Examining the impact of air pollution, climate change, and social determinants of health on asthma and environmental justice.

PURPOSE OF REVIEW: In this review, we discuss the current literature examining the impact air pollution and climate change has on asthma onset, control, and exacerbation. This review also addresses the risk of exposure to specific disproportionately affected communities, highlighting health disparities in exposure and asthma outcomes. RECENT FINDINGS: Recent studies have shifted from highlighting the associations between asthma exacerbations and indoor and outdoor air pollution. Studies are now focused on confirming the association of asthma incidence from these same exposures. Many studies have linked particulate matter to adverse asthma outcomes, however, the pollutant exposures that pose the greatest risk and the effect of natural disasters fueled by climate change are under current study. Some studies have observed that the true burden that pollutant exposures have on asthma outcomes occurs at the intersection of exposure and vulnerability. Future studies in this area will address social determinants of health, societal factors such as redlining and other systemic racism practices. SUMMARY: Although decades of research support the causal link between gaseous and particulate air pollution and the exacerbation of preexisting asthma, recent studies suggest air pollution can cause incident (new onset) asthma. Studies have started to focus on the underlying drivers of poor outcomes in asthma. Many of the structural impediments to high quality asthma care at the society level (e.g. poverty, redlining, systemic racism) also are risk factors for worsened climate events and air pollution exposure. The individuals in these disproportionately affected groups are doubly affected by worsened exposure and worsened access to care for the resultant asthma exacerbations or incident asthma. More research is needed to understand the specific climate and air pollution mitigation efforts where disproportionately affected communities would derive the most benefit.

Real-life Assessment of BioFire FilmArray Pneumonia Panel in Adults Hospitalized With Respiratory Illness.

BACKGROUND: Inability to identify the microbial etiology of lower respiratory tract infection leads to unnecessary antibiotic use. We evaluated the utility of the BioFire FilmArray Pneumonia Panel (BioFire PN) to inform microbiologic diagnosis. METHODS: Hospitalized adults with respiratory illness were recruited; sputa and clinical/laboratory data were collected. Sputa were cultured for bacteria and tested with BioFire PN. Microbial etiology was adjudicated by 4 physicians. Bacterial polymerase chain reaction (PCR) was compared with culture and clinical adjudication. RESULTS: Of 298 sputa tested, BioFire PN detected significantly more pathogens (350 bacteria, 16 atypicals, and 164 viruses) than sputum culture plus any standard-of-care testing (91% vs 60%, P < .0001). When compared with culture, the sensitivity of BioFire PN for individual bacteria was 46% to 100%; specificity, 61% to 100%; and negative predictive value, 92% to 100%. Cases were adjudicated as viral (n = 58) and bacterial (n = 100). PCR detected bacteria in 55% of viral cases and 95% of bacterial (P < .0001). High serum procalcitonin and bacterial adjudication were more often associated with sputa with 106 or 107 copies detected. CONCLUSIONS: Multiplex PCR testing of sputa for bacteria is useful to rule out bacterial infection with added value to detect viruses and atypical bacteria.

Are Black and Latino adolescents being asked if they use electronic cigarettes and advised not to use them? Results from a community-based survey.

Objective: This study aimed to explore whether African American/Black and Hispanic/Latino adolescents are being asked about electronic cigarette (e-cigarette) use (vaping) and advised not to use them. Methods: In 2021, adolescents (N = 362) with no vaping history, self-identified as African American/Black and/or Hispanic/Latino, and able to read and speak English and/or Spanish were recruited through partner schools and community-based organizations. Participants completed a survey reporting sociodemographic characteristics (e.g., race/ethnicity, gender, and language of preference) and they were asked about e-cigarette use and/or were advised not to use them by a health professional. Results: In total, 12% of African American/Black and 5% of Hispanic/Latino participants reported not seeing a health professional in the year prior to enrollment. Of the participants who reported visiting a health professional, 50.8% reported being asked and advised about vaping. Over one-quarter (28.4%) of participants were neither asked nor advised regarding vaping. Compared to English-speaking participants, Spanish-speaking participants were significantly less likely to be asked about e-cigarette use (45.2 vs. 63.9%, p = 0.009) and advised not to use them (40.3 vs. 66.9%, p < 0.001). Moreover, compared to African American/Black participants, Hispanic/Latino participants were significantly less likely to be advised not to use e-cigarettes (52.9 vs. 68.6%, p = 0.018). Furthermore, compared to male participants, female participants were significantly less likely to be advised not to use e-cigarettes (51.3 vs. 68.2%, p = 0.003). Conclusion: Compared to English-speaking participants, Spanish-speaking participants were significantly less likely to self-report being asked about e-cigarette use and advised not to use them. Moreover, Hispanic/Latino and female adolescents were significantly less likely to self-report being advised not to use e-cigarettes compared to their Black/African American and male counterparts. Future research is needed to improve health professional attention toward asking about and advising against vaping among adolescents.

