Relationship between recent short-acting β-agonist use and subsequent asthma exacerbations

PubMed Central

Paris, Jason; Peterson, Edward L.; Wells, Karen; Pladevall, Manel; Burchard, Esteban G.; Choudhry, Shweta; Lanfear, David E.; Williams, L. Keoki

2009-01-01

Background US national guidelines recommend assessing short-acting β-agonist (SABA) medication use as a marker of asthma severity and control. However, the relationship between recent SABA use and asthma exacerbations is not currently known. Objective To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes. Methods We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan. Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills. Cox proportional hazards models were used to examine the prospective relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control (ie, oral corticosteroids use, asthma-related emergency department visits, and asthma-related hospitalizations). We separately accounted for SABA metered-dose inhaler (MDI) and SABA nebulizer use. Results Of the 2,056 patients who met study criteria, 1,569 (76.3%) had used a SABA medication in their baseline year. After adjusting for potential confounders, SABA nebulizer use was associated with asthma-related emergency department visits (adjusted hazard ratio [aHR], 6.32; 95% confidence interval [CI], 2.38 to 16.80) and asthma-related hospitalizations (aHR, 21.62; 95% CI, 3.17 to 147.57). In contrast, frequency of SABA MDI use was not associated with these outcomes. Conclusions Frequency of SABA use during a 3-month period was associated with poor asthma outcomes. The relationship with poor asthma outcomes was strongest for SABA nebulizer use, suggesting that the type of SABA used is also of prognostic importance. PMID:19055201

Body mass index trajectory classes and incident asthma in childhood: results from 8 European Birth Cohorts--a Global Allergy and Asthma European Network initiative.

PubMed

Rzehak, Peter; Wijga, Alet H; Keil, Thomas; Eller, Esben; Bindslev-Jensen, Carsten; Smit, Henriette A; Weyler, Joost; Dom, Sandra; Sunyer, Jordi; Mendez, Michelle; Torrent, Maties; Vall, Oriol; Bauer, Carl-Peter; Berdel, Dietrich; Schaaf, Beate; Chen, Chih-Mei; Bergström, Anna; Fantini, Maria P; Mommers, Monique; Wahn, Ulrich; Lau, Susanne; Heinrich, Joachim

2013-06-01

The causal link between body mass index (BMI) or obesity and asthma in children is still being debated. Analyses of large longitudinal studies with a sufficient number of incident cases and in which the time-dependent processes of both excess weight and asthma development can be validly analyzed are lacking. We sought to investigate whether the course of BMI predicts incident asthma in childhood. Data from 12,050 subjects of 8 European birth cohorts on asthma and allergies were combined. BMI and doctor-diagnosed asthma were modeled during the first 6 years of life with latent growth mixture modeling and discrete time hazard models. Subpopulations of children were identified with similar standardized BMI trajectories according to age- and sex-specific "World Health Organization (WHO) child growth standards" and "WHO growth standards for school aged children and adolescents" for children up to age 5 years and older than 5 years, respectively (BMI-SDS). These types of growth profiles were analyzed as predictors for incident asthma. Children with a rapid BMI-SDS gain in the first 2 years of life had a higher risk for incident asthma up to age 6 years than children with a less pronounced weight gain slope in early childhood. The hazard ratio was 1.3 (95% CI, 1.1-1.5) after adjustment for birth weight, weight-for-length at birth, gestational age, sex, maternal smoking in pregnancy, breast-feeding, and family history of asthma or allergies. A rapid BMI gain at 2 to 6 years of age in addition to rapid gain in the first 2 years of life did not significantly enhance the risk of asthma. Rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Mechanisms altering airway smooth muscle cell Ca+ homeostasis in two asthma models.

PubMed

Kellner, Julia; Tantzscher, Juliane; Oelmez, Hamza; Edelmann, Martin; Fischer, Rainald; Huber, Rudolf Maria; Bergner, Albrecht

2008-01-01

Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist-induced Ca(2+) increase in ASMC have been reported in asthma. The aim of this study was to investigate mechanisms underlying these changes. Murine tracheal smooth muscle cells (MTSMC) from T-bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine-induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Acetylcholine-induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild-type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine-induced Ca(2+) transients could be reversed by blocking inositol-3-phosphate receptors. We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright 2008 S. Karger AG, Basel.

Cost-effectiveness and Budget Impact of Routine Use of Fractional Exhaled Nitric Oxide Monitoring for the Management of Adult Asthma Patients in Spain.

PubMed

Sabatelli, L; Seppälä, U; Sastre, J; Crater, G

Fractional exhaled nitric oxide (FeNO) is a marker for type 2 airway inflammation. The objective of this study was to evaluate the cost-effectiveness and budget impact of FeNO monitoring for management of adult asthma in Spain. A cost-effectiveness analysis model was used to evaluate the effect on costs of adding FeNO monitoring to asthma management. Over a 1-year period, the model estimated the incremental cost per quality-adjusted life year and incremental number of exacerbations avoided when FeNO monitoring was added to standard guideline-driven asthma care compared with standard care alone. Univariate and multivariate sensitivity analyses were applied to explore uncertainty in the model. A budget impact model was used to examine the impact of FeNO monitoring on primary care costs across the Spanish health system. The results showed that adding FeNO to standard asthma care saved €62.53 per patient-year in the adult population and improved quality-adjusted life years by 0.026 per patient-year. The budget impact analysis revealed a potential net yearly saving of €129 million if FeNO monitoring had been used in primary care settings in Spain. The present economic model shows that adding FeNO to the treatment algorithm can considerably reduce costs and improve quality of life when used to manage asthma in combination with current treatment guidelines.

Th2 cytokine antagonists: potential treatments for severe asthma.

PubMed

Hansbro, Philip M; Scott, Grace V; Essilfie, Ama-Tawiah; Kim, Richard Y; Starkey, Malcolm R; Nguyen, Duc H; Allen, Paul D; Kaiko, Gerard E; Yang, Ming; Horvat, Jay C; Foster, Paul S

2013-01-01

Asthma is a major disease burden worldwide. Treatment with steroids and long acting β-agonists effectively manage symptoms in many patients but do not treat the underlying cause of disease and have serious side effects when used long term and in children. Therapies targeting the underlying causes of asthma are urgently needed. T helper type 2 (Th2) cells and the cytokines they release are clinically linked to the presentation of all forms of asthma. They are the primary drivers of mild to moderate and allergic asthma. They also play a pathogenetic role in exacerbations and more severe asthma though other factors are also involved. Much effort using animal models and human studies has been dedicated to the identification of the pathogenetic roles of these cells and cytokines and whether inhibition of their activity has therapeutic benefit in asthma. We discuss the current status of Th2 cytokine antagonists for the treatment of asthma. We also discuss the potential for targeting Th2-inducing cytokines, Th2 cell receptors and signaling as well as the use of Th2 cell antagonists, small interfering oligonucleotides, microRNAs, and combination therapies. Th2 antagonists may be most effective in particular asthma subtypes/endotypes where specific cytokines are known to be active through the analysis of biomarkers. Targeting common receptors and pathways used by these cytokines may have additional benefit. Animal models have been valuable in identifying therapeutic targets in asthma, however the results from such studies need to be carefully interpreted and applied to appropriately stratified patient cohorts in well-designed clinical studies and trials.

Cockroach Allergy

MedlinePlus

... and Allergies Are Asthma and Allergies Disabilities? Helping Students Manage Asthma at School Allergies Types of Allergies ... Society Burden of Asthma on Minorities Asthma Inhaler Design My Life With Asthma Report Why Patient Engagement ...

Mold Allergy

MedlinePlus

... and Allergies Are Asthma and Allergies Disabilities? Helping Students Manage Asthma at School Allergies Types of Allergies ... Society Burden of Asthma on Minorities Asthma Inhaler Design My Life With Asthma Report Why Patient Engagement ...

Nocturnal Asthma

MedlinePlus

... caused by an upper airway obstruction Treatment and Management Treatment of any underlying causes of nocturnal asthma ... trials . Asthma Types Allergic Asthma Nocturnal Asthma Patients & Visitors Giving For Professionals About Us Treatment & Programs Health ...

Modeling of Regional Climate Change Effects on Ground-Level Ozone and Childhood Asthma

PubMed Central

Sheffield, Perry E.; Knowlton, Kim; Carr, Jessie L.; Kinney, Patrick L.

2011-01-01

Background The adverse respiratory effects of ground-level ozone are well-established. Ozone is the air pollutant most consistently projected to increase under future climate change. Purpose To project future pediatric asthma emergency department visits associated with ground-level ozone changes, comparing 1990s to 2020s. Methods This study assessed future numbers of asthma emergency department visits for children aged 0–17 years using (1) baseline New York City metropolitan area emergency department rates, (2) a dose–response relationship between ozone levels and pediatric asthma emergency department visits, and (3) projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by a global-to-regional climate change and atmospheric chemistry model. Sensitivity analyses included population projections and ozone precursor changes. This analysis occurred in 2010. Results In this model, climate change could cause an increase in regional summer ozone-related asthma emergency department visits for children aged 0–17 years of 7.3% across the New York City metropolitan region by the 2020s. This effect diminished with inclusion of ozone precursor changes. When population growth is included, the projections of morbidity related to ozone are even larger. Conclusions The results of this analysis demonstrate that the use of regional climate and atmospheric chemistry models make possible the projection of local climate change health effects for specific age groups and specific disease outcomes – such as emergency department visits for asthma. Efforts should be made to improve on this type of modeling to inform local and wider-scale climate change mitigation and adaptation policy. PMID:21855738

Models for estimating and projecting global, regional and national prevalence and disease burden of asthma: protocol for a systematic review.

PubMed

Bhuia, Mohammad Romel; Nwaru, Bright I; Weir, Christopher J; Sheikh, Aziz

2017-05-17

Models that have so far been used to estimate and project the prevalence and disease burden of asthma are in most cases inadequately described and irreproducible. We aim systematically to describe and critique the existing models in relation to their strengths, limitations and reproducibility, and to determine the appropriate models for estimating and projecting the prevalence and disease burden of asthma. We will search the following electronic databases to identify relevant literature published from 1980 to 2017: Medline, Embase, WHO Library and Information Services and Web of Science Core Collection. We will identify additional studies by searching the reference list of all the retrieved papers and contacting experts. We will include observational studies that used models for estimating and/or projecting prevalence and disease burden of asthma regarding human population of any age and sex. Two independent reviewers will assess the studies for inclusion and extract data from included papers. Data items will include authors' names, publication year, study aims, data source and time period, study population, asthma outcomes, study methodology, model type, model settings, study variables, methods of model derivation, methods of parameter estimation and/or projection, model fit information, key findings and identified research gaps. A detailed critical narrative synthesis of the models will be undertaken in relation to their strengths, limitations and reproducibility. A quality assessment checklist and scoring framework will be used to determine the appropriate models for estimating and projecting the prevalence anddiseaseburden of asthma. We will not collect any primary data for this review, and hence there is no need for formal National Health Services Research Ethics Committee approval. We will present our findings at scientific conferences and publish the findings in the peer-reviewed scientific journal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Anti-inflammatory effects of tilmicosin in a noninfectious mouse model of allergic asthma.

PubMed

Ci, Xinxin; Chu, Xiao; Xiang, Hua; Li, Xiangchao; Deng, Xuming

2011-12-01

Tilmicosin, a semi-synthetic tylosin-derived macrolide antibiotic commonly used by veterinarians, has been shown to possess anti-inflammatory activity. However, possible use in asthma treatment has not yet been studied. In this study, we investigated the anti-inflammatory properties of tilmicosin using a murine asthma model. BALB/c mice were sensitized and challenged by intraperitoneal (i.p.) or nasal administration of ovalbumin. Tilmicosin (10 and 20 mg/kg) treatment resulted in a marked reduction in the presence of several types of immune cells and cytokines in the bronchoalveolar lavage fluids of mice. Levels of ovalbumin-specific Immunoglobulin E (IgE) were significantly decreased following treatment with tilmicosin (10 and 20 mg/kg). Histological studies using H&E (haematoxylin and eosin) and AB-PAS (alcian blue-periodic acid-Schiff) staining demonstrated that tilmicosin substantially inhibited both ovalbumin-induced inflammatory cells in lung tissues and goblet cell hyperplasia in the airway. These findings provided new insight into the immunopharmacological role of tilmicosin in terms of its effects in a murine model of asthma.

Tobacco Product Use Among Youths With and Without Lifetime Asthma - Florida, 2016.

PubMed

Reid, Keshia M; Forrest, Jamie R; Porter, Lauren

2018-06-01

The increasing availability of diverse tobacco products has led to complex tobacco product use patterns among youths (1). Use by youths of products containing nicotine in any form is unsafe (2); among young persons with asthma, use of combustible tobacco products, particularly cigarettes, is associated with worsening symptoms, poor asthma control, and an increased need for medical management (3,4). Studies suggest that youths with asthma adopt health risk behaviors, including tobacco product use, at rates similar to or higher than those of youths without asthma (3-7); however, these studies are often limited to a partial list of tobacco product types among high school students. To assess current use (≥1 days during the past 30 days) of one or more of five tobacco product types (cigarettes, electronic cigarettes [defined as e-cigarettes, e-cigars, vape pipes, vaping pens, e-hookah, and hookah pens], hookah, smokeless tobacco, or cigars) among Florida middle school (grades 6-8) and high school (grades 9-12) students with or without a previous medical diagnosis of asthma, the Florida Department of Health analyzed data from the 2016 Florida Youth Tobacco Survey (FYTS). In 2016, 11.1% of middle school and 27.9% of high school students with asthma, and 7.9% of middle school and 24.2% of high school students without asthma, reported any current tobacco product use. Current use of each tobacco product type was considerably higher among students with asthma than among those without asthma. E-cigarettes were the most commonly used tobacco product type reported by middle and high school students with asthma (7.9% and 19.6%, respectively) and without asthma (5.8% and 17.2%, respectively). Statewide tobacco prevention strategies could help reduce all forms of tobacco product use among youths, particularly among those with asthma.

Effects of Asian Dust Particles on the Early-Stage Antigen-Induced Immune Response of Asthma in NC/Nga Mice.

PubMed

Kurai, Jun; Watanabe, Masanari; Sano, Hiroyuki; Hantan, Degejirihu; Tohda, Yuji; Shimizu, Eiji

2016-11-16

Asian dust (AD) can aggravate airway inflammation in asthma, but the association between AD and the development of asthma remains unclear. This study aimed to investigate the effects of AD on the early stage of antigen sensitization using a mouse model of asthma, as well as the role of leukotrienes (LTs) in antigen-induced airway inflammation potentiated by AD particles. NC/Nga mice were co-sensitized by intranasal instillation of AD particles and/or Dermatophagoides farinae (Df) for five consecutive days. Df-sensitized mice were stimulated with an intranasal Df challenge at seven days. Mice were treated with the type 1 cysteinyl LT (CysLT₁) receptor antagonist orally 4 h before and 1 h after the allergen challenge. At 24 h post-challenge, the differential leukocyte count, inflammatory cytokines, and LTs in bronchoalveolar lavage fluid were assessed, and airway inflammation was evaluated histopathologically. AD augmented neutrophilic and eosinophilic airway inflammation with increased CysLTs and dihydroxy-LT in a mouse model of asthma. The CysLT₁ receptor antagonist was shown to attenuate both neutrophilic and eosinophilic airway inflammation augmented by AD. Therefore, exposure to AD may be associated with the development of asthma and LTs may play important roles in airway inflammation augmented by AD.

IL-23 secreted by bronchial epithelial cells contributes to allergic sensitization in asthma model: role of IL-23 secreted by bronchial epithelial cells.

PubMed

Lee, Hyun Seung; Park, Da-Eun; Lee, Ji-Won; Chang, Yuna; Kim, Hye Young; Song, Woo-Jung; Kang, Hye-Ryun; Park, Heung-Woo; Chang, Yoon-Seok; Cho, Sang-Heon

2017-01-01

IL-23 has been postulated to be a critical mediator contributing to various inflammatory diseases. Dermatophagoides pteronyssinus (Der p) is one of the most common inhalant allergens. However, the role of IL-23 in Der p-induced mouse asthma model is not well understood, particularly with regard to the development of allergic sensitization in the airways. The objective of this study was to evaluate roles of IL-23 in Der p sensitization and asthma development. BALB/c mice were repeatedly administered Der p intranasally to develop Der p allergic sensitization and asthma. After Der p local administration, changes in IL-23 expression were examined in lung tissues and primary epithelial cells. Anti-IL-23p19 antibody was given during the Der p sensitization period, and its effects were examined. Effects of anti-IL-23p19 antibody at bronchial epithelial levels were also examined in vitro. The expression of IL-23 at bronchial epithelial layers was increased after Der p local administration in mouse. In Der p-induced mouse models, anti-IL-23p19 antibody treatment during allergen sensitization significantly diminished Der p allergic sensitization and several features of allergic asthma including the production of Th2 cytokines and the population of type 2 innate lymphoid cells in lungs. The activation of dendritic cells in lung-draining lymph nodes was also reduced by anti-IL-23 treatment. In murine lung alveolar type II-like epithelial cell line (MLE-12) cells, IL-23 blockade prevented cytokine responses to Der p stimulation, such as IL-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-33, and also bone marrow-derived dendritic cell activation. In conclusion, IL-23 is another important bronchial epithelial cell-driven cytokine which may contribute to the development of house dust mite allergic sensitization and asthma. Copyright © 2017 the American Physiological Society.

Evolving Concepts of Asthma

PubMed Central

Ray, Anuradha; Wenzel, Sally E.

2015-01-01

Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapies treated most patients with asthma similarly, with bronchodilators and corticosteroids, but these therapies had varying degrees of success. Similarly, despite initial studies that identified an underlying type 2 inflammation in the airways of patients with asthma, biologic therapies targeted toward these type 2 pathways were unsuccessful in all patients. These observations led to increased interest in phenotyping asthma. Clinical approaches, both biased and later unbiased/statistical approaches to large asthma patient cohorts, identified a variety of patient characteristics, but they also consistently identified the importance of age of onset of disease and the presence of eosinophils in determining clinically relevant phenotypes. These paralleled molecular approaches to phenotyping that developed an understanding that not all patients share a type 2 inflammatory pattern. Using biomarkers to select patients with type 2 inflammation, repeated trials of biologics directed toward type 2 cytokine pathways saw newfound success, confirming the importance of phenotyping in asthma. Further research is needed to clarify additional clinical and molecular phenotypes, validate predictive biomarkers, and identify new areas for possible interventions. PMID:26161792

Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications.

PubMed

Robinson, D; Humbert, M; Buhl, R; Cruz, A A; Inoue, H; Korom, S; Hanania, N A; Nair, P

2017-02-01

Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems. A number of well-recognized biomarkers have been linked to mechanisms involved in type 2 airway inflammation, including fractional exhaled nitric oxide, serum IgE, periostin, and blood and sputum eosinophils. These type 2 cytokines are targets for pharmaceutical intervention, and a number of therapeutic options are under clinical investigation for the management of patients with uncontrolled severe asthma. Anticipating and understanding the heterogeneity of asthma and subsequent improved characterization of different phenotypes and endotypes must guide the selection of treatment to meet individual patients' needs. © 2017 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Inflammation with Airway Remodeling.

PubMed

Woo, L N; Guo, W Y; Wang, X; Young, A; Salehi, S; Hin, A; Zhang, Y; Scott, J A; Chow, C W

2018-05-02

Animal models of allergic airways inflammation are useful tools in studying the pathogenesis of asthma and potential therapeutic interventions. The different allergic airways inflammation models available to date employ varying doses, frequency, duration and types of allergen, which lead to the development of different features of asthma; showing varying degrees of airways inflammation and hyper-responsiveness (AHR) and airways remodeling. Models that also exhibit airway remodeling, a key feature of asthma, in addition to AHR and airway inflammation typically require 5-12 weeks to develop. In this report, we describe a 4-week mouse model of house dust mite (HDM)-induced allergic airways inflammation, and compare the phenotypic features of two different doses of HDM exposures (10 µg and 25 µg) for 5 days/week with a well-characterized 8-week chronic HDM model. We found that 4 weeks of intranasal HDM (25 µg in 35 µl saline; 5 days/week) resulted in AHR, airway inflammation and airway remodeling that were comparable to the 8-week model. We conclude that this new 4-week HDM model is another useful tool in studies of human asthma that offers advantages of shorter duration for development and decreased costs when compared to other models that require longer durations of exposure (5-12 weeks) to develop.

Air pollution and asthma severity in adults

PubMed Central

Rage, Estelle; Siroux, Valérie; Künzli, Nino; Pin, Isabelle; Kauffmann, Francine

2009-01-01

Objectives There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. Methods Asthma severity over the last 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The 4-class severity score integrated clinical events and type of treatment. The 5-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991–1995. The second consisted in spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). Results Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O3-8hr) and the number of days (O3-days) with 8-hour ozone averages above 110 μg.m−3 (for a 36-day increase, equivalent to the inter quartile range, in O3-days, odds ratio (95% confidence interval) 2.22 (1.61–3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO2. Both exposure assessment methods and severity scores resulted in very similar findings. SO2 correlated with severity but reached statistical significance only for the model based assignment of exposure. Conclusions The observed associations between asthma severity and air pollution, in particular O3, support the hypothesis that air pollution at levels far below current standards increases asthma severity. PMID:19017701

Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-α Pathway

PubMed Central

Kim, Joo Young; Sohn, Jung Ho; Choi, Je-Min; Lee, Jae-Hyun; Hong, Chein-Soo; Lee, Joo-Shil; Park, Jung-Won

2012-01-01

The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model. PMID:23094102

The role of trait mindfulness in quality of life and asthma control among adolescents with asthma.

PubMed

Cillessen, Linda; van de Ven, Monique O; Karremans, Johan C

2017-08-01

The current study focused on the role of trait mindfulness in asthma-related quality of life (QoL) and asthma control in adolescent asthma patients. Furthermore, potential underlying mechanisms (general and asthma-specific stress) of this relationship were investigated. In this cross-sectional study, questionnaire data of 94 adolescents with asthma that were prescribed daily asthma medication were included. Two Structural Equation Models (SEMs), a direct model and an indirect model, were tested. We found that trait mindfulness was directly related to asthma-related QoL, but not to asthma control. The relationship between trait mindfulness and asthma-related QoL was explained by asthma-specific, but not by general stress. Furthermore, an indirect relation from mindfulness to asthma control via asthma-specific stress was found. Cross-sectional evidence for a relation between mindfulness and asthma-related QoL is found. These findings may point to the possibility that an intervention aimed at increasing mindfulness could be a promising tool to improve asthma-related QoL in adolescents via a decrease in asthma-specific stress. Copyright © 2017. Published by Elsevier Inc.

TSLP: A Key Regulator of Asthma Pathogenesis.

PubMed

West, Erin E; Kashyap, Mohit; Leonard, Warren J

2012-12-01

Asthma is a complex disorder of the airways that is characterized by T helper type 2 (Th2) inflammation. The pleiotrophic cytokine TSLP has emerged as an important player involved in orchestrating the inflammation seen in asthma and other atopic diseases. Early research elucidated the role of TSLP on CD4 + T cells, and recent work has revealed the impact of TSLP on multiple cell types. Furthermore, TSLP plays an important role in the sequential progression of atopic dermatitis to asthma, clarifying the key role of TSLP in the pathogenesis of asthma, a finding with therapeutic implications.

Patient preferences for community pharmacy asthma services: a discrete choice experiment.

PubMed

Naik-Panvelkar, Pradnya; Armour, Carol; Rose, John M; Saini, Bandana

2012-10-01

Specialized community pharmacy services, involving the provision of disease state management and care by pharmacists, have been developed and trialled and have demonstrated very good health outcomes. Most of these services have been developed from a healthcare professional perspective. However, for the future uptake and long-term sustainability of these services as well as for better and sustained health outcomes for patients, it is vital to gain an understanding of patients' preferences. We can then structure healthcare services to match these preferences and needs rather than around clinical viewpoints alone. The aim of this study was to elicit patient preferences for pharmacy-based specialized asthma services using a discrete choice experiment and to explore the value/importance that patients place on the different attributes of the asthma service. The existence of preference heterogeneity in the population was also investigated. The study was conducted with asthma patients who had recently experienced a specialized asthma management service at their pharmacy in New South Wales, Australia. Pharmacists delivering the asthma service mailed out the discrete choice questionnaires to participating patients at the end of 6 months of service provision. A latent class (LC) model was used to investigate each patient's strength of preference and preference heterogeneity for several key attributes related to asthma service provision: frequency of visits, access to pharmacist, interaction with pharmacy staff, availability of a private area for consultation, provision of lung function testing, type and depth of advice provision, number of days with asthma symptoms and cost of service. Eighty useable questionnaires (of 170 questionnaires sent out) were received (response rate 47.1%). The study identified various key elements of asthma services important to patients. Further, the LC analysis revealed three classes with differing patient preferences for levels of asthma service provision. Patients in the Minimalistic Model class valued provision of lung function testing and preferred more frequent service visits. Cost of service had a negative effect on service preference for patients in this class. Patients in the Partial Model class mainly derived utility from the provision of lung function testing and comprehensive advice at the pharmacy and also wanted more frequent service visits. The Holistic Model class patients considered all attributes of the service to be important when making a choice. While the majority of the service attributes had a positive effect on preference for patients in this class, cost of service and days with symptoms of asthma had a negative effect on service preference. These patients also preferred fewer service visits. The study identified various key attributes that are important to patients with respect to community pharmacy-based asthma services. The results also demonstrate the existence of preference heterogeneity in the population. Asthma service providers need to take these findings into consideration in the design and development of future service models so as to increase their uptake and ensure their long-term sustainability.

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

PubMed Central

Ionescu, Lavinia I.; Alphonse, Rajesh S.; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R.; Walsh, Kenneth

2012-01-01

Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow–derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the TH2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10–induced and IL-10–secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma. PMID:21903873

Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.

PubMed

Ionescu, Lavinia I; Alphonse, Rajesh S; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R; Walsh, Kenneth; Thébaud, Bernard

2012-02-01

Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.

Targeting key proximal drivers of type 2 inflammation in disease.

PubMed

Gandhi, Namita A; Bennett, Brandy L; Graham, Neil M H; Pirozzi, Gianluca; Stahl, Neil; Yancopoulos, George D

2016-01-01

Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype. More recently, efficacy was extended into a broad population of people with asthma. This argues that the Type 2 inflammation is broadly relevant across the severe asthma population if the key upstream drivers are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has shown significant clinical activity in diseases that are often co-morbid with asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting the hypothesis that targeting a central 'driver pathway' could benefit multiple allergic diseases.

Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma?

PubMed

Tournoy, K G; Hove, C; Grooten, J; Moerloose, K; Brusselle, G G; Joos, G F

2006-01-01

Non-specific anti-inflammatory medication is actually the treatment of choice for controlling the T-helper type 2 (Th-2) cell-driven airway inflammation in asthma. The induction of counterbalancing Th-1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side-effects. This is therefore probably not a valid option for the treatment of asthma. With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen-induced airway disease. The induction of antigen-specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non-atopic individuals and have the potential of becoming an effective means of preventing allergen-induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen-induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.

Multidimensional assessment of severe asthma: A systematic review and meta-analysis.

PubMed

Clark, Vanessa L; Gibson, Peter G; Genn, Grayson; Hiles, Sarah A; Pavord, Ian D; McDonald, Vanessa M

2017-10-01

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes. © 2017 Asian Pacific Society of Respirology.

Quality of asthma care under different primary care models in Canada: a population-based study.

PubMed

To, Teresa; Guan, Jun; Zhu, Jingqin; Lougheed, M Diane; Kaplan, Alan; Tamari, Itamar; Stanbrook, Matthew B; Simatovic, Jacqueline; Feldman, Laura; Gershon, Andrea S

2015-02-14

Previous research has shown variations in quality of care and patient outcomes under different primary care models. The objective of this study was to use previously validated, evidence-based performance indicators to measure quality of asthma care over time and to compare quality of care between different primary care models. Data were obtained for years 2006 to 2010 from the Ontario Asthma Surveillance Information System, which uses health administrative databases to track individuals with asthma living in the province of Ontario, Canada. Individuals with asthma (n=1,813,922) were divided into groups based on the practice model of their primary care provider (i.e., fee-for-service, blended fee-for-service, blended capitation). Quality of asthma care was measured using six validated, evidence-based asthma care performance indicators. All of the asthma performance indicators improved over time within each of the primary care models. Compared to the traditional fee-for-service model, the blended fee-for-service and blended capitation models had higher use of spirometry for asthma diagnosis and monitoring, higher rates of inhaled corticosteroid prescription, and lower outpatient claims. Emergency department visits were lowest in the blended fee-for-service group. Quality of asthma care improved over time within each of the primary care models. However, the amount by which they improved differed between the models. The newer primary care models (i.e., blended fee-for-service, blended capitation) appear to provide better quality of asthma care compared to the traditional fee-for-service model.

Type 2 innate lymphoid cells: at the cross-roads in allergic asthma.

PubMed

van Rijt, Leonie; von Richthofen, Helen; van Ree, Ronald

2016-07-01

Allergic asthma is a chronic inflammatory disease of the lower airways that affects millions of people worldwide. Allergic asthma is a T helper 2 cell (Th2)-mediated disease, in which Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 are closely associated with the symptoms. IL-4 is needed by B cells to switch toward an IgE response, IL-5 recruits and activates eosinophils while IL-13 increases mucus production. The identification of type 2 innate lymphoid cells (ILC2), which are able to rapidly produce large amounts of IL-5 and IL-13 in response to epithelial derived cytokines, implicated a new key player besides Th2 cells. ILCs constitute a family of innate lymphocytes distinct from T and B cells. ILC2s are located in various epithelial compartments in mice and human, including the lung. The recent finding of increased numbers of ILC2s in the airways of severe asthma patients prompts further research to clarify their immunological function. Murine studies have shown that ILC2s are an early innate source of IL-5 and IL-13 after allergen exposure, which induce airway eosinophilic infiltration, mucus hyperproduction, and airway hyperresponsiveness but not allergen-specific IgE production. ILC2s contribute to the initiation as well as to the maintenance of the adaptive type 2 immune response. Here, we review the recent progress on our understanding of the role of ILC2s in the immunopathology of allergic asthma, in particular by studies using murine models which have elucidated fundamental mechanisms by which ILC2s act.

A systematic review of predictive models for asthma development in children.

PubMed

Luo, Gang; Nkoy, Flory L; Stone, Bryan L; Schmick, Darell; Johnson, Michael D

2015-11-28

Asthma is the most common pediatric chronic disease affecting 9.6 % of American children. Delay in asthma diagnosis is prevalent, resulting in suboptimal asthma management. To help avoid delay in asthma diagnosis and advance asthma prevention research, researchers have proposed various models to predict asthma development in children. This paper reviews these models. A systematic review was conducted through searching in PubMed, EMBASE, CINAHL, Scopus, the Cochrane Library, the ACM Digital Library, IEEE Xplore, and OpenGrey up to June 3, 2015. The literature on predictive models for asthma development in children was retrieved, with search results limited to human subjects and children (birth to 18 years). Two independent reviewers screened the literature, performed data extraction, and assessed article quality. The literature search returned 13,101 references in total. After manual review, 32 of these references were determined to be relevant and are discussed in the paper. We identify several limitations of existing predictive models for asthma development in children, and provide preliminary thoughts on how to address these limitations. Existing predictive models for asthma development in children have inadequate accuracy. Efforts to improve these models' performance are needed, but are limited by a lack of a gold standard for asthma development in children.

Proximity to Industrial Food Animal Production and Asthma Exacerbations in Pennsylvania, 2005-2012.

PubMed

Rasmussen, Sara G; Casey, Joan A; Bandeen-Roche, Karen; Schwartz, Brian S

2017-03-31

The research on industrial food animal production (IFAP) and asthma exacerbations in the United States has relied on small sample sizes and/or self-reported outcomes. We assessed associations of proximity to large-scale and densely stocked swine and dairy/veal IFAP with three types of asthma exacerbations: hospitalizations, emergency encounters, and oral corticosteroid (OCS) medication orders from Geisinger Clinic in Pennsylvania. We used a diagnosis code ( International Classification of Diseases, 9th Revision, Clinical Modification code 493.x) and medication orders from electronic health records to identify these exacerbations among asthma patients ( n = 35,269) from 2005-2012. We compared residential proximity to swine or dairy/veal IFAP (dichotomized as <3 miles (4.8 km) or ≥3 miles) among asthma patients with and without exacerbations and estimated odds ratios using multilevel logistic regression. In adjusted models, proximity to IFAP was associated (odds ratio (95% confidence interval)) with OCS orders (1.11 (1.04-1.19)) and hospitalizations (1.29 (1.15-1.46)), but not emergency encounters (1.12 (0.91-1.37)). This study contributes to growing evidence that IFAP may impact health, in this case clinically-documented asthma exacerbations. No prior study has evaluated the association of IFAP and clinically-documented asthma exacerbations in the United States.

ADAM33 polymorphisms are associated with asthma and a distinctive palm dermatoglyphic pattern

PubMed Central

XUE, WEILIN; HAN, WEI; ZHOU, ZHAO-SHAN

2013-01-01

A close correlation between asthma and palm dermatoglyphic patterns has been observed in previous studies, but the underlying genetic mechanisms have not been investigated. A disintegrin and metalloprotein-33 (ADAM33) polymorphisms are important in the development of asthma and other atopic diseases. To investigate the underlying mechanisms of the association between asthma and distinctive palm dermatoglyphic patterns, thirteen ADAM33 single-nucleotide polymorphisms (SNPs) were analyzed for the association between asthma and palm dermatoglyphic patterns in a population of 400 asthmatic patients and 200 healthy controls. Based on the results, five SNPs, rs44707 (codominant model, P=0.031; log-additive model, P=0.0084), rs2787094 (overdominant model, P=0.049), rs678881 (codominant model, P=0.028; overdominant model, P=0.0083), rs677044 (codominant model, P=0.013; log-additive model, P=0.0033) and rs512625 (dominant model, P=0.033), were associated with asthma in this population. Two SNPs, rs44707 (dominant model, P=0.042) and rs2787094 (codominant model, P=0.014; recessive model, P=0.0038), were observed in the asthma patients with the distinctive palm pattern. As rs44707 and rs2787094 are associated with asthma and a distinctive palm pattern, the data suggest that ADAM33 polymorphisms are correlated with asthma and may be the underlying genetic basis of the association between asthma and palm dermatoglyphic patterns. PMID:24141861

The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review

PubMed Central

Fathima, Mariam; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol L.

Objective The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. Methods An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Results Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. Conclusions The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist. PMID:24367463

The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review.

PubMed

Fathima, Mariam; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol L

2013-10-01

The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist.

Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines.

PubMed

Brasier, Allan R; Victor, Sundar; Boetticher, Gary; Ju, Hyunsu; Lee, Chang; Bleecker, Eugene R; Castro, Mario; Busse, William W; Calhoun, William J

2008-01-01

Asthma is a heterogeneous clinical disorder. Methods for objective identification of disease subtypes will focus on clinical interventions and help identify causative pathways. Few studies have explored phenotypes at a molecular level. We sought to discriminate asthma phenotypes on the basis of cytokine profiles in bronchoalveolar lavage (BAL) samples from patients with mild-moderate and severe asthma. Twenty-five cytokines were measured in BAL samples of 84 patients (41 severe, 43 mild-moderate) using bead-based multiplex immunoassays. The normalized data were subjected to statistical and informatics analysis. Four groups of asthmatic profiles could be identified on the basis of unsupervised analysis (hierarchical clustering) that were independent of treatment. One group, enriched in patients with severe asthma, showed differences in BAL cellular content, reductions in baseline pulmonary function, and enhanced response to methacholine provocation. Ten cytokines were identified that accurately predicted this group. Classification methods for predicting methacholine sensitivity were developed. The best model analysis predicted hyperresponders with 88% accuracy in 10 trials by using a 10-fold cross-validation. The cytokines that contributed to this model were IL-2, IL-4, and IL-5. On the basis of this classifier, 3 distinct hyperresponder classes were identified that varied in BAL eosinophil count and PC20 methacholine. Cytokine expression patterns in BAL can be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Further biomarker discovery in BAL may be informative.

The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship.

PubMed

Colice, Gene; Price, David; Gerhardsson de Verdier, Maria; Rabon-Stith, Karma; Ambrose, Christopher; Cappell, Katherine; Irwin, Debra E; Juneau, Paul; Vlahiotis, Anna

2017-01-01

DPP-4 may regulate immunological pathways implicated in asthma. Assessing whether DPP-4 inhibitor (DPP-4i) use might affect asthma control is clinically important because DPP-4i use in type 2 diabetes mellitus management (T2DM) is increasing. This study evaluated associations between DPP-4i use and asthma control. This was a retrospective, observational, matched cohort study using administrative claims in the MarketScan ® Commercial Claims and Encounters (Commercial) and Medicare Supplemental and Coordination of Benefits (Medicare Supplemental) databases. Adult asthma patients initiating an oral DPP-4i or a non-DPP-4i between November 1, 2006 and March 31, 2014 were included. Patients were followed for asthma-related outcomes for 12 months after initiation of the antidiabetes medication. Outcomes included risk-domain asthma control (RDAC), defined as no asthma hospitalizations, no lower respiratory tract infections, and no oral corticosteroid (OCS) prescriptions; overall asthma control (RDAC criteria plus limited short-acting beta agonist use); treatment stability (RDAC criteria plus no increase of ≥50% in inhaled corticosteroid dose or addition of other asthma therapy); and severe asthma exacerbation rates (asthma-related hospitalizations, emergency room visits, or acute treatments with OCS). Comparisons were made between two matched cohorts (DPP-4i vs. non-DPP-4i initiators) using multivariable logistic regression and generalized linear modeling. Covariates included baseline demographic and clinical characteristics related to asthma and T2DM. The adjusted odds of achieving RDAC (odds ratio [OR]: 1.05; 95% CI: 0.964 to 1.147), overall asthma control (OR: 1.04; 95% CI: 0.956 to 1.135), and treatment stability (OR: 1.04; 95% CI: 0.949 to 1.115) did not differ between the DPP-4i and non-DPP-4i cohorts. A difference was not found between cohorts in severe asthma exacerbation rates during the 12 months following initiation of antidiabetes treatment (mean = 0.32 vs. 0.34 exacerbations per subject-year, respectively; p =0.064). Asthma control was similar between patients initiating DPP-4i and non-DPP-4i antidiabetes medications, suggesting no association between DPP-4i use and asthma control.

Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

PubMed Central

Wang, Wenrui; Zhu, Rongrong; Xie, Qian; Li, Ang; Xiao, Yu; Li, Kun; Liu, Hui; Cui, Daxiang; Chen, Yihan; Wang, Shilong

2012-01-01

Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy. PMID:22888226

Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

PubMed

Deliu, M; Yavuz, T S; Sperrin, M; Belgrave, D; Sahiner, U M; Sackesen, C; Kalayci, O; Custovic, A

2018-01-01

Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

A current picture of asthma diagnosis, severity, and control in a low-income minority preteen population.

PubMed

Clark, Noreen M; Dodge, Julia A; Shah, Smita; Thomas, Lara J; Andridge, Rebecca R; Awad, Daniel

2010-03-01

Asthma severity, control, type of medical regimen provided, and compliance with it are not well understood in minority patients at the transition stage from childhood to adolescence. Describe the level of asthma severity and control and the clinical regimens provided to a large population of low-income, African American children at this developmentally significant period. Parents of 1292 children with asthma among 6827 preteens in 19 middle schools in predominantly African American (94%), low-income neighborhoods in Detroit, Michigan, were enrolled in the study. Data were collected through self-administered survey and telephone interviews and were useable for 936 participants. Study queries related to demographics, asthma symptoms, and medication use. Mixed effects models with a random intercept for school were used to determine severity and control and the association of medical regimens to these. Sixty-seven percent of children with probable asthma had received a physician's diagnosis. Being female was associated with being undiagnosed (p = .02). Forty-seven with no diagnosis had persistent asthma and 10% of these were classified as severe. Sixty-eight percent with a diagnosis and asthma medicine prescriptions were not controlled. Compliant use of controller medicine was associated with poorer asthma control compared to noncompliant controller users (p = .04) and reliever-only users (p < .001). Thirty-nine percent of children had controller medicine; of those 40% were not compliant with controller use; 9% nebulized their controller medicine. Care provided low-income minority children at an important stage in their development was not consistent with guidelines for asthma control. Therapy choices for treatment did not account for the actual level of their symptoms. Lack of an asthma diagnosis was significant in the population. Adolescent girls were at risk for not receiving a diagnosis. Patient compliance with asthma regimens was limited. Both clinician and patient education regarding effective asthma management appears needed regarding preteens in low-income minority communities.

Asthma Diagnosis, Severity, Control and Medication Use In Low Income Minority Preteens

PubMed Central

Clark, Noreen M.; Dodge, Julia A.; Shah, Smita; Thomas, Lara J.; Andridge, Rebecca R.; Awad, Daniel

2010-01-01

Background Asthma severity, control, type of medical regimen provided and compliance with it are not well understood in minority patients at the transition stage from childhood to adolescence. Objective Identify factors in clinical practice and patient behavior associated with negative outcomes for children at this developmentally significant period. Methods Parents of 1292 children with asthma among 6827 pre-teens in 19 middle schools in predominantly African American (94%), low income neighborhoods in Detroit, Michigan were enrolled. Data collected through self administered survey and telephone interviews were useable for 936 parents. Study queries related to demographics, asthma symptoms, and medication use. Mixed effects models with a random intercept for school used to determine severity and control and association of medical regimens to these. Results Sixty-seven percent children with probable asthma had received a physician's diagnosis. Being female was associated with being undiagnosed (p=0.02); 47% with no diagnosis had persistent asthma and 68% with a diagnosis and asthma medicines were not controlled. Over half with a diagnosis and no medicine were not controlled. Thirty nine percent had controller medicine; 40% were not compliant with controller use; 9% nebulized controller medicine. Compliant use of controller medicine was not associated with asthma control (p=0.001). Conclusions Lack of an asthma diagnosis was significant in these low income communities. Adolescent girls were at risk for not receiving a diagnosis. Regimens provided children at an important stage in their development were not consistent with therapies recommended for asthma control. Patient compliance with asthma regimens was low. Both clinical and patient education regarding effective asthma management is needed regarding pre teens in low income minority communities. Clinical Implications Diagnosis and medical therapy choices for low income, African American pre-adolescents may not account for the actual level of their symptoms. Asthma is likely to be uncontrolled at this significant developmental stage in this population. Girls may be at risk for diagnosis failure. PMID:20170321

Monitoring asthma control in children with allergies by soft computing of lung function and exhaled nitric oxide.

PubMed

Pifferi, Massimo; Bush, Andrew; Pioggia, Giovanni; Di Cicco, Maria; Chinellato, Iolanda; Bodini, Alessandro; Macchia, Pierantonio; Boner, Attilio L

2011-02-01

Asthma control is emphasized by new guidelines but remains poor in many children. Evaluation of control relies on subjective patient recall and may be overestimated by health-care professionals. This study assessed the value of spirometry and fractional exhaled nitric oxide (FeNO) measurements, used alone or in combination, in models developed by a machine learning approach in the objective classification of asthma control according to Global Initiative for Asthma guidelines and tested the model in a second group of children with asthma. Fifty-three children with persistent atopic asthma underwent two to six evaluations of asthma control, including spirometry and FeNO. Soft computing evaluation was performed by means of artificial neural networks and principal component analysis. The model was then tested in a cross-sectional study in an additional 77 children with allergic asthma. The machine learning method was not able to distinguish different levels of control using either spirometry or FeNO values alone. However, their use in combination modeled by soft computing was able to discriminate levels of asthma control. In particular, the model is able to recognize all children with uncontrolled asthma and correctly identify 99.0% of children with totally controlled asthma. In the cross-sectional study, the model prospectively identified correctly all the uncontrolled children and 79.6% of the controlled children. Soft computing analysis of spirometry and FeNO allows objective categorization of asthma control status.

Altered expression of IL-18 binding protein and IL-18 receptor in basophils and mast cells of asthma patients.

PubMed

Wang, Zhiyun; Liu, Zhining; Wang, Ling; Wang, Junling; Chen, Liping; Xie, Hua; Zhang, Huiyun; He, Shaoheng

2018-05-01

IL-18 is likely to contribute to asthma. However, little is known regarding the role of IL-18 binding protein (BP) and IL-18 receptor (R) in asthma. Because the action of IL-18 in the body is regulated by IL-18BP and mast cells and basophils are key cell types involved in asthma, we investigated the expression of IL-18, IL-18BP and IL-18R in basophils and mast cells using flow cytometry and a mouse asthma model. We found that among basophils, approximately 53% and 51% were IL-18 + , 85% and 81% were IL-18BP + basophils, and 19.8% and 8.6% were IL-18R + in healthy control (HC) and asthmatic blood, respectively. The allergens tested had little effect on the expression of IL-18 and related factors. Only 3.5%, 14.3% and 2.4% of dispersed mast cells expressed IL-18, IL-18BP and IL-18R, respectively, in asthmatic sputum. In a mouse asthma model, OVA-sensitized mice exhibited decreased IL-18BP + but increased IL-18R + basophils in their blood. IL-18 increased the number of basophils but eliminated IL-18BP + basophils in mouse blood. IL-18 increased the number of mast cells and IL-18R + mast cells in the lung as well as increased the mast cell numbers and IL-18BP + mast cells in the bronchoalveolar lavage fluid (BALF) of OVA-sensitized mice. Thus, basophils and mast cells may be involved in asthma pathogenesis via an IL-18-associated mechanism. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Modelling Drug Administration Regimes for Asthma: A Romanian Experience

ERIC Educational Resources Information Center

Andras, Szilard; Szilagyi, Judit

2010-01-01

In this article, we present a modelling activity, which was a part of the project DQME II (Developing Quality in Mathematics Education, for more details see http://www.dqime.uni-dortmund.de) and some general observations regarding the maladjustments and rational errors arising in such type of activities.

Racial Disparities in Asthma Hospitalizations Following Implementation of the Smoke-Free Air Law, Michigan, 2002–2012

PubMed Central

Marchese, Michelle E.; Miller, Corinne E.; Wahl, Robert L.; Li, Yun

2015-01-01

Introduction Exposure to secondhand smoke has immediate adverse respiratory and cardiovascular effects. A growing body of literature examining health trends following the implementation of public smoking bans has demonstrated reductions in the rates of myocardial infarction and stroke, but there has been no extensive work examining asthma hospitalizations. The aim of this study was to determine the impact of the Michigan Smoke-Free Air Law (SFA law) on the rate of asthma hospitalizations among adults in Michigan and to determine any differential effects by race or sex. Methods Data on adult asthma hospitalizations were obtained from the Michigan Inpatient Database (MIDB). Poisson regression was used to model relative risks for asthma hospitalization following the SFA law with adjustments for sex, race, age, insurance type, and month of year. Race-based and sex-based analyses were performed. Results In the first year following implementation of the SFA law, adjusted adult asthma hospitalization rates decreased 8% (95% confidence interval [CI], 7%–10%; P < .001). While asthma hospitalization rates for both blacks and whites declined in the 12 months following implementation of the SFA law, blacks were 3% more likely to be hospitalized for asthma than whites (95% CI, 0%–7%; P = .04). The rate of decline in adult asthma hospitalizations did not differ by sex. Conclusion The implementation of the SFA law was associated with a reduction in adult asthma hospitalization rates, with a greater decrease in hospitalization rates for whites compared with blacks. These results demonstrate that the SFA law is protecting the public’s health and saving health care costs. PMID:26583573

Self-reported asthma and allergies in top athletes compared to the general population - results of the German part of the GA2LEN-Olympic study 2008

PubMed Central

2010-01-01

Background Prevalence of asthma and allergies in top athletes is high. However, most previous studies did not include a general population comparison group. We aimed to compare the prevalence of asthma, allergies and medical treatment in different groups of German top athletes to the general population. Methods Prior to the 2008 Summer Olympic Games, 291 German candidates for participation (65%) completed a questionnaire on respiratory and allergic symptoms. Results were compared to those of a general population study in Germany (n = 2425, response 68%). Furthermore, associations between types of sports and the self-reported outcomes were calculated. All models were adjusted for age, sex, level of education and smoking. Results Athletes reported significantly more doctors' diagnosed asthma (17% vs. 7%), more current use of asthma medication (10% vs. 4%) and allergic rhinitis (25% vs. 17%) compared to the general population. After adjustment, top athletes only had an increased Odds Ratio for doctor's diagnosed asthma (OR: 1.6; 95% CI 1.1-2.5). Compared to the general population, athletes in endurance sports had an increased OR for doctor's diagnosed asthma (2.4; 1.5-3.8) and current use of asthma medication (1.8; 1.0-3.4). In this group, current wheeze was increased when use of asthma medication was taken into account (1.8; 1.1-2.8). For other groups of athletes, no significantly increased ORs were observed. Conclusions Compared to the general population, an increased risk of asthma diagnosis and treatment was shown for athletes involved in endurance sports. This might be due to a better medical surveillance and treatment of these athletes. PMID:21118543

Innate lymphoid cells and asthma.

