Indoor Air Sources of Outdoor Air Pollution: Health Consequences, Policy, and Recommendations: An Official American Thoracic Society Workshop Report.

Indoor sources of air pollution worsen indoor and outdoor air quality. Thus, identifying and reducing indoor pollutant sources would decrease both indoor and outdoor air pollution, benefit public health, and help address the climate crisis. As outdoor sources come under regulatory control, unregulated indoor sources become a rising percentage of the problem. This American Thoracic Society workshop was convened in 2022 to evaluate this increasing proportion of indoor contributions to outdoor air quality. The workshop was conducted by physicians and scientists, including atmospheric and aerosol scientists, environmental engineers, toxicologists, epidemiologists, regulatory policy experts, and pediatric and adult pulmonologists. Presentations and discussion sessions were centered on 1) the generation and migration of pollutants from indoors to outdoors, 2) the sources and circumstances representing the greatest threat, and 3) effective remedies to reduce the health burden of indoor sources of air pollution. The scope of the workshop was residential and commercial sources of indoor air pollution in the United States. Topics included wood burning, natural gas, cooking, evaporative volatile organic compounds, source apportionment, and regulatory policy. The workshop concluded that indoor sources of air pollution are significant contributors to outdoor air quality and that source control and filtration are the most effective measures to reduce indoor contributions to outdoor air. Interventions should prioritize environmental justice: Households of lower socioeconomic status have higher concentrations of indoor air pollutants from both indoor and outdoor sources. We identify research priorities, potential health benefits, and mitigation actions to consider (e.g., switching from natural gas to electric stoves and transitioning to scent-free consumer products). The workshop committee emphasizes the benefits of combustion-free homes and businesses and recommends economic, legislative, and education strategies aimed at achieving this goal.

Adverse Health Impacts of Outdoor Air Pollution, Including from Wildland Fires, in the United States: "Health of the Air," 2018-2020.

Rationale: Adverse health impacts from outdoor air pollution occur across the United States, but the magnitude of these impacts varies widely by geographic region. Ambient pollutant concentrations, emission sources, baseline health conditions, and population sizes and distributions are all important factors that need to be taken into account to quantify local health burdens. Objectives: To determine health impacts from ambient air pollution concentrations in the United States that exceed the levels recommended by the American Thoracic Society. Methods: Using a methodology that has been well established in previous "Health of the Air" reports, this study provides policy-relevant estimates for every monitored county and city in the United States for the adverse health impacts of outdoor pollution concentrations using U.S. Environmental Protection Agency design values for years 2018-2020. Additionally, for the first time, the report includes adverse birth outcomes as well as estimates of health impacts specifically attributable to wildland fires using an exposure dataset generated through Community Multiscale Air Quality simulations. Results: The adverse health burdens attributable to air pollution occur across the entire age spectrum, including adverse birth outcomes (10,660 preterm and/or low-weight births; 95% confidence interval [CI], 3,180-18,330), in addition to mortality impacts (21,300 avoidable deaths; 95% CI, 16,180-26,200), lung cancer incidence (3,000 new cases; 95% CI, 1,550-4,390), multiple types of cardiovascular and respiratory morbidity (748,660 events; 95% CI, 326,050-1,057,080), and adversely impacted days (52.4 million days; 95% CI, 7.9-92.4 million days). Two different estimates of mortality impacts from wildland fires were created based on assumptions regarding the underlying toxicity of particles from wildland fires (low estimate of 4,080 deaths, 95% CI, 240-7,890; middle estimate of 28,000 deaths, 95% CI, 27,300-28,700). Conclusions: This year's report identified sizable health benefits that would be expected to occur across the United States with compliance with more health-protective air quality standards such as those recommended by the American Thoracic Society. This study also indicates that a large number of excess deaths are attributable to emissions from wildland fires; air quality management strategies outside what is required by the Clean Air Act will be needed to best address this important source of air pollution and its associated health risks.

Post-infection treatment with the E protein inhibitor BIT225 reduces disease severity and increases survival of K18-hACE2 transgenic mice infected with a lethal dose of SARS-CoV-2.

