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Background: Settled dust has been used in studies to assess exposures to allergens and other biologically active components, but it has not been considered in the aggregate in relation to respiratory health outcomes in the general population.Objective: We addressed whether total house dust weight, an index of total dust exposure, was associated with respiratory health outcomes in the National Survey of Lead and Allergens in Housing (1998-1999) (NSLAH).Methods: NSLAH was a cross-sectional survey designed to represent permanently occupied housing units in the United States. In each household, a questionnaire was administered and settled dust was vacuumed from five locations. Linear regression models were used to identify predictors of dust weight; logistic regression models were used to examine the relationship between dust weight and asthma and wheeze.Results: Dust weight samples were available for 829 households, and survey information was available for 2,456 participants (children and adults). Lower income, older homes, household pets, having a smoker in the house, and less frequent cleaning predicted higher dust weight levels in U.S. households. Higher levels of dust weight were associated with greater odds of current asthma and wheeze. The strongest associations were seen for wheeze [adjusted odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.21-3.28 for bedroom bed dust; OR = 2.81; 95% CI, 1.52-5.21 for upholstery dust). These associations persisted when adjusting for allergen and endotoxin exposures.Conclusions: Dust weight, an index of total dust exposure in the home, may contribute to respiratory outcomes independently of the exposure to specific components. [ABSTRACT FROM AUTHOR]

Background: The National Asthma Education and Prevention Program guidelines emphasize environmental control as an integral part of asthma management; however, limited national-level data exist on how clinicians implement environmental control recommendations., Objective: We analyzed data on clinicians' self-reported use of recommended environmental control practices in a nationally representative sample (n = 1645) of primary care physicians, asthma specialists, and advanced practice providers from the National Asthma Survey of Physicians, a supplemental questionnaire to the 2012 National Ambulatory Medical Care Survey., Methods: We examined clinician and practice characteristics as well as clinicians' decisions and strategies regarding environmental trigger assessment and environmental control across provider groups. Regression modeling was used to identify clinician and practice characteristics associated with implementation of guideline recommendations., Results: A higher percentage of specialists assessed asthma triggers at home, school, and/or work than primary care or advanced practice providers (almost always: 53.6% vs 29.4% and 23.7%, respectively, P  < .001). Almost all clinicians (>93%) recommended avoidance of secondhand tobacco smoke, whereas recommendations regarding cooking appliances (eg, proper ventilation) were infrequent. Although assessment and recommendation practices differed between clinician groups, modeling results showed that clinicians who reported almost always assessing asthma control were 5- to 6-fold more likely to assess environmental asthma triggers. Use of asthma action plans was also strongly associated with implementation of environmental control recommendations., Conclusions: Environmental assessment and recommendations to patients varied among asthma care providers. High adherence to other key guideline components, such as assessing asthma control, was associated with environmental assessment and recommendation practices on environmental control., Competing Interests: Supported in part by the Intramural Research Program of the 10.13039/100000002National Institutes of Health, the 10.13039/100000066National Institute of Environmental Health Sciences (Z01-ES-025041), and through a contract to Social & Scientific Systems funded by the National Institute of Environmental Health Sciences (HHSN273201600002I). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the US Environmental Protection Agency. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

Despite the prominent use of complex survey data and the growing popularity of machine learning methods in epidemiologic research, few machine learning software implementations offer options for handling complex samples. A major challenge impeding the broader incorporation of machine learning into epidemiologic research is incomplete guidance for analyzing complex survey data, including the importance of sampling weights for valid prediction in target populations. Using data from 15, 820 participants in the 1988-1994 National Health and Nutrition Examination Survey cohort, we determined whether ignoring weights in gradient boosting models of all-cause mortality affected prediction, as measured by the F1 score and corresponding 95% confidence intervals. In simulations, we additionally assessed the impact of sample size, weight variability, predictor strength, and model dimensionality. In the National Health and Nutrition Examination Survey data, unweighted model performance was inflated compared to the weighted model (F1 score 81.9% [95% confidence interval: 81.2%, 82.7%] vs 77.4% [95% confidence interval: 76.1%, 78.6%]). However, the error was mitigated if the F1 score was subsequently recalculated with observed outcomes from the weighted dataset (F1: 77.0%; 95% confidence interval: 75.7%, 78.4%). In simulations, this finding held in the largest sample size (N = 10,000) under all analytic conditions assessed. For sample sizes <5,000, sampling weights had little impact in simulations that more closely resembled a simple random sample (low weight variability) or in models with strong predictors, but findings were inconsistent under other analytic scenarios. Failing to account for sampling weights in gradient boosting models may limit generalizability for data from complex surveys, dependent on sample size and other analytic properties. In the absence of software for configuring weighted algorithms, post-hoc re-calculations of unweighted model performance using weighted observed outcomes may more accurately reflect model prediction in target populations than ignoring weights entirely., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Oxidative stress plays a key role in the pathogenesis of respiratory diseases; however, studies on antioxidant vitamins and respiratory outcomes have been conflicting. We evaluated whether lower serum levels of vitamins A, C, D, and E are associated with respiratory morbidity and mortality in the U.S. adult population., Methods: We conducted a pooled analysis of data from the 1988-1994 and 1999-2006 National Health and Nutrition Examination Survey (participants aged ≥ 20 years). We estimated covariate-adjusted odds ratios (aOR) per interquartile decrease in each serum vitamin level to quantify associations with respiratory morbidity, and covariate-adjusted hazard ratios (aHR) to quantify associations with respiratory mortality assessed prospectively through 2015. Vitamin supplementation and smoking were evaluated as potential effect modifiers., Results: Lower serum vitamin C increased the odds of wheeze among all participants (overall aOR: 1.08, 95% CI: 1.01-1.16). Among smokers, lower serum α-tocopherol vitamin E increased the odds of wheeze (aOR: 1.11, 95% CI: 1.04-1.19) and chronic bronchitis/emphysema (aOR: 1.13, 95% CI: 1.03-1.24). Conversely, lower serum γ-tocopherol vitamin E was associated with lower odds of wheeze and chronic bronchitis/emphysema (overall aORs: 0.85, 95% CI: 0.79-0.92 and 0.85, 95% CI: 0.76-0.95, respectively). Lower serum vitamin C was associated with increased chronic lower respiratory disease (CLRD) mortality in all participants (overall aHR: 1.27, 95% CI: 1.07-1.51), whereas lower serum 25-hydroxyvitamin D (25-OHD) tended to increase mortality from CLRD and influenza/pneumonia among smokers (aHR range: 1.33-1.75). Mortality from influenza/ pneumonia increased with decreasing serum vitamin A levels in all participants (overall aHR: 1.21, 95% CI: 0.99-1.48). In pooled analysis, vitamin C deficiency and 25-OHD insufficiency were associated with mortality from influenza/pneumonia, increasing mortality risk up to twofold., Conclusions: Our analysis of nationally representative data on over 34,000 participants showed that lower serum levels of vitamins A, C, D, and α-tocopherol vitamin E are associated with increased respiratory morbidity and/or mortality in U.S. adults. The results underscore the importance of antioxidant vitamins in respiratory health., (© 2022. The Author(s).)

Background: Bisphenols F (BPF) and S (BPS) are bisphenol A (BPA) analogs used as substitutes in consumer products. Despite previous reports of BPA's association with asthma, no studies have examined its structural analogs in relation to asthma and allergy outcomes., Objective: To examine the association of urinary BPF, BPS, and BPA with asthma and hay fever in a US representative sample., Methods: We analyzed data from 3,538 participants aged 12 years or older in the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Children aged 6-11 years (N = 738), who did not have all covariate data available, were analyzed separately. Covariate-adjusted logistic regression was used to assess the association of the exposures with the outcomes., Results: BPF, BPS, and BPA were detected in 57.1%, 88.4%, and 94.8% of the urine samples, respectively. Urinary BPF detection was positively associated with current asthma (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16-2.04) and hay fever (OR: 1.66, 95% CI: 1.12-2.46). Urinary BPS was associated with increased odds of current asthma in men (OR: 1.64, 95% CI: 1.13-2.40) and urinary BPA was associated with increased odds of asthma without hay fever in children aged 6-11 years (OR: 2.65, 95% CI: 1.05-6.68)., Conclusion: Our nationally-representative findings document that BPF and BPS exposure is common in the US and that exposure to these BPA analogs is associated with asthma and/or hay fever. Our results suggest that BPF and BPS may not be safe alternatives to BPA; however, prospective studies should be conducted to confirm these results., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Published by Elsevier Inc.)

