Comparison of the rate of healthcare encounters for influenza from source-specific PM2.5 before and after tier 3 vehicle standards in New York state.

BACKGROUND: Influenza healthcare encounters in adults associated with specific sources of PM2.5 is an area of active research. OBJECTIVE: Following 2017 legislation requiring reductions in emissions from light-duty vehicles, we hypothesized a reduced rate of influenza healthcare encounters would be associated with concentrations of PM2.5 from traffic sources in the early implementation period of this regulation (2017-2019). METHODS: We used the Statewide Planning and Research Cooperative System (SPARCS) to study adult patients hospitalized (N = 5328) or treated in the emergency department (N = 18,247) for influenza in New York State. Using a modified case-crossover design, we estimated the excess rate (ER) of influenza hospitalizations and emergency department visits associated with interquartile range increases in source-specific PM2.5 concentrations (e.g., spark-ignition emissions [GAS], biomass burning [BB], diesel [DIE]) in lag day(s) 0, 0-3 and 0-6. We then evaluated whether ERs differed after Tier 3 implementation (2017-2019) compared to the period prior to implementation (2014-2016). RESULTS: Each interquartile range increase in DIE in lag days 0-6 was associated with a 21.3% increased rate of influenza hospitalization (95% CI: 6.9, 37.6) in the 2014-2016 period, and a 6.3% decreased rate (95% CI: -12.7, 0.5) in the 2017-2019 period. The GAS/influenza excess rates were larger in the 2017-2019 period than the 2014-2016 period for emergency department visits. We also observed a larger ER associated with increased BB in the 2017-2019 period compared to the 2014-2016 period. IMPACT STATEMENT: We present an accountability study on the impact of the early implementation period of the Tier 3 vehicle emission standards on the association between specific sources of PM2.5 air pollution on influenza healthcare encounters in New York State. We found that the association between gasoline emissions and influenza healthcare encounters did not lessen in magnitude between periods, possibly because the emissions standards were not yet fully implemented. The reduction in the rates of influenza healthcare encounters associated with diesel emissions may be reflective of past policies to reduce the toxicity of diesel emissions. Accountability studies can help policy makers and environmental scientists better understand the timing of pollution changes and associated health effects.

A case-crossover study of ST-elevation myocardial infarction and organic carbon and source-specific PM2.5 concentrations in Monroe County, New York.

Background: Previous work reported increased rates of cardiovascular hospitalizations associated with increased source-specific PM2.5 concentrations in New York State, despite decreased PM2.5 concentrations. We also found increased rates of ST elevation myocardial infarction (STEMI) associated with short-term increases in concentrations of ultrafine particles and other traffic-related pollutants in the 2014-2016 period, but not during 2017-2019 in Rochester. Changes in PM2.5 composition and sources resulting from air quality policies (e.g., Tier 3 light-duty vehicles) may explain the differences. Thus, this study aimed to estimate whether rates of STEMI were associated with organic carbon and source-specific PM2.5 concentrations. Methods: Using STEMI patients treated at the University of Rochester Medical Center, compositional and source-apportioned PM2.5 concentrations measured in Rochester, a time-stratified case-crossover design, and conditional logistic regression models, we estimated the rate of STEMI associated with increases in mean primary organic carbon (POC), secondary organic carbon (SOC), and source-specific PM2.5 concentrations on lag days 0, 0-3, and 0-6 during 2014-2019. Results: The associations of an increased rate of STEMI with interquartile range (IQR) increases in spark-ignition emissions (GAS) and diesel (DIE) concentrations in the previous few days were not found from 2014 to 2019. However, IQR increases in GAS concentrations were associated with an increased rate of STEMI on the same day in the 2014-2016 period (Rate ratio [RR] = 1.69; 95% CI = 0.98, 2.94; 1.73 µg/m3). In addition, each IQR increase in mean SOC concentration in the previous 6 days was associated with an increased rate of STEMI, despite imprecision (RR = 1.14; 95% CI = 0.89, 1.45; 0.42 µg/m3). Conclusion: Increased SOC concentrations may be associated with increased rates of STEMI, while there seems to be a declining trend in adverse effects of GAS on triggering of STEMI. These changes could be attributed to changes in PM2.5 composition and sources following the Tier 3 vehicle introduction.

Tuberculosis screening for patients on biologic Medications: A Single-Center experience and Society guideline Review, Monroe County, New York, 2018-2021.

Rationale: Biologic medications for immune-mediated inflammatory diseases may increase the risk of tuberculosis (TB) reactivation, but data on screening for TB in low TB prevalence areas are limited. Objective: To assess the real-world practice patterns of TB screening among prescribers of biologic medications. Methods: We conducted a retrospective observational study at a single, university-based healthcare facility in a low TB prevalence area. We enrolled adult patients prescribed a biologic medication between October 2018 and December 2021, and collected data on demographics, biologic medications and TB test results. For patients with positive TB tests, further data including prescriber specialty and response to positive tests were obtained. We reviewed pertinent major society guidelines/ consensus statements regarding TB screening among patients treated with biologic medications. Results: 4,085 patients were included. 3024 (74.0%) had at least one screening TB test and 42 were positive. Among patients treated with tumor necrosis factor-alpha (TNFα) inhibitors, 1779 of 2129 patients (83.6%) underwent TB testing and 25 (1.4%) were positive. Most with positive TB test results were prescribed biologic medication by gastroenterology (11 patients, 26%), dermatology (12, 29%), or rheumatology (15, 36%) providers. 32 (76%) patients had imaging and roughly half were treated for latent TB infection. Biologic medications were temporarily held for 27 patients (67%). Nine out of 13 society guidelines recommend TB screening for TNFα inhibitors but have differing recommendations for other biologic medications. Conclusions: Significant practice pattern differences in TB screening for patients receiving biologic medications exist. Multiple society guidelines continue to recommend TB screening even for drugs with no known increased risk of TB reactivation.

PM2.5 and its components and respiratory disease healthcare encounters - Unanticipated increased exposure-response relationships in recent years after environmental policies.

Prior studies reported excess rates (ERs) of cardiorespiratory events associated with short-term increases in PM2.5 concentrations, despite implementation of pollution-control policies. In 2017, Federal Tier 3 light-duty vehicle regulations began, and to-date there have been no assessments of population health effects of the policy. Using the NYS Statewide Planning and Research Cooperative System (SPARCS) database, we obtained hospitalizations and ED visits with a principal diagnosis of asthma or chronic obstructive pulmonary disease (COPD) for residents living within 15 miles of six urban PM2.5 monitoring sites in NYS (2014-2019). We used a time-stratified case-crossover design and conditional logistic regression (adjusting for ambient temperature, relative humidity, and weekday) to estimate associations between PM2.5, POC (primary organic carbon), SOC (secondary organic carbon), and rates of respiratory disease hospitalizations and emergency department (ED) visits from 2014 to 2019. We evaluated demographic disparities in these relative rates and compared changes in ERs before (2014-2016) and after Tier 3 implementation (2017-2019). Each interquartile range increase in PM2.5 was associated with increased ERs of asthma or COPD hospitalizations and ED visits in the previous 7 days (ERs ranged from 1.1%-3.1%). Interquartile range increases in POC were associated with increased rates of asthma ED visits (lag days 0-6: ER = 2.1%, 95% CI = 0.7%, 3.6%). Unexpectedly, the ERs of asthma admission and ED visits associated with PM2.5, POC, and SOC were higher during 2017-2019 (after Tier 3) than 2014-2016 (before Tier-3). Chronic obstructive pulmonary disease analyses showed similar patterns. Excess Rates were higher in children (<18 years; asthma) and seniors (≥65 years; COPD), and Black, Hispanic, and NYC residents. In summary, unanticipated increases in asthma and COPD ERs after Tier-3 implementation were observed, and demographic disparities in asthma/COPD and PM2.5, POC, and SOC associations were also observed. Future work should confirm findings and investigate triggering of respiratory events by source-specific PM.

Fruit flavors in electronic cigarettes (ECIGs) are associated with nocturnal dry cough: A population longitudinal analysis.

Evidence from in vitro and animal models has identified the pulmonary toxicity of flavors in electronic cigarettes (ECIGs); however, less is known from epidemiological studies about the effects of flavors in the respiratory health. This study examined the longitudinal association between exposure to ECIGs flavors and nocturnal dry cough among ECIGs users. A secondary analysis of data from the Population Assessment of Tobacco and Health Study (2014-2019) was conducted. The study population included adults who provided information (n = 18,925) for a total of 38,638 observations. Weighted-incidence estimates and weighted- generalized estimating equation models were performed to assess unadjusted and adjusted associations. The weighted incidence proportion (WIP) of nocturnal dry cough was significantly higher among current (WIP:16.6%; 95%CI 10.5, 21.2) and former fruit flavored ECIGs users (WIP:16.6%; 95%CI 11.3, 21.9) as compared to non-ECIGs users (WIP:11.1%; 95%CI 10.6, 11.6). Current ECIGs users of fruit flavors showed 40% higher risk of reporting cough than non-ECIGs users (aRR:1.40, 95%CI 1.01, 1.94). Former ECIGs users of multiple flavors and other flavors had 300% and 66% higher risk to develop cough, respectively (aRR:3.33, 95%CI 1.51, 7.34 and aRR:1.66, 95%CI 1.0.9, 2.51), relative to non-ECIGs users. We observed a significantly higher risk of developing nocturnal dry cough in the past 12 months in current and former ECIGs users of fruit flavors and in former ECIGs users of multiple flavors. To the extent that cough may serve as an early indicator of respiratory inflammation and potential disease risk, the association between ECIGs use and cough raises potential concerns.

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.

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.

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.

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.