The Coronavirus envelope (E) protein is a small structural protein with ion channel activity that plays an important role in virus assembly, budding, immunopathogenesis and disease severity. The viroporin E is also located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we evaluated in vitro antiviral activity, mechanism of action and in vivo efficacy of BIT225 for the treatment of SARS-CoV-2 infection. BIT225 showed broad-spectrum direct-acting antiviral activity against SARS-CoV-2 in Calu3 and Vero cells with similar potency across 6 different virus strains. BIT225 inhibited ion channel activity of E protein but did not inhibit endogenous currents or calcium-induced ion channel activity of TMEM16A in Xenopus oocytes. BIT225 administered by oral gavage for 12 days starting 12 hours before infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (100% survival, n = 12), while all vehicle-dosed animals reached a mortality endpoint by Day 9 across two studies (n = 12). When treatment started at 24 hours after infection, body weight loss, and mortality were also prevented (100% survival, n = 5), while 4 of 5 mice maintained and increased body weight and survived when treatment started 48 hours after infection. Treatment efficacy was dependent on BIT225 dose and was associated with significant reductions in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. These results validate viroporin E as a viable antiviral target and support the clinical study of BIT225 for treatment and prophylaxis of SARS-CoV-2 infection.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

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.

Pulmonary and Critical Care Considerations for e-Cigarette, or Vaping, Product Use-Associated Lung Injury.

BACKGROUND: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU. RESEARCH QUESTION: What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI? STUDY DESIGN AND METHODS: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts. RESULTS: Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes. INTERPRETATION: Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.

Global Health Impacts for Economic Models of Climate Change: A Systematic Review and Meta-Analysis.

Rationale: Avoiding excess health damages attributable to climate change is a primary motivator for policy interventions to reduce greenhouse gas emissions. However, the health benefits of climate mitigation, as included in the policy assessment process, have been estimated without much input from health experts. Objectives: In accordance with recommendations from the National Academies in a 2017 report on approaches to update the social cost of greenhouse gases (SC-GHG), an expert panel of 26 health researchers and climate economists gathered for a virtual technical workshop in May 2021 to conduct a systematic review and meta-analysis and recommend improvements to the estimation of health impacts in economic-climate models. Methods: Regionally resolved effect estimates of unit increases in temperature on net all-cause mortality risk were generated through random-effects pooling of studies identified through a systematic review. Results: Effect estimates and associated uncertainties varied by global region, but net increases in mortality risk associated with increased average annual temperatures (ranging from 0.1% to 1.1% per 1°C) were estimated for all global regions. Key recommendations for the development and utilization of health damage modules were provided by the expert panel and included the following: not relying on individual methodologies in estimating health damages; incorporating a broader range of cause-specific mortality impacts; improving the climate parameters available in economic models; accounting for socioeconomic trajectories and adaptation factors when estimating health damages; and carefully considering how air pollution impacts should be incorporated in economic-climate models. Conclusions: This work provides an example of how subject-matter experts can work alongside climate economists in making continued improvements to SC-GHG estimates.

Excess Morbidity and Mortality Associated with Air Pollution above American Thoracic Society Recommended Standards, 2017-2019.

