williams, Cheryl A. Winkler, Ryan D. Hernandez, Dara G. Torgerson, and Esteban G. Burchard
- Subjects
Genetics ,0303 health sciences ,business.industry ,Genetic genealogy ,Genetic admixture ,Genome-wide association study ,Single-nucleotide polymorphism ,medicine.disease ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Genetic variation ,medicine ,1000 Genomes Project ,business ,Imputation (genetics) ,030304 developmental biology ,Asthma - Abstract
BackgroundShort-acting B2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the U.S 1, 2. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma3ObjectiveTo identify genetic variants that may contribute to differences in BDR in African Americans with asthma.MethodsWe performed a genome-wide association study of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase 3 genotypes. We used linear regression models adjusting for age, sex, body mass index and genetic ancestry to test for an association between BDR and genotype at single nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1,830 Latinos (Total=2,779). Lastly, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. Two additional populations of 416 Latinos and 1,325 African Americans were used to replicate significant associations.ResultsWe identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p=7.69 × 10−9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958, and rs7081864, p≤5 × 10−8).ConclusionsOur findings indicate that both population specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.Key messagesA GWAS for BDR in African American children with asthma identified an intergenic population specific variant at 9q21 to be associated with increased bronchodilator drug response (BDR).A meta-analysis of GWAS across African Americans and Latinos identified shared genetic variants at 10q21 in the intron of PRKG1 to be associated with differences in BDR.Further genetic studies need to be performed in diverse populations to identify the full set of genetic variants that contribute to BDR.
- Published
- 2017
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23. The Lung Corps’ Approach to Reducing Health Disparities in Respiratory Disease
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Meghan E. McGarry, Joshua Galanter, Esteban G. Burchard, Neeta Thakur, Patricia W. Finn, and Sam S. Oh
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Respiratory Tract Diseases ,education ,Population ,Race and health ,Health Services Accessibility ,fluids and secretions ,parasitic diseases ,Pulmonary Medicine ,medicine ,Humans ,Healthcare Disparities ,Societies, Medical ,Health policy ,Respiratory health ,education.field_of_study ,Health professionals ,business.industry ,Health Policy ,Public health ,Respiratory disease ,Health Status Disparities ,medicine.disease ,United States ,Health equity ,Family medicine ,ATS Reports ,business - Abstract
Health disparities are prevalent across diseases of the respiratory system, and are major sources of morbidity and mortality among disadvantaged populations in the United States. The American Thoracic Society (ATS) aims to reduce disparities that are both avoidable and unjust. In meeting this goal, the ATS is committed to creating the Lung Corps, a diverse group of senior, mid-level, and junior clinicians, trainees, researchers, and public health practitioners to help achieve health equality. This will be achieved through the following mechanisms: (1) increase awareness of health disparities; (2) empower health professionals with the knowledge and tools to address disparities; (3) shape research agendas to focus on the root causes, to identify modifiable targets, and to promote innovative approaches to reduce disparities; and (4) develop and advocate for health-related policies and regulations that improve the respiratory health of the population. To ensure success, the Lung Corps will interact with other societies, agencies, and organizations to effect elimination of disparities in respiratory health. The ATS is committed to identifying and addressing health disparities to improve the overall health of individuals affected by respiratory diseases.
- Published
- 2014
24. Normalization of Sweat Chloride Concentration and Clinical Improvement With Ivacaftor in a Patient With Cystic Fibrosis With Mutation S549N
- Author
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Dennis W. Nielson and Meghan E. McGarry
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Cystic Fibrosis ,Sweat chloride ,Gating ,Quinolones ,Pharmacology ,Aminophenols ,Critical Care and Intensive Care Medicine ,Cystic fibrosis ,SWEAT ,Ivacaftor ,Chlorides ,Internal medicine ,medicine ,Humans ,Cystic fibrosis sweat test ,Selected Reports ,In patient ,Child ,Sweat ,business.industry ,medicine.disease ,Transepithelial chloride transport ,Endocrinology ,Mutation ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
The cystic fibrosis (CF) protein forms an anion channel in epithelial cells, and the absence or defective function of this channel results in the clinical manifestations of CF. CF is an autosomal recessive disorder, and its many disease-causing mutations divide into five or six classes. There are 10 known class 3 gating mutations, the most common of which is G551D. Ivacaftor is a drug that in vitro increases open time and transepithelial chloride transport in all 10 gating mutations, but it is approved for use only in patients with the G551D mutation. We report complete normalization of sweat chloride concentration and rapid clinical improvement over 6 weeks of treatment with ivacaftor in a patient with CF with the gating mutation S549N. The findings suggest that ivacaftor should be considered for use in patients with any of the known gating mutations.
