Biomedical subjects

Nadia N Hansel

Publications and source records attributed to Nadia N Hansel.

13 recordsLinked to original sources

PubMed2026

Systemic Platelet Activation and Respiratory Exacerbations, Pulmonary Symptoms, and Mortality among Current and Former Smokers in SPIROMICS.

RATIONALE: Platelet activation is elevated in chronic obstructive pulmonary disease (COPD) and associated with self-reported respiratory symptoms. Observational studies link the antiplatelet drug aspirin to lower exacerbation rates and fewer symptoms. However, it is unknown if platelet activation predicts incident respiratory exacerbations or mortality. OBJECTIVE: Is systemic platelet activation prospectively associated with respiratory exacerbations and mortality among ever-smokers with or at risk for COPD? METHODS: We measured two systemic platelet activation biomarkers, urinary 11-dehydro-thromboxane B2 (11dTxB2) and plasma soluble CD40 ligand (sCD40L), at baseline in self-reported aspirin non-users in the longitudinal SPIROMICS cohort. Adjusted generalized negative binomial and linear mixed-effects models assessed associations between these biomarkers and prospective rates of total and severe exacerbations, plus cross-sectional and longitudinal respiratory health (St. George's Respiratory Questionnaire, COPD Assessment Test, modified Medical Research Council questionnaire, and six minute walk distance). Cox proportional hazard and competing risk models evaluated associations between platelet activation biomarkers and all-cause and cause-specific mortality. RESULTS: Among 2,711 participants, 1,572 (58.0%) reported aspirin non-use; of these, 1,433 and 1,437 had 11dTxB2 and sCD40L measured, respectively. Over a median 6.6 years, a two-fold higher baseline 11dTxB2 was associated with increased rates of total (8.8%; 95%CI: 0.4-17.8%) and severe (18.1%; 95%CI: 5.1-32.6%) exacerbations. Although there were no significant interactions, there was a trend toward higher severe exacerbation rates among current cigarettes smokers and those with COPD. There were no significant results for sCD40L. Among aspirin non-users, higher 11dTxB2, but not sCD40L, was associated with worse cross-sectional respiratory health and modestly increased all-cause mortality over a median 8.2 years (adjusted hazard ratio 1.11; 95%CI: 1.00-1.24). After covariate adjustment, there were no associations with longitudinal respiratory health or cause-specific mortality. CONCLUSIONS: Systemic platelet activation, measured by urinary 11dTxB2, is a statistically significant but modest predictor of respiratory exacerbations and all-cause mortality in individuals with or at risk for COPD, suggesting its potential utility as a prognostic and predictive biomarker for antiplatelet therapy trials. CLINICAL TRIAL REGISTRATION: NCT01969344.

aspirin↗

PubMed2026

A Quantitative Lung Mucin Score to Identify Chronic Bronchitis.

BACKGROUND: We previously demonstrated that sputum total mucin concentration is an objective marker for chronic bronchitis (CB). This current study introduces a novel Mucin Quantitative Score (MUCQ) that combines total mucin concentration and mucin composition to improve the assessment of risk, onset of clinically diagnosed disease, and progression of muco-obstructive lung diseases. METHODS: Patients from the SPIROMICS (SubPopulations and InteRmediate Outcome Measures in COPD Study) cohort were classified as having CB, or not, based on clinical questionnaires. Using the measured total mucin, MUC5AC, and MUC5B concentrations in sputum samples, we calculated MUCQ as [Total mucin]×([MUC5AC]÷[MUC5B])÷100 μg/ml, which is a unitless, weighted concentration score. Our primary outcome was the net reclassification of patients with a diagnosis of CB, or not, based on total mucin concentrations in their sputum compared with using the MUCQ score. Participants were first classified as CB- positive or -negative using a total mucin concentration threshold of 2306 μg/ml, then reclassified using the MUCQ threshold of 4.30. Associated z statistics and a P value for the primary outcome are reported. RESULTS: Among 164 patients in the SPIROMICS cohort with clinically defined CB, using the MUCQ score up-classified 18 patients who were currently smoking to a diagnosis of CB and down-classified 5 patients who were currently smoking and 3 control participants who had never smoked, compared with the classification of CB was based on total mucin concentrations alone (P=0.001). In addition, MUCQ correlated with other clinical and pathological indices of chronic airway disease and airway obstruction. CONCLUSIONS: The MUCQ metric was superior in distinguishing patients with CB compared to a total mucin concentration. Trials are needed to ascertain the prospective use of MUCQ metrics in research and clinical settings for assessment, management, and tracking therapeutic responses in CB and potentially other muco-obstructive conditions. (Funded by the National Institutes of Health and others.).

