A Longitudinal Study of Sick Building Syndrome (SBS) among Pupils in Relation to SO2, NO2, O3 and PM10 in Schools in China

There are fewer longitudinal studies from China on symptoms as described for the sick building syndrome (SBS). Here, we performed a two-year prospective study and investigated associations between environmental parameters such as room temperature, relative air humidity (RH), carbon dioxide (CO₂), nitrogen dioxide (NO₂), sulphur dioxide (SO₂), ozone (O₃), particulate matter (PM₁₀), and health outcomes including prevalence, incidence and remission of SBS symptoms in junior high schools in Taiyuan, China. Totally 2134 pupils participated at baseline, and 1325 stayed in the same classrooms during the study period (2010–2012). The prevalence of mucosal symptoms, general symptoms and symptoms improved when away from school (school-related symptoms) was 22.7%, 20.4% and 39.2%, respectively, at baseline, and the prevalence increased during follow-up (P<0.001). At baseline, both indoor and outdoor SO₂ were found positively associated with prevalence of school-related symptoms. Indoor O₃ was shown to be positively associated with prevalence of skin symptoms. At follow-up, indoor PM₁₀ was found to be positively associated with new onset of skin, mucosal and general symptoms. CO₂ and RH were positively associated with new onset of mucosal, general and school-related symptoms. Outdoor SO₂ was positively associated with new onset of skin symptoms, while outdoor NO₂ was positively associated with new onset of skin, general and mucosal symptoms. Outdoor PM₁₀ was found to be positively associated with new onset of skin, general and mucosal symptoms as well as school-related symptoms. In conclusion, symptoms as described for SBS were commonly found in school children in Taiyuan City, China, and increased during the two-year follow-up period. Environmental pollution, including PM₁₀, SO₂ and NO₂, could increase the prevalence and incidence of SBS and decrease the remission rate. Moreover, parental asthma and allergy (heredity) and pollen or pet allergy (atopy) can be risk factors for SBS.     

Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study

Background

Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship.

Methodology/Principal Findings

30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxides (NO₂), ozone (O₃) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM₁₀, SO₂, NO₂, O₃, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM₁₀ (ORs = 1.36 per 31 µg/m³; 95% CI, 1.08–1.72), SO₂ (ORs = 1.38 per 21 µg/m³; 95%CI, 1.12–1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO₂ (ORs = 1.48 per 21 µg/m³; 95%CI, 1.21–1.80), NO₂ (ORs = 1.26 per 10 µg/m³; 95%CI, 1.01–1.56), and current asthma with O₃ (ORs = 1.55 per 23 µg/m³; 95%CI, 1.18–2.04) only among females.

Conclusion/Significance

Ambient air pollutions were more evident in males without an allergic predisposition and more associations were detected in females with allergic predisposition.     

Fungal content of air samples from some asthmatic childrens’ homes in Mexico City

Fungal particles can be considered a potential risk factor in children causing asthma, rhinitis, and allergy. However, a direct relationship between mold exposure and respiratory symptoms is difficult to establish, particularly if volumetric results are not well documented, as is often the case in Mexico. In order to assess mold exposure in some asthmatic childrens’ homes, eight asthmatic children were selected. For each child, lung function was measured by spirometry and the flow expiratory volume drop in the first second (FEV₁) as well as the CVF were estimated at 5, 10 and 15 min, after a running period on a treadmill. Exercise induced asthma (EIA) was defined as a FEV₁ drop <10% or FEV₁/CVF drop >10%. Atopy was estimated by skin testing of allergen extracts. Each room was volumetrically sampled using Burkard Personal samplers, every week for a month and with different degrees of activity. Fungal composition was mostly dominated by allergenic molds, spores smaller than 10 μm and non-seasonal molds. Concentrations ranged from 0 to 2087 CFU/m³ and 102 553–29 522 200 spores/m³, being significantly higher in indoor air, but the differences between rooms or weeks were not significant, either for CFUs (P>0.27) or for total particles (P>0.80). In general, mold counts were dominated byPenicillium spp. andCladosporium spp. especiallyP. aurantiogriseum andC. cladosporioides. We observed that the median concentration values were in general higher for children with exercise induced asthma (EIA). But the differences were significant only for EIA and degree, of asthma particularly for total (P=0.038), mycotoxin producers (P<0.009), seasonal molds (P<0.006) andPenicillium spp. (P=0.012). Total spore counts showed the highest median values in children without EIA, moderate asthma degree and no atopy. Significant differences were found for almost all spore, type groupings when comparing the presence of EIA (P<0.05) or asthma degree categories (P<0.030), but no differences were observed for atopy (P>0.21). We conclude that respiratory symptoms as described by EIA, asthma severity and atopy may give a good correlation with fungal concentrations and especially comparisons based on their physical and chemical properties.     

Early needle senescence and thinning of the crown structure of Picea abies as induced by chronic SO2 pollution. II. Field data basis, model results and tolerance limits

Field data on the sulphur and cation budget of growing Norway spruce canopies (Picea abies [L.] Karst.) are summarized. They are used to test a spruce decline model capable of quantifying effects of chronic SO₂ pollution on spruce forests. At ambient SO₂ concentrations, acute SO₂ damage is rare, but exposure to polluted air produces reversible thinning of the canopy structure with a half-time of a few years. Canopy thinning in the spruce decline model is highest (i) at elevated SO₂ pollution, (ii) in the mountains, (iii) at unfertilized sites with poor K⁺, Mg²⁺ or Zn²⁺ supply, (iv) at low spruce litter decomposition rates, and (v) acidic, shallow soils at high annual precipitation rates in the field and vice versa. Model application using field data from Würzburg (moderate SO₂ pollution, alkaline soils, no spruce decline) and from the Erzgebirge (extreme SO₂ pollution, acidic soils in the mountains, massive spruce decline) predicts canopy thinning by 2–11% in Würzburg and by 45–70% in the Erzgebirge. The model also predicts different SO₂-tolerance limits for Norway spruce depending on the site elevation and on the nutritional status of the needles. If needle loss of more than 25% (damage class 2) is taken to indicate ‘real damage’ exceeding natural variances, then for optimum soil conditions SO₂ tolerance limits range from (27.3 ± 7.4) μg m^?3 to (62.6 ± 16.5) μg m^?3. For shallow and acidic soils, SO₂ tolerance limits range from (22.0 ± 5.5) μg m^?3 to (37.4 ± 7.5) μ m^?3. These tolerance limits, which are calculated on an ecophysiological data basis for Norway spruce are close to epidemiological SO₂-toIerance limits as recommended by the IUFRO, UN-ECE and WHO. The observed statistical regression slope of the plot (damaged spruce trees vs. SO₂-pollution) in west Germany is confirmed by modelling (6% error). Model application to other forest trees allows deduction of the observed sequence of SO₂-sensitivity: Abies > Picea > Pinus > Fagus > Quercus. Thus, acute phytotoxicity of SO₂ seems not to be involved in ‘forest decline’. Chronic SO₂-pollution induces massive canopy thinning of Abies alba and Picea abies only at unfavourable sites, where natural stress factors and secondary effects of SO₂pollution act together to produce tree decline.     

Lung epithelium injury biomarkers in workers exposed to sulphur dioxide in a non-ferrous smelter

Serum Clara cell protein (CC16) and surfactant-associated protein D (SP-D) were measured in 161 workers exposed to sulphur dioxide (SO₂) in a non-ferrous smelter. Seventy workers from a blanket manufacture served as referents. Exposure to SO₂ and tobacco smoking were associated with a decrease of CC16 and an increase of SP-D in serum. Tobacco smoking and exposure SO₂ interacted synergistically to decrease serum CC16 but not to increase serum SP-D. While further illustrating the potential of serum CC16 and SP-D, our study confirms that SO₂ can cause airways damage at exposure levels below current occupational exposure limits.     

