The Cabarrus County COVID-19 Prevalence and Immunity (C3PI) Study: design, methods, and baseline characteristics.

OBJECTIVES: Coronavirus Disease 2019 (COVID-19) is a viral illness with public health importance. The Cabarrus County COVID-19 Prevalence and Immunity (C3PI) Study is a prospective, longitudinal cohort study designed to contribute valuable information on community prevalence of active COVID-19 infection and SARS-CoV-2 antibodies as the pandemic and responses to it have and continue to evolve. We present the rationale, study design, and baseline characteristics of the C3PI Study. METHODS: We recruited 1,426 participants between June 2020 and August 2020 from the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) Study Community Registry and Biorepository, a previously established, community-based, longitudinal cohort. Participants completed a baseline survey and follow-up surveys every two weeks. A nested weighted, random sub-cohort (n=300) was recruited to measure the incidence and prevalence of active COVID-19 infection and SARS-CoV-2 IgG antibodies. RESULTS: The sub-cohort was younger (56 vs 61 years), had more men (39.0% vs 30.9%), and a higher proportion of Hispanic (11.0% vs 5.1%) and Black participants (17.0% vs 8.2%) compared with the overall cohort. They had similar anthropometrics and medical histories, but a greater proportion of the sub-cohort had a higher educational degree (36.1% vs 31.3%) and reported a pre-pandemic annual household income of >$90,000 (57.1% vs 47.9%). CONCLUSION: This study is part of a multisite consortium that will provide critical data on the epidemiology of COVID-19 and community perspectives about the pandemic, behaviors and mitigation strategies, and individual and community burden in North Carolina.

Medicare utilization, screening, and costs among participants in the Southeastern Diabetes Initiative: A population-based evaluation.

AIMS: Type 2 diabetes mellitus imposes significant burdens on patients and health care systems. Population-level interventions are being implemented to reach large numbers of patients at risk of or diagnosed with diabetes. We describe a population-based evaluation of the Southeastern Diabetes Initiative (SEDI) from the perspective of a payer, the Centers for Medicare & Medicaid Services (CMS). The purpose of this paper is to describe the population-based evaluation approach of the SEDI intervention from a Medicare utilization and cost perspective. METHODS: We measured associations between the SEDI intervention and receipt of diabetes screening (i.e., HbA1c test, eye exam, lipid profile), health care resource use, and costs among intervention enrollees, compared with a control cohort of Medicare beneficiaries in geographically adjacent counties. RESULTS: The intervention cohort had slightly lower 1-year screening in 2 of 3 domains (4% for HbA1c; 9% for lipid profiles) in the post-intervention period, compared with the control cohort. The SEDI intervention cohort did not have different Medicare utilization or total Medicare costs in the post-intervention period from surrounding control counties. CONCLUSIONS: Our analytic approach may be useful to others evaluating CMS demonstration projects in which population-level health is targeted for improvement in a well-defined clinical population.

Using electronic health record data for substance use Screening, Brief Intervention, and Referral to Treatment among adults with type 2 diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. METHODS: We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. DISCUSSION: By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions.

Supervised vs unsupervised exercise for intermittent claudication: A systematic review and meta-analysis.

BACKGROUND: Supervised exercise (SE) is widely accepted as an effective therapy for intermittent claudication (IC), but its use is limited by cost. Unsupervised exercise (UE) represents a less costly alternative. We assessed the comparative effectiveness of SE vs UE in patients with IC. METHODS AND RESULTS: We searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews and identified 27 unique studies (24 randomized controlled trials, 4 observational studies) that evaluated the comparative effectiveness of SE vs UE in 2074 patients with IC. Compared with UE, SE was associated with a moderate improvement in maximal walking distance at 6 months (effect size 0.77, 95% CI 0.36-1.17, P < .001) and 12 months (effect size 0.56, 95% CI 0.34-0.77, P < .001). Supervised exercise also improved claudication distance to a moderate extent compared with UE at 6 months (effect size 0.63, 95% CI 0.40-0.85, P < .001) and 12 months (effect size 0.41, 95% CI 0.18-0.65, P = .001). There was no difference in the Short Form-36 quality of life at 6 months (effect size -0.05, 95% CI -0.50 to 0.41, P = .84) or walking impairment questionnaire distance (effect size 0.24, 95% CI -0.03 to 0.50, P = .08) or speed (effect size 0.26, 95% CI -0.06 to 0.59, P = .11). CONCLUSIONS: In claudication patients, SE is more effective than UE at improving maximal walking and claudication distances, yet there is no difference in general quality of life or patient-reported community-based walking. Further studies are needed to investigate the relationship between functional gain and disease-specific quality of life.

