HIGH THROUGHPUT QUANTITATION OF HUMAN NEUTROPHIL RECRUITMENT AND FUNCTIONAL RESPONSES IN AN AIR-BLOOD BARRIER ARRAY.

Dysregulated neutrophil recruitment drives many pulmonary diseases, but most preclinical screening methods are unsuited to evaluate pulmonary neutrophilia, limiting progress towards therapeutics. Namely, high throughput therapeutic screening systems typically exclude critical neutrophilic pathophysiology, including blood-to-lung recruitment, dysfunctional activation, and resulting impacts on the air-blood barrier. To meet the conflicting demands of physiological complexity and high throughput, we developed an assay of 96-well Leukocyte recruitment in an Air-Blood Barrier Array (L-ABBA-96) that enables in vivo -like neutrophil recruitment compatible with downstream phenotyping by automated flow cytometry. We modeled acute respiratory distress syndrome (ARDS) with neutrophil recruitment to 20 ng/mL epithelial-side interleukin 8 (IL-8) and found a dose dependent reduction in recruitment with physiologic doses of baricitinib, a JAK1/2 inhibitor recently FDA-approved for severe COVID-19 ARDS. Additionally, neutrophil recruitment to patient-derived cystic fibrosis sputum supernatant induced disease-mimetic recruitment and activation of healthy donor neutrophils and upregulated endothelial e-selectin. Compared to 24-well assays, the L-ABBA-96 reduces required patient sample volumes by 25 times per well and quadruples throughput per plate. Compared to microfluidic assays, the L-ABBA-96 recruits two orders of magnitude more neutrophils per well, enabling downstream flow cytometry and other standard biochemical assays. This novel pairing of high-throughput in vitro modeling of organ-level lung function with parallel high-throughput leukocyte phenotyping substantially advances opportunities for pathophysiological studies, personalized medicine, and drug testing applications.

Collection of Nitrogen Dioxide for Nitrogen and Oxygen Isotope Determination─Laboratory and Environmental Chamber Evaluation.

The family of atmospheric oxides of nitrogen, NOy (e.g., nitrogen oxides (NOx) + nitric acid (HNO3) + nitrous acid (HONO) + peroxyacetyl nitrate (PAN) + particulate nitrate (pNO3-) + other), have an influential role in atmospheric chemistry, climate, and the environment. The nitrogen (δ15N) and oxygen (δ18O and Δ17O) stable isotopes of NOy are novel tools for potentially tracking emission sources and quantifying oxidation chemistry. However, there is a lack of well-established methods, particularly for speciated gas-phase components of NOy, to accurately quantify δ15N, δ18O, and Δ17O. This work presents controlled laboratory experiments and complex chamber α-pinene/NOx oxidation experiments of a sampling apparatus constructed for the simultaneous capture of multiple NOy species for isotope analysis using a series of coated denuders, with a focus on nitrogen dioxide (NO2•). The laboratory tests indicate complete NO2• capture for the targeted concentration of 15 ppbv for at least 24 h collections at 10 liters per minute, with δ15N and δ18O precisions of ±1.3‰ and 1.0‰, respectively, and minimal (2.2% ± 0.1%) NO2• collection on upstream denuders utilized for the capture of HNO3 and other acidic gases. The multispecies NOy collection system showed excellent concentration correlations with online instrumentation for both HNO3 and NO2• and isotope reproducibility of ±1.7‰, ±1.8‰, and ±0.7‰ for δ15N, δ18O, and Δ17O, respectively, for replicate experiments and highly time-resolved collections. This work demonstrates a new method that can enable the simultaneous collection of HNO3 and NO2• for accurate quantification of concentration and isotopic composition.

Photolysis of Gas-Phase Atmospherically Relevant Monoterpene-Derived Organic Nitrates.

