Christian Bime

Asthma Symptom Utility Index: Reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients

BACKGROUND The evaluation of asthma symptoms is a core outcome measure in asthma clinical research. The Asthma Symptom Utility Index (ASUI) was developed to assess the frequency and severity of asthma symptoms. The psychometric properties of the ASUI are not well characterized, and a minimal important difference (MID) is not established. OBJECTIVES We assessed the reliability, validity, and responsiveness to change of the ASUI in a population of adult asthmatic patients. We also sought to determine the MID for the ASUI. METHODS Adult asthmatic patients (n = 1648) from 2 previously completed multicenter randomized trials were included. Demographic information, spirometric results, ASUI scores, and other asthma questionnaire scores were obtained at baseline and during follow-up visits. Participants also kept a daily asthma diary. RESULTS The internal consistency reliability of the ASUI was 0.74 (Cronbach α). Test-retest reliability was 0.76 (intraclass correlation). Construct validity was demonstrated by significant correlations between ASUI scores and Asthma Control Questionnaire scores (Spearman correlation r = -0.79; 95% CI, -0.85 to -0.75; P < .001) and Mini Asthma Quality of Life Questionnaire scores (r = 0.59; 95% CI, 0.51-0.61; P < .001). Responsiveness to change was demonstrated, with significant differences between mean changes in ASUI scores across groups of participants differing by 10% in percent predicted FEV(1) (P < .001) and by 0.5 points in Asthma Control Questionnaire scores (P < .001). Anchor-based and statistical methods support an MID for the ASUI of 0.09 points. CONCLUSIONS The ASUI is reliable, valid, and responsive to changes in asthma control over time. The MID of the ASUI (range of scores, 0-1) is 0.09.

Association of dietary soy genistein intake with lung function and asthma control: A post-hoc analysis of patients enrolled in a prospective multicentre clinical trial

BACKGROUND Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. AIMS To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. METHODS A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV(1))) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. RESULTS Participants with little or no genistein intake had a lower baseline FEV(1) than those with a moderate or high intake (2.26 L vs. 2.53 L and 2.47 L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. CONCLUSIONS In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.

Measures of asthma control.

Purpose of review Over the past decade, the concept of asthma control as distinct from asthma severity has been clearly defined. Well controlled asthma is the goal of therapy in all asthma patients. This review is a comprehensive description of the tools currently available for a methodical assessment of different aspects of asthma control in clinical practice and research. Recent findings Several questionnaires for assessing asthma control have been extensively validated in adults. In children, validation data are less extensive. Considerable overlap exists between asthma control measures and measures of asthma-specific quality of life. Asthma-specific quality-of-life questionnaires have been used as primary outcome measures in major clinical trials evaluating asthma therapy. Biomarkers that reflect eosinophilic inflammation of the airways are used as intermediate outcome measures to reflect the biological basis of asthma control. There is some controversy, however, over which biomarkers are best incorporated into therapeutic algorithms that attempt to achieve maximal asthma control while minimizing treatment intensity. Summary In designing clinical studies to evaluate different asthma therapies, researchers will find this review to be a useful resource in terms of choosing the appropriate tool for assessing asthma control. This is also a valuable resource for a methodical assessment of response to asthma therapy in routine clinical care.

Decreased In-Hospital Mortality after Lobectomy Using Video-assisted Thoracoscopic Surgery Compared with Open Thoracotomy

Rationale: There is a paucity of data regarding the optimal surgical approach for lung lobectomy. Lobectomy performed by video‐assisted thoracoscopic surgery (VATS) has been associated with lower morbidity as compared with lobectomy performed by thoracotomy. However, no multicenter studies have shown improved mortality with VATS lobectomy compared with open surgical lobectomy. Objectives: We used data from the United States Healthcare Cost and Utilization Project Nationwide Inpatient Sample database from 2009 to 2012 to compare VATS with open lobectomy for in‐hospital mortality and other short‐term outcomes. Methods: We used International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes to identify the patients undergoing lobectomy. We used 1:1 ratio propensity matching with the nearest neighbor method without replacement to generate matched pairs. Measurements and Main Results: Over the 4‐year period, 27,451 patients underwent lobectomy. The majority of these procedures were performed by thoracotomy (65%) as compared with VATS (35%). A total of 9,393 matched pairs were created. VATS lobectomy was associated with significantly lower in‐hospital mortality when compared with thoracotomy (1.3% vs. 2.5%, P < 0.001). A shorter length of hospital stay was observed for those undergoing VATS lobectomy (6.21 vs. 8.75 d, P < 0.001). The overall rate of perioperative complications was low, with those undergoing VATS being less likely to have any perioperative morbidity. Conclusions: In recent years, the use of VATS for lobectomy has increased relative to thoracotomy. This trend has coincided with increased survival and shorter length of stay for VATS lobectomy compared with thoracotomy. Further studies are needed to identify comorbidities that identify ideal candidates for VATS lobectomy.

Pulmonary Embolism with Right Ventricular Dysfunction: Who Should Receive Thrombolytic Agents?

