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Biomedical subjects

Tina V Hartert

Publications and source records attributed to Tina V Hartert.

At least 19 recordsLinked to original sources
PubMed2026

Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.

BACKGROUND: In ∼10% of asthma patients, symptoms remain uncontrolled despite maximal treatment, representing an unmet clinical need. The causal variants, genes and pathways underlying genetic risk factors have not been fully elucidated, and it is unclear whether there are unique genetic risk factors for this asthma subtype. METHODS: We used electronic healthcare records linked to UK Biobank to identify asthma patients with high treatment burden and/or worse outcomes. We performed a genome-wide association study (GWAS) with this case population and healthy controls. We sought replication for associated (p≤5×10-6) signals in four independent studies (12 152 cases and 32 316 controls). Replicated signals were fine-mapped and linked to genes and pathways. RESULTS: In total, 7681 participants met our case definition and showed enrichment for adult-onset asthma, female gender and higher body mass index compared to asthma individuals not meeting case criteria. GWAS with 7681 cases and 38 405 controls revealed 21 reproducible association signals that had previously been associated with asthma, but had a larger effect size in our study. Variant-to-gene mapping highlighted 85 candidate genes, five of which were considered high confidence (BACH2, D2HGDH, IL1RL1, RPS26, SMAD3). CONCLUSION: We present the first use of electronic healthcare records in UK Biobank to identify a subtype of asthma enriched for patients with high treatment burden and/or worse outcomes. Our findings support the role of known asthma genes, highlighting genetic risk variants with stronger effect in these groups of patients. The prioritised genes provide potential therapeutic opportunities for this difficult-to-treat patient population.

Journal Article↗
PubMed2026

Upper airway microbiome interacts with GSDMB and ORMDL3 asthma risk SNPs to influence early-life wheeze risk.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the chromosome 17q12-q21 region and, independently, early-life nasal microbiota dominated by Moraxella, Streptococcus, or Haemophilus (MSH) increase risk of chronic wheeze and asthma development. OBJECTIVE: We sought to determine whether 17q12-q21 risk SNPs and nasal microbiota interact to modulate childhood wheeze risk. METHODS: Nasal wash samples from 12-month-old infants in 2 birth cohorts, COAST (Childhood Origins of Asthma; n = 180) and URECA (Urban Environment and Childhood Asthma; n = 139), underwent 16S ribosomal RNA variable region 4 sequencing. Nasal microbiota dominated by MSH or Corynebacterium, Dolosigranulum, Staphylococcus, or Bacillus (CDSB) were assessed. Paired blood was genotyped for 9 17q12-q21 risk SNPs. Logistic regression tested interactions between 17q12-q21 SNPs and MSH or CDSB on wheeze risk in the first 3 years of life. A549 lung epithelial cells, CRISPR-edited to encode the rs7216389 risk genotype (rs7216389TT) were compared to the heterozygous (rs7216389CT) line using bulk RNA sequencing. RESULTS: SNPs, particularly those in the ORMDL3 (rs8076131; odds ratio [OR]: 1.72; 95% CI: 1.09-2.71; Pint = .031) and GSDMB (rs2305480; OR: 1.72; 95% CI: 1.09-2.71; Pint = 0.042; and rs7216389; OR: 1.73; 95% CI: 1.09-2.70; Pint = .047) genes, interact with MSH microbiota to increase early-life wheeze risk (false discovery rate Pint = .016 for all), while interactions with CDSB reduce risk. A549 airway epithelial cells homozygous for rs7216389TT exhibited decreased expression of genes involved in antimicrobial responses and neutrophil recruitment and evidence increased microbial adherence compared with the heterozygous cell line. CONCLUSION: Airway microbiota interact with SNPs at the 17q12-q21 locus in genes involved in sphingolipid metabolism and intracellular antimicrobial responses, to modulate wheeze risk.

Humans↗
PubMed2006

Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation.