Background: Endotoxin is ubiquitous in the environment, but its clustering with indoor allergens is not well characterized. This study examined the clustering patterns of endotoxin with allergens in house dust and their association with asthma outcomes., Methods: We analyzed data from 6963 participants of the 2005-2006 National Health and Nutrition Examination Survey. House dust sampled from bedroom floor and bedding was evaluated for endotoxin and allergens from fungi, cockroach, dog, cat, mites, and rodents. Two-step cluster analysis and logistic regressions were performed to identify the clustering patterns and their associations with current asthma and wheeze in the past 12 months, adjusting for covariates., Results: Of the homes, 17.8% had low endotoxin and allergen levels in house dust (Cluster 1). High endotoxin level clustered with Alternaria and pet allergens in the homes of participants with a high socioeconomic status who own pets (Cluster 2) (48.9%). High endotoxin clustered with Aspergillus, dust mites, cockroach, and rodent allergens in the homes of participants with low socioeconomic status (Cluster 3) (33.3%). Compared to Cluster 1, Cluster 2 was associated with higher asthma prevalence (OR 1.42, 95% CI: 1.06-1.91) and wheeze (OR 1.32, 95% CI: 1.07-1.63). Cluster 3 was positively associated with wheeze only in participants sensitized to inhalant allergens (OR 1.42, 95% CI: 1.06-1.91) or exposed to tobacco smoke (OR 1.72, 95% CI: 1.15-2.60)., Conclusions: The clustering of endotoxin with allergens in dust from homes with pets or of people with low socioeconomic status is associated with asthma and wheeze.

Background: Endotoxin has been reported to be associated with chronic bronchitis or emphysema (CBE) at high occupational exposures. However, whether levels found in domestic environments have similar effects is unknown., Objectives: We aimed to study the association between house dust endotoxin and CBE in a sample representative of the U.S. population., Methods: We analyzed data from 3,393 participants ≥20 y old from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. House dust from bedding and from bedroom floors was analyzed for endotoxin content. NHANES participants received questionnaires and underwent examination as well as extensive laboratory testing. Logistic regression was used to examine the association of endotoxin levels with CBE diagnosis and symptoms, adjusting for covariates. The survey design and weights were applied so that estimates were nationally representative and so that statistical inferences were made appropriately., Results: The median endotoxin concentration in house dust was 14.61 EU/mg dust, and CBE was reported by 8.2% of participants. In the adjusted analysis, one unit (EU/mg) increase in log 10 -transformed endotoxin concentrations was associated with a 27% increase in the odds of CBE diagnosis [OR=1.27 (95% CI: 1.00, 1.61)] and a 78% increase in the odds of chronic bronchitis symptoms (defined as cough and phlegm for ≥3 mo in a year for ≥2 y) [OR=1.78 (95% CI: 1.01, 3.12)]. Sensitization to inhalant allergens ( p =0.001) modified the relationship between endotoxin and CBE diagnosis, with stronger associations observed in sensitized participants [OR=2.46 (95% CI: 1.72, 3.50) for a unit increase in log 10 -endotoxin]., Conclusions: In a population-based sample of U.S. adults, endotoxin levels in homes were associated with a self-reported history of CBE diagnosis and chronic bronchitis symptoms, with stronger associations among people sensitized to inhalant allergens. https://doi.org/10.1289/EHP2452.

