Grouping strategies for assessing and managing persistent and mobile substances.

Background: Persistent, mobile and toxic (PMT), or very persistent and very mobile (vPvM) substances are a wide class of chemicals that are recalcitrant to degradation, easily transported, and potentially harmful to humans and the environment. Due to their persistence and mobility, these substances are often widespread in the environment once emitted, particularly in water resources, causing increased challenges during water treatment processes. Some PMT/vPvM substances such as GenX and perfluorobutane sulfonic acid have been identified as substances of very high concern (SVHCs) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. With hundreds to thousands of potential PMT/vPvM substances yet to be assessed and managed, effective and efficient approaches that avoid a case-by-case assessment and prevent regrettable substitution are necessary to achieve the European Union's zero-pollution goal for a non-toxic environment by 2050. Main: Substance grouping has helped global regulation of some highly hazardous chemicals, e.g., through the Montreal Protocol and the Stockholm Convention. This article explores the potential of grouping strategies for identifying, assessing and managing PMT/vPvM substances. The aim is to facilitate early identification of lesser-known or new substances that potentially meet PMT/vPvM criteria, prompt additional testing, avoid regrettable use or substitution, and integrate into existing risk management strategies. Thus, this article provides an overview of PMT/vPvM substances and reviews the definition of PMT/vPvM criteria and various lists of PMT/vPvM substances available. It covers the current definition of groups, compares the use of substance grouping for hazard assessment and regulation, and discusses the advantages and disadvantages of grouping substances for regulation. The article then explores strategies for grouping PMT/vPvM substances, including read-across, structural similarity and commonly retained moieties, as well as the potential application of these strategies using cheminformatics to predict P, M and T properties for selected examples. Conclusions: Effective substance grouping can accelerate the assessment and management of PMT/vPvM substances, especially for substances that lack information. Advances to read-across methods and cheminformatics tools are needed to support efficient and effective chemical management, preventing broad entry of hazardous chemicals into the global market and favouring safer and more sustainable alternatives.

Sewage sludge biochars as effective PFAS-sorbents.

The use of sewage sludge to produce biochar-based sorbents for per- and polyfluoroalkyl substances (PFAS) removal from water and soil may be an economically and environmentally sustainable waste management option. This study compared the sorption of six perfluorinated carboxylic acids (PFCAs) by two sewage sludge biochars (SSBCs) and one wood chip biochar (WCBC), dry pyrolyzed at 700 °C. Batch sorption tests were conducted by adding individual PFCAs and a PFCA-mixture to pure biochars and mixtures of biochar and a sandy soil (1.3% TOC). PFAS-sorption to the SSBCs exhibited log-linear biochar-water distribution coefficients (log Kd), comparable to those previously reported for commercial activated carbons (e.g., 5.73 ± 0.02 for perfluorooctanoic acid at 1 µg/L). The strong sorption of PFCAs was attributed to the SSBCs relatively high pore volumes in the pore size range that can accommodate these compounds. Sorption was attenuated by the presence of soil (by factors 3-10), by the presence of a mixture of PFCAs (by factors of 6-532) and by both together (by factors of 8-6581), indicating strongly competitive sorption between PFCA-congeners, and less severe sorption attenuation by soil organic matter. These findings could enable sustainable value chains for SSBs in soil remediation and water filtration solutions.

Weight of evidence tools in the prediction of acute fish toxicity.

Acute fish toxicity (AFT) is a key endpoint in nearly all regulatory implementations of environmental hazard assessments of chemicals globally. Although it is an early tier assay, the AFT assay is complex and uses many juvenile fish each year for the registration and assessment of chemicals. Thus, it is imperative to seek animal alternative approaches to replace or reduce animal use for environmental hazard assessments. A Bayesian Network (BN) model has been developed that brings together a suite of lines of evidence (LoEs) to produce a probabilistic estimate of AFT without the testing of additional juvenile fish. Lines of evidence include chemical descriptors, mode of action (MoA) assignment, knowledge of algal and daphnid acute toxicity, and animal alternative assays such as fish embryo tests and in vitro fish assays (e.g., gill cytotoxicity). The effort also includes retrieval, assessment, and curation of quality acute fish toxicity data because these act as the baseline of comparison with model outputs. An ideal outcome of this effort would be to have global applicability, acceptance and uptake, relevance to predominant fish species used in chemical assessments, be expandable to allow incorporation of future knowledge, and data to be publicly available. The BN model can be conceived as having incorporated principles of tiered assessment and whose outcomes will be directed by the available evidence in combination with prior information. We demonstrate that, as additional evidence is included in the prediction of a given chemical's ecotoxicity profile, both the accuracy and the precision of the predicted AFT can increase. Ultimately an improved environmental hazard assessment will be achieved. Integr Environ Assess Manag 2023;19:1220-1234. © 2022 SETAC.

