Significant predictors of poor quality of life in older asthmatics.

BACKGROUND: Morbidity and mortality from asthma are high in older adults and quality of life (QOL) might be lower, although standardized measurements of QOL have not been validated in this population. OBJECTIVE: To determine predictors of asthma-related QOL in older adults. METHODS: Allergy and pulmonary outpatients (n = 164) at least 65 years old with an objective diagnosis of asthma completed the Mini-Asthma Quality of Life Questionnaire (mAQLQ). Demographics, medical history, and mean value for daily elemental carbon attributable to traffic, a surrogate for diesel exposure, were obtained. Regression analysis was used to determine predictors of mAQLQ scores. RESULTS: Total mAQLQ (mean ± SD 5.4 ± 1.1) and symptom, emotional, and activity domain scores were similar to those of younger populations, whereas environmental domain scores (4.4 ± 1.7) appeared lower. Poorer mAQLQ scores were significantly associated with emergency department visits (adjusted ß [aß] = -1.3, where ß values indicate the strength and direction of association, P < .0001) and with poorer scores on the Asthma Control Questionnaire (aß = -0.7, P < .0001). Greater ECAT exposure (aß = -1.6, P < .02), female sex (aß = -0.4, P < .006), body mass index of at least 30 kg/m(2) (aß = -0.4, P < .01), gastroesophageal reflux (aß = -0.4, P < .01), nonatopic status (aß = -0.5, P < .002), and asthma onset before 40 years of age (aß = -0.5, P < .004) were significantly associated with poorer mAQLQ scores. CONCLUSION: The mAQLQ scores in older adults with stable asthma were similar to those in younger populations and were predictive of other measurements of asthma control, verifying that the mAQLQ is an appropriate tool in older adults with asthma. Traffic pollution exposure was the strongest predictor of poorer asthma-related QOL in older adults with asthma.

Traffic pollution is associated with early childhood aeroallergen sensitization.

BACKGROUND: No large, prospective, epidemiologic study has investigated the association between diesel exhaust particle (DEP) exposure and early aeroallergen sensitization and allergic rhinitis (AR) at 4 years of age. OBJECTIVE: To determine how exposure to traffic exhaust during infancy is associated with aeroallergen sensitization and AR at 4 years of age and the predictive utility of the wheal area at 1 to 3 years of age on AR at 4 years of age. METHODS: Infants born to aeroallergen sensitized parents were evaluated annually with skin prick tests to 15 aeroallergens with measurement of wheal areas. At 4 years of age, AR was defined as at least one positive aeroallergen skin prick test result and the presence of sneezing and a runny nose without a cold or flu. Infant (DEP) exposure was estimated using data from 27 air sampling monitors and a land use regression model. RESULTS: Complete data were available for 634 children at 4 years of age. Prevalence of AR increased annually from 6.9% to 21.9%. A positive trend was observed for high DEP exposure and aeroallergen sensitization at 2 and 3 years of age (odds ratio, 1.40; 95% confidence interval, 0.97-2.0) and (odds ratio, 1.35; 95% confidence interval, 0.98-1.85) but not with AR. At 2 years of age, every 1-mm(2) increase in the wheal area of timothy and Alternaria significantly increased the odds of AR at 4 years of age. At 3 years of age, every 1-mm(2) increase in the wheal area of fescue, dog, and Penicillium significantly increased the odds of AR at 4 years of age. CONCLUSION: DEP exposure enhances the risk of early aeroallergen sensitization. Aeroallergen wheal area at 2 and 3 years of age is associated with AR at 4 years of age.

Early-life mold and tree sensitivity is associated with allergic eosinophilic rhinitis at 4 years of age.