Rationale: Although endotoxin is a recognized cause of environmental lung disease, how its relationship with respiratory outcomes varies with climate is unknown., Objective: To examine the endotoxin predictors as well as endotoxin association with asthma, wheeze, and sensitization to inhalant allergens in various US climate regions., Methods: We analyzed data on 6963 participants in the National Health and Nutrition Examination Survey. Endotoxin measurements of house dust from bedroom floor and bedding were performed at the University of Iowa. Linear and logistic regression analyses were used to identify endotoxin predictors and assess endotoxin association with health outcomes., Results: The overall median house dust endotoxin was 16.2 EU/mg; it was higher in mixed-dry/hot-dry regions (19.7 EU/mg) and lower in mixed-humid/marine areas (14.8 EU/mg). Endotoxin predictors and endotoxin association with health outcomes significantly differed across climate regions. In subarctic/very cold/cold regions, log 10 -endotoxin was significantly associated with higher prevalence of wheeze outcomes (OR:1.48, 95% CI:1.19-1.85 for any wheeze, OR:1.48, 95% CI:1.22-1.80 for exercise-induced wheeze, OR:1.50, 95% CI:1.13-1.98 for prescription medication for wheeze, and OR:1.95, 95% CI:1.50-2.54 for doctor/ER visit for wheeze). In hot-humid regions, log 10 -endotoxin was positively associated with any wheeze (OR:1.66, 95% CI:1.04-2.65) and current asthma (OR:1.56, 95% CI:1.11-2.18), but negatively with sensitization to any inhalant allergens (OR:0.83, 95% CI:0.74-0.92)., Conclusion: Endotoxin predictors and endotoxin association with asthma and wheeze differ across U.S. climate regions. Endotoxin is associated positively with wheeze or asthma in cold and hot-humid regions, but negatively with sensitization to inhalant allergens in hot-humid climates., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood., Objectives: We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects., Methods: The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 ( TLR4 ), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term., Results: There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×10 3 /μL (95% CI: 0.070, 0.301×10 3 /μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15)., Conclusions: This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661.

Background: In bipolar disorder (BD), seasonality of symptoms is common and disturbances in circadian rhythms have been reported., Objectives: We identified high-penetrance families in a geographically restricted area in Northern Fennoscandia and studied the seasonal variation of clinical symptoms among BD subjects and their healthy relatives., Design: We explored the clinical characteristics of subjects living in Northern Fennoscandia, with extreme annual variation in daylight. Among known indigenous high-risk families for BD, we compared the affected ones (N=16) with their healthy relatives (N=15), and also included 18 healthy non-related controls from the same geographical area. Seasonal fluctuation in clinical measures was followed up at the 4 most demarcated photoperiodic time points of the annual cycle: around the summer solstice and autumn equinox in 2013, the winter solstice in 2013/2014, and the spring equinox in 2014. In the baseline, lifetime manic symptoms [Mood Disorder Questionnaire (MDQ)] and morningness-eveningness questionnaire type (MEQ) were registered, whereas in the follow-up, depressive [Beck Depression Inventory (BDI)] and distress [General Health Questionnaire (GHQ-12)] symptoms and alcohol consumption and sleep were recorded., Results: Possibly indicative or statistically significant differences in symptoms between the affected subjects and their healthy relatives were the BDI winter (13.3 vs. 2.6, t=-2.51, p=0.022) and spring scores (12.6 vs. 3.2, t=-1.97, p=0.063) and GHQ winter (4.2 vs. 0.82, t=-2.08, p=0.052) and spring scores (3.8 vs. 0.82, t=-1.97, p=0.063). Scores were higher among the affected subjects, exceeding a possibly diagnostic threshold (10 and 3) at all the time points, and without the notable seasonality which was observed among the healthy relatives. In the overall population, MDQ and MEQ scores had an inverse correlation (-0.384, significant at 0.016), indicating increased lifetime manic behaviour among "the night owl" chronotype subjects., Conclusions: In an Arctic population sample, we found different seasonal fluctuation in mood and distress symptoms and sleep duration scores between subjects with bipolar spectrum disorders and their healthy relatives. Despite the relatively small sample size, the results indicate that the symptoms and signs of BD relate to a disturbance in seasonal variation. Seasonal variation can be considered as an interesting endophenotype for BD and a promising target for further genetic studies.