A Bayesian Approach to Incorporating Spatiotemporal Variation and Uncertainty Limits into Modeling of Predicted Environmental Concentrations from Chemical Monitoring Campaigns.

Environmental monitoring studies provide key information to assess ecosystem health. Results of chemical monitoring campaigns can be used to identify the exposure scenarios of regulatory concern. In environmental risk assessment (ERA), measured concentrations of chemicals can be used to model predicted environmental concentrations (PECs). As the PEC is, by definition, a predicted variable, it is highly dependent on the underlying modeling approach from which it is derived. We demonstrate the use of Bayesian distributional regression models to derive PECs by incorporating spatiotemporal conditional variances, and limits of quantification (LOQ) and detection (LOD) as de facto data censoring. Model accuracies increase when incorporating spatiotemporal conditional variances, and the inclusion of LOQ and LOD results in potentially more robust PEC distributions. The methodology is flexible, credibly quantifies uncertainty, and can be adjusted to different scientific and regulatory needs. Posterior sampling allows to express PECs as distributions, which makes this modeling procedure directly compatible with other Bayesian ERA approaches. We recommend the use of Bayesian modeling approaches with chemical monitoring data to make realistic and robust PEC estimations and encourage the scientific debate about the benefits and challenges of Bayesian methodologies in the context of ERA.

Quantification of an Adverse Outcome Pathway Network by Bayesian Regression and Bayesian Network Modeling.

The adverse outcome pathway (AOP) framework has gained international recognition as a systematic approach linking mechanistic processes to toxicity endpoints. Nevertheless, successful implementation into risk assessments is still limited by the lack of quantitative AOP models (qAOPs) and assessment of uncertainties. The few published qAOP models so far are typically based on data-demanding systems biology models. Here, we propose a less data-demanding approach for quantification of AOPs and AOP networks, based on regression modeling and Bayesian networks (BNs). We demonstrate this approach with the proposed AOP #245, "Uncoupling of photophosphorylation leading to reduced ATP production associated growth inhibition," using a small experimental data set from exposure of Lemna minor to the pesticide 3,5-dichlorophenol. The AOP-BN reflects the network structure of AOP #245 containing 2 molecular initiating events (MIEs), 3 key events (KEs), and 1 adverse outcome (AO). First, for each dose-response and response-response (KE) relationship, we quantify the causal relationship by Bayesian regression modeling. The regression models correspond to dose-response functions commonly applied in ecotoxicology. Secondly, we apply the fitted regression models with associated uncertainty to simulate 10 000 response values along the predictor gradient. Thirdly, we use the simulated values to parameterize the conditional probability tables of the BN model. The quantified AOP-BN model can be run in several directions: 1) prognostic inference, run forward from the stressor node to predict the AO level; 2) diagnostic inference, run backward from the AO node; and 3) omnidirectionally, run from the intermediate MIEs and/or KEs. Internal validation shows that the AOP-BN can obtain a high accuracy rate, when run is from intermediate nodes and when a low resolution is acceptable for the AO. Although the performance of this AOP-BN is limited by the small data set, our study demonstrates a proof-of-concept: the combined use of Bayesian regression modeling and Bayesian network modeling for quantifying AOPs. Integr Environ Assess Manag 2021;17:147-164. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Evaluation of a Bayesian Network for Strengthening the Weight of Evidence to Predict Acute Fish Toxicity from Fish Embryo Toxicity Data.