PubMed

Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

2014-04-01

Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Assessment of variations in control of asthma over time.

PubMed

Combescure, C; Chanez, P; Saint-Pierre, P; Daurès, J P; Proudhon, H; Godard, P

2003-08-01

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Pollen exposure and hospitalization due to asthma exacerbations: daily time series in a European city.

PubMed

Osborne, Nicholas J; Alcock, Ian; Wheeler, Benedict W; Hajat, Shakoor; Sarran, Christophe; Clewlow, Yolanda; McInnes, Rachel N; Hemming, Deborah; White, Mathew; Vardoulakis, Sotiris; Fleming, Lora E

2017-10-01

Exposure to pollen can contribute to increased hospital admissions for asthma exacerbation. This study applied an ecological time series analysis to examine associations between atmospheric concentrations of different pollen types and the risk of hospitalization for asthma in London from 2005 to 2011. The analysis examined short-term associations between daily pollen counts and hospital admissions in the presence of seasonal and long-term patterns, and allowed for time lags between exposure and admission. Models were adjusted for temperature, precipitation, humidity, day of week, and air pollutants. Analyses revealed an association between daily counts (continuous) of grass pollen and adult hospital admissions for asthma in London, with a 4-5-day lag. When grass pollen concentrations were categorized into Met Office pollen 'alert' levels, 'very high' days (vs. 'low') were associated with increased admissions 2-5 days later, peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days. Increased admissions were also associated with 'high' versus 'low' pollen days at a 3-day lag. Results from tree pollen models were inconclusive and likely to have been affected by the shorter pollen seasons and consequent limited number of observation days with higher tree pollen concentrations. Future reductions in asthma hospitalizations may be achieved by better understanding of environmental risks, informing improved alert systems and supporting patients to take preventive measures.

Pollen exposure and hospitalization due to asthma exacerbations: daily time series in a European city

NASA Astrophysics Data System (ADS)

Osborne, Nicholas J.; Alcock, Ian; Wheeler, Benedict W.; Hajat, Shakoor; Sarran, Christophe; Clewlow, Yolanda; McInnes, Rachel N.; Hemming, Deborah; White, Mathew; Vardoulakis, Sotiris; Fleming, Lora E.

2017-10-01

Exposure to pollen can contribute to increased hospital admissions for asthma exacerbation. This study applied an ecological time series analysis to examine associations between atmospheric concentrations of different pollen types and the risk of hospitalization for asthma in London from 2005 to 2011. The analysis examined short-term associations between daily pollen counts and hospital admissions in the presence of seasonal and long-term patterns, and allowed for time lags between exposure and admission. Models were adjusted for temperature, precipitation, humidity, day of week, and air pollutants. Analyses revealed an association between daily counts (continuous) of grass pollen and adult hospital admissions for asthma in London, with a 4-5-day lag. When grass pollen concentrations were categorized into Met Office pollen `alert' levels, `very high' days (vs. `low') were associated with increased admissions 2-5 days later, peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days. Increased admissions were also associated with `high' versus `low' pollen days at a 3-day lag. Results from tree pollen models were inconclusive and likely to have been affected by the shorter pollen seasons and consequent limited number of observation days with higher tree pollen concentrations. Future reductions in asthma hospitalizations may be achieved by better understanding of environmental risks, informing improved alert systems and supporting patients to take preventive measures.

Body Mass Index and Comorbidities in Adult Severe Asthmatics

PubMed Central

Bruno, Andreina; Pace, Elisabetta; Cibella, Fabio; Chanez, Pascal

2014-01-01

Both severe asthma and obesity are growing health problems. Severe asthma leads to a poor quality of life. The relationship among BMI, comorbidities, and severe asthma control in adults is still unclear. The aim of the study is to better understand the effect of the comorbidities as atopy, type II diabetes, OSAS, gastroesophageal reflux, hypertension, cardiovascular diseases, osteoporosis, infections, and psychological factors with BMI on asthma control in a cohort of adult severe asthmatics. One hundred and two patients were enrolled in a cross-sectional study assessing asthma control, treatments, pulmonary function, inflammatory markers, and comorbidities. Patients were divided into 3 classes according to BMI: normal weight, overweight, and obese. We found that the optimal state of asthma control is lower. whereas the score of Asthma Control Questionnaire, the number of asthma exacerbations during last year, the oral corticosteroids requirement during the previous year, and the LABA treatments are higher in obese than in overweight and normal weight severe asthmatics. The number of subjects with type II diabetes and OSAS are higher among obese and overweight patients than in normal weight asthmatics. In conclusion, BMI represents per se a factor for the deterioration in disease control in severe asthma. PMID:24987694

The association of intrafamilial violence against children with symptoms of atopic and non-atopic asthma: A cross-sectional study in Salvador, Brazil.

PubMed

Bonfim, Camila Barreto; dos Santos, Darci Neves; Barreto, Maurício Lima

2015-12-01

This study aims to describe the types of intrafamilial violence perpetrated against children according to living conditions, family factors, and child characteristics, and to identify the association between types of intrafamilial violence and asthma symptoms in atopic and non-atopic children. A cross-sectional study was carried out with 1,370 caregivers as part of the Social Changes, Asthma and Allergy in Latin America (SCAALA) study, conducted in 2006 in Brazil. The study population was selected by random sampling. The main outcome measures were atopic and non-atopic asthma. We investigate the association between intrafamilial violence and asthma symptoms in atopic and non-atopic children. A backward multivariate logistic polytomous regression was performed to verify the main association. Nonviolent discipline (NVD) and maltreatment nonviolent discipline (MNVD) were positively associated with non-atopic asthma symptoms (NVD: odds ratio (OR)=1.95/95% confidence interval (CI)=1.17-3.25; MNVD: OR=1.95/95% CI=1.19-3.20). However, for the most severe intrafamilial violence, this association was not found after control of potential confounders. This study demonstrates the effect of types of intrafamilial violence on non-atopic asthma. Intrafamilial violence against children represents one more component in the determination of non-atopic asthma in Latin America. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Innate lymphoid cells in asthma: Will they take your breath away?

PubMed Central

Kim, Hye Young; Umetsu, Dale. T.; Dekruyff, Rosemarie H.

2016-01-01

Asthma is a complex and heterogeneous disease that is characterized by airway hyperreactivity (AHR) and airway inflammation. Although asthma was long thought to be driven by allergen-reactive Th2 cells, it has recently become clear that the pathogenesis of asthma is more complicated and associated with multiple pathways and cell types. A very exciting recent development was the discovery of innate lymphoid cells (ILCs) as key players in the pathogenesis of asthma. ILCs do not express antigen receptors but react promptly to “danger signals” from inflamed tissue and produce an array of cytokines that direct the ensuing immune response. The roles of ILCs may differ in distinct asthma phenotypes. ILC2s may be critical for initiation of adaptive immune responses in inhaled allergen-driven AHR, but may also function independently of adaptive immunity, mediating influenza-induced AHR. ILC2s also contribute to resolution of lung inflammation through their production of amphiregulin. Obesity-induced asthma, is associated with expansion of IL-17A-producing ILC3s in the lungs. Furthermore, ILCs may also contribute to steroid-resistant asthma. Although the precise roles of ILCs in different types of asthma are still under investigation, it is clear that inhibition of ILC function represents a potential target that could provide novel treatments for asthma. PMID:26891006

Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.

PubMed

Bochkov, Yury A; Watters, Kelly; Ashraf, Shamaila; Griggs, Theodor F; Devries, Mark K; Jackson, Daniel J; Palmenberg, Ann C; Gern, James E

2015-04-28

Members of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared with other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We report here that expression of human cadherin-related family member 3 (CDHR3) enables the cells normally unsusceptible to RV-C infection to support both virus binding and replication. A coding single nucleotide polymorphism (rs6967330, C529Y) was previously linked to greater cell-surface expression of CDHR3 protein, and an increased risk of wheezing illnesses and hospitalizations for childhood asthma. Compared with wild-type CDHR3, cells transfected with the CDHR3-Y529 variant had about 10-fold increases in RV-C binding and progeny yields. We developed a transduced HeLa cell line (HeLa-E8) stably expressing CDHR3-Y529 that supports RV-C propagation in vitro. Modeling of CDHR3 structure identified potential binding sites that could impact the virus surface in regions that are highly conserved among all RV-C types. Our findings identify that the asthma susceptibility gene product CDHR3 mediates RV-C entry into host cells, and suggest that rs6967330 mutation could be a risk factor for RV-C wheezing illnesses.

Role of community pharmacists in asthma - Australian research highlighting pathways for future primary care models.

PubMed

Saini, B; Krass, I; Smith, L; Bosnic-Anticevich, S; Armour, C

2011-01-01

Asthma is one of the most common chronic conditions affecting the Australian population. Amongst primary healthcare professionals, pharmacists are the most accessible and this places pharmacists in an excellent position to play a role in the management of asthma. Globally, trials of many community pharmacy-based asthma care models have provided evidence that pharmacist delivered interventions can improve clinical, humanistic and economic outcomes for asthma patients. In Australia, a decade of coordinated research efforts, in various aspects of asthma care, has culminated in the implementation trial of the Pharmacy Asthma Management Service (PAMS), a comprehensive disease management model.There has been research investigating asthma medication adherence through data mining, ways in which usual asthma care can be improved. Our research has focused on self-management education, inhaler technique interventions, spirometry trials, interprofessional models of care, and regional trials addressing the particular needs of rural communities. We have determined that inhaler technique education is a necessity and should be repeated if correct technique is to be maintained. We have identified this effectiveness of health promotion and health education, conducted within and outside the confines of the pharmacy, in public for a and settings such as schools, and established that this outreach role is particularly well received and increases the opportunity for people with asthma to engage in their asthma management.Our research has identified that asthma patients have needs which pharmacists delivering specialized models of care, can address. There is a lot of evidence for the effectiveness of asthma care by pharmacists, the future must involve integration of this role into primary care.

Weather elements, chemical air pollutants and airborne pollen influencing asthma emergency room visits in Szeged, Hungary: performance of two objective weather classifications

NASA Astrophysics Data System (ADS)

Makra, László; Puskás, János; Matyasovszky, István; Csépe, Zoltán; Lelovics, Enikő; Bálint, Beatrix; Tusnády, Gábor

2015-09-01

Weather classification approaches may be useful tools in modelling the occurrence of respiratory diseases. The aim of the study is to compare the performance of an objectively defined weather classification and the Spatial Synoptic Classification (SSC) in classifying emergency department (ED) visits for acute asthma depending from weather, air pollutants, and airborne pollen variables for Szeged, Hungary, for the 9-year period 1999-2007. The research is performed for three different pollen-related periods of the year and the annual data set. According to age and gender, nine patient categories, eight meteorological variables, seven chemical air pollutants, and two pollen categories were used. In general, partly dry and cold air and partly warm and humid air aggravate substantially the symptoms of asthmatics. Our major findings are consistent with this establishment. Namely, for the objectively defined weather types favourable conditions for asthma ER visits occur when an anticyclonic ridge weather situation happens with near extreme temperature and humidity parameters. Accordingly, the SSC weather types facilitate aggravating asthmatic conditions if warm or cool weather occur with high humidity in both cases. Favourable conditions for asthma attacks are confirmed in the extreme seasons when atmospheric stability contributes to enrichment of air pollutants. The total efficiency of the two classification approaches is similar in spite of the fact that the methodology for derivation of the individual types within the two classification approaches is completely different.

Weather elements, chemical air pollutants and airborne pollen influencing asthma emergency room visits in Szeged, Hungary: performance of two objective weather classifications.

PubMed

Makra, László; Puskás, János; Matyasovszky, István; Csépe, Zoltán; Lelovics, Enikő; Bálint, Beatrix; Tusnády, Gábor

2015-09-01

Weather classification approaches may be useful tools in modelling the occurrence of respiratory diseases. The aim of the study is to compare the performance of an objectively defined weather classification and the Spatial Synoptic Classification (SSC) in classifying emergency department (ED) visits for acute asthma depending from weather, air pollutants, and airborne pollen variables for Szeged, Hungary, for the 9-year period 1999-2007. The research is performed for three different pollen-related periods of the year and the annual data set. According to age and gender, nine patient categories, eight meteorological variables, seven chemical air pollutants, and two pollen categories were used. In general, partly dry and cold air and partly warm and humid air aggravate substantially the symptoms of asthmatics. Our major findings are consistent with this establishment. Namely, for the objectively defined weather types favourable conditions for asthma ER visits occur when an anticyclonic ridge weather situation happens with near extreme temperature and humidity parameters. Accordingly, the SSC weather types facilitate aggravating asthmatic conditions if warm or cool weather occur with high humidity in both cases. Favourable conditions for asthma attacks are confirmed in the extreme seasons when atmospheric stability contributes to enrichment of air pollutants. The total efficiency of the two classification approaches is similar in spite of the fact that the methodology for derivation of the individual types within the two classification approaches is completely different.

Prevalence and duration of social security benefits allowed to workers with asthma in Brazil in 2008.

PubMed

Branco, Anadergh Barbosa de Abreu; Ildefonso, Simone de Andrade Goulart

2012-01-01

To determine the prevalence and duration of social security benefits (SSBs) claims to registered workers with asthma in Brazil by the Brazilian National Institute of Social Security in 2008. This was a retrospective, descriptive study, based on information obtained from the Brazilian Unified Benefit System database, on the number of SSB claims granted to registered workers with asthma in 2008. The reference population was the monthly mean number of workers registered in the Brazilian Social Registry Database in 2008. The variables studied were type of economic activity, gender, age, and type/duration of the SSB claim. The relationship between work and asthma was evaluated by the prevalence ratio (PR) between work-related and non-work-related SSB claims for asthma. In 2008, 2,483 SSB claims were granted for asthma, with a prevalence of 7.5 allowances per 100,000 registered workers. The prevalence was higher among females than among males (PR = 2.1 between the sexes). Workers > 40 years of age were 2.5 times more likely to be granted an SSB claim for asthma than were younger workers. The prevalence was highest among workers engaged in the following types of economic activity: sewage, wood and wood product manufacturing, and furniture manufacturing (78.8, 22.4, and 22.2 claims/100,000 registered workers, respectively). The median (interquartile range) duration of SSB claims for asthma was 49 (28-87) days. Asthma is a major cause of sick leave, and its etiology has a strong occupational component. This has a major impact on employers, employees, and the social security system. Being female, being > 40 years of age, and working in the areas of urban sanitation/sewage, wood and wood product manufacturing, and furniture manufacturing increase the chance of sick leave due to asthma.

A Mechanistic Role for Type III IFN-λ1 in Asthma Exacerbations Mediated by Human Rhinoviruses

PubMed Central

Miller, E. Kathryn; Hernandez, Johanna Zea; Wimmenauer, Vera; Shepherd, Bryan E.; Hijano, Diego; Libster, Romina; Serra, M. Elina; Bhat, Niranjan; Batalle, Juan P.; Mohamed, Yassir; Reynaldi, Andrea; Rodriguez, Andrea; Otello, Monica; Pisapia, Nestor; Bugna, Jimena; Bellabarba, Miguel; Kraft, David; Coviello, Silvina; Ferolla, F. Martin; Chen, Aaron; London, Stephanie J.; Siberry, George K.; Williams, John V.

2012-01-01

Rationale: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear. Objectives: To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing. Methods: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma. Measurements and Main Results: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21–2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-λ1 levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-λ1, children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57–2.46; P = 0.66). Conclusions: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-λ1 responses mediate exacerbations caused by HRV. Modulation of IFN- λ1 should be studied as a therapeutic target for exacerbations caused by HRV. PMID:22135341

Mitochondrial Function in Allergic Disease.

PubMed

Iyer, Divyaanka; Mishra, Navya; Agrawal, Anurag

2017-05-01

The connections between allergy, asthma and metabolic syndrome are becoming increasingly clear. Recent research suggests a unifying mitochondrial link between the diverse phenotypes of these interlinked morbidities. The scope of this review is to highlight cellular mechanisms, epidemiology and environmental allergens influencing mitochondrial function and its importance in allergy and asthma. We briefly also consider the potential of mitochondria-targeted therapies in prevention and cure. Recent research has shown allergy, asthma and metabolic syndrome to be linked to mitochondrial dysfunction. Environmental pollutants and allergens are observed to cause mitochondrial dysfunction, primarily by inducing oxidative stress and ROS production. Malfunctioning mitochondria change the bioenergetics of the cell and its metabolic profile to favour systemic inflammation, which drives all three types of morbidities. Given the existing experimental evidence, approaches targeting mitochondria (e.g. antioxidant therapy and mitochondrial replacement) are being conducted in relevant disease models-with some progressing towards clinical trials, making mitochondrial function the focus of translational therapy research in asthma, allergy and linked metabolic syndrome.

Adenosine Triphosphate Promotes Allergen-Induced Airway Inflammation and Th17 Cell Polarization in Neutrophilic Asthma.

PubMed

Zhang, Fang; Su, Xin; Huang, Gang; Xin, Xiao-Feng; Cao, E-Hong; Shi, Yi; Song, Yong

2017-01-01

Adenosine triphosphate (ATP) is a key mediator to alert the immune dysfunction by acting on P2 receptors. Here, we found that allergen challenge caused an increase of ATP secretion in a murine model of neutrophilic asthma, which correlated well with neutrophil counts and interleukin-17 production. When ATP signaling was blocked by intratracheal administration of the ATP receptor antagonist suramin before challenge, neutrophilic airway inflammation, airway hyperresponsiveness, and Th17-type responses were reduced significantly. Also, neutrophilic inflammation was abrogated when airway ATP levels were locally neutralized using apyrase. Furthermore, ATP promoted the Th17 polarization of splenic CD4 + T cells from DO11.10 mice in vitro. In addition, ovalbumin (OVA) challenge induced neutrophilic inflammation and Th17 polarization in DO11.10 mice, whereas administration of suramin before challenge alleviated these parameters. Thus, ATP may serve as a marker of neutrophilic asthma, and local blockade of ATP signaling might provide an alternative method to prevent Th17-mediated airway inflammation in neutrophilic asthma.

DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

EPA Science Inventory

Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

Mouse Models Applied to the Research of Pharmacological Treatments in Asthma.

PubMed

Marqués-García, Fernando; Marcos-Vadillo, Elena

2016-01-01

Models developed for the study of asthma mechanisms can be used to investigate new compounds with pharmacological activity against this disease. The increasing number of compounds requires a preclinical evaluation before starting the application in humans. Preclinical evaluation in animal models reduces the number of clinical trials positively impacting in the cost and in safety. In this chapter, three protocols for the study of drugs are shown: a model to investigate corticoids as a classical treatment of asthma; a protocol to test the effects of retinoic acid (RA) on asthma; and a mouse model to test new therapies in asthma as monoclonal antibodies.

Two distinct phenotypes of asthma in elite athletes identified by latent class analysis.

PubMed

Couto, Mariana; Stang, Julie; Horta, Luís; Stensrud, Trine; Severo, Milton; Mowinckel, Petter; Silva, Diana; Delgado, Luís; Moreira, André; Carlsen, Kai-Håkon

2015-01-01

Clusters of asthma in athletes have been insufficiently studied. Therefore, the present study aimed to characterize asthma phenotypes in elite athletes using latent class analysis (LCA) and to evaluate its association with the type of sport practiced. In the present cross-sectional study, an analysis of athletes' records was carried out in databases of the Portuguese National Anti-Doping Committee and the Norwegian School of Sport Sciences. Athletes with asthma, diagnosed according to criteria given by the International Olympic Committee, were included for LCA. Sports practiced were categorized into water, winter and other sports. Of 324 files screened, 150 files belonged to asthmatic athletes (91 Portuguese; 59 Norwegian). LCA retrieved two clusters: "atopic asthma" defined by allergic sensitization, rhinitis and allergic co-morbidities and increased exhaled nitric oxide levels; and "sports asthma", defined by exercise-induced respiratory symptoms and airway hyperesponsiveness without allergic features. The risk of developing the phenotype "sports asthma" was significantly increased in athletes practicing water (OR = 2.87; 95% CI [1.82-4.51]) and winter (OR = 8.65; 95% CI [2.67-28.03]) sports, when compared with other athletes. Two asthma phenotypes were identified in elite athletes: "atopic asthma" and "sports asthma". The type of sport practiced was associated with different phenotypes: water and winter sport athletes had three- and ninefold increased risk of "sports asthma". Recognizing different phenotypes is clinically relevant as it would lead to distinct targeted treatments.

Occupational asthma and allergy in the detergent industry: new developments.

PubMed

Sarlo, Katherine; Kirchner, Donald B

2002-04-01

This review highlights the latest developments in the control of enzyme-induced occupational asthma and allergy (rhinitis and conjunctivitis) in the detergent industry. The industry has developed guidelines for the safe handling of enzymes in order to reduce the risk of occupational allergy and asthma. Those manufacturing facilities that follow all of the guidelines enjoy very low or no cases of asthma and allergy among workers exposed to enzymes. The key to the success of the management of enzyme-induced allergy and asthma is prospective surveillance for the development of enzyme-specific IgE antibody before the onset of allergic symptoms. This allows for continuing interventions to reduce exposures, so as to minimize or eliminate those associated with symptoms. Workers with IgE to enzymes can still continue to work in the industry symptom-free for their entire career. This indicates that exposures needed to induce sensitization are different and probably lower than exposures needed to elicit enzyme allergic symptoms. The experience of the detergent enzyme industry in controlling occupational allergens can be applied to other industries. The detergent enzyme story can be viewed as a model for the control of type 1 protein allergens in the workplace.

A Comparison of an Individually Tailored and a Standardized Asthma Self-Management Education

ERIC Educational Resources Information Center

Shackelford, Judy; Bachman, Jean H.

2009-01-01

Background: Asthma is one of the most prevalent chronic diseases in the United States and can be life-threatening. There are a rising number of adults with asthma that cannot be prevented or cured but may be controlled. Self-management education is essential for long-term asthma control; however, the most effective type of education is unknown.…

A Systematic Review of the Literature on Screening for Exercise-Induced Asthma: Considerations for School Nurses

ERIC Educational Resources Information Center

Worrell, Kelly; Shaw, Michele R.; Postma, Julie; Katz, Janet R.

2015-01-01

Asthma is a major cause of illness, missed school days, and hospitalization in children. One type of asthma common in children is exercise-induced asthma (EIA). EIA causes airway narrowing with symptoms of cough and shortness of breath during exercise. The purpose of this article is to review the literature relevant to screening children and…

Pet ownership is associated with increased risk of non-atopic asthma and reduced risk of atopy in childhood: findings from a UK birth cohort.

PubMed

Collin, S M; Granell, R; Westgarth, C; Murray, J; Paul, E; Sterne, J A C; John Henderson, A

2015-01-01

Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma. To investigate whether pet ownership during pregnancy and childhood was associated with asthma and atopy at the age of 7 in a UK population-based birth cohort. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time points from pregnancy to the age of 7 with asthma, atopy (grass, house dust mite, and cat skin prick test) and atopic vs. non-atopic asthma at the age of 7 using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. A total of 3768 children had complete data on pet ownership, asthma, and atopy. Compared with non-ownership, continuous ownership of any pet (before and after the age of 3) was associated with 52% lower odds of atopic asthma [odds ratio (OR) 0.48, 95% CI 0.34-0.68]. Pet ownership tended to be associated with increased risk of non-atopic asthma, particularly rabbits (OR 1.61, 1.04-2.51) and rodents (OR 1.86, 1.15-3.01), comparing continuous vs. non-ownership. Pet ownership was consistently associated with lower odds of sensitization to grass, house dust mite, and cat allergens, but rodent ownership was associated with higher odds of sensitization to rodent allergen. Differential effects of pet ownership on atopic vs. non-atopic asthma were evident for all pet types. Pet ownership during pregnancy and childhood in this birth cohort was consistently associated with a reduced risk of aeroallergen sensitization and atopic asthma at the age of 7, but tended to be associated (particularly for rabbits and rodents) with an increased risk of non-atopic asthma. The opposing effects on atopy vs. non-atopic asthma might be considered by parents when they are deciding whether to acquire a pet. © 2014 John Wiley & Sons Ltd.

Pet ownership is associated with increased risk of non-atopic asthma and reduced risk of atopy in childhood: findings from a UK birth cohort

PubMed Central

Collin, S.M.; Granell, R; Westgarth, C; Murray, J; Paul, E; Sterne, J.A.C.; Henderson, A. John

2014-01-01

Background Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma. Objective To investigate whether pet ownership during pregnancy and childhood was associated with asthma and atopy at age 7 years in a UK population-based birth cohort. Methods Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time-points from pregnancy to age 7 years with asthma, atopy (grass, house-dust mite, and cat skin prick test) and atopic versus non-atopic asthma at age 7 years using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy and family adversity. Results 3,768 children had complete data on pet ownership, asthma and atopy. Compared with non-ownership, continuous ownership of any pet (before and after age 3 years) was associated with 52% lower odds of atopic asthma (odds ratio [OR] 0.48, 95% CI 0.34–0.68). Pet ownership tended to be associated with increased risk of non-atopic asthma, particularly rabbits (OR 1.61, 1.04–2.51) and rodents (OR 1.86, 1.15–3.01), comparing continuous versus non-ownership. Pet ownership was consistently associated with lower odds of sensitization to grass, house-dust mite and cat allergens, but rodent ownership was associated with higher odds of sensitization to rodent allergen. Differential effects of pet ownership on atopic versus non-atopic asthma were evident for all pet types. Conclusions Pet ownership during pregnancy and childhood in this birth cohort was consistently associated with a reduced risk of aeroallergen sensitization and atopic asthma at age 7 years, but tended to be associated (particularly for rabbits and rodents) with an increased risk of non-atopic asthma. Clinical relevance The opposing effects on atopy versus non-atopic asthma might be considered by parents when they are deciding whether to acquire a pet. PMID:25077415

Flavonoids and Asthma

PubMed Central

Tanaka, Toshio; Takahashi, Ryo

2013-01-01

Asthma is a chronic disease, characterized by airway inflammation, airflow limitation, hyper-reactivity and airway remodeling. It is believed that asthma is caused by the interaction between genetic and environmental factors. The prevalence of allergic diseases, including asthma, has increased worldwide during the past two decades. Although the precise reasons that have caused this increase remain unknown, dietary change is thought to be one of the environmental factors. Flavonoids, which are polyphenolic plant secondary metabolites ubiquitously present in vegetables, fruits and beverages, possess antioxidant and anti-allergic traits, as well as immune-modulating activities. Flavonoids are powerful antioxidants and anti-allergic nutrients that inhibit the release of chemical mediators, synthesis of Th2 type cytokines, such as interleukin (IL)-4 and IL-13, and CD40 ligand expression by high-affinity immunoglobulin E (IgE) receptor-expressing cells, such as mast cells and basophils. They also inhibit IL-4-induced signal transduction and affect the differentiation of naïve CD4+ T cells into effector T-cells through their inhibitory effect on the activation of the aryl hydrocarbon receptor. Various studies of flavonoids in asthmatic animal models have demonstrated their beneficial effects. The results of several epidemiological studies suggest that an increase in flavonoid intake is beneficial for asthma. Moreover, clinical trials of flavonoids have shown their ameliorative effects on symptoms related to asthma. However, these human studies are currently limited; further validation is required to clarify whether an appropriate intake of flavonoids may constitute dietary treatment and for part of a preventive strategy for asthma. PMID:23752494

Mediating pathways from central obesity to childhood asthma: a population-based longitudinal study.

PubMed

Chih, An-Hsuan; Chen, Yang-Ching; Tu, Yu-Kang; Huang, Kuo-Chin; Chiu, Tai-Yuan; Lee, Yungling Leo

2016-09-01

The mediating pathways linking obesity and asthma are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma.In the Taiwan Children Health Study, we collected data on an open cohort of children aged 9-13 years. Children's respiratory outcomes, atopic conditions, obesity measures and pulmonary function were surveyed annually between 2010 and 2012. Exhaled nitric oxide fraction concentrations were recorded in 2012. Generalised estimating equations and general linear models were used to examine the associations between central obesity, possible mediators and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma.Central obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the active asthma model, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the lifetime wheeze model. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models.Decline in pulmonary function is the most important pathway in central obesity related asthma. Pulmonary function screening should be applied to obese children for asthma risk prediction. Copyright ©ERS 2016.

Regulatory T cells and type 2 innate lymphoid cell-dependent asthma.

PubMed

Aron, J L; Akbari, O

2017-08-01

Group 2 innate lymphoid cells (ILC2s) are a recently identified group of cells with the potent capability to produce Th2-type cytokines such as interleukin (IL)-5 and IL-13. Several studies suggest that ILC2s play an important role in the development of allergic diseases and asthma. Activation of pulmonary ILC2s in murine models lacking T and B cells induces eosinophilia and airway hyper-reactivity (AHR), which are cardinal features of asthma. More importantly, numerous recent studies have highlighted the role of ILC2s in asthma persistence and exacerbation among human subjects, and thus, regulation of pulmonary ILC2s is a major area of investigation aimed at curbing allergic lung inflammation and exacerbation. Emerging evidence reveals that a group of regulatory T cells, induced Tregs (iTregs), effectively suppress the production of ILC2-driven, pro-inflammatory cytokines IL-5 and IL-13. The inhibitory effects of iTregs are blocked by preventing direct cellular contact or by inhibiting the ICOS-ICOS-ligand (ICOSL) pathway, suggesting that both direct contact and ICOS-ICOSL interaction are important in the regulation of ILC2 function. Also, cytokines such as IL-10 and TGF-β1 significantly reduce cytokine secretion by ILC2s. Altogether, these new findings uncover iTregs as potent regulators of ILC2 activation and implicate their utility as a therapeutic approach for the treatment of ILC2-mediated allergic asthma and respiratory disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics.

PubMed

Tsolakis, N; Malinovschi, A; Nordvall, L; Janson, C; Borres, M P; Alving, K

2018-06-01

Atopic asthma is associated with elevated type-2 biomarkers such as fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count. However, increased type 2 markers have also been reported in traditionally defined non-atopic asthma. To determine a clinically useful level of IgE sensitization for ruling out type 2 asthma. Asthmatics (N = 408; age 10-35 years) were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: ≥0.35 kU A /L for at least one test (n = 326) or <0.35 kU A /L for both tests (n = 82). Τhe latter group was subsequently divided into 2 groups: IgE 0.10-0.34 kU A /L (n = 34) and IgE < 0.10 kU A /L (n = 48). The relationships between type 2 biomarkers, and inadequate asthma control (ACT < 20), reduced lung function (FEV 1  < 80%), recent asthma attacks and airway hyperresponsiveness (AHR) to methacholine were determined. In univariate analyses, at least one type 2 marker related to each asthma outcome in subjects with IgE ≥0.35 kU A /L. In subjects with IgE 0.10-0.34 kU A /L, elevated FeNO related to reduced lung function (P = .008) and B-Eos to AHR (P = .03). No associations were found in subjects with IgE < 0.10 kU A /L. In multivariate analysis, a relationship between FeNO and reduced lung function remained in subjects with IgE < 0.35 kU A /L (P = .03). Clinically relevant elevation of type 2 biomarkers was seen in young asthmatics with IgE antibodies <0.35 kU A /L, but not those with IgE < 0.10 kU A /L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement. © 2018 John Wiley & Sons Ltd.

Occupational agriculture organic dust exposure and its relationship to asthma and airway inflammation in adults.

PubMed

Wunschel, Javen; Poole, Jill A

2016-06-01

Recent studies have made advances into understanding the complex agriculture work exposure environment in influencing asthma in adults. The objective of this study is to review studies of occupational agricultural exposures including dust, animal, and pesticide exposures with asthma in adult populations. PubMed databases were searched for articles pertaining to farming, agriculture, asthma, occupational asthma, airway inflammation, respiratory disease, lung disease, pesticides, and organic dust. Studies chosen were published in or after 1999 that included adults and asthma and farming/agricultural work or agricultural exposures and airway inflammatory disease measurements. The data remain inconclusive. Several retrospective studies demonstrate agricultural work to be protective against asthma in adults, especially with increased farming exposure over time. In contrast, other studies find increased risk of asthma with farming exposures, especially for the non-atopic adult. Mechanistic and genetic studies have focused on defining the wide variety and abundance of microorganisms within these complex organic dusts that trigger several pattern recognition receptor pathways to modulate the hosts' response. Asthma risk depends on the interplay of genetic factors, gender, atopic predisposition, type of livestock, pesticide exposure, and magnitude and duration of exposure in the adult subject. Longer exposure to occupational farming is associated with decreased asthma risk. However, studies also suggest that agricultural work and multiple types of livestock are independent risk factors for developing asthma. Prospective and longitudinal studies focusing on genetic polymorphisms, objective assessments, and environmental sampling are needed to further delineate the influence of agriculture exposure in the adult worker.

Transcription factor RBP-J-mediated signalling regulates basophil immunoregulatory function in mouse asthma model.

PubMed

Qu, Shuo-Yao; He, Ya-Long; Zhang, Jian; Wu, Chang-Gui

2017-09-01

Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma. Bone marrow BA were prepared by bone marrow cell culture in the presence of recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of the CD49b + microbeads. The recombination signal binding protein J (RBP-J -/- ) BA were co-cultured with T cells, and the supernatant and the T-cell subtypes were examined. The results indicated disruption of the capacity of BA for antigen presentation alongside an up-regulation of the immunoregulatory function. This was possibly due to the low expression of OX40L in the RBP-J -/- BA. Basophils were adoptively transferred to ovalbumin-sensitized recipient mice, to establish an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid, airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were determined. Overall, our results indicate that the RBP-J-mediated Notch signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J influences the immunoregulatory functions of BA, which include activation of T cells and their differentiation into T helper cell subtypes. The Notch signalling pathway is a potential therapeutic target for BA-based immunotherapy against asthma. © 2017 John Wiley & Sons Ltd.

Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model

PubMed Central

Park, Soojin; Chung, Hwan-Suck; Shin, Dasom; Jung, Kyung-Hwa; Lee, Hyunil; Moon, Junghee; Bae, Hyunsu

2016-01-01

Foxp3 is a master regulator of CD4+CD25+ regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4+ or CD8+ cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3DTR mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma. PMID:27633092

The Joint Commission Children’s Asthma Care Quality Measures and Asthma Readmissions

PubMed Central

Fassl, Bernhard A.; Nkoy, Flory L.; Stone, Bryan L.; Srivastava, Rajendu; Simon, Tamara D.; Uchida, Derek A.; Koopmeiners, Karmella; Greene, Tom; Cook, Lawrence J.

2012-01-01

BACKGROUND AND OBJECTIVES: The Joint Commission introduced 3 Children’s Asthma Care (CAC 1–3) measures to improve the quality of pediatric inpatient asthma care. Validity of the commission’s measures has not yet been demonstrated. The objectives of this quality improvement study were to examine changes in provider compliance with CAC 1–3 and associated asthma hospitalization outcomes after full implementation of an asthma care process model (CPM). METHODS: The study included children aged 2 to 17 years who were admitted to a tertiary care children’s hospital for acute asthma between January 1, 2005, and December 31, 2010. The study was divided into 3 periods: preimplementation (January 1, 2005–December 31, 2007), implementation (January 1, 2008–March 31, 2009), and postimplementation (April 1, 2009–December 31, 2010) periods. Changes in provider compliance with CAC 1–3 and associated changes in hospitalization outcomes (length of stay, costs, PICU transfer, deaths, and asthma readmissions within 6 months) were measured. Logistic regression was used to control for age, gender, race, insurance type, and time. RESULTS: A total of 1865 children were included. Compliance with quality measures before and after the CPM implementation was as follows: 99% versus 100%, CAC-1; 100% versus 100%, CAC-2; and 0% versus 87%, CAC-3 (P < .01). Increased compliance with CAC-3 was associated with a sustained decrease in readmissions from an average of 17% to 12% (P = .01) postimplementation. No change in other outcomes was observed. CONCLUSIONS: Implementation of the asthma CPM was associated with improved compliance with CAC-3 and with a delayed, yet significant and sustained decrease in hospital asthma readmission rates, validating CAC-3 as a quality measure. Due to high baseline compliance, CAC-1 and CAC-2 are of questionable value as quality measures. PMID:22908110

The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model.

PubMed

Fabian, M Patricia; Stout, Natasha K; Adamkiewicz, Gary; Geggel, Amelia; Ren, Cizao; Sandel, Megan; Levy, Jonathan I

2012-09-18

In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date. We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%), which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold. Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates. We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens), medication compliance, seasonality, and medical history on asthma outcomes (symptom-days, medication use, hospitalizations, and emergency room visits). The model can be used to evaluate building interventions and green building construction practices on pollutant concentrations, energy savings, and asthma healthcare utilization costs, and demonstrates the value of a simulation approach for studying complex diseases such as asthma.

The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model

PubMed Central

2012-01-01

Background In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date. Methods We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%), which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold. Results Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates. Conclusions We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens), medication compliance, seasonality, and medical history on asthma outcomes (symptom-days, medication use, hospitalizations, and emergency room visits). The model can be used to evaluate building interventions and green building construction practices on pollutant concentrations, energy savings, and asthma healthcare utilization costs, and demonstrates the value of a simulation approach for studying complex diseases such as asthma. PMID:22989068

Airway structural alterations selectively associated with severe asthma.

PubMed

Benayoun, Laurent; Druilhe, Anne; Dombret, Marie-Christine; Aubier, Michel; Pretolani, Marina

2003-05-15

To identify airway pathologic abnormalities selectively associated with severe asthma, we examined 10 control subjects, 10 patients with intermittent asthma, 15 patients with mild-to-moderate persistent asthma, 15 patients with severe persistent asthma, and 10 patients with chronic obstructive pulmonary disease. Bronchial biopsies were assessed for epithelial integrity; subepithelial basement membrane (SBM) thickness; collagen type III deposition; eosinophil, neutrophil, and fibroblast numbers; mucous gland and airway smooth muscle (ASM) areas; SBM-ASM distance; ASM hypertrophy (increased cell size); and the expression of the contractile proteins alpha-actin, smooth muscle myosin heavy-chain isoforms, myosin light-chain kinase, and the phosphorylated form of the regulatory light chain of myosin. Neither mucosal eosinophilia nor neutrophilia, epithelial damage, or SBM thickness reflected asthma severity. In contrast, higher numbers of fibroblasts (p < 0.001), an increase in collagen type III deposition (p < 0.020), larger mucous gland (p < 0.040) and ASM (p < 0.001) areas, augmented ASM cell size (p < 0.001), and myosin light-chain kinase expression (p < 0.005) distinguished patients with severe persistent asthma from patients with milder disease or with chronic obstructive pulmonary disease. Stepwise multivariate regression analysis established that fibroblast numbers and ASM cell size were negatively associated with prebronchodilator and postbronchodilator FEV1 values in patients with asthma. We conclude that fibroblast accumulation and ASM hypertrophy in proximal airways are selective determinants of severe persistent asthma.

Sunny hours and variations in the prevalence of asthma in schoolchildren according to the International Study of Asthma and Allergies (ISAAC) Phase III in Spain

NASA Astrophysics Data System (ADS)

Arnedo-Pena, Alberto; García-Marcos, Luis; Fernández-Espinar, Jorge Fuertes; Bercedo-Sanz, Alberto; Aguinaga-Ontoso, Ines; González-Díaz, Carlos; Carvajal-Urueña, Ignacio; Busquet-Monge, Rosa; Suárez-Varela, Maria Morales; de Andoin, Nagore García; Batlles-Garrido, Juan; Blanco-Quirós, Alfredo; Varela, Angel López-Silvarrey; García-Hernández, Gloria

2011-05-01

The objective of this study was to estimate the relationship between the prevalence of asthma in schoolchildren aged 6-7 years and 13-14 years and the mean annual sunny hours (MASH) in Spain, and to explore predictive models for asthma prevalence. The prevalence of asthma was obtained from the International Study of Asthma and Allergies (ISAAC) Phase III 2002-2003, and climate and socio-economic variables from official sources. Nine centres were studied and a further four centres, two of which are in ISAAC, to test the predictive models. Logistic regression was used to estimate adjusted prevalence rates of asthma for each centre, and multiple regression models to study the effects of MASH and other meteorological and socio-economic variables. The adjusted prevalence rate of asthma decreased 0.6% [95% confidence interval (CI) 0.4-0.8%] for the 6-7 years group and 1.1% (95% CI 0.8-1.3%) for the 13-14 years group with an increase in the MASH of 100 h. Relative humidity was negatively associated with asthma in the older age group, and gross province product per capita (GPP) was positively associated with asthma in the younger age group. The predictive models, which included MASH, gender, relative humidity, and GPP, anticipated prevalence rates of asthma without significant differences between the levels observed and those expected in 9 of the11 measurements carried out. The results indicate that sunny hours have a protective effect on the prevalence of asthma in schoolchildren.

Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning.

PubMed

Ross, Mindy K; Yoon, Jinsung; van der Schaar, Auke; van der Schaar, Mihaela

2018-01-01

Pediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. Our objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype. We applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes. Four phenotypes were discovered in both datasets: allergic not obese (A + /O - ), obese not allergic (A - /O + ), allergic and obese (A + /O + ), and not allergic not obese (A - /O - ). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A + /O + children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo (P = 0.011). The PP algorithm performed significantly better (P < 0.001) than traditional machine learning algorithms for both short- and long-term asthma control prediction. Asthma control and bronchodilator response were the features most predictive of short-term asthma control, regardless of type of controller medication or phenotype. Bronchodilator response and serum eosinophils were the most predictive features of asthma control, regardless of type of controller medication or phenotype. Advanced statistical machine learning approaches can be powerful tools for discovery of phenotypes based on treatment response and can aid in asthma control prediction in complex medical conditions such as asthma.

Assessing the knowledge to practice gap: The asthma practices of community pharmacists

PubMed Central

Guirguis, Lisa M.

2017-01-01

Background: Community pharmacists are well positioned to identify patients with poorly controlled asthma and trained to optimize asthma therapy. Yet, over 90% of patients with asthma live with uncontrolled disease. We sought to understand the current state of asthma management in practice in Alberta and explore the potential use of the Chat, Check and Chart (CCC) model to enhance pharmacists’ care for patients with asthma. Methods: An 18-question survey was used to examine pharmacists’ monitoring of asthma control and prior use of the CCC tools. Descriptive statistics were used to characterize the response rate, sample demographics, asthma management and CCC use. Survey validity and reliability were established. Results: One hundred randomly selected pharmacists completed the online survey with a 40% (100/250) response rate. A third of responding pharmacists reported talking to most patients about asthma symptoms and medication, with a greater focus on talking with patients on new prescriptions over those with ongoing therapies. Fewer than 1 in 10 pharmacists routinely talked to most patients about asthma action plans (AAPs). The majority of pharmacists (76%) were familiar with the CCC model, and 83% of those reported that the CCC model influenced their practice anywhere from somewhat (45%) to a great deal (38%). Both scales had good reliability, and factor analysis provided support for scale validity. Conclusions: There was considerable variability in pharmacists’ activities in monitoring asthma. Pharmacists rarely used AAPs. The CCC model had a high level of self-reported familiarity, use and influence among pharmacists. PMID:29317938

Using the Health Belief Model to Understand School Nurse Asthma Management

ERIC Educational Resources Information Center

Quaranta, Judith E.; Spencer, Gale A.

2015-01-01

Ten million children in the United States have asthma. Since children are in school about 6 hr a day, school nurses are positioned to intervene and influence asthma outcomes. A descriptive correlational study was designed to investigate performance of school nurses' asthma management behaviors in relationship to asthma knowledge, asthma attitude,…

Asthma interventions in primary schools--a review.

PubMed

Al Aloola, Noha A; Naik-Panvelkar, Pradnya; Nissen, Lisa; Saini, Bandana

2014-10-01

To explore, in depth, the literature for evidence supporting asthma interventions delivered within primary schools and to identify any "gaps" in this research area. A literature search using electronic search engines (i.e. Medline, PubMed, Education Resources Information Center (ERIC), International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and Informit) and the search terms "asthma", "asthma intervention" and "school-based asthma education program" (and derivatives of these keywords) was conducted. Twenty-three articles met the inclusion criteria; of these eight were Randomised Controlled Trials. There was much variety in the type, content, delivery and outcome measures in these 23 studies. The most common intervention type was asthma education delivery. Most studies demonstrated improvement in clinical and humanistic markers, for example, asthma symptoms medication use (decrease in reliever medication use or decrease in the need for rescue oral steroid), inhaler use technique and spacer use competency, lung function and quality of life. Relatively few studies explored the effect of the intervention on academic outcomes. Most studies did not report on the sustainability or cost effectiveness of the intervention tested. Another drawback in the literature was the lack of details about the intervention and inconsistency in instruments selected for measuring outcomes. School-based asthma interventions regardless of their heterogeneity have positive clinical, humanistic, health economical and academic outcomes.

A Multi-factorial Model for Examining Racial and Ethnic Disparities in Acute Asthma Visits by Children

PubMed Central

Feldman, Jonathan M.; Serebrisky, Denise; Spray, Amanda

2012-01-01

Background Causes of children’s asthma health disparities are complex. Parents’ asthma illness representations may play a role. Purpose The study aims to test a theoretically based, multi-factorial model for ethnic disparities in children’s acute asthma visits through parental illness representations. Methods Structural equation modeling investigated the association of parental asthma illness representations, sociodemographic characteristics, health care provider factors, and social–environmental context with children’s acute asthma visits among 309 White, Puerto Rican, and African American families was conducted. Results Forty-five percent of the variance in illness representations and 30% of the variance in acute visits were accounted for. Statistically significant differences in illness representations were observed by ethnic group. Approximately 30% of the variance in illness representations was explained for whites, 23% for African Americans, and 26% for Puerto Ricans. The model accounted for >30% of the variance in acute visits for African Americans and Puerto Ricans but only 19% for the whites. Conclusion The model provides preliminary support that ethnic heterogeneity in asthma illness representations affects children’s health outcomes. PMID:22160799

Applying the Social Ecological Model to Creating Asthma-Friendly Schools in Louisiana

ERIC Educational Resources Information Center

Nuss, Henry J.; Hester, Laura L.; Perry, Mark A.; Stewart-Briley, Collette; Reagon, Valamar M.; Collins, Pamela

2016-01-01

Background: In 2010, the Louisiana Asthma Management and Prevention Program (LAMP) implemented the Asthma-Friendly Schools Initiative in high-risk Louisiana populations. The social ecological model (SEM) was used as a framework for an asthma program implemented in 70 state K-12 public schools over 2 years. Methods: Activities included a needs…

The natural course of eczema from birth to age 7 years and the association with asthma and allergic rhinitis: a population-based birth cohort study.

PubMed

Shen, Chian-Yin; Lin, Ming-Chih; Lin, Heng-Kuei; Lin, Ching-Heng; Fu, Lin-Shien; Fu, Yun-Chin

2013-01-01

Although "atopic march" is a popular concept, the relationship between eczema and subsequent asthma is far from clear. However, some cohort studies have shown the possibility of two different allergic phenotypes in those who present with early eczema in terms of their persistency. We checked the cohort data from 308,849 children born in 2000 in Taiwan, to evaluate the different courses of eczema and their relationships to subsequent asthma and allergic rhinitis (AR) at age 7 years. We examined the age prevalence of eczema, asthma, and AR up to 7 years of age. We grouped all cases according to their course of eczema, as well as wheezing, and determined the rates of asthma and AR at age 7 years. We checked the adjusted risk factors by multiple logistic regression model. We also examined the distributions of wheezing types in different eczema groups. We found the "atopic march" pattern of allergic diseases based on their age prevalence. Early eczema was associated with asthma and AR at the age of 7 years. Those with eczema symptoms persisting after 36 months of age had a higher risk than those with transient eczema. Early wheeze also contributed to asthma and AR later in childhood. In addition, late-onset eczema had a completely different wheeze distribution compared with other groups and also had a higher risk for asthma and AR than transient eczema. In conclusion, different eczema phenotypes could be found in this population-based cohort. This article emphasizes the special attention to the persistency and late-onset eczema in clinical practice.