Humans↗

PubMed2024

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

BACKGROUND: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. OBJECTIVES: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. METHODS/DISCUSSION: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. CONCLUSION: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

SPIROMICS↗

PubMed2023

A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD.

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

Humans↗

PubMed2007

Gene expression profiling in human asthma.

Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperreactivity, mucus hypersecretion, and airflow obstruction. Despite recent advances, the genetic regulation of asthma pathogenesis is still largely unknown. Gene expression profiling techniques are well suited to study complex diseases and hold substantial promise for identifying novel genes and pathways in asthma; however, relatively few studies have been completed in human asthma. The few studies that have been done have identified many novel candidate genes and pathways in asthma pathogenesis, including ALOX15 and serine proteinase inhibitors cathepsin C and G. The interpretation of results of these studies should be cautious, as limitations include small sample sizes and heterogeneity of study populations and tissues sampled. In the future, the promise of gene expression studies would be enhanced by the use of larger sample sizes and attempts to standardize phenotype, sample collection techniques, and analysis. As the field of expression profiling in asthma advances, we hope it will improve our understanding of critical questions about mechanisms involved in susceptibility to the disease, as well as help to personalize care by improving appropriate selection of patients for prevention and treatment strategies.

Asthma↗

PubMed2007

African Americans with asthma: genetic insights.

It has been well established that genetic factors strongly affect susceptibility to asthma and its associated traits. It is less clear to what extent genetic variation contributes to the ethnic disparities observed for asthma morbidity and mortality. Individuals of African descent with asthma have more severe asthma, higher IgE levels, a higher degree of steroid dependency, and more severe clinical symptoms than individuals of European descent with asthma but relatively few studies have focused on this particularly vulnerable ethnic group. Similar underrepresentation exists for other minorities, including Hispanics. In this review, a summary of linkage and association studies in populations of African descent is presented, and the role of linkage disequilibrium in the dissection of a complex trait such as asthma is discussed. Consideration for the impact of population stratification in recently admixed populations (i.e., European, African) is essential in genetic association studies focusing on African ancestry groups. With the most recent update on the International HapMap Project, efficient selection of haplotype tagging single nucleotide polymorphisms (htSNPs) for African Americans has accelerated and efficiency of htSNPs chosen from one population to represent other continental groups (e.g., African) has been demonstrated. Cutting-edge approaches, such as genomewide association studies, admixture mapping, and phylogenetic analyses, offer new opportunities for dissecting the genetic basis for asthma in populations of African descent.

Black or African American↗

PubMed2006

Mortality in patients hospitalized for asthma exacerbations in the United States.

RATIONALE: Hospitalizations for asthma exacerbations are common in the United States, but there are no national estimates of outcomes in this population. It is also not known if race disparities in asthma deaths exist among hospitalized patients. OBJECTIVES: To estimate outcomes of patients hospitalized for asthma in the United States and to determine if the risk of death in this population is higher among black patients compared with white patients. METHODS: We used the Nationwide Inpatient Sample for 2000. Admissions for asthma exacerbations among patients > 5 yr of age were included. Mortality was the primary outcome; secondary outcomes were length of stay and total hospital charges. MEASUREMENTS AND MAIN RESULTS: In-hospital asthma mortality was 0.5% (99% confidence interval [CI], 0.4-0.6), with mean hospital stay of 2.7 d (99% CI, 2.6-2.8 d) and 9,078 dollars (99% CI, 8,300-9,855 dollars) in hospital charges. Deaths in this population accounted for about one-third of all asthma deaths reported in the United States. Black patients hospitalized for asthma exacerbations were less likely to die when compared with white patients (0.3 vs. 0.6%; p < 0.001). However, in multivariable analyses, there were no significant race differences in hospital deaths. CONCLUSIONS: Mortality among patients hospitalized for asthma exacerbations accounts for one-third of all deaths from asthma. The higher overall risk of death from asthma in black patients compared with white patients in the United States is not explained by race differences in hospital deaths and therefore is attributable to factors preceding hospitalization.

Adolescent↗

PubMed2006

Asthma-related health status determinants of environmental control practices for inner-city preschool children.

