RESUMO
This study evaluates the possible association between refractory ceramic fiber (RCF) exposure and all causes of death. Current and former employees (n = 1,119) hired from 1952 to 1999 at manufacturing facilities in New York (NY) state and Indiana were included. Work histories and quarterly plant-wide sampling from 1987 to 2015 provided cumulative fiber exposure (CFE) estimates. The full cohort was evaluated as well as individuals with lower and higher exposure, <45 and ≥45 fiber-months/cc. The Life-Table-Analysis-System was used for all standardized mortality rates (SMRs). Person-years at risk were accumulated from start of employment until 12/31/2019 or date of death. There was no significant association with all causes, all cancers, or lung cancer in any group. In the higher exposed, there was a significant elevation in both malignancies of the "urinary organs" (SMR = 3.59, 95% confidence interval [CI] 1.44, 7.40) and "bladder or other urinary site" (SMR = 4.04, 95% CI 1.10, 10.36), which persisted in comparison to regional mortality rates from NY state and Niagara County. However, six of the nine workers with urinary cancers were known smokers. In the lower exposed, there was a significant elevation in malignancies of the lymphatic and hematopoietic system (SMR = 2.54, 95% CI 1.27, 4.55) and leukemia (SMR = 4.21, 95% CI 1.69, 8.67). There was one pathologically unconfirmed mesothelioma death. A second employee currently living with a pathologically confirmed mesothelioma was identified, but the SMR was non-significant when both were included in the analyses. The association of these two mesothelioma cases with RCF exposure alone is unclear because of potential past exposure to asbestos.
Assuntos
Neoplasias Pulmonares , Mesotelioma , Neoplasias , Doenças Profissionais , Exposição Ocupacional , Cerâmica , Estudos de Coortes , Humanos , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Neoplasias/mortalidade , Doenças Profissionais/complicações , Doenças Profissionais/mortalidade , Exposição Ocupacional/efeitos adversosRESUMO
OBJECTIVE: We previously reported that children exposed to secondhand smoke (SHS) that carried variants in the NAT1 gene had over two-fold higher hair cotinine levels. Our objective was to determine if NAT1 polymorphisms confer increased risk for developing asthma in children exposed to SHS. METHODS: White participants in the Cincinnati Childhood Allergy and Air Pollution Study (n = 359) were genotyped for 10 NAT1 variants. Smoke exposure was defined by hair cotinine and parental report. Asthma was objectively assessed by spirometry and methacholine challenge. Findings were replicated in the Genomic Control Cohort (n = 638). RESULTS: Significant associations between 5 NAT1 variants and asthma were observed in the CCAAPS exposed group compared to none in the unexposed group. There was a significant interaction between NAT1 rs13253389 and rs4921581 with smoke exposure (p = 0.02, p = 0.01) and hair cotinine level (p = 0.048, p = 0.042). Children wildtype for rs4921581 had increasing asthma risk with increasing hair cotinine level, whereas those carrying the NAT1 minor allele had an increased risk of asthma regardless of cotinine level. In the GCC, 13 NAT1 variants were associated with asthma in the smoke-exposed group, compared to 0 in the unexposed group, demonstrating gene-level replication. CONCLUSIONS: Variation in the NAT1 gene modifies asthma risk in children exposed to secondhand-smoke. To our knowledge, this is the first report of a gene-environment interaction between NAT1 variants, smoke exposure, cotinine levels, and pediatric asthma. NAT1 genotype may have clinical utility as a biomarker of increased asthma risk in children exposed to smoke.
Assuntos
Arilamina N-Acetiltransferase/genética , Asma/epidemiologia , Asma/genética , Cotinina/análise , Isoenzimas/genética , Poluição por Fumaça de Tabaco/análise , Alelos , Criança , Pré-Escolar , Exposição Ambiental , Feminino , Genótipo , Cabelo/química , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único , Espirometria , População BrancaRESUMO
BACKGROUND: Asthma phenotypes are currently not amenable to primary prevention or early intervention because their natural history cannot be reliably predicted. Clinicians remain reliant on poorly predictive asthma outcome tools because of a lack of better alternatives. OBJECTIVE: We sought to develop a quantitative personalized tool to predict asthma development in young children. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study (n = 762) birth cohort were used to identify factors that predicted asthma development. The Pediatric Asthma Risk Score (PARS) was constructed by integrating demographic and clinical data. The sensitivity and specificity of PARS were compared with those of the Asthma Predictive Index (API) and replicated in the Isle of Wight birth cohort. RESULTS: PARS reliably predicted asthma development in the Cincinnati Childhood Allergy and Air Pollution Study (sensitivity = 0.68, specificity = 0.77). Although both the PARS and API predicted asthma in high-risk children, the PARS had improved ability to predict asthma in children with mild-to-moderate asthma risk. In addition to parental asthma, eczema, and wheezing apart from colds, variables that predicted asthma in the PARS included early wheezing (odds ratio [OR], 2.88; 95% CI, 1.52-5.37), sensitization to 2 or more food allergens and/or aeroallergens (OR, 2.44; 95% CI, 1.49-4.05), and African American race (OR, 2.04; 95% CI, 1.19-3.47). The PARS was replicated in the Isle of Wight birth cohort (sensitivity = 0.67, specificity = 0.79), demonstrating that it is a robust, valid, and generalizable asthma predictive tool. CONCLUSIONS: The PARS performed better than the API in children with mild-to-moderate asthma. This is significant because these children are the most common and most difficult to predict and might be the most amenable to prevention strategies.
