Ambient temperature exposure causes lung function impairment: The evidence from Controlled Temperature Study in Healthy Subjects (CTSHS).

BACKGROUND: The effect of non-optimal ambient temperatures (low and high temperatures) on lung function and the underlying mechanisms remains unclear. METHODS: Forty-three (20 males, 23 females) healthy non-obese volunteers with an average of 23.9 years participated in the controlled temperature study. All volunteers underwent three temperature exposures in a sequence (moderate [18 °C], low [6 °C], and high [30 °C] temperatures) lasting 12 h with air pollutants controlled. lung function parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) were determined in each exposure. Blood and urine samples were collected after each exposure and assayed for inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)] and oxidative damage markers [protein carbonylation (PCO), 4-hydroxy-2-nominal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F2α (8-isoPGF2α), and 8-hydroxy-2-deoxyguanosine (8-OHdG)]. Mixed-effects models were constructed to assess the changes of the above indexes under low or high temperatures relative to moderate temperature, and then the repeated measures correlation analyses were performed. RESULTS: Compared with moderate temperature, a 2.20% and 2.59% net decrease in FVC, FEV1, and a 5.68% net increase for PEF were observed under low-temperature exposure, while a 1.59% net decrease in FVC and a 7.29% net increase in PEF under high-temperature exposure were found (all P < 0.05). In addition, low temperature elevated inflammatory markers (PCT, PLR, and NLR) and oxidative damage markers (8-isoPGF2α, 8-OHdG), and high temperature elevated HNE-MA. Repeated measures correlation analyses revealed that PCT (r = -0.33) and NLR (r = -0.31) were negatively correlated with FVC and HNE-MA (r = -0.35) and 8-OHdG (r = -0.31) were negatively correlated with the FEV1 under low-temperature exposure (all P < 0.05). CONCLUSION: Non-optimal ambient temperatures exposure alters lung function, inflammation, and oxidative damage. Inflammation and oxidative damage might be involved in low temperature-related lung function reduction.

Dibutyl phthalate exposure alters T-cell subsets in blood from allergen-sensitized volunteers.

Phthalates are ubiquitous environmental contaminants associated with allergic disease in epidemiological and animal studies. This investigation aims to support these associations by interrogating systemic immune effects in allergen-sensitized volunteers after controlled indoor air exposure to a known concentration of dibutyl phthalate (DBP). The phthalate-allergen immune response (PAIR) study enrolled 16 allergen-sensitized participants to a double-blinded, randomized, crossover exposure to two conditions (DBP or control air for 3 hr), each followed immediately by inhaled allergen challenge. Peripheral blood immune cell composition and activation along with inflammatory mediators were measured before and after exposure. DBP exposure prior to the inhaled allergen challenge increased the percentage of CD4+ T helper cells and decreased the percentage of regulatory T cells (3 hr and 20 hr post-exposure), while only modest overall effects were observed for inflammatory mediators. The cells and mediators affected by the phthalate exposure were generally not overlapping with the endpoints affected by allergen inhalation alone. Thus, in distinction to our previously published effects on lung function, DBP appears to alter endpoints in peripheral blood that are not necessarily enhanced by allergen alone. Further studies are needed to clarify the role of phthalate-induced systemic effects in disease pathogenesis.

Impact of Exposure to Diesel Exhaust on Inflammation Markers and Proteases in Former Smokers with Chronic Obstructive Pulmonary Disease: A Randomized, Double-blinded, Crossover Study.

Rationale: There is growing evidence that chronic obstructive pulmonary disease (COPD) can be caused and exacerbated by air pollution exposure. Objectives: To document the impact of short-term air pollution exposure on inflammation markers, proteases, and antiproteases in the lower airways of older adults with and without COPD. Methods: Thirty participants (10 ex-smokers with mild to moderate COPD and 20 healthy participants [9 ex-smokers and 11 never-smokers]), with an average age of 60 years, completed this double-blinded, controlled, human crossover exposure study. Each participant was exposed to filtered air (control) and diesel exhaust (DE), in washout-separated 2-hour periods, in a randomly assigned order. Bronchoscopy was performed 24 hours after exposure to collect lavage. Cell counts were performed on blood and airway samples. ELISAs were performed to measure acute inflammatory proteins, matrix proteinases, and antiproteases in the airway and blood samples. Measurements and Main Results: In former smokers with COPD, but not in the other participants, exposure to DE increased serum amyloid A (effect estimate, 1.67; 95% confidence interval [CI], 1.21-2.30; P = 0.04) and matrix metalloproteinase 10 (effect estimate, 2.61; 95% CI, 1.38-4.91; P = 0.04) in BAL. Circulating lymphocytes were increased after DE exposure (0.14 [95% CI, 0.05-0.24] cells × 109/L; P = 0.03), irrespective of COPD status. Conclusions: A controlled human crossover study of DE exposure reveals that former smokers with COPD may be susceptible to an inflammatory response compared with ex-smokers without COPD or never-smoking healthy control participants. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).

Ozone exposure and prothrombosis: Mechanistic insights from a randomized controlled exposure trial.

Epidemiological studies have associated ozone exposure with cardiovascular diseases, but the molecular mechanisms were not elucidated. We performed an untargeted serum proteomic analysis in a randomized, crossover, controlled exposure trial. We recruited 32 healthy young adults and asked them to receive filtered air and 200-ppb ozone exposures for 2 h in a random order before serum collection. Linear mixed-effect models were used to identify differentially expressed proteins (DEPs) between the two exposures and Gene Ontology enrichment and ingenuity pathway analysis were performed to determine their biological function. A total of 56 DEPs were identified. For example, acute ozone exposure increased coagulation factor X and factor VII-activating protease by 20.96% and 28.35%, respectively. Whereas, protein Z, protein Z-dependent protease inhibitor, and plasminogen decreased by 13.62%, 33.54%, and 10.47%, respectively. We also observed a 42.32% decrease in paraoxonase 3 and evident changes in four apolipoproteins. Additionally, we found 18.21% and 95.82% increases in L-selectin and ß2-microglobulin, respectively, and significant changes in three complements. DEPs and enriched pathways suggest that short-term ozone exposure may promote coagulation, suppress fibrinolysis, disrupt lipoprotein metabolism, activate immune responses, and affect the complement system. These findings provide additional insights into the mechanisms linking acute ozone exposure to thrombosis.

Effects of Traffic-Related Air Pollution on Exercise Endurance, Dyspnea, and Cardiorespiratory Responses in Health and COPD: A Randomized, Placebo-Controlled, Crossover Trial.

BACKGROUND: Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD. RESEARCH QUESTION: Does exposure before exercise to TRAP (DE titrated to 300 µg/m3 particulate matter < 2.5 µm in diameter [DE300]) show greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild to moderate COPD compared with former smokers with normal spirometry and healthy control participants? STUDY DESIGN AND METHODS: In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy control participants, nine former smokers without COPD, and nine former smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 h separated by a minimum of 4 weeks. Participants performed symptom-limited constant load cycling tests within 2.5 h of exposure with detailed cardiorespiratory and exertional symptom measurements. RESULTS: A significant negative effect of TRAP on exercise endurance time was found in healthy control participants (DE300 vs FA, 10.2 ± 8.2 min vs 12.9 ± 9.5 min, respectively; P = .03), but not in former smokers without COPD (10.1 ± 6.9 min vs 12.2 ± 8.0 min, respectively; P = .57) or former smokers with COPD (9.8 ± 6.4 min vs 8.4 ± 6.6 min, respectively; P = .31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy control participants. INTERPRETATION: Contrary to our hypothesis, it was the healthy control participants, rather than the former smokers with and without COPD, who were negatively impacted by TRAP during exercise. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02236039; URL: www. CLINICALTRIALS: gov.

Spanish Society of Allergology and Clinical Immunology (SEAIC) Vision of Drug Provocation Tests.