The use of fish embryo toxicity (FET) data for hazard assessments of chemicals, in place of acute fish toxicity (AFT) data, has long been the goal for many environmental scientists. The FET test was first proposed as a replacement to the standardized AFT test nearly 15 y ago, but as of now, it has still not been accepted as a standalone replacement by regulatory authorities such as the European Chemicals Agency (ECHA). However, the ECHA has indicated that FET data can be used in a weight of evidence (WoE) approach, if enough information is available to support the conclusions related to the hazard assessment. To determine how such a WoE approach could be applied in practice has been challenging. To provide a conclusive WoE for FET data, we have developed a Bayesian network (BN) to incorporate multiple lines of evidence to predict AFT. There are 4 different lines of evidence in this BN model: 1) physicochemical properties, 2) AFT data from chemicals in a similar class or category, 3) ecotoxicity data from other trophic levels of organisms (e.g., daphnids and algae), and 4) measured FET data. The BN model was constructed from data obtained from a curated database and conditional probabilities assigned for the outcomes of each line of evidence. To evaluate the model, 20 data-rich chemicals, containing a minimum of 3 AFT and FET test data points, were selected to ensure a suitable comparison could be performed. The results of the AFT predictions indicated that the BN model could accurately predict the toxicity interval for 80% of the chemicals evaluated. For the remaining chemicals (20%), either daphnids or algae were the most sensitive test species, and for those chemicals, the daphnid or algal hazard data would have driven the environmental classification. Integr Environ Assess Manag 2020;16:452-460. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

UV radiation affects antipredatory defense traits in Daphnia pulex.

In aquatic environments, prey perceive predator threats by chemical cues called kairomones, which can induce changes in their morphology, life histories, and behavior. Predator-induced defenses have allowed for prey, such as Daphnia pulex, to avert capture by common invertebrate predators, such as Chaoborus sp. larvae. However, the influence of additional stressors, such as ultraviolet radiation (UVR), on the Daphnia-Chaoborus interaction is not settled as UVR may for instance deactivate the kairomone. In laboratory experiments, we investigated the combined effect of kairomones and UVR at ecologically relevant levels on induced morphological defenses of two D. pulex clones. We found that kairomones were not deactivated by UVR exposure. Instead, UVR exposure suppressed induced morphological defense traits of D. pulex juveniles under predation threat by generally decreasing the number of neckteeth and especially by decreasing the size of the pedestal beneath the neckteeth. UVR exposure also decreased the body length, body width, and tail spine length of juveniles, likely additionally increasing the vulnerability to Chaoborus predation. Our results suggest potential detrimental effects on fitness and survival of D. pulex subject to UVR stress, with consequences on community composition and food web structure in clear and shallow water bodies.

Toxicity of microplastics and natural particles in the freshwater dipteran Chironomus riparius: Same same but different?

Microplastics (MP) are contaminants of emerging concern in aquatic ecosystems. While the number of studies is rapidly increasing, a comparison of the toxicity of MP and natural particulate matter is largely missing. In addition, research focusses on the impacts of hydrophobic chemicals sorbed to plastics. However, the interactive effects of MP and hydrophilic, dissolved chemicals remain largely unknown. Therefore, we conducted chronic toxicity studies with larvae of the freshwater dipteran Chironomus riparius exposed to unplasticised polyvinyl chloride MP (PVC-MP) as well as kaolin and diatomite as reference materials for 28 days. In addition, we investigated the effects of particles in combination with the neonicotinoid imidacloprid in a multiple-stressor experiment. High concentrations of kaolin positively affected the chironomids. In contrast, exposure to diatomite and PVC-MP reduced the emergence and mass of C. riparius. Likewise, the toxicity of imidacloprid was enhanced in the presence of PVC-MP and slightly decreased in the co-exposure with kaolin. Overall, parallel experiments and chemical analysis indicate that the toxicity of PVC-MP was not caused by leached or sorbed chemicals. Our study demonstrates that PVC-MP induce more severe effects than both natural particulate materials. However, the latter are not benign per se, as the case of diatomite highlights. Considering the high, environmentally irrelevant concentrations needed to induce adverse effects, C. riparius is insensitive to exposures to PVC-MP.

Modelling ROS formation in boreal lakes from interactions between dissolved organic matter and absorbed solar photon flux.

Concentrations of dissolved organic matter (DOM) are increasing in a large number of lakes across the Northern hemisphere. This browning serves a dual role for biota by protecting against harmful ultraviolet radiation, while also absorbing photosynthetically active radiation. The photochemical activation of DOM and subsequent formation of reactive oxygen species (ROS) is a potentially harmful side effect, but can be difficult to measure directly in situ. In this study, we combine a data set of physico-chemical properties from 71 Nordic lakes with in vitro ROS formation quantum yields to predict ROS formations across a representative boreal ecosystem gradient. For the upper centimeter of the water column, we calculate ROS formations in the range of 7.93-12.56 µmol L-1 h-1. In the first meter, they range between 1.69 and 6.69 µmol L-1 h-1 and in the remaining depth the range is 0.01-0.46 µmol L-1 h-1. These ROS formations are comparable with previously field-measured hydrogen peroxide formation rates and likely affect both phyto- and zooplankton, as well as lake chemistry. Interestingly, wavelengths of the visible spectrum (>400 nm) contribute more than half of the overall ROS formation in surface-near water layers. The association between DOM and ROS formation was found to be two-fold. While DOM promotes ROS formation in the first centimeters of the water column, the shading effect of light attenuation overpowers this with increasing depth. In the context of water browning, our results indicate the emergence of an underestimated oxidative stress environment for lake biota in the upper centimeters of the water column.

Ultrastructural Alterations in Thyrocytes of Zebrafish ( Danio rerio) after Exposure to Propylthiouracil and Perchlorate.

Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorate (PER; 0-5,000 µg/L) for 5 weeks in a modified early life-stage test. None of the treatments caused significant mortality (no observed effect concentrations for survival ≥50 mg/L [PTU] and ≥5,000 µg/L [PER]). PTU induced dose-dependent alterations in the rough endoplasmic reticulum (rER) in all exposure groups, whereas only the 2 highest PER exposure groups (500 and 5,000 µg/L) resulted in alterations of the rER. Both substances caused an increase in the numbers of lysosomes and mitochondria, with mitochondria displaying distorted cristae. Increased mitochondrial diameters were only observed in the PTU treatment. PER-exposed samples displayed an increase in apical microvilli. The highest PTU concentration (50 mg/L) showed first signs of cellular degeneration. Ultrastructural changes in zebrafish thyrocytes thus appear specific for different chemicals, most likely depending on their specific modes of action. Additional knowledge of subcellular changes in thyrocytes can help to better understand and interpret existing histological data in the future.

Baseline and oxidative DNA damage in marine invertebrates.

Anthropogenic pollutants produce oxidative stress in marine organisms, directly or following generation of reactive oxygen species (ROS), potentially resulting in increased accumulation of DNA strand breaks quantified. The aim of this study is to quantify baseline levels of DNA strand breaks in marine species from four phyla and to assess relative sensitivity to oxidative stress as well as ability to recover. DNA strand breaks were determined using a formamidopyrimidine DNA glycosylase (Fpg)-amended comet assay in circulating cells from blue mussel (Mytilus edulis), shore crab (Carcinus maenas), sea star (Asterias rubens), and vase tunicate (Ciona intestinalis). Lymphocytes from Atlantic cod (Gadus morhua) were used as a reference. In addition to immediate analysis, cells from all species were exposed ex vivo to two concentrations of hydrogen peroxide (H2O2) at 25 or 250 µM prior to assay. Mean baseline DNA strand breaks were highest for cells from sea star (34%) followed by crab (25%), mussel (22%), tunicate (17%), and cod (14%). Circulating cells from invertebrates were markedly more sensitive to oxidative stress compared to cod lymphocytes. DNA strand breaks exceeded 80% for sea star, crab, and mussel cells following exposure to the lowest H2O2 concentration. There was no recovery for cells from any species following 1 hr in buffer. This study provides an in-depth analysis of DNA integrity for ecologically important species representing 4 phyla. Data indicate that circulating cells from invertebrates are more sensitive to oxidative stress than cells from fish as evidenced by DNA strand breaks. Future studies need to address the extent to which DNA strand breaks may exert consequences for body maintenance costs in marine invertebrates.

Gradient evolution of body colouration in surface- and cave-dwelling Poecilia mexicana and the role of phenotype-assortative female mate choice.

Ecological speciation assumes reproductive isolation to be the product of ecologically based divergent selection. Beside natural selection, sexual selection via phenotype-assortative mating is thought to promote reproductive isolation. Using the neotropical fish Poecilia mexicana from a system that has been described to undergo incipient ecological speciation in adjacent, but ecologically divergent habitats characterized by the presence or absence of toxic H2S and darkness in cave habitats, we demonstrate a gradual change in male body colouration along the gradient of light/darkness, including a reduction of ornaments that are under both inter- and intrasexual selection in surface populations. In dichotomous choice tests using video-animated stimuli, we found surface females to prefer males from their own population over the cave phenotype. However, female cave fish, observed on site via infrared techniques, preferred to associate with surface males rather than size-matched cave males, likely reflecting the female preference for better-nourished (in this case: surface) males. Hence, divergent selection on body colouration indeed translates into phenotype-assortative mating in the surface ecotype, by selecting against potential migrant males. Female cave fish, by contrast, do not have a preference for the resident male phenotype, identifying natural selection against migrants imposed by the cave environment as the major driver of the observed reproductive isolation.

Effects of the anti-thyroidal compound potassium-perchlorate on the thyroid system of the zebrafish.

The increasing pollution of aquatic habitats with anthropogenic compounds has led to various test strategies to detect hazardous chemicals. However, information on effects of pollutants in the thyroid system in fish, which is essential for growth, development and parts of reproduction, is still scarce. Other vertebrate groups such as amphibians or mammals are well-studied; so the need for further knowledge especially in fish as a favored vertebrate model test organism is evident. Modified early life-stage tests were carried out with zebrafish exposed to the known thyroid inhibitor potassium perchlorate (0, 62.5, 125, 250, 500 and 5000 µg/L) to identify adverse effects on the hypothalamic-pituitary-thyroid axis. Especially higher perchlorate concentrations led to conspicuous alterations in thyroidal tissue architecture and to effects in the pituitary. In the thyroid, severe hyperplasia at concentrations ≥ 500 µg/L together with an increase in follicle number could be detected. The most sensitive endpoint was the colloid, which showed alterations at ≥ 250 µg/L. The tinctorial properties and the texture of the colloid changed dramatically. Interestingly, effects on epithelial cell height were minor. The pituitary revealed significant proliferations of TSH-producing cells resulting in alterations in the ratio of adeno- to neurohypophysis. The liver as the main site of T4 deiodination showed severe glycogen depletion at concentrations ≥ 250 µg/L. In summary, the thyroid system in zebrafish showed effects by perchlorate from concentrations ≥ 250 µg/L, thus documenting a high sensitivity of the zebrafish thyroid gland for goitrogens. In the future, such distinct alterations could lead to a better understanding and identification of potential thyroid-disrupting chemicals.

Pharmacokinetic evaluation of olopatadine for the treatment of allergic rhinitis and conjunctivitis.

INTRODUCTION: Olopatadine hydrochloride is an antihistamine and mast cell stabilizer available in three forms, including oral, intranasal and ocular preparations. Most of the practical applications focus on the use of olopatadine for the treatment of allergic rhinitis and conjunctivitis via intranasal and ocular routes. AREAS COVERED: This article was formed from a comprehensive literature search with information taken from meta-analyses, systematic reviews, treatment guidelines and clinical studies on children and adults. Articles that have been selected evaluate the use of intranasal and ocular antihistamines and their role in allergic rhinitis and conjunctivitis. EXPERT OPINION: Olopatadine is significantly more effective than placebos in alleviating the symptoms of allergic rhinitis and conjunctivitis. Olopatadine is a viable alternative and addition to the mainstay therapy of these conditions with intranasal steroids and oral antihistamines. The compliance of the patients would be improved if a once-per-day formulation of olopatadine was developed for intranasal application. The future treatments of allergic rhinitis will probably involve a combination of intranasal antihistamine and steroid because clinical trials have demonstrated an improved efficacy without a significant increase in adverse effects.

Racial and ethnic disparities in diagnosed and possible undiagnosed asthma among public-school children in Chicago.

OBJECTIVES: We examined racial and ethnic disparities in the total potential burden of asthma in low-income, racially/ethnically heterogeneous Chicago schools. METHODS: We used the Brief Pediatric Asthma Screen Plus (BPAS+) and the Spanish BPAS+, validated, caregiver-completed respiratory questionnaires, to identify asthma and possible asthma among students in 14 racially/ethnically diverse public elementary schools. RESULTS: Among 11490 children, we demonstrated a high lifetime prevalence (12.2%) as well as racial and ethnic disparities in diagnosed asthma, but no disparities in prevalences of possible undiagnosed asthma. Possible asthma cases boost the total potential burden of asthma to more than 1 in 3 non-Hispanic Black and Puerto Rican children. CONCLUSIONS: There are significant racial and ethnic disparities in diagnosed asthma among inner-city schoolchildren in Chicago. However, possible undiagnosed asthma appears to have similar prevalences across racial/ethnic groups and contributes to a high total potential asthma burden in each group studied. A better understanding of underdiagnosis is needed to address gaps in asthma care and intervention for low-income communities.

Validation of the Spanish and English versions of the asthma portion of the Brief Pediatric Asthma Screen Plus among Hispanics.

BACKGROUND: The health and health care needs of non-English-speaking Hispanic families with children are poorly understood, in part because they are often excluded from research owing to language barriers. Instruments that are valid in English and Spanish are necessary to accurately evaluate the magnitude of asthma prevalence and morbidity among Hispanics. OBJECTIVE: To establish the sensitivity and specificity of the English and Spanish versions of the asthma portion of the Brief Pediatric Asthma Screen Plus (BPAS+) in a low-income Hispanic population. METHODS: The validation sample consisted of 145 children whose parents completed the BPAS+ in Spanish and 78 whose parents completed it in English. Bilingual clinicians conducted the examinations on which the clinical assessments were based. We compared the BPAS+ results with the clinical assessment findings to determine the sensitivity and specificity of the BPAS + among Hispanics in terms of identifying children who warrant further medical evaluation for asthma. RESULTS: The sensitivity and specificity of the asthma portion of the Spanish BPAS+ were 74% and 86%, respectively. The sensitivity and specificity of the asthma portion of the English BPAS+ were 61% and 83%, respectively. CONCLUSIONS: The asthma portion of the BPAS+, a valid screen for identifying children who are in need of further evaluation for potentially undiagnosed asthma, is valid for low-income Hispanics in Spanish and English. As the Hispanic population continues to grow, it is imperative that researchers have English and Spanish instruments that are valid for this population.

Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations.

RATIONALE: Recent genetic studies have implicated integrins in asthma and atopy susceptibility. We therefore evaluated the integrin-beta3 gene (ITGB3), an integrin gene within an asthma linkage peak on chromosome 17, as a candidate for susceptibility to asthma- and atopy-related phenotypes. METHODS AND MEASUREMENTS: We genotyped and performed association tests on 19 single nucleotide polymorphisms in ITGB3 in the Hutterites, a founder population, and in three outbred replication populations. MAIN RESULTS: Variation in ITGB3 was strongly associated with susceptibility to bronchial hyperresponsiveness and protection from allergic sensitization to mold allergens in this population. Three independent case-control populations representing Caucasians and African Americans were used to replicate this finding, also revealing ITGB3 alleles that are associated with asthma susceptibility and protection from mold allergen sensitization. CONCLUSIONS: This study provides evidence that ITGB3 plays a role in the pathogenesis of asthma and sensitization to mold allergens.

Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.

Asthma affects nearly 14 million people worldwide and has been steadily increasing in frequency for the past 50 years. Although environmental factors clearly influence the onset, progression, and severity of this disease, family and twin studies indicate that genetic variation also influences susceptibility. Linkage of asthma and related phenotypes to chromosome 6p21 has been reported in seven genome screens, making it the most replicated region of the genome. However, because many genes with individually small effects are likely to contribute to risk, identification of asthma susceptibility loci has been challenging. In this study, we present evidence from four independent samples in support of HLA-G as a novel asthma and bronchial hyperresponsiveness susceptibility gene in the human leukocyte antigen region on chromosome 6p21, and we speculate that this gene might contribute to risk for other inflammatory diseases that show linkage to this region.

Development and validation of school-based asthma and allergy screening questionnaires in a 4-city study.

BACKGROUND: Asthma and allergies are commonly undiagnosed in children. Schools provide settings for potentially accessing almost all children for asthma and allergy screening. OBJECTIVE: To evaluate the feasibility and validity of using a questionnaire-based screening tool to identify undiagnosed asthma and respiratory allergies in children in kindergarten to grade 6. METHODS: A student questionnaire (SQ) and a parent questionnaire (PQ) were developed, administered in 4 diverse communities, and validated against standardized clinical assessments. Children without diagnosed asthma and representing a range of symptoms participated in a validation study that consisted of independent, standardized, clinical assessments. Sensitivity, specificity, and predictive values for questionnaire items were evaluated against expert consensus designations. RESULTS: A total of 190 children (age range, 7-13 years) completed the validation study. Affirmative responses to individual questions from either the SQ or PQ regarding asthma and allergy were modestly to moderately predictive of the clinical assessments (odds ratios, generally 2.5-5.0). When considering a positive asthma screen as affirmative responses to 3 of the best 7 SQ asthma questions, the odds ratio for asthma was 9.3 (95% confidence interval, 4.1-21.1), with 80% sensitivity and 70% specificity. Considering the allergy screen as positive based on affirmative response to either of the 2 SQ allergy questions yielded 81% sensitivity and 42% specificity. CONCLUSIONS: Either a 9-item SQ or a 10-item PQ can be used in diverse settings to screen for asthma and respiratory allergies. The SQ, obtained by directly screening students, may provide a sensitive approach for detecting children with previously undiagnosed asthma and allergies.