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Objective. To determine the relation between the moderating fee and the frequency of consultations to emergency services in patients with asthma who belong to the contributory insurance regime in Colombia. Methods. A retrospective cohort - analytical observational study was conducted which included contributors over the age of 18 with a diagnosis of asthma, users of the contributory regime who were registered in the database for calculating the Capitation Unit between the years 2012 and 2014; the patients were recruited during 2013 and the cohort was followed for one year from the admission date; the consultation frequency at the emergency service was used as the outcome variable, the influence of the principal confounding variables was evaluated, and a model of negative binomial regression for data analysis was applied. Results. 54 516 asthmatic patients with their comorbidities were included, of which 13.69% consulted emergency services. After controlling by the Charlson index and age of emergency consultation, the risk of consulting emergency services is 1.1 times more frequent in level 3 of the moderating fee with respect to level 1. Conclusions. It is suggested that moderating fee could behave as an access barrier to health services in asthmatic patients. It is recommended that studies to evaluate this hypothesis more precisely be carried out. [ABSTRACT FROM AUTHOR]

Background: Asthma exacerbations in children often require medications, urgent care, and hospitalization. Multiple environmental triggers have been associated with asthma exacerbations, including particulate matter 2.5 (PM2.5) and ozone, which are primarily generated by motor vehicle exhaust. There is mixed evidence as to whether proximity to highways increases risk of asthma exacerbations.Methods: To evaluate the impact of highway proximity, we assessed the association between asthma exacerbations and the distance of child's primary residence to two types of roadways in Durham County, North Carolina, accounting for other patient-level factors. We abstracted data from the Duke University Health System electronic health record (EHR), identifying 6208 children with asthma between 2014 and 2019. We geocoded each child's distance to roadways (both 35 MPH+ and 55 MPH+). We classified asthma exacerbation severity into four tiers and fitted a recurrent event survival model to account for multiple exacerbations.Results: There was a no observed effect of residential distance from 55+ MPH highway (Hazard Ratio: 0.98 (95% confidence interval: 0.94, 1.01)) and distance to 35+ MPH roadway (Hazard Ratio: 0.98 (95% confidence interval: 0.83, 1.15)) and any asthma exacerbation. Even those children living closest to highways (less 0.25 miles) had no increased risk of exacerbation. These results were consistent across different demographic strata.Conclusions: While the results were non-significant, the characteristics of the study sample - namely farther distance to roadways and generally good ambient environmental pollution may contribute to the lack of effect. Compared to previous studies, which often relied on self-reported measures, we were able to obtain a more objective assessment of outcomes. Overall, this work highlights the opportunity to use EHR data to study environmental impacts on disease. [ABSTRACT FROM AUTHOR]

Abstract Objectives Asthma can be triggered by various factors due to different etiologies. Environmental factors remain a common trigger of asthma, especially amongst children, and such ambient exposures can be harder to avoid compared to behavioral triggers. As such, the contribution of environmental factors may be enhanced when considering repeat asthma cases compared to initial presentations. To test this hypothesis, we assessed associations between ambient temperature and hospital admissions for asthma in Hong Kong and stratified admission records into first and repeat asthma hospitalizations. Methods The daily number of asthma hospitalizations among children aged 0–5 years in Hong Kong during 2007–2011 was regressed on daily mean temperature using distributed lagged nonlinear models, with adjustment for seasonal patterns, day-of-week effects, and other meteorological factors and air-pollutants. Analyses were stratified by summer/winter and by type of admission (first admission and repeated admission). Results About 33% of the 12284 asthma hospitalizations were repeat admissions. Repeat admissions demonstrated higher sensitivity to high temperature in the summer. During this period, high temperatures were associated with increased risk of repeat admission but not with first admissions: RR (95% CI) comparing 31 °C vs. 29 °C across lags 0–15 days was 3.40 (1.26, 9.18) and 0.74 (0.31, 1.77) for repeat and first admissions respectively. In the cold season, all admissions increased with falls in temperature, with slightly stronger associations apparent for repeat admissions compared to first admission: 1.20 (1.00, 1.44) vs. 1.10 (0.96, 1.26) respectively comparing risk at 15 °C vs. 12 °C across lags 0–5 days. Conclusions To our knowledge, this is the first study to show stronger associations between ambient temperature and repeat asthma admissions compared to first admissions. The higher sensitivity among those experiencing repeat admissions may allow for more personalized disease management. Given the substantial differences in associations by admission type, future studies of ambient exposures on asthma should consider analyzing the two groups separately. Highlights • About 33% of childhood asthma admissions among the study population were repeat admission cases. • Repeat admissions cases were found significantly more sensitive to high temperature than first admissions. • This study suggested combining first- and repeat- asthma cases in temperature-asthma study may bias the association, in particular under high temperature. [ABSTRACT FROM AUTHOR]

Objectives: While asthma presents various clinical forms with different levels of severity, it is unclear whether asthma severities are a consequence of disease management or varied etiologies. We sought to investigate this question. Methods: This paper presents a cross-sectional study of 113,671 Israeli adolescents. Prevalence rates of mild and moderate-to-severe asthma over a 24-year period were calculated and multivariate regression models (outcomes: different asthma severity, reference: subjects without asthma) were performed to analyze associations with anthropometric indices and socio-demographic variables, in males and females separately. Results: The prevalence of mild asthma increased until birth years 1976-1980 and then steadily decreased. In contrast, the prevalence of moderate-to-severe asthma was relatively stable until birth years 1976-1980, then rose steeply until 1986-1990 and subsequently plateaued in the early 1990s. Obesity was positively associated with both mild and moderate-to-severe asthma in males (Odds Ratio (OR) [95%CIs]: 1.61 [1.37-1.89] and 1.63 [1.34-1.98], respectively) and females (1.54 [1.10-2.16] and 1.54 [1.20-1.98], respectively). Family size greater than three siblings was negatively associated with both mild and moderate-to-severe asthma in males (0.62 [0.56-0.68] and 0.59 [0.52-0.68]) and females (0.71 [0.60-0.83] and 0.73 [0.63-0.83]). In contrast, in males, underweight was only associated with mild asthma (1.54 [1.22-1.94]) but not with moderate-to-severe asthma. In females, overweight was only associated with moderate-to-severe asthma (1.21 [1.00-1.46]) and rural residence was only associated with mild asthma (1.26 [1.09-1.47]). Conclusions: The differences between mild and moderate-to-severe asthma enhance asthma phenotype characterization, with respect to secular trends and associated variables, and indicate varied etiologies. [ABSTRACT FROM AUTHOR]

Objective: To identify challenges that disadvantaged adults with asthma face in mitigating social and environmental factors associated with poor symptom control. Methods: Using a community-engaged approach, we partnered with a community health center in New Haven, CT to conduct in-person interviews and a written survey of asthmatic adults with poor symptom control. Using the constant comparative method, we analyzed participant interviews to establish emerging themes and identify common barriers to improved outcomes. Through a written survey utilizing clinically validated questions, we assessed information on access to medical care, asthma control, and selected social and environmental risk factors. Results: Twenty-one patients (mean age 47, 62% female, 71% Black, 95% insured by Medicaid) participated. The average Asthma Control Test (ACT) score was 11.6. Seventy-six percent of participants were currently employed and of those, 75% reported work-related symptoms. Among participants currently in housing, 59% reported exposure to domiciliary mice and 47% to mold. We identified three themes that summarize the challenges the study participants face: 1) Lack of knowledge about home and workplace asthma triggers; 2) Lack of awareness of legal rights or resources available to mitigate adverse conditions in the home or work environment; and 3) Fear of retaliation from landlords or employers, including threats of eviction, sexual assault, and job loss. Conclusion: Patients with poorly controlled asthma in a disadvantaged urban northeast community identified common barriers in both the domestic and work environments that impeded attainment of symptom control. These challenges may be best addressed through legal advocacy for those most at risk. [ABSTRACT FROM AUTHOR]

Abstract Allergic asthma is a chronic inflammatory disease of the airways. T lymphocytes play an important role in the pathogenesis of asthma. The voltage-gated Kv1.3 potassium channel is a target for the preferential inhibition of T EM cells. In this study, we investigate the effects of PAP-1, a selective inhibitor of Kv1.3 channel, on the treatment of the neutrophilic asthma model. PAP-1 (40 mg/kg) was injected intraperitoneally into ovalbumin (OVA)-lipopolysaccharide (LPS)-challenged BALB/c mice. We found that the expression of the Kv1.3 channel in the lung tissues, and the intensity of the Kv current in the asthmatic mice increased clearly compared with those in normal control. PAP-1 significantly reduced airway hyperresponsiveness (AHR), inflammatory cell count in the bronchoalveolar lavage fluids (BALF) and serum, and attenuated airway inflammation in a histological examination of the asthmatic mice. Moreover, PAP-1 inhibited the OVA-LPS-induced imbalance of Th1/Th2, Treg/Th17 lymphocytes, and reduced levels of IL-4 and IL-17, inducing an increase in the production of IFN-γ and IL-10. Furthermore, the activation of the extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) pathway in the lungs of the asthmatic mice was suppressed by PAP-1. We also found that PD-98059, an inhibitor of ERK, had a similar effect with PAP-1 in terms of regulating the imbalance of Th1/Th2, Treg/Th17 cytokines. However, PD-98059 could not further influence cytokine changes when the cells were treated with PAP-1. The results suggest that ERK acts as a downstream regulator of inhibitors of the Kv1.3 channel in neutrophilic asthma. In conclusion, the inhibitor of the Kv1.3 channel has therapeutic potential for treating asthma. Highlights • Expression and activities of Kv1.3 channel in lung tissue in asthmatic mice • PAP-1 significantly reduced the airway hyperresponsiveness and airway, inflammation in asthmatic mice. • PAP-1 inhibited OVA-LPS induced imbalance of Th1/Th2,Treg/Th17 lymphocytes. • The mechanism may relate to the inhibiting the ERK-NF-κB signaling pathway [ABSTRACT FROM AUTHOR]

Abstract Background Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways. Objectives The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and health outcomes (“meeting-in-the-middle”), thus shedding light on mechanisms and reinforcing causality. Methods We applied a statistical approach named ‘meet-in-the-middle’ to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases (CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways. Results A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26, 2.55] per increase by 5000 particles/cm3). Further, we have identified several metabolic pathways that potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD. Conclusions Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD. Highlights • Strong association of long-term ultrafine particle exposure with adult-onset asthma • Linoleate metabolism and carnitine shuttle as “meeting-in-the-middle” pathways. • Metabolic pathways mediate the air pollution effects on health outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the essential factors to be considered before the development of asthma treatment plan which include ensuring proper diagnosis of severe asthma, considering phenotypes and endotypes, and understanding advantages and disadvantages of available therapies. The clinical trial evidence for add-on asthma treatment options including pharmacologic therapies, omalizumab and reslizumab is explored. The associated biomarkers of asthma are also tackled.

The article discusses the need to consider age-related factors in the diagnosis and management of asthma as etiology, presentation, and progression of the disease may vary across age groups. It notes a presumptive diagnosis of asthma that can be made based on patient history, risk factors, and clinical examination. The development of nonpharmacologic and pharmacologic treatments as the cornerstones of long-term treatment that should be a part of each patient's action plan is tackled.

The article discusses the evolution of concepts in the asthma management landscape in the U.S. being considered as a common condition that imposes substantial patient, health care system, and socioeconomic burdens. Topics include the understanding of asthma etiology, the progress in the diagnosis of asthma, and the management of asthma in primary care. The role of primary care providers (PCPs) in teaching patients for effective self-management is also tackled.

Environmental factors underlie more than one-fifth of deaths and disability worldwide. Globally, both indoor and outdoor particulate matter pollution are leading risk factors for reduced quality of life and death. Nurses are in a key position to assess particulate matter exposure and to intervene, providing population, community, family, and individual risk reduction and care. This article presents a case study describing one patient's experiences with asthma and multiple comorbidities, an overview of particulate matter exposure and health, and management strategies for practice. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin (IL)‐17 is a major contributor to the pathogenesis of allergic asthma. Developmental endothelial locus‐1 (Del‐1) is an endothelial cell‐secreted protein known to inhibit IL‐17 expression. However, little is known about the association between Del‐1 and IL‐17 in the pathogenesis of allergic asthma. Using bronchoalveolar lavage fluid (BALF) and peripheral blood samples collected from allergic asthmatic patients and controls, we explored the role of Del‐1 in relation to IL‐17 in allergic asthma. We found that the negative correlation between Del‐1 and IL‐17 was significant in BALF of allergic asthmatics. Del‐1 treatment inhibited the expression of IL‐17, the differentiation of IL‐17‐secreting leukocytes and associated cytokines. Contrarily, IL‐17 levels were increased after treatment with anti‐Del‐1 mAb. Consistent with this, Del‐1 treatment led to downregulation of IL‐5, CCL5 and IL‐4, thus reducing secretion of eosinophil cationic protein. Furthermore, Del‐1 significantly downregulated the expression of ICAM‐1 and may have the potential to reduce leukocyte transendothelial migration. Our data demonstrate that Del‐1 can negatively regulate IL‐17 and its proinflammatory function, thereby limiting airway inflammation in allergic asthmatics, and suggest Del‐1 as a potential candidate for prevention and treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Abstract: Background: Treatment non‐adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. Objectives: To evaluate treatment adherence and causes of non‐adherence in a large asthma Chinese population. To analyze newly‐diagnosed patients' adherence first time. Methods: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow‐up phone calls were carried out for recording subjects' treatment adherence based on their self‐reports. Subjects who reported non‐adherence were additionally asked to choose the primary non‐adherence cause from a list of nine potential causes. Results: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly‐diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly‐diagnosed patients were three times more likely to become non‐adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30‐39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non‐adherence was “relief of symptoms after short‐term controller medication use” (43.8%). Conclusions: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs – Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) – were measured at three timepoints (maternal serum in pregnancy week 34–36 and child serum at ages 5 and 13 years) and their association with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR-unvaccinated children, higher levels of the five PFASs at age 5 years were associated with increased odds of asthma at ages 5 and 13. The associations were reversed among MMR-vaccinated children. Prenatal PFAS exposure was not associated with childhood asthma or allergic diseases regardless of MMR vaccination status. In conclusion, PFAS exposure at age 5 was associated with increased risk of asthma among a small subgroup of MMR-unvaccinated children but not among MMR-vaccinated children. While PFAS exposure may impact immune system functions, this study suggests that MMR vaccination might be a potential effect-modifier. [ABSTRACT FROM AUTHOR]

Cytomegalovirus ( CMV) IgG antibodies have been associated with inflammaging and immunosenescence. We aimed to assess the presence of CMV DNA in the blood of adult and elderly patients with bronchial asthma to establish potential association of CMV DNAemia with asthma and asthma characteristics. Eighty-five elderly asthmatics, 74 younger asthma patients, and 114 age-matched controls were recruited. The CMV DNA was detected using commercial artus assay in 10.7% of asthma patients, but was negative in all control individuals. The secondary assay identified CMV DNA in 41.5% of asthmatics and 13.3% of control subjects ( P < .001). Presence of CMV DNA was associated with an increased risk of asthma and CMV DNA copy numbers correlated with some asthma traits, including respiratory parameters and exhaled breath nitric oxide. We conclude that CMV infection is associated with asthma and may contribute to the pathogenesis of asthmatic inflammation. [ABSTRACT FROM AUTHOR]

There is a lack of reports focusing on the course of atopic dermatitis (AD) with respect to its evolution and association with other allergic diseases and parameters. This study gives the review of results concerning the evaluation of different parameters in patients suffering from AD older than 14 years of age. This study evaluates the occurrence of food allergy, food intolerance, inhalant allergy, occurrence of asthma bronchiale, allergic rhinitis, peripheral blood eosinophilia, family history of atopy, onset of AD and the severity of AD according to the SCORAD index. [ABSTRACT FROM AUTHOR]

Background: Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis. Methods: Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx. 1000 participants. We used Mendelian randomization (MR), a method of causal inference that uses genetic variants as instrumental variables, to infer the direction of association between DNA methylation and asthma. Results: We identified 302 CpGs associated with current asthma status (FDR-adjusted P value < 0.05) and 445 with current wheeze status at 7.5 years, with substantial overlap between the two. Genes annotated to the 302 associated CpGs were enriched for pathways related to movement of cellular/subcellular components, locomotion, interleukin-4 production and eosinophil migration. All associations attenuated when adjusted for eosinophil and neutrophil cell count estimates. At 16.5 years, two sites were associated with current asthma after adjustment for cell counts. The CpGs mapped to the AP2A2 and IL5RA genes, with a - 2.32 [95% CI - 1.47, - 3.18] and - 2.49 [95% CI - 1.56, - 3.43] difference in percentage methylation in asthma cases respectively. Two-sample bi-directional MR indicated a causal effect of asthma on DNA methylation at several CpG sites at 7. 5 years. However, associations did not persist after adjustment for multiple testing. There was no evidence of a causal effect of asthma on DNA methylation at either of the two CpG sites at 16.5 years. Conclusion: The majority of observed associations are driven by higher eosinophil cell counts in asthma cases, acting as an intermediate phenotype, with important implications for future studies of DNA methylation in atopic diseases. [ABSTRACT FROM AUTHOR]

Cockroach allergens can lead to serious allergy and asthma symptoms. Termites are evolutionarily related to cockroaches, cohabitate in human dwellings, and represent an increasing pest problem in the United States. The Formosan subterranean termite (Coptotermes formosanus) is one of the most common species in the southern United States. Several assays were used to determine if C. formosanus termite proteins cross-react with cockroach allergens. Expressed sequence tag and genomic sequencing results were searched for homology to cockroach allergens using BLAST 2.2.21 software. Whole termite extracts were analyzed by mass-spectrometry, immunoassay with IgG and scFv antibodies to cockroach allergens, and human IgE from serum samples of cockroach allergic patients. Expressed sequence tag and genomic sequencing results indicate greater than 60% similarity between predicted termite proteins and German and American cockroach allergens, including Bla g 2/Per a 2, Bla g 3/Per a 3, Bla g 5, Bla g 6/Per a 6, Bla g 7/Per a 7, Bla g 8, Per a 9, and Per a 10. Peptides from whole termite extract were matched to those of the tropomyosin (Bla g 7), arginine kinase (Per a 9), and myosin (Bla g 8) cockroach allergens by mass-spectrometry. Immunoblot and ELISA testing revealed cross-reaction between several proteins with IgG and IgE antibodies to cockroach allergens. Several termite proteins, including the hemocyanin and tropomyosin orthologs of Blag 3 and Bla g 7, were shown to crossreact with cockroach allergens. This work presents support for the hypothesis that termite proteins may act as allergens and the findings could be applied to future allergen characterization, epitope analysis, and clinical studies. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous disease characterized by numerous phenotypes relating to age of onset, triggers, comorbidities, severity (assessed by multiple exacerbations, lung function pattern) and finally the inflammatory cells involved in the pathophysiologic pathway. These phenotypes can vary over time in relation to changes in the principal triggers involved in the aetiology of the disease. Nevertheless, in a patient with multiple allergies and early-onset disease (defined as multiple sensitizations and allergic comorbidities), the prognosis of asthma is poor with a high risk of persistence and severity of the disease during childhood. Future research will focus on classifying phenotypes into groups based on pathophysiologic mechanisms (endotypes) and the biomarkers attached to these endotypes, which could predict prognosis and lead to targeted therapy. Currently, these biomarkers are related to inflammatory cells associated with the asthma endotype, essentially eosinophils and neutrophils (and related cytokines) attached to Th-2 and non Th-1 pathways, respectively. The most severe asthma (refractory asthma) is linked to neutrophil-derived inflammation (frequently associated with female sex, obesity and possibly disorganized airway microbiota) encountered in very young children or teenagers. Severe asthma is also linked to or a marked eosinophil inflammatory process (frequently associated with multiple atopy and, more rarely, with non-atopic hypereosinophilic asthma in children) and frequently encountered in teenagers. Severe phenotypes of asthma could also play a role in the origin of chronic obstructive pulmonary disease in adult life. [ABSTRACT FROM AUTHOR]

Increased ambient concentration of particulate matters are considered as one of major causes for increased prevalence or exacerbation of asthma or asthma like symptoms. Recently, possible temporal variation in risks of PM on mortality has been suggested. We investigated short-term effect of both PM 10 and PM 2.5 on asthma hospitalization, and assessed temporal variation of PM risks in Seoul, Korea, 2003–2011. Generalized additive model was used to estimate PM risks on asthma hospitalization with consideration by long-term trend, influenza epidemic, day of week, meteorological factors. To assess temporal variation of PM risks, year-round PM risks were estimated. Stratified analysis by season and age-group were also conducted. Estimated RRs of PM on asthma hospitalization by an increase of 10㎍/㎥were 1.0084 (95% CI: 1.0041–1.0127) and 1.0156 (95% CI: 1.0055–1.0259) respectively with 7-days lag periods (lag06). PM 2.5 had stronger effect than PM 10 for all age group. Elderly group was most affected by PM. For the analysis of temporal variation of PM risks, we found increasing trend in total population and the elderly group. In the season-specific analysis, we also found increasing trend in winter for PM 10 , and in spring for PM 2.5 . PM 10 and PM 2.5 has adverse effect on asthma hospitalization with evidence suggesting temporal variation in PM risks. Further research will be needed to confirm the temporal variation of PM risk on asthma hospitalization, and to identify casual factors affecting this temporal variation. This study results could be evidentiary materials for establishing valid public health policies to reduce health burden or economic burden of asthma. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation induced by OVA was reduced after mKG treatment. A total of twenty-four metabolites involved in seven metabolic pathways were identified as potential biomarkers in the development of allergic asthma. Among them, myristic acid (L3 or P2), sphinganine (L6 or P4), and lysoPC(15:0) (L12 or P16) were detected both in lung tissue and plasma. Additionally, L-acetylcarnitine (L1), thromboxane B2 (L2), 10-HDoHE (L10), and 5-HETE (L11) were first reported to be potential biomarkers associated with allergic asthma. The treatment of mKG mediated all of those potential biomarkers except lysoPC(15:0) (P16). The anti-asthma mechanism of mKG can be achieved through the comprehensive regulation of multiple perturbed biomarkers and metabolic pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: The biological mechanisms by which cleaning products and disinfectants -- an emerging risk factor -- affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G ×E) may help identify new genes related to adult-onset asthma. OBJECTIVES: We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma. METHODS: Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway -- based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G χ E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons. RESULTS: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking. CONCLUSIONS: Using a pathway-based selection process, we identified novel genes potentially involved in adult asthma by interaction with occupational exposure. These genes play a role in the NF-KB pathway, which is involved in inflammation. CITATION: Rava M, Ahmed I, Kogevinas M, Le Moual N, Bouzigon E, Curjuric I, Dizier MH, Dumas O, Gonzalez JR, Imboden M, Mehta AJ, Tubert-Bitter P, Zock JP, Jarvis D, Probst-Hensch NM, Demenais F, Nadif R. 2017. Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three European studies. Environ Health Perspect 125:207-214; http://dx.doi.org/10.1289/EHP376 [ABSTRACT FROM AUTHOR]

It is well known that sensitization against fungi is closely associated with severity of asthma. Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component b-glucan, as well as some component(s) in house dust mite (HDM) extract. However, the roles of Dectin-1 in HDM-induced allergic airway inflammation remain unclear. In this study, we used Dectin-1-deficient (Clec7a-/-) mice to examine whether Dectin-1 is involved in HDM-induced allergic airway inflammation. We found that HDM-induced eosinophil and neutrophil recruitment into the airways was significantly attenuated in Clec7a-/- mice compared with that in wild-type mice. In addition, HDM-induced IL-5, IL-13, and IL-17 production from mediastinum lymph node cells was reduced in HDM-sensitized Clec7a-/- mice. Dectin-1 was expressed on CD11b+ dendritic cells (DCs), an essential DC subset for the development of allergic inflammation, but not on CD103+ DCs, plasmacytoid DCs, or lung epithelial cells. Transcriptome analysis revealed that the expression of chemokine/chemokine receptors, including CCR7, which is indispensable for DC migration to draining lymph nodes, was decreased in Clec7a-/- DCs. In accordance with these results, the number of HDM-labeled CD11b+ DCs in mediastinum lymph nodes was significantly reduced in Clec7a-/- mice compared with wild-type mice. Taken together, these results suggest that Dectin-1 expressed on CD11b+ DCs senses some molecule(s) in HDM extract and plays a critical role in the induction of HDM-induced allergic airway inflammation by inducing the expression of chemokine/chemokine receptors in DCs. [ABSTRACT FROM AUTHOR]

Background We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). Methods 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. Results E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV 1 /FVC ratio during the ICS treatment ( r = −0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV 1 /FVC and V 50,%pred ( p < 0.001), and significantly higher FeNO and sputum eosinophil percentages ( p = 0.008 and p < 0.001, respectively). Conclusions The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients. [ABSTRACT FROM AUTHOR]

Objective We investigate the association between adult asthma and wealth, testing whether the disease impairs wealth accumulation (social selection model) or if wealth protects against asthma (social causation model). Methods We use the National Longitudinal Survey of Youth ( n = 7,644) and linear and logistic regressions to estimate the association between wealth and asthma. Changes in relative wealth following an asthma diagnosis and asthma status by increases in wealth through inheritance provide evidence on the causal direction. Results Asthma, particularly severe asthma, is associated with lower wealth. Wealth ranking does not change after a diagnosis of asthma, but inheriting a substantial sum is associated with a lower risk of severe asthma. Conclusion Wealth appears to protect against severe asthma, supporting the social causation model of disease. [ABSTRACT FROM AUTHOR]

Background: Asthma, involving 5-10% of global population, has a heterogeneous distribution in the community regardless of age and its prevalence and incidence tend to grow worldwide as reported by many recent epidemiologic surveys. Materials and Methods: The present study aimed to survey the prevalence of asthma symptoms in Tehran as the first attempt in terms of situation analysis of the disease in the Iranian society by using relevant parts of the European Community Respiratory Health Survey (ECRHS) questionnaire. Results: Wheezing was reported in 48% of males and 34% of females in the age range of 20-44 years, around 50% of which was associated with breathlessness or cold. , the people who answered "yes" to the questions 1 (wheezing), 4 (coughing), 5 (asthma history) or 7 (nasal allergy) were totally 211 among whom 124 (58.8%) were males and the rest (41.2%) were females. Conclusion: Asthma symptoms decrease the quality of life and impose high costs on the healthcare system in many countries. A low rate of participants had been informed about their asthma by physicians and not all of them were taking medications. Risk factor analysis and control is strongly advised in order to lessen the prevalence of the disease and symptoms. Air pollution, smoking, unhealthy life style and many personal and social factors need to be assessed and eliminated. It seems that a- second phase- ECRH survey should be conducted to assess the situation of asthma through population of Tehran. [ABSTRACT FROM AUTHOR]

Toluene diisocyanate (TDI) is a leading cause of chemical-induced occupational asthma which impacts workers in a variety of industries worldwide. Recently, the robust regulatory potential of regulatory T cells (Tregs) has become apparent, including their functional role in the regulation of allergic disease; however, their function in TDI-induced sensitization has not been explored. To elucidate the kinetics, phenotype, and function of Tregs during TDI sensitization, BALB/c mice were dermally exposed (on each ear) to a single application of TDI (0.5-4% v/v) or acetone vehicle and endpoints were evaluated via RT-PCR and flow cytometry. The draining lymph node (dLN) Treg population expanded significantly 4, 7, and 9 days after single 4% TDI exposure. This population was identified using a variety of surface and intracellular markers and was found to be phenotypically heterogeneous based on increased expression of markers including CD103, CCR6, CTLA4, ICOS, and Neuropilin-1 during TDI sensitization. Tregs isolated from TDI-sensitized mice were significantly more suppressive compared with their control counterparts, further supporting a functional role for Tregs during TDI sensitization. Last, Tregs were depleted prior to TDI sensitization and an intensified sensitization response was observed. Collectively, these data indicate that Tregs exhibit a functional role during TDI sensitization. Because the role of Tregs in TDI sensitization has not been previously elucidated, these data contribute to the understanding of the immunologic mechanisms of chemical induced allergic disease. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess whether smoking status among individuals in late adolescence (19-22 years) with asthma was associated with socioeconomic status (SES) defined by HOUSES, an individual-housing-based SES measure.Methods: A population-based cross-sectional study was conducted among the 1988-1989 Olmsted County, Minnesota Birth Cohort, with physician-diagnosed asthma and that lived in the community during the study period (November 1, 2008-October 31, 2012). Using a z score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated and categorized into quartiles. Smoking status (both current and past smoker) was compared among subjects with different SES as measured by HOUSES using logistic regression, adjusting for age and sex.Results: Among 289 eligible subjects, 287 (99%) were successfully geo-coded to real property data for HOUSES. Of the 257 subjects whose smoke exposure was recorded, 70 (27%) had a history of smoking (either past or current). An inverse association was observed between HOUSES and smoking status after accounting for age, gender, and General Medical Examination status (adjusted OR = 0.39, 95% CI = 0.18-0.87 for comparing highest vs. lowest HOUSES in quartile; overall P = .02).Conclusions: A significant proportion of individuals with asthma in late adolescence was smokers during the study period, disproportionally affecting those with lower SES. [ABSTRACT FROM AUTHOR]

Exposure to indoor allergens plays an important role in the etiology of asthma. This study was designed to quantify indoor allergens from homes of families that had at least one case of childhood asthma at home in a southwestern city of Iran. The relationship between the indoor allergen levels and home characteristics was also investigated. Dust samples were collected from the bedrooms and the kitchens of 35 homes where children with persistent asthma were living. The levels of indoor allergens were measured by enzyme linked immunosorbent assay (ELISA). Detectable amounts of mite, mouse and cockroach allergens were found in all evaluated places. None of our patients were exposed to a threshold concentration of indoor allergen for sensitizing at home. Regarding of mite allergens, the levels of Der f1 were significantly higher than Der p1 and a direct correlation was observed between living in an apartment and Der f1 levels. Moreover, Fel d1 (cat) and Bla g1 (cockroach) allergens were found in the children's bedrooms more frequently than those in the kitchens. In this study, direct associations were obtained between Bla g1 allergen and the duration of occupancy and between Fel d1 and average home size. A total of 34.2% of the patients showed positive skin reactions to at least one of the tested allergens as 17.1% of them showed reactivity to D. pteronyssinus. Proper controlling of cockroaches and mice by public health officials would be a practical approach to avoid inducing asthma or worsening the symptoms. [ABSTRACT FROM AUTHOR]

Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy. [ABSTRACT FROM AUTHOR]

Background: Atopic diseases are a major burden of disease on a global scale. Regarding their aetiology, the early years of life are assumed to play a crucial role. In addition, there is growing evidence that elucidating the impact of cross-generational effects and epigenetic mechanisms such as DNA methylation can substantially widen the scientific knowledge of the occurrence and progression of these diseases. We are thus aiming at following the course of asthma, allergies, and potential risk factors for their occurrence across three generations by establishing a birth cohort in the offspring of an existing population-based cohort.Methods/design: 2051 young adults who have been recruited in 1995 for Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and who have subsequently been followed-up by the Study on Occupational Allergy Risks (SOLAR) are asked bi-annually since 2009 if they conceived a child in the meantime. If parenthood is reported, parents are invited to enrol along with their children in the ACROSSOLAR cohort. Participation involves completing a questionnaire assessing general and health-related information about the course of the pregnancy and the first year of life of their children. Subsequently, the children are followed up until primary school age when asthma and allergies can be diagnosed reliably. In addition, DNA for epigenetic analysis will be collected and analysed. Longitudinal data analysis techniques will then be used to assess potential associations between early-life exposures and onset of childhood asthma and allergies taking into account epigenetics.Discussion: Birth cohorts are especially suited to elucidate the impact of genetic predisposition, epigenetics, exposures during the first years of life, and gene-environment interactions on the occurrence and progression of asthma and allergies. By building upon an existing cohort, ACROSSOLAR offers a unique and cost-effective opportunity to investigate the aetiology of atopic disease in a prospective and cross-generational way. [ABSTRACT FROM AUTHOR]

Background: Heterogeneous airway narrowing and closure are characteristics of asthma. However, they have never been quantified by direct measurements of parallel sister airways obtained from image data, and the anatomical basis of these processes remains unknown.Methods: Seven normal and nine asthmatic subjects underwent high-resolution CT, before and after methacholine challenge. Mean lumen areas of the entire airways were measured in 28 and 24 parallel sister airway pairs (a pair of airways arising from the same bifurcation) respectively (range 1.0-8.7 mm diameter). Heterogeneous narrowing was defined as the median difference in percentage narrowing between parallel sister airways. Forced oscillatory respiratory resistance (Rrs) and spirometry were measured before and after methacholine challenge conducted while supine.Results: The airways of asthmatics were smaller at baseline, and following bronchoconstriction there were similar decreases in FEV1, increases in Rrs and mean narrowing of airways for asthmatic and non-asthmatic groups. Non-asthmatics required higher doses of methacholine than asthmatics to achieve the same changes. However, parallel heterogeneity (median (IQR) 33% (27-53%) vs 11% (9-18%), p<0.001) and airway closure (24.1% and 7.7%, p=0.001, χ(2)) were greater in asthmatics versus non-asthmatics.Conclusion: We found clear evidence of differences in airway behaviour in the asthmatic group. Asthmatic airways were narrower at baseline and responded to inhaled methacholine by more heterogeneous narrowing of parallel sister airways and greater airway closure. [ABSTRACT FROM AUTHOR]

Background: Interleukins (IL) 4 and 13 genes and their receptors (R) are the key cytokines which amplify inflammatory reactions in asthma. Objective: This study aimed to investigate the association ofIL 4, 4 R, 13and13 Rgenes polymorphism with asthma in Indian children. Methods: In this hospital-based case-control study, included were children aged 1–15 years recruited as diagnosed cases of bronchial asthma, according to EPR 2007 and excluded were subjects with other respiratory diseases. Children with no present or past history of asthma were enrolled as controls. Spirometry was done in cases age ≥ 6 years. Gene–gene interaction was evaluated using binary logistic regression. Results: From October 2010 to July 2013, 275 cases and 275 controls were recruited. Gene–gene interactions between C1112T inIL 13and Ile50Val inIL 4 R gene polymorphisms were found to be statistically significant (OR = 2.37, 95% CI = 1.04–5.42,p = 0.040). Individuals with CT and GG genotype of C1112T inIL 13and Ile50Val inIL 4 R were at twice the risk for the development of asthma compared to individuals with both non-risk genotypes. Conclusion: The data suggests that gene–gene interactions betweenIL 13andIL 4 R genes may play an important role in asthma among Indian children. [ABSTRACT FROM AUTHOR]

Background: The prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study.Methods: Cross-sectional studies were performed among 7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Créteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions.Results: Asthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47-3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the dietary factors was associated with BHR.Conclusions: Diet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy. [ABSTRACT FROM AUTHOR]

Background: Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. Objective: We aimed to investigate the association between air pollution and adult onset asthma. Methods: Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect. Results: In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 μg/m3; p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 μg/m3; p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 μg/m3), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 μg/m3), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10-5/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles × meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 μg/m3). Conclusions: Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed. Citation: Jacquemin B, Siroux V, Sanchez M, Carsin AE, Schikowski T, Adam M, Bellisario V, Buschka A, Bono R, Brunekreef B, Cai Y, Cirach M, Clavel-Chapelon F, Declercq C, de Marco R, de Nazelle A, Ducret-Stich RE, Ferretti VV, Gerbase MW, Hardy R, Heinrich J, Janson C, Jarvis D, Al Kanaani Z, Keidel D, Kuh D, Le Moual N, Nieuwenhuijsen MJ, Marcon A, Modig L, Pin I, Rochat T, Schindler C, Sugiri D, Stempfelet M, Temam S, Tsai MY, Varraso R, Vienneau D, Vierkotter A, Hansell AL, Kramer U, Probst-Hensch NM, Sunyer J, Kunzli N, Kauffmann F. 2015. Ambient air pollution and adult asthma incidence in six European cohorts (ESCAPE). Environ Health Perspect 123:613-621; [ABSTRACT FROM AUTHOR]

Summary: Many reports have been published concerning how psychosocial stress influences the occurrence and progression of allergic diseases such as bronchial asthma and atopic dermatitis. As for asthma, a typical allergic disease often accompanied by psychosomatic related problems, the Global Initiative for Asthma (GINA), international medical guidelines for asthma, describes psychosocial problems as causative factors of poor asthma control and as risk factors for asthma exacerbation, even if symptoms are well controlled. However, because there is little high quality evidence for effective treatments for asthma patients with psychosocial problems, concrete assessments and treatments for such problems is scarcely described in GINA. Therefore, psychosomatic intervention for asthma patients is not effectively conducted on a worldwide scale. In contrast, the "Japanese Guidelines for the Diagnosis and Treatment of Psychosomatic Diseases" describe the assessment and treatment of psychosomatic disorders in detail. In the guidelines, psychosocial factors are classified into five categories; 1) Relation between stress and asthma occurrence or progression, 2) Relation between emotion and asthma symptoms, 3) Problems related to a patient's character and behaviors, 4) Problems of daily life and Quality of Life (QOL), and 5) Problems related to family relationships and life history. The employment of a self-administered questionnaire, the "Psychosomatic Questionnaire related to Asthmatic Occurrence and Progression", is useful for clarifying psychosocial factors and for setting up treatment strategies according to the problems identified. The Japanese guidelines have been proven to be useful, but empirical evidence for their effectiveness is still relatively limited. It will be necessary in the future to accumulate high-quality evidence and to revise the psychosomatic approaches in the guidelines that are universally valid. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is an etiologically complex disease and develops by the interaction of multiple genes and environmental factors. Previous studies suggested a linkage between the interferon-gamma ( INFG) gene cluster in the chromosome 12q region and susceptibility to asthma. Methods: This meta-analysis was undertaken to examine the relationship between +874A/T and CA-repeat polymorphisms in INFG gene and asthma. Eligible articles were accumulated via online databases in October 2013. A total of nine articles were included that were associated with the +874A/T polymorphism, involving 470 cases and 574 controls, as well as articles involving CA-repeat polymorphisms, which included 365 cases and 517 controls. The meta-analysis was performed for heterogeneity and calculation of pooled odds ratio and evaluation of publication bias by Egger's linear regression test. Results: The differences between IFNG polymorphism and the susceptibility to asthma may vary across ethnicities and ages, and also that the allelic frequencies of the AA genotypes in IFNG at +874 is associated with an increased risk of asthma in the Chinese Han adult population; additionally, CA14 occurrence in the first intron can increase the risk of asthma in the Japanese population. Conclusion: Our findings suggested that some polymorphisms in the IFNG gene could act as high prevalence-susceptibility markers of asthma. Larger scale studies are warranted to address these associations among different ethnic populations, ages and the severity of asthma prognosis. [ABSTRACT FROM AUTHOR]

Background: Evaluation of the prevalence and incidence of asthma and research into its etiology often rely on self-reported information. We conducted this analysis to investigate reliability in reporting asthma history across categories of demographic and socio-economic characteristics. Methods: We analyzed data from 3109 participants in the Coronary Artery Risk Development in Young Adults study, a longitudinal study of African-American and white adults. Responses to self-administered questionnaires completed at 15- and 20-year follow-up exams were used to evaluate agreement in reporting asthma history and age at diagnosis and assess variation in agreement across categories of demographic and health-related characteristics. Results: A history of asthma was reported by 12% of participants at the 15-year exam and 11% of participants at the 20-year exam, with 97% agreement and an overall Kappa coefficient of 0.845 (95% confidence interval: 0.815-0.874). Kappa coefficients were higher among women than men and increased monotonically across categories of educational attainment. One-hundred eight participants (35%) reported exactly the same age at diagnosis at the two time points; for another 120 (39%), the difference in reported ages was ≤2 years. Age at asthma diagnosis reported at the 20-year exam was, on an average, 1 year (SD: 5.2) older than that reported at the 15-year exam. Conclusions: Five-year reliability in self-reported asthma history is high, and variation in reporting age at diagnosis is low across categories of participant characteristics. Nevertheless, agreement in responses at two times does not guarantee that self-administered questionnaires are sensitive tools for detecting a true asthma history. [ABSTRACT FROM AUTHOR]

The article discusses a scientific study of lung function in individuals from infancy to late adolescence with a focus on what factors are associated with changes in function. Topics include the impact that gender, asthma, and maternal asthma have on lung function, the correlation between infant onset atopy, maternal smoking, and low lung function, and expiratory flow limitation in lung function.

Objective: The objective of this study is to compare the effects of inhaled beclomethasone with oral montelukast in long term management of moderate persistent asthma in children. Design: Quasi experimental study. Period: 6 months, from July 20,2007 to January 20, 2008. Settings: Out patient paediatric department at Fauji Foundation hospital, Rawalpindi. Material and Methods: 80 children between 5-12yrs of age presenting with moderate persistent asthma, divided in two groups of 40 each. Group A treated with beclomethasone inhaler while Group B was started on oral montelukast. Drugs effect was recorded on a 2 wkly proforma for 8 weeks. Results: There were 54(67.5%) male and 26(33%) female. Most common triggering factor seen in 54(67.5%) patients was recent history of respiratory tract infection, exposure to carpet dust in 43(53.75%), cigarette smoke in 42(52.5%),recent psychological stress in 28(35%) , pollen allergy in 26 (32.5%) , pets exposure in 8 (10%) and to mite was noticed in 5(6.25%) children. Marked improvement was observed in day time cough in group A with 10(25%) patients being free of cough with inhaler, while 20(50%) showed mild intermittent symptoms. 1(2.5%) showed mild persistent symptoms. In Group B 3(7.5%) patients were symptom free, 23(57.5%)with mild intermittent and 4(10%) with mild persistant symptoms while 6(15%) continued to have moderate persistent symptoms. P value was 0.01. Regarding day time breathlessness, P value was significant of 0.258. Similarly marked improvement was observed in night symptoms of breathlessness, cough and sleeplessness in both groups. P value was less than 0.05 in majority of the variables showing statistically significant improvement with inhaled beclomethasone than with oral montelukast. Conclusions: Inhaled beclomethasone is superior to oral montelukast in controlling chronic symptoms of childhood asthma. [ABSTRACT FROM AUTHOR]

This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for asthma in Taipei, Taiwan. Hospital admissions for asthma and ambient air pollution data for Taipei were obtained for the period of 2006–2010. The relative risk of hospital admissions for asthma was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased asthma admissions were significantly associated with PM2.5levels both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 6–18%) and 3% (95% CI = 0–8%) elevation in admissions for asthma, respectively. In the two-pollutant models, PM2.5levels remained significant for increased asthma admissions after inclusion of SO2or O3both on warm and cool days. This study provides evidence that higher levels of PM2.5elevate the risk of hospital admissions for asthma in Taiwan. [ABSTRACT FROM PUBLISHER]