- Published
- 2013
25. Minorities Are Underrepresented in Clinical Trials of Pharmaceutical Agents for Cystic Fibrosis
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Meghan E. McGarry and Susanna A. McColley
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Cystic Fibrosis ,minority groups ,Ethnic group ,Alternative medicine ,Cystic fibrosis ,ethnic groups ,03 medical and health sciences ,Race (biology) ,Congenital ,0302 clinical medicine ,Rare Diseases ,Clinical Research ,Medicine ,Humans ,030212 general & internal medicine ,Lung ,Original Research ,African Americans ,clinical trials ,Clinical Trials as Topic ,Patient registry ,Asian ,business.industry ,Hispanic or Latino ,medicine.disease ,Clinical trial ,Black or African American ,Asian Americans ,Cross-Sectional Studies ,030228 respiratory system ,Family medicine ,business - Abstract
RationaleMembers of racial or ethnic minorities make up an appreciable proportion of patients with cystic fibrosis (CF) and have worse outcomes than non-Latino white individuals. Between 1,999 and 2014, the CF Foundation Patient Registry reported an increase in minorities from 5 to 8.2% for Latinos, from 3 to 4.6% for black individuals and from 1.4 to 3.1% for "Other."ObjectivesTo evaluate the representation of racial and ethnic minorities in pharmacology clinical trials for CF.MethodsWe analyzed pharmacology clinical trials in CF published between 1999 and 2015 by searching PubMed and published study reference lists for qualifying study reports. We examined whether the race and ethnicity of study subjects were reported and, if so, what percentage of subjects represented major minority groups.Measurements and main resultsAmong 147 pharmacology clinical trials, only 19.7% reported the race or ethnicity of study subjects. Latinos were verified as included in 7.5% of clinical trials, black individuals in 6.8%, and Asians in 2.0%. Inclusion of subjects described as "Other race" was reported in 7.5% of trials. In 29 clinical trials that reported race and ethnicity, the percentage of minorities included as subjects was 2.0% for Latinos, 1.0% for black individuals, and 0.1% for Asians.ConclusionsAlthough CF disproportionately affects non-Latino white individuals, members of other racial or ethnic groups are proportionally underrepresented in CF pharmacology clinical trials. Inadequate inclusion of minorities and failure to report the racial or ethnic background of study subjects limits information about factors influencing drug response and may contribute to health disparities for minorities with CF.
- Published
- 2016
26. In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies
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Meghan E. McGarry, Dennis W. Nielson, Beate Illek, Walter E. Finkbeiner, Lorna Zlock, Sabrina Olshansky, Courtney Moreno, and Ngoc P. Ly
- Subjects
0301 basic medicine ,Male ,Cystic Fibrosis ,sweat chloride concentration ,Respiratory System ,Administration, Oral ,Cystic Fibrosis Transmembrane Conductance Regulator ,Quinolones ,Aminophenols ,Chloride ,Cystic fibrosis ,Pulmonary function testing ,Ivacaftor ,Congenital ,0302 clinical medicine ,CFTR ,Chloride Channel Agonists ,Sweat ,Lung ,Cross-Over Studies ,biology ,integumentary system ,personalized medicine ,Middle Aged ,Cystic fibrosis transmembrane conductance regulator ,Treatment Outcome ,Administration ,Female ,medicine.drug ,Pulmonary and Respiratory Medicine ,Oral ,Adult ,medicine.medical_specialty ,Adolescent ,Article ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,Young Adult ,Rare Diseases ,N-of-1 studies ,Chlorides ,In vivo ,Clinical Research ,Internal medicine ,medicine ,Humans ,human nasal epithelium ,Bronchiectasis ,business.industry ,Potentiator ,medicine.disease ,CFTR modulators ,030104 developmental biology ,Endocrinology ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,biology.protein ,ivacaftor ,business - Abstract