Early needle senescence and thinning of the crown structure of Picea abies as induced by chronic SO2pollution. I. Model deduction and analysis

Regarding time ranges of years, a rationale has been developed which is capable of explaining observed ‘spruce decline’ symptoms observed when spruce is exposed to air containing ambient levels of SO₂. It integrates and interrelates (i) ecophysiological data (tree morphology, assimilate partitioning, canopy turnover, senescence physiology, stomatal conductance, canopy throughfall, sulphur metabolism, tonoplast symport), (ii) pedological data (soil leaching, cation recycling, litter decomposition, forest nutrition), and (iii) meteorological data (site elevation, length of the annual trunk growth period, SO₂-pollution). Furthermore, it can explain field observations at numerous sites of spruce decline in central Europe where SO₂ is implicated as a factor of forest decline: (i) thinning of the canopy structure; (ii) early needle senescence; (iii) cation deficiency; (iv) low SO₂ tolerance at sites with depleted soils in the mountains; (v) synergism of SO₂pollution and acidic precipitation; (vi) recovery after liming, fertilization and after decreasing SO₂ pollution; and (vii) higher SO₂ tolerances of deciduous angiosperms. Different SO₂tolerance strategies are identified that are employed by more SO₂-tolerant tree species. Ecophysiological SO₂tolerance factors interact in a complex synergistic or antagonistic manner. It is concluded that chronic SO₂ pollution at ambient concentrations predisposes mainly evergreen gymnosperms to suffer under synergistic environmental stresses (frost, drought, pathogens, etc.). Thinning of the crown structure is massive at extreme sites, where several stresses act simultaneously on the trees (depleted soils, high SO₂ pollution, acidic rain, etc.). Mathematical formulations allow precise definitions of terms such as cooperativity, synergism, antagonism, vitality, predisposition, latency, etc. This universal rationale, which is applicable to all tree species, is exemplified here for Norway spruce (Picea abies [L.] Karst.). Integration of parameters yields an ordinary differential equation, which can be solved analytically. It predicts reversible dynamics of crown structures and gives an ecophysiological background to‘damage’.     

Exhaled nitric oxide and clinical phenotypes of childhood asthma

Whether exhaled NO helps to identify a specific phenotype of asthmatic patients remains debated. Our aims were to evaluate whether exhaled NO (FENO_0.05) is independently associated (1) with underlying pathophysiological characteristics of asthma such as airway tone (bronchodilator response) and airway inflammation (inhaled corticosteroid [ICS]-dependant inflammation), and (2) with clinical phenotypes of asthma.We performed multivariate (exhaled NO as dependent variable) and k-means cluster analyses in a population of 169 asthmatic children (age ± SD: 10.5 ± 2.6 years) recruited in a monocenter cohort that was characterized in a cross-sectional design using 28 parameters describing potentially different asthma domains: atopy, environment (tobacco), control, exacerbations, treatment (inhaled corticosteroid and long-acting bronchodilator agonist), and lung function (airway architecture and tone).Two subject-related characteristics (height and atopy) and two disease-related characteristics (bronchodilator response and ICS dose > 200 μg/d) explained 36% of exhaled NO variance. Nine domains were isolated using principal component analysis. Four clusters were further identified: cluster 1 (47%): boys, unexposed to tobacco, with well-controlled asthma; cluster 2 (26%): girls, unexposed to tobacco, with well-controlled asthma; cluster 3 (6%): girls or boys, unexposed to tobacco, with uncontrolled asthma associated with increased airway tone, and cluster 4 (21%): girls or boys, exposed to parental smoking, with small airway to lung size ratio and uncontrolled asthma. FENO_0.05 was not different in these four clusters.In conclusion, FENO_0.05 is independently linked to two pathophysiological characteristics of asthma (ICS-dependant inflammation and bronchomotor tone) but does not help to identify a clinically relevant phenotype of asthmatic children.     

