We measured fractional exhaled nitric oxide (FENO), spirometry, blood pressure, oxygen saturation of the blood (SaO2), and pulse rate in 16 older subjects with asthma or chronic obstructive pulmonary disease (COPD) in Seattle, Washington. Data were collected daily for 12 days. We simultaneously collected PM10 and PM2.5 (particulate matter ≤10 μm or ≤2.5 μm, respectively) filter samples at a central outdoor site, as well as outside and inside the subjects’ homes. Personal PM10 filter samples were also collected. All filters were analyzed for mass and light absorbance. We analyzed within-subject associations between health outcomes and air pollution metrics using a linear mixed-effects model with random intercept, controlling for age, ambient relative humidity, and ambient temperature. For the 7 subjects with asthma, a 10 μg/m3 increase in 24-hr average outdoor PM10 and PM2.5 was associated with a 5.9 [95% confidence interval (CI), 2.9–8.9] and 4.2 ppb (95% CI, 1.3–7.1) increase in FENO, respectively. A 1 μg/m3 increase in outdoor, indoor, and personal black carbon (BC) was associated with increases in FENO of 2.3 ppb (95% CI, 1.1–3.6), 4.0 ppb (95% CI, 2.0–5.9), and 1.2 ppb (95% CI, 0.2–2.2), respectively. No significant association was found between PM or BC measures and changes in spirometry, blood pressure, pulse rate, or SaO2 in these subjects. Results from this study indicate that FENO may be a more sensitive marker of PM exposure than traditional health outcomes and that particle-associated BC is useful for examining associations between primary combustion constituents of PM and health outcomes.

Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (E) to PM2.5 (PM with aerodynamic diameter ≤2.5 μm) into its indoor-generated (Eig) and ambient-generated (Eag) components for 19 children with asthma. We then compared Eig and Eag to changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, Eag was marginally associated with increases in eNO [5.6 ppb per 10-μg/m3 increase in PM2.5; 95% confidence interval (CI), −0.6 to 11.9; p = 0.08]. Eig was not associated with eNO (−0.19 ppb change per 10μg/m3). Our predictive model allowed us to estimate Eag and Eig for all 19 children. For those combined estimates, only Eag was significantly associated with an increase in eNO (Eag: 5.0 ppb per 10-μg/m3 increase in PM2.5; 95% CI, 0.3 to 9.7; p = 0.04; Eig: 3.3 ppb per 10-μg/m3 increase in PM2.5; 95% CI, −1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM2.5 exposure is consistently associated with increases in eNO and the indoor-generated component is less strongly associated with eNO.

Treatment-resistant depression affects up to 20% of individuals suffering from major depressive disorder (MDD). The medications currently available to treat depression, including serotonin re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), fail to produce adequate remission of depressive symptoms for a large number of patients. The monoamine hypothesis upon which these medications are predicated should be expanded and revised as research elucidates alternative mechanisms of depression and effective methods to treat the underlying pathologic consequences. Research into the role of tryptophan degradation and the kynurenine pathway in the setting of inflammation has brought new insight into potential etiologies of MDD. Further investigation into the connection between inflammatory mediators, tryptophan degradation, and MDD can provide many targets for novel antidepressant therapies. Thus, this review will highlight the role of the kynurenine pathway in the pathophysiology of depression, as well as a novel therapeutic target to classic and new modulators to treat depression based on findings from preclinical and clinical studies.

Exposure to traffic-related air pollution is associated with risk of cardiovascular disease and mortality. We examined whether exposure to diesel exhaust increased blood pressure in human subjects. We analyzed data from 45 nonsmoking subjects, age 18–49 in double-blinded, crossover exposure studies, randomized to order. Each subject was exposed to diesel exhaust, maintained at 200 μg/m3 of fine particulate matter, and filtered air for 120 minutes on days separated by at least two weeks. We measured blood pressure pre-exposure, at 30-minute intervals during exposure, and 3, 5, 7 and 24 hours from exposure initiation, and analyzed changes from pre-exposure values. Compared with filtered air, systolic blood pressure increased at all points measured during and after diesel exhaust exposure; the mean effect peaked between 30 and 60 minutes after exposure initiation (3.8 mmHg [95% CI: −0.4, 8.0] and 5.1 mmHg [95% CI: 0.7, 9.5] respectively). Sex and metabolic syndrome did not modify this effect. Combining readings between 30 and 90 minutes, diesel exhaust exposure resulted in a 4.4 mmHg increase in systolic blood pressure, adjusted for participant characteristics and exposure perception (95% CI: 1.1, 7.7, p=0.0009). There was no significant effect on heart rate or diastolic pressure. Diesel exhaust inhalation was associated with a rapid, measurable increase in systolic, but not diastolic, blood pressure in young nonsmokers, independent of perception of exposure. This controlled trial in humans confirms findings from observational studies. The effect may be important on a population basis given the worldwide prevalence of exposure to traffic-related air pollution.

Epidemiologic studies report consistent adverse health effects of particulate matter (PM) air pollution in population studies (U.S. EPA 2001). However, describing the adverse health effects of fine PM exposure at the individual subject level remains a high priority. Studies designed to provide information concerning these adverse effects include panel studies with subjects followed for several days or longer, clinical exposure studies, and toxicologic studies, including controlled exposures of human subjects. Panel studies are usually designed to combine intensive personal, indoor and/or outdoor air monitoring in conjunction with measures of specific health outcomes. Recent panel studies have concentrated on subjects believed to be susceptible to air pollution, such as those with preexisting respiratory or cardiac disease. As a consequence, the health end points commonly measured are lung function, symptoms and medication use, arterial oxygen saturation, blood pressure, and heart rate variability. Recent results from panel studies indicate several adverse health effects associated with exposure to PM with aerodynamic diameters ≤ 2.5 µm (PM 2.5 ). In the United States, decreased heart rate variability was associated with indoor or outdoor PM 2.5 in 26 elderly subjects in Baltimore, Maryland (Liao et al. 1999), in healthy subjects in Boston, Massachusetts (Magari et al.

The findings indicate that maternal age, parity, primary caregiver status and duration of post-partum depression are associated with the language development of the child.

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The objective of this study was to evaluate associations between short-term (hourly) exposures to particulate matter with aerodynamic diameters < 2.5 μm (PM2.5) and the fractional concentration of nitric oxide in exhaled breath (FeNO) in children with asthma participating in an intensive panel study in Seattle, Washington. The exposure data were collected with tapered element oscillation microbalance (TEOM) PM2.5 monitors operated by the local air agency at three sites in the Seattle area. FeNO is a marker of airway inflammation and is elevated in individuals with asthma. Previously, we reported that offline measurements of FeNO are associated with 24-hr average PM2.5 in a panel of 19 children with asthma in Seattle. In the present study using the same children, we used a polynomial distributed lag model to assess the association between hourly lags in PM2.5 exposure and FeNO levels. Our model controlled for age, ambient NO levels, temperature, relative humidity, and modification by use of inhaled corticosteroids. We found that FeNO was associated with hourly averages of PM2.5 up to 10–12 hr after exposure. The sum of the coefficients for the lag times associated with PM2.5 in the distributed lag model was 7.0 ppm FeNO. The single-lag-model FeNO effect was 6.9 [95% confidence interval (CI), 3.4 to 10.6 ppb] for a 1-hr lag, 6.3 (95% CI, 2.6 to 9.9 ppb ) for a 4-hr lag, and 0.5 (95% CI, −1.1 to 2.1 ppb) for an 8-hr lag. These data provide new information concerning the lag structure between PM2.5 exposure and a respiratory health outcome in children with asthma.