Assuntos
Asma/diagnóstico , Negro ou Afro-Americano , Hipersensibilidade Alimentar/epidemiologia , Projetos de Pesquisa , Asma/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Sons Respiratórios , Fatores de Risco , Sensibilidade e Especificidade , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Continuing use of analog film and digital chest radiography for screening and surveillance for pneumoconiosis and tuberculosis in lower and middle income countries raises questions of equivalence of disease detection. This study compared analog to digital images for intra-rater agreement across formats and prevalence of changes related to silicosis and tuberculosis among South African gold miners using the International Labour Organization classification system. METHODS: Miners with diverse radiological presentations of silicosis and tuberculosis were recruited. Digital and film chest images on each subject were classified by four expert readers. RESULTS: Readings of film and soft copy digital images showed no significant differences in prevalence of tuberculosis or silicosis, and intra-rater agreement across formats was fair to good. Hard copy images yielded higher prevalences. CONCLUSION: Film and digital soft copy images show consistent prevalence of findings, and generally fair to good intra-rater agreement for findings related to silicosis and tuberculosis.
Assuntos
Pulmão/diagnóstico por imagem , Mineradores , Intensificação de Imagem Radiográfica/métodos , Radiografia Torácica/métodos , Silicose/diagnóstico por imagem , Tuberculose Pulmonar/diagnóstico por imagem , Adulto , Infecções por HIV/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Silicose/epidemiologia , África do Sul/epidemiologia , Tuberculose Pulmonar/epidemiologiaRESUMO
OBJECTIVES: Vermiculite ore containing Libby amphibole asbestos (LAA) was mined in Libby, MT, from the 1920s-1990. Recreational and residential areas in Libby were contaminated with LAA. This objective of this study was to characterize childhood exposure to LAA and investigate its association with respiratory health during young adulthood. METHODS: Young adults who resided in Libby prior to age 18 completed a health and activity questionnaire, pulmonary function testing, chest x-ray and HRCT scan. LAA exposure was estimated based on participant report of engaging in activities with potential LAA exposure. Quantitative LAA estimates for activities were derived from sampling data and literature reports. RESULTS: A total of 312 participants (mean age 25.1 years) were enrolled and reported respiratory symptoms in the past 12 months including pleuritic chest pain (23%), regular cough (17%), shortness of breath (18%), and wheezing or whistling in the chest (18%). Cumulative LAA exposure was significantly associated with shortness of breath (aOR = 1.12, 95% CI 1.01-1.25 per doubling of exposure). Engaging in recreational activities near Rainy Creek Road (near the former mine site) and the number of instances heating vermiculite ore to make it expand or pop were also significantly associated with respiratory symptoms. LAA exposure was not associated with pulmonary function or pleural or interstitial changes on either chest x-ray or HRCT. CONCLUSIONS: Pleural or interstitial changes on x-ray or HRCT were not observed among this cohort of young adults. However, childhood exposure to LAA was significantly associated with respiratory symptoms during young adulthood. Pleuritic chest pain, in particular, has been identified as an early symptom associated with LAA exposure and therefore warrants continued follow-up given findings of progressive disease in other LAA exposed populations.
Assuntos
Amiantos Anfibólicos/toxicidade , Exposição Ambiental , Pulmão/fisiopatologia , Doenças Respiratórias/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Pulmão/patologia , Masculino , Mineração , Montana/epidemiologia , Testes de Função Respiratória , Doenças Respiratórias/induzido quimicamente , Adulto JovemRESUMO
AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers. METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes. RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results. CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.
Assuntos
Caulim/toxicidade , Fibras Minerais/toxicidade , Exposição Ocupacional , Doenças Respiratórias/etiologia , Doenças Respiratórias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Razão de Chances , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood. OBJECTIVE: We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children. METHODS: The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes. RESULTS: DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children. CONCLUSION: These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.
Assuntos
Alérgenos/efeitos adversos , Asma/induzido quimicamente , Suscetibilidade a Doenças , Memória Imunológica , Material Particulado/efeitos adversos , Animais , Animais Recém-Nascidos , Asma/sangue , Asma/imunologia , Asma/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/patologia , Masculino , Camundongos , Modelos Imunológicos , Pyroglyphidae/química , Pyroglyphidae/imunologia , Baço/imunologia , Baço/patologia , Células Th17/imunologia , Células Th17/patologia , Células Th2/imunologia , Células Th2/patologia , Emissões de VeículosRESUMO
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.