BACKGROUND: Nasal eosinophils are a biomarker for allergic rhinitis (AR) and are associated with increased symptom severity. OBJECTIVE: To identify predictors of allergic eosinophilic rhinitis (AER) in early childhood in children at higher risk for chronic allergic respiratory disorders. METHODS: In the Cincinnati Childhood Allergy and Air Pollution Study, infants born to aeroallergen-sensitized and symptomatic parents were examined and underwent skin prick testing (SPT) annually to 15 aeroallergens from 1 to 4 years of age. Wheal circumferences were traced and scanned and areas were determined by computer planimetry. At 4 years, AER was defined as (1) at least 1 positive aeroallergen SPT result, (2) presence of sneezing and runny nose without a cold or influenza, and (3) nasal eosinophilia of at least 5%. Wheal areas at 1 to 3 years were analyzed for an association with AER compared with children without AR. RESULTS: At 4 years, 487 children completed rhinitis health histories, SPT, and nasal sampling. Ninety-nine children (22.8%) had AR. Thirty-eight children had AER (8.8% of total sample and 38.4% of AR sample, respectively). At 3 years, for every 1-mm(2) increase in Penicillium species (adjusted odds ratio 1.18, 95% confidence interval 1.06-1.32, P = .002) and maple (adjusted odds ratio 1.07, 95% confidence interval 1.01-1.13, P = .02), wheal area significantly increased the risk of AER at 4 years of age. CONCLUSION: Allergic eosinophilic rhinitis was identified in 8.8% of children at 4 years of age. Age 3 years was the earliest that aeroallergen SPT wheal areas were predictive of AER. Skin testing at 3 years identifies children at risk for an AR phenotype with nasal eosinophilia.

Chronic traffic pollution exposure is associated with eosinophilic, but not neutrophilic inflammation in older adult asthmatics.

OBJECTIVE: Airway inflammatory patterns in older asthmatics are poorly understood despite high asthma-related morbidity and mortality. In this study, we sought to define the relationship between exposure to traffic pollutants, biomarkers in induced sputum, and asthma control in older adults. METHODS: Induced sputum was collected from 35 non-smoking adults ≥65 years with a physician's diagnosis of asthma and reversibility with a bronchodilator or a positive methacholine challenge. Patients completed the Asthma Control Questionnaire (ACQ), and Elemental Carbon Attributable to Traffic (ECAT), a surrogate for chronic diesel particulate exposure, was determined. Equal numbers of subjects with high (≥0.39 µg/m(3)) versus low (<0.39 µg/m(3)) ECAT were included. Differential cell counts were performed on induced sputum, and myeloperoxidase (MPO) and eosinophil peroxidase (EPO) were measured in supernatants. Regression analyses were used to evaluate the relationship between sputum findings, ACQ scores, and ECAT. RESULTS: After adjustment for potential confounders, subjects with poorly controlled asthma based on ACQ ≥ 1.5 (n = 7) had significantly higher sputum eosinophils (median = 4.4%) than those with ACQ < 1.5 (n = 28; eosinophils = 2.6%; ß = 10.1 [95% CI = 0.1-21.0]; p = 0.05). Subjects with ACQ ≥ 1.5 also had significantly higher sputum neutrophils (84.2% versus 65.2%; ß = 7.1 [0.2-14.6]; p = 0.05). Poorly controlled asthma was associated with higher sputum EPO (ß = 2.4 [0.2-4.5], p = 0.04), but not MPO (p = 0.9). High ECAT was associated with higher eosinophils (ß = 10.1 [1.8-18.4], p = 0.02) but not higher neutrophils (p = 0.6). CONCLUSIONS: Poorly controlled asthma in older adults is associated with eosinophilic and neutrophilic inflammation. Chronic residential traffic pollution exposure may be associated with eosinophilic, but not neutrophilic inflammation in older asthmatics.

Infant origins of childhood asthma associated with specific molds.