Viral infections are important causes of asthma exacerbations in children, and lower respiratory tract infections (LRTIs), caused by viruses such as respiratory syncytial virus (RSV) and rhinovirus (RV), are a leading cause of bronchiolitis in infants. Infants hospitalized with bronchiolitis are at significantly increased risk for both recurrent wheezing and childhood asthma. To date, studies addressing the incidence of asthma after bronchiolitis severe enough to warrant hospitalization have focused almost exclusively on RSV, but a number of recent studies suggest that other respiratory pathogens, including RV, may contribute as well. It is not known whether viral bronchiolitis directly contributes to asthma causation or simply identifies infants at risk for subsequent wheezing, as from an atopic predisposition or preexisting abnormal lung function. Alternatively, the properties of the infecting virus may be important. Thus, many possible determinants exist that may contribute to the severity of bronchiolitis and the subsequent development of asthma. One such determinant is the potential involvement of genetic susceptibility loci to asthma after viral bronchiolitis, a critical area that is just beginning to be evaluated. By clarifying the roles of both host- (genetic) and virus- (environment) specific factors that contribute to the frequency and severity of viral LRTI, it may be possible to determine if severe LRTIs cause asthma, or if asthma susceptibility predisposes patients to severe LRTI in response to viral infection. Characterizing these relationships offers the potential of identifying at-risk hosts in whom preventing or delaying infection could alter the phenotypic expression of asthma.

Animals↗
PubMed2006

Smoking rates among pregnant women in Tennessee, 1990-2001.

BACKGROUND: Pregnant smokers represent a major public health challenge. The objective of this study was to determine trends in smoking during pregnancy in Tennessee, a state with one of the highest smoking burdens in the nation, and to confirm characteristics of high-risk groups to target for smoking prevention. METHODS: Population-based cohort study of pregnant women in Tennessee who delivered live births from 1990-2001. Trends in smoking were determined by maternal age, race and insurance status using vital records and Medicaid data. Characteristics of women who smoked during pregnancy were described for 2001. RESULTS: Among 900,986 pregnant women in the cohort, there were statewide decreases in smoking rates during pregnancy; however, smoking among pregnant women younger than 25 years in Medicaid increased from 1996 to 2001: among whites from 31% to 34%, and among blacks from 6% to 9% (P values for trend shifts <0.0001). Characteristics of pregnant women who smoked during pregnancy included white race, Medicaid enrollment, nonurban residence, and less than a high school education. CONCLUSIONS: Smoking rates increased significantly among pregnant women <25 years enrolled in Medicaid between 1996 and 2001. Tennessee needs smoking cessation and prevention efforts that target young, low-income women with less than a high school education.

Adult↗
PubMed2006

Cessation of asthma medication in early pregnancy.

OBJECTIVE: The objective of the study was to determine whether women alter their use of asthma medications during pregnancy. STUDY DESIGN: Weekly asthma medication use was determined from prescription claims data in a cohort of 112,171 pregnant women aged 15 to 44 years who were continuously enrolled in the Tennessee Medicaid program prior to their singleton pregnancy and who delivered a singleton birth during 1995 to 2001. Change in asthma medication use was evaluated using generalized estimating equation analyses. RESULTS: Women with asthma significantly (P < or = 0.0005) decreased their asthma medication use from 5 to 13 weeks of pregnancy. During the first trimester, there was a 23% decline in inhaled corticosteroid prescriptions, a 13% decline in short-acting beta-agonist prescriptions, and a 54% decline in rescue corticosteroid prescriptions. CONCLUSIONS: Utilization of all categories of asthma medications decreased in early pregnancy, with the largest declines occurring for inhaled and rescue corticosteroids.

Adolescent↗
PubMed2006

The relationship of rhinovirus-associated asthma hospitalizations with inhaled corticosteroids and smoking.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adrenal Cortex Hormones↗
PubMed2006

Influenza vaccination during pregnancy: opinions and practices of obstetricians in an urban community.

BACKGROUND: Influenza vaccination is recommended for all women who will be pregnant during the influenza season; however, little is known about the attitudes of physicians regarding vaccination of pregnant women. METHODS: We conducted a survey of all the fellows of the American College of Obstetricians and Gynecologists (ACOG) who live and practice in Nashville, Tennessee, focusing on physician knowledge, practices, and opinions regarding influenza vaccination of pregnant RESULTS: Thirty-seven of 58 (64%) eligible physicians participated. Obstetrician opinion on the earliest influenza vaccine administration for healthy pregnant women was 62% during the second trimester, 32% during the first trimester, and 6% felt that the vaccine should not be given during pregnancy. All physicians responded that pregnant women with an underlying high risk condition should be vaccinated. CONCLUSION: Practicing obstetricians differ in their preferences regarding the timing of influenza vaccine administration in pregnant women. Obstetrician and patient opinion and practice should be studied and considered in developing vaccine guidelines and vaccine implementation strategies.

Adult↗
PubMed2005

Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults.

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.

Acute Disease↗
PubMed2005

Asthma as a risk factor for invasive pneumococcal disease.