BACKGROUND: Asthma guidelines recommend environmental control practices (ECPs) to improve asthma health. In the inner city, where asthma morbidity is high, it is not known whether children's health status affects the use of ECPs. OBJECTIVE: To investigate health status determinants of ECPs in the homes of children with asthma. METHODS: Caregivers of children aged 2 to 6 years with (n = 150) and without (n = 150) asthma completed a survey about ECPs. Atopic status was determined by means of skin prick testing. RESULTS: Most ECPs were similarly practiced, regardless of whether the child had asthma. Only pet avoidance was more common in children with asthma (30% vs 19%). Asthma severity and recent acute health care visits for asthma were not associated with ECP use. Most ECPs were not linked to allergen sensitization (eg, mite and mouse), although cockroach-sensitized children were more likely to have cockroach control than nonsensitized individuals (65% vs 45%). Caregivers of asthmatic children with rhinitis were more likely than those without rhinitis to report ECPs, including pet avoidance (44% vs 15%), smoking avoidance (78% vs 53%), cockroach control (65% vs 42%), mouse control (78% vs 42%), air-conditioning (45% vs 24%), and allergyproof covers (7% vs 0%). CONCLUSIONS: The presence of asthma, asthma severity, and allergen sensitization seem to have little relationship to ECP use in the homes of inner-city children. Rhinitis was consistently linked to ECPs, which suggests that caregivers may make changes in the home environment for upper airway but not lower airway symptoms.

Air Pollution, Indoor↗

PubMed2005

Oligonucleotide-microarray analysis of peripheral-blood lymphocytes in severe asthma.

CD4 + lymphocytes play a key role in asthma pathogenesis, but much remains unknown about the genetic mechanisms that affect disease severity. In this study we sought to investigate global patterns of gene expression in CD4 + lymphocytes isolated from subjects with severe asthma through the use of microarray technology. CD4 + lymphocytes were separated from peripheral blood, total RNA was purified, and biotinylated complementary RNA was prepared and hybridized to Affymetrix HU133 chips (Affymetrix, Santa Clara, Calif). Using the robust multi-chip average procedure, we compared the messenger RNA expression profiles of more than 33,000 genes of CD4 + lymphocytes in subjects with severe ( n = 5) and mild ( n = 5) asthma. Forty genes had 2-fold mean expression differences or greater. Thirty-seven genes were up-regulated, including transforming growth factor-beta and those involved in T-cell activation, proliferation, and cytoskeletal changes. Three genes were down-regulated, including the T-cell-receptor delta locus. This study demonstrates a method by which CD4 + lymphocytes can be extracted from blood for the purpose of microarray analysis. Furthermore, we show that T-lymphocytes from the peripheral blood of subjects with severe and mild asthma differ in their gene-expression profiles, supporting the view that asthma is a systemic disease. These differentially expressed genes identify potential molecular targets for preventive and therapeutic options for severe asthma.

Adult↗

PubMed2004

Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes.

BACKGROUND: Recent worldwide reports of community-onset skin abscesses, outbreaks of furunculosis, and severe pneumonia associated with methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosome mec (SCCmec) type IV indicate that MRSA infections are evolving into a community-related problem. The majority of cases reported to date involve skin and soft-tissue infections, with severe pneumonia representing a relatively rare phenomenon. During a 2-month period in the winter of 2003-2004, four healthy adults presented to 1 of 2 Baltimore hospitals with severe necrotizing MRSA pneumonia in the absence of typical risk factors for MRSA infection. METHODS: Patients' MRSA isolates were characterized by strain typing with use of pulsed-field gel electrophoresis and SCCmec typing with use of a multiplex polymerase chain reaction (PCR) assay and detection of PVL genes by PCR. RESULTS: All 4 patients' MRSA isolates carried the PVL genes and the SCCmec type IV element and belonged to the USA300 pulsed-field type. These 3 findings are among the typical characteristics of community-onset MRSA strains. In addition, 2 of our patients had concomitant influenza A diagnosed, which likely contributed to the severity of their presentation. CONCLUSIONS: To our knowledge, these patients represent the first reported North American adults with severe community-onset MRSA pneumonia caused by strains carrying the PVL genes.

Adult↗

PubMed2004

Quality of life in tuberculosis: a review of the English language literature.

