The Importance of Circulation in Airway Management: Preventing Post-Intubation Hypotension in The Trauma Bay.

OBJECTIVE: To identify the modifiable and non-modifiable risk factors associated with post-intubation hypotension (PIH) among trauma patients who required endotracheal intubation (ETI) in the trauma bay. SUMMARY BACKGROUND DATA: ETI has been associated with hemodynamic instability, termed PIH, yet its risk factors in trauma patients remain under-investigated. METHODS: This is a prospective observational study at a level I trauma center over 4 years (2019-2022). All adult (≥18) trauma patients requiring ETI in the trauma bay were included. Blood pressure was monitored both pre- and post-intubation. Multivariable logistic regression analysis was performed to identify the modifiable and non-modifiable factors associated with PIH. RESULTS: 708 patients required ETI in the trauma bay, of which, 435 (61.4%) developed PIH. The mean (SD) age was 43 (21) and 71% were male. Median [IQR] arrival GCS was 7 [3-13]. Patients who developed PIH had a lower mean (SD) pre-intubation SBP (118 (46) vs. 138 (28), P<0.001) and higher median [IQR] ISS (27 [21-38] vs. 21 [9-26], P<0.001). Multivariable regression analysis identified BMI>25, increasing ISS, penetrating injury, spinal cord injury, Pre-intubation PRBC requirements, and diabetes mellitus as non-modifiable risk factors associated with increased odds of PIH. In contrast, pre-intubation administration of 3% hypertonic saline and vasopressors were identified as the modifiable factors significantly associated with reduced PIH. CONCLUSION: More than half of the patients requiring ETI in the trauma bay developed PIH. This study identified modifiable and non-modifiable risk factors that influence the development of PIH, which will help physicians when considering ETI upon patient arrival. LEVEL OF EVIDENCE: Level III, Prognostic Study.

Zircons reveal the history of fluctuations in oxidation state of crustal magmatism and supercontinent cycle.

We apply a zircon redox index to a global compilation of detrital zircons to track the variation of oxidation state, expressed as ΔFMQ, through Earth's history. Those from I-type rocks, which comprise mantle and crustal igneous protoliths, including tonalite-trondhjemite-granodiorites (TTGs), generally have a high oxidation state (ΔFMQ > 0). In contrast, zircons from igneous rocks derived from supracrustal source rocks (S-type) are commonly reduced (ΔFMQ < 0). With the probability density function derived from the Gaussian-Kernel-Density-Estimation, we use the maximum likelihood estimation (MLE) to distinguish S-type from I-type zircons through Earth's history using zircon redox. Voluminous S-type magma production shows a ca. 600 Ma cyclicity that is closely related to the supercontinent cycle. We link a cyclic drop in redox values after 2.6 Ga to periodic S-type magma generation associated with burial and melting of metasedimentary rocks during supercontinent assembly and amalgamation. The ΔFMQ of the detrital zircons rise at ∼3.5 Ga followed by a consistent average ΔFMQ > 0 over the last 3 Ga. Given that the redox state of magmas is independent of crustal thickness and silica variation, and elevated values are likely more closely related to tectonic setting, we suggest that the consistent average ΔFMQ > 0 from ca. 3.5 Ga onwards relates to recycling of oceanic lithosphere back into the mantle in what eventually became established as subduction zones. The more reduced magmas associated with sedimentary sources, became established at 2.6 Ga, presumably in response to continental rocks rising above sea-level, and follow peaks of productivity associated with the supercontinent cycle.

Right Ventricular Dysfunction Patterns among Patients with COVID-19 in the Intensive Care Unit: A Retrospective Cohort Analysis.

Rationale: Right ventricular (RV) dysfunction is common among patients hospitalized with coronavirus disease (COVID-19); however, its epidemiology may depend on the echocardiographic parameters used to define it. Objectives: To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among patients with COVID-19 admitted to the intensive care unit (ICU), as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality. Methods: We conducted a retrospective cohort study of ICU patients with COVID-19 between March 4, 2020, and March 4, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation, respectively, were defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality was assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at the time of transthoracic echocardiogram, and Acute Physiology and Chronic Health Evaluation II score. Results: A total of 116 patients were included, of whom 69% had RV dysfunction by one or more parameters, and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction were the presence of three abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RV fractional area change (24% vs. 36%; P = 0.001), worse RVFWS (16.3% vs. 19.1%; P = 0.005), higher RV systolic pressure (45 mm Hg vs. 31 mm Hg; P = 0.001) but similar TAPSE (13 mm vs. 13 mm; P = 0.30) compared with those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (odds ratio, 2.91; 95% confidence interval, 1.01-9.44), as was the presence of at least two parameter abnormalities. Conclusions: ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

Transitioning from epicutaneous to oral peanut immunotherapy.

Introduction: Epicutaneous immunotherapy (EPIT) has been tested in clinical trials for children with peanut allergy (PA) for its safety and efficacy in inducing desensitization. Aside from peanut avoidance and symptom management, oral immunotherapy (OIT) is another option for PA patients. However, OIT can be associated with adverse events and pose safety concerns to children and their caregivers. Methods: This study assessed 27 children who successfully completed a peanut EPIT trial. 18 of them transitioned to peanut OIT with starting doses ranging from 10-600 mg of peanut protein. Our aim was to learn more about the EPIT to OIT experience through descriptive survey responses and to gather information that may support the sequential use of the two immunotherapies for safe and positive outcomes that may not be achieved by either alone. Results: Overall, children and their caregivers had less anxiety about starting OIT after having had peanut exposure through EPIT. Most children who transitioned from EPIT to OIT had no or minor symptoms initially, with symptoms lessening later in OIT. Most were also able to maintain or increase their peanut dose over time, achieving maintenance doses of 60-2,000 mg. Discussion: In comparison with current literature on OIT for PA in children, the reported symptoms appeared less severe and less prevalent in the EPIT to OIT group. However, there were 3 participants who withdrew from OIT due to the development of intolerable symptoms. This study provides initial data in support of EPIT to OIT, and larger randomized controlled trials assessing effectiveness of the two therapies together are warranted.

Association between Obesity and Length of COVID-19 Hospitalization: Unexpected Insights from the American Heart Association National COVID-19 Registry.

Background: The mechanism for possible association between obesity and poor clinical outcomes from Coronavirus Disease 2019 (COVID-19) remains unclear. Methods: We analyzed 22,915 adult COVID-19 patients hospitalized from March 2020 to April 2021 to non-intensive care using the American Heart Association National COVID Registry. A multivariable Poisson model adjusted for age, sex, medical history, admission respiratory status, hospitalization characteristics, and laboratory findings was used to calculate length of stay (LOS) as a function of body mass index (BMI). We similarly analyzed 5,327 patients admitted to intensive care for comparison. Results: Relative to normal BMI subjects, overweight, class I obese, and class II obese patients had approximately half-day reductions in LOS (-0.469 days, P<0.01; -0.480 days, P<0.01; -0.578 days, P<0.01, respectively). Conclusion: The model identified a dose-dependent, inverse relationship between BMI category and LOS for COVID-19, which was not seen when the model was applied to critically ill patients.

Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome.

BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.

Constrictive Pericarditis Revealing Rare Case of ALH Amyloidosis With Underlying Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia).

We present a case of pericardial amyloidosis with associated lymphoplasmacytic lymphoma in a patient with chronic worsening shortness of breath and cough. This case highlights the wide variation in the presentation of cardiac amyloidosis, and the rare occurrence of clinically significant light-chain and heavy-chain amyloidosis in the pericardium. (Level of Difficulty: Advanced.).

Virtual Reality Reduces Pediatric Anxiety During Food Allergy Clinical Trials: A Pilot Randomized, Pragmatic Study.

Phlebotomy procedures required in food allergy (FA) diagnosis and clinical trials often induce fear and anxiety for pediatric patients. The primary aim of this study was to determine whether virtual reality (VR) applications were effective in reducing anxiety for pediatric FA patients undergoing phlebotomy during FA clinical trials. Secondary aims assessed fear, pain, procedural compliance, and adverse events. Participants undergoing phlebotomy were enrolled and randomized to a VR group or standard of care (SOC) group for this prospective pilot randomized, pragmatic study. Participants in the VR group played interactive applications on a customized Samsung Gear VR headset and those in the SOC group received the standard of care. Participants' anxiety, fear, and pain were assessed with the Children's Anxiety Meter, Children's Fear Scale, and FACES pain scale pre, during, and post phlebotomy procedure. Compliance was assessed using the modified Induction Compliance Checklist during the procedure and compared between two groups. Forty-nine participants were randomized to VR (n = 26) and SOC (n = 23) groups. Although both the VR and SOC groups experienced a decrease in anxiety and fear from pre- to post-procedure, those in the VR group experienced less anxiety and fear during the procedure than SOC participants. Similarly, both groups experienced an increase in pain from pre- to post-procedure; however, the VR group reported less pain during the procedure than SOC. Fewer symptoms of procedural non-compliance were reported in the VR group. Interactive VR applications may be an effective tool for reducing fear, anxiety, and pain during phlebotomy for FA clinical trials.

Land-use emissions play a critical role in land-based mitigation for Paris climate targets.

Scenarios that limit global warming to below 2 °C by 2100 assume significant land-use change to support large-scale carbon dioxide (CO2) removal from the atmosphere by afforestation/reforestation, avoided deforestation, and Biomass Energy with Carbon Capture and Storage (BECCS). The more ambitious mitigation scenarios require even greater land area for mitigation and/or earlier adoption of CO2 removal strategies. Here we show that additional land-use change to meet a 1.5 °C climate change target could result in net losses of carbon from the land. The effectiveness of BECCS strongly depends on several assumptions related to the choice of biomass, the fate of initial above ground biomass, and the fossil-fuel emissions offset in the energy system. Depending on these factors, carbon removed from the atmosphere through BECCS could easily be offset by losses due to land-use change. If BECCS involves replacing high-carbon content ecosystems with crops, then forest-based mitigation could be more efficient for atmospheric CO2 removal than BECCS.

The effect of future ambient air pollution on human premature mortality to 2100 using output from the ACCMIP model ensemble.

Ambient air pollution from ground-level ozone and fine particulate matter (PM2.5) is associated with premature mortality. Future concentrations of these air pollutants will be driven by natural and anthropogenic emissions and by climate change. Using anthropogenic and biomass burning emissions projected in the four Representative Concentration Pathway scenarios (RCPs), the ACCMIP ensemble of chemistry-climate models simulated future concentrations of ozone and PM2.5 at selected decades between 2000 and 2100. We use output from the ACCMIP ensemble, together with projections of future population and baseline mortality rates, to quantify the human premature mortality impacts of future ambient air pollution. Future air pollution-related premature mortality in 2030, 2050 and 2100 is estimated for each scenario and for each model using a health impact function based on changes in concentrations of ozone and PM2.5 relative to 2000 and projected future population and baseline mortality rates. Additionally, the global mortality burden of ozone and PM2.5 in 2000 and each future period is estimated relative to 1850 concentrations, using present-day and future population and baseline mortality rates. The change in future ozone concentrations relative to 2000 is associated with excess global premature mortality in some scenarios/periods, particularly in RCP8.5 in 2100 (316 thousand deaths/year), likely driven by the large increase in methane emissions and by the net effect of climate change projected in this scenario, but it leads to considerable avoided premature mortality for the three other RCPs. However, the global mortality burden of ozone markedly increases from 382,000 (121,000 to 728,000) deaths/year in 2000 to between 1.09 and 2.36 million deaths/year in 2100, across RCPs, mostly due to the effect of increases in population and baseline mortality rates. PM2.5 concentrations decrease relative to 2000 in all scenarios, due to projected reductions in emissions, and are associated with avoided premature mortality, particularly in 2100: between -2.39 and -1.31 million deaths/year for the four RCPs. The global mortality burden of PM2.5 is estimated to decrease from 1.70 (1.30 to 2.10) million deaths/year in 2000 to between 0.95 and 1.55 million deaths/year in 2100 for the four RCPs, due to the combined effect of decreases in PM2.5 concentrations and changes in population and baseline mortality rates. Trends in future air pollution-related mortality vary regionally across scenarios, reflecting assumptions for economic growth and air pollution control specific to each RCP and region. Mortality estimates differ among chemistry-climate models due to differences in simulated pollutant concentrations, which is the greatest contributor to overall mortality uncertainty for most cases assessed here, supporting the use of model ensembles to characterize uncertainty. Increases in exposed population and baseline mortality rates of respiratory diseases magnify the impact on premature mortality of changes in future air pollutant concentrations and explain why the future global mortality burden of air pollution can exceed the current burden, even where air pollutant concentrations decrease.

Breast Cancer Survivorship and Cardiovascular Disease: Emerging Approaches in Cardio-Oncology.

OPINION STATEMENT: Cardiovascular disease (CVD) and breast cancer cause substantial morbidity and mortality in women and are major public health concerns in the USA. While aggressive screening and targeted, advanced treatment for breast cancer have had a measurable impact on breast cancer survival, treatment is not without significant cardiotoxic effects. Anthracycline-based chemotherapy can lead to left ventricular dysfunction and failure, as well as a decline in exercise tolerance and cardio-pulmonary reserve despite preserved ejection fraction. Trastuzumab, a newer monoclonal antibody targeting the Her2 receptor used in the treatment of Her2+ cancer, is also linked to left ventricular dysfunction, although the long-term cardiac effects are presently unclear. Radiation treatment particularly for left-sided breast cancer has been associated with increased rates of ischemic heart disease. As women have increasing survival and cure rates from early breast cancer, long-term consequences on the heart that are secondary to therapy are a major concern. These need to be identified, treated, and avoided when possible. Further research and clear surveillance guidelines are needed to aid the practicing clinician in CVD prevention in breast cancer survivors.

NOTCH1 regulates matrix gla protein and calcification gene networks in human valve endothelium.

Valvular and vascular calcification are common causes of cardiovascular morbidity and mortality. Developing effective treatments requires understanding the molecular underpinnings of these processes. Shear stress is thought to play a role in inhibiting calcification. Furthermore, NOTCH1 regulates vascular and valvular endothelium, and human mutations in NOTCH1 can cause calcific aortic valve disease. Here, we determined the genome-wide impact of altering shear stress and NOTCH signaling on human aortic valve endothelium. mRNA-sequencing of primary human aortic valve endothelial cells (HAVECs) with or without knockdown of NOTCH1, in the presence or absence of shear stress, revealed NOTCH1-dependency of the atherosclerosis-related gene connexin 40 (GJA5), and numerous repressors of endochondral ossification. Among these, matrix gla protein (MGP) is highly expressed in aortic valve and vasculature, and inhibits soft tissue calcification by sequestering bone morphogenetic proteins (BMPs). Altering NOTCH1 levels affected MGP mRNA and protein in HAVECs. Furthermore, shear stress activated NOTCH signaling and MGP in a NOTCH1-dependent manner. NOTCH1 positively regulated endothelial MGP in vivo through specific binding motifs upstream of MGP. Our studies suggest that shear stress activates NOTCH1 in primary human aortic valve endothelial cells leading to downregulation of osteoblast-like gene networks that play a role in tissue calcification.

Megacities and climate change - A brief overview.

Cities have developed into the hotspots of human economic activity. From the appearance of the first cities in the Neolithic to 21st century metropolis their impact on the environment has always been apparent. With more people living in cities than in rural environments now it becomes crucial to understand these environmental impacts. With the immergence of megacities in the 20th century and their continued growth in both, population and economic power, the environmental impact has reached the global scale. In this paper we examine megacity impacts on atmospheric composition and climate. We present basic concepts, discuss various definitions of footprints, summarize research on megacity impacts and assess the impact of megacity emissions on air quality and on the climate at the regional to global scale. The intention and ambition of this paper is to give a comprehensive but brief overview of the science with regard to megacities and the environment.

Global air quality and climate.

Emissions of air pollutants and their precursors determine regional air quality and can alter climate. Climate change can perturb the long-range transport, chemical processing, and local meteorology that influence air pollution. We review the implications of projected changes in methane (CH(4)), ozone precursors (O(3)), and aerosols for climate (expressed in terms of the radiative forcing metric or changes in global surface temperature) and hemispheric-to-continental scale air quality. Reducing the O(3) precursor CH(4) would slow near-term warming by decreasing both CH(4) and tropospheric O(3). Uncertainty remains as to the net climate forcing from anthropogenic nitrogen oxide (NO(x)) emissions, which increase tropospheric O(3) (warming) but also increase aerosols and decrease CH(4) (both cooling). Anthropogenic emissions of carbon monoxide (CO) and non-CH(4) volatile organic compounds (NMVOC) warm by increasing both O(3) and CH(4). Radiative impacts from secondary organic aerosols (SOA) are poorly understood. Black carbon emission controls, by reducing the absorption of sunlight in the atmosphere and on snow and ice, have the potential to slow near-term warming, but uncertainties in coincident emissions of reflective (cooling) aerosols and poorly constrained cloud indirect effects confound robust estimates of net climate impacts. Reducing sulfate and nitrate aerosols would improve air quality and lessen interference with the hydrologic cycle, but lead to warming. A holistic and balanced view is thus needed to assess how air pollution controls influence climate; a first step towards this goal involves estimating net climate impacts from individual emission sectors. Modeling and observational analyses suggest a warming climate degrades air quality (increasing surface O(3) and particulate matter) in many populated regions, including during pollution episodes. Prior Intergovernmental Panel on Climate Change (IPCC) scenarios (SRES) allowed unconstrained growth, whereas the Representative Concentration Pathway (RCP) scenarios assume uniformly an aggressive reduction, of air pollutant emissions. New estimates from the current generation of chemistry-climate models with RCP emissions thus project improved air quality over the next century relative to those using the IPCC SRES scenarios. These two sets of projections likely bracket possible futures. We find that uncertainty in emission-driven changes in air quality is generally greater than uncertainty in climate-driven changes. Confidence in air quality projections is limited by the reliability of anthropogenic emission trajectories and the uncertainties in regional climate responses, feedbacks with the terrestrial biosphere, and oxidation pathways affecting O(3) and SOA.

The effects of tropospheric ozone on net primary productivity and implications for climate change.

Tropospheric ozone (O(3)) is a global air pollutant that causes billions of dollars in lost plant productivity annually. It is an important anthropogenic greenhouse gas, and as a secondary air pollutant, it is present at high concentrations in rural areas far from industrial sources. It also reduces plant productivity by entering leaves through the stomata, generating other reactive oxygen species and causing oxidative stress, which in turn decreases photosynthesis, plant growth, and biomass accumulation. The deposition of O(3) into vegetation through stomata is an important sink for tropospheric O(3), but this sink is modified by other aspects of environmental change, including rising atmospheric carbon dioxide concentrations, rising temperature, altered precipitation, and nitrogen availability. We review the atmospheric chemistry governing tropospheric O(3) mass balance, the effects of O(3) on stomatal conductance and net primary productivity, and implications for agriculture, carbon sequestration, and climate change.

The Louisiana emergency department behavioral health challenge.

Hurricane Katrina uncovered and exaggerated Louisiana's behavioral health crisis. Patients with mental illness are backlogged in emergency rooms across the state, unable to access inpatient psychiatric treatment. Post-Katrina, part of the department of psychiatry of the Louisiana State University (LSU) New Orleans was displaced to Huey P. Long Medical Center (HPLMC) in Pineville, Louisiana. While displaced, LSU wrote a grant to develop a psychiatric emergency room service at HPLMC and in the process experienced a number of barriers to optimal behavioral healthcare in the emergency department (ED). The ED plays an essential role in our state's system of care for the mentally ill. However, EDs throughout the nation traditionally have not had the provisions necessary for optimal behavioral healthcare. In this article, we will address barriers to implementing proper provisions for sound behavioral healthcare in the ED. We will outline an affordable and available mental health personnel infrastructure that integrates with the ED's medical model of care, and improves quality of care of the mentally ill and the functional level of the ED, as well as the morale and job satisfaction of ED healthcare providers.

The use of genotyping in antimalarial clinical trials: a systematic review of published studies from 1995-2005.

BACKGROUND: The use of genotyping to distinguish recrudescent from new infections is currently recommended for all clinical antimalarial efficacy trials by the World Health Organization. However, genotyping-adjusted drug efficacy estimates may vary between trials due to the use of different genotyping methods and to the different settings in which these methods are applied. METHODS: A systematic review of all clinical antimalarial efficacy trials published from 1995-2005 was performed to characterize the use of genotyping, including the methods used and the effect of these methods on estimates of drug efficacy. RESULTS: In a multivariate analysis, the method of interpretation of genotyping results, the studied therapy, the location of the trial, and the duration of study follow-up all had statistically significant effects on the percent of genotyped outcomes classified as new infections. CONCLUSION: Criteria for defining appropriate, standardized genotyping methods for use in different settings are needed to enable more accurate estimates of antimalarial drug efficacy and better comparison between trials. The advantages and disadvantages of different genotyping methods and their potential impact in various settings are discussed.

The contribution from shipping emissions to air quality and acid deposition in Europe.

A global three-dimensional Lagrangian chemistry-transport model STOCHEM is used to describe the European regional acid deposition and ozone air quality impacts along the Atlantic Ocean seaboard of Europe, from the SO2, NOx, VOCs and CO emissions from international shipping under conditions appropriate to the year 2000. Model-derived total sulfur deposition from international shipping reaches over 200 mg S m(-2) yr(-1) over the southwestern approaches to the British Isles and Brittany. The contribution from international shipping to surface ozone concentrations during the summertime, peaks at about 6 ppb over Ireland, Brittany and Portugal. Shipping emissions act as an external influence on acid deposition and ozone air quality within Europe and may require control actions in the future if strict deposition and air quality targets are to be met.

Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma.

Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase II enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Pro187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction-restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case-parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2-0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure.