Impact of Clinical Characteristics and Biomarkers on AIRQ Exacerbation Prediction Ability.

BACKGROUND: Complex models combining impairment-based control assessments with clinical characteristics and biomarkers have been developed to predict asthma exacerbations. The composite Asthma Impairment and Risk Questionnaire (AIRQ) with adjustments for demographics (age, sex, race, body mass index [BMI]) predicts 12-month exacerbation occurrence similarly to these more complex models. OBJECTIVE: To examine whether AIRQ exacerbation prediction is enhanced when models are adjusted for a wider range of clinical characteristics and biomarkers. METHODS: Patients aged ≥12 years completed monthly online surveys regarding exacerbation-related oral corticosteroid use, emergency-department/urgent-care visits, and hospitalizations. Univariate logistic regressions to predict exacerbations were performed with sociodemographics, comorbidities, exacerbation history, lung function, blood eosinophils, immunoglobulin E, and fractional exhaled nitric oxide. Significant (P≤0.05) variables were included in multivariable logistic regressions with and without AIRQ control categories to predict 12-month exacerbations (log odds ratio [OR], 95% Wald confidence interval [CI]). Model performances were compared. RESULTS: Over 12 months, 1070 patients (70% female; mean[SD] age 43.9[19.4] years; 22% non-White; BMI[SD] 30.6[8.7]) completed ≥1 survey (mean[SD] 10.5[2.8]). In the multivariable analysis, AIRQ control category adjusted for significant clinical characteristics and biomarkers was predictive of ≥1 exacerbation: OR(95%CI) not well-controlled vs well-controlled: 1.93(1.41-2.62), very poorly controlled vs well-controlled: 3.81(2.65-5.47). Receiver operating characteristic area under the curve for this more complex model of exacerbation prediction (AUC=0.72) did not differ from AIRQ (AUC=0.70). Models with AIRQ performed better than those without AIRQ (AUC=0.67, P<0.05). CONCLUSION: Costly and time-consuming complex modeling with clinical characteristics and biomarkers does not enhance the strong exacerbation prediction ability of AIRQ.

Impact of automated data flow and reminders on adherence and resource utilization for remotely monitoring physical activity in individuals with stroke or chronic obstructive pulmonary disease.

As rehabilitation advances into the era of digital health, remote monitoring of physical activity via wearable devices has the potential to change how we provide care. However, uncertainties about patient adherence and the significant resource requirements needed create challenges to adoption of remote monitoring into clinical care. Here we aim to determine the impact of a novel digital application to overcome these barriers. The Rehabilitation Remote Monitoring Application (RRMA) automatically extracts data about physical activity collected via a Fitbit device, screens the data for adherence, and contacts the participant if adherence is low. We compare adherence and estimate the resources required (i.e., time and financial) to perform remote monitoring of physical activity with and without the RRMA in two patient groups. Seventy-three individuals with stroke or chronic obstructive pulmonary disease completed 28 days of monitoring physical activity with the RRMA, while 62 individuals completed 28 days with the data flow processes being completed manually. Adherence (i.e., the average percentage of the day that the device was worn) was similar between groups (p=0.85). However, the RRMA saved an estimated 123.8 minutes or $50.24 per participant month when compared to manual processes. These results demonstrate that automated technologies like the RRMA can maintain patient adherence to remote monitoring of physical activity while reducing the time and financial resources needed. Applications like the RRMA can facilitate the adoption of remote monitoring in rehabilitation by reducing barriers related to adherence and resource requirements.

Computational Deconvolution of Cell Type-Specific Gene Expression in COPD and IPF Lungs Reveals Disease Severity Associations.