Towards a Race-Neutral System of Pulmonary Function Test Results Interpretation.

It has been observed widely that, on average, Black individuals in the United States have lower FVC than White individuals, which is thought to reflect a combination of genetic, environmental, and socioeconomic factors that are difficult to disentangle. Debate therefore persists even after the American Thoracic Society's 2023 guidelines recommending race-neutral pulmonary function test (PFT) result interpretation strategies. Advocates of race-based PFT results interpretation argue that it allows for more precise measurement and will minimize disease misclassification. In contrast, recent studies have shown that low lung function in Black patients has clinical consequences. Furthermore, the use of race-based algorithms in medicine in general is increasingly being questioned for its risk of perpetuating structural health care disparities. Given these concerns, we believe it is time to adopt a race-neutral approach, but note that more research is urgently needed to understand how race-neutral approaches impact PFT results interpretation, clinical decision-making, and patient outcomes. In this brief case-based discussion, we offer a few examples of how a race-neutral PFT results interpretation strategy will impact individuals from racial and ethnic minority groups at different scenarios and stages of life.

Effectively utilizing publicly available databases for cancer target evaluation.

The majority of compounds designed against cancer drug targets do not progress to become approved drugs, mainly due to lack of efficacy and/or unmanageable toxicity. Robust target evaluation is therefore required before progressing through the drug discovery process to reduce the high attrition rate. There are a wealth of publicly available databases that can be mined to generate data as part of a target evaluation. It can, however, be challenging to learn what databases are available, how and when they should be used, and to understand the associated limitations. Here, we have compiled and present key, freely accessible and easy-to-use databases that house informative datasets from in vitro, in vivo and clinical studies. We also highlight comprehensive target review databases that aim to bring together information from multiple sources into one-stop portals. In the post-genomics era, a key objective is to exploit the extensive cell, animal and patient characterization datasets in order to deliver precision medicine on a patient-specific basis. Effective utilization of the highlighted databases will go some way towards supporting the cancer research community achieve these aims.

The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

Gene Expression Risk Scores for COVID-19 Illness Severity.

BACKGROUND: The correlates of coronavirus disease 2019 (COVID-19) illness severity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are incompletely understood. METHODS: We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2 infection clinically adjudicated as having mild, moderate, or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and nonsevere COVID-19. RESULTS: Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus nonsevere illness, we identified >4000 genes differentially expressed (false discovery rate < 0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T-cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated receiver operating characteristic-area under the curve [ROC-AUC] = 0.98), and need for intensive care in an independent cohort (ROC-AUC = 0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort. CONCLUSIONS: These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.

Association between weight loss and mortality in idiopathic pulmonary fibrosis.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that has no cure. Many current research efforts center on diagnostic and therapeutic modalities for IPF while other risk factors affecting disease pathogenesis receive less attention. Emerging data support the clinical importance of weight loss in patients with IPF. However, factors associated with weight loss and the impact of weight loss on mortality remain incompletely explored. OBJECTIVES: Explore the association between weight loss and transplant-free survival in patients with IPF and identify clinical variables associated with weight loss in this population. METHODS: Kaplan-Meier and Cox proportional hazard regression analyses were generated and stratified by weight loss or use of antifibrotic medications. Conditional logistic regression was used to evaluate for factors associated with weight loss. RESULTS: There was a significant increase in mortality in patients who lost ≥ 5% of their body weight loss (HR 2.21, [1.29, 4.43] p = .021). The use of supplemental oxygen (adjusted OR 13.16), and ≥ 200 mL loss of FVC over 1 year (adjusted OR 5.44) were both associated with a ≥ 5% weight loss in the year following a diagnosis of IPF. The use of antifibrotic medication did not significantly change median transplant-free survival in patients who lost more than ≥ 5% of their body mass. CONCLUSIONS: Weight loss over the first year following a diagnosis of IPF is strongly associated with decreased transplant-free survival. More research is needed to determine the mechanisms surrounding weight loss in patients with IPF.

The effect of air pollution on the transcriptomics of the immune response to respiratory infection.