Redemption of asthma pharmaceuticals among stainless steel and mild steel welders: a nationwide follow-up study.

PubMed

Kristiansen, Pernille; Jørgensen, Kristian Tore; Hansen, Johnni; Bonde, Jens Peter

2015-08-01

The purpose was to examine bronchial asthma according to cumulative exposure to fume particulates conferred by stainless steel and mild steel welding through a proxy of redeemed prescribed asthma pharmaceuticals. A Danish national company-based historical cohort of 5,303 male ever-welders was followed from 1995 to 2011 in the Danish Medicinal Product Registry to identify the first-time redemption of asthma pharmaceuticals including beta-2-adrenoreceptor agonists, adrenergic drugs for obstructive airway diseases and inhalable glucocorticoids. Lifetime exposure to welding fume particulates was estimated by combining questionnaire data on welding work with a welding exposure matrix. The estimated exposure accounted for calendar time, welding intermittence, type of steel, welding methods, local exhaustion and welding in confined spaces. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a Cox proportional hazards model adjusting for potential confounders and taking modifying effects of smoking into account. The average incidence of redemption of asthma pharmaceuticals in the cohort was 16 per 1,000 person year (95% CI 10-23 per 1,000 person year). A moderate nonsignificant increased rate of redemption of asthma medicine was observed among high-level exposed stainless steel welders in comparison with low-level exposed welders (HR 1.54, 95% CI 0.76-3.13). This risk increase was driven by an increase risk among non-smoking stainless steel welders (HR 1.46, 95% CI 1.06-2.02). Mild steel welding was not associated with increased risk of use asthma pharmaceuticals. The present study indicates that long-term exposure to stainless steel welding is related to increased risk of asthma in non-smokers.

Vegetation diversity protects against childhood asthma: results from a large New Zealand birth cohort.

PubMed

Donovan, Geoffrey H; Gatziolis, Demetrios; Longley, Ian; Douwes, Jeroen

2018-05-07

We assessed the association between the natural environment and asthma in 49,956 New Zealand children born in 1998 and followed up until 2016 using routinely collected data. Children who lived in greener areas, as measured by the normalized difference vegetation index, were less likely to be asthmatic: a 1 s.d. increase in normalized difference vegetation index was associated with a 6.0% (95% CI 1.9-9.9%) lower risk of asthma. Vegetation diversity was also protective: a 1 s.d. increase in the number of natural land-cover types in a child's residential meshblock was associated with a 6.7% (95% CI 1.5-11.5%) lower risk. However, not all land-cover types were protective. A 1 s.d. increase in the area covered by gorse (Ulex europaeus) or exotic conifers, both non-native, low-biodiversity land-cover types, was associated with a 3.2% (95% CI 0.0-6.0%) and 4.2% (95% CI 0.9-7.5%) increased risk of asthma, respectively. The results suggest that exposure to greenness and vegetation diversity may be protective of asthma.

The healthy learner model for student chronic condition management--part II: the asthma initiative.

PubMed

Erickson, Cecelia DuPlessis; Splett, Patricia L; Mullett, Sara Stoltzfus; Jensen, Charlotte; Belseth, Stephanie Bisson

2006-12-01

The Healthy Learner Asthma Initiative (HLAI) was designed as a comprehensive, school-community initiative to improve asthma management and produce healthy learners. National asthma guidelines were translated into components of asthma management in the school setting that defined performance expectations and lead to greater quality and consistency of asthma care. The HLAI incorporated evidence-based practice and introduced the role of the asthma resource nurse. Leadership, capacity building, and strong partnerships among school nurses, students, families, and health care providers were essential to the implementation and sustainability of the HLAI. Professional school nursing and evaluation were defined as key requisites to a successful initiative. Evaluation results indicated positive effects on nursing practice, fewer asthma visits to the health office, and better attendance among students who received asthma care in the school health office. The HLAI provided the basis for development of the Healthy Learner Model for Student Chronic Condition Management.

A descriptive and comparative study of the prevalence of depressive and anxiety disorders in low-income adults with type 2 diabetes and other chronic illnesses.

PubMed

Thomas, Janet; Jones, Glenn; Scarinci, Isabel; Brantley, Phillip

2003-08-01

To determine whether type 2 diabetes contributes to the presence of depressive and anxiety disorder diagnoses in low-income adults with hypertension, asthma, and/or arthritis. Using a cross-sectional design, this study administered a structured diagnostic interview to low-income primary care patients diagnosed with type 2 diabetes, hypertension, arthritis, and asthma, as well as to those with no chronic illness (n = 326), to determine the 12-month prevalence of depressive and anxiety disorders. A logistic regression (LR) model was used to assess whether a diagnosis of depression and/or anxiety was associated with type 2 diabetes after adjusting for known risk factors. A high prevalence rate of depressive and/or anxiety disorders was found in the total sample (29%) and in all three illness groups: type 2 diabetes (36%), other chronic illnesses (24%), and no chronic illness (31%). Using LR, a main effect was detected for illness group when age and education were controlled (chi(2) = 22.66, df 4, P = 0.000). Specifically, the odds of occurrence of a depressive and/or anxiety disorder in those with comorbid type 2 diabetes were twice that in the nondiabetic, chronically ill comparison group (odds ratio 2.26, 95% CI 1.28-4.01, P = 0.005). These results suggest a positive contribution of type 2 diabetes to increased rates of depressive and/or anxiety disorders in patients with hypertension, asthma, and/or arthritis and support prior research that type 2 diabetes may serve as an indicator of depression and anxiety in low-income adults treated in primary care clinics.

A prospective cohort study on ambient air pollution and respiratory morbidities including childhood asthma in adolescents from the western Cape Province: study protocol.

PubMed

Olaniyan, Toyib; Jeebhay, Mohamed; Röösli, Martin; Naidoo, Rajen; Baatjies, Roslynn; Künzil, Nino; Tsai, Ming; Davey, Mark; de Hoogh, Kees; Berman, Dilys; Parker, Bhawoodien; Leaner, Joy; Dalvie, Mohamed Aqiel

2017-09-16

There is evidence from existing literature that ambient air pollutant exposure in early childhood likely plays an important role in asthma exacerbation and other respiratory symptoms, with greater effect among asthmatic children. However, there is inconclusive evidence on the role of ambient air pollutant exposures in relation to increasing asthma prevalence as well as asthma induction in children. At the population level, little is known about the potential synergistic effects between pollen allergens and air pollutants since this type of association poses challenges in uncontrolled real life settings. In particular, data from sub-Sahara Africa is scarce and virtually absent among populations residing in informal residential settlements. A prospective cohort study of 600 school children residing in four informal settlement areas with varying potential ambient air pollutant exposure levels in the Western Cape in South Africa is carried-out. The study has two follow-up periods of at least six-months apart including an embedded panel study in summer and winter. The exposure assessment component models temporal and spatial variability of air quality in the four study areas over the study duration using land-use regression modelling (LUR). Additionally, daily pollen levels (mould spores, tree, grass and weed pollen) in the study areas are recorded. In the panel study asthma symptoms and serial peak flow measurements is recorded three times daily to determine short-term serial airway changes in relation to varying ambient air quality and pollen over 10-days during winter and summer. The health outcome component of the cohort study include; the presence of asthma using a standardised ISAAC questionnaire, spirometry, fractional exhaled nitric-oxide (FeNO) and the presence of atopy (Phadiatop). This research applies state of the art exposure assessment approaches to characterize the effects of ambient air pollutants on childhood respiratory health, with a specific focus on asthma and markers of airway inflammation (FeNO) in South African informal settlement areas by considering also pollen counts and meteorological factors. The study will generate crucial data on air pollution and asthma in low income settings in sub-Sahara Africa that is lacking in the international literature.

Validation of the Asthma Illness Representation Scale-Spanish (AIRS-S).

PubMed

Sidora-Arcoleo, Kimberly Joan; Feldman, Jonathan; Serebrisky, Denise; Spray, Amanda

2010-05-01

To expand knowledge surrounding parental illness representations (IRs) of their children's asthma, it is imperative that culturally appropriate survey instruments are developed and validated for use in clinical and research settings. The Asthma Illness Representation Scale (AIRS) provides a structured assessment of the key components of asthma IRs, allowing the health care provider (HCP) to quickly identify areas of discordance with the professional model of asthma management. The English AIRS was developed and validated among a geographically and ethnically diverse sample. The authors present the validation results of the AIRS-S (Spanish) from a sample of Mexican and Puerto Rican parents. The AIRS was translated and back translated per approved methodologies. Factor analysis, internal reliability, external validity, and 2-week test-retest reliability (on a subsample) were carried out and results compared with the validated English version. Data were obtained from 80 Spanish-speaking Mexican and Puerto Rican parents of children with asthma. The sample was recruited from two school-based health centers and a free medical clinic in Phoenix, Arizona, and a hospital-based asthma clinic in Bronx, New York. The original Nature of Asthma Symptoms, Facts About Asthma, and Attitudes Towards Medication Use subscales emerged. Remaining factors were a mixture of items with no coherent or theoretical distinction between them. Interpretation of results is limited due to not meeting the minimum requirement of 5 observations/item. Cronbach's alpha coefficients for the total score (alpha = .77) and majority of subscales (alpha range = .53-.77) were acceptable and consistent with the English version. Parental reports of a positive relationship with the HCP significantly predicted AIRS scores congruent with the professional model; longer asthma duration was associated with beliefs aligned with the lay model; and AIRS scores congruent with the professional model were related to lower asthma severity. Stability in AIRS-S scores over 2 weeks was demonstrated. The AIRS-S is a culturally appropriate instrument that can be used by HCPs to ascertain Spanish-speaking parents' asthma illness beliefs and assess discordance with the professional model of asthma management. This information can be used by the HCP when discussing parent's asthma management strategies for their children during clinical encounters.

The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

PubMed

Rojanasarot, Sirikan; Carlson, Angeline M

2018-04-01

The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

Comparative study of Korean White Ginseng and Korean Red Ginseng on efficacies of OVA-induced asthma model in mice.

PubMed

Lim, Chi-Yeon; Moon, Jeong-Min; Kim, Bu-Yeo; Lim, Se-Hyun; Lee, Guem-San; Yu, Hak-Sun; Cho, Su-In

2015-01-01

Korean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white ginseng (WG) or red ginseng (RG), according to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in a mouse model of acute asthma. To produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. WG and RG extracts were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a in serum were investigated. Cytokine production by lymphocytes isolated from peribronchial lymph nodes and histopathological changes was also examined. In OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG-treated OVA-sensitized mice than in the OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG- and RG-treated OVA mice compared with OVA controls. In this study, WG and RG showed antiasthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

Graphene Oxide Attenuates Th2-Type Immune Responses, but Augments Airway Remodeling and Hyperresponsiveness in a Murine Model of Asthma

PubMed Central

2015-01-01

Several lines of evidence indicate that exposure to nanoparticles (NPs) is able to modify airway immune responses, thus facilitating the development of respiratory diseases. Graphene oxide (GO) is a promising carbonaceous nanomaterial with unique physicochemical properties, envisioned for a multitude of medical and industrial applications. In this paper, we determined how exposure to GO modulates the allergic pulmonary response. Using a murine model of ovalbumin (OVA)-induced asthma, we revealed that GO, given at the sensitization stage, augmented airway hyperresponsiveness and airway remodeling in the form of goblet cell hyperplasia and smooth muscle hypertrophy. At the same time, the levels of the cytokines IL-4, IL-5, and IL-13 were reduced in broncho-alveolar lavage (BAL) fluid in GO-exposed mice. Exposure to GO during sensitization with OVA decreased eosinophil accumulation and increased recruitment of macrophages in BAL fluid. In line with the cytokine profiles, sensitization with OVA in the presence of GO stimulated the production of OVA-specific IgG2a and down-regulated the levels of IgE and IgG1. Moreover, exposure to GO increased the macrophage production of the mammalian chitinases, CHI3L1 and AMCase, whose expression is associated with asthma. Finally, molecular modeling has suggested that GO may directly interact with chitinase, affecting AMCase activity, which has been directly proven in our studies. Thus, these data show that GO exposure attenuates Th2 immune response in a model of OVA-induced asthma, but leads to potentiation of airway remodeling and hyperresponsiveness, with the induction of mammalian chitinases. PMID:24847914

A cost-effectiveness threshold analysis of a multidisciplinary structured educational intervention in pediatric asthma.

PubMed

Rodriguez-Martinez, Carlos E; Sossa-Briceño, Monica P; Castro-Rodriguez, Jose A

2018-05-01

Asthma educational interventions have been shown to improve several clinically and economically important outcomes. However, these interventions are costly in themselves and could lead to even higher disease costs. A cost-effectiveness threshold analysis would be helpful in determining the threshold value of the cost of educational interventions, leading to these interventions being cost-effective. The aim of the present study was to perform a cost-effectiveness threshold analysis to determine the level at which the cost of a pediatric asthma educational intervention would be cost-effective and cost-saving. A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a single uncontrolled before-and-after study performed with Colombian asthmatic children. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The main outcome was the variable "quality-adjusted life-years" (QALYs). A deterministic threshold sensitivity analysis showed that the asthma educational intervention will be cost-saving to the health system if its cost is under US$513.20. Additionally, the analysis showed that the cost of the intervention would have to be below US$967.40 in order to be cost-effective. This study identified the level at which the cost of a pediatric asthma educational intervention will be cost-effective and cost-saving for the health system in Colombia. Our findings could be a useful aid for decision makers in efficiently allocating limited resources when planning asthma educational interventions for pediatric patients.

Vitamin D and Bronchial Asthma: An overview of the last five years

PubMed Central

Hall, Sannette C.; Agrawal, Devendra K.

2017-01-01

Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations and overall worse outcomes in patients with asthma. Given the increase in the prevalence of asthma over the last few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Several studies have found that low serum levels of vitamin D (< 20 ng/ml) are associated with increased exacerbations, increased airway inflammation, decreased lung function and poor prognosis in asthmatic patients. Results from the in vitro and in vivo studies in animals and human have suggested that supplementation with vitamin D can ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support the beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women and adults have primarily found little-to-no effect of vitamin D supplementation on improved asthma symptoms, onset or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency does influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce anti-inflammatory effects. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in bronchial asthma. PMID:28449868

Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis

PubMed Central

Crider, Krista S; Cordero, Amy M; Qi, Yan Ping; Mulinare, Joseph; Dowling, Nicole F; Berry, Robert J

2016-01-01

Background Childhood asthma has become a critical public health problem because of its high morbidity and increasing prevalence. The impact of nutrition and other exposures during pregnancy on long-term health and development of children has been of increasing interest. Objective We performed a systematic review and meta-analysis of the association of folate and folic acid intake during pregnancy and risk of asthma and other allergic outcomes in children. Design We performed a systematic search of 8 electronic databases for articles that examined the association between prenatal folate or folic acid exposure and risk of asthma and other allergic outcomes (eg, allergy, eczema, and atopic dermatitis) in childhood. We performed a meta-analysis by using a random-effects model to derive a summary risk estimate of studies with similar exposure timing, exposure assessment, and outcomes. Results Our meta-analysis provided no evidence of an association between maternal folic acid supplement use (compared with no use) in the prepregnancy period through the first trimester and asthma in childhood (summary risk estimate: 1.01; 95% CI: 0.78, 1.30). Because of substantial heterogeneity in exposures and outcomes, it was not possible to generate summary measures for other folate indicators (eg, blood folate concentrations) and asthma or allergy-related outcomes; however, the preponderance of primary risk estimates was not elevated. Conclusions Our findings do not support an association between periconceptional folic acid supplementation and increased risk of asthma in children. However, because of the limited number and types of studies in the literature, additional research is needed. PMID:24004895

Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation.

PubMed

Cho, Josalyn L; Ling, Morris F; Adams, David C; Faustino, Lucas; Islam, Sabina A; Afshar, Roshi; Griffith, Jason W; Harris, Robert S; Ng, Aylwin; Radicioni, Giorgia; Ford, Amina A; Han, Andre K; Xavier, Ramnik; Kwok, William W; Boucher, Richard; Moon, James J; Hamilos, Daniel L; Kesimer, Mehmet; Suter, Melissa J; Medoff, Benjamin D; Luster, Andrew D

2016-10-05

Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4 + T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin, and increased mucin MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC subjects, suggesting differences in the airway epithelial response to inflammation. Finally, AA subjects had increased airway smooth muscle mass at baseline measured in vivo using novel orientation-resolved optical coherence tomography. Our data demonstrate that the development of allergic asthma is dependent on the responsiveness of allergen-specific CD4 + T cells to innate type 2 mediators as well as increased sensitivity of airway epithelial cells and smooth muscle to type 2 inflammation. Copyright © 2016, American Association for the Advancement of Science.

Emerging mechanisms and novel targets in allergic inflammation and asthma.

PubMed

Weiss, Scott T

2017-12-04

Airway inflammation is key to the severity and persistence of asthma. Recent studies have revealed novel immune mechanisms that target dendritic cells, T helper 2 cytokines, regulatory T cells, and type 2 innate lymphoid cells in allergic inflammation, as well as novel approaches that target airway smooth muscle in asthma. These advances inform the development of new targeted treatments for allergic inflammation and asthma with the potential to provide therapeutic benefit.

Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients.

PubMed

Silkoff, Philip E; Laviolette, Michel; Singh, Dave; FitzGerald, J Mark; Kelsen, Steven; Backer, Vibeke; Porsbjerg, Celeste M; Girodet, Pierre-Olivier; Berger, Patrick; Kline, Joel N; Chupp, Geoffrey; Susulic, Vedrana S; Barnathan, Elliot S; Baribaud, Frédéric; Loza, Matthew J

2017-09-01

The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects. We explored this data set to define type 2 inflammation based on airway mucosal IL-13-driven gene expression and how this related to clinically accessible biomarkers. IL-13-driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression. Expression of airway mucosal CCL26, periostin, and IL-13-IVS all facilitated segregation of subjects into type 2-high and type 2-low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm 3 ) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26-high status. Clinical variables did not differ between subjects with type 2-high and type 2-low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression. A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13-IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient selection for novel type 2 therapeutics. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Diet and Asthma: Is It Time to Adapt Our Message?

PubMed Central

Scott, Hayley A.

2017-01-01

Asthma is a chronic respiratory disorder which is associated with airway inflammation. Environmental factors, in association with genetic susceptibility, play a critical role in asthma pathophysiology. Inhaled allergens, smoke exposure, indoor and outdoor air pollution are common triggers of asthma symptoms. Although the role of diet has clearly established mechanisms in diseases such as cardiovascular disease, type 2 diabetes, and cancer, it is not commonly identified as a causal factor in asthma. However, some dietary patterns, such as the Western diet, which includes a high intake of refined grains, processed and red meats, and desserts, have pro-inflammatory effects. On the contrary, the Mediterranean diet, with high intake of fruits and vegetables has anti-inflammatory properties. The influence of food on asthma outcomes is of growing interest, but dietary habits of asthma patients are not commonly investigated in clinical practice. In this review, we focus on the impact of diet on asthma risk and asthma control. We also detail the influence of diet on obese patients with asthma. PMID:29117118

Review of family relational stress and pediatric asthma: the value of biopsychosocial systemic models.

PubMed

Wood, Beatrice L; Miller, Bruce D; Lehman, Heather K

2015-06-01

Asthma is the most common chronic disease in children. Despite dramatic advances in pharmacological treatments, asthma remains a leading public health problem, especially in socially disadvantaged minority populations. Some experts believe that this health gap is due to the failure to address the impact of stress on the disease. Asthma is a complex disease that is influenced by multilevel factors, but the nature of these factors and their interrelations are not well understood. This paper aims to integrate social, psychological, and biological literatures on relations between family/parental stress and pediatric asthma, and to illustrate the utility of multilevel systemic models for guiding treatment and stimulating future research. We used electronic database searches and conducted an integrated analysis of selected epidemiological, longitudinal, and empirical studies. Evidence is substantial for the effects of family/parental stress on asthma mediated by both disease management and psychobiological stress pathways. However, integrative models containing specific pathways are scarce. We present two multilevel models, with supporting data, as potential prototypes for other such models. We conclude that these multilevel systems models may be of substantial heuristic value in organizing investigations of, and clinical approaches to, the complex social-biological aspects of family stress in pediatric asthma. However, additional systemic models are needed, and the models presented herein could serve as prototypes for model development. © 2015 Family Process Institute.

Development of an International School Nurse Asthma Care Coordination Model

PubMed Central

Garwick, Ann W.; Svavarsdóttir, Erla Kolbrun; Seppelt, Ann M.; Looman, Wendy S.; Anderson, Lori S.; Örlygsdóttir, Brynja

2015-01-01

Aim To identify and compare how school nurses in Reykjavik, Iceland and St. Paul, Minnesota coordinated care for youth with asthma (ages 10–18) and to develop an asthma school nurse care coordination model. Background Little is known about how school nurses coordinate care for youth with asthma in different countries. Design A qualitative descriptive study design using focus group data. Methods Six focus groups with 32 school nurses were conducted in Reykjavik (n=17) and St. Paul (n=15) using the same protocol between September 2008 – January 2009. Descriptive content analytic and constant comparison strategies were used to categorize and compare how school nurses coordinated care, which resulted in the development of an International School Nurse Asthma Care Coordination Model. Findings Participants in both countries spontaneously described a similar asthma care coordination process that involved information gathering, assessing risk for asthma episodes, prioritizing health care needs and anticipating and planning for student needs at the individual and school levels. This process informed how they individualized symptom management, case management and/or asthma education. School nurses played a pivotal part in collaborating with families, school and health care professionals to ensure quality care for youth with asthma. Conclusions Results indicate a high level of complexity in school nurses’ approaches to asthma care coordination that were responsive to the diverse and changing needs of students in school settings. The conceptual model derived provides a framework for investigators to use in examining the asthma care coordination process of school nurses in other geographic locations. PMID:25223389

Weight Loss Decreases Inherent and Allergic Methacholine Hyperresponsiveness in Mouse Models of Diet-Induced Obese Asthma

PubMed Central

Ather, Jennifer L.; Chung, Michael; Hoyt, Laura R.; Randall, Matthew J.; Georgsdottir, Anna; Daphtary, Nirav A.; Aliyeva, Minara I.; Suratt, Benjamin T.; Bates, Jason H. T.; Irvin, Charles G.; Russell, Sheila R.; Forgione, Patrick M.; Dixon, Anne E.

2016-01-01

Obese asthma presents with inherent hyperresponsiveness to methacholine or augmented allergen-driven allergic asthma, with an even greater magnitude of methacholine hyperresponsiveness. These physiologic parameters and accompanying obese asthma symptoms can be reduced by successful weight loss, yet the underlying mechanisms remain incompletely understood. We implemented mouse models of diet-induced obesity, dietary and surgical weight loss, and environmental allergen exposure to examine the mechanisms and mediators of inherent and allergic obese asthma. We report that the methacholine hyperresponsiveness in these models of inherent obese asthma and obese allergic asthma manifests in distinct anatomical compartments but that both are amenable to interventions that induce substantial weight loss. The inherent obese asthma phenotype, with characteristic increases in distal airspace tissue resistance and tissue elastance, is associated with elevated proinflammatory cytokines that are reduced with dietary weight loss. Surprisingly, bariatric surgery–induced weight loss further elevates these cytokines while reducing methacholine responsiveness to levels similar to those in lean mice or in formerly obese mice rendered lean through dietary intervention. In contrast, the obese allergic asthma phenotype, with characteristic increases in central airway resistance, is not associated with increased adaptive immune responses, yet diet-induced weight loss reduces methacholine hyperresponsiveness without altering immunological variables. Diet-induced weight loss is effective in models of both inherent and allergic obese asthma, and our examination of the fecal microbiome revealed that the obesogenic Firmicutes/Bacteroidetes ratio was normalized after diet-induced weight loss. Our results suggest that structural, immunological, and microbiological factors contribute to the manifold presentations of obese asthma. PMID:27064658

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase-Knockout Mice.

PubMed

Forkuo, Gloria S; Kim, Hosu; Thanawala, Vaidehi J; Al-Sawalha, Nour; Valdez, Daniel; Joshi, Radhika; Parra, Sergio; Pera, Tonio; Gonnella, Patricia A; Knoll, Brian J; Walker, Julia K L; Penn, Raymond B; Bond, Richard A

2016-08-01

Mice lacking the endogenous β2-adrenoceptor (β2AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chronic administration of β2AR agonists to PNMT-KO mice restores the phenotype. Based on these and other studies showing differential effects of various β2AR ligands on the asthma phenotype, we have speculated that the permissive effect of endogenous epinephrine and exogenous β2AR agonists on allergic lung inflammation can be explained by qualitative β2AR signaling. The β2AR can signal through at least two pathways: the canonical Gαs-cAMP pathway and a β-arrestin-dependent pathway. Previous studies suggest that β-arrestin-2 is required for allergic lung inflammation. On the other hand, cell-based assays suggest antiinflammatory effects of Gαs-cAMP signaling. This study was designed to test whether the in vitro antiinflammatory effects of phosphodiesterase 4 inhibitors, known to increase intracellular cAMP in multiple airway cell types, attenuate the asthma-like phenotype produced by the β2AR agonists formoterol and salmeterol in vivo in PNMT-KO mice, based on the hypothesis that skewing β2AR signaling toward Gαs-cAMP pathway is beneficial. Airway inflammatory cells, epithelial mucus production, and airway hyperresponsiveness were quantified. In Ova S/C PNMT-KO mice, formoterol and salmeterol restored the asthma-like phenotype comparable to Ova S/C wild-type mice. However, coadministration of either roflumilast or rolipram attenuated this formoterol- or salmeterol-driven phenotype in Ova S/C PNMT-KO. These findings suggest that amplification of β2AR-mediated cAMP by phosphodiesterase 4 inhibitors attenuates the asthma-like phenotype promoted by β-agonists.

METHODS FOR CLUSTERING TIME SERIES DATA ACQUIRED FROM MOBILE HEALTH APPS.

PubMed

Tignor, Nicole; Wang, Pei; Genes, Nicholas; Rogers, Linda; Hershman, Steven G; Scott, Erick R; Zweig, Micol; Yvonne Chan, Yu-Feng; Schadt, Eric E

2017-01-01

In our recent Asthma Mobile Health Study (AMHS), thousands of asthma patients across the country contributed medical data through the iPhone Asthma Health App on a daily basis for an extended period of time. The collected data included daily self-reported asthma symptoms, symptom triggers, and real time geographic location information. The AMHS is just one of many studies occurring in the context of now many thousands of mobile health apps aimed at improving wellness and better managing chronic disease conditions, leveraging the passive and active collection of data from mobile, handheld smart devices. The ability to identify patient groups or patterns of symptoms that might predict adverse outcomes such as asthma exacerbations or hospitalizations from these types of large, prospectively collected data sets, would be of significant general interest. However, conventional clustering methods cannot be applied to these types of longitudinally collected data, especially survey data actively collected from app users, given heterogeneous patterns of missing values due to: 1) varying survey response rates among different users, 2) varying survey response rates over time of each user, and 3) non-overlapping periods of enrollment among different users. To handle such complicated missing data structure, we proposed a probability imputation model to infer missing data. We also employed a consensus clustering strategy in tandem with the multiple imputation procedure. Through simulation studies under a range of scenarios reflecting real data conditions, we identified favorable performance of the proposed method over other strategies that impute the missing value through low-rank matrix completion. When applying the proposed new method to study asthma triggers and symptoms collected as part of the AMHS, we identified several patient groups with distinct phenotype patterns. Further validation of the methods described in this paper might be used to identify clinically important patterns in large data sets with complicated missing data structure, improving the ability to use such data sets to identify at-risk populations for potential intervention.

Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

PubMed

Christenson, Stephanie A; Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S; Postma, Dirkje S; Lenburg, Marc E; Spira, Avrum; Woodruff, Prescott G

2015-04-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

Asthma related medication use and exacerbations in children and adolescents with type 1 diabetes.

PubMed

Ahmadizar, Fariba; Souverein, Patrick C; Arets, Hubertus G M; de Boer, Anthonius; Maitland-van der Zee, Anke H

2016-11-01

To investigate the use of asthma medication and occurrence of asthma exacerbations up to 5 years before and after the onset of type 1 diabetes mellitus (T1DM) in children and adolescents. Children and adolescents younger than 19 years with at least 2 insulin prescriptions between 1999 and 2009 classified as T1DM cohort (n = 915) and a 4 times larger reference cohort (n = 3,590) with the same age and gender were identified from the Dutch PHARMO Record Linkage System. The date of first insulin dispensing was selected as the index date. The 5-year prevalence rate of asthma medication use in the T1DM cohort (23.2%) was significantly higher than the reference cohort (18.3%) after the onset of diabetes. No statistically significant difference between the two cohorts was observed in the use of specific types of asthma medication except for short acting muscarinic antagonists that were significantly more used in the T1DM cohort (5.5%) compared with the reference cohort (0.62%) after the onset of diabetes. The incidence rate of asthma medication use declined over time with a peak in the T1DM cohort the 1st year after the onset of diabetes. Furthermore, 1 year after the index date there was a peak in incidence rate of asthma exacerbations in both T1DM (7.8 per 1,000 person year) and reference (6.8 per 1,000 person year) cohorts. T1DM is associated with statistically significantly higher asthma medication use after the onset of T1DM, especially in the 1st year after the onset of diabetes. Pediatr Pulmonol. 2016;51:1113-1121. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Patients' expectations of asthma treatment.

PubMed

Mancuso, Carol A; Rincon, Melina; Robbins, Laura; Charlson, Mary E

2003-12-01

A multicomponent model has been developed to explain patients' unmet expectations of medical care. The model proposes that expectations are related to patients' personal experiences with illness, perceived vulnerability to disease, transmitted knowledge, and perceived severity of disease. The objective of this cross-sectional study was to determine whether this model can be applied to patients' unrealistic expectations of treatment outcomes, specifically expecting to be cured of asthma. In total, 230 patients observed in a primary care practice in New York City were interviewed in person with open-ended questions about their expectations of asthma treatment. Responses were analyzed with qualitative techniques to generate categories of expectations. Patients had a mean age of 41 +/- 11 years, 21% were white, 30% African American, 42% Latino, and 7% other groups. Major categories of expectations were generated from patients' responses and included symptom relief (expected by 52%), cure (36%), improved physical function (21%), and improved psychological well-being (15%). The category of expecting a cure was assessed with patients' responses to the following items representing components of the model: 1) resource utilization and medication requirements for asthma (representing severity of disease); 2) perceived quality of asthma care and satisfaction with care (representing past asthma experiences); 3) the Asthma Self-Efficacy Scale (representing perceived vulnerability to exacerbations); and 4) experiences of social network contacts with asthma and the Check Your Asthma IQ survey (representing transmitted knowledge). In bivariate analysis, patients who expected a cure were more likely to be Latino or Native American or Asian (p = 0.02), to have never required oral corticosteroids (p = 0.004), to be dissatisfied with the status of their asthma (p = 0.008), to know others who were limited by asthma (p = 0.03), to have worse Asthma Self-Efficacy Scale scores (p = 0.002), to have worse Check Your Asthma IQ scores (p = 0.04), and to currently be taking inhaled corticosteroids (p = 0.03). In multivariate analysis, worse asthma self-efficacy (p = 0.008), never having required oral corticosteroids (p = 0.005), and currently taking inhaled corticosteroids (p = 0.05) remained associated with expecting a cure. As a result of this study, we found that patients have multiple expectations of asthma treatment, including realistic expectations such as symptom relief and improved function, as well as unrealistic expectations, specifically to be cured of asthma. A multicomponent model of patient and disease characteristics was associated with this unrealistic expectation. These findings indicate that clinicians can intervene in diverse areas to foster realistic expectations of treatment outcomes among asthma patients.

Comparative evaluation of two asthma care quality measures among Medicaid beneficiaries.

PubMed

Samnaliev, Mihail; Baxter, Jeffrey D; Clark, Robin E

2009-05-01

The relative performance of asthma care quality measures has not been evaluated in Medicaid populations. Using complete claims and pharmaceutical data for 19,076 patients with persistent asthma (based on Health Effectiveness and Data Information Set criteria) in five Medicaid populations, we compared the following two measures of asthma care quality: filling prescriptions for controller asthma medications within 1 year and the ratio of controller medication to the total number of asthma medication prescriptions filled within 1 year. We calculated whether meeting each quality measure was associated with decreased odds of emergency department (ED) treatment episodes. We then compared the odds ratios, receiver operating characteristic (ROC) curves, and deviances between models, using each measure to predict ED utilization in Medicaid populations. Although meeting each measure was associated with lower odds of ED utilization, this decrease was larger if the controller asthma medication measure was met rather than the ratio measure. Additionally, models using the controller medication measure had greater areas under the ROC curve and smaller deviances than models using the ratio measure. Both administrative measures of asthma care quality were associated with lower odds of ED utilization. The controller medication measure of asthma care quality may be better than the ratio measure in relation to emergency asthma care utilization by Medicaid beneficiaries.

Forecasting asthma-related hospital admissions in London using negative binomial models.

PubMed

Soyiri, Ireneous N; Reidpath, Daniel D; Sarran, Christophe

2013-05-01

Health forecasting can improve health service provision and individual patient outcomes. Environmental factors are known to impact chronic respiratory conditions such as asthma, but little is known about the extent to which these factors can be used for forecasting. Using weather, air quality and hospital asthma admissions, in London (2005-2006), two related negative binomial models were developed and compared with a naive seasonal model. In the first approach, predictive forecasting models were fitted with 7-day averages of each potential predictor, and then a subsequent multivariable model is constructed. In the second strategy, an exhaustive search of the best fitting models between possible combinations of lags (0-14 days) of all the environmental effects on asthma admission was conducted. Three models were considered: a base model (seasonal effects), contrasted with a 7-day average model and a selected lags model (weather and air quality effects). Season is the best predictor of asthma admissions. The 7-day average and seasonal models were trivial to implement. The selected lags model was computationally intensive, but of no real value over much more easily implemented models. Seasonal factors can predict daily hospital asthma admissions in London, and there is a little evidence that additional weather and air quality information would add to forecast accuracy.

Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

PubMed

Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

2017-03-04

Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved Guideline Adherence With Integrated Sickle Cell Disease and Asthma Care.

PubMed

McClain, Brandi L; Ivy, Zalaya K; Bryant, Valencia; Rodeghier, Mark; DeBaun, Michael R

2016-07-01

In children with sickle cell disease (SCD), concomitant asthma is associated with increased morbidity and mortality when compared with children with SCD without asthma. Despite the well-established burden of asthma in children with SCD, no paradigm of care exists for the co-management of these two diseases. To address this gap, an integrated SCD and asthma clinic was created in a community health center that included (1) a dual respiratory therapist/asthma case manager; (2) an SCD nurse practitioner with asthma educator certification; (3) an onsite pulmonary function test laboratory; (4) a pediatric hematologist with expertise in managing SCD and asthma; and (5) application of the National Asthma Education and Prevention Program guidelines. A before (2010-2012) and after (2013-2014) study design was used to assess for improved quality of care with implementation of an integrative care model among 61 children with SCD and asthma followed from 2010 to 2014. Asthma action plan utilization after initial diagnosis increased with the integrative care model (n=16, 56% before, 100% after, p=0.003), as did the use of spirometry in children aged ≥5 years (n=41, 65% before, 95% after, p<0.001) and correction of lower airway obstruction (n=10, 30% before, 80% after, p=0.03). Although the use of an integrative care model for SCD and asthma improved evidence-based asthma care, longer follow-up and evaluation will be needed to determine the impact on SCD-related morbidity. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma.

PubMed

Phillips, Jonathan E; Renteria, Lorena; Burns, Lisa; Harris, Paul; Peng, Ruoqi; Bauer, Carla M T; Laine, Dramane; Stevenson, Christopher S

2016-06-01

In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR. Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation.

Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma

PubMed Central

Renteria, Lorena; Burns, Lisa; Harris, Paul; Peng, Ruoqi; Bauer, Carla M.T.; Laine, Dramane; Stevenson, Christopher S.

2016-01-01

Abstract Background: In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. Methods: This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. Results: RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR. Conclusions: Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation. PMID:27111445

Associations between ozone, PM2.5, and four pollen types on emergency department pediatric asthma events during the warm season in New Jersey: a case-crossover study.

PubMed

Gleason, Jessie A; Bielory, Leonard; Fagliano, Jerald A

2014-07-01

Asthma is one of the most common chronic diseases among school-aged children in the United States. Environmental respiratory irritants exacerbate asthma among children. Understanding the impact of a variety of known and biologically plausible environmental irritants and triggers among children in New Jersey - ozone, fine particulate matter (PM2.5), tree pollen, weed pollen, grass pollen and ragweed - would allow for informed public health interventions. Time-stratified case-crossover design was used to study the transient impact of ozone, PM2.5 and pollen on the acute onset of pediatric asthma. Daily emergency department visits were obtained for children aged 3-17 years with a primary diagnosis of asthma during the warm season (April through September), 2004-2007 (inclusive). Bi-directional control sampling was used to select two control periods for each case for a total of 65,562 inclusion days. Since the period of exposure prior to emergency department visit may be the most clinically relevant, lag exposures were investigated (same day (lag0), 1, 2, 3, 4, and 5 as well as 3-day and 5-day moving averages). Multivariable conditional logistic regression controlling for holiday, school-in-session indicator, and 3-day moving average for temperature and relative humidity was used to examine the associations. Odds ratios are based on interquartile range (IQR) increases or 10 unit increases when IQR ranges were narrow. Single-pollutant models as well as multipollutant models were examined. Stratification on gender, race, ethnicity and socioeconomic status was explored. The associations with ozone and PM2.5 were strongest on the same day (lag0) of the emergency department visit (RR IQR=1.05, 95% CI 1.04-1.06) and (RR IQR=1.03, 95% CI 1.02-1.04), respectively, with a decreasing lag effect. Tree and weed pollen were associated with pediatric ED visits; the largest magnitudes of association was with the 5-day average (RR IQR=1.23, 95% CI 1.21-1.25) and (RR 10=1.13, 95% CI 1.12-1.14), respectively. Grass pollen was only minimally associated with the outcome while ragweed had a negative association. The ambient air pollutant ozone is associated with increases in pediatric emergency department asthma visits during the warm weather season. The different pollen types showed different associations with the outcome. High levels of tree pollen appear to be an important risk factor in asthma exacerbations. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevention of Asthma Exacerbation in a Mouse Model by Simultaneous Inhibition of NF-κB and STAT6 Activation Using a Chimeric Decoy Strategy.

PubMed

Miyake, Tetsuo; Miyake, Takashi; Sakaguchi, Makoto; Nankai, Hirokazu; Nakazawa, Takahiro; Morishita, Ryuichi

2018-03-02

Transactivation of inflammatory and immune mediators in asthma is tightly regulated by nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6). Therefore, we investigated the efficacy of simultaneous inhibition of NF-κB and STAT6 using a chimeric decoy strategy to prevent asthma exacerbation. The effects of decoy oligodeoxynucleotides were evaluated using an ovalbumin-induced mouse asthma model. Ovalbumin-sensitized mice received intratracheal administration of decoy oligodeoxynucleotides 3 days before ovalbumin challenge. Fluorescent-dye-labeled decoy oligodeoxynucleotides could be detected in lymphocytes and macrophages in the lung, and activation of NF-κB and STAT6 was inhibited by chimeric decoy oligodeoxynucleotide transfer. Consequently, treatment with chimeric or NF-κB decoy oligodeoxynucleotides protected against methacholine-induced airway hyperresponsiveness, whereas the effect of chimeric decoy oligodeoxynucleotides was significantly greater than that of NF-κB decoy oligodeoxynucleotides. Treatment with chimeric decoy oligodeoxynucleotides suppressed airway inflammation through inhibition of overexpression of interleukin-4 (IL-4), IL-5, and IL-13 and inflammatory infiltrates. Histamine levels in the lung were reduced via suppression of mast cell accumulation. A significant reduction in mucin secretion was observed due to suppression of MUC5AC gene expression. Interestingly, the inhibitory effects on IL-5, IL-13, and histamine secretion were achieved by transfer of chimeric decoy oligodeoxynucleotides only. This novel therapeutic approach could be useful to treat patients with various types of asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

School-Based Pediatric Asthma Surveillance in Massachusetts from 2005 to 2009

ERIC Educational Resources Information Center

Medaglia, Frances; Knorr, Robert S.; Condon, Suzanne K.; Charleston, Alicia C.

2013-01-01

Background: Asthma is the most common chronic disease among children today, yet surveillance is limited to national and state estimates which can vary over time, by location and by population types. This article describes a comprehensive statewide school-based asthma surveillance program and examines 5?years of surveillance data. Methods: After…

Greater involvement of neurokinins found in Guinea pig models of severe asthma compared with mild asthma.

PubMed

Mukaiyama, Osamu; Morimoto, Kiyoshi; Nosaka, Emi; Takahashi, Sakiko; Yamashita, Makoto

2004-08-01

Involvement of neurokinins in asthma has been previously pointed out by several reports. However, the relationship between neurokinins and the severity of asthma has remained unclear. We developed a model of mild asthma (model I) and severe asthma (model II) in guinea pigs, and investigated the function of neurokinins in both models. In models I and II, systemically sensitized guinea pigs were made to inhale ovalbumin once and three times, respectively. Substance P (SP) and neurokinin A (NKA) concentrations in the bronchoalveolar lavage fluid (BALF) were measured in models I and II. Then, the effects of a capsaicin pretreatment, which depletes neurokinins, in both animal models on airway narrowing induced by the last ovalbumin inhalation, airway hyperresponsiveness to inhaled methacholine, and eosinophil accumulation in BALF, were investigated. SP concentration tended to increase and the NKA concentration increased significantly in model II, but not in model I. Capsaicin pretreatment significantly inhibited the late bronchial response that was observed 2-6 h after the last ovalbumin inhalation, airway hyperresponsiveness and eosinophil accumulation in model II. On the other hand, it had no effects on the responses in model I. It is suggested that the more severe the disease, the greater the involvement of neurokinins. Copyright 2004 S. Karger AG, Basel

DOES VITAMIN D DEFICIENCY CONTRIBUTE TO THE SEVERITY OF ASTHMA IN CHILDREN AND ADULTS?

PubMed

Ahmed, Syed Zaryab; Jaleel, Anila; Hameed, Kamran; Qazi, Salman; Suleman, Ahsan

2015-01-01

Role of vitamin D in the health of bones has been well established for over decades; It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named "the sunshine vitamin". As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma.

INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

EPA Science Inventory

Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

Effect of inhaled corticosteroids on bronchial asthma in Japanese athletes.

PubMed

Hoshino, Yoshifumi; Koya, Toshiyuki; Kagamu, Hiroshi; Tsukioka, Keisuke; Toyama, Mio; Sakagami, Takuro; Hasegawa, Takashi; Narita, Ichiei; Arakawa, Masaaki; Suzuki, Eiichi

2015-04-01

Asthma has a higher prevalence in athlete populations such as Olympic athletes than in the general population. Correct diagnosis and management of asthma in athletes is important for symptom control and avoidance of doping accusations. However, few reports are available on asthma treatment in the athlete population in clinical practice. In this study, we focused on the clinical efficacy of inhaled corticosteroid (ICS) for asthma in a Japanese athlete population. The study subjects included athletes who visited the Niigata Institute for Health and Sports Medicine, Niigata, Japan for athletic tests and who were diagnosed with asthma on the basis of respiratory symptoms and positive results in a bronchodilator or bronchial provocation test such as exercise, hypertonic saline, or methacholine provocation. The athletes received ICS alone for at least 3 months, and the clinical background, sports type, and treatment efficacy were analyzed. The study population comprised 80 athletes (59 men and 21 women) with a median age of 16.0 years. Regarding sports type, 28 athletes engaged in winter sports (35%), 22 in endurance sports (27.5%), and 25 in indoor sports (31.3%). Although ICS is the primary treatment in athlete asthma, 16.3% of the athletes showed an unsatisfactory response to treatment according to the Global Evaluation of Treatment Effectiveness (GETE). These subjects were characterized by a decreased response to methacholine and lower values for FEV1/FVC and type 2 helper T cell (Th2)-associated biomarkers relative to responsive athletes. In multivariate analysis, FEV1/FVC and the logarithm to the base 10 of the IgE level were independently associated with the ICS response. These data suggest that ICS is effective for asthma in most athletes. However, certain asthmatic athletes are less responsive to ICS than expected. The pathogenesis in these subjects may differ from that of conventional asthma characterized by chronic allergic airway inflammation. Copyright © 2014 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Asthma, surgery, and general anesthesia: a review.

PubMed

Tirumalasetty, Jyothi; Grammer, Leslie C

2006-05-01

Over 20 million Americans are affected with asthma. Many will require some type of surgical procedure during which their asthma management should be optimized. Preoperative assessment of asthma should include a specialized history and physical as well as pulmonary function testing. In many asthmatic patients, treatment with systemic corticosteroids and bronchodilators is indicated to prevent the inflammation and bronchoconstriction associated with endotracheal intubation. The use of corticosteroids has not been shown to adversely affect wound healing or increase the rate of infections postoperatively. Preoperative systemic corticosteroids may be used safely in the majority of patients to decrease asthma-related morbidity.

The Healthy Learner Model for Student Chronic Condition Management--Part II: The Asthma Initiative

ERIC Educational Resources Information Center

Erickson, Cecelia DuPlessis; Splett, Patricia L.; Mullett, Sara Stoltzfus; Jensen, Charlotte; Belseth, Stephanie Bisson

2006-01-01

The Healthy Learner Asthma Initiative (HLAI) was designed as a comprehensive, school-community initiative to improve asthma management and produce healthy learners. National asthma guidelines were translated into components of asthma management in the school setting that defined performance expectations and lead to greater quality and consistency…

Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment.

PubMed

Durack, Juliana; Lynch, Susan V; Nariya, Snehal; Bhakta, Nirav R; Beigelman, Avraham; Castro, Mario; Dyer, Anne-Marie; Israel, Elliot; Kraft, Monica; Martin, Richard J; Mauger, David T; Rosenberg, Sharon R; Sharp-King, Tonya; White, Steven R; Woodruff, Prescott G; Avila, Pedro C; Denlinger, Loren C; Holguin, Fernando; Lazarus, Stephen C; Lugogo, Njira; Moore, Wendy C; Peters, Stephen P; Que, Loretta; Smith, Lewis J; Sorkness, Christine A; Wechsler, Michael E; Wenzel, Sally E; Boushey, Homer A; Huang, Yvonne J

2017-07-01

Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Community pharmacy-based asthma services--what do patients prefer?

PubMed

Naik Panvelkar, Pradnya; Armour, Carol; Saini, Bandana

2010-12-01

Patient preferences can influence the outcomes of treatment and so understanding and organizing health-care services around these preferences is vital. To explore patient preferences for types of community pharmacy-based asthma services, to investigate the influence of "experience" in molding preferences for such services, and to identify aspects of the services that patients prefer over others. Semistructured face-to-face interviews were conducted with a convenience sample of two types of asthma patients: (1) those naïve to a specialized asthma service and (2) those who had experienced a specialized asthma service. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed. Eighteen interviews were conducted (8 experienced patients, 10 naïve patients). The majority of the patients wanted the pharmacist to play a greater role in their asthma management. Patients experiencing increased levels of service had increased levels of expectations as well as more specific preferences for various aspects of the service. The key aspects of an asthma service that all patients wanted their pharmacists to provide were the provision of information about asthma and its medications, lung function testing and monitoring of their asthma, and checking/correcting their inhaler technique. Patients also expressed a desire for skilled communication and behavioral aspects from the pharmacist such as friendliness, empathy, attentiveness, and dedicated time. Patients highlighted the importance of privacy in the pharmacy. There was a high level of satisfaction toward the currently delivered asthma service among both naïve and experienced patients. The provision of the specialized service was associated with increased patient loyalty to the particular pharmacy. All patients indicated a willingness to participate in future pharmacy-delivered specialized asthma services. Elements of the specialized pharmacy-based asthma services important from a patient's perspective were identified. It would be important to identify the strength and magnitude of patient's preferences for different elements of such services. Future pharmacy-based services should incorporate patient preferences and tailor services to patient's needs to ensure their long-term viability.

Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease

PubMed Central

Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S.; Postma, Dirkje S.; Lenburg, Marc E.; Spira, Avrum; Woodruff, Prescott G.

2015-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma. PMID:25611785

Treating asthma with a self-management model of illness behaviour in an Australian community pharmacy setting.