Comparative Effectiveness of Medical Therapy, Supervised Exercise, and Revascularization for Patients With Intermittent Claudication: A Network Meta-analysis.

BACKGROUND: There are limited data on the comparative effectiveness of medical therapy, supervised exercise, and revascularization to improve walking and quality of life in patients with intermittent claudication (IC). HYPOTHESIS: Supervised exercise and revascularization was superior to medical therapy in IC. METHODS: We studied the comparative effectiveness of exercise training, medications, endovascular intervention, and surgical revascularization on outcomes including functional capacity (walking distance and timing), quality of life, and mortality. We searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews from January 1995 to August 2012 for relevant English-language studies. Two investigators independently collected data. Meta-analyses with random-effects models of direct comparisons were supplemented by mixed-treatment analyses to incorporate data from placebo comparisons, head-to-head comparisons, and multiple treatment arms. RESULTS: Thirty-five unique studies evaluated treatment modalities in 7475 patients with IC. Compared with usual care, only exercise training improved both maximal walking distance (150 meters; 95% confidence interval: 35-266 meters, P = 0.01) and initial claudication distance (39 meters; 95% confidence interval: 9-65 meters, P = 0.003). All modalities were associated with improved quality of life (Short Form-36 physical functioning score) compared with usual care, but there were no differences between treatments. There were insufficient safety data to assess treatment-related complications. All-cause mortality was not significantly different between modalities. CONCLUSIONS: Evidence is insufficient to determine treatment superiority for improving quality of life and walking parameters in IC patients. Further studies with attention to study design, standardized efficacy and safety endpoints, and appropriate subgroup reporting are necessary to determine comparative effectiveness.

Data-driven asthma endotypes defined from blood biomarker and gene expression data.

The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes) driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels.

Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

BACKGROUND: Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. METHODS AND RESULTS: We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. CONCLUSIONS: Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted.

Dual antiplatelet therapy with or without oral anticoagulation in the postdischarge management of acute coronary syndrome patients with an indication for long term anticoagulation: a systematic review.

Currently, there is a lack of consensus among guidelines for the postdischarge treatment of patients presenting with acute coronary syndrome (ACS) who have a long-term indication for anticoagulation. We conducted a systematic review comparing the safety and effectiveness of dual antiplatelet therapy (DAPT) and triple therapy (TT; defined as DAPT plus an oral anticoagulant) in patients with ACS and a long-term indication for anticoagulation. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews published between January 1995 and September 2013. Each investigator screened and abstracted data, assessed applicability and quality, and graded the strength of evidence. Meta-analysis of direct comparison was performed when outcomes and follow-up periods were comparable. Fourteen observational studies were identified that contained comparative effectiveness data on DAPT versus TT. No difference in the odds of mortality (OR 1.04, 95% CI 0.59-1.83) or stroke (OR 1.01, 95% CI 0.38-2.67) at 1-5 years was found between TT and DAPT. Major bleeding at 1-5 years (OR 1.46, 95% CI 1.07-2.00) and nonfatal MI at 1-5 years (OR 1.85, 95% CI 1.13-3.02) occurred more frequently in patients receiving TT. The results of this systematic review demonstrate that treatment with TT was associated with increased rates of nonfatal MI and major bleeding when compared with treatment with DAPT in the postdischarge management of ACS patients with an indication for oral anticoagulation. Until results of ongoing randomized trials assessing antithrombotic therapies define optimal management strategies, the current analysis suggests using caution when prescribing TT to these patients.

Comparative effectiveness of endovascular and surgical revascularization for patients with peripheral artery disease and critical limb ischemia: systematic review of revascularization in critical limb ischemia.

