Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 µm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1ß. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for  PM2.5 air pollutants  and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.

Air Pollution-Related Neurotoxicity Across the Life Span.

Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system diseases and disorders likely reflects shared vulnerability of their inflammatory and oxidative stress-based mechanisms and a corresponding ability to produce brain metal dyshomeo-stasis. Future research to define the responsible contaminants of air pollution underlying this neurotoxicity is critical to understanding mechanisms of these diseases and disorders and protecting public health.

Health Effects of Wildfire Smoke Exposure.

We review current knowledge on the trends and drivers of global wildfire activity, advances in the measurement of wildfire smoke exposure, and evidence on the health effects of this exposure. We describe methodological issues in estimating the causal effects of wildfire smoke exposures on health and quantify their importance, emphasizing the role of nonlinear and lagged effects. We conduct a systematic review and meta-analysis of the health effects of wildfire smoke exposure, finding positive impacts on all-cause mortality and respiratory hospitalizations but less consistent evidence on cardiovascular morbidity. We conclude by highlighting priority areas for future research, including leveraging recently developed spatially and temporally resolved wildfire-specific ambient air pollution data to improve estimates of the health effects of wildfire smoke exposure.

Air Pollution and Mortality at the Intersection of Race and Social Class.

BACKGROUND: Black Americans are exposed to higher annual levels of air pollution containing fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) than White Americans and may be more susceptible to its health effects. Low-income Americans may also be more susceptible to PM2.5 pollution than high-income Americans. Because information is lacking on exposure-response curves for PM2.5 exposure and mortality among marginalized subpopulations categorized according to both race and socioeconomic position, the Environmental Protection Agency lacks important evidence to inform its regulatory rulemaking for PM2.5 standards. METHODS: We analyzed 623 million person-years of Medicare data from 73 million persons 65 years of age or older from 2000 through 2016 to estimate associations between annual PM2.5 exposure and mortality in subpopulations defined simultaneously by racial identity (Black vs. White) and income level (Medicaid eligible vs. ineligible). RESULTS: Lower PM2.5 exposure was associated with lower mortality in the full population, but marginalized subpopulations appeared to benefit more as PM2.5 levels decreased. For example, the hazard ratio associated with decreasing PM2.5 from 12 µg per cubic meter to 8 µg per cubic meter for the White higher-income subpopulation was 0.963 (95% confidence interval [CI], 0.955 to 0.970), whereas equivalent hazard ratios for marginalized subpopulations were lower: 0.931 (95% CI, 0.909 to 0.953) for the Black higher-income subpopulation, 0.940 (95% CI, 0.931 to 0.948) for the White low-income subpopulation, and 0.939 (95% CI, 0.921 to 0.957) for the Black low-income subpopulation. CONCLUSIONS: Higher-income Black persons, low-income White persons, and low-income Black persons may benefit more from lower PM2.5 levels than higher-income White persons. These findings underscore the importance of considering racial identity and income together when assessing health inequities. (Funded by the National Institutes of Health and the Alfred P. Sloan Foundation.).

Personal Strategies to Reduce the Cardiovascular Impacts of Environmental Exposures.

Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality. Other evidence may support physical activity, dietary modification, omega-3 fatty acid supplementation, and indoor and in-vehicle air conditioning as viable strategies to minimize adverse health effects. There is currently insufficient data to recommend specific personal approaches to reduce the adverse cardiovascular effects of noise pollution. Public health advisories for periods of extreme heat or cold should be observed, with limited evidence supporting a warm ambient home temperature and physical activity as strategies to limit the cardiovascular harms of temperature extremes. Perfluoroalkyl and polyfluoroalkyl substance exposure can be reduced by avoiding contact with perfluoroalkyl and polyfluoroalkyl substance-containing materials; blood or plasma donation and cholestyramine may reduce total body stores of perfluoroalkyl and polyfluoroalkyl substances. However, the cardiovascular impact of these interventions has not been examined. Limited utilization of pesticides and safe handling during use should be encouraged. Finally, vasculotoxic metal exposure can be decreased by using portable air cleaners, home water filtration, and awareness of potential contaminants in ground spices. Chelation therapy reduces physiological stores of vasculotoxic metals and may be effective for the secondary prevention of cardiovascular disease.

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Premature mortality related to United States cross-state air pollution.

Outdoor air pollution adversely affects human health and is estimated to be responsible for five to ten per cent of the total annual premature mortality in the contiguous United States1-3. Combustion emissions from a variety of sources, such as power generation or road traffic, make a large contribution to harmful air pollutants such as ozone and fine particulate matter (PM2.5)4. Efforts to mitigate air pollution have focused mainly on the relationship between local emission sources and local air quality2. Air quality can also be affected by distant emission sources, however, including emissions from neighbouring federal states5,6. This cross-state exchange of pollution poses additional regulatory challenges. Here we quantify the exchange of air pollution among the contiguous United States, and assess its impact on premature mortality that is linked to increased human exposure to PM2.5 and ozone from seven emission sectors for 2005 to 2018. On average, we find that 41 to 53 per cent of air-quality-related premature mortality resulting from a state's emissions occurs outside that state. We also find variations in the cross-state contributions of different emission sectors and chemical species to premature mortality, and changes in these variations over time. Emissions from electric power generation have the greatest cross-state impacts as a fraction of their total impacts, whereas commercial/residential emissions have the smallest. However, reductions in emissions from electric power generation since 2005 have meant that, by 2018, cross-state premature mortality associated with the commercial/residential sector was twice that associated with power generation. In terms of the chemical species emitted, nitrogen oxides and sulfur dioxide emissions caused the most cross-state premature deaths in 2005, but by 2018 primary PM2.5 emissions led to cross-state premature deaths equal to three times those associated with sulfur dioxide emissions. These reported shifts in emission sectors and emission species that contribute to premature mortality may help to guide improvements to air quality in the contiguous United States.

Emergency department visits respond nonlinearly to wildfire smoke.

Air pollution negatively affects a range of health outcomes. Wildfire smoke is an increasingly important contributor to air pollution, yet wildfire smoke events are highly salient and could induce behavioral responses that alter health impacts. We combine geolocated data covering all emergency department (ED) visits to nonfederal hospitals in California from 2006 to 2017 with spatially resolved estimates of daily wildfire smoke PM[Formula: see text] concentrations and quantify how smoke events affect ED visits. Total ED visits respond nonlinearly to smoke concentrations. Relative to a day with no smoke, total visits increase by 1 to 1.5% in the week following low or moderate smoke days but decline by 6 to 9% following extreme smoke days. Reductions persist for at least a month. Declines at extreme levels are driven by diagnoses not thought to be acutely impacted by pollution, including accidental injuries and several nonurgent symptoms, and declines come disproportionately from less-insured populations. In contrast, health outcomes with the strongest physiological link to short-term air pollution increase dramatically in the week following an extreme smoke day: We estimate that ED visits for asthma, COPD, and cough all increase by 30 to 110%. Data from internet searches, vehicle traffic sensors, and park visits indicate behavioral changes on high smoke days consistent with declines in healthcare utilization. Because low and moderate smoke days vastly outweigh high smoke days, we estimate that smoke was responsible for an average of 3,010 (95% CI: 1,760-4,380) additional ED visits per year 2006 to 2017. Given the increasing intensity of wildfire smoke events, behavioral mediation is likely to play a growing role in determining total smoke impacts.

Air pollution and suicide in rural and urban America: Evidence from wildfire smoke.

Air pollution poses well-established risks to physical health, but little is known about its effects on mental health. We study the relationship between wildfire smoke exposure and suicide risk in the United States in 2007 to 2019 using data on all deaths by suicide and satellite-based measures of wildfire smoke and ambient fine particulate matter (PM2.5) concentrations. We identify the causal effects of wildfire smoke pollution on suicide by relating year-over-year fluctuations in county-level monthly smoke exposure to fluctuations in suicide rates and compare the effects across local areas and demographic groups that differ considerably in their baseline suicide risk. In rural counties, an additional day of smoke increases monthly mean PM2.5 by 0.41 µg/m3 and suicide deaths by 0.11 per million residents, such that a 1-µg/m3 (13%) increase in monthly wildfire-derived fine particulate matter leads to 0.27 additional suicide deaths per million residents (a 2.0% increase). These effects are concentrated among demographic groups with both high baseline suicide risk and high exposure to outdoor air: men, working-age adults, non-Hispanic Whites, and adults with no college education. By contrast, we find no evidence that smoke pollution increases suicide risk among any urban demographic group. This study provides large-scale evidence that air pollution elevates the risk of suicide, disproportionately so among rural populations.

Quantifying fire-specific smoke exposure and health impacts.

Rapidly changing wildfire regimes across the Western United States have driven more frequent and severe wildfires, resulting in wide-ranging societal threats from wildfires and wildfire-generated smoke. However, common measures of fire severity focus on what is burned, disregarding the societal impacts of smoke generated from each fire. We combine satellite-derived fire scars, air parcel trajectories from individual fires, and predicted smoke PM2.5 to link source fires to resulting smoke PM2.5 and health impacts experienced by populations in the contiguous United States from April 2006 to 2020. We quantify fire-specific accumulated smoke exposure based on the cumulative population exposed to smoke PM2.5 over the duration of a fire and estimate excess asthma-related emergency department (ED) visits as a result of this exposure. We find that excess asthma visits attributable to each fire are only moderately correlated with common measures of wildfire severity, including burned area, structures destroyed, and suppression cost. Additionally, while recent California fires contributed nearly half of the country's smoke-related excess asthma ED visits during our study period, the most severe individual fire was the 2007 Bugaboo fire in the Southeast. We estimate that a majority of smoke PM2.5 comes from sources outside the local jurisdictions where the smoke is experienced, with 87% coming from fires in other counties and 60% from fires in other states. Our approach could enable broad-scale assessment of whether specific fire characteristics affect smoke toxicity or impact, inform cost-effectiveness assessments for allocation of suppression resources, and help clarify the growing transboundary nature of local air quality.

Air pollution, genetic susceptibility, and the risk of atrial fibrillation: A large prospective cohort study.

To date, no study has explored the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of atrial fibrillation (AF). This study was designed to investigate the separate and joint effects of long-term exposure to air pollutants and genetic susceptibility on the risk of AF events. This study included 401,251 participants without AF at baseline from UK Biobank. We constructed a polygenic risk score and categorized it into three categories. Cox proportional hazards models were fitted to assess the separate and joint effects of long-term exposure to air pollutants and genetics on the risk of AF. Additionally, we further evaluated the effect modification of genetic susceptibility. The hazard ratios and corresponding 95% confidence intervals of incident AF for per interquartile range increase in particulate matter with an aerodynamic diameter smaller than 2.5 µm (PM2.5) or 10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxide (NOx) were 1.044 (1.025, 1.063), 1.063 (1.044, 1.083), 1.061 (1.042, 1.081), and 1.039 (1.023, 1.055), respectively. For the combined effects, participants exposed to high air pollutants levels and high genetic risk had approximately 149.2% (PM2.5), 181.7% (PM10), 170.2% (NO2), and 157.2% (NOx) higher risk of AF compared to those with low air pollutants levels and low genetic risk, respectively. Moreover, the significant additive interactions between PM10 and NO2 and genetic risk on AF risk were observed, with around 16.4% and 35.1% of AF risk could be attributable to the interactive effects. In conclusion, long-term exposure to air pollutants increases the risk of AF, particularly among individuals with high genetic susceptibility.

Incident dementia and long-term exposure to constituents of fine particle air pollution: A national cohort study in the United States.

Growing evidence suggests that fine particulate matter (PM2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+), and soil dust (DUST). To investigate the impact of long-term exposure to PM2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM2.5 and its major constituents. An interquartile range increase in PM2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM2.5 constituents, associations remained significant for BC, OM, SO42-, and NH4+ for both end points (even after adjustments of other constituents), among which BC and SO42- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM2.5 is significantly associated with higher rates of incident dementia and AD and that SO42-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

The Urban Environment and Cardiometabolic Health.

Urban environments contribute substantially to the rising burden of cardiometabolic diseases worldwide. Cities are complex adaptive systems that continually exchange resources, shaping exposures relevant to human health such as air pollution, noise, and chemical exposures. In addition, urban infrastructure and provisioning systems influence multiple domains of health risk, including behaviors, psychological stress, pollution, and nutrition through various pathways (eg, physical inactivity, air pollution, noise, heat stress, food systems, the availability of green space, and contaminant exposures). Beyond cardiometabolic health, city design may also affect climate change through energy and material consumption that share many of the same drivers with cardiometabolic diseases. Integrated spatial planning focusing on developing sustainable compact cities could simultaneously create heart-healthy and environmentally healthy city designs. This article reviews current evidence on the associations between the urban exposome (totality of exposures a person experiences, including environmental, occupational, lifestyle, social, and psychological factors) and cardiometabolic diseases within a systems science framework, and examines urban planning principles (eg, connectivity, density, diversity of land use, destination accessibility, and distance to transit). We highlight critical knowledge gaps regarding built-environment feature thresholds for optimizing cardiometabolic health outcomes. Last, we discuss emerging models and metrics to align urban development with the dual goals of mitigating cardiometabolic diseases while reducing climate change through cross-sector collaboration, governance, and community engagement. This review demonstrates that cities represent crucial settings for implementing policies and interventions to simultaneously tackle the global epidemics of cardiovascular disease and climate change.

Air Pollution, Built Environment, and Early Cardiovascular Disease.

As the world's population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related risk factors. While epidemiological studies have examined the role of a few environmental factors with early cardiovascular disease, the relationship with the broader environment remains poorly defined. In this article, we provide a brief overview of studies that have examined the impact of the environment including the built physical environment, discuss current challenges in the field, and suggest potential directions for future research. Additionally, we highlight the clinical implications of these findings and propose multilevel interventions to promote cardiovascular health among children and young adults.

Household Air Pollution and Child Lung Function: The Ghana Randomized Air Pollution and Health Study.

Rationale: The impact of a household air pollution (HAP) stove intervention on child lung function has been poorly described. Objectives: To assess the effect of a HAP stove intervention for infants prenatally to age 1 on, and exposure-response associations with, lung function at child age 4. Methods: The Ghana Randomized Air Pollution and Health Study randomized pregnant women to liquefied petroleum gas (LPG), improved biomass, or open-fire (control) stove conditions through child age 1. We quantified HAP exposure by repeated maternal and child personal carbon monoxide (CO) exposure measurements. Children performed oscillometry, an effort-independent lung function measurement, at age 4. We examined associations between Ghana Randomized Air Pollution and Health Study stove assignment and prenatal and infant CO measurements and oscillometry using generalized linear regression models. We used reverse distributed lag models to examine time-varying associations between prenatal CO and oscillometry. Measurements and Main Results: The primary oscillometry measure was reactance at 5 Hz, X5, a measure of elastic and inertial lung properties. Secondary measures included total, large airway, and small airway resistance at 5 Hz, 20 Hz, and the difference in resistance at 5 Hz and 20 Hz (R5, R20, and R5-20, respectively); area of reactance (AX); and resonant frequency. Of the 683 children who attended the lung function visit, 567 (83%) performed acceptable oscillometry. A total of 221, 106, and 240 children were from the LPG, improved biomass, and control arms, respectively. Compared with control, the improved biomass stove condition was associated with lower reactance at 5 Hz (X5 z-score: ß = -0.25; 95% confidence interval [CI] = -0.39, -0.11), higher large airway resistance (R20 z-score: ß = 0.34; 95% CI = 0.23, 0.44), and higher AX (AX z-score: ß = 0.16; 95% CI = 0.06, 0.26), which is suggestive of overall worse lung function. The LPG stove condition was associated with higher X5 (X5 score: ß = 0.16; 95% CI = 0.01, 0.31) and lower small airway resistance (R5-20 z-score: ß = -0.15; 95% CI = -0.30, 0.0), which is suggestive of better small airway function. Higher average prenatal CO exposure was associated with higher R5 and R20, and distributed lag models identified sensitive windows of exposure between CO and X5, R5, R20, and R5-20. Conclusions: These data support the importance of prenatal HAP exposure on child lung function. Clinical trial registered with www.clinicaltrials.gov (NCT01335490).

High-Efficiency Particulate Air Filters for Preventing Wildfire-related Asthma Complications: A Cost-Effectiveness Study.

Rationale: Air pollution caused by wildfire smoke is linked to adverse health outcomes, especially for people living with asthma. Objectives: To evaluate whether government rebates for high-efficiency particulate air (HEPA) filters, which reduce concentrations of smoke particles indoors, are cost effective in managing asthma and preventing exacerbations in British Columbia (BC), Canada. Methods: We used a Markov model to analyze health states for asthma control, exacerbation severity, and death over a retrospective time horizon of 5 years (2018-2022). Concentrations of wildfire smoke-derived particulate matter with an aerodynamic diameter ⩽2.5 µm (PM2.5) from the Canadian Optimized Statistical Smoke Exposure Model and relevant literature informed the model. The base-case analysis assumed continuous use of a HEPA filter. Costs and quality-adjusted life-years (QALYs) resulting from varying rebates were computed for each Health Service Delivery Area (HSDA). Measurements and Main Results: In the base-case analysis, HEPA filter use resulted in increased costs of $83.34 (SE, $1.03) and increased QALYs of 0.0011 (SE, 0.0001) per person. The average incremental cost-effectiveness ratio among BC HSDAs was $74,652/QALY (SE, $3,517), with incremental cost-effectiveness ratios ranging from $40,509 to $89,206 per QALY in HSDAs. Across the province, the intervention was projected to prevent 4,418 exacerbations requiring systemic corticosteroids, 643 emergency department visits, and 425 hospitalizations during the 5-year time horizon. A full rebate was cost effective in 1 of the 16 HSDAs across BC. The probability of cost-effectiveness ranged from 0.1% to 74.8% across HSDAs. A $100 rebate was cost effective in most HSDAs. Conclusions: The cost-effectiveness of HEPA filters in managing wildfire smoke-related asthma issues in BC varies by region. Government rebates up to two-thirds of the filter cost are generally cost effective, with a full rebate being cost effective only in Kootenay Boundary.

Long-Term Exposure to Low Concentrations of Ambient Benzene and Mortality in a National English Cohort.

Background: Benzene affects human health through environmental exposure in addition to occupational contact. However, few studies have examined the associations between long-term exposure to low concentrations of ambient benzene and mortality risks in nonoccupational settings.Methods: This prospective cohort study consists of 393,042 participants without stroke, myocardial infarction, or cancer at baseline from the UK Biobank. Annual average concentrations of benzene for each year during follow-up were measured using air dispersion models. The main outcomes were all-cause mortality and mortality from specific causes. Cox proportional-hazards models with time-varying exposure measurements were used to estimate the hazard ratios and 95% confidence intervals (CIs) for mortality risks. Restricted cubic spline models were used to estimate exposure-response relationships.Measurements and Main Results: With each interquartile range increase in the average annual concentration of benzene, the adjusted hazard ratios of mortality risk from all causes, cardiovascular disease, cancer, and respiratory disease were 1.26 (95% CI, 1.24-1.27), 1.24 (95% CI, 1.21-1.28), 1.27 (95% CI, 1.25-1.29), and 1.25 (95% CI, 1.20-1.30), respectively. The monotonically increasing exposure-response curves showed no threshold and plateau within the observed concentration range. Furthermore, the effect of benzene exposure on mortality persisted across different subgroups and was somewhat stronger in younger and White people (P for interaction < 0.05).Conclusions: Long-term exposure to low concentrations of ambient benzene significantly increases mortality risk in the general population. Ambient benzene represents a potential threat to public health, and further investigations are needed to support timely pollution regulation and health protection.

Airway Tree Caliber and Susceptibility to Pollution-associated Emphysema: MESA Air and Lung Studies.

Rationale: Airway tree morphology varies in the general population and may modify the distribution and uptake of inhaled pollutants. Objectives: We hypothesized that smaller airway caliber would be associated with emphysema progression and would increase susceptibility to air pollutant-associated emphysema progression. Methods: MESA (Multi-Ethnic Study of Atherosclerosis) is a general population cohort of adults 45-84 years old from six U.S. communities. Airway tree caliber was quantified as the mean of airway lumen diameters measured from baseline cardiac computed tomography (CT) (2000-2002). Percentage emphysema, defined as percentage of lung pixels below -950 Hounsfield units, was assessed up to five times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scan (2010-2018). Long-term outdoor air pollutant concentrations (particulate matter with an aerodynamic diameter ⩽2.5 µm, oxides of nitrogen, and ozone) were estimated at the residential address with validated spatiotemporal models. Linear mixed models estimated the association between airway tree caliber and emphysema progression; modification of pollutant-associated emphysema progression was assessed using multiplicative interaction terms. Measurements and Main Results: Among 6,793 participants (mean ± SD age, 62 ± 10 yr), baseline airway tree caliber was 3.95 ± 1.1 mm and median (interquartile range) of percentage emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95% confidence interval, 0.54-0.96%) higher in the smallest compared with largest airway tree caliber quartile. Airway tree caliber also modified air pollutant-associated emphysema progression. Conclusions: Smaller airway tree caliber was associated with accelerated emphysema progression and modified air pollutant-associated emphysema progression. A better understanding of the mechanisms of airway-alveolar homeostasis and air pollutant deposition is needed.

Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California.

Rationale: Particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 µm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.