BACKGROUND: The specific cause or causes of asthma development must be identified to prevent this disease. OBJECTIVE: Our hypothesis was that specific mold exposures are associated with childhood asthma development. METHODS: Infants were identified from birth certificates. Dust samples were collected from 289 homes when the infants were 8 months of age. Samples were analyzed for concentrations of 36 molds that comprise the Environmental Relative Moldiness Index (ERMI) and endotoxin, house dust mite, cat, dog, and cockroach allergens. Children were evaluated at age 7 years for asthma based on reported symptoms and objective measures of lung function. Host, environmental exposure, and home characteristics evaluated included a history of parental asthma, race, sex, upper and lower respiratory tract symptoms, season of birth, family income, cigarette smoke exposure, air conditioning, use of a dehumidifier, presence of carpeting, age of home, and visible mold at age 1 year and child's positive skin prick test response to aeroallergens and molds at age 7 years. RESULTS: Asthma was diagnosed in 24% of the children at age 7 years. A statistically significant increase in asthma risk at age 7 years was associated with high ERMI values in the child's home in infancy (adjusted relative risk for a 10-unit increase in ERMI value, 1.8; 95% CI, 1.5-2.2). The summation of levels of 3 mold species, Aspergillus ochraceus, Aspergillus unguis, and Penicillium variabile, was significantly associated with asthma (adjusted relative risk, 2.2; 95% CI, 1.8-2.7). CONCLUSION: In this birth cohort study exposure during infancy to 3 mold species common to water-damaged buildings was associated with childhood asthma at age 7 years.

Asking the right questions to ascertain early childhood secondhand smoke exposures.

Secondhand smoke is associated with a myriad of adverse health outcomes. Therefore, it is essential for clinicians to ask precise questions about exposures, particularly for children. We present 4 questions that incorporate several locations of exposure and provide a more comprehensive account of children's smoke exposures than maternal smoking alone.

Unraveling the relationship between aeroallergen sensitization, gender, second-hand smoke exposure, and impaired lung function.

BACKGROUND: Contradictory findings on the differential effects of second-hand smoke (SHS) on lung function in girls and boys may result from masked relationships between host and environmental factors. Allergic sensitization may augment the relationship between SHS and decreased lung function, although its role in relation to the inconsistent gender differences in children has not been elucidated. HYPOTHESIS: We hypothesize that there will be differences between boys and girls related to early-life allergic sensitization and exposure to SHS on pulmonary function later in childhood. METHODS: Participants in this study (n = 486) were drawn from the Cincinnati Childhood Allergy and Air Pollution (CCAAPS) birth cohort study consisting of 46% girls. Allergic sensitization was assessed by skin prick test (SPT) to 15 aeroallergens at ages 2, 4, and 7, while pulmonary function and asthma diagnosis occurred at age 7. SHS exposure was measured by hair cotinine at ages 2 and/or 4. Gender differences of SHS exposure on pulmonary function among children with positive SPTs at ages 2, 4, and 7 as well as first- and higher-order interactions were examined by multiple linear regression. Interactions significant in the multivariate models were also examined via stratification. Comparisons within and between stratified groups were assessed by examining the slope of the parameter estimates/beta coefficients and associated p-values and confidence intervals. RESULTS: Increased cotinine levels were significantly associated with decreases in FEV(1) (-0.03 l, p < 0.05), peak expiratory flow (-0.07 l/s, p < 0.05), and FEF (25-75%) (-0.06 l/s, p < 0.01). The interaction between cotinine and sensitization at age 2 was borderline significant (p = 0.10) in the FEF(25-75%) model and showed an exposure response effect according to the number of positive SPTs at age 2; zero (-0.06 l/s, p < 0.01), one (-0.09 l/s, p < 0.05), or two or more positive SPTs (-0.30 l/s, p < 0.01). Despite increased polysensitization among boys, the association between cotinine and FEF(25-75%) among girls, with two or more positive SPTs at age 2, showed the greatest deficits in FEF(25-75%) (-0.34 l/s vs. -0.05 l/s and -0.06 l/s for non-sensitized girls and boys, respectively. Girls with two or more positive SPTs showed a twofold greater decrease in FEF(25-5%) (-0.34 l/s; 95% CI: -0.55, -0.13) compared to boys with the same degree of allergic sensitization (-0.18 l/s; 95% CI: -0.41, 0.06), although this difference was not statistically significant. CONCLUSIONS: Reductions in lung function were observed among children exposed to SHS, and the number of aeroallergen-positive SPTs at age 2 modifies this relationship. Girls experiencing early childhood allergic sensitization and high SHS exposure are at greater risk of decreased lung function later in childhood compared to non-sensitized girls and boys and demonstrate greater deficits compared to boys with similar degrees of sensitization.

Asthma in the elderly: risk factors and impact on physical function.

BACKGROUND: The incidence rate of asthma has increased in all age groups in the past 40 years. Asthma in older adults is underdiagnosed and undertreated, resulting in suboptimal asthma control. OBJECTIVE: The objectives of the study are to evaluate differences in host characteristics between older patients with asthma and persons who do not have asthma and how these differences impact overall quality of life. METHODS: Patients older than age 60 years were recruited from the general population for this case/control and nested cohort study. A complete medical history, physical examination, skin prick testing (SPT), spirometry, and exhaled nitric oxide (ENO) measurements were performed. Quality of life was assessed through the standardized SF-36v2 questionnaire. Quality of life scores, spirometry, ENO, and aeroallergen sensitization differences were compared between older patients with asthma and control patients. RESULTS: The mean age of the 77 patients evaluated was 68.7 ± 7.2 years, with 59 (77%) being female. A higher rate of SPT positivity was found in patients with asthma (88.9%) compared with controls (51.2%) (P = .007). The mean percent predicted forced expiratory volume in 1 second (FEV1) at baseline was lower in the asthma group (73.7 ± 21.9%) compared with controls (89.6 ± 19.1%) (P = .007). For quality of life assessed by the SF-36v2 questionnaire, the asthma group had worse general health, increased bodily pain, and worse overall physical health compared with controls (P = .02; .021; .01). CONCLUSION: Older adults with asthma have a higher rate of allergic sensitization, decreased lung function, and significantly worse quality of life compared with controls.

Validating childhood symptoms with physician-diagnosed allergic rhinitis.

BACKGROUND: Multiple population-based and high-risk cohort studies use parental questionnaire responses to define allergic rhinitis (AR) in children. Individual questionnaire items have not been validated by comparison with physician-diagnosed AR (PDAR). OBJECTIVE: To identify routine clinical questions that best agree with a physician diagnosis of AR and can be used for early case identification. METHODS: Children participating in a longitudinal birth cohort study were evaluated at ages 1 through 4 and at age 7 (n = 531) using questionnaires, physical examinations, and skin prick tests (SPT) with 15 aeroallergens (AG). Parents answered 3 stem questions pertaining to their child, including presence of nasal symptoms absent a cold/flu (ISAAC-validated question), presence of hayfever, and ocular itch. Substem questions were answered with details regarding seasonality, nasal triggers, and ocular seasonality. A global assessment of allergic diseases, including AR, was performed by a specialty-trained clinician. Percent agreement, sensitivity, specificity, and positive predictive values were assessed for individual stem and substem questions. RESULTS: Positive response to having hayfever and presence of ocular symptoms had the highest specificity (84% and 69%, respectively) and the highest percent agreement (74% and 68%) with PDAR. Identification of triggers for nasal and ocular symptoms had the highest sensitivity (89%). Positive predictive values ranged from 31 to 39%. Combining 2 responses with highest agreement increased specificity for PDAR to 91%. CONCLUSION: Responses to hayfever and ocular symptoms had better specificity and percent agreement with PDAR than the ISAAC-validated questionnaire item. Combining 2 rhinitis questions sharply increases specificity and may improve diagnostic accuracy of clinical questions.

Poor asthma control and exposure to traffic pollutants and obesity in older adults.

BACKGROUND: Environmental and host predictors of asthma control in older asthmatic patients (>65 years old) are poorly understood. OBJECTIVE: To examine the effects of residential exposure to traffic exhaust and other environmental and host predictors on asthma control in older adults. METHODS: One hundred four asthmatic patients 65 years of age or older from allergy and pulmonary clinics in greater Cincinnati, Ohio, completed the validated Asthma Control Questionnaire (ACQ), pulmonary function testing, and skin prick testing to 10 common aeroallergens. Patients had a physician's diagnosis of asthma, had significant reversibility in forced expiratory volume in 1 second or a positive methacholine challenge test result, and did not have chronic obstructive pulmonary disease. The mean daily residential exposure to elemental carbon attributable to traffic (ECAT) was estimated using a land-use regression model. Regression models were used to evaluate associations among independent variables, ACQ scores, and the number of asthma exacerbations, defined as acute worsening of asthma symptoms requiring prednisone use, in the past year. RESULTS: In the adjusted model, mean daily residential exposure to ECAT greater than 0.39 µg/m(3) was significantly associated with poorer asthma control based on ACQ scores (adjusted ß = 2.85; 95% confidence interval [CI], 0.58-5.12; P = .02). High ECAT levels were also significantly associated with increased risk of asthma exacerbations (adjusted odds ratio, 3.24; 95% CI, 1.01-10.37; P = .05). A significant association was found between higher body mass index and worse ACQ scores (adjusted ß = 1.15; 95% CI, 0.53-1.76; P < .001). Atopic patients (skin prick test positive) had significantly better ACQ scores than nonatopic patients (adjusted ß = -0.39; 95% CI, -0.67 to -0.11; P < .01). CONCLUSION: Higher mean daily residential exposure to traffic exhaust, obesity, and nonatopic status are associated with poorer asthma control among older asthmatic patients.