BACKGROUND: The risk of invasive pneumococcal disease among persons with asthma is unknown. METHODS: We conducted a nested case-control study to examine the association between asthma and invasive pneumococcal disease. The study population included persons 2 to 49 years of age who were enrolled in Tennessee's Medicaid program (TennCare) for more than one year during the study period (1995 through 2002) and who resided in counties participating in a prospective laboratory-based program of surveillance for invasive pneumococcal disease. For each subject with invasive pneumococcal disease, 10 age-matched controls without invasive pneumococcal disease were randomly selected from the same population. TennCare files were queried to identify the presence of coexisting conditions that confer a high risk of pneumococcal disease. For the purpose of our study, asthma was defined by documentation of one or more inpatient or emergency-department diagnoses of asthma, two outpatient diagnoses, or the use of asthma-related medications. High-risk asthma was defined as asthma requiring admission to a hospital or a visit to an emergency department, the use of rescue therapy or long-term use of oral corticosteroids, or the dispensing of three or more prescriptions for beta-agonists within the year before enrollment in the study. RESULTS: A total of 635 persons with invasive pneumococcal disease and 6350 controls were identified, of whom 114 (18.0 percent) and 516 (8.1 percent), respectively, had asthma. Persons with asthma had an increased risk of invasive pneumococcal disease (adjusted odds ratio, 2.4; 95 percent confidence interval, 1.9 to 3.1) as compared with controls. Among those without coexisting conditions, the annual incidence of invasive pneumococcal disease was 4.2 episodes per 10,000 persons with high-risk asthma and 2.3 episodes per 10,000 persons with low-risk asthma, as compared with 1.2 episodes per 10,000 persons without asthma. CONCLUSIONS: Asthma is an independent risk factor for invasive pneumococcal disease. The risk among persons with asthma was at least double that among controls.

Adolescent↗
PubMed2005

Seasonality of invasive pneumococcal disease: temporal relation to documented influenza and respiratory syncytial viral circulation.

BACKGROUND: Seasonal fluctuation in the incidence of invasive pneumococcal disease has been attributed to winter virus exposure (e.g., influenza and respiratory syncytial virus [RSV]). Evidence of a direct correlation of invasive pneumococcal disease with laboratory-confirmed virus seasons, however, is limited. Using two prospective surveillance networks, the temporal relation between invasive pneumococcal disease and isolation of circulating winter viruses was explored. METHODS: Episodes of invasive pneumococcal disease in five Tennessee counties were collected prospectively from January 1995 through June 2002. Virus seasons were defined using prospective laboratory-based surveillance. Correlation between weekly identification of invasive pneumococcal disease and laboratory isolation of RSV and influenza, as well as comparisons of the frequencies of invasive pneumococcal disease episodes during viral and nonviral seasons were determined. RESULTS: A total of 4147 invasive pneumococcal disease episodes were identified. Weekly frequency of invasive pneumococcal disease correlated directly with the weekly frequency of isolation of RSV (r = 0.56, P <0.001) and influenza (r= 0.40, P <0.001). The average weekly frequency of invasive pneumococcal disease during RSV and influenza seasons was higher than during the nonviral seasons (P <0.001 for each year). CONCLUSION: Weekly episodes of invasive pneumococcal disease correlated temporally with laboratory-confirmed weekly isolation of RSV and influenza, and the incidence of invasive pneumococcal disease was increased when these viruses were circulating in the community.

Adolescent↗
PubMed2005

Racial differences in asthma morbidity during pregnancy.

OBJECTIVE: Little is known about racial differences in asthma outcomes during pregnancy. We performed a cohort study to estimate racial differences in maternal asthma outcomes in a low-income population of pregnant women in which blacks and whites have similar medical care access and benefits. METHODS: We conducted a population-based cohort study of asthma-related morbidity in black and white pregnant women enrolled in Tennessee's Medicaid Program, TennCare. Pregnant women were identified through TennCare enrollment files linked to birth certificates, 1995-2001. Prepregnancy, women with asthma were identified using International Classification of Diseases, 9th Revision, codes for health care visits and pharmacy files for asthma medication. Adjusted relative rates (RR) of rescue corticosteroid prescriptions, emergency department (ED) visits, and hospitalizations during pregnancy were compared by race using Poisson regression. RESULTS: We identified 4,315 women with asthma (4%) from a population of 112,171 pregnant women of black or white race with at least 180 days of continuous enrollment in TennCare before pregnancy. Blacks were more likely to receive a course of rescue corticosteroids than whites (14.6% versus 11.9%, adjusted RR 1.35, 95% confidence interval [CI] 1.14-1.61), have an emergency department visit (16.7% versus 8.7%, adjusted RR 1.89, 95% CI 1.57-2.27), or be hospitalized for asthma (9.0% versus 5.2%, adjusted RR 1.73, 95% CI 1.34-2.24). CONCLUSION: Pregnant women with asthma had high asthma-related morbidity. Black women had clinically significantly more morbidity than whites. There is a need to improve the medical care of low-income women with asthma, particularly black women. LEVEL OF EVIDENCE: II-2.

