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Sample records for allergic asthma methods

  1. Genetics Home Reference: allergic asthma

    MedlinePlus

    ... Understand Genetics Home Health Conditions allergic asthma allergic asthma Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Asthma is a breathing disorder characterized by inflammation of ...

  2. The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods

    PubMed Central

    2014-01-01

    Background This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. Methods/Design The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim. The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre

  3. Eosinophilic Inflammation in Allergic Asthma

    PubMed Central

    Possa, Samantha S.; Leick, Edna A.; Prado, Carla M.; Martins, Mílton A.; Tibério, Iolanda F. L. C.

    2013-01-01

    Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma. PMID:23616768

  4. Asthma and Respiratory Allergic Disease

    EPA Science Inventory

    The pathogenesis of non-communicable diseases such as allergy is complex and poorly understood. The causes of chronic allergic diseases including asthma involve to a large extent, immunomodulation of the adaptive and particularly the innate immune systems and are markedly influen...

  5. [Epigenetics in allergic diseases and asthma].

    PubMed

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. PMID:27055949

  6. Current and future biomarkers in allergic asthma.

    PubMed

    Zissler, U M; Esser-von Bieren, J; Jakwerth, C A; Chaker, A M; Schmidt-Weber, C B

    2016-04-01

    Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-type-specific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value. PMID:26706728

  7. The united allergic airway: Connections between allergic rhinitis, asthma, and chronic sinusitis

    PubMed Central

    Miller, Michaela D.; Simon, Ronald A.

    2012-01-01

    Background: The united allergic airway is a theory that connects allergic rhinitis (AR), chronic rhinosinusitis, and asthma, in which seemingly disparate diseases, instead of being thought of separately, are instead viewed as arising from a common atopic entity. Objective: This article describes patients with such diseases; explores ideas suggesting a unified pathogenesis; elucidates the various treatment modalities available, emphasizing nasal corticosteroids and antihistamines; and provides an update of the literature. Methods: A literature review was conducted. Conclusion: The aggregation of research suggests that AR, asthma, and chronic rhinosinusitis are linked by the united allergic airway, a notion that encompasses commonalities in pathophysiology, epidemiology, and treatment. PMID:22643942

  8. Asthma, Allergic Rhinitis, and Sleep Problems in Urban Children

    PubMed Central

    Koinis-Mitchell, Daphne; Kopel, Sheryl J.; Boergers, Julie; Ramos, Kara; LeBourgeois, Monique; McQuaid, Elizabeth L.; Esteban, Cynthia A.; Seifer, Ronald; Fritz, Gregory K.; Klein, Robert B.

    2015-01-01

    Objectives: In this study, we examine the association of asthma (asthma symptoms, asthma control, lung function) and sleep problems in a group of urban children. The role of allergic rhinitis (AR), a comorbid condition of asthma, on children's sleep problems is also examined. Finally, we investigate whether sleep hygiene moderates the association between asthma and sleep problems, and whether there are differences in these associations based on ethnic background. Methods: Non-Latino White, Latino, and African American urban children with asthma (n = 195) ages 7–9 (47% female) and their primary caregivers participated in a baseline visit involving interview-based questionnaires on demographics, asthma and rhinitis control, and caregiver report of children's sleep problems and sleep hygiene. Children and their caregivers participated in a clinical evaluation of asthma and AR, followed by a month monitoring period of children's asthma using objective and subjective methods. Results: Total sleep problem scores were higher in children of the sample who were from African American and Latino backgrounds, compared to non-Latino white children. Poor asthma control was predictive of higher levels of sleep problems in the entire sample. Poorer AR control also was related to more sleep problems, over and above children's asthma in the sample. This association was more robust in non-Latino white children. Poor sleep hygiene heightened the association between poor asthma control and sleep problems in the entire sample and in African American children. Conclusions: Multidisciplinary interventions integrating the co-management of asthma, AR, and the effects of both illnesses on children's sleep, need to be developed and tailored to children and their families' ethnic background. Citation: Koinis-Mitchell D, Kopel SJ, Boergers J, Ramos K, LeBourgeois M, McQuaid EL, Esteban CA, Seifer R, Fritz GK, Klein RB. Asthma, allergic rhinitis, and sleep problems in urban children. J Clin

  9. Epigenetic regulation of asthma and allergic disease

    PubMed Central

    2014-01-01

    Epigenetics of asthma and allergic disease is a field that has expanded greatly in the last decade. Previously thought only in terms of cell differentiation, it is now evident the epigenetics regulate many processes. With T cell activation, commitment toward an allergic phenotype is tightly regulated by DNA methylation and histone modifications at the Th2 locus control region. When normal epigenetic control is disturbed, either experimentally or by environmental exposures, Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to daughter cells with cell replication but they can also be inherited through generations. In animal models, with constant environmental pressure, epigenetically determined phenotypes are amplified through generations and can last up to 2 generations after the environment is back to normal. In this review on the epigenetic regulation of asthma and allergic diseases we review basic epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then cover the transgenerational inheritance model of epigenetic traits and discuss how this could relate the amplification of asthma and allergic disease prevalence and severity through the last decades. Finally, we discuss recent epigenetic association studies for allergic phenotypes and related environmental risk factors as well as potential underlying mechanisms for these associations. PMID:24932182

  10. Fetal growth and risk of childhood asthma and allergic disease

    PubMed Central

    Tedner, S G; Örtqvist, A K; Almqvist, C

    2012-01-01

    Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

  11. [The gene or genes of allergic asthma?].

    PubMed

    Demoly, P; Bousquet, J; Godard, P; Michel, F B

    1993-05-15

    Asthma is a multifactorial disease in which the hereditary component has been demonstrated by familial and identical twin studies. Allergy is important in the aetiology of asthma and is characterized by a hyperreaction to allergens triggering predominantly the immunoglobulines E. The levels of these antibodies are found to be elevated even in non allergic asthmatics. The majority of genetic research in this area is focused on either the genes of the specific immune response or that of the non allergic response. These are the genes of the class II MHC, and the APY gene on chromosome 11q respectively. The modern techniques of molecular genetics and in particular those of inverse genetics have recently contributed to a more comprehensive understanding of this disease. PMID:8316547

  12. Environmental risk factors and allergic bronchial asthma.

    PubMed

    D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S

    2005-09-01

    The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic

  13. Allergic rhinitis and asthma in the athlete.

    PubMed

    Randolph, Christopher C

    2006-01-01

    The pathogenesis, epidemiology, presentation, diagnosis, and management of allergic rhinitis and asthma in the recreational and elite athlete are discussed in this study. There is an increased prevalence of allergic rhinitis and asthma in the elite athlete related to the enhanced ventilation with entrainment of inhalants including allergens as well as irritants such as pollutants in the urban athlete, chlorine in the swimmer, and cold air in the hockey player in the training environment. The history as well as objective exercise challenge and skin-prick tests to inhalants or in vitro allergen testing are essential in conjunction with a comprehensive physical exam to diagnosis of allergic rhinitis and/or asthma in the athlete. This is particularly necessary for the elite or competitive athlete who often has poor insight into the symptoms. Management is with appropriate inhaled steroids and/or leukotriene antagonists for the upper (nasal) and lower airways with avoidance of inhaled allergens and/or appropriate immunotherapy where relevant. The optimal management of the athlete results in minimum medication with minimum adverse side effects and optimal outcome. Proper adherence to antidoping regulations and application for use exemption in competitive athletes is recommended. The athlete should be encouraged to pursue the selected sports activity without limitations. PMID:16724626

  14. A dual role for complement in allergic asthma.

    PubMed

    Köhl, Jörg; Wills-Karp, Marsha

    2007-06-01

    Complement is an ancient danger-sensor system of innate immunity, providing first-line defence against pathogens. Concordant with its pro-inflammatory properties, complement contributes to airway inflammation, hyperresponsiveness and mucus production during the effector phase of allergic asthma. In contrast to these pro-allergic properties, complement can also protect from the development of the maladaptive Th2-biased immune response that drives airway inflammation and hyperreactivity in allergic asthma. As such, selective targeting of pro-allergic complement pathways appears an attractive therapeutic option in allergic asthma. PMID:17475559

  15. Allergic asthma biomarkers using systems approaches

    PubMed Central

    Sircar, Gaurab; Saha, Bodhisattwa; Bhattacharya, Swati G.; Saha, Sudipto

    2013-01-01

    Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS) platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery. PMID:24409194

  16. Allergic and nonallergic asthma in children: are they distinct phenotypes?

    PubMed

    Mahdaviani, Seyed Alireza; Mohajerani, Seyed Amir; Fakhri, Mohammad; Ebrahimi, Mazaher; Bashardoost, Bahram; Razavi, Seyed Jafar; Toolabi, Masoumeh; Tajik, Ali; Khalilzadeh, Soheila; Masjedi, Mohamad Reza

    2014-10-01

    The aim of current study is to describe clinical similarities and differences between atopic and non-atopic asthma in children. In a cross-sectional study, 95 asthmatic children (75 allergics and 20 nonallergics) were included in the study. Demographic, clinical, and familial history were compared between two groups. There was no significant differences between variables like sex, age of onset (p=0.75), severity (p=0.70), and family history among the two groups (p=0.42). Patients with allergic asthma were significantly older than those with non- allergic asthma (11.28 ± 3.19 and 9.75 ± 2.35 years, respectively, p=0.02). The controversy lingers over the presence of a completely distinct phenotype of non-atopic asthma in children. Our study suggested that phenotypes of allergic and non-allergic asthma in children were not entirely distinct. PMID:25150079

  17. Do mouse models of allergic asthma mimic clinical disease?

    PubMed

    Epstein, Michelle M

    2004-01-01

    Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing (1). the factors influencing the pathophysiological responses during

  18. DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES TO PENICILLIUM CHRYSOGENUM

    EPA Science Inventory

    ABSTRACT
    Indoor mold has been associated with development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and its viable conidia can induce allergic responses in a mouse model of allergic penicilliosis. The hypothesis o...

  19. Allergic reaction to mint leads to asthma.

    PubMed

    Szema, Anthony M; Barnett, Tisha

    2011-01-01

    Respiratory and cutaneous adverse reactions to mint can result from several different mechanisms including IgE-mediated hypersensitivity, delayed-type hypersensitivity (contact dermatitis), and nonimmunologic histamine release. Reactions to cross-reacting plants of the Labiatae family, such as oregano and thyme, as well as to the chemical turpentine, may clue the clinician in on the diagnosis of mint allergy. Contact dermatitis can result from menthol in peppermint. Contact allergens have been reported in toothpastes, which often are mint-flavored. Allergic asthma from mint is less well-recognized. A case of a 54-year-old woman with dyspnea on exposure to the scent of peppermint is presented in whom mint exposure, as seemingly innocuous as the breath of others who had consumed Tic Tac candies, exacerbated her underlying asthma. This case highlights the importance of testing with multiple alternative measures of specific IgE to mint, including skin testing with mint extract, and skin testing with fresh mint leaves. Additionally, this cases suggests that asthma can result from inhaling the scent of mint and gives consideration to obtaining confirmatory pre- and postexposure pulmonary function data by both impulse oscillometry and spirometry. PMID:22852115

  20. Allergic sensitization to ornamental plants in patients with allergic rhinitis and asthma.

    PubMed

    Aydin, Ömür; Erkekol, Ferda Öner; Misirloigil, Zeynep; Demirel, Yavuz Selim; Mungan, Dilşad

    2014-01-01

    Ornamental plants (OPs) can lead to immediate-type sensitization and even asthma and rhinitis symptoms in some cases. This study aimed to evaluate sensitization to OPs in patients with asthma and/or allergic rhinitis and to determine the factors affecting the rate of sensitization to OPs. A total of 150 patients with asthma and/or allergic rhinitis and 20 healthy controls were enrolled in the study. Demographics and disease characteristics were recorded. Skin-prick tests were performed with a standardized inhalant allergen panel. Skin tests by "prick-to-prick" method with the leaves of 15 Ops, which are known to lead to allergenic sensitization, were performed. Skin tests with OPs were positive in 80 patients (47.1%). There was no significant difference between OP sensitized and nonsensitized patients in terms of gender, age, number of exposed OPs, and duration of exposure. Skin test positivity rate for OPs was significantly high in atopic subjects, patients with allergic rhinitis, food sensitivity, and indoor OP exposure, but not in patients with pollen and latex allergy. Most sensitizing OPs were Yucca elephantipes (52.5%), Dieffenbachia picta (50.8%), and Euphorbia pulcherrima (47.5%). There was significant correlation between having Saintpaulia ionantha, Croton, Pelargonium, Y. elephantipes, and positive skin test to these plants. Sensitivity to OPs was significantly higher in atopic subjects and patients with allergic rhinitis, food allergy, and indoor OP exposure. Furthermore, atopy and food sensitivity were found as risk factors for developing sensitization to indoor plants. Additional trials on the relationship between sensitization to OPs and allergic symptoms are needed. PMID:24717779

  1. Allergen-specific immunotherapy in pediatric allergic asthma

    PubMed Central

    2016-01-01

    Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma. PMID:27489785

  2. Allergen-specific immunotherapy in pediatric allergic asthma.

    PubMed

    Yukselen, Ayfer

    2016-07-01

    Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma. PMID:27489785

  3. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    SciTech Connect

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  4. Key Mediators in the Immunopathogenesis of Allergic Asthma

    PubMed Central

    Hall, Sannette; Agrawal, Devendra K.

    2014-01-01

    Asthma is described as a chronic inflammatory disorder of the conducting airways. It is characterized by reversible airway obstruction, eosinophil and Th2 infiltration, airway hyper-responsiveness and airway remodeling. Our findings to date have largely been dependent on work done using animal models, which have been instrumental in broadening our understanding of the mechanism of the disease. However, using animals to model a uniquely human disease is not without its drawbacks. This review aims to examine some of the key mediators and cells of allergic asthma learned from animal models and shed some light on emerging mediators in the pathogenesis allergic airway inflammation in acute and chronic asthma. PMID:24933589

  5. Platelets promote allergic asthma through the expression of CD154.

    PubMed

    Tian, Jun; Zhu, Tianyi; Liu, Juan; Guo, Zhenhong; Cao, Xuetao

    2015-11-01

    Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe leukocyte infiltration and lung inflammation, elevated IgE production and strengthened T helper 2 (Th2) responses in asthma-induced mice. Accordingly, platelet depletion compromised allergic asthma progression. Cd154-deficient platelets failed to promote asthma development, indicating the requirement of CD154 for platelets to promote asthma progression. The mechanistic study showed that platelets inhibited the induction of Foxp3(+) regulatory T cells both in vivo and in vitro at least partially through CD154, providing an explanation for the increase of Th2 responses by platelet transfer. Our study reveals the previously unknown role of platelet CD154 in the promotion of asthma progression by polarizing Th2 responses and inhibiting regulatory T-cell generation and thus provides a potential clue for allergic disease interventions. PMID:25418472

  6. Prevalence of self-reported smoking experimentation in adolescents with asthma or allergic rhinitis

    PubMed Central

    Fernandes, Silvia de Sousa Campos; de Andrade, Cláudia Ribeiro; Caminhas, Alessandra Pinheiro; Camargos, Paulo Augusto Moreira; Ibiapina, Cássio da Cunha

    2016-01-01

    Objective: To determine the prevalence of smoking experimentation among adolescents with asthma or allergic rhinitis. Methods: This was a cross-sectional study involving adolescent students (13-14 years of age) in the city of Belo Horizonte, Brazil. The participants completed the Centers for Disease Control and Prevention and International Study of Asthma and Allergies in Childhood questionnaires, both of which have been validated for use in Brazil. We calculated the prevalence of smoking experimentation in the sample as a whole, among the students with asthma symptoms, and among the students with allergic rhinitis symptoms, as well as in subgroups according to gender and age at smoking experimentation. Results: The sample comprised 3,325 adolescent students. No statistically significant differences were found regarding gender or age. In the sample as a whole, the prevalence of smoking experimentation was 9.6%. The mean age for smoking experimentation for the first time was 11.1 years of age (range, 5-14 years). Among the adolescents with asthma symptoms and among those with allergic rhinitis symptoms, the prevalence of self-reported smoking experimentation was 13.5% and 10.6%, respectively. Conclusions: The proportion of adolescents with symptoms of asthma or allergic rhinitis who reported smoking experimentation is a cause for concern, because there is strong evidence that active smoking is a risk factor for the occurrence and increased severity of allergic diseases. PMID:27167427

  7. Janus Kinase-3 Dependent Inflammatory Responses in Allergic Asthma

    PubMed Central

    Malaviya, Rama; Laskin, Debra L.; Malaviya, Ravi

    2010-01-01

    Summary Allergic asthma is a chronic inflammatory condition of the lung characterized by reversible airway obstruction, high serum immunoglobulin (Ig) E levels, and chronic airway inflammation. A number of cells including mast cells, T-cells, macrophages and dendritic cells play a role in the pathogenesis of the disease. Janus Kinase (JAK) −3, a nonreceptor protein tyrosine kinase, traditionally known to mediate cytokine signaling, also regulates functional responses of these cells. In this review the role of JAK-3 in regulating various pathogenic processes in allergic asthma is discussed. We propose that targeting JAK-3 is a rationale approach to control the inflammatory responses of multiple cell types responsible for the pathogenesis of allergic asthma. PMID:20430118

  8. Role of Interferon-λ in Allergic Asthma.

    PubMed

    Koch, Sonja; Finotto, Susetta

    2015-01-01

    Type III interferons (IFNs), or IFN-λ, are known to have potent antiviral and antiproliferative activities. It inhibits viral replication and upregulates cytotoxic responses to virally infected cells. Besides these characteristics, IFN-λ also has additional activities in the immune system. In fact, it induces the proliferation of Foxp3-expressing regulatory T cells mediated in part by dendritic cells and inhibit the production of IL-5 and IL-13 in vitro. Regulatory T cells and the Th2 cytokines like IL-5 and IL-13 play important roles in the pathogenesis of allergic asthma. In humans, there seems to be an inverse link between IFN-λ and the severity of allergic asthma and allergic asthma exacerbations. Asthmatic patients, without a detectable viral infection show an inverse correlation between IL-28 and IL-29 mRNA levels and severity of allergic responses in the airways. These additional features of IFN-λ that affect the adaptive immune system make it a potential immunotherapeutic agent for the treatment of allergic asthma. PMID:25592858

  9. Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

    PubMed Central

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2011-01-01

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

  10. Weighted Road Density and Allergic Disease in Children at High Risk of Developing Asthma

    PubMed Central

    Hansell, Anna L.; Rose, Nectarios; Cowie, Christine T.; Belousova, Elena G.; Bakolis, Ioannis; Ng, Kitty; Toelle, Brett G.; Marks, Guy B.; Almqvist, plus Catarina; Ampon, Rosario D; Ayer, Julian; Bird, Tessa; Brew, Bronwyn K; Britton, Warwick J; Celermajer, David; Cowell, Christopher T; Crisafulli, Daniele; Criss, Sally; Davis, Stella; Nabil Ezz, Wafaa; Forbes, Samantha; Garden, Frances L; Kemp, Andrew S; Knezevic, Natalia; Krause, William; Leeder, Stephen R; Mellis, Craig M; Mihrshahi, Seema; Neumann, Mark; Peat, Jennifer K; Quinones-Lucio, Andres; Skilton, Michael; Tattam, Anne; Tovey, Euan R; Vanlaar, Carl H.; Vukasin, Nicola; Wainwright, Craig; Webb, Karen L; Weber-Chrysochoou, Christina; Woolcock, Ann J; Zhou, Jie

    2014-01-01

    Background Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma. Methods We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis. Results Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06–1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01–1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03–1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children. Conclusion Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma. PMID:24949625

  11. Challenges in the management of severe allergic asthma in the elderly

    PubMed Central

    Ozturk, Ayse Bilge; Iliaz, Sinem

    2016-01-01

    Little is known about the features of asthma and allergy in the elderly. A significant number of elderly patients with asthma have uncontrolled and severe asthma. This review aims to provide an analysis of the literature on the assessment and phenotype of severe allergic asthma in the elderly. Gaps and pitfalls in diagnostic and therapeutic approaches, as well as management of severe allergic asthma in the elderly, are also discussed. PMID:27051308

  12. Asthma and Allergic Diseases in Pregnancy: A Review

    PubMed Central

    2009-01-01

    Asthma and allergic disorders can affect the course and outcome of pregnancy. Pregnancy itself may also affect the course of asthma and related diseases. Optimal management of these disorders during pregnancy is vital to ensure the welfare of the mother and the baby. Specific pharmacological agents for treatment of asthma or allergic diseases must be cautiously selected and are discussed here with respect to safety considerations in pregnancy. Although most drugs do not harm the fetus, this knowledge is incomplete. Any drug may carry a small risk that must be balanced against the benefits of keeping the mother and baby healthy. The goals and principles of management for acute and chronic asthma, rhinitis, and dermatologic disorders are the same during pregnancy as those for asthma in the general population. Diagnosis of allergy during pregnancy should mainly consist of the patient's history and in vitro testing. The assured and well-evaluated risk factors revealed for sensitization in mother and child are very limited, to date, and include alcohol consumption, exposure to tobacco smoke, maternal diet and diet of the newborn, drug usage, and insufficient exposure to environmental bacteria. Consequently, the recommendations for primary and secondary preventive measures are also very limited in number and verification. PMID:21151812

  13. PSYCHOLOGICAL AND ALLERGIC ASPECTS OF ASTHMA.

    ERIC Educational Resources Information Center

    HIRT, MICHAEL L.

    FOCUSED HISTORICALLY AND CHOSEN TO STIMULATE RESEARCH IN PSYCHOSOCIAL IMPLICATIONS OF ASTHMA, THE COLLECTION CONTAINS 18 PAPERS BY DIFFERENT AUTHORS. AREAS OF PSYCHOSOMATIC MEDICINE COVERED ARE (1) PRINCIPLES OF RESEARCH (ONE ARTICLE), (2) HISTORICAL DEVELOPMENTS, THEORETICAL MODELS, AND CORE PROBLEMS (THREE ARTICLES), AND (3) THE HYPOTHESIS,…

  14. The Role of Prostaglandins in Allergic Lung Inflammation and Asthma

    PubMed Central

    Claar, Dru; Hartert, Tina V.; Peebles, R. Stokes

    2015-01-01

    Prostaglandins are products of the cyclooxygenase pathway of arachidonic acid metabolism. There are five primary prostaglandins, PGD2, PGE2, PGF2, PGI2, and thromboxane B2, all of which signal through distinct seven transmembrane, G-protein coupled receptors. Some prostaglandins may counteract the actions of others, or even the same prostaglandin may have opposing physiologic or immunologic effects, depending on the specific receptor through which it signals. In this review, we will examine the effects of cyclooxygenase activity and the various prostaglandins on allergic airway inflammation and physiology that is associated with asthma. We also highlight the potential therapeutic benefit of targeting prostaglandins in allergic lung inflammation and asthma based on basic science, animal model, and human studies. PMID:25541289

  15. Potassium ion channels and allergic asthma.

    PubMed

    Kocmalova, M; Oravec, M; Adamkov, M; Sadlonova, V; Kazimierova, I; Medvedova, I; Joskova, M; Franova, S; Sutovska, M

    2015-01-01

    High-conductive calcium-sensitive potassium channels (BK+Ca) and ATP-sensitive potassium (K+ATP) channels play a significant role in the airway smooth muscle cell and goblet cell function, and cytokine production. The present study evaluated the therapeutic potential of BK+Ca and K+ATP openers, NS 1619 and pinacidil, respectively, in an experimental model of allergic inflammation. Airway allergic inflammation was induced with ovalbumine in guinea pigs during 21 days, which was followed by a 14-day treatment with BK+Ca and K+ATP openers. The outcome measures were airway smooth muscle cells reactivity in vivo and in vitro, cilia beating frequency and the level of exhaled NO (ENO), and the level of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid. The openers of both channels decreased airway smooth muscle cells reactivity, cilia beating frequency, and cytokine levels in the serum. Furthermore, NS1619 reduced ENO and inflammatory cells infiltration. The findings confirmed the presence of beneficial effects of BK+Ca and K+ATP openers on airway defence mechanisms. Although both openers dampened pro-inflammatory cytokines and mast cells infiltration, an evident anti-inflammatory effect was provided only by NS1619. Therefore, we conclude that particularly BK+Ca channels represent a promising new drug target in treatment of airway's allergic inflammation. PMID:25315623

  16. Analysis of the quality of life of patients with asthma and allergic rhinitis after immunotherapy

    PubMed Central

    Szynkiewicz, Ewa; Cegła, Bernadeta; Bartuzi, Zbigniew

    2016-01-01

    Aim To assess the quality of life of Polish patients with asthma and/or allergic rhinitis before the implementation and after 30–36 months of immunotherapy. Material and methods Two hundred patients have been involved in the study: 101 with allergic asthma and 99 with pollinosis. In order to collect research material, the Polish versions of AQLQ (Asthma Quality of Life) and RQLQ (Rhinoconjunctivitis Quality of Life) questionnaires have been used. The self-administered questionnaires concerned such data as age, sex and the patients’ subjective evaluation of their quality of life. Results The average increase in quality of life of patients with asthma was 0.84 and of patients with allergic rhinitis – 1.50. A hypothesis was made that changes of quality of life in each examined group differed significantly. A test for two fractions showed that for patients with asthma it was 7.74 and for patients with allergic rhinitis – 10.38. A statistical analysis showed no such relation in the group of patients with asthma (coefficient of correlation = 0.08) and a slight correlation in the group of patients with allergic rhinitis (coefficient of correlation = 0.20). Applied tests did not show any significant differences, which means that an average increase in quality of life does not depend on sex and age of both examined groups. Conclusions On the basis of the research conducted among patients before and after a 3-year period of immunotherapy, the following conclusions have been drawn: 1) immunotherapy significantly improves the objective quality of life in both groups; 2) a slight correlation has been identified between the objective and subjective dimension of quality of life amongst patients with asthma, what contributes to a better quality of life; 3) in both study groups, no significant relationship between gender or age and improvement in quality of life has been noted; 4) immunotherapy, from the point of view of the improvement of quality of life, is a valuable

  17. Clara cells drive eosinophil accumulation in allergic asthma.

    PubMed

    Sonar, S S; Ehmke, M; Marsh, L M; Dietze, J; Dudda, J C; Conrad, M L; Renz, H; Nockher, W A

    2012-02-01

    Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma. PMID:21828027

  18. Potential of Immunoglobulin A to Prevent Allergic Asthma

    PubMed Central

    Gloudemans, Anouk K.; Lambrecht, Bart N.; Smits, Hermelijn H.

    2013-01-01

    Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies. PMID:23690823

  19. Potential of immunoglobulin A to prevent allergic asthma.

    PubMed

    Gloudemans, Anouk K; Lambrecht, Bart N; Smits, Hermelijn H

    2013-01-01

    Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies. PMID:23690823

  20. Understanding allergic asthma from allergen inhalation tests.

    PubMed

    Cockcroft, Donald W; Hargreave, Fredrick E; O'Byrne, Paul M; Boulet, Louis-Philippe

    2007-10-01

    The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors' involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic) airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta(2)-agonist-induced increase in airway response to allergen (including eosinophilic inflammation), advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a multicentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma. PMID:17948142

  1. Application of vitamin E to antagonize SWCNTs-induced exacerbation of allergic asthma.

    PubMed

    Li, Jinquan; Li, Li; Chen, Hanqing; Chang, Qing; Liu, Xudong; Wu, Yang; Wei, Chenxi; Li, Rui; Kwan, Joseph K C; Yeung, King Lun; Xi, Zhuge; Lu, Zhisong; Yang, Xu

    2014-01-01

    The aggravating effects of zero-dimensional, particle-shaped nanomaterials on allergic asthma have been previously investigated, but similar possible effects of one-dimensional shaped nanomaterials have not been reported. More importantly, there are no available means to counteract the adverse nanomaterial effects to allow for their safe use. In this study, an ovalbumin (OVA)-sensitized rat asthma model was established to investigate whether single walled carbon nanotubes (SWCNTs) aggravate allergic asthma. The results showed that SWCNTs in rats exacerbated OVA-induced allergic asthma and that this exacerbation was counteracted by concurrent administration vitamin E. A mechanism involving the elimination of reactive oxygen species, downregulation of Th2 responses, reduced Ig production, and the relief of allergic asthma symptoms was proposed to explain the antagonistic effects of vitamin E. This work could provide a universal strategy to effectively protect people with allergic asthma from SWCNTs or similar nanomaterial-induced aggravating effects. PMID:24589727

  2. Allergic Rhinitis and Asthma in Southern Croatia: Impact of Sensitization to Ambrosia elatior

    PubMed Central

    Cvitanović, Slavica; Znaor, Ljubo; Kanceljak-Macan, Božica; Macan, Jelena; Gudelj, Ivan; Grbić, Dragica

    2007-01-01

    Aim To identify pollen types in southern Croatia and investigate the impact of sensitization to Ambrosia elatior (A. elatior) on symptoms and treatment of patients with seasonal allergic rhinitis and/or asthma. Methods The study recruited 120 patients from Split-Dalmatian County with seasonal rhinitis and asthma symptoms and positive skin prick test to one or more common inhaled allergens. Patients with positive skin prick test and increased specific IgE to A. elatior (n = 56) were included in the follow-up study during the A. elatior pollen season. Rhinitis and asthma symptoms were scored and drug treatment recorded using standardized questionnaires. Also, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and eosinophil count in peripheral blood were measured. Type and pollen concentration of A. elatior in the air over the nine-week pollen season were determined on the glass slides using the gravimetric method. The results were expressed as the proportion of A. elatior pollen in the total pollen. Results Fifty-six of 120 patients (46.7%) were sensitized to A. elatior. Its proportion in total pollen peaked to 12% in the first week of September. Forty-one patients who completed the follow-up study showed a significantly higher score of symptoms during this peak period than in the beginning of the pollen season for seasonal allergic rhinitis (median±interquartile range, 50 ± 11 vs 7 ± 4; P<0.001) and for seasonal allergic asthma (median±interquartile range, 12 ± 2 vs 0 ± 0; P<0.001). Conclusion A. elatior is an important cause of seasonal allergic rhinitis and asthma and must be included in the routine diagnostic procedures in southern Croatia. PMID:17309141

  3. The impact of Vitamin D deficiency on asthma, allergic rhinitis and wheezing in children: An emerging public health problem

    PubMed Central

    Bener, Abdulbari; Ehlayel, Mohammad S.; Bener, Hale Z.; Hamid, Qutayba

    2014-01-01

    Background: Vitamin D deficiency has been declared a public health problem for both adults and children worldwide. Asthma and related allergic diseases are the leading causes of morbidity in children. The objective of this study was to investigate the potential role of Vitamin D deficiency in childhood asthma and other allergic diseases such as allergic rhinitis and wheezing. Materials and Methods: This cross-sectional study was conducted in Primary Health Care Centers (PHCs), from March 2012 to October 2013. A total of 2350 Qatari children below the age of 16 were selected from PHCs, and 1833 agreed to participate in this study giving a response rate of (78%). Face-to-face interviews with parents of all the children were based on a questionnaire that included variables such as socio-demographic information, assessment of nondietary covariates, Vitamin D intake, type of feeding, and laboratory investigations. Their health status was assessed by serum Vitamin D (25-hydoxyvitamin D), family history and body mass index. Results: Most of the children who had asthma (38.5%), allergic rhinitis (34.8%) and wheezing (35.7%) were below 5 years. Consanguinity was significantly higher in parents of children with allergic rhinitis (48.6%), followed by those with asthma (46.4%) and wheezing (40.8%) than in healthy children (35.9%) (P < 0.001). The proportion of severe Vitamin D deficiency was significantly higher in children with wheezing (23.4%), allergic rhinitis (18.5%), and asthma (17%) than in healthy children (10.5%). Exposure to the sun was significantly less in Vitamin D deficient children with asthma (60.3%), allergic rhinitis (62.5%) and wheezing (64.4%) than in controls (47.1%) (P = 0.008). It was found that Vitamin D deficiency was a significant correlate for asthma (odds ratio [OR] =2.31; P < 0.001), allergic rhinitis (OR = 1.59; P < 0.001) and wheezing (relative risk = 1.29; P = 0.05). Conclusion: The study findings revealed a high prevalence of Vitamin D

  4. Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

    PubMed

    Gao, Yi; Zhaoyu, Liu; Xiangming, Fang; Chunyi, Lin; Jiayu, Pan; Lu, Shen; Jitao, Chen; Liangcai, Chen; Jifang, Liu

    2016-09-01

    Abietic acid (AA), one of the terpenoids isolated from Pimenta racemosa var. grissea, has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-allergic effects of AA remain unclear. The aim of this study was to investigate the anti-allergic effects of AA in an ovalbumin (OVA)-induced asthma murine model. The model of mouse asthma was established by induction of OVA. AA (10, 20, 40mg/kg) was administered by oral gavage 1h after the OVA treatment on days 21 to 23. At 24h after the last challenge, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to assess pathological changes, cytokines production, and NF-κB expression. The results showed that AA attenuated lung histopathologic changes, inflammatory cells infiltration, and bronchial hyper-responsiveness. AA also inhibited OVA-induced the nitric oxide (NO), IL-4, IL-5, IL-13, and OVA-specific IgE production, as well as NF-κB activation. In conclusion, the current study demonstrated that AA exhibited protective effects against OVA-induced allergic asthma in mice and the possible mechanism was involved in inhibiting NF-κB activation. PMID:27318791

  5. CROSS REACTIVITY IN ALLERGIC ASTHMA-LIKE RESPONSES BETWEEN MOLD AND HOUSE DUST MITE IN MICE

    EPA Science Inventory

    Molds are ubiquitous in the environment and exposures to molds contribute to various human diseases including allergic asthma. Some mold allergens have been implicated as the causal agent for allergic asthma. Western blot analysis demonstrated IgE-binding cross-reactivity among m...

  6. Safety of Grass Pollen Sublingual Immunotherapy for Allergic Rhinitis in Concomitant Asthma.

    PubMed

    Sahadevan, A; Cusack, R; Lane, S J

    2015-01-01

    Seasonal allergic rhinitis (AR) occurs predominantly as a result of grass pollen allergy. Grass pollen sublingual immunotherapy (SLIT) has been proven effective in treating AR1. SLIT is currently licensed for use in AR with concomitant stable mild asthma. There is evidence that SLIT improves asthma control when primarily used to treat AR2. The aim was to assess the safety of SLIT in patients with severe seasonal allergic rhinitis who have co-existing stable mild asthma. The secondary aim was to determine whether asthma control improved post SLIT. There was no deterioration in asthma control after 6-36 months of SLIT. 27/30 (90%) patients' asthma control remained stable or indeed improved (p < 0.021). Of this 15 (50%) patients' asthma improved. There was no statistically significant change in their asthma pharmacotherapy after SLIT (p = 0.059). In conclusion, grass pollen SLIT is safe and can potentially treat dual allergic rhinitis- mild asthmatic patients. PMID:26817287

  7. Is Folate Status a Risk Factor for Asthma or Other Allergic Diseases?

    PubMed Central

    Wang, Ting; Zhang, Hong-Ping; Zhang, Xin; Liang, Zong-An; Ji, Yu-Lin

    2015-01-01

    Purpose It is controversial whether folate status is a risk factor for the development of asthma or other allergic diseases. This study was conducted to investigate whether indirect or direct exposure to folate and impaired folate metabolism, reflected as methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism, would contribute to the development of asthma and other allergic diseases. Methods Electronic databases were searched to identify all studies assessing the association between folate status and asthma or other allergic diseases. Two reviewers independently assessed the eligibility of studies and extracted data. The relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CI) was calculated and pooled. Results Twenty-six studies (16 cohort, 7 case-control, and 3 cross-sectional studies) were identified. Maternal folic acid supplementation was not associated with the development of asthma, atopic dermatitis (AD), eczema, and sensitization in the offspring, whereas exposure during early pregnancy was related to wheeze occurrence in the offspring (RR=1.06, 95% CI=[1.02-1.09]). The TT genotype of MTHFR C677T polymorphism was at high risk of asthma (OR=1.41, 95% CI=[1.07-1.86]). Conclusions It is indicated that maternal folic acid supplementation during early pregnancy may increase the risk of wheeze in early childhood and that the TT genotype of MTHFR C677T polymorphism impairing folic acid metabolism would be at high risk of asthma development. These results might provide additional information for recommendations regarding forced folate consumption or folic acid supplements during pregnancy based on its well-established benefits for the prevention of congenital malformations. However, currently available evidence is of low quality which is needed to further elucidate. PMID:26333700

  8. Improved asthma control in patients with severe, persistent allergic asthma after 12 months of nightly temperature-controlled laminar airflow: an observational study with retrospective comparisons

    PubMed Central

    Schauer, Uwe; Bergmann, Karl-Christian; Gerstlauer, Michael; Lehmann, Sylvia; Gappa, Monika; Brenneken, Amelie; Schulz, Christian; Ahrens, Peter; Schreiber, Jens; Wittmann, Michael; Hamelmann, Eckard

    2015-01-01

    Introduction Continuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma. Objective The objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients’ regular medication. Methods This multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study. Results Data from 30 patients (mean age 28; range 8–70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months. Conclusions The addition of TLA to the patients’ regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma. PMID:26557252

  9. Systems Biology of Asthma and Allergic Diseases: A Multiscale Approach

    PubMed Central

    Bunyavanich, Supinda; Schadt, Eric E.

    2014-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article, we review the technologies and approaches for system-wide profiling as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually-captured health profiles will contribute to more accurate systems biology views of asthma and allergy. PMID:25468194

  10. Mouse models of acute exacerbations of allergic asthma.

    PubMed

    Kumar, Rakesh K; Herbert, Cristan; Foster, Paul S

    2016-07-01

    Most of the healthcare costs associated with asthma relate to emergency department visits and hospitalizations because of acute exacerbations of underlying chronic disease. Development of appropriate animal models of acute exacerbations of asthma is a necessary prerequisite for understanding pathophysiological mechanisms and assessing potential novel therapeutic approaches. Most such models have been developed using mice. Relatively few mouse models attempt to simulate the acute-on-chronic disease that characterizes human asthma exacerbations. Instead, many reported models involve relatively short-term challenge with an antigen to which animals are sensitized, followed closely by an unrelated triggering agent, so are better described as models of potentiation of acute allergic inflammation. Triggers for experimental models of asthma exacerbations include (i) challenge with high levels of the sensitizing allergen (ii) infection by viruses or fungi, or challenge with components of these microorganisms (iii) exposure to environmental pollutants. In this review, we examine the strengths and weaknesses of published mouse models, their application for investigation of novel treatments and potential future developments. PMID:26922049

  11. Perinatal and Early Childhood Environmental Factors Influencing Allergic Asthma Immunopathogenesis

    PubMed Central

    Gaffin, Jonathan M.; Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda

    2014-01-01

    Background The prevalence of asthma has increased dramatically over the past several decades. While hereditary factors are highly important, the rapid rise outstrips the pace of genomic variation. Great emphasis has been placed on potential modifiable early life exposures leading to childhood asthma. Methods We reviewed the recent medical literature for important studies discussing the role of the perinatal and early childhood exposures and the inception of childhood asthma. Results and Discussion Early life exposure to allergens (House dust mite (HDM), furred pets, cockroach, rodent and mold)air pollution (nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), and particulate matter (PM)) and viral respiratory tract infections (Respiratory syncytial virus (RSV) and human rhinovirus (hRV)) have been implicated in the development of asthma in high risk children. Conversely, exposure to microbial diversity in the perinatal period may diminish the development of atopy and asthma symptoms. PMID:24952205

  12. Thymol attenuates allergic airway inflammation in ovalbumin (OVA)-induced mouse asthma.

    PubMed

    Zhou, Ershun; Fu, Yunhe; Wei, Zhengkai; Yu, Yuqiang; Zhang, Xichen; Yang, Zhengtao

    2014-07-01

    Thymol, a naturally occurring monocyclic phenolic compound derived from Thymus vulgaris (Lamiaceae), has been reported to exhibit anti-inflammatory property in vivo and vitro. However, the mechanism of thymol is not clear. The aim of the present study was to investigate the effects of thymol on allergic inflammation in OVA-induced mice asthma and explore its mechanism. The model of mouse asthma was established by the induction of OVA. Thymol was orally administered at a dose of 4, 8, and 16 mg/kg body weight 1h before OVA challenge. At 24h after the last challenge, mice were sacrificed, and the data were collected by various experimental methods. The results revealed that pretreatment with thymol reduced the level of OVA-specific IgE, inhibited recruitment of inflammatory cells into airway, and decreased the levels of IL-4, IL-5, and IL-13 in BALF. Moreover, the pathologic changes of lung tissues were obviously ameliorated and goblet cell hyperplasia was effectively inhibited by the pretreatment of thymol. In addition, thymol reduced the development of airway hyperresponsiveness and blocked the activation of NF-κB pathway. All data suggested that thymol ameliorated airway inflammation in OVA-induced mouse asthma, possibly through inhibiting NF-κB activation. These findings indicated that thymol may be used as an alternative agent for treating allergic asthma. PMID:24785965

  13. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    PubMed Central

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though

  14. Traffic exposure associated with allergic asthma and allergic rhinitis in adults. A cross-sectional study in southern Sweden

    PubMed Central

    Lindgren, Anna; Stroh, Emilie; Nihlén, Ulf; Montnémery, Peter; Axmon, Anna; Jakobsson, Kristina

    2009-01-01

    Background There is conflicting evidence that traffic-related air pollution is a risk factor for allergic conditions. Few studies have investigated this in adults. In adults, a high proportion of asthma, rhinitis and eczema is triggered by non-allergic factors. We investigated traffic as a risk factor for allergic versus non-allergic asthma and rhinitis, and eczema, in adults. A questionnaire from 2000 (n = 9319, 18–77 years) provided individual data about disease outcome and self-reported traffic exposure. Additional exposure assessments were obtained using Geographical Informations Systems (GIS). Residential addresses were linked to the national Swedish Road Database and to a pollutant database with modelled annual means of NOx (Nitrogen Oxids). Results Living within 100 m from a road with a traffic intensity of >10 cars/min (24 hour mean) was associated with prevalence of current asthma reported to be triggered by allergic factors (OR = 1.83, 95% CI = 1.23–2.72) and with allergic rhinitis (OR = 1.30, 95%CI = (1.05–1.61). No relation was seen with asthma or rhinitis triggered by other factors. Living within 100 m of a road with >10 cars/min was also associated with hand-eczema during the last 12 months (OR = 1.63, 95% CI = 1.19–2.23), but not with allergic eczema or diagnosed hand-eczema. Consistent results were seen using self-reported traffic, but the associations with NOx were less consistent. Conclusion Exposure to traffic was associated with a higher prevalence of allergic asthma and allergic rhinitis, but not with asthma or rhinitis triggered by non-allergic factors. This difference was suggested by the overall pattern, but only clear using GIS-measured traffic intensity as a proxy for traffic exposure. An association was also found with hand-eczema during the last 12 months. We suggest that asthma and rhinitis should not be treated as homogenous groups when estimating effects from traffic in adults. PMID:19419561

  15. Modulation of lung inflammation by vessel dilator in a mouse model of allergic asthma

    PubMed Central

    Wang, Xiaoqin; Xu, Weidong; Kong, Xiaoyuan; Chen, Dongqing; Hellermann, Gary; Ahlert, Terry A; Giaimo, Joseph D; Cormier, Stephania A; Li, Xu; Lockey, Richard F; Mohapatra, Subhra; Mohapatra, Shyam S

    2009-01-01

    Background Atrial natriuretic peptide (ANP) and its receptor, NPRA, have been extensively studied in terms of cardiovascular effects. We have found that the ANP-NPRA signaling pathway is also involved in airway allergic inflammation and asthma. ANP, a C-terminal peptide (amino acid 99–126) of pro-atrial natriuretic factor (proANF) and a recombinant peptide, NP73-102 (amino acid 73–102 of proANF) have been reported to induce bronchoprotective effects in a mouse model of allergic asthma. In this report, we evaluated the effects of vessel dilator (VD), another N-terminal natriuretic peptide covering amino acids 31–67 of proANF, on acute lung inflammation in a mouse model of allergic asthma. Methods A549 cells were transfected with pVD or the pVAX1 control plasmid and cells were collected 24 hrs after transfection to analyze the effect of VD on inactivation of the extracellular-signal regulated receptor kinase (ERK1/2) through western blot. Luciferase assay, western blot and RT-PCR were also performed to analyze the effect of VD on NPRA expression. For determination of VD's attenuation of lung inflammation, BALB/c mice were sensitized and challenged with ovalbumin and then treated intranasally with chitosan nanoparticles containing pVD. Parameters of airway inflammation, such as airway hyperreactivity, proinflammatory cytokine levels, eosinophil recruitment and lung histopathology were compared with control mice receiving nanoparticles containing pVAX1 control plasmid. Results pVD nanoparticles inactivated ERK1/2 and downregulated NPRA expression in vitro, and intranasal treatment with pVD nanoparticles protected mice from airway inflammation. Conclusion VD's modulation of airway inflammation may result from its inactivation of ERK1/2 and downregulation of NPRA expression. Chitosan nanoparticles containing pVD may be therapeutically effective in preventing allergic airway inflammation. PMID:19615076

  16. Consumption of Artificially-Sweetened Soft Drinks in Pregnancy and Risk of Child Asthma and Allergic Rhinitis

    PubMed Central

    Maslova, Ekaterina; Strøm, Marin; Olsen, Sjurdur F.; Halldorsson, Thorhallur I.

    2013-01-01

    Background Past evidence has suggested a role of artificial sweeteners in allergic disease; yet, the evidence has been inconsistent and unclear. Objective To examine relation of intake of artificially-sweetened beverages during pregnancy with child asthma and allergic rhinitis at 18 months and 7 years. Methods We analyzed data from 60,466 women enrolled during pregnancy in the prospective longitudinal Danish National Birth Cohort between 1996 and 2003. At the 25th week of gestation we administered a validated Food Frequency Questionnaire which asked in detail about intake of artificially-sweetened soft drinks. At 18 months, we evaluated child asthma using interview data. We also assessed asthma and allergic rhinitis through a questionnaire at age 7 and by using national registries. Current asthma was defined as self-reported asthma diagnosis and wheeze in the past 12 months. We examined the relation between intake of artificially-sweetened soft drinks and child allergic disease outcomes and present here odds ratios with 95% CI comparing daily vs. no intake. Results At 18 months, we found that mothers who consumed more artificially-sweetened non-carbonated soft drinks were 1.23 (95% CI: 1.13, 1.33) times more likely to report a child asthma diagnosis compared to non-consumers. Similar results were found for child wheeze. Consumers of artificially-sweetened carbonated drinks were more likely to have a child asthma diagnosis in the patient (1.30, 95% CI: 1.01, 1.66) and medication (1.13, 95% CI: 0.98, 1.29) registry, as well as self-reported allergic rhinitis (1.31, 95% CI: 0.98, 1.74) during the first 7 years of follow-up. We found no associations for sugar-sweetened soft drinks. Conclusion Carbonated artificially-sweetened soft drinks were associated with registry-based asthma and self-reported allergic rhinitis, while early childhood outcomes were related to non-carbonated soft drinks. These results suggest that consumption of artificially-sweetened soft drinks

  17. Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4

    PubMed Central

    2011-01-01

    Background Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4. Methods T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM) allergic rhinitics (R), 18 HDM allergic rhinitics and asthmatics (AR), 13 non allergic asthmatics (A) and 20 controls, with or without anti-co-receptors antibodies. Results In asthmatics (A+AR), a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR), allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4. Conclusions T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics. PMID:21356099

  18. Systemic and local eosinophil inflammation during the birch pollen season in allergic patients with predominant rhinitis or asthma

    PubMed Central

    Kämpe, Mary; Stålenheim, Gunnemar; Janson, Christer; Stolt, Ingrid; Carlson, Marie

    2007-01-01

    Background The aim of the study was to investigate inflammation during the birch pollen season in patients with rhinitis or asthma. Methods Subjects with birch pollen asthma (n = 7) or rhinitis (n = 9) and controls (n = 5) were studied before and during pollen seasons. Eosinophils (Eos), eosinophil cationic protein (ECP) and human neutrophil lipocalin were analysed. Results Allergic asthmatics had a larger decline in FEV1 after inhaling hypertonic saline than patients with rhinitis (median) (-7.0 vs.-0.4%, p = 0.02). The asthmatics had a lower sesonal PEFR than the rhinitis group. The seasonal increase in B-Eos was higher among patients with asthma (+0.17 × 109/L) and rhinitis (+0.27 × 109/L) than among controls (+0.01 × 109/L, p = 0.01). Allergic asthmatics and patients with rhinitis had a larger increase in sputum ECP (+2180 and +310 μg/L) than the controls (-146 μg/L, p = 0.02). No significant differences in inflammatory parameters were found between the two groups of allergic patients. Conclusion Patients with allergic asthma and rhinitis have the same degree of eosinophil inflammation. Despite this, only the asthmatic group experienced an impairment in lung function during the pollen season. PMID:17967188

  19. Control of Allergic Rhinitis and Asthma Test (CARAT): dissemination and applications in primary care.

    PubMed

    Azevedo, Pedro; Correia de Sousa, Jaime; Bousquet, Jean; Bugalho-Almeida, António; Del Giacco, Stefano R; Demoly, Pascal; Haahtela, Tari; Jacinto, Tiago; Garcia-Larsen, Vanessa; van der Molen, Thys; Morais-Almeida, Mário; Nogueira-Silva, Luis; Pereira, Ana M; Rodríguez, Miguel Román; Silva, Bárbara G; Tsiligianni, Ioanna G; Yaman, Hakan; Yawn, Barbara; Fonseca, João A

    2013-03-01

    Asthma frequently occurs in association with allergic rhinitis and a combined management approach has been suggested. The Control of Allergic Rhinitis and Asthma Test (CARAT) is the first questionnaire to assess control of both diseases concurrently. However, to have an impact on healthcare it needs to be disseminated and adopted. In this paper we discuss the dissemination of CARAT in different countries and its possible applications in primary care. At present, the adaptation of CARAT for use in different languages and cultures is being led by volunteer researchers and clinicians in 15 countries. Website and smartphone applications have been developed, and a free open model of distribution was adopted to contribute to the dissemination of CARAT. Examples of dissemination activities include distribution of leaflets and posters, educational sessions on the use of the questionnaire in the follow-up of patients, development of clinical studies, collaborations with professional organisations and health authorities, and the inclusion of CARAT in clinical guidelines. The adoption of innovations is an important challenge in healthcare today, and research on the degree of success of dissemination strategies using suitable methods and metrics is much needed. We propose that CARAT can be used in a range of settings and circumstances in primary care for clinical, research and audit purposes, within the overall aim of increasing awareness of the level of disease control and strengthening the partnership between patients and doctors in the management of asthma and rhinitis. PMID:23412110

  20. Atopic Manifestations: Dermatitis, Allergic Rhinitis and Asthma in Patients With Hypogammaglobulinemia

    PubMed Central

    Dadkhah, Minoo; Aghamohammadi, Asghar; Movahedi, Masoud; Gharagozlou, Mohammad

    2015-01-01

    Background: Most of the hypogammaglobulinemic patients have a clinical history in favor of allergic respiratory disease. Nevertheless, in these patients the importance and prevalence of atopic disorders have not been completely explained. Objectives: This study was aimed to evaluate atopic manifestations (dermatitis, allergic rhinitis and asthma) and pulmonary function in patients with hypogammaglobulinemia. Patients and Methods: We used the international study of asthma and allergies in childhood (ISAAC) questionnaire in forty-five patients diagnosed with hypogammaglobulinemia and spirometry was done in 41 patients older than 5 years. Results: Spirometry results were normal in 21 (51%), and showed obstructive in 15 (37%) and restrictive pattern in 5 (12%) of the 41 patients who were evaluated. By the end of the study, asthma was diagnosed in nine (20%) patients and other atopies (rhinitis and dermatitis) identified in 10 (22%), and four (9%), respectively. Conclusions: Atopic conditions should be investigated in the hypogammaglobulinemic patients and the prevalence in these patients may be higher than in normal population. Also, it is recommended to perform a pulmonary function test as a routine procedure in patients with hypogammaglobulinemia and atopy should be assessed in these patients. PMID:26495093

  1. Report of a patient with complex composites of hepatitis B virus, allergic asthma and diabetes

    PubMed Central

    Athari, Seyyed Shamsadin; Omidi, Razie

    2014-01-01

    HBV is a non-cytopathic virus and cell mediated immune response against this. Humoral mediated immune response are responsible for allergic diseases. Balance between these two subsets of Th CD4+ cells are result of the immune system response. A 56 year old woman presented with chronic HBV infection, allergic asthma, type 2 diabetes mellitus and high blood pressure and high blood lipid. Patients should be followed for the allergic and autoimmune diseases along with their viral reactivation. PMID:25183147

  2. γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation

    PubMed Central

    Zhang, Weixi; Zhang, Xueya; Sheng, Anqun; Weng, Cuiye; Zhu, Tingting; Zhao, Wei; Li, Changchong

    2015-01-01

    T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly suppressed Th17-cell responses in spleen and reduced IL-17 levels in serum. These findings suggest that GSI directly regulates Th17 responses through a Notch signaling-dependent pathway in mouse model of allergic asthma, supporting the notion that GSI is a potential therapeutic agent for the treatment of allergic asthma. PMID:26339131

  3. Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma

    PubMed Central

    Xiao, Xiaojun; Zeng, Xiaowei; Zhang, Xinxin; Ma, Li; Liu, Xiaoyu; Yu, Haiqiong; Mei, Lin; Liu, Zhigang

    2013-01-01

    Background Pollen allergy is the most common allergic disease. However, tropical pollens, such as those of Palmae, have seldom been investigated compared with the specific immunotherapy studies done on hyperallergenic birch, olive, and ragweed pollens. Although poly(lactic-co-glycolic acid) (PLGA) has been extensively applied as a biodegradable polymer in medical devices, it has rarely been utilized as a vaccine adjuvant to prevent and treat allergic disease. In this study, we investigated the immunotherapeutic effects of recombinant Caryota mitis profilin (rCmP)-loaded PLGA nanoparticles and the underlying mechanisms involved. Methods A mouse model of allergenic asthma was established for specific immunotherapy using rCmP-loaded PLGA nanoparticles as the adjuvant. The model was evaluated by determining airway hyperresponsiveness and levels of serum-specific antibodies (IgE, IgG, and IgG2a) and cytokines, and observing histologic sections of lung tissue. Results The rCmP-loaded PLGA nanoparticles effectively inhibited generation of specific IgE and secretion of the Th2 cytokine interleukin-4, facilitated generation of specific IgG2a and secretion of the Th1 cytokine interferon-gamma, converted the Th2 response to Th1, and evidently alleviated allergic symptoms. Conclusion PLGA functions more appropriately as a specific immunotherapy adjuvant for allergen vaccines than does conventional Al(OH)3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed herein offer a promising avenue for specific immunotherapy in allergic asthma. PMID:24376349

  4. Screening and functional pathway analysis of genes associated with pediatric allergic asthma using a DNA microarray

    PubMed Central

    LU, LI-QUN; LIAO, WEI

    2015-01-01

    The present study aimed to identify differentially expressed genes (DEGs) associated with pediatric allergic asthma, and to analyze the functional pathways of the selected target genes, in order to explore the pathogenesis of the disease. The GSE18965 gene expression profile was downloaded from the Gene Expression Omnibus database and was preprocessed. This gene expression profile consisted of seven normal samples and nine samples from patients with pediatric allergic asthma. The DEGs between the normal and pediatric allergic asthma samples were screened using limma package in R, and the cut-off value was set at false discovery rate <0.05 and log fold change >1. Following hierarchical clustering of the DEGs based on the expression profiles, the up- and downregulated genes underwent a functional enrichment analysis by topological approach (P<0.05), using the Database for Annotation, Visualization and Integrated Discovery. A total of 127 DEGs were identified between the normal and pediatric allergic asthma samples. The up- and downregulated genes were significantly enriched in the actin filament-based process and the monosaccharide metabolic process, respectively. Seven downregulated DEGs (M6PR, TPP1, GLB1, NEU1, ACP2, LAMP1 and HGSNAT) were identified in the lysosomal pathway, with P=6.4×10−9. These results suggested that variation in lysosomal function, triggered by the seven downregulated genes, may lead to aberrant functioning of the T lymphocytes, resulting in asthma. Further research regarding the treatment of pediatric allergic asthma through targeting lysosomal function is required. PMID:25633562

  5. 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.

  6. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

    PubMed Central

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-01-01

    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. PMID:27251783

  7. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis.

    PubMed

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-01-01

    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. PMID:27251783

  8. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.; Haitchi, Hans Michael

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  9. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.

    PubMed Central

    Bonini, S; Lambiase, A; Bonini, S; Angelucci, F; Magrini, L; Manni, L; Aloe, L

    1996-01-01

    Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma. Images Fig. 2 PMID:8855290

  10. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma.

    PubMed

    Schmudde, Inken; Laumonnier, Yves; Köhl, Jörg

    2013-02-01

    Allergic asthma is a chronic disease of the airways in which maladaptive Th2 and Th17 immune responses drive airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Airway epithelial and pulmonary vascular endothelial cells in concert with different resident and monocyte-derived dendritic cells (DC) play critical roles in allergen sensing and consecutive activation of TH cells and their differentiation toward TH2 and TH17 effector or regulatory T cells (Treg). Further, myeloid-derived regulatory cells (MDRC) act on TH cells and either suppress or enhance their activation. The complement-derived anaphylatoxins (AT) C3a and C5a are generated during initial antigen encounter and regulate the development of maladaptive immunity at allergen sensitization. Here, we will review the complex role of ATs in activation and modulation of different DC populations, MDRCs and CD4⁺ TH cells. We will also discuss the potential impact of ATs on the regulation of the pulmonary stromal compartment as an important means to regulate DC functions. PMID:23694705

  11. A Systematic Review on the Development of Asthma and Allergic Diseases in Relation to International Immigration: The Leading Role of the Environment Confirmed

    PubMed Central

    Cabieses, Báltica; Uphoff, Eleonora; Pinart, Mariona; Antó, Josep Maria; Wright, John

    2014-01-01

    Background The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been contradictory, particularly on the interplay between allergic diseases and understudied social determinants of health like migration status. This review aimed at providing evidence for the association between migration status and asthma and allergies, and to explore the mechanisms between migration status and the development of asthma and allergies. Methods and Findings Systematic review on asthma and allergies and immigration status in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled odds ratio (OR) of the prevalence of asthma in immigrants compared to the host population was 0.60 (95% CI 0.45–0.84), and the pooled OR for allergies was 1.01 (95% CI 0.62–1.69). The pooled OR for the prevalence of asthma in first generation versus second generation immigrants was 0.37 (95% CI 0.25–0.58). Comparisons between populations in their countries of origin and those that emigrated vary depending on their level of development; more developed countries show higher rates of asthma and allergies. Conclusions Our findings suggest a strong influence of the environment on the development of asthma and allergic diseases throughout the life course. The prevalence of asthma is generally higher in second generation than first generation immigrants. With length of residence in the host country the prevalence of asthma and allergic diseases increases steadily. These findings are consistent across study populations, host countries, and children as well as adults. Differences have been found to be significant when tested in a linear model, as well as when comparing between early and later age of migration, and between shorter and longer time of residence. PMID:25141011

  12. Urban Tree Canopy and Asthma, Wheeze, Rhinitis, and Allergic Sensitization to Tree Pollen in a New York City Birth Cohort

    PubMed Central

    Lovasi, Gina S.; O’Neil-Dunne, Jarlath P.M.; Lu, Jacqueline W.T.; Sheehan, Daniel; Perzanowski, Matthew S.; MacFaden, Sean W.; King, Kristen L.; Matte, Thomas; Miller, Rachel L.; Hoepner, Lori A.; Perera, Frederica P.

    2013-01-01

    Background: Urban landscape elements, particularly trees, have the potential to affect airflow, air quality, and production of aeroallergens. Several large-scale urban tree planting projects have sought to promote respiratory health, yet evidence linking tree cover to human health is limited. Objectives: We sought to investigate the association of tree canopy cover with subsequent development of childhood asthma, wheeze, rhinitis, and allergic sensitization. Methods: Birth cohort study data were linked to detailed geographic information systems data characterizing 2001 tree canopy coverage based on LiDAR (light detection and ranging) and multispectral imagery within 0.25 km of the prenatal address. A total of 549 Dominican or African-American children born in 1998–2006 had outcome data assessed by validated questionnaire or based on IgE antibody response to specific allergens, including a tree pollen mix. Results: Tree canopy coverage did not significantly predict outcomes at 5 years of age, but was positively associated with asthma and allergic sensitization at 7 years. Adjusted risk ratios (RRs) per standard deviation of tree canopy coverage were 1.17 for asthma (95% CI: 1.02, 1.33), 1.20 for any specific allergic sensitization (95% CI: 1.05, 1.37), and 1.43 for tree pollen allergic sensitization (95% CI: 1.19, 1.72). Conclusions: Results did not support the hypothesized protective association of urban tree canopy coverage with asthma or allergy-related outcomes. Tree canopy cover near the prenatal address was associated with higher prevalence of allergic sensitization to tree pollen. Information was not available on sensitization to specific tree species or individual pollen exposures, and results may not be generalizable to other populations or geographic areas. PMID:23322788

  13. Vitamin E and D regulation of allergic asthma immunopathogenesis

    PubMed Central

    Cook-Mills, Joan M.; Avila, Pedro C.

    2014-01-01

    Asthma occurs as complex interactions of the environmental and genetics. Clinical studies and animal models of asthma indicate dietary factors such as vitamin E and vitamin D as protective for asthma risk. In this review, we discuss opposing regulatory functions of tocopherol isoforms of vitamin E and regulatory functions of vitamin D in asthma and how the variation in global prevalence of asthma may be explained, at least in part, by these dietary components. PMID:25175918

  14. Comparative responses to nasal allergen challenge in allergic rhinitic subjects with or without asthma

    PubMed Central

    2011-01-01

    Background Nasal allergen challenge (NAC) is useful to study the pathophysiology of rhinitis, and multiple challenges may more adequately approximate natural exposure. Objective To determine the effect of 4 consecutive daily NAC, on clinical and inflammatory parameters in rhinitics with or without asthma. Methods Rhinitic subjects were recruited: 19 with mild asthma and 13 without asthma. Subjects underwent a control challenge (normal saline) followed by 4 consecutive daily NAC. Allergen challenge consisted of spraying the chosen allergen extract into each nostril until a positive nasal response occurred. Symptoms were recorded on a Likert scale, and oral peak expiratory and nasal peak inspiratory flows allowed assessment of a nasal blockage index (NBI), for a period of 7 hours. Induced sputum and nasal lavage were performed on control day and after 1 and 4 days of NAC. Results Compared with the control day, there was a significant increase in symptom scores and NBI 10 minutes after each last daily NAC in both groups (p < 0.05). Symptom scores and NBI were similar for the 2 groups, except for nasal obstruction and rhinorrhea, which were more marked in subjects with asthma and rhinitis, respectively. Nasal lavage eosinophils were increased after 4 days of challenges in both groups, but there was no change in sputum eosinophils. No cumulative effect or any late response were observed in any of the groups over the challenge period. Conclusion Multiple NAC may be a useful tool to study the pathophysiology of allergic rhinitis or its relationships with asthma. Trial registration ClinicalTrials.gov NCT01286129 PMID:21507261

  15. RELATIVE POTENCY OF FUNGAL EXTRACTS IN INDUCING ALLERGIC ASTHMA-LIKE RESPONSES IN BALB/C MICE

    EPA Science Inventory

    Indoor mold has been associated with the development of allergic asthma. However, relative potency of molds in the induction of allergic asthma is not clear. In this study, we tested the relative potency of fungal extracts (Metarizium anisophilae [MACA], Stachybotrys ...

  16. Nanoparticle uptake by airway phagocytes after fungal spore challenge in murine allergic asthma and chronic bronchitis

    PubMed Central

    2014-01-01

    Background In healthy lungs, deposited micrometer-sized particles are efficiently phagocytosed by macrophages present on airway surfaces; however, uptake of nanoparticles (NP) by macrophages appears less effective and is largely unstudied in lung disease. Using mouse models of allergic asthma and chronic obstructive pulmonary disease (COPD), we investigated NP uptake after challenge with common biogenic ambient air microparticles. Methods Bronchoalveolar lavage (BAL) cells from diseased mice (allergic asthma: ovalbumin [OVA] sensitized and COPD: Scnn1b-transgenic [Tg]) and their respective healthy controls were exposed ex vivo first to 3-μm fungal spores of Calvatia excipuliformis and then to 20-nm gold (Au) NP. Electron microscopic imaging was performed and NP uptake was assessed by quantitative morphometry. Results Macrophages from diseased mice were significantly larger compared to controls in OVA-allergic versus sham controls and in Scnn1b-Tg versus wild type (WT) mice. The percentage of macrophages containing AuNP tended to be lower in Scnn1b-Tg than in WT mice. In all animal groups, fungal spores were localized in macrophage phagosomes, the membrane tightly surrounding the spore, whilst AuNP were found in vesicles largely exceeding NP size, co-localized in spore phagosomes and occasionally, in the cytoplasm. AuNP in vesicles were located close to the membrane. In BAL from OVA-allergic mice, 13.9 ± 8.3% of all eosinophils contained AuNP in vesicles exceeding NP size and close to the membrane. Conclusions Overall, AuNP uptake by BAL macrophages occurred mainly by co-uptake together with other material, including micrometer-sized ambient air particles like fungal spores. The lower percentage of NP containing macrophages in BAL from Scnn1b-Tg mice points to a change in the macrophage population from a highly to a less phagocytic phenotype. This likely contributes to inefficient macrophage clearance of NP in lung disease. Finally, the AuNP containing

  17. Time trends of the prevalence of asthma and allergic disease in Austrian children.

    PubMed

    Schernhammer, E S; Vutuc, C; Waldhör, T; Haidinger, G

    2008-03-01

    After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6-7 yr and 1516 children aged 12-14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6-7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12-14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors. PMID:18086231

  18. Allergic rhinitis and asthma: inflammation in a one-airway condition

    PubMed Central

    Jeffery, Peter K; Haahtela, Tari

    2006-01-01

    Background Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. Discussion In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. Conclusion Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites. PMID:17140423

  19. The Impact of Aspergillus fumigatus Viability and Sensitization to Its Allergens on the Murine Allergic Asthma Phenotype

    PubMed Central

    Pandey, Sumali; Hoselton, Scott A.; Schuh, Jane M.

    2013-01-01

    Aspergillus fumigatus is a ubiquitously present respiratory pathogen. The outcome of a pulmonary disease may vary significantly with fungal viability and host immune status. Our objective in this study was (1) to assess the ability of inhaled irradiation-killed or live A. fumigatus spores to induce allergic pulmonary disease and (2) to assess the extent to which inhaled dead or live A. fumigatus spores influence pulmonary symptoms in a previously established allergic state. Our newly developed fungal delivery apparatus allowed us to recapitulate human exposure through repeated inhalation of dry fungal spores in an animal model. We found that live A. fumigatus spore inhalation led to a significantly increased humoral response, pulmonary inflammation, and airway remodeling in naïve mice and is more likely to induce allergic asthma symptoms than the dead spores. In contrast, in allergic mice, inhalation of dead and live conidia recruited neutrophils and induced goblet cell metaplasia. This data suggests that asthma symptoms might be exacerbated by the inhalation of live or dead spores in individuals with established allergy to fungal antigens, although the extent of symptoms was less with dead spores. These results are likely to be important while considering fungal exposure assessment methods and for making informed therapeutic decisions for mold-associated diseases. PMID:24063011

  20. Immunization with live influenza viruses in an experimental model of allergic bronchial asthma: infection and vaccination

    PubMed Central

    Chirkova, Tatiana; Petukhova, Galina; Korenkov, Daniil; Naikhin, Anatoliy; Rudenko, Larisa

    2008-01-01

    Background  Asthmatics in particular have a need for influenza vaccines because influenza infection is a frequent cause of hospitalization of patients with bronchial asthma. Currently, only inactivated influenza vaccines are recommended for influenza prevention in asthma sufferers. Objective  The aim of our study was to analyze and compare the effects of influenza infection and vaccination with live attenuated influenza vaccine (LAIV) on different phases of experimental murine allergic bronchial asthma (acute asthma and remission phase) and on subsequent exposure to allergen in sensitized animals. Methods  Ovalbumin (OVA)‐specific serum IgE levels, IL‐4 production by spleen and lung lymphocytes, and histological changes in the lungs of mice infected with pathogenic virus or LAIV were studied at two phases of OVA‐induced bronchial asthma (acute asthma and remission). Results  Infection with pathogenic virus both in acute asthma and remission led to asthma exacerbation associated with the production of OVA‐specific IgE, IL‐4 and significant inflammatory infiltration in airways. Infection, even after complete virus clearance, induced the aggravation of lung inflammation and IgE production in asthmatic mice additionally exposed to OVA. Immunization with LAIV at remission did not enhance allergic inflammatory changes in the lung, OVA‐specific IgE or IL‐4 production. Then after additional OVA exposure, histological and immunological changes in these mice were the same as in the control group. Conclusions  Influenza infection provokes asthma exacerbation regardless of the disease phase. Immunization with LAIV during the remission phase of bronchial asthma is safe and does not interfere upon subsequent contact of asthma sufferers with allergen. PMID:19453421

  1. New occupational and environmental causes of asthma and extrinsic allergic alveolitis.

    PubMed

    Fishwick, David

    2012-12-01

    Asthma and extrinsic allergic alveolitis (EAA) remain prevalent respiratory diseases and the cause of a significant disease burden. This article reviews the recent occupational and environmental causes described for these conditions. Even over the limited time spam addressed by this article, novel agents and new data relating to already suggested causes have been described. Various types of work tasks or exposures are described that appear to cause both asthma and EAA. Isocyanates, the best example of dual potential to cause asthma and EAA are discussed, as is the new understanding of the role metal-working fluids play when causing respiratory diseases. PMID:23153603

  2. The genetics of asthma and allergic disease: a 21st century perspective.

    PubMed

    Ober, Carole; Yao, Tsung-Chieh

    2011-07-01

    Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits. PMID:21682736

  3. Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis.

    PubMed

    Hevia, Arancha; Milani, Christian; López, Patricia; Donado, Carmen D; Cuervo, Adriana; González, Sonia; Suárez, Ana; Turroni, Francesca; Gueimonde, Miguel; Ventura, Marco; Sánchez, Borja; Margolles, Abelardo

    2016-01-01

    Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 ± 10.98 years old) and compare it with the fecal microbiota of 22 healthy controls (age 39.29 ± 9.21 years old) using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha-diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long-term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients. PMID:26840903

  4. Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis

    PubMed Central

    Hevia, Arancha; Milani, Christian; López, Patricia; Donado, Carmen D.; Cuervo, Adriana; González, Sonia; Suárez, Ana; Turroni, Francesca; Gueimonde, Miguel; Ventura, Marco; Sánchez, Borja; Margolles, Abelardo

    2016-01-01

    Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 ± 10.98 years old) and compare it with the fecal microbiota of 22 healthy controls (age 39.29 ± 9.21 years old) using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha-diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long-term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients. PMID:26840903

  5. High-Fat and Low-Carbohydrate Diets Are Associated with Allergic Rhinitis But Not Asthma or Atopic Dermatitis in Children

    PubMed Central

    Kim, So Young; Sim, Songyong; Park, Bumjung; Kim, Jin-Hwan; Choi, Hyo Geun

    2016-01-01

    Background Numerous studies have suggested that nutritional intake is related to allergic diseases. Although conflicting results exist, fat intake is often associated with allergic diseases. We investigated the relationship between allergic diseases and nutritional intake after adjusting for various demographic and socioeconomic factors in a large, representative sample of Korean children. Methods A total of 3,040 participants, aged 4 to 13 years old, were enrolled in the present study from the Korean National Health and Nutrition Examination Survey (KNHANES), 2010–2012. Nutritional intake data, including total calories, protein, fat, carbohydrate, vitamin A, vitamin C, thiamine, riboflavin, and niacin, were retrieved from the survey using the complete 24-hour recall method. The associations between each nutritional factor and allergic rhinitis/asthma/atopic dermatitis were analyzed using simple and multiple logistic regression analyses with complex sampling. Age, sex, body mass index (BMI), number of household members, income level, and region of residence were adjusted for as covariates. Results Of the participants, 22.1%, 6.0%, and 15.5% suffered from allergic rhinitis, asthma, and atopic dermatitis, respectively. Allergic rhinitis was significantly correlated with high-fat and low-carbohydrate diets. The adjusted odds ratio (AOR) was 1.25 (95% CIs = 1.06–1.46, P = 0.007) for fat intake, denoting a 10% increase. Carbohydrate intake (10% increase) was negatively related to allergic rhinitis with an AOR of 0.84 (95% CIs = 0.74–0.95, P = 0.004). No other significant relationships were found between the retrieved nutritional factors and either asthma or atopic dermatitis. Conclusion Allergic rhinitis was related to high-fat and low-carbohydrate diets. Although the underlying mechanisms and causal relationships remain elusive, the present study provides reliable evidence regarding the associations between nutritional factors and allergic rhinitis by considering

  6. The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma

    PubMed Central

    Shen, Chia-Rui; Juang, Horng-Heng; Chen, Hui-Shan; Yang, Ching-Jen; Wu, Chia-Jen; Lee, Meng-Hua; Hwang, Yih-Shiou; Kuo, Ming-Ling; Chen, Ya-Shan; Chen, Jeen-Kuan; Liu, Chao-Lin

    2015-01-01

    Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase) may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA)-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression. PMID:26580611

  7. Link between allergic asthma and airway mucosal infection suggested by proteinase-secreting household fungi.

    PubMed

    Porter, P; Susarla, S C; Polikepahad, S; Qian, Y; Hampton, J; Kiss, A; Vaidya, S; Sur, S; Ongeri, V; Yang, T; Delclos, G L; Abramson, S; Kheradmand, F; Corry, D B

    2009-11-01

    Active fungal proteinases are powerful allergens that induce experimental allergic lung disease strongly resembling atopic asthma, but the precise relationship between proteinases and asthma remains unknown. Here, we analyzed dust collected from the homes of asthmatic children for the presence and sources of active proteinases to further explore the relationship between active proteinases, atopy, and asthma. Active proteinases were present in all houses and many were derived from fungi, especially Aspergillus niger. Proteinase-active dust extracts were alone insufficient to initiate asthma-like disease in mice, but conidia of A. niger readily established a contained airway mucosal infection, allergic lung disease, and atopy to an innocuous bystander antigen. Proteinase produced by A. niger enhanced fungal clearance from lung and was required for robust allergic disease. Interleukin 13 (IL-13) and IL-5 were required for optimal clearance of lung fungal infection and eosinophils showed potent anti-fungal activity in vitro. Thus, asthma and atopy may both represent a protective response against contained airway infection due to ubiquitous proteinase-producing fungi. PMID:19710638

  8. Role of breast regression protein-39/YKL-40 in asthma and allergic responses

    PubMed Central

    Elias, Jack A

    2010-01-01

    BRP-39 and its human homolog YKL-40 have been regarded as a prototype of chitinase-like proteins (CLP) in mammals. Exaggerated levels of YKL-40 protein and/or mRNA have been noted in a number of diseases characterized by inflammation, tissue remodeling, and aberrant cell growth. Asthma is an inflammatory disease characterized by airway hyperresponsiveness and airway remodeling. Recently, the novel regulatory role of BRP-39/YKL-40 in the pathogenesis of asthma has been demonstrated both in human studies and allergic animal models. The levels of YKL-40 are increased in the circulation and lungs from asthmatics where they correlate with disease severity, and CHI3L1 polymorphisms correlate with serum YKL-40 levels, asthma and abnormal lung function. Animal studies using BRP-39 null mutant mice demonstrated that BRP-39 was required for optimal allergen sensitization and Th2 inflammation. These studies suggest the potential use of BRP-39 as a biomarker as well as a therapeutic target for asthma and other allergic diseases. Here, we present an overview of chitin/chitinase biology and summarize recent findings on the role of BRP-39 in the pathogenesis of asthma and allergic responses. PMID:20224674

  9. The prevalence and risk factors of asthma and allergic diseases among working adolescents.

    PubMed

    Cakir, Erkan; Ersu, Refika; Uyan, Zeynep Seda; Oktem, Sedat; Varol, Nezih; Karakoc, Fazilet; Karadag, Bulent; Akyol, Mesut; Dagli, Elif

    2010-01-01

    Certain occupational groups are known to be at particularly high risk of developing allergic diseases. The objective of the present study was to evaluate the prevalence of allergic diseases among working adolescents. The International Study of Asthma and Allergies in Childhood questionnaire was used. Four hundred and thirty six adolescents working in motor, lathe-finish, coiffure and textile and 366 high school students as control group were enrolled to the study. Mean age was 16.8 +/- 1.2 years and 82.9% of them were male. There was no significant difference among groups for ever and current wheezing while doctor diagnosed asthma was higher in lathe- finish group (p = 0.036). Family history of allergy, history of allergic rhinitis, and active smoking were found to be risk factors for asthma and related symptoms. Working in coiffure (p = 0.054), and textile (p = 0.003) were significant risk factors for ever allergic rhinitis. Working in lathe finish (p = 0.023), coiffure (p = .002), and textile (p < 0.001) were associated with a higher risk for current allergic rhinitis. Working in coiffure was a risk factor for ever eczema (p = 0.008) and doctor diagnosed eczema (p = 0.014). It was concluded that working in lathe-finish was associated with doctor diagnosed asthma and active smoking was a risk factor for asthma and related symptoms. Working in coiffure, textile and lathe- finish were risk factors for rhinitis, and working in coiffure was a risk factor for eczema. Preventive measures should be taken at the onset of employment in order to prevent or reduce the detrimental effects of exposures in these occupational groups. PMID:21038780

  10. Estrogen Signaling Modulates Allergic Inflammation and Contributes to Sex Differences in Asthma

    PubMed Central

    Keselman, Aleksander; Heller, Nicola

    2015-01-01

    Asthma is a chronic airway inflammatory disease that affects ~300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or “hard-to-treat” asthma. Puberty, menstruation, pregnancy, menopause, and oral contraceptives are known to contribute to disease outcome in women, suggesting a role for estrogen and other hormones impacting allergic inflammation. Currently, the mechanisms underlying these sex differences are poorly understood, although the effect of sex hormones, such as estrogen, on allergic inflammation is gaining interest. Asthma presents as a heterogeneous disease. In typical Th2-type allergic asthma, interleukin (IL)-4 and IL-13 predominate, driving IgE production and recruitment of eosinophils into the lungs. Chronic Th2-inflammation in the lung results in structural changes and activation of multiple immune cell types, leading to a deterioration of lung function over time. Most immune cells express estrogen receptors (ERα, ERβ, or the membrane-bound G-protein-coupled ER) to varying degrees and can respond to the hormone. Together these receptors have demonstrated the capacity to regulate a spectrum of immune functions, including adhesion, migration, survival, wound healing, and antibody and cytokine production. This review will cover the current understanding of estrogen signaling in allergic inflammation and discuss how this signaling may contribute to sex differences in asthma and allergy. PMID:26635789

  11. Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

    PubMed

    Bousquet, J; Schünemann, H J; Samolinski, B; Demoly, P; Baena-Cagnani, C E; Bachert, C; Bonini, S; Boulet, L P; Bousquet, P J; Brozek, J L; Canonica, G W; Casale, T B; Cruz, A A; Fokkens, W J; Fonseca, J A; van Wijk, R Gerth; Grouse, L; Haahtela, T; Khaltaev, N; Kuna, P; Lockey, R F; Lodrup Carlsen, K C; Mullol, J; Naclerio, R; O'Hehir, R E; Ohta, K; Palkonen, S; Papadopoulos, N G; Passalacqua, G; Pawankar, R; Price, D; Ryan, D; Simons, F E R; Togias, A; Williams, D; Yorgancioglu, A; Yusuf, O M; Aberer, W; Adachi, M; Agache, I; Aït-Khaled, N; Akdis, C A; Andrianarisoa, A; Annesi-Maesano, I; Ansotegui, I J; Baiardini, I; Bateman, E D; Bedbrook, A; Beghé, B; Beji, M; Bel, E H; Ben Kheder, A; Bennoor, K S; Bergmann, K C; Berrissoul, F; Bieber, T; Bindslev Jensen, C; Blaiss, M S; Boner, A L; Bouchard, J; Braido, F; Brightling, C E; Bush, A; Caballero, F; Calderon, M A; Calvo, M A; Camargos, P A M; Caraballo, L R; Carlsen, K H; Carr, W; Cepeda, A M; Cesario, A; Chavannes, N H; Chen, Y Z; Chiriac, A M; Chivato Pérez, T; Chkhartishvili, E; Ciprandi, G; Costa, D J; Cox, L; Custovic, A; Dahl, R; Darsow, U; De Blay, F; Deleanu, D; Denburg, J A; Devillier, P; Didi, T; Dokic, D; Dolen, W K; Douagui, H; Dubakiene, R; Durham, S R; Dykewicz, M S; El-Gamal, Y; El-Meziane, A; Emuzyte, R; Fiocchi, A; Fletcher, M; Fukuda, T; Gamkrelidze, A; Gereda, J E; González Diaz, S; Gotua, M; Guzmán, M A; Hellings, P W; Hellquist-Dahl, B; Horak, F; Hourihane, J O'B; Howarth, P; Humbert, M; Ivancevich, J C; Jackson, C; Just, J; Kalayci, O; Kaliner, M A; Kalyoncu, A F; Keil, T; Keith, P K; Khayat, G; Kim, Y Y; Koffi N'goran, B; Koppelman, G H; Kowalski, M L; Kull, I; Kvedariene, V; Larenas-Linnemann, D; Le, L T; Lemière, C; Li, J; Lieberman, P; Lipworth, B; Mahboub, B; Makela, M J; Martin, F; Marshall, G D; Martinez, F D; Masjedi, M R; Maurer, M; Mavale-Manuel, S; Mazon, A; Melen, E; Meltzer, E O; Mendez, N H; Merk, H; Mihaltan, F; Mohammad, Y; Morais-Almeida, M; Muraro, A; Nafti, S; Namazova-Baranova, L; Nekam, K; Neou, A; Niggemann, B; Nizankowska-Mogilnicka, E; Nyembue, T D; Okamoto, Y; Okubo, K; Orru, M P; Ouedraogo, S; Ozdemir, C; Panzner, P; Pali-Schöll, I; Park, H S; Pigearias, B; Pohl, W; Popov, T A; Postma, D S; Potter, P; Rabe, K F; Ratomaharo, J; Reitamo, S; Ring, J; Roberts, R; Rogala, B; Romano, A; Roman Rodriguez, M; Rosado-Pinto, J; Rosenwasser, L; Rottem, M; Sanchez-Borges, M; Scadding, G K; Schmid-Grendelmeier, P; Sheikh, A; Sisul, J C; Solé, D; Sooronbaev, T; Spicak, V; Spranger, O; Stein, R T; Stoloff, S W; Sunyer, J; Szczeklik, A; Todo-Bom, A; Toskala, E; Tremblay, Y; Valenta, R; Valero, A L; Valeyre, D; Valiulis, A; Valovirta, E; Van Cauwenberge, P; Vandenplas, O; van Weel, C; Vichyanond, P; Viegi, G; Wang, D Y; Wickman, M; Wöhrl, S; Wright, J; Yawn, B P; Yiallouros, P K; Zar, H J; Zernotti, M E; Zhong, N; Zidarn, M; Zuberbier, T; Burney, P G; Johnston, S L; Warner, J O

    2012-11-01

    Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children. PMID:23040884

  12. ALLERGIC ASTHMA AND THE DEVELOPING IMMUNE SYSTEM: A PILOT STUDY

    EPA Science Inventory

    Rationale: The predisposition towards atopic disease begins early in life, and that the risk of developing asthma is heightened following prenatal exposure to some compounds. Nonetheless, the effect of gestational aeroallergen exposure on the developing immune system is unclear....

  13. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells.

    PubMed

    Arnold, Isabelle C; Dehzad, Nina; Reuter, Sebastian; Martin, Helen; Becher, Burkhard; Taube, Christian; Müller, Anne

    2011-08-01

    Atopic asthma is a chronic disease of the airways that has taken on epidemic proportions in the industrialized world. The increase in asthma rates has been linked epidemiologically to the rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies. In this study, we have utilized mouse models of allergic airway disease induced by ovalbumin or house dust mite allergen to experimentally examine a possible inverse correlation between H. pylori and asthma. H. pylori infection efficiently protected mice from airway hyperresponsiveness, tissue inflammation, and goblet cell metaplasia, which are hallmarks of asthma, and prevented allergen-induced pulmonary and bronchoalveolar infiltration with eosinophils, Th2 cells, and Th17 cells. Protection against asthma was most robust in mice infected neonatally and was abrogated by antibiotic eradication of H. pylori. Asthma protection was further associated with impaired maturation of lung-infiltrating dendritic cells and the accumulation of highly suppressive Tregs in the lungs. Systemic Treg depletion abolished asthma protection; conversely, the adoptive transfer of purified Treg populations was sufficient to transfer protection from infected donor mice to uninfected recipients. Our results thus provide experimental evidence for a beneficial effect of H. pylori colonization on the development of allergen-induced asthma. PMID:21737881

  14. Allergic Rhinitis and Its Impact on Asthma in Asia Pacific and the ARIA Update 2008

    PubMed Central

    Bunnag, Chaweewan; Khaltaev, Nikolai; Bousquet, Jean

    2012-01-01

    Abstract: The prevalence of allergic diseases such as allergic rhinitis (AR) and asthma are markedly increasing to epidemic proportions worldwide as societies adopt Western lifestyles. An estimated 300 million persons worldwide have asthma, about 50% of whom live in developing countries, and about 400 million people suffer from AR. AR has a marked impact on quality of life, socially, at school, and in the workplace and is a huge socioeconomic burden. Thus, there was clearly a need for a global evidence-based guideline not only for managing AR but also highlighting the interactions between the upper and lower airways including diagnosis, epidemiology, common risk factors, management, and prevention. The Allergic Rhinitis and its Impact on Asthma (ARIA) document was first published in 2001 as a state-of-the-art document for the specialist, the general practitioner, and other health care professionals. Subsequent research and increasing knowledge have resulted in the ARIA 2008 update. The present review summarizes the ARIA update with particular emphasis on the current status of AR and asthma in Asia Pacific. PMID:23268481

  15. Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial.

    PubMed

    de Boer, J Daan; Berger, Marieke; Majoor, Christof J; Kager, Liesbeth M; Meijers, Joost C M; Terpstra, Sanne; Nieuwland, Rienk; Boing, Anita N; Lutter, René; Wouters, Diana; van Mierlo, Gerard J; Zeerleder, Sacha S; Bel, Elisabeth H; van't Veer, Cornelis; de Vos, Alex F; van der Zee, Jaring S; van der Poll, Tom

    2015-12-01

    Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.We conducted a randomised, double-blind, placebo-controlled, proof-of-concept study in house dust mite (HDM) allergic asthma patients. Patients were randomised to receive intravenous rhAPC (24 µg·kg(-1)·h(-1); n=12) or placebo (n=12) for 11 h. 4 h after the start of infusion, a first bronchoscopy was performed to challenge one lung segment with saline (control) and a contralateral segment with a combination of HDM extract and lipopolysaccharide (HDM+LPS), thereby mimicking environmental house dust exposure. A second bronchoscopy was conducted 8 h after intrabronchial challenge to obtain bronchoalveolar lavage fluid (BALF).rhAPC did not influence HDM+LPS induced procoagulant changes in the lung. In contrast, rhAPC reduced BALF leukocyte counts by 43% relative to placebo, caused by an inhibitory effect on neutrophil influx (64% reduction), while leaving eosinophil influx unaltered. rhAPC also reduced neutrophil degranulation products in the airways.Intravenous rhAPC attenuates HDM+LPS-induced neutrophil migration and protein release in allergic asthma patients by an effect that does not rely on coagulation inhibition. PMID:26381519

  16. Atopic dermatitis, asthma and allergic rhinitis in general practice and the open population: a systematic review

    PubMed Central

    Pols, D. H. J.; Wartna, J. B.; Moed, H.; van Alphen, E. I.; Bohnen, A. M.; Bindels, P. J. E.

    2016-01-01

    Objective To examine whether significant differences exist between the self-reported prevalence of atopic disorders in the open population compared with physician diagnosed prevalence of atopic disorders in general practice. Methods Medline (OvidSP), PubMed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed for articles providing data on the prevalence of asthma, allergic rhinitis and eczema in a GP setting. Studies were only included when they had a cross-sectional or cohort design and included more than 100 children (aged 0-18 years) in a general practice setting. All ISAAC studies (i.e. the open population) that geographically matched a study selected from the first search, were also included. A quality assessment was conducted. The primary outcome measures were prevalence of eczema, asthma and allergic rhinitis in children aged 0-18 years. Results The overall quality of the included studies was good. The annual and lifetime prevalences of the atopic disorders varied greatly in both general practice and the open population. On average, the prevalence of atopic disorders was higher in the open population. Conclusion There are significant differences between the self-reported prevalence of atopic disorders in the open population compared with physician diagnosed prevalence of atopic disorders in general practice. Data obtained in the open population cannot simply be extrapolated to the general practice setting. This should be taken into account when considering a research topic or requirements for policy development. GPs should be aware of the possible misclassification of allergic disorders in their practice. Key PointsEpidemiological data on atopic disorders in children can be obtained from various sources, each having its own advantages and limitations.On average, the prevalence of atopic disorders is higher in the open population.GPs should take into account the possible

  17. Secretory leukocyte protease inhibitor plays an important role in the regulation of allergic asthma in mice.

    PubMed

    Marino, Rafael; Thuraisingam, Thusanth; Camateros, Pierre; Kanagaratham, Cynthia; Xu, Yong Zhong; Henri, Jennifer; Yang, Jingxuan; He, Guoan; Ding, Aihao; Radzioch, Danuta

    2011-04-01

    Secretory leukocyte protease inhibitor (SLPI) is an anti-inflammatory protein that is observed at high levels in asthma patients. Resiquimod, a TLR7/8 ligand, is protective against acute and chronic asthma, and it increases SLPI expression of macrophages in vitro. However, the protective role played by SLPI and the interactions between the SLPI and resiquimod pathways in the immune response occurring in allergic asthma have not been fully elucidated. To evaluate the role of SLPI in the development of asthma phenotypes and the effect of resiquimod treatment on SLPI, we assessed airway resistance and inflammatory parameters in the lungs of OVA-induced asthmatic SLPI transgenic and knockout mice and in mice treated with resiquimod. Compared with wild-type mice, allergic SLPI transgenic mice showed a decrease in lung resistance (p < 0.001), airway eosinophilia (p < 0.001), goblet cell hyperplasia (p < 0.001), and plasma IgE levels (p < 0.001). Allergic SLPI knockout mice displayed phenotype changes significantly more severe compared with wild-type mice. These phenotypes included lung resistance (p < 0.001), airway eosinophilia (p < 0.001), goblet cell hyperplasia (p < 0.001), cytokine levels in the lungs (p < 0.05), and plasma IgE levels (p < 0.001). Treatment of asthmatic transgenic mice with resiquimod increased the expression of SLPI and decreased inflammation in the lungs; resiquimod treatment was still effective in asthmatic SLPI knockout mice. Taken together, our study showed that the expression of SLPI protects against allergic asthma phenotypes, and treatment by resiquimod is independent of SLPI expression, displayed through the use of transgenic and knockout SLPI mice. PMID:21335488

  18. The natural compound nujiangexanthone A suppresses mast cell activation and allergic asthma.

    PubMed

    Lu, Yue; Cai, Shuangfan; Nie, Jia; Li, Yangyang; Shi, Guochao; Hao, Jimin; Fu, Wenwei; Tan, Hongsheng; Chen, Shilin; Li, Bin; Xu, Hongxi

    2016-01-15

    Mast cells play an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. The genus Garcinia of the family Guttiferae is well known as a prolific source of polycyclic polyprenylated acylphloroglucinols and bioactive prenylated xanthones, which exhibit various biological activities including antibacterial, antifungal, anti-inflammatory, antioxidant, and cytotoxic effects. Nujiangexanthone A (N7) is a novel compound isolated from the leaves of Garcinia nujiangensis. In this paper, we sought to determine the anti-allergic and anti-inflammation activity of N7 in vivo and its mechanism in vitro. We found N7 suppressed IgE/Ag induced mast cell activiation, including degranulation and production of cytokines and eicosanoids, through inhibiting Src kinase activity and Syk dependent pathways. N7 inhibited histamine release, prostaglandin D2 and leukotriene C4 generation in mast cell dependent passive cutaneous anaphylaxis animal model. We also found N7 inhibited the IL-4, IL-5, IL-13 and IgE levels in ovalbumin-induced asthma model. Histological studies demonstrated that N7 substantially inhibited OVA-induced cellular infiltration and increased mucus production in the lung tissue. Our study reveals the anti-allergic function of N7, thereby suggesting the utility of this compound as a possible novel agent for preventing mast cell-related immediate and delayed allergic diseases. PMID:26571438

  19. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma.

    PubMed

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; de Carvalho, Katharinne Ingrid Moraes; da Silva Mendes, Diego; Melo, Christianne Bandeira; Martins, Marco Aurélio; da Silva Dias, Celidarque; Piuvezam, Márcia Regina; Bozza, Patrícia T

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca(++) influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. PMID:23994558

  20. 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 ...

  1. Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives.

    PubMed

    Samitas, Konstantinos; Delimpoura, Vasiliki; Zervas, Eleftherios; Gaga, Mina

    2015-12-01

    Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes. PMID:26621973

  2. Nasal irrigation for chronic sinus symptoms in patients with allergic rhinitis, asthma and nasal polyposis: a hypothesis generating study

    PubMed Central

    Rabago, David P.; Guerard, Emily; Bukstein, Don

    2009-01-01

    Background Rhinosinusitis is a common, expensive disorder with a significant impact on patients' quality-of-life. Chronic sinus symptoms are associated with allergic rhinitis, asthma, and nasal polyposis. Saline nasal irrigation is an adjunctive therapy for rhinosinusitis and sinus symptoms. Prior studies suggest that HSNI may be effective for symptoms associated with allergy, asthma and nasal polyposis. Objective To assess the degree to which subjects using nasal irrigation for chronic sinus symptoms also reported improvements in symptoms related to allergy, asthma or nasal polyposis. Design Qualitative study using in-depth long interviews. Participants 28 participants in a prior qualitative nasal irrigation study. Intervention Daily nasal irrigation. Outcome Qualitative transcripts Results Transcripts of interviews were systematically examined. Twelve of 21 subjects with allergic rhinitis spontaneously reported that HSNI improved symptoms. Two of seven subjects with asthma and one of two subjects with nasal polyposis reported a positive association between HSNI use and asthma or nasal polyposis symptoms. Transcript content was organized into themes which included: 1) HSNI resulted in improvement of allergic rhinitis and asthma symptoms, and 2) HSNI should be used for symptoms of allergic rhinitis. Conclusions This hypothesis generating study offers suggestive qualitative evidence that in patients with frequent rhinosinusitis and daily sinus symptoms, symptoms of concomitant allergic rhinitis, asthma or polyposis may also improve with HSNI. The parent studies offer strong evidence that HSNI is an effective adjunctive treatment for symptoms of chronic rhinosinusitis. Larger prospective studies are needed in patients with these diagnoses. PMID:18593081

  3. Resident alveolar macrophages suppress while recruited monocytes promote allergic lung inflammation in murine models of asthma

    PubMed Central

    Zasłona, Zbigniew; Przybranowski, Sally; Wilke, Carol; van Rooijen, Nico; Teitz-Tennenbaum, Seagal; Osterholzer, John J.; Wilkinson, John E.; Moore, Bethany B.; Peters-Golden, Marc

    2014-01-01

    The role and origin of alveolar macrophages (AMs) in asthma are incompletely defined. We sought to clarify these issues in the context of acute allergic lung inflammation utilizing house dust mite and ovalbumin murine models. Use of liposomal clodronate to deplete resident AMs (rAMs) resulted in increased levels of inflammatory cytokines and eosinophil numbers in lavage fluid and augmented histopathologic evidence of lung inflammation, suggesting a suppressive role of rAMs. Lung digests of asthmatic mice revealed an increased percentage of Ly6Chigh/CD11bpos inflammatory monocytes. Clodronate depletion of circulating monocytes, by contrast, resulted in an attenuation of allergic inflammation. A CD45.1/CD45.2 chimera model demonstrated that recruitment at least partially contributes to the AM pool in irradiated non-asthmatic mice, but its contribution was no greater in asthma. Ki-67 staining of AMs supported a role for local proliferation, which was increased in asthma. Our data demonstrate that rAMs dampen, while circulating monocytes promote, early events in allergic lung inflammation. Moreover, maintenance of the AM pool in the early stages of asthmatic inflammation depends on local proliferation but not recruitment. PMID:25225663

  4. The role of autophagy in allergic inflammation: a new target for severe asthma

    PubMed Central

    Liu, Jing-Nan; Suh, Dong-Hyeon; Trinh, Hoang Kim Tu; Chwae, Yong-Joon; Park, Hae-Sim; Shin, Yoo Seob

    2016-01-01

    Autophagy has been investigated for its involvement in inflammatory diseases, but its role in asthma has been little studied. This study aimed to explore the possible role of autophagy and its therapeutic potential in severe allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) on days 0 and 14, followed by primary OVA challenge on days 28–30. The mice received a secondary 1 or 2% OVA challenge on days 44–46. After the final OVA challenge, the mice were assessed for airway responsiveness (AHR), cell composition and cytokine levels in bronchoalveolar lavage fluid (BALF). LC3 expression in lung tissue was measured by western blot and immunofluorescence staining. Autophagosomes were detected by electron microscopy. 3-Methyladenine (3-MA) treatment and Atg5 knockdown were applied to investigate the potential role of autophagy in allergic asthma mice. AHR, inflammation in BALF and LC3 expression in lung tissue were significantly increased in the 2% OVA-challenged mice compared with the 1% OVA-challenged mice (P<0.05). In addition, eosinophils showed prominent formation of autophagosomes and increased LC3 expression compared with other inflammatory cells in BALF and lung tissue. After autophagy was inhibited by 3-MA and Atg5 shRNA treatment, AHR, eosinophilia, interleukin (IL)-5 levels in BALF and histological inflammatory findings were much improved. Finally, treatment with an anti-IL-5 antibody considerably reduced LC3 II expression in lung homogenates. Our findings suggest that autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. PMID:27364893

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

    PubMed

    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; Poynter, Matthew E

    2016-08-01

    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

  6. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.

    PubMed

    Johnson, Jill R; Folestad, Erika; Rowley, Jessica E; Noll, Elisa M; Walker, Simone A; Lloyd, Clare M; Rankin, Sara M; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-04-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607

  7. The Effects of Maekmoondong-Tang on Cockroach Extract-Induced Allergic Asthma

    PubMed Central

    Sohn, Sung-Hwa; Jung, Kyung-Hwa; Lee, Kun-young; Yeom, Yu Rim; Kim, Gae-Eun; Jung, Sungki; Jung, Heejae; Bae, Hyunsu

    2014-01-01

    Maekmoondong-tang (MMDT) has long been used in Asian countries to treat respiratory diseases. However, the precise mechanisms underlying its effects on asthma are unknown. This study was conducted to evaluate the protective effects of MMDT in a cockroach allergen (CKA-)induced animal model of allergic asthma. After being challenged with CKA, the number of macrophages, eosinophils, neutrophils, lymphocytes, and total cells in the bronchoalveolar lavage fluid (BALF) was evaluated. The Th2 specific cytokines IL-4, IL-5, and IL-13 were also analyzed in BALF along with IgE levels in serum. For histological analysis, hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and immunohistochemical staining were performed. In addition, airway hyperresponsiveness was assessed by noninvasive plethysmography. The cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in the MMDT-treated groups compared with the cockroach extract-injected (CKA) groups. In addition, the IgE, IL-4, IL-5, and IL-13 levels were significantly decreased in the MMDT group. MMDT treatment also significantly attenuated airway hyperresponsiveness. These results demonstrated that MMDT significantly reduced the hallmark signs of asthma: elevated serum IgE, airway eosinophilia, airway remodeling, mucus hypersecretion, and airway hyperresponsiveness. The remarkable antiasthmatic effects of MMDT suggest its therapeutic potential in allergic asthma treatment. PMID:24723965

  8. 'Real-life' effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review.