The controlled drug provocation test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Adverse drug reactions (ADRs) are an increasingly common presenting complaint in both primary and specialized care. In Spain, ADRs are usually assessed via the allergology department, which rules out immunological mechanisms in up to 90% of cases. An adequate approach to ADRs clearly impacts the costs and efficacy of the treatments prescribed by other specialists. Consequently, if we did not use DPTs, patients would require more expensive, more toxic, and less effective treatments in many cases. In recent years, many new drugs have been developed. This document is intended to be a practical guideline for the management of DPTs according to the vision of the Spanish Allergology Society. The diagnostic work-up begins with a detailed clinical history. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although cross-reactivity is common, DPTs can confirm the diagnosis and help to find an alternative drug. Programmed individualized patient management based on the type of drug to be studied and the patient´s comorbidities usually enables a solution to be found in most cases.

Metabolites of 2- and 3-Monochloropropanediol (2- and 3-MCPD) in Humans: Urinary Excretion of 2-Chlorohydracrylic Acid and 3-Chlorolactic Acid after Controlled Exposure to a Single High Dose of Fatty Acid Esters of 2- and 3-MCPD.

SCOPE: Fatty acid esters of 2-monochloropropane-1,3-diol (2-MCPD) and 3-monochloropropane-1,2-diol (3-MCPD) are formed during the deodorization of vegetable oils. After lipase-catalyzed hydrolysis in the intestine, 2- and 3-MCPD are absorbed, but their ensuing human metabolism is unknown. METHODS AND RESULTS: The compounds 2-chlorohydracrylic acid (2-ClHA) and 3-chlorolactic acid (3-ClLA) resulting from oxidative metabolism of 2-MCPD and 3-MCPD, respectively, are identified and quantified in human urine samples. An exposure study with 12 adults is conducted to determine the urinary excretion of 2-ClHA and 3-ClLA. The participants eat 12 g of hazelnut oil containing 24.2 mg kg-1 2-MCPD and 54.5 mg kg-1 3-MCPD in the form of fatty acid esters. Average daily amounts of "background" excretion before the exposure are 69 nmol 2-ClHA and 3.0 nmol 3-ClLA. The additional mean excretion due to the uptake of the hazelnut oil amounts to 893 nmol 2-ClHA (34.0% of the 2-MCPD dose) and 16.4 nmol 3-ClLA (0.28% of the 3-MPCD dose). CONCLUSIONS: The products of oxidative metabolism of 2- and 3-MCPD, 2-ClHA, and 3-ClLA, are described for the first time in humans. Due to the lack of specificity, the metabolites may not be used as exposure biomarkers to low doses of bound 2- and 3-MCPD, respectively.

Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults.

BACKGROUND: Fine particulate matter (PM2.5) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies. METHODS: To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM2.5, in the form of concentrated ambient particles (mean: 37.8 µg/m3, SD 6.5), and filtered air (mean: 2.1 µg/m3, SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure. RESULTS: Low-level PM2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM2.5 concentration (37.8 µg/m3) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV1) and FEV1/ forced vital capacity (FEV1/FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure. CONCLUSIONS: This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM2.5 particles at levels near the PM2.5 US NAAQS standard. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov ; Identifier: NCT03232086 . The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.

Nanotoxicology: The Need for a Human Touch?

With the ever-expanding number of manufactured nanomaterials (MNMs) under development there is a vital need for nanotoxicology studies that test the potential for MNMs to cause harm to health. An extensive body of work in cell cultures and animal models is vital to understanding the physicochemical characteristics of MNMs and the biological mechanisms that underlie any detrimental actions to cells and organs. In human subjects, exposure monitoring is combined with measurement of selected health parameters in small panel studies, especially in occupational settings. However, the availability of further in vivo human data would greatly assist the risk assessment of MNMs. Here, the potential for controlled inhalation exposures of MNMs in human subjects is discussed. Controlled exposures to carbon, gold, aluminum, and zinc nanoparticles in humans have already set a precedence to demonstrate the feasibility of this approach. These studies have provided considerable insight into the potential (or not) of nanoparticles to induce inflammation, alter lung function, affect the vasculature, reach the systemic circulation, and accumulate in other organs. The need for further controlled exposures of MNMs in human volunteers - to establish no-effect limits, biological mechanisms, and provide vital data for the risk assessment of MNMs - is advocated.