Combustion related particulate matter air pollution (PM) is associated with an increased risk of respiratory infections in adults. The exact mechanism underlying this association has not been determined. We hypothesized that increased concentrations of combustion related PM would result in dysregulation of the innate immune system. This epidemiological study includes 111 adult patients hospitalized with respiratory infections who underwent transcriptional analysis of their peripheral blood. We examined the association between gene expression at the time of hospitalization and ambient measurements of particulate air pollutants in the 28 days prior to hospitalization. For each pollutant and time lag, gene-specific linear models adjusting for infection type were fit using LIMMA (Linear Models For Microarray Data), and pathway/gene set analyses were performed using the CAMERA (Correlation Adjusted Mean Rank) program. Comparing patients with viral and/or bacterial infection, the expression patterns associated with air pollution exposure differed. Adjusting for the type of infection, increased concentrations of Delta-C (a marker of biomass smoke) and other PM were associated with upregulation of iron homeostasis and protein folding. Increased concentrations of black carbon (BC) were associated with upregulation of viral related gene pathways and downregulation of pathways related to antigen presentation. The pollutant/pathway associations differed by lag time and by type of infection. This study suggests that the effect of air pollution on the pathogenesis of respiratory infection may be pollutant, timing, and infection specific.

Gene Expression Risk Scores for COVID-19 Illness Severity.

BACKGROUND: The correlates of COVID-19 illness severity following infection with SARS-Coronavirus 2 (SARS-CoV-2) are incompletely understood. METHODS: We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2-infection clinically adjudicated as having mild, moderate or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and non-severe COVID. RESULTS: Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus non-severe illness, we identified >4000 genes differentially expressed (FDR<0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated ROC-AUC=0.98), and need for intensive care in an independent cohort (ROC-AUC=0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort. CONCLUSION: These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.

E-cigarette exposures, respiratory tract infections, and impaired innate immunity: a narrative review.

Electronic cigarettes (e-cigarettes) are commonly used devices by adolescents and young adults. Since their introduction, the popularity of e-cigarettes has increased significantly with close to twenty percent of United States high school students reporting current use in 2020. As the number of e-cigarette users has increased, so have reports of vaping related health complications. Overall, respiratory tract infections remain one of the top ten leading causes of death in the US for every age group. Specific to the pediatric population, lower respiratory tract infections are the leading cause for hospitalization. This review highlights the current evidence behind e-cigarette exposure and its association with impaired innate immune function and the risk of lower respiratory tract infections. To date, various preclinical models have evaluated the direct effects of e-cigarette exposure on the innate immune system. More specifically, e-cigarette exposure impairs certain cell types of the innate immune system including the airway epithelium, lung macrophage and neutrophils. Identified effects of e-cigarette exposure common to the lung's innate immunity include abnormal mucus composition, reduced epithelial barrier function, impaired phagocytosis and elevated systemic markers of inflammation. These identified impairments in the lung's innate immunity have been shown to increase adhesion of certain bacteria and fungi as well as to increase virulence of common respiratory pathogens such as influenza virus, Staphylococcus aureus or Streptococcus pneumoniae. Information summarized in this review will provide guidance to healthcare providers, policy advocates and researchers for making informed decisions regarding the associated respiratory health risks of e-cigarette use in pediatric and young adults.

Perceptions of Tobacco Product-Specific COVID-19 Risk and Changes in Tobacco Use Behaviors Among Smokers, E-Cigarette Users, and Dual Users.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) is a public health crisis, but its effects on tobacco users remain ill-defined. This report aimed to assess the relationship between tobacco product-specific risk perceptions for COVID-19 and changes in tobacco use since the start of the pandemic. METHODS: A sample (n = 776) of past-30 day exclusive smokers (n = 238), exclusive e-cigarette users (n = 143), and dual users (n = 395) residing in the US and aged 18 or older were collected using Mechanical Turk from April 27 to June 8, 2020. Adjusted associations between tobacco product-specific COVID-19 risk perceptions (ie risk that smokers/vapers are at for COVID-19 relative to non-smokers/non-vapers) and changes in tobacco use since the pandemic began were assessed using partial proportional odds models. RESULTS: A majority of those who used cigarettes (63.7%) and e-cigarettes (56.1%) felt that the risk of COVID-19 was greater for users of their tobacco product than for non-users. Twenty-four percent of smokers had increased their cigarette use since the start of the pandemic and 28.0% had decreased. Similarly, 27.3% of e-cigarette users had increased their e-cigarette use since the start of the pandemic and 23.8% had decreased. Higher risk perceptions for COVID-19 were associated with reductions in tobacco use since the pandemic began for exclusive e-cigarette users and dual users. CONCLUSIONS: These findings provide the support that tobacco product-specific COVID-19 risk perceptions may be an important correlate of changes in tobacco use during the pandemic. Targeted information to inform tobacco users regarding their risks for COVID-19 is needed during this public health crisis. IMPLICATIONS: Few published studies have investigated the relationship between tobacco product-specific risk perceptions for COVID-19 and changes in tobacco product use since the pandemic began. This study enhances the current literature by providing evidence that higher tobacco product-specific risk perceptions for COVID-19 are associated with reductions in tobacco use since the pandemic began for exclusive e-cigarette users and dual users of cigarettes and e-cigarettes. Additionally, daily tobacco users may be more likely to have increased their tobacco use than non-daily users. These findings emphasize the importance of disseminating targeted health information to tobacco users regarding COVID-19 risks.