Assessment of Modeled Indoor Air Concentrations of Particulate Matter,Gaseous Pollutants,and Volatile Organic Compounds Emitted from Candles

Candle burning is regarded as an important source of airborne pollutants in indoor environments. Indoor concentrations of aldehydes, benzo(a)pyrene, sulphur dioxide (SO₂), nitrogen oxides (NO_x), and particulate matter (PM) produced from the burning of scented candles and raw materials with different melting point/oil content (50/1, 55/9, and 65/6) were predicted using a single compartment mass balance model and compared to regulatory or guideline limits. Scented candles may be responsible for indoor acrolein concentrations that could become relevant to health only in the case of chronic exposure. Indoor concentrations of fine PM and SO₂ emitted from 65/6 wax burning under worst-case environmental and behavioral conditions were greater than their respective acute guideline limits. However, other waxes had levels of PM and SO₂ well below the recommended values. Indoor concentrations of nitrogen dioxide emitted from raw wax burning should be further investigated. The degree of pureness of raw waxes significantly affected the predicted indoor concentrations of PM and SO₂. In particular, 65/6 wax was criticized for its high content of impurities.     

Bird species richness and densities in relation to sulphur dioxide gradients and environmental variables

The expansion of coal-fired power stations in South Africa has resulted in growing environmental concerns as they are the largest emitters of sulphur dioxide (SO₂). Sulphur dioxide emissions from power plants pose a potential threat to avian populations. However, the effect of SO₂ pollution on bird communities is poorly understood. Using point counts we investigated the relationships of bird species richness and species-specific density with SO₂ concentrations around Matimba power station. Environmental parameters were derived from remotely sensed data and data reduction was performed using principal component analysis. Generalised linear mixed models were then used to infer the relationships of bird species richness and species-specific densities with SO₂ concentrations and the environmental variables. Our results revealed that SO₂-polluted air had no influence on bird species richness and densities in our study sites, but SO₂ levels were below annual national ambient air quality standards. Vegetation productivity was found to have a greater influence on species densities than SO₂ pollution. Monitoring of bird population changes around Matimba power station once neighbouring Medupi power station is fully operational is recommended, as SO₂ content of the air will increase significantly, and species may be sensitive to this increase in SO₂ levels.     

A model‐based quantitative assessment of the carbon benefits of introducing iLUC factors in the European Renewable Energy Directive

The European Commission has a mandate from the EU's Renewable Energy and Fuel Quality Directives to propose a methodology, consistent with the best available science, to address indirect land use change (iLUC). One proposed solution to the iLUC problem is the application of iLUC factors in European fuels policy – it is widely expected that should the EU adopt such iLUC factors, they would be based on iLUC modelling using the International Food Policy Research Institute's (IFPRI) MIRAGE model. Taking the iLUC factors from IFPRI MIRAGE as our central estimate, we use Monte Carlo analysis on a simple model of potential biofuel pathways for Europe to assess the likely average carbon saving from three possible European biofuel policy scenarios: no action on iLUC; raised GHG thresholds for direct emissions savings; and the introduction of iLUC factors. We find that without iLUC factors (or some other effective iLUC minimization approach) European biofuel mandates are unlikely to deliver significant GHG emissions benefits in 2020, and have a substantial probability of increasing net GHG emissions. In contrast, the implementation of iLUC factors is likely to significantly increase the carbon savings from EU biofuel policy. With iLUC factors, it is likely that most permitted pathways would conform to the Renewable Energy Directive requirement for a minimum 50% GHG reduction compared to fossil fuels.     