    PubMed

    Abraham, I; Alhossan, A; Lee, C S; Kutbi, H; MacDonald, K

    2016-05-01

    We reviewed 24 'real-life' effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short- and long-term benefit of anti-IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life - thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2-4 years, and the majority of omalizumab-treated patients may benefit for many years. Omalizumab has positive short- and long-term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes. PMID:26644231

  9. Thalidomide attenuates airway hyperresponsiveness and eosinophilic inflammation in a murine model of allergic asthma.

    PubMed

    Asano, Toshiaki; Kume, Hiroaki; Taki, Fumitaka; Ito, Satoru; Hasegawa, Yoshinori

    2010-01-01

    Asthma is characterized by chronic eosinophilic inflammation and hyperresponsiveness of the airways. We hypothesized that thalidomide, which has numerous immunomodulatory properties, may have anti-inflammatory effects in allergic asthma. BALB/c mice sensitized and challenged with ovalbumin (OVA) were treated orally with thalidomide (30, 100, or 300 mg/kg) or a vehicle. When thalidomide was administered to OVA-challenged mice, the number of eosinophils in bronchoalveolar lavage fluid (BALF) was significantly decreased. The numbers of inflammatory cells other than eosinophils were not reduced by thalidomide. Thalidomide inhibited the elevated levels of interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-alpha) in BALF by OVA challenges. Histological analysis of the lung revealed that both the infiltration of inflammatory cells and the hyperplasia of goblet cells were significantly suppressed by thalidomide treatment. Furthermore, thalidomide significantly inhibited the response to methacholine induced by OVA challenges. Taken together, thalidomide treatment decreased airway inflammation and hyperresponsiveness in a murine model of allergic asthma. These results might provide an opportunity for the development of novel therapeutics to treat severe asthma. PMID:20522972

  10. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

    PubMed Central

    Folestad, Erika; Rowley, Jessica E.; Noll, Elisa M.; Walker, Simone A.; Lloyd, Clare M.; Rankin, Sara M.; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-01-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607

  11. Tim1 and Tim3 are not essential for experimental allergic asthma

    PubMed Central

    Barlow, J L; Wong, S H; Ballantyne, S J; Jolin, H E; McKenzie, A N J

    2011-01-01

    Background Initial studies suggested that polymorphisms in Tim1 and Tim3 contribute to the development of airway hyperreactivity (AHR) in an acute mouse model of asthma. This was also mirrored in human genetic studies where polymorphisms in Tim1 and Tim3 have been associated with atopic populations. Objective Further studies using anti-Tim1 or -Tim3 antibodies, or Tim fusion proteins, have also suggested that these molecules may function as regulators of type-1 and type-2 immunity. However, their role in the development of AHR and airway inflammation remains unclear. Given the proposed roles for Tim1 and Tim3 in type-1 and type-2 responses, we sought to determine whether these molecules were important in regulating antigen-driven lung allergy and inflammation. Method We used Tim1- and Tim3-deficient mice and determined how the development of allergic lung inflammation was affected. Results AHR was induced normally in the absence of both Tim1 and Tim3, although Tim1-deficient mice did show a small but significant decrease in cell infiltration in the lung and blood eosinophilia. Although Tim3 was expressed on CD4+ T cells in the allergic lung, Tim1 expression was restricted to CD86+ B cells. Conclusions and clinical relevance Thus, Tim1 and Tim3 are not essential for the induction of the type-2 response in lung allergy. This is contrary to what was proposed in a number of other studies using neutralizing and activating antibodies and questions the clinical relevance of Tim1 and Tim3 for novel allergy therapies. Cite this as: J. L. Barlow, S. H. Wong, S. J. Ballantyne, H. E. Jolin and A. N. J. McKenzie, Clinical & Experimental Allergy, 2011 (41) 1012–1021. PMID:21470319

  12. Home air-conditioning, traffic exposure, and asthma and allergic symptoms among preschool children.

    PubMed

    Zuraimi, Mohamed Sultan; Tham, Kwok-Wai; Chew, Fook-Tim; Ooi, Peng-Lim; Koh, David

    2011-02-01

    Epidemiological data suggest that traffic exposures can influence asthma and allergic symptoms among preschool children; however, there is no information on risk reduction via home air-conditioning (AC). The aim of this study is to evaluate the associations of self-reported traffic densities with asthma and allergic symptoms among preschool children and determine whether AC is an effect modifier. A cross-sectional study adopting an expanded and modified ISAAC--International Study of Asthma and Allergies in Childhood conducted on randomly selected 2994 children living in homes without any indoor risk factors. Specific information on demographics, indoor home risk factors, and traffic variables were obtained. Adjusted prevalence ratios (PR) and 95% confidence interval (CI) were determined by Cox proportional hazard regression model with assumption of a constant risk period controlled for covariates. We found dose-response significant relationships between validated self-reported traffic densities and asthma and rhinitis symptoms. Among children sleeping in non-air-conditioned homes, there were stronger associations between asthma and rhinitis symptoms studied. PRs for heavy traffic density were 2.06 for wheeze (95% CI 0.97-4.38), 2.89 for asthma (1.14-7.32), 1.73 for rhinitis (1.00-2.99), and 3.39 for rhinoconjunctivitis (1.24-9.27). There were no associations found for children sleeping in air-conditioned homes. Our results suggest that AC in the bedroom modifies the health effects of traffic among preschool children. This finding suggests that attention should also be paid to ventilation characteristics of the homes to remediate health-related traffic pollution problems. PMID:20561230

  13. 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. PMID:26965110

  14. A systematic review of socioeconomic position in relation to asthma and allergic diseases.

    PubMed

    Uphoff, Eleonora; Cabieses, Báltica; Pinart, Mariona; Valdés, Macarena; Antó, Josep Maria; Wright, John

    2015-08-01

    The role of socioeconomic position (SEP) in the development of asthma and allergies is unclear, with some pointing to the risks of low SEP and other research pointing in the direction of higher SEP being associated with higher prevalence rates. The aim of this systematic review is to clarify associations between SEP and the prevalence of asthma and allergies. Out of 4407 records identified, 183 were included in the analysis. Low SEP was associated with a higher prevalence of asthma in 63% of the studies. Research on allergies, however, showed a positive association between higher SEP and illness in 66% of studies. Pooled estimates for the odds ratio of disease for the highest compared with the lowest SEP confirmed these results for asthma (unadjusted OR 1.38, 95% CI 1.37-1.39), allergies in general (OR 0.67, 95% CI 0.62-0.72), atopic dermatitis (unadjusted OR 0.72, 95% CI 0.61-0.83) and allergic rhinoconjunctivitis (unadjusted OR 0.52, 95% CI 0.46-0.59). Sensitivity analyses with a subsample of high-quality studies led to the same conclusion. Evidence from this systematic review suggests that asthma is associated with lower SEP, whereas the prevalence of allergies is associated with higher SEP. PMID:25537562

  15. Phthalate metabolites in urine and asthma, allergic rhinoconjunctivitis and atopic dermatitis in preschool children.

    PubMed

    Callesen, Michael; Bekö, Gabriel; Weschler, Charles J; Langer, Sarka; Brive, Lena; Clausen, Geo; Toftum, Jørn; Sigsgaard, Torben; Høst, Arne; Jensen, Tina Kold

    2014-07-01

    Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3-5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of "allergy friendly" products by parents of children with allergic disease in the current study in contrast to studies conducted earlier. PMID:24388279

  16. Effects of Swimming on the Inflammatory and Redox Response in a Model of Allergic Asthma.

    PubMed

    Brüggemann, T R; Ávila, L C M; Fortkamp, B; Greiffo, F R; Bobinski, F; Mazzardo-Martins, L; Martins, D F; Duarte, M M M F; Dafre, A; Santos, A R S; Silva, M D; Souza, L F; Vieira, R P; Hizume-Kunzler, D C

    2015-06-01

    In this study we hypothesized that swimming during sensitization phase could result in a preventive effect in mice with allergic asthma. Swiss mice were divided into 4 groups: Control and Swimming (non-sensitized), OVA and OVA+Swimming (sensitized). The allergic inflammation was induced by 2 intraperitoneal injections and 4 aerosol challenges using ovalbumin. Swimming sessions were performed at high intensity over 3 weeks. 48 h after the last challenge mice were euthanized. Swimming decreased OVA-increased total IgE, IL-1, IL-4, IL-5 and IL-6 levels, as well as the number of total cells, lymphocytes and eosinophils in bronchoalveolar lavage fluid, (p<0.05). Simultaneously, swimming also increased IL-10 and glutathione levels in the Swimming and OVA+Swimming groups (p<0.05). The levels of glutathione peroxidase and catalase were increased only in the Swimming group when compared to all groups (p<0.05). 21 days of swimming resulted in an attenuation of pulmonary allergic inflammation followed by an increase of glutathione levels in the OVA group. Swimming only increased the levels of glutathione peroxidase and catalase in non-sensitized mice (p<0.05). These data suggest that the pulmonary anti-inflammatory effects produced by 3 weeks of high-intensity swimming in this model of OVA-induced asthma may be, at least partly, modulated by reduced oxidative stress and increased IL-10 production. PMID:25837246

  17. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    SciTech Connect

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina; and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  18. Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

    PubMed

    Lee, Chen-Chen; Lee, Yueh-Lun; Wang, Chien-N; Tsai, Hsing-Chuan; Chiu, Chun-Lung; Liu, Leroy F; Lin, Hung-Yun; Wu, Reen

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation. PMID:26916919

  19. Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells.

    PubMed

    Mathias, Louisa J; Khong, Sacha M L; Spyroglou, Lisa; Payne, Natalie L; Siatskas, Christopher; Thorburn, Alison N; Boyd, Richard L; Heng, Tracy S P

    2013-12-15

    Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment. PMID:24249728

  20. Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells.

    PubMed

    Ou-Yang, Hai-Feng; Huang, Yun; Hu, Xing-Bin; Wu, Chang-Gui

    2011-12-01

    Mesenchymal stem cells (MSCs) have significant immunomodulatory effects in the development of acute lung inflammation and fibrosis. However, it is still unclear as to whether MSCs could attenuate allergic airway inflammation in a mouse model of asthma. We firstly investigated whether exogenous MSCs can relocate to lung tissues in asthmatic mice and analyzed the chemotactic mechanism. Then, we evaluated the in vivo immunomodulatory effect of exogenous MSCs in asthma. MSCs (2 × 10(6)) were administered through the tail vein to mice one day before the first airway challenge. Migration of MSCs was evaluated by flow cytometry. The immunomodulatory effect of MSCs was evaluated by cell counting in bronchoalveolar lavage fluid (BALF), histology, mast cell degranulation, airway hyperreactivity and cytokine profile in BALF. Exogenous MSCs can migrate to sites of inflammation in asthmatic mice through a stromal cell-derived factor-1α/CXCR4-dependent mechanism. MSCs can protect mice against a range of allergic airway inflammatory pathologies, including the infiltration of inflammatory cells, mast cell degranulation and airway hyperreactivity partly via shifting to a T-helper 1 (Th1) from a Th2 immune response to allergens. So, immunotherapy based on MSCs may be a feasible, efficient therapy for asthma. PMID:22114062

  1. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases.

    PubMed

    Miyata, Jun; Arita, Makoto

    2015-01-01

    Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found naturally in fish oil and are commonly thought to be anti-inflammatory nutrients, with protective effects in inflammatory diseases including asthma and allergies. The mechanisms of these effects remain mostly unknown but are of great interest for their potential therapeutic applications. Large numbers of epidemiological and observational studies investigating the effect of fish intake or omega-3 fatty acid supplementation during pregnancy, lactation, infancy, childhood, and adulthood on asthmatic and allergic outcomes have been conducted. They mostly indicate protective effects and suggest a causal relationship between decreased intake of fish oil in modernized diets and an increasing number of individuals with asthma or other allergic diseases. Specialized pro-resolving mediators (SPM: protectins, resolvins, and maresins) are generated from omega-3 fatty acids such as EPA and DHA via several enzymatic reactions. These mediators counter-regulate airway eosinophilic inflammation and promote the resolution of inflammation in vivo. Several reports have indicated that the biosynthesis of SPM is impaired, especially in severe asthma, which suggests that chronic inflammation in the lung might result from a resolution defect. This article focuses on the beneficial aspects of omega-3 fatty acids and offers recent insights into their bioactive metabolites including resolvins and protectins. PMID:25572556

  2. Link between environmental air pollution and allergic asthma: East meets West

    PubMed Central

    Zhang, Qingling; Qiu, Zhiming; Huang, Shau-Ku

    2015-01-01

    With the levels of outdoor air pollution from industrial and motor vehicle emissions rising rapidly in the fastly-industrializing countries of South East Asia, the prevalence of asthma and allergic diseases has also been increasing to match those in the West. Epidemiological and experimental exposure studies indicate a harmful impact of outdoor air pollution from vehicles and factories both on the development of allergic diseases and asthma and the increase in asthma symptoms and exacerbations. The level of outdoor pollution in Asia is much higher and more diverse than those encountered in Western countries. This may increase the impact of outdoor pollution on health, particularly lung health in Asia. This review discusses the constituents of air pollution in Asia with a special focus on studies in mainland China and Taiwan where the levels of pollution have reached high levels and where such high levels particularly in winter can cause a thick haze that reduces visibility. The onus remains on regulatory and public health authorities to curb the sources of pollution so that the health effects on the population particularly those with lung and cardiovascular diseases and with increased susceptibility can be mitigated. PMID:25694814

  3. Origin, Localization, and Immunoregulatory Properties of Pulmonary Phagocytes in Allergic Asthma

    PubMed Central

    Hoffmann, Franziska; Ender, Fanny; Schmudde, Inken; Lewkowich, Ian P.; Köhl, Jörg; König, Peter; Laumonnier, Yves

    2016-01-01

    Allergic asthma is a chronic inflammatory disease of the airways that is driven by maladaptive T helper 2 (Th2) and Th17 immune responses against harmless, airborne substances. Pulmonary phagocytes represent the first line of defense in the lung where they constantly sense the local environment for potential threats. They comprise two distinct cell types, i.e., macrophages and dendritic cells (DC) that differ in their origins and functions. Alveolar macrophages quickly take up most of the inhaled allergens, yet do not deliver their cargo to naive T cells sampling in draining lymph nodes. In contrast, pulmonary DCs instruct CD4+ T cells develop into Th2 and Th17 effectors, initiating the maladaptive immune responses toward harmless environmental substances observed in allergic individuals. Unraveling the mechanisms underlying this mistaken identity of harmless, airborne substances by innate immune cells is one of the great challenges in asthma research. The identification of different pulmonary DC subsets, their role in antigen uptake, migration to the draining lymph nodes, and their potential to instruct distinct T cell responses has set the stage to unravel this mystery. However, at this point, a detailed understanding of the spatiotemporal resolution of DC subset localization, allergen uptake, processing, autocrine and paracrine cellular crosstalk, and the humoral factors that define the activation status of DCs is still lacking. In addition to DCs, at least two distinct macrophage populations have been identified in the lung that are either located in the airway/alveolar lumen or in the interstitium. Recent data suggest that such populations can exert either pro- or anti-inflammatory functions. Similar to the DC subsets, detailed insights into the individual roles of alveolar and interstitial macrophages during the different phases of asthma development are still missing. Here, we will provide an update on the current understanding of the origin, localization

  4. Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma

    PubMed Central

    Brazier, Peter; Schauer, Uwe; Hamelmann, Eckard; Holmes, Steve; Pritchard, Clive; Warner, John O

    2016-01-01

    Introduction Chronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service (NHS). Temperature-controlled laminar airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on treatment option that is non-invasive and has been shown in clinical studies to improve quality of life for patients with poorly controlled allergic asthma. The objective of this study was to quantify the cost-effectiveness of TLA (Airsonett AB) technology as an add-on to standard asthma management drug therapy in the UK. Methods The main performance measure of interest is the incremental cost per quality-adjusted life year (QALY) for patients using TLA in addition to usual care versus usual care alone. The incremental cost of TLA use is based on an observational clinical study monitoring the incidence of exacerbations with treatment valued using NHS cost data. The clinical effectiveness, used to derive the incremental QALY data, is based on a randomised double-blind placebo-controlled clinical trial comprising participants with an equivalent asthma condition. Results For a clinical cohort of asthma patients as a whole, the incremental cost-effectiveness ratio (ICER) is £8998 per QALY gained, that is, within the £20 000/QALY cost-effectiveness benchmark used by the National Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates that ICER values range from £18 883/QALY for the least severe patients through to TLA being dominant, that is, cost saving as well as improving quality of life, for individuals with the most severe and poorly controlled asthma. Conclusions Based on our results, Airsonett TLA is a cost-effective addition to treatment options for stage 4/5 patients. For high-risk individuals with more severe and less well controlled asthma, the use of TLA therapy to reduce incidence of hospitalisation would be a cost

  5. 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...

  6. Impact of Atopy on Asthma and Allergic Rhinitis in the Cohort for Reality and Evolution of Adult Asthma in Korea

    PubMed Central

    Jang, An-Soo; Kim, Sang-Heon; Kim, Tae-Bum; Park, Heung-Woo; Kim, Sae-Hoon; Chang, Yoon-Seok; Lee, Jae Hyun; Cho, You Sook; Park, Jung Won; Nahm, Dong-Ho; Cho, Young-Joo; Cho, Sang-Heon; Yoon, Ho Joo; Choi, Byoung-Whui; Moon, Hee-Bom

    2013-01-01

    Purpose Atopy is an important cause of asthma. Few data on the prevalence of atopy or comparisons with clinical characteristics of asthma in Korean patients have been published. We evaluated the effects of atopy on clinical profiles and airway inflammation in Korean asthmatics. Methods We retrospectively enrolled 1,492 asthmatics from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) cohort who had undergone skin prick tests for aeroallergens. The patients' clinical characteristics, lung function, PC20, and sputum and blood inflammatory cell counts were compared based on the presence or absence of atopy. Atopy was defined as one or more positive reactions (A/H ratio >1) on a skin prick test. Results Among 11 aeroallergens, house dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus) were the most prevalent cause of a positive skin prick test. As compared with non-atopic asthmatics, atopic asthmatics showed early onset of the disease. Atopic patients with asthma had a higher FEV1, FVC, and FEV1/FVC as compared with non-atopic patients with asthma. In addition, asthmatics without atopy had more uncontrolled asthma (P=0.001) and severe rhinitis (P<0.05) as compared with atopic asthmatics. Smoking, as measured in pack years, was higher in the non-atopic asthmatics than in the atopic asthmatics. The erythrocyte sedimentation rate was higher in non-atopic asthmatics than in the atopic asthmatics and patients with non-atopic asthma had a higher sputum neutrophil count than did those with atopic asthma. Conclusions Our data indicate that atopic asthmatics had an early onset of disease and high IgE levels, while the non-atopic asthmatics had decreased lung function and a high sputum neutrophil count, suggesting that a different approach is needed to treat atopic asthma. PMID:23638312

  7. Probiotics for treatment and primary prevention of allergic diseases and asthma: looking back and moving forward.

    PubMed

    West, Christina E; Jenmalm, Maria C; Kozyrskyj, Anita L; Prescott, Susan L

    2016-06-01

    Microbial ecosystems cover the surface of the human body and it is becoming increasingly clear that our modern environment has profound effects on microbial composition and diversity. A dysbiotic gut microbiota has been associated with allergic diseases and asthma in cross-sectional and observational studies. In an attempt to restore this dysbiosis, probiotics have been evaluated in randomized controlled trials. Here, we review treatment and primary prevention studies, recent meta-analyses, and discuss the current understanding of the role of probiotics in this context. Many meta-analyses have shown a moderate benefit of probiotics for eczema prevention, whereas there is less evidence of a benefit for other allergic manifestations. Because of very low quality evidence and heterogeneity between studies, specific advice on the most effective regimens cannot yet be given - not even for eczema prevention. To be able to adopt results into specific recommendations, international expert organizations stress the need for well-designed studies. PMID:26821735

  8. Thuja orientalis reduces airway inflammation in ovalbumin-induced allergic asthma.

    PubMed

    Shin, In-Sik; Shin, Na-Rae; Jeon, Chan-Mi; Kwon, Ok-Kyoung; Hong, Ju-Mi; Kim, Hui-Seong; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2015-09-01

    Thuja orientalis (TO) may be used as a herbal remedy for the treatment of numerous inflammatory diseases. In the present study, the effects of TO were evaluated on airway inflammation in ovalbumin (OVA)‑induced allergic asthma and RAW264.7 murine macrophage cells. The effects of TO on the production of proinflammatory mediators, were determined in RAW264.7 cells that had been stimulated with lipopolysaccharide (LPS). Furthermore, an in vivo experiment was performed on mice that were sensitized to OVA and then received an OVA airway challenge. TO was administered by daily oral gavage at a dose of 30 mg/kg, 21‑23 days after the initial OVA sensitization. TO was shown to reduce nitric oxide production and reduce the relative mRNA expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)‑6, cyclooxygenase‑2, matrix metalloproteinase (MMP)‑9, and tumor necrosis factor‑α in RAW264.7 cells stimulated with LPS. In addition, TO markedly decreased the inflammatory cell counts in bronchial alveolar lavage fluid, reduced the levels of IL‑4, IL‑5, IL‑13, eotaxin and immunoglobulin E, and reduced airway hyperresponsivenes, in the OVA sensitized mice. Furthermore, TO attenuated airway inflammation and mucus hypersecretion, induced by the OVA challenge of the lung tissue. TO also reduced the expression of iNOS and MMP‑9 in lung tissue. In conclusion, TO exerted anti‑inflammatory effects in an OVA‑induced allergic asthma model, and in LPS‑stimulated RAW264.7 cells. These results suggest that TO may be a useful therapeutic agent for the treatment of inflammatory diseases, including allergic asthma. PMID:26063078

  9. Intratracheal instillation of pravastatin for the treatment of murine allergic asthma: a lung-targeted approach to deliver statins

    PubMed Central

    Zeki, Amir A; Bratt, Jennifer M; Chang, Kevin Y; Franzi, Lisa M; Ott, Sean; Silveria, Mark; Fiehn, Oliver; Last, Jerold A; Kenyon, Nicholas J

    2015-01-01

    Systemic treatment with statins mitigates allergic airway inflammation, TH2 cytokine production, epithelial mucus production, and airway hyperreactivity (AHR) in murine models of asthma. We hypothesized that pravastatin delivered intratracheally would be quantifiable in lung tissues using mass spectrometry, achieve high drug concentrations in the lung with minimal systemic absorption, and mitigate airway inflammation and structural changes induced by ovalbumin. Male BALB/c mice were sensitized to ovalbumin (OVA) over 4 weeks, then exposed to 1% OVA aerosol or filtered air (FA) over 2 weeks. Mice received intratracheal instillations of pravastatin before and after each OVA exposure (30 mg/kg). Ultra performance liquid chromatography – mass spectrometry was used to quantify plasma, lung, and bronchoalveolar lavage fluid (BALF) pravastatin concentration. Pravastatin was quantifiable in mouse plasma, lung tissue, and BALF (BALF > lung > plasma for OVA and FA groups). At these concentrations pravastatin inhibited airway goblet cell hyperplasia/metaplasia, and reduced BALF levels of cytokines TNFα and KC, but did not reduce BALF total leukocyte or eosinophil cell counts. While pravastatin did not mitigate AHR, it did inhibit airway hypersensitivity (AHS). In this proof-of-principle study, using novel mass spectrometry methods we show that pravastatin is quantifiable in tissues, achieves high levels in mouse lungs with minimal systemic absorption, and mitigates some pathological features of allergic asthma. Inhaled pravastatin may be beneficial for the treatment of asthma by having direct airway effects independent of a potent anti-inflammatory effect. Statins with greater lipophilicity may achieve better anti-inflammatory effects warranting further research. PMID:25969462

  10. Intratracheal instillation of pravastatin for the treatment of murine allergic asthma: a lung-targeted approach to deliver statins.

    PubMed

    Zeki, Amir A; Bratt, Jennifer M; Chang, Kevin Y; Franzi, Lisa M; Ott, Sean; Silveria, Mark; Fiehn, Oliver; Last, Jerold A; Kenyon, Nicholas J

    2015-05-11

    Systemic treatment with statins mitigates allergic airway inflammation, TH2 cytokine production, epithelial mucus production, and airway hyperreactivity (AHR) in murine models of asthma. We hypothesized that pravastatin delivered intratracheally would be quantifiable in lung tissues using mass spectrometry, achieve high drug concentrations in the lung with minimal systemic absorption, and mitigate airway inflammation and structural changes induced by ovalbumin. Male BALB/c mice were sensitized to ovalbumin (OVA) over 4 weeks, then exposed to 1% OVA aerosol or filtered air (FA) over 2 weeks. Mice received intratracheal instillations of pravastatin before and after each OVA exposure (30 mg/kg). Ultra performance liquid chromatography - mass spectrometry was used to quantify plasma, lung, and bronchoalveolar lavage fluid (BALF) pravastatin concentration. Pravastatin was quantifiable in mouse plasma, lung tissue, and BALF (BALF > lung > plasma for OVA and FA groups). At these concentrations pravastatin inhibited airway goblet cell hyperplasia/metaplasia, and reduced BALF levels of cytokines TNFα and KC, but did not reduce BALF total leukocyte or eosinophil cell counts. While pravastatin did not mitigate AHR, it did inhibit airway hypersensitivity (AHS). In this proof-of-principle study, using novel mass spectrometry methods we show that pravastatin is quantifiable in tissues, achieves high levels in mouse lungs with minimal systemic absorption, and mitigates some pathological features of allergic asthma. Inhaled pravastatin may be beneficial for the treatment of asthma by having direct airway effects independent of a potent anti-inflammatory effect. Statins with greater lipophilicity may achieve better anti-inflammatory effects warranting further research. PMID:25969462

  11. Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma.

    PubMed

    Piyadasa, Hadeesha; Altieri, Anthony; Basu, Sujata; Schwartz, Jacquie; Halayko, Andrew J; Mookherjee, Neeloffer

    2016-01-01

    House dust mite (HDM) challenge is commonly used in murine models of allergic asthma for preclinical pathophysiological studies. However, few studies define objective readouts or biomarkers in this model. In this study we characterized immune responses and defined molecular markers that are specifically altered after HDM challenge. In this murine model, we used repeated HDM challenge for two weeks which induced hallmarks of allergic asthma seen in humans, including airway hyper-responsiveness (AHR) and elevated levels of circulating total and HDM-specific IgE and IgG1. Kinetic studies showed that at least 24 h after last HDM challenge results in significant AHR along with eosinophil infiltration in the lungs. Histologic assessment of lung revealed increased epithelial thickness and goblet cell hyperplasia, in the absence of airway wall collagen deposition, suggesting ongoing tissue repair concomitant with acute allergic lung inflammation. Thus, this model may be suitable to delineate airway inflammation processes that precede airway remodeling and development of fixed airway obstruction. We observed that a panel of cytokines e.g. IFN-γ, IL-1β, IL-4, IL-5, IL-6, KC, TNF-α, IL-13, IL-33, MDC and TARC were elevated in lung tissue and bronchoalveolar fluid, indicating local lung inflammation. However, levels of these cytokines remained unchanged in serum, reflecting lack of systemic inflammation in this model. Based on these findings, we further monitored the expression of 84 selected genes in lung tissues by quantitative real-time PCR array, and identified 31 mRNAs that were significantly up-regulated in lung tissue from HDM-challenged mice. These included genes associated with human asthma (e.g. clca3, ear11, il-13, il-13ra2, il-10, il-21, arg1 and chia1) and leukocyte recruitment in the lungs (e.g. ccl11, ccl12 and ccl24). This study describes a biosignature to enable broad and systematic interrogation of molecular mechanisms and intervention strategies for

  12. Presence of other allergic disease modifies the effect of early childhood traffic-related air pollution exposure on asthma prevalence.

    PubMed

    Dell, Sharon D; Jerrett, Michael; Beckerman, Bernard; Brook, Jeffrey R; Foty, Richard G; Gilbert, Nicolas L; Marshall, Laura; Miller, J David; To, Teresa; Walter, Stephen D; Stieb, David M

    2014-04-01

    Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5-9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case-control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08-1.98; 1.37, 95% CI 1.00-1.86; and 1.60, 95% CI 1.09-2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10-1.89; 1.31, 95% CI 1.02-1.67; and 1.60, 95% CI 1.16-2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma. PMID:24472824

  13. Differential control of CD4+ T cell subsets by the PD-1/PD-L1 axis in allergic asthma

    PubMed Central

    McAlees, Jaclyn W.; Lajoie, Stephane; Dienger, Krista; Sproles, Alyssa A.; Richgels, Phoebe K.; Yang, Yanfen; Khodoun, Marat; Azuma, Miyuki; Yagita, Hideo; Fulkerson, Patricia C.; Wills-Karp, Marsha; Lewkowich, Ian P.

    2015-01-01

    Studies examining the role of PD-1 family members in allergic asthma have yielded conflicting results. Using a mouse model of allergic asthma, we find that blockade of PD-1/PD-L1 has distinct influences on different CD4+ T cell subsets. PD-1/PD-L1 blockade enhances AHR not by altering the magnitude of the underlying Th2 immune response, but by allowing the development of a concomitant Th17 immune response. Supporting differential CD4+ T cell responsiveness to PD-1-mediated inhibition, naïve PD-1−/− mice displayed elevated Th1 and Th17 levels, but diminished Th2 cytokine levels, ligation of PD-1 limited cytokine production by in vitro-polarized Th1 and Th17 cells, but slightly enhanced cytokine production by in vitro-polarized Th2 cells, and PD-1 ligation enhanced Th2 cytokine production by naïve T cells cultured under non-polarizing conditions. These data demonstrate that different CD4+ T cell subsets respond differentially to PD-1 ligation and may explain some of the variable results observed in control of allergic asthma by the PD-1 family members. As the PD-1/PD-L1 axis limits asthma severity by constraining Th17 cell activity, this suggests that severe allergic asthma may be associated with a defective PD-1/PD-L1 regulatory axis in some individuals. PMID:25630305

  14. Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US.

    PubMed

    Mudarri, David H

    2016-01-01

    Two foundational methods for estimating the total economic burden of disease are cost of illness (COI) and willingness to pay (WTP). WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$) of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3-4.7) billion for allergic rhinitis, $1.9 (1.1-2.3) billion for acute bronchitis, $15.1 (9.4-20.6) billion for asthma morbidity, and $1.7 (0.4-4.5) billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality. PMID:27313630

  15. Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US

    PubMed Central

    2016-01-01

    Two foundational methods for estimating the total economic burden of disease are cost of illness (COI) and willingness to pay (WTP). WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$) of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3–4.7) billion for allergic rhinitis, $1.9 (1.1–2.3) billion for acute bronchitis, $15.1 (9.4–20.6) billion for asthma morbidity, and $1.7 (0.4–4.5) billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality. PMID:27313630

  16. Ligustrazine improves blood circulation by suppressing Platelet activation in a rat model of allergic asthma.

    PubMed

    Wang, Yajuan; Zhu, Huizhi; Tong, Jiabing; Li, Zegeng

    2016-07-01

    Chuan-xiong (Ligusticum wallichii) is a traditional herbal medicine in Eastern Asia, but the effect of its active component ligustrazine remains unclear. We explored its effect and possible mechanism in a well-characterized rat model of allergic asthma. Ligustrazine suppressed bronchial hyper-responsiveness to methacholine, and suppressed lung inflammation in asthmatic rats. Ligustrazine exhibited potent immuno-modulatory and anti-inflammatory effects: it suppressed lymphocyte and eosinophil mobilization, and reduced cytokine IL-5 and IL-13 production significantly in lung tissues from asthmatic rats (P<0.05). Further histological examinations clearly demonstrated that ligustrazine improved blood circulation and ameliorated platelet activation, aggregation and adhesion, which induced sustained infiltration and activation of various inflammatory cells, including lymphocytes and eosinophils, followed by synthesis and release of a variety of pro-inflammatory mediators and cytokines. The present study suggests that ligustrazine is a potent agent for the treatment of allergic asthma due to its strong anti-inflammatory and immuno-modulatory properties. PMID:27362664

  17. Treatment of allergic asthma: Modulation of Th2 cells and their responses

    PubMed Central

    2011-01-01

    Atopic asthma is a chronic inflammatory pulmonary disease characterised by recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell-mediated inflammatory response in the airways. It is currently treated and, more or less, controlled depending on severity, with bronchodilators e.g. long-acting beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs such as corticosteroids (inhaled or oral), leukotriene modifiers, theophyline and anti-IgE therapy. Unfortunately, none of these treatments are curative and some asthmatic patients do not respond to intense anti-inflammatory therapies. Additionally, the use of long-term oral steroids has many undesired side effects. For this reason, novel and more effective drugs are needed. In this review, we focus on the CD4+ Th2 cells and their products as targets for the development of new drugs to add to the current armamentarium as adjuncts or as potential stand-alone treatments for allergic asthma. We argue that in early disease, the reduction or elimination of allergen-specific Th2 cells will reduce the consequences of repeated allergic inflammatory responses such as lung remodelling without causing generalised immunosuppression. PMID:21867534

  18. Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma.

    PubMed

    Wang, Wei; Li, Ping; Yang, Jiong

    2015-08-01

    Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate inflammatory and autoimmune diseases. The purpose of this study was to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma. IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qPCR). The frequencies of cytotoxic T cells (Tc)1, Tc2 and Tc17 cells were measured by flow cytometry. Plasma levels of IL-35, interferon (IFN)-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson's test. IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients and healthy controls. More importantly, plasma IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma. Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. PMID:26547705

  19. A critical role for C5L2 in the pathogenesis of experimental allergic asthma.

    PubMed

    Zhang, Xun; Schmudde, Inken; Laumonnier, Yves; Pandey, Manoj K; Clark, Jennifer R; König, Peter; Gerard, Norma P; Gerard, Craig; Wills-Karp, Marsha; Köhl, Jörg

    2010-12-01

    The complement fragment C5a plays dual roles in the development of experimental allergic asthma. It protects from pulmonary allergy by a regulatory effect on dendritic cells during allergen sensitization, but is proallergic during the effector phase. C5a can bind to two distinct receptors (i.e., C5a receptor and C5a receptor-like 2 [C5L2]). The functional role of C5L2 in vivo remains enigmatic. In this study, we show in two models of OVA- and house dust mite (HDM)-induced experimental allergic asthma that C5L2-deficient mice are protected from the development of airway hyperresponsiveness, Th2 cytokine production, eosinophilic airway inflammation, serum IgE, or mucus production. Surprisingly, HDM-induced experimental asthma in C5L2-deficient mice was associated with increased pulmonary IL-17A production and increased airway neutrophil numbers. To directly assess the role of C5L2 on myeloid dendritic cells (mDCs) during allergen sensitization, we performed single or repeated adoptive transfers of C5L2-deficient mDCs into wild-type mice. HDM-pulsed C5L2-deficient mDCs induced strong Th2 cytokine production, which was associated with marked IFN-γ and IL-17A production, decreased eosinophil numbers, and reduced IgE production as compared with HDM-pulsed mDCs from wild-type mice. HDM stimulation of C5L2(-/-) mDCs in vitro resulted in production of Th17-promoting cytokine IL-23, which was absent in wild-type mDCs. Our findings suggest that C5L2 acts at the mDC/T cell interface to control the development of Th1 and Th17 cells in response to airway HDM exposure. Furthermore, it drives Th2 immune responses independent of mDCs, suggesting a complex role for C5L2 in the development of experimental allergic asthma. PMID:20974988

  20. IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma.

    PubMed

    Böhm, Livia; Maxeiner, Joachim; Meyer-Martin, Helen; Reuter, Sebastian; Finotto, Susetta; Klein, Matthias; Schild, Hansjörg; Schmitt, Edgar; Bopp, Tobias; Taube, Christian

    2015-02-01

    Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells. PMID:25527785

  1. Mechanistic impact of outdoor air pollution on asthma and allergic diseases

    PubMed Central

    Zhang, Qingling; Qiu, Zhiming; Chung, Kian Fan

    2015-01-01

    Over the past decades, asthma and allergic diseases, such as allergic rhinitis and eczema, have become increasingly common, but the reason for this increased prevalence is still unclear. It has become apparent that genetic variation alone is not sufficient to account for the observed changes; rather, the changing environment, together with alterations in lifestyle and eating habits, are likely to have driven the increase in prevalence, and in some cases, severity of disease. This is particularly highlighted by recent awareness of, and concern about, the exposure to ubiquitous environmental pollutants, including chemicals with oxidant-generating capacities, and their impact on the human respiratory and immune systems. Indeed, several epidemiological studies have identified a variety of risk factors, including ambient pollutant gases and airborne particles, for the prevalence and the exacerbation of allergic diseases. However, the responsible pollutants remain unclear and the causal relationship has not been established. Recent studies of cellular and animal models have suggested several plausible mechanisms, with the most consistent observation being the direct effects of particle components on the generation of reactive oxygen species (ROS) and the resultant oxidative stress and inflammatory responses. This review attempts to highlight the experimental findings, with particular emphasis on several major mechanistic events initiated by exposure to particulate matters (PMs) in the exposure-disease relationship. PMID:25694815

  2. CARMA1 is necessary for optimal T cell responses in a murine model of allergic asthma.

    PubMed

    Ramadas, Ravisankar A; Roche, Marly I; Moon, James J; Ludwig, Thomas; Xavier, Ramnik J; Medoff, Benjamin D

    2011-12-15

    CARMA1 is a lymphocyte-specific scaffold protein necessary for T cell activation. Deletion of CARMA1 prevents the development of allergic airway inflammation in a mouse model of asthma due to a defect in naive T cell activation. However, it is unknown if CARMA1 is important for effector and memory T cell responses after the initial establishment of inflammation, findings that would be more relevant to asthma therapies targeted to CARMA1. In the current study, we sought to elucidate the role of CARMA1 in T cells that have been previously activated. Using mice in which floxed CARMA1 exons can be selectively deleted in T cells by OX40-driven Cre recombinase (OX40(+/Cre)CARMA1(F/F)), we report that CD4(+) T cells from these mice have impaired T cell reactivation responses and NF-κB signaling in vitro. Furthermore, in an in vivo recall model of allergic airway inflammation that is dependent on memory T cell function, OX40(+/Cre)CARMA1(F/F) mice have attenuated eosinophilic airway inflammation, T cell activation, and Th2 cytokine production. Using MHC class II tetramers, we demonstrate that the development and maintenance of Ag-specific memory T cells is not affected in OX40(+/Cre)CARMA1(F/F) mice. In addition, adoptive transfer of Th2-polarized OX40(+/Cre)CARMA1(F/F) Ag-specific CD4(+) T cells into wild-type mice induces markedly less airway inflammation in response to Ag challenge than transfer of wild-type Th2 cells. These data demonstrate a novel role for CARMA1 in effector and memory T cell responses and suggest that therapeutic strategies targeting CARMA1 could help treat chronic inflammatory disorders such as asthma. PMID:22075698

  3. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies

    PubMed Central

    2012-01-01

    Background Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5) are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. Methods We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs) or filtered air for 8 h (7:00 AM - 3:00 PM). Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF) and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Results Similar CAPs mass concentrations were generated in Detroit (542 μg/m3) and Grand Rapids (519 μg/m3). Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase), eosinophils (90%), and total protein (300%) compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Conclusions Despite inhalation exposure to the same mass concentration of urban PM2.5, disparate health

  4. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma.

    PubMed

    Yarova, Polina L; Stewart, Alecia L; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A; P Lowe, Alexander P; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J; Ford, William R; Broadley, Kenneth J; Rietdorf, Katja; Chang, Wenhan; Bin Khayat, Mohd E; Ward, Donald T; Corrigan, Christopher J; T Ward, Jeremy P; Kemp, Paul J; Pabelick, Christina M; Prakash, Y S; Riccardi, Daniela

    2015-04-22

    Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyperreactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

  5. Chrysin alleviates allergic inflammation and airway remodeling in a murine model of chronic asthma.

    PubMed

    Yao, Jing; Jiang, Mingzi; Zhang, Yunshi; Liu, Xing; Du, Qiang; Feng, Ganzhu

    2016-03-01

    Asthma is a chronic airway inflammatory disorder and progresses mainly due to airway remodeling. Chrysin, a natural flavonoid, has been reported to possess multiple biologic activities, including anti-inflammation, anti-oxidation and anti-proliferation. The present study aimed to investigate whether chrysin could relieve allergic airway inflammation and remodeling in a murine model of chronic asthma and the mechanism involved. The female BALB/c mice sensitized and challenged with ovalbumin (OVA) successfully developed airway hyperresponsiveness (AHR), inflammation and remodeling. The experimental data showed that chrysin could alleviate OVA-induced AHR. Chrysin could also reduce OVA-induced increases in the number of inflammatory cells, especially eosinophils, interleukin (IL) -4, and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum. The decreased interferon-γ (IFN-γ) level in BALF was also upregulated by chrysin. In addition, inflammatory cell infiltration, goblet cell hyperplasia and the expression of α-smooth muscle actin (α-SMA) around bronchioles were suppressed by chrysin. Furthermore, the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) could be decreased by chrysin, which are associated with airway smooth muscle cell (ASMC) proliferation. These results indicate the promising therapeutic effect of chrysin on chronic asthma, especially the progression of airway remodeling. PMID:26780233

  6. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

    PubMed Central

    Yarova, Polina L.; Stewart, Alecia L.; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A.; Lowe, Alexander P. P.; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C.; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J.; Ford, William R.; Broadley, Kenneth J.; Rietdorf, Katja; Chang, Wenhan; Khayat, Mohd E. Bin; Ward, Donald T.; Corrigan, Christopher J.; Ward, Jeremy P. T.; Kemp, Paul J.; Pabelick, Christina M.; Prakash, Y. S.; Riccardi, Daniela

    2016-01-01

    Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

  7. Asthma and other allergic diseases in 13-14-year-old schoolchildren in Urmia, Iran. [corrected].

    PubMed

    Rahimi Rad, M H; Hejazi, M E; Behrouzian, R

    2007-01-01

    We determined the prevalence and risk factors of asthma, allergic rhinitis and atopic eczema in 3000 13-14-year-old schoolchildren in Urmia, Islamic Republic of Iran. We used the International Study of Asthma and Allergies in Childhood (ISAAC) written and video questionnaires. With the written questionnaire, the prevalence of current symptoms (within the past 12 months) was: wheeze 14.5%, allergic rhinitis 23.6% and eczema 10.1%. Self-reported asthma ever was only 2.1%. With the video questionnaire, the prevalence of wheeze was lower; 7.4% for wheeze at rest ever and 4.6% during the past 12 months. Boys had a significantly higher prevalence for most items examined except for eczema. PMID:18290392

  8. Respiratory and allergic diseases: from upper respiratory tract infections to asthma.

    PubMed

    Jaber, Raja

    2002-06-01

    Patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions, and fruits and vegetables (at least five servings a day). Physicians may need to be more cautious when prescribing antibiotics to children in their first year of life when they are born to families with a history of atopy. More research is needed to establish whether supplementation with probiotics (lactobacillus and bifidobacterium) during the first year of life or after antibiotic use decreases the risk of developing asthma and allergic rhinitis. Despite a theoretic basis for the use of vitamin C supplements in asthmatic patients, the evidence is still equivocal, and long-term studies are needed. The evidence is stronger for exercise-induced asthma, in which the use of vitamin C supplementation at a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma. Long-term studies of fish oil and vitamin C are needed for more definite answers. For the patient interested in incorporating nutritional approaches, vitamin C and fish oils have a safe profile. However, aspirin-sensitive individuals should avoid fish oils, and red blood cell magnesium levels may help in making the decision whether to use additional magnesium supplements. Combination herbal formulas should be used in the treatment of asthma with medical supervision and in collaboration with an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia and gingko, may be used singly as adjuncts to a comprehensive plan of care if the patient and practitioner have an interest in trying them while staying alert for drug-herb interactions. No data on the long-term use of these single herbs in asthma exist. For the motivated

  9. Complete right lung agenesis presenting with bronchial asthma and allergic rhinitis.

    PubMed

    Kushwaha, Ram Avadh Singh; Ranganath, T G; Garg, Rajiv; Anand, Shipra

    2012-01-01

    A 26 year-old lady presented with episodic breathlessness, chest tightness, recurrent nasal obstruction and excessive sneezing, mainly during change of season along with opacity of the right hemithorax on chest x-ray. Further detailed work-up including spirometry, high-resolution CT scan of the thorax and fibre-optic bronchoscopy confirmed complete right lung agenesis in patients with bronchial asthma and allergic rhinitis. Complete control of symptoms was achieved with formeterol 6 μg and mometasone 200 μg (via dry powder inhaler) and intranasal fluticasone 50 μg (nasal spray) 2 puffs twice daily and oral montelukast 10 mg with levocetirizine 5 mg once daily. PMID:23001088

  10. Idiopathic Pulmonary Hemosiderosis With Allergic Asthma Diagnosis in a Pediatric Patient.

    PubMed

    Eldem, İrem; İleri, Talia; İnce, Elif; Asarcikli, Fikret; Pekpak, Esra; Çakmakli, Hasan F; Ceyhan, Koray; Uysal, Zümrüt

    2015-10-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder with unknown pathogenesis that usually presents in the first decade of life. As a result of diffuse alveolar hemorrhage, respiratory symptoms such as cough attacks, hemoptysis, dyspnea, and recurrent and refractory iron-deficiency anemia (IDA) are observed. We present an 8-year-old girl who was followed up with recurrent IDA and allergic asthma and later diagnosed with IPH. IPH was confirmed by the presence of hemosiderin-laden macrophages in bronchoalveolar lavage obtained by bronchoscopy and exclusion of the secondary causes of pulmonary hemosiderosis. Glucocorticoids and iron supplementation were started. Clinical and laboratory improvement was observed with therapy. Our case illustrates that refractory/recurrent IDA with any pulmonary symptoms may be the only presenting feature of IPH. PMID:26241728

  11. Phosphodiesterase 4B is essential for TH2-cell function and development of airway hyperresponsiveness in allergic asthma

    PubMed Central

    Catherine Jin, S.-L.; Goya, Sho; Nakae, Susumu; Wang, Dan; Bruss, Matthew; Hou, Chiaoyin; Umetsu, Dale; Conti, Marco

    2010-01-01

    Background Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. Objectives We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and TH2-driven inflammatory responses. Methods Wild-type and PDE4B−/− mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and TH2 cytokine production were determined in cultured bronchial lymph node cells. Results Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased TH2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, TH2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the TH1 cytokine IFN-γ was not affected in PDE4B−/− mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. Conclusion By relieving a cAMP-negative constraint, PDE4B plays an essential role in TH2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment. PMID:21047676

  12. Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice.

    PubMed

    Ren, Jiling; Hu, Lizhi; Yang, Jing; Yang, Liang; Gao, Fei; Lu, Ping; Fan, Mengyu; Zhu, Yunjuan; Liu, Junyan; Chen, Lingling; Gupta, Shimpy; Yang, Xi; Liu, Peimei

    2016-05-01

    Allergic asthma is a chronic inflammatory disease mediated by Th2 cell immune responses. Currently, immunotherapies based on immune deviation are attractive, preventive, and therapeutic strategies for asthma. Many studies have shown that intracellular bacterial infections such as mycobacteria and their components can suppress asthmatic reactions by enhancing Th1 responses, while helminth infections and their proteins can inhibit allergic asthma via immune regulation. However, some helminth proteins such as SmP40, the major egg antigen of Schistosoma mansoni, are found as Th1 type antigens. Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions. PMID:26840774

  13. Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

    PubMed Central

    Aoki, Haruka; Mogi, Chihiro; Okajima, Fumikazu

    2014-01-01

    An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR), infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs) in severe acidic pH (of less than 6.0)-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases. PMID:25197168

  14. Role of Tyk-2 in Th9 and Th17 cells in allergic asthma.

    PubMed

    Übel, Caroline; Graser, Anna; Koch, Sonja; Rieker, Ralf J; Lehr, Hans A; Müller, Mathias; Finotto, Susetta

    2014-01-01

    In a murine model of allergic asthma, we found that Tyk-2((-/-)) asthmatic mice have induced peribronchial collagen deposition, mucosal type mast cells in the lung, IRF4 and hyperproliferative lung Th2 CD4(+) effector T cells over-expressing IL-3, IL-4, IL-5, IL-10 and IL-13. We also observed increased Th9 cells expressing IL-9 and IL-10 as well as T helper cells expressing IL-6, IL-10 and IL-21 with a defect in IL-17A and IL-17F production. This T helper phenotype was accompanied by increased SOCS3 in the lung of Tyk-2 deficient asthmatic mice. Finally, in vivo treatment with rIL-17A inhibited local CD4(+)CD25(+)Foxp3(+) T regulatory cells as well as Th2 cytokines without affecting IL-9 in the lung. These results suggest a role of Tyk-2 in different subsets of T helper cells mediated by SOCS3 regulation that is relevant for the treatment of asthma, cancer and autoimmune diseases. PMID:25109392

  15. Subepithelial Accumulation of Versican in a Cockroach Antigen-Induced Murine Model of Allergic Asthma.

    PubMed

    Reeves, Stephen R; Kaber, Gernot; Sheih, Alyssa; Cheng, Georgiana; Aronica, Mark A; Merrilees, Mervyn J; Debley, Jason S; Frevert, Charles W; Ziegler, Steven F; Wight, Thomas N

    2016-06-01

    The extracellular matrix (ECM) is an important contributor to the asthmatic phenotype. Recent studies investigating airway inflammation have demonstrated an association between hyaluronan (HA) accumulation and inflammatory cell infiltration of the airways. The ECM proteoglycan versican interacts with HA and is important in the recruitment and activation of leukocytes during inflammation. We investigated the role of versican in the pathogenesis of asthmatic airway inflammation. Using cockroach antigen (CRA)-sensitized murine models of allergic asthma, we demonstrate increased subepithelial versican in the airways of CRA-treated mice that parallels subepithelial increases in HA and leukocyte infiltration. During the acute phase, CRA-treated mice displayed increased gene expression of the four major versican isoforms, as well as increased expression of HA synthases. Furthermore, in a murine model that examines both acute and chronic CRA exposure, versican staining peaked 8 days following CRA challenge and preceded subepithelial leukocyte infiltration. We also assessed versican and HA expression in differentiated primary human airway epithelial cells from asthmatic and healthy children. Increases in the expression of versican isoforms and HA synthases in these epithelial cells were similar to those of the murine model. These data indicate an important role for versican in the establishment of airway inflammation in asthma. PMID:27126823

  16. Sex-specific lung remodeling and inflammation changes in experimental allergic asthma.

    PubMed

    Antunes, Mariana A; Abreu, Soraia C; Silva, Adriana L; Parra-Cuentas, Edwin R; Ab'Saber, Alexandre M; Capelozzi, Vera L; Ferreira, Tatiana P T; Martins, Marco A; Silva, Patricia M R; Rocco, Patricia R M

    2010-09-01

    There is evidence that sex and sex hormones influence the severity of asthma. Airway and lung parenchyma remodeling and the relationship of ultrastructural changes to airway responsiveness and inflammation in male, female, and oophorectomized mice (OVX) were analyzed in experimental chronic allergic asthma. Seventy-two BALB/c mice were randomly divided into three groups (n=24/each): male, female, and OVX mice, whose ovaries were removed 7 days before the start of sensitization. Each group was further randomized to be sensitized and challenged with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, collagen fiber content in airways and lung parenchyma, the volume proportion of smooth muscle-specific actin in alveolar ducts and terminal bronchiole, the amount of matrix metalloproteinase (MMP)-2 and MMP-9, and the number of eosinophils and interleukin (IL)-4, IL-5, and transforming growth factor (TGF)-β levels in bronchoalveolar lavage fluid were higher in female than male OVA mice. The response of OVX mice was similar to that of males, except that IL-5 remained higher. Nevertheless, after OVA provocation, airway responsiveness to methacholine was higher in males compared with females and OVX mice. In conclusion, sex influenced the remodeling process, but the mechanisms responsible for airway hyperresponsiveness seemed to differ from those related to remodeling. PMID:20634353

  17. The histamine H4 -receptor (H4 R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice.

    PubMed

    Hartwig, Christina; Munder, Antje; Glage, Silke; Wedekind, Dirk; Schenk, Heiko; Seifert, Roland; Neumann, Detlef

    2015-04-01

    Via the histamine H4 -receptor (H4 R), histamine promotes the pathogenesis of experimental allergic asthma in mice. Application of H4 R antagonists during sensitization as well as during provocation reduces the severity of the disease. However, the specific cell types functionally expressing H4 R in experimental allergic asthma have not been well characterized in vivo. In this study, we identified the cell type(s) responsible for H4 R activity in experimental asthma and related physiological mechanisms. Using H4 R-deficient mice, we studied the role of H4 R in the sensitization and effector phase. DCs lacking H4 R expression during the in vitro sensitization reaction resulted in effector T cells unable to induce an entire eosinophilic inflammation in the lung upon adoptive transfer in vivo. Recipient mice lacking H4 R expression, which were adoptively transferred with H4 R(+/+) T cells polarized in the presence of H4 R(+/+) DCs, showed reduced signs of inflammation and ameliorated lung function. Here, we provide in vivo evidence that in experimental asthma in mice the H4 R specifically regulates activation of DCs during sensitization, while in the effector phase the H4 R is active in cells involved in the activation of eosinophils, and possibly other cells. A putative therapy targeting the H4 R may be an option for asthma patients developing IL-5-dependent eosinophilia. PMID:25501767

  18. Prevalence and risk factors of asthma and allergic diseases in primary schoolchildren living in Bushehr, Iran: phase I, III ISAAC protocol.