BACKGROUND: For patients with critical limb ischemia (CLI), the optimal treatment to enhance limb preservation, prevent death, and improve functional status is unknown. We performed a systematic review and meta-analysis to assess the comparative effectiveness of endovascular revascularization and surgical revascularization in patients with CLI. METHODS: We systematically searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1995 to August 2012. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects, with endovascular treatment as the control group. RESULTS: We identified a total of 23 studies, including 1 randomized controlled trial, which reported no difference in amputation-free survival at 3 years (odds ratio [OR] 1.22, 95% CI 0.84-1.77) and all-cause mortality (OR 1.07, 0.73-1.56) between the 2 treatments. Meta-analysis of the observational studies showed a statistically nonsignificant reduction in all-cause mortality at 6 months (11 studies, OR 0.85, 0.57-1.27) and amputation-free survival at 1 year (2 studies, OR 0.76, 0.48-1.21) in patients treated with endovascular revascularization. There was no difference in overall death, amputation, or amputation-free survival at ≥2 years. CONCLUSIONS: The currently available literature suggests that there is no difference in clinical outcomes for patients with CLI treated with endovascular or surgical revascularization. There is a paucity of high-quality data available to guide clinical decision making, especially as it pertains to patient subgroups or anatomical considerations.

Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis.

BACKGROUND: Current treatments for pulmonary arterial hypertension (PAH) have been shown to improve dyspnea, 6-min walk distance (6MWD), and pulmonary hemodynamics, but few studies were designed to compare treatment regimens or assess the impact of treatment on mortality. METHODS: We conducted a systematic review to evaluate the comparative effectiveness and safety of monotherapy or combination therapy for PAH using endothelin receptor antagonists, phosphodiesterase inhibitors, or prostanoids. We searched English-language publications of comparative studies that reported intermediate or long-term outcomes associated with drug therapy for PAH. Two investigators abstracted data and rated study quality and applicability. RESULTS: We identified 28 randomized controlled trials involving 3,613 patients. We found no studies that randomized treatment-naive patients to monotherapy vs combination therapy. There was insufficient statistical power to detect a mortality difference associated with treatment. All drug classes demonstrated increases in 6MWD when compared with placebo, and combination therapy showed improved 6MWD compared with monotherapy. For hospitalization, the OR was lower in patients taking endothelin receptor antagonists or phosphodiesterase-5 inhibitors compared with placebo (OR, 0.34 and 0.48, respectively). CONCLUSIONS: Although no studies were powered to detect a mortality reduction, monotherapy was associated with improved 6MWD and reduced hospitalization rates. Our findings also suggest an improvement in 6MWD when a second drug is added to monotherapy.

Evaluating cough assessment tools: a systematic review.

BACKGROUND: Little is known about the comparative validity, reliability, or responsiveness of instruments for assessing cough frequency or impact, where the term impact encompasses both cough severity and the impact of cough on health-related quality of life. METHODS: We conducted a systematic review to evaluate instruments that assess cough frequency or impact in adults, adolescents, and children with acute or chronic cough. RESULTS: Seventy-eight studies were included, of which eight were randomized controlled trials and 70 were observational studies. In all age groups, audio and video electronic recording devices had good reliability compared with other methods of assessing cough frequency but had variable correlation with other cough assessments, such as visual analog scale scores, quality-of-life questionnaires, cough diaries, and tussigenic challenges. Among adult and adolescent patients, the Leicester Cough Questionnaire (LCQ) and the Cough-Specific Quality-of-Life Questionnaire (CQLQ) were valid and reliable, showing high intraclass and test-retest correlations. Among children, the Parent Cough-Specific Quality of Life Questionnaire and Pediatric Cough Questionnaire were valid and reliable. CONCLUSIONS: Electronic recording devices can be valid assessments of cough frequency. The LCQ and CQLQ for adults and the Parent Cough-Specific Quality of Life questionnaire for children are valid instruments for assessing cough impact. There is limited but insufficient evidence to determine the reliability or concurrent validity of the different types of cough diaries or visual analog scale scores. There are also limited data to support the responsiveness of recording devices. There is good responsiveness data for the LCQ and CQLQ, but more evidence is needed.

Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis.

BACKGROUND: Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population. METHODS: We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments. RESULTS: We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied. CONCLUSIONS: Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

The patient centered medical home. A systematic review.

BACKGROUND: The patient-centered medical home (PCMH) describes mechanisms for organizing primary care to provide high quality care across the full range of individuals' health care needs.It is being widely implemented by provider organizations and third party payers. PURPOSE: To describe approaches for PCMH implementation and summarize evidence for effects on patient and staff experiences,process of care, and clinical and economic outcomes. DATA SOURCES: PubMed (through 6 December 2011), Cumulative Index to Nursing & Allied Health Literature, and the Cochrane Database of Systematic Reviews (through 29 June 2012). STUDY SELECTION: English-language trials and longitudinal observational studies that met criteria for the PCMH, as defined by the Agency for Healthcare Research and Quality, and included populations with multiple conditions. DATA EXTRACTION: Information on study design, populations, interventions,comparators, financial models, implementation methods,outcomes, and risk of bias were abstracted by 1 investigator and verified by another. DATA SYNTHESIS: In 19 comparative studies, PCMH interventions had a small positive effect on patient experiences and small to moderate positive effects on the delivery of preventive care services(moderate strength of evidence). Staff experiences were also improved by a small to moderate degree (low strength of evidence).Evidence suggested a reduction in emergency department visits(risk ratio [RR], 0.81 [95% CI, 0.67 to 0.98]) but not in hospital admissions (RR, 0.96 [CI, 0.84 to 1.10]) in older adults (low strength of evidence). There was no evidence for overall cost savings. LIMITATION: Systematic review is challenging because of a lack of consistent definitions and nomenclature for PCMH. CONCLUSION: The PCMH holds promise for improving the experiences of patients and staff and potentially for improving care processes,but current evidence is insufficient to determine effects on clinical and most economic outcomes

Closing the quality gap: revisiting the state of the science (vol. 2: the patient-centered medical home).

OBJECTIVES: As part of the Closing the Quality Gap: Revisiting the State of the Science series of the Agency for Healthcare Research and Quality (AHRQ), this systematic review sought to identify completed and ongoing evaluations of the comprehensive patient-centered medical home (PCMH), summarize current evidence for this model, and identify evidence gaps. DATA SOURCES: We searched PubMed®, CINAHL®, and the Cochrane Database of Systematic Reviews for published English-language studies, and a wide variety of databases and Web resources to identify ongoing or recently completed studies. REVIEW METHODS: Two investigators per study screened abstracts and full-text articles for inclusion, abstracted data, and performed quality ratings and evidence grading. Our functional definition of PCMH was based on the definition used by AHRQ. We included studies that explicitly claimed to be evaluating PCMH and those that did not but which met our functional definition. RESULTS: Seventeen studies with comparison groups evaluated the effects of PCMH (Key Question [KQ] 1). Older adults in the United States were the most commonly studied population (8 of 17 studies). PCMH interventions had a small positive impact on patient experiences (including patient-perceived care coordination) and small to moderate positive effects on preventive care services (moderate strength of evidence [SOE]). Staff experiences were also improved by a small to moderate degree (low SOE). There were too few studies to estimate effects on clinical or most economic outcomes. Twenty-one of 27 studies reported approaches that addressed all 7 major PCMH components (KQ 2), including team-based care, sustained partnership, reorganized care or structural changes to care, enhanced access, coordinated care, comprehensive care, and a systems-based approach to quality. A total of 51 strategies were used to address the 7 major PCMH components. Twenty-two of 27 studies reported information on financial systems used to implement PCMH, implementation strategies, and/or organizational learning strategies for implementing PCMH (KQ 3). The 31 studies identified in the horizon scan of ongoing PCMH studies (KQ 4) were broadly representative of the U.S. health care system, both in geography and in the complexity of private and public health care payers and delivery networks. CONCLUSIONS: Published studies of PCMH interventions often have similar broad elements, but precise components of care varied widely. The PCMH holds promise for improving the experiences of patients and staff, and potentially for improving care processes. However, current evidence is insufficient to determine effects on clinical and most economic outcomes. Ongoing studies identified through the horizon scan have potential to greatly expand the evidence base relating to PCMH.

Mechanistic indicators of childhood asthma (MICA) study: piloting an integrative design for evaluating environmental health.