Background: Allergic sensitization is a risk factor for asthma and allergic diseases. The relationship between ambient air pollution and allergic sensitization is unclear., Objective: To investigate the relationship between ambient air pollution and allergic sensitization in a nationally representative sample of the US population., Methods: We linked annual average concentrations of nitrogen dioxide (NO2), particulate matter ≤10 μm (PM10), particulate matter ≤2.5 μm (PM2.5), and summer concentrations of ozone (O3), to allergen-specific immunoglobulin E (IgE) data for participants in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). In addition to the monitor-based air pollution estimates, we used the Community Multiscale Air Quality (CMAQ) model to increase the representation of rural participants in our sample. Logistic regression with population-based sampling weights was used to calculate adjusted prevalence odds ratios per 10 ppb increase in O3 and NO2, per 10 μg/m(3) increase in PM10, and per 5 μg/m(3) increase in PM2.5 adjusting for race, gender, age, socioeconomic status, smoking, and urban/rural status., Results: Using CMAQ data, increased levels of NO2 were associated with positive IgE to any (OR 1.15, 95% CI 1.04, 1.27), inhalant (OR 1.17, 95% CI 1.02, 1.33), and indoor (OR 1.16, 95% CI 1.03, 1.31) allergens. Higher PM2.5 levels were associated with positivity to indoor allergen-specific IgE (OR 1.24, 95% CI 1.13, 1.36). Effect estimates were similar using monitored data., Conclusions: Increased ambient NO2 was consistently associated with increased prevalence of allergic sensitization., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Environmental exposures to phthalates, particularly high-molecular-weight (HMW) phthalates, are suspected to contribute to allergy., Objective: We assessed whether phthalate metabolites are associated with allergic symptoms and sensitization in a large nationally representative sample., Methods: We used data on urinary phthalate metabolites and allergic symptoms (hay fever, rhinitis, allergy, wheeze, asthma) and sensitization from participants ≥ 6 years of age in the National Health and Nutrition Examination Survey (NHANES) 2005-2006. Allergen sensitization was defined as a positive response to at least one of 19 specific IgE antigens (≥ 0.35 kU/L). Odds ratios (ORs) per one log10 unit change in phthalate concentration were estimated using logistic regression adjusting for age, race, body mass index, gender, creatinine, and cotinine. Separate analyses were conducted for children (6-17 years of age) and adults., Results: The HMW phthalate metabolite monobenzyl phthalate (MBzP) was the only metabolite positively associated with current allergic symptoms in adults (wheeze, asthma, hay fever, and rhinitis). Mono-(3-carboxypropyl) phthalate and the sum of diethylhexyl phthalate metabolites (both representing HMW phthalate exposures) were positively associated with allergic sensitization in adults. Conversely, in children, HMW phthalate metabolites were inversely associated with asthma and hay fever. Of the low-molecular-weight phthalate metabolites, monoethyl phthalate was inversely associated with allergic sensitization in adults (OR = 0.79; 95% CI: 0.70, 0.90)., Conclusion: In this cross-sectional analysis of a nationally representative sample, HMW phthalate metabolites, particularly MBzP, were positively associated with allergic symptoms and sensitization in adults, but there was no strong evidence for associations between phthalates and allergy in children 6-17 years of age.

Background: Most studies investigating the role of residential mouse allergen exposures in asthma have focused on inner-city populations., Objective: We examined whether elevated mouse allergen levels were associated with occupants' asthma status in a nationally representative sample of U.S. households., Methods: Data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed 831 housing units inhabited by 2,456 individuals in 75 different locations throughout the United States. The survey obtained information on demographics, household characteristics, and occupants' health status by questionnaire and environmental observations. We used a polyclonal immunoassay to assess concentrations of mouse urinary protein (MUP) in vacuumed dust collected from various indoor sites., Results: Of the surveyed homes, 82% had detectable levels of MUP, and in 35% of the homes, MUP concentrations exceeded 1.6 microg/g, a level that has been associated with increased mouse allergen sensitization rates. Current asthma, defined as having doctor-diagnosed asthma and asthma symptoms in the preceding 12 months, was positively associated with increased MUP levels. The observed association was modified by atopic status; in allergic individuals, elevated MUP levels (>1.6 microg/g) increased the odds of having asthma symptoms [adjusted OR=1.93; 95% confidence interval (CI), 1.14-3.27], but we found no association in those who did not report allergies (adjusted OR=0.69; 95% CI, 0.33-1.44)., Conclusions: In allergic asthma, residential mouse allergen exposure is an important risk factor for asthma morbidity.

Background: Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children's respiratory health are not well characterized., Methods: Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment., Results: Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07-2.29] and without colds (OR = 1.44, 95% CI: 1.05-1.97). For smoking in the home, the strongest associations were seen for cough (OR = 1.74, 95% CI: 1.17-2.60) and phlegm production (OR = 2.25, 95% CI: 1.36-3.72) without colds among children who lived with two or more smokers., Conclusions: Chinese children living with smokers or in coal-burning homes are at increased risk for respiratory impairment. While economic development in China may decrease coal burning by providing cleaner fuels for household energy use, the increasing prevalence of cigarette smoking is a growing public health concern due to its effects on children. Adverse effects of tobacco smoke exposure were seen despite the low rates of maternal smoking (3.6%) in this population.