Genetic variation in small proline rich protein 2B as a predictor for asthma among children with eczema.

BACKGROUND: Small proline rich protein 2B (SPRR2B) is a skin and lung epithelial protein associated with allergic inflammation in mice that has not been evaluated in human atopic diseases. OBJECTIVE: To determine whether single-nucleotide polymorphisms (SNPs) in SPRR2B are associated with childhood eczema and with the phenotype of childhood eczema combined with asthma. METHODS: Genotyping for SPRR2B and filaggrin (FLG) was performed in 2 independent populations: the Cincinnati Childhood Allergy & Air Pollution Study (CCAAPS; N = 762; birth-age, 4 years) and the Greater Cincinnati Pediatric Clinical Repository (GCPCR; N = 1152; ages 5-10 years). Eczema and eczema plus asthma were clinical outcomes based on parental report and clinician's diagnosis. Genetic analyses were restricted to whites and adjusted for sex in both cohorts and adjusted for environmental covariates in CCAAPS. RESULTS: Variants in SPRR2B were not significantly associated with eczema in either cohort after Bonferroni adjustment. Children from both cohorts with the CC genotype of the SPRR2B rs6693927 SNP were at 4 times the risk for eczema plus asthma (adjusted odds ratio, 4.1; 95% confidence interval, 1.5-10.9; P = .005 in CCAAPS; and adjusted odds ratio, 4.0; 95% confidence interval, 1.8-9.1; P < .001 in the GCPCR), however. SNPs in SPRR2B were not in strong linkage disequilibrium with the R501X and del2282 FLG mutations, and these findings were independent of FLG. CONCLUSIONS: An SNP in SPRR2B was predictive of asthma among white children with eczema from 2 independent populations. SPRR2B polymorphisms may serve as important predictive markers for the combined eczema plus asthma phenotype.

Opposing effects of cat and dog ownership and allergic sensitization on eczema in an atopic birth cohort.

OBJECTIVE: To examine risk factors for eczema at age 4 years. STUDY DESIGN: Beginning at 1 year of age, infants of atopic parents (n = 636) had annual clinical evaluations and skin prick tests (SPTs) to 15 aeroallergens and milk and egg. Parents completed validated surveys on eczema and environmental exposures. House dust samples were evaluated for allergens and endotoxin. Eczema was defined as a parental report of scratching, and redness, "raised bumps," or dry skin/scaling for 6 of the last 12 months. RESULTS: At age 4 years, a total of 90 children (14%) had eczema. Not having a dog before 1 year of age and being dog SPT+ at 1, 2, or 3 years of age conferred a 4-fold higher risk for eczema at age 4 years (adjusted odds ratio [aOR] = 3.9 [1.6-9.2]; P = .002). Among dog owners, however, dog SPT+ was not associated with significantly increased risk (aOR 1.3 [0.3-6.8]; P = .8). Among children with cats before 1 year of age, cat SPT+ conferred significantly increased risk for eczema (aOR = 13.3 [3.1-57.9]; P < .001). Among non-cat owners, cat SPT+ was not associated with increased risk (aOR = 1.1 [0.5-2.7]; P = .8). CONCLUSION: Dog ownership significantly reduced the risk for eczema at age 4 years among dog-sensitized children, cat ownership combined with cat sensitization significantly increased the risk.