Rationale: Over the past year, the American Thoracic Society (ATS), led by its Environmental Health Policy Committee, has reviewed the most current air quality scientific evidence and has revised their recommendations to 8 µg/m3 and 25 µg/m3 for long- and short-term fine particulate matter (PM2.5) and reaffirmed the recommendation of 60 ppb for ozone to protect the American public from the known adverse health effects of air pollution. The current U.S. Environmental Protection Agency (EPA) standards, in contrast, expose the American public to pollution levels that are known to result in significant morbidity and mortality. Objectives: To provide county-level estimates of annual air pollution-related health outcomes across the United States using the most recent federal air quality data, and to support the ATS's recent update to the long-term PM2.5 recommended standard. This study is presented as part of the annual ATS/Marron Institute "Health of the Air" report. Methods: Daily air pollution values were obtained from the EPA's air quality system for monitored counties in the United States from 2017-2019. Concentration-response functions used in the EPA's regulatory review process were applied to pollution increments corresponding to differences between the rolling 3-year design values and ATS-recommended levels for long-term PM2.5 (8 µg/m3), short-term PM2.5 (25 µg/m3), and ground-level ozone (O3; 60 ppb). Health impacts were estimated at the county level in locations with valid monitoring data. Results: Meeting ATS recommendations throughout the country prevents an estimated 14,650 (95% confidence interval [CI], 8,660-22,610) deaths; 2,950 (95% CI, 1,530-4,330) lung cancer incidence events; 33,100 (95% CI, 7,300-71,000) morbidities, and 39.8 million (95% CI, 14.6-63.3 million) impacted days annually. This prevents 11,850 more deaths; 2,580 more lung cancer incidence events; 25,400 more morbidities; and 27.2 million more impacted days than meeting EPA standards alone. Conclusions: Significant health benefits to be gained by U.S. communities that work to meet ATS-recommended air quality standards have now been identified under scenarios meeting the new ATS recommendation for long-term PM2.5 (8 µg/m3). The "Health of the Air" report presents an opportunity for air quality managers to quantify local health burdens and EPA officials to update their standards to reflect the latest science.

Human Immunodeficiency Virus Type 1 Vpu Inhibitor, BIT225, in Combination with 3-Drug Antiretroviral Therapy: Inflammation and Immune Cell Modulation.

BIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1-infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point-soluble CD163, a marker of monocyte/macrophage inflammation-was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals. Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194).

Trends in Excess Morbidity and Mortality Associated with Air Pollution above American Thoracic Society-Recommended Standards, 2008-2017.

Rationale: Air quality improvements are increasingly difficult to come by as modern pollution control technologies and measures have been widely implemented in the United States. Although there have been dramatic improvements in air quality over the last several decades, it is important to evaluate changes in the health impacts of air pollution for a more recent time period to better understand the current trajectory of air quality improvements. Objectives: To provide county-level estimates of annual air pollution-related health outcomes across the United States and to evaluate these trends from 2008 to 2017, presented as part of the annual American Thoracic Society (ATS)/Marron Institute "Health of the Air" report. Methods: Daily air pollution values were obtained from the U.S. Environmental Protection Agency's Air Quality System for monitors in the United States from 2008 to 2017. Concentration-response functions used in the ATS/Marron Institute "Health of the Air" report were applied to the pollution increments corresponding to differences between the rolling 3-year design values (reported as the third year) and ATS-recommended levels for annual particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5; 11 µg/m3), short-term PM2.5 (25 µg/m3), and ozone (O3; 60 ppb). Health impacts were estimated at the county level in locations with valid monitor data. Results: Annual excess mortality in the United States due to air pollution levels greater than recommended by the ATS decreased from approximately 12,600 (95% confidence interval [CI], 5,470-21,040) in 2010 to 7,140 (95% CI, 2,290-14,040) in 2017. This improvement can be attributed almost entirely to reductions in PM2.5-related mortality, which decreased by approximately 60% (reduced from 8,330 to 3,260 annual deaths), whereas O3-related mortality remained largely unchanged, other than year-to-year variability, over the same time period (reduced from 4,270 to 3,880 annual deaths). Conclusions: Improvements in health impacts attributable to ambient PM2.5 concentrations have been observed across most regions of the United States over the last decade, although the rate of these improvements has leveled off in recent years. Despite two revisions of the National Ambient Air Quality Standards strengthening the standard for O3 in 2008 and 2015, there has not yet been a substantial improvement in the health impacts attributable to O3 during this time period. In many U.S. cities, an increase in the exposed population over the last decade has outpaced the improvements in ambient O3 concentrations, resulting in a net increase in O3-related health impacts over time.

Optimizing Home Oxygen Therapy. An Official American Thoracic Society Workshop Report.

More than 1.5 million adults in the United States use supplemental oxygen for a variety of respiratory disorders to improve their quality of life and prolong survival. This document describes recommendations from a multidisciplinary workshop convened at the ATS International Conference in 2017 with the goal of optimizing home oxygen therapy for adults. Ideal supplemental oxygen therapy is patient-specific, provided by a qualified clinician, includes an individualized prescription and therapeutic education program, and offers oxygen systems that are safe, promote mobility, and treat hypoxemia. Recently, patients and clinicians report a growing number of problems with home oxygen in the United States. Oxygen users experience significant functional, mechanical, and financial problems and a lack of education related to their oxygen equipment-problems that impact their quality of life. Health care providers report a lack of readily accessible resources needed to prescribe oxygen systems correctly and efficiently. Patients with certain lung diseases are affected more than others because of physically unmanageable or inadequate portable systems. Analysis is needed to quantify the unintended impact that the Centers for Medicare and Medicaid Services Competitive Bidding Program has had on patients receiving supplemental oxygen from durable medical equipment providers. Studies using effectiveness and implementation research designs are needed to develop and evaluate new models for patient education, identify effective ways for stakeholders to interface, determine the economic benefit of having respiratory therapists perform in-home education and follow-up testing, and collaborate with technology companies to improve portable oxygen devices. Generation of additional evidence of the benefit of supplemental oxygen across the spectrum of advanced lung diseases and the development of clinical practice guidelines should both be prioritized.

Survey of International Members of the American Thoracic Society on Climate Change and Health.

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed international members of the society to assess perceptions, clinical experiences, and preferred policy responses related to global climate change. A recruitment email was sent by the ATS President in October 2015 to 5,013 international members. Subsequently, four reminder emails were sent to nonrespondents. Responses were received from 489 members in 68 countries; the response rate was 9.8%. Half of respondents reported working in countries in Asia (25%) or Europe (25%), with the remainder in South America (18%), North America (Canada and Mexico) (18%), Australia or New Zealand (9%), and Africa (6%). Survey estimate confidence intervals were ± 5% or smaller. A high percentage of international ATS survey respondents judged that climate change is happening (96%), that it is driven by human activity (70%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (80%). A majority of respondents also indicated they are already observing health impacts of climate change among their patients; most commonly as increases in chronic disease severity from air pollution (88%), allergic symptoms from exposure to plants or mold (72%), and severe weather injuries (69%). An even larger majority anticipated seeing these climate-related health impacts in the next two decades. Respondents further indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. International ATS respondents, like their counterparts in the U.S., observed that human health is already adversely affected by climate change, and support responses to address this situation.

American Thoracic Society and Marron Institute Report. Estimated Excess Morbidity and Mortality Caused by Air Pollution above American Thoracic Society-Recommended Standards, 2011-2013.

Estimates of the health impacts of air pollution are needed to make informed air quality management decisions at both the national and local levels. Using design values of ambient pollution concentrations from 2011-2013 as a baseline, the American Thoracic Society (ATS) and the Marron Institute of Urban Management estimated excess morbidity and mortality in the United States attributable to exposure to ambient ozone (O3) and fine particulate matter (PM2.5) at levels above the American Thoracic Society-recommended standards. Within the subset of counties with valid design values for each pollutant, 14% had PM2.5 concentrations greater than the ATS recommendation, whereas 91% had O3 concentrations greater than the ATS recommendation. Approximately 9,320 excess deaths (69% from O3; 31% from PM2.5), 21,400 excess morbidities (74% from O3; 26% from PM2.5), and 19,300,000 adversely impacted days (88% from O3; 12% from PM2.5) in the United States each year are attributable to pollution exceeding the ATS-recommended standards. California alone is responsible for 37% of the total estimated health impacts, and the next three states (Pennsylvania, Texas, and Ohio) together contributed to 20% of the total estimates. City-specific health estimates are provided in this report and through an accompanying online tool to help inform air quality management decisions made at the local level. Riverside and Los Angeles, California have the most to gain by attaining the ATS recommendations for O3 and PM2.5. This report will be revised and updated regularly to help cities track their progress.