RATIONALE: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n>1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity. METHODS: We analyzed lung tissue RNA-seq data from 1026 subjects (COPD, n=465; IPF, n=213; control, n=348) from the Lung Tissue Research Consortium. We performed RNA-seq deconvolution, querying thirty-eight discrete cell-type varieties in the lungs. We tested whether deconvoluted cell-type abundance and cell type-specific gene expression were associated with disease severity. RESULTS: The abundance score of twenty cell types significantly differed between IPF and control lungs. In IPF subjects, eleven and nine cell types were significantly associated with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), respectively. Aberrant basaloid cells, a rare cells found in fibrotic lungs, were associated with worse FVC and DLCO in IPF subjects, indicating that this aberrant epithelial population increased with disease severity. Alveolar type 1 and vascular endothelial (VE) capillary A were decreased in COPD lungs compared to controls. An increase in macrophages and classical monocytes was associated with lower DLCO in IPF and COPD subjects. In both diseases, lower non-classical monocytes and VE capillary A cells were associated with increased disease severity. Alveolar type 2 cells and alveolar macrophages had the highest number of genes with cell type-specific differential expression by disease severity in COPD and IPF. In IPF, genes implicated in the pathogenesis of IPF, such as matrix metallopeptidase 7, growth differentiation factor 15, and eph receptor B2, were associated with disease severity in a cell type-specific manner. CONCLUSION: Utilization of RNA-seq deconvolution enabled us to pinpoint cell types present in the lungs that are associated with the severity of COPD and IPF. This knowledge offers valuable insight into the alterations within tissues in more advanced illness, ultimately providing a better understanding of the underlying pathological processes that drive disease progression.

Advancing assessment of asthma control with a composite tool: The Asthma Impairment and Risk Questionnaire.

BACKGROUND: National and international asthma guidelines and reports do not include control tools that combine impairment assessment with exacerbation history in one instrument. OBJECTIVE: To analyze the performance of the composite Asthma Impairment and Risk Questionnaire (AIRQ) in assessing both domains of control and predicting exacerbation risk compared with the Global Initiative for Asthma (GINA) 4-question symptom control tool (GINA SCT), Asthma Control Test (ACT), and physician expert opinion (EO) informed by GINA SCT responses and appraisal of GINA-identified risk factors for poor asthma outcomes. METHODS: Multivariable logistic regressions evaluated AIRQ and GINA SCT as predictors of ACT. McNemar's test compared the proportion of patients categorized at baseline as completely or well-controlled by each assessment but with current impairment or previous-year and subsequent-year exacerbations. RESULTS: The analysis included 1064 patients aged 12 years or older; mean (SD) age 43.8 years (19.3); 70% female; 79% White; and 6% Hispanic or Latino. AIRQ and GINA SCT were highly predictive of ACT well-controlled vs not well-controlled and very poorly controlled (receiver operator characteristic area under curve AIRQ = 0.90, GINA SCT = 0.86, P = .03 AIRQ vs GINA SCT) and ACT very poorly controlled vs well-controlled and not well-controlled asthma (receiver operator characteristic area under curve AIRQ = 0.91, GINA SCT = 0.87, P = .01 AIRQ vs GINA SCT). AIRQ rated fewer patients as having completely or well-controlled asthma who had current impairment (P < .01) or with previous-year and subsequent-year exacerbations (P < .001) than did GINA SCT, ACT, and EO. CONCLUSION: AIRQ performs better in assessing both domains of current control and predicting exacerbation risk than do control tools and EO informed by GINA SCT and risk factors for poor asthma outcomes.

FEV1Q: a race-neutral approach to assessing lung function.

BACKGROUND: Forced expiratory volume in 1 s quotient (FEV1Q) is a simple approach to spirometry interpretation that compares measured lung function to a lower boundary. This study evaluated how well FEV1Q predicts survival compared with current interpretation methods and whether race impacts FEV1Q. METHODS: White and Black adults with complete spirometry and mortality data from the National Health and Nutrition Examination Survey (NHANES) III and the United Network for Organ Sharing (UNOS) database for lung transplant referrals were included. FEV1Q was calculated as FEV1 divided by 0.4 L for females or 0.5 L for males. Cumulative distributions of FEV1 were compared across races. Cox proportional hazards models tested mortality risk from FEV1Q adjusting for age, sex, height, smoking, income and among UNOS individuals, referral diagnosis. Harrell's C-statistics were compared between absolute FEV1, FEV1Q, FEV1/height2, FEV1 z-scores and FEV1 % predicted. Analyses were stratified by race. RESULTS: Among 7182 individuals from NHANES III and 7149 from UNOS, 1907 (27%) and 991 (14%), respectively, were Black. The lower boundary FEV1 values did not differ between Black and White individuals in either population (FEV1 first percentile difference ≤0.01 L; p>0.05). Decreasing FEV1Q was associated with increasing hazard ratio (HR) for mortality (NHANES III HR 1.33 (95% CI 1.28-1.39) and UNOS HR 1.18 (95% CI 1.12-1.23)). The associations were not confounded nor modified by race. Discriminative power was highest for FEV1Q compared with alternative FEV1 approaches in both Black and White individuals. CONCLUSIONS: FEV1Q is an intuitive and simple race-neutral approach to interpreting FEV1 that predicts survival better than current alternative methods.