High environmental relative moldiness index during infancy as a predictor of asthma at 7 years of age.

BACKGROUND: Mold exposures may contribute to the development of asthma, but previous studies have lacked a standardized approach to quantifying exposures. OBJECTIVE: To determine whether mold exposures at the ages of 1 and/or 7 years were associated with asthma at the age of 7 years. METHODS: This study followed up a high-risk birth cohort from infancy to 7 years of age. Mold was assessed by a DNA-based analysis for the 36 molds that make up the Environmental Relative Moldiness Index (ERMI) at the ages of 1 and 7 years. At the age of 7 years, children were evaluated for allergic sensitization and asthma based on symptom history, spirometry, exhaled nitric oxide, and airway reversibility. A questionnaire was administered to the parent regarding the child's asthma symptoms and other potential cofactors. RESULTS: At the age of 7 years, 31 of 176 children (18%) were found to be asthmatic. Children living in a high ERMI value (≥5.2) home at 1 year of age had more than twice the risk of developing asthma than those in low ERMI value homes (<5.2) (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 1.10-6.26). Of the other covariates, only parental asthma (aOR, 4.0; 95% CI, 1.69-9.62) and allergic sensitization to house dust mite (aOR, 4.1; 95% CI, 1.55-11.07) were risk factors for asthma development. In contrast, air-conditioning at home reduced the risk of asthma development (aOR, 0.3; 95% CI, 0.14-0.83). A high ERMI value at 7 years of age was not associated with asthma at 7 years of age. CONCLUSIONS: Early exposure to molds as measured by ERMI at 1 year of age, but not 7 years of age, significantly increased the risk for asthma at 7 years of age.

Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis.

BACKGROUND: Infant predictors of early childhood allergic rhinitis (AR) are poorly understood. OBJECTIVE: We sought to identify environmental exposures and host factors during infancy that predict AR at age 3 years. METHODS: High-risk children from greater Cincinnati were followed annually from ages 1 to 3 years. AR was defined as sneezing, runny, or blocked nose in the prior 12 months and a positive skin prick test (SPT) response to 1 or more aeroallergens. Environmental and standardized medical questionnaires determined exposures and clinical outcomes. Primary activity area dust samples were analyzed for house dust endotoxin (HDE) and (1-3)-beta-D-glucan. Fine particulate matter sampled at 27 monitoring stations was used to estimate personal elemental carbon attributable to traffic exposure by using a land-use regression model. RESULTS: Of 361 children in this analysis, 116 had AR, and 245 were nonatopic and nonsymptomatic. Prolonged breast-feeding in African American children (adjusted odds ratio [aOR], 0.8; 95% CI, 0.6-0.9) and multiple children in the home during infancy was protective against AR (aOR, 0.4; 95% CI, 0.2-0.8). Food SPT response positivity and tree SPT response positivity in infancy increased the risk of AR at age 3 years (aOR of 4.4 [95% CI, 2.1-9.2] and aOR of 6.8 [95% CI, 2.5-18.7], respectively). HDE exposure was associated with AR; the effect was dependent on exposure level. Elemental carbon attributable to traffic and environmental tobacco smoke exposure showed no effect on AR. CONCLUSION: Prolonged breast-feeding in African American subjects and multiple children in the home during infancy reduced the risk of AR at age 3 years. SPT response positivity to food and tree allergens enhanced risk. The HDE effect on AR was related to exposure.

Exposure to traffic exhaust and night cough during early childhood: the CCAAPS birth cohort.