Adolescent↗
PubMed2004

Reduction in high rates of antibiotic-nonsusceptible invasive pneumococcal disease in tennessee after introduction of the pneumococcal conjugate vaccine.

BACKGROUND: Invasive pneumococcal disease (IPD) is a burgeoning problem, with rates of antibiotic-nonsusceptible IPD, in particular, increasing during the past decade. One measure to combat IPD is vaccination with the recently introduced 7-valent pneumococcal conjugate vaccine (PCV). METHODS: To evaluate the effects of the introduction of PCV in 2000 on the epidemiology of antibiotic-nonsusceptible IPD, a database of IPD cases from January 1995 through December 2002 identified through active surveillance in 5 Tennessee counties was examined. For each case, clinical data were collected, and antibiotic susceptibility testing and serotyping were performed on available isolates. RESULTS: Among children younger than 2 years, IPD rates peaked at 235 cases per 100,000 in 1999 before decreasing, after PCV licensure, to 46 cases per 100,000 in 2002 (P<.001). The proportion of penicillin-nonsusceptible IPD isolates from this age group declined from 59.8% in 1999 to 30.4% in 2002 (P<.01). After 2001, similar decreases in IPD rates and in the proportion of antibiotic-nonsusceptible isolates recovered were seen among persons aged 2 years and older (P<.01). Rates of IPD due to PCV-associated serotypes declined after PCV introduction in all age groups (P<.001), whereas the rate of IPD due to nonvaccine serotypes increased among persons aged 2 years and older. CONCLUSIONS: In the 2 years since licensure, widespread PCV vaccination of children has resulted in dramatic declines in the proportion of antibiotic-nonsusceptible isolates in Tennessee. PCV vaccination of children also appears to be a highly effective method for reducing the burden of IPD in adults.

Anti-Bacterial Agents↗
PubMed2004

Elimination of racial differences in invasive pneumococcal disease in young children after introduction of the conjugate pneumococcal vaccine.

BACKGROUND: Racial differences in the epidemiology of invasive pneumococcal disease (IPD) have been widely recognized, but the impact of conjugate pneumococcal vaccine (PCV) introduction in 2000 on these differences has not been extensively studied. METHODS: IPD episodes in 5 Tennessee counties from January 1995 through December 2002 were collected prospectively using the Centers for Disease Control and Prevention's Active Bacterial Core Surveillance system (ABCs). Trained nurses collected clinical data, and antibiotic susceptibility testing was performed on available isolates. RESULTS: Before vaccine licensure, IPD rates were highest in children younger than 2 years and in blacks. The disparity in IPD rates between blacks and whites younger than 2 years of age substantially diminished after PCV introduction. In 1999, the IPD rate in black children younger than 2 years was 340.2 per 100,000, representing 176.5 more events per 100,000 than in white children (P < 0.001). In 2002, this rate had decreased 83% to 57.4 per 100,000, similar to the rate in white children (39.6 per 100,000; P = 0.31). Before vaccine licensure, a higher percentage of isolates from whites were antibiotic-nonsusceptible. In 2002, the proportion of antibiotic-nonsusceptible pneumococcal isolates was similar in whites and blacks of all ages for the first time during the study period (P > 0.05 for separate comparisons of penicillin, cephalosporin and erythromycin nonsusceptibility). These changes occurred despite a lower PCV vaccination coverage in Tennessee in blacks than in whites (31.2% versus 47.6%). CONCLUSIONS: With conjugate pneumococcal vaccine introduction in Tennessee, racial differences in the incidence rates of IPD have largely been eliminated, particularly in young children.

Adolescent↗
PubMed2003

Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season.