Background Allergic reactions to the common house plant Hoya compacta (HC) have not previously been described. Aims To confirm HC as the cause of rhinoconjunctivitis in three horticultural workers. Methods Greenhouse working conditions were reproduced in our challenge chamber. Results All three cases developed rhinoconjunctivitis when working with HC plants. A control challenge was performed in two cases with iceberg lettuce causing no symptoms. Nasal volume measured by acoustic rhinometry (AR) fell after all three active challenges, but also after one of the control challenges. Conclusions Our study confirms that HC may cause occupational rhinoconjunctivitis and asthma through a Type I hypersensitivity reaction. Specific inhalation challenges, nasal nitric oxide measurement and AR may be useful additional tools in supporting such diagnoses for occupational physicians to consider. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between inflammatory cytokine levels and airway remodeling in bronchial asthma patients. Methods 106 patients with bronchial asthma were divided into exacerbation group and stable groups, there were 61 cases, 45 cases, separately, 40 cases of healthy people were selected as control group. IL-2, IL-5, VEGF, bFGF, TGF-β 1 levels were detected. Results Compared with the control group, the levels of VEGF, bFGF, TGF-β1 in stable group were significantly increased ( P < 0.05) . Compared with the control group and the stable group, the levels of VEGF, bFGF, TGF-β1 in exacerbation group were significantly increased ( P < 0.05) . The levels of IL-5 in stable group patients were significantly higher than the control group (P< 0.05) . The levels of IL-2 and IL-5 in exacerbation group patients were significantly higher than than those in the control group and the stable group patients (P < 0.05) . IL-2 and TGF-β1 showed a significant positive correlation (F < 0.05), IL-5 and VEGF, bFGF, and TGF-β1 showed significant positive correlation (P< 0.05) . Conclusion The imbalance of inflammatory cytokine levels is closely related to airway fibrosis induced by VEGF, bFGF and TGF-β1 in bronchial asthma patients, these two factors work together to lead to bronchial asthma progress. [ABSTRACT FROM AUTHOR]

Linker for activation of T cells (LAT) is a key adaptor in the T cell receptor (TCR) signaling pathway. The expression of LAT is lower in asthmatic patients than that in healthy people, but there is little knowledge about the mechanism underlying this phenomenon. This study was aimed to determine whether LAT-PLC-γ1 interaction was involved in the development of asthma. It was shown that the phosphorylation of PLC-γ1 decreased in the asthmatic mouse model and Th2 cell differentiated CD4+ T cells. In addition, depleted endogenous PLC-γ1 promoted CD4+ T cells to differentiate into IL-4-Productor. It was therefore concluded that the low level of LAT-PLC-γ1 interaction was associated with Th2 polarized differentiation, and this may contribute to the etiology of asthma. [ABSTRACT FROM AUTHOR]

Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture-based microbial analysis. In the low-income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years. The current analysis included 13 asthma cases and 28 controls. Next-generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio ( OR) 4.80 (95% confidence interval ( CI) 1.04-22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk ( OR 21.0, 95% CI 2.16-204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next-generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community. [ABSTRACT FROM AUTHOR]

The article discusses epidemiology, clinical characteristics, and management of occupational asthma. Topics explored include common agents that cause asthma such as animal allergens, plant products, and enzymes, the occupational asthma risks faced by farmers, office workers, and pharmaceutical industry employees, and the effectiveness of immunotherapy in addressing asthma symptoms.

Abstract: It has been suggested that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To test whether mitochondrial variants influence the risk of asthma, we analyzed 16,158 mtSNPs in a sample of 372 asthmatic children and 395 healthy children using the DNA pooling technique and genome wide association analysis. Stratified analysis by sex was performed to explain the differences observed between sexes in the etiology of asthma. Different variants were detected to be significant in the sample of girls and boys with the smallest adjusted p values being 1.4×10−09 (mt5295) and 3.6×10−12 (mt16158), respectively. Most of the significant locations found in boys are within the CYB gene and the non-coding region. For girls, most of the significant mtSNPs lie within NADH-dehydrogenase-subunits. The variants reported here have not previously been described in connection with asthma. Although further studies in other cohorts are needed to confirm these findings our study highlights the importance of the mitochondria among the factors that contribute to the risk of asthma. [Copyright &y& Elsevier]

Background Hyperpolarised ³He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood. Objective To better understand the determinants of ventilation defects in asthma, we evaluated wellestablished clinical as well as ³He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma. Methods Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3rd to 5th generation airway wall area and wall thickness per cent and lumen area. Results Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of ³He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV1)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV1 by 20% ( p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04). Conclusions Subjects with asthma with ³He ventilation defects were older with significantly worse airway hyperresponsiveness, inflammation and airway remodelling but similar FEV1 as subjects with asthma without defects; hyperpolarised ³He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways. [ABSTRACT FROM AUTHOR]

In the majority of cases, asthma and chronic obstructive pulmonary disease (COPD) are two clearly distinct disease entities. However, in some patients there may be significant overlap between the two conditions. This constitutes an important area of concern because these patients are generally excluded from randomised controlled trials (mostly because of smoking history in the case of asthma or because of significant bronchodilator reversibility in the case of COPD). As a result, their pathobiology, prognosis and response to therapy are largely unknown. This may lead to suboptimal management and can limit the development of more personalised therapeutic options. Emerging genetic and molecular information coupled with new bioinformatics capabilities provide novel information that can pave the way towards a new taxonomy of airway diseases. In this paper we question the current value of the terms 'asthma' and 'COPD' as still useful diagnostic labels; discuss the scientific and clinical progress made over the past few years towards unravelling the complexity of airway diseases, from the definition of clinical phenotypes and endotypes to a better understanding of cellular and molecular networks as key pathogenic elements of human diseases (so-called systems medicine); and summarise a number of ongoing studies with the potential to move the field towards a new taxonomy of airways diseases and, hopefully, a more personalised approach to medicine, in which the focus will shift from the current goal of treating diseases as best as possible to the so-called P4 medicine, a new type of medicine that is predictive, preventive, personalised and participatory. [ABSTRACT FROM AUTHOR]

: In a systematic review and meta-analysis, Jasper Been and colleagues investigate the association between preterm birth and the development of wheezing disorders in childhood. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]