Changes in Spirometry Interpretative Strategies: Implications for Classifying COPD and Predicting Exacerbations.

BACKGROUND: Recent guidelines for spirometry interpretation recommend both race-neutral reference equations and use of z score thresholds to define severity of airflow obstruction. RESEARCH QUESTION: How does the transition from race-specific to race-neutral equations impact severity classifications for patients with COPD when using % predicted vs z score thresholds, and do changes in severity correspond to clinical risk? STUDY DESIGN AND METHODS: This retrospective cohort study included Black and White patients with COPD and available spirometry from the Johns Hopkins Health System. Global Lung Function Initiative (GLI) 2012 (race-specific) equations and GLI Global (race-neutral) equations were used to determine FEV1 % predicted and z score values. Patients were classified as having mild, moderate, or severe disease according to % predicted or z score thresholds. Associations between a change in severity classification from race-specific to race-neutral with COPD exacerbations and all-cause hospitalizations were evaluated using logistic regression. RESULTS: This cohort included 13,324 patients, of whom 9,232 patients (69.3%) were White (mean age, 65.7 years) and 4,092 patients (30.7%) were Black (mean age, 61.1 years). More Black than White patients showed a change in severity classification between approaches when using % predicted thresholds (20.2% vs 6.1%; P < .001), but not with z score thresholds (12.6% vs 12.3%; P = .68). An increased severity classification with a race-neutral approach was associated with increased risk of exacerbation when using z score thresholds (OR, 2.34; 95% CI, 1.51-3.63), but not when using % predicted thresholds (OR, 1.08; 95% CI, 0.61-1.93). A decreased severity classification with a race-neutral approach was associated with lower risk of exacerbation with both % predicted (OR, 0.49; 95% CI, 0.28-0.87) and z score (OR 0.67; 95% CI, 0.50-0.90) thresholds. INTERPRETATION: The proportions of Black and White individuals reclassified were similar with z score thresholds, and changes in severity corresponded to clinical risk with z scores. These results support recent recommendations for use of race-neutral equations and z score thresholds for spirometry interpretation.

Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT).

BACKGROUND: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics. METHODS: In DISRUPT, a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of IV exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at Day 14 in the MRSA population. RESULTS: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at Day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) vs. 60.6% (antibiotics alone; 20/33) (P = 0.392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported. CONCLUSIONS: Exebacase + antibiotics failed to improve clinical response at Day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of Day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis.

Assessing meaningful change in the Asthma Impairment and Risk Questionnaire.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, yes/no, equally weighted control tool. Lower scores indicate better control. Moreover, 7 impairment items reflect previous 2-week symptoms, and 3 risk items assess previous 12-month exacerbations. The Follow-up AIRQ for use between annual assessments has a 3-month recall period for exacerbation items. OBJECTIVE: To evaluate the responsiveness of the AIRQ over time and identify a minimal important difference (MID). METHODS: The AIRQ longitudinal study data were analyzed from patients with asthma aged 12 years and older. Anchor-based methods assessed differences in AIRQ scores relative to Patient Global Impression of Change, the accepted MIDs for St. George's Respiratory Questionnaire and Asthma Control Test, and exacerbation occurrence over 12 months. Baseline and 12-month data reflected 12-month recall AIRQ scores; Follow-up AIRQ scores were used for 3-, 6-, and 9-month analyses. RESULTS: A total of 1070 patients were included. The Patient Global Impression of Change rating of "much improved" was associated with AIRQ mean score changes from baseline to months 3, 6, 9, and 12 of -2.0, -1.9, -1.9, and -1.8, respectively. The mean AIRQ score change among patients who met the St. George's Respiratory Questionnaire MID (≥4-point decrease) was -1.8 at 6 and 12 months. The AIRQ mean scores decreased from baseline by -2.2 to -2.5 points at months 3, 6, 9, and 12 for patients who met the Asthma Control Test MID (≥ 3-point increase). A 2-point higher baseline AIRQ score was associated with a 1.7 odds ratio of 12-month exacerbation occurrence (95% CI, 1.53-1.89). CONCLUSION: A change score of 2 is recommended as the AIRQ MID.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Diffusing Capacity as a Predictor of Hospitalizations in a Clinical Cohort of Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) hospitalizations are a major burden on patients. Diffusing capacity of the lung for carbon monoxide (DlCO) is a potential predictor that has not been studied in large cohorts. Objectives: This study used electronic health record data to evaluate whether clinically obtained DlCO predicts COPD hospitalizations. Methods: We performed time-to-event analyses of individuals with COPD and DlCO measurements from the Johns Hopkins COPD Precision Medicine Center of Excellence. Cox proportional hazard methods were used to model time from DlCO measurement to first COPD hospitalization and composite first hospitalization or death, adjusting for age, sex, race, body mass index, smoking status, forced expiratory volume in 1 second (FEV1), history of prior COPD hospitalization, and comorbidities. To identify the utility of including DlCO in risk models, area under the receiver operating curve (AUC) values were calculated for models with and without DlCO. Results were externally validated in a separate analogous cohort. Results: Of 2,793 participants, 368 (13%) had a COPD hospitalization within 3 years. In adjusted analyses, for every 10% decrease in DlCO% predicted, risk of COPD hospitalization increased by 10% (hazard ratio, 1.1; 95% confidence interval, 1.1-1.2; P < 0.001). Similar associations were observed for COPD hospitalizations or death. The model including demographics, comorbidities, FEV1, DlCO, and prior COPD hospitalizations performed well, with an AUC of 0.85 and an AUC of 0.84 in an external validation cohort. Conclusions: Diffusing capacity is a strong predictor of COPD hospitalizations in a clinical cohort of individuals with COPD, independent of airflow obstruction and prior hospitalizations. These findings support incorporation of DlCO in risk assessment of patients with COPD.

Analysis of a 5-year, evidenced-based, rational blood utilisation project in a South African regional hospital.

BACKGROUND: Blood products are a lifesaving but limited resource, particularly in resource-limited settings. Evidence-based transfusion criteria tailored to local hospitals have shown great promise in reducing costs, minimising shortages, and ameliorating the morbidity and mortality associated with liberal blood product usage. We implemented the "Saving Blood, Saving Lives" project to: promote responsible blood product use and reduce blood product ordering inefficiencies and expenditure. METHODS: A comprehensive change management programme, preceded by 3 months of clinical department consultation and training, was implemented. A new evidence-based protocol for blood product utilisation was developed, together with an accountability form. This form was used in monthly audit meetings to refine policies, identify new problems, improve communication, and to drive hospital staff accountability and training. The primary measure of the programme's success was the change in the number of red cell concentrate units ordered. RESULTS: Project implementation required minimal time and no additional budget or staff. Annual red cell concentrate usage reduced from 7211 units in year one to 4077 units in year 5 (p < 0.001). Similar reductions were seen in freeze-dried plasma and platelet usage, as well as administrative costs. Total project saving, adjusted to baseline admission numbers, amounted to over R46 million ($2.5 million). CONCLUSIONS: As a change management programme centred the "Saving Blood, Saving Lives" project, was able to significantly reduce blood product-related administration and expenditure by implementing evidence-based transfusion criteria. The programme is simple, replicable and cost effective, making it ideally suited for use in resource-constrained environments.

Clonal Somatic Mutations in Chronic Lung Diseases Are Associated with Reduced Lung Function.

Rationale: Constantly exposed to the external environment and mutagens such as tobacco smoke, human lungs have one of the highest somatic mutation rates among all human organs. However, the relationship of these mutations to lung disease and function is not known. Objectives: To identify the prevalence and significance of clonal somatic mutations in chronic lung diseases. Methods: We analyzed the clonal somatic mutations from 1,251 samples of normal and diseased noncancerous lung tissue RNA sequencing with paired whole-genome sequencing from the Lung Tissue Research Consortium. We examined the associations of somatic mutations with lung function, disease status, and computationally deconvoluted cell types in two of the most common diseases represented in our dataset, chronic obstructive pulmonary disease (COPD; 29%) and idiopathic pulmonary fibrosis (IPF; 13%). Measurements and Main Results: Clonal somatic mutational burden was associated with reduced lung function in both COPD and IPF. We identified an increased prevalence of clonal somatic mutations in individuals with IPF compared with normal control subjects and individuals with COPD independent of age and smoking status. IPF clonal somatic mutations were enriched in disease-related and airway epithelial-expressed genes such as MUC5B in IPF. Patients who were MUC5B risk variant carriers had increased odds of developing somatic mutations of MUC5B that were explained by increased expression of MUC5B. Conclusions: Our identification of an increased prevalence of clonal somatic mutation in diseased lung that correlates with airway epithelial gene expression and disease severity highlights for the first time the role of somatic mutational processes in lung disease genetics.

In Vitro Validation of a Novel Continuous Intra-Abdominal Pressure Measurement System (TraumaGuard).

Introduction: Intra-abdominal pressure (IAP) has been recognized as an important vital sign in critically ill patients. Due to the high prevalence and incidence of intra-abdominal hypertension in surgical (trauma, burns, cardiac) and medical (sepsis, liver cirrhosis, acute kidney injury) patients, continuous IAP (CIAP) monitoring has been proposed. This research was aimed at validating a new CIAP monitoring device, the TraumaGuard from Sentinel Medical Technologies, against the gold standard (height of a water column) in an in vitro setting and performing a comparative analysis among different CIAP measurement technologies (including two intra-gastric and two intra-bladder measurement devices). A technical and clinical guideline addressing the strengths and weaknesses of each device is provided as well. Methods: Five different CIAP measurement devices (two intra-gastric and three intra-vesical), including the former CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, were validated against the gold standard water column pressure in a bench-top abdominal phantom. The impacts of body temperature and bladder fill volume (for the intra-vesical methods) were evaluated for each system. Subsequently, 48 h of continuous monitoring (n = 2880) on top of intermittent IAP (n = 300) readings were captured for each device. Using Pearson's and Lin's correlations, concordance, and Bland and Altman analyses, the accuracy, precision, percentage error, correlation and concordance coefficients, bias, and limits of agreement were calculated for all the different devices. We also performed error grid analysis on the CIAP measurements to provide an overview of the involved risk level due to wrong IAP measurements and calculated the area under the curve and time above a certain IAP threshold. Lastly, the robustness of each system in tracking the dynamic variations of the raw IAP signal due to respirations and heartbeats was evaluated as well. Results: The TraumaGuard was the only technology able to measure the IAP with an empty artificial bladder. No important temperature dependency was observed for the investigated devices except for the Spiegelberg, which displayed higher IAP values when the temperature was increased, but this could be adjusted through recalibration. All the studied devices showed excellent ability for IAP monitoring, although the intra-vesical IAP measurements seem more reliable. In general, the TraumaGuard, Accuryn, and Serenno showed better accuracy compared to intra-gastric measurement devices. On average, biases of +0.71, +0.93, +0.29, +0.25, and -0.06 mm Hg were observed for the CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, respectively. All of the equipment showed percentage errors smaller than 25%. Regarding the correlation and concordance coefficients, the Serenno and TraumaGuard showed the best results (R2 = 0.98, p = 0.001, concordance coefficient of 99.5%). Error grid analysis based on the Abdominal Compartment Society guidelines showed a very low associated risk level of inappropriate treatment strategies due to erroneous IAP measurements. Regarding the dynamic tracings of the raw IAP signal, all the systems can track respiratory variations and derived parameters; however, the CiMON was slightly superior compared to the other technologies. Conclusions: According to the research guidelines of the Abdominal Compartment Society (WSACS), this in vitro study shows that the TraumaGuard can be used interchangeably with the gold standard for measuring continuous IAP, even in an empty artificial bladder. Confirmation studies with the TraumaGuard in animals and humans are warranted to further validate these findings.

"It's a cause I believe in": factors motivating participation and engagement in longitudinal, respiratory-focused research studies.

BACKGROUND: Key to the success of any prospective cohort study is the effective recruitment and retention of participants, but the specific factors that influence younger adults of the Millennial generation to participate in research are not well-understood. The objective of this qualitative study was to identify factors that motivated participation and engagement in longitudinal research studies focused on respiratory health among a diverse group of young adults. METHODS: We conducted qualitative, semi-structured interviews with 50 younger adult participants (aged 25-35 years) regarding factors influencing their participation in longitudinal research studies. Thematic analysis was used to develop, organize, and tabulate the frequency of key themes. In exploratory analyses, we examined for patterns in the distribution of key themes across racial, ethnic, or socioeconomic groups. RESULTS: Participants identified several key themes that affected their willingness to participate in longitudinal studies. These included the health-related benefits generated by research (both to the individual and to society at-large), factors related to the institution and study team conducting the research, concerns regarding unethical and/or unrepresentative study design, and barriers to participation in research. Certain factors may be more impactful to underrepresented groups, including concerns regarding data privacy and confidentiality. CONCLUSIONS: In this diverse group of younger adults, we identified specific factors that motivated participation and predicted high engagement in longitudinal research studies focused on respiratory health. Implementing and integrating these factors into study protocols may improve recruitment and retention, including among participants who are historically underrepresented in research.

Bronchodilator response does not associate with asthma control or symptom burden among patients with poorly controlled asthma.

PURPOSE: The purpose of this study was to determine how four different definitions of bronchodilator response (BDR) relate to asthma control and asthma symptom burden in a large population of participants with poorly controlled asthma. PROCEDURES: We examined the baseline change in FEV1 and FVC in response to albuterol among 931 participants with poorly controlled asthma pooled from three clinical trials conducted by the American Lung Association - Airways Clinical Research Centers. We defined BDR based on four definitions and analyzed the association of each with asthma control as measured by the Asthma Control Test or Asthma Control Questionnaire, and asthma symptom burden as measured by the Asthma Symptom Utility Index. MAIN FINDINGS: A BDR was seen in 31-42% of all participants, depending on the definition used. There was good agreement among responses (kappa coefficient 0.73 to 0.87), but only 56% of participants met all four definitions for BDR. A BDR was more common in men than women, in Blacks compared to Whites, in non-smokers compared to smokers, and in non-obese compared to obese participants. Among those with poorly controlled asthma, 35% had a BDR compared to 25% of those with well controlled asthma, and among those with a high symptom burden, 34% had a BDR compared to 28% of those with a low symptom burden. After adjusting for age, sex, height, race, obesity and baseline lung function, none of the four definitions was associated with asthma control or symptom burden. CONCLUSION: A BDR is not associated with asthma control or symptoms in people with poorly controlled asthma, regardless of the definition of BDR used. These findings question the clinical utility of a BDR in assessing asthma control and symptoms.

The pathophysiological impact of intra-abdominal hypertension in pigs.

BACKGROUND: Intra-abdominal hypertension and abdominal compartment syndrome are common with clinically significant consequences. We investigated the pathophysiological effects of raised IAP as part of a more extensive exploratory animal study. The study design included both pneumoperitoneum and mechanical intestinal obstruction models. METHODS: Forty-nine female swine were divided into six groups: a control group (Cr; n = 5), three pneumoperitoneum groups with IAPs of 20mmHg (Pn20; n = 10), 30mmHg (Pn30; n = 10), 40mmHg (Pn40; n = 10), and two mechanical intestinal occlusion groups with IAPs of 20mmHg (MIO20; n = 9) and 30mmHg (MIO30; n = 5). RESULTS: There were significant changes (p<0.05) noted in all organ systems, most notably systolic blood pressure (SBP) (p<0.001), cardiac index (CI) (p = 0.003), stroke volume index (SVI) (p<0.001), mean pulmonary airway pressure (MPP) (p<0.001), compliance (p<0.001), pO2 (p = 0.003), bicarbonate (p = 0.041), hemoglobin (p = 0.012), lipase (p = 0.041), total bilirubin (p = 0.041), gastric pH (p<0.001), calculated glomerular filtration rate (GFR) (p<0.001), and urine output (p<0.001). SVV increased progressively as the IAP increased with no obvious changes in intravascular volume status. There were no significant differences between the models regarding their impact on cardiovascular, respiratory, renal and gastrointestinal systems. However, significant differences were noted between the two models at 30mmHg, with MIO30 showing worse metabolic and hematological parameters, and Pn30 and Pn40 showing a more rapid rise in creatinine. CONCLUSIONS: This study identified and quantified the impact of intra-abdominal hypertension at different pressures on several organ systems and highlighted the significance of even short-lived elevations. Two models of intra-abdominal pressure were used, with a mechanical obstruction model showing more rapid changes in metabolic and haematological changes. These may represent different underlying cellular and vascular pathophysiological processes, but this remains unclear.