INTRODUCTION: Tuberculosis (TB) studies have concentrated on clinical outcomes; few studies have examined the impact of TB on patients' quality of life (QOL). METHODS: A systematic review of published medical literature using specific MESH terms: [Tuberculosis] and 1-[Outcome], 2-[Outcome Assessment], 3-[Quality of Life], 4-[Mood Disorder], 5-[Cost and Cost Analysis], 6-[Religion], 7-[Perception], 8-[Social Support], 9-[Optimism], 10-[Stress], 11-[Signs and Symptoms], and 12-[Cost of Illness]. This yielded 1972 articles; 60 articles met inclusion criteria and were reviewed. RESULTS: TB somatic symptoms have been well studied, but there were no studies of effects on physical functioning or general health perceptions. Patients tend to be worried, frustrated, or disappointed by their diagnosis, but it is unknown how emotional health changes with treatment. Diagnosed patients are less likely to find work, and less able to work and care for their families. TB creates the greatest financial burden on the poor. In developing, countries, patients and their families are ostracized by society, and families sometimes ostracize patients; the extent of TB's social stigma in the developed countries is unknown. CONCLUSION: There has been relatively little research on TB QOL and even less in developed countries. A better understanding may help improve treatment regimens, adherence to treatment, and functioning and well-being of people with TB.

Humans↗

PubMed2004

Quality of life in tuberculosis: patient and provider perspectives.

Tuberculosis (TB) is a persistent problem in the United States; however, little is known about its impact on functioning and quality of life (QOL) among people with TB. The purpose of this study is to describe the impact of TB on patients' QOL by using focus groups to assess the domains of QOL that are affected. Participants included patients (n = 10) who received treatment for active TB and physicians (n = 4) and nurses (n = 9) caring for patients with TB at a public health clinic in Baltimore, Maryland. TB affected all predicted domains of QOL, including general health perceptions, somatic sensation, psychological health, spiritual well-being, and physical, social and role functioning. Social stigmatization, isolation, pill burden, long duration of therapy, sexual dysfunction, loss of income, and fear were additional specific problems related to TB. Surprisingly, 11% (33) of the comments described benefits of TB illness, including increased spirituality and improved life perspectives. In addition, four additional QOL domains and three elements of treatment specific to TB which substantially impact QOL were identified. While patients and clinicians both identified issues in many areas of QOL, only patients mentioned the impact on sexual function, spirituality and improved life perspectives. Despite available curative therapy, TB and its treatment still have significant short and long-term consequences on patients' QOL.

Adult↗

PubMed2004

Hospitalizations for tuberculosis in the United States in 2000: predictors of in-hospital mortality.

STUDY OBJECTIVES: Despite curative therapy, mortality remains high for hospitalized patients with tuberculosis (TB) in the United States. The purpose of this study was to describe the characteristics of hospitalized patients with TB and to identify patient characteristics associated with in-hospital mortality. DESIGN, SETTING, AND PATIENTS: Using the 2000 Nationwide Inpatient Sample, representing 20% of US hospital admissions, we identified 2,279 hospital admissions with a primary diagnosis of TB (International Classification of Diseases, ninth revision, codes, 010.xx to 018.xx). MEASUREMENTS AND RESULTS: Mortality was the main outcome measure. Logistic regression analyses were performed including age, gender, race, insurance status, income, Deyo-adapted Charlson comorbidity index (DCI), HIV status, hospital admission source, and hospital characteristics as explanatory variables. A disproportionate number of patients hospitalized with TB were men (64%), nonwhite (72%), lived in areas with median incomes of < $35,000 (50%), and had publicly funded health insurance (49%) or no health insurance (17%). The mortality rate for patients hospitalized for TB was greater than that for non-TB hospital admissions (4.9% vs 2.4%, respectively; p < 0.001). Patients with TB who died during hospitalization were older (mean age, 65.1 vs 49.4 years, respectively; p < 0.001), had greater comorbid illness (DCI, 1.1 vs 0.55, respectively; p < 0.001), required longer hospitalizations (19.9 vs 13.9 days, respectively; p < 0.001), and accumulated substantially higher charges ($79,585 vs $31,610, respectively; p < 0.001) than did patients with TB who were alive at hospital discharge. In a multivariable analysis, older age, comorbid illnesses, and emergency department admissions were independently associated with mortality. The total charges for TB hospitalizations in the United States in 2000 exceeded $385 million. CONCLUSIONS: Despite public health efforts, patients who are hospitalized with TB are frequently admitted through emergency care settings, have a high risk of in-hospital mortality, and incur substantial hospital charges. To improve TB health outcomes, more vigorous clinical management and prevention strategies should especially target older patients and those with comorbid medical conditions.

Comorbidity↗