Vessel noise levels drive behavioural responses of humpback whales with implications for whale-watching.

Disturbance from whale-watching can cause significant behavioural changes with fitness consequences for targeted whale populations. However, the sensory stimuli triggering these responses are unknown, preventing effective mitigation. Here, we test the hypothesis that vessel noise level is a driver of disturbance, using humpback whales (Megaptera novaeangliae) as a model species. We conducted controlled exposure experiments (n = 42) on resting mother-calf pairs on a resting ground off Australia, by simulating whale-watch scenarios with a research vessel (range 100 m, speed 1.5 knts) playing back vessel noise at control/low (124/148 dB), medium (160 dB) or high (172 dB) low frequency-weighted source levels (re 1 µPa RMS@1 m). Compared to control/low treatments, during high noise playbacks the mother's proportion of time resting decreased by 30%, respiration rate doubled and swim speed increased by 37%. We therefore conclude that vessel noise is an adequate driver of behavioural disturbance in whales and that regulations to mitigate the impact of whale-watching should include noise emission standards.

Whale-watching is a multi-billion-dollar industry that is growing around the world. Typically, tour operators use boats to transport tourists into coastal waters to see groups of whales, dolphins or porpoises. There is, however, accumulating evidence that boat-based whale-watching negatively affects the way these animals behave and so many countries have put guidelines in place to mitigate activities that may disturb the animals. These guidelines generally stipulate the boat's angle of approach, how close the boat can get and the speed at which it can pass by the animals. In general, these guidelines are based on the assumption that the animals are disturbed by the closeness of the whale-watching boats. However, whales, dolphins and porpoises have very sensitive hearing, and only have a short range of vision underwater. Therefore, it seems plausible that the animals hear whale-watching boats long before they see them and so the loudness of underwater noise from the boats may be enough to disturb these animals' behaviour. To test this hypothesis, Sprogis et al. performed experiments where they simulated a whale-watching vessel approaching humpback whale mothers and calves who were resting off the northwest coast of Australia. A small motorised research boat travelling at a low speed passed different mother-calf pairs at a target distance of 100 meters, which is a common whale-watching distance guideline in many countries. The boat had an underwater speaker that played recordings of the boat noise at different volumes, while a drone with a video camera flew overhead to record the whales' behaviours in detail and to identify individual animals. These "controlled exposure experiments" showed that the quiet boat noise did not appear to disturb the mothers and calves. However, compared to when the quiet boat passed the animals the louder boat noise decreased how long the mother whale rested on the surface by 30%, made her swim 37% faster, and doubled the number of breaths she took per minute. If there are many disturbances from humans, then it can negatively impact the energy the mother and calf have available for nursing, fending off males and predators, and migrating back to their feeding ground nearer the Earth's poles. Based on these findings, it is shown that the loudness of the underwater noise from boats can explain why whales may be disturbed during whale-watching activities. To help reduce this disturbance, Sprogis et al. recommend that noise emission standards should be added to the current whale-watching regulations such that boats should be as quiet as possible and ideally around the volume of the ambient background noise. This would allow operators to approach the animals in a responsible, sustainable manner and offer tourists a view of undisturbed wildlife.

Acute changes in lung function following controlled exposure to cookstove air pollution in the subclinical tests of volunteers exposed to smoke (STOVES) study.