Though studies have investigated the association between air pollution and respiratory health outcomes in children, few have focused on night cough. The study objective was to simultaneously evaluate family factors (i.e., race, gender, maternal and paternal asthma, and breastfeeding), health (allergen sensitization and wheezing symptoms), home factors (dog, cat, mold, endotoxin, and dust mite), and other environmental exposures (traffic exhaust and second-hand tobacco smoke) for associations with recurrent dry night cough (RNC) during early childhood. A structural equation model with repeat measures was developed assessing RNC at ages one, two, and three. The prevalence of RNC was relatively large and similar at ages, one, two, and three at 21.6%, 17.3%, and 21.1%, respectively. Children exposed to the highest tertile of traffic exhaust had an estimated 45% increase in risk of RNC compared with children less exposed (adjusted OR 1.45, 95% CI: 1.09, 1.94). Also, wheezing was associated with a 76% higher risk of RNC (adjusted OR 1.76, 95% CI: 1.36, 2.26). A protective trend for breastfeeding was found with a 27% reduction in risk associated with breastfeeding (adjusted OR 0.73, 95% CI: 0.53, 1.01). No other factors were significant. These results suggest that traffic exhaust exposure may be a risk factor for night cough in young children.

Exposure to traffic-related particles and endotoxin during infancy is associated with wheezing at age 3 years.

RATIONALE: Murine models demonstrate a synergistic production of reactive oxygen species on coexposure to diesel exhaust particles and endotoxin. OBJECTIVES: It was hypothesized that coexposure to traffic-related particles and endotoxin would have an additive effect on persistent wheezing during early childhood. METHODS: Persistent wheezing at age 36 months was assessed in the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk birth cohort. A time-weighted average exposure to traffic-related particles was determined by applying a land-use regression model to the homes, day cares, and other locations where children spent time from birth through age 36 months. Indoor levels of endotoxin were measured from dust samples collected before age 12 months. The relationship between dichotomized (or=75th percentile) traffic-related particle and endotoxin exposure and persistent wheezing, controlling for potential covariates, was examined. MEASUREMENTS AND MAIN RESULTS: Persistent wheezing at age 36 months was significantly associated with exposure to increased levels of traffic-related particles before age 12 months (OR = 1.75; 95% confidence interval, 1.07-2.87). Coexposure to endotoxin had a synergistic effect with traffic exposure on persistent wheeze (OR = 5.85; 95% confidence interval, 1.89-18.13) after adjustment for significant covariates. CONCLUSIONS: The association between traffic-related particle exposure and persistent wheezing at age 36 months is modified by exposure to endotoxin. This finding supports prior toxicological studies demonstrating a synergistic production of reactive oxygen species after coexposure to diesel exhaust particles and endotoxin. The effect of early versus later exposure to traffic-related particles, however, remains to be studied because of the high correlation between exposure throughout the first 3 years of life.

Associations between multiple environmental exposures and Glutathione S-Transferase P1 on persistent wheezing in a birth cohort.

OBJECTIVE: To determine the impact of environmental exposures (diesel exhaust particle [DEP], environmental tobacco smoke [ETS], and mold) that may contribute to oxidative stress on persistent wheezing in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort and to determine how the impact of these exposures is modified by the GST-P1 Ile105Val polymorphism. STUDY DESIGN: A land-use regression model was used to derive an estimate of each child's DEP exposure. ETS exposure was determined by questionnaire data. Each child's home was evaluated for visible mold by a trained professional. Children in the CCAAPS cohort were genotyped for the GST-P1 polymorphism (n = 570). Persistent wheezing was defined as wheezing at both 12 and 24 months. RESULTS: High DEP exposure conferred increased risk for wheezing phenotypes but only among the Val(105) allele carriers. Infants with multiple exposures were significantly more likely to persistently wheeze despite their genotype. CONCLUSION: There is evidence for an environmental effect of DEP among carriers of the GST-P1 Val(105) allele in the development of persistent wheezing in children. The protective effect of the GST-P1 Ile(105) genotype may be overwhelmed by multiple environmental exposures that converge on oxidative stress pathways.

Environmental tobacco smoke and interleukin 4 polymorphism (C-589T) gene: environment interaction increases risk of wheezing in African-American infants.