PubMed

Smith, Lorraine; Bosnic-Anticevich, Sinthia Z; Mitchell, Bernadette; Saini, Bandana; Krass, Ines; Armour, Carol

2007-04-01

Asthma affects a considerable proportion of the population worldwide and presents a significant health problem in Australia. Given its chronic nature, effective asthma self-management approaches are important. However, despite research and interventions targeting its treatment, the management of asthma remains problematic. This study aimed to develop, from a theoretical basis, an asthma self-management model and implement it in an Australian community pharmacy setting in metropolitan Sydney, using a controlled, parallel-groups repeated-measures design. Trained pharmacists delivered a structured, step-wise, patient-focused asthma self-management program to adult participants over a 9-month period focusing on identification of asthma problems, goal setting and strategy development. Data on process- clinical- and psychosocial-outcome measures were gathered. Results showed that participants set an average of four new goals and six repeated goals over the course of the intervention. Most common goal-related themes included asthma triggers, asthma control and medications. An average of nine strategies per participant was developed to achieve the set goals. Common strategies involved visiting a medical practitioner for review of medications, improving adherence to medications and using medications before exercise. Clinical and psychosocial outcomes indicated significant improvements over time in asthma symptom control, asthma-related self-efficacy and quality of life, and negative affect. These results suggest that an asthma self-management model of illness behaviour has the potential to provide patients with a range of process skills for self-management, and deliver improvements in clinical and psychosocial indicators of asthma control. The results also indicate the capacity for the effective delivery of such an intervention by pharmacists in Australian community pharmacy settings.

Fluctuations in air pollution give risk warning signals of asthma hospitalization

NASA Astrophysics Data System (ADS)

Hsieh, Nan-Hung; Liao, Chung-Min

2013-08-01

Recent studies have implicated that air pollution has been associated with asthma exacerbations. However, the key link between specific air pollutant and the consequent impact on asthma has not been shown. The purpose of this study was to quantify the fluctuations in air pollution time-series dynamics to correlate the relationships between statistical indicators and age-specific asthma hospital admissions. An indicators-based regression model was developed to predict the time-trend of asthma hospital admissions in Taiwan in the period 1998-2010. Five major pollutants such as particulate matters with aerodynamic diameter less than 10 μm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) were included. We used Spearman's rank correlation to detect the relationships between time-series based statistical indicators of standard deviation, coefficient of variation, skewness, and kurtosis and monthly asthma hospitalization. We further used the indicators-guided Poisson regression model to test and predict the impact of target air pollutants on asthma incidence. Here we showed that standard deviation of PM10 data was the most correlated indicators for asthma hospitalization for all age groups, particularly for elderly. The skewness of O3 data gives the highest correlation to adult asthmatics. The proposed regression model shows a better predictability in annual asthma hospitalization trends for pediatrics. Our results suggest that a set of statistical indicators inferred from time-series information of major air pollutants can provide advance risk warning signals in complex air pollution-asthma systems and aid in asthma management that depends heavily on monitoring the dynamics of asthma incidence and environmental stimuli.

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds

PubMed Central

Jarvis, J; Seed, M; Elton, R; Sawyer, L; Agius, R

2005-01-01

Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard. PMID:15778257

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

PubMed

Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

2017-08-31

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Asthma control and productivity loss in those with work-related asthma: A population-based study.

PubMed

Wong, Alyson; Tavakoli, Hamid; Sadatsafavi, Mohsen; Carlsten, Chris; FitzGerald, J Mark

2017-06-01

In Canada, asthma is the third leading cause of work loss, yet little is known about the associated productivity loss. The goal of this study was to look at the relationship between asthma control and productivity loss, particularly contrasting those with work-related asthma (WRA) and non-work-related asthma (NWRA). A population-based random sample of adults with asthma in British Columbia, Canada, was prospectively recruited. Asthma control was graded according to Global Initiative for Asthma classification, while productivity loss and presence of WRA was assessed using questionnaires. Ordinal regression models were then used to associate WRA with asthma control. Generalized linear models were applied to estimate the average productivity loss associated with different levels of asthma control among those with WRA and NWRA. The study included 300 employed adults. Sixty (20%) had WRA. The odds of being controlled were significantly lower in those with WRA (OR = 0.23, 95% CI: 0.09, 0.56; P < 0.01). Those with WRA and uncontrolled asthma had a significant difference in productivity loss due to presenteeism ($659.1 [95% CI: 12.9, 1581.5; P = 0.04]), but not absenteeism ($88.7 [95% CI: -86.5, 279.6; P = 0.35]), when compared to those with NWRA and uncontrolled asthma. There was no significant difference when a similar comparison was made for those with controlled or partially controlled asthma. WRA is associated with worse asthma control and increased productivity loss. Presenteeism makes a significant contribution to productivity loss and should be considered when evaluating the overall economic burden of asthma, particularly WRA.

Clinical documentation variations and NLP system portability: a case study in asthma birth cohorts across institutions.

PubMed

Sohn, Sunghwan; Wang, Yanshan; Wi, Chung-Il; Krusemark, Elizabeth A; Ryu, Euijung; Ali, Mir H; Juhn, Young J; Liu, Hongfang

2017-11-30

To assess clinical documentation variations across health care institutions using different electronic medical record systems and investigate how they affect natural language processing (NLP) system portability. Birth cohorts from Mayo Clinic and Sanford Children's Hospital (SCH) were used in this study (n = 298 for each). Documentation variations regarding asthma between the 2 cohorts were examined in various aspects: (1) overall corpus at the word level (ie, lexical variation), (2) topics and asthma-related concepts (ie, semantic variation), and (3) clinical note types (ie, process variation). We compared those statistics and explored NLP system portability for asthma ascertainment in 2 stages: prototype and refinement. There exist notable lexical variations (word-level similarity = 0.669) and process variations (differences in major note types containing asthma-related concepts). However, semantic-level corpora were relatively homogeneous (topic similarity = 0.944, asthma-related concept similarity = 0.971). The NLP system for asthma ascertainment had an F-score of 0.937 at Mayo, and produced 0.813 (prototype) and 0.908 (refinement) when applied at SCH. The criteria for asthma ascertainment are largely dependent on asthma-related concepts. Therefore, we believe that semantic similarity is important to estimate NLP system portability. As the Mayo Clinic and SCH corpora were relatively homogeneous at a semantic level, the NLP system, developed at Mayo Clinic, was imported to SCH successfully with proper adjustments to deal with the intrinsic corpus heterogeneity. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Development of an asthma disease management program in a children's hospital.

PubMed

Miller, Kelly; Ward-Smith, Peggy; Cox, Karen; Jones, Erika M; Portnoy, Jay M

2003-11-01

The incidence, morbidity, and mortality of asthma have been increasing at an alarming rate, making asthma the most common chronic illness of childhood. An asthma disease management program was developed to improve the care and management of patients with asthma--a comprehensive health care delivery model that was designed to improve the management of patients with asthma was designed and implemented. The goal of the program was to provide high-quality interventions for those children diagnosed with asthma. The asthma disease management program at Children's Mercy Hospital improved the care received, decreased costs, and improved the quality of life for those children with asthma.

Patient perceptions of asthma-related financial burden: public vs. private health insurance in the United States.

PubMed

Patel, Minal R; Caldwell, Cleopatra H; Song, Peter X K; Wheeler, John R C

2014-10-01

Given the complexity of the health insurance market in the United States and the confusion that often stems from these complexities, patient perception about the value of health insurance in managing chronic disease is important to understand. To examine differences between public and private health insurance in perceptions of financial burden with managing asthma, outcomes, and factors that explain these perceptions. Secondary analysis was performed using baseline data from a randomized clinical trial that were collected through telephone interviews with 219 African American women seeking services for asthma and reporting perceptions of financial burden with asthma management. Path analysis with multigroup models and multiple variable regression analyses were used to examine associations. For public (P < .001) and private (P < .01) coverage, being married and more educated were indirectly associated with greater perceptions of financial burden through different explanatory pathways. When adjusted for multiple morbidities, asthma control, income, and out-of-pocket expenses, those with private insurance used fewer inpatient (P < .05) and emergency department (P < .001) services compared with those with public insurance. When also adjusted for health insurance, greater financial burden was associated with more urgent office visits (P < .001) and lower quality of life (P < .001). African American women who perceive asthma as a financial burden regardless of health insurance report more urgent health care visits and lower quality of life. Burden may be present despite having and being able to generate economic resources and health insurance. Further policy efforts are indicated and special attention should focus on type of coverage. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A twin study of early-childhood asthma in Puerto Ricans.

PubMed

Bunyavanich, Supinda; Silberg, Judy L; Lasky-Su, Jessica; Gillespie, Nathan A; Lange, Nancy E; Canino, Glorisa; Celedón, Juan C

2013-01-01

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood. To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤ 3 years old. 678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages 1 and 3 years: physician-diagnosed asthma, asthma medication use in the past year, and ≥ 1 hospitalization for asthma in the past year. Models were additionally adjusted for early-life environmental tobacco smoke exposure, sex, and age. The prevalences of physician-diagnosed asthma, asthma medication use, and hospitalization for asthma were 11.6%, 10.8%, 4.9% at age 1 year, and 34.1%, 40.1%, and 8.5% at 3 years, respectively. Shared environmental effects contributed to the majority of variance in susceptibility to physician-diagnosed asthma and asthma medication use in the first year of life (84%-86%), while genetic effects drove variance in all phenotypes (45%-65%) at age 3 years. Early-life environmental tobacco smoke, sex, and age contributed to variance in susceptibility. Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children.

Full-chain health impact assessment of traffic-related air pollution and childhood asthma.

PubMed

Khreis, Haneen; de Hoogh, Kees; Nieuwenhuijsen, Mark J

2018-05-01

Asthma is the most common chronic disease in children. Traffic-related air pollution (TRAP) may be an important exposure contributing to its development. In the UK, Bradford is a deprived city suffering from childhood asthma rates higher than national and regional averages and TRAP is of particular concern to the local communities. We estimated the burden of childhood asthma attributable to air pollution and specifically TRAP in Bradford. Air pollution exposures were estimated using a newly developed full-chain exposure assessment model and an existing land-use regression model (LUR). We estimated childhood population exposure to NO x and, by conversion, NO 2 at the smallest census area level using a newly developed full-chain model knitting together distinct traffic (SATURN), vehicle emission (COPERT) and atmospheric dispersion (ADMS-Urban) models. We compared these estimates with measurements and estimates from ESCAPE's LUR model. Using the UK incidence rate for childhood asthma, meta-analytical exposure-response functions, and estimates from the two exposure models, we estimated annual number of asthma cases attributable to NO 2 and NO x in Bradford, and annual number of asthma cases specifically attributable to traffic. The annual average census tract levels of NO 2 and NO x estimated using the full-chain model were 15.41 and 25.68 μg/m 3 , respectively. On average, 2.75 μg/m 3 NO 2 and 4.59 μg/m 3 NO x were specifically contributed by traffic, without minor roads and cold starts. The annual average census tract levels of NO 2 and NO x estimated using the LUR model were 21.93 and 35.60 μg/m 3 , respectively. The results indicated that up to 687 (or 38% of all) annual childhood asthma cases in Bradford may be attributable to air pollution. Up to 109 cases (6%) and 219 cases (12%) may be specifically attributable to TRAP, with and without minor roads and cold starts, respectively. This is the first study undertaking full-chain health impact assessment of TRAP and childhood asthma in a disadvantaged population with public concern about TRAP. It further adds to scarce literature exploring the impact of different exposure assessments. In conservative estimates, air pollution and TRAP are estimated to cause a large, but largely preventable, childhood asthma burden. Future progress with childhood asthma requires a move beyond the prevalent disease control-based approach toward asthma prevention. Copyright © 2018 Elsevier Ltd. All rights reserved.

S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.

PubMed

Yoon, Sun-Young; Hong, Gyong Hwa; Kwon, Hyouk-Soo; Park, Sunjoo; Park, So Young; Shin, Bomi; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-06-03

Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.

Dietary patterns and asthma prevalence, incidence and control.

PubMed

Barros, R; Moreira, A; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Lopes, C; Severo, M; Moreira, P

2015-11-01

The increased asthma prevalence in westernized societies has been suggested to be related to environment exposures and lifestyle changes, particularly diet. We aimed to explore the association between dietary patterns and asthma prevalence, incidence and control in a nationally representative population. Data from 32,644 adults, 53% female, from the 4th Portuguese National Health Survey were analysed. Prevalence of asthma was 5.3%; 'current asthma', defined by asthma symptoms within previous year, 3.5%; 'current medicated asthma' defined by use of asthma medication within previous year, 3.0%; 'current severe asthma' defined by emergency visit because of asthma within previous year, 1.4%; and 'incident asthma', 0.2%. Dietary patterns (DP) were identified by latent trait models based on dietary intake. Unconditional logistic regression models were performed to analyse association between DP and asthma. Age, gender, education, family income, proxy reporting information, smoking, body mass index and physical activity level were analysed as confounders. Two of the five identified DP were associated with asthma: 'high fat, sugar and salt' DP (positively correlated with pastry, chocolate and sweet desserts, candies, salty snacks, chips, fruit juices, soft drinks and alcoholic beverages consumption at snacks) was associated with asthma prevalence (OR = 1.13, 95% CI = 1.03, 1.24) and current severe asthma (OR = 1.23, 95% CI = 1.03, 1.48), while 'fish, fruit and vegetables' DP (positively correlated with fish, vegetables and fruit intake at meals) was negatively associated with current (OR = 0.84, 95% CI = 0.73, 0.98), and current medicated asthma (OR = 0.84, 95% CI = 0.72, 0.98), after adjustment for confounders. Our results suggest a protective association between 'fish, vegetables and fruit' DP and current asthma and current medicated asthma, and a detrimental association between 'high fat, sugar and salt' DP and severe asthma prevalence, further supporting the rational for diet and lifestyle intervention studies in asthma based on whole dietary patterns and physical activity. © 2015 John Wiley & Sons Ltd.

Forecasting peak asthma admissions in London: an application of quantile regression models.

PubMed

Soyiri, Ireneous N; Reidpath, Daniel D; Sarran, Christophe

2013-07-01

Asthma is a chronic condition of great public health concern globally. The associated morbidity, mortality and healthcare utilisation place an enormous burden on healthcare infrastructure and services. This study demonstrates a multistage quantile regression approach to predicting excess demand for health care services in the form of asthma daily admissions in London, using retrospective data from the Hospital Episode Statistics, weather and air quality. Trivariate quantile regression models (QRM) of asthma daily admissions were fitted to a 14-day range of lags of environmental factors, accounting for seasonality in a hold-in sample of the data. Representative lags were pooled to form multivariate predictive models, selected through a systematic backward stepwise reduction approach. Models were cross-validated using a hold-out sample of the data, and their respective root mean square error measures, sensitivity, specificity and predictive values compared. Two of the predictive models were able to detect extreme number of daily asthma admissions at sensitivity levels of 76 % and 62 %, as well as specificities of 66 % and 76 %. Their positive predictive values were slightly higher for the hold-out sample (29 % and 28 %) than for the hold-in model development sample (16 % and 18 %). QRMs can be used in multistage to select suitable variables to forecast extreme asthma events. The associations between asthma and environmental factors, including temperature, ozone and carbon monoxide can be exploited in predicting future events using QRMs.

Forecasting peak asthma admissions in London: an application of quantile regression models

NASA Astrophysics Data System (ADS)

Soyiri, Ireneous N.; Reidpath, Daniel D.; Sarran, Christophe

2013-07-01

Asthma is a chronic condition of great public health concern globally. The associated morbidity, mortality and healthcare utilisation place an enormous burden on healthcare infrastructure and services. This study demonstrates a multistage quantile regression approach to predicting excess demand for health care services in the form of asthma daily admissions in London, using retrospective data from the Hospital Episode Statistics, weather and air quality. Trivariate quantile regression models (QRM) of asthma daily admissions were fitted to a 14-day range of lags of environmental factors, accounting for seasonality in a hold-in sample of the data. Representative lags were pooled to form multivariate predictive models, selected through a systematic backward stepwise reduction approach. Models were cross-validated using a hold-out sample of the data, and their respective root mean square error measures, sensitivity, specificity and predictive values compared. Two of the predictive models were able to detect extreme number of daily asthma admissions at sensitivity levels of 76 % and 62 %, as well as specificities of 66 % and 76 %. Their positive predictive values were slightly higher for the hold-out sample (29 % and 28 %) than for the hold-in model development sample (16 % and 18 %). QRMs can be used in multistage to select suitable variables to forecast extreme asthma events. The associations between asthma and environmental factors, including temperature, ozone and carbon monoxide can be exploited in predicting future events using QRMs.

SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model.

PubMed

Wu, Hui-Mei; Fang, Lei; Shen, Qi-Ying; Liu, Rong-Yu

2015-10-01

c-Jun N-terminal kinase (JNK) relays extracellular stimuli through phosphorylation cascades that lead to various cell responses. In the present study, we aimed to investigate the effect of the JNK inhibitor SP600125 on the resolution of airway inflammation, and the underlying mechanism using a murine acute asthma model. Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) on day 0, and challenged with OVA on day 14-20. Meanwhile, some of the mice were treated with SP600125 (30 mg/kg) intraperitoneally 2 h before each challenge. The airway inflammation was evaluated by counting the numbers of various types of inflammatory cells in bronchoalveolar lavage fluid (BALF), histopathology, cytokines production and mucus secretion in individual mouse. In addition, we analyzed the protein levels of phosphorylated JNK and TLR9 in the lung tissues. SP600125 markedly reduced the invasion of inflammatory cells into the peribronchial regions, and decreased the numbers of eosinophils, monocytes, neutrophils and lymphocytes in BALF. SP600125 also reduced the level of plasma OVA-specific IgE, lowered the production of pro-inflammatory cytokines in BALF and alleviated mucus secretion. Meanwhile, SP600125 inhibited OVA-induced, increased expression of p-JNK and TLR9 in the lung tissues. Collectively, our data demonstrated that SP600125 promoted resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. The JNK-TLR9 pathway may be a new therapeutic target in the treatment for the allergic asthma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence of asthmatic symptoms in Lebanese patients with type 1 diabetes and their unaffected siblings compared to age-matched controls.

PubMed

Taleb, Nadine; Bou Khalil, Pierre; Zantout, Mira S; Zalloua, Pierre; Azar, Sami T

2010-12-01

Patients with type 1 diabetes (a TH1 disease) have been reported to be at a lower risk of developing asthma (a TH2 disease). Both diseases are affected by environmental and genetic factors. Our objective is to examine this relationship in Lebanon, a Middle-Eastern country, where no previous similar studies are available. This is a cross-sectional observational study conducted at the Chronic Care Center, a referral medical center for type 1 diabetics. Patients with type 1 diabetes aged 6-39 years old, their unaffected siblings and age-matched control completed the International Primary Care Airways Group asthma screening questionnaire. The prevalence of asthma symptoms was compared among the three groups and separately within a subgroup of diabetics in relation to their carrier state of previously collected genetic data. Among 305 diabetics, 776 siblings and 187 controls, diabetics were at lower risk of having any asthma symptoms than controls; OR 0.48 (95% CI 0.32-0.72, p < 0.001) and siblings were at lower risk than diabetics and controls; OR 0.64 (95% CI 0.45-0.91, p = 0.01) and 0.28 (95% CI 0.19-0.42, p < 0.001), respectively. Among 66 diabetics, carriers of the HLA-DQB1*0201 allele were at lower risk of having any asthma symptoms than non-carriers (25.5 vs. 53.3%, p = 0.04). Only a statistically non-significant trend of higher risk was observed in carriers of HLA-DQB1*0301 and G allele at the 49 (A/G) nucleotide of CTLA-4 gene. The TH1-TH2 paradigm might partially explain these findings, since siblings were the least to report asthma symptoms. Future research is needed with diagnostic tests for asthma and extensive genetic testing.

Risk Factors in Preschool Children for Predicting Asthma During the Preschool Age and the Early School Age: a Systematic Review and Meta-Analysis.

PubMed

Bao, Yixia; Chen, Zhimin; Liu, Enmei; Xiang, Li; Zhao, Deyu; Hong, Jianguo

2017-11-18

The aim of this study was to identify risk factors of asthma among children < 6 years old (preschool age) for predicting asthma during the preschool age and early school age (≤ 10 years of age). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017. Prospective or retrospective cohort and case-control studies were included. Studies had to have evaluated risk factors or a predictive model for developing asthma in children ≤ 6 years of age or persistent asthma in early school age. A total of 17 studies were included in the analysis. Factors associated with developing asthma in children ≤ 10 years of age (both pre-school and early school age) included male gender (pooled OR = 1.70, P < 0.001), atopic dermatitis (pooled OR = 2.02, P < 0.001), a family history of asthma (pooled OR = 2.20, P < 0.001), and serum IgE levels ≥ 60 kU/l or having specific IgE (pooled OR = 2.36, P < 0.001). A history of exposure to smoke or wheezing was also associated with persistent asthma in early school age (pooled OR = 1.51, P = 0.030 and pooled OR = 2.59, P < 0.001, respectively). In general, asthma predictive models (e.g., API, PIAMA, PAPS) had relatively low sensitivity (range, 21% to 71.4%) but high specificity (range, 69% to 98%). The study found that male gender, exposure to smoke, atopic dermatitis, family history of asthma, history of wheezing, and serum IgE level ≥ 60 kU/l or having specific IgE were significantly associated with developing asthma by either preschool or early school age. Asthma predictive models can be developed by those risk factors.

A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.

PubMed

Forno, Erick; Wang, Ting; Yan, Qi; Brehm, John; Acosta-Perez, Edna; Colon-Semidey, Angel; Alvarez, Maria; Boutaoui, Nadia; Cloutier, Michelle M; Alcorn, John F; Canino, Glorisa; Chen, Wei; Celedón, Juan C

2017-10-01

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

Cutting edge: guinea pigs with a natural C3a-receptor defect exhibit decreased bronchoconstriction in allergic airway disease: evidence for an involvement of the C3a anaphylatoxin in the pathogenesis of asthma.

PubMed

Bautsch, W; Hoymann, H G; Zhang, Q; Meier-Wiedenbach, I; Raschke, U; Ames, R S; Sohns, B; Flemme, N; Meyer zu Vilsendorf, A; Grove, M; Klos, A; Köhl, J

2000-11-15

Asthma is a major cause of morbidity worldwide with prevalence and severity still increasing at an alarming pace. Hallmarks of this disease include early-phase bronchoconstriction with subsequent eosinophil infiltration, symptoms that may be mimicked in vivo by the complement-derived C3a anaphylatoxin, following its interaction with the single-copy C3aR. We analyzed the pathophysiological role of the C3a anaphylatoxin in a model of experimental OVA-induced allergic asthma, using an inbred guinea pig strain phenotypically unresponsive to C3a. Molecular analysis of this defect revealed a point mutation within the coding region of the C3aR that creates a stop codon, thereby effectively inactivating gene function. When challenged by OVA inhalation, sensitized animals of this strain exhibited a bronchoconstriction decreased by approximately 30% in comparison to the corresponding wild-type strain. These data suggest an important role of C3a in the pathogenesis of asthma and define a novel target for drug intervention strategies.

An evaluation of a community pharmacy-based rural asthma management service.

PubMed

Saini, Bandana; Filipovska, Julija; Bosnic-Anticevich, Sinthia; Taylor, Susan; Krass, Ines; Armour, Carol

2008-04-01

To compare the effect of a pharmacist-delivered rural asthma management service (RAMS) on health outcomes for people with asthma in a rural/regional area with 'standard care' delivered through community pharmacies. A parallel group controlled repeated measures study. Community pharmacies in Central West New South Wales. Standardised protocols and resources based on national asthma management guidelines, delivered by specially trained community pharmacists. Patients visited the pharmacy at baseline and 1, 3 and 6 months after baseline in the intervention group and at baseline plus 6 months after baseline in the control group. The intervention pharmacists (n = 12) were trained to deliver the RAMS model, while control pharmacists (n = 8) provided standard asthma care to their recruited patients. Fifty-one and 39 patients were recruited by intervention and control pharmacists. Asthma severity score which was a composite score based on recency, frequency and severity of asthma symptoms, and asthma history. Data compared at the final visit between groups indicated that the RAMS patient group demonstrated a significant reduction in the asthma severity scores (7.9 +/- 2.6 versus 10.4 +/- 2.6, P < 0.001); a reduction in the risk of non-adherence to medication scores (1.6 +/- 0.7 versus 2.3 +/- 1.1, P < 0.001); and an increase in the proportion of patients owning a written action plan (50% versus 23%, P = 0.04). These results indicated that the community pharmacy-based RAMS model can improve asthma outcomes for patients in rural settings, and similar models for asthma and other chronic diseases should be tested rigorously and adopted in rural primary care practice.

Adipose tissue content and distribution in children and adolescents with bronchial asthma.

PubMed

Umławska, Wioleta

2015-02-01

The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

Glutathione redox regulates airway hyperresponsiveness and airway inflammation in mice.

PubMed

Koike, Yoko; Hisada, Takeshi; Utsugi, Mitsuyoshi; Ishizuka, Tamotsu; Shimizu, Yasuo; Ono, Akihiro; Murata, Yukie; Hamuro, Junji; Mori, Masatomo; Dobashi, Kunio

2007-09-01

Glutathione is the major intracellular redox buffer. We have shown that glutathione redox status, which is the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC) regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL-12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are characteristic of asthma and trigger off an inflammation. Accordingly, we studied the effects of the intracellular glutathione redox status on airway hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is a membrane-permeating GSH precursor, to elevate the intracellular GSH level and GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1 cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE directly inhibited chemokine-induced eosinophil chemotaxis without affecting eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.

Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma.

PubMed

Kim, Dong Eon; Lee, Yonghyun; Kim, MinGyo; Lee, Soyoung; Jon, Sangyong; Lee, Seung-Hyo

2017-09-01

Although asthma, a chronic inflammatory airway disease, is relatively well-managed by inhaled corticosteroids, the side effects associated with the long-term use of these agents precipitate the need for alternative therapeutic options based on differing modes of action. Bilirubin, a potent endogenous antioxidant, and anti-inflammatory molecule have been shown to ameliorate asthmatic symptoms; however, its clinical translation has been limited owing to its water insolubility and associated potential toxicity. Here we report the first application of bilirubin-based nanoparticles (BRNPs) as a nanomedicine for the treatment of allergic lung inflammatory disease. BRNPs were prepared directly from self-assembly of PEGylated bilirubin in aqueous solution and had a hydrodynamic diameter of ∼100 nm. Because allergen-specific type 2 T-helper (Th2) cells play a key role in the pathogenesis and progression of allergic asthma, the effects of BRNPs on Th2 immune responses were investigated both in vivo and in vitro. BRNPs after intravenous injection (i.v.) showed much higher serum concentration and a longer circulation time of bilirubin than the intraperitoneal injection (i.p.) of BRNPs or unconjugated bilirubin (UCB). The anti-asthmatic effects of BRNPs were assessed in a mouse model of allergen-induced asthma. Compared with UCB, treatment with BRNPs suppressed the symptoms of experimental allergic asthma and dramatically ameliorated Th2-related allergic lung inflammation. Consistent with these results, BRNPs caused a reduction of Th2 cell populations and the expression of related cytokines by antibody-stimulated CD4 + T cells in vitro. Therefore, our results establish BRNPs as an important immunomodulatory agent that may be useful as a therapeutic for allergic lung inflammatory disease and other immune-mediated disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Childhood incident asthma and traffic-related air pollution at home and school.

PubMed

McConnell, Rob; Islam, Talat; Shankardass, Ketan; Jerrett, Michael; Lurmann, Fred; Gilliland, Frank; Gauderman, Jim; Avol, Ed; Künzli, Nino; Yao, Ling; Peters, John; Berhane, Kiros

2010-07-01

Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children's Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO(2)), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25-1.82] and near schools (HR 1.45; 95% CI, 1.06-1.98). Ambient NO(2) measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18-4.01). In models with both NO(2) and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO(2) was attenuated (HR 1.37; 95% CI, 0.69-2.71). Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.

Mega-dose vitamin C attenuated lung inflammation in mouse asthma model.

PubMed

Jeong, Young-Joo; Kim, Jin-Hee; Kang, Jae Seung; Lee, Wang Jae; Hwang, Young-Il

2010-12-01

Asthma is a Th2-dependent disease mediated by IgE and Th2 cytokines, and asthmatic patients suffer from oxidative stresses from abnormal airway inflammation. Vitamin C is a micro-nutrient functioning as an antioxidant. When administered at a mega-dose, vitamin C has been reported to shift immune responses toward Th1. Thus, we tried to determine whether vitamin C exerted beneficial effects in asthma animal model. Asthma was induced in mice by sensitizing and challenging with ovalbumin. At the time of challenge, 3~5 mg of vitamin C was administered and the effects were evaluated. Vitamin C did not modulate Th1/Th2 balance in asthma model. However, it decreased airway hyperreactivity to methacholine, decreased inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration. These results suggest that vitamin C administered at the time of antigen challenge exerted anti-inflammatory effects. Further studies based on chronic asthma model are needed to evaluate a long-term effect of vitamin C in asthma. In conclusion, even though vitamin C did not show any Th1/Th2 shifting effects in this experiment, it still exerted moderate anti-inflammatory effects. Considering other beneficial effects and inexpensiveness of vitamin C, mega-dose usage of vitamin C could be a potential supplementary modality for the management of asthma.

An analysis of asthma hospitalizations, air pollution, and weather conditions in Los Angeles County, California.

PubMed

Delamater, Paul L; Finley, Andrew O; Banerjee, Sudipto

2012-05-15

There is now a large body of literature supporting a linkage between exposure to air pollutants and asthma morbidity. However, the extent and significance of this relationship varies considerably between pollutants, location, scale of analysis, and analysis methods. Our primary goal is to evaluate the relationship between asthma hospitalizations, levels of ambient air pollution, and weather conditions in Los Angeles (LA) County, California, an area with a historical record of heavy air pollution. County-wide measures of carbon monoxide (CO), nitrogen dioxide (NO(2)), ozone (O(3)), particulate matter<10 μm (PM(10)), particulate matter<2.5 μm (PM(2.5)), maximum temperature, and relative humidity were collected for all months from 2001 to 2008. We then related these variables to monthly asthma hospitalization rates using Bayesian regression models with temporal random effects. We evaluated model performance using a goodness of fit criterion and predictive ability. Asthma hospitalization rates in LA County decreased between 2001 and 2008. Traffic-related pollutants, CO and NO(2), were significant and positively correlated with asthma hospitalizations. PM(2.5) also had a positive, significant association with asthma hospitalizations. PM(10), relative humidity, and maximum temperature produced mixed results, whereas O(3) was non-significant in all models. Inclusion of temporal random effects satisfies statistical model assumptions, improves model fit, and yields increased predictive accuracy and precision compared to their non-temporal counterparts. Generally, pollution levels and asthma hospitalizations decreased during the 9 year study period. Our findings also indicate that after accounting for seasonality in the data, asthma hospitalization rate has a significant positive relationship with ambient levels of CO, NO(2), and PM(2.5). Copyright © 2012 Elsevier B.V. All rights reserved.

Associations between ozone and morbidity using the Spatial Synoptic Classification system

PubMed Central

2011-01-01

Background Synoptic circulation patterns (large-scale tropospheric motion systems) affect air pollution and, potentially, air-pollution-morbidity associations. We evaluated the effect of synoptic circulation patterns (air masses) on the association between ozone and hospital admissions for asthma and myocardial infarction (MI) among adults in North Carolina. Methods Daily surface meteorology data (including precipitation, wind speed, and dew point) for five selected cities in North Carolina were obtained from the U.S. EPA Air Quality System (AQS), which were in turn based on data from the National Climatic Data Center of the National Oceanic and Atmospheric Administration. We used the Spatial Synoptic Classification system to classify each day of the 9-year period from 1996 through 2004 into one of seven different air mass types: dry polar, dry moderate, dry tropical, moist polar, moist moderate, moist tropical, or transitional. Daily 24-hour maximum 1-hour ambient concentrations of ozone were obtained from the AQS. Asthma and MI hospital admissions data for the 9-year period were obtained from the North Carolina Department of Health and Human Services. Generalized linear models were used to assess the association of the hospitalizations with ozone concentrations and specific air mass types, using pollutant lags of 0 to 5 days. We examined the effect across cities on days with the same air mass type. In all models we adjusted for dew point and day-of-the-week effects related to hospital admissions. Results Ozone was associated with asthma under dry tropical (1- to 5-day lags), transitional (3- and 4-day lags), and extreme moist tropical (0-day lag) air masses. Ozone was associated with MI only under the extreme moist tropical (5-day lag) air masses. Conclusions Elevated ozone levels are associated with dry tropical, dry moderate, and moist tropical air masses, with the highest ozone levels being associated with the dry tropical air mass. Certain synoptic circulation patterns/air masses in conjunction with ambient ozone levels were associated with increased asthma and MI hospitalizations. PMID:21609456

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

PubMed Central

Antal, Péter; Kiszel, Petra Sz.; Gézsi, András; Hadadi, Éva; Virág, Viktor; Hajós, Gergely; Millinghoffer, András; Nagy, Adrienne; Kiss, András; Semsei, Ágnes F.; Temesi, Gergely; Melegh, Béla; Kisfali, Péter; Széll, Márta; Bikov, András; Gálffy, Gabriella; Tamási, Lilla; Falus, András; Szalai, Csaba

2012-01-01

Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA). This method uses Bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the Bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated. With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2–1.8); p = 3×10−4). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics. In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance. PMID:22432035

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years.

PubMed

Hall, Sannette C; Agrawal, Devendra K

2017-05-01

Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations, and overall poor outcomes in patients with asthma. Given the increase in the prevalence of asthma over the past few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in treating bronchial asthma. Using the key terms [Vitamin D, asthma, clinical trials, in vivo and in vitro studies], the [PubMed, Google Scholar] databases were searched for [clinical trials, original research articles, meta-analyses, and reviews], English-language articles published from [2012] to the present. Articles that were [Articles that did not meet these criteria were excluded] excluded from the analysis. Several studies have found that low serum levels of vitamin D (< 20 ng/mL) are associated with increased exacerbations, increased airway inflammation, decreased lung function, and poor prognosis in asthmatic patients. Results from in vitro and in vivo studies in animals and humans have suggested that supplementation with vitamin D may ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support a beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women, and adults have primarily found little to no effect of vitamin D supplementation on improved asthma symptoms, onset, or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency may influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce antiinflammatory effects. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Adverse Childhood Events are Related to the Prevalence of Asthma and Chronic Obstructive Pulmonary Disorder Among Adult Women in Hawaii.

PubMed

Remigio-Baker, Rosemay A; Hayes, Donald K; Reyes-Salvail, Florentina

2015-12-01

In the US, women surpass men in the prevalence of lung diseases. Limited studies exist on the association of adverse childhood events (ACEs) to asthma and chronic obstructive pulmonary disorder (COPD) particularly among women and cohorts of understudied populations (e.g., Pacific Islanders). This study evaluated the ACEs-asthma and ACEs-COPD relationships among women in Hawaii and the contribution of poor health factors (smoking, binge drinking, and obesity) in these associations. Using data from 3363 women in the Behavioral Risk Factor Surveillance System-Hawaii, we assessed how self-reported ACEs [count and type (household dysfunction, and physical, verbal and sexual abuse)] relate to asthma and COPD. Multivariable log-binomial regression, accounting for the sampling design, and model adjustments for socio-demographics, healthcare access, emotional support, current smoking, binge drinking, and BMI status were used to generate prevalence ratios. For every increase in ACE count, the likelihood for asthma increased by 7 % (CI = 1.02-1.13), and for COPD, by 21 % (CI = 1.12-1.31) accounting for socio-demographics, healthcare access, and emotional support. Verbal abuse was also associated with greater likelihood for asthma independent of these covariates (PR = 1.43, CI = 1.14-1.79). Household dysfunction (PR = 1.82, CI = 1.15-2.82) and physical (PR = 2.01, CI = 1.20-3.37), verbal (PR = 2.24, CI = 1.38-3.65) and sexual (PR = 1.81, CI = 1.10-2.97) abuse were all associated with COPD using similar adjustments. Additional adjustment for smoking, binge drinking, and BMI status did not impact the ACE-asthma associations and only modestly attenuated the ACE-COPD relationships. Primary and secondary prevention of ACEs may optimize the health of young girls in Hawaii, and reduce the burden of asthma and COPD among women in the state.

Adverse Childhood Events Are Related to the Prevalence of Asthma and Chronic Obstructive Pulmonary Disorder Among Adult Women In Hawaii

PubMed Central

Remigio-Baker, Rosemay A.; Hayes, Donald K; Reyes-Salvail, Florentina

2015-01-01

PURPOSE In the US, women surpass men in the prevalence of lung diseases. Limited studies exist on the association of adverse childhood events (ACEs) to asthma and COPD particularly among women and cohorts of understudied populations (e.g. Pacific Islanders). This study evaluated the ACEs-asthma and ACEs-COPD relationships among women in Hawaii and the contribution of poor health factors (smoking, binge drinking and obesity) in these associations. METHODS Using data from 3,363 women in the Behavioral Risk Factor Surveillance System-Hawaii, we assessed how self-reported ACEs (count and type [household dysfunction, and physical, verbal and sexual abuse]) relate to asthma and COPD. Multivariable log-binomial regression, accounting for the sampling design, and model adjustments for socio-demographics, healthcare access, emotional support, current smoking, binge drinking and BMI status were used to generate prevalence ratios. RESULTS For every increase in ACE count, the likelihood for asthma increased by 7% (CI=1.02–1.13), and for COPD, by 21% (CI=1.12–1.31) accounting for socio-demographics, healthcare access and emotional support. Verbal abuse was also associated with greater likelihood for asthma independent of these covariates (PR=1.43, CI=1.14–1.79). Household dysfunction (PR=1.82, CI=1.15–2.82) and physical (PR=2.01, CI=1.20–3.37), verbal (PR=2.24, CI=1.38–3.65) and sexual (PR=1.81, CI=1.10–2.97) abuse were all associated with COPD using similar adjustments. Additional adjustment for smoking, binge drinking and BMI status did not impact the ACE-asthma associations and only modestly attenuated the ACE-COPD relationships. CONCLUSIONS Primary and secondary prevention of ACEs may optimize the health of young girls in Hawaii, and reduce the burden of asthma and COPD among women in the state. PMID:26267594

RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

PubMed Central

Arikkatt, Jaisy; Ullah, Md Ashik; Short, Kirsty Renfree; Zhang, Vivan; Gan, Wan Jun; Loh, Zhixuan; Werder, Rhiannon B; Simpson, Jennifer; Sly, Peter D; Mazzone, Stuart B; Spann, Kirsten M; Ferreira, Manuel AR; Upham, John W; Sukkar, Maria B; Phipps, Simon

2017-01-01

Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target. DOI: http://dx.doi.org/10.7554/eLife.21199.001 PMID:28099113

Serum periostin relates to type-2 inflammation and lung function in asthma: Data from the large population-based cohort Swedish GA(2)LEN.

PubMed

James, A; Janson, C; Malinovschi, A; Holweg, C; Alving, K; Ono, J; Ohta, S; Ek, A; Middelveld, R; Dahlén, B; Forsberg, B; Izuhara, K; Dahlén, S-E

2017-11-01

Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear. To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics. Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life. Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma. We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Tobacco Control Laws and Pediatric Asthma.

PubMed

Hatoun, Jonathan; Davis-Plourde, Kendra; Penti, Brian; Cabral, Howard; Kazis, Lewis

2018-01-01

Exposure to environmental tobacco smoke increases pediatric asthma severity. Strict, state-level tobacco control reduces smoking. The Child Asthma Call-Back Survey (Child ACBS) is a nationally representative survey of the guardians of children with asthma. The American Lung Association's annual State of Tobacco Control report grades tobacco control laws in each state including a tax grade (cigarette excise tax relative to the national mean), and a smoke-free air grade (number of locations where smoking is prohibited). We joined Child ACBS data from 2006 to 2010 with corresponding state and year tobacco grades. In the primary analysis, we investigated the effect of state tax grades on a child's asthma severity by using a logistic regression model adjusting for year. A secondary analysis assessed the impact of smoke-free air grades on in-home smoking. Our analysis included 12 860 Child ACBS interviews from 35 states over 5 years, representing over 24 million individuals. We merged 112 unique State of Tobacco Control grades with patient data by state and year. A higher tax grade was associated with reduced severity (adjusted odds ratio = 1.40; P = .007, 95% confidence interval: 1.10-1.80). A better smoke-free air grade was not associated with decreased in-home smoking after adjusting for confounding by income and type of residence. A stronger tobacco tax is associated with reduced asthma severity. Further study is needed to determine the effect of smoke-free air laws on in-home environmental. This work supports ongoing efforts to strengthen tobacco control through federal and state regulations. Copyright © 2018 by the American Academy of Pediatrics.

Household biomass fuel use, asthma symptoms severity, and asthma underdiagnosis in rural schoolchildren in Nigeria: a cross-sectional observational study.

PubMed

Oluwole, Oluwafemi; Arinola, Ganiyu O; Huo, Dezheng; Olopade, Christopher O

2017-01-05

In 2014, the International Study of Asthma and Allergies in Childhood (ISAAC) reported that the highest prevalence of symptoms of severe asthma was found in the low- and middle-income countries (LMICs), including Nigeria. While exposure to biomass fuel use may be an important risk factor in the development of asthma, its association with asthma symptoms severity has not been well-established. The aim of this study is to extend the spectrum of environmental risk factors that may be contributing towards increasing asthma morbidity, especially asthma symptoms severity in rural schoolchildren in Nigeria and to examine possible asthma underdiagnosis among this population. Authors conducted a cross-sectional survey in three rural communities in Nigeria. Asthma symptoms were defined according to the ISAAC criteria. Information on the types of household fuel used for cooking was used to determine household cooking fuel status. Asthma symptoms severity was defined based on frequencies of wheeze, day- and night-time symptoms, and speech limitations. Logistic regression analyses were used to explore associations. A total of 1,690 Nigerian schoolchildren participated in the study. Overall, 37 (2.2%) had diagnosed asthma and 413 (24.4%) had possible asthma (asthma-related symptoms but not diagnosed asthma). Children from biomass fuel households had higher proportion of possible asthma (27.7 vs. 22.2%; p < 0.05) and symptoms of severe asthma (18.2 vs. 7.6%; p = 0.048). In adjusted analyses, biomass fuel use was associated with increased odds of severe symptoms of asthma [odds ratios (OR) = 2.37; 95% CI: 1.16-4.84], but not with possible asthma (OR = 1.22; 95% CI: 0.95-1.56). In rural Nigerian children with asthma symptoms, the use of biomass fuel for cooking is associated with an increased risk of severe asthma symptoms. There is additional evidence that rural children might be underdiagnosed for asthma.

Pediatric asthma hospitalizations among urban minority children and the continuity of primary care.

PubMed

Utidjian, Levon H; Fiks, Alexander G; Localio, A Russell; Song, Lihai; Ramos, Mark J; Keren, Ron; Bell, Louis M; Grundmeier, Robert W

2017-12-01

To examine the effect of ambulatory health care processes on asthma hospitalizations. A retrospective cohort study using electronic health records was completed. Patients aged 2-18 years receiving health care from 1 of 5 urban practices between Jan 1, 2004 and Dec 31, 2008 with asthma documented on their problem list were included. Independent variables were modifiable health care processes in the primary care setting: (1) use of asthma controller medications; (2) regular assessment of asthma symptoms; (3) use of spirometry; (4) provision of individualized asthma care plans; (5) timely influenza vaccination; (6) access to primary healthcare; and (7) use of pay for performance physician incentives. Occurrence of one or more asthma hospitalizations was the primary outcome of interest. We used a log linear model (Poisson regression) to model the association between the factors of interest and number of asthma hospitalizations. 5,712 children with asthma were available for analysis. 96% of the children were African American. The overall hospitalization rate was 64 per 1,000 children per year. None of the commonly used asthma-specific indicators of high quality care were associated with fewer asthma hospitalizations. Children with documented asthma who experienced a lack of primary health care (no more than one outpatient visit at their primary care location in the 2 years preceding hospitalization) were at higher risk of hospitalization compared to those children with a greater number of visits (incidence rate ratio 1.39; 95% CI 1.09-1.78). In children with asthma, more frequent primary care visits are associated with reduced asthma hospitalizations.

Development, implementation, and evaluation of a community pharmacy-based asthma care model.

PubMed

Saini, Bandana; Krass, Ines; Armour, Carol

2004-11-01

Pharmacists are uniquely placed in the healthcare system to address critical issues in asthma management in the community. Various programs have shown the benefits of a pharmacist-led asthma care program; however, no such programs have previously been evaluated in Australia. To measure the impact of a specialized asthma service provided through community pharmacies in terms of objective patient clinical, humanistic, and economic outcomes. A parallel controlled design, where 52 intervention patients and 50 control patients with asthma were recruited in 2 distinct locations, was used. In the intervention area, pharmacists were trained and delivered an asthma care model, with 3 follow-up visits over 6 months. This model was evaluated based on clinical, humanistic, and economic outcomes compared between and within groups. There was a significant reduction in asthma severity in the intervention group, 2.6 +/- 0.5 to 1.6 +/- 0.7 (mean +/- SD; p < 0.001) versus the control group, 2.3 +/- 0.7 to 2.4 +/- 0.5. In the intervention group, peak flow indices improved from 82.7% +/- 8.2% at baseline to 87.4% +/- 8.9% (p < 0.001) at the final visit, and there was a significant reduction in the defined daily dose of albuterol used by patients, from 374.8 +/- 314.8 microg at baseline to 198.4 +/- 196.9 microg at the final visit (p < 0.015). There was also a statistically significant improvement in perceived control of asthma and asthma-related knowledge scores in the intervention group compared with the control group between baseline and the final visit. Annual savings of $132.84(AU) in medication costs per patient and $100,801.20 for the whole group, based on overall severity reduction, were demonstrated. Based on the results of this study, it appears that a specialized asthma care model offers community pharmacists an opportunity to contribute toward improving asthma management in the Australian community.

Peripheral killer cells do not differentiate between asthma patients with or without fixed airway obstruction.

PubMed

Tubby, Carolyn; Negm, Ola H; Harrison, Timothy; Tighe, Patrick J; Todd, Ian; Fairclough, Lucy C

2017-06-01

The three main types of killer cells - CD8 + T cells, NK cells and NKT cells - have been linked to asthma and chronic obstructive pulmonary disease (COPD). However, their role in a small subset of asthma patients displaying fixed airway obstruction (FAO), similar to that seen in COPD, has not been explored. The objective of the present study was to investigate killer cell numbers, phenotype and function in peripheral blood from asthma patients with FAO, asthma patients without FAO, and healthy individuals. Peripheral CD8 + T cells (CD8 + CD3 + CD56 - ), NK cells (CD56 + CD3 - ) and NKT-like cells (CD56 + CD3 + ) of 14 asthma patients with FAO (post-bronchodilator FEV/FVC <0.7, despite clinician-optimised treatment), 7 asthma patients without FAO (post-bronchodilator FEV/FVC ≥ 0.7), and 9 healthy individuals were studied. No significant differences were seen between the number, receptor expression, MAPK signalling molecule expression, cytotoxic mediator expression, and functional cytotoxicity of peripheral killer cells from asthma patients with FAO, asthma patients without FAO and healthy individuals. Peripheral killer cell numbers or functions do not differentiate between asthma patients with or without fixed airway obstruction.

Adult-Onset Asthma Becomes the Dominant Phenotype among Women by Age 40 Years. The Longitudinal CARDIA Study

PubMed Central

Qualls, Clifford; Schuyler, Mark; Arynchyn, Alexander; Alvarado, Jesse H.; Smith, Lewis J.; Jacobs, David R.

2013-01-01

Rationale: Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported. Objectives: To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset. Methods: This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort in the United States over a 25-year period. Adult- and pediatric-onset asthma phenotypes were studied, as defined by age at onset of 18 years or older. Subjects with asthma were categorized by sex, obesity, atopy, smoking, and race by mean age/examination year, using a three-way analysis of covariance model. Natural history of disease was examined using probabilities derived from a Markov chain model. Measurements and Main Results: Asthma of adult onset became the dominant (i.e., exceeded 50%) phenotype in women by age 40 years. The age by which adult-onset asthma became the dominant phenotype was further lowered for obese, nonatopic, ever-smoking, or white women. The prevalence trend with increasing time for adult-onset disease was greater among subjects with nonatopic than atopic asthma among both sexes. Furthermore, adult-onset asthma had remarkable sex-related differences in risk factors. In both sexes, the quiescent state for adult-onset asthma was less frequent and also “less stable” over time than for pediatric-onset asthma. Conclusions: Using a large national cohort, this study challenges the dictum that most asthma in adults originates in childhood. Studies of the differences between pediatric- and adult-onset asthma may provide greater insight into the phenotypic heterogeneity of asthma. PMID:23802814

Neighborhood poverty, urban residence, race/ethnicity, and asthma: Rethinking the inner-city asthma epidemic.

PubMed

Keet, Corinne A; McCormack, Meredith C; Pollack, Craig E; Peng, Roger D; McGowan, Emily; Matsui, Elizabeth C

2015-03-01

Although it is thought that inner-city areas have a high burden of asthma, the prevalence of asthma in inner cities across the United States is not known. We sought to estimate the prevalence of current asthma in US children living in inner-city and non-inner-city areas and to examine whether urban residence, poverty, or race/ethnicity are the main drivers of asthma disparities. The National Health Interview Survey 2009-2011 was linked by census tract to data from the US Census and the National Center for Health Statistics. Multivariate logistic regression models adjusted for sex; age; race/ethnicity; residence in an urban, suburban, medium metro, or small metro/rural area; poverty; and birth outside the United States, with current asthma and asthma morbidity as outcome variables. Inner-city areas were defined as urban areas with 20% or more of households at below the poverty line. We included 23,065 children living in 5,853 census tracts. The prevalence of current asthma was 12.9% in inner-city and 10.6% in non-inner-city areas, but this difference was not significant after adjusting for race/ethnicity, region, age, and sex. In fully adjusted models black race, Puerto Rican ethnicity, and lower household income but not residence in poor or urban areas were independent risk factors for current asthma. Household poverty increased the risk of asthma among non-Hispanics and Puerto Ricans but not among other Hispanics. Associations with asthma morbidity were very similar to those with prevalent asthma. Although the prevalence of asthma is high in some inner-city areas, this is largely explained by demographic factors and not by living in an urban neighborhood. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Predicting Children's Asthma Hospitalizations: Rural and Urban Differences in Texas

ERIC Educational Resources Information Center

Grineski, Sara E.

2009-01-01

Asthma is the number one chronic health condition facing children today; however, little is known about rural-urban inequalities in asthma. This "area effects on health" study examines rural-urban differences in childhood asthma hospitalizations within the state of Texas using negative binomial regression models. Effects associated with…

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis.

PubMed

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-06-01

Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results. Instead of model antigens, gradually relevant allergens such as house dust mite in asthma, and food allergens like peanut, apple and peach in food allergy research were used. Novel engineered mouse models such as a mouse with a T-cell receptor for house dust mite allergen Der p 1, or with transgenic human hFcγR genes, facilitated the investigation of single molecules of interest. Whole-body plethysmography has become a state-of-the-art in-vivo readout in asthma research. In food allergy and anaphylaxis research, novel techniques were developed allowing real-time monitoring of in-vivo effects following allergen challenge. Networks to share tissues were established as an effort to reduce animal experiments in allergy which cannot be replaced by in-vitro measures. Natural and artificial animal models were used to explore the pathophysiology of asthma, food allergy and anaphylaxis and to improve prophylactic and therapeutic measures. Especially the novel mouse models mimicking molecular aspects of the complex immune network in asthma, food allergy and anaphylaxis will facilitate proof-of-concept studies under controlled conditions.

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis

PubMed Central

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-01-01

Purpose of review Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. Recent findings While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results. Instead of model antigens, gradually relevant allergens such as house dust mite in asthma, and food allergens like peanut, apple and peach in food allergy research were used. Novel engineered mouse models such as a mouse with a T-cell receptor for house dust mite allergen Der p 1, or with transgenic human hFcγR genes, facilitated the investigation of single molecules of interest. Whole-body plethysmography has become a state-of-the-art in-vivo readout in asthma research. In food allergy and anaphylaxis research, novel techniques were developed allowing real-time monitoring of in-vivo effects following allergen challenge. Networks to share tissues were established as an effort to reduce animal experiments in allergy which cannot be replaced by in-vitro measures. Summary Natural and artificial animal models were used to explore the pathophysiology of asthma, food allergy and anaphylaxis and to improve prophylactic and therapeutic measures. Especially the novel mouse models mimicking molecular aspects of the complex immune network in asthma, food allergy and anaphylaxis will facilitate proof-of-concept studies under controlled conditions. PMID:28346234

The use of remotely sensed environmental data in the study of asthma disease

NASA Astrophysics Data System (ADS)

Ayres-Sampaio, D.; Teodoro, A. C.; Freitas, A.; Sillero, N.

2012-09-01

Despite the growing use of Remote Sensing (RS) data in epidemiological studies, several diseases, including asthma, have not been studied yet using RS potentialities. Asthma is a chronic inflammatory disorder of the airway that affects people of all ages throughout the world. The expression of this disease can be influenced by some environmental factors such as allergens, air pollution or climate conditions. In this study, we modeled the distribution of asthma in each season, using Maximum entropy (Maxent) model and presence data obtained from a national database with asthma public hospitals admissions in Mainland Portugal, with discharges between years 2003 and 2008. We considered data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to retrieve estimates of near-surface air temperature and relative humidity. Land-use regression (LUR) models were developed to produce estimates of three pollutants: PM10, NO2, and CO. Moreover, MODIS Normalized Difference Vegetation Index (NDVI) was also used in the construction of Maxent models. All Maxent models predicted similar suitable areas and obtained acceptable area under the curve (AUC) values (~0.75) of the ROC plot. Our results show a strong relationship between asthma presence and NO2, suggesting that asthmatic people living in urban areas with high traffic volume have an increased risk of suffering asthma attacks. Furthermore, there is evidence of the effect of PM10, CO, and RH (during the Summer) in asthma expression. RS data have a great potential but also presents limitations that should be addressed to allow studying more complex diseases.

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics.

PubMed

Jones, Anya C; Troy, Niamh M; White, Elisha; Hollams, Elysia M; Gout, Alexander M; Ling, Kak-Ming; Kicic, Anthony; Stick, Stephen M; Sly, Peter D; Holt, Patrick G; Hall, Graham L; Bosco, Anthony

2018-01-24

Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDM S ) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDM S -wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

PubMed

Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid

2017-05-01

Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Time for a new language for asthma control: results from REALISE Asia

PubMed Central

Price, David; David-Wang, Aileen; Cho, Sang-Heon; Ho, James Chung-Man; Jeong, Jae-Won; Liam, Chong-Kin; Lin, Jiangtao; Muttalif, Abdul Razak; Perng, Diahn-Warng; Tan, Tze-Lee; Yunus, Faisal; Neira, Glenn

2015-01-01

Purpose Asthma is a global health problem, and asthma prevalence in Asia is increasing. The REcognise Asthma and LInk to Symptoms and Experience Asia study assessed patients’ perception of asthma control and attitudes toward treatment in an accessible, real-life adult Asian population. Patients and methods An online survey of 2,467 patients with asthma from eight Asian countries/regions, aged 18–50 years, showed greater than or equal to two prescriptions in previous 2 years and access to social media. Patients were asked about their asthma symptoms, exacerbations and treatment type, views and perceptions of asthma control, attitudes toward asthma management, and sources of asthma information. Results Patients had a mean age of 34.2 (±7.4) years and were diagnosed with asthma for 12.5 (±9.7) years. Half had the Global Initiative for Asthma-defined uncontrolled asthma. During the previous year, 38% of patients visited the emergency department, 33% were hospitalized, and 73% had greater than or equal to one course of oral corticosteroids. About 90% of patients felt that their asthma was under control, 82% considered their condition as not serious, and 59% were concerned about their condition. In all, 66% of patients viewed asthma control as managing attacks and 24% saw it as an absence of or minimal symptoms. About 14% of patients who correctly identified their controller inhalers had controlled asthma compared to 6% who could not. Conclusion Patients consistently overestimated their level of asthma control contrary to what their symptoms suggest. They perceived control as management of exacerbations, reflective of a crisis-oriented mind-set. Interventions can leverage on patients’ trust in health care providers and desire for self-management via a new language to generate a paradigm shift toward symptom control and preventive care. PMID:26445555

Digital Health Intervention for Asthma: Patient-Reported Value and Usability.

PubMed

Merchant, Rajan; Inamdar, Rubina; Henderson, Kelly; Barrett, Meredith; Su, Jason G; Riley, Jesika; Van Sickle, David; Stempel, David

2018-06-04

Although digital health tools are increasingly recognized as effective in improving clinical outcomes such as asthma control and medication adherence, few studies have assessed patient experiences and perception of value. The aim of this study was to evaluate patient satisfaction, perception of usability and value, and desire to continue after 12 months of using a digital health intervention to support asthma management. Participants were enrolled in a randomized controlled study evaluating the impact of a digital health platform for asthma management. Participants used electronic inhaler sensors to track medication use and accessed their information in a digital health platform. Electronic surveys were administered to intervention arm participants aged 12 years and older after 12 months of use. The survey assessed asthma control, patient satisfaction with the sensor device, and perception of the usability and value of the digital health platform through closed-ended and open-ended questions. Logistic regression models were used to assess the impact of participants' characteristics on survey completion, satisfaction, and perception of value. Of the 207 intervention arm participants aged 12 years and older, 89 submitted survey responses (42.9% response rate). Of these 89 participants, 70 reported being very satisfied (79%, 70/89) or somewhat satisfied (20%, 18/89) with the inhaler sensor device. Moreover, 93% (83/89) expressed satisfaction with the reports, and 90% (80/89) found the information from the reports useful for learning about their asthma. In addition, 72% (64/89) of the participants reported that they were interested in continuing to use the sensor and platform beyond the study. There were no significant differences in satisfaction with the device or the platform across participants' characteristics, including device type, age, sex, insurance type, asthma control, or syncing history; however, participants with smartphones and longer participation were more likely to take the survey. Electronic sensors and a digital health platform were well received by participants who reported satisfaction and perceived value. These results were consistent across multiple participants' characteristics. These findings can add to a limited literature to keep improving digital health interventions and ensure the meaningful and enduring impact on patient outcomes. ©Rajan Merchant, Rubina Inamdar, Kelly Henderson, Meredith Barrett, Jason G Su, Jesika Riley, David Van Sickle, David Stempel. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 04.06.2018.

β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.

PubMed

Lin, Rui; Choi, Yeon Ho; Zidar, David A; Walker, Julia K L

2018-06-01

Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4 + T-helper cell type 2 (Th2) cells are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of β-arrestin (β-arr)-2 and that CD4 + T cells from these mice displayed significantly reduced CCL22-mediated chemotaxis. Because CCL22-mediated activation of CCR4 plays a role in Th2 cell regulation in asthmatic inflammation, we hypothesized that CCR4-mediated migration of CD4 + Th2 cells to the lung in asthma may use β-arr-dependent signaling. To test this hypothesis, we assessed the effect of various signaling inhibitors on CCL22-induced chemotaxis using in vitro-polarized primary CD4 + Th2 cells from β-arr2-knockout and wild-type mice. Our results show, for the first time, that CCL22-induced, CCR4-mediated Th2 cell chemotaxis is dependent, in part, on a β-arr2-dependent signaling pathway. In addition, we show that this chemotactic signaling mechanism involves activation of P-p38 and Rho-associated protein kinase. These findings point to a proinflammatory role for β-arr2-dependent signaling and support β-arr2 as a novel therapeutic target in asthma.

Associations between Neighborhood Walkability and Incident and Ongoing Asthma in Children.

PubMed

Simons, Elinor; Dell, Sharon D; Moineddin, Rahim; To, Teresa

2018-06-01

Childhood asthma has shown variable associations with children's physical activity. Neighborhood walkability captures community features that promote walking and is protective against some chronic conditions, such as obesity and diabetes. We evaluated associations between home neighborhood walkability and incident and ongoing childhood asthma. In this population-based cohort study, we used prospectively collected administrative healthcare data for the Province of Ontario housed at the Institute for Clinical Evaluative Sciences. We followed an administrative data cohort of 326,383 Toronto children born between 1997 and 2003, inclusive, until ages 8-15 years. Home neighborhood walkability quintile was measured using a validated walkability index with four dimensions: population density, dwelling density, access to retail and services, and street connectivity. Incident asthma was defined by time of entry into the validated Ontario Asthma Surveillance Information System database, which requires two outpatient visits for asthma within two consecutive years or any hospitalization for asthma and follows children with asthma longitudinally starting at any age. Associations between walkability and incident asthma were examined using Cox proportional hazards models. Associations between ongoing asthma and walkability in each year of life were examined using generalized linear mixed models. Twenty-one percent of children (n = 69,628) developed incident asthma and were followed longitudinally in the Ontario Asthma Surveillance Information System database. Low birth home neighborhood walkability was associated with an increased incidence of asthma (hazard ratio, 1.11; 95% confidence interval, 1.08-1.14). Among children with asthma, low walkability in a given year of a child`s life was associated with greater odds of ongoing asthma in the same year (odds ratio, 1.12; 95% confidence interval, 1.09-1.14). Children living in neighborhoods with low walkability were at increased risk of incident and ongoing asthma. Neighborhood walkability improvement, such as by adding pedestrian paths to improve street connectivity, offers potential strategies to contribute to primary asthma prevention.

Does pre-hospital telephone communication with a clinician result in more appropriate medication administration by parents during childhood asthma exacerbations?

PubMed

Garro, A C; Fearon, D; Koinis-Mitchell, D; McQuaid, E L

2009-11-01

The National Heart, Lung and Blood Institute asthma guidelines recommend that parents communicate with a clinician during childhood asthma exacerbations when symptoms worsen or do not improve with initial therapy. This study tested the hypothesis that communication by parents with a clinician before an Emergency Department visit was associated with more appropriate medication administration for children with asthma exacerbations. This was a retrospective cohort study using data gathered from parents of children presenting with an asthma exacerbation to the emergency department. The communicating cohort included parents who communicated by telephone with a clinician during the exacerbation and the non-communicating cohort included parents who did not. Multivariate logistic regression models were used to test three hypotheses; communication with a clinician is associated with (1) administration of short-acting beta-agonists (SABAs), (2) increased dosing frequency of SABAs, and (3) administration of an oral corticosteroid. A total of 199 subjects were enrolled, with 104 (52.3%) in the communicating and 95 (47.7%) in the non-communicating cohort. There was an association between communication and provider practice type, with children who received routine care from a private practice provider more likely to communicate with the clinician than children in hospital-based clinics or community health centers (Adjusted OR 1.9, 95% CI 1.0-3.7). Impoverished children and children insured by Medicaid were less likely to communicate with a clinician (controlling for provider type). Parents who communicated with a clinician were more likely to administer a SABA (adjusted OR 3.6, 95% CI 1.3-9.4) and an oral corticosteroid (adjusted OR 3.3, 95% CI 1.3-8.4) but were not more likely to administer a SABA with increased dosing frequency (adjusted OR 0.9, 95% CI 0.5-1.6). Parents of children with asthma exacerbations who communicated with clinicians were more likely to administer SABAs and an oral corticosteroid before bringing their child to an emergency department. Frequency of SABA dosing was not associated with communication. Clinicians providing telephone advice to parents need to provide explicit instructions about medication administration, emphasizing the frequency with which SABAs should be administered.

Chloral hydrate for sedation of children with asthma during dental treatment.

PubMed

Abdulhamid, I; Tremblay, M; Stenger, J; Tutag Lehr, V

2016-06-01

We hypothesised that chloral hydrate is safe and effective for sedation during dental treatments for children with mild asthma. We evaluated the safety and efficacy of chloral hydrate by measuring changes in heart rate (HR), transcutaneous oxygen saturation, (SpO2), asthma score, behaviour, types and frequency of adverse reactions associated with chloral hydrate were assessed throughout treatment. Children (<10 years old) with mild asthma undergoing dental treatments received a single 65 mg/kg oral dose of chloral hydrate liquid 1 hour prior to treatment in an open label trial. Heart rate (HR), SpO2, asthma score, behaviour, types and frequency of adverse reactions associated with chloral hydrate were assessed throughout treatment. Asthma score was obtained before and after treatment. Thirty minutes after treatment, SpO2, HR, and level of consciousness was assessed. Twenty four children were enrolled and 92% (22/24) recovered from sedation without respiratory depression. Two experienced mild respiratory depression related to chloral hydrate. Asthma was not a contributing factor as they did not experience wheezing, cough, tachypnoea, or retractions. Inhaled nitrous oxide supplemented chloral hydrate sedation in 63% (15/24) children to achieve effective cooperation. Three children had a SpO2 <95% (2 during treatment, 1 during recovery). Chloral hydrate 65 mg/kg administered a as single oral dose appears to be safe with respect to disease exacerbation for children with mild asthma undergoing dental treatment. Due to ineffective sedation and mild respiratory depression associated with chloral hydrate, newer, easily titrated medications, such as midazolam, may offer advantages.

The association between asthma and absenteeism among working adults in the United States: results from the 2008 medical expenditure panel survey.

PubMed

Wu, Chung-Hsuen; Erickson, Steven R

2012-09-01

The purpose of this study was to evaluate the association between asthma status and the occurrence and length of work absences among the US working adults. A cross-sectional study was conducted using the 2008 Medical Expenditure Panel Survey (MEPS). Employed respondents between ages 18 and 55 years were included. The association between asthma status (whether respondents have asthma or not) and occurrence of absences and the length of time per absence was evaluated using a two-part model. A multivariate logistic regression as the first part of the model was to estimate the probability of being absent from work at least once during the observation period as a function of asthma status. A multivariate negative binomial regression as the second part of the model was used to assess whether the length of each absence from work was associated with asthma status among respondents who reported at least one absence from work. Sociodemographic, socioeconomic, employment-related, health status, and comorbidity variables were included in each model as covariates. Of 12,161 respondents, 8.2% reported having asthma, which accounted for 10.4 million working adults in the United States in 2008. Employed adults with asthma were more likely to report having at least one absence from work compared to those without asthma in bivariate analyses (26.2% vs. 16.2%, p < .01). After adjusting for the number of comorbid chronic conditions and other covariates, there was no significant difference between having asthma and absenteeism among respondents (odds ratio (OR) = 1.31, 95% confidence interval (CI) = 0.99-1.72, rate ratio (RR) = 1.25, 95% CI = 0.91-1.72). Overall burden of illness as measured by comorbidity indices and perceived health status, but not asthma alone, contributes to absenteeism as well as the number of days off during each occurrence among employed people. It is important for health services researchers to consider overall burden of illness when examining the association between a general outcome such as absence from work and specific conditions such as asthma.

Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors.

PubMed

Wen, Hui-Ju; Chiang, Tung-Liang; Lin, Shio-Jean; Guo, Yue Leon

2015-05-01

Symptoms of atopic disease start early in human life. Predicting risk for childhood asthma by early-life exposure would contribute to disease prevention. A birth cohort study was conducted to investigate early-life risk factors for childhood asthma and to develop a predictive model for the development of asthma. National representative samples of newborn babies were obtained by multistage stratified systematic sampling from the 2005 Taiwan Birth Registry. Information on potential risk factors and children's health was collected by home interview when babies were 6 months old and 5 yr old, respectively. Backward stepwise regression analysis was used to identify the risk factors of childhood asthma for predictive models that were used to calculate the probability of childhood asthma. A total of 19,192 children completed the study satisfactorily. Physician-diagnosed asthma was reported in 6.6% of 5-yr-old children. Pre-pregnancy factors (parental atopy and socioeconomic status), perinatal factors (place of residence, exposure to indoor mold and painting/renovations during pregnancy), and postnatal factors (maternal postpartum depression and the presence of atopic dermatitis before 6 months of age) were chosen for the predictive models, and the highest predicted probability of asthma in 5-yr-old children was 68.1% in boys and 78.1% in girls; the lowest probability in boys and girls was 4.1% and 3.2%, respectively. This investigation provides a technique for predicting risk of childhood asthma that can be used to developing a preventive strategy against asthma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors associated with adolescent and caregiver reported problems in using asthma medications.

PubMed

Sleath, Betsy; Carpenter, Delesha M; Walsh, Kathleen E; Davis, Scott A; Watson, Claire Hayes; Lee, Charles; Loughlin, Ceila E; Garcia, Nacire; Reuland, Daniel S; Tudor, Gail

2018-04-18

The purpose of this study was to: (a) describe the types of medication problems/concerns youth with asthma and their caregivers reported and (b) examine the association between socio-demographic characteristics and youth and caregiver reported medication problems/concerns. English-and Spanish-speaking youth ages 11-17 with persistent asthma were recruited at four pediatric clinics. Youth were interviewed and caregivers completed questionnaires about reported asthma medication concerns/problems. Multiple logistic regression was used to analyze the data. Three hundred and fifty-nine youth were recruited. Eighty percent of youth and 70% of caregivers reported one or more problems in using asthma medications. The most commonly reported problems by youth were: (a) hard to remember when to take the asthma medication (54%) and (b) hard to use asthma medication at school (34%). Younger children were significantly more likely to report difficulty in understanding their asthma medication's directions and difficulty reading the print on the medication's package. Caregivers' top-reported problem was that it is hard for their child to remember to take their asthma medications (49%). Caregivers without Medicaid were significantly more likely to express difficulty paying for their child's asthma medications. Difficulty remembering to take asthma medication was a significant problem for youth and their caregivers. Providers should work with youth and their caregivers to identify asthma medication problems and discuss strategies to address those problems.

Beyond Reading Alone: The Relationship Between Aural Literacy And Asthma Management

PubMed Central

Rosenfeld, Lindsay; Rudd, Rima; Emmons, Karen M.; Acevedo-García, Dolores; Martin, Laurie; Buka, Stephen

2010-01-01

Objectives To examine the relationship between literacy and asthma management with a focus on the oral exchange. Methods Study participants, all of whom reported asthma, were drawn from the New England Family Study (NEFS), an examination of links between education and health. NEFS data included reading, oral (speaking), and aural (listening) literacy measures. An additional survey was conducted with this group of study participants related to asthma issues, particularly asthma management. Data analysis focused on bivariate and multivariable logistic regression. Results In bivariate logistic regression models exploring aural literacy, there was a statistically significant association between those participants with lower aural literacy skills and less successful asthma management (OR:4.37, 95%CI:1.11, 17.32). In multivariable logistic regression analyses, controlling for gender, income, and race in separate models (one-at-a-time), there remained a statistically significant association between those participants with lower aural literacy skills and less successful asthma management. Conclusion Lower aural literacy skills seem to complicate asthma management capabilities. Practice Implications Greater attention to the oral exchange, in particular the listening skills highlighted by aural literacy, as well as other related literacy skills may help us develop strategies for clear communication related to asthma management. PMID:20399060

Neutrophilic inflammation is associated with altered airway hydration in stable asthmatics.

PubMed

Loughlin, Ceila E; Esther, Charles R; Lazarowski, Eduardo R; Alexis, Neil E; Peden, David B

2010-01-01

Airway dehydration is a potential trigger of bronchoconstriction in exercise-induced asthma; however, its role in stable asthma has not been explored. Using sputum percent solids, as an indicator of airway hydration, we sought relationships between airway hydration and other known markers of neutrophilic (TH1) and allergic (TH2) inflammation in stable asthma. Thirty-seven atopic subjects with stable asthma and 15 healthy controls underwent sputum induction. Sputum was analyzed for percent solids, cell counts, cellular and biochemical markers of inflammation and purines. Sputum percent solids was significantly elevated in stable asthmatics vs. controls and positively correlated with markers of neutrophilic/TH1-type inflammation (neutrophils, IL-8 and AMP). Sputum percent solids were not correlated with markers of allergic/TH2-type inflammation. These data suggest a direct relationship between neutrophil inflammation and airway hydration in stable asthmatics. Copyright 2009 Elsevier Ltd. All rights reserved.

The public health implications of asthma.

PubMed Central

Bousquet, Jean; Bousquet, Philippe J.; Godard, Philippe; Daures, Jean-Pierre

2005-01-01

Asthma is a very common chronic disease that occurs in all age groups and is the focus of various clinical and public health interventions. Both morbidity and mortality from asthma are significant. The number of disability-adjusted life years (DALYs) lost due to asthma worldwide is similar to that for diabetes, liver cirrhosis and schizophrenia. Asthma management plans have, however, reduced mortality and severity in countries where they have been applied. Several barriers reduce the availability, affordability, dissemination and efficacy of optimal asthma management plans in both developed and developing countries. The workplace environment contributes significantly to the general burden of asthma. Patients with occupational asthma have higher rates of hospitalization and mortality than healthy workers. The surveillance of asthma as part of a global WHO programme is essential. The economic cost of asthma is considerable both in terms of direct medical costs (such as hospital admissions and the cost of pharmaceuticals) and indirect medical costs (such as time lost from work and premature death). Direct costs are significant in most countries. In order to reduce costs and improve quality of care, employers and health plans are exploring more precisely targeted ways of controlling rapidly rising health costs. Poor control of asthma symptoms is a major issue that can result in adverse clinical and economic outcomes. A model of asthma costs is needed to aid attempts to reduce them while permitting optimal management of the disease. This paper presents a discussion of the burden of asthma and its socioeconomic implications and proposes a model to predict the costs incurred by the disease. PMID:16175830

Length of Stay, Conditional Length of Stay, and Prolonged Stay in Pediatric Asthma

PubMed Central

Silber, Jeffrey H; Rosenbaum, Paul R; Even-Shoshan, Orit; Shabbout, Mayadah; Zhang, Xuemei; Bradlow, Eric T; Marsh, Roger R

2003-01-01

Objective To understand differences in length of stay for asthma patients between New York State and Pennsylvania across children's and general hospitals in order to better guide policy. Data Sources/Study Setting All pediatric admissions for asthma in the states of Pennsylvania and New York using claims data obtained from each state for the years 1996–1998, n=38,310. Study Design A retrospective cohort design to model length of stay (LOS), the probability of prolonged stay, conditional length of stay (CLOS or the LOS after stay is prolonged), and the probability of readmission, controlling for patient factors, state, location and hospital type. Analytic Methods Logit models were used to estimate the probability of prolonged stay and readmission. The LOS and the CLOS were estimated with Cox regression. Model variables included comorbidities, income, race, distance from hospital, and insurance type. Prolonged stay was based on a Hollander-Proschan “New-Worse-Than-Used” test, corresponding to a three-day stay. Principal Findings The LOS was longer in New York than Pennsylvania, and the probabilities of prolonged stay and readmission were much higher in New York than Pennsylvania. However, once an admission was prolonged, there were no differences in CLOS between states (when readmissions were not added to the LOS calculation). In both states, children's hospitals and general hospitals had similar adjusted LOS. Conclusions Management of asthma appears more efficient in Pennsylvania than New York: Less severe patients are discharged faster in Pennsylvania than New York; once discharged, patients are less likely to be readmitted in Pennsylvania than New York. However, once a stay is prolonged, there is little difference between New York and Pennsylvania, suggesting medical care for severely ill patients is similar across states. Differences between children's and general hospitals were small as compared to differences between states. We conclude that policy initiatives in New York, and other states, should focus their efforts on improving the care provided to less severe patients in order to help reduce overall length of stay. PMID:12822916

Asthma Management in Minority Children: Practical Insights for Clinicians, Researchers, and Public Health Planners.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

This monograph summarizes asthma management conclusions developed by five studies funded under a 5-year federal program titled "Interventions for the Control of Asthma among Black and Hispanic Children." The research goals were to develop model, replicable programs to reduce asthma morbidity; decrease inappropriate use of health care…

Neighborhood Poverty, Urban Residence, Race/ethnicity and Asthma: Rethinking the Inner-city Asthma Epidemic

PubMed Central

Keet, Corinne A.; McCormack, Meredith C.; Pollack, Craig E.; Peng, Roger D.; McGowan, Emily; Matsui, Elizabeth C.

2015-01-01

Background Although it is thought that inner-city areas have a high burden of asthma, the prevalence of asthma in inner-cities across the U.S. is not known. Objective To estimate the prevalence of current asthma in U.S. children living in inner-city and non-inner city areas, and to examine whether urban residence, poverty or race/ethnicity are the main drivers of asthma disparities. Methods The National Health Interview Survey 2009–2011 was linked by census tract to data from the U.S. Census and the National Center for Health Statistics. Multivariate logistic regression models adjusted for sex, age, race/ethnicity, residence in an urban, suburban, medium metro or small metro/rural area, poverty, and birth outside the U.S. with current asthma and asthma morbidity as outcome variables. Inner-city areas were defined as urban areas with ≥20% of households below the poverty line. Results 23,065 children living in 5,853 census tracts were included. The prevalence of current asthma was 12.9% in inner-city and 10.6% in non-inner-city areas, but this difference was not significant after adjusting for race/ethnicity, region, age and sex. In fully adjusted models, Black race, Puerto Rican ethnicity and lower household income, but not residence in poor or urban areas, were independent risk factors for current asthma. Household poverty increased the risk of asthma among non-Hispanics and Puerto Ricans but not among other Hispanics. Associations with asthma morbidity were very similar to prevalent asthma. Conclusions Although the prevalence of asthma is high in some inner-city areas, this is largely explained by demographic factors and not by living in an urban neighborhood. PMID:25617226

Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

PubMed

Muraro, Antonella; Lemanske, Robert F; Hellings, Peter W; Akdis, Cezmi A; Bieber, Thomas; Casale, Thomas B; Jutel, Marek; Ong, Peck Y; Poulsen, Lars K; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Seys, Sven F; Agache, Ioana

2016-05-01

In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A simulation model of building intervention impacts on indoor environmental quality, pediatric asthma, and costs.

PubMed

Fabian, Maria Patricia; Adamkiewicz, Gary; Stout, Natasha Kay; Sandel, Megan; Levy, Jonathan Ian

2014-01-01

Although indoor environmental conditions can affect pediatric asthmatic patients, few studies have characterized the effect of building interventions on asthma-related outcomes. Simulation models can evaluate such complex systems but have not been applied in this context. We sought to evaluate the impact of building interventions on indoor environmental quality and pediatric asthma health care use, and to conduct cost comparisons between intervention and health care costs and energy savings. We applied our previously developed discrete event simulation model (DEM) to simulate the effect of environmental factors, medication compliance, seasonality, and medical history on (1) pollutant concentrations indoors and (2) asthma outcomes in low-income multifamily housing. We estimated health care use and costs at baseline and subsequent to interventions, and then compared health care costs with energy savings and intervention costs. Interventions, such as integrated pest management and repairing kitchen exhaust fans, led to 7% to 12% reductions in serious asthma events with 1- to 3-year payback periods. Weatherization efforts targeted solely toward tightening a building envelope led to 20% more serious asthma events, but bundling with repairing kitchen exhaust fans and eliminating indoor sources (eg, gas stoves or smokers) mitigated this effect. Our pediatric asthma model provides a tool to prioritize individual and bundled building interventions based on their effects on health and costs, highlighting the tradeoffs between weatherization, indoor air quality, and health. Our work bridges the gap between clinical and environmental health sciences by increasing physicians' understanding of the effect that home environmental changes can have on their patients' asthma. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Persistent activation of an innate immune axis translates respiratory viral infection into chronic lung disease

PubMed Central

Kim, Edy Y.; Battaile, John T.; Patel, Anand C.; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H.; Benoit, Loralyn A.; Byers, Derek E.; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W.; Morton, Jeffrey D.; Castro, Mario; Polineni, Deepika; Patterson, G. Alexander; Schwendener, Reto A.; Allard, John D.; Peltz, Gary; Holtzman, Michael J.

2008-01-01

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of a chronic lung disease that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after infection with a common type of respiratory virus is cleared to trace levels of noninfectious virus. Unexpectedly, the chronic inflammatory disease arises independently of an adaptive immune response and is driven by IL-13 produced by macrophages stimulated by CD1d-dependent TCR-invariant NKT cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a novel NKT cell-macrophage innate immune axis. PMID:18488036

Divergent transcriptional profiles in pediatric asthma patients of low and high socioeconomic status.

PubMed

Miller, Gregory E; Chen, Edith; Shalowitz, Madeleine U; Story, Rachel E; Leigh, Adam K K; Ham, Paula; Arevalo, Jesusa M G; Cole, Steve W

2018-06-01

There are marked socioeconomic disparities in pediatric asthma control, but the molecular origins of these disparities are not well understood. To fill this gap, we performed genome-wide expression profiling of monocytes and T-helper cells from pediatric asthma patients of lower and higher socioeconomic status (SES). Ninety-nine children with asthma participated in a cross-sectional assessment. Out of which 87% were atopic, and most had disease of mild (54%) or moderate (29%) severity. Children were from lower-SES (n = 49; household income <$50 000) or higher-SES (n = 50; household income >$140 000) families. Peripheral blood monocytes and T-helper cells were isolated for genome-wide expression profiling of mRNA. Lower-SES children had worse asthma quality of life relative to higher-SES children, by both their own and their parents' reports. Although the groups had similar disease severity and potential confounds were controlled, their transcriptional profiles differed notably. The monocytes of lower-SES children showed transcriptional indications of up-regulated anti-microbial and pro-inflammatory activity. The T-helper cells of lower-SES children also had comparatively reduced expression of genes encoding γ-interferon and tumor necrosis factor-α, cytokines that orchestrate Type 1 responses. They also showed up-regulated activity of transcription factors that polarize cells towards Type 2 responses and promote Th17 cell maturation. Collectively, these patterns implicate pro-inflammatory monocytes and Type 2 cytokine activity as mechanisms contributing to worse asthma control among lower-SES children. © 2018 Wiley Periodicals, Inc.

Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

PubMed

Moreno-Alvarez, Paola; Sánchez-Guerrero, Edgar; Martínez-Cordero, Erasmo; Hernández-Pando, Rogelio; Campos, María G; Cetina, Lucely; Bazán-Perkins, Blanca

2010-04-01

Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

Use of predictive algorithms in-home monitoring of chronic obstructive pulmonary disease and asthma: A systematic review.

PubMed

Sanchez-Morillo, Daniel; Fernandez-Granero, Miguel A; Leon-Jimenez, Antonio

2016-08-01

Major reported factors associated with the limited effectiveness of home telemonitoring interventions in chronic respiratory conditions include the lack of useful early predictors, poor patient compliance and the poor performance of conventional algorithms for detecting deteriorations. This article provides a systematic review of existing algorithms and the factors associated with their performance in detecting exacerbations and supporting clinical decisions in patients with chronic obstructive pulmonary disease (COPD) or asthma. An electronic literature search in Medline, Scopus, Web of Science and Cochrane library was conducted to identify relevant articles published between 2005 and July 2015. A total of 20 studies (16 COPD, 4 asthma) that included research about the use of algorithms in telemonitoring interventions in asthma and COPD were selected. Differences on the applied definition of exacerbation, telemonitoring duration, acquired physiological signals and symptoms, type of technology deployed and algorithms used were found. Predictive models with good clinically reliability have yet to be defined, and are an important goal for the future development of telehealth in chronic respiratory conditions. New predictive models incorporating both symptoms and physiological signals are being tested in telemonitoring interventions with positive outcomes. However, the underpinning algorithms behind these models need be validated in larger samples of patients, for longer periods of time and with well-established protocols. In addition, further research is needed to identify novel predictors that enable the early detection of deteriorations, especially in COPD. Only then will telemonitoring achieve the aim of preventing hospital admissions, contributing to the reduction of health resource utilization and improving the quality of life of patients. © The Author(s) 2016.

Aqueous Extract of Gumiganghwal-tang, a Traditional Herbal Medicine, Reduces Pulmonary Fibrosis by Transforming Growth Factor-β1/Smad Signaling Pathway in Murine Model of Chronic Asthma.

PubMed

Jeon, Woo-Young; Shin, In-Sik; Shin, Hyeun-Kyoo; Jin, Seong Eun; Lee, Mee-Young

2016-01-01

Gumiganghwal-tang is a traditional herbal prescription that is used widely for the treatment of the common cold and inflammatory diseases in Korea and other Asian countries. In this study, we investigated the protective effects of a Gumiganghwal-tang aqueous extract (GGTA) against airway inflammation and pulmonary fibrosis using a mouse model of chronic asthma. Chronic asthma was modeled in BALB/c mice via sensitization/challenge with an intraperitoneal injection of 1% ovalbumin (OVA) and inhalation of nebulized 1% OVA for 4 weeks. GGTA (100 mg/kg or 200 mg/kg) was also administered by oral gavage once a day for 4 weeks. We investigated the number of inflammatory cells, production of T-helper type 2 (Th2) cytokines, chemokine and the total transforming growth factor-β1 (TGF-β1) in bronchoalveolar lavage fluid (BALF); the levels of immunoglobulin E (IgE) in the plasma; the infiltration of inflammatory cells in lung tissue; and the expression of TGF-β1, Smad-3, and collagen in lung tissue. Our results revealed that GGTA lowered the recruitment of inflammatory cells (particularly, lymphocyte); and decreased the production of Th2 cytokines, chemokine and total TGF-β1; and attenuated the levels of total and OVA-specific IgE; and decreased the infiltration of inflammatory cells. Moreover, GGTA significantly reduced the expression of TGF-β1 and Smad-3, and lowered collagen deposition. These results indicate that GGTA reduces airway inflammation and pulmonary fibrosis by regulating Th2 cytokines production and the TGF-β1/Smad-3 pathway, thus providing a potential treatment for chronic asthma.

Revisiting the Hispanic health paradox: the relative contributions of nativity, country of origin, and race/ethnicity to childhood asthma.

PubMed

Camacho-Rivera, Marlene; Kawachi, Ichiro; Bennett, Gary G; Subramanian, S V

2015-06-01

This study examined the relationship between race and Hispanic ethnicity, maternal and child nativity, country of origin and asthma among 2,558 non-Hispanic white and Hispanic children across 65 Los Angeles neighborhoods. A series of two-level multilevel models were estimated to examine the independent effects of race, ethnicity, and country of origin on childhood asthma. Lifetime asthma prevalence was reported among 9% of children, with no significant differences between Hispanics and non-Hispanic whites overall. However, in fully adjusted models, Hispanic children of non-Mexican origin reported higher odds of asthma compared to non-Hispanic white children. A protective nativity effect was also observed among children of foreign born mothers compared to US born mothers. Our study provides evidence in support of the heterogeneity of childhood asthma by Hispanic ethnicity and maternal nativity. These findings suggest moving beyond solely considering racial/ethnic classifications which could mask subgroups at increased risk of childhood asthma.

Treating childhood asthma in Singapore: when West meets East.

PubMed Central

Connett, G. J.; Lee, B. W.

1994-01-01

Though Western medicines and ideas about asthma have become popular in many Asian nations, local beliefs about treatment prevail. The multiracial society of Singapore shows a variety of beliefs about causes of asthma attacks (for example, the balance of yin and yang) and types of treatment--herbal remedies, inhaled versus eaten medicines, the influence of Ramadan. Many of the cultural practices mentioned are probably preserved among south east Asian minorities residing in the United Kingdom. Eastern treatments typically take a holistic approach to asthma and do not ignore the psychosomatic component of the disorder. Images p1282-a PMID:8205023

"Looking out for each other": a qualitative study on the role of social network interactions in asthma management among adult Latino patients presenting to an emergency department.

PubMed

Pai, Sucheta; Boutin-Foster, Carla; Mancuso, Carol A; Loganathan, Raghu; Basir, Riyad; Kanna, Balavenkatesh

2014-09-01

The objective of this study was to identify the types of interactions between asthma patients and their social networks such as close family and friends that influence the management of asthma. Participants were Latino adults presenting for a repeat visit to the emergency department for asthma treatment. Qualitative interviews were conducted with 76 participants. They were asked to describe the experiences of their social networks that have asthma and how interactions with these individuals influenced their own asthma management. Responses were transcribed and analyzed using Grounded Theory as a qualitative analytic approach. Responses were assigned codes; similar codes were grouped into concepts and then categorized to form overarching themes. Four themes emerged: (1) Perceptions of severity of asthma may be based on the experiences of social networks; (2) Economic factors may contribute to the sharing and borrowing of asthma medications between patients and their social networks; (3) Economic factors may contribute to using home remedies instead of prescribed medications; (4) Social network members may be unaware of the factors that trigger asthma and therefore, contribute to asthma exacerbations. This study identified important social network interactions that may impact asthma management in Latino adults. These results can be used to broaden the current focus of asthma self-management programs to incorporate discussions on the role of social networks. A focus on social network interactions addresses the social epidemiology of asthma and advances our understanding of root causes that may underlie the high prevalence of asthma in many Latino communities.

Developing an interactive story for children with asthma.

PubMed

Wyatt, Tami H; Li, Xueping; Huang, Yu; Farmer, Rachel; Reed, Delanna; Burkhart, Patricia V

2013-06-01

Despite advancements in asthma treatment and diagnosis, asthma still remains the number 1 cause for hospitalizations in school-aged children. This usability study aimed to develop a child-friendly interactive narrative, Okay with Asthma v2.0, based on the Biopsychosocial Family Model using feedback from children. This fun and kid-friendly program encourages children to manage their own asthma with the help of peers, families, communities, and health care services. With these support structures, children can identify and avoid triggers, monitor their asthma, manage their condition with medications based on an action plan, and learn to live happily with asthma. Copyright © 2013 Elsevier Inc. All rights reserved.

An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

PubMed

Norris Reinero, Carol R; Decile, Kendra C; Berghaus, Roy D; Williams, Kurt J; Leutenegger, Christian M; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2004-10-01

Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Does IFN-γ play a role on the pathogenesis of non-atopic asthma in Latin America children?

PubMed

Figueiredo, Camila Alexandrina; Rodrigues, Laura Cunha; Alcantara-Neves, Neuza Maria; Cooper, Philip J; Amorim, Leila Denise; Silva, Nivea Bispo; Cruz, Alvaro A; Barreto, Mauricio Lima

2012-12-19

In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children.

Sparse modeling of spatial environmental variables associated with asthma

PubMed Central

Chang, Timothy S.; Gangnon, Ronald E.; Page, C. David; Buckingham, William R.; Tandias, Aman; Cowan, Kelly J.; Tomasallo, Carrie D.; Arndt, Brian G.; Hanrahan, Lawrence P.; Guilbert, Theresa W.

2014-01-01

Geographically distributed environmental factors influence the burden of diseases such as asthma. Our objective was to identify sparse environmental variables associated with asthma diagnosis gathered from a large electronic health record (EHR) dataset while controlling for spatial variation. An EHR dataset from the University of Wisconsin’s Family Medicine, Internal Medicine and Pediatrics Departments was obtained for 199,220 patients aged 5–50 years over a three-year period. Each patient’s home address was geocoded to one of 3,456 geographic census block groups. Over one thousand block group variables were obtained from a commercial database. We developed a Sparse Spatial Environmental Analysis (SASEA). Using this method, the environmental variables were first dimensionally reduced with sparse principal component analysis. Logistic thin plate regression spline modeling was then used to identify block group variables associated with asthma from sparse principal components. The addresses of patients from the EHR dataset were distributed throughout the majority of Wisconsin’s geography. Logistic thin plate regression spline modeling captured spatial variation of asthma. Four sparse principal components identified via model selection consisted of food at home, dog ownership, household size, and disposable income variables. In rural areas, dog ownership and renter occupied housing units from significant sparse principal components were associated with asthma. Our main contribution is the incorporation of sparsity in spatial modeling. SASEA sequentially added sparse principal components to Logistic thin plate regression spline modeling. This method allowed association of geographically distributed environmental factors with asthma using EHR and environmental datasets. SASEA can be applied to other diseases with environmental risk factors. PMID:25533437

Sparse modeling of spatial environmental variables associated with asthma.

PubMed

Chang, Timothy S; Gangnon, Ronald E; David Page, C; Buckingham, William R; Tandias, Aman; Cowan, Kelly J; Tomasallo, Carrie D; Arndt, Brian G; Hanrahan, Lawrence P; Guilbert, Theresa W

2015-02-01

Geographically distributed environmental factors influence the burden of diseases such as asthma. Our objective was to identify sparse environmental variables associated with asthma diagnosis gathered from a large electronic health record (EHR) dataset while controlling for spatial variation. An EHR dataset from the University of Wisconsin's Family Medicine, Internal Medicine and Pediatrics Departments was obtained for 199,220 patients aged 5-50years over a three-year period. Each patient's home address was geocoded to one of 3456 geographic census block groups. Over one thousand block group variables were obtained from a commercial database. We developed a Sparse Spatial Environmental Analysis (SASEA). Using this method, the environmental variables were first dimensionally reduced with sparse principal component analysis. Logistic thin plate regression spline modeling was then used to identify block group variables associated with asthma from sparse principal components. The addresses of patients from the EHR dataset were distributed throughout the majority of Wisconsin's geography. Logistic thin plate regression spline modeling captured spatial variation of asthma. Four sparse principal components identified via model selection consisted of food at home, dog ownership, household size, and disposable income variables. In rural areas, dog ownership and renter occupied housing units from significant sparse principal components were associated with asthma. Our main contribution is the incorporation of sparsity in spatial modeling. SASEA sequentially added sparse principal components to Logistic thin plate regression spline modeling. This method allowed association of geographically distributed environmental factors with asthma using EHR and environmental datasets. SASEA can be applied to other diseases with environmental risk factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma

PubMed Central

Louten, Jennifer; Mattson, Jeanine D.; Malinao, Maria-Christina; Li, Ying; Emson, Claire; Vega, Felix; Wardle, Robert L.; Van Scott, Michael R.; Fick, Robert B.; McClanahan, Terrill K.; de Waal Malefyt, Rene; Beaumont, Maribel

2012-01-01

Background Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Objective Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. Methods The total protein content from thymic stromal lymphopoietin transgenic (TSLP Tg) mouse BAL fluid was ascertained by shotgun proteomics analysis. A subset of these potential markers was further analyzed in BAL fluid, BAL cell mRNA, and lung tissue mRNA during the stages of asthma and following corticosteroid treatment. Validation was conducted in murine and NHP models of allergic asthma. Results Over 40 proteins were increased in the BAL fluid of TSLP Tg mice that were also detected by qRT-PCR in lung tissue and BAL cells, as well as in OVA-sensitive mice and house dust mite-sensitive NHP. Previously undescribed as asthma biomarkers, KLK1, Reg3γ, ITLN2, and LTF were modulated in asthmatic mice, and Clca3, Chi3l4 (YM2), and Ear11 were the first lung biomarkers to increase during disease and the last biomarkers to decline in response to therapy. In contrast, GP-39, LCN2, sICAM-1, YM1, Epx, Mmp12, and Klk1 were good indicators of early therapeutic intervention. In NHP, AMCase, sICAM-1, CLCA1, and GP-39 were reduced upon treatment with corticosteroids. Conclusions and clinical relevance These results significantly advance our understanding of the biomarkers present in various tissue compartments in animal models of asthma, including those induced early during asthma and modulated with therapeutic intervention, and show that BAL cells (or their surrogate, induced sputum cells) are a viable choice for biomarker examination. PMID:22837640

Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma.

PubMed

Demehri, Shadmehr; Morimoto, Mitsuru; Holtzman, Michael J; Kopan, Raphael

2009-05-19

Asthma is a common allergic lung disease frequently affecting individuals with a prior history of eczema/atopic dermatitis (AD); however, the mechanism underlying the progression from AD to asthma (the so-called "atopic march") is unclear. Here we show that, like humans with AD, mice with skin-barrier defects develop AD-like skin inflammation and are susceptible to allergic asthma. Furthermore, we show that thymic stromal lymphopoietin (TSLP), overexpressed by skin keratinocytes, is the systemic driver of this bronchial hyper-responsiveness. As an AD-like model, we used mice with keratinocyte-specific deletion of RBP-j that sustained high systemic levels of TSLP. Antigen-induced allergic challenge to the lung airways of RBP-j-deficient animals resulted in a severe asthmatic phenotype not seen in similarly treated wild-type littermates. Elimination of TSLP signaling in these animals blocked the atopic march, demonstrating that high serum TSLP levels were required to sensitize the lung to allergic inflammation. Furthermore, we analyzed outbred K14-TSLP(tg) mice that maintained high systemic levels of TSLP without developing any skin pathology. Importantly, epidermal-derived TSLP was sufficient to trigger the atopic march, sensitizing the lung airways to inhaled allergens in the absence of epicutaneous sensitization. Based on these findings, we propose that in addition to early treatment of the primary skin-barrier defects, selective inhibition of systemic TSLP may be the key to blocking the development of asthma in AD patients.

Helminthic therapy: using worms to treat immune-mediated disease.