Background: Exposure to household air pollution generated as a result of cooking and heating is a leading contributor to global disease. The effects of cookstove-generated air pollution on adult lung function, however, remain uncertain.Objectives: We investigated acute responses in lung function following controlled exposures to cookstove-generated air pollution.Methods: We recruited 48 healthy adult volunteers to undergo six two-hour treatments: a filtered-air control and emissions from five different stoves with fine particulate matter (PM2.5) targets from 10 to 500 µg/m3. Spirometry was conducted prior to exposure and immediately, and three and 24 h post-exposure. Mixed-effect models were used to estimate differences in post-exposure lung function for stove treatments versus control.Results: Immediately post-exposure, lung function was lower compared to the control for the three highest PM2.5-level stoves. The largest differences were for the fan rocket stove (target 250 µg/m3; forced vital capacity (FVC): -60 mL, 95% confidence interval (95% CI) -135, 15; forced expiratory volume (FEV1): -51 mL, 95% CI -117, 16; mid-expiratory flow (FEF25-75): -116 mL/s, 95% CI -239, 8). At 3 h post-exposure, lung function was lower compared to the control for all stove treatments; effects were of similar magnitude for all stoves. At 24 h post-exposure, results were consistent with a null association for FVC and FEV1; FEF25-75 was lower relative to the control for the gasifier, fan rocket, and three stone fire.Conclusions: Patterns suggesting short-term decreases in lung function follow from exposure to cookstove air pollution even for stove exposures with low PM2.5 levels.

A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers.

Sensory irritation is an acute adverse effect caused by chemicals that stimulate chemoreceptors of the upper respiratory tract or the mucous membranes of the outer eye. The avoidance of this end point is of uttermost importance in regulatory toxicology. In this study, repeated exposures to ethyl acrylate were analyzed to investigate possible carryover effects from day to day for different markers of sensory irritation. Thirty healthy subjects were exposed for 4 h on five subsequent days to ethyl acrylate at concentrations permitted by the German occupational exposure limit at the time of study. Ratings of eye irritation as well as eye blinking frequencies indicate the elicitation of sensory irritation. These markers of sensory irritation showed a distinct time course on every single day. However, cumulative carryover effects could not be identified across the week for any marker. The rhinological and biochemical markers could not reveal hints for more pronounced sensory irritation. Neither increased markers of neurogenic inflammation nor markers of immune response could be identified. Furthermore, the performance on neurobehavioral tests was not affected by ethyl acrylate and despite the strong odor of ethyl acrylate the participants improved their performances from day to day. While the affected physiological marker, the increased eye blinking frequency stays roughly on the same level across the week, subjective markers like perception of eye irritation decrease slightly from day to day though the temporal pattern of, i.e., eye irritation perception stays the same on each day. A hypothetical model of eye irritation time course derived from PK/PD modeling of the rabbit eye could explain the within-day time course of eye irritation ratings repeatedly found in this study more precisely.

Effects of short-term exposure to fine and ultrafine particles from indoor sources on arterial stiffness - A randomized sham-controlled exposure study.

OBJECTIVES: Particulate air pollution is linked to adverse cardiovascular effects, including arterial stiffness. The aim of the study was to investigate the effect of short-term exposure to indoor fine and ultrafine particles on augmentation index (AIx), augmentation pressure (AP), and pulse wave velocity (PWV), early signs of vascular damage. METHODS: We analyzed the association of particle emissions from typical indoor sources (candle burning - CB, toasting bread - TB, and frying sausages - FS) with changes in pulse wave analysis indices in 55 healthy adults in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2 h exposure. AIx and AP were measured before, directly, 2, 4 and 24 h after exposure. PWV was measured directly and 24 h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and AIx, AP and PWV. RESULTS: The highest mean PMC was observed during FS reaching a maximum of 210 µg/m3 PM10. The maximal PNC for UFP <100 nm was reached during CB with 2.3 million particles/cm3. PSC was similar across all three exposures (about 3000 µm2/cm³). Strongest associations between different particles metrics and arterial stiffness indices could be observed for UFP from CB and FS and for PMC from TB. The highest mean increase could be observed for the UFP fraction <10 nm, measured during CB, and AIx with an increase of 9.5%-points (95%-CI: 3.1; 15.9). PSC seemed to follow the pattern of PNC. PM10 and PM2.5 from TB led to clear changes in AIx with biggest increases for PM10 of 5.8%-points (95%-CI: 3.2; 8.4) 2 h after exposure and for PM2.5 of 8.1%-points (95%-CI: 2.5; 13.7) directly after exposure. CONCLUSIONS: Our study indicates effects of indoor exposure to fine and ultrafine particles on systemic arterial stiffness indices that depend on the indoor source as well as on particle metric. Differences in size-specific physical characteristics of source-specific particles might account for these differential effects. We did not observe clear and stable associations of indoor particle exposure and PWV.

Cardiovascular function and ozone exposure: The Multicenter Ozone Study in oldEr Subjects (MOSES).

BACKGROUND: To date, there have been relatively few studies of acute cardiovascular responses to controlled ozone inhalation, although a number of observational studies have reported significant positive associations between both ambient ozone levels and acute cardiovascular events and long-term ozone exposure and cardiovascular mortality. OBJECTIVES: We hypothesized that short-term controlled exposure to low levels of ozone in filtered air would induce autonomic imbalance, repolarization abnormalities, arrhythmia, and vascular dysfunction. METHODS: This randomized crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol, from June 2012 to April 2015. Subjects were exposed for 3 h in random order to 0 ppb (filtered air), 70 ppb ozone, and 120 ppb ozone, alternating 15 min of moderate exercise with 15 min of rest. A suite of cardiovascular endpoints was measured the day before, the day of, and up to 22 h after each exposure. Mixed effect linear and logit models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. Site and time were included in the models. RESULTS: We found no significant effects of ozone exposure on any of the primary or secondary measures of autonomic function, repolarization, ST segment change, arrhythmia, or vascular function (systolic blood pressure and flow-mediated dilation). CONCLUSIONS: In this multicenter study of older healthy women and men, there was no convincing evidence for acute effects of 3-h, relatively low-level ozone exposures on cardiovascular function. However, we cannot exclude the possibility of effects with higher ozone concentrations, more prolonged exposure, or in subjects with underlying cardiovascular disease. Further, we cannot exclude the possibility that exposure to ambient ozone and other pollutants in the days before the experimental exposures obscured or blunted cardiovascular biomarker response to the controlled ozone exposures.

Protecting the photosynthetic performance of snap bean under free air ozone exposure.

Tropospheric ozone (O3) is a major air pollutant and causes serious injury to vegetation. To protect sensitive plants from O3 damage, several agrochemicals have been assessed, including cytokinin (e.g., kinetin, KIN) and ethylenediurea (EDU) with cytokinin-like activity. In higher plant, leaves are primarily injured by O3 and protective agrochemicals are often applied by leaf spraying. To our knowledge, the mitigating abilities of EDU and KIN have not been compared directly in a realistic setup. In the present research, impacts of elevated O3 (2× ambient O3, 24hr per day, for 8days) on an O3 sensitive line (S156) of snap bean (Phaseolus vulgaris), which is often used for biomonitoring O3 pollution, were studied in a free air controlled exposure system. The day before starting the O3 exposure, plants were sprayed with a solution of EDU (300ppm), KIN (1mmol/L) or distilled water, to compare their protective abilities. The results demonstrated that 2× ambient O3 inhibited net photosynthetic rate and stomatal conductance, increased the minimal fluorescence yield of the dark-adapted state, decreased the maximal quantum yield of PSII photochemistry, and led to visible injury. KIN and EDU alleviated the reduction of the photosynthetic performance, and visible injury under O3 fumigation. The plants sprayed with EDU showed greater ability to mitigate the O3 damage than those sprayed with KIN. Chlorophyll fluorescence imaging may have detected more precisely the differences in O3 response across the leaf than the conventional fluorometer.

Do individuals with asthma experience airway hyper-responsiveness after exposure to nitrogen dioxide?

The current 100 ppb short-term National Ambient Air Quality Standard for NO2, and EPA's determination of a causal association for respiratory effects, are based in part on controlled human exposure studies evaluating airway hyper-responsiveness (AHR). A meta-analysis by Goodman et al. (2009) found increased AHR at 100 ppb NO2 but no clear concentration-response relationship up to 600 ppb, and an overall lack of an AHR effect for studies involving exercise or exposure to allergens. Several factors have been suggested to explain why effects on AHR are observed while people are at rest, but not during exercise or after exposure to allergens. These include an exercise-induced refractory period; partial reversal of bronchospasm from use of forced expiration maneuvers; and greater airway responsiveness of participants exposed to NO2 at rest. We reviewed the scientific evidence to determine whether there is biological support for these factors and found that none sufficiently explained the lack of an effect during exercise or after exposure to allergens. In the absence of either a consistent concentration-response or a plausible explanation for the paradoxical AHR findings, the biological significance of these findings is uncertain and provides equivocal support for NO2 as a causal factor of AHR at these exposure levels.

Arterial blood pressure responses to short-term exposure to fine and ultrafine particles from indoor sources - A randomized sham-controlled exposure study of healthy volunteers.

OBJECTIVES: Particulate air pollution is linked to adverse cardiovascular effects. The aim of the study was to investigate the effect of short-term exposure to indoor particles on blood pressure (BP). METHODS: We analyzed the association of particle emissions from indoor sources (candle burning, toasting bread, frying sausages) with BP changes in 54 healthy volunteers in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2h exposure. Systolic and diastolic blood pressure were measured before, during, directly, 2, 4 and 24h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and BP. RESULTS: BP significantly increased with increasing PMC, PSC and PNC resulting from toasting bread. For example, an increase per 10µg/m3 PM10 and PM2.5, systolic BP increased at all time points with largest changes 1h after exposure initiation of 1.5mmHg (95%-CI: 1.1; 1.9) and of 2.2mmHg (95%-CI: 1.3; 3.1), respectively. CONCLUSIONS: Our study suggests an association of short-term exposure to fine and ultrafine particles emitted from toasting bread with increases in BP. Particles emitted from frying sausages and candle burning did not consistently affect BP.

Effect of Pile-Driving Sounds on the Survival of Larval Fish.

Concern exists about the potential effects of pile-driving sounds on fish, but evidence is limited, especially for fish larvae. A device was developed to expose larvae to accurately reproduced pile-driving sounds. Controlled exposure experiments were carried out to examine the lethal effects in common sole larvae. No significant effects were observed at zero-to-peak pressure levels up to 210 dB re 1 µPa(2) and cumulative sound exposure levels up to 206 dB re 1 µPa(2)·s, which is well above the US interim criteria for nonauditory tissue damage in fish. Experiments are presently being carried out for European sea bass and herring larvae.

Are the elements of the proposed ozone National Ambient Air Quality Standards informed by the best available science?

The United States Environmental Protection Agency (US EPA) issues National Ambient Air Quality Standards (NAAQS) for six criteria pollutants, including ozone. Each standard has four elements: an indicator, level, averaging time, and form. Ozone levels (i.e., air concentrations) alone in scientific studies are not directly comparable to the "level" element of the NAAQS because the standard considers the level in the context of its relation to the remaining elements. Failure to appreciate this has led to misunderstandings regarding NAAQS that would be health-protective. This can be seen with controlled human ozone exposure studies, which often involved small numbers of people exercising quasi-continuously for a long duration at an intensity not common in the general population (and unlikely achievable by most sensitive individuals), under worst-case exposure profiles. In addition, epidemiology studies have used different averaging times and have had methodological limitations that may have biased results. Such considerations can make it difficult to compare ozone levels and results across studies and to appropriately apply them in a NAAQS evaluation. Relating patterns and circumstances of exposure, and exposure measurements, to all elements of the NAAQS can be challenging, but if US EPA fully undertook this, it would be evident that available evidence does not indicate that proposed lower ozone standards would be more health protective than the current one.