Assuntos
Acer/imunologia , Eosinofilia/imunologia , Penicillium/imunologia , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/imunologia , Alérgenos/imunologia , Biomarcadores , Pré-Escolar , Eosinófilos/imunologia , Feminino , Humanos , Masculino , Mucosa Nasal/imunologia , Estudos Prospectivos , Testes CutâneosRESUMO
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.
Assuntos
Poluentes Atmosféricos/imunologia , Poluição do Ar/efeitos adversos , Alérgenos/imunologia , Rinite Alérgica/epidemiologia , Emissões de Veículos/toxicidade , Poluentes Atmosféricos/efeitos adversos , Alternaria/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Exposição por Inalação , Masculino , Pais , Penicillium/imunologia , Estudos Prospectivos , Testes Cutâneos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Epithelial genes have previously been associated with asthma but only explain a small fraction of heritability. In part, this might be due to epistasis, which is often not considered. OBJECTIVE: We sought to determine independent and epistatic associations between filaggrin (FLG), serine protease inhibitor Kazal-type 5 (SPINK5), and thymic stromal lymphopoietin (TSLP) gene variants and childhood asthma. METHODS: Using a candidate gene approach, we genotyped 29 variants in FLG, SPINK5, and TSLP in asthmatic, allergic, and nonallergic nonasthmatic white and black children participating in the well-phenotyped Greater Cincinnati Pediatric Clinic Repository. Associations with asthma were also assessed in 6 replication populations. RESULTS: We observed independent associations of variants in SPINK5 (P = .003) and TSLP (P = .006) with childhood asthma; a SPINK5 single nucleotide polymorphism was replicated. In subjects with 1 or more SPINK5 risk alleles, the absence of the TSLP protective minor alleles was associated with a significant increase in asthma (67% vs 53%, P = .0017). In contrast, the presence or absence of TSLP minor alleles did not affect asthma risk in subjects without the SPINK5 risk alleles. The SPINK5 and TSLP epistasis was replicated in a black population (P = .036) who did not display independent association with variants in these genes. CONCLUSIONS: Our results support epistasis between SPINK5 and TSLP, which contributes to childhood asthma. These findings emphasize the importance of using biology to inform analyses to identify genetic susceptibility to complex diseases. The results from our study have clinical relevance and support that the therapeutic effects of anti-TSLP therapy in asthmatic patients might be dependent on SPINK5 genotype.
Assuntos
Asma/genética , Citocinas/genética , Epistasia Genética , Proteínas de Filamentos Intermediários/genética , Proteínas Secretadas Inibidoras de Proteinases/genética , Adolescente , População Negra , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Proteínas Filagrinas , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo Genético , Inibidor de Serinopeptidase do Tipo Kazal 5 , População Branca , Linfopoietina do Estroma do TimoRESUMO
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.
Assuntos
Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Inquéritos e Questionários/normas , Poluição por Fumaça de Tabaco/efeitos adversos , Pré-Escolar , Cotinina/análise , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Ontário/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Prognóstico , Radioimunoensaio , Fatores Socioeconômicos , Fatores de TempoRESUMO
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.
Assuntos
Alérgenos/imunologia , Asma/fisiopatologia , Hipersensibilidade/fisiopatologia , Pulmão/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Alérgenos/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Cotinina/urina , Feminino , Seguimentos , Humanos , Hipersensibilidade/imunologia , Imunização , Pulmão/imunologia , Masculino , Fatores Sexuais , Espirometria , Estados UnidosRESUMO
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.
Assuntos
Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Sazonal/diagnóstico , Inquéritos e Questionários , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Exposição Ambiental/efeitos adversos , Medicina Baseada em Evidências , Prova Pericial , Humanos , Lactente , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Estados UnidosRESUMO
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.
Assuntos
Asma/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Eczema/genética , Polimorfismo de Nucleotídeo Único , Asma/complicações , Asma/diagnóstico , Biomarcadores , Criança , Pré-Escolar , Estudos de Coortes , Eczema/complicações , Eczema/diagnóstico , Feminino , Proteínas Filagrinas , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Lactente , Recém-Nascido , Proteínas de Filamentos Intermediários/genética , Masculino , Deleção de SequênciaRESUMO
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.
Assuntos
Animais Domésticos/imunologia , Dermatite Atópica/imunologia , Eczema/imunologia , Exposição Ambiental/efeitos adversos , Imunização , Fatores Etários , Alérgenos , Análise de Variância , Animais , Gatos , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Dermatite Atópica/genética , Cães , Eczema/epidemiologia , Eczema/genética , Feminino , Predisposição Genética para Doença , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Razão de Chances , Prognóstico , Medição de Risco , Testes CutâneosRESUMO
BACKGROUND: Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. METHODS: Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. RESULTS: Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. CONCLUSION: No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described.
Assuntos
Cerâmica , Pulmão/fisiopatologia , Fibras Minerais/toxicidade , Exposição Ocupacional/efeitos adversos , Adulto , Envelhecimento/fisiologia , Monitoramento Ambiental/métodos , Métodos Epidemiológicos , Monitoramento Epidemiológico , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Minerais/análise , Exposição Ocupacional/análise , Espirometria/métodos , Capacidade Vital/fisiologiaRESUMO
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.