PubMed

Elliott, David E; Weinstock, Joel V

2009-01-01

There is an epidemic of immune-mediated disease in highly-developed industrialized countries. Such diseases, like inflammatory bowel disease, multiple sclerosis and asthma increase in prevalence as populations adopt modern hygienic practices. These practices prevent exposure to parasitic worms (helminths). Epidemiologic studies suggest that people who carry helminths have less immune-mediated disease. Mice colonized with helminths are protected from disease in models of colitis, encephalitis, Type 1 diabetes and asthma. Clinical trials show that exposure to helminths reduce disease activity in patients with ulcerative colitis or Crohn's disease. This chapter reviews some of the work showing that colonization with helminths alters immune responses, against dysregulated inflammation. These helminth-host immune interactions have potentially important implications for the treatment of immune-mediated diseases.

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

PubMed Central

Carlsen, Kai-Håkon; Mowinckel, Petter; Wijga, Alet H.; Brunekreef, Bert; Torrent, Maties; Roberts, Graham; Arshad, S. Hasan; Kull, Inger; Krämer, Ursula; von Berg, Andrea; Eller, Esben; Høst, Arne; Kuehni, Claudia; Spycher, Ben; Sunyer, Jordi; Chen, Chih-Mei; Reich, Andreas; Asarnoj, Anna; Puig, Carmen; Herbarth, Olf; Mahachie John, Jestinah M.; Van Steen, Kristel; Willich, Stefan N.; Wahn, Ulrich; Lau, Susanne; Keil, Thomas; Wickman, Magnus; Hallner, Eva; Alm, Johan; Almqvist, Catarina; Wennergren, Göran; Alm, Bernt; Heinrich, Joachim; Smit, Henriette A.; Thijs, Carel; Mommers, Monique; Bindslev-Jensen, Carsten; Halken, Susanne; Fantini, Maria Pia; Bravi, Francesca; Porta, Daniela; Forastiere, Francesco; Custovic, Adnan; Dubakiene, Ruta; Mahachie, Jestinah

2012-01-01

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given. PMID:22952649

Mesenchymal stem cells suppress lung inflammation and airway remodeling in chronic asthma rat model via PI3K/Akt signaling pathway

PubMed Central

Lin, Hai-Yan; Xu, Lei; Xie, Shuan-Shuan; Yu, Fei; Hu, Hai-Yang; Song, Xiao-Lian; Wang, Chang-Hui

2015-01-01

Background: Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases’ research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model. Methods: First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ovalbumin-induced asthma rats. The total cells in a bronchial alveolar lavage fluid (BALF) and inflammatory mediators in BALF and serum were measured. Histological examination of lung tissue was performed to estimate the pathological changes. Additionally, the expression of phosphorylated-Akt (p-Akt) in all groups was measured by western blot and immunohistochemistry (IHC). Results: Compared to normal control group, the degree of airway inflammation and airway remodeling was significantly increased in asthma group. On the contrary, they were obviously inhibited in MSCs transplantation group. Moreover, the expression of p-Akt was increased in lung tissues of asthmatic rats, and suppressed by MSCs transplantation. Conclusion: Our results demonstrated that MSCs transplantation could suppress lung inflammation and airway remodeling via PI3K/Akt signaling pathway in rat asthma model. PMID:26464637

Association of SERPINE2 With Asthma

PubMed Central

Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Soto-Quiros, Manuel E.; Avila, Lydiana; Celedón, Juan C.; Lange, Christoph; Mariani, Thomas J.; Lasky-Su, Jessica; Hersh, Craig P.; Raby, Benjamin A.; Silverman, Edwin K.; Weiss, Scott T.; DeMeo, Dawn L.

2011-01-01

Background: The “Dutch hypothesis” suggests that asthma and COPD have common genetic determinants. The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2) gene previously has been associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes. Methods: We measured the association of 39 SERPINE2 single-nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios from the Childhood Asthma Management Program (CAMP), and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population control subjects. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci. Results: Nine of 39 SNPs had P < .05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 people with childhood asthma. Six of 19 SNPs had P < .05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The expression quantitative trait loci revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV1 in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs associated with both asthma- and COPD-related phenotypes. Conclusions: Our results weakly support SERPINE2 as a Dutch hypothesis candidate gene through nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD. PMID:21436250

Priorities for future research into asthma diagnostic tools: A PAN-EU consensus exercise from the European asthma research innovation partnership (EARIP).

PubMed

Garcia-Marcos, L; Edwards, J; Kennington, E; Aurora, P; Baraldi, E; Carraro, S; Gappa, M; Louis, R; Moreno-Galdo, A; Peroni, D G; Pijnenburg, M; Priftis, K N; Sanchez-Solis, M; Schuster, A; Walker, S

2018-02-01

The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two-stage e-Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face-to-face workshop. The three most important diagnostic/predictive tools ranked were as follows: "New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring," "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath." © 2018 John Wiley & Sons Ltd.

Association of hospitalizations for asthma with seasonal and pandemic influenza.

PubMed

Gerke, Alicia K; Yang, Ming; Tang, Fan; Foster, Eric D; Cavanaugh, Joseph E; Polgreen, Philip M

2014-01-01

Although influenza has been associated with asthma exacerbations, it is not clear the extent to which this association affects health care use in the United States. The first goal of this project was to determine whether, and to what extent, the incidence of asthma hospitalizations is associated with seasonal variation in influenza. Second, we used influenza trends (2000-2008) to help predict asthma admissions during the 2009 H1N1 influenza pandemic. We identified all hospitalizations between 1998 and 2008 in the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project during which a primary diagnosis of asthma was recorded. Separately, we identified all hospitalizations during which a diagnosis of influenza was recorded. We performed time series regression analyses to investigate the association of monthly asthma admissions with influenza incidence. Finally, we applied these time series regression models using 1998-2008 data, to forecast monthly asthma admissions during the 2009 influenza pandemic. Based on time series regression models, a strong, significant association exists between concurrent influenza activity and incidence of asthma hospitalizations (P-value < 0.0001). Use of influenza data to predict asthma admissions during the 2009 H1N1 pandemic improved the mean squared prediction error by 60.2%. Influenza activity in the population is significantly associated with asthma hospitalizations in the United States, and this association can be exploited to more accurately forecast asthma admissions. Our results suggest that improvements in influenza surveillance, prevention and treatment may decrease hospitalizations of asthma patients. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Characteristics of Perimenstrual Asthma and Its Relation to Asthma Severity and Control

PubMed Central

Rao, Chitra K.; Moore, Charity G.; Bleecker, Eugene; Busse, William W.; Calhoun, William; Castro, Mario; Chung, Kian Fan; Erzurum, Serpil C.; Israel, Elliot; Curran-Everett, Douglas

2013-01-01

Background: Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. Methods: Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. Results: Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. Conclusions: PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype. PMID:23632943

Influence of antibiotic use in early childhood on asthma and allergic diseases at age 5.

PubMed

Yamamoto-Hanada, Kiwako; Yang, Limin; Narita, Masami; Saito, Hirohisa; Ohya, Yukihiro

2017-07-01

In the past few decades, the prevalence of allergic diseases has increased rapidly worldwide. At the same time, the overuse of antibiotics has been observed, especially in Japan. To elucidate the association of early childhood antibiotic use with allergic diseases in later childhood at 5 years of age. Relevant data were extracted from the hospital-based birth cohort study, the Tokyo Children's Health, Illness and Development Study. To identify signs of asthma and allergic diseases in children, the International Study of Asthma and Allergies in Childhood questionnaire was used. Logistic regression models were applied to estimate the effect of antibiotic use on outcomes in later life. Antibiotic exposure in children within the first 2 years of life was associated with current asthma (adjusted odds ratio [aOR] 1.72, 95% confidence interval [CI] 1.10-2.70), current atopic dermatitis (aOR 1.40, 95% CI 1.01-1.94), and current allergic rhinitis (aOR 1.65, 95% CI 1. 05-2.58) at 5 years of age. Analysis of the associations by type of antibiotics showed that cephem was associated with current asthma (aOR 1.97, 95% CI 1.23-3.16) and current rhinitis (aOR 1.82, 95% CI 1.12-2.93), and macrolide was associated with current atopic dermatitis (aOR 1.58, 95% CI 1.07-2.33). Our findings suggest that antibiotic use within the first 2 years of life was a risk factor for current asthma, current atopic dermatitis, and current allergic rhinitis in 5-year-old children. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Spatiotemporal patterns of childhood asthma hospitalization and utilization in Memphis Metropolitan Area from 2005 to 2015.

PubMed

Oyana, Tonny J; Podila, Pradeep; Wesley, Jagila Minso; Lomnicki, Slawo; Cormier, Stephania

2017-10-01

To identify the key risk factors and explain the spatiotemporal patterns of childhood asthma in the Memphis metropolitan area (MMA) over an 11-year period (2005-2015). We hypothesize that in the MMA region this burden is more prevalent among urban children living south, downtown, and north of Memphis than in other areas. We used a large-scale longitudinal electronic health record database from an integrated healthcare system, Geographic information systems (GIS), and statistical and space-time models to study the spatiotemporal distributions of childhood asthma at census tract level. We found statistically significant spatiotemporal clusters of childhood asthma in the south, west, and north of Memphis city after adjusting for key covariates. The results further show a significant increase in temporal gradient in frequency of emergency department (ED) visits and inpatient hospitalizations from 2009 to 2013, and an upward trajectory from 4 per 1,000 children in 2005 to 16 per 1,000 children in 2015. The multivariate logistic regression identified age, race, insurance, admit source, encounter type, and frequency of visits as significant risk factors for childhood asthma (p < 0.05). We observed a greater asthma burden and healthcare utilization for African American (AA) patients living in a high-risk area than those living in a low-risk area in comparison to the white patients: AA vs. white [odds ratio (OR) = 3.03, 95% confidence interval (CI): 2.75-3.34]; and Hispanic vs. white (OR = 1.62, 95% CI: 1.21-2.17). These findings provide a strong basis for developing geographically tailored population health strategies at the neighborhood level for young children with chronic respiratory conditions.

Conserved steroid hormone homology converges on NFκB to modulate inflammation in asthma

PubMed Central

Payne, Asha S.; Freishtat, Robert J.

2012-01-01

Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity [1], yet has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing. Despite the complex pathogenesis of asthma, steroid hormones (e.g. glucocorticoids) are ubiquitous in the acute and chronic management of all types of asthma. Overall, steroid hormones are a class of widely-relevant, biologically-active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they employ rapid, non-genomic actions to affect cellular products. Steroid hormones are comprised of several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggest that each of these is part of dynamic system of hormone interaction, likely involving overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these three groups of steroid hormones (i.e. glucocorticoids, sex steroid hormones, and secosteroids), identifying NFκB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (e.g. glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be better understanding of the interplay of classical, non-classical, and non-genomic steroid hormone function. However, clues from the conserved homology steroid hormone structure and function and signaling pathways, offer insight into a possible model of steroid hormone regulation of inflammation in asthma through common NFκB-mediated downstream events. PMID:22183120

Seasonal asthma in Melbourne, Australia, and some observations on the occurrence of thunderstorm asthma and its predictability

PubMed Central

Sutherland, Michael F.; Johnston, Fay H.; Lampugnani, Edwin R.; McCarthy, Michael A.; Jacobs, Stephanie J.; Pezza, Alexandre B.; Newbigin, Edward J.

2018-01-01

We examine the seasonality of asthma-related hospital admissions in Melbourne, Australia, in particular the contribution and predictability of episodic thunderstorm asthma. Using a time-series ecological approach based on asthma admissions to Melbourne metropolitan hospitals, we identified seasonal peaks in asthma admissions that were centred in late February, June and mid-November. These peaks were most likely due to the return to school, winter viral infections and seasonal allergies, respectively. We performed non-linear statistical regression to predict daily admission rates as functions of the seasonal cycle, weather conditions, reported thunderstorms, pollen counts and air quality. Important predictor variables were the seasonal cycle and mean relative humidity in the preceding two weeks, with higher humidity associated with higher asthma admissions. Although various attempts were made to model asthma admissions, none of the models explained substantially more variation above that associated with the annual cycle. We also identified a list of high asthma admissions days (HAADs). Most HAADs fell in the late-February return-to-school peak and the November allergy peak, with the latter containing the greatest number of daily admissions. Many HAADs in the spring allergy peak may represent episodes of thunderstorm asthma, as they were associated with rainfall, thunderstorms, high ambient grass pollen levels and high humidity, a finding that suggests thunderstorm asthma is a recurrent phenomenon in Melbourne that occurs roughly once per five years. The rarity of thunderstorm asthma events makes prediction challenging, underscoring the importance of maintaining high standards of asthma management, both for patients and health professionals, especially during late spring and early summer. PMID:29649224

Urbanization factors associated with childhood asthma and prematurity: a population-based analysis aged from 0 to 5 years in Taiwan by using Cox regression within a hospital cluster model.

PubMed

Lin, Sheng-Chieh; Lin, Hui-Wen

2015-04-01

Childhood asthma and premature birth are both common; however, no studies have reported urbanization association between asthma and prematurity and the duration of prematurity affect asthma development. We use Taiwan Longitudinal Health Insurance Database (LHID) to explore association between asthma and prematurity among children by using a population-based analysis. This is a retrospective cohort study with registration data derived from Taiwan LHID. We evaluated prematurely born infants and children aged <5 years (n = 532) and age-matched control patients (n = 60505) using Cox proportional hazard regression analysis within a hospital cluster model. Of the 61 037 examinees, 14 012 experienced asthma during the 5-year follow-up, including 161 (72.26 per 1000 person-years) infants and children born prematurely and 13 851 (40.27 per 1000 person-years) controls. The hazard ratio for asthma during 5-year follow-up period was 1.95 (95% confidence interval = 1.67-2.28) among children born prematurely. Boys born prematurely aged 0-2 years were associated with higher asthma rates compared with girls in non-premature and premature groups. Living in urban areas, those born prematurely were associated with higher rates of asthma compared with non-prematurity. Those born prematurely lived in northern region had higher asthma hazard ratio than other regions. Our analyses indicated that sex, age, urbanization level, and geographic region are significantly associated with prematurity and asthma. Based on cumulative asthma-free survival curve generated using the Kaplan-Meier method, infants born prematurely should be closely monitored to see if they would develop asthma until the age of 6 years.

Animal models of asthma: utility and limitations.

PubMed

Aun, Marcelo Vivolo; Bonamichi-Santos, Rafael; Arantes-Costa, Fernanda Magalhães; Kalil, Jorge; Giavina-Bianchi, Pedro

2017-01-01

Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila , rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.

Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma.

PubMed

Matsuda, Akira; Hirota, Tomomitsu; Akahoshi, Mitsuteru; Shimizu, Makiko; Tamari, Mayumi; Miyatake, Akihiko; Takahashi, Atsushi; Nakashima, Kazuko; Takahashi, Naomi; Obara, Kazuhiko; Yuyama, Noriko; Doi, Satoru; Kamogawa, Yumiko; Enomoto, Tadao; Ohshima, Koichi; Tsunoda, Tatsuhiko; Miyatake, Shoichiro; Fujita, Kimie; Kusakabe, Moriaki; Izuhara, Kenji; Nakamura, Yusuke; Hopkin, Julian; Shirakawa, Taro

2005-10-01

The extracellular matrix glycoprotein tenascin-C (TNC) has been accepted as a valuable histopathological subepithelial marker for evaluating the severity of asthmatic disease and the therapeutic response to drugs. We found an association between an adult asthma and an SNP encoding TNC fibronectin type III-D (Fn-III-D) domain in a case-control study between a Japanese population including 446 adult asthmatic patients and 658 normal healthy controls. The SNP (44513A/T in exon 17) strongly associates with adult bronchial asthma (chi2 test, P=0.00019, Odds ratio=1.76, 95% confidence interval=1.31-2.36). This coding SNP induces an amino acid substitution (Leu1677Ile) within the Fn-III-D domain of the alternative splicing region. Computer-assisted protein structure modeling suggests that the substituted amino acid locates at the outer edge of the beta-sheet in Fn-III-D domain and causes instability of this beta-sheet. As the TNC fibronectin-III domain has molecular elasticity, the structural change may affect the integrity and stiffness of asthmatic airways. In addition, TNC expression in lung fibroblasts increases with Th2 immune cytokine stimulation. Thus, Leu1677Ile may be valuable marker for evaluating the risk for developing asthma and plays a role in its pathogenesis.

A simulation model of building intervention impacts on indoor environmental quality, pediatric asthma, and costs

PubMed Central

Fabian, Maria Patricia; Adamkiewicz, Gary; Stout, Natasha Kay; Sandel, Megan; Levy, Jonathan Ian

2013-01-01

Background Although indoor environmental conditions can affect pediatric asthmatics, few studies have characterized the impact of building interventions on asthma-related outcomes. Simulation models can evaluate such complex systems but have not been applied in this context. Objective To evaluate the impacts of building interventions on indoor environmental quality and pediatric asthma healthcare utilization, and to conduct cost comparisons between intervention and healthcare costs, and energy savings. Methods We applied our previously developed discrete event simulation model (DEM) to simulate the effect of environmental factors, medication compliance, seasonality, and medical history on: 1) pollutant concentrations indoors, and 2) asthma outcomes in low-income multi-family housing. We estimated healthcare utilization and costs at baseline and subsequent to interventions, and then compared healthcare costs to energy savings and intervention costs. Results Interventions such as integrated pest management and repairing kitchen exhaust fans led to 7–12% reductions in serious asthma events with 1–3 year payback periods. Weatherization efforts targeted solely towards tightening a building envelope led to 20% more serious asthma events, but bundling with repairing kitchen exhaust fans and eliminating indoor sources (e.g. gas stoves or smokers) mitigated this impact. Conclusion Our pediatric asthma model provides a tool to prioritize individual and bundled building interventions based on their impact on health and cost, and highlighting the tradeoffs between weatherization, indoor air quality, and health. Our work bridges the gap between clinical and environmental health sciences by increasing physicians’ understanding of the impact that home environmental changes can have on their patients’ asthma. PMID:23910689

Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK).

PubMed

Heaney, Liam G; Djukanovic, Ratko; Woodcock, Ashley; Walker, Samantha; Matthews, John G; Pavord, Ian D; Bradding, Peter; Niven, Robert; Brightling, Chris E; Chaudhuri, Rekha; Arron, Joseph R; Choy, David F; Cowan, Douglas; Mansur, Adel; Menzies-Gow, Andrew; Adcock, Ian; Chung, Kian F; Corrigan, Chris; Coyle, Peter; Harrison, Timothy; Johnston, Sebastian; Howarth, Peter; Lordan, James; Sabroe, Ian; Bigler, Jeannette; Smith, Dirk; Catley, Matthew; May, Richard; Pierre, Lisa; Stevenson, Chris; Crater, Glenn; Keane, Frank; Costello, Richard W; Hudson, Val; Supple, David; Hardman, Tim

2016-02-01

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

PubMed

Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

2017-11-01

Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

The correlation between parental education and their knowledge of asthma.

PubMed

Radic, S D; Milenkovic, B A; Gvozdenovic, B S; Zivkovic, Z M; Pesic, I M; Babic, D D

2014-01-01

To evaluate the impact of parental education on the success of Asthma Educational Intervention (AEI). AEI took place after the children's hospitalisation. Parental asthma knowledge was assessed at three time points: before AEI, immediately after, and 12 months later. The Intervention (I) group of parents (N=231) received complete AEI. The Control (C) group of parents (N=71) received instructions for proper use of asthma medications and the handbook. Asthma knowledge in I group increased immediately after the AEI (p<0.01), and had not changed (p>0.05) 12 months later. There were four subgroups in group I divided based on education level: elementary school, high school, college, and university degrees. Taking into account the parental education level, there were no differences in the baseline and final knowledge of asthma between subgroups (p>0.05). The number of asthma exacerbations decreased after AEI (5.96:2.50, p<0.01), regardless of the parental degree. Knowledge of asthma in group C did not improve during the study (p=0.17). Final asthma knowledge was higher in group I compared to group C (p<0.01). The parental education level did not influence the level of asthma knowledge after the AEI. The motivation and the type of asthma education had the greatest input on the final results. All parents should be educated about asthma regardless of their general education. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma.

PubMed

Chen, Ruchong; Smith, Steven G; Salter, Brittany; El-Gammal, Amani; Oliveria, John Paul; Obminski, Caitlin; Watson, Rick; O'Byrne, Paul M; Gauvreau, Gail M; Sehmi, Roma

2017-09-15

Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma. Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge. ILC2 (lin - FcεRI - CD45 + CD127 + ST2 + ) and CD4 + T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4 + T cells was investigated in vitro. A significant increase in total, IL-5 + , IL-13 + , and CRTH2 + ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5 + , and IL-13 + , but not CRTH2 + , CD4 + T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4 + cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5 + ILC2 at all time points and allergen-induced changes in IL-5 + CD4 + cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types. Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4 + T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO.

PubMed

Ketelaar, M E; van de Kant, K D; Dijk, F N; Klaassen, E M; Grotenboer, N S; Nawijn, M C; Dompeling, E; Koppelman, G H

2017-11-01

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Estimating Wisconsin asthma prevalence using clinical electronic health records and public health data.

PubMed

Tomasallo, Carrie D; Hanrahan, Lawrence P; Tandias, Aman; Chang, Timothy S; Cowan, Kelly J; Guilbert, Theresa W

2014-01-01

We compared a statewide telephone health survey with electronic health record (EHR) data from a large Wisconsin health system to estimate asthma prevalence in Wisconsin. We developed frequency tables and logistic regression models using Wisconsin Behavioral Risk Factor Surveillance System and University of Wisconsin primary care clinic data. We compared adjusted odds ratios (AORs) from each model. Between 2007 and 2009, the EHR database contained 376,000 patients (30,000 with asthma), and 23,000 (1850 with asthma) responded to the Behavioral Risk Factor Surveillance System telephone survey. AORs for asthma were similar in magnitude and direction for the majority of covariates, including gender, age, and race/ethnicity, between survey and EHR models. The EHR data had greater statistical power to detect associations than did survey data, especially in pediatric and ethnic populations, because of larger sample sizes. EHRs can be used to estimate asthma prevalence in Wisconsin adults and children. EHR data may improve public health chronic disease surveillance using high-quality data at the local level to better identify areas of disparity and risk factors and guide education and health care interventions.

Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.

PubMed

Scott, Kate M; Von Korff, Michael; Alonso, Jordi; Angermeyer, Matthias C; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Kessler, Ronald C; Kovess, Viviane; Ono, Yutaka; Ormel, Johan; Posada-Villa, José

2008-11-01

To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (

Integration of Airborne Aerosol Prediction Systems and Vegetation Phenology to Track Pollen for Asthma Alerts in Public Health Decision Support Systems

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.; Sprigg, William A.; Huete, Alfredo; Pejanovic, Goran; Nickovic,Slobodan; Ponce-Campos, Guillermo; Krapfl, Heide; Budge, Amy; Zelicoff, Alan; VandeWater, Peter K.;

The Chronic Care Model: A Collaborative Approach to Preventing and Treating Asthma in Infants and Young Children

ERIC Educational Resources Information Center

Wessel, Lois; Spain, Jacqueline

2005-01-01

The authors that a collaborative approach between parents and professionals is the best way to care for a young child with asthma. They use Ed Wagner's transdisciplinary 1998 Chronic Care Model as their preferred method for collaboration. More than 5 million children in the U.S. are currently affected by asthma, and a growing body of evidence…

Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1

PubMed Central

Qi, Huibin; Kurosky, Alexander; Jennings, Kristofer; Sun, Qian; Boldogh, Istvan; Sur, Sanjiv

2015-01-01

We sought to identify cells and cytokines in bronchoalveolar lavage (BAL) fluids that distinguish asthma from healthy control subjects and those that distinguish controlled asthma from uncontrolled asthma. Following informed consent, 36 human subjects were recruited for this study. These included 11 healthy control subjects, 15 subjects with controlled asthma with FEV1≥80% predicted and 10 subjects with uncontrolled asthma with FEV1 <80% predicted. BAL fluid was obtained from all subjects. The numbers of different cell types and the levels of 48 cytokines were measured in these fluids. Compared to healthy control subjects, patients with asthma had significantly more percentages of eosinophils and neutrophils, IL-1RA, IL-1α, IL-1β, IL-2Rα, IL-5, IL-6, IL-7, IL-8, G-CSF, GROα (CXCL1), MIP-1β (CCL4), MIG (CXCL9), RANTES (CCL5) and TRAIL in their BAL fluids. The only inflammatory markers that distinguished controlled asthma from uncontrolled asthma were neutrophil percentage and IL-8 levels, and both were inversely correlated with FEV1. We examined whether grouping asthma subjects on the basis of BAL eosinophil % or neutrophil % could identify specific cytokine profiles. The only differences between neutrophil-normal asthma (neutrophil≤2.4%) and neutrophil-high asthma (neutrophils%>2.4%) were a higher BAL fluid IL-8 levels, and a lower FEV1 in the latter group. By contrast, compared to eosinophil-normal asthma (eosinophils≤0.3%), eosinophil-high asthma (eosinophils>0.3%) had higher levels of IL-5, IL-13, IL-16, and PDGF-bb, but same neutrophil percentage, IL-8, and FEV1. Our results identify neutrophils and IL-8 are the only inflammatory components in BAL fluids that distinguish controlled asthma from uncontrolled asthma, and both correlate inversely with FEV1. PMID:26011707

Advances and Evolving Concepts in Allergic Asthma.

PubMed

Tung, Hui-Ying; Li, Evan; Landers, Cameron; Nguyen, An; Kheradmand, Farrah; Knight, J Morgan; Corry, David B

2018-02-01

Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis. Phthalates, another common class of chemical pollutant found in the built environment, are emerging as potentially important mediators or attenuators of asthma. Other biological products such as endotoxin have also been confirmed to be protective in both the indoor and outdoor contexts. Proasthmatic factors are believed to activate, and in some instances initiate, pathologic inflammatory cascades through complex interactions with pattern recognition receptors (PRRs) expressed on many cell types, but especially airway epithelial cells. PRRs initiate the release of proallergic cytokines such as interleukin (IL)-33, IL-25, and others that coordinate activation of innate lymphoid cells type 2 (ILC2), T helper type 2 cells, and immunoglobulin E-secreting B cells that together promote additional inflammation and the major airway remodeling events (airway hyperresponsiveness, mucus hypersecretion) that promote airway obstruction. Proteinases, with airway fungi and viruses being potentially important sources, are emerging as critically important initiators of these inflammatory cascades in part through their effects on clotting factors such as fibrinogen. Recent clinical trials have demonstrated that targeting inflammatory pathways orchestrated through IL-4, IL-5, IL-13, and the prostaglandin receptor CRTH2 is potentially highly effective in adult asthma. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Exploration and research of community management model for asthmatic children].

PubMed

Li, Jingpeng; Wei, Hong; Li, Xuejun; Wang, Mengmeng; Wang, Genxiang; Zhao, Shunying

2014-05-01

To study the efficacy of community management model of bronchial asthma in children. Through community outreach and clinic, 120 cases of children with asthma were enrolled from the 11 000 children aged 0 to 14 in Zhanlanlu area, and a community management model of asthma was established according to the Global Initiative for Asthma requirements combined with the actual situation of the community, both physicians and patients participated in case identification, file creation, and long-term standardized management. Through repeated medical education, the telephone hotline and interactive network of asthma among physicians, children and parents, a physician-patient relationship was established. The data of standardized medication, scheduled re-visit to the hospital, frequency of asthma attacks, antibiotic use, medical expenses, the loss of parents work hours etc. before and after the implementation of community management model were analyzed and compared. After implementation of community management model, the use of systemic corticosteroids (19.4%), oral medication (31.6%) was significantly lower than those before implementation (68.3% and 90.0%) (χ(2) = 51.9, 41.1, P < 0.01), use of inhaled corticosteroids (76.5%) and oral leukotriene receptor antagonist (79.6%) was significantly higher compared with control and before management level (10.0%), χ(2) = 106.0, P < 0.01. The days of attacks of asthma (4.6 ± 2.3), the use of antibiotics (16.2 ± 6.1), (5.7 ± 2.9) and the cost of treatment significantly decreased. In 16 cases (13.3%) two-way referral was applied. In this study, the dropout rate was 18.3%, by telephone and network supervision of lost cases, re-education, made some children return to management, eventually the dropout rate was 9.2%. Enrollment of children with bronchial asthma into community management model made the children adhere to the management regularly and a standardized management was achieved.

A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ) and Type 2 Inflammation (IL-5 and IL-13).

PubMed

Hansel, Trevor T; Tunstall, Tanushree; Trujillo-Torralbo, Maria-Belen; Shamji, Betty; Del-Rosario, Ajerico; Dhariwal, Jaideep; Kirk, Paul D W; Stumpf, Michael P H; Koopmann, Jens; Telcian, Aurica; Aniscenko, Julia; Gogsadze, Leila; Bakhsoliani, Eteri; Stanciu, Luminita; Bartlett, Nathan; Edwards, Michael; Walton, Ross; Mallia, Patrick; Hunt, Toby M; Hunt, Trevor L; Hunt, Duncan G; Westwick, John; Edwards, Matthew; Kon, Onn Min; Jackson, David J; Johnston, Sebastian L

2017-05-01

Rhinovirus infection is a major cause of asthma exacerbations. We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations. We used nasosorption on days 0, 2-5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n=28) and healthy non-atopic controls (n=11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay. Following rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P<0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-γ, IFN-λ/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0-7, all P<0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P<0.01) and levels increased by days 3 and 4 (P<0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-γ, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P<0.05). Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Asthma, Type 1 and Type 2 Diabetes Mellitus, and Inflammatory Bowel Disease amongst South Asian Immigrants to Canada and Their Children: A Population-Based Cohort Study

PubMed Central

Benchimol, Eric I.; Manuel, Douglas G.; To, Teresa; Mack, David R.; Nguyen, Geoffrey C.; Gommerman, Jennifer L.; Croitoru, Kenneth; Mojaverian, Nassim; Wang, Xuesong; Quach, Pauline; Guttmann, Astrid

2015-01-01

BACKGROUND There is a high and rising rate of immune-mediated diseases in the Western world. Immigrants from South Asia have been reported to be at higher risk upon arrival to the West. We determined the risk of immune-mediated diseases in South Asian and other immigrants to Ontario, Canada, and their Ontario-born children. METHODS Population-based cohorts of patients with asthma, type 1 diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD) were derived from health administrative data. We determined the standardized incidence, and the adjusted risk of these diseases in immigrants from South Asia, immigrants from other regions, compared with non-immigrant residents of Ontario. The risk of these diseases in the Ontario-born children of immigrants were compared to the children of non-immigrants. RESULTS Compared to non-immigrants, adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33-0.67) was low amongst immigrant children from South Asia. However, the risk in Ontario-born children of South Asian immigrants relative to the children of non-immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated for IBD (IRR 0.90, 95%CI 0.65-1.22). CONCLUSION Early-life environmental exposures may trigger a genetic predisposition to the development of asthma and IBD in South Asian immigrants and their Canada-born children. PMID:25849480

Asthma, type 1 and type 2 diabetes mellitus, and inflammatory bowel disease amongst South Asian immigrants to Canada and their children: a population-based cohort study.

PubMed

Benchimol, Eric I; Manuel, Douglas G; To, Teresa; Mack, David R; Nguyen, Geoffrey C; Gommerman, Jennifer L; Croitoru, Kenneth; Mojaverian, Nassim; Wang, Xuesong; Quach, Pauline; Guttmann, Astrid

2015-01-01

There is a high and rising rate of immune-mediated diseases in the Western world. Immigrants from South Asia have been reported to be at higher risk upon arrival to the West. We determined the risk of immune-mediated diseases in South Asian and other immigrants to Ontario, Canada, and their Ontario-born children. Population-based cohorts of patients with asthma, type 1 diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD) were derived from health administrative data. We determined the standardized incidence, and the adjusted risk of these diseases in immigrants from South Asia, immigrants from other regions, compared with non-immigrant residents of Ontario. The risk of these diseases in the Ontario-born children of immigrants were compared to the children of non-immigrants. Compared to non-immigrants, adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33-0.67) was low amongst immigrant children from South Asia. However, the risk in Ontario-born children of South Asian immigrants relative to the children of non-immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated for IBD (IRR 0.90, 95%CI 0.65-1.22). Early-life environmental exposures may trigger a genetic predisposition to the development of asthma and IBD in South Asian immigrants and their Canada-born children.

Improving asthma management among African-American children via a community health worker model: findings from a Chicago-based pilot intervention.

PubMed

Margellos-Anast, Helen; Gutierrez, Melissa A; Whitman, Steven

2012-05-01

Asthma affects 25-30% of children living in certain disadvantaged Chicago neighborhoods, a rate twice the national prevalence (13%). Children living in poor, minority communities tend to rely heavily on the emergency department (ED) for asthma care and are unlikely to be properly medicated or educated on asthma self-management. A pilot project implemented and evaluated a community health worker (CHW) model for its effectiveness in reducing asthma morbidity and improving the quality of life among African-American children living in disadvantaged Chicago neighborhoods. Trained CHWs from targeted communities provided individualized asthma education during three to four home visits over 6 months. The CHWs also served as liaisons between families and the medical system. Seventy children were enrolled into the pilot phase between 15 November 2004 and 15 July 2005, of which 96% were insured by Medicaid and 54% lived with a smoker. Prior to starting, the study was approved by an institutional review board. Data on 50 children (71.4%) who completed the entire 12-month evaluation phase were analyzed using a before and after study design. Findings indicate improved asthma control. Specifically, symptom frequency was reduced by 35% and urgent health resource utilization by 75% between the pre- and post-intervention periods. Parental quality of life also improved by a level that was both clinically and statistically significant. Other important outcomes included improved asthma-related knowledge, decreased exposure to asthma triggers, and improved medical management. The intervention was also shown to be cost-effective, resulting in an estimated $5.58 saved per dollar spent on the intervention. Findings suggest that individualized asthma education provided by a trained, culturally competent CHW is effective in improving asthma management among poorly controlled, inner-city children. Further studies are needed to affirm the findings and assess the model's generalizability.

Asthma exacerbation and proximity of residence to major roads: a population-based matched case-control study among the pediatric Medicaid population in Detroit, Michigan

PubMed Central

2011-01-01

Background The relationship between asthma and traffic-related pollutants has received considerable attention. The use of individual-level exposure measures, such as residence location or proximity to emission sources, may avoid ecological biases. Method This study focused on the pediatric Medicaid population in Detroit, MI, a high-risk population for asthma-related events. A population-based matched case-control analysis was used to investigate associations between acute asthma outcomes and proximity of residence to major roads, including freeways. Asthma cases were identified as all children who made at least one asthma claim, including inpatient and emergency department visits, during the three-year study period, 2004-06. Individually matched controls were randomly selected from the rest of the Medicaid population on the basis of non-respiratory related illness. We used conditional logistic regression with distance as both categorical and continuous variables, and examined non-linear relationships with distance using polynomial splines. The conditional logistic regression models were then extended by considering multiple asthma states (based on the frequency of acute asthma outcomes) using polychotomous conditional logistic regression. Results Asthma events were associated with proximity to primary roads with an odds ratio of 0.97 (95% CI: 0.94, 0.99) for a 1 km increase in distance using conditional logistic regression, implying that asthma events are less likely as the distance between the residence and a primary road increases. Similar relationships and effect sizes were found using polychotomous conditional logistic regression. Another plausible exposure metric, a reduced form response surface model that represents atmospheric dispersion of pollutants from roads, was not associated under that exposure model. Conclusions There is moderately strong evidence of elevated risk of asthma close to major roads based on the results obtained in this population-based matched case-control study. PMID:21513554

An official American Thoracic Society Workshop Report: presentations and discussion of the fifth Jack Pepys Workshop on Asthma in the Workplace. Comparisons between asthma in the workplace and non-work-related asthma.

PubMed

Malo, Jean-Luc; Tarlo, Susan M; Sastre, Joaquin; Martin, James; Jeebhay, Mohamed F; Le Moual, Nicole; Heederik, Dick; Platts-Mills, Thomas; Blanc, Paul D; Vandenplas, Olivier; Moscato, Gianna; de Blay, Frédéric; Cartier, André

2015-07-01

The fifth Jack Pepys Workshop on Asthma in the Workplace focused on the similarities and differences of work-related asthma (WRA) and non-work-related asthma (non-WRA). WRA includes occupational asthma (OA) and work-exacerbated asthma (WEA). There are few biological differences in the mechanisms of sensitization to environmental and occupational allergens. Non-WRA and OA, when due to high-molecular-weight agents, are both IgE mediated; it is uncertain whether OA due to low-molecular-weight agents is also IgE mediated. Risk factors for OA include female sex, a history of upper airway symptoms, and a history of bronchial hyperresponsiveness. Atopy is a risk factor for OA due to high-molecular-weight agents, and exposure to cleaning agents is a risk factor for both OA and non-WRA. WEA is important among workers with preexisting asthma and may overlap with irritant-induced asthma, a type of OA. Induced sputum cytology can confirm airway inflammation, but specific inhalation challenge is the reference standard diagnostic test. Inhalation challenges are relatively safe, with the most severe reactions occurring with low-molecular-weight agents. Indirect health care costs account for about 50% of total asthma costs. Workers with poor asthma control (WRA or non-WRA) are less likely to be employed. Income loss is a major contributor to the indirect costs of WRA. Overall, asthma outcomes probably are worse for adult-onset than for childhood-onset asthma but better for OA than adult-onset non-WRA. Important aspects of management of OA are rapid and proper confirmation of the diagnosis and reduction of exposure to sensitizers or irritants at work and home.

An Official American Thoracic Society Workshop Report: Presentations and Discussion of the Fifth Jack Pepys Workshop on Asthma in the Workplace. Comparisons between Asthma in the Workplace and Non–Work-related Asthma

PubMed Central

Malo, Jean-Luc; Sastre, Joaquin; Martin, James; Jeebhay, Mohamed F.; Le Moual, Nicole; Heederik, Dick; Platts-Mills, Thomas; Blanc, Paul D.; Vandenplas, Olivier; Moscato, Gianna; de Blay, Frédéric; Cartier, André

2015-01-01

The fifth Jack Pepys Workshop on Asthma in the Workplace focused on the similarities and differences of work-related asthma (WRA) and non–work-related asthma (non-WRA). WRA includes occupational asthma (OA) and work-exacerbated asthma (WEA). There are few biological differences in the mechanisms of sensitization to environmental and occupational allergens. Non-WRA and OA, when due to high-molecular-weight agents, are both IgE mediated; it is uncertain whether OA due to low-molecular-weight agents is also IgE mediated. Risk factors for OA include female sex, a history of upper airway symptoms, and a history of bronchial hyperresponsiveness. Atopy is a risk factor for OA due to high-molecular-weight agents, and exposure to cleaning agents is a risk factor for both OA and non-WRA. WEA is important among workers with preexisting asthma and may overlap with irritant-induced asthma, a type of OA. Induced sputum cytology can confirm airway inflammation, but specific inhalation challenge is the reference standard diagnostic test. Inhalation challenges are relatively safe, with the most severe reactions occurring with low-molecular-weight agents. Indirect health care costs account for about 50% of total asthma costs. Workers with poor asthma control (WRA or non-WRA) are less likely to be employed. Income loss is a major contributor to the indirect costs of WRA. Overall, asthma outcomes probably are worse for adult-onset than for childhood-onset asthma but better for OA than adult-onset non-WRA. Important aspects of management of OA are rapid and proper confirmation of the diagnosis and reduction of exposure to sensitizers or irritants at work and home. PMID:26203621

Anti-inflammatory effects of Boletus edulis polysaccharide on asthma pathology.

PubMed

Wu, Songquan; Wang, Guangli; Yang, Ruhui; Cui, Yubao

2016-01-01

Asthma is a chronic airway disease common around the world. The burden of this disease could be reduced with new and effective treatments. Here, the efficacy of a polysaccharide extract from the Boletus edulis (BEP) mushroom, which has demonstrated anti-inflammatory properties, was tested in a mouse model of asthma. Five groups of BaLB/C mice were developed; one group served as a control and did not have asthma induction. The other four groups of mice were sensitized by ovalbumin challenge. FinePointe™ RC animal airway resistance and pulmonary compliance was used to assess airway function in asthma models. Three of the 4 model groups received treatments: one received pravastatin, one received dexamethasone, and one received BEP. Histopathology of lung tissues was performed using H&E and AB-PAS staining. Levels of cytokines IL-4 and IFN-g were detected using ELISA, qRT-PCR, and Western blotting. Cyclophilin A was measured by Western blot, and flow cytometry was used to determine the proportion of CD4 + CD25 + FOXP3 + Treg cells. BEP treatment resulted in improvements in lung pathology, IL-4 level (P<0.05), and IFN-γ level (P<0.05) similar to traditional dexamethasone treatment. Further, the proportion of anti-inflammatory CD4 + CD25 + FOXP3 + Treg cells significantly increased (P<0.05) compared to untreated asthma models, and expression of cyclophilin A significantly decreased (P<0.05). Thus, Boletus edulis polysaccharide reduces pro-inflammatory responses and increases anti-inflammatory responses in mouse models of asthma, suggesting this may be a novel treatment method.

Anti-inflammatory effects of Boletus edulis polysaccharide on asthma pathology

PubMed Central

Wu, Songquan; Wang, Guangli; Yang, Ruhui; Cui, Yubao

2016-01-01

Asthma is a chronic airway disease common around the world. The burden of this disease could be reduced with new and effective treatments. Here, the efficacy of a polysaccharide extract from the Boletus edulis (BEP) mushroom, which has demonstrated anti-inflammatory properties, was tested in a mouse model of asthma. Five groups of BaLB/C mice were developed; one group served as a control and did not have asthma induction. The other four groups of mice were sensitized by ovalbumin challenge. FinePointe™ RC animal airway resistance and pulmonary compliance was used to assess airway function in asthma models. Three of the 4 model groups received treatments: one received pravastatin, one received dexamethasone, and one received BEP. Histopathology of lung tissues was performed using H&E and AB-PAS staining. Levels of cytokines IL-4 and IFN-g were detected using ELISA, qRT-PCR, and Western blotting. Cyclophilin A was measured by Western blot, and flow cytometry was used to determine the proportion of CD4+CD25+FOXP3+ Treg cells. BEP treatment resulted in improvements in lung pathology, IL-4 level (P<0.05), and IFN-γ level (P<0.05) similar to traditional dexamethasone treatment. Further, the proportion of anti-inflammatory CD4+CD25+FOXP3+ Treg cells significantly increased (P<0.05) compared to untreated asthma models, and expression of cyclophilin A significantly decreased (P<0.05). Thus, Boletus edulis polysaccharide reduces pro-inflammatory responses and increases anti-inflammatory responses in mouse models of asthma, suggesting this may be a novel treatment method. PMID:27830033

Polycyclic Aromatic Hydrocarbon Exposure and Wheeze in a Cohort of Children with Asthma in Fresno, CA

PubMed Central

Gale, Sara L.; Noth, Elizabeth M.; Mann, Jennifer; Balmes, John; Hammond, S. Katharine; Tager, Ira B.

2014-01-01

Polycyclic aromatic hydrocarbons (PAHs) are found widely in the ambient air and result from combustion of various fuels and industrial processes. PAHs have been associated with adverse human health effects such as cognitive development, childhood IQ, and respiratory health. The Fresno Asthmatic Children’s Environment Study (FACES) enrolled 315 children ages 6-11 years with asthma in Fresno, CA and followed the cohort from 2000 to 2008. Subjects were evaluated for asthma symptoms in up to three 14-day panels per year. Detailed ambient pollutant concentrations were collected from a central site and outdoor pollutants were measured at 83 homes for at least one 5-day period. Measurements of particle-bound PAHs were used with land use regression models to estimate individual exposures to PAHs with 4-, 5- or 6-member rings (PAH456) and phenanthrene for the cohort (approximately 22 000 individual daily estimates). We used a cross-validation based algorithm for model fitting and a generalized estimated equation approach to account for repeated measures. Multiple lags and moving averages of PAH exposure were associated with increased wheeze for each of the three types of PAH exposure estimates. The odds ratios for asthmatics exposed to PAHs (ng/m3) ranged from 1.01 (95% CI, 1.00-1.02) to 1.10 (95% CI, 1.04-1.17)]. This trend for increased wheeze persisted among all PAHs measured. Phenanthrene was found to have a higher relative impact on wheeze. These data provide further evidence that PAHs contribute to asthma morbidity. PMID:22549720

Polycyclic aromatic hydrocarbon exposure and wheeze in a cohort of children with asthma in Fresno, CA.

PubMed

Gale, Sara L; Noth, Elizabeth M; Mann, Jennifer; Balmes, John; Hammond, S Katharine; Tager, Ira B

2012-07-01

Polycyclic aromatic hydrocarbons (PAHs) are found widely in the ambient air and result from combustion of various fuels and industrial processes. PAHs have been associated with adverse human health effects such as cognitive development, childhood IQ, and respiratory health. The Fresno Asthmatic Children's Environment Study enrolled 315 children aged 6-11 years with asthma in Fresno, CA and followed the cohort from 2000 to 2008. Subjects were evaluated for asthma symptoms in up to three 14-day panels per year. Detailed ambient pollutant concentrations were collected from a central site and outdoor pollutants were measured at 83 homes for at least one 5-day period. Measurements of particle-bound PAHs were used with land-use regression models to estimate individual exposures to PAHs with 4-, 5-, or 6-member rings (PAH456) and phenanthrene for the cohort (approximately 22,000 individual daily estimates). We used a cross-validation-based algorithm for model fitting and a generalized estimated equation approach to account for repeated measures. Multiple lags and moving averages of PAH exposure were associated with increased wheeze for each of the three types of PAH exposure estimates. The odds ratios for asthmatics exposed to PAHs (ng/m(3)) ranged from 1.01 (95% CI, 1.00-1.02) to 1.10 (95% CI, 1.04-1.17). This trend for increased wheeze persisted among all PAHs measured. Phenanthrene was found to have a higher relative impact on wheeze. These data provide further evidence that PAHs contribute to asthma morbidity.

The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma.

PubMed

Reeder, Kristen M; Dunaway, Chad W; Blackburn, Jonathan P; Yu, Zhihong; Matalon, Sadis; Hastie, Annette T; Ampleford, Elizabeth J; Meyers, Deborah A; Steele, Chad

2018-06-15

Asthmatics sensitized to fungi are reported to have more severe asthma, yet the immunopathogenic pathways contributing to this severity have not been identified. In a pilot assessment of human asthmatics, those subjects sensitized to fungi demonstrated elevated levels of the common γ-chain cytokine IL-7 in lung lavage fluid, which negatively correlated with the lung function measurement PC20. Subsequently, we show that IL-7 administration during experimental fungal asthma worsened lung function and increased the levels of type 2 cytokines (IL-4, IL-5, IL-13), proallergic chemokines (CCL17, CCL22) and proinflammatory cytokines (IL-1α, IL-1β). Intriguingly, IL-7 administration also increased IL-22, which we have previously reported to drive immunopathogenic responses in experimental fungal asthma. Employing IL22 Cre R26R eYFP reporter mice, we identified γδ T cells, iNKT cells, CD4 T cells and ILC3s as sources of IL-22 during fungal asthma; however, only iNKT cells were significantly increased after IL-7 administration. IL-7-induced immunopathogenesis required both type 2 and IL-22 responses. Blockade of IL-7Rα in vivo resulted in attenuated IL-22 production, lower CCL22 levels, decreased iNKT cell, CD4 T-cell and eosinophil recruitment, yet paradoxically increased dynamic lung resistance. Collectively, these results suggest a complex role for IL-7 signaling in allergic fungal asthma.

Eosinophilic Endotype of Asthma.

PubMed

Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

2016-08-01

Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS).

PubMed

Movin, Maria; Garden, Frances L; Protudjer, Jennifer L P; Ullemar, Vilhelmina; Svensdotter, Frida; Andersson, David; Kruse, Andreas; Cowell, Chris T; Toelle, Brett G; Marks, Guy B; Almqvist, Catarina

2017-04-01

Understanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex-specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence. Our longitudinal study included participants with a family history of asthma born during 1997-1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories. In total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex-specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex. We identified sex-specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only. © 2016 Asian Pacific Society of Respirology.

Predictors of perceived asthma control among patients managed in primary care clinics.