BACKGROUND Appropriate management of pulmonary embolism patients with right ventricular dysfunction is uncertain. Recent guidelines have stressed the need for more data on the use of thrombolytic agents in the stable pulmonary embolism patient with right ventricular dysfunction. The objective of this study is to investigate the hypothesis that thrombolytic therapy in hemodynamically stable pulmonary embolism patients with right ventricular dysfunction is not associated with improved mortality. METHODS We did a retrospective analysis using multi-institutional observational data from the Nationwide Inpatient Sample database. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes were used to identify the patients with pulmonary embolism and right ventricular dysfunction. In-hospital mortality was defined as the primary outcome of interest. RESULTS Over the 4 years of the study period, 3668 patients with right ventricular dysfunction and pulmonary embolism were found, of which 3253 patients were identified as having hemodynamically stable right-sided heart failure with pulmonary embolism. There was no significant difference in mortality between hemodynamically stable pulmonary embolism patients with right ventricular dysfunction who received thrombolytic agents compared with those who did not. When outcomes were assessed for patients with right ventricular dysfunction and hemodynamic instability, a significant improvement in mortality was noted for patients with right ventricular dysfunction who received thrombolytic agents, which confirmed previous reports that thrombolytic therapy decreases mortality in pulmonary embolism patients who are hemodynamically unstable. CONCLUSION Our data support the use of less aggressive treatment for stable pulmonary embolism patients with right ventricular dysfunction. These results argue against the reflexive use of thrombolytic agents in stable pulmonary embolism patients with right ventricular dysfunction.

Assessing upper-extremity motion: An innovative method to quantify functional capacity in patients with chronic obstructive pulmonary disease

Background Assessment of functional capacity is important in directing chronic obstructive pulmonary disease (COPD) care (e.g., rehabilitation and discharge readiness), and in predicting outcomes (e.g., exacerbation, hospitalization, and mortality). The 6-minute walk distance (6MWD) test for functional capacity assessment, may be time-consuming and burdensome. Objective The purpose of the current study was to evaluate an upper-extremity function (UEF) test for assessing functional capacity in older adults with COPD. Methods In this cross-sectional study, 49 older adults (≥55 years) with diagnosed COPD were recruited, and pulmonary function measures and 6MWD were obtained. Participants wore wireless sensors on forearm and upper-arm and performed rapid elbow flexion for 20 seconds (the UEF test). Slowness was assessed by measuring elbow speed, and acceleration and weakness (muscle strength) were assessed by measuring power of movement and elbow moment. Results Speed, power, and moment UEF parameters were independently associated with 6MWD, when controlling for age, gender, and body mass index (BMI) (r = 0.78, p < .001). Elbow moment showed significant Pearson correlations with all pulmonary function measures and maximal inspiratory/expiratory pressure measures (r = 0.35–0.69, p<0.02). Conclusions Results show promise of a quick upper-extremity measure of functional capacity in patients with COPD, and as an outcome measure in clinical COPD trials.

Extracorporeal Membrane Oxygenation for ARDS: National Trends in the United States 2008–2012

INTRODUCTION: Recent advances in technology and protocols have made the use of extracorporeal membrane oxygenation (ECMO) a viable rescue therapy for patients with ARDS who present with refractory hypoxemia. Despite the lack of strong evidence supporting the use of ECMO in ARDS, its use seems to be increasing. We sought to determine recent trends in the use of ECMO for ARDS. We also assessed trends in mortality among patients with ARDS in whom ECMO was used. METHODS: We performed a retrospective analysis using the largest all-payer in-patient healthcare database in the United States, the Healthcare Cost and Utilization project, the National In-patient Sample database from 2008 to 2012. Subjects with ARDS were identified using carefully chosen International Classification of Diseases, Ninth Revision codes. RESULTS: We found that in 2008, about 1 in 1,000 subjects with ARDS underwent ECMO. Over the subsequent 4-y time period, there was a 0.19% absolute increase and 70% relative increase in the use of ECMO for ARDS. The mortality rate among subjects with ARDS in whom ECMO was used declined from 78% in 2008 to 64% in 2012. We also found a trend toward a reduction in hospital stay among survivors. CONCLUSION: In the United States, between 2008 and 2012, there was an increasing trend toward the use of ECMO in patients with ARDS that coincided with a slight increase in survival among these patients.

Reactive oxygen species–associated molecular signature predicts survival in patients with sepsis

Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)–associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies.

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor

Rationale: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. Objectives: To identify genetic susceptibility targets for ARDS. Methods: A genome‐wide association study was performed on 232 African American patients with ARDS and 162 at‐risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS‐ and ventilator‐induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort. Measurements and Main Results: Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P‐selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator‐induced (twofold increase) and LPS‐induced (5.7‐fold increase) murine lung injury models compared with controls. Furthermore, Selplg−/− mice exhibited significantly reduced LPS‐induced inflammatory lung injury compared with wild‐type C57/B6 mice. Finally, an antibody that neutralizes P‐selectin glycoprotein ligand 1 significantly attenuated LPS‐induced lung inflammation. Conclusions: These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.

Health Disparities in Asthma

In the United States, several demographic groups have a disproportionately higher burden of asthma morbidity and mortality when compared to the general population. These demographic groups include racial and ethnic minorities, women, children, residents of inner cities, and economically disadvantaged populations. Observed disparities in asthma burden are probably explained by a complex interaction of multiple factors including; patient-related factors, provider-related factors, health care system-related factors, social, and environmental factors. The importance of studying and addressing asthma health disparities has been emphasized in recent reports by the Centers for Disease Control and Prevention (CDC). There is an urgent need to understand the factors that contribute to asthma health disparities and identify strategies that would reduce asthma disparities. To inform future research and guide intervention strategies aimed at addressing asthma health disparities, conceptual models of the mechanisms that link various factors associated with asthma health disparities have been proposed. These frameworks are a good starting point for guiding future intervention studies that seek to address these disparities.