OBJECTIVES: A population-based assessment of maternal and perinatal morbidity related to respiratory illness during influenza season among pregnant women has not been published. The objectives of this investigation were to describe and quantify the impact of respiratory hospitalization during pregnancy on serious maternal and perinatal morbidity. STUDY DESIGN: A matched cohort study using an administrative database of pregnant women enrolled in the Tennessee Medicaid population to determine pregnancy outcomes associated with respiratory hospitalizations during influenza season. Pregnant women aged 15 to 44 years with a respiratory hospitalization during influenza seasons 1985-1993 were matched by gestational age and presence of comorbidity with pregnant control subjects without a respiratory hospitalization. RESULTS: During the eight influenza seasons studied, 293 women with singleton pregnancies had respiratory disease hospitalizations (5.1:1000). Women with asthma had high rates of such hospitalization (59.7:1000). Compared with matched controls, women with respiratory hospitalizations had similar modes of delivery, delivery length of stay, and episodes of preterm labor. The prevalence of prematurity and low birth weight among infants born to such women was likewise similar between the two groups. CONCLUSION: In this population of pregnant women, those with asthma accounted for half of all respiratory-related hospitalizations during influenza seasons, with 6% of pregnant women with asthma requiring respiratory hospitalization during influenza season, (odds ratio 10.63, 95% CI, 8.18-13.83, compared with women without a medical comorbidity). We detected no significant increase in adverse perinatal outcomes associated with respiratory hospitalizations during influenza season.

Adult↗
PubMed2002

Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma.

BACKGROUND: Little is known about the morbidity and mortality among older adults with asthma requiring hospital care. OBJECTIVES: To determine whether an initial hospital visit for asthma was associated with an increase in use of inhaled corticosteroids (CCS) at discharge, and to identify risk factors for recurrent asthma hospital visits and death. METHODS: A retrospective cohort analysis identified 93,174 persons 65 years and older enrolled in the Tennessee Medicaid program for at least 1 year and free of asthma hospital visits during that year; 510 survived a single hospital visit for asthma in 1992 and comprised the study population. Main outcome measures included recurrent hospital visit for asthma and all-cause mortality during the year after an asthma hospital visit. RESULTS: Among the 510 study subjects, 10% were on inhaled CCS at admission compared with 11% at discharge. Twenty-three percent of the population had recurrent asthma hospital visits and 12% died during 1-year followup. Asthma severity was the strongest independent risk factor for both a recurrent hospital visit [relative risk for moderate to severe disease 1.92 (1.01 to 3.66), and for near-fatal disease 2.28 (1.01 to 5.13), respectively] and death [relative risk for moderate to severe disease 2.99 (1.07 to 8.32) and for near-fatal disease 4.44 (1.34 to 4.69), respectively]. CONCLUSIONS: In this population, older adults with an exacerbation of asthma requiring hospital care experienced significant morbidity and mortality. An acute hospital visit for an asthma exacerbation did not result in initiation of inhaled CCS therapy. Asthma severity predicted both recurrent hospital visits and all-cause mortality among older adults with asthma requiring hospital care.

Acute Disease↗
PubMed2002

Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema.

Bradykinin and substance P have been implicated as mediators in angiotensin-converting enzyme inhibitor (ACEI)-associated angioedema. Studies investigating the metabolism of bradykinin in sera from patients with a history of ACEI-associated angioedema and controls suggest that there is a defect in a non-ACE, non-kininase I pathway of bradykinin degradation, such as the aminopeptidase P (APP)/dipeptidyl peptidase IV (DPPIV) pathway. This study tested the hypothesis that serum APP or DPPIV activity is decreased in patients with ACEI-associated angioedema. APP and DPPIV activity were measured in sera collected from patients during ACEI-associated angioedema, from patients with a remote history of ACEI-associated angioedema, and from normotensive and untreated hypertensive controls. The effects of acute and chronic ACEI and corticosteroid treatment on serum DPPIV activity were also assessed. DPPIV activity was similar in normotensive volunteers (37.8 +/- 6.3 nmol/mL per min), in untreated hypertensive subjects who had been exposed previously to ACEI without angioedema (36.2 +/- 4.3 nmol/mL per min), in hypertensive patients with a remote history of angioedema (35.1 +/-8.5 nmol/mL per min), and in chronically ACEI-treated hypertensive subjects (36.1 +/- 5.6 nmol/mL per min). DPPIV activity decreased with increasing age (R(2)=0.10, P=0.016). Subject group significantly affected DPPIV activity (F=6.208, P=0.016) such that DPPIV activity was significantly lower in patients with ACEI-associated angioedema (26.9 +/- 4.1 nmol/mL per min) than in normotensive controls, in previously ACEI-exposed untreated hypertensive volunteers, or in ACEI-treated hypertensive volunteers, even after controlling for age. There was no effect of acute ACE inhibition or corticosteroids on DPPIV activity. With respect to APP activity, there was no difference between groups. These results suggest that DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema.

Adult↗