Prevalence,natural history,and relationship of wheezy bronchitis and asthma in children. An epidemiological study

Three randomly selected groups of 7-year-old schoolchildren in Melbourne with mild wheezy bronchitis, with moderate wheezy bronchitis, and with asthma were compared with a control group, and the patients followed up until 10 years of age. Comparison showed that if there was any significant difference between the study groups and the controls it was usually present in all these study groups. It was considered that children with wheezy bronchitis and asthma were from the same population with the same underlying basic disorder, and that there was a wide spectrum in various aspects of the natural history of the disorder.About 11% of all children aged 10 years had had some asthmatic episodes. Seventy per cent. of these children ceased having asthma before 10 years of age, while about 30% (3·7% of the whole community) continued to have episodes. There was a highly significant correlation between early age of onset, the frequency of episodes in the first year of symptoms, and the persistence of asthmatic episodes up to 10 years of age.Ten per cent. of all children with asthmatic episodes continued to have symptoms as severely at 10 years as at an earlier period. In this group the onset of symptoms was almost always before 3 years of age, there was a high frequency of episodes in the first year of symptoms, and boys and girls were affected in the ratio of 7:3.     

Sex-Based Differences in Asthma among Preschool and School-Aged Children in Korea

The purpose of this study was to explore risk factors related to asthma prevalence among preschool and school-aged children using a representative national dataset from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2009–2011. We evaluated the demographic information, health status, household environment, socioeconomic status, and parents’ health status of 3,542 children aged 4–12 years. A sex-stratified multivariate logistic regression was used to obtain adjusted prevalence odds ratios (ORs) and 95% confidence intervals after accounting for primary sample units, stratification, and sample weights. The sex-specific asthma prevalence in the 4- to 12-year-old children was 7.39% in boys and 6.27% in girls. Boys and girls with comorbid atopic dermatitis were more likely to have asthma than those without atopic dermatitis (boys: OR = 2.20, p = 0.0071; girls: OR = 2.33, p = 0.0031). Boys and girls with ≥1 asthmatic parent were more likely to have asthma than those without asthmatic parents (boys: OR = 3.90, p = 0.0006; girls: OR = 3.65, p = 0.0138). As girls got older, the prevalence of asthma decreased (OR = 0.90, p = 0.0408). Girls residing in rural areas were 60% less likely to have asthma than those residing in urban areas (p = 0.0309). Boys with ≥5 family members were more likely to have asthma than those with ≤3 family members (OR = 2.45, p = 0.0323). The factors related to asthma prevalence may differ depending on sex in preschool and school-aged children. By understanding the characteristics of sex-based differences in asthma, individualized asthma management plans may be established clinically.     

Biological pollution and its relationship with respiratory symptoms indicative of asthma, Bucaramanga, Colombia

Introduction. Indoorair pollution may play an important role in development and exacerbation of asthma in children. Objective. The association between the presence of indoor biological contaminants and respiratory symptoms related to asthma was assessed in preschool children. Materials and methods. This cross-sectional study was undertaken in Bucaramanga, Colombia, and included children <7 years of age living in two urban areas of with different levels of outdoor air pollution. The 678 children were an average of 3.5 years of age. Respiratory symptoms indicative of asthma and indoor air pollutants were assessed by previously validated questionnaires.. Biological samples potentially containing mites and fungi were collected by standardized laboratory methods. The log binomial regression model was used for multivariate analysis, using adjusted prevalence ratios (PR). Results. The prevalence of asthmatic respiratory symptoms was 8.0%; (95% C.I: 5.6-9.6), without significant differences between the two areas. Binomial model analysis showed that asthma symptoms were associated with mites (PR 1.78; 95% C.I. 1.0-3.0), Acremonium sp (PR 6.24; 95 C.I.: 3.8-10.0) and a history of child pneumonia (PR 4.0; 95% C.I. 2.5-6.4), allergic rhinitis (PR 1.9; 95% C.I.: 1.2-3.1), prematurity (PR 3.4; 95% C.I. 1.8-6.5), parents with asthma (PR 2.6; 95% C.I. 1.4-5.0) and pet ownership (PR 0.4; 95% C.I. 0.2-0.9). Conclusions. The indoor exposure to biological contaminants (dust mites and fungi), history of prematurity, pneumonia, rhinitis and family history of asthma increased the occurence of symptoms suggestive of asthma in young children.     

Differences in candidate gene association between European ancestry and African American asthmatic children

Background

Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.

Methodology/Principal Findings

Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.

Conclusions/Significance

We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry.     

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation

Hyaluronan (HA) is a large (>1500 kDa) polysaccharide of the extracellular matrix that has been linked to severity and inflammation in asthma. During inflammation, HA becomes covalently modified with heavy chains (HC-HA) from inter-α-inhibitor (IαI), which functions to increase its avidity for leukocytes. Our murine model of allergic pulmonary inflammation suggested that HC-HA may contribute to inflammation, adversely effecting lower airway remodeling and asthma severity. Our objective was to characterize the levels of HA and HC-HA in asthmatic subjects and to correlate these levels with asthma severity. We determined the levels and distribution of HA and HC-HA (i) from asthmatic and control lung tissue, (ii) in bronchoalveolar lavage fluid obtained from non-severe and severe asthmatics and controls, and (iii) in serum and urine from atopic asthmatics after an experimental asthma exacerbation. HC-HA distribution was observed (i) in the thickened basement membrane of asthmatic lower airways, (ii) around smooth muscle cells of the asthmatic submucosa, and (iii) around reserve cells of the asthmatic epithelium. Patients with severe asthma had increased HA levels in bronchoalveolar lavage fluid that correlated with pulmonary function and nitric oxide levels, whereas HC-HA was only observed in a patient with non-severe asthma. After an experimental asthma exacerbation, serum HA was increased within 4 h after challenge and remained elevated through 5 days after challenge. Urine HA and HC-HA were not significantly different. These data implicate HA and HC-HA in the pathogenesis of asthma severity that may occur in part due to repetitive asthma exacerbations over the course of the disease.     

Assessing the Effects of Climate Change on Waterborne Microorganisms: Implications for EU and U.S. Water Policy

Despite advances in water treatment, outbreaks of waterborne diseases still occur in developed regions including the United States and Europe Union (EU). Water quality impairments attributable to elevated concentrations of fecal indicator bacteria, and associated with health risk, are also very common. Research suggests that the impact of such microorganisms on public health may be intensified by the effects of climate change. At present, the major regulatory frameworks in these regions (i.e., the US Clean Water Act [CWA] and the EU Water Framework Directive [WFD]), do not explicitly address risks posed by climate change. This article reviews existing U.S. and EU water quality regulatory legislation for robustness to climate change and suggests watershed modeling approaches to inform additional pollution control measures given the likely impacts on microbial fate and transport. Comprehensive analysis of future climate and water quality scenarios may only be achievable through the use of watershed-scale models. Unless adaptation measures are generated and incorporated into water policy, the potential threat posed to humans from exposure to waterborne pathogens may be amplified. Such adaptation measures will assist in achieving the aims of the EU WFD and US CWA and minimize impacts of climate change on microbial water quality.     

Endotoxin as a determinant of asthma and wheeze among rural dwelling children and adolescents: A case--control study

ABSTRACT: BACKGROUND: The association between endotoxin exposure and asthma is complex and has been associated with rural living. We examined the relationship between domestic endotoxin and asthma or wheeze among rural school-aged children (6--18 years) and assessed the interaction between endotoxin and other characteristics with these outcomes. METHODS: Between 2005 and 2007 we conducted a case--control study of children 6--18 years in the rural region of Humboldt, Canada. Cases (n = 102) reported doctor-diagnosed asthma or wheeze in the past year. Controls (n = 208) were randomly selected from children without asthma or wheeze. Data were collected to ascertain symptoms, asthma history and indoor environmental exposures (questionnaire), endotoxin (dust collection from the play area floor and child's mattress), and tobacco smoke exposure (saliva collection). Statistical testing was completed using multiple logistic regression to account for potential confounders and to assess interaction between risk factors. A stratified analysis was also completed to examine the effect of personal history of allergy. RESULTS: Among children aged 6--12 years, mattress endotoxin concentration (EU/mg) and load (EU/m2) were inversely associated with being a case [odds ratio (OR) = 0.44, 95 % confidence interval (CI) = 0.20-0.98; and OR = 0.38, 95 % CI = 0.20-0.75, respectively]. These associations were not observed in older children or with play area endotoxin. CONCLUSIONS: Our results suggest that endotoxin exposure might be protective for asthma or wheeze. The protective effect is found in younger school-aged, non-allergic children. These results may help explain the inconsistencies in previous studies and suggest that the protective effects of endotoxin in the prevention of atopy and asthma or wheeze are most effective earlier in life.     

Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma

β₂-adrenergic receptor (β₂AR) agonists (β₂-agonist) are the most commonly used therapy for acute relief in asthma, but chronic use of these bronchodilators paradoxically exacerbates airway hyper-responsiveness. Activation of βARs by β-agonist leads to desensitization (inactivation) by phosphorylation through G-protein coupled receptor kinases (GRKs) which mediate β-arrestin binding and βAR internalization. Resensitization occurs by dephosphorylation of the endosomal βARs which recycle back to the plasma membrane as agonist-ready receptors. To determine whether the loss in β-agonist response in asthma is due to altered βAR desensitization and/or resensitization, we used primary human airway smooth muscle cells (HASMCs) isolated from the lungs of non-asthmatic and fatal-asthmatic subjects. Asthmatic HASMCs have diminished adenylyl cyclase activity and cAMP response to β-agonist as compared to non-asthmatic HASMCs. Confocal microscopy showed significant accumulation of phosphorylated β₂ARs in asthmatic HASMCs. Systematic analysis of desensitization components including GRKs and β-arrestin showed no appreciable differences between asthmatic and non-asthmatic HASMCs. However, asthmatic HASMC showed significant increase in PI3Kγ activity and was associated with reduction in PP2A activity. Since reduction in PP2A activity could alter receptor resensitization, endosomal fractions were isolated to assess the agonist ready β₂ARs as a measure of resensitization. Despite significant accumulation of β₂ARs in the endosomes of asthmatic HASMCs, endosomal β₂ARs cannot robustly activate adenylyl cyclase. Furthermore, endosomes from asthmatic HASMCs are associated with significant increase in PI3Kγ and reduced PP2A activity that inhibits β₂AR resensitization. Our study shows that resensitization, a process considered to be a homeostasis maintaining passive process is inhibited in asthmatic HASMCs contributing to β₂AR dysfunction which may underlie asthma pathophysiology and loss in asthma control.     

5岁以下哮喘患儿血清过敏原病例对照研究及相关性分析

摘要 目的：探讨5岁以下哮喘儿童与血清特异性过敏原（specific IgE,sIgE）的分布情况。方法：本研究采用免疫印迹法对 2019 年1月至 2019 年12月在西安交通大学第二附属医院住院的5岁以下62例哮喘患儿和49例喘息患儿的行血清特异性过敏原检测,对比分析5岁以下哮喘和喘息儿童过敏原分布情况及与哮喘的发病关系。结果：户尘螨、猫毛皮屑、狗毛皮屑、蒿草、葎草、桤杨柳山毛榉橡胡桃、烟曲霉、念珠菌点青霉分枝孢霉交链孢霉黑曲霉吸入过敏原和花生黄豆、腰果开心果榛子杏仁核桃、虾蟹、桃苹果芒果荔枝草莓食物过敏原这12类过敏原在哮喘组与喘息组有显著差异（P<0.05）,与哮喘发病有关。多因素logistic回归分析结果显示户尘螨、猫毛皮屑、坚果类、霉菌、水果类是哮喘发病的危险因素（P<0.05）。户尘螨、猫毛皮屑和虾蟹是男性哮喘患儿发病的危险因素,念珠菌点青霉分枝孢霉交链孢霉黑曲霉是女性哮喘患儿发病的危险因素（P<0.05）。结论：血清特异性（sIgE）过敏原在哮喘与喘息患儿中分布不同,同时发现过敏原在哮喘患儿中存在性别差异,故对哮喘患儿进行过敏性检测可以作为回避过敏原的依据。