SummaryRationale Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, decreases sweat chloride concentration, and improves pulmonary function in 6% of cystic fibrosis (CF) patients with specific CFTR mutations. Ivacaftor increases chloride transport in many other CFTR mutations in non-human cells, if CFTR is in the epithelium. Some CF patients have CFTR in the epithelium with residual CFTR function. The effect of ivacaftor in these patients is unknown. Methods This was a series of randomized, crossover N-of-1 trials of ivacaftor and placebo in CF patients ≥8 years old with potential residual CFTR function (intermediate sweat chloride concentration, pancreatic sufficient, or mild bronchiectasis on chest CT). Human nasal epithelium (HNE) was obtained via nasal brushing and cultured. Sweat chloride concentration change was the in vivo outcome. Chloride current change in HNE cultures with ivacaftor was the in vitro outcome. Results Three subjects had decreased sweat chloride concentration (−14.8 to −40.8 mmol/L, P
- Published
- 2016
27. Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma
- Author
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Meghan E. McGarry, William Rodriguez-Cintron, Pedro C. Avila, Kirsten Bibbins-Domingo, Jose R. Rodriguez-Santana, Rajesh Kumar, Luisa N. Borrell, Saunak Sen, Michael A. LeNoir, Neeta Thakur, Harold J. Farber, Emerita Brigino-Buenaventura, Shannon Thyne, Kelley Meade, Adam Davis, Celeste Eng, Esteban G. Burchard, Denise Serebrisky, Elizabeth Castellanos, and Sam S. Oh
- Subjects
Male ,Cross-sectional study ,Respiratory System ,Critical Care and Intensive Care Medicine ,Adrenal Cortex Hormones ,Bronchodilator ,Medicine ,Child ,Lung ,Original Research ,Pediatric ,Hispanic or Latino ,Blacks ,Bronchodilator Agents ,Treatment Outcome ,Inhalation ,Administration ,Respiratory ,Female ,Cardiology and Cardiovascular Medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Clinical Sciences ,Black People ,FEV1/FVC ratio ,Clinical Research ,Internal medicine ,Administration, Inhalation ,Humans ,Albuterol ,Obesity ,Asthma ,Retrospective Studies ,Nutrition ,business.industry ,Case-control study ,Retrospective cohort study ,medicine.disease ,respiratory tract diseases ,Logistic Models ,Cross-Sectional Studies ,Case-Control Studies ,Physical therapy ,Leukotriene Antagonists ,business - Abstract
BackgroundObesity is associated with poor asthma control, increased asthma morbidity, and decreased response to inhaled corticosteroids. We hypothesized that obesity would be associated with decreased bronchodilator responsiveness in children and adolescents with asthma. In addition, we hypothesized that subjects who were obese and unresponsive to bronchodilator would have worse asthma control and would require more asthma controller medications.MethodsIn the Study of African Americans, Asthma, Genes, and Environments (SAGE II) and the Genes-environments and Admixture in Latino Americans (GALA II) study, two identical, parallel, case-control studies of asthma, we examined the association between obesity and bronchodilator response in 2,963 black and Latino subjects enrolled from 2008 to 2013 using multivariable logistic regression. Using bronchodilator responsiveness, we compared asthma symptoms, controller medication usage, and asthma exacerbations between nonobese (< 95th% BMI) and obese (≥ 95th% BMI) subjects.ResultsThe odds of being bronchodilator unresponsive were 24% (OR, 1.24; 95% CI, 1.03-1.49) higher among obese children and adolescents compared with their not obese counterparts after adjustment for age, race/ethnicity, sex, recruitment site, baseline lung function (FEV1/FVC), and controller medication. Bronchodilator-unresponsive obese subjects were more likely to report wheezing (OR, 1.38; 95% CI, 1.13-1.70), being awakened at night (OR, 1.34; 95% CI, 1.09-1.65), using leukotriene receptor inhibitors (OR, 1.33; 95% CI, 1.05-1.70), and using inhaled corticosteroid with long-acting β2-agonist (OR, 1.37; 95% CI, 1.05-1.78) than were their nonobese counterpart. These associations were not seen in the bronchodilator-responsive group.ConclusionsObesity is associated with bronchodilator unresponsiveness among black and Latino children and adolescents with asthma. The findings on obesity and bronchodilator unresponsiveness represent a unique opportunity to identify factors affecting asthma control in blacks and Latinos.
- Published
- 2015
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