BACKGROUND: Asthma is a common complex disease responsible for considerable morbidity and mortality, particularly in urban minority populations. The Mechanistic Indicators of Childhood Asthma study was designed to pilot an integrative approach in children's health research. The study incorporates exposure metrics, internal dose measures, and clinical indicators to decipher the biological complexity inherent in diseases such as asthma and cardiovascular disease with etiology related to gene-environment interactions. METHODS/DESIGN: 205 non-asthmatic and asthmatic children, (9-12 years of age) from Detroit, Michigan were recruited. The study includes environmental measures (indoor and outdoor air, vacuum dust), biomarkers of exposure (cotinine, metals, total and allergen specific Immunoglobulin E, polycyclic aromatic hydrocarbons, volatile organic carbon metabolites) and clinical indicators of health outcome (immunological, cardiovascular and respiratory). In addition, blood gene expression and candidate SNP analyses were conducted. DISCUSSION: Based on an integrative design, the MICA study provides an opportunity to evaluate complex relationships between environmental factors, physiological biomarkers, genetic susceptibility and health outcomes. PROJECT APPROVAL: IRB Number 05-EPA-2637: The human subjects' research protocol was reviewed by the Institutional Review Board (IRB) of the University of North Carolina; the IRB of Westat, Inc., the IRB of the Henry Ford Health System; and EPA's Human Subjects' Research Review Official.

Increased plasma reactive oxidant levels and their relationship to blood cells, total IgE, and allergen-specific IgE levels in asthmatic children.

Asthma is a disorder characterized by inflammation of the airways. Oxidative stress may play a role in the pathophysiology of several diseases including asthma. Characterizing biomarkers of oxidative stress in the context of other systemic measures of immune function or inflammation could provide insight regarding underlying mechanisms inducing asthma. We evaluated whether oxidative stress in the form of plasma reactive oxidants differs between asthmatic and non-asthmatic children and elucidate relationships between plasma reactive oxidants and other asthma-related immunological markers. Plasma reactive oxidants, white blood cell counts, total serum immunoglobulin E(IgE), and a multi-allergen-specific IgE screen were measured in 74 asthmatic and 74 non-asthmatic children(9 to 13 years of age) from the Detroit, Michigan area. Plasma reactive oxidants were measured using a lucigenin-based chemiluminescence assay. Plasma reactive oxidants, eosinophils, and neutrophils(absolute counts and percent of total white blood cell counts), total IgE, and allergen-specific IgE levels were elevated in asthmatics after adjusting for age, gender, and ethnicity. IgE(total or allergen-specific), eosinophils and neutrophils were not significantly associated with plasma reactive oxidant levels. The association between plasma reactive oxidants and asthma status was similar when eosinophils, neutrophils, total IgE, or allergen-specific IgE were included as possible confounders in multivariate logistic regression models. In conclusion, plasma reactive oxidants are elevated in asthmatics and appear to be an independent predictor of asthma status. Measurement of plasma reactive oxidants may be a useful adjunct diagnostic tool and potential mechanistic indicator relevant to the study of asthma and asthma exacerbation.

Increased plasma reactive oxidant levels and their relationship to blood cells, total IgE, and allergen-specific IgE levels in asthmatic children.

Asthma is a disorder characterized by inflammation of the airways. Oxidative stress may play a role in the pathophysiology of several diseases including asthma. Characterizing biomarkers of oxidative stress in the context of other systemic measures of immune function or inflammation could provide insight regarding underlying mechanisms inducing asthma. We evaluated whether oxidative stress in the form of plasma reactive oxidants differs between asthmatic and non-asthmatic children and elucidate relationships between plasma reactive oxidants and other asthma-related immunological markers. Plasma reactive oxidants, white blood cell counts, total serum immunoglobulin E (IgE), and a multi-allergen-specific IgE screen were measured in 74 asthmatic and 74 non-asthmatic children (9 to 13 years of age) from the Detroit, Michigan area. Plasma reactive oxidants were measured using a lucigenin-based chemiluminescence assay. Plasma reactive oxidants, eosinophils, and neutrophils (absolute counts and percent of total white blood cell counts), total IgE, and allergen-specific IgE levels were elevated in asthmatics after adjusting for age, gender, and ethnicity. IgE (total or allergen-specific), eosinophils and neutrophils were not significantly associated with plasma reactive oxidant levels. The association between plasma reactive oxidants and asthma status was similar when eosinophils, neutrophils, total IgE, or allergen-specific IgE were included as possible confounders in multivariate logistic regression models. In conclusion, plasma reactive oxidants are elevated in asthmatics and appear to be an independent predictor of asthma status. Measurement of plasma reactive oxidants may be a useful adjunct diagnostic tool and potential mechanistic indicator relevant to the study of asthma and asthma exacerbation.