PubMed

Eilayyan, Owis; Gogovor, Amede; Mayo, Nancy; Ernst, Pierre; Ahmed, Sara

2015-01-01

To estimate the extent to which symptom status, physical activity, beliefs about medications, self-efficacy, emotional status, and healthcare utilization predict perceived asthma control over a period of 16 months among a primary care population. The current study is a secondary analysis of data from a longitudinal study that examined health outcomes of asthma among participants recruited from primary care clinics. Path analysis, based on the Wilson and Cleary and International Classification of Functioning, Disability and Health frameworks, was used to estimate the predictors of perceived asthma control. The path analysis identified initial perceived asthma control asthma (β = 0.43, p < 0.0001), symptoms (β = 0.35, p < 0.0001), physical activity (β = 0.27, p < 0.0001), and self-efficacy (β = 0.29, p < 0.0001) as significant predictors of perceived asthma control (total effects, i.e., direct and indirect), while emotional status (β = 0.08, p = 0.03) was a significant indirect predictor through physical activity. The model explained 24 % of the variance of perceived asthma control. Overall, the model fits the data well (χ (2) = 6.65, df = 6, p value = 0.35, root-mean-square error of approximation = 0.02, Comparative Fit Index = 0.999, and weighted root-mean-square residual = 0.27). Initial perceived asthma control, current symptoms status, physical activity, and self-efficacy can be used to identify individuals likely to have good perceived asthma control in the future. Emotional status also has an impact on perceived asthma control mediated through physical activity and should be considered when planning patient management. Identifying these predictors is important to help the care team tailor interventions that will allow individuals to optimally manage their asthma, to prevent exacerbations, to prevent other respiratory-related chronic disease, and to maximize quality of life.

Relationship of self-reported asthma severity and urgent health care utilization to psychological sequelae of the September 11, 2001 terrorist attacks on the World Trade Center among New York City area residents.

PubMed

Fagan, Joanne; Galea, Sandro; Ahern, Jennifer; Bonner, Sebastian; Vlahov, David

2003-01-01

Posttraumatic psychological stress may be associated with increases in somatic illness, including asthma, but the impact of the psychological sequelae of the September 11, 2001 terrorist attacks on physical illness has not been well documented. The authors assessed the relationship between the psychological sequelae of the attacks and asthma symptom severity and the utilization of urgent health care services for asthma since September 11. The authors performed a random digit dial telephone survey of adults in the New York City (NYC) metropolitan area 6 to 9 months after September 11, 2001. Two thousand seven hundred fifty-five demographically representative adults including 364 asthmatics were recruited. The authors assessed self-reported asthma symptom severity, emergency room (ER) visits, and unscheduled physician office visits for asthma since September 11. After adjustment for asthma measures before September 11, demographics, and event exposure in multivariate models posttraumatic stress disorder (PTSD) were a significant predictor of self-reported moderate-to-severe asthma symptoms (OR = 3.4; CI = 1.2-9.4), seeking care for asthma at an ER since September 11 (OR = 6.6; CI = 1.6-28.0), and unscheduled physician visits for asthma since September 11 (OR = 3.6; CI = 1.1-11.5). The number of PTSD symptoms was also significantly related to moderate-to-severe asthma symptoms and unscheduled physician visits since September 11. Neither a panic attack on September 11 nor depression since September 11 was an independent predictor of asthma severity or utilization in multivariate models after September 11. PTSD related to the September 11 terrorist attacks contributed to symptom severity and the utilization of urgent health care services among asthmatics in the NYC metropolitan area.

Association between Allergic Rhinitis and Asthma Control in Peruvian School Children: A Cross-Sectional Study

PubMed Central

Uceda, Mónica; Ziegler, Otto; Lindo, Felipe; Herrera-Pérez, Eder

2013-01-01

Background. Asthma and allergic rhinitis are highly prevalent conditions that cause major illness worldwide. This study aimed to assess the association between allergic rhinitis and asthma control in Peruvian school children. Methods. A cross-sectional study was conducted among 256 children with asthma recruited in 5 schools from Lima and Callao cities. The outcome was asthma control assessed by the asthma control test. A score test for trend of odds was used to evaluate the association between allergic rhinitis severity and the prevalence of inadequate asthma control. A generalized linear regression model was used to estimate the adjusted prevalence ratios of inadequate asthma control. Results. Allergic rhinitis was present in 66.4% of the population with asthma. The trend analysis showed a positive association between allergic rhinitis and the probability of inadequate asthma control (P < 0.001). It was associated with an increased prevalence of inadequate asthma control, with adjusted prevalence ratios of 1.53 (95% confidence interval: 1.19−1.98). Conclusion. This study indicates that allergic rhinitis is associated with an inadequate level of asthma control, giving support to the recommendation of evaluating rhinitis to improve asthma control in children. PMID:23984414

Capsaicin-evoked cough responses in asthmatic patients: Evidence for airway neuronal dysfunction.

PubMed

Satia, Imran; Tsamandouras, Nikolaos; Holt, Kimberley; Badri, Huda; Woodhead, Mark; Ogungbenro, Kayode; Felton, Timothy W; O'Byrne, Paul M; Fowler, Stephen J; Smith, Jaclyn A

2017-03-01

Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored. We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses. Capsaicin inhalational challenge was performed, and cough responses were analyzed by using nonlinear mixed-effects modeling to estimate the maximum cough response evoked by any concentration of capsaicin (E max ) and the capsaicin dose inducing half-maximal response (ED 50 ). Ninety-seven patients with stable asthma (median age, 23 years [interquartile range, 21-27 years]; 60% female) and 47 healthy volunteers (median age, 38 years [interquartile range, 29-47 years]; 64% female) were recruited. Asthmatic patients had higher E max and lower ED 50 values than healthy volunteers. E max values were 27% higher in female subjects (P = .006) and 46% higher in patients with nonatopic asthma (P = .003) compared with healthy volunteers. Also, patients with atopic asthma had a 21% lower E max value than nonatopic asthmatic patients (P = .04). The ED 50 value was 65% lower in female patients (P = .0001) and 71% lower in all asthmatic patients (P = .0008). ED 50 values were also influenced by asthma control and serum IgE levels, whereas E max values were related to 24-hour cough frequency. Age, body mass index, FEV 1 , PC 20 , fraction of exhaled nitric oxide, blood eosinophil counts, and inhaled steroid treatment did not influence cough parameters. Patients with stable asthma exhibited exaggerated capsaicin-evoked cough responses consistent with neuronal dysfunction. Nonatopic asthmatic patients had the highest cough responses, suggesting this mechanism might be most important in type 2-low asthma phenotypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Oxidative stress biomarkers and asthma characteristics in adults of the EGEA study.

PubMed

Andrianjafimasy, Miora; Zerimech, Farid; Akiki, Zeina; Huyvaert, Helene; Le Moual, Nicole; Siroux, Valérie; Matran, Régis; Dumas, Orianne; Nadif, Rachel

2017-12-01

Asthma is an oxidative stress related disease, but associations with asthma outcomes are poorly studied in adults. We aimed to study the associations between several biomarkers related to oxidative stress and various asthma outcomes.Cross-sectional analyses were conducted in 1388 adults (mean age 43 years, 44% with asthma) from the Epidemiological Study of the Genetics and Environment of Asthma (EGEA2). Three blood antioxidant enzyme activities (biomarkers of response to oxidative stress) and exhaled breath condensate 8-isoprostanes and plasma fluorescent oxidation products (FlOPs) levels (two biomarkers of damage) were measured. Associations between biomarkers and 1) ever asthma and 2) asthma attacks, asthma control and lung function in participants with asthma were evaluated using regression models adjusted for age, sex and smoking.Biomarkers of response were unrelated to asthma outcomes. Higher 8-isoprostane levels were significantly associated with ever asthma (odds ratio for one interquartile range increase 1.28 (95% CI 1.06-1.67). Among participants with asthma, 8-isoprostane levels were negatively associated with adult-onset asthma (0.63, 0.41-0.97) and FlOPs levels were positively associated with asthma attacks (1.33, 1.07-1.65), poor asthma control (1.30, 1.02-1.66) and poor lung function (1.34, 1.04-1.74).Our results suggest that 8-isoprostanes are involved in childhood-onset asthma and FlOPs are linked to asthma expression. Copyright ©ERS 2017.

Effects of temperature variation between neighbouring days on daily hospital visits for childhood asthma: a time-series analysis.

PubMed

Li, K; Ni, H; Yang, Z; Wang, Y; Ding, S; Wen, L; Yang, H; Cheng, J; Su, H

2016-07-01

To identify the relationship between temperature variation between neighbouring days (TVN) and hospital visits for childhood asthma in age- and sex-specific groups. An ecological design was used to explore the effect of TVN on hospital visits for childhood asthma. A Poisson generalised linear regression model combined with a distributed lag non-linear model was used to analyse the association between TVN and hospital visits for childhood asthma. All hospital visits for childhood asthma from June 2010 to July 2013 were included (n = 17,022). Daily climate data were obtained from Hefei Meteorological Bureau. A significant correlation was found between TVN and hospital visits for childhood asthma in age- and sex-specific groups. For different gender groups, the effect of TVN on childhood asthma was the greatest at 3 and 5 days lag for males and females. For different age groups, the effect of TVN on childhood asthma was the greatest at 1 and 5 days lag for 0-4 years and 5-14 years children, respectively. A 1 °C increase in TVN was associated with a 4.2% (95% confidence interval 0.9-7.6%) increase in hospital visits for childhood asthma. TVN is associated with hospital visits for childhood asthma. Once the temperature change rapidly, guardians will be urged to pay more attention to their children's health, which may reduce the morbidity of childhood asthma. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Ambient air pollution, traffic noise and adult asthma prevalence: a BioSHaRE approach.

PubMed

Cai, Yutong; Zijlema, Wilma L; Doiron, Dany; Blangiardo, Marta; Burton, Paul R; Fortier, Isabel; Gaye, Amadou; Gulliver, John; de Hoogh, Kees; Hveem, Kristian; Mbatchou, Stéphane; Morley, David W; Stolk, Ronald P; Elliott, Paul; Hansell, Anna L; Hodgson, Susan

2017-01-01

We investigated the effects of both ambient air pollution and traffic noise on adult asthma prevalence, using harmonised data from three European cohort studies established in 2006-2013 (HUNT3, Lifelines and UK Biobank).Residential exposures to ambient air pollution (particulate matter with aerodynamic diameter ≤10 µm (PM 10 ) and nitrogen dioxide (NO 2 )) were estimated by a pan-European Land Use Regression model for 2007. Traffic noise for 2009 was modelled at home addresses by adapting a standardised noise assessment framework (CNOSSOS-EU). A cross-sectional analysis of 646 731 participants aged ≥20 years was undertaken using DataSHIELD to pool data for individual-level analysis via a "compute to the data" approach. Multivariate logistic regression models were fitted to assess the effects of each exposure on lifetime and current asthma prevalence.PM 10 or NO 2 higher by 10 µg·m -3 was associated with 12.8% (95% CI 9.5-16.3%) and 1.9% (95% CI 1.1-2.8%) higher lifetime asthma prevalence, respectively, independent of confounders. Effects were larger in those aged ≥50 years, ever-smokers and less educated. Noise exposure was not significantly associated with asthma prevalence.This study suggests that long-term ambient PM 10 exposure is associated with asthma prevalence in western European adults. Traffic noise is not associated with asthma prevalence, but its potential to impact on asthma exacerbations needs further investigation. Copyright ©ERS 2017.

The impact of the parental illness representation on disease management in childhood asthma.

PubMed

Yoos, H Lorrie; Kitzman, Harriet; Henderson, Charles; McMullen, Ann; Sidora-Arcoleo, Kimberly; Halterman, Jill S; Anson, Elizabeth

2007-01-01

Despite significant advances in treatment modalities, morbidity due to childhood asthma has continued to increase, particularly for poor and minority children. To describe the parental illness representation of asthma in juxtaposition to the professional model of asthma and to evaluate the impact of that illness representation on the adequacy of the child's medication regimen. Parents (n = 228) of children with asthma were interviewed regarding illness beliefs using a semistructured interview. The impact of background characteristics, parental beliefs, the child's symptom interpretation, and the parent-healthcare provider (HCP) relationship on the adequacy of the child's medication regimen were evaluated. The parental and professional models of asthma differ markedly. Demographic risk factors (p = .005), low parental education (p < .0001), inaccurate symptom evaluation by the child (p = .02), and a poor parent-HCP relationship (p < .0001) had a negative effect on the parental illness representation. A parental illness representation concordant with the professional model of asthma (p = .05) and more formal asthma education (p = .02) had a direct positive effect on the medication regimen. Demographic risk factors (p = .006) and informal advice-seeking (p = .0003) had a negative impact on the regimen. The parental illness representation mediated the impact of demographic risk factors (p = .10), parental education (p =.07), and the parent-HCP relationship (p = .06) on the regimen. Parents and HCPs may come to the clinical encounter with markedly different illness representations. Establishing a partnership with parents by eliciting and acknowledging parental beliefs is an important component of improving disease management.

Stem cells in animal asthma models: a systematic review.

PubMed

Srour, Nadim; Thébaud, Bernard

2014-12-01

Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

PubMed

Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Predicting phenotypes of asthma and eczema with machine learning

PubMed Central

2014-01-01

Background There is increasing recognition that asthma and eczema are heterogeneous diseases. We investigated the predictive ability of a spectrum of machine learning methods to disambiguate clinical sub-groups of asthma, wheeze and eczema, using a large heterogeneous set of attributes in an unselected population. The aim was to identify to what extent such heterogeneous information can be combined to reveal specific clinical manifestations. Methods The study population comprised a cross-sectional sample of adults, and included representatives of the general population enriched by subjects with asthma. Linear and non-linear machine learning methods, from logistic regression to random forests, were fit on a large attribute set including demographic, clinical and laboratory features, genetic profiles and environmental exposures. Outcome of interest were asthma, wheeze and eczema encoded by different operational definitions. Model validation was performed via bootstrapping. Results The study population included 554 adults, 42% male, 38% previous or current smokers. Proportion of asthma, wheeze, and eczema diagnoses was 16.7%, 12.3%, and 21.7%, respectively. Models were fit on 223 non-genetic variables plus 215 single nucleotide polymorphisms. In general, non-linear models achieved higher sensitivity and specificity than other methods, especially for asthma and wheeze, less for eczema, with areas under receiver operating characteristic curve of 84%, 76% and 64%, respectively. Our findings confirm that allergen sensitisation and lung function characterise asthma better in combination than separately. The predictive ability of genetic markers alone is limited. For eczema, new predictors such as bio-impedance were discovered. Conclusions More usefully-complex modelling is the key to a better understanding of disease mechanisms and personalised healthcare: further advances are likely with the incorporation of more factors/attributes and longitudinal measures. PMID:25077568

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.

PubMed

Liu, Lu; Wang, Lin-Peng; He, Shan; Ma, Yan

2018-05-01

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of IgE antibodies by B cells and a decrease of the interferon-γ/interleukin-4 (Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine (CM) research on the mechanisms and effificacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the PubMed and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specifific immunoglobulin E, inflflammatory cell infifiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

Childhood-Onset Asthma in Smokers. Association between CT Measures of Airway Size, Lung Function, and Chronic Airflow Obstruction

PubMed Central

Hardin, Megan E.; Come, Carolyn E.; San José Estépar, Raúl; Ross, James C.; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K.; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K.; Crapo, James D.; Lynch, David A.; Make, Barry; Barr, R. Graham; Hersh, Craig P.; Washko, George R.

2014-01-01

Rationale and Objectives: Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. Methods: We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Measurements and Main Results: Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. Conclusion: In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764). PMID:25296268

Childhood-onset asthma in smokers. association between CT measures of airway size, lung function, and chronic airflow obstruction.

PubMed

Diaz, Alejandro A; Hardin, Megan E; Come, Carolyn E; San José Estépar, Raúl; Ross, James C; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K; Crapo, James D; Lynch, David A; Make, Barry; Barr, R Graham; Hersh, Craig P; Washko, George R

2014-11-01

Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Saccharomyces cerevisiae-Derived Mannan Does Not Alter Immune Responses to Aspergillus Allergens.

PubMed

Lew, D Betty; LeMessurier, Kim S; Palipane, Maneesha; Lin, Yanyan; Samarasinghe, Amali E

2018-01-01

Severe asthma with fungal sensitization predominates in the population suffering from allergic asthma, to which there is no cure. While corticosteroids are the mainstay in current treatment, other means of controlling inflammation may be beneficial. Herein, we hypothesized that mannan from Saccharomyces cerevisiae would dampen the characteristics of fungal allergic asthma by altering the pulmonary immune responses. Using wild-type and transgenic mice expressing the human mannose receptor on smooth muscle cells, we explored the outcome of mannan administration during allergen exposure on the pathogenesis of fungal asthma through measurement of cardinal features of disease such as inflammation, goblet cell number, and airway hyperresponsiveness. Mannan treatment did not alter most hallmarks of allergic airways disease in wild-type mice. Transgenic mice treated with mannan during allergen exposure had an equivalent response to non-mannan-treated allergic mice except for a prominent granulocytic influx into airways and cytokine availability. Our studies suggest no role for mannan as an inflammatory regulator during fungal allergy.

Guinea pig models of asthma.

PubMed

McGovern, Alice E; Mazzone, Stuart B

2014-12-01

Described in this unit are methods for establishing guinea pig models of asthma. Sufficient detail is provided to enable investigators to study bronchoconstriction, cough, airway hyperresponsiveness, inflammation, and remodeling. Copyright © 2014 John Wiley & Sons, Inc.

Choosing wisely: adherence by physicians to recommended use of spirometry in the diagnosis and management of adult asthma.

PubMed

Sokol, Kristin C; Sharma, Gulshan; Lin, Yu-Li; Goldblum, Randall M

2015-05-01

The National Asthma Education and Prevention Program (NAEPP) and the American Thoracic Society provide guidelines stating that physicians should use spirometry in the diagnosis and management of asthma. The aim of this study was to evaluate the trends, over a 10-year period, in the utilization of spirometry in patients newly diagnosed with asthma. We hypothesized that spirometry use would increase in physicians who care for asthma patients, especially since 2007, when the revised NAEPP guidelines were published. This retrospective cohort analysis of spirometry use in subjects newly diagnosed with asthma used a privately insured adult population for the years 2002-2011. Our primary outcome of interest was spirometry performed within a year (± 365 days) of the initial date of asthma diagnosis. We also examined the type of asthma medications prescribed. In all, 134,208 patients were found to have a diagnosis of asthma. Only 47.6% had spirometry performed within 1 year of diagnosis. Younger patients, males, and those residing in the Northeast were more likely to receive spirometry. Spirometry use began to decline in 2007. Patients cared for by specialists were more likely to receive spirometry than those cared for by primary care physicians; 80.1% vs 23.3%, respectively. Lastly, even without spirometry, a significant portion of patients (78.3%) was prescribed asthma drugs. Our study suggests that spirometry is underutilized in newly diagnosed asthma patients. Moreover, the use of controller medications in those diagnosed with asthma without spirometry remains high. Copyright © 2015 Elsevier Inc. All rights reserved.

Platelet–Eosinophil Interactions As a Potential Therapeutic Target in Allergic Inflammation and Asthma

PubMed Central

Shah, Sajeel A.; Page, Clive P.; Pitchford, Simon C.

2017-01-01

The importance of platelet activation during hemostasis is well understood. An understanding of these mechanisms has led to the use of several classes of anti-platelet drugs to inhibit aggregation for the prevention of thrombi during cardiovascular disease. It is now also recognized that platelets can function very differently during inflammation, as part of their role in the innate immune response against pathogens. This dichotomy in platelet function occurs through distinct physiological processes and alternative signaling pathways compared to that of hemostasis (leading to platelet aggregation) and is manifested as increased rheological interactions with leukocytes, the ability to undergo chemotaxis, communication with antigen-presenting cells, and direct anti-pathogen responses. Mounting evidence suggests platelets are also critical in the pathogenesis of allergic diseases such as asthma, where they have been associated with antigen presentation, bronchoconstriction, bronchial hyperresponsiveness, airway inflammation, and airway remodeling in both clinical and experimental studies. In particular, platelets have been reported bound to eosinophils in the blood of patients with asthma and the incidence of these events increases after both spontaneous asthma attacks in a biphasic manner, or after allergen challenge in the clinic. Platelet depletion in animal models of allergic airway inflammation causes a profound reduction in eosinophil recruitment to the lung, suggesting that the association of platelets with eosinophils is indeed an important event during eosinophil activation. Furthermore, in cases of severe asthma, and in animal models of allergic airways inflammation, platelet–eosinophil complexes move into the lung through a platelet P-selectin-mediated, eosinophil β1-integrin activation-dependent process, while platelets increase adherence of eosinophils to the vascular endothelium in vitro, demonstrating a clear interaction between these cell types in allergic inflammatory diseases. This review will explore non-thrombotic platelet activation in the context of allergy and the association of platelets with eosinophils, to reveal how these phenomena may lead to the discovery of novel therapeutic targets. PMID:28848732

Asthma and subjective sleep disordered breathing in a large cohort of urban adolescents.

PubMed

Zandieh, Stephanie O; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M; Bruzzese, Jean-Marie

2017-01-02

Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. 12% reported SDB symptoms. Older and bi-racial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p <.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p <.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma.

Asthma and Subjective Sleep Disordered Breathing in a Large Cohort of Urban Adolescents

PubMed Central

Zandieh, Stephanie O.; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M.; Bruzzese, Jean-Marie

2017-01-01

Objective Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. Methods 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. Results 12% reported SDB symptoms. Older and biracial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p<.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p<.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. Conclusions In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma. PMID:27740900

Predictors of quality of life: A quantitative investigation of the stress-coping model in children with asthma

PubMed Central

Peeters, Yvette; Boersma, Sandra N; Koopman, Hendrik M

2008-01-01

Background Aim of this study is to further explore predictors of health related quality of life in children with asthma using factors derived from to the extended stress-coping model. While the stress-coping model has often been used as a frame of reference in studying health related quality of life in chronic illness, few have actually tested the model in children with asthma. Method In this survey study data were obtained by means of self-report questionnaires from seventy-eight children with asthma and their parents. Based on data derived from these questionnaires the constructs of the extended stress-coping model were assessed, using regression analysis and path analysis. Results The results of both regression analysis and path analysis reveal tentative support for the proposed relationships between predictors and health related quality of life in the stress-coping model. Moreover, as indicated in the stress-coping model, HRQoL is only directly predicted by coping. Both coping strategies 'emotional reaction' (significantly) and 'avoidance' are directly related to HRQoL. Conclusion In children with asthma, the extended stress-coping model appears to be a useful theoretical framework for understanding the impact of the illness on their quality of life. Consequently, the factors suggested by this model should be taken into account when designing optimal psychosocial-care interventions. PMID:18366753

Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis.

PubMed

Zhao, Dong-Dong; Yu, Dan-Dan; Ren, Qiong-Qiong; Dong, Bao; Zhao, Feng; Sun, Ye-Huan

2017-04-01

As for the association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to pediatric asthma, results of published studies yielded conflicts. A systematic review was conducted on the relationship between childhood asthma and VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236). PubMed, Web of Science, CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) database were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated. Overall results suggested that there was a statistically significant association between ApaI polymorphism and childhood asthma in homozygote model (OR = 1.674, 95%CI = 1.269-2.208, P < 0.001) and allele model (OR = 1.221, 95%CI = 1.084-1.375, P = 0.001). Stratification by ethnicity revealed a statistical association in Asians (OR = 1.389, 95%CI = 1.178-1.638, P < 0.001). There was some evidence of an association between BsmI polymorphism and childhood asthma in the homozygote (OR = 1.462, 95%CI = 1.016-2.105, P = 0.041) and allele models (OR = 1.181, 95%CI = 1.006-1.386, P = 0.042). This association reached significance only in the Caucasian group (OR = 1.236, 95%CI = 1.029-1.485, P = 0.023). For FokI, a statistical association was detected in dominant model (OR = 1.281, 95%CI = 1.055-1.555, P = 0.012); this association was significant in allele model (OR = 1.591, 95%CI = 1.052-2.405, P = 0.028) in Caucasian. ApaI polymorphism plays a particular role in childhood asthma in Asians. FokI polymorphism may be connected with pediatric asthma in Caucasian population. And BsmI polymorphism marginally contributes to childhood asthma susceptibility, while there might be no association between TaqI polymorphism and childhood asthma risk. Pediatr Pulmonol. 2017;52:423-429. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Eotaxin-rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response

PubMed Central

Asosingh, Kewal; Vasanji, Amit; Tipton, Aaron; Queisser, Kimberly; Wanner, Nicholas; Janocha, Allison; Grandon, Deepa; Anand-Apte, Bela; Rothenberg, Marc. E.; Dweik, Raed; Erzurum, Serpil C.

2016-01-01

Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge, and prior to airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and murine model of asthma. Exvivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wildtype mice transplanted with eotaxin-1/2 deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, while adoptive transfer of proangiogenic progenitor cells from wildtype mice in an atopic asthma model into the eotaxin-1/2 deficient mice led to angiogenesis and airway inflammation. The findings indicate that TH2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation. PMID:26810221

Estimating Wisconsin Asthma Prevalence Using Clinical Electronic Health Records and Public Health Data

PubMed Central

Tomasallo, Carrie D.; Hanrahan, Lawrence P.; Tandias, Aman; Chang, Timothy S.; Cowan, Kelly J.

2014-01-01

Objectives. We compared a statewide telephone health survey with electronic health record (EHR) data from a large Wisconsin health system to estimate asthma prevalence in Wisconsin. Methods. We developed frequency tables and logistic regression models using Wisconsin Behavioral Risk Factor Surveillance System and University of Wisconsin primary care clinic data. We compared adjusted odds ratios (AORs) from each model. Results. Between 2007 and 2009, the EHR database contained 376 000 patients (30 000 with asthma), and 23 000 (1850 with asthma) responded to the Behavioral Risk Factor Surveillance System telephone survey. AORs for asthma were similar in magnitude and direction for the majority of covariates, including gender, age, and race/ethnicity, between survey and EHR models. The EHR data had greater statistical power to detect associations than did survey data, especially in pediatric and ethnic populations, because of larger sample sizes. Conclusions. EHRs can be used to estimate asthma prevalence in Wisconsin adults and children. EHR data may improve public health chronic disease surveillance using high-quality data at the local level to better identify areas of disparity and risk factors and guide education and health care interventions. PMID:24228643

The integrated care of asthma in Switzerland (INCAS)-study: Patients' perspective of received asthma care and their interest in asthma education.

PubMed

Dürr, Selina; Hersberger, Kurt E; Zeller, Andreas; Scheuzger, Jonas; Miedinger, David; Gregoriano, Claudia; Leuppi, Jörg D; Steurer-Stey, Claudia

2016-11-01

For successful long-term asthma care, self-management education is a cornerstone. Little is known about associations between patients' interest in education, asthma control and care delivery. We compared patients' characteristics, asthma control and patients' perspective about asthma care in subjects with and without interest in asthma education. Moreover, we assessed reasons, why patients denied participating in asthma education. Baseline data of 223 patients with asthma (age 43 ± 12 years, 38% male, 58% non-smokers, 13% current smokers), who participated in a multicentre longitudinal controlled study, are reported. At baseline, patients completed the Asthma Control Test (ACT), the Patient Assessment Chronic Illness Care questionnaire (PACIC 5A) and stated their interest in an asthma education programme. Overall, 34% of all participants showed uncontrolled asthma. One hundred and twenty-five (56%) patients were interested in education. Compared to patients without interest, they were characterised by male gender (p = 0.013), worse asthma control (p < 0.001), and perception of lower quality of chronic asthma care delivery, in particular lower self-management support (p < 0.001). Main reasons for rejecting asthma education were having sufficient asthma knowledge, having only mild asthma, receiving adequate medical support and lack of time. More than half of the patients were interested in asthma education. Interest was associated with worse asthma control and lower receipt of care according to the Chronic Care Model. Considering these aspects, this approach may help to improve care quality and allow targeting interventions to those patients who are interested in becoming active participants in their care and who might benefit most.

Factors related to poor asthma control in Latvian asthma patients between 2013 and 2015

PubMed Central

Smits, Dins; Brigis, Girts; Pavare, Jana; Maurina, Baiba; Barengo, Noël Christopher

2017-01-01

Objectives To investigate whether beliefs about asthma medication, cognitive and emotional factors are related to poor asthma control in a sample of Latvian asthma patients in 2015. Design Cross-sectional, self-administered survey. Subjects Three hundred and fifty two asthma patients (mean age 57.5 years) attending outpatient pulmonologist consultations in Riga, Latvia during September 2013 to December 2015. The sample size was calculated to detect a prevalence of poor asthma control of 50% with a margin of error of 5% and a power of 95%. Main outcome measures The validated Beliefs about Medication Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Good asthma control was assessed using the asthma control test (ACT), a validated five-item scale that reliably assesses asthma control over a recall period of four weeks. Logistic regression models were used to predict poor asthma control. Results Patients who had a good control of asthma medication (OR 0.70; 95% CI 0.61–0.79) or were confident that their asthma medication improves illness (OR 0.84; 95% CI 0.74–0.95) had a reduced risk of poor asthma control. The more symptoms (OR 1.63; 95% CI 1.44–1.84) the asthma patients perceived or the more their illness affects their life, the higher the probability of poor asthma control (OR 1.47; 95% CI 1.31–1.65). Some beliefs of necessity and concerns of asthma medication were also statistically significantly related to poor asthma control. Conclusions Beliefs of necessity of asthma medication, cognitive and emotional illness perception factors correlate well with poor asthma control in Latvian patients. PMID:28585881

Improving predictive asthma algorithms with modelled environment data for Scotland: an observational cohort study protocol.

PubMed

Soyiri, Ireneous N; Sheikh, Aziz; Reis, Stefan; Kavanagh, Kimberly; Vieno, Massimo; Clemens, Tom; Carnell, Edward J; Pan, Jiafeng; King, Abby; Beck, Rachel C; Ward, Hester J T; Dibben, Chris; Robertson, Chris; Simpson, Colin R

2018-05-20

Asthma has a considerable, but potentially, avoidable burden on many populations globally. Scotland has some of the poorest health outcomes from asthma. Although ambient pollution, weather changes and sociodemographic factors have been associated with asthma attacks, it remains unclear whether modelled environment data and geospatial information can improve population-based asthma predictive algorithms. We aim to create the afferent loop of a national learning health system for asthma in Scotland. We will investigate the associations between ambient pollution, meteorological, geospatial and sociodemographic factors and asthma attacks. We will develop and implement a secured data governance and linkage framework to incorporate primary care health data, modelled environment data, geospatial population and sociodemographic data. Data from 75 recruited primary care practices (n=500 000 patients) in Scotland will be used. Modelled environment data on key air pollutants at a horizontal resolution of 5 km×5 km at hourly time steps will be generated using the EMEP4UK atmospheric chemistry transport modelling system for the datazones of the primary care practices' populations. Scottish population census and education databases will be incorporated into the linkage framework for analysis. We will then undertake a longitudinal retrospective observational analysis. Asthma outcomes include asthma hospitalisations and oral steroid prescriptions. Using a nested case-control study design, associations between all covariates will be measured using conditional logistic regression to account for the matched design and to identify suitable predictors and potential candidate algorithms for an asthma learning health system in Scotland.Findings from this study will contribute to the development of predictive algorithms for asthma outcomes and be used to form the basis for our learning health system prototype. The study received National Health Service Research Ethics Committee approval (16/SS/0130) and also obtained permissions via the Public Benefit and Privacy Panel for Health and Social Care in Scotland to access, collate and use the following data sets: population and housing census for Scotland; Scottish education data via the Scottish Exchange of Data and primary care data from general practice Data Custodians. Analytic code will be made available in the open source GitHub website. The results of this study will be published in international peer reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.

PubMed

Zoratti, Edward; Havstad, Suzanne; Wegienka, Ganesa; Nicholas, Charlotte; Bobbitt, Kevin R; Woodcroft, Kimberley J; Ownby, Dennis R; Johnson, Christine Cole

2014-07-01

Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population. To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults. Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbol myristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vs nonallergic asthma phenotypes with those without asthma. T-helper cell type (TH) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P < .01). As expected, young adults with a history of an allergic asthma phenotype exhibited a TH2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effect modification of perinatal exposure to air pollution and childhood asthma incidence

PubMed Central

Lavigne, Éric; Bélair, Marc-André; Rodriguez Duque, Daniel; Do, Minh T.; Stieb, David M.; Hystad, Perry; van Donkelaar, Aaron; Martin, Randall V.; Crouse, Daniel L.; Crighton, Eric; Chen, Hong; Burnett, Richard T.; Weichenthal, Scott; Villeneuve, Paul J.; To, Teresa; Brook, Jeffrey R.; Johnson, Markey; Cakmak, Sabit; Yasseen, Abdool S.; Walker, Mark

2018-01-01

Perinatal exposure to ambient air pollution has been associated with childhood asthma incidence; however, less is known regarding the potential effect modifiers in this association. We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma. 761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6 years) were estimated using Cox regression models. 110 981 children with asthma were identified. In models adjusted for postnatal exposures, second-trimester exposures to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5 μm (hazard ratio (HR) per interquartile range (IQR) increase 1.07, 95% CI 1.06–1.09) and nitrogen dioxide (HR per IQR increase 1.06, 95% CI 1.03–1.08) were associated with childhood asthma development. Enhanced impacts were found among children born to mothers with asthma, who smoked during pregnancy or lived in urban areas during pregnancy, males and children born preterm or of low birthweight. Prenatal exposure to air pollution may have a differential impact on the risk of asthma development, according to maternal and infant characteristics. PMID:29419440

Short-term effects of airborne pollens on asthma attacks as seen by general practitioners in the Greater Paris area, 2003-2007.

PubMed

Huynh, Bich Tram; Tual, Séverine; Turbelin, Clément; Pelat, Camille; Cecchi, Lorenzo; D'Amato, Gennaro; Blanchon, Thierry; Annesi-Maesano, Isabella

2010-09-01

To investigate for the first time the short-term effects of airborne pollen counts on general practitioner (GP) consultations for asthma attacks in the Greater Paris area between 2003-2007. Counts were available for common pollens (Betula, Cupressa, Fraxinus and Poaceae). Weekly data on GP visits for asthma attacks were obtained from the French GP Sentinel Network. A quasi-Poisson regression with generalised additive models was implemented. Short-term effects of pollen counts were assessed using single and multi-pollen models after adjustment for air pollution and influenza. A mean weekly incidence rate of 25.4 cases of asthma attacks per 100,000 inhabitants was estimated during the study period. The strongest significant association between asthma attacks and pollen counts was registered for grass (Poaceae) in the same week of asthma attacks, with a slight reduction of the effect observed in the multi-pollen model. Adjusted relative risk for Poaceae was 1.54 (95% CI: 1.33-1.79) with an inter-quartile range increase of 17.6 grains/m3 during the pollen season. For the first time, a significant short-term association was observed between Poaceae pollen counts and consultations for asthma attacks as seen by GPs. These findings need to be confirmed by more consistent time-series and investigations on a daily basis.

Poor asthma control and exposure to traffic pollutants and obesity in older adults

PubMed Central

Epstein, Tolly G.; Ryan, Patrick H.; LeMasters, Grace K.; Bernstein, Cheryl K.; Levin, Linda S.; Bernstein, Jonathan A.; Villareal, Manuel S.; Bernstein, David I.

2015-01-01

Background Environmental and host predictors of asthma control in older asthmatic patients (>65 years old) are poorly understood. Objective To examine the effects of residential exposure to traffic exhaust and other environmental and host predictors on asthma control in older adults. Methods One hundred four asthmatic patients 65 years of age or older from allergy and pulmonary clinics in greater Cincinnati, Ohio, completed the validated Asthma Control Questionnaire (ACQ), pulmonary function testing, and skin prick testing to 10 common aeroallergens. Patients had a physician’s diagnosis of asthma, had significant reversibility in forced expiratory volume in 1 second or a positive methacholine challenge test result, and did not have chronic obstructive pulmonary disease. The mean daily residential exposure to elemental carbon attributable to traffic (ECAT) was estimated using a land-use regression model. Regression models were used to evaluate associations among independent variables, ACQ scores, and the number of asthma exacerbations, defined as acute worsening of asthma symptoms requiring prednisone use, in the past year. Results In the adjusted model, mean daily residential exposure to ECAT greater than 0.39 µg/m3 was significantly associated with poorer asthma control based on ACQ scores (adjusted β = 2.85; 95% confidence interval [CI], 0.58–5.12; P = .02). High ECAT levels were also significantly associated with increased risk of asthma exacerbations (adjusted odds ratio, 3.24; 95% CI, 1.01–10.37; P = .05). A significant association was found between higher body mass index and worse ACQ scores (adjusted β = 1.15; 95% CI, 0.53–1.76; P < .001). Atopic patients (skin prick test positive) had significantly better ACQ scores than nonatopic patients (adjusted β = −0.39; 95% CI, −0.67 to −0.11; P < .01). Conclusion Higher mean daily residential exposure to traffic exhaust, obesity, and nonatopic status are associated with poorer asthma control among older asthmatic patients. PMID:22626595

Testing evidence routine practice: Using an implementation framework to embed a clinically proven asthma service in Australian community pharmacy.

PubMed

Fuller, Joanne M; Saini, Bandana; Bosnic-Anticevich, Sinthia; Garcia Cardenas, Victoria; Benrimoj, Shalom I; Armour, Carol

Community pharmacists are well placed and evidence clearly demonstrates that they can be suitably trained to deliver professional services that improve the management of asthma patients in clinical, economic and humanistic terms. However the gap between this evidence and practice reality remains wide. In this study we measure the implementation process as well as the service benefits of an asthma service model. Using an effectiveness-implementation hybrid design, a defined implementation process (progression from Exploration through Preparation and Testing to Operation stages) supporting an asthma service (promoting asthma control and inhaler technique) was tested in 17 community pharmacies across metropolitan Sydney. Seven pharmacies reached the Operation stage of implementation. Eight pharmacies reached the Testing stage of implementation and two pharmacies did not progress beyond the Preparation stage of implementation. A total of 128 patients were enrolled in the asthma service with 110 patients remaining enrolled at the close of the study. Asthma control showed a positive trend throughout the service with the overall proportion of patients with 'poor' asthma control at baseline decreasing from 72% to 57% at study close. There was a statistically significant increase in the proportion of patients with correct inhaler technique from 12% at Baseline (Visit 1) to 33% at Visit 2 and 57% at study close. Implementation of the asthma service varied across pharmacies. Different strategies specific to practice sites at different stages of the implementation model may result in greater uptake of professional services. The asthma service led to improved patient outcomes overall with a positive trend in asthma control and significant change in inhaler technique. Copyright © 2017 Elsevier Inc. All rights reserved.

Obesity increases the prevalence and the incidence of asthma and worsens asthma severity.

PubMed

Barros, R; Moreira, P; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Moreira, A

2017-08-01

We aimed to explore the association between obesity and asthma prevalence, incidence and severity. The study included 32,644 adults, 52.6% female, from a representative sample of the 4th Portuguese National Health Survey. The following asthma definitions were used: ever asthma (ever medical doctor asthma diagnosis), current asthma (asthma within the last 12 months), current persistent asthma (required asthma medication within the last 12 months), current severe asthma (attending an emergency department because of asthma within the last 12 months), and incident asthma (asthma diagnosis within the last 12 months). Body mass index was calculated based on self-reported weight and height and categorised according to WHO classification. Logistic regression models adjusted for confounders were performed. Prevalence of ever asthma was 5.3%, current asthma 3.5%, current persistent asthma 3.0%, current severe asthma 1.4%, and incident asthma 0.2%. Prevalence of obesity was 16%, overweight 37.6%, normal weight 44.6% and underweight 0.2%. Being overweight, obesity class I and II, and obesity class III were associated with an OR (95% CI) with ever asthma 1.22 (1.21-1.24), 1.39 (1.36-1.41), 3.24 (3.08-3.40) respectively; current asthma 1.16 (1.14-1.18), 1.86 (1.82-1.90), 4.73 (4.49-4.98) respectively; current persistent asthma 1.08 (1.06-1.10), 2.06 (2.01-2.10), 5.24 (4.96-5.53), and current severe asthma 1.36 (1.32-1.40), 1.50 (1.45-1.55) and 3.70 (3.46-3.95), respectively. Considering the incidence of asthma, obesity more than quadrupled the odds (OR = 4.46, 95% CI 4.30, 4.62). Obesity is associated in a dose dependent way with an increase of prevalent and incident asthma, and it seems to increase the odds of a more persistent and severe asthma phenotype independently of socio-demographic determinants, physical activity, and dietary patterns. Our results provide rational for future lifestyle intervention studies for weight reduction in the obesity-asthma phenotype. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

EC-18, a synthetic monoacetyldiglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol), attenuates the asthmatic response in an aluminum hydroxide/ovalbumin-induced model of asthma.

PubMed

Shin, In-Sik; Shin, Na-Rae; Jeon, Chan-Mi; Kwon, Ok-Kyoung; Sohn, Ki-Young; Lee, Tae-Suk; Kim, Jae-Wha; Ahn, Kyung-Seop; Oh, Sei-Ryang

2014-01-01

EC-18 is a synthetic monoacetyldiaglyceride that is a major constituent in antlers of Sika deer (Cervus nippon Temmenick). In this study, we evaluated the protective effects of EC-18 on Th2-type cytokines, eosinophil infiltration, and other factors in an aluminum hydroxide/ovalbumin (OVA)-induced murine asthma model. Mice were sensitized on days 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On days 21, 22 and 23 after the initial sensitization, the mice received an airway challenge with OVA for 1h using an ultrasonic nebulizer. EC-18 was administered to mice by oral gavage at doses of 30mg/kg and 60mg/kg once daily from day 18 to 23. Methacholine responsiveness was measured 24h after the final OVA challenge, and the bronchoalveolar lavage fluid (BALF) was collected 48h after the final OVA challenge. EC-18 significantly reduced methacholine responsiveness, T helper type 2 (Th2) cytokines, eotaxin-1, immunoglobulin (Ig) E, IgG, and the number of inflammatory cells. In addition, EC-18-treated mice exhibited the reduction in the expression of inducible nitric oxide synthase (iNOS) in lung tissue. In the histological analysis using hematoxylin-eosin stain and periodic acid-Schiff stain, EC-18 attenuated the infiltration of inflammatory cells into the airway and reduced the level of mucus production. Our results showed that EC-18 effectively suppressed the asthmatic response induced by OVA challenge. These effects were considered to be associated with iNOS suppression. In conclusion, this study suggests that EC-18 may be a therapeutic agent for allergic asthma. Copyright © 2013 Elsevier B.V. All rights reserved.

Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

PubMed

Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

2018-04-19

Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

How does patient-provider communication influence adherence to asthma medications?

PubMed

Young, Henry N; Len-Rios, Maria E; Brown, Roger; Moreno, Megan M; Cox, Elizabeth

2017-04-01

To assess hypothesized pathways through which patient-provider communication impacts asthma medication adherence. A national sample of 452 adults with asthma reported assessments of patient-provider communication, proximal outcomes (understanding of asthma self-management, patient-provider agreement, trust in the clinician, involvement in care, motivation), and adherence to asthma medications. Structural equation modeling was used to examine hypothesized pathways. Significantly positive direct pathways were found between patient-provider communication and all proximal outcomes. Only positive indirect pathways, operating through trust and motivation, were found between patient-provider communication and medication adherence. Patient-provider communication influences many desirable proximal outcomes, but only influences adherence through trust and motivation. To promote better adherence to asthma medication regimens and, ultimately positive asthma outcomes, healthcare providers can focus on implementing communication strategies that strengthen patients' trust and increase patient motivation to use asthma medications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The neonatal methylome as a gatekeeper in the trajectory to childhood asthma.

PubMed

DeVries, Avery; Vercelli, Donata

2017-04-01

Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome. All of these studies specifically surveyed human DNA methylation and involved a genome-wide component. In combination, their results broaden our understanding of asthma pathogenesis and the role the methylome plays in this process.

Comparative Effectiveness on Cognitive Asthma Outcomes of the SHARP Academic Asthma Health Education and Counseling Program and a Non-Academic Program

PubMed Central

Kintner, Eileen; Cook, Gwendolyn; Marti, C. Nathan; Stoddard, Debbie; Gomes, Melissa; Harmon, Phyllis; Van Egeren, Laurie A.

2018-01-01

Asthma morbidity and mortality is higher among older school-age children and early adolescents than other age groups across the lifespan. NIH recommended expanding asthma education to schools and community settings to meet cognitive outcomes that have an impact on morbidity and mortality. Guided by the acceptance of asthma model, an evidence-guided, comprehensive school-based academic health education and counseling program, Staying Healthy—Asthma Responsible & Prepared™ (SHARP), was developed. The program complements existing school curricula by integrating biology, psychology, and sociology content with related spelling, math, and reading and writing assignments. Feasibility, benefits, and efficacy have been established. We compared the effectiveness of SHARP to a non-academic program, Open Airways for Schools, in improving asthma knowledge and reasoning about symptom management. A two-group, cluster-randomized, single-blinded design was used with a sample of 205 students in grades 4–5 with asthma and their caregivers. Schools were matched prior to randomization. The unit of analysis was the student. Certified elementary school teachers delivered the programs during instructional time. Data were collected from student/caregiver dyads at baseline and at 1, 12, and 24 months after the intervention. In multilevel modeling, students enrolled in the academic SHARP program demonstrated significant (p<.001) improvement in asthma knowledge and reasoning over students enrolled in the non-academic program. Knowledge advantages were retained at 24 months. Findings support delivery in schools of the SHARP academic health education program for students with asthma. PMID:26296595

Comparative Effectiveness on Cognitive Asthma Outcomes of the SHARP Academic Asthma Health Education and Counseling Program and a Non-Academic Program.

PubMed

Kintner, Eileen; Cook, Gwendolyn; Marti, C Nathan; Stoddard, Debbie; Gomes, Melissa; Harmon, Phyllis; Van Egeren, Laurie A

2015-12-01

Asthma morbidity and mortality is higher among older school-age children and early adolescents than other age groups across the lifespan. NIH recommended expanding asthma education to schools and community settings to meet cognitive outcomes that have an impact on morbidity and mortality. Guided by the acceptance of asthma model, an evidence-guided, comprehensive school-based academic health education and counseling program, Staying Healthy-Asthma Responsible & Prepared™ (SHARP), was developed. The program complements existing school curricula by integrating biology, psychology, and sociology content with related spelling, math, and reading and writing assignments. Feasibility, benefits, and efficacy have been established. We compared the effectiveness of SHARP to a non-academic program, Open Airways for Schools, in improving asthma knowledge and reasoning about symptom management. A two-group, cluster-randomized, single-blinded design was used with a sample of 205 students in grades 4-5 with asthma and their caregivers. Schools were matched prior to randomization. The unit of analysis was the student. Certified elementary school teachers delivered the programs during instructional time. Data were collected from student/caregiver dyads at baseline and at 1, 12, and 24 months after the intervention. In multilevel modeling, students enrolled in the academic SHARP program demonstrated significant (p< .001) improvement in asthma knowledge and reasoning over students enrolled in the non-academic program. Knowledge advantages were retained at 24 months. Findings support delivery in schools of the SHARP academic health education program for students with asthma. © 2015 Wiley Periodicals, Inc.

Air pollution is associated with primary health care visits for asthma in Sweden: A case-crossover design with a distributed lag non-linear model.

PubMed

Taj, Tahir; Jakobsson, Kristina; Stroh, Emilie; Oudin, Anna

2016-05-01

Air pollution can increase the symptoms of asthma and has an acute effect on the number of emergency room visits and hospital admissions because of asthma, but little is known about the effect of air pollution on the number of primary health care (PHC) visits for asthma. To investigate the association between air pollution and the number of PHC visits for asthma in Scania, southern Sweden. Data on daily PHC visits for asthma were obtained from a regional healthcare database in Scania, which covers approximately half a million people. Air pollution data from 2005 to 2010 were obtained from six urban background stations. We used a case-crossover study design and a distributed lag non-linear model in the analysis. The air pollution levels were generally within the EU air quality guidelines. The mean number of daily PHC visits for asthma was 34. The number of PHC visits increased by 5% (95% confidence interval (CI): 3.91-6.25%) with every 10µg m(-3) increase in daily mean NO2 lag (0-15), suggesting that daily air pollution levels are associated with PHC visits for asthma. Even though the air quality in Scania between 2005 and 2010 was within EU's guidelines, the number of PHC visits for asthma increased with increasing levels of air pollution. This suggests that as well as increasing hospital and emergency room visits, air pollution increases the burden on PHC due to milder symptoms of asthma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Presentations to Alberta emergency departments for asthma: a time series analysis.

PubMed

Rosychuk, Rhonda J; Youngson, Erik; Rowe, Brian H

2015-08-01

Asthma is a common chronic respiratory condition, and exacerbations may cause individuals to seek care in emergency departments (EDs). This study examines the monthly patterns of asthma presentations to EDs in Alberta, Canada. All presentations to the ED for asthma from April 1999 to March 2011 were extracted from provincial administrative health databases. Data included age, sex, and health zone of residence. Crude rates per 100,000 population were calculated. Seasonal autoregressive integrated moving average (SARIMA) time-series models were developed. There were a total of 362,430 ED presentations for asthma, and the monthly rate of presentation declined from 115.5 to 41.6 per 100,000 during the study period. Males made 50.1% of ED presentations, and adults made 52.8%. The absolute number of ED presentations for asthma declined in each of the five administrative health zones in the province, with smaller percentage decreases seen in the most urbanized zones (32.1%) than the other zones (46.9%). One SARIMA model closely predicted overall presentation rates as well as the rates of ED presentations for age and zone subgroups. These models showed strong seasonal components, with the strongest estimates occurring for the pediatric subgroup and the southernmost provincial zone. Rates of ED presentations for asthma have been declining in this province during the past decade. The reasons for this decline warrant further exploration. The SARIMA models quantified the temporal patterns and may be helpful for planning research and health care service needs. © 2015 by the Society for Academic Emergency Medicine.

Recent developments in the role of reactive oxygen species in allergic asthma

PubMed Central

Qu, Jingjing; Li, Yuanyuan; Zhong, Wen

2017-01-01

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma. PMID:28203435

Psychological characteristics of patients with asthma.

PubMed

Bulcun, Emel; Turkel, Yakup; Oguztürk, Omer; Dag, Ersel; Visal Buturak, S; Ekici, Aydanur; Ekici, Mehmet

2018-01-01

Psychological distress of patients with asthma may be reduced when they learned to live with their illness. Asthma can change the psychological and personality characteristics. We aim to investigate the psychological and personality characteristics of patients with asthma using MMPI (Minnesota Multiphasic Personality Inventory). Thirty-three adult patients with asthma (23 female and 10 male) and 20 healthy controls (14 females and 6 males) were enrolled in this study. Psychometric evaluation was made with the Turkish version of the MMPI. The patients were separated into two groups according to the duration of symptoms (recent-onset asthma < 10 years, long-standing asthma ≥10 years). Patients with asthma compared with control group had significantly higher the rate of clinical elevation on depression, hysteria, psychasthenia and social introversion. Patients with recent-onset asthma compared with long-standing asthma have significantly higher the rate of clinical elevation on depression, hysteria, psychopathic deviate, psychasthenia and social introversion. MMPI mean t score in patients with recent-onset asthma was higher than patients with long-standing asthma. MMPI mean t score in patients with asthma was negatively associated with the symptom duration in multivariate model. Patients with asthma have relatively more inactivity, anergia, guilt, pessimism, nonspecific physical complaints, irrational fears and introvert. Patients with long-standing asthma have less psychological distress, suggesting that learned to cope with his illness. © 2016 John Wiley & Sons Ltd.

Variation in Airway Responsiveness of Male C57BL/6 Mice from 5 Vendors

PubMed Central

Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

2012-01-01

Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors. PMID:23043804

Sex Differences in Asthma: A Key Role of Androgen-Signaling in Group 2 Innate Lymphoid Cells.

PubMed

Laffont, Sophie; Blanquart, Eve; Guéry, Jean-Charles

2017-01-01

Infectious diseases, autoimmune diseases, and also allergy differentially affect women and men. In general, women develop strongest immune responses and thus the proportion of infected individuals and the severity of many viral, bacterial, or parasitic infections are increased in men. However, heightened immunity in women makes them more susceptible than men to autoimmunity and allergy. While sex differences in immunity are well documented, little is known about the cellular and molecular mechanisms underlying these immunological differences, particularly in allergic asthma. Asthma is a chronic inflammation of the airways mediated by exacerbated type 2 immune responses. Sex differences have been reported in the incidence, prevalence, and severity of asthma. While during childhood, males are more susceptible to asthma than females, there is a switch at the onset of puberty as for many other allergic diseases. This decrease of asthma incidence around puberty in males suggests that hormonal mediators could play a protective role in the susceptibility to allergic responses in male. Group 2 innate lymphoid cells (ILC2s) have recently emerged as critical players in the initiation of allergic responses, but also in the resolution of parasitic infection, through their capacity to rapidly and potently produce type 2 cytokines. This review will cover the current understanding of the impact of sex-linked factors in allergic inflammation, with a particular focus on the role of sex hormones on the development and function of tissue-resident ILC2s.

Risk of asthma and allergic outcomes in the offspring in relation to maternal food consumption during pregnancy: a Finnish birth cohort study.

PubMed

Erkkola, Maijaliisa; Nwaru, Bright I; Kaila, Minna; Kronberg-Kippilä, Carina; Ilonen, Jorma; Simell, Olli; Veijola, Riitta; Knip, Mikael; Virtanen, Suvi M

2012-03-01

Epidemiological and immunological studies suggest that maternal diet during pregnancy might affect the development of allergic diseases in the offspring. The authors set out to study the effect of maternal food consumption during pregnancy on the emergence of the International Study of Asthma and Allergies in Childhood (ISAAC)-based allergic outcomes: asthma, allergic rhinitis, and wheeze by the 5 yr of age. Data from 2441 children at 5 yr of age were analyzed within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study, a population-based birth cohort study. Maternal diet was assessed with a validated food frequency questionnaire. In multiple regression models adjusted for known confounders, low maternal consumption of leafy vegetables (adjusted odds ratio [aOR]: 1.55; 95% CI: 1.21, 1.98), malaceous fruits (aOR: 1.45; 95% CI: 1.15, 1.84), and chocolate (aOR: 1.36; 95% CI: 1.09, 1.70) were positively associated with the risk of wheeze in children. High maternal consumption of fruit and berry juices was positively associated with the risk of allergic rhinitis (aOR: 1.40; 95% CI: 1.03, 1.90) in children. No associations were observed between maternal food consumption and asthma. Development of allergic diseases in preschool children may be influenced by intrauterine exposure to maternal diet. © 2012 John Wiley & Sons A/S.

Improved quality-of-life of caregivers of children with asthma through guideline-based management.

PubMed

Sheikh, Shahid I; Pitts, Judy; Ryan-Wenger, Nancy A; Kotha, Kavitha; McCoy, Karen S; Stukus, David R

2017-09-01

The quality of life (QOL) of caregivers of children with asthma may be related to children's responses to asthma management. To evaluate change in QOL over time of caregivers of children with asthma through guideline-based management. This was a 3-year prospective cohort study of children with asthma referred to our pediatric asthma center. Families completed Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), the Asthma Control Test™ (ACT), and reported the number of days/month of albuterol use and wheezing at each clinic visit. We enrolled 143 children, ages 7-17 years (mean = 10.6 ± 2.9), 56.6% male, 70.6% Caucasian. Patients were managed by the same MD (n = 65,45.5%) or APN (n = 78,54.5%) over time. The mean total PACQLQ significantly increased over the 3-year period (F = 67.418, p < .001). Total scores at the first visit were 4.8 ± 1.6, which improved to 6.1 ± 1 at the 3-month follow-up visit. This improvement was sustained at the 1, 2, and 3-year clinic visits. PACQLQ emotional function (F = 60.798, p < .001) and activity limitation (F = 41.517, p < .001) domains significantly improved as well. PACQLQ scores were significantly associated with improved ACT scores (r = .37 to .47, p < .05), fewer days/month of albuterol use (r = -.25 to -.36., p < .05), and wheezing (r = -.28 to -.33, p < .05). There were no significant differences in PACQLQ, or asthma clinical outcome measures between MD and APN providers. Use of National Asthma Education and Prevention Program (NAEPP) guidelines significantly improved QOL of caregivers of children with asthma and in asthma-related symptoms. Improvements over time were independent of type of providers.

Relationship between Intracellular Magnesium Level, Lung Function, and Level of Asthma Control in Children with Chronic Bronchial Asthma.

PubMed

Sein, Htwe Htwe; Whye Lian, Cheah; Juan Loong, Kok; Sl Ng, Josephine; Rahardjai, Andy; Sultan, Mohamed Ameenudeen

2014-01-01

This study aimed to determine the intracellular (red blood cell (RBC)) magnesium levels in children with chronic bronchial asthma and to determine the relationship between the magnesium level and peak expiratory flow rate (PEFR), type of asthma treatment, and level of asthma control. A cross-sectional study was conducted at the Paediatric Clinic, Sarawak General Hospital. A total of 100 children, aged 6-12 years with chronic bronchial asthma, were recruited according to the study criteria. Venous blood samples were obtained to measure the intracellular (RBC) magnesium level using the GBC Avanta Flame Atomic Absorption Spectrophotometer. Mean age was 8.57 (SD 1.18) years, and 63% of the participants were male. Mean duration of asthma was 62.2 (SD 32.3) months. A normal intracellular magnesium level was found in 95% of the participants, with a mean of 2.27 (SD 0.33) mmol/L. Two-thirds of the participants had a normal peak flow expiratory rate (> 80% of predicted value). About 85% were using both reliever and controller. Almost half of the participants (49%) had chronic asthma that was well-controlled. No significant relationship was found between magnesium level and age (r = -0.089, P = 0.379), gender (t = 0.64, P = 0.52), duration of asthma (r = -0.03, P = 0.74), PEFR (t = 0.41, P = 0.68), current level of asthma control (t = 0.02, P = 0.97), and current treatment (t = 0.414, P = 0.680). There was no significant intracellular magnesium deficiency in children with chronic bronchial asthma. There was no significant relationship between therapeutic medications used for treatment of children with chronic asthma and intracellular magnesium levels.

Social determinants of childhood asthma symptoms: an ecological study in urban Latin America.

PubMed

Fattore, Gisel L; Santos, Carlos A T; Barreto, Mauricio L

2014-04-01

Asthma is an important public health problem in urban Latin America. This study aimed to analyze the role of socioeconomic and environmental factors as potential determinants of asthma symptoms prevalence in children from Latin American (LA) urban centers. We selected 31 LA urban centers with complete data, and an ecological analysis was performed. According to our theoretical framework, the explanatory variables were classified in three levels: distal, intermediate, and proximate. The association between variables in the three levels and prevalence of asthma symptoms was examined by bivariate and multivariate linear regression analysis weighed by sample size. In a second stage, we fitted several linear regression models introducing sequentially the variables according to the predefined hierarchy. In the final hierarchical model Gini Index, crowding, sanitation, variation in infant mortality rates and homicide rates, explained great part of the variance in asthma prevalence between centers (R(2) = 75.0 %). We found a strong association between socioeconomic and environmental variables and prevalence of asthma symptoms in LA urban children, and according to our hierarchical framework and the results found we suggest that social inequalities (measured by the Gini Index) is a central determinant to explain high prevalence of asthma in LA.

Folate and asthma.

PubMed

Blatter, Joshua; Han, Yueh-Ying; Forno, Erick; Brehm, John; Bodnar, Lisa; Celedón, Juan C

2013-07-01

Findings from experimental studies and animal models led to the hypothesis that folic acid supplementation during pregnancy confers an increased risk of asthma. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between folate status and asthma. In industrialized nations, the prevalence of asthma was rising before widespread fortification of foodstuffs with folic acid or folate supplementation before or during pregnancy, thus suggesting that changes in folate status are an unlikely explanation for "the asthma epidemic." Consistent with this ecologic observation, evidence from human studies does not support moderate or strong effects of folate status on asthma. Given known protective effects against neural tube and cardiac defects, there is no reason to alter current recommendations for folic acid supplementation during conception or pregnancy based on findings for folate and asthma. Although we believe that there are inadequate data to exclude a weak effect of maternal folate status on asthma or asthma symptoms, such effects could be examined within the context of very large (and ongoing) birth cohort studies. At this time, there is no justification for funding new studies of folate and asthma.

Adenylyl cyclase type 9 gene polymorphisms are associated with asthma and allergy in Brazilian children.

PubMed

Teixeira, Helena M P; Alcantara-Neves, Neuza M; Barreto, Maurício; Figueiredo, Camila A; Costa, Ryan S

2017-02-01

Asthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders. The aim of this study was to investigate how polymorphisms in the ADCY9 are associated with asthma and allergic markers. The study comprised 1309 subjects from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was accomplished using the Illumina 2.5 Human Omni bead chip. Logistic regression was used to assess the association between allergy markers and ADCY9 variation in PLINK 1.07 software with adjustments for sex, age, helminth infection and ancestry markers. The ADCY9 candidate gene was associated with different phenotypes, such as asthma, specific IgE, skin prick test, and cytokine production. Among 133 markers analyzed, 29 SNPs where associated with asthma and allergic markers in silico analysis revealed the functional impact of the 6 SNPs on ADCY9 expression. It can be concluded that polymorphisms in the ADCY9 gene are significantly associated with asthma and/or allergy markers. We believe that such polymorphisms may lead to increased expression of adenylyl cyclase with a consequent increase in immunoregulatory activity. Therefore, these SNPs may offer an impact on the occurrence of these conditions in admixture population from countries such as Brazil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiomics Data Triangulation for Asthma Candidate Biomarkers and Precision Medicine.

PubMed

Pecak, Matija; Korošec, Peter; Kunej, Tanja

2018-06-01

Asthma is a common complex disorder and has been subject to intensive omics research for disease susceptibility and therapeutic innovation. Candidate biomarkers of asthma and its precision treatment demand that they stand the test of multiomics data triangulation before they can be prioritized for clinical applications. We classified the biomarkers of asthma after a search of the literature and based on whether or not a given biomarker candidate is reported in multiple omics platforms and methodologies, using PubMed and Web of Science, we identified omics studies of asthma conducted on diverse platforms using keywords, such as asthma, genomics, metabolomics, and epigenomics. We extracted data about asthma candidate biomarkers from 73 articles and developed a catalog of 190 potential asthma biomarkers (167 human, 23 animal data), comprising DNA loci, transcripts, proteins, metabolites, epimutations, and noncoding RNAs. The data were sorted according to 13 omics types: genomics, epigenomics, transcriptomics, proteomics, interactomics, metabolomics, ncRNAomics, glycomics, lipidomics, environmental omics, pharmacogenomics, phenomics, and integrative omics. Importantly, we found that 10 candidate biomarkers were apparent in at least two or more omics levels, thus promising potential for further biomarker research and development and precision medicine applications. This multiomics catalog reported herein for the first time contributes to future decision-making on prioritization of biomarkers and validation efforts for precision medicine in asthma. The findings may also facilitate meta-analyses and integrative omics studies in the future.

Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model.

PubMed

Eggo, Rosalind M; Scott, James G; Galvani, Alison P; Meyers, Lauren Ancel

2016-02-23

Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses--the "common cold" viruses--are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41-49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17-21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the "back-to-school" asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics.

Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model

PubMed Central

Scott, James G.; Galvani, Alison P.; Meyers, Lauren Ancel

2016-01-01

Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses—the “common cold” viruses—are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41–49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17–21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the “back-to-school” asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics. PMID:26858436

The Airway Microbiome in Severe Asthma: Associations with Disease Features and Severity

PubMed Central

Huang, Yvonne J.; Nariya, Snehal; Harris, Jeffrey M.; Lynch, Susan V.; Choy, David F.; Arron, Joseph R.; Boushey, Homer

2015-01-01

Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions Specific microbiota are associated with and may modulate inflammatory processes in severe asthma and related phenotypes. Airway dysbiosis in severe asthma appears to differ from that observed in milder asthma in the setting of inhaled corticosteroid use. PMID:26220531

Preventive asthma care delivery in the primary care office: missed opportunities for children with persistent asthma symptoms.

PubMed

Yee, Alison B; Fagnano, Maria; Halterman, Jill S

2013-01-01

To describe which National Heart Lung and Blood Institute preventive actions are taken for children with persistent asthma symptoms at the time of a primary care visit and determine how care delivery varies by asthma symptom severity. We approached children (2 to 12 years old) with asthma from Rochester, NY, in the waiting room at their doctor's office. Eligibility required current persistent symptoms. Caregivers were interviewed via telephone within 2 weeks after the visit regarding specific preventive care actions delivered. Bivariate and regression analyses assessed the relationship between asthma symptom severity and actions taken during the visit. We identified 171 children with persistent asthma symptoms (34% black, 64% Medicaid) from October 2009 to January 2011 at 6 pediatric offices. Overall delivery of guideline-based preventive actions during visits was low. Children with mild persistent symptoms were least likely to receive preventive care. Regression analyses controlling for demographics and visit type (acute or follow-up asthma visit vs non-asthma-related visit) confirmed that children with mild persistent asthma symptoms were less likely than those with more severe asthma symptoms to receive preventive medication action (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.14-0.84), trigger reduction discussion (OR 0.39, 95% CI 0.19-0.82), recommendation of follow-up (OR 0.40, 95% CI 0.19-0.87), and receipt of action plan (OR 0.37, 95% CI 0.16-0.86). Many children with persistent asthma symptoms do not receive recommended preventive actions during office visits, and children with mild persistent symptoms are the least likely to receive care. Efforts to improve guideline-based asthma care are needed, and children with mild persistent asthma symptoms warrant further consideration. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Association between Serum 25-Hydroxy Vitamin D Levels and the Prevalence of Adult-Onset Asthma.

PubMed

Cherrie, Mark P C; Sarran, Christophe; Osborne, Nicholas J

2018-05-29

The major circulating metabolite of vitamin D (25(OH)D) has been implicated in the pathogenesis for atopic dermatitis, asthma and other allergic diseases due to downstream immunomodulatory effects. However, a consistent association between 25(OH)D and asthma during adulthood has yet to be found in observational studies. We aimed to test the association between 25(OH)D and asthma during adulthood and hypothesised that this association would be stronger in non-atopic participants. Using information collected on the participants of the 1958 birth cohort, we developed a novel measure of atopic status using total and specific IgE values and reported history of eczema and allergic rhinitis. We designed a nested case-control analysis, stratified by atopic status, and using logistic regression models investigated the association between 25(OH)D measured at age 46 years with the prevalence of asthma and wheezy bronchitis at age 50 years, excluding participants who reported ever having asthma or wheezy bronchitis before the age of 42. In the fully adjusted models, a 10 nmol/L increase in serum 25(OH)D prevalence had a significant association with asthma (aOR 0.94; 95% CI 0.88⁻1.00). There was some evidence of an atopic dependent trend in the association between 25(OH)D levels and asthma. Further analytical work on the operationalisation of atopy status would prove useful to uncover whether there is a role for 25(OH)D and other risk factors for asthma.

Parental psychosocial stress and asthma morbidity in Puerto Rican twins.

PubMed

Lange, Nancy E; Bunyavanich, Supinda; Silberg, Judy L; Canino, Glorisa; Rosner, Bernard A; Celedón, Juan C

2011-03-01

Little is known about paternal psychosocial factors and childhood asthma. We sought to examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children. Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 year and again about their child's asthma at age 3 years. Fathers were asked about symptoms of posttraumatic stress disorder (PTSD), depression, and antisocial behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood. After multivariable adjustment, paternal PTSD symptoms, depression, and antisocial behavior were each associated with increased asthma symptoms at age 1 year (eg, odds ratio, 1.08 for each 1-point increase in PTSD score; 95% CI, 1.03-1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (odds ratio for each 1-point increase in symptoms, 1.16; 95% CI, 1.00-1.36). In an analysis combining 1- and 3-year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma. Both paternal and maternal psychosocial factors can influence asthma morbidity in young Puerto Rican children. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Effects of the phosphodiesterase type 4 inhibitor roflumilast on early and late allergic response and airway hyperresponsiveness in Aspergillus-fumigatus-sensitized mice.

PubMed

Hoymann, Heinz-Gerd; Wollin, Lutz; Muller, Meike; Korolewitz, Regina; Krug, Norbert; Braun, Armin; Beume, Rolf

2009-01-01

Inhibitory effects of roflumilast on responses characteristic of allergic asthma were investigated in a fungal asthma model in BALB/c mice. Mice were sensitized with Aspergillus antigen (Afu) and exposed to Afu or vehicle, and given roflumilast 1 or 5 mg/kg. Early airway response (EAR) and late airway hyperresponsiveness (AHR) to methacholine were measured via plethysmography. Bronchoalveolar lavage (BAL) was used to assess inflammatory cell count. In Afu-exposed mice, roflumilast dose-dependently reduced the EAR [26% at 1 mg/kg (NS) and 94% at 5 mg/kg (p < 0.01)] and AHR [46% at 1 mg/kg (NS) and 128% at 5 mg/kg (p < 0.05)]. Roflumilast 5 mg/kg reduced neutrophil, eosinophil and lymphocyte counts [87% (p < 0.01), 40% (NS) and 67% (p < 0.01), respectively] in BAL fluid versus controls. In this model, roflumilast inhibited the EAR, suppressed AHR and reduced inflammatory cell infiltration. 2009 S. Karger AG, Basel.

Diet, interleukin-17, and childhood asthma in Puerto Ricans.

PubMed

Han, Yueh-Ying; Forno, Erick; Brehm, John M; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Rivera-Soto, Winna; Campos, Hannia; Litonjua, Augusto A; Alcorn, John F; Canino, Glorisa; Celedón, Juan C

2015-10-01

Dietary patterns might influence the pathogenesis of asthma in Puerto Ricans, the ethnic group most affected by this disease in the United States. To examine the association among diet, T-helper cell type 17 cytokines, and asthma in Puerto Rican children. As part of a case-control study of 678 Puerto Rican children 6 to 14 years old in San Juan, participants completed a 75-item questionnaire on the child's food consumption in the prior week. Foods were aggregated into 7 groups: fruits, vegetables, grains, protein foods, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group, plasma T-helper cell type 17 cytokine levels, and asthma. Based on this analysis, a food score (range -2 [unhealthy diet: high consumption of dairy products and sweets, low consumption of vegetables and grains] to +2 [healthy diet: high consumption of grains and vegetables, low consumption of dairy and sweets]) was created to identify dietary patterns. High consumption of grains was associated with lower odds of asthma (adjusted odds ratio [aOR] 0.52, 95% confidence interval [CI] 0.33-0.82), whereas frequent consumption of dairy products (aOR 1.93, 95% CI 1.32-2.84) or sweets (aOR 1.82, 95% CI 1.08-2.72) was associated with higher odds of asthma. A healthier diet (each 1-point increment in food score) was associated with lower levels of interleukin-17F (β = -1.48 pg/mL, 95% CI -1.78 to -1.20) and with 36% decreased odds of asthma (aOR 0.64, 95% CI 0.53-0.77). A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with lower levels of interleulin-17F and decreased odds of childhood asthma in Puerto Ricans. Copyright © 2015. Published by Elsevier Inc.

Development and evaluation of an innovative model of inter-professional education focused on asthma medication use

PubMed Central

2014-01-01

Background Inter-professional learning has been promoted as the solution to many clinical management issues. One such issue is the correct use of asthma inhaler devices. Up to 80% of people with asthma use their inhaler device incorrectly. The implications of this are poor asthma control and quality of life. Correct inhaler technique can be taught, however these educational instructions need to be repeated if correct technique is to be maintained. It is important to maximise the opportunities to deliver this education in primary care. In light of this, it is important to explore how health care providers, in particular pharmacists and general medical practitioners, can work together in delivering inhaler technique education to patients, over time. Therefore, there is a need to develop and evaluate effective inter-professional education, which will address the need to educate patients in the correct use of their inhalers as well as equip health care professionals with skills to engage in collaborative relationships with each other. Methods This mixed methods study involves the development and evaluation of three modules of continuing education, Model 1, Model 2 and Model 3. A fourth group, Model 4, acting as a control. Model 1 consists of face-to-face continuing professional education on asthma inhaler technique, aimed at pharmacists, general medical practitioners and their practice nurses. Model 2 is an electronic online continuing education module based on Model 1 principles. Model 3 is also based on asthma inhaler technique education but employs a learning intervention targeting health care professional relationships and is based on sociocultural theory. This study took the form of a parallel group, repeated measure design. Following the completion of continuing professional education, health care professionals recruited people with asthma and followed them up for 6 months. During this period, inhaler device technique training was delivered and data on patient inhaler technique, clinical and humanistic outcomes were collected. Outcomes related to professional collaborative relationships were also measured. Discussion Challenges presented included the requirement of significant financial resources for development of study materials and limited availability of validated tools to measure health care professional collaboration over time. PMID:24708800

Development and evaluation of an innovative model of inter-professional education focused on asthma medication use.

PubMed

Bosnic-Anticevich, Sinthia Z; Stuart, Meg; Mackson, Judith; Cvetkovski, Biljana; Sainsbury, Erica; Armour, Carol; Mavritsakis, Sofia; Mendrela, Gosia; Travers-Mason, Pippa; Williamson, Margaret

2014-04-07

Inter-professional learning has been promoted as the solution to many clinical management issues. One such issue is the correct use of asthma inhaler devices. Up to 80% of people with asthma use their inhaler device incorrectly. The implications of this are poor asthma control and quality of life. Correct inhaler technique can be taught, however these educational instructions need to be repeated if correct technique is to be maintained. It is important to maximise the opportunities to deliver this education in primary care. In light of this, it is important to explore how health care providers, in particular pharmacists and general medical practitioners, can work together in delivering inhaler technique education to patients, over time. Therefore, there is a need to develop and evaluate effective inter-professional education, which will address the need to educate patients in the correct use of their inhalers as well as equip health care professionals with skills to engage in collaborative relationships with each other. This mixed methods study involves the development and evaluation of three modules of continuing education, Model 1, Model 2 and Model 3. A fourth group, Model 4, acting as a control.Model 1 consists of face-to-face continuing professional education on asthma inhaler technique, aimed at pharmacists, general medical practitioners and their practice nurses.Model 2 is an electronic online continuing education module based on Model 1 principles.Model 3 is also based on asthma inhaler technique education but employs a learning intervention targeting health care professional relationships and is based on sociocultural theory.This study took the form of a parallel group, repeated measure design. Following the completion of continuing professional education, health care professionals recruited people with asthma and followed them up for 6 months. During this period, inhaler device technique training was delivered and data on patient inhaler technique, clinical and humanistic outcomes were collected. Outcomes related to professional collaborative relationships were also measured. Challenges presented included the requirement of significant financial resources for development of study materials and limited availability of validated tools to measure health care professional collaboration over time.

Air pollution and asthma control in the Epidemiological study on the Genetics and Environment of Asthma

PubMed Central

Jacquemin, Bénédicte; Kauffmann, Francine; Pin, Isabelle; Le Moual, Nicole; Bousquet, Jean; Gormand, Frédéric; Just, Jocelyne; Nadif, Rachel; Pison, Christophe; Vervloet, Daniel; Künzli, Nino; Siroux, Valérie

2012-01-01

Background The associations between exposure to air pollution and asthma control are not well known. The objective is to assess the association between long term exposure to NO2, O3 and PM10 and asthma control in the EGEA2 study (2003–2007). Methods Modeled outdoor NO2, O3 and PM10 estimates were linked to each residential address using the 4-km grid air pollutant surface developed by the French Institute of Environment for 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006–2009 GINA guidelines. Multinomial and ordinal logistic regressions were conducted adjusted on sex, age, BMI, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control (symptoms, exacerbations and lung function) was assessed. Odds Ratios (ORs) are reported per Inter Quartile Range (IQR). Results Median concentrations (μg.m−3) were 32(IQR 25–38) for NO2 (n=465), 46(41–52) for O3 and 21(18–21) for PM10 (n=481). In total, 44%, 29% and 27% had controlled, partly-controlled and uncontrolled asthma. The ordinal ORs for O3 and PM10 with asthma control were 1.69(95%CI 1.22–2.34) and 1.35(95%CI 1.13–1.64) respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, atopy, season of examination or BMI. Both pollutants were associated with each of the three main domains of control. Conclusions The results suggest that long-term exposure to PM10 and O3 is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function. Abstract Word count: 250 Key words: air pollution, asthma, asthma control PMID:21690606

Air pollution and asthma control in the Epidemiological study on the Genetics and Environment of Asthma.

PubMed

Jacquemin, Bénédicte; Kauffmann, Francine; Pin, Isabelle; Le Moual, Nicole; Bousquet, Jean; Gormand, Frédéric; Just, Jocelyne; Nadif, Rachel; Pison, Christophe; Vervloet, Daniel; Künzli, Nino; Siroux, Valérie

2012-09-01

The associations between exposure to air pollution and asthma control are not well known. The objective of this study was to assess the association between long-term exposure to NO(2), O(3) and PM(10) and asthma control in the follow-up of the Epidemiological study on the Genetics and Environment of Asthma (EGEA2) (2003-2007). Modelled outdoor NO(2), O(3) and PM(10) estimates were linked to each residential address using the 4 km grid air pollutant surface developed by the French Institute of Environment in 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006-2009 Global Initiative for Asthma guidelines. Multinomial and ordinal logistic regressions were conducted adjusted for sex, age, body mass index, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control (symptoms, exacerbations and lung function) was assessed. ORs are reported per IQR. Median concentrations (in micrograms per cubic metre) were 32 (IQR 25-38) for NO(2) (n=465), 46 (41-52) for O(3) and 21 (18-21) for PM(10) (n=481). In total, 44%, 29% and 27% had controlled, partly controlled and uncontrolled asthma, respectively. The ordinal ORs for O(3) and PM(10) with asthma control were 1.69 (95% CI 1.22 to 2.34) and 1.35 (95% CI 1.13 to 1.64), respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, atopy, season of examination or body mass index. Both pollutants were associated with each of the three main domains of control. The results suggest that long-term exposure to PM(10) and O(3) is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function.

The association between asthma control, health care costs, and quality of life in France and Spain

PubMed Central

2013-01-01

Background Current asthma management guidelines are based on the level of asthma control. The impact of asthma control on health care resources and quality of life (QoL) is insufficiently studied. EUCOAST study was designed to describe costs and QoL in adult patients according to level of asthma control in France and Spain. Methods An observational cost of illness study was conducted simultaneously in both countries among patients age greater or equal to 18 with a diagnosis of asthma for at least 12 months. Patients were recruited prospectively by GPs in 2010 in four waves to avoid a seasonal bias. Health care resources utilization of the three months before the inclusion was collected through physician questionnaires. Asthma control was evaluated using 2009 GINA criteria over a 3-month period. QoL was assessed using EQ-5D-3L®. Results 2,671 patients (France: 1,154; Spain: 1,517) were enrolled. Asthma was controlled in 40.6% [95% CI: 37.7% - 43.4%] and 29.9% [95% CI: 27.6% - 32.3%] of French and Spanish patients respectively. For all types of costs, the percentage of patients using health care resources varied significantly according to the level of asthma control. The average cost (euros/3-months/patient) of controlled asthma was €85.4 (SD: 153.5) in France compared with €314.0 (SD: 2,160.4) for partially controlled asthma and €537.9 (SD: 2,355.7) for uncontrolled asthma (p<0.0001). In Spain, the corresponding figures were €152.6 (SD: 162.1), €241.2 (SD: 266.8), and €556.8 (SD: 762.4). EQ-5D-3L® score was higher (p<0.0001) in patients with controlled asthma compared to partially controlled and uncontrolled asthma in both countries (respectively 0.88; 0.78; 0.63 in France and 0.89; 0.82; 0.69 in Spain). Conclusions In both countries, patients presenting with uncontrolled asthma had a significantly higher asthma costs and lower scores of Qol compared to the others. PMID:23517484

Metabolic syndrome and asthma.

PubMed

Garmendia, Jenny V; Moreno, Dolores; Garcia, Alexis H; De Sanctis, Juan B

2014-01-01

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen.

PubMed

Gabriele, Lucia; Schiavoni, Giovanna; Mattei, Fabrizio; Sanchez, Massimo; Sestili, Paola; Butteroni, Cinzia; Businaro, Rita; Mirchandani, Ananda; Niedbala, Wanda; Liew, Foo Y; Afferni, Claudia

2013-09-01

Cypress pollen causes respiratory syndromes with different grades of severity, including asthma. IL-33, its receptor ST2, and dendritic cells (DCs) have been implicated in human respiratory allergy. We sought to define a new mouse model of allergy to cypress pollen that recapitulates clinical parameters in allergic patients and to evaluate the implications of DCs and the IL-33/ST2 pathway in this pathology. BALB/c mice, either wild-type or ST2 deficient (ST2(-/-)), were sensitized and challenged with the Cupressus arizonica major allergen nCup a 1. Local and systemic allergic responses were evaluated. Pulmonary cells were characterized by means of flow cytometry. DCs were stimulated with nCup a 1 and tested for their biological response to IL-33 in coculture assays. nCup a 1 causes a respiratory syndrome closely resembling human pollinosis in BALB/c mice. nCup a 1-treated mice exhibit the hallmarks of allergic pathology associated with pulmonary infiltration of eosinophils, T cells, and DCs and a dominant TH2-type immune response. IL-33 levels were increased in lungs and sera of nCup a 1-treated mice and in subjects with cypress allergy. The allergen-specific reaction was markedly reduced in ST2(-/-) mice, which showed fewer infiltrating eosinophils, T cells, and DCs in the lungs. Finally, stimulation of DCs with nCup a 1 resulted in ST2 upregulation that endowed DCs with increased ability to respond to IL-33-mediated differentiation of IL-5- and IL-13-producing CD4 T cells. Our findings define a novel preclinical model of allergy to cypress pollen and provide the first evidence of a functionally relevant linkage between pollen allergens and TH2-polarizing activity by DCs through IL-33/ST2. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

PubMed

Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

2015-01-01

CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model

PubMed Central

Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

2015-01-01

CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical. PMID:25751125

Centenarian Rates and Life Expectancy Related to the Death Rates of Multiple Sclerosis, Asthma, and Rheumatoid Arthritis and the Incidence of Type 1 Diabetes in Children.

PubMed

Lens-Pechakova, Lilia S

2016-02-01

The autoimmune diseases are among the 10 leading causes of death for women and the number two cause of chronic illness in America as well as a predisposing factor for cardiovascular diseases and cancer. Patients of some autoimmune diseases have shown a shorter life span and are a model of accelerated immunosenescence. Conversely, centenarians are used as a model of successful aging and have shown several immune parameters that are better preserved and lower levels of autoantibodies. The study reported here focused on clarifying the connection between longevity and some autoimmune and allergic diseases in 29 developed Organisation for Economic Co-operation and Development (OECD) countries, because multidisciplinary analyses of the accelerated or delayed aging data could show a distinct relationship pattern, help to identify common factors, and determine new important factors that contribute to longevity and healthy aging. The relationships between the mortality rates data of multiple sclerosis (MS), rheumatoid arthritis (RA), asthma, the incidence of type 1 diabetes (T1D) from one side and centenarian rates (two sets) as well as life expectancy data from the other side were assessed using regression models and Pearson correlation coefficients. The data obtained correspond to an inverse linear correlation with different degrees of linearity. This is the first observation of a clear tendency of diminishing centenarian rates or life expectancy in countries having higher death rates of asthma, MS, and RA and a higher incidence of T1D in children. The conclusion is that most probably there are common mechanistic pathways and factors affecting the above diseases and at the same time but in the opposite direction the processes of longevity. Further study, comparing genetic data, mechanistic pathways, and other factors connected to autoimmune diseases with those of longevity could clarify the processes involved, so as to promote longevity and limit the expansion of those diseases in the younger and older population.

Effectiveness of a School-based Academic Asthma Health Education and Counseling Program on Fostering Acceptance of Asthma in Older School-age Students with Asthma

PubMed Central

Kintner, Eileen K.; Cook, Gwendolyn; Marti, C. Nathan; Gomes, Melissa; Meeder, Linda; Van Egeren, Laurie A.

2014-01-01

Purpose The purpose was to evaluate the effectiveness of the academic asthma education and counseling SHARP program on fostering psychosocial acceptance of asthma. Design and Methods This was a phase III, two-group, cluster randomized, single-blinded, longitudinal study. Students from grades 4 and 5 (N = 205) with asthma and their caregivers completed surveys at pre-intervention and at 1, 12, and 24 months post-intervention. Analysis involved multilevel modeling. Results All students demonstrated significant improvement in aspects of acceptance; students in SHARP demonstrated significant improvement in openness to sharing and connectedness with teachers over students in the control condition. Practice Implications The SHARP program offers a well-tested, effective program for psychosocial acceptance of asthma, which is welcomed by schools. PMID:25443593

Association Between 17q12-21 Variants and Asthma in Japanese Women: rs11650680 Polymorphism as Potential Genetic Marker for Asthma

PubMed Central

Tanaka, Keiko; Arakawa, Masashi

2014-01-01

Epidemiological evidence on the relationship between single-nucleotide polymorphisms (SNPs) rs7216389 and rs11650680 on chromosome 17q12-21 and asthma is inconsistent. We examined this issue in young adult Japanese women. Case subjects were 202 women who had been diagnosed with asthma by a doctor, while 1290 women without doctor-diagnosed asthma served as control subjects. Adjustments were made for age and the presence of older siblings. There were no significant associations between SNP rs7216389 and asthma. Compared with the CC genotype of SNP rs11650680, the CT genotype, but not the TT genotype, was significantly inversely associated with asthma: the adjusted odds ratio for the CT genotype was 0.67 (95% confidence interval: 0.46–0.96). This inverse relationship was significant in women with late-onset asthma, but not in those with early-onset asthma. Under the dominant model, a significant inverse association was found between rs11650680 and asthma in women without older siblings, but not in those with older siblings; the interaction, however, was not significant. This is the first study to show that the CT genotype of SNP rs11650680 was significantly inversely associated with asthma, especially adult-onset asthma. We could not find evidence for interactions between rs11650680 and older siblings affecting asthma. PMID:24735179

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

NASA Astrophysics Data System (ADS)

Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

2016-06-01

We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

The effects of pulmonary diseases on histologic types of lung cancer in both sexes: a population-based study in Taiwan.

PubMed

Huang, Jing-Yang; Jian, Zhi-Hong; Nfor, Oswald Ndi; Ku, Wen-Yuan; Ko, Pei-Chieh; Lung, Chia-Chi; Ho, Chien-Chang; Pan, Hui-Hsien; Huang, Chieh-Ying; Liang, Yu-Chiu; Liaw, Yung-Po

2015-11-02

The associations between pulmonary diseases (asthma, chronic obstructive pulmonary disease [COPD], and tuberculosis [TB]) and subsequent lung cancer risk have been reported, but few studies have investigated the association with different histologic types of lung cancer. Patients newly diagnosed with lung cancer from 2004 to 2008 were identified from the National Health Insurance Research Database in Taiwan. Histologic types of lung cancer were further confirmed using the Taiwan Cancer Registry Database. Cox proportional hazards regression was used to calculate the hazard ratio (HR) of asthma, COPD, and TB and to estimate the risk of specific types of lung cancer. During the study period, 32,759 cases of lung cancer were identified from 15,219,024 insurants aged 20 years and older. In men and women, the adjusted HR estimates of squamous cell carcinoma were respectively 1.37 (95 % confidence interval [CI], 1.21-1.54) and 2.10 (95 % CI, 1.36-3.23) for TB, 1.52 (95 % CI, 1.42-1.64) and 1.50 (95 % CI, 1.21-1.85) for asthma, and 1.66 (95 % CI, 1.56-1.76) and 1.44 (95 % CI, 1.19-1.74) for COPD. Similarly, the adjusted HR estimates of adenocarcinoma were respectively 1.33 (95 % CI, 1.19-1.50) and 1.86 (95 % CI, 1.57-2.19) for TB, 1.13 (95 % CI, 1.05-1.21) and 1.18 (95 % CI, 1.09-1.28) for asthma, and 1.50 (95 % CI, 1.42-1.59) and 1.33 (95 % CI, 1.25-1.42) for COPD. The HRs of small cell carcinoma were respectively 1.24 (95 % CI, 1.01-1.52) and 2.23 (95 % CI, 1.17-4.25) for TB, 1.51 (95 % CI, 1.35-1.69) and 1.63 (95 % CI, 1.16-2.27) for asthma, and 1.39 (95 % CI, 1.26-1.53) and 1.78 (95 % CI, 1.33-2.39) for COPD. Asthma, COPD, and TB were associated with an increased risk of all major subtypes of lung cancer. The risk was the highest among women with TB.

Policy and System Change and Community Coalitions: Outcomes From Allies Against Asthma

PubMed Central

Lachance, Laurie; Doctor, Linda Jo; Gilmore, Lisa; Kelly, Cindy; Krieger, James; Lara, Marielena; Meurer, John; Friedman Milanovich, Amy; Nicholas, Elisa; Rosenthal, Michael; Stoll, Shelley C.; Wilkin, Margaret

2010-01-01

Objectives. We assessed policy and system changes and health outcomes produced by the Allies Against Asthma program, a 5-year collaborative effort by 7 community coalitions to address childhood asthma. We also explored associations between community engagement and outcomes. Methods. We interviewed a sample of 1477 parents of children with asthma in coalition target areas and comparison areas at baseline and 1 year to assess quality-of-life and symptom changes. An extensive tracking and documentation procedure and a survey of 284 participating individuals and organizations were used to ascertain policy and system changes and community engagement levels. Results. A total of 89 policy and system changes were achieved, ranging from changes in interinstitutional and intrainstitutional practices to statewide legislation. Allies children experienced fewer daytime (P = .008) and nighttime (P = .004) asthma symptoms than comparison children. In addition, Allies parents felt less helpless, frightened, and angry (P = .01) about their child's asthma. Type of community engagement was associated with number of policy and system changes. Conclusions. Community coalitions can successfully achieve asthma policy and system changes and improve health outcomes. Increased core and ongoing community stakeholder participation rather than a higher overall number of participants was associated with more change. PMID:20299641

Asthma and the environment.

PubMed

Rosenstreich, David L; Moday, Heather J; Hudes, Golda

2003-01-01

Asthma is an environmental disease that is caused in most patients by the continual inhalation of allergens. There are many different types of indoor and outdoor allergens and the exact sensitivities to these vary between people. Thorough and continuous allergen removal is the safest and most cost-effective means of treating asthma and should be undertaken in every patient. Environmental control should be done by every asthmatic regardless of perceived or actual allergic sensitivity, both because allergy testing has a significant false-negative rate because prolonged exposure to allergen will produce new sensitivities.

Protection from experimental asthma by an endogenous bronchodilator.

PubMed

Que, Loretta G; Liu, Limin; Yan, Yun; Whitehead, Gregory S; Gavett, Stephen H; Schwartz, David A; Stamler, Jonathan S

2005-06-10

Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.

Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

PubMed

Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

2011-08-01

Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. Copyright © 2011 Elsevier B.V. All rights reserved.

Parental psychosocial stress and asthma morbidity in Puerto Rican twins

PubMed Central

Lange, Nancy E.; Bunyavanich, Supinda; Silberg, Judy L.; Canino, Glorisa; Rosner, Bernard A.; Celedón, Juan C.

2010-01-01

Background Little is known about paternal psychosocial factors and childhood asthma. Objective To examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children. Methods Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 and again about their child’s asthma at age 3. Fathers were asked about symptoms of post-traumatic stress disorder (PTSD), depression, and anti-social behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood. Results After multivariable adjustment, paternal PTSD symptoms, depression, and anti-social behavior were each associated with increased asthma symptoms at age 1 (e.g., OR =1.08 for each 1-point increase in PTSD score, 95% CI=1.03–1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (OR for each 1-point increase in symptoms=1.16, 95% CI=1.00–1.36]). In an analysis combining 1 and 3 year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma. Conclusions Both paternal and maternal psychosocial factors may influence asthma morbidity in young Puerto Rican children. PMID:21194742

Positive exercise test and obstructive spirometry in young male conscripts associated with persistent asthma 20 years later.

PubMed

Lindström, Irmeli; Suojalehto, Hille; Lindholm, Harri; Pallasaho, Paula; Luukkonen, Ritva; Karjalainen, Jouko; Lauerma, Antti; Karjalainen, Antti

2012-12-01

Asthma often begins in childhood or early adulthood and is a common disease among conscripts. The identification of long-term predictive factors for persistent asthma may lead to improved treatment opportunities and better disease control. Our aim was to study the prognostic factors of the severity of asthma among 40-year-old male conscripts whose asthma began in youth. We studied 119 conscripts who were referred to the Central Military Hospital during 1987-1990 due to asthma and who attended a follow-up visit approximately 20 years later. Asthma severity was evaluated during military service according to the medical records, and 20 years later during a follow-up visit using Global Initiative for Asthma guidelines. We used the results of lung function and allergy tests at baseline as predictors of current persistent asthma. Compared with baseline, asthma was less severe at follow-up: 11.8% of subjects were in remission, 42.0% had intermittent asthma, 10.9% had mild persistent asthma, and 35.3% had moderate/severe persistent asthma (p < .001). In multivariate models, a positive exercise test at baseline yielded an odds ratio (OR) of 3.2 (95% CI 1.0-9.8, p = .046), a decreased FEV1/FVC % predicted an OR of 4.0 (95% CI 1.7-9.3, p = .002), and a decreased FEF50% % predicted an OR of 2.8 (95% CI 1.3-6.4, p = .012) for current persistent asthma. About half of the men had persistent asthma at the 20-year follow-up. Positive exercise tests and obstructive spirometry results were related to the persistence of asthma and may be useful long-term prognostic factors for asthma severity.

High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations: A prospective cohort study.

PubMed

Bjerregaard, A; Laing, I A; Backer, V; Sverrild, A; Khoo, S-K; Chidlow, G; Sikazwe, C; Smith, D W; Le Souëf, P; Porsbjerg, C

2017-08-01

The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033). Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies. © 2017 John Wiley & Sons Ltd.

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

PubMed Central

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-01-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

PubMed

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-08-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

Pulmonary eosinophilia associated with montelukast

PubMed Central

Franco, J.; Artes, M. J.

1999-01-01

Antileukotriene drugs are new therapeutic agents that have recently been approved for the treatment of asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have been reported to be associated with zafirlukast, a cysteinyl leukotriene type 1 receptor antagonist. So far no other leukotriene modifier has been associated with the syndrome. The case history is presented of a man with allergic rhinitis and asthma who had received intermittent pulse therapy with oral corticosteroids. Pulmonary eosinophilia developed while he was receiving treatment with montelukast, a chemically distinct cysteinyl leukotriene type 1 receptor antagonist. After discontinuation of montelukast therapy and administration of systemic corticosteroids the patient's symptoms reversed rapidly and there was prompt resolution of the pulmonary infiltrates. We believe that cysteinyl leukotriene type 1 receptor antagonists are safe and effective drugs for most patients with asthma but caution is needed for those with more severe disease who require systemic corticosteroids, especially if they show characteristics of the atypical allergic diathesis seen in the prodromal phase of Churg-Strauss syndrome.

 PMID:10335014

Sustainable Benefits of a Community Hospital-Based Paediatric Asthma Clinic.

PubMed

Kuzik, Brian A; Chen, Chee P; Hansen, Miriam J; Montgomery, Paula L

2017-01-01

In 2011, we reported that our paediatric asthma clinic (PAC) appeared to significantly reduce the burden of paediatric asthma in our community. Supported by these results, the PAC underwent a gradual threefold expansion while maintaining the same model of care. We now report on the outcome of that expansion and demonstrate that our PAC continues to significantly reduce the burden of paediatric asthma in our community. As previously, newly enrolled PAC patients continue to show a 12-month reduction in asthma-related emergency department (ED) visits and admissions exceeding 60% and 80%, respectively. This consistent short-term benefit, coupled with clinic expansion, has contributed to a significant improvement in our rate of paediatric asthma-related ED visits or hospitalizations when compared to other Ontario hospitals.

Accessible Modelling of Complexity in Health (AMoCH) and associated data flows: asthma as an exemplar.

PubMed

Liyanage, Harshana; Luzi, Daniela; De Lusignan, Simon; Pecoraro, Fabrizio; McNulty, Richard; Tamburis, Oscar; Krause, Paul; Rigby, Michael; Blair, Mitch

2016-04-18

Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1) to describe the data and information flows in clinical practice to information scientists, (2) to compare health systems and care pathways, (3) to understand how clinical cases are recorded in record systems and (4) to model health care business models.Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain.Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar.Method The four steps in our process are:1. Drawing a rich picture, following Checkland's soft systems methodology;2. Constructing data flow diagrams (DFDs);3. Creating Unified Modelling Language (UML) use case diagrams to describe the interaction of the key actors with the system;4. Activity diagrams, either UML activity diagram or business process modelling notation diagram.Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding.Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of new or confirmed diagnosis.

RELATIVE POTENCY OF MOLD AND HOUSE DUST MITE EXTRACTS IN INDUCING ALLERGIC RESPONSES IN BALB/C MICE

EPA Science Inventory

Rationale: Mold has been associated with the exacerbation of allergic asthma. However, its role in induction of allergic asthma is not clear. Using a previously developed mouse model for allergic asthma, we compared potencies of two fungal extracts (Metarhizium anisop...