    PubMed

    Farrokhi, Shokrollah; Gheybi, Mohammad Kazzem; Movahhed, Ali; Dehdari, Reyhaneh; Gooya, Mostafa; Keshvari, Saman; Gholampour, Hossein; Mansourian, Zohreh; Khosravi, Yasaman; Ghahramani, Forough; Zandi, Sahar; Etemadan, Razieh; Tahmasebi, Rahim; Reaisi, Alireza; Keshmiri, Saeed; Fadaizadeh, Lida; Masjedi, Mohammad Reza

    2014-10-01

    Asthma and allergic diseases present a major health burden. Information on the prevalence of these diseases indicates that these diseases are increasing in various parts of the world. It was hoped that this study would be helpful to health system policy-makers in planning allergy prevention programs in the region.The prevalence of asthma and allergic diseases and relation between the various risk factors involved were assessed among schoolchildren in the city of Bushehr, Iran. The ISAAC Phase I and III questionnaires were completed by parents of 1280 children aged 6-7 years and self-completed by 1115 students aged 13-14 years.The prevalence of atopic eczema, allergic rhinitis and asthma among 6-7 year-old students were 12.1%, 11.8% and 6.7%, respectively. While, the prevalence of these diseases among 13-14 year-old students were found to be 19%, 30% and 7.6%, respectively. There was an association between asthma and allergic rhinitis as well as eczema (p<0.05). Consumption of fast food as a risk factor was significantly associated with asthma (p=0.03).The prevalence of asthma and allergic diseases was high among schoolchildren in the city of Bushehr, Iran. Also an association was observed between the fast food consumption and asthma. PMID:25150076

  19. Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma

    PubMed Central

    Ryman-Rasmussen, Jessica P.; Tewksbury, Earl W.; Moss, Owen R.; Cesta, Mark F.; Wong, Brian A.; Bonner, James C.

    2009-01-01

    Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT. PMID:18787175

  20. Exposure to Triclosan Augments the Allergic Response to Ovalbumin in a Mouse Model of Asthma

    PubMed Central

    Anderson, Stacey E.; Franko, Jennifer; Kashon, Michael L.; Anderson, Katie L.; Hubbs, Ann F.; Lukomska, Ewa; Meade, B. Jean

    2015-01-01

    During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375–1.5 mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 μg) and aluminum hydroxide (0.5 mg) on days 1 and 10 and challenged with OVA (125 μg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens. PMID:23192912

  1. Exposure to triclosan augments the allergic response to ovalbumin in a mouse model of asthma.

    PubMed

    Anderson, Stacey E; Franko, Jennifer; Kashon, Michael L; Anderson, Katie L; Hubbs, Ann F; Lukomska, Ewa; Meade, B Jean

    2013-03-01

    During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375-1.5mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 µg) and aluminum hydroxide (0.5mg) on days 1 and 10 and challenged with OVA (125 µg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens. PMID:23192912

  2. The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients.

    PubMed

    Liu, Jing Nan; Shin, Yoo Seob; Yoo, Hye-Soo; Nam, Young Hee; Jin, Hyun Jung; Ye, Young-Min; Nahm, Dong-Ho; Park, Hae-Sim

    2014-05-01

    Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammation pathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthma with rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88 healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcal superantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameters were retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%, and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, and TSST-1 were also significantly higher in group I (0.300±1.533 kU/L, 0.663±2.933 kU/L, and 0.581±1.931 kU/L) and group II (0.502±2.011 kU/L, 0.695±3.337 kU/L, and 1.067±4.688 kU/L) compared to those in group III (0.03±0.133 kU/L, 0.03±0.14 kU/L, and 0.028±0.112 kU/L). The prevalence of serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higher in patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE to TSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR and AR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation. PMID:24843803

  3. No exacerbation but impaired anti-viral mechanisms in a rhinovirus-chronic allergic asthma mouse model.

    PubMed

    Rochlitzer, Sabine; Hoymann, Heinz-Gerd; Müller, Meike; Braun, Armin

    2014-01-01

    Severe asthma and viral-induced asthma exacerbations represent a high unmet medical need as no therapy is currently available for these patients. HRV (human rhinovirus) is prominently associated with asthma exacerbations in humans. The aim of the present study was to establish a mouse model of severe asthma with additional rhinovirus infection to investigate the interplay between chronic allergic airway inflammation and acute respiratory viral infection. Balb/c mice were sensitized with HDM (house dust mite) extract (25 μg in 50 μl of saline) by i.n. (intranasal) delivery to the lung over 7 weeks. HRV1B (HRV serotype 1B) inoculation was performed i.n. on the last 3 days. Therapeutic treatment with FP (fluticasone propionate) was performed to assess steroid efficacy. Lung resistance was measured invasively to assess AHR (airway hyper-responsiveness). BAL (bronchoalveolar lavage) differential cell count, cytokines, lung histology and the proliferative and cytokine response of MLN (mediastinal lymph node) cells upon in vitro restimulation were analysed. Chronic HDM application induced a strong Th2-skewed eosinophilic airway inflammation and AHR, which was not exacerbated by superimposed HRV1B infection. Therapeutic steroid intervention in the chronic HDM model reduced BAL eosinophil cell counts, cytokine levels and AHR, while neutrophil numbers were unaffected. Steroid efficacy against inflammatory readouts was maintained during additional HRV1B infection. Animals with chronic allergic airway inflammation exhibited a diminished immune response towards superimposed HRV1B infection compared with HRV1B alone, as induction of the anti-viral and pro-inflammatory cytokines IFN (interferon)-α, IFN-γ and IL (interleukin)-12 were suppressed. Although superimposed HRV1B infection did not provoke asthma exacerbation in this severe model, a deficient anti-viral immune response to HRV1B was present under chronic allergic airway inflammatory conditions. Thus, this model is

  4. A study of granulocyte respiratory burst in patients with allergic bronchial asthma.

    PubMed

    Vargas, L; Patiño, P J; Montoya, F; Vanegas, A C; Echavarría, A; García de Olarte, D

    1998-02-01

    The respiratory burst of phagocytes plays an important role in the tissue damage that accompanies the inflammatory response. One of these conditions is allergic bronchial asthma, therefore, to evaluate the activation state of peripheral granulocytes the generation of reactive oxygen metabolites was evaluated using Luminol-enhanced chemiluminescence (LCL) and reduction of cytochrome C by superoxide. The resting granulocytes of the asthmatic patients under crisis showed a higher LCL compared to the noncrisis patients and control subjects. The granulocytes stimulated with PMA presented a significant increase in the respiratory burst in both groups of asthmatics. The granulocytes of noncrisis asthmatics challenged with Ops-Zym and with fMLP + Ops-Zym showed a higher metabolic activity, whereas the asthmatics under crisis presented no difference between reactive oxygen generation and that of the control group. The quantitative analysis of superoxide generation by granulocytes of the same patients did not show differences among the groups. Our findings suggest that the granulocytes of crisis and noncrisis asthmatics seem to be in a hyperreactive state and with a higher metabolic response when compared to the control group. However, the patients present a different behavior depending on stimulus used to activate cells. This could indicate that in peripheral blood exist different granulocyte populations depending on the inflammatory response taking place in the respiratory tract. PMID:9484649

  5. Intranasal mite allergen induces allergic asthma-like responses in NC/Nga mice.

    PubMed

    Shibamori, Masafumi; Ogino, Keiki; Kambayashi, Yasuhiro; Ishiyama, Hironobu

    2006-01-25

    Airway responses induced by intranasal administration of mite allergen without adjuvant were studied in NC/Nga mice. A crude extract of Dermatophagoides farinae (Df) was administered for 5 consecutive days and a single intranasal challenge booster dose was given 1 week after the last sensitization. 24 h after the single challenge, the airway hyperresponsiveness (AHR) was measured and the bronchoalveolar lavage fluid (BALF) was analyzed for numbers of eosinophils and neutrophils, and both cytokine and chemokine levels. There were marked increases in number of eosinophils in the BALF, AHR, Th2 cytokines (IL-5 and IL-13), and chemokine (eotaxin-1 and eotaxin-2) levels in the BALF following Df exposure. C57BL/6N, A/J, BALB/c, and CBA/JN mouse strains were also exposed to Df crude extract, but all of the measured responses were strongest in NC/Nga mice. Furthermore, Df-exposed NC/Nga mice showed the goblet cell hyperplasia, pulmonary eosinophilic inflammation, and increases in both total serum IgE and Df-specific IgG1. After intranasal exposure of NC/Nga mice to crude extract of Dermatophagoides pteronyssinus, the BALF eosinophilia and AHR were similar to responses induced by Df. None of the study parameters were increased in response to intranasal exposure to ovalbumin. These data demonstrated that NC/Nga mice developed allergic asthma-like responses after intranasal exposure to mite allergens. PMID:16229861

  6. The immunoregulatory and fibrotic roles of activin A in allergic asthma

    PubMed Central

    Hardy, C L; Rolland, J M; O'Hehir, R E

    2015-01-01

    Activin A, a member of the TGF-β superfamily of cytokines, was originally identified as an inducer of follicle stimulating hormone release, but has since been ascribed roles in normal physiological processes, as an immunoregulatory cytokine and as a driver of fibrosis. In the last 10–15 years, it has also become abundantly clear that activin A plays an important role in the regulation of asthmatic inflammation and airway remodelling. This review provides a brief introduction to the activin A/TGF-β superfamily, focussing on the regulation of receptors and signalling pathways. We examine the contradictory evidence for generalized pro- vs. anti-inflammatory effects of activin A in inflammation, before appraising its role in asthmatic inflammation and airway remodelling specifically by evaluating data from both murine models and clinical studies. We identify key issues to be addressed, paving the way for safe exploitation of modulation of activin A function for treatment of allergic asthma and other inflammatory lung diseases. PMID:25962695

  7. Zingiber mioga (Thunb.) Roscoe attenuates allergic asthma induced by ovalbumin challenge.

    PubMed

    Shin, Na-Rae; Shin, In-Sik; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Hui-Seong; Oh, Sei-Ryang; Hahn, Kyu-Woung; Ahn, Kyung-Seop

    2015-09-01

    Zingiber mioga (Thunb.) Roscoe (ZM) is a traditional medicine, used to treat inflammatory diseases. The present study aimed to evaluate the inhibitory effects of ZM on the inflammatory response in lipopolysaccharide (LPS)‑stimulated RAW264.7 murine macrophage cells and in a mouse model of ovalbumin (OVA)‑induced allergic asthma. Mice received OVA sensitization on day 0 and 14, and were challenged with OVA between days 21 and 23. ZM was administered to the mice at a dose of 30 mg/kg, 1 h prior to OVA challenge. In LPS‑stimulated RAW264.7 cells, ZM significantly decreased nitric oxide (NO) and tumor necrosis factor (TNF)‑α production in a concentration‑dependent manner, and mRNA expression of inducible NO synthase (iNOS), TNF‑α and matrix metalloproteinase (MMP)‑9 was reduced. In addition, treatment with ZM decreased the inflammatory cell count in bronchoalveolar lavage fluid from the mice, and reduced the expression of interleukin (IL)‑4, IL‑5, IL‑13, eotaxin and immunoglobulin E. ZM also reduced airway hyperresponsiveness in OVA‑challenged mice, and attenuated the infiltration of inflammatory cells and mucus production in the airways, with a decrease in the expression of iNOS and MMP‑9 in lung tissue. In conclusion, the results of the present study indicate that ZM effectively inhibits inflammatory responses. Therefore, it may be that ZM has potential as a therapeutic agent for use in inflammatory diseases. PMID:26063513

  8. Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study

    PubMed Central

    Matricardi, Paolo M; Rosmini, Francesco; Riondino, Silvia; Fortini, Michele; Ferrigno, Luigina; Rapicetta, Maria; Bonini, Sergio

    2000-01-01

    Objective To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. Design Retrospective case-control study. Participants 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. Setting Air force school in Caserta, Italy. Main outcome measures Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis. Results Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18% v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0.70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). Conclusion Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries. PMID:10669445

  9. Glutathione modulation during sensitization as well as challenge phase regulates airway reactivity and inflammation in mouse model of allergic asthma.

    PubMed

    Nadeem, Ahmed; Siddiqui, Nahid; Alharbi, Naif O; Alharbi, Mohammad M; Imam, Faisal; Sayed-Ahmed, Mohamed M

    2014-08-01

    Glutathione, being a major intracellular redox regulator has been shown to be implicated in regulation of airway reactivity and inflammation. However, no study so far has investigated the effect of glutathione depletion/repletion during sensitization and challenge phases separately, which could provide an important insight into the pathophysiology of allergic asthma. The aim of the present study was to evaluate the role of glutathione depletion/repletion during sensitization and challenge phases separately in a mouse model of allergic asthma. Buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase or N-acetyl cysteine (NAC), a thiol donor were used for depletion or repletion of glutathione levels respectively during both sensitization and challenge phases separately followed by assessment of airway reactivity, inflammation and oxidant-antioxidant balance in allergic mice. Depletion of glutathione with BSO during sensitization as well as challenge phase worsened allergen induced airway reactivity/inflammation and caused greater oxidant-antioxidant imbalance as reflected by increased NADPH oxidase expression/reactive oxygen species (ROS) generation/lipid peroxides formation and decreased total antioxidant capacity. On the other hand, repletion of glutathione pool by NAC during sensitization and challenge phases counteracted allergen induced airway reactivity/inflammation and restored oxidant-antioxidant balance through a decrease in NADPH oxidase expression/ROS generation/lipid peroxides formation and increase in total antioxidant capacity. Taken together, these findings suggest that depletion or repletion of glutathione exacerbates or ameliorates allergic asthma respectively by regulation of airway oxidant-antioxidant balance. This might have implications towards increased predisposition to allergy by glutathione depleting environmental pollutants. PMID:24742380

  10. Fullerene carbon-70 derivatives dampen anaphylaxis and allergic asthma pathogenesis in mice

    NASA Astrophysics Data System (ADS)

    Norton, Sarah Brooke

    Fullerenes are carbon nanospheres that can be solublized by the addition of polar chemical groups to the carbon cage, forming fullerene derivatives. One specifically derivatized fullerene compound, termed C 70-Tetragylocolate (C70-TGA), has been shown to stabilize mast cell responses in vitro thus we hypothesized it may have an effect on mast cell-driven diseases such as asthma and systemic anaphylaxis. To observe the effects of C70-TGA on systemic anaphylaxis, mice were subjected to a model of passive systemic anaphylaxis. In this model, mice were injected with DNP-specific IgE 16 hours prior to challenge, then treated with C 70-TGA. Immediately prior to DNP challenge, mice were subjected to a second injection of C70-TGA. Following DNP challenge, body temperature was recorded and blood was collected for quantitation of histamine levels. Treatment with C70-TGA significantly reduced body temperature drop associated with systemic anaphylaxis and serum histamine levels. To observe the effects of C70-TGA on chronic features of asthma in vivo, we utilized a heavily MC influenced model of asthma pathogenesis. Mice were sensitized by intraperitoneal (i.p.) injection of ovalbumin (OVA) in saline, challenged intranasally (i.n.) with OVA, and one of two treatment strategies was pursued. In one, C70-TGA was given i.n. throughout disease development. In the other, C70-TGA was given following an initial set of challenges to allow disease to develop prior to treatment; mice were then re-challenged with OVA to assess the effect on established disease. We found that C70-TGA treatment significantly reduced airway inflammation and eosinophilia and dramatically reduced bronchoconstriction in either model. Cytokines IL-4 and IL-5 and serum IgE levels are significantly reduced in C70-TGA treated animals. Interestingly, we also saw an increase in the anti-inflammatory eicosanoid 11, 12-epoxyeicosatreinoic acid (11,12-EET) in the BAL fluid, suggesting the involvement of this mediator in

  11. [Comparative characterization of the microflora of the upper respiratory tract mucous membranes in bronchial asthma and allergic persistent rhinitis].

    PubMed

    Romanenko, E E; Baturo, A P; Ulisko, I N

    2005-01-01

    A total of 250 patients with diagnosed bronchial asthma (BA) were examined by microbiological methods. Among them--188 children and 62 adults. In 87 patients the microflora of nasal mucosa was studied, in 40--of pharynx only and in 123 patients--both the nasal and the pharynx. For comparative analysis earlier data obtained in 69 patients with persistent allergic rhinitis (PAR) were used. The cultures isolated from the nasal mucosa of BA patients were shown to number 18 genera and 42 species, while among those isolated from pharynx mucosa 20 genera and 40 species. Monocultures were isolated from the nasal mucosa only in 23% of the examined patients and from the pharynx mucosa--only in 1.42%. Associations with different numbers of components were isolated from nasal and pharynx mucosa (2 to 6, 2 to 8 respectively). Staphylococcus aureus was regarded as the main species of nasal biocenosis in BA and PAR, as well as pharynx biocenosis in BA. Besides, in BA other Staphylococcus species (schleiferi, caprae, capitis, hominis, etc.), reversely related to the main species, could be isolated from both mucous membranes. Similarities and differences in microflora of biocenoses in both nosological forms, confirming links between PAR and BA, are considered. PMID:15881942

  12. Differentiating Asthma Phenotypes in Young Adults through Polyclonal Cytokine Profiles

    PubMed Central

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

    2014-01-01

    Background Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiological and clinical studies. While allergic asthma and non-allergic asthma are frequently combined into one disease category in observational research and clinical trials, few studies have investigated the extent to which these two separate phenotypes are associated with distinct cytokine immunological profiles in a representative young adult population. Objective To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and non-allergic asthma among a population-based birth cohort evaluated as young adults. Methods Subjects included 18–21 year-old members (n=540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. PMA-stimulated whole blood IL4, IL5, IL10, IL12, IL13, IL17A, IL17F, IL22 and IFNγ secretory responses were analyzed for associations comparing participants with allergic versus non-allergic asthma phenotypes to those without asthma. Results Th2-polarized responses, measured as higher mean IL5 and IL13 secretion and lower ratios of IFNγ and IL12 to three Th2 cytokines IL4, IL5, or IL13, were observed only in allergic asthmatics. Non-allergic asthma was associated with Th1-polarized responses including higher adjusted IFNγ secretion compared to both allergic asthmatics and surprisingly, to those without asthma [OR=2.5 (1.2–5.1), p<0.01]. Conclusions As expected, young adults with a history of an allergic asthma phenotype exhibit a Th2-polarized cytokine response after polyclonal stimulation. However, Th1-polarization was observed in subjects with a history of non-allergic asthma. Allergic and non-allergic asthma are associated with etiologically distinct immune endotypes underscoring the importance of discriminating these endotypes in research analyses and clinical management. PMID:24801891

  13. Hyaluronan stimulates ex vivo B lymphocyte chemotaxis and cytokine production in a murine model of fungal allergic asthma.

    PubMed

    Ghosh, Sumit; Hoselton, Scott A; Wanjara, Steve B; Carlson, Jennifer; McCarthy, James B; Dorsam, Glenn P; Schuh, Jane M

    2015-07-01

    Allergic asthma is a chronic inflammatory disease of the airways characterized by excessive eosinophilic and lymphocytic inflammation with associated changes in the extracellular matrix (ECM) resulting in airway wall remodeling. Hyaluronan (HA) is a nonsulfated glycosaminoglycan ECM component that functions as a structural cushion in its high molecular mass (HMM) but has been implicated in metastasis and other disease processes when it is degraded to smaller fragments. However, relatively little is known about the role HA in mediating inflammatory responses in allergy and asthma. In the present study, we used a murine Aspergillus fumigatus inhalational model to mimic human disease. After observing in vivo that a robust B cell recruitment followed a massive eosinophilic egress to the lumen of the allergic lung and corresponded with the detection of low molecular mass HA (LMM HA), we examined the effect of HA on B cell chemotaxis and cytokine production in the ex vivo studies. We found that LMM HA functioned through a CD44-mediated mechanism to elicit chemotaxis of B lymphocytes, while high molecular mass HA (HMM HA) had little effect. LMM HA, but not HMM HA, also elicited the production of IL-10 and TGF-β1 in these cells. Taken together, these findings demonstrate a critical role for ECM components in mediating leukocyte migration and function which are critical to the maintenance of allergic inflammatory responses. PMID:25698348

  14. WORKSHOP ON STATUS OF TEST METHODS FOR ASSESSING POTENTIAL OF CHEMICALS TO INDUCE RESPIRATORY ALLERGIC REACTIONS

    EPA Science Inventory

    Because of the association between allergy and asthma and the increasing incidence of morbidity and mortality due to asthma, there is growing concern over the potential of industrial chemicals to produce allergic reactions in the respiratory tract. Two classes of chemicals have b...

  15. Inhibitory effects of Pycnogenol® (French maritime pine bark extract) on airway inflammation in ovalbumin-induced allergic asthma.

    PubMed

    Shin, In-Sik; Shin, Na-Rae; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Jong-Choon; Oh, Sei-Ryang; Hahn, Kyu-Woung; Ahn, Kyung-Seop

    2013-12-01

    Pycnogenol® (PYC) is a standardized extracts from the bark of the French maritime pine (Pinus maritime) and used as a herbal remedy for various diseases. In this study, we evaluated the effects of PYC on airway inflammation using a model of ovalbumin (OVA)-induced allergic asthma and RAW264.7 cells. PYC decreased nitric oxide production and reduced the interleukine (IL)-1β and IL-6 levels in LPS-stimulated RAW264.7 cells. PYC also reduced the expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 and enhanced the expression of hemeoxygenase (HO)-1. In the in vivo experiment, PYC decreased the inflammatory cell count and the levels of IL-4, IL-5, IL-13, and immunoglobulin (Ig) E in BALF or serum. These results are consistent with the histological analysis findings, which showed that PYC attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, PYC enhanced the expression of HO-1. In contrast, PYC inhibited the elevated expression of iNOS and MMP-9 proteins induced by OVA challenge. In conclusion, PYC exhibits protective effects against OVA-induced asthma and LPS-stimulated RAW264.7 cells. These results suggest that PYC has potential as a therapeutic agent for the treatment of allergic asthma. PMID:24120901

  16. Alveolar macrophage-derived vascular endothelial growth factor contributes to allergic airway inflammation in a mouse asthma model.

    PubMed

    Song, C; Ma, H; Yao, C; Tao, X; Gan, H

    2012-06-01

    Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor that correlates with vascular permeability and remodelling in asthma. Recently, alveolar macrophages (AM) were shown to be an important source of VEGF during lung injury. Our previous studies demonstrated that AM are an important subset of macrophages in the initiation of asthmatic symptoms. Here, we further investigated whether AM-derived VEGF was required for allergic airway inflammation in asthma. In this study, we reported that the expression of VEGF in AM was significantly increased after allergen challenge. Depleting AM or neutralizing VEGF in alveolus prevented ovalbumin (OVA)-induced asthma-related inflammation by inhibiting the infiltration of inflammatory cells in the lung, reduced the level of the cytokines, IL-4, IL-5, and IL-13, in the bronchoalveolar lavage fluid (BALF) and decreased airway hyperresponsiveness (AHR). Moreover, the inhibition of miR-20b increased the protein level of VEGF in normal AM; conversely, increasing miR-20b in asthmatic AM resulted in decreased VEGF protein levels. These findings suggest that AM-derived VEGF is necessary for allergic airway inflammation in asthmatic mice and miR-20b negatively regulates this expression. PMID:22324377

  17. Increased Mast Cell Density and Airway Responses to Allergic and Non-Allergic Stimuli in a Sheep Model of Chronic Asthma

    PubMed Central

    Van der Velden, Joanne; Barker, Donna; Barcham, Garry; Koumoundouros, Emmanuel; Snibson, Kenneth

    2012-01-01

    Background Increased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen. Methodology/Principal Findings MC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MCT and MCTC respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase. MCT and MCTC density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MCTC/MCT ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MCT and MCTC density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MCT density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01). Conclusions MCT and MCTC density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation. PMID:22606346

  18. Associations between home dampness and presence of molds with asthma and allergic symptoms among young children in the tropics.

    PubMed

    Tham, Kwok Wai; Zuraimi, Mohamed Sultan; Koh, David; Chew, Fook Tim; Ooi, Peng Lim

    2007-08-01

    Existing literature has shown that home dampness increases indoor mold burden and is associated with increased allergic symptoms among young children in temperate environments. There is no report of any studies of similar nature in the tropics where conditions are characterized typically by high temperatures and humidity with rainfall throughout the year. To evaluate if there are associations between the prevalence of current asthma and allergic symptoms in young children (age 1.5-6 yr) with dampness and indoor mold in children's bedrooms in a tropical environment. A cross-sectional study adopting an expanded and modified ISAAC--International Study on Asthma and Allergies in Children--questionnaire for the evaluation of asthma and allergies was conducted on 6794 children (4759 responded--70%) attending 120 randomly selected daycare centers. Specific information on demographics, home dampness, and the visible presence of indoor molds were obtained. The prevalence ratios (PR) and 95% confidence interval (CI) were determined by Cox proportional hazard regression model with assumption of a constant risk period as recommended for cross-sectional studies. The calculated PRs were controlled for age, gender, ethnicity, socio-economic status, type of housing, maternal and paternal atopy, respiratory infections, environmental tobacco smoke (ETS) exposure, and food allergy. After adjusting for potential confounding effects, home dampness was observed to be significantly associated with current symptoms of rhinoconjunctivitis (adjusted PR 1.53, 95% CI: 1.00-2.33). The visible presence of mold was significantly associated with current symptoms of rhinitis (PR 1.55, 95% CI: 1.16-2.07) and rhinoconjunctivitis (PR 2.38, 95% CI: 1.51-3.75). Indoor dampness and mold in children's bedroom are important risk factors associated with allergic symptoms in young children in Singapore. PMID:17617809

  19. The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma

    PubMed Central

    2014-01-01

    Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma. PMID:25365789

  20. Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment

    PubMed Central

    Thijs, Willemien; Janssen, Kirsten; van Schadewijk, Annemarie M.; Papapoulos, Socrates E.; le Cessie, Saskia; Middeldorp, Saskia; Melissant, Christian F.; Rabe, Klaus F.; Hiemstra, Pieter S.

    2015-01-01

    Background Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)2D3) affects these antimicrobial peptide levels. Methods The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. Results Levels of neutrophil α-defensins (human neutrophil peptides 1–3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)2D3. Conclusion Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D. PMID:26545199

  1. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    PubMed

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  2. Cheonggukjang ethanol extracts inhibit a murine allergic asthma via suppression of mast cell-dependent anaphylactic reactions.

    PubMed

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Chai, Ok Hee; Shon, Dong-Hwa

    2014-01-01

    Cheonggukjang (CGJ), a traditional Korean fermented soybean food, exerts immunomodulatory effects. Asthma is the most common chronic allergic disease to be associated with immune response to environmental allergens. In the pathogenesis of asthma, histamine is one of the important inflammatory mediators released from granules of mast cells. In this study, we evaluated the therapeutic effect of CGJ on a mouse model of ovalbumin (OVA)-induced asthma via the suppression of histamine release. C57BL/6 mice were sensitized by intraperitoneal injection of OVA or a phosphate-buffered saline (PBS) control and then challenged with OVA inhalation. Mice were treated intraperitoneally with either 70% ethanol-extracted CGJ (CGJE) (100 mg/kg/day) or equivalent PBS. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. To elucidate the mechanisms of asthma inhibition by CGJE treatment, we also examined degranulation and histamine release of compound 48/80-induced rat peritoneal mast cells (RPMCs). Treatment with CGJE downregulated the number of eosinophils and monocytes in the lungs of mice challenged with OVA and suppressed histopathological changes, such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. Moreover, CGJE alleviated compound 48/80-induced mast cell degranulation and histamine release from RPMCs through inhibition of calcium (Ca²⁺) uptake as well as ear swelling by infiltration of inflammatory cells. These findings demonstrated that CGJE can be used as an antiasthmatic dietary supplements candidate for histamine-mediated asthma. PMID:24456365

  3. Cheonggukjang Ethanol Extracts Inhibit a Murine Allergic Asthma via Suppression of Mast Cell-Dependent Anaphylactic Reactions

    PubMed Central

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong

    2014-01-01

    Abstract Cheonggukjang (CGJ), a traditional Korean fermented soybean food, exerts immunomodulatory effects. Asthma is the most common chronic allergic disease to be associated with immune response to environmental allergens. In the pathogenesis of asthma, histamine is one of the important inflammatory mediators released from granules of mast cells. In this study, we evaluated the therapeutic effect of CGJ on a mouse model of ovalbumin (OVA)-induced asthma via the suppression of histamine release. C57BL/6 mice were sensitized by intraperitoneal injection of OVA or a phosphate-buffered saline (PBS) control and then challenged with OVA inhalation. Mice were treated intraperitoneally with either 70% ethanol-extracted CGJ (CGJE) (100 mg/kg/day) or equivalent PBS. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. To elucidate the mechanisms of asthma inhibition by CGJE treatment, we also examined degranulation and histamine release of compound 48/80-induced rat peritoneal mast cells (RPMCs). Treatment with CGJE downregulated the number of eosinophils and monocytes in the lungs of mice challenged with OVA and suppressed histopathological changes, such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. Moreover, CGJE alleviated compound 48/80-induced mast cell degranulation and histamine release from RPMCs through inhibition of calcium (Ca2+) uptake as well as ear swelling by infiltration of inflammatory cells. These findings demonstrated that CGJE can be used as an antiasthmatic dietary supplements candidate for histamine-mediated asthma. PMID:24456365

  4. A comparison between intratracheal and inhalation delivery of Aspergillus fumigatus conidia in the development of fungal allergic asthma in C57BL/6 mice

    PubMed Central

    Samarasinghe, Amali E.; Hoselton, Scott A.; Schuh, Jane M.

    2010-01-01

    Summary Allergic asthma is a debilitating disease of the airways characterized by airway hyperresponsiveness, eosinophilic inflammation, goblet cell metaplasia with associated mucus hypersecretion, and airway wall remodelling events, particularly subepithelial fibrosis and smooth muscle cell hyperplasia. Animal models that accurately mimic these hallmarks of allergic airways disease are critical for studying mechanisms associated with the cellular and structural changes that lead to disease pathogenesis. Aspergillus fumigatus, is a common aeroallergen of human asthmatics. The intratracheal (IT) delivery of A. fumigatus conidia into the airways of sensitized mice has been described as a model of allergic disease. Here, we compared the IT model with a newly developed inhalation (IH) challenge model. The IH model allowed multiple fungal exposures, which resulted in an exacerbation to the allergic asthma phenotype. Increased recruitment of eosinophils and lymphocytes, the hallmark leukocytes of asthma, were noted with the IH model as compared to the IT model in which macrophages and neutrophils were more prominent. Immunoglobulin E (IgE) production was significantly greater after IH challenge, while that of IgG2a was higher after IT challenge. Airway wall remodelling was pronounced in IH-treated mice, particularly after multiple allergen challenges. Although the IT model may be appropriate for the examination of the played by innate cells in the acute response to fungus, it fails to consistently reproduce the chronic remodelling hallmarks of allergic asthma. The ability of the IH challenge to mimic these characteristics recommends it as a model suited to study these important events. PMID:21215951

  5. A comparison between intratracheal and inhalation delivery of Aspergillus fumigatus conidia in the development of fungal allergic asthma in C57BL/6 mice.

    PubMed

    Samarasinghe, Amali E; Hoselton, Scott A; Schuh, Jane M

    2011-01-01

    Allergic asthma is a debilitating disease of the airways characterized by airway hyperresponsiveness, eosinophilic inflammation, goblet cell metaplasia with associated mucus hypersecretion, and airway wall remodelling events, particularly subepithelial fibrosis and smooth muscle cell hyperplasia. Animal models that accurately mimic these hallmarks of allergic airways disease are critical for studying mechanisms associated with the cellular and structural changes that lead to disease pathogenesis. Aspergillus fumigatus, is a common aeroallergen of human asthmatics. The intratracheal (IT) delivery of A. fumigatus conidia into the airways of sensitized mice has been described as a model of allergic disease. Here, we compared the IT model with a newly developed inhalation (IH) challenge model. The IH model allowed multiple fungal exposures, which resulted in an exacerbation to the allergic asthma phenotype. Increased recruitment of eosinophils and lymphocytes, the hallmark leukocytes of asthma, was noted with the IH model as compared to the IT model in which macrophages and neutrophils were more prominent. Immunoglobulin E (IgE) production was significantly greater after IH challenge, while that of IgG(2a) was higher after IT challenge. Airway wall remodelling was pronounced in IH-treated mice, particularly after multiple allergen challenges. Although the IT model may be appropriate for the examination of the played by innate cells in the acute response to fungus, it fails to consistently reproduce the chronic remodelling hallmarks of allergic asthma. The ability of the IH challenge to mimic these characteristics recommends it as a model suited to study these important events. PMID:21215951

  6. Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma.

    PubMed

    Kamekura, Ryuta; Shigehara, Katsunori; Miyajima, Satsuki; Jitsukawa, Sumito; Kawata, Koji; Yamashita, Keiji; Nagaya, Tomonori; Kumagai, Ayako; Sato, Akinori; Matsumiya, Hiroshi; Ogasawara, Noriko; Seki, Nobuhiko; Takano, Kenichi; Kokai, Yasuo; Takahashi, Hiroki; Himi, Tetsuo; Ichimiya, Shingo

    2015-06-01

    Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR+Asthma). To determine the pathophysiologic features of AR and AR+Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR+Asthma patients. The results showed polarization of Tfh2 cells within Tfh cell subsets in both AR and AR+Asthma cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR+Asthma cases. Moreover, we found significant correlations of fractional exhaled nitric oxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma. PMID:25829231

  7. Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

    PubMed Central

    Zietkowski, Ziemowit; Skiepko, Roman; Tomasiak, Maria M; Bodzenta-Lukaszyk, Anna

    2007-01-01

    Background Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients. Methods The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed. Results In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline FENO and the increase in FENO or BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed. Conclusion The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients. PMID:17973986

  8. Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthma.

    PubMed

    Staab, Elizabeth B; Sanderson, Sam D; Wells, Sandra M; Poole, Jill A

    2014-08-01

    Allergic asthma is a chronic inflammatory airway disease arising from an aberrant immune response following exposure to environmental stimuli in genetically susceptible persons. The complement component 5 (C5)/C5a Receptor (C5aR/CD88) signaling pathway has been implicated in both experimental allergic asthma and human asthmatic disease. Targeting the C5a/C5aR signaling pathway in rodent models has been shown to either enhance or reduce allergic asthma consequences. Treatment with a recombinant humanized monoclonal antibody directed against C5 has shown unclear results in patients with asthma. The objective of this proof-of-concept animal study was to determine whether the low molecular weight C5aR peptidomimetic antagonist, PMX205, would reduce experimental allergic asthma consequences in mice. PMX205 or vehicle control was administered subcutaneously to BALB/c mice prior to and during standard ovalbumin (OVA) allergen sensitization and aerosolized challenge phases. PMX205 substantially reduced OVA-induced total cell (60%), neutrophil (66%) and eosinophil (65%) influxes in lavage fluid sampling. There were also significant reductions in OVA-induced lavage fluid IL-13 protein and lung Th2 cytokine gene expression with PMX205 administration. PMX205 treatment also diminished OVA-induced lung parenchyma cellular infiltration. PMX205 administration did not reduce OVA-induced serum IgE levels or epithelial mucous/goblet cell generation. There was no evidence of toxicity observed with PMX205 treatment in saline or OVA-challenged animals. These data provide evidence that pharmacologic blockade of C5aR by a low molecular weight antagonist (PMX205) reduces airway inflammatory cell and cytokine responses in experimental allergic asthma, and suggests that PMX205 might represent a novel therapeutic agent for reducing asthmatic outcomes. PMID:24859057

  9. AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

    EPA Science Inventory

    Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

  10. Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine.

    PubMed

    Agache, Ioana; Akdis, Cezmi A

    2016-07-01

    Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management. PMID:27282212

  11. Elm tree (Ulmus parvifolia) bark bioprocessed with Mycelia of Shiitake (Lentinus edodes) mushrooms in liquid Culture: Composition and mechanism of protection against allergic asthma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the antiasthma effect of a bioprocessed Ulmus parvifolia bark extract (BPUBE) from Lentinus edodes liquid mycelia culture against allergic asthma biomarkers in U266B1 leukemia cells and OVA-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cel...

  12. Pharmacodynamic evaluation of RP3128, a novel and potent CRAC channel inhibitor in guinea pig models of allergic asthma.

    PubMed

    Sutovska, Martina; Kocmalova, Michaela; Franova, Sona; Vakkalanka, Swaroop; Viswanadha, Srikant

    2016-02-01

    The increase in intracellular Ca(2+) levels through the activation of Ca(2+) release-activated Ca(2+) (CRAC) channels is essential for mediating a wide scale of immune cell responses. Emerging evidence indicates an involvement of abnormal CRAC channel activity in human diseases such as certain types of immunodeficiency, autoimmunity and allergic disorders. This objective of this study was to evaluate the therapeutic potency of a novel CRAC channel inhibitor, RP3128, in experimental models of allergic asthma using guinea pigs. Ovalbumin-induced allergic airway inflammation was determined upon acute and long-term (14 days) oral administration of RP3128. In vivo changes in specific airways resistance (sRaw) and amplitude of isometric contraction (mN) of ASM (in vitro) were estimated to evaluate bronchodilatory effect upon acute and long-term administration of RP3128 or salbutamol. Exhaled nitric oxide (eNO), immunohistochemical and histological analysis of cellular infiltration in airways tissue, and levels of cytokines in plasma as well as bronchoalveolar lavage fluid (BALF), were determined using Bio-Plex® 200 System (BIO-RAD, USA). Ciliary beat frequency (CBF, in Hz) was estimated using a high-speed video camera and LabVIEW™ Software. Additionally, the impact of RP3128 and budesonide on mucociliary clearance was determined. Acute and long-term administration of RP3128 resulted in significant bronchodilation. Long-term administration of RP3128 exceeded the bronchodilatory effect of salbutamol and significantly decreased eNO and cytokine levels in plasma and BALF, which together with histological and immunohistochemical analysis validated its anti-inflammatory effect compared to budesonide. Data demonstrate the therapeutic potential of RP3128 in respiratory diseases causally associated with allergic inflammation. PMID:26724844

  13. Association between reduced copy-number at T-cell receptor gamma (TCRγ) and childhood allergic asthma: a possible role for somatic mosaicism

    PubMed Central

    Walsh, Kyle; Bracken, Michael B.; Murk, William K.; Hoh, Josephine; DeWan, Andrew T.

    2010-01-01

    Asthma is a chronic inflammatory disease of the lungs which affects more than 6.5 million American children. A family-based genome-wide association study of copy-number variation identified an association between decreased copy-number at TCRγ and childhood allergic asthma. TCRγ encodes the T-cell receptor gamma glycoprotein, a cell-surface protein found on T-cells and involved in cell-mediated immunity. Using quantitative real-time PCR, we sought to determine if copy-number variation at TCRα, TCRβ or TCRγ was associated with childhood allergic asthma in an independent cohort of 94 cases and 455 controls using DNA from buccal swabs. Copy-number variation at these loci is well-known, but appears to be dominated by somatic mutations. Genotyping results indicated that copy-number variants at these genes are largely somatic mutations, as inheritance did not show Mendelian consistency. In these mosaic cell populations, copy-number was significantly reduced among asthmatic children at TCRγ (p = 0.0199), but was not associated at TCRα or TCRβ (p = 0.7972 and 0.8585, respectively). These findings support the association between reduced copy-number at TCRγ and childhood allergic asthma. Further work is needed to resolve whether reduced copy-number at TCRγ predisposes individuals to asthma, or whether deletion of this gene is a somatic response to the disease. PMID:20553737

  14. Absence of α4 but not β2 integrins restrains development of chronic allergic asthma using mouse genetic models

    PubMed Central

    Banerjee, Ena Ray; Jiang, Yi; Henderson, William R.; Latchman, Yvette; Papayannopoulou, Thalia

    2013-01-01

    Objective Chronic asthma is characterized by ongoing recruitment of inflammatory cells and airway hyperresponsiveness leading to structural airway remodeling. Although α4β1 and β2 integrins regulate leukocyte migration in inflammatory diseases and play decisive roles in acute asthma, their role has not been explored under the chronic asthma setting. To extend our earlier studies with α4Δ/Δ and β2−/− mice, which showed that both a4 and b2 integrins have nonredundant regulatory roles in acute ovalbumin (OVA)-induced asthma, we explored to what extent these molecular pathways control development of structural airway remodeling in chronic asthma. Materials and Methods Control, α4Δ/Δ, and β2−/−mouse groups, sensitized by intraperitoneal OVA as allergen, received intratracheal OVA periodically over days 8 to 55 to induce a chronic asthma phenotype. Post-OVA assessment of inflammation and pulmonary function (airway hyperresponsiveness), together with airway modeling measured by goblet cell metaplasia, collagen content of lung, and transforming growth factor β1 expression in lung homogenates, were evaluated. Results In contrast to control and β2−/− mice, α4Δ/Δ mice failed to develop and maintain the composite chronic asthma phenotype evaluated as mentioned and subepithelial collagen content was comparable to baseline. These data indicate that β2 integrins, although required for inflammatory migration in acute asthma, are dispensable for structural remodeling in chronic asthma. Conclusion α4 integrins appear to have a regulatory role in directing transforming growth factor β-induced collagen deposition and structural alterations in lung architecture likely through interactions of Th2 cells, eosinophils, or mast cells with endothelium, resident airway cells, and/or extracellular matrix. PMID:19463772

  15. Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

    PubMed Central

    Weinmayr, Gudrun; Forastiere, Francesco; Büchele, Gisela; Jaensch, Andrea; Strachan, David P.; Nagel, Gabriele

    2014-01-01

    Background Childhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated. Methods Cross-sectional studies of stratified random samples of 8–12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated. Results Overweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, −0.90, 95%-confidence interval: −1.33%; −0.47%, for overweight and −2.46%, 95%-confidence interval: −3.84%; −1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null. Conclusions Our data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders. PMID:25474308

  16. The effect of a herbal water-extract on histamine release from mast cells and on allergic asthma.

    PubMed

    Haggag, Eman G; Abou-Moustafa, Magda A; Boucher, William; Theoharides, Theoharis C

    2003-01-01

    A water extract of a mixture of eight herbs (chamomile, saffron, anise, fennel, caraway, licorice, cardomom and black seed) was tested for its inhibitory effect on histamine released from rat peritoneal mast cells stimulated either by compound 48/80 or be IgE/anti-IgE. The effect of the herb extract was compared to that of the flavonoid quercetin. The herbal water-extract inhibited histamine released from chemically- and immunologically-induced cells by 81% and 85%, respectively; quercetin treated cells were inhibited by 95% and 97%, respectively. The clinical results showed significant improvements of sleep discomfort, cough frequency and cough intensity in addition to increased percentages of FEV1/FVC in patients suffering from allergic asthma, who used the herbal tea compared to those who used the placebo tea. PMID:15277119

  17. Association of allergic asthma emergency room visits with the main biological and chemical air pollutants.

    PubMed

    Makra, László; Matyasovszky, István; Bálint, Beatrix

    2012-08-15

    Joint effect of biological (pollen) and chemical air pollutants on asthma emergency room (ER) visits was analyzed for Szeged region of Southern Hungary. Our database of a nine-year period (1999-2007) includes daily number of asthma emergency room (ER) visits, and daily mean concentrations of CO, PM(10), NO, NO(2), O(3) and SO(2), furthermore two pollen variables (Ambrosia and total pollen excluding Ambrosia), as well. The analysis was performed for ER visits of asthma bronchiale using two age groups (adults and the elderly) of males and females for three seasons. Factor analysis was performed in order to clarify the relative importance of the pollutant variables affecting asthma ER visits. Asthma ER visits denote notably stronger associations with the pollutants in adult male than in adult female patients both for the pollen season of Ambrosia and the pollen-free season. Furthermore, adults are substantially more sensitive to severe asthma attack than the elderly for the season of total pollen excluding Ambrosia pollen. The joint effect of the chemical and pollen variables is the highest for the asthma ER cases in the pollen season of Ambrosia, basically due to the extra impact of the total pollen excluding Ambrosia pollen and partly due to Ambrosia pollen. A nonparametric regression technique was applied to discriminate between events of ER visit-no ER visit using pollen and chemical pollutants as explaining variables. Based on multiple correlations, the strongest relationships between ER visits and pollutants are observed during the pollen-free season. The elderly group with asthma bronchiale is characterized by weaker relationships between ER visits and pollutants compared to adults. Ratio of the number of correct decisions on the events of ER visit-no ER visit is lowest for the season of total pollen excluding Ambrosia pollen. Otherwise, similar conclusions hold as those received by multiple correlations. PMID:22750174

  18. Does traffic exhaust contribute to the development of asthma and allergic sensitization in children: findings from recent cohort studies

    PubMed Central

    2009-01-01

    The aim of this review was to assess the evidence from recent prospective studies that long-term traffic pollution could contribute to the development of asthma-like symptoms and allergic sensitization in children. We have reviewed cohort studies published since 2002 and found in PubMed in Oct 2008. In all, 13 papers based on data from 9 cohorts have evaluated the relationship between traffic exposure and respiratory health. All surveys reported associations with at least some of the studied respiratory symptoms. The outcome varied, however, according to the age of the child. Nevertheless, the consistency in the results indicates that traffic exhaust contributes to the development of respiratory symptoms in healthy children. Potential effects of traffic exhaust on the development of allergic sensitization were only assessed in the four European birth cohorts. Long-term exposure to outdoor air pollutants had no association with sensitization in ten-year-old schoolchildren in Norway. In contrast, German, Dutch and Swedish preschool children had an increased risk of sensitization related to traffic exhaust despite fairly similar levels of outdoor air pollution as in Norway. Traffic-related effects on sensitization could be restricted to individuals with a specific genetic polymorphism. Assessment of gene-environment interactions on sensitization has so far only been carried out in a subgroup of the Swedish birth cohort. Further genetic association studies are required and may identify individuals vulnerable to adverse effects from traffic-related pollutants. Future studies should also evaluate effects of traffic exhaust on the development and long term outcome of different phenotypes of asthma and wheezing symptoms. PMID:19371435

  19. Association of allergic rhinitis or asthma with pollen and chemical pollutants in Szeged, Hungary, 1999-2007

    NASA Astrophysics Data System (ADS)

    Makra, László; Matyasovszky, István; Bálint, Beatrix; Csépe, Zoltán

    2014-07-01

    The effect of biological (pollen) and chemical air pollutants on respiratory hospital admissions for the Szeged region in Southern Hungary is analysed. A 9-year (1999-2007) database includes—besides daily number of respiratory hospital admissions—daily mean concentrations of CO, PM10, NO, NO2, O3 and SO2. Two pollen variables ( Ambrosia and total pollen excluding Ambrosia) are also included. The analysis was performed for patients with chronic respiratory complaints (allergic rhinitis or asthma bronchiale) for two age categories (adults and the elderly) of males and females. Factor analysis was performed to clarify the relative importance of the pollutant variables affecting respiratory complaints. Using selected low and high quantiles corresponding to probability distributions of respiratory hospital admissions, averages of two data sets of each air pollutant variable were evaluated. Elements of these data sets were chosen according to whether actual daily patient numbers were below or above their quantile value. A nonparametric regression technique was applied to discriminate between extreme and non-extreme numbers of respiratory admissions using pollen and chemical pollutants as explanatory variables. The strongest correlations between extreme patient numbers and pollutants can be observed during the pollen season of Ambrosia, while the pollen-free period exhibits the weakest relationships. The elderly group with asthma bronchiale is characterised by lower correlations between extreme patient numbers and pollutants compared to adults and allergic rhinitis, respectively. The ratio of the number of correct decisions on the exceedance of a quantile resulted in similar conclusions as those obtained by using multiple correlations.

  20. Association of allergic rhinitis or asthma with pollen and chemical pollutants in Szeged, Hungary, 1999-2007.

    PubMed

    Makra, László; Matyasovszky, István; Bálint, Beatrix; Csépe, Zoltán

    2014-07-01

    The effect of biological (pollen) and chemical air pollutants on respiratory hospital admissions for the Szeged region in Southern Hungary is analysed. A 9-year (1999-2007) database includes--besides daily number of respiratory hospital admissions--daily mean concentrations of CO, PM10, NO, NO2, O3 and SO2. Two pollen variables (Ambrosia and total pollen excluding Ambrosia) are also included. The analysis was performed for patients with chronic respiratory complaints (allergic rhinitis or asthma bronchiale) for two age categories (adults and the elderly) of males and females. Factor analysis was performed to clarify the relative importance of the pollutant variables affecting respiratory complaints. Using selected low and high quantiles corresponding to probability distributions of respiratory hospital admissions, averages of two data sets of each air pollutant variable were evaluated. Elements of these data sets were chosen according to whether actual daily patient numbers were below or above their quantile value. A nonparametric regression technique was applied to discriminate between extreme and non-extreme numbers of respiratory admissions using pollen and chemical pollutants as explanatory variables. The strongest correlations between extreme patient numbers and pollutants can be observed during the pollen season of Ambrosia, while the pollen-free period exhibits the weakest relationships. The elderly group with asthma bronchiale is characterised by lower correlations between extreme patient numbers and pollutants compared to adults and allergic rhinitis, respectively. The ratio of the number of correct decisions on the exceedance of a quantile resulted in similar conclusions as those obtained by using multiple correlations. PMID:23558448

  1. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma

    PubMed Central

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-01-01

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10–20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy. PMID:26694364

  2. Asthma

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Asthma KidsHealth > For Kids > Asthma Print A A A ... it can take several days. continue Who Gets Asthma? No one really knows why one person's airways ...

  3. Effects of provinol and its combinations with clinically used antiasthmatics on airway defense mechanisms in experimental allergic asthma.

