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In the United States, the coronavirus disease-2019 (COVID-19) pandemic has disproportionally affected Black, Latinx, and Indigenous populations, immigrants, and economically disadvantaged individuals. Such historically marginalized groups are more often employed in low-wage jobs without health insurance and have higher rates of infection, hospitalization, and death from COVID-19 than non-Latinx White individuals. Mistrust in the health care system, language barriers, and limited health literacy have hindered vaccination rates in minorities, further exacerbating health disparities rooted in structural, institutional, and socioeconomic inequities. In this article, we discuss the lessons learned over the last 2years and how to mitigate health disparities moving forward.

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function.

Antiphospholipid syndrome (APLS) is an acquired is auto immune disorder that is defined by the presence of antibodies known as antiphospholipid antibodies in addition to clinical thrombosis and/ or poor obstetric outcome. Although the incidence remains unknown, 10% to 15% of women with a history of recurrent pregnancy loss will meet the criteria for APLS. In these Patients, the annual incidence of deep vein thrombosis and stroke is 1.46% and 0.32% respectively. Compared with the annual incidence in the general population of 0.1% for deep vein thrombosis and 0.1% for stroke.1

Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.

Aim: The aim of this study was to assess effectiveness of foot massage on incisional pain and sleep pattern among post caesarean mothers. Background: Cesarean section (C.S) is the birth of fetus through a trans-abdominal incision in the uterus. Persistent post-operative pain is a well- known consequence of caesarean section. Some studies have found alternative methods such as acuapressure, aromatherapy and massage therapy to be fairly effective for treatment of post caesarean pain and improve the quality of sleep pattern. Foot massage appears to be effective, in expensive, low risk, flexible and easily applied. So, foot massage was used to assess its effect on incisional pain and sleep pattern among post caesarean mothers. Design: A quasi-experimental pretest-posttest control group research design was used with non-probability purposive sampling technique to selected sample. Material and Methods: Sample of 60 post caesarean mothers from selected hospitals, 30 each in experimental group and control group were selected. Assessment of level of incisional pain was done by using standardized numerical pain rating scale whereas assessment of sleep pattern was done by using modified Groningen sleep quality index scale. Analysis was done by using both descriptive and inferential statistics. Findings: Findings showed that in experimental group, 93.24% post caesarean mothers had mild level of pain and 6.66% had moderate level of incisional pain. Whereas in control group, 40% had mild level of pain and 60% had moderate level of pain. On the other hand, 93.33 % post caesarean mothers had good sleep and 6.66% had poor quality of sleep pattern. Whereas in control group 100% post caesarean mothers had poor sleep pattern. Conclusion: Thus, the study concluded that the difference between mean pretest and posttest score was found statistically significant at p < 0.05 level in experimental group. Hence, research hypothesis was accepted and it revealed that there was impact of foot massage among post caesarean mothers in experimental group.

Rationale: Hypoxemia associated with acute exacerbations of chronic obstructive pulmonary disease (COPD) often resolves with time. Current guidelines recommend that patients recently discharged with supplemental home oxygen after hospitalization should not have renewal of the prescription without assessment for hypoxemia. Understanding patterns of home oxygen reassessment is an opportunity to improve quality and value in home oxygen prescribing and may provide future targets for deimplementation. Objectives: We sought to measure the frequency of home oxygen reassessment within 90 days of hospitalization for COPD and determine the potential population eligible for deimplementation. Methods: We performed a cohort study of patients ≥40 years hospitalized for COPD at five Veterans Affairs facilities who were prescribed home oxygen at discharge. Our primary outcome was the frequency of reassessment within 90 days by oxygen saturation (Sp(O(2))) measurement. Secondary outcomes included the proportion of patients potentially eligible for discontinuation (Sp(O(2)) > 88%) and patients in whom oxygen was discontinued. Our primary exposures were treatment with long-acting bronchodilators, prior history of COPD exacerbation, smoking status, and pulmonary hypertension. We used a mixed-effects Poisson model to measure the association between patient-level variables and our outcome, clustered by site. We also performed a positive deviant analysis using chart review to uncover system processes associated with high-quality oxygen prescribing. Results: A total of 287 of 659 (43.6%; range 24.8–78.5% by site) patients had complete reassessment within 90 days. None of our patient-level exposures were associated with oxygen reassessment. Nearly half of those with complete reassessment were eligible for discontinuation on the basis of Medicare guidelines (43.2%; n = 124/287). When using the newest evidence available by the Long-Term Oxygen Treatment Trial, most of the cohort did not have resting hypoxemia (84.3%; 393/466) and would be eligible for discontinuation. The highest-performing Veterans Affairs facility had four care processes to support oxygen reassessment and discontinuation, versus zero to one at all other sites. Conclusions: Fewer than half of patients prescribed home oxygen after a COPD exacerbation are reassessed within 90 days. New system processes supporting timely reassessment and discontinuation of unnecessary home oxygen therapy could improve the quality and value of care.

Study Objectives Sleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures. Methods We included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity–Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality. Results After adjustment for all co-variates, increasing PSQI scores (range 0–21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035). Conclusions Poor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control. Clinical Trial Registration Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/.

Rationale: African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives: To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods: In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George's Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. Measurements and Main Results: Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson's Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P

Introduction Primary care-based interventions that promote nurturing caregiving relationships and early relational health may help mitigate toxic stress and promote resilience in children. This pilot study aims to: (1) describe a novel group-based, psychoeducational primary care intervention for children experiencing adverse childhood experiences (ACEs) (“The Resiliency Clinic”), (2) assess program feasibility and acceptability, and (3) explore effects on child/caregiver behavioral health. Methods Intervention design centered on promoting supportive caregiving, caregiver/child self-regulation and co-regulation and teaching evidence-based stress management tools. Program feasibility and acceptability were assessed through attendance data and caregiver focus groups. Behavioral health measures were obtained at baseline and 8-month follow-up. Results Of 101 eligible families, 38 (37.6%) enrolled and attended a median of 3.00 (mean = 2.95, sd = 1.75) out of 6 sessions. Caregivers reported high satisfaction and benefits including stress management tools and connection with staff and other parents. There were modest, statistically non-significant improvements in caregiver stress (d = 0.23) and child executive functioning (d = 0.27). Discussion In conclusion, a group intervention teaching supportive caregiving and stress mitigation is feasible and acceptable for many families in an urban federally qualified health center (FQHC) with a signal for modest improvements in behavioral health. Future program iterations will seek to address participation barriers and expand the intervention’s capacity to promote early relational health.

The practice of using race or ethnicity in medicine to explain differences between individuals is being called into question because it may contribute to biased medical care and research that perpetuates health disparities and structural racism. A commonly cited example is the use of race or ethnicity in the interpretation of pulmonary function test (PFT) results, yet the perspectives of practicing pulmonologists and physiologists are missing from this discussion. This discussion has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain. We review the underlying sources of differences in lung function, including those that may be captured by race or ethnicity, and demonstrate how the current practice of PFT measurement and interpretation is imperfect in its ability to describe accurately the relationship between function and health outcomes. We summarize the arguments against using race-specific equations as well as address concerns about removing race from the interpretation of PFT results. Further, we outline knowledge gaps and critical questions that need to be answered to change the current approach of including race or ethnicity in PFT results interpretation thoughtfully. Finally, we propose changes in interpretation strategies and future research to reduce health disparities.

Black, Latinx, and Indigenous people in the United States experience a disproportionate burden of asthma and atopic dermatitis. The study of these disease disparities has focused on proximal socioenvironmental exposures and on the biomechanistic (including genetic) differences between racial and ethnic groups. Although biomedical research in allergy and immunology stands to benefit from the inclusion of diverse study populations, the narrow focus on biologic mechanisms disregards the complexity of interactions across biologic and structural factors, including the effects of structural racism. Structural racism is the totality of ways in which society fosters discrimination by creating and reinforcing inequitable systems through intentional policies and practices sanctioned by government and institutions. It is embedded across multiple levels, including the economic, educational, health care, and judicial systems, which are manifested in inequity in the physical and social environment. In this review, we present a conceptual framework and pull from the literature to demonstrate how structural racism is a root cause of atopic disease disparities by way of residential segregation, socioeconomic position, and mass incarceration, which may lead to aberrations in the innate and adaptive immune response and the augmentation of physiologic stress responses, contributing to a disproportionate disease burden for racial and ethnic populations.

Background: Well-designed clinical research needs to obtain information that is applicable to the general population. However, most current studies fail to include substantial cohorts of racial/ethnic minority populations. Such underrepresentation may lead to delayed diagnosis or misdiagnosis of disease, wide application of approved interventions without appropriate knowledge of their usefulness in certain populations, and development of recommendations that are not broadly applicable. Goals: To develop best practices for recruitment and retention of racial/ethnic minorities for clinical research in pulmonary, critical care, and sleep medicine. Methods: The American Thoracic Society convened a workshop in May of 2019. This included an international interprofessional group from academia, industry, the NIH, and the U.S. Food and Drug Administration, with expertise ranging from clinical and biomedical research to community-based participatory research methods and patient advocacy. Workshop participants addressed historical and current mistrust of scientific research, systemic bias, and social and structural barriers to minority participation in clinical research. A literature search of PubMed and Google Scholar was performed to support conclusions. The search was not a systematic review of the literature. Results: Barriers at the individual, interpersonal, institutional, and federal/policy levels were identified as limiting to minority participation in clinical research. Through the use of a multilevel framework, workshop participants proposed evidence-based solutions to the identified barriers. Conclusions: To date, minority participation in clinical research is not representative of the U.S. and global populations. This American Thoracic Society research statement identifies potential evidence-based solutions by applying a multilevel framework that is anchored in community engagement methods and patient advocacy.

BackgroundAsthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.ObjectiveWe sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.MethodsWe leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.ResultsWe identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P=6.8×10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P=.002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P=.008). Our findings were replicated in an independent childhood asthma study in Latinos (P=5.3×10-3, combined P=2.6×10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P&nbsp

BackgroundAir pollution exposure is associated with disease severity, progression and mortality in patients with idiopathic pulmonary fibrosis (IPF). Combined impacts of environmental and socioeconomic factors on outcomes in patients with IPF are unknown. The objectives of this study were to characterise the relationships between relative environmental and social disadvantage with clinical outcomes in patients with IPF.MethodsPatients with IPF were identified from a longitudinal database at University of California, San Francisco. Residential addresses were geocoded and linked to the CalEnviroScreen 3.0 (CES), a tool that quantifies environmental burden in California communities, combining population, environmental and pollution vulnerability into individual and composite scores (higher scores indicating greater disadvantage). Unadjusted and adjusted linear and logistic regression and Fine and Gray proportional hazards models were used.Results603 patients were included. Higher CES was associated with lower baseline forced vital capacity ( β =−0.073, 95% CI −0.13 to −0.02; p=0.006) and diffusion capacity of the lung for carbon monoxide ( β =−0.11, 95% CI −0.16 to −0.06; pConclusionsHigher environmental exposures and vulnerability were associated with lower baseline lung function and lower antifibrotic use, suggesting that relative socioenvironmental disadvantage has meaningful impacts on patients with IPF.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

Objective: Asthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the high­est asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor broncho­dilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environ­ment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions as­sociated with BDR in Puerto Rican children with asthma. Setting: Genetic, environmental, and psycho-social data from the Genes-environ­ments and Admixture in Latino Americans (GALA II) case-control study. Participants: Our discovery dataset con­sisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma. Main Outcomes Measures: We assessed the association of pairwise interaction mod­els with BDR using ViSEN (Visualization of Statistical Epistasis Networks). Results: We identified a non-linear interac­tion between Native American genetic ancestry and air pollution significantly as­sociated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population. Conclusions: Decreased Native American ancestry coupled with increased air pollu­tion exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR’s phenotypic complexity, and emphasizes the importance of integrating social, environmental, and bi­ological data to further our understanding of complex disease. Ethn Dis. 2021;31(1):77- 88; doi:10.18865/ed.31.1.77

Author(s): Thakur, Neeta; Lovinsky-Desir, Stephanie; Bime, Christian; Wisnivesky, Juan P; Celedon, Juan C

Author(s): Vanderburg, Sky; Alipanah, Narges; Crowder, Rebecca; Yoon, Christina; Wang, Richard; Thakur, Neeta; Slown, Kristin; Shete, Priya B; Rofael, Martin; Metcalfe, John Z; Merrifield, Cindy; Marquez, Carina; Malcolm, Katherine; Lipnick, Michael; Jain, Vivek; Gomez, Antonio; Burns, Gregory; Brown, Lillian B; Berger, Christopher; Auyeung, Vincent; Cattamanchi, Adithya; Hendrickson, Carolyn M | Abstract: BACKGROUND:Following early implementation of public health measures, San Francisco has experienced a slow rise and a low peak level of coronavirus disease 2019 (COVID-19) cases and deaths. METHODS AND FINDINGS:We included all patients with COVID-19 pneumonia admitted to the intensive care unit (ICU) at the safety net hospital for San Francisco through April 8, 2020. Each patient had ≥15 days of follow-up. Among 26 patients, the median age was 54 years (interquartile range, 43 to 62), 65% were men, and 77% were Latinx. Mechanical ventilation was initiated for 11 (42%) patients within 24 hours of ICU admission and 20 patients (77%) overall. The median duration of mechanical ventilation was 13.5 days (interquartile range, 5 to 20). Patients were managed with lung protective ventilation (tidal volume l8 ml/kg of ideal body weight and plateau pressure ≤30 cmH2O on 98% and 78% of ventilator days, respectively). Prone positioning was used for 13 of 20 (65%) ventilated patients for a median of 5 days (interquartile range, 2 to 10). Seventeen (65%) patients were discharged home, 1 (4%) was discharged to nursing home, 3 (12%) were discharged from the ICU, and 2 (8%) remain intubated in the ICU at the time of this report. Three (12%) patients have died. CONCLUSIONS:Good outcomes were achieved in critically ill patients with COVID-19 by using standard therapies for acute respiratory distress syndrome (ARDS) such as lung protective ventilation and prone positioning. Ensuring hospitals can deliver sustained high-quality and evidence-based critical care to patients with ARDS should remain a priority.

BackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables.ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 617 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to identify interaction effects. We performed analyses in the full dataset and in sex-stratified subsets. Analysis in the full dataset identified six significant interactions associated with BDR, the strongest of which was an interaction between prenatal smoke exposure, age, and global African ancestry (IG: 1.09%, p=0.005). Sex-stratified analyses yielded additional significant, but divergent, results for females and males, indicating the presence of sex-specific effects.ConclusionsOur study identified novel interaction effects significantly influencing BDR in African American children with asthma. Notably, we found that the impact of higher-order interactions was greater than that of pairwise or main effects on BDR highlighting the complexity of the network of genetic and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods emphasizing the importance of employing statistical methods optimized to detect both linear and non-linear interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

Purpose of ReviewUsing the WHO Conceptual Framework for Action on the Social Determinants of Health, this review provides a discussion of recent epidemiologic, mechanistic, and intervention studies of structural and social determinants of health and asthma outcomes covering the period from 2014 to 2019.Recent FindingsA majority of studies and interventions to date focus on the intermediary determinants of health (e.g., housing), which as the name suggests, exist between the patient and the upstream structural determinants of health (e.g., housing policy). Race/ethnicity remains a profound social driver of asthma disparities with cumulative risk from many overlapping determinants. A growing number of studies on asthma are beginning to elucidate the underlying mechanisms that connect social determinants to human disease. Several effective interventions have been developed, though a need for large-scale policy research and innovation remains.SummaryStrong evidence supports the key role of the structural determinants, which generate social stratification and inequity, in the development and progression of asthma; yet, interventions in this realm are challenging to develop and therefore infrequent. Proximal, intermediary determinants have provided a natural starting point for interventions, though structural interventions have the most potential for major impact on asthma outcomes. Further research to investigate the interactive effect of multiple determinants, as well as intervention studies, specifically those that are cross-sector and propose innovative strategies to target structural determinants, are needed to address asthma morbidities, and more importantly, close the asthma disparity gap.

Background Asthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables. Results We evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 233 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to quantify interaction effects using an information-theory metric known as Information Gain (IG). We performed analyses in the full dataset and in sex-stratified subsets. Our analyses identified several interaction models significantly, and suggestively, associated with BDR. The strongest interaction significantly associated with BDR was a pairwise interaction between pre-natal smoke exposure and socioeconomic status (full dataset IG: 2.78%, p = 0.001; female IG: 7.27%, p = 0.004)). Sex-stratified analyses yielded divergent results for females and males, indicating the presence of sex-specific effects. Conclusions Our study identified novel interaction effects significantly, and suggestively, associated with BDR in African American children with asthma. Notably, we found that all of the interactions identified by ViSEN were “pure” interaction effects, in that they were not the result of strong main effects on BDR, highlighting the complexity of the network of biological and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods, thus emphasizing the importance of employing statistical methods optimized to detect both additive and non-additive interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

Cancer disparities research is motivated by persistent inequities in cancer outcomes by race, ethnicity, social status, neighborhood location, and other subpopulation characteristics. These inequities have proven to be persistent and difficult to alter. Part of the reason for the frustration with slow progress is a lack of appreciation of the long-term nature of the undertaking. It is highly likely that the disparities observed in adulthood find their origins in young adulthood, if not earlier. A long-term perspective is needed, recognizing that successes may take many years to realize. This commentary presents the experience of the Center for Health And Risk in Minority youth and young adults project, which is a comprehensive center of excellence funded by the National Institute of Minority Health and Health Disparities for addressing disparities and chronic disease prevention in minority youth and young adults. The use of logic models is advanced for this kind of research because they can provide a theory of change and illustrate the course of knowledge translation over time. Logic models for cancer disparities research can place individual project activities in a realistic context that at one time indicates what is possible and reasonable to expect during the duration of a typical research project as well as the future steps that need to be taken on the way to an expected ultimate impact on cancer inequities.

Background Asthma disproportionately affects minority populations and is associated with psychosocial stress such as racial/ethnic discrimination. We aimed to examine the association of perceived discrimination with asthma and poor asthma control in African American and Latino youth. Methods We included African American (n = 954), Mexican American (n = 1,086), other Latino (n = 522), and Puerto Rican Islander (n = 1,025) youth aged 8 to 21 years from the Genes-Environments and Admixture in Latino Americans study and the Study of African Americans, Asthma, Genes, and Environments. Asthma was defined by physician diagnosis, and asthma control was defined based on the National Heart, Lung, and Blood Institute guidelines. Perceived racial/ethnic discrimination was assessed by the Experiences of Discrimination questionnaire, with a focus on school, medical, and public settings. We examined the associations of perceived discrimination with each outcome and whether socioeconomic status (SES) and global African ancestry modified these associations. Results African American children reporting any discrimination had a 78% greater odds of experiencing asthma (OR, 1.78; 95% CI, 1.33-2.39) than did those not reporting discrimination. Similarly, African American children faced increased odds of poor asthma control with any experience of discrimination (OR, 1.97; 95% CI, 1.42-2.76) over their counterparts not reporting discrimination. These associations were not observed among Latino children. We observed heterogeneity of the association between reports of discrimination and asthma according to SES, with reports of discrimination increasing the odds of having asthma among low-SES Mexican American youth (interaction P = .01) and among high-SES other Latino youth (interaction P = .04). Conclusions Perceived discrimination is associated with increased odds of asthma and poorer control among African American youth. SES exacerbates the effect of perceived discrimination on having asthma among Mexican American and other Latino youth.

Background Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures. Objective We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups. Methods We included 1849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1136 Mexican Americans, and 218 other Latino children) aged 8 to 21 years from 4 urban regions in the United States. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the United States. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study), adjusting for demographic, socioenvironmental, and clinical variables. Results For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the United States), greater levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (P = .009 and .02, respectively). Similarly, high language acculturation was associated with increased FEV1 compared with low language acculturation (P = .02). There was insufficient evidence of heterogeneity for associations across Latino subgroups. Conclusions Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is an important factor to consider in the management of Latino youth with asthma.

RationaleAdverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking.ObjectivesTo assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry.MethodsThe study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry.Measurements and main resultsA 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function.ConclusionsEarly-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

Background Adverse Childhood Experiences (ACEs) are associated with behavioral, mental, and clinical outcomes in children. Tools that are easy to incorporate into pediatric practice, effectively screen for adversities, and identify children at high risk for poor outcomes are lacking. Objective To examine the relationship between caregiver-reported child ACEs and related life events with health outcomes. Participants and setting Participants (0–11 years) were recruited from the University of California San Francisco Benioff’s Children Hospital Oakland Primary Care Clinic. There were 367 participants randomized. Methods Participants were randomized 1:1:1 to item-level (item response), aggregate-level (total number of exposures), or no screening for ACEs (control arm) with the PEdiatric ACEs and Related Life Event Screener (PEARLS). We assessed 10 ACE categories capturing abuse, neglect, and household challenges, as well as 7 additional categories. Multivariable regression models were conducted. Results Participants reported a median of 2 (IQR 1–5) adversities with 76 % (n = 279) reporting at least one adversity; participants in the aggregate-level screening arm, on average, disclosed 1 additional adversity compared to item-level screening (p = 0.01). Higher PEARLS scores were associated with poorer perceived child general health (adjusted B = −0.94, 95 %CI: −1.26, −0.62) and Global Executive Functioning (adjusted B = 1.99, 95 %CI: 1.51, 2.46), and greater odds of stomachaches (aOR 1.14; 95 %CI: 1.04–1.25) and asthma (aOR 1.08; 95 %CI 1.00, 1.17). Associations did not differ by screening arm. Conclusion In a high-risk pediatric population, ACEs and other childhood adversities remain an independent predictor of poor health. Increased efforts to screen and address early-life adversity are necessary.