Acute myocardial infarction associated with unconventional natural gas development: A natural experiment.

BACKGROUND: Whereas it is plausible that unconventional natural gas development (UNGD) may adversely affect cardiovascular health, little is currently known. We investigate whether UNGD is associated with acute myocardial infarction (AMI). METHODS: In this observational study leveraging the natural experiment generated by New York's ban on hydraulic fracturing, we analyzed the relationship between age- and sex-specific county-level AMI hospitalization and mortality rates and three UNGD drilling measures. This longitudinal panel analysis compares Pennsylvania and New York counties on the Marcellus Shale observed over 2005-2014 (N = 2840 county-year-quarters). RESULTS: A hundred cumulative wells is associated with 0.26 more hospitalizations per 10,000 males 45-54y.o. (95% CI 0.07,0.46), 0.40 more hospitalizations per 10,000 males 65-74y.o. (95% CI 0.09,0.71), 0.47 more hospitalizations per 10,000 females 65-74y.o. (95% CI 0.18,0.77) and 1.11 more hospitalizations per 10,000 females 75y.o.+ (95% CI 0.39,1.82), translating into 1.4-2.8% increases. One additional well per square mile is associated with 2.63 more hospitalizations per 10,000 males 45-54y.o. (95% CI 0.67,4.59) and 9.7 hospitalizations per 10,000 females 75y.o.+ (95% CI 1.92,17.42), 25.8% and 24.2% increases, respectively. As for mortality rates, a hundred cumulative wells is associated with an increase of 0.09 deaths per 10,000 males 45-54y.o. (95% CI 0.02,0.16), a 5.3% increase. CONCLUSIONS: Cumulative UNGD is associated with increased AMI hospitalization rates among middle-aged men, older men and older women as well as with increased AMI mortality among middle-aged men. Our findings lend support for increased awareness about cardiovascular risks of UNGD and scaled-up AMI prevention as well as suggest that bans on hydraulic fracturing can be protective for public health.

Neurodegenerative hospital admissions and long-term exposure to ambient fine particle air pollution.

PURPOSE: Long-term exposure to ambient fine particle (PM2.5) concentrations has been associated with an increased rate or risk of neurodegenerative conditions, but individual PM sources have not been previously examined in relation to neurodegenerative diseases. METHODS: Using the Statewide Planning and Research Cooperative System database, we studied 63,287 hospital admissions with a primary diagnosis of either Alzheimer's disease, dementia, or Parkinson's disease for New York State residents living within 15 miles from six PM2.5 monitoring sites. In addition to PM2.5 concentrations, we studied seven specific PM2.5 sources: secondary sulfate, secondary nitrate, biomass burning, diesel, spark-ignition emissions, pyrolyzed organic rich, and road dust. We estimated the rate of neurodegenerative hospital admissions associated with increased concentration of PM2.5 and individual PM2.5 sources average concentrations in the previous 0-29, 0-179, and 0-364 days. RESULTS: Increases in ambient PM2.5 concentrations were not consistently associated with increased hospital admissions rates. Increased source-specific PM2.5 concentrations were associated with both increased (e.g., secondary sulfates and diesel emissions) and decreased rates (e.g., secondary nitrate and spark-ignition vehicular emissions) of neurodegenerative admissions. CONCLUSIONS: We did not observe clear associations between overall ambient PM2.5 concentrations or source-apportioned ambient PM2.5 contributions and rates of neurologic disease hospitalizations.