OBJECTIVES: To determine whether infants exposed to environmental tobacco smoke (ETS) having the interleukin 4 (IL-4) or interleukin 13 (IL-13) gene polymorphisms were at increased risk of wheezing. STUDY DESIGN: A birth cohort of 758 infants was evaluated annually by a questionnaire, physical examination, and skin prick testing. DNA samples from 560 children were genotyped for IL-4 C-589T and IL-13 C-1112T. The relationship of ETS exposure and genotype with the outcome of wheezing was analyzed. RESULTS: At the time of evaluation, mean age was 13.4 +/- 2.2 months. The prevalence of sensitization was 29%, and wheezing without a cold was 26.2%. The interaction of ETS exposure and the CT/TT genotypes for IL-4 C-589T showed a significant association with wheezing (odds ratio: 10.84; 95% confidence interval: 1.12-104.64, P = .04) in African-American infants. CONCLUSIONS: In African-American infants with a family history of atopy, the interaction of ETS and IL-4 C-589T demonstrated a 10-fold risk associated with wheezing without a cold.

Estenosis Tricuspídea Severa secundaria a enfermedad carcinoide cardiaca: presentación de caso clínico y revisión de la literatura / Severe Tricuspid Stenosis Secondary to Cardiac Carcinoid Disease: Case Report and Literature Review

RESUMEN: La estenosis tricuspídea (ET) es una valvulopatía infrecuente cuyas principales etiologías son la enfermedad reumática y la endocarditis infecciosa. En raras ocasiones puede deberse a un fenómeno carcinoide subyacente, en lo que se conoce como la enfermedad carcinoide cardiaca (ECC). Esta condición lleva a la fibrosis del endocardio del ventriculo derecho, principalmente de sus válvulas, lo cual puede provocar falla cardiaca derecha, complicando el pronóstico. En este artículo se presenta un caso de una ET severa por una posible ECC, en conjunto con las imagenes ecocardiográficas obtenidas durante el abordaje diagnóstico (imágenes bidimensionales, imagen multiplanar y ecocardiografía en 3D). Se discuten las implicaciones clínicas, los retos diagnósticos, las opciones terapeuticas y el pronóstico de esta rara entidad.

ABSTRACT Severe Tricuspid Stenosis Secondary to Cardiac Carcinoid Disease: Case Report and Literature Review Tricuspid stenosis is an unfrequent valvulopathy that can be caused by multiple etiologies, including rheumatic disease and infectious endocarditis. In rare occasions, it occurs in the context of a carcinoid syndrome, in what is known as carcinoid heart disease. This condition causes fibrosis of the valves and the endocardium of the right ventricule, which can progress into right ventricular failure, worsening the patient's prognosis. In this article, we present a case of a severe tricuspid stenosis in which this ethiology is suspected. We show the echocardiographic images obtained for the diagnosis (two-dimensional imaging, multimodal imaging and 3D echocardiography), and we discuss the clinical and diagnostic implications, therapeutic options and prognosis of this rare condition.

A comparison of proximity and land use regression traffic exposure models and wheezing in infants.

BACKGROUND: We previously reported an association between infant wheezing and residence < 100 m from stop-and-go bus and truck traffic. The use of a proximity model, however, may lead to exposure misclassification. OBJECTIVE: Results obtained from a land use regression (LUR) model of exposure to truck and bus traffic are compared with those obtained with a proximity model. The estimates derived from the LUR model were then related to infant wheezing. METHODS: We derived a marker of diesel combustion--elemental carbon attributable to traffic sources (ECAT)--from ambient monitoring results of particulate matter with aerodynamic diameter < 2.5 microm. We developed a multiple regression model with ECAT as the outcome variable. Variables included in the model were locations of major roads, bus routes, truck traffic count, and elevation. Model parameter estimates were applied to estimate individual ECAT levels at infants' homes. RESULTS: The levels of estimated ECAT at the monitoring stations ranged from 0.20 to 1.02 microg/m(3). A LUR model of exposure with a coefficient of determination (R(2)) of 0.75 was applied to infants' homes. The mean (+/- SD) ambient exposure of ECAT for infants previously categorized as unexposed, exposed to stop-and-go traffic, or exposed to moving traffic was 0.32 +/- 0.06, 0.42 +/- 0.14, and 0.49 +/- 0.14 microg/m(3), respectively. Levels of ECAT from 0.30 to 0.90 mug/m(3) were significantly associated with infant wheezing. CONCLUSIONS: The LUR model resulted in a range of ECAT individually derived for all infants' homes that may reduce the exposure misclassification that can arise from a proximity model.