Organic nitrates (ONs) can impact spatial distribution of reactive nitrogen species and ozone formation in the atmosphere. While photolysis of ONs is known to result in the release of NO2 back to the atmosphere, the photolysis rate constants and mechanisms of monoterpene-derived ONs (MT-ONs) have not been well constrained. We investigated the gas-phase photolysis of three synthetic ONs derived from α-pinene, ß-pinene, and d-limonene through chamber experiments. The measured photolysis rate constants ranged from (0.55 ± 0.10) × 10-5 to (2.3 ± 0.80) × 10-5 s-1 under chamber black lights. When extrapolated to solar spectral photon flux at a solar zenith angle of 28.14° in summer, the photolysis rate constants were in the range of (4.1 ± 1.4) × 10-5 to (14 ± 6.7) × 10-5 s-1 (corresponding to lifetimes of 2.0 ± 0.96 to 6.8 ± 2.4 h) and (1.7 ± 0.60) × 10-5 to (8.3 ± 4.0) ×10-5 s-1 (3.3 ± 1.6 to 17 ± 6.0 h lifetimes) by using wavelength-dependent and average quantum yields, respectively. Photolysis mechanisms were proposed based on major products detected during photolysis. A zero-dimensional box model was further employed to simulate the photolysis of α-pinene-derived ON under ambient conditions. We found that more than 99% of α-pinene-derived ON can be converted to inorganic nitrogen within 12 h of irradiation and ozone was formed correspondingly. Together, these findings show that photolysis is an important atmospheric sink for MT-ONs and highlight their role in NOx recycling and ozone chemistry.

Designing better cloth masks: The effect of fabric and attachment-style on discomfort.

Cloth masks are a tool for controlling community transmission during pandemics, as well as during other outbreak situations. However, cloth masks vary in their designs, and the consequences of this variability for their effectiveness as source control have received little attention, particularly in terms of user discomfort and problematic mask-wearing behaviors. In the present studies, common design parameters of cloth masks were systematically varied to ascertain their effect(s) on the subjective discomfort and frequency of problematic mask-wearing behaviors, which detract from the effectiveness of cloth masks as source control. The type of fabric comprising a mask (flannel or twill made of 100% cotton) and the attachment-style of a mask (i.e., ear loops or fabric ties) were varied in adults (18 to 65 years) and children (ages 6 to 11 years). For adults, ear loops were less comfortable than ties (p = .035) and were associated with greater face- (p = .005) and mask-touching (p = .001). Children, however, found flannel masks to be more breathable than twill masks (p = .007) but touched their masks more frequently when wearing a mask made of flannel than twill (p = .033). Common design parameters of cloth masks not only affect user discomfort and behavior but do so differently in adults and children. To improve the effectiveness of cloth masks as source control, the present studies highlight the importance of measuring the effect(s) of design decisions on user discomfort and behavior in different populations.

Linking Cell Health and Reactive Oxygen Species from Secondary Organic Aerosols Exposure.

Oxidative stress is a possible mechanism by which ambient fine particulate matter (PM) exerts adverse biological effects. While multiple biological effects and reactive oxygen species (ROS) production have been observed upon PM exposure, whether the biological effects are ROS-mediated remains unclear. Secondary organic aerosols (SOA) constitute a major fraction of fine PM and can contribute substantially to its toxicity. In this work, we measured three types of cell responses (mitochondrial membrane potential (MMP), caspase 3/7 activity, and ROS) and investigated their associations upon exposure to SOA formed from anthropogenic (naphthalene) and biogenic (α-pinene) precursors. MMP and caspase 3/7 activity (an early indicator of apoptosis) are key indicators of cell health, and changes of them could occur downstream of ROS-mediated pathways. We observed a significant increase in caspase 3/7 activity after SOA exposure, suggesting that apoptosis is an important pathway of cell death induced by SOA. We further found strong associations between a decrease in MMP and increase in caspase 3/7 activity with an increase in cellular ROS level. These results suggest that cell health is largely dependent on the cellular ROS level, highlighting oxidative stress as a key mechanism for biological effects from SOA exposure. Linear regression analyses reveal greater changes of the three cellular responses with increasing carbon oxidation state (OSc) of SOA, suggesting that SOA are more toxic when they are more oxidized. Overall, our work provides critical insights into the associations between cell health and ROS level upon SOA exposure and proposes that OSc could be a suitable proxy to assess the overall SOA toxicity.

Vapors Are Lost to Walls, Not to Particles on the Wall: Artifact-Corrected Parameters from Chamber Experiments and Implications for Global Secondary Organic Aerosol.

Atmospheric models of secondary organic aerosol (OA) (SOA) typically rely on parameters derived from environmental chambers. Chambers are subject to experimental artifacts, including losses of (1) particles to the walls (PWL), (2) vapors to the particles on the wall (V2PWL), and (3) vapors to the wall directly (VWL). We present a method for deriving artifact-corrected SOA parameters and translating these to volatility basis set (VBS) parameters for use in chemical transport models (CTMs). Our process involves combining a box model that accounts for chamber artifacts (Statistical Oxidation Model with a TwO-Moment Aerosol Sectional model (SOM-TOMAS)) with a pseudo-atmospheric simulation to develop VBS parameters that are fit across a range of OA mass concentrations. We found that VWL led to the highest percentage change in chamber SOA mass yields (high NOx: 36-680%; low NOx: 55-250%), followed by PWL (high NOx: 8-39%; low NOx: 10-37%), while the effects of V2PWL are negligible. In contrast to earlier work that assumed that V2PWL was a meaningful loss pathway, we show that V2PWL is an unimportant SOA loss pathway and can be ignored when analyzing chamber data. Using our updated VBS parameters, we found that not accounting for VWL may lead surface-level OA to be underestimated by 24% (0.25 µg m-3) as a global average or up to 130% (9.0 µg m-3) in regions of high biogenic or anthropogenic activity. Finally, we found that accurately accounting for PWL and VWL improves model-measurement agreement for fine mode aerosol mass concentrations (PM2.5) in the GEOS-Chem model.

Non-linear effects of secondary organic aerosol formation and properties in multi-precursor systems.

Secondary organic aerosol (SOA) contributes significantly to ambient fine particulate matter that affects climate and human health. Monoterpenes represent an important class of biogenic volatile organic compounds (VOCs) and their oxidation by nitrate radicals poses a substantial source of SOA globally. Here, we investigate the formation and properties of SOA from nitrate radical oxidation of two common monoterpenes, α-pinene and limonene. When two monoterpenes are oxidized simultaneously, we observe a ~50% enhancement in the formation of SOA from α-pinene and a ~20% reduction in limonene SOA formation. The change in SOA yields is accompanied by pronounced changes in aerosol chemical composition and volatility. These non-linear effects are not observed in a sequential oxidation experiment. Our results highlight that unlike currently assumed in atmospheric models, the interaction of products formed from individual VOCs should be accounted for to accurately describe SOA formation and its climate and health impacts.

Investigating the Sources of Urban Air Pollution Using Low-Cost Air Quality Sensors at an Urban Atlanta Site.

Advances in low-cost sensors (LCS) for monitoring air quality have opened new opportunities to characterize air quality in finer spatial and temporal resolutions. In this study, we deployed LCS that measure both gas (CO, NO, NO2, and O3) and particle concentrations and co-located research-grade instruments in Atlanta, GA, to investigate the capability of LCS in resolving air pollutant sources using non-negative matrix factorization (NMF) in a moderately polluted urban area. We provide a comparison of applying the NMF technique to both normalized and non-normalized data sets. We identify four factors with different temporal trends and properties for both normalized and non-normalized data sets. Both normalized and non-normalized LCS data sets can resolve primary organic aerosol (POA) factors identified from research-grade instruments. However, applying normalization provides factors with more diverse compositions and can resolve secondary organic aerosol (SOA). Results from this study demonstrate that LCS not only can be used to provide basic mass concentration information but also can be used for in-depth source apportionment studies even in an urban setting with complex pollution mixtures and relatively low aerosol loadings.

Synthesis and Hydrolysis of Atmospherically Relevant Monoterpene-Derived Organic Nitrates.

The partition of gas-phase organic nitrates (ONs) to aerosols and subsequent hydrolysis are regarded as important loss mechanisms for ON species. However, the hydrolysis mechanisms and the major factors controlling the hydrolysis lifetime are not fully understood. In this work, we synthesized seven monoterpene-derived ONs and systematically investigated their hydrolysis in bulk solutions at different pH values. The hydrolysis lifetimes ranged from 12.9 min to 8.5 h for allylic primary ON and tertiary ONs, but secondary ONs were stable at neutral pH. The alkyl substitution numbers, functional groups, and carbon skeletons were three important factors controlling hydrolysis rates. Tertiary and secondary ONs were found to hydrolyze via the acid-catalyzed unimolecular (SN1) mechanism, while a competition of SN1 and bimolecular (SN2) mechanisms accounted for the hydrolysis of primary ONs. The consistency of experimental and theoretical hydrolysis rates calculated by density functional theory further supported the proposed mechanisms. Reversible reactions including hydrolysis and nitration were first reported to explain the hydrolysis of ONs, highlighting the possibility that particulate nitric acid can participate in nitration to generate new nitrogen-containing compounds. These findings demonstrate that ON hydrolysis is a complex reaction that proceeds via different mechanisms and is controlled by various parameters.

Critical Role of Simultaneous Reduction of Atmospheric Odd Oxygen for Winter Haze Mitigation.

The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.

In-flight particulate matter concentrations in commercial flights are likely lower than other indoor environments.

Air quality in indoor environments can have significant impacts on people's health, comfort, and productivity. Particulate matter (PM; also referred to as aerosols) is an important type of air pollutant, and exposure to outdoor PM has been associated with a variety of diseases. In addition, there is increasing recognition and concern of airborne transmission of viruses, including severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2), especially in indoor environments. Despite its importance, indoor PM data during the COVID-19 pandemic are scarce. In this work, we measured and compared particle number and mass concentrations in aircraft cabins during commercial flights with various indoor environments in Atlanta, GA, during July 2020, including retail stores, grocery stores, restaurants, offices, transportation, and homes. Restaurants had the highest particle number and mass concentrations, dominated by cooking emissions, while in-flight aircraft cabins had the lowest observed concentrations out of all surveyed spaces.

Formation of Oxidized Gases and Secondary Organic Aerosol from a Commercial Oxidant-Generating Electronic Air Cleaner.

The COVID-19 pandemic increased the demand for indoor air cleaners. While some commercial electronic air cleaners can be effective in reducing primary pollutants and inactivating bioaerosol, studies on the formation of secondary products from oxidation chemistry during their use are limited. Here, we measured oxygenated volatile organic compounds (OVOCs) and the chemical composition of particles generated from a hydroxyl radical generator in an office. During operation, enhancements in OVOCs, especially low-molecular-weight organic acids, were detected. Rapid increases in particle number and mass concentrations were observed, corresponding to the formation of highly oxidized secondary organic aerosol (SOA) (O:C ∼ 1.3), with an enhanced signal at m/z 44 (CO2+) in the organic mass spectra. These results suggest that organic acids generated during VOC oxidation contributed to particle nucleation and SOA formation. Nitrate, sulfate, and chloride also increased during the oxidation without a corresponding increase in ammonium, suggesting organic nitrate, organic sulfate, and organic chloride formation. As secondary species are reported to have detrimental health effects, further studies should not be limited to the inactivation of bioaerosol or reduction of particular VOCs, but should also evaluate potential OVOCs and SOA formation from electronic air cleaners in different indoor environments.

Time-Resolved Single-Cell Assay for Measuring Intracellular Reactive Oxygen Species upon Exposure to Ambient Particulate Matter.

Health risks associated with exposure to ambient particulate matter (PM) are a major concern around the world. Adverse PM health effects have been proposed to be linked to oxidative stress through the generation of reactive oxygen species (ROS). In vitro cellular assays can provide insights into components or characteristics of PM that best account for its toxicity at a cellular level. However, most current assays report cell population averages and are mostly time endpoint measurements and thus provide no temporal information. This poses limitations on our understanding of PM health effects. In this study, we developed a microfluidic assay that can measure cellular ROS responses at the single-cell level and evaluate temporal dynamic behavior of single cells. We first established a protocol that enables culturing cells in our microfluidic platform and that can provide reproducible ROS readouts. We further examined the heterogeneous ROS responses of cell populations and tracked the dynamics of individual cellular responses upon exposure to different concentrations of PM extracts. Our results show that in an alveolar macrophage cell line, cellular ROS responses are highly heterogeneous. ROS responses from different cells can vary over an order of magnitude, and large coefficients of variation at each timepoint measurement indicate a high variability. The dynamic behavior of single-cell responses is strongly dependent on PM concentrations. Our work serves as a proof-of-principle demonstration of the capability of our microfluidic technology to study time-resolved single-cell responses upon PM exposure. We envision applying this high-resolution, high-content assay to investigate a wide array of single-cell responses (beyond ROS) upon exposure to different types of PM in the future.

Enveloped Virus Inactivation on Personal Protective Equipment by Exposure to Ozone.

Ozone is a highly oxidizing gas easily generated from atmospheric oxygen with inexpensive equipment and is commonly used for the disinfection of municipal water, foods, and surfaces. We report tests of the ability of ozone to inactivate enveloped respiratory viruses (influenza A virus and respiratory syncytial virus), chosen as more easily handled surrogates for SARS-CoV-2, on N95 respirators and other personal protective equipment (PPE) commonly used in hospitals. At 20 ppm, an ozone concentration easily achieved by standard commercial equipment, the viruses were inactivated with high efficiency as long as the relative humidity was above a threshold value of approximately 50%. In the absence of humidity control, disinfection is more variable and requires considerably longer exposure under relatively dry conditions. This report extends the observations of a previous publication (http://doi.org/10.1080/01919510902747969) to hospital-relevant materials and provides additional details about the relationship of humidity to the antiviral activity of ozone. Home CPAP disinfection devices using ozone can provide effective results for individuals. Ozone did not appear to degrade any of the materials tested except for elastic bands if strained during treatment (such as by the pressure exerted by stapled attachment to N95 respirators). The filtration efficiency of N95 respirator material was not compromised. Overall, we recommend exposures of at least 40 minutes to 20 ppm ozone and >70% relative humidity at ambient temperatures (21-24°C) for 4-log (99.99%) reduction of viral infectivity on a variety of PPE, including gowns, face shields, and respirators. Shorter exposure times are likely to be effective under these conditions, but at the risk of some variability for different materials. Higher ozone concentrations and higher humidity levels promoted faster inactivation of viruses. Our work suggests that ozone exposure can be a widely accessible method for disinfecting PPE, permitting safer re-use for healthcare workers and patients alike in times of shortage.

Response of the Aerodyne Aerosol Mass Spectrometer to Inorganic Sulfates and Organosulfur Compounds: Applications in Field and Laboratory Measurements.

Organosulfur compounds are important components of secondary organic aerosols (SOA). While the Aerodyne high-resolution time-of-flight aerosol mass spectrometer (AMS) has been extensively used in aerosol studies, the response of the AMS to organosulfur compounds is not well-understood. Here, we investigated the fragmentation patterns of organosulfurs and inorganic sulfates in the AMS, developed a method to deconvolve total sulfate into components of inorganic and organic origins, and applied this method in both laboratory and field measurements. Apportionment results from laboratory isoprene photooxidation experiment showed that with inorganic sulfate seed, sulfate functionality of organic origins can contribute ∼7% of SOA mass at peak growth. Results from measurements in the Southeastern U.S. showed that 4% of measured sulfate is from organosulfur compounds. Methanesulfonic acid was estimated for measurements in the coastal and remote marine boundary layer. We explored the application of this method to unit mass-resolution data, where it performed less well due to interferences. Our apportionment results demonstrate that organosulfur compounds could be a non-negligible source of sulfate fragments in AMS laboratory and field data sets. A reevaluation of previous AMS measurements over the full range of atmospheric conditions using this method could provide a global estimate/constraint on the contribution of organosulfur compounds.

Southeast Atmosphere Studies: learning from model-observation syntheses.

Concentrations of atmospheric trace species in the United States have changed dramatically over the past several decades in response to pollution control strategies, shifts in domestic energy policy and economics, and economic development (and resulting emission changes) elsewhere in the world. Reliable projections of the future atmosphere require models to not only accurately describe current atmospheric concentrations, but to do so by representing chemical, physical and biological processes with conceptual and quantitative fidelity. Only through incorporation of the processes controlling emissions and chemical mechanisms that represent the key transformations among reactive molecules can models reliably project the impacts of future policy, energy and climate scenarios. Efforts to properly identify and implement the fundamental and controlling mechanisms in atmospheric models benefit from intensive observation periods, during which collocated measurements of diverse, speciated chemicals in both the gas and condensed phases are obtained. The Southeast Atmosphere Studies (SAS, including SENEX, SOAS, NOMADSS and SEAC4RS) conducted during the summer of 2013 provided an unprecedented opportunity for the atmospheric modeling community to come together to evaluate, diagnose and improve the representation of fundamental climate and air quality processes in models of varying temporal and spatial scales. This paper is aimed at discussing progress in evaluating, diagnosing and improving air quality and climate modeling using comparisons to SAS observations as a guide to thinking about improvements to mechanisms and parameterizations in models. The effort focused primarily on model representation of fundamental atmospheric processes that are essential to the formation of ozone, secondary organic aerosol (SOA) and other trace species in the troposphere, with the ultimate goal of understanding the radiative impacts of these species in the southeast and elsewhere. Here we address questions surrounding four key themes: gas-phase chemistry, aerosol chemistry, regional climate and chemistry interactions, and natural and anthropogenic emissions. We expect this review to serve as a guidance for future modeling efforts.

Secondary Organic Aerosol (SOA) from Nitrate Radical Oxidation of Monoterpenes: Effects of Temperature, Dilution, and Humidity on Aerosol Formation, Mixing, and Evaporation.

Nitrate radical (NO3) oxidation of biogenic volatile organic compounds (BVOC) is important for nighttime secondary organic aerosol (SOA) formation. SOA produced at night may evaporate the following morning due to increasing temperatures or dilution of semivolatile compounds. We isothermally dilute the oxidation products from the limonene+NO3 reaction at 25 °C and observe negligible evaporation of organic aerosol via dilution. The SOA yields from limonene+NO3 are approximately constant (∼174%) at 25 °C and range from 81 to 148% at 40 °C. Based on the difference in yields between the two temperatures, we calculated an effective enthalpy of vaporization of 117-237 kJ mol-1. The aerosol yields at 40 °C can be as much as 50% lower compared to 25 °C. However, when aerosol formed at 25 °C is heated to 40 °C, only about 20% of the aerosol evaporates, which could indicate a resistance to aerosol evaporation. To better understand this, we probe the possibility that SOA from limonene+NO3 and ß-pinene+NO3 reactions is highly viscous. We demonstrate that particle morphology and evaporation is dependent on whether SOA from limonene is formed before or during the formation of SOA from ß-pinene. This difference in particle morphology is present even at high relative humidity (∼70%).

The Essential Role for Laboratory Studies in Atmospheric Chemistry.

Laboratory studies of atmospheric chemistry characterize the nature of atmospherically relevant processes down to the molecular level, providing fundamental information used to assess how human activities drive environmental phenomena such as climate change, urban air pollution, ecosystem health, indoor air quality, and stratospheric ozone depletion. Laboratory studies have a central role in addressing the incomplete fundamental knowledge of atmospheric chemistry. This article highlights the evolving science needs for this community and emphasizes how our knowledge is far from complete, hindering our ability to predict the future state of our atmosphere and to respond to emerging global environmental change issues. Laboratory studies provide rich opportunities to expand our understanding of the atmosphere via collaborative research with the modeling and field measurement communities, and with neighboring disciplines.

Nitrate radicals and biogenic volatile organic compounds: oxidation, mechanisms, and organic aerosol.

Oxidation of biogenic volatile organic compounds (BVOC) by the nitrate radical (NO3) represents one of the important interactions between anthropogenic emissions related to combustion and natural emissions from the biosphere. This interaction has been recognized for more than 3 decades, during which time a large body of research has emerged from laboratory, field, and modeling studies. NO3-BVOC reactions influence air quality, climate and visibility through regional and global budgets for reactive nitrogen (particularly organic nitrates), ozone, and organic aerosol. Despite its long history of research and the significance of this topic in atmospheric chemistry, a number of important uncertainties remain. These include an incomplete understanding of the rates, mechanisms, and organic aerosol yields for NO3-BVOC reactions, lack of constraints on the role of heterogeneous oxidative processes associated with the NO3 radical, the difficulty of characterizing the spatial distributions of BVOC and NO3 within the poorly mixed nocturnal atmosphere, and the challenge of constructing appropriate boundary layer schemes and non-photochemical mechanisms for use in state-of-the-art chemical transport and chemistry-climate models. This review is the result of a workshop of the same title held at the Georgia Institute of Technology in June 2015. The first half of the review summarizes the current literature on NO3-BVOC chemistry, with a particular focus on recent advances in instrumentation and models, and in organic nitrate and secondary organic aerosol (SOA) formation chemistry. Building on this current understanding, the second half of the review outlines impacts of NO3-BVOC chemistry on air quality and climate, and suggests critical research needs to better constrain this interaction to improve the predictive capabilities of atmospheric models.