    PubMed

    Kazimierová, I; Jošková, M; Pecháňová, O; Šutovská, M; Fraňová, S

    2015-01-01

    Our previous studies show that provinol, a polyphenolic compound, has anti-inflammatory activity during allergic inflammation. In the present study we investigated the effects of provinol and its combinations with clinically used antiasthmatics: budesonide or theophylline on airway defense mechanisms during experimental allergic asthma. Separate groups of guinea pigs were treated during the course of 21-day ovalbumin sensitization with provinol (20 mg/kg/day, p.o.), or budesonide (1 mM by inhalation), or theophylline (10 mg/kg/day, i.p.), and with a half-dose combination of provinol+budesonide or provinol+theophylline. Airways defense mechanisms: cough reflex and specific airway resistance (sRaw) were evaluated in vivo. Tracheal smooth muscle reactivity and mucociliary clearance were examined in vitro. The findings were that provinol caused significant decreases in sRaw and in tracheal smooth muscle contractility, a suppression of cough reflex, and positively modulated ciliary beat frequency. The bronchodilatory and antitussive effects of provinol were comparable with those of budesonide and theophylline. Provinol given as add-on treatment significantly potentiated the effects of budesonide or theophylline, although the doses of each were halved. We conclude that provinol not only has bronchodilatory and antitussive effects, but also potentiates similar effects exerted by budesonide and theophylline. PMID:25315622

  4. Serum Amyloid A (SAA) Activates the NLRP3 Inflammasome and Promotes TH17 Allergic Asthma in Mice

    PubMed Central

    Ather, Jennifer L.; Ckless, Karina; Martin, Rebecca; Foley, Kathryn L.; Suratt, Benjamin T.; Boyson, Jonathan E.; Fitzgerald, Katherine A.; Flavell, Richard A.; Eisenbarth, Stephanie C.; Poynter, Matthew E.

    2011-01-01

    Interleukin (IL)-1β is a cytokine critical to several inflammatory diseases in which pathogenic TH17 responses are implicated. Activation of the NLRP3 inflammasome by microbial and environmental stimuli can enable the caspase-1 dependent processing and secretion of IL-1β. The acute phase protein serum amyloid A (SAA) is highly induced during inflammatory responses, wherein it participates in systemic modulation of innate and adaptive immune responses. Elevated levels of IL-1β, SAA, and IL-17 are present in subjects with severe allergic asthma, yet the mechanistic relationship between these mediators has yet to be identified. Herein, we demonstrate that Saa3 is expressed in the lung of mice exposed to several mixed Th2/Th17-polarizing allergic sensitization regimens. SAA instillation into the lungs elicits robust TLR2-, MyD88-, and IL-1-dependent pulmonary neutrophilic inflammation. Furthermore, SAA drives production of IL-1α, IL-1β, IL-6, IL-23, and PGE2, causes dendritic cell maturation, and requires TLR2, MyD88, and the NLRP3 inflammasome for secretion of IL-1β by dendritic cells and macrophages. CD4+ T cells polyclonally stimulated in the presence of conditioned media from SAA-exposed dendritic cells produced IL-17 and the capacity of polyclonally-stimulated splenocytes to secrete IL-17 is dependent upon IL-1, TLR2, and the NLRP3 inflammasome. Additionally, in a model of allergic airway inflammation, administration of SAA to the lungs functions as an adjuvant to sensitize mice to inhaled ovalbumin, resulting in leukocyte influx after antigen challenge and a predominance of IL-17 production from restimulated splenocytes that is dependent upon IL-1 receptor signaling. PMID:21622869

  5. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization.

    PubMed

    D'Amato, Gennaro; Holgate, Stephen T; Pawankar, Ruby; Ledford, Dennis K; Cecchi, Lorenzo; Al-Ahmad, Mona; Al-Enezi, Fatma; Al-Muhsen, Saleh; Ansotegui, Ignacio; Baena-Cagnani, Carlos E; Baker, David J; Bayram, Hasan; Bergmann, Karl Christian; Boulet, Louis-Philippe; Buters, Jeroen T M; D'Amato, Maria; Dorsano, Sofia; Douwes, Jeroen; Finlay, Sarah Elise; Garrasi, Donata; Gómez, Maximiliano; Haahtela, Tari; Halwani, Rabih; Hassani, Youssouf; Mahboub, Basam; Marks, Guy; Michelozzi, Paola; Montagni, Marcello; Nunes, Carlos; Oh, Jay Jae-Won; Popov, Todor A; Portnoy, Jay; Ridolo, Erminia; Rosário, Nelson; Rottem, Menachem; Sánchez-Borges, Mario; Sibanda, Elopy; Sienra-Monge, Juan José; Vitale, Carolina; Annesi-Maesano, Isabella

    2015-01-01

    The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods - all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts

  6. IL-17RA Signaling in Airway Inflammation and Bronchial Hyperreactivity in Allergic Asthma.

    PubMed

    Willis, Cynthia R; Siegel, Lori; Leith, Anh; Mohn, Deanna; Escobar, Sabine; Wannberg, Sharon; Misura, Kira; Rickel, Erika; Rottman, James B; Comeau, Michael R; Sullivan, John K; Metz, Daniela P; Tocker, Joel; Budelsky, Alison L

    2015-12-01

    Asthma is a heterogeneous disease characterized by airway inflammation and hyperreactivity. IL-17 receptor A (IL-17RA) is a shared receptor subunit required for activity of IL-17 family cytokines, including IL-17A and IL-25. IL-17A and IL-25 induce different proinflammatory responses, and concentrations are elevated in subjects with asthma. However, the individual contributions of IL-17A and IL-25 to disease pathogenesis are unclear. We explored proinflammatory activities of the IL-17 pathway in models of pulmonary inflammation and assessed its effects on contractility of human bronchial airway smooth muscle. In two mouse models, IL-17RA, IL-17RB, or IL-25 blockade reduced airway inflammation and airway hyperreactivity. Individually, IL-17A and IL-25 enhanced contractility of human bronchial smooth muscle induced by methacholine or carbachol. IL-17A had more pronounced effects on methacholine-induced contractility in bronchial rings from donors with asthma compared with donors without asthma. Blocking the IL-17 pathway via IL-17RA may be a useful therapy for some patients with asthma by reducing pulmonary inflammation and airway hyperreactivity. PMID:25919006

  7. Prevention of Influenza Virus-Induced Immunopathology by TGF-β Produced during Allergic Asthma

    PubMed Central

    Furuya, Yoichi; Furuya, Andrea K. M.; Roberts, Sean; Sanfilippo, Alan M.; Salmon, Sharon L.; Metzger, Dennis W.

    2015-01-01

    Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists to directly demonstrate the impact of asthma on susceptibility to influenza infection. Using a mouse model, we now report that asthmatic mice are actually significantly more resistant to a lethal influenza virus challenge. Notably, the observed increased resistance was not attributable to enhanced viral clearance, but instead, was due to reduced lung inflammation. Asthmatic mice exhibited a significantly reduced cytokine storm, as well as reduced total protein levels and cytotoxicity in the airways, indicators of decreased tissue injury. Further, asthmatic mice had significantly increased levels of TGF-β1 and the heightened resistance of asthmatic mice was abrogated in the absence of TGF-β receptor II. We conclude that a transient increase in TGF-β expression following acute asthma can induce protection against influenza-induced immunopathology. PMID:26407325

  8. So-Cheong-Ryong-Tang, a herbal medicine, modulates inflammatory cell infiltration and prevents airway remodeling via regulation of interleukin-17 and GM-CSF in allergic asthma in mice

    PubMed Central

    Kim, Hyung-Woo; Lim, Chi-Yeon; Kim, Bu-Yeo; Cho, Su-In

    2014-01-01

    Background: So-Cheong-Ryong-Tang (SCRT), herbal medicine, has been used for the control of respiratory disease in East Asian countries. However, its therapeutic mechanisms, especially an inhibitory effect on inflammatory cell infiltration and airway remodeling in allergic asthma are unclear. Objective: The present study investigated the mechanism of antiasthmatic effects of SCRT in allergic asthma in mice. Materials and Methods: We investigated the influence of SCRT on levels of interleukin-17 (IL-17), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-4, and interferon gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF), ovalbumin (OVA)-specific IgE in serum, and histopathological changes in allergen-induced asthma. Results: So-Cheong-Ryong-Tang decreased levels of IL-17 and GM-CSF in BALF. IL-4, a Th2-driven cytokine, was also decreased by SCRT, but IFN-γ, a Th1-driven cytokine, was not changed. Levels of OVA-specific IgE in serum were also decreased by SCRT. With SCRT treatment, histopathological findings showed reduced tendency of inflammatory cell infiltration, and prevention from airway remodeling such as epithelial hyperplasia. Conclusion: In this study, we firstly demonstrated that regulation of IL-17 and GM-CSF production may be one of the mechanism contributed to a reduction of inflammatory cell infiltration and prevention from airway remodeling. PMID:25298667

  9. Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients.

    PubMed

    Alvarez, M J; Olaguibel, J M; Garcia, B E; Tabar, A I; Urbiola, E

    2000-06-01

    Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A-BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge-induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short-evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A-BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]-5) were analyzed, before and 24 h after A-BPT. Methacholine BHR, assessed before and 32 h after the A-BPT, was defined by M-PD20 values and, when possible, by maximal response plateau (MRP). The A-BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late-phase responses (LPR). M-PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P = 0.025). The A-BPT induced no change in sputum albumin, tryptase, or IL-5 values. We conclude as follows: 1) In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA. 2) MRP levels increased in both AA and AR patients after allergen challenge; however, M-PD20 values

  10. Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

    PubMed Central

    Temesi, Gergely; Virág, Viktor; Hadadi, Éva; Ungvári, Ildikó; Fodor, Lili E; Bikov, András; Nagy, Adrienne; Gálffy, Gabriella; Tamási, Lilla; Horváth, Ildikó; Kiss, András; Hullám, Gábor; Gézsi, András; Sárközy, Péter; Antal, Péter; Buzás, Edit

    2014-01-01

    Purpose Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma. Methods In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreover, gene expression levels were measured by RT PCR in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi-square tests, and logistic regression were carried out in order to assess associations of SNP frequency and expression level with asthma. Permutation tests were performed to account for multiple hypothesis testing. Results The frequency of 4 SNPs in 2 genes differed significantly between asthmatic and control subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds ratio of 0.64 (0.51-0.80; P=7×10-5) in SCIN and 0.56 (0.42-0.76; P=1.2×10-4) in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were significantly lower in the sputum of asthmatics. Conclusions Three potentially novel asthma-associated genes were identified based on mouse experiments and human studies. PMID:25374748

  11. SUSCEPTIBILITY FACTORS FOR THE DEVELOPMENT OF ALLERGIC LUNG DISEASE AND ASTHMA

    EPA Science Inventory


    Environmental Issue: More than 17 million people in the United States had asthma in 1998, which represents a doubling of the incidence in the previous 20 years. Since changes in the genetic makeup of the population take generations to occur, this increase must be related to ...

  12. Upregulation of Tim-3 on CD4+ T cells is associated with Th1/Th2 imbalance in patients with allergic asthma

    PubMed Central

    Tang, Fei; Wang, Fukun; An, Liyun; Wang, Xianling

    2015-01-01

    T cell Ig and mucin domain-containing molecule-3 (Tim-3) is a negative regulator preferentially expressed on Th1 cells. Allergic asthma is a clinical syndrome well characterized by Th1/Th2 imbalance. To investigate the role of Tim-3 in the pathogenesis of asthma and its relationship with Th1/Th2 imbalance, a total of 40 patients with allergic asthma and 40 healthy controls were enrolled. Expression of Tim-3 and Th1/Th2 imbalance as well as the relationship between them was analyzed by flow cytometry and real-time PCR. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro and anti-Tim-3 was used to block Tim-3 signaling; Th1/Th2 cytokines in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). CD4+ T cells and B cells were sorted and co-cultured in vitro, and anti-Tim-3 was used to block Tim-3 signaling; Total IgG/IgE in the culture supernatant was detected by ELISA. The mRNA level of T-bet and IFN-γ were significantly decreased in allergic asthma patients, while GATA-3 and IL-4 were significantly increased. Expression of Tim-3 on CD4+ T cells was much higher in allergic asthma patients and it was negatively correlated with T-bet/GATA-3 ratio or IFN-γ/IL-4 ratio. Blocking of Tim-3 significantly increased Th1 cytokines (TNF-α and IFN-γ) and decreased Th2 cytokines (IL-4, IL-5, IL-13) in the culture supernatant of PBMCs. Blocking of Tim-3 dramatically reduced the production of IgG and IgE in the co-culture supernatant of CD4+ T cells and B cells. In conclusion, Tim-3 was up-regulated in allergic asthma patients and related with the Th1/Th2 imbalance. Blocking of Tim-3 may be of therapeutic benefit by enhancing the Th1 cytokines response, down-regulating the Th2 cytokines response, and reducing IgG/IgE production. PMID:26064278

  13. Imbalance of Peripheral Th17 and Regulatory T Cells in Children with Allergic Rhinitis and Bronchial Asthma.

    PubMed

    Tao, Baohong; Ruan, Guiying; Wang, Dongguo; Li, Yong; Wang, Zhuping; Yin, Genquan

    2015-06-01

    The purpose of the present study is to investigate the prevalence of Th17 and regulatory T (Treg) cells in children with allergic rhinitis (AR) accompanying with bronchial asthma (BA). 24 children with AR, 22 children with BA, 18 children with AR accompanying with BA, and 20 healthy controls were recruited. The prevalence of peripheral blood Th17 and Treg cells were determined by flow cytometry. mRNA expression of retinoid-acid receptor-related orphan receptor (ROR)-γt and forkhead box P3 (Foxp3) were determined by realtime polymerase chain reaction. Cytokine expressions in plasma were determined by enzyme linked immunosorbent assay. The frequency of Th17 cells, ROR-γt mRNA expression, and the plasma levels of IL-17 were significantly higher, while Treg cells and Transforming growth factor (TGF)-β1 were significantly lower in children with AR accompanying with BA compared with those in children with AR or BA alone or control subjects. In children with allergic airway disease, total IgE levels were positively correlated to the frequency of Th17 cells (r=0.607, p<0.01), plasma IL-17 levels, and negatively correlated to the frequency of Treg cells (r=-0.429, p<0.01) and TGF-β1 levels (r=-0.224, p<0.01). While Forced expiratory volume in one second (FEV1) (% predicted) was negatively correlated to the frequency of Th17 cells (r=-0.602, p<0.01), plasma IL-17 levels (r=-0.577, p<0.01), and positively correlated to the frequency of Treg cells r=0.504, p<0.01) and TGF-β1 levels (r=0.231, p<0.05). Our results demonstrate that the imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR accompanying with BA. PMID:26546895

  14. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma

    PubMed Central

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S.; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3−/−) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3−/− mice compared with wild-type mice after OVA challenge, consistently with fewer CD4+ T cells from AQP3−/− mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  15. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma.

    PubMed

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-Ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA challenge, consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  16. Helicobacter pylori neutrophil-activating protein: a potential Treg modulator suppressing allergic asthma?

    PubMed

    Sehrawat, Anjna; Sinha, Siddharth; Saxena, Abhishek

    2015-01-01

    The ultimate aim of the immune system is to eliminate pathogens without being harmful to the host. But what if eliminating the pathogen in itself is discomforting for the host? One such emerging case is of Helicobacter pylori. Modern medicine, infantile vaccination, and ultra-hygienic conditions have led to progressive disappearance of H. pylori in different parts of the world. However, the adversities caused by H. pylori's absence are much larger than those caused by its presence. Asthma is rising as an epidemic in last few decades and several reports suggest an inverse-relationship between H. pylori's persistence and early-life onset asthma. Regulatory T cells play an important role in both the cases. This is further supported by experiments on mouse-models. Hence, need of the hour is to discern the relationship between H. pylori and its host and eliminating its negative impacts without disturbing our indigenous microbiota. To resolve whether H. pylori is a pathogen or an amphibiont is another important side. This review explores the biological basis of H. pylori-induced priming of immune system offering resistance to childhood-onset asthma. HP-NAP-Tregs interaction has been predicted using molecular docking and dynamic simulation. PMID:26082756

  17. Allergic bronchial asthma due to Dermatophagoides pteronyssinus hypersensitivity can be efficiently treated by inoculation of allergen-antibody complexes.

    PubMed Central

    Machiels, J J; Somville, M A; Lebrun, P M; Lebecque, S J; Jacquemin, M G; Saint-Remy, J M

    1990-01-01

    Antigen-antibody complexes were made from allergens of the common house dust mite, Dermatophagoides pteronyssinus (Dpt) and an excess of purified autologous specific antibodies. These complexes have been used to treat Dpt-hypersensitive patients who suffered from chronic bronchial asthma. Clinical symptoms and medication intake were followed by filling in diary cards. Peak expiratory flow, measured four times a day, was also followed. Intradermal skin tests and bronchial challenge tests were performed with allergen together with an evaluation of nonspecific bronchial reactivity. Specific IgE and IgG antibodies were assayed after separation from the bulk of serum immunoglobulins by immunoadsorption. The study was carried out over two years according to a double-blind protocol. Intradermal inoculation of antigen-antibody complexes resulted in a marked reduction of both clinical and medication scores. No systemic side-effects were observed and only mild wheal and flare reactions were noted at the injection site. The treatment showed a drastic reduction of specific skin and bronchial reactivities with only marginal effects on nonspecific bronchial reactivity. Concentrations of specific IgE antibodies decreased significantly during the first weeks of treatment and remained at these lower values throughout the study. Specific IgG antibodies actually decreased in the majority of treated patients. The total amount of allergen used in this study was less than 1% of the amount currently used for conventional hyposensitization with the same allergen. These findings show that antigen-antibody complex inoculation is an efficient and safe means of treating allergic bronchial asthma and that the mechanism of action is likely to differ from conventional hyposensitization. PMID:2318962

  18. Pharmacological characterization of SB 202235, a potent and selective 5-lipoxygenase inhibitor: effects in models of allergic asthma.

    PubMed

    Chabot-Fletcher, M C; Underwood, D C; Breton, J J; Adams, J L; Kagey-Sobotka, A; Griswold, D E; Marshall, L A; Sarau, H M; Winkler, J D; Hay, D W

    1995-06-01

    The peptidoleukotrienes and leukotriene B4, formed from arachidonic acid through the action of 5-lipoxygenase (5-LO), exert a spectrum of biological effects. It has been proposed that potent and selective 5-LO inhibitors will be effective therapy in diseases in which the peptidoleukotrienes and leukotriene B4 have been implicated, such as asthma and arthritis. The novel compound (S)-N-hydroxy-N-(2,3-dihydro-6-phenylmethoxy-3-benzyofuranyl )urea (SB 202235) was evaluated as a selective inhibitor of 5-LO in a cell-free system as well as in various cellular assays. In addition, the potential therapeutic value of SB 202235 was assessed in preclinical models of allergic asthma. The activity of the 5-LO enzyme isolated from rat basophilic leukemia-1 cells was inhibited by SB 202235 in a concentration-dependent manner with an IC50 value of 1.9 microM. Consistent with its ability to inhibit 5-LO, SB 202235 inhibited the production of leukotriene B4 by human monocytes and in human whole blood (IC50 values of 1.5 microM and 1.1 microM, respectively). The selectivity of SB 202235 was confirmed by its lack of effect against several other enzymes and receptors. SB 202235 potently and effectively inhibited the contraction produced by a single concentration of ovalbumin in guinea pig trachea (IC50 = 20 microM) and of anti-IgE in human bronchus (IC50 = 2 microM). SB 202235 (3-30 microM) also inhibited the contraction of guinea pig trachea in response to increasing concentration of ovalbumin. When administered orally (30 mg/kg) to conscious guinea pigs, SB 202235 attenuated antigen-induced broncho-constriction and the subsequent eosinophil influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7791085

  19. Asthma

    MedlinePlus

    Asthma is a chronic disease that affects your airways. Your airways are tubes that carry air in and out ... you have asthma, the inside walls of your airways become sore and swollen. That makes them very ...

  20. Home Dampness Signs in Association with Asthma and Allergic Diseases in 4618 Preschool Children in Urumqi, China-The Influence of Ventilation/Cleaning Habits.

    PubMed

    Lin, Zhijing; Zhao, Zhuohui; Xu, Huihui; Zhang, Xin; Wang, Tingting; Kan, Haidong; Norback, Dan

    2015-01-01

    There is an increasing prevalence of childhood asthma and allergic diseases in mainland of China. Few studies investigated the indoor dampness, ventilation and cleaning habits and their interrelationship with childhood asthma and allergic diseases. A large-scale cross-sectional study was performed in preschool children in Urumqi, China. Questionnaire was used to collect information on children's health, home dampness and ventilation/cleaning (V/C) habits. Multiple logistic regressions were applied to analyze the associations between childhood asthma/allergic diseases and each sign of home dampness, dampness levels, each V/C habit and total V/C scores. The associations between dampness and health were further performed by strata analyses in two groups with low and high V/C scores. Totally 4618(81.7%) of 5650 children returned the questionnaire. Reports on home dampness were most common for water condensation on windows (20.8%) followed by damp beddings (18.0%). The most common ventilation measure was the use of exhaust fan in bathroom (59.3%), followed by daily home cleaning (48.3%), frequently putting beddings to sunshine (29.9%) and frequently opening windows in winter (8.4%). There were positive associations between the 6 signs of home dampness and children's health particularly the symptoms last 12 months. By comparing with the reference dampness level (dampness scored 0), both the low dampness (scored 1~2) level and the high dampness level (scored 3~6) showed significantly increasing associations with childhood symptoms. There were crude negative associations between V/C habits and childhood health but not significant adjusting for home dampness levels. The risks of home dampness on children's health were lower in the group with higher V/C score but the differences were not statistically significant. Home dampness is a potential risk factor for childhood asthma and allergic symptoms in preschool children in Urumqi, China. No significant effects were observed

  1. Home Dampness Signs in Association with Asthma and Allergic Diseases in 4618 Preschool Children in Urumqi, China-The Influence of Ventilation/Cleaning Habits

    PubMed Central

    Lin, Zhijing; Zhao, Zhuohui; Xu, Huihui; Zhang, Xin; Wang, Tingting; Kan, Haidong; Norback, Dan

    2015-01-01

    There is an increasing prevalence of childhood asthma and allergic diseases in mainland of China. Few studies investigated the indoor dampness, ventilation and cleaning habits and their interrelationship with childhood asthma and allergic diseases. A large-scale cross-sectional study was performed in preschool children in Urumqi, China. Questionnaire was used to collect information on children’s health, home dampness and ventilation/cleaning (V/C) habits. Multiple logistic regressions were applied to analyze the associations between childhood asthma/allergic diseases and each sign of home dampness, dampness levels, each V/C habit and total V/C scores. The associations between dampness and health were further performed by strata analyses in two groups with low and high V/C scores. Totally 4618(81.7%) of 5650 children returned the questionnaire. Reports on home dampness were most common for water condensation on windows (20.8%) followed by damp beddings (18.0%). The most common ventilation measure was the use of exhaust fan in bathroom (59.3%), followed by daily home cleaning (48.3%), frequently putting beddings to sunshine (29.9%) and frequently opening windows in winter (8.4%). There were positive associations between the 6 signs of home dampness and children’s health particularly the symptoms last 12 months. By comparing with the reference dampness level (dampness scored 0), both the low dampness (scored 1~2) level and the high dampness level (scored 3~6) showed significantly increasing associations with childhood symptoms. There were crude negative associations between V/C habits and childhood health but not significant adjusting for home dampness levels. The risks of home dampness on children’s health were lower in the group with higher V/C score but the differences were not statistically significant. Home dampness is a potential risk factor for childhood asthma and allergic symptoms in preschool children in Urumqi, China. No significant effects were

  2. Cholesterol‐sensing liver X receptors stimulate Th2‐driven allergic eosinophilic asthma in mice

    PubMed Central

    Smet, Muriel; Van Hoecke, Lien; De Beuckelaer, Ans; Vander Beken, Seppe; Naessens, Thomas; Vergote, Karl; Willart, Monique; Lambrecht, Bart N.; Gustafsson, Jan‐Åke; Steffensen, Knut R.

    2016-01-01

    Abstract Introduction Liver X receptors (LXRs) are nuclear receptors that function as cholesterol sensors and regulate cholesterol homeostasis. High cholesterol has been recognized as a risk factor in asthma; however, the mechanism of this linkage is not known. Methods To explore the importance of cholesterol homeostasis for asthma, we investigated the contribution of LXR activity in an ovalbumin‐ and a house dust mite‐driven eosinophilic asthma mouse model. Results In both models, airway inflammation, airway hyper‐reactivity, and goblet cell hyperplasia were reduced in mice deficient for both LXRα and LXRβ isoforms (LXRα−/−β−/−) as compared to wild‐type mice. Inversely, treatment with the LXR agonist GW3965 showed increased eosinophilic airway inflammation. LXR activity contributed to airway inflammation through promotion of type 2 cytokine production as LXRα−/−β−/− mice showed strongly reduced protein levels of IL‐5 and IL‐13 in the lungs as well as reduced expression of these cytokines by CD4+ lung cells and lung‐draining lymph node cells. In line herewith, LXR activation resulted in increased type 2 cytokine production by the lung‐draining lymph node cells. Conclusions In conclusion, our study demonstrates that the cholesterol regulator LXR acts as a positive regulator of eosinophilic asthma in mice, contributing to airway inflammation through regulation of type 2 cytokine production. PMID:27621817

  3. Neonatal aerosol exposure to Bermuda grass allergen prevents subsequent induction of experimental allergic feline asthma: evidence for establishing early immunologic tolerance.

    PubMed

    Heller, M C; Lee-Fowler, T M; Liu, H; Cohn, L A; Reinero, C R

    2014-07-15

    Allergic asthma is increasing in industrialized countries, especially in children. Rodent and human studies suggest an opportunity to "prevent" asthma in the perinatal period. The aims of this study were to create a more "natural" model of feline asthma by exposing offspring of asthmatic queens to Bermuda grass allergen (BGA) by inhalation only, and to investigate maternal-fetal-infant interactions in the development of asthma. Kittens from asthmatic queens were divided into four groups: maternal exposure to aerosolized BGA during the third trimester, neonatal exposure to aerosolized BGA in the first three months of life, both maternal and neonatal exposure, or saline control. Kittens failing to achieve an asthmatic phenotype based on bronchoalveolar lavage fluid (BALF) analysis by 6 months underwent traditional sensitization: adjuvanted allergen injection, intranasal allergen, and aerosol challenges. BALF was collected at 3, 4 and 6 months, and after sensitization at 8 months, and analyzed for eosinophil counts and BGA-specific IgG and IgA. Intradermal testing (IDT) was performed at 6 and 7 months. At six months none of the kittens had airway eosinophilia, BGA-specific IgG or IgA, and were non-responsive to IDT. After sensitization, kittens receiving neonatal aerosolization failed to develop airway eosinophilia as seen in the controls. Kittens exposed to BGA aerosols, either in-utero or neonatally, continued to lack IDT response. Chronic exposure to BGA aerosols failed to induce asthma in kittens, and instead tolerized the kittens to BGA. This is the first evidence that neonatal intervention could potentially "prevent" allergic asthma in cats. PMID:24704287

  4. Asthma

    MedlinePlus

    ... Month with a Google+ Hangout on Air for parents and caregivers to learn how to help control a child's asthma so that they can breathe ... parents build up their asthma team. Jose, his parents, a doctor and a nurse, ... forces to help Jose control his asthma. The video is recorded in Spanish ...

  5. Prevention and treatment of allergic asthma in pregnancy: from conventional drugs to new therapeutical approaches.

    PubMed

    Cadavid, Angela P; Bannenberg, Gérard L; Arck, Petra C; Fitzgerald, Justine S; Markert, Udo R

    2011-05-01

    Different conventional anti-asthmatic and anti-allergic drugs are commonly used in pregnancy, including inhaled corticosteroids, long- and short-acting β-agonists, leukotriene modifiers, cromolyn, and theophylline. Alternatively, immunotherapy with allergens before and during pregnancy is accepted as a causal treatment of allergies, but the allergy specifity and severity in combination with a variety of application protocols and procedures cause wide heterogenity of this treatment principle. Furthermore, the pharmacokinetic characteristics and the US Food and Drug Administration (FDA) classification of conventional anti-allergic drugs and immunological implications of immunotherapy are summarized in this review, and insights on fetal programming of allergies are introduced. We propose a potential perspective of treatment with anti-inflammatory and pro-resolving mediators, such as lipoxins, resolvins and protectins; these are lipid mediators physiologically generated during the immune response from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. This proposal fits with the recently appreciated approaches to allergy prevention for the newborn child by a balanced maternal nutrition and omega-3 long-chain polyunsaturated fatty acid consumption. PMID:21342121

  6. Indoor Pollutant Hexabromocyclododecane Has a Modest Immunomodulatory Effect on House Dust Mite Induced Allergic Asthma in Mice.

    PubMed

    Canbaz, Derya; Logiantara, Adrian; Hamers, Timo; van Ree, Ronald; van Rijt, Leonie S

    2016-01-01

    Hexabromocyclododecane (HBCD) has been recognized as an indoor pollutant. HBCD is added as a flame retardant to many consumer products and leaches from the products into house dust. HBCD might be potentially hazardous to the airways because of inhalation of house dust. Sensitization to house dust mite (HDM) is a risk factor for the development of allergic asthma. In this study, we examined whether HBCD can affect the immune response to HDM allergens. Bone-marrow-derived dendritic cells (BMDCs) were exposed simultaneously to HBCD and HDM in vitro. HBCD enhanced oxidative stress in HDM-pulsed BMDCs, which was accompanied by a higher production of Interleukin (IL)-6 and -10. Adoptive transfer of HDM/HBCD-exposed BMDCs into naı̈ve mice resulted in enhanced levels of IL-17A after inhalational challenge with HDM. Direct mucosal exposure to HBCD during HDM inhalation enhanced IL-4 or IL-17A production, depending on the HDM extract used, but did not aggravate the eosinophilic airway inflammation or airway hyper-reactivity. Our results indicate that exposure to HBCD can have a mild immune-modulating effect by enhancing the inflammatory cytokine production in response to inhaled HDM in mice. PMID:26633745

  7. Epithelial barrier function: at the frontline of asthma immunology and allergic airway inflammation

    PubMed Central

    Georas, Steve N.; Rezaee, Fariba

    2014-01-01

    Airway epithelial cells form a barrier to the outside world, and are at the frontline of mucosal immunity. Epithelial apical junctional complexes are multi-protein subunits that promote cell-cell adhesion and barrier integrity. Recent studies in the skin and GI tract suggest that disruption of cell-cell junctions is required to initiate epithelial immune responses, but how this applies to mucosal immunity in the lung is not clear. Increasing evidence indicates that defective epithelial barrier function is a feature of airway inflammation in asthma. One challenge in this area is that barrier function and junctional integrity are difficult to study in the intact lung, but innovative approaches should provide new knowledge in this area in the near future. In this article, we review the structure and function of epithelial apical junctional complexes, emphasizing how regulation of the epithelial barrier impacts innate and adaptive immunity. We discuss why defective epithelial barrier function may be linked to Th2 polarization in asthma, and propose a rheostat model of barrier dysfunction that implicates the size of inhaled allergen particles as an important factor influencing adaptive immunity. PMID:25085341

  8. Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.

    PubMed

    Mikolka, P; Mokra, D; Drgova, A; Petras, M; Mokry, J

    2012-04-01

    In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma. PMID:22653905

  9. Acute painful paraplegia in a 49-year-old man with allergic asthma.

    PubMed

    Sorino, Claudio; Agati, Sergio; Milani, Giuseppe; Maspero, Annarosa

    2014-01-01

    We present a case of a 49-year-old man, with a 10-year history of bronchial asthma and nasal polyposis, who developed acutely painful paraplegia and paresthesias. Laboratory data showed elevated blood creatine kinase levels and myoglobinuria, which were diagnostic for rhabdomyolysis but only partially explained the neurological deficit. Electrophysiological studies revealed a sensorimotor neuropathy of multiple mononeuritis type. The patient also had leucocytosis with marked eosinophilia and antineutrophil cytoplasmic autoantibodies. Bronchial biopsies showed inflammatory infiltrates with a prevalence of eosinophils. All these findings led us to diagnose eosinophilic granulomatosis with polyangiitis, a systemic vasculitis with almost constant respiratory tract involvement and good response to corticosteroid treatment. This can also affect other organs including the nervous system, while muscular involvement is unusual. Some diseases deserve attention in differential diagnosis. Histology can support the diagnosis which remains essentially clinical. Steroid sparing agents/immunosuppressants are suggested for extensive disease. PMID:24980994

  10. Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma

    PubMed Central

    Lee, Jihyung; Kim, Tae Hoon; Murray, Fiona; Li, Xiangli; Choi, Sara S.; Broide, David H.; Corr, Maripat; Lee, Jongdae; Webster, Nicholas J. G.; Insel, Paul A.; Raz, Eyal

    2015-01-01

    The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes Gαs in mouse CD11c+ cells (GnasΔCD11c mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by GnasΔCD11c DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies. PMID:25605931

  11. An Overlook to the Characteristics and Roles Played by Eotaxin Network in the Pathophysiology of Food Allergies: Allergic Asthma and Atopic Dermatitis.

    PubMed

    Ahmadi, Zahra; Hassanshahi, Gholamhossein; Khorramdelazad, Hossein; Zainodini, Nahid; Koochakzadeh, Leila

    2016-06-01

    Investigations revealed substantial parts accomplished by chemokines specifically eotaxins and their specific receptors. They are functionally involved in the modulation of the pathologic state of tissue inflammation which is as a result of allergic reactions. Chemokines as small proteins with approximately 8-10 kDa molecular weight are considered and fit in the bigger family of cytokines, containing basic heparin-binding polypeptide mediators. Chemokines actively interfere in the processes of selective, oriented leukocyte (including eosinophil) recruitment. As eminent from their name, more specifically, eotaxins are specialized for eosinophils' oriented locomotion toward allergic inflamed regions. To date, three members are defined for eotaxin subfamily as follows: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), all of them bind to and activate CCR3 but have a low level of homology and appear to exhibit different physiological potentials. Allergy is described as a clinical state in which a pathologic hypersensitivity reaction is always initiated throughout an immunologic mechanism; similar to other immunologic reactions, an allergic reaction could also either be antibody or cell mediated. This type of allergic reactions occurs in all age groups and damages several different organs, having a significant impact on the emotional and social health of patients and their families and relatives. Concerning introductory comments introduced above, the authors of the present review attempted to collect and provide the latest evidences and information regarding the correlation between expression of eotaxin family members and allergy, in a wider extent, in two important allergic disorders: atopic asthma (AA) and atopic dermatitis (AD). Overall, concerning the most recent articles published within the database in the life sciences literature regarding the fundamental role(s) played by eotaxins in the pathogenesis of AA and AD, the authors of the current article

  12. Gene-environment interactions in asthma and allergic diseases: challenges and perspectives.

    PubMed

    Kauffmann, Francine; Demenais, Florence

    2012-12-01

    The concept of gene-environment (GxE) interactions has dramatically evolved in the last century and has now become a central theme in studies that assess the causes of human disease. Despite the numerous efforts to discover genes associated in asthma and allergy through various approaches, including the recent genome-wide association studies, investigation of GxE interactions has been mainly limited to candidate genes, candidate environmental exposures, or both. This review discusses the various strategies from hypothesis-driven strategies to the full agnostic search of GxE interactions with an illustration from recently published articles. Challenges raised by each piece of the puzzle (ie, phenotype, environment, gene, and analysis of GxE interaction) are put forward, and tentative solutions are proposed. New perspectives to integrate various types of data generated by new sequencing technologies and to progress toward a systems biology approach of disease are outlined. The future of a molecular network-based approach of disease to which GxE interactions are related requires space for innovative and multidisciplinary research. Assembling the various parts of a puzzle in a complex system could well occur in a way that might not necessarily follow the rules of logic. PMID:23195523

  13. Respiratory Allergic Disorders.

    PubMed

    Woloski, Jason Raymond; Heston, Skye; Escobedo Calderon, Sheyla Pamela

    2016-09-01

    Allergic asthma refers to a chronic reversible bronchoconstriction influenced by an allergic trigger, leading to symptoms of cough, wheezing, shortness of breath, and chest tightness. Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis, occurring when bronchi become colonized by Aspergillus species. The clinical picture is dominated by asthma complicated by recurrent episodes of bronchial obstruction, fever, malaise, mucus production, and peripheral blood eosinophilia. Hypersensitivity pneumonitis is a syndrome associated with lung inflammation from the inhalation of airborne antigens, such as molds and dust. PMID:27545731

  14. Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice.

    PubMed

    Park, Bum Soo; Hong, Gwan Ui; Ro, Jai Youl

    2013-05-01

    Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice. PMID:23560633

  15. Asthma.

    PubMed

    Bergmann, Karl-Christian

    2014-01-01

    'Asthma' is derived from the Greek root ασθμαινω, meaning 'gasp for breath'. The term originally did not define a disease, but was employed to describe respiratory symptoms of a variety of pulmonary conditions. Over the centuries, several models have been proposed to understand the pathophysiologic abnormalities of asthma. By the beginning of the 20th century, asthma was seen to be a unique illness characterized by 'spasmodic afflictions of the bronchial tubes'. Consistent with the nature of asthma as a complex disease, the models for asthma pathogenesis have become increasingly complex. Research has moved from antiquated ideas to a descriptive functional approach to one that relies on pathophysiology in cellular and molecular biology, immunology, microbiology and genetics/genomics. As more advanced technologies for measuring lung function were developed, the features of asthma were steadily unraveled and its pathophysiology clarified. Asthma was shown to be associated with transient increases in airway resistance, reductions in forced expiratory volumes and flows, hyperinflation of the lungs and increased work of breathing, as well as abnormalities in the distribution of ventilation, perfusion and arterial blood gases. Today, asthma is seen as a chronic inflammatory disease which is not yet fully understood in its pathophysiology; therefore, therapy is still on the path to becoming optimal. PMID:24925386

  16. Allergies, asthma, and dust

    MedlinePlus

    Allergic rhinitis - dust ... make allergies or asthma worse are called triggers. Dust is a common trigger. When your asthma or allergies become worse due to dust, you are said to have a dust allergy. ...

  17. Allergies, asthma, and molds

    MedlinePlus

    Allergic rhinitis - mold ... make allergies or asthma worse are called triggers. Mold is a common trigger. When your asthma or allergies become worse due to mold, you are said to have a mold allergy. ...

  18. Asthma

    MedlinePlus

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q& ... exercise. It's a great way to keep the body and mind healthy, so if you get exercise-induced asthma ...

  19. Common aeroallergens in patients with asthma and allergic rhinitis living in southwestern part of Iran: based on skin prick test reactivity.

    PubMed

    Farrokhi, Shokrollah; Gheybi, Mohammad Kazzem; Movahed, Ali; Tahmasebi, Rahim; Iranpour, Dariush; Fatemi, Atena; Etemadan, Razieh; Gooya, Mostafa; Zandi, Sahar; Ashourinejad, Hamid; Alavizadeh, Sara; Khoddami, Shaghayegh

    2015-04-01

    Aeroallergens continue to have a key role in the pathogenesis of asthma and allergic diseases and have recently received increased attention in medical research throughout the world. The prevalence of aeroallergens vary in different regions, depending on the type of climate. The aim of the present study was to determine prevalence of the sensitivity to aeroallergens among patients with asthma and allergic rhinitis (AR), based on skin prick test (SPT) reactivity in the province of Bushehr, Iran. In this cross-sectional study, 743 patients were enrolled. The participants had asthma and AR and reacted to at least one allergen with SPT. Skin prick test with standard extracts including house dust mites (HDMs), animal dander, molds and pollens were performed on patients according to the herbal geography of the area. The male to female ratio and mean age of the patients were 1.03 and 27.6± 15.4 year, respectively. Out of 567 patients with AR, the common aeroallergens were HDMs (88.5%), molds (82.9%), animal dander (79.5%), weeds (77.6%), trees (75.5%) and grass pollen (71.5%). Moreover, among 176 patients with asthma, the prevalence of aeroallergens were HDMs (90.5 %), molds (80.7%), animal dander (77.5%), weeds (73.3%), trees (73.3%) and grass pollen (67.9%). The sensitivity to animal dander, Chenopodium album and Russian thistle pollens were significantly associated with the severity of AR. Moreover, sensitivity to animal dander such as cat and feather of birds, cockroach, Bermuda grass and Chenopodium album pollens were significantly associated with the severity of asthma. The results of this study revealed that HDM was the most common sensitizing aeroallergen in patients with asthma and AR. Molds and animal dander as indoor allergens were also common aeroallergens. We suggest that the hot weather and ambient humidity in the region may be the main cause of the change in the pattern of SPT reactivity. PMID:25780879

  20. A Systematic and Narrative Review of Acupuncture Point Application Therapies in the Treatment of Allergic Rhinitis and Asthma during Dog Days

    PubMed Central

    Wen, Cai-Yu-Zhu; Liu, Ya-Fei; Zhou, Li; Zhang, Hong-Xing; Tu, Sheng-Hao

    2015-01-01

    Acupuncture point application therapies, including San-Fu-Tie and San-Fu-Jiu, have been widely employed to treat diseases with attacks in winter during dog days in China. The therapies combine Chinese herbal medicine and acupuncture points with the nature. However, the previous studies were reported to be unsystematic and incomplete. To develop a more comprehensive understanding of the effects of acupuncture point application therapies on allergic rhinitis and asthma, a systematic review of the literature up to 2015 was conducted. After filtering, eighteen randomized controlled trials (RCTs) involving 1,785 subjects were included. This systematic and narrative review shows that acupuncture point application therapies have been extensively applied in the treatment of allergic rhinitis and asthma with advantages of favorable treatment effect, convenient operation, receiving patients' good acceptability and compliance, and few side effects. Meanwhile, the study elaborated the operating process of San-Fu-Tie and San-Fu-Jiu in detail. The review may provide a reference for clinical application in future. However, the efficacy, safety, and mechanisms of San-Fu-Tie and San-Fu-Jiu in treating the above diseases need to be validated by more well-designed and fully powered RCTs in a larger population of patients. PMID:26543488

  1. Effect of dexamethasone and Nigella sativa on inducible nitric oxide synthase in the lungs of a murine model of allergic Asthma.

    PubMed

    Abdel-Aziz, Mohamed; Abass, Ayman; Zalata, Khaled; Abd Al-Galel, Tarek; Allam, Umamma; Karrouf, Gamal

    2014-10-01

    The aim of this study was to investigate the effects of Nigella sativa (NS) fixed oil in comparison to dexamethasone (Dex) on inducible nitric oxide synthase (iNOS), peripheral blood eosinophils (PBE), allergen specific serum IgG1 and interleukins and airway inflammation in a murine model of allergic asthma. Thirty-one mice were divided into four groups. Group I (n = 6) served as the control group. Group II (n = 10) mice were sensitized intraperitoneally and challenged intratracheally with cone albumin with no treatment. Group III(n = 6) mice were sensitized, challenged, and treated with Dex for 17 days starting at 24 hours after the first challenge. Group IV (n = 9) mice were sensitized, challenged, and treated with NS fixed oil for 17 days as well. For all groups, the following procedures were carried out: immunohistochemical study of iNOS in lung tissues, detection of PBE percentage, and histopathological examination of lung tissues for inflammatory cells. Lung tissue iNOS expression increased in sensitized, non-treated mice compared with controls, but this increase was not significant. NS fixed oil treatment significantly reduced PBE and lung inflammation but did not significantly reduce lung tissue iNOS expression compared with the control group. These effects were comparable to the effects of Dex. These results suggest that Nigella sativa exhibits immunomodulatory and anti-inflammatory effect which may be useful for treatment of allergic asthma. PMID:25150073

  2. Simvastatin Inhibits Goblet Cell Hyperplasia and Lung Arginase in a Mouse Model of Allergic Asthma: A Novel Treatment for Airway Remodeling?

    PubMed Central

    Zeki, Amir A.; Bratt, Jennifer M.; Rabowsky, Michelle; Last, Jerold A.; Kenyon, Nicholas J.

    2010-01-01

    Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function, and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. The statins are cholesterol-lowering drugs that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting step of cholesterol biosynthesis in the mevalonate pathway. These drugs have been associated with improved respiratory health and ongoing clinical trials are testing their therapeutic potential in asthma. We hypothesized that simvastatin treatment of ovalbumin-exposed mice would attenuate early features of airway remodeling, by a mevalonate-dependent mechanism. BALB/c mice were initially sensitized to ovalbumin, and then exposed to 1% ovalbumin aerosol for 2 weeks after sensitization for a total of six exposures. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) were injected intraperitoneally before each ovalbumin exposure. Treatment with simvastatin attenuated goblet cell hyperplasia, arginase-1 protein expression, and total arginase enzyme activity, but did not alter airway hydroxyproline content or transforming growth factor-β1. Inhibition of goblet cell hyperplasia by simvastatin was mevalonate-dependent. No appreciable changes to airway smooth muscle cells were observed in any of the control or treatment groups. In conclusion, in an acute mouse model of allergic asthma, simvastatin inhibited early hallmarks of airway remodeling, indicators that can lead to airway thickening and fibrosis. Statins are potentially novel treatments for airway remodeling in asthma. Further studies utilizing sub-chronic or chronic allergen exposure models are needed to extend these initial findings. PMID:21078495

  3. Differential effects of endogenous and exogenous interferon-gamma on immunoglobulin E, cellular infiltration, and airway responsiveness in a murine model of allergic asthma.

    PubMed

    Hofstra, C L; Van Ark, I; Hofman, G; Nijkamp, F P; Jardieu, P M; Van Oosterhout, A J

    1998-11-01

    The inflammatory response as seen in human allergic asthma is thought to be regulated by Th2 cells. It has been shown that interferon-gamma (IFN-gamma) can downregulate the proliferation of Th2 cells and therefore might be of therapeutic use. In the present study we have investigated the in vivo role of endogenous and exogenous IFN-gamma in a murine model with features reminiscent of human allergic asthma. IFN-gamma gene knockout (GKO) and wild-type mice were sensitized with ovalbumin and exposed to repeated ovalbumin aerosol challenges. In addition, wild-type mice were treated with intraperitoneal or nebulized recombinant murine IFN-gamma during the challenge period. Sensitized wild-type mice exhibited upregulated ovalbumin-specific IgE in serum, and airway hyperresponsiveness and infiltration of eosinophils and mononuclear cells in the bronchoalveolar lavage fluid (BALF) after ovalbumin challenge. In contrast, in GKO mice only reduced eosinophilic infiltration in the BALF was observed after ovalbumin challenge. In wild-type mice, parenteral IFN-gamma treatment downregulated ovalbumin-specific IgE levels in serum, and airway hyperresponsiveness and cellular infiltration in the BALF, whereas aerosolized IFN-gamma treatment only suppressed airway hyperresponsiveness. In vitro experiments showed that these effects of IFN-gamma appear not to be mediated via a direct effect on the cytokine production of antigen-specific Th2 cells. These data indicate that airway hyperresponsiveness can be downregulated by IFN-gamma locally in the airways, whereas for downregulation of IgE and cellular infiltration systemic IFN-gamma is needed. The present study shows that exogenous IFN-gamma can downregulate the allergic response via an antigen-specific T-cell independent mechanism, but at the same time endogenous IFN-gamma plays a role in an optimal response. PMID:9806748

  4. Asthma.

    PubMed Central

    Calverley, P. M.

    1996-01-01

    Bronchial asthma is now recognised to be a major cause of morbidity and even mortality in people of all ages. Two important ideas have changed our approach to asthma management. The first is understanding that asthma is a chronic inflammatory disorder which needs regular treatment with anti-inflammatory drugs such as inhaled corticosteroids to prevent further attacks. The second development is the availability of prescribable peak flow meters, which allows both confident diagnosis and early prediction of relapse. Asthma management guidelines provide a logical treatment framework for most patients, but a few difficult cases still consume large amounts of medical time. The commonest problem is one of compliance with treatment which may respond to patient education, although this is not universally so. Other problems include misdiagnosis, acid reflux and, rarely, true corticosteroid-resistant asthma. Several potentially important new treatments have been developed. These include longer acting anticholinergic drugs, drugs with bronchodilator and some anti-inflammatory properties which antagonise or inhibit the production of leukotrienes, sub-types of phosphodiesterase inhibitor with anti-inflammatory properties and immunosuppressive drugs such as cyclosporin. Ultimately these new treatments must be rigorously tested and integrated into a care plan that remains centred on patient education. PMID:8746278

  5. Titanium dioxide nanoparticles augment allergic airway inflammation and Socs3 expression via NF-κB pathway in murine model of asthma.

    PubMed

    Mishra, Vani; Baranwal, Vikas; Mishra, Rohit K; Sharma, Shivesh; Paul, Bholanath; Pandey, Avinash C

    2016-06-01

    Titanium dioxide nanoparticles (nTiO2) previously considered to possess relatively low toxicity both in vitro and in vivo, although classified as possibly carcinogenic to humans. Also, their adjuvant potential has been reported to promote allergic sensitization and modulate immune responses. Previously, in OVA induced mouse model of asthma we found high expression of Socs3 and low expression of Stat3 and IL-6. However, a clear understanding regarding the signaling pathways associated with nTiO2 adjuvant effect in mouse model of asthma is lacking. In the present study we investigated the status of Stat3/IL-6 and Socs3 and their relationship with NF-κB, with nTiO2 as an adjuvant in mouse model of asthma. nTiO2 when administered with ovalbumin (OVA) during sensitization phase augmented airway hyper-responsiveness (AHR), biochemical markers of lung damage and a mixed Th2/Th1 dependent immune response. At the same time, we observed significant elevation in the levels of Stat3, Socs3, NF-κB, IL-6 and TNF-α. Furthermore, transient in vivo blocking of NF-κB by NF-κB p65 siRNA, downregulated the expression of Socs3, IL-6 and TNF-α. Our study, thus, shows that nTiO2 exacerbate the inflammatory responses in lungs of pre-sensitized allergic individuals and that these changes are regulated via NF-κB pathway. PMID:27057692

  6. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells.

    PubMed

    Lin, Chu-Lun; Hsiao, George; Wang, Ching-Chiung; Lee, Yueh-Lun

    2016-08-01

    Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and possesses various biological activities. Herein, we investigated the antiallergic effects of imperatorin in asthmatic mice and explored the immunomodulatory actions of imperatorin on immune cells. We used a murine model of ovalbumin (OVA)-induced asthma to evaluate the therapeutic potential of imperatorin. Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to clarify whether imperatorin exerts an antiallergic effect through altering the ability of DCs to regulate T cells. Oral administration of imperatorin to OVA-sensitized and -challenged mice decreased serum OVA-specific immunoglobulin E (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated airway inflammation in a dose-dependent manner. Notably, secretions of Th2 cytokines and chemokines were reduced, and numbers of interleukin (IL)-10-producing regulatory T cells (Tregs) increased in imperatorin-treated mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared to fully mature DCs, imperatorin-treated DCs expressed high levels of the inducible costimulatory ligand (ICOSL) and Jagged1 molecules, and had the regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell proliferation and cytokine production. Imperatorin may possess therapeutic potential against Th2-mediated allergic asthma not only via stimulating DC induction of Tregs but also via direct inhibition of Th2 cell activation. These findings provide new insights into how imperatorin affects the Th2 immune response and the development of imperatorin as a Treg-type immunomodulatory agent to treat allergic asthma. PMID:27185659

  7. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma.

    PubMed

    Nemeth, Krisztian; Keane-Myers, Andrea; Brown, Jared M; Metcalfe, Dean D; Gorham, James D; Gorham, Jared D; Bundoc, Virgilio G; Bundoc, Victor G; Hodges, Marcus G; Jelinek, Ivett; Madala, Satish; Karpati, Sarolta; Mezey, Eva

    2010-03-23

    Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-beta production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions--specifically therapy resistant asthma--might also be a likely target of the recently discovered cellular therapy approach using BMSCs. PMID:20231466

  8. Allergic rhinitis

    PubMed Central

    2011-01-01

    Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually a long-standing condition that often goes undetected in the primary-care setting. The classic symptoms of the disorder are nasal congestion, nasal itch, rhinorrhea and sneezing. A thorough history, physical examination and allergen skin testing are important for establishing the diagnosis of allergic rhinitis. Second-generation oral antihistamines and intranasal corticosteroids are the mainstay of treatment. Allergen immunotherapy is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for allergic rhinitis is not effective or is not tolerated. This article provides an overview of the pathophysiology, diagnosis, and appropriate management of this disorder. PMID:22166009

  9. Immune-Modulatory Effects of Bu-Zhong-Yi-Qi-Tang in Ovalbumin-Induced Murine Model of Allergic Asthma

    PubMed Central

    Yang, Sien-Hung; Kao, Ting-I; Chiang, Bor-Luen; Chen, Hsing-Yu; Chen, Kuang-Hua; Chen, Jiun-Liang

    2015-01-01

    Background Bu-zhong-yi-qi-tang (BZYQT), an herbal formula of traditional Chinese medicine, has been an effective regimen of allergic diseases for nearly 800 years. Our previous report has demonstrated its anti-inflammatory effects in patients with perennial allergic rhinitis, and the aim of this study is to investigate the anti-asthmatic effect of BZYQT. Methods Female BALB/cByJNarl mice were sensitized with normal saline (control group) or OVA. Mice sensitized by OVA were fed with distilled water (OVA group), oral 0.5 g/Kg (low-dose group) or 1 g/Kg (high-dose group) of BZYQT solution once daily on days 36-40 besides their routine diet. Airway hyper-responsiveness (AHR), eosinophil infiltration, levels of cytokines and total immunoglobulin E (IgE) in broncho-alveolar lavage fluid (BALF) were determined. The lungs and tracheas were removed, and histopathologic examination was subsequently performed. Results AHR was significantly reduced in both low- and high-dose BZYQT groups compared with the OVA group after inhalation of the highest dose of methacholine (50 mg/ml). The levels of eotaxin, Th2-related cytokines (IL-4, IL-5, IL-13), IgE, and eosinophil infiltration in BALF were significantly decreased in both BZYQT groups compared with the OVA group. Histopathologic examination revealed that eosinophil infiltration of the lung and trachea tissues was remarkably attenuated in both BZYQT groups. Conclusions Oral administration of BZYQT solution may exert anti-asthmatic effect by relieving AHR in OVA-sensitized mice, which is compatible with our clinical experience. Although detailed mechanism is to be determined, we surmise that it may be correlated with the immune-modulatory effects of inhibiting Th2 responses on the basis of our limited results. PMID:26035827

  10. Asthma

    MedlinePlus

    ... Burks AW, et al, eds. In: Middleton's Allergy Principles and Practice . 8th ed. Philadelphia, PA: Elsevier Mosby; 2014:chap 55. Lugogo N, Que LG, Gilstrap DL, Kraft M. Asthma: clinical diagnosis and management. In: Broaddus VC, Mason RJ, Ernst JD, et ...

  11. Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice.

    PubMed

    Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

    2016-02-01

    Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA)-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA-sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes

  12. Tuberculosis, bacillus Calmette-Guérin vaccination, and allergic disease: findings from the International Study of Asthma and Allergies in Childhood Phase Two.

    PubMed

    Flohr, Carsten; Nagel, Gabriele; Weinmayr, Gudrun; Kleiner, Andrea; Williams, Hywel C; Aït-Khaled, Nadia; Strachan, David P

    2012-06-01

    Some have suggested a protective effect of tuberculosis (TB) infection on allergic disease risk, but few studies have examined the association between the two. We therefore investigated whether TB disease and bacillus Calmette-Guérin (BCG) vaccination in early life protect against allergic disease. Information on allergic disease symptoms, past TB disease, and BCG vaccination as well as potential confounding factors was gathered by parental questionnaire from a randomly selected subset of 23,901 8- to 12-yr-old schoolchildren in 20 centers in both developed and developing countries. Children were also physically examined for flexural eczema and underwent skin prick testing. Pooled odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) across study centers were calculated, using random effects meta-analysis models. There were 245 (1.0%) reported cases of TB disease, and 66.3% (15,857) of all children received the BCG vaccine. Asthma, hay fever, and flexural eczema symptoms in the past year as well as flexural eczema on skin examination were all positively linked to a history of TB (adjusted pooled OR 'wheeze in the past year' = 2.27, 95% CI 1.52-3.41; adjusted pooled OR 'hay fever symptoms in the past year' = 2.23, 1.22-4.09; adjusted pooled OR 'flexural eczema symptoms in the past year' = 3.21, 2.01-5.12; adjusted pooled OR 'flexural eczema on skin examination' = 4.04, 1.71-9.56). Even higher risk estimates were seen for severe asthma and eczema symptoms [adjusted OR = 4.02 (2.17-7.47) and adjusted OR = 6.31 (2.19-18.17), respectively]. There was no significant association between past TB and skin prick test positivity (adjusted pooled OR = 1.32, 0.87-2.02). BCG vaccination during the first year of life was also not associated with any of the allergy outcomes. We found a uniform positive association between TB and all allergic disease outcomes, including eczema on skin examination. As this was a cross-sectional study, it is unclear whether this

  13. INDOOR MOLDS AND ALLERGIC POTENTIAL

    EPA Science Inventory

    Rationale: Damp/moldy environments have been associated with asthma exacerbation, but mold¿s role in allergic asthma induction is less clear. Recently, 5 molds were statistically associated with water-damaged asthmatic homes in the Cleveland area. The asthma exacerbation...

  14. Imaging of Asthma.

    PubMed

    Richards, John Caleb; Lynch, David; Koelsch, Tilman; Dyer, Debra

    2016-08-01

    Asthma is one of the most common diseases of the lung. Asthma manifests with common, although often subjective and nonspecific, imaging features at radiography and high-resolution computed tomography. The primary role of imaging is not to make a diagnosis of asthma but to identify complications, such as allergic bronchopulmonary aspergillosis, or mimics of asthma, such as hypersensitivity pneumonitis. This article reviews the imaging features of asthma as well as common complications and mimics. PMID:27401624

  15. The Relationship between Maternal Atopy and Childhood Asthma in Pretoria, South Africa.

    PubMed

    Abbott, Salome; Becker, Piet; Green, Robin J

    2013-01-01

    Introduction. Asthma is the commonest chronic condition of children. Diagnosis of this condition remains difficult. Many surrogate markers are used, such as documenting evidence of atopy. Method. A random sample of asthmatic children and their mothers attending the Children's Chest and Allergy Clinic at Steve Biko Academic Hospital were enrolled. Children were classified as having atopic or nonatopic asthma. Mothers completed a questionnaire to uncover atopic features. Results. Along with their mothers, 64 children with atopic asthma and 36 with nonatopic asthma were studied. The proportion of children with atopic asthma does not differ for mothers with and without a positive SPT (P = 0.836), a history of asthma (P = 0.045), symptoms suggestive of an allergic disease (P = 1.000), or who were considered to be allergic (P = 0.806). The odds ratio of a child having atopic asthma when having a mother with a doctor diagnosed history of asthma is 4.76, but the sensitivity is low (21.9%). Conclusion. The data demonstrates that all maternal allergic or asthmatic associations are poor predictors of childhood atopic asthma. Despite the increased risk of atopic asthma in a child to a mother that has a doctor diagnosis of asthma (OR 4.76 P = 0.045), this is a poor predictor of atopic asthma (sensitivity 21.9%). PMID:23724245

  16. Lipopolysaccharide enhances FcεRI-mediated mast cell degranulation by increasing Ca2+ entry through store-operated Ca2+ channels: implications for lipopolysaccharide exacerbating allergic asthma.

    PubMed

    Yang, Chengbin; Mo, Xucheng; Lv, Jingzhang; Liu, Xiaoyu; Yuan, Meichun; Dong, Ming; Li, Li; Luo, Xinping; Fan, Xinmin; Jin, Zhe; Liu, Zhigang; Liu, Jie

    2012-12-01

    Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not fully understood. This study investigated the effect of LPS on antigen-stimulated mast cell degranulation and the underlying mechanisms. We found that LPS enhanced degranulation in RBL-2H3 cells and mouse peritoneal mast cells upon FcεRI activation, in a dose- and time-dependent manner. Parallel to the alteration of degranulation, LPS increased FcεRI-activated Ca(2+) mobilization, as well as Ca(2+) entry through store-operated calcium channels (SOCs) evoked by thapsigargin. Blocking Ca(2+) entry through SOCs completely abolished LPS enhancement of mast cell degranulation. Consistent with functional alteration of SOCs, LPS increased mRNA and protein levels of Orai1 and STIM1, two major subunits of SOCs, in a time-dependent manner. In addition, LPS increased the mRNA level of Toll-like receptor 4 (TLR4) in a time-dependent manner. Blocking TLR4 with Cli-095 inhibited LPS, increasing transcription and expression of SOC subunits. Concomitantly, the effect of LPS enhancement of Ca(2+) mobilization and mast cell degranulation was largely reduced by Cli-095. Administration of LPS (1 μg) in vivo aggravated airway hyperreactivity and inflammatory reactions in allergic asthmatic mice. Histamine levels in serum and bronchoalveolar lavage fluid were increased by LPS treatment. In addition, Ca(2+) mobilization was enhanced in peritoneal mast cells isolated from LPS-treated asthmatic mice. Taken together, these results imply that LPS enhances mast cell degranulation, which potentially contributes to LPS exacerbating allergic asthma. Lipopolysaccharide increases Ca(2+) entry through SOCs by upregulating transcription and expression of SOC subunits, mainly through interacting with TLR4 in mast cells, resulting in enhancement of mast cell degranulation upon antigen stimulation. PMID:22581748

  17. Birth cohorts in asthma and allergic diseases: report of a NIAID/NHLBI/MeDALL joint workshop.

    PubMed

    Bousquet, Jean; Gern, James E; Martinez, Fernando D; Anto, Josep M; Johnson, Christine C; Holt, Patrick G; Lemanske, Robert F; Le Souëf, Peter N; Tepper, Robert S; von Mutius, Erika R M; Arshad, S Hasan; Bacharier, Leonard B; Becker, Allan; Belanger, Kathleen; Bergström, Anna; Bernstein, David I; Cabana, Michael D; Carroll, Kecia N; Castro, Mario; Cooper, Philip J; Gillman, Matthew W; Gold, Diane R; Henderson, John; Heinrich, Joachim; Hong, Soo-Jong; Jackson, Daniel J; Keil, Thomas; Kozyrskyj, Anita L; Lødrup Carlsen, Karin C; Miller, Rachel L; Momas, Isabelle; Morgan, Wayne J; Noel, Patricia; Ownby, Dennis R; Pinart, Mariona; Ryan, Patrick H; Schwaninger, Julie M; Sears, Malcolm R; Simpson, Angela; Smit, Henriette A; Stern, Debra A; Subbarao, Padmaja; Valenta, Rudolf; Wang, Xiaobin; Weiss, Scott T; Wood, Robert; Wright, Anne L; Wright, Rosalind J; Togias, Alkis; Gergen, Peter J

    2014-06-01

    Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. PMID:24636091

  18. Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma.

    PubMed

    Cho, Kyu-Sup; Park, Mi-Kyung; Kang, Shin-Ae; Park, Hee-Young; Hong, Sung-Lyong; Park, Hye-Kyung; Yu, Hak-Sun; Roh, Hwan-Jung

    2014-01-01

    Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production. PMID:25246732

  19. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model.

    PubMed

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan

    2016-09-01

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2weeks. 48h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocyte count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. PMID:27343405

  20. Impact of omalizumab on treatment of severe allergic asthma in UK clinical practice: a UK multicentre observational study (the APEX II study)

    PubMed Central

    Niven, Robert M; Saralaya, Dinesh; Chaudhuri, Rekha; Masoli, Matthew; Clifton, Ian; Mansur, Adel H; Hacking, Victoria; McLain-Smith, Susan; Menzies-Gow, Andrew

    2016-01-01

    Objective To describe the impact of omalizumab on asthma management in patients treated as part of normal clinical practice in the UK National Health Service (NHS). Design A non-interventional, mixed methodology study, combining retrospective and prospective data collection for 12 months pre-omalizumab and post-omalizumab initiation, respectively. Setting Data were collected in 22 UK NHS centres, including specialist centres and district general hospitals in the UK. Participants 258 adult patients (aged ≥16 years; 65% women) with severe persistent allergic asthma treated with omalizumab were recruited, of whom 218 (84.5%) completed the study. Primary and secondary outcome measures The primary outcome measure was change in mean daily dose of oral corticosteroids (OCS) between the 12-month pre-omalizumab and post-omalizumab initiation periods. A priori secondary outcome measures included response to treatment, changes in OCS dosing, asthma exacerbations, lung function, employment/education, patient-reported outcomes and hospital resource utilisation. Results The response rate to omalizumab at 16 weeks was 82.4%. Comparing pre-omalizumab and post-omalizumab periods, the mean (95% CIs) daily dose of OCS decreased by 1.61 (−2.41 to −0.80) mg/patient/day (p<0.001) and hospital exacerbations decreased by 0.97 (−1.19 to −0.75) exacerbations/patient (p<0.001). Compared with baseline, lung function, assessed by percentage of forced expiratory volume in 1 s, improved by 4.5 (2.7 to 6.3)% at 16 weeks (p<0.001; maintained at 12 months) and patient quality of life (Asthma Quality of Life Questionnaire) improved by 1.38 (1.18 to 1.58) points at 16 weeks (p<0.001, maintained at 12 months). 21/162 patients with complete employment data gained employment and 6 patients lost employment in the 12-month post-omalizumab period. The mean number of A&E visits, inpatient hospitalisations, outpatient visits (excluding for omalizumab) and number of bed days

  1. Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma

    PubMed Central

    Guo, Sheng; Wu, Liangxia; Zhang, Jianhua

    2016-01-01

    Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation. PMID:26974537

  2. Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome.

    PubMed

    Li, Hong-Tao; Zhang, Tian-Tuo; Chen, Zhuang-Gui; Ye, Jin; Liu, Hui; Zou, Xiao-Ling; Wang, Yan-Hong; Yang, Hai-Ling

    2015-09-01

    Given the relationship between allergic rhinitis (AR) and asthma, it can be hypothesized that reducing upper airway inflammation by targeting oligodeoxynucleotides with CpG motifs (CpG-ODN) specifically to the upper airway via intranasal administration in a small volume (10 μL) might improve lower airway (asthma) outcomes. The goal of this study was to investigate the therapeutic efficacy of 10 μL of intranasal versus intradermal administration of CpG-ODN in suppressing lower airway inflammation and methacholine-induced airway hyperreactivity (AHR) in mice subjected to ovalbumin (OVA)-induced combined allergic rhinitis and asthma syndrome (CARAS). OVA-sensitized BALB/c mice were subjected to upper-airway intranasal OVA exposure three times per week for 3 weeks. Then, CpG-ODN was administered to a subset of these mice 1h after intranasal OVA exposure, followed by five days of OVA aerosol challenges, thereby targeting OVA to the lower airways. Immunologic variables and nasal symptoms were evaluated. The results showed that the CARAS mice exhibited significant increases in bronchoalveolar lavage fluid (BALF) and splenocytes Th2-associated cytokine production, OVA-specific serum IgE, and AHR, as well as nose and lung pathologies. Intranasal administration of CpG-ODN significantly reduced Th2-associated cytokine production, the percentage of eosinophils in the BALF, the IL-4 and IL-5 concentrations in the supernatants of cultured OVA-challenged splenic lymphocytes, the serum OVA-specific IgE levels, the peribronchial inflammation score in the lungs, and the severity of nose pathology and nasal symptoms. However, intradermal administration of CpG-ODN did not significantly reduce the aforementioned parameters. In conclusion, intranasal treatment with CpG-ODN attenuated AR and significantly alleviated lower airway inflammation and AHR in the CARAS model. CpG-ODN therapy was more effective when administered intranasally than when administered intradermally. The current

  3. Allergic rhinitis

    MedlinePlus

    ... your symptoms. Skin testing is the most common method of allergy testing. If your doctor determines you ... Others cause little or no sleepiness. Antihistamine nasal sprays work well for treating allergic rhinitis. Ask your ...

  4. Diesel exhaust particle induction of IL17A contributes to severe asthma

    PubMed Central

    Brandt, Eric B.; Kovacic, Melinda Butsch; Lee, Gerald B.; Gibson, Aaron M.; Acciani, Thomas H.; Le Cras, Timothy D.; Ryan, Patrick H.; Budelsky, Alison L.; Khurana Hershey, Gurjit K.

    2013-01-01

    Background IL-17A has been implicated in severe forms of asthma. However, the factors that promote IL-17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEP) are a major component of traffic related air pollution and are implicated in asthma pathogenesis and exacerbation. Objective To determine the mechanism by which DEP exposure impacts asthma severity using human and mouse studies. Methods Balb/c mice were challenged with DEP +/− house dust mite extract (HDM). Airway inflammation and function, BALF cytokine levels, and flow cytometry of lung T cells were assessed. The impact of DEP exposure on frequency of asthma symptoms and serum cytokine levels was determined in children with allergic asthma. Results In mice, exposure to DEP alone did not induce asthma. DEP and HDM co-exposure markedly enhanced AHR compared to HDM alone and generated a mixed Th2 and Th17 response, including IL-13+IL-17A+ double producing T-cells. IL-17A neutralization prevented DEP-induced exacerbation of AHR. Among 235 high DEP-exposed children with allergic asthma, 32.2% had more frequent asthma symptoms over a 12 month period, compared to only 14.2% in the low DEP-exposed group (p=0.002). Additionally, high DEP-exposed children with allergic asthma had nearly six times higher serum IL-17A levels compared with low DEP-exposed children. Conclusions Expansion of Th17 cells contributes to DEP-mediated exacerbation of allergic asthma. Neutralization of IL-17A may be a useful potential therapeutic strategy to counteract the asthma promoting effects of traffic related air pollution especially in highly exposed severe allergic asthmatics. PMID:24060272

  5. Halting the allergic march.

    PubMed

    Van Bever, Hugo P; Samuel, Sudesh T; Lee, Bee Wah

    2008-04-01

    The prevalence of childhood allergic diseases, such as allergic asthma, allergic rhinitis, and atopic dermatitis, has increased exponentially. In Singapore, the prevalence of asthma at all ages exceeds 20%, and around 50% of Singaporean children show features of an underlying allergy. The exact environmental causes for the increase of allergic diseases have not yet been identified, but most researchers agree that a decreased bacterial load in young children may be one of the reasons for the increase. However, the causes of allergy are multiple, and the development of an allergic disease is the result of complex interactions between genetic constitution and environmental factors. In this review article, different aspects of allergic sensitization are covered, including prenatal and postnatal sensitization. The phenomenon of the "allergic march" (switching from one clinical expression of allergy to another) and its underlying mechanisms are discussed. The last part of this review article is on prevention and treatment of allergic diseases, including the role of bacterial products (probiotics, prebiotics, and synbiotics) and the role of immunotherapy, including sublingual immunotherapy. PMID:23283392

  6. Management of Allergic Rhinitis

    PubMed Central

    Sausen, Verra O.; Marks, Katherine E.; Sausen, Kenneth P.; Self, Timothy H.

    2005-01-01

    Allergic rhinitis is the most common chronic childhood disease. Reduced quality of life is frequently caused by this IgE-mediated disease, including sleep disturbance with subsequent decreased school performance. Asthma and exercise-induced bronchospasm are commonly seen concurrently with allergic rhinitis, and poorly controlled allergic rhinitis negatively affects asthma outcomes. Nonsedating antihistamines or intranasal azelastine are effective agents to manage allergic rhinitis, often in combination with oral decongestants. For moderate to severe persistent disease, intranasal corticosteroids are the most effiective agents. Some patients require concomitant intranasal corticosteroids and nonsedating antihistamines for optimal management. Other available agents include leukotriene receptor antagonists, intranasal cromolyn, intranasal ipratropium, specific immunotherapy, and anti-IgE therapy. PMID:23118635

  7. Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma.

    PubMed

    Raju, Kalidhindi Rama Satyanarayana; Ambhore, Nilesh S; Mulukutla, Shashank; Gupta, Saurabh; Murthy, Vishakantha; Kumar, M N Kiran; Madhunapantula, Subba Rao V; Kuppuswamy, Gowthamarajan; Elango, Kannan

    2016-02-01

    Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients. PMID:26643666

  8. [Genetic study of allergic diseases].

    PubMed

    Zhang, Yuan; Zhang, Luo

    2012-09-01

    Allergic diseases mentioned in this review is regarding to I type allergic inflammation induced by an IgE-mediated reaction, including asthma, allergic rhinitis, atopic dermatitis and food allergy. It is convinced that allergic diseases belong to multiple genes diseases and are controlled by both genetic and environmental factors. Meanwhile there exists gene-gene as well as gene-environment interactions during the development of the disease. The aim of this review is to summarize the toolkit, advance, inherent difficulties and future clinical application prospect in genetic studies of allergic disease. PMID:23214325

  9. Inflammatory Marker sTREM-1 Reflects the Clinical Stage and Respiratory Tract Obstruction in Allergic Asthma Bronchiale Patients and Correlates with Number of Neutrophils

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Dzurilla, Martin; Vrlik, Mojmir; Novosadova, Helena; Tedlova, Eva; Urban, Stefan; Hornakova, Edita; Seligova, Marianna; Durmanova, Vladimira; Penz, Peter; Javor, Juraj; Paulovicova, Ema

    2012-01-01

    The knowledge that asthma is an inflammatory disorder has prompted us to investigate the plasma levels of a new inflammatory marker sTREM-1 that is released from the surfaces of activated neutrophils and monocytes. The plasma levels of sTREM-1 were analysed by a sandwich ELISA test in the cohort of 76 patients with allergic asthma bronchiale and 39 healthy controls. Our results revealed more than 3.5 times higher levels of sTREM-1 in AB patients (92.3 pg/mL ± 125.6) compared with healthy subjects (25.7 pg/mL ± 9.2; P = 0.0001). Higher levels of sTREM-1 were found also in patients with exacerbated AB (170.5 pg/mL ± 78.2) compared with nonexacerbated AB patients (59.1 ± 78.2; P < 0.0001), patients with respiratory tract obstruction (176.4 pg/mL ± 177.8), than those without obstruction (51.99 pg/mL ± 64.0; P < 0.0001) and patients with anti-IgE therapy (P < 0.0001). Levels of sTREM-1 correlated with number of leucocytes (P = 0.002), and absolute number of neutrophils (P = 0.001). Elevated plasma levels of sTREM-1 reflect the severity, state of exacerbation, presence of respiratory tract obstruction in AB patients and together with increased number of neutrophils point to the role of neutrophils in inflammation accompanying AB. PMID:22829716

  10. Cbl-b Deficiency in Mice Results in Exacerbation of Acute and Chronic Stages of Allergic Asthma

    PubMed Central

    Carson, William F.; Guernsey, Linda A.; Singh, Anurag; Secor, Eric R.; Wohlfert, Elizabeth A.; Clark, Robert B.; Schramm, Craig M.; Kunkel, Steven L.; Thrall, Roger S.

    2015-01-01

    Mice sensitized to ovalbumin (OVA) develop allergic airway disease (AAD) with short-term daily OVA aerosol challenge; inflammation resolves with long-term OVA aerosol exposure, resulting in local inhalational tolerance (LIT). Cbl-b is an E3 ubiquitin ligase involved with CD28 signaling; Cbl-b−/− effector T cells are resistant to regulatory T cell-mediated suppression in vitro and in vivo. The present study utilized Cbl-b−/− mice to investigate the role of Cbl-b in the development of AAD and LIT. Cbl-b−/− mice exhibited increased airway inflammation during AAD, which failed to resolve with long-term OVA aerosol exposure. Exacerbation of inflammation in Cbl-b−/− mice correlated with increased proinflammatory cytokine levels and expansion of effector T cells in the BAL during AAD, but did not result in either a modulation of lymphocyte subsets in systemic tissues or in OVA-specific IgE in serum. These results implicate a role for Cbl-b in the resolution of allergic airway inflammation. PMID:26635806

  11. Association of Rhinovirus Infections with Asthma

    PubMed Central

    Gern, James E.; Busse, William W.

    1999-01-01

    Rhinoviruses are the most common cause of the common cold, but they can cause more severe illnesses in people with underlying lung disorders such as asthma, chronic obstructive pulmonary disease, or cystic fibrosis. Epidemiologic studies with sensitive detection methods such as PCR have identified rhinovirus infection as a major source of asthma exacerbations in both children and adults, especially during the spring and fall. Since rhinoviruses cause little tissue destruction, it is presumed that the immune response to the infection may play an important role in the pathogenesis of rhinovirus-induced exacerbations of asthma. This review examines the epidemiologic association between rhinovirus infections and exacerbations of asthma and outlines current information on immune responses to rhinovirus infection and potential connections between antiviral responses and preexisting allergic inflammation. Finally, current and future strategies for treating rhinovirus infections and virus-induced exacerbations of asthma are discussed. PMID:9880472

  12. Antagonism of TIM-1 blocks the development of disease in a humanized mouse model of allergic asthma.

    PubMed

    Sonar, Sanchaita Sriwal; Hsu, Yen-Ming; Conrad, Melanie Lynn; Majeau, Gerard R; Kilic, Ayse; Garber, Ellen; Gao, Yan; Nwankwo, Chioma; Willer, Gundi; Dudda, Jan C; Kim, Hellen; Bailly, Véronique; Pagenstecher, Axel; Rennert, Paul D; Renz, Harald

    2010-08-01

    Studies in mice and humans have revealed that the T cell, immunoglobulin, mucin (TIM) genes are associated with several atopic diseases. TIM-1 is a type I membrane protein that is expressed on T cells upon stimulation and has been shown to modulate their activation. In addition to a recently described interaction with dendritic cells, TIM-1 has also been identified as a phosphatidylserine recognition molecule, and several protein ligands have been proposed. Our understanding of its activity is complicated by the possibility that TIM-1 possesses multiple and diverse binding partners. In order to delineate the function of TIM-1, we generated monoclonal antibodies directed to a cleft formed within the IgV domain of TIM-1. We have shown here that antibodies that bind to this defined cleft antagonize TIM-1 binding to specific ligands and cells. Notably, these antibodies exhibited therapeutic activity in a humanized SCID model of experimental asthma, ameliorating inflammation, and airway hyperresponsiveness. Further experiments demonstrated that the effects of the TIM-1-specific antibodies were mediated via suppression of Th2 cell proliferation and cytokine production. These results demonstrate that modulation of the TIM-1 pathway can critically influence activated T cells in a humanized disease model, suggesting that TIM-1 antagonists may provide potent therapeutic benefit in asthma and other immune-mediated disorders. PMID:20628202

  13. Obesity is a risk factor for allergic rhinitis in children of Wuhan (China)

    PubMed Central

    Yang, Huang; Zhen, Long

    2016-01-01

    Background The relationship between obesity and allergic diseases in children of China is unclear. Objective To analysis the relationship between obesity and overweight and the prevalence of allergic diseases and the impact of gender. Methods Questionnaire based on those used in National Study of Asthma and Allergies in Childhood in China. The study included 3,327 participants (23.7% aged 2–6 years, 65.8% aged 7–12 years, 10.5% aged 13–14 years) in Wuhan City. Allergic diseases were determined by physicians. Results Overweight was found in 35.68% of participants (8.96% of 2–6 years old, 32.83% of 7–12 years old, and 48.57% of 13–14 years old), obesity in 12.53% (4.18%, 12.01%, and 4.29%, respectively). Obesity (odds ratio [OR], 1.33) increased the prevalence of allergic rhinitis and atopic dermatitis. Obesity (OR, 1.48) affected the incidence of allergic rhinitis in girls. There was no relationship between body mass index (BMI) and asthma in child from Wuhan City. Obesity and overweight did not affect the frequency of asthma, food allergy, and drug allergy. Conclusion Obesity increased the prevalence of allergic rhinitis and atopic dermatitis in child. Higher BMI was no relationship with the prevalence of asthma, food allergy, and drug allergy. PMID:27141483

  14. Gender Associated High Body Mass Index in Allergic Diseases

    PubMed Central

    Lokaj-Berisha, Violeta; Gacaferri-Lumezi, Besa; Minci–Bejtullahu, Ganimete; Latifi-Pupovci, Hatixhe; Karahoda–Gjurgjeala, Natyra; Berisha, Naser; Morina, Teuta

    2014-01-01

    BACKGROUND: The increasing prevalence of allergic diseases and atopy is affected by sex, age and lifestyle factors. Obesity and excess weight are reported to be potential risk factors for atopy and specifically for asthma symptoms in children and adults. OBJECTIVE: To assess the relation between body mass index (BMI) and allergic diseases in patients of both genders, as well as association of BMI with atopy in healthy subjects. METHODS: BMI (kg/m2), skin-prick test and total serum immunoglobulin E levels were assessed in 139 subjects: 109 were patients with allergic diseases (M to F ratio was 51:58) and 30 were healthy controls (M to F ratio was 6:24). RESULTS: The study population was grouped into asthma, asthmarhinitis, rhinitis, Urticaria oreczema and controls by BMI and sex. Females with the highest BMI were in asthma and urticaria/eczema group. Males with the highest BMI were in asthmarhinitis and urticariaeczema group. High BMI was associated with atopy in both genders of healthy controls. High levels of total IgE were in male allergic patients. CONCLUSION: High BMI was associated with asthma in females, urticaria/eczema in both genders and atopy in both genders of healthy controls. Higher levels of total IgE were concluded in male patients.

  15. Asthma Action Plan

    MedlinePlus

    ... Cold or warm water used with detergent and bleach can also be effective. • Wash the sheets and ... hot water or cooler water with detergent and bleach. Ë Cockroaches Many people with asthma are allergic ...

  16. Allergies, asthma, and pollen

    MedlinePlus

    Allergic rhinitis - pollen ... them is your first step toward feeling better. Pollen is a trigger for many people who have allergies and asthma. The types of pollens that are triggers vary from person to person ...

  17. 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. PMID:27155030

  18. Association between exposure to antimicrobial household products and allergic symptoms

    PubMed Central

    Hong, Soyoung; Kwon, Ho-Jang; Choi, Won-Jun; Lim, Wan Ryung; Kim, Jeonghoon; Kim, KyooSang

    2014-01-01

    Objectives Antimicrobial chemicals are used in a variety of household and personal care products. Exposure to antimicrobial household products has been hypothesized to lead to allergic diseases in children. Methods We investigated antimicrobial household product exposure and allergic symptoms in Korean children. An antimicrobial exposure (AE) score was derived. To examine the symptoms of allergic diseases (current wheeze, current rhinitis, and current eczema) in the past 12 months, we used a questionnaire based on the core module of the International Study of Asthma and Allergies in Children. Complete data for the analysis were available for 25,805 of the 35,590 (72.5%) children. Results The prevalence of current allergic diseases was as follows: wheeze, 5.6%; allergic rhinitis, 32.6%; and eczema, 17.7%. The mean (standard deviation) AE score was 14.3 (9.3) (range: 0-40). Compared with subjects with a low AE score (reference), subjects with a high AE score (fourth quartile) were more likely to have symptoms of wheezing and allergic rhinitis (adjusted odds ratio [aOR] for wheezing 1.24, 95% confidence interval [CI], 1.05-1.45, p for trend=0.24; aOR for allergic rhinitis 1.30, 95% CI, 1.20-1.40, p<0.01). Conclusions These findings suggest that frequent use of antimicrobial household products was associated with current wheeze and current allergic rhinitis. PMID:25420879

  19. Role of Insulin-like Growth Factor Binding Protein-3 in Allergic Airway Remodeling

    PubMed Central

    Veraldi, Kristen L.; Gibson, Bethany T.; Yasuoka, Hidekata; Myerburg, Michael M.; Kelly, Elizabeth A.; Balzar, Silvana; Jarjour, Nizar N.; Pilewski, Joseph M.; Wenzel, Sally E.; Feghali-Bostwick, Carol A.

    2009-01-01

    Rationale: The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established. Objectives: We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling. Methods: We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor–stimulated primary epithelial cells. Measurements and Main Results: IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I. Conclusions: Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I–stimulated airway epithelial cells during allergic inflammation. PMID:19608721

  20. Indoor mildew odour in old housing was associated with adult allergic symptoms, asthma, chronic bronchitis, vision, sleep and self-rated health: USA NHANES, 2005-2006.

    PubMed

    Shiue, Ivy

    2015-09-01

    A recent systematic review and meta-analysis has shown the effect of indoor mildew odour on allergic rhinitis risk, but its relation to other common chronic health outcomes in adults has not been investigated. Therefore, it was aimed to examine the relationship of indoor mildew odour and common health outcomes in adults in a national and population-based setting. Data was retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006, including the available information on demographics, housing characteristics, self-reported health conditions and urinary concentrations of environmental chemicals. T test, chi-squared test and survey-weighted logistic regression modelling were performed. Of all American adults (n = 4979), 744 (15.1%) reported indoor mildew odour or musty smell in their households. People who reported indoor mildew odour or musty smell also reported poorer self-rated health, sleep complaints, chronic bronchitis, asthma attack, itchy rash, sneezing and poor vision. In addition, people who reported indoor mildew odour or musty smell also tended to reside in older housing that were built 20 years earlier. However, there were no significant statistical associations found between indoor mildew odour or musty smell and urinary concentrations of environmental chemicals, which was also found to be associated with old housing. People who lived in older housing with indoor mildew odour or musty smell tended to have chronic health problems. To protect occupants in old housing from chronic illnesses associated with indoor mildew odour, elimination of the odour sources should be explored in future research and therefore public health and housing programs. Graphical abstract Pathway from old housing to musty smell, environmental chemicals and then health outcomes. PMID:25971810

  1. Allergic Rhinitis: A neglected disease — A community based assessment among adults in Delhi

    PubMed Central

    Sinha, B; Vibha; Singla, R; Chowdhury, R

    2015-01-01

    Background and Objectives: Allergic Rhinitis is rather erroneously viewed as a trivial disease. It is important in that it can significantly affect quality of life. There is paucity of community based prevalence studies on the disease in India. This study was planned to assess the prevalence of allergic rhinitis in adults, the proportion of asthmatics among them, risk factors associated and treatment seeking behaviour among the patients. Materials and Methods: A community based cross sectional study was conducted in Mehrauli, South Delhi among 1200 adults, aged 30 years and over selected by systematic random sampling from two randomly selected wards. A pre-tested questionnaire was used to collect information regarding symptoms, risk factors and treatment seeking behaviour. Allergic Rhinitis was diagnosed as per ARIA guidelines. Spirometry was done to diagnose asthma among them. Multivariate logistic regression analysis was done to find the association of risk factors with disease. Results: The prevalence of Allergic Rhinitis was found to be 11% (132 subjects) and 33.3% (44 patients) among them also had asthma. Overcrowding (aOR = 6.4), absence of cross-ventilation (aOR = 2.5), occupational exposure to dust/smoke (aOR = 2.1), tobacco smoking (aOR = 2.1), family history of allergic diseases (aOR = 2.7) and clinical allergy (aOR = 10.2) were found to be independent risk factors associated with Rhinitis. More patients of Rhinitis with asthma (75%) took treatment, relative to those without asthma (40%) who, mostly relied on home remedies (42%) or, did not seek any treatment (18%) (P = 0.031). Interpretations and Conclusion: The burden of Allergic Rhinitis is high with a considerable overlap with asthma. These allergic diseases and emphasize the importance of early and regular treatment. PMID:26119436

  2. Chronic Diseases: Asthma and You | NIH MedlinePlus the Magazine

    MedlinePlus

    ... who have other risk factors—parents with asthma, eczema (an allergic skin condition), allergies—are at highest ... nasal passages, and allergic skin conditions (such as eczema). You can still have asthma even if you ...

  3. Maternal Influences over Offspring Allergic Responses

    PubMed Central

    2015-01-01

    Asthma occurs as a result of complex interactions of environmental and genetic factors. Clinical studies and animal models of asthma indicate offspring of allergic mothers have increased risk of development of allergies. Environmental factors including stress-induced corticosterone and vitamin E isoforms during pregnancy regulate the risk for offspring development of allergy. In this review, we discuss mechanisms for the development of allergic disease early in life, environmental factors that may impact the development of risk for allergic disease early in life, and how the variation in global prevalence of asthma may be explained, at least in part, by some environmental components. PMID:25612797

  4. 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...

  5. A novel method for detecting inpatient pediatric asthma encounters using administrative data.

    PubMed

    Knighton, Andrew J; Flood, Andrew; Harmon, Brian; Smith, Patti; Crosby, Carrie; Payne, Nathaniel R

    2014-08-01

    Multiple methods for detecting asthma encounters are used today in public surveillance, quality reporting, and clinical research. Failure to detect asthma encounters can make it difficult to measure the scope and effectiveness of hospital or community-based interventions important in comparative effectiveness research and accountable care. Given the pairing of asthma with certain respiratory conditions, the objective of this study was to develop and test an asthma detection algorithm with specificity and sensitivity using 2 criteria: (1) principal discharge diagnosis and (2) asthma diagnosis code position. A medical record review was conducted (n=191) as the gold standard for identifying asthma encounters given objective criteria. The study team observed that for certain principal respiratory diagnoses (n=110), the observed odds ratio that encounters were for asthma when asthma was coded in the second or third code position was not significantly different than when asthma was coded as the principal diagnosis, 0.36 (P=0.42) and 0.18 (P=0.14), respectively. In contrast, the observed odds ratio was significantly different when asthma was coded in the fourth or fifth positions (P<.001). This difference remained after adjusting for covariates. Including encounters with asthma in 1 of the 3 first positions increased the detection sensitivity to 0.84 [95% confidence interval (CI): 0.76-0.92] while increasing the false positive rate to 0.19 [95% CI: 0.07-0.31]. Use of the proposed algorithm significantly improved the reporting accuracy [0.83 95%CI:0.76-0.90] over use of (1) the principal diagnosis alone [0.55 95% CI:0.46-0.64] or (2) all encounters with asthma 0.66 [95% CI:0.57-0.75]. Bed days resulting from asthma encounters increased 64% over use of the principal diagnosis alone. Given these findings, an algorithm using certain respiratory principal diagnoses and asthma diagnosis code position can reliably improve asthma encounter detection for population-based health

  6. Characterization of Rhinitis According to the Asthma Status in Adults Using an Unsupervised Approach in the EGEA Study

    PubMed Central

    Burte, Emilie; Bousquet, Jean; Varraso, Raphaëlle; Gormand, Frédéric; Just, Jocelyne; Matran, Régis; Pin, Isabelle; Siroux, Valérie

    2015-01-01

    Background The classification of rhinitis in adults is missing in epidemiological studies. Objective To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach. Methods 983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401). Results Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis. Conclusion This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables. PMID:26309034

  7. Allergic inflammation--innately homeostatic.

    PubMed

    Cheng, Laurence E; Locksley, Richard M

    2015-03-01

    Allergic inflammation is associated closely with parasite infection but also asthma and other common allergic diseases. Despite the engagement of similar immunologic pathways, parasitized individuals often show no outward manifestations of allergic disease. In this perspective, we present the thesis that allergic inflammatory responses play a primary role in regulating circadian and environmental inputs involved with tissue homeostasis and metabolic needs. Parasites feed into these pathways and thus engage allergic inflammation to sustain aspects of the parasitic life cycle. In response to parasite infection, an adaptive and regulated immune response is layered on the host effector response, but in the setting of allergy, the effector response remains unregulated, thus leading to the cardinal features of disease. Further understanding of the homeostatic pressures driving allergic inflammation holds promise to further our understanding of human health and the treatment of these common afflictions. PMID:25414367

  8. Allergic rhinitis

    MedlinePlus

    ... allergic to, such as dust, animal dander, or pollen. Symptoms can also occur when you eat a ... article focuses on allergic rhinitis due to plant pollens. This type of allergic rhinitis is commonly called ...

  9. Local Allergic Rhinitis.

    PubMed

    Campo, Paloma; Salas, María; Blanca-López, Natalia; Rondón, Carmen

    2016-05-01

    This review focuses on local allergic rhinitis, a new phenotype of allergic rhinitis, commonly misdiagnosed as nonallergic rhinitis. It has gained attention over last decade and can affect patients from all countries, ethnic groups and ages, impairing their quality of life, and is frequently associated with conjunctivitis and asthma. Diagnosis is based on clinical history, the demonstration of a positive response to nasal allergen provocation test and/or the detection of nasal sIgE. A positive basophil activation test may support the diagnosis. Recent studies have demonstrated that allergen immunotherapy is an effective immune-modifying treatment, highlighting the importance of early diagnosis. PMID:27083105

  10. Allergic diseases and air pollution

    PubMed Central

    Lee, Suh-Young; Chang, Yoon-Seok

    2013-01-01

    The prevalence of allergic diseases has been increasing rapidly, especially in developing countries. Various adverse health outcomes such as allergic disease can be attributed to rapidly increasing air pollution levels. Rapid urbanization and increased energy consumption worldwide have exposed the human body to not only increased quantities of ambient air pollution, but also a greater variety of pollutants. Many studies clearly demonstrate that air pollutants potently trigger asthma exacerbation. Evidence that transportation-related pollutants contribute to the development of allergies is also emerging. Moreover, exposure to particulate matter, ozone, and nitrogen dioxide contributes to the increased susceptibility to respiratory infections. This article focuses on the current understanding of the detrimental effects of air pollutants on allergic disease including exacerbation to the development of asthma, allergic rhinitis, and eczema as well as epigenetic regulation. PMID:23956961

  11. Asthma in children and adolescents in Brazil: contribution of the International Study of Asthma and Allergies in Childhood (ISAAC)

    PubMed Central

    Solé, Dirceu; Camelo-Nunes, Inês Cristina; Wandalsen, Gustavo Falbo; Mallozi, Marcia Carvalho

    2014-01-01

    Objective: To assess asthma among Brazilian pediatric population applying the International Study of Asthma and Allergies in Childhood (ISAAC), an internationally standardized and validated protocol. Data sources: ISAAC was conceived to maximize the value of epidemiologic studies on asthma and allergic diseases, establishing a standardized method (self-applicable written questionnaire and/or video questionnaire) capable to facilitate the international collaboration. Designed to be carried out in three successive and dependent phases, the ISAAC gathered a casuistic hitherto unimaginable in the world and in Brazil. This review included data gathered from ISAAC official Brazilian centers and others who used this method. Data synthesis: At the end of the first phase, it has been documented that the prevalence of asthma among Brazilian schoolchildren was the eighth among all centers participating all over the world. Few centers participated in the second phase and investigated possible etiological factors, especially those suggested by the first phase, and brought forth many conjectures. The third phase, repeated seven years later, assessed the evolutionary trend of asthma and allergic diseases prevalence in centers that participated simultaneously in phases I and III and in other centers not involved in phase I. Conclusions: In Brazil, the ISAAC study showed that asthma is a disease of high prevalence and impact in children and adolescents and should be seen as a Public Health problem. Important regional variations, not well understood yet, and several risk factors were found, which makes us wonder: is there only one or many asthmas in Brazil? PMID:24676199

  12. Therapeutic strategies for allergic diseases

    NASA Astrophysics Data System (ADS)

    Barnes, Peter J.

    1999-11-01

    Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.

  13. Occurrence of Common Allergic Diseases in Children with Idiopathic Nephrotic Syndrome

    PubMed Central

    Wei, Chang-Ching; Lin, Cheng-Li; Shen, Te-Chun; Sung, Fung-Chang

    2015-01-01

    Background Clinical and immunological studies have consistently shown a possible link between atopy and idiopathic nephrotic syndrome (INS). However, whether allergic diseases occur after INS develops is unknown. Methods From Taiwan’s National Health Insurance database, 1340 children with newly diagnosed INS and 5360 non-INS matched controls were identified in 2000–2007. By the end of 2008, the incidences and hazard ratios of four allergic diseases (allergic conjunctivitis, allergic rhinitis, atopic dermatitis, and asthma) were calculated. Results The incidence rates of all four allergic diseases were greater in the INS cohort than in the non-INS cohort in all age groups and decreased sharply as age increased in both cohorts. Children with INS had the highest adjusted hazard ratio (4.13; 95% confidence interval [CI], 2.50–6.83) for atopic dermatitis and the lowest adjusted hazard ratio (1.71; 95% CI, 1.39–2.09) for allergic rhinitis. Most of the allergic diseases appeared within 2–6 months after INS developed, and the incidences declined with increasing follow-up duration. Conclusions Allergic disorders are common in children with INS, especially within the first year after diagnosis. The role of INS in the development of allergic disorders should be elucidated to establish innovative disease intervention programs. PMID:25843432

  14. Genetics of Allergic Diseases

    PubMed Central

    Ortiz, Romina A.; Barnes, Kathleen C.

    2015-01-01

    The allergic diseases are complex phenotypes for which a strong genetic basis has been firmly established. Genome-wide association studies (GWAS) has been widely employed in the field of allergic disease, and to date significant associations have been published for nearly 100 asthma genes/loci, in addition to multiple genes/loci for AD, AR and IgE levels, for which the overwhelming number of candidates are novel and have given a new appreciation for the role of innate as well as adaptive immune-response genes in allergic disease. A major outcome of GWAS in allergic disease has been the formation of national and international collaborations leading to consortia meta-analyses, and an appreciation for the specificity of genetic associations to sub-phenotypes of allergic disease. Molecular genetics has undergone a technological revolution, leading to next generation sequencing (NGS) strategies that are increasingly employed to hone in on the causal variants associated with allergic diseases. Unmet needs in the field include the inclusion of ethnically and racially diverse cohorts, and strategies for managing ‘big data’ that is an outcome of technological advances such as sequencing. PMID:25459575

  15. Genetic risk factors for the development of allergic disease identified by genome-wide association

    PubMed Central

    Portelli, M A; Hodge, E; Sayers, I

    2015-01-01

    An increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Allergic diseases are complex and development involves both environmental and genetic factors. Although the existence of a genetic component for allergy was first described almost 100 years ago, progress in gene identification has been hindered by lack of high throughput technologies to investigate genetic variation in large numbers of subjects. The development of Genome-Wide Association Studies (GWAS), a hypothesis-free method of interrogating large numbers of common variants spanning the entire genome in disease and non-disease subjects has revolutionised our understanding of the genetics of allergic disease. Susceptibility genes for asthma, AR and AD have now been identified with confidence, suggesting there are common and distinct genetic loci associated with these diseases, providing novel insights into potential disease pathways and mechanisms. Genes involved in both adaptive and innate immune mechanisms have been identified, notably including multiple genes involved in epithelial function/secretion, suggesting that the airway epithelium may be particularly important in asthma. Interestingly, concordance/discordance between the genetic factors driving allergic traits such as IgE levels and disease states such as asthma have further supported the accumulating evidence for heterogeneity in these diseases. While GWAS have been useful and continue to identify novel genes for allergic diseases through increased sample sizes and phenotype refinement, future approaches will integrate analyses of rare variants, epigenetic mechanisms and eQTL approaches, leading to greater insight into the genetic basis of these diseases. Gene identification will improve our understanding of disease mechanisms and generate potential

  16. The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation

    PubMed Central

    Sy, Chandler B.; Siracusa, Mark C.

    2016-01-01

    Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2-associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin. PMID:27378934

  17. [Pseudotumoral allergic bronchopulmonary aspergillosis].

    PubMed

    Otero González, I; Montero Martínez, C; Blanco Aparicio, M; Valiño López, P; Verea Hernando, H

    2000-06-01

    Allergic bronchopulmonary aspergillosis (ABPA) develops as the result of a hypersensitivity reaction to fungi of the genus Aspergillus. Clinical and radiological presentation can be atypical, requiring a high degree of suspicion on the part of the physician who treats such patients. We report the cases of two patients with APBA in whom the form of presentation--with few asthma symptoms, images showing lobar atelectasia and hilar adenopathy--led to an initial suspicion of lung cancer. PMID:10932345

  18. Transcutaneous immunotherapy via laser-generated micropores efficiently alleviates allergic asthma in Phl p 5–sensitized mice

    PubMed Central

    Bach, D; Weiss, R; Hessenberger, M; Kitzmueller, S; Weinberger, E E; Krautgartner, W D; Hauser-Kronberger, C; Boehler, C; Thalhamer, J; Scheiblhofer, S

    2012-01-01

    Abstract Background Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser-generated micropores to subcutaneous injection. Methods BALB/c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen Phl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant-free Phl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; Phl p 5–specific serum levels of IgG1, IgG2a, and IgE; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed. Results Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in Th2-associated cytokine secretion, transcutaneous application revealed a general downregulation of Th1/Th2/Th17 responses. Successful therapy was associated with induction of IgG2a and an increase in FOXP3+ CD4+ T cells. Conclusions Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy-associated boosting of systemic Th2 immunity. Immunotherapy via laser-microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy. PMID:22947064

  19. [Allergic inflammation in respiratory system].

    PubMed

    An, Lifeng; Wang, Yanshu; Li, Lin

    2015-02-01

    The pathophysiology of allergic disease such as asthma and allergic rhinitis tell the similar story: when the endogenous and exogenous inflammatory mechanisms occur disorder, the body may begin with inflammatory cell activation, namely through the release of cytokine and inflammatory mediator role in the corresponding target cells, activate the sensory nerve fiber, acting on the cell organ specificity effect, clinical symptoms. This article is divided into the following five parts focused on the research progress of allergic inflammatory diseases: (1) inflammatory cells; (2) staphylococcus aureus superantigen; (3) small molecules (cytokines, inflammatory mediators, lipid classes medium); (4) nerve fibers and effect cells; (5) genetic and epigenetic factors. PMID:26012309

  20. Variation in Uteroglobin-Related Protein 1 (UGRP1) gene is associated with Allergic Rhinitis in Singapore Chinese

    PubMed Central

    2011-01-01

    Background Uteroglobin-Related Protein 1 (UGRP1) is a secretoglobulin protein which has been suggested to play a role in lung inflammation and allergic diseases. UGRP1 has also been shown to be an important pneumoprotein, with diagnostic potential as a biomarker of lung damage. Previous genetic studies evaluating the association between variations on UGRP1 and allergic phenotypes have yielded mixed results. The aim of this present study was to identify genetic polymorphisms in UGRP1 and investigate if they were associated with asthma and allergic rhinitis in the Singapore Chinese population. Methods Resequencing of the UGRP1 gene was conducted on 40 randomly selected individuals from Singapore of ethnic Chinese origin. The polymorphisms identified were then tagged and genotyped in a population of 1893 Singapore Chinese individuals. Genetic associations were evaluated in this population comparing 795 individuals with allergic rhinitis, 718 with asthma (of which 337 had both asthma and allergic rhinitis) and 717 healthy controls with no history of allergy or allergic diseases. Results By resequencing the UGRP1 gene within our population, we identified 11 novel and 16 known single nucleotide polymorphisms (SNPs). TagSNPs were then genotyped, revealing a significant association between rs7726552 and allergic rhinitis (Odds Ratio: 0.81, 95% Confidence Interval: 0.66-0.98, P = 0.039). This association remained statistically significant when it was analyzed genotypically or when stratified according to haplotypes. When variations on UGRP1 were evaluated against asthma, no association was observed. Conclusion This study documents the association between polymorphisms in UGRP1 and allergic rhinitis, suggesting a potential role in its pathogenesis. PMID:21410962

  1. Optimum predictors of childhood asthma: persistent wheeze or the asthma predictive index?

    PubMed Central

    Amin, Priyal; Levin, Linda; Epstein, Tolly; Ryan, Pat; LeMasters, Grace; Khurana- Hershey, Gurjit; Reponen, Tina; Villareal, Manuel; Lockey, James; Bernstein, David I.

    2014-01-01

    Background The Asthma Predictive Index (API) and persistent wheezing phenotypes are associated with childhood asthma, but previous studies have not assessed their ability to predict objectively confirmed asthma. Objective To determine whether the University of Cincinnati API (ucAPI) and/or persistent wheezing at age three can accurately predict objectively confirmed asthma at age seven. Methods Data from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a high risk prospective birth cohort, was used. Asthma was defined as: parent-reported or physician-diagnosed asthma objectively confirmed by a change in FEV1 of ≥ 12% post bronchodilator or a positive methacholine challenge (PC20 ≤ 4 mg/ml); or prior treatment with daily asthma controller medication(s). Multivariate logistic regression was used to investigate the relationship between confirmed asthma at age seven and a positive ucAPI (adapted and modified from prior published API definitions) and persistent wheezing at age three. Results At age seven, 103 of 589 (17.5%) children satisfied the criteria for asthma. Confirmed asthma at age seven was significantly associated with a positive ucAPI (adjusted [a]OR=13.3; 95% CI [7.0–25.2]; p<0.01) and the persistent wheezing phenotype (aOR = 9.8 [4.9–19.5]; p <0.01) at age three. Allergic persistent wheezing was associated with a significantly higher risk of asthma (aOR = 10.4 [4.1–26.0]; p<0.01) than non-allergic persistent wheezing (aOR = 5.4 [2.04–14.06]; p <0.01). Conclusions Both a positive ucAPI and persistent wheeze at age 3 years were associated with objectively confirmed asthma at age seven; however the highest risk was associated with ucAPI. These results demonstrate that the ucAPI as a clinically useful tool for predicting future asthma in school-age children. PMID:25439361

  2. Allergic diseases among children: nutritional prevention and intervention.

    PubMed

    Hendaus, Mohamed A; Jomha, Fatima A; Ehlayel, Mohammad

    2016-01-01

    Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for

  3. Allergic diseases among children: nutritional prevention and intervention

    PubMed Central

    Hendaus, Mohamed A; Jomha, Fatima A; Ehlayel, Mohammad

    2016-01-01

    Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for

  4. Examining Impacts of Allergic Diseases on Psychological Problems and Tobacco Use in Korean Adolescents: The 2008–2011 Korean National Health and Nutrition Examination Survey

    PubMed Central

    Chun, Yoon Hong; Han, Kyungdo; Park, Yong-Gyu; Yoon, Jong-seo; Kim, Hyun Hee; Kim, Jin Tack; Jeong, Dae Chul

    2015-01-01

    Purpose Asthma during adolescence can induce social, psychological, and behavioral problems. We examined the impact of asthma and other allergic diseases on psychological symptoms and health risk behaviors among South Korean adolescents. Methods In this population-based cross-sectional study, 3192 adolescents (10–18 years of age) participating in the 2008–2011 Korean National Health and Nutrition Examination Survey were enrolled. Psychological problems associated with clinically diagnosed asthma, allergic rhinitis, and atopic dermatitis were assessed using questionnaires and surveys. Data was analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, sex, body mass index, smoking experience, and alcohol use. Results Asthma and atopic dermatitis were associated with a higher prevalence of depression (17.2% and 13%, respectively). After adjusting for the covariates, asthma patients were approximately two times as likely to have depression as non-allergic participants (odds ratio, 1.81; 95% confidence interval, 1.22–2.68). Psychosocial stress significantly increased in the following order: no allergy, any allergy without asthma, asthma only, and asthma with any allergy (p for linear trend = 0.01). The asthma without other allergies group showed the highest prevalence of cigarette smoking (p = 0.007). Conclusions In this study, asthma with or without other allergies was significantly related to increases in depression, psychosocial stress, and smoking experience. Thus, care should be taken to adjust treatment to account for the psychological symptoms and health risk behaviors common among asthmatic adolescents. PMID:25897790

  5. The Head-off Environmental Asthma in Louisiana (HEAL) Study—Methods and Study Population

    PubMed Central

    Kennedy, Suzanne; Mvula, Mosanda M.; Jaffee, Katy; Wildfire, Jeremy; Thornton, Eleanor; Cohn, Richard D.; Grimsley, L. Faye; Mitchell, Herman; El-Dahr, Jane; Sterling, Yvonne; Martin, William J.; White, LuAnn; Stephens, Kevin U.; Lichtveld, Maureen

    2012-01-01

    Background: In the city of New Orleans, Louisiana, and surrounding parishes (NOLA), children with asthma were perilously impacted by Hurricane Katrina as a result of disrupted health care, high home mold and allergen levels, and high stress. Objectives: The Head-off Environmental Asthma in Louisiana (HEAL) study was conducted to examine relationships between the post-Katrina environment and childhood asthma in NOLA and assess a novel asthma counselor intervention that provided case management and guidance for reducing home mold and allergen levels. Methods: Children (4–12 years old) with moderate-to-severe asthma were recruited from NOLA schools. Over 1 year, they received two clinical evaluations, three home environmental evaluations, and the asthma intervention. Quarterly end points included symptom days, medication use, and unscheduled emergency department or clinic visits. A community advisory group was assembled and informed HEAL at all phases. Results: Of the children (n = 182) enrolled in HEAL, 67% were African American, and 25% came from households with annual incomes < $15,000. HEAL children were symptomatic, averaging 6.6 symptom days in the 2 weeks before baseline, and had frequent unscheduled visits to clinics or emergency departments (76% had at least one unscheduled visit in the preceding 3 months). In this report, we describe study design and baseline characteristics of HEAL children. Conclusions: Despite numerous challenges faced by investigators, study staff, and participants, including destroyed infrastructure, disrupted lives, and lost jobs, HEAL was successful in terms of recruitment and retention, the high quality of data collected that will provide insight into asthma-allergen relationships, and the asthma intervention. This success was attributable to using an adaptive approach and refining processes as needed. PMID:22895349

  6. [Definition and clinic of the allergic rhinitis].

    PubMed

    Spielhaupter, Magdalena

    2016-03-01

    The allergic rhinitis is the most common immune disorder with a lifetime prevalence of 24% and one of the most common chronic diseases at all--with tendency to rise. It occurs in childhood and influences the patients' social life, school performance and labour productivity. Furthermore the allergic rhinitis is accompanied by a lot of comorbidities, including conjunctivitis, asthma bronchiale, food allergy, neurodermatitis and sinusitis. For example the risk for asthma is 3.2-fold higher for adults with allergic rhinitis than for healthy people. PMID:27120868

  7. Occupational asthma in Japan.

    PubMed

    Dobashi, Kunio

    2012-07-01

    Research into occupational asthma (OA) in Japan has been led by the Japanese Society of Occupational and Environmental Allergy. The first report about allergic OA identified konjac asthma. After that, many kinds of OA have been reported. Cases of some types of OA, such as konjac asthma and sea squirt asthma, have been dramatically reduced by the efforts of medical personnel. Recently, with the development of new technologies, chemical antigen-induced asthma has increased in Japan. Due to advances in anti-asthma medication, control by medical treatment tends to be emphasized and the search for causative antigens seems to be neglected. Furthermore, we do not have a Japanese guideline for diagnosis and management of OA. This article discusses the current state of OA in Japan. PMID:22872819

  8. IκB kinase β inhibitor, IMD-0354, prevents allergic asthma in a mouse model through inhibition of CD4(+) effector T cell responses in the lung-draining mediastinal lymph nodes.

    PubMed

    Maślanka, Tomasz; Otrocka-Domagała, Iwona; Zuśka-Prot, Monika; Mikiewicz, Mateusz; Przybysz, Jagoda; Jasiecka, Agnieszka; Jaroszewski, Jerzy J

    2016-03-15

    IκB kinase (IKK) is important for nuclear factor (NF)-κB activation under inflammatory conditions. It has been demonstrated that IMD-0354, i.e. a selective inhibitor of IKKβ, inhibited allergic inflammation in a mouse model of ovalbumin (OVA)-induced asthma. The present study attempts to shed light on the involvement of CD4(+) effector (Teff) and regulatory (Treg) T cells in the anti-asthmatic action of IMD-0354. The animals were divided into three groups: vehicle treated, PBS-sensitized/challenged mice (PBS group); vehicle treated, OVA-sensitized/challenged mice (OVA group); and IMD-0354-treated, OVA-sensitized/challenged mice. The analyzed parameters included the absolute counts of Treg cells (Foxp3(+)CD25(+)CD4(+)), activated Teff cells (Foxp3(-)CD25(+)CD4(+)) and resting T cells (CD25(-)CD4(+)) in the mediastinal lymph nodes (MLNs), lungs and peripheral blood. Moreover, lung histopathology was performed to evaluate lung inflammation. It was found that the absolute number of cells in all studied subsets was considerably increased in the MLNs and lungs of mice from OVA group as compared to PBS group. All of these effects were fully prevented by treatment with IMD-0354. Histopathological examination showed that treatment with IMD-0354 protected the lungs from OVA-induced allergic airway inflammation. Our results indicate that IMD-0354 exerts anti-asthmatic action, at least partially, by blocking the activation and clonal expansion of CD4(+) Teff cells in the MLNs, which, consequently, prevents infiltration of the lungs with activated CD4(+) Teff cells. The beneficial effects of IMD-0354 in a mouse model of asthma are not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of inducible Treg cells. PMID:26868187

  9. Mechanisms of occupational asthma.

    PubMed

    Maestrelli, Piero; Boschetto, Piera; Fabbri, Leonardo M; Mapp, Cristina E

    2009-03-01

    Inhalation of agents in the workplace can induce asthma in a relatively small proportion of exposed workers. Like nonoccupational asthma, occupational asthma is probably the result of multiple genetic, environmental, and behavioral influences. It is important that occupational asthma be recognized clinically because it has serious medical and socioeconomic consequences. Environmental factors that can affect the initiation of occupational asthma include the intrinsic characteristics of causative agents as well as the influence of the level and route of exposure at the workplace. The identification of host factors, polymorphisms, and candidate genes associated with occupational asthma may improve our understanding of mechanisms involved in asthma. High-molecular-weight compounds from biological sources and low-molecular-weight chemicals cause occupational asthma after a latent period of exposure. Although the clinical, functional, and pathologic features of occupational asthma caused by low-molecular-weight agents resemble those of allergic asthma, the failure to detect specific IgE antibodies against most low-molecular-weight agents has resulted in a search for alternative or complementary physiopathologic mechanisms leading to airway sensitization. Recent advances have been made in the characterization of the immune response to low-molecular-weight agents. In contrast, the mechanism of the type of occupational asthma that occurs without latency after high-level exposure to irritants remains undetermined. PMID:19281901

  10. Nitric Oxide Oxidation Products are Increased in the Epithelial Lining Fluid of Children with Persistent Asthma

    PubMed Central

    Fitzpatrick, Anne M.; Brown, Lou Ann S.; Holguin, Fernando; Teague, W. Gerald

    2009-01-01

    Background Children with severe allergic asthma have persistent airway inflammation and oxidant stress. Objectives We hypothesized that children with severe allergic asthma would have increased concentrations of the NO oxidation products nitrite, nitrate, and nitrotyrosine in the proximal and distal airway epithelial lining fluid (ELF). We further hypothesized that NO oxidation products would be associated with higher exhaled nitric oxide (FENO), greater allergic sensitization, and lower pulmonary function. Methods Bronchoalveolar lavage (BAL) was obtained from 15 children with mild-to-moderate asthma, 30 children with severe allergic asthma, 5 non-asthmatic children and 20 non-smoking adults. The BAL was divided into proximal and distal portions and nitrite, nitrate, and nitrotyrosine were quantified. Results Children with mild-to-moderate and severe allergic asthma had increased concentrations of nitrite (adult control: 15 ± 3; pediatric control: 23 ± 4; mild-to-moderate asthma: 56 ± 26; severe asthma: 74 ± 18 µM), nitrate (37 ± 13 vs. 145 ± 38 vs. 711 ± 155 vs. 870 ± 168 µM) and nitrotyrosine (2 ± 1 vs. 3 ± 1 vs. 9 ± 3 vs. 10 ± 4 µM) in the proximal ELF. Similar results were seen in the distal ELF although the concentrations were significantly lower (p < 0.05 for each). Although univariate analyses revealed no associations between NO oxidation products and clinical features, multivariate analyses revealed FENO to be a significant predictor of NO oxidation in asthmatic children. Conclusions NO oxidation products are increased in the ELF of asthmatic children. The relationship between FENO and airway nitrosative stress is complicated and requires further study. PMID:19895987

  11. ALLERGIC POTENTIAL OF INDOOR MOLDS

    EPA Science Inventory

    Many fungi have been associated with allergic lung disease, but few are well studied and even fewer allergens of fungal origin are well characterized. Exposure to damp moldy environments has been associated with the exacerbation of asthma, but the role of molds in the induction o...

  12. Pharmacogenetics of asthma in children

    PubMed Central

    Matsui, Eiko; Nishimura, Akane; Kaneko, Hideo

    2010-01-01

    Allergic diseases such as bronchial asthma and atopic dermatitis develop by a combination of genetic and environmental factors. Several candidate causative genes of asthma and atopy have been reported as the genetic factors. The clinical features of patients and causes of diseases vary. Therefore, personalized medicine (tailor-made medicine) is necessary for the improvement of quality of life (QOL) and for asthma cure. Pharmacogenetics is very important for personalized medicine. Here, we present the genetics and pharmacogenetics of asthma in children. Finally, we show the guideline for personalized medicine for asthma, particularly in childhood, including the pharmacogenetics of anti-asthmatic drugs, preliminarily produced by the authors. PMID:20224673

  13. The association between maternal psychological stress and inflammatory cytokines in allergic young children

    PubMed Central

    Koriyama, Chihaya; Yamamoto, Megumi; Anan, Ayumi; Shibata, Eiji; Kawamoto, Toshihiro

    2016-01-01

    Background. Previous studies have shown that psychological stress is linked to asthma prevalence. Parental psychological stress may potentially influence inflammatory responses in their allergic children. The purpose of this study is to clarify the association between maternal psychological status and inflammatory response of allergic young children. Methods. The study subjects were 152 young allergic children (median age: 13 months) who had not shown any allergic symptoms in the past one month. mRNA expression levels of the inflammatory response genes IL-6, IL-8, IL-10 and IL-22 were quantified by qRT-PCR. Maternal psychological status was assessed by standardized questionnaires: the Centre for Epidemiological Studies Depression Scale (CES-D) for depression and the Japanese Perceived Stress Scale (JPSS) for perceived stress. Results. A significant positive association was observed between maternal CES-D scores and IL-6 mRNA expression in the children with asthma. The JPSS scores were also positively associated with IL-8 mRNA expression in asthmatic children and IL-6 mRNA expression in children with allergic rhinitis. Similar trends were observed among children positive for house dust mite-specific IgE, but these associations were not significant. Conclusion. This study supports the hypothesis that maternal psychological stress affects the inflammatory response in their allergic children. PMID:26819847

  14. Allergic Conjunctivitis

    MedlinePlus

    ... water. This is called conjunctivitis, also known as “pink eye.” Causes & Risk Factors What causes allergic conjunctivitis? ... example, if you are allergic to pollen or mold, stay indoors when pollen and mold levels are ...

  15. Role of platelets in allergic airway inflammation.

    PubMed

    Idzko, Marco; Pitchford, Simon; Page, Clive

    2015-06-01

    Increasing evidence suggests an important role for platelets and their products (e.g., platelet factor 4, β-thromboglobulin, RANTES, thromboxane, or serotonin) in the pathogenesis of allergic diseases. A variety of changes in platelet function have been observed in patients with asthma, such as alterations in platelet secretion, expression of surface molecules, aggregation, and adhesion. Moreover, platelets have been found to actively contribute to most of the characteristic features of asthma, including bronchial hyperresponsiveness, bronchoconstriction, airway inflammation, and airway remodeling. This review brings together the current available data from both experimental and clinical studies that have investigated the role of platelets in allergic airway inflammation and asthma. It is anticipated that a better understanding of the role of platelets in the pathogenesis of asthma might lead to novel promising therapeutic approaches in the treatment of allergic airway diseases. PMID:26051948

  16. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    PubMed

    Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling. PMID:25785861

  17. A Pilot Study on BMI, Serum Testosterone and Estradiol Levels in Allergic Male Patients

    PubMed Central

    Lokaj-Berisha, Violeta; Gacaferri-Lumezi, Besa; Berisha, Naser; Gashi-Hoxha, Sanije

    2015-01-01

    BACKGROUND: The dramatic increase in the prevalence of high body mass index (BMI) increases the prevalence of allergic diseases, both in adults and children and obesity is associated with hypogonadism in adult males. AIM: We aimed to evaluate the effect of high body mass index on plasma concentrations of testosterone and estradiol in young pubertal and adult males with allergic diseases. MATERIAL AND METHODS: Morning fasting blood samples were obtained form 51 allergic patients and 6 healthy volunteer males between the ages 11-57 years (Mean 26.9, DS ± 11.9 years). Total testosterone, estradiol, FSH and LH concentrations were measured by radioimmunoassay. All participants were subjected to skin prick tests with test kit G aeroallergens, and BMI was calculated according to the body weight divided by the square of height (kg/m2). RESULTS: Low levels of testosterone and high levels of estradiol were associated with high BMI only in patients with asthma/rhinitis, but not in asthma patients. Allergic dermatitis/urticaria group along with healthy controls were overweight but within normal ranges for total testosterone and estradiol concentrations. Patients with allergic rhinitis were within normal ranges for BMI, total testosterone and estradiol concentrations. CONCLUSION: High BMI is not always associated with low levels of testosterone and high levels of estradiol in our patients with allergic diseases, but low levels of testosterone are present in patients with asthma and asthma/rhinitis although not among patients with rhinitis only. Our results should be confirmed in a larger group of participants.

  18. Triclosan Exposure and Allergic Sensitization in Norwegian Children

    PubMed Central

    Bertelsen, Randi J.; Longnecker, Matthew P.; Løvik, Martinus; Calafat, Antonia M.; Carlsen, Kai-Håkon; London, Stephanie J.; Carlsen, Karin C. Lødrup

    2012-01-01

    Background Exposure to the synthetic antimicrobial chemical, triclosan, used in personal care products, has been hypothesized to lead to allergic disease. We investigated whether triclosan exposure was associated with allergic sensitization and symptoms in 10-year old Norwegian children. Methods Urinary concentrations of triclosan were measured in one first morning void from 623 children, collected 2001– 2004. Logistic regression models, controlling for urine specific gravity, parental allergic disease, maternal education, and household income, were fitted for allergic sensitization (either skin prick test positivity or serum specific IgE ≥0.35 kU/L to at least one of 15 evaluated inhalant and food allergens), current rhinitis, and current asthma (questionnaire and exercise challenge test). Results The adjusted odds ratio (aOR) for allergic sensitization among those in the fourth quartile of triclosan concentration was 2.0 (95% confidence interval (CI): 1.1, 3.4) compared with the reference group (< the limit of detection) and the aOR per log10 unit increase in triclosan was 1.2 (95% CI: 1.0, 1.4). The aOR for current rhinitis was 1.9 (95% CI: 1.1, 3.4) for the fourth quartile and 1.2 (95% CI:0.97, 1.4) per log10 unit increase in triclosan. Conclusion Triclosan concentrations were associated with allergic sensitization, especially inhalant and seasonal allergens rather thanfood allergens. Current rhinitis was associated with the highest levels of triclosan, whereas no association was seen for current asthma. These results are consistent with recent findings in other studies and provide additional evidence for an association between triclosan and allergy. PMID:23146048

  19. Association between severity of asthma and degree of chronic rhinosinusitis

    PubMed Central

    Lin, David C.; Chandra, Rakesh K.; Tan, Bruce K.; Zirkle, Whitney; Conley, David B.; Grammer, Leslie C.; Kern, Robert C.; Schleimer, Robert P.; Peters, Anju T.

    2012-01-01

    Background There is a clinical association between asthma and chronic rhinosinusitis (CRS). This study was designed to determine whether severity of coexistent asthma affects the clinical presentation of CRS. Methods Cross-sectional analysis was performed of prospectively collected data in 187 patients with CRS who were evaluated in a large, tertiary academic nasal and sinus center. Patients were stratified into three groups based on asthma status using National Institutes of Health criteria: (1) nonasthmatic, (2) intermittent/mild asthma, (3) or moderate/severe asthma. Results Mean Lund-Mackay scores were 9.7, 11.6, and 15.6, respectively. ANOVA testing with post-hoc Tukey analysis revealed that Lund-MacKay scores were significantly greater in group 3 than either group 1 (p < 0.05) or group 2 (p < 0.01). The prevalence of allergic sensitization was 72.4, 82.8, and 100% in groups 1, 2, and 3, respectively (p < 0.03). The prevalence of nasal polyposis was 31.4% in group 1, 48.3% in group 2, and 94.4% in group 3 (p < 0.0001). No differences were observed regarding demographic factors or the incidence of the triad of aspirin sensitivity, asthma, and nasal polyposis among those with different severities of asthma. Conclusion Increasing severity of asthma is associated with advancing radiological severity of CRS and a greater prevalence of allergic sensitization and nasal polyposis. This large adult series shows that asthma severity may have a significant correlation with the presentation of CRS. This study adds to the growing support for the unified airway theory. PMID:21819754

  20. Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children

    PubMed Central

    Bunyavanich, Supinda; Rifas-Shiman, Sheryl L.; Platts-Mills, Thomas A.; Workman, Lisa; Sordillo, Joanne E.; Camargo, Carlos A.; Gillman, Matthew W.; Gold, Diane R.; Litonjua, Augusto A.

    2014-01-01

    Background Maternal diet during pregnancy may influence childhood allergy and asthma. Objective To examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma. Methods We studied 1277 mother-child pairs from a United States pre-birth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood. Results Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least one food allergen (28.0%). Higher maternal peanut intake (each additional z-score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (OR 0.53, 95%CI 0.30–0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR 0.83, 95%CI 0.69–0.99) and allergic rhinitis (OR 0.85, 95%CI 0.74–0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR 0.64, 95%CI 0.46–0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs 3.6 to 8.1). Conclusion Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma. PMID:24522094

  1. Effect of current exposure to Der p 1 on asthma symptoms, airway inflammation, and bronchial hyperresponsiveness in mite-allergic asthmatics.

    PubMed

    Alvarez, M J; Olaguibel, J M; Acero, S; García, B E; Tabar, A I; Urbiola, E

    2000-02-01

    The existence of a dose-response relationship between indoor allergen exposure and sensitization has been widely described, but the effect of allergen exposure on asthma activity (symptoms, bronchial hyperresponsiveness [BHR], and inflammation) is not clear. Our aim was to determine the existence of an association among current exposure to mite allergens and symptoms, BHR, and airway inflammation assessed in blood and sputum from asthmatic patients sensitized to Dermatophagoides pteronyssinus. We selected 31 mild and recently diagnosed (12-24 months) asthma patients sensitized to D. pteronyssinus. Allergenic exposure (Der p 1, Der 2) was assessed by a commercial assay based on monoclonal antibodies (mAb), carried out on the dust samples collected from patients' beds in a standardized way. Patients completed an asthma symptom questionnaire and underwent skin tests, methacholine bronchial challenge, and sputum induction. Sputum cell profile was analyzed and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin(IL)-5 levels were quantified in sputum supernatant. Total eosinophil numbers and ECP levels were measured in blood samples. Most patients were exposed to Der p 1 levels under 2 microg/g of dust. Der p 1 exposure was higher among the subjects with positive sputum tryptase detection (P = 0.020). Der p 1 levels showed a trend toward correlation with asthma symptoms (P = 0.066, r = 0.36) and correlated with sputum tryptase levels (P = 0.032, r = 0.42). No relationship between BHR, eosinophilic inflammation, and allergenic exposure was found. Our results suggest that asthma symptoms and lung mast-cell activation are at least partially dependent on current allergen exposure. The lack of correlation between mite exposure, eosinophilic inflammation, and BHR supports the role of other factors that enhance the immunologic response initiated by allergen, increasing the activity of asthma. PMID:10726735

  2. Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation.

    PubMed

    Kerzel, Sebastian; Rogosch, Tobias; Struecker, Benjamin; Maier, Rolf F; Kabesch, Michael; Zemlin, Michael

    2016-06-15

    The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis. PMID:27183570

  3. Polycyclic aromatic hydrocarbon exposure and pediatric asthma in children: a case–control study

    PubMed Central

    2013-01-01

    Background Bronchial asthma is one of the most prevalent diseases in Arab children. Environmental pollution has been suggested to be considered causative of asthma, nasal symptoms and bronchitis in both children and adult. The objectives of this study were to evaluate the association between serum polycyclic aromatic hydrocarbons (PAHs) levels, asthma and allergic outcomes among Saudi children aged up to 15 yrs. We hypothesized that increased serum PAHs are associated with allergy, asthma, or respiratory symptoms. Methods A total of 195 Saudi children (98 asthma pediatric patients and 97 healthy controls) were randomly selected from the Riyadh Cohort Study for inclusion. The diagnosis of Asthma was based on established pediatric diagnosis and medications taken. Results Asthma related markers showed highly significant differences between children with and without asthma. Thus IgE, resistin and IL-4 were significantly increased (p 0.004, 0.001 and 0.003, respectively) in children with asthma compared with non-asthma control subjects. GMCSF, IFN-γ, IL-5, IL-8 and IL-10, on the other hand, were significantly decreased in children with asthma (p 0.003, 0.03, 0.001, 0.004 and 0.03, respectively). Strong associations between serum PAHs levels and biomarkers of childhood asthma were detected in Arabic children. Data confirmed the role of naphthalene, 4H-cyclobenta[def]phenanthrene, 1,2-benzanthracene, chrysene and benzo(e)acephenanthrylene in childhood asthma; levels of these PAHs were correlated with asthma related biomarkers including IgE, resistin, GMCSF and IFN-γ as well as IL-4, IL-5, IL-8 and IL-10 cytokines. Conclusions This data highlight the pivotal role of specific PAHs in childhood asthma. PMID:23286340

  4. Clinical and allergic sensitization characteristics of allergic rhinitis among the elderly population in Istanbul, Turkey.

    PubMed

    Ozturk, Ayse Bilge; Ozyigit, Leyla Pur; Olmez, Merve Ozata

    2015-04-01

    Prevalence of allergic rhinitis (AR) in elderly population in Turkey is not known. Studies on the prevalence and features of allergy in older adults are needed to identify safe and effective diagnostic/therapeutic methods for elderly AR patients. We aimed to identify the clinical and allergic characteristics of sensitization to aeroallergens among individuals aged ≥60 years with allergic rhinitis admitted to an allergy outpatient clinic in Istanbul. Of 109 patients, 33.9 % were atopic. Sixty-five percent of subjects were sensitized to Dermatophagoides pteronyssinus, 17 % to a grass-pollen mixture, 8 % to Aspergillus fumigatus, and 8 % to Blattella germanica. There was no difference between mono- and polysensitized patients in terms of the duration of rhinitis and symptom severity. No significant difference was observed between the two groups according to age, sex, smoking status, AR onset (<40 or ≥40 years), or duration/severity of disease. There was no significant difference between the two groups in the prevalence of asthma and conjunctivitis, (p = 0.256). Atopic dermatitis/eczema was more prevalent in those with AR (p = 0.046). Clinical characteristics of AR in the elderly could be different from those in non-allergic patients, and the prevalence of allergy may be higher than expected. PMID:25680346

  5. Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses promoting asthma susceptibility

    PubMed Central

    Brandt, Eric B.; Biagini Myers, Jocelyn M.; Acciani, Thomas H.; Ryan, Patrick H.; Sivaprasad, Umasundari; Ruff, Brandy; LeMasters, Grace K.; Bernstein, David I.; Lockey, James; LeCras, Timothy D.; Khurana Hershey, Gurjit K.

    2015-01-01

    Background Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbation, however the underlying mechanisms remain poorly understood. Objective To examine the impact of DEP exposure on the generation and persistence of allergen-specific memory T-cells in asthma and translate these findings by determining the impact of early DEP exposure on the prevalence of allergic asthma in children. Methods The impact of DEP on HDM-specific memory responses was determined using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort were analyzed to determine the impact of the DEP exposure on asthma outcomes. Results DEP co-exposure with HDM resulted in persistent Th2/Th17 CD127+ effector/memory cells in the lungs, spleen and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased levels of Th2 cytokines in only mice that had been previously exposed to both HDM and DEP versus HDM alone. Based on these data, we examined whether DEP exposure was similarly associated increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the CCAAPS birth cohort. Early life exposure to high DEP was associated with significantly increased asthma prevalence among allergic children, but not among non-allergic children. Conclusion These findings suggest that DEP exposure results in accumulation of allergen specific Th2/Th17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma. PMID:25748065

  6. Allergic Mechanisms in Eosinophilic Esophagitis

    PubMed Central

    Wechsler, Joshua B; Bryce, Paul J

    2014-01-01

    Paralleling the overall trend in allergic diseases, Eosinophilic Esophagitis is rapidly increasing in incidence. It is associated with food antigen-triggered, eosinophil-predominant inflammation and the pathogenic mechanisms have many similarities to other chronic atopic diseases, such as eczema and allergic asthma. Studies in animal models and from patients over the last 15 years have suggested that allergic sensitization leads to food-specific IgE and T-helper lymphocyte type 2 cells, both of which appear to contribute to the pathogenesis along with basophils, mast cells, and antigen-presenting cells. This review will outline our current understandings of the allergic mechanisms that drive eosinophilic esophagitis, drawing from clinical and translational studies in humans as well as experimental animal models. PMID:24813516

  7. Epigenomics and allergic disease

    PubMed Central

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2014-01-01

    Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment. PMID:24283882

  8. Proteinase activated receptor-2-mediated dual oxidase-2 up-regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma.

    PubMed

    Nadeem, Ahmed; Alharbi, Naif O; Vliagoftis, Harissios; Tyagi, Manoj; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M

    2015-07-01

    Airway epithelial cells (AECs) express a variety of receptors, which sense danger signals from various aeroallergens/pathogens being inhaled constantly. Proteinase-activated receptor 2 (PAR-2) is one such receptor and is activated by cockroach allergens, which have intrinsic serine proteinase activity. Recently, dual oxidases (DUOX), especially DUOX-2, have been shown to be involved in airway inflammation in response to Toll-like receptor activation. However, the association between PAR-2 and DUOX-2 has not been explored in airways of allergic mice. Therefore, this study investigated the contribution of DUOX-2/reactive oxygen species (ROS) signalling in airway reactivity and inflammation after PAR-2 activation. Mice were sensitized intraperitoneally with intact cockroach allergen extract (CE) in the presence of aluminium hydroxide followed by intranasal challenge with CE. Mice were then assessed for airway reactivity, inflammation, oxidative stress (DUOX-2, ROS, inducible nitric oxide synthase, nitrite, nitrotyrosine and protein carbonyls) and apoptosis (Bax, Bcl-2, caspase-3). Challenge with CE led to up-regulation of DUOX-2 and ROS in AECs with concomitant increases in airway reactivity/inflammation and parameters of oxidative stress, and apoptosis. All of these changes were significantly inhibited by intranasal administration of ENMD-1068, a small molecule antagonist of PAR-2 in allergic mice. Administration of diphenyliodonium to allergic mice also led to improvement of allergic airway responses via inhibition of the DUOX-2/ROS pathway; however, these effects were less pronounced than PAR-2 antagonism. The current study suggests that PAR-2 activation leads to up-regulation of the DUOX-2/ROS pathway in AECs, which is involved in regulation of airway reactivity and inflammation via oxidative stress and apoptosis. PMID:25684443

  9. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

    PubMed

    Dharajiya, Nilesh; Vaidya, Swapnil; Sinha, Mala; Luxon, Bruce; Boldogh, Istvan; Sur, Sanjiv

    2009-01-01

    According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation. PMID:20027288

  10. Prevention of asthma.

    PubMed

    Kaufman, H S; Frick, O L

    1981-11-01

    Infants born of allergic mothers but normal fathers, who had eczema and who were fed cows' milk, had a significantly greater incidence of asthma (P less than 0.001) than infants with a similar history but who were breast-fed. An analysis of all breast-fed infants in the study showed that they were less likely to develop asthma than those who were bottle-fed (P less than 0.06). There was a lower incidence of allergy in infants born of families with allergic mothers and normal fathers, than in families in which both parents were allergic (P less than 0.02). In skin tests of both breast or bottle-fed babies, the two most common allergens eliciting reactions were egg and cat dander. PMID:7333001

  11. OCCUPATIONAL ALLERGY AND ASTHMA AMONG SALT WATER FISH PROCESSING WORKERS

    PubMed Central

    Jeebhay, Mohamed F; Robins, Thomas G; Miller, Mary E; Bateman, Eric; Smuts, Marius; Baatjies, Roslynn; Lopata, Andreas L

    2010-01-01

    Background Fish processing is a common economic activity in Southern Africa. The aim of this study was to determine the prevalence and host determinants of allergic symptoms, allergic sensitization, bronchial hyper-responsiveness and asthma among workers processing saltwater fish. Methods A cross-sectional study was conducted on 594 currently employed workers in two processing plants involved in pilchard canning and fishmeal processing. A modified European Community Respiratory Health Survey (ECRHS) questionnaire was used. Skin prick tests (SPT) used extracts of common airborne allergens, fresh fish (pilchard, anchovy, maasbanker, mackerel, red eye) and fishmeal. Spirometry and methacholine challenge tests (tidal breathing method) used ATS guidelines. Results Work-related ocular-nasal symptoms (26%) were more common than asthma symptoms (16%). The prevalence of atopy was 36%, while 7% were sensitized to fish species and 26% had NSBH (PC20 ≤ 8 mg/ml or ≥12% increase in FEV1 post bronchodilator). The prevalence of probable occupational asthma was 1.8% and fish allergic rhino-conjunctivitis 2.6%. Women were more likely to report work-related asthma symptoms (OR=1.94) and have NSBH (OR=3.09), while men were more likely to be sensitized to fish (OR=2.06) and have airway obstruction (OR=4.17). Atopy (OR=3.16) and current smoking (OR=2.37), but not habitual seafood consumption were associated with sensitization to fish. Conclusions Based on comparison with previous published studies, the prevalence of occupational asthma to salt water fish is lower than due to shellfish. The gendered distribution of work and exposures in fish processing operations together with atopy and cigarette smoking are important determinants of occupational allergy and asthma. PMID:18726880

  12. New therapies for allergic rhinitis.

    PubMed

    Braido, Fulvio; Sclifò, Francesca; Ferrando, Matteo; Canonica, Giorgio Walter

    2014-04-01

    Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules. PMID:24504526

  13. Epidemiology of bronchial asthma in school children (10–16 years) in Srinagar

    PubMed Central

    Qureshi, Uruj Altaf; Bilques, Sufoora; ul Haq, Inaam; Khan, Muhammad Saleem; Qurieshi, Mariya Amin; Qureshi, Umar Amin

    2016-01-01

    Objectives: To assess the epidemiological profile of asthma in school going children in Srinagar, Kashmir. Study design: Cross-sectional study. Setting: Thirty-one schools with proportionate representation from both government and private schools as well as from primary, middle, and high schools. Participants: School children aged 10–16 years with equal representation of sex and all ages. Main Outcome Measure: Prevalence of current and past asthma. Methods and Results: After administering a modified pretested questionnaire, peak expiratory flow measurement was carried. Children who had asthma-like symptoms or positive family history of asthma or physician-labeled asthma were subjected to spirometry and bronchodilator reversibility. Out of 806 children, bronchial asthma was seen in 60 (prevalence of 7.4%) which included 34 boys and 26 girls. Majority of asthmatic children (78.3% [n = 47]) had probable asthma; 6.7% (n = 4) had definite asthma; and 15% (n = 9) had physician-diagnosed asthma. Majority of children had intermittent asthma (78.3% [n = 47]). Mild persistent asthma was seen in 12.7% (n = 7) and 10% (n = 6) had moderate persistent asthma. None of the children had severe persistent asthma. The prevalence of current asthma was 3.2% (n = 26). On univariate analysis, the factors found to be statistically significant were family history of asthma (odds ratio [OR] =8.174; confidence interval [CI] =4.403–15.178), seasonal cough (OR = 4.266; CI = 2.336–7.791), allergic rhinitis (OR = 2.877; CI = 1.414–5.852), atopic dermatitis (OR = 6.597; CI = 2.72–16.004), and obesity (OR = 6.074; CI = 2.308–18.034). On multivariate analysis, family history, seasonal cough, allergic rhinitis, atopic dermatitis, and obesity were found to be significant independent risk factors. Conclusions: Srinagar qualifies as a low prevalence area for bronchial asthma in the age group of 10–16 years. Majority of children had mild intermittent asthma resulting in under diagnosis and

  14. Nerve growth factor and asthma.

    PubMed

    Bonini, S; Lambiase, A; Lapucci, G; Properzi, F; Bresciani, M; Bracci Laudiero, M L; Mancini, M J; Procoli, A; Micera, A; Sacerdoti, G; Bonini, S; Levi-Schaffer, F; Rasi, G; Aloe, L

    2002-01-01

    An increasing body of evidence shows that nerve growth factor (NGF) exerts biological activity not only on the central and peripheral nervous system, but also on the immune system thereby influencing allergic diseases and asthma. (1) NGF circulating levels are increased in patients with allergic diseases and asthma, and are related to the severity of the inflammatory process and disease. In vernal keratoconjunctivitis, NGF plasma levels correlate with the number of mast cells infiltrating the conjunctiva, and NGF mRNA is increased in nasal mucosal scrapings of patients with allergic rhinitis who have high levels of NGF in serum and nasal fluids; NGF is further increased in nasal fluids after specific allergen challenge. (2) NGF is produced and released by several modulatory and effector cells of allergic inflammation and asthma, for example T-helper 2 lymphocytes, mast cells and eosinophils. (3) NGF receptors are expressed on the conjunctival epithelium of patients with allergic conjunctivitis and the number of NGF-receptor positive cells is increased in the conjunctiva of these patients. Indeed, local administration of NGF induces fibroblast activation and healing processes of human corneal ulcers, which suggests that NGF plays a role in tissue remodelling processes occurring in asthma. (4) NGF increases airway hyperreactivity to histamine in an animal model of asthma, while anti-NGF treatment reduces airway hyperreactivity induced by ovalbumin topical challenge in the sensitized mouse. PMID:12144547

  15. Regulation of the development of asthmatic inflammation by in situ CD4(+)Foxp3 (+) T cells in a mouse model of late allergic asthma.

    PubMed

    Nakashima, Tomomi; Hayashi, Toshiharu; Mizuno, Takuya

    2014-10-01

    CD4(+)Foxp3(+)T cells (Tregs) mediate homeostatic peripheral tolerance by suppressing helper T2 cells in allergy. However, the regulation of asthmatic inflammation by local (in situ) Tregs in asthma remains unclear. BALB/c mice sensitized and challenged with ovalbumin (OVA) (asthma group) developed asthmatic inflammation with eosinophils and lymphocytes, but not mast cells. The number of Tregs in the circulation, pulmonary lymph nodes (pLNs), and thymi significantly decreased in the asthma group compared to the control group without OVA sensitization and challenge in the effector phase. The development of asthmatic inflammation is inversely related to decreased Tregs with reduced mRNA expression such as interleukin (IL)-4, transforming growth factor-β1, and IL-10, but not interferon-γ, in pLNs. Moreover, M2 macrophages increased in the local site. The present study suggests that Tregs, at least in part, may regulate the development of asthmatic inflammation by cell-cell contact and regional cytokine productions. PMID:24854160

  16. Expression of the High Affinity IgE Receptor by Neutrophils of Individuals with Allergic Asthma is Both Minimal and Insensitive to Regulation by Serum IgE

    PubMed Central

    Mora, Juanita; Riggs, Emily K.; Fu, Jun; MacGlashan, Donald W.; Fox, Susan A.; Yu, Byung; Tobin, Mary C.; Thomas, Larry L.

    2009-01-01

    We evaluated the hypothesis that serum IgE regulates neutrophil FcεRI expression in the same manner as described for other FcεRI+ cells. FcεRI expression by neutrophils of 40 asthma subjects and 20 control subjects did not correlate with serum IgE levels, whereas FcεRI expression by basophils of the same subjects showed a highly significant correlation. The level of FcεRI expression by neutrophils of both asthma and control subjects was approximately 1% of that for basophil FcεRI expression. IgE+ neutrophils were minimally detectable, and FcεRI α subunit was not detected in Western blots of neutrophil membranes and cytosol. The neutrophil FcεRI did not support anti-IgE stimulated superoxide release or IgE-induced increase in neutrophil survival. We conclude that FcεRI expression by neutrophils of both asthma patients and control individuals is minimal at best and that, if present, neutrophil FcεRI expression, unlike that of other human FcεRI+ cells, is not regulated by serum IgE. PMID:19359220

  17. Development and validation of RP-HPLC method to determine anti-allergic compound in Thai traditional remedy called Benjalokawichien.

    PubMed

    Sakpakdeejaroen, Intouch; Juckmeta, Thana; Itharat, Arunporn

    2014-08-01

    Benjalokawichien (BLW) or Ya-Ha-Rak (HR) is a traditional remedy in the Nationaldrug list of herbal medicinal products AD 2012 of Thailand. For traditional use, BLW is used as antipyretic agent. It also has anti-allergic effect, particularly treating allergic rash. The ethanolic extract of BLW exhibited anti-allergic activity via inhibitory effect against a release ofbeta-hexosaminidase in RBL-2H3 cell line. Pectolinarigenin has been identified as the active compound ofBLW extract. In this study, a reversed-phase high performance liquid chromatography (RP-HPLC) method was developed in order to control quality ofpreparation in three aspects such as chemical fingerprint, quantification and stability of the ethanolic extract. The RP-HPLC was performed with a gradient mobile phase composed of 0.1% ortho phosphoric acid and acetronitrile, and peaks were detected at 331 nm. Based on validation results, this analytical method is precise, accurate and stable for quantitative determination ofpectolinarigenin. The amount ofpectolinarigenin in Benjalokawichien extract determined by this method was 18.50 mg/g ofextract. Therefore, this method could be consideredfor quality control ofBLWextract. PMID:25518297

  18. A small molecule, orally active, α4β1/α4β7 dual antagonist reduces leukocyte infiltration and airway hyper-responsiveness in an experimental model of allergic asthma in Brown Norway rats

    PubMed Central

    Cortijo, Julio; Sanz, María-Jesús; Iranzo, Arantxa; Montesinos, José Luis; Nabah, Yafa Naim Abu; Alfón, José; Gómez, Luis A; Merlos, Manuel; Morcillo, Esteban J

    2006-01-01

    α4β1 and α4β7 integrins are preferentially expressed on eosinophils and mononuclear leukocytes and play critical roles in their recruitment to inflammatory sites. We investigated the effects of TR14035, a small molecule, α4β1/α4β7 dual antagonist, in a rat model of allergic asthma. Actively sensitized rats were challenged with aerosol antigen or saline on day 21, and the responses evaluated 24 and 48-h later. TR14035 (3 mg kg−1, p.o.) was given 1-h before and 4-h after antigen or saline challenge. Airway hyper-responsiveness to intravenous 5-hydroxytryptamine was suppressed in TR14035-treated rats. Eosinophil, mononuclear cell and neutrophil counts, and eosinophil peroxidase and protein content in the bronchoalveolar lavage fluid (BALF) were decreased in TR14035-treated rats. Histological study showed a marked reduction of lung inflammatory lesions by TR14035. At 24-h postchallenge, antigen-induced lung interleukin (IL)-5 mRNA upregulation was suppressed in TR14035-treated rats. By contrast, IL-4 levels in BALF were not significantly affected by TR14035 treatment. IL-4 selectively upregulates vascular cell adhesion molecule-1 (VCAM-1), which is the main endothelial ligand of α4 integrins. Intravital microscopy within the rat mesenteric microcirculation showed that 24-h exposure to 1 μg per rat of IL-4 induced a significant increase in leukocyte rolling flux, adhesion and emigration. These responses were decreased by 48, 100 and 99%, respectively in animals treated with TR14035. In conclusion, TR14035, by acting on α4β1 and α4β7 integrins, is an orally active inhibitor of airway leukocyte recruitment and hyper-responsiveness in animal models with potential interest for the treatment of asthma. PMID:16432509

  19. Childhood obesity and risk of allergy or asthma.

    PubMed

    Raj, Dinesh; Kabra, Sushil K; Lodha, Rakesh

    2014-11-01

    The simultaneous increment in the prevalence of obesity and allergic diseases suggests a possible link between them. This review focuses on the consequences of obesity on allergic diseases, especially asthma in children and adolescents, and evaluates the available evidence on the possible mechanisms. Obesity is related more strongly to nonatopic than atopic asthma, suggesting non-eosinophilic inflammation and Th1 polarization. Among other allergic diseases, the association is more consistent with eczema compared to allergic rhinitis/rhinoconjunctivitis. The mechanisms of asthma in obese individuals could involve mechanical effects of obesity on lung function, adipokines-mediated inflammation, shared factors (diet, genetics, sedentary lifestyle) and comorbidities. PMID:25282288

  20. [Allergic inflamation of the lower airways in patients with allergic rhinitis].

    PubMed

    Stefanović, Lj; Balaban, J; Stosović, R; Mitrović, N; Djurasinović, M; Tanurdzić, S

    1994-01-01

    Reporting two of our cases we wanted to point to a great dilemma related to the final diagnosis. Recently, such cases have been more frewuently seen, since in all patients with allergic rhinitis conditions of the lower airways is examined before the administration of the specific immunotherapy. Therefore, we may see patients who are still free of pulmonary sings, despite of positive specific and/or non specific bronchoprovocative tests. The presented cases with evidenced allergic rhinitis are probably in the phase of development of allergic bronchial asthma, the phase of "allergic inflammation" of the lower airways, not clinically manifested yet. PMID:18173213

  1. FEF(25-75) might be a predictive factor for bronchial inflammation and bronchial hyperreactivity in adolescents with allergic rhinitis.

    PubMed

    Ciprandi, G; Tosca, M A; Castellazzi, A M; Cairello, F; Salpietro, C; Arrigo, T; Miraglia Del Giudice, M

    2011-10-01

    Allergic rhinitis and asthma are closely associated. Bronchial hyperreactivity (BHR) is a pathophysiological characteristic of asthma. Allergic inflammation is characterized by eosinophilic infiltrate and may by indirectly assessed by exhaled nitric oxide (FeNO). Forced expiratory flow between 25 percent and 75 percent of vital capacity (FEF25-75) may predict BHR in adult patients with allergic rhinitis. The aim of this study was to evaluate the presence of BHR in a large group of adolescents with allergic rhinitis and whether FEF25-75 might be related with BHR and FeNO. Methods 150 adolescents with allergic rhinitis were enrolled. Clinical examination, skin prick test, spirometry, methacholine challenge, and FeNO were performed in all patients. Results Severe BHR is quite frequent in allergic adolescents. Impaired FEF25-75 values (such as less than 65 percent of predicted) constitute a relevant predictive factor for severe BHR (OR 4.4). FeNO levels were significantly related with BHR. Conclusion This study provides evidence that impaired FEF25-75 values might predict severe BHR and BHR is related with FeNO in adolescents. Therefore, BHR should be suspected in adolescents with low FEF25-75 values. PMID:22032781

  2. Allergic rhinitis - what to ask your doctor - child

    MedlinePlus

    ... How do I find out when smog or pollution is worse in our area? What does my ... More Allergen Allergic rhinitis Allergies - overview Allergy testing - skin Asthma and allergy - resources Common cold Sneezing Patient ...

  3. Allergic rhinitis - what to ask your doctor - adult

    MedlinePlus

    ... How do I find out when smog or pollution is worse in my area? Am I taking ... More Allergen Allergic rhinitis Allergies - overview Allergy testing - skin Asthma and allergy - resources Common cold Sneezing Patient ...

  4. Bee venom phospholipase A2 suppresses allergic airway inflammation in an ovalbumin-induced asthma model through the induction of regulatory T cells.

    PubMed

    Park, Soojin; Baek, Hyunjung; Jung, Kyung-Hwa; Lee, Gihyun; Lee, Hyeonhoon; Kang, Geun-Hyung; Lee, Gyeseok; Bae, Hyunsu

    2015-12-01

    Bee venom (BV) is one of the alternative medicines that have been widely used in the treatment of chronic inflammatory diseases. We previously demonstrated that BV induces immune tolerance by increasing the population of regulatory T cells (Tregs) in immune disorders. However, the major component and how it regulates the immune response have not been elucidated. We investigated whether bee venom phospholipase A2 (bvPLA2) exerts protective effects that are mediated via Tregs in OVA-induced asthma model. bvPLA2 was administered by intraperitoneal injection into control and OVA-challenged mice. The Treg population, total and differential bronchoalveolar lavage fluid (BALF) cell count, Th2 cytokines, and lung histological features were assessed. Treg depletion was used to determine the involvement of Treg migration and the reduction of asthmatic symptoms. The CD206-dependence of bvPLA2-treated suppression of airway inflammation was evaluated in OVA-challenged CD206(-/-) mice. The bvPLA2 treatment induced the Tregs and reduced the infiltration of inflammatory cells into the lung in the OVA-challenged mice. Th2 cytokines in the bronchoalveolar lavage fluid (BALF) were reduced in bvPLA2-treated mice. Although bvPLA2 suppressed the number of inflammatory cells after OVA challenge, these effects were not observed in Treg-depleted mice. In addition, we investigated the involvement of CD206 in bvPLA2-mediated immune tolerance in OVA-induced asthma model. We observed a significant reduction in the levels of Th2 cytokines and inflammatory cells in the BALF of bvPLA2-treated OVA-induced mice but not in bvPLA2-treated OVA-induced CD206(-/-) mice. These results demonstrated that bvPLA2 can mitigate airway inflammation by the induction of Tregs in an OVA-induced asthma model. PMID:26734460

  5. Asthma Outcomes: Asthma Symptoms

    PubMed Central

    Krishnan, Jerry A.; Lemanske, Robert F.; Canino, Glorisa J.; Elward, Kurtis S.; Kattan, Meyer; Matsui, Elizabeth C.; Mitchell, Herman; Sutherland, E. Rand; Minnicozzi, Michael

    2014-01-01

    Background Respiratory symptoms are commonly used to assess the impact of patient-centered interventions. Objective At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to propose which measurements of asthma symptoms should be used as a standardized measure in future clinical research studies. Methods Asthma symptom instruments were classified as daily diaries (prospectively recording symptoms between research visits) or retrospective questionnaires (completed at research visits). We conducted a systematic search in PubMed and a search for articles that cited key studies describing development of instruments. We classified outcome instruments as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011. Results Four instruments (3 daily diaries, 1 for adults and 2 for children; and 1 retrospective questionnaire for adults) were identified. Minimal clinically important differences have not been established for these instruments, and validation studies were only conducted in a limited number of patient populations. Validity of existing instruments may not be generalizable across racial-ethnic or other subgroups. Conclusions An evaluation of symptoms should be a core asthma outcome measure in clinical research. However, available instruments have limitations that preclude selection of a core instrument. The working group participants propose validation studies in diverse populations, comparisons of diaries versus retrospective questionnaires, and evaluations of symptom assessment alone versus composite scores of asthma control. PMID:22386505

  6. Endotoxin Exposure Is a Risk Factor for Asthma

    PubMed Central

    Thorne, Peter S.; Kulhánková, Katarina; Yin, Ming; Cohn, Richard; Arbes, Samuel J.; Zeldin, Darryl C.

    2005-01-01

    Background: Although research has shown that early life exposure to household endotoxin protects against development of allergies, studies are less clear on the relationship between household endotoxin exposure and prevalence of wheezing and asthma. We as- sayed 2,552 house dust samples in a representative nationwide sam- ple to explore relationships between endotoxin exposures and risk factors for asthma, asthma symptoms, and medication use. Methods: House dust was vacuum-sampled from five locations within homes and assayed for endotoxin. Health, demographic, and housing information was assessed through questionnaire and on-site evaluation of 2,456 residents of 831 homes selected to represent the demographics of the United States. Results: Endotoxin concentration (EU/mg) and load (EU/m2) were highly correlated (r = 0.73–0.79). Geometric mean endotoxin concentrations were as follows (in EU/mg): bedroom floors, 35.3 (5th–95th percentile, 5.0–260); bedding, 18.7 (2.0–142); family room floors, 63.9 (11.5–331); sofas, 44.8 (6.4–240); and kitchen floors, 80.5 (9.8–512). Multivariate analysis demonstrated significant relationships between increasing endotoxin levels and diagnosed asthma, asthma symptoms in the past year, current use of asthma medications, and wheezing among residents of the homes. These relationships were strongest for bedroom floor and bedding dust and were observed in adults only. Modeling the joint effect of bedding and bedroom floor endotoxin on recent asthma symptoms yielded an adjusted odds ratio of 2.83 (95% confidence interval, 1.01–7.87). When stratified by allergy status, allergic subjects with higher endotoxin exposure were no more likely to have diagnosed asthma or asthma symptoms than nonallergic subjects. Conclusion: This study demonstrates that household endotoxin exposure is a significant risk factor for increased asthma prevalence. PMID:16141442

  7. Eosinophilic pleural effusion complicating allergic bronchopulmonary aspergillosis.

    PubMed

    Kirschner, Austin N; Kuhlmann, Erica; Kuzniar, Tomasz J

    2011-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is primarily a disease of patients with cystic fibrosis or asthma, who typically present with bronchial obstruction, fever, malaise, and expectoration of mucus plugs. We report a case of a young man with a history of asthma who presented with cough, left-sided pleuritic chest pain and was found to have lobar atelectasis and an eosinophilic, empyematous pleural effusion. Bronchoscopy and sputum cultures grew Aspergillus fumigatus, and testing confirmed strong allergic response to this mold, all consistent with a diagnosis of ABPA. This novel and unique presentation of ABPA expands on the differential diagnosis of eosinophilic pleural effusions. PMID:21311176

  8. Improved Diagnosis of the Polysensitized Allergic Rhinitis Patients Using Component Resolved Diagnosis Method.

    PubMed

    Mohamad Yadzir, Zailatul Hani; Bakhtiar, Faizal; Misnan, Rosmilah; Abdullah, Noormalin; Leecyous, Brenda; Murad, Shahnaz

    2016-04-01

    Allergy diagnosis needs to be improved in polysensitized patients due to the existence of possible confounding factors in this type of patients. Component resolved diagnosis (CRD) is a new concept in the investigation of polysensitized patients. The aim of this study was to evaluate if the utilization of ImmunoCAP ISAC improve the diagnosis of the polysensitized allergic rhinitis patients. Skin prick test (SPT) to 58 crude allergen extracts and CRD (ImmunoCAP ISAC) were carried out for 5 polysensitized allergic rhinitis patients. Two patients had a shellfish allergy and avoidance of shellfish was the only way to prevent an allergic reaction. In contrast, although the remaining three patients had low risk for shellfish allergy, but they were the best candidates for immunotherapy using mite extracts. CRD and particularly ImmunoCAP ISAC have proven to be a valuable diagnostic tool in polysensitized patients. ImmunoCAP ISAC helps refine the individual patient's sensitization profile and predict the potential risk of allergic reactions and improve the selection of patients for immunotherapy. PMID:27090369

  9. Heat shock protein X purified from Mycobacterium tuberculosis enhances the efficacy of dendritic cells-based immunotherapy for the treatment of allergic asthma.

    PubMed

    Kim, Hye-Young; Kang, Hyun Kyu; Cho, Joon; Jung, In Duk; Yoon, Gun Young; Lee, Min-Goo; Shin, Sung Jae; Park, Won Sun; Park, Jong-Hwan; Ryu, Seung-Wook; Park, Yeong-Min; You, Ji Chang

    2015-03-01

    Dendritic cells play an important role in determining whether naïve T cells mature into either Th1 or Th2 cells. We determined whether heat-shock protein X (HspX) purified from Mycobacterium tuberculosis regulates the Th1/Th2 immune response in an ovalbumin (OVA)-induced murine model of asthma. HspX increased interferon-gamma, IL-17A, -12 and transforming growth factor (TGF)-β production and T-bet gene expression but reduced IL-13 production and GATA-3 gene expression. HspX also inhibited asthmatic reactions as demonstrated by an increase in the number of eosinophils in bronchoalveolar lavage fluid, inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decrease of regulatory T cells in the mediastinal lymph nodes. This study provides evidence that HspX plays critical roles in the amelioration of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of HspX with respect to its effects on a murine model of asthma. PMID:25560695

  10. Allergic rhinitis.

    PubMed

    Mygind, Niels

    2014-01-01

    Allergic rhinitis is a very frequent disease with a prevalence of 15-20%. Symptoms are most pronounced in young people while, for some unknown reason, the elderly become clinically hyposensitized. Pollen is the cause of seasonal allergic rhinitis, and house dust mite and animals are the main causes of perennial allergic rhinitis. Histamine is the main cause of sneezing and hypersecretion, while other mediators probably also play a role in nasal blockage. In polyposis, a local denervation is an important cause of vascular leakage, edema and polyp formation. Antihistamines have a positive effect on sneezing and hypersecretion, but not on blockage. As they have a quick onset of action they are useful in patients with mild and occasional symptoms. A nasal steroid is preferable in patients with persistent symptoms, since it is more effective on all nasal symptoms. Short-term use of a systemic steroid can be a valuable adjunct to topical treatment, especially in nasal polyposis, when there is a temporary failure of topical treatment in a blocked nose. A nasal vasoconstrictor can be added for short-term treatment, and an ipratropium spray can be beneficial in perennial non-allergic rhinitis, when watery secretion is the dominant symptom. Immunotherapy can be added in allergic rhinitis, when pharmacotherapy is insufficient. This chapter is based on the author's personal experience with allergic rhinitis, as a patient, a doctor and a researcher. Therefore, it is not a balanced review and the references will be highly selected as they largely consist of the author's own publications. As the text is mainly based on personal research, steroids are described in detail, while, with regard to immunotherapy, the reader is referred to another chapter. In addition to allergic rhinitis, nasal polyposis will be described. It was formerly believed to be an allergic disease, but we now know that it is not. However, with regard to histopathology and drug responsiveness this disease is

  11. A new, rapid in vivo method to evaluate allergic responses through distinctive distribution of a fluorescent-labeled immune complex: Potential to investigate anti-allergic effects of compounds administered either systemically or topically to the skin.

    PubMed

    Yamaki, Kouya; Yoshino, Shin

    2016-01-01

    We herein established a new method to evaluate allergic responses in mice rapidly and easily with ethical improvement by reducing the number of animals used. A single intravenous injection of a mixture of anti-OVA monoclonal IgE and fluorescein-ovalbumin (FITC-OVA) induced the distinctive spotted distribution of FITC-OVA in skin, named "ASDIS (Anaphylaxis-dependent Spotted Distribution of a fluorescent-labeled Immune complex in Skin)", and this was easily detected by in vivo imaging. The parallel induction of hypothermia, scratching, serum histamine increases, and ASDIS as well as the inhibition of ASDIS by either the systemic administration of a histamine H1 receptor antagonist or mast cell-depleting antibody suggested that our method, which only required 15 min, induced these allergic responses including ASDIS. Relatively mild but significant ASDIS was induced also in mice with passive systemic anaphylaxis by the method, requiring 2 separate days. The painting of anti-histamines on the skin markedly reduced ASDIS in the painted area only, suggesting the potential of this model to simultaneously compare the anti-allergic effects of several candidate compounds with control drugs in the same mice. ASDIS was suggested to originate from extravasated FITC-OVA/OE-1 immune complexes from blood to skin tissues other than mast cells. Our new method has the advantages of rapidity, easy method, and lower animal numbers to evaluate anti-allergic compounds as well as the characteristics of the used antibody, antigen, labeling molecules, additives, and other formulations. Our model for inducing ASDIS may contribute to the development of anti-allergic drugs, especially those intended for application to the skin. PMID:26643682

  12. Probiotics for allergic respiratory diseases--putting it into perspective.

    PubMed

    Singh, Meenu; Ranjan Das, Rashmi

    2010-03-01

    Respiratory allergies include allergic rhinitis, sinusitis and asthma. Increasing attention on pathogenesis of allergic airway diseases has given rise to "atopic march" hypothesis i.e. clinical features of atopic eczema occur first and precede the development of asthma and allergic rhinitis. The "hygiene hypothesis" proposes that the increase in allergic diseases reflects a decrease in infections during childhood. Clinical trials also suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Probiotics are live organisms which exert a beneficial effect in the prevention as well as treatment of allergic diseases through modification of immune system of host via gut ecosystem. Intestinal microbiota differs in infants who later develop allergic diseases, and feeding probiotics to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics in prevention as well as treatment of respiratory allergy. We hereby discuss the status of probiotics in respiratory allergy. PMID:19725896

  13. The Novel 10-Item Asthma Prediction Tool: External Validation in the German MAS Birth Cohort

    PubMed Central

    Grabenhenrich, Linus B.; Reich, Andreas; Fischer, Felix; Zepp, Fred; Forster, Johannes; Schuster, Antje; Bauer, Carl-Peter; Bergmann, Renate L.; Bergmann, Karl E.; Wahn, Ulrich; Keil, Thomas; Lau, Susanne

    2014-01-01

    Background A novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma. Objective We aimed to externally validate the proposed asthma prediction method in a German birth cohort. Methods The MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years. Results For 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9% vs. 16% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45% vs. 48%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome ‘physicians’ diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89). Conclusion The novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings. PMID:25536057

  14. Resurvey of symptomatics of the Jaipur district population and suggestion for alternative diagnostic criteria of asthma for epidemiological surveys

    PubMed Central

    Gupta, Prahlad Rai; Bansal, Ankit; Singh, Anupam

    2016-01-01

    Introduction: The prevalence of asthma in Jaipur district of Rajasthan was reported as 0.96% in an earlier survey. It was far below the national average of 2.38%. It was reasoned then that this could be due to under diagnosis of asthma in the Jaipur population. Material and Methods: A resurvey of the symptomatics, not diagnosed as asthma at time of the original survey was, therefore, undertaken. The resurvey data were analysed and those who now fulfilled the twin criteria for diagnosis of asthma, as used in the original survey, were diagnosed as having asthma. The original data of these newly diagnosed asthma patients were reanalyzed in search for an alternative diagnostic criterion. Results: Of the 382 symptomatics, 344 (90%) could be resurveyed and of them, 85 now fulfilled the twin diagnostic criteria for asthma. The reanalysis of the original survey data of these patients revealed that presence of shortness of breath (SOB) had the highest sensitivity, the presence of allergic symptoms in self or the family had the highest specificity and the presence of wheezing had the highest odds ratio (OR) for diagnosing asthma. Further, the OR for diagnosing asthma increased further and was highest with the presence of SOB and 2 additional symptoms. With the use of the “symptom criteria” for diagnosis of asthma i.e. the presence of SOB with 2 additional symptoms, it would have been possible to diagnose majority of the missed cases at the time of the original survey itself. Conclusions: Based on this study data it can be concluded that (a) the twin criteria for diagnosing asthma as used in earlier surveys led to under diagnosis of asthma and (b) the use of symptom criteria alone effectively checks the problem of under diagnosis of asthma. The symptom criteria are being suggested as an alternative method for use in future epidemiological surveys on asthma. PMID:26933304

  15. METALS, PARTICLES AND IMPACT UPON PULMONARY ALLERGIC RESPONSES

    EPA Science Inventory


    The increase in allergic asthma over the past few decades has prompted investigations into whether air pollution may affect either the incidence or severity of allergic lung disease. Population studies have demonstrated that as air pollution rises, symptoms, medication use a...

  16. Occupational asthma

    MedlinePlus

    Asthma - occupational exposure; Irritant-induced reactive airways disease ... the workplace can trigger asthma symptoms, leading to occupational asthma. The most common triggers are wood dust, grain ...

  17. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis.

    PubMed

    Chawes, Bo L K

    2011-05-01

    Allergic- and non-allergic rhinitis are very common diseases in childhood in industrialized countries. Although these conditions are widely trivialized by both parents and physicians they induce a major impact on quality of life for the affected children and a substantial drainage of health care resources. Unfortunately, diagnostic specificity is hampered by nonspecific symptom history and lack of reliable diagnostic tests which may explain why the pathology behind such diagnoses is poorly understood. Improved understanding of the pathophysiology of allergic- and non-allergic rhinitis in young children may contribute to the discovery of new mechanisms involved in pathogenesis and help direct future research to develop correctly timed preventive measures as well as adequate monitoring and treatment of children with rhinitis. Asthma is a common comorbidity in subjects with allergic rhinitis and epidemiological surveys have suggested a close connection between upper and lower airway diseases expressed as the "united airways concept". Furthermore, an association between upper and lower airway diseases also seems to exist in non-atopic individuals. Nevertheless, the nature of this association is poorly understood and there is a paucity of data objectivizing this association in young children. The aim of this thesis was to describe pathology in the upper and lower airways in young children from the COPSAC birth cohort with investigator-diagnosed allergic- and non-allergic rhinitis. Nasal congestion is a key symptom in both allergic- and non-allergic rhinitis, and eosinophilic inflammation is a hallmark of the allergic diseases. In paper I, we studied nasal eosinophilia and nasal airway patency assessed by acoustic rhinometry in children with allergic rhinitis, non-allergic rhinitis and healthy controls. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling

  18. Allergic Reactions

    MedlinePlus

    ... immune system identifies pollen as an invader or allergen. Your immune system overreacts by producing antibodies called ... IgE has specific "radar" for each type of allergen. That's why some people are only allergic to ...

  19. Exercise-induced asthma. What family physicians should do.

    PubMed Central

    D'Urzo, A.

    1995-01-01

    Exercise-induced asthma is described as a transitory increase in airway resistance during or after vigorous exercise. Nearly 90% of patients with chronic asthma and 40% of allergic nonasthmatic patients have the condition. Family physicians should try to educate patients about their asthma and, barring contraindications, encourage them to participate in regular physical activity. PMID:8563507

  20. Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

    PubMed Central

    Ferreira, Manuel A. R.; Matheson, Melanie C.; Tang, Clara S.; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K.; Duffy, David L.; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D.; Eriksson, Nicholas; Madden, Pamela A.; Abramson, Michael J.; Holt, Patrick G.; Heath, Andrew C.; Hunter, Michael; Musk, Bill; Robertson, Colin F.; Le Souëf, Peter; Montgomery, Grant W.; Henderson, A. John; Tung, Joyce Y.; Dharmage, Shyamali C.; Brown, Matthew A.; James, Alan; Thompson, Philip J.; Pennell, Craig; Martin, Nicholas G.; Evans, David M.; Hinds, David A.; Hopper, John L.

    2014-01-01

    Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. PMID:24388013

  1. DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BAL/C MICE

    EPA Science Inventory

    Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

  2. DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BALB/MICE

    EPA Science Inventory

    Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

  3. The Microbiome in Asthma

    PubMed Central

    Huang, Yvonne J.; Boushey, Homer A.

    2014-01-01

    The application of recently developed sensitive, specific, culture-independent tools for identification of microbes is transforming concepts of microbial ecology, including concepts of the relationships between the vast, complex populations of microbes associated with ourselves and with states of health and disease. While most work initially focused on the community of microbes (microbiome) in the gastrointestinal tract and its relationships to gastrointestinal disease, interest has expanded to include study of the relationships of the microbiome of the airways to asthma and its phenotypes, and to the relationships between the gastrointestinal microbiome, development of immune function, and predisposition to development of allergic sensitization and asthma. We here provide our perspective on the findings of studies of differences in the airway microbiome in patients with asthma vs. healthy subjects, and of studies of relationships between environmental microbiota, gut microbiota, immune function, and the development of asthma, and additionally provide our perspective on how these findings suggest in broad outline a rationale for approaches involving directed manipulation of the gut and airway microbiome for treatment and prevention of allergic asthma. PMID:25567040

  4. Vehicular Exhaust Particles Promote Allergic Airway Inflammation via an Aryl Hydrocarbon Receptor-Notch Signaling Cascade

    PubMed Central

    Xia, Mingcan; Viera-Hutchins, Loida; Garcia-Lloret, Maria; Rivas, Magali Noval; Wise, Petra; MGhee, Sean A.; Chatila, Zena K.; Daher, Nancy; Sioutas, Constantinos; Chatila, Talal A.

    2015-01-01

    Background Traffic-related particulate matter (PM) has been linked to heightened incidence of asthma and allergic diseases. However, molecular mechanisms by which PM exposure promote allergic diseases remain elusive. Objective We sought to determine the expression, function and regulation of pathways involved in the promotion by PM of allergic airway inflammation. Methods We employed gene expression transcriptional profiling, in vitro culture assays, and vivo murine models of allergic airway inflammation. Results We identified genes of the Notch pathway, most notably Jagged 1 (Jag1), as targets of PM induction in human monocytes and murine dendritic cells (DCs). PM, especially ultrafine particles (UFP), upregulated T helper cytokine, IgE production and allergic airway inflammation in mice in a Jag1 and Notch-dependent manner especially in the context of the pro-asthmatic IL-4 receptor allele Il4raR576. PM-induced Jag1 expression was mediated by the aryl hydrocarbon receptor (AhR), which bound to and activated AhR response elements in the Jag1 promoter. Pharmacological antagonism of AhR or its lineage-specific deletion in CD11c+ cells abrogated the augmentation of airway inflammation by PM. Conclusion PM activate an AhR-Jag1-Notch cascade to promote allergic airway inflammation in concert with pro-asthmatic alleles. PMID:25825216

  5. A 9-year Trend in the Prevalence of Allergic Disease Based on National Health Insurance Data

    PubMed Central

    Yoo, Byoungin; Park, Yoonhyung; Park, Kwanjun; Kim, Hoseob

    2015-01-01

    Objectives: To investigate trends in the prevalence of allergic disease over a 9-year period. Methods: Using National Health Insurance Service (NHIS) data, the annual number of patients with allergic disease was obtained for each regional subdivisions (small cities, counties, and districts) from 2003 to 2011. Annual populations for each sub-region were obtained and used to calculate the standardized prevalence. To compare prevalence within the study period, data was standardized spatially and temporally. For standardization, demographic data was used to obtain the registered population and demographic structure for 2010, which was used to perform direct standardization of previous years. In addition, a geographic information system (GIS) was used to visualize prevalence for individual sub-regions, and allergic diseases were categorized into five groups according to prevalence. Results: The nationwide outpatient prevalence of allergic rhinitis increased approximately 2.3-fold, from 1.27% in 2003 to 2.97% in 2013, while inpatient prevalence also increased approximately 2.4-fold,. The outpatient prevalence of asthma increased 1.2-fold, and inpatient prevalence increased 1.3-fold. The outpatient prevalence of atopic dermatitis decreased approximately 12%, and inpatient prevalence decreased 5%. Conclusions: There was a large difference between prevalence estimated from actual treatment data and prevalence based on patients’ self-reported data, particularly for allergic rhinitis. Prevalence must continually be calculated and trends should be analyzed for the efficient management of allergic diseases. To this end, prevalence studies using NHIS claims data may be useful. PMID:26639744

  6. Cleaning agents and asthma.

    PubMed

    Quirce, S; Barranco, P

    2010-01-01

    Although cleaners represent a significant part of the working population worldwide, they remain a relatively understudied occupational group. Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. Cleaning workers are exposed to a large variety of cleaning products containing both irritants and sensitizers, as well as to common indoor allergens and pollutants. Thus, the onset or aggravation of asthma in this group could be related to an irritant-induced mechanism or to specific sensitization. The main sensitizers contained in cleaning products are disinfectants, quaternary ammonium compounds (such as benzalkonium chloride), amine compounds, and fragrances.The strongest airway irritants in cleaning products are bleach (sodium hypochlorite), hydrochloric acid, and alkaline agents (ammonia and sodium hydroxide), which are commonly mixed together. Exposure to the ingredients of cleaning products may give rise to both new-onset asthma, with or without a latency period, and work-exacerbated asthma. High-level exposure to irritants may induce reactive airways dysfunction syndrome. Cleaning workers may also have a greater relative risk of developing asthma due to prolonged low-to-moderate exposure to respiratory irritants. In addition, asthma-like symptoms without confirmed asthma are also common after exposure to cleaning agents. In many cleaners, airway symptoms induced by chemicals and odors cannot be explained by allergic or asthmatic reactions. These patients may have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity, and this condition is termed airway sensory hyperreactivity. PMID:21313993

  7. dsRNA-induced changes in gene expression profiles of primary nasal and bronchial epithelial cells from patients with asthma, rhinitis and controls

    PubMed Central

    2014-01-01

    Background Rhinovirus infections are the most common cause of asthma exacerbations. The complex responses by airway epithelium to rhinovirus can be captured by gene expression profiling. We hypothesized that: a) upper and lower airway epithelium exhibit differential responses to double-stranded RNA (dsRNA), and b) that this is modulated by the presence of asthma and allergic rhinitis. Objectives Identification of dsRNA-induced gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. Methods This study had a cross-sectional design including 18 subjects: 6 patients with allergic asthma with concomitant rhinitis, 6 patients with allergic rhinitis, and 6 healthy controls. Comparing 6 subjects per group, the estimated false discovery rate was approximately 5%. RNA was extracted from isolated and cultured primary epithelial cells from nasal biopsies and bronchial brushings stimulated with dsRNA (poly(I:C)), and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and the Bioconductor Limma package. Overrepresentation of gene ontology groups were captured by GeneSpring GX12. Results In total, 17 subjects completed the study successfully (6 allergic asthma with rhinitis, 5 allergic rhinitis, 6 healthy controls). dsRNA-stimulated upper and lower airway epithelium from asthma patients demonstrated significantly fewer induced genes, exhibiting reduced down-regulation of mitochondrial genes. The majority of genes related to viral responses appeared to be similarly induced in upper and lower airways in all groups. However, the induction of several interferon-related genes (IRF3, IFNAR1, IFNB1, IFNGR1, IL28B) was impaired in patients with asthma. Conclusions dsRNA differentially changes transcriptional profiles of primary nasal and bronchial epithelial cells from patients with allergic

  8. Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation

    PubMed Central

    Hosoki, Koa; Boldogh, Istvan; Sur, Sanjiv

    2016-01-01

    Purpose of review To discuss the presence and role of neutrophils in asthma and allergic diseases, and outline importance of pollen and cat dander-induced innate neutrophil recruitment in induction of allergic sensitization and allergic inflammation. Recent findings Uncontrolled asthma is associated with elevated numbers of neutrophils, and levels of neutrophil-attracting chemokine IL-8 and IL-17 in BAL fluids. These parameters negatively correlate with lung function. Pollen allergens and cat dander recruit neutrophils to the airways in a TLR4, MD2 and CXCR2-dependent manner. Repeated recruitment of activated neutrophils by these allergens facilitates allergic sensitization and airway inflammation. Inhibition of neutrophil recruitment with CXCR2 inhibitor, disruption of TLR4, or siRNA against MD2 also inhibits allergic inflammation. The molecular mechanisms by which neutrophils shift the inflammatory response of the airways to inhaled allergens to an allergic phenotype is an area of active research. Summary Recent studies have revealed that neutrophil recruitment is important in development of allergic sensitization and inflammation. Inhibition of neutrophils recruitment may be strategy to control allergic inflammation. PMID:26694038

  9. Copy Number Variation Burden on Asthma Subgenome in Normal Cohorts Identifies Susceptibility Markers

    PubMed Central

    Vishweswaraiah, Sangeetha; Veerappa, Avinash M; Mahesh, Padukudru A; Jahromi, Sareh R

    2015-01-01

    Purpose Asthma is a complex disease caused by interplay of genes and environment on the genome of an individual. Copy number variations (CNVs) are more common compared to the other variations that disrupt genome organization. The effect of CNVs on asthma subgenome has been less studied compared to studies on the other variations. We report the assessments of CNV burden in asthma genes of normal cohorts carried out in different geographical areas of the world and discuss the relevance of the observation with respect to asthma pathogenesis. Methods CNV analysis was performed using Affymerix high-resolution arrays, and various bioinformatics tools were used to understand the influence of genes on asthma pathogenesis. Results This study identified 61 genes associated with asthma and provided various mechanisms and pathways underlying asthma pathogenesis. CCL3L1, ADAM8, and MUC5B were the most prevalent asthma genes. Among them, CCL3L1 was found across all 12 populations in varying copy number states. This study also identified the inheritance of asthma-CNVs from parents to offspring creating the latent period for manifestation of asthma. Conclusions This study revealed CNV burden with varying copy number states and identified susceptibility towards the disease manifestation. It can be hypothesized that primary CNVs may not be the initiating event in the pathogenesis of asthma and additional preceding mutations or CNVs may be required. The initiator or primary CNVs sensitize normal cohorts leading to an increased probability of accumulating mutations or exposure to allergic stimulating agents that can augment the development of asthma. PMID:25749760

  10. Long-term exposure to house dust mite leads to suppression of allergic airway disease despite persistent lung inflammation

    PubMed Central

    Bracken, Sonali J.; Adami, Alexander J.; Szczepanek, Steven M.; Ehsan, Mohsin; Natarajan, Prabitha; Guernsey, Linda A.; Shahriari, Neda; Rafti, Ektor; Matson, Adam P.; Schramm, Craig M.; Thrall, Roger S.

    2015-01-01

    Background Allergic asthma is a major cause of worldwide morbidity and results from inadequate immune regulation in response to innocuous, environmental antigens. The need exists to understand the mechanisms that promote non-reactivity to human-relevant allergens such as house dust mite (HDM) in order to develop curative therapies for asthma. The aim of our study was to compare the effects of short-, intermediate- and long-term HDM administration in a murine asthma model and determine the ability of long-term HDM exposure to suppress allergic inflammation. Methods C57BL/6 mice were intranasally instilled with HDM for short-term (2 weeks), intermediate-term (5 weeks) and long-term (11 weeks) periods to induce allergic airway disease (AAD). Severity of AAD was compared across all stages of the model via both immunologic and pulmonary parameters. Results Short- and intermediate-term HDM exposure stimulated development of AAD that included eosinophilia in the bronchoalveolar lavage fluid (BAL), pronounced airway hyper-reactivity (AHR), and evidence of lung inflammation. Long-term HDM exposure promoted suppression of AAD, with loss of BAL eosinophilia and AHR despite persistent mononuclear inflammation in the lungs. Suppression of AAD with long-term HDM exposure was associated with an increase in both Foxp3+ regulatory T cells and IL-10+ alveolar macrophages at the site of inflammation. Conclusions This model recapitulates key features of human asthma and may facilitate investigation into the mechanisms that promote immunological tolerance against clinically relevant aeroallergens. PMID:25924733

  11. Allergic and asthmatic reactions to alcoholic drinks.

    PubMed

    Vally, Hassan; Thompson, Philip J

    2003-03-01

    Alcoholic drinks are capable of triggering a wide range of allergic and allergic-like responses, including rhinitis, itching, facial swelling, headache, cough and asthma. Limited epidemiological data suggests that many individuals are affected and that sensitivities occur to a variety of drinks, including wine, beer and spirits. In surveys of asthmatics, over 40% reported the triggering of allergic or allergic-like symptoms following alcoholic drink consumption and 30 - 35% reported worsening of their asthma. Sensitivity to ethanol itself can play a role in triggering adverse responses, particularly in Asians, which is due mainly to a reduced capacity to metabolize acetaldehyde. In Caucasians, specific non-alcohol components are the main cause of sensitivities to alcoholic drinks. Allergic sensitivities to specific components of beer, spirits and distilled liquors have been described. Wine is clearly the most commonly reported trigger for adverse responses. Sensitivities to wine appear to be due mainly to pharmacological intolerances to specific components, such as biogenic amines and the sulphite additives. Histamine in wine has been associated with the triggering of a wide spectrum of adverse symptoms, including sneezing, rhinitis, itching, flushing, headache and asthma. The sulphite additives in wine have been associated with triggering asthmatic responses. Clinical studies have confirmed sensitivities to the sulphites in wine in limited numbers of individuals, but the extent to which the sulphites contribute to wine sensitivity overall is not clear. The aetiology of wine-induced asthmatic responses may be complex and may involve several co-factors. PMID:12745410

  12. The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation.

    PubMed

    Joskova, M; Sutovska, M; Durdik, P; Koniar, D; Hargas, L; Banovcin, P; Hrianka, M; Khazaei, V; Pappova, L; Franova, S

    2016-01-01

    Overproduction of mucus is a hallmark of asthma. The aim of this study was to identify potentially effective therapies for removing excess mucus. The role of voltage-gated (Kir 6.1, KCa 1.1) and store-operated ion channels (SOC, CRAC) in respiratory cilia, relating to the tracheal ciliary beat frequency (CBF), was compared under the physiological and allergic airway conditions. Ex vivo experiments were designed to test the local effects of Kir 6.1, KCa 1.1 and CRAC ion channel modulators in a concentration-dependent manner on the CBF. Cilia, obtained with the brushing method, were monitored by a high-speed video camera and analyzed with ciliary analysis software. In natural conditions, a Kir 6.1 opener accelerated CBF, while CRAC blocker slowed it in a concentration-dependent manner. In allergic inflammation, the effect of Kir 6.1 opener was insignificant, with a tendency to decrease CBF. A cilio-inhibitory effect of a CRAC blocker, while gently reduced by allergic inflammation, remained significant. A KCa 1.1 opener turned out to significantly enhance the CBF under the allergic OVA-sensitized conditions. We conclude that optimally attuned concentration of KCa 1.1 openers or special types of bimodal SOC channel blockers, potentially given by inhalation, might benefit asthma. PMID:27369295

  13. Airway oxidative stress causes vascular and hepatic inflammation via upregulation of IL-17A in a murine model of allergic asthma.

    PubMed

    Al-Harbi, Naif O; Nadeem, Ahmed; Al-Harbi, Mohammed M; Ansari, Mushtaq A; AlSharari, Shakir D; Bahashwan, Saleh A; Attia, Sabry M; Al-Hosaini, Khaled A; Al Hoshani, Ali R; Ahmad, Sheikh F

    2016-05-01

    Oxidants are generated in asthmatic airways due to infiltration of inflammatory leukocytes and resident cells in the lung. Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide radical may leak into systemic circulation when generated in uncontrolled manner and may impact vasculature. Our previous studies have shown an association between airway inflammation and systemic inflammation; however so far none has investigated the impact of airway oxidative inflammation on hepatic oxidative stress and Th1/Th2/Th17 cytokine markers in liver/vasculature in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of systemic/hepatic Th1/Th2/Th17 cytokines balance and hepatic oxidative stress. Mice were sensitized intraperitoneally with cockroach extract (CE) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with CE. Mice were then assessed for systemic/hepatic inflammation through assessment of Th1/Th2/Th17 cytokines and oxidative stress (iNOS, protein nitrotyrosine, lipid peroxides and myeloperoxidase activity). Challenge with CE led to increased Th2/Th17 cytokines in blood/liver and hepatic oxidative stress. However, only Th17 related pro-inflammatory markers were upregulated by hydrogen peroxide (H2O2) inhalation in vasculature and liver, whereas antioxidant treatment, N-acetyl cysteine (NAC) downregulated them. Hepatic oxidative stress was also upregulated by H2O2 inhalation, whereas NAC attenuated it. Therefore, our study shows that airway oxidative inflammation may contribute to systemic inflammation through upregulation of Th17 immune responses in blood/liver and hepatic oxidative stress. This might predispose these patients to increased risk for the development of cardiovascular disorders. PMID:26953647

  14. [Occupational asthma].

    PubMed

    Pauli, G; Bessot, J C; Gourdon, C

    1992-12-01

    The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, biological tests, respiratory function tests and non-specific tests of bronchial hyperreactivity and specific bronchial provocation test. The history search for the presence of an atopic state, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests run into the same snags. Respiratory function and non-specific bronchial provocation tests, confirm the diagnosis of asthma and enable the medium and long term prognostic to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen aerosols, realistic tests, and tests using exposure chambers to achieve true test doses. The products responsible for occupational asthma are multiple. The different substances are characterised in a simplified manner: first animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivates) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry. PMID:1296320

  15. Chemical respiratory allergy and occupational asthma: what are the key areas of uncertainty?

    PubMed

    Isola, Daniel; Kimber, Ian; Sarlo, Katherine; Lalko, Jon; Sipes, I Glenn

    2008-04-01

    There is increasing concern about the association of respiratory disease with indoor air quality and environmental atmospheric pollution. Associated with this is the fact that in many countries there has been a significant increase in the prevalence of asthma. Against this background there is a need to address the toxicological, occupational and public health problems associated with the ability of some chemicals to cause allergic sensitization of the respiratory tract and occupational asthma. By definition allergic sensitization of the respiratory tract to chemicals is dependent upon the stimulation of an adaptive immune response that leads to development of respiratory allergy and/or asthma. Although IgE antibody is associated typically with respiratory sensitization to protein allergens, there is less certainty about the role played by antibodies of this type in chemical respiratory allergy and occupational asthma. There are currently no validated or widely accepted methods/models for the identification and characterization of chemicals that have the potential to induce allergic sensitization of the respiratory tract. These and other areas of uncertainty were debated during the course of and following a two day Workshop. The primary purpose of the Workshop was to consider the important clinical and toxicological issues associated with chemical respiratory allergy, and to identify key questions that need to be answered if real progress is to be made. PMID:18300327

  16. Allergic Rhinitis.

    PubMed

    Kakli, Hasan A; Riley, Timothy D

    2016-09-01

    Among the atopic disorders, allergic rhinitis is the most prevalent. Patients who suffer from allergic rhinitis sustain significant morbidity and loss of productivity. Cardinal symptoms include nasal congestion, rhinorrhea, sneezing, and nasal itching, although multiple related symptoms may occur. Causes should be ruled out with a thorough history and physical examination, with particular attention to red flag or atypical symptoms. Skin testing or serum sampling can confirm diagnosis and also guide therapy. Therapy is multimodal, tailored to a particular patient's symptom burden and quality of life. PMID:27545735

  17. Uncontrolled asthma and recurring pulmonary opacities: just asthma?

    PubMed Central

    Davidsen, Jesper Rømhild; Madsen, Poul Henning; Laursen, Christian B

    2014-01-01

    In asthma, when comorbidities and common causes of poor control have been considered and treated, the clinician may speculate, ‘Is it all asthma?’. In patients with uncontrolled atopic asthma with recurring episodes of symptoms mimicking pneumonia, the suspicion of allergic bronchopulmonary aspergillosis (ABPA) should remain high. ABPA is caused by a complex immunological hypersensitivity reaction to colonisation with Aspergillus fumigatus in the bronchial tree, and is characterised by the presence of atopic asthma, blood eosinophilia, migrating pulmonary opacities and potential bronchiectasis. This case report describes a delay in diagnosing ABPA which was imitating pneumonia. The clinician should pay increased attention to ABPA and test for this in patients with uncontrolled asthma with an ongoing requirement for oral corticosteroids and/or antibiotics and with pulmonary opacities on chest imaging. PMID:24862414

  18. The relationships among birth season, sunlight exposure during infancy, and allergic disease

    PubMed Central

    Hwang, Jung Min; Oh, Se Hyun

    2016-01-01

    Purpose The recent increase in the prevalence of allergic diseases is hypothetically attributed to immune dysregulation in turn caused by a reduction in exposure to sunlight. We explored relationships between birth season, sunlight exposure, exercise duration, and an allergic disease. Methods We performed a questionnaire-based survey on allergic diseases among elementary school students. Birth time was categorized according to the season (summer and winter). Results The prevalence of atopic dermatitis (AD) "symptoms ever" was higher in the children born in winter than in those born in summer (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.03-1.49; P=0.024). Birth in winter was associated with an increase in the "symptoms in the past 12 months" prevalence of food allergy (FA) (aOR, 1.56; 95% CI, 1.09-2.24; P=0.015). The lifetime prevalence of allergic diseases except FA was higher in the children whose parents considered their sunlight exposure prior to 24 months of ageas inadequate than those who considered their exposure as adequate ("diagnosis ever" asthma: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; allergic rhinitis [AR]: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; AD: aOR, 1.26; 95% CI, 1.06-1.51; P=0.01). Neither recent sunlight exposure nor exercise duration was associated with the prevalence of an allergic disease. Conclusion Birth in winter may be associated with development of AD and FA. Inadequate sunlight exposure before the age of 24 months might possibly increase the risks of development of asthma, AR, and AD. PMID:27279886

  19. Steroids in allergic disease.

    PubMed

    Webb, D R

    1981-09-01

    From the experience above, it may be concluded that corticosteroid therapy in allergic disease has become more effective than ever before. The expected variations in usage of new important pharmacologic agents is seen with special clarity in the use of corticosteroids. The wide acclaim for the "miracle drug of the 1950's", which followed penicillin of the 1940's, soon gave away to anguish about side-effects that threatened to abolish its use entirely in the late 1950's. The 1960's brought alternate day therapy for chronic usage and recognition that short term usage was relatively safe. The 1970's saw proliferation of topically active steroids similar to those so important to the practice of Dermatology in the previous decade. Results in treating asthma and nasal diseases have been excellent and extensive research for adverse effects has been largely unrevealing. PMID:6793795

  20. Advances in Pediatric Asthma in 2013: Coordinating Asthma Care

    PubMed Central

    Szefler, Stanley J.

    2014-01-01

    Last year’s Advances in Pediatric Asthma: Moving Toward Asthma Prevention concluded that: “We are well on our way to creating a pathway around wellness in asthma care and also to utilize new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.” This year’s summary will focus on recent advances in pediatric asthma on pre- and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding potential therapeutic targets for altering the course of asthma in children as indicated in Journal of Allergy and Clinical Immunology publications in 2013 and early 2014. Recent reports continue to shed light on methods to understand factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention as well as new immunomodulators. It will now be important to carefully assess risk factors for the development of asthma as well as the risk for asthma exacerbations and to improve the way we communicate this information in the health care system. This will allow parents, primary care physicians, specialists and provider systems to more effectively intervene in altering the course of asthma and to further reduce asthma morbidity and mortality. PMID:24581430

  1. Seasonal Risk Factors for Asthma Exacerbations among Inner City Children

    PubMed Central

    Teach, Stephen J.; Gergen, Peter J.; Szefler, Stanley J.; Mitchell, Herman E.; Calatroni, Agustin; Wildfire, Jeremy; Bloomberg, Gordon; Kercsmar, Carolyn; Liu, Andrew H.; Makhija, Melanie; Matsui, Elizabeth; Morgan, Wayne; O'Connor, George; Busse, William W.

    2015-01-01

    Background Exacerbations of asthma remain common even in children and adolescents despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective Define host risk factors for asthma exacerbations unique to their season of occurrence. Methods This is a retrospective analysis of patients aged 6-20 years who comprised the control groups of the Asthma Control Evaluation trial and the Inner City Anti-IgE Therapy for Asthma trial. Univariate and multivariate models were constructed to determine if patient demographic and historical factors, allergic sensitization, fractional exhaled nitric oxide, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results The analysis included 400 patients (54.5% male; 59.0% African American; median age 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis, impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis, exacerbation in the previous season was the strongest predictor in fall and winter while a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions Among a large cohort of inner city children with asthma, patient risk factors for exacerbations vary by season. Thus, individual patient information may be beneficial in strategies to prevent these seasonal events. Clinical Implications Inner city children remain at risk for asthma exacerbations despite appropriate therapy. Because their risk factors vary by season, strategies to prevent them may need to differ as

  2. Assessment of Allergic Rhinitis Websites in Korea

    PubMed Central

    Chang, Moon Young; Han, Doo Hee; Moon, Il Joon; Kim, Seung-Tae; Kim, Dong-Young; Lee, Chul Hee; Min, Yang-Gi

    2010-01-01

    Objectives The internet has become an important source of medical information and a great amount of information related to allergic rhinitis (AR) is available on the internet. However, the quality of this information is still a matter of debate. Therefore, this study was conducted to assess the AR-related information on Korean websites. Methods The key word "allergic rhinitis" was entered into 4 popular search engines, and this led to identifying 40 websites. After being categorized according to authorship, the informational value of these websites was evaluated using 4 different assessment tools such as the Journal of the American Medical Association (JAMA) benchmarks, the DISCERN questionnaire, the Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 Update and the Health On the Net (HON) code. Results The 40 websites containing AR-related information were categorized according to their authorship as Western physician: 20, Oriental physician: 14, commercial: 1, and others: 5. The mean citation frequencies of the JAMA benchmarks and the ARIA 2008 Update concepts was 1.23 out of 4 and 4.33 out of 8, respectively, while the mean DISCERN score was 1.92 out of 5. When the websites were evaluated based on the type of authorship, the mean citation frequencies of the ARIA 2008 Update concepts were Western physician: 5.35, Oriental physician: 2.64. Additionally, three websites authored by Western physicians and 13 authored by Oriental physicians contained unreliable information. Among these 16 websites, only 3 websites met the requirements for the HON code "Justification". Conclusion AR-related information available on Korean websites is of variable quality and not all of the information provided is justifiable. Thus, performing surveillance of the medical information on these websites is necessary. Furthermore, common criteria that can be used to evaluate the websites created by both Western and Oriental physicians are also needed. PMID:20379400

  3. The role of Probiotics in allergic diseases

    PubMed Central

    Michail, Sonia

    2009-01-01

    Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders. PMID:19946408

  4. [Research advances in association between pediatric obesity and bronchial asthma].

    PubMed

    Zhu, Lian; Xu, Zhi-Liang; Cheng, Yan-Yang

    2016-07-01

    This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor. PMID:27412555

  5. Asthma Quiz

    MedlinePlus

    ... Asthma is a chronic disease that requires ongoing management. Personalized plans for treatment may include medications, an asthma action plan, and environmental control measures to avoid your child's asthma triggers. ...

  6. [Infectious-allergic bronchopulmonary paecilomycosis].

    PubMed

    Akhunova, A M

    1991-01-01

    Primary or secondary infection of the lungs with fungi of the Paecilomyces family (P. variotii and P. viridis) gives rise to the development of infectious allergic bronchopulmonary paecilomycosis characterized by the presence of chronic allergic interstitial pneumonia and obstructive bronchitis, bronchial asthma, total and pulmonary eosinophilia, the presence of the tissue parasitic form of the fungus in sputum, blood, pulmonary tissue, the presence of allergen-specific IgE and/or IgG antibodies in patients' sera, immediate or double (20 min and 6 h) reaction of the skin to administration of allergen of Paecilomyces, by not infrequent combination of lung damage and impairment of other organs as well as by chronic relapses. PMID:1805416

  7. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  8. [Recent advances in allergic rhinitis].

    PubMed

    Liang, Meijun; Xu, Rui; Xu, Geng

    2015-02-01

    Allergic rhinitis (AR) clinically expressed by sneezing, rhinorrhea, nasal itching and congestion is an allergen-driven mucosal inflammatory disease which is modulated by immunoglobulin E. Epidemiological studies have indicated that prevalence of AR continues to increase, and it has been a worldwide health problem that places a significant healthcare burden on individuals and society. Given the evolving understanding of the process by which an allergen is recognized and the roles of mediators which account for AR progress, the pathogenesis of AR has become clearer. Current studies have demonstrated local allergic rhinitis (LAR) that patients with both sug- gestive symptoms of AR and a negative diagnostic test for atopy may have local allergic inflammation is a prevalent entity in patients evaluated with rhinitis, but further research remains needed. Management of AR includes aller- gen avoidance, pharmacological treatment and allergen-specific immunotherapy. Recently montelukast has exhibited previously undocumented anti-inflammatory properties, leukotriene receptor antagonists therefore may serve a more important role in the treatment of AR. Not only has immunotherapy proved its efficacy, but also been able to alter disease course and thereby mitigate progression to asthma. Thus immunotherapy can be initiated while receiving pharmacotherapy, especially in children with AR. As clinical guidelines, the ARIA (Allergic Rhinitis and its Impact on Asthma) provides basic principles of effective treatment of AR. Besides, choosing an appropriate treatment strategy should be based on the severity and chronicity of patient's symptom. The aim of this review was to provide an update mainly on the pathophysiology, epidemiology, and management of AR. PMID:26012287

  9. Tryptophan Metabolism in Allergic Disorders.

    PubMed

    Gostner, Johanna M; Becker, Katrin; Kofler, Heinz; Strasser, Barbara; Fuchs, Dietmar

    2016-01-01

    Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-x03B3; (IFN-x03B3;). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may

  10. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  11. The puzzle of immune phenotypes of childhood asthma.

    PubMed

    Landgraf-Rauf, Katja; Anselm, Bettina; Schaub, Bianca

    2016-12-01

    Asthma represents the most common chronic childhood disease worldwide. Whereas preschool children present with wheezing triggered by different factors (multitrigger and viral wheeze), clinical asthma manifestation in school children has previously been classified as allergic and non-allergic asthma. For both, the underlying immunological mechanisms are not yet understood in depth in children. Treatment is still prescribed regardless of underlying mechanisms, and children are not always treated successfully. This review summarizes recent key findings on the complex mechanisms of the development and manifestation of childhood asthma. Whereas traditional classification of childhood asthma is primarily based on clinical symptoms like wheezing and atopy, novel approaches to specify asthma phenotypes are under way and face challenges such as including the stability of phenotypes over time and transition into adulthood. Epidemiological studies enclose more information on the patient's disease history and environmental influences. Latest studies define endotypes based on molecular and cellular mechanisms, for example defining risk and protective single nucleotide polymorphisms (SNPs) and new immune phenotypes, showing promising results. Also, regulatory T cells and recently discovered T helper cell subtypes such as Th9 and Th17 cells were shown to be important for the development of asthma. Innate lymphoid cells (ILC) could play a critical role in asthma patients as they produce different cytokines associated with asthma. Epigenetic findings showed different acetylation and methylation patterns for children with allergic and non-allergic asthma. On a posttranscriptional level, miRNAs are regulating factors identified to differ between asthma patients and healthy controls and also indicate differences within asthma phenotypes. Metabolomics is another exciting chapter important for endotyping asthmatic children. Despite the development of new biomarkers and the discovery of

  12. Acute stress affects the physiology and behavior of allergic mice.

    PubMed

    Sutherland, M A; Shome, G P; Hulbert, L E; Krebs, N; Wachtel, M; McGlone, J J

    2009-09-01

    Physical and psychological stressors have been implicated in acute asthma exacerbation. The objective of the current study was to determine the effects of forced swimming stress (FST) on allergic pulmonary inflammation in BALB/c mice. Eighty female mice were allocated to one of four treatments arranged in a 2 x 2 factorial consisting of two levels of allergy and two levels of stress. The effects of stress and allergy were assessed by examination of cytokines and leukocyte differentials in the bronchoalveolar lavage fluid, corticosterone and immunoglobulin (Ig) E in the plasma, leukocyte differentials in the peripheral blood, natural killer cytotoxicity, and histopathology of the lungs. Behavior was recorded during the FST. Stress and allergy increased plasma corticosterone in mice. Allergy increased IgE concentrations and pulmonary inflammation. Interleukin-4 was greater among allergic stressed and non-stressed mice and stressed, non-allergic mice compared with non-stressed, non-allergic mice. Interleukin-5 (IL-5) and 6 (IL-6) were greater among allergic stressed and non-stressed mice compared with non-allergic mice. Interleukin-5 and 6 were reduced among stressed-allergic mice compared with non-stressed, allergic mice. Stress and allergy shifted mice towards a T-helper 2 response as shown by increased interleukin-4. Stress reduced IL-5 and IL-6 in allergic mice but not non-allergic mice. Pulmonary inflammation was not reduced among allergic stressed mice in spite of elevated glucocorticoids. Mice induced to be allergic responded to FST differently than non-allergic mice. Our findings suggest that stress induces a differential response among allergic and non-allergic mice. PMID:19527741

  13. Quality of Life in Adolescents With Mild Asthma

    PubMed Central

    Hallstrand, Teal S.; Curtis, J. Randall; Aitken, Moira L.; Sullivan, Sean D.

    2007-01-01

    Summary The majority of individuals with asthma have mild disease, often in conjunction with allergic rhinitis and exercise-induced bronchoconstriction (EIB). Although health-related quality-of-life (HRQoL) is reduced in moderate to severe asthma and allergic rhinitis, little is known about the effect of mild asthma, mild allergic rhinitis, and EIB on HRQoL outcomes. The objective of this study was to determine the effect of mild asthma, allergic rhinitis, and EIB on HRQoL. A cross-sectional study was conducted of 160 adolescent athletes participating in a screening program to detect EIB. Generic HRQoL was assessed with the teen version of the pediatric quality-of-life inventory (PedsQL™). Prior diagnoses of asthma, allergic rhinitis, and EIB, and current symptoms of dyspnea during exercise and asthma, were recorded. Lung function and the presence of EIB were determined by spirometry before and after an exercise challenge test. Adolescent athletes with a prior physician diagnosis of asthma had a lower HRQoL scale summary score (P < 0.01) and lower physical functioning, emotional functioning, and school functioning domain scores (P values, 0.01–0.02) in comparison to adolescent athletes with no prior diagnosis of these disorders. Athletes with a prior diagnosis of asthma reported dyspnea during exercise more frequently than did those without asthma (P < 0.001). Adolescent athletes with dyspnea during exercise had a lower scale summary score, and lower physical functioning, general well-being, and emotional functioning domain scores (P values, 0.02–0.03). These data show that mild asthma and dyspnea without asthma significantly affect HRQoL. Symptoms of dyspnea during exercise are common in asthma and are associated with lower HRQoL. The clinical significance of these differences in HRQoL is unclear. PMID:14618647

  14. Monitoring asthma in children.

    PubMed

    Pijnenburg, Mariëlle W; Baraldi, Eugenio; Brand, Paul L P; Carlsen, Kai-Håkon; Eber, Ernst; Frischer, Thomas; Hedlin, Gunilla; Kulkarni, Neeta; Lex, Christiane; Mäkelä, Mika J; Mantzouranis, Eva; Moeller, Alexander; Pavord, Ian; Piacentini, Giorgio; Price, David; Rottier, Bart L; Saglani, Sejal; Sly, Peter D; Szefler, Stanley J; Tonia, