Associations between mitochondrial biomarkers, urban residential exposures and childhood asthma outcomes over 6 months.

Determining biomarkers of responses to environmental exposures and evaluating whether they predict respiratory outcomes may help optimize environmental and medical approaches to childhood asthma. Relative mitochondrial (mt) DNA abundance and other potential mitochondrial indicators of oxidative stress may provide a sensitive metric of the child's shifting molecular responses to its changing environment. We leveraged two urban childhood cohorts (Environmental Control as Add-on Therapy in Childhood Asthma (ECATCh); Columbia Center for Children's Environmental Health (CCCEH)) to ascertain whether biomarkers in buccal mtDNA associate with airway inflammation and altered lung function over 6 months of time and capture biologic responses to multiple external stressors such as indoor allergens and fine particulate matter (PM2.5). Relative mtDNA content was amplified by qPCR and methylation of transfer RNA phenylalanine/rRNA 12S (TF/RNR1), cytochrome c oxidase (CO1), and carboxypeptidase O (CPO) was measured by pyrosequencing. Data on residential exposures and respiratory outcomes were harmonized between the two cohorts. Repeated measures and multiple regression models were utilized to assess relationships between mitochondrial biomarkers, respiratory outcomes, and residential exposures (PM2.5, allergens), adjusted for potential confounders and time-varying asthma. We found across the 6 month visits, a 0.64 fold higher level of TF/RNR1 methylation was detected among those with asthma in comparison to those without asthma ((parameter estimate (PE) 0.64, standard error 0.28, p = 0.03). In prospective analyses, CPO methylation was associated with subsequent reduced forced vital capacity (FVC; PE -0.03, standard error 0.01, p = 0.02). Bedroom dust mouse allergen, but not indoor PM2.5, was associated with higher methylation of TF/RNR1 (PE 0.015, standard error 0.006, p = 0.01). Select mtDNA measures in buccal cells may indicate children's responses to toxic environmental exposures and associate selectively with asthma and lung function.

Antagonistic Effect of Colistin on Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus in In Vitro and In Vivo Studies.

As concerns arise that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concurrent colistin administration, we evaluated the effect of colistin on vancomycin efficacy against MRSA via in vitro and in vivo studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCCmec II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the vancomycin MIC of MRSA following colistin exposure and evaluated the effect of a vancomycin-colistin combination using time-kill assays. We also assessed the in vivo antagonistic effect by administering vancomycin, colistin, and a combination of these two in a neutropenic murine thigh infection model. In the checkerboard assays, vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 µg/ml following colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the vancomycin concentration was twice the MIC. In the murine thigh infection model with ST5-MRSA and USA100, vancomycin monotherapy reduced the number of CFU/muscle >1 log10 compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of colistin on vancomycin treatment. This study suggests that exposure to colistin may reduce the susceptibility to vancomycin of certain MRSA strains. Combination therapy with vancomycin and colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA infection.

Diagnostic usefulness of differential time to positivity in neutropenic cancer patients with suspected catheter-related candidemia.

Methods for distinguishing catheter-related candidemia (CRC) from non-CRC before catheter removal remain limited. We thus evaluated the diagnostic performance of differential time to positivity (DTP) to diagnose CRC in neutropenic cancer patients with suspected CRC. Of the 35 patients enrolled, 15 (43%) with CRC (six definite and nine probable) and 17 (49%) with non-CRC were finally analyzed. Based on the receiver operating characteristic curve, the optimal cutoff value of DTP for diagnosing CRC was ≥1.45 hours with the sensitivity 80% (95% confidence interval [CI], 51-95) and specificity 100% (95% CI, 80-100), respectively.

Diagnostic performance of immunohistochemistry for the aspergillosis and mucormycosis.

OBJECTIVE: To investigate the accuracy of immunohistochemistry (IHC) tests for distinguishing between mucormycosis and aspergillosis and compare the clinical characteristics of mucormycosis patients according to galactomannan (GM) results. METHODS: We evaluated diagnostic performance of IHC test with tissue sections of patients with culture-proven invasive fungal infection. In addition, we conducted PCR assay with tissue sections of mucormycosis patients with positive GM results to evaluate the possibility of co-infection. RESULTS: In culture-proven mucormycosis (n = 13) and aspergillosis (n = 20), the sensitivity and specificity of IHC test were both 100% for mucormycosis and 85% and 100%, respectively, for aspergillosis. Among the 53 patients who met the modified criteria for proven mucormycosis and had GM assay results, 24 (45%) were positive. Compared with those with negative GM results (n = 29), mucormycosis patients with positive GM results had significantly higher incidence of gastrointestinal tract infections (6/24 [25%] vs 0/29 [0%], P = .006) and were more likely to be histomorphologically diagnosed as aspergillosis (7/24 [29%] vs 2/29 [7%], P = .06). PCR assay amplified both Aspergillus- and Mucorales-specific DNA in 6 of these 24 cases. CONCLUSIONS: Immunohistochemistry tests seem useful for compensating for the limitations of histomorphologic diagnosis in distinguishing between mucormycosis and aspergillosis. Some proven mucormycosis patients with positive GM results had histopathology consistent with aspergillosis and gastrointestinal mucormycosis. In addition, about one quarter of these patients revealed the evidence of co-infection with aspergillosis by PCR assay.

Neurocysticercosis: Clinical Characteristics and Changes from 26 Years of Experience in an University Hospital in Korea.

The prevalence of human taeniasis has decreased in Korea. The stool egg positive proportion decreased from 1.9% in 1971 to 0% in 2004 in nationwide surveys. The neurocysticercosis (NCC) is also presumed to decrease. However, detailed information regarding the recent status of NCC in Korea is lacking. We retrospectively reviewed NCC cases from 1990 to 2016 at Asan Medical Center, a 2700-bed tertiary referral hospital in Korea. We identified patients based on clinical symptoms, brain imaging, pathology and serological assay. The cases were classified as parenchymal, extraparenchymal, and mixed NCC. Eighty-one patients were included in the analysis. The mean age was 54.5 years, and 79.0% were male. The number of NCC cases was highest from 1995 to 1999, and continuously decreased thereafter. Forty (49.4%) patients had parenchymal NCC, while 25 (30.9%) patients had extraparenchymal NCC, and 16 (19.8%) patients had mixed NCC. The seizure and headache were most common symptom of parenchymal NCC and extraparenchymal NCC respectively. Hydrocephalus was more common in extraparenchymal NCC, and patients with extraparenchymal NCC were more likely to require a ventriculoperitoneal shunt. Cases of NCC are decreasing accordingly with human taeniasis and lesion location was the most important determinant of clinical presentation and outcome of NCC in Korea.

Assessment of exposure to air pollution in children: Determining whether wearing a personal monitor affects physical activity.

Personal air pollution monitoring in research studies should not interfere with usual patterns of behavior and bias results. In an urban pediatric cohort study we tested whether wearing an air monitor impacted activity time based on continuous watch-based accelerometry. The majority (71%) reported that activity while wearing the monitor mimicked normal activity. Correspondingly, variation in activity while wearing versus not wearing the monitor did not differ greatly from baseline variation in activity (P = 0.84).

Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children.

BACKGROUND: Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 µm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. METHODS: Six day integrated levels of air pollutants were measured from children's homes (age 9-14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. RESULTS: Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25-75% of FVC [FEF25-75]). CONCLUSIONS: Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children.

Pyranopyran-1,8-dione, an Active Compound from Vitices Fructus, Attenuates Cigarette-Smoke Induced Lung Inflammation in Mice.

Previously, we isolated and identified pyranopyran-1,8-dione (PPY) from Viticis Fructus, as a bioactive compound possessing anti-inflammatory properties. The present study was aimed to evaluate the preventive benefit of PPY on cigarette-smoke (CS)-induced lung inflammation. C57BL/6 mice were exposed to CS for 2 weeks while PPY was administrated by oral injection 2 h before CS exposure. To validate the anti-inflammatory effects of PPY, the numbers of immune cells in the bronchoalveolar lavage fluid were counted. Proinflammatory cytokines (Tumor necrosis factor-α: TNF-α, IL-6) and keratinocyte chemokine (KC/CXCL1) were also measured. Histopathologic analysis and cellular profiles showed that inflammatory cell infiltrations were significantly decreased in peribronchial and perivascular area by PPY treatment. The alveolar destruction by CS was markedly ameliorated by PPY treatment. In addition, the TNF-α, IL-6, and KC levels were declined in the PPY groups. These observations suggest that PPY has a preventive potential for lung inflammatory diseases.

Physical activity, black carbon exposure and airway inflammation in an urban adolescent cohort.

OBJECTIVE: Regular physical activity can improve cardiopulmonary health; however, increased respiratory rates and tidal volumes during activity may increase the effective internal dose of air pollution exposure. Our objective was to investigate the impact of black carbon (BC) measured by personal sampler on the relationship between physical activity and fractional exhaled nitric oxide (FeNO), a marker of airway inflammation. We hypothesized that higher personal BC would attenuate the protective effect of physical activity on airway inflammation. METHODS: We performed a cross-sectional study nested in a birth cohort of African American and Dominican children living in the Bronx and Northern Manhattan, New York City. Children were recruited based on age (target 9-14 year olds) and presence (n=70) or absence (n=59) of current asthma. Children wore wrist mounted accelerometers for 6 days and were classified as 'active' if they had ≥60min of moderate-to-vigorous activity (MVA) each day and 'non-active' if they had <60min of MVA on any given day, based on CDC guidelines. Personal BC measured using a MicroAeth, was assessed during two 24-h periods, at the beginning and end of physical activity assessment. High BC was defined as the upper tertile of BC measured with personal sampler. FeNO measurements were sampled at the beginning and end of the of physical activity assessment. RESULTS: In multivariable linear regression models, 'active' children had 25% higher personal BC concentrations (p=0.02) and 20% lower FeNO (p=0.04) compared to 'non-active' children. Among children with high personal BC (n=33), there was no relationship between activity and FeNO (p=1.00). The significant protective relationship between activity and airway inflammation was largely driven by children with lower personal BC (n=96, p=0.04). CONCLUSIONS: Children that live in an urban environment and are physically active on a daily basis have higher personal exposure to BC. High BC offsets the protective relationship between physical activity and airway inflammation.

Repeatedly high polycyclic aromatic hydrocarbon exposure and cockroach sensitization among inner-city children.

BACKGROUND: Exposures to traffic-related air pollutants including polycyclic aromatic hydrocarbons (PAH) have been associated with the development and exacerbation of asthma. However, there is limited evidence on whether these pollutants are associated with the development of cockroach sensitization, a strong risk factor for urban asthma. We hypothesized that repeatedly high PAH exposure during childhood would be associated with increased risk of new cockroach sensitization. METHODS: As part of the research being conducted by the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study in New York, a spot urine sample was collected from children at age 5 years (2003-2008) and again at age 9-10 years (2008-2012; n=248) and analyzed for 10 PAH metabolites. Repeatedly high PAH (High-High) exposure was defined as measures above median for age 5 PAH metabolites at both time points. Child blood samples at age 5 and 9 years were analyzed for total, anti-cockroach, mouse, dust mite, cat and dog IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. RESULTS: Individual PAH metabolite levels, except for 1-naphthol (1-OH-NAP), increased by 10-60% from age 5 to age 9-10. The prevalence of cockroach sensitization increased from 17.6% (33/188) at age 5 to 33.0% (62/188) at 9 years (p=0.001). After controlling for potential covariates including cockroach sensitization at age 5 in regression analyses, positive associations were found between repeatedly high exposure (High-High) to 1-OH-NAP, 3-hydroxyphenanthrene (3-OH-PHEN), or 1-hydroxypyrene (1-OH-PYR) and cockroach sensitization at age 9 (p-values<0.05). Compared to Low-Low exposure, the relative risk (RR) [95% CI] with repeatedly high exposure was 1.83 [1.06-3.17] for 1-OH-NAP, 1.54 [1.06-2.23] for 3-OH-PHEN, and 1.59 [1.04-2.43] for 1-OH-PYR. CONCLUSIONS: Repeatedly high levels of urinary PAH metabolites during childhood may increase likelihood of sensitization to cockroach allergen in urban inner-city children at age 9 years.

Vitex rotundifolia L. prevented airway eosinophilic inflammation and airway remodeling in an ovalbumin-induced asthma mouse model.

Vitex rotundifolia L. (VR) as long been used in China and Korea in traditional medicine. This study was conducted to evaluate the ability of Vitex rotundifolia L. to prevent airway inflammation and remodeling in an ovalbumin (OVA)-induced murine asthma model. The total cell number and number of inflammatory cells in the bronchoalveolar lavage (BAL) fluid were counted. The levels of cytokines in the BAL fluid and serum IgE levels were measured using an ELISA. For histological analysis, hematoxylin and eosin staining, periodic acid-Schiff staining and immunohistochemistry were evaluated. The release of total cells into the BAL fluid was significantly inhibited in OVA-induced asthmatic mice treated with VR extract. In addition, eosinophilia and lymphocytosis were reduced significantly in mice that received VR extract. Furthermore, levels of the T(h)2 cytokines IL-4 and IL-5 and pro-inflammatory cytokine TNF-α in the BAL fluid and total IgE in serum were markedly suppressed by VR extract. OVA-specific IgE in the serum and IL-13 in the BAL fluid were decreased, but not significantly. The allergic effects of VR extract were accompanied by a reduction in airway hyperresponsiveness. Additionally, morphologic findings demonstrated that VR extract substantially inhibited OVA-induced eosinophilia, goblet cell hyperplasia and smooth muscle mass production. This finding suggests that VR extract may have pharmacological effects that would be useful for the treatment of asthma via the inhibition of the T(h)2 response and airway remodeling.

Polycyclic aromatic hydrocarbon exposure, obesity and childhood asthma in an urban cohort.

BACKGROUND: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) from traffic emissions and other combustion sources, and childhood obesity, have been implicated as risk factors for developing asthma. However, the interaction between these two on asthma among young urban children has not been studied previously. METHODS: Exposure to early childhood PAHs was measured by two week residential indoor monitoring at age 5-6 years in the Columbia Center for Children's Environmental Health birth cohort (n=311). Semivolatile [e.g., methylphenanthrenes] and nonvolatile [e.g., benzo(a)pyrene] PAHs were monitored. Obesity at age 5 was defined as a body mass index (BMI) greater than or equal to the 95th percentile of the year 2000 age- and sex-specific growth charts (Center for Disease Control). Current asthma and recent wheeze at ages 5 and 7 were determined by validated questionnaires. Data were analyzed using a modified Poisson regression in generalized estimating equations (GEE) to estimate relative risks (RR), after adjusting for potential covariates. RESULTS: Neither PAH concentrations or obesity had a main effect on asthma or recent wheeze. In models stratified by presence/absence of obesity, a significant positive association was observed between an interquartile range (IQR) increase in natural log-transformed 1-methylphenanthrene (RR [95% CI]: 2.62 [1.17-5.88] with IQRln=0.76), and 9-methylphenanthrene (2.92 [1.09-7.82] with IQRln=0.73) concentrations and asthma in obese children (n=63). No association in non-obese (n=248) children was observed at age 5 (Pinteraction<0.03). Similar associations were observed for 3-methylphenanthrene, 9-methylphenanthrene, and 3,6-dimethylphenanthrene at age 7. CONCLUSIONS: Obese young children may be more likely to develop asthma in association with greater exposure to PAHs, and methylphenanthrenes in particular, than non-obese children.

Time trends of polycyclic aromatic hydrocarbon exposure in New York City from 2001 to 2012: assessed by repeat air and urine samples.

BACKGROUND: Exposure to air pollutants including polycyclic aromatic hydrocarbons (PAH), and specifically pyrene from combustion of fuel oil, coal, traffic and indoor sources, has been associated with adverse respiratory health outcomes. However, time trends of airborne PAH and metabolite levels detected via repeat measures over time have not yet been characterized. We hypothesized that PAH levels, measured repeatedly from residential indoor and outdoor monitors, and children׳s urinary concentrations of PAH metabolites, would decrease following policy interventions to reduce traffic-related air pollution. METHODS: Indoor PAH (particle- and gas-phase) were collected for two weeks prenatally (n=98), at age 5/6 years (n=397) and age 9/10 years (n=198) since 2001 and at all three age-points (n=27). Other traffic-related air pollutants (black carbon and PM2.5) were monitored indoors simultaneous with PAH monitoring at ages 5/6 (n=403) and 9/10 (n=257) between 2005 and 2012. One third of the homes were selected across seasons for outdoor PAH, BC and PM2.5 sampling. Using the same sampling method, ambient PAH, BC and PM2.5 also were monitored every two weeks at a central site between 2007 and 2012. PAH were analyzed as semivolatile PAH (e.g., pyrene; MW 178-206) (∑8PAH(semivolatile): Including pyrene (PYR), phenanthrene (PHEN), 1-methylphenanthrene (1-MEPH), 2-methylphenanthrene (2-MEPH), 3-methylphenanthrene (3-MEPH), 9-methylphenanthrene (9-MEPH), 1,7-dimethylphenanthrene (1,7-DMEPH), and 3,6-dimethylphenanthrene (3,6-DMEPH)) and the sum of eight nonvolatile PAH (∑8PAH(nonvolatile): Including benzo[a]anthracene (BaA), chrysene/iso-chrysene (Chry), benzo[b]fluoranthene (BbFA), benzo[k]fluoranthene (BkFA), benzo[a]pyrene (BaP), indeno[1,2,3-c,d]pyrene (IP), dibenzo[a,h]anthracene (DahA), and benzo[g,h,i]perylene (BghiP); MW 228-278). A spot urine sample was collected from children at child ages 3, 5, 7 and 9 between 2001 and 2012 and analyzed for 10 PAH metabolites. RESULTS: Modest declines were detected in indoor BC and PM2.5 levels between 2005 and 2012 (Annual percent change [APC]=-2.08% [p=0.010] and -2.18% [p=0.059] for BC and PM2.5, respectively), while a trend of increasing pyrene levels was observed in indoor and outdoor samples, and at the central site during the comparable time periods (APC=4.81%, 3.77% and 7.90%, respectively; p<0.05 for all). No significant time trend was observed in indoor ∑8PAH(nonvolatile) levels between 2005 and 2012; however, significant opposite trends were detected when analyzed seasonally (APC=-8.06% [p<0.01], 3.87% [p<0.05] for nonheating and heating season, respectively). Similarly, heating season also affected the annual trends (2005-2012) of other air pollutants: the decreasing BC trend (in indoor/outdoor air) was observed only in the nonheating season, consistent with dominating traffic sources that decreased with time; the increasing pyrene trend was more apparent in the heating season. Outdoor PM2.5 levels persistently decreased over time across the seasons. With the analyses of data collected over a longer period of time (2001-2012), a decreasing trend was observed in pyrene (APC=-2.76%; p<0.01), mostly driven by measures from the nonheating season (APC=-3.54%; p<0.01). In contrast, levels of pyrene and naphthalene metabolites, 1-hydroxypyrene and 2-naphthol, increased from 2001 to 2012 (APC=6.29% and 7.90% for 1-hydroxypyrene and 2-naphthol, respectively; p<0.01 for both). CONCLUSIONS: Multiple NYC legislative regulations targeting traffic-related air pollution may have led to decreases in ∑8PAH(nonvolatile) and BC, especially in the nonheating season. Despite the overall decrease in pyrene over the 2001-2012 periods, a rise in pyrene levels in recent years (2005-2012), that was particularly evident for measures collected during the heating season, and 2-naphthol, indicates the contribution of heating oil combustion and other indoor sources to airborne pyrene and urinary 2-naphthol.

Comparison of extraction phases for a two-phase culture of a recombinant E. coli producing retinoids.

To prevent degradation of intracellular retinoids through in situ extraction from the cells, a two-phase culture system was performed. Several organic solvents, including n-alkanes, mineral oils and cosmetic raw materials, were applied as the extraction phase. Of the n-alkanes, n-decane had the highest retinoid production as 134 mg/l after 72 h. For mineral oil, light and heavy mineral oil gave retinoid productions of 158 and 174 mg/l after 96 h, respectively. Of other materials, isopropyl myristate gave the highest retinoid production of 181 mg/l. These results indicate that many types of oils can be applied for retinoid production, and optimization of the in situ extraction process will lead to further improve of economical production for the industrial purpose.

Inhibitory effects of Stemona tuberosa on lung inflammation in a subacute cigarette smoke-induced mouse model.

BACKGROUND: Stemona tuberosa has long been used in Korean and Chinese medicine to ameliorate various lung diseases such as pneumonia and bronchitis. However, it has not yet been proven that Stemona tuberosa has positive effects on lung inflammation. METHODS: Stemona tuberosa extract (ST) was orally administered to C57BL/6 mice 2 hr before exposure to CS for 2 weeks. Twenty-four hours after the last CS exposure, mice were sacrificed to investigate the changes in the expression of cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), chemokines such as keratinocyte-derived chemokine (KC) and inflammatory cells such as macrophages, neutrophils, and lymphocytes from bronchoalveolar lavage fluid (BALF). Furthermore, we compared the effect of ST on lung tissue morphology between the fresh air, CS exposure, and ST treatment groups. RESULTS: ST significantly decreased the numbers of total cells, macrophages, neutrophils, and lymphocytes in the BALF of mice that were exposed to CS. Additionally, ST reduced the levels of cytokines (TNF-α, IL-6) and the tested chemokine (KC) in BALF, as measured by enzyme-linked immunosorbent assay (ELISA). We also estimated the mean alveolar airspace (MAA) via morphometric analysis of lung tissues stained with hematoxylin and eosin (H&E). We found that ST inhibited the alveolar airspace enlargement induced by CS exposure. Furthermore, we observed that the lung tissues of mice treated with ST showed ameliorated epithelial hyperplasia of the bronchioles compared with those of mice exposed only to CS. CONCLUSIONS: These results indicate that Stemona tuberosa has significant effects on lung inflammation in a subacute CS-induced mouse model. According to these outcomes, Stemona tuberosa may represent a novel therapeutic herb for the treatment of lung diseases including COPD.

Early-life cockroach allergen and polycyclic aromatic hydrocarbon exposures predict cockroach sensitization among inner-city children.

BACKGROUND: Sensitization to cockroach is one of the strongest identified risk factors for greater asthma morbidity in low-income urban communities; however, the timing of exposures relevant to the development of sensitization has not been elucidated fully. Furthermore, exposure to combustion byproducts, including polycyclic aromatic hydrocarbons (PAHs), can augment the development of allergic sensitization. OBJECTIVE: We sought to test the hypotheses that domestic cockroach allergen measured prenatally would predict cockroach sensitization in early childhood and that this association would be greater for children exposed to higher PAH concentrations. METHODS: Dominican and African American pregnant women living in New York City were enrolled. In the third trimester expectant mothers wore personal air samplers for measurement of 8 nonvolatile PAHs and the semivolatile PAH pyrene, and dust was collected from homes for allergen measurement. Glutathione-S-transferase µ 1 (GSTM1) gene polymorphisms were measured in children. Allergen-specific IgE levels were measured from the children at ages 2, 3, 5, and 7 years. RESULTS: Bla g 2 in prenatal kitchen dust predicted cockroach sensitization at the ages of 5 to 7 years (adjusted relative risk [RR], 1.15; P = .001; n = 349). The association was observed only among children with greater than (RR, 1.22; P = .001) but not less than (RR, 1.07; P = .24) the median sum of 8 nonvolatile PAH levels. The association was most pronounced among children with higher PAH levels and null for the GSTM1 gene (RR, 1.54; P = .001). CONCLUSIONS: Prenatal exposure to cockroach allergen was associated with a greater risk of allergic sensitization. This risk was increased by exposure to nonvolatile PAHs, with children null for the GSTM1 mutation particularly vulnerable.

The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease.

BACKGROUND: In this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD). METHODS: Mice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral injection. To investigate the effects of PM014, we assessed PM014 functions in vivo, including immune cell infiltration, cytokine profiles in bronchoalveolar lavage (BAL) fluid and histopathological changes in the lung. The efficacy of PM014 was compared with that of the recently developed anti-COPD drug, roflumilast. RESULTS: PM014 substantially inhibited immune cell infiltration (neutrophils, macrophages, and lymphocytes) into the airway. In addition, IL-6, TNF-α and MCP-1 were decreased in the BAL fluid of PM014-treated mice compared to cigarette smoke stimulated mice. These changes were more prominent than roflumilast treated mice. The expression of PAS-positive cells in the bronchial layer was also significantly reduced in both PM014 and roflumilast treated mice. CONCLUSIONS: These data suggest that PM014 exerts strong therapeutic effects against CS induced, COPD-like lung inflammation. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for COPD treatment.

Antibiotics use patterns in end-of-life cancer patients and medical staff's perception of antimicrobial stewardship programs.

BACKGROUND/AIMS: While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff. METHODS: Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff's perceptions of antibiotics in cancer patients with EOL. RESULTS: Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST. CONCLUSION: Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient's right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.

Characteristics of peak exposure to black carbon pollution in school, commute and home environments among school children in an urban community.

Although real-time personal exposure monitoring devices have the ability to capture a wealth of data regarding fluctuations in pollutant levels, only a few studies have defined 'peaks' in black carbon (BC) exposure utilizing high-resolution data. Furthermore, studies to assess and characterize various features of peak exposure are very limited especially among children. A better understanding of characteristics of BC peak exposure would improve our understanding of health risks associated with BC. By capturing personal BC exposure at 5-min intervals using a real-time monitor during 24-hr monitoring periods among children in New York City (NYC), we defined 'peak characteristics' in 4 different ways across three major microenvironments (school vs. commute vs. home): 1) mean concentrations of BC across the 3 microenvironments, 2) 'peak duration' or time spent above the peak threshold (i.e., ≥1.5 µg/m3), 3) 'peak intensity' or the rate of exposure, defined as time spent above the threshold within each microenvironment divided by the total time spent in the microenvironment and 4) a novel metric of 'peak variability', defined as frequency of peaks (i.e., data points with +50% and -50% changes compared to the preceding and the subsequent data points), divided by the total time spent in the microenvironment. While peak duration was greatest at home, the intensity of peak exposure was greatest during commute hours, despite the short time spent in commute (p < 0.05). Peak variability was highest during commute, yet lowest in home environments (p < 0.05), particularly during non-sleeping hours. Children residing in a high-density urban setting spent on average, 5.4 hr per day above our peak threshold (≥1.5 µg/m3) in their everyday environments. Policies that limit children's exposure during high traffic periods and improved efforts to increase the number of vehicles using clean air technology could reduce the intensity of peaks and peak variability in children's BC exposure.

Repeated exposure to polycyclic aromatic hydrocarbons and asthma: effect of seroatopy.

BACKGROUND: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs), can induce asthma. However, the effects of early repeated PAH exposure over time on different asthma phenotypes have not been examined. OBJECTIVE: To assess associations between repeated PAH exposure, measured from prenatal personal and residential indoor monitors in children's homes, and asthma in an inner-city cohort. METHODS: Prenatal exposure was assessed by personal air monitoring during 48 hours and exposure at 5 to 6 years of age by 2-week residential monitoring in the Columbia Center for Children's Environmental Health cohort. PAH was dichotomized into pyrene (representative semivolatile PAH) and the sum of 8 nonvolatile PAHs. High exposure to each was defined as measures above the median at both repeated time points. Asthma and wheeze were determined by validated questionnaires at ages 5 to 6 years. Children with specific IgE levels greater than 0.35 IU/mL to any of 5 indoor allergens were considered seroatopic. RESULTS: Among all 354 children, repeated high exposure to pyrene was associated with asthma (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.13-3.20). Among 242 nonatopic children, but not those sensitized to indoor allergens (n = 87) or with elevated total IgE levels (n = 171), high pyrene levels were associated positively with asthma (OR, 2.89; 95% CI, 1.77-5.69), asthma medication use (OR, 2.28; 95% CI, 1.13-4.59), and emergency department visits for asthma (OR, 2.43; 95% CI, 1.20-4.91). Associations between the levels of the 8 nonvolatile PAHs and asthma were not observed, even when stratifying by seroatopy. CONCLUSION: Nonatopic children may be more susceptible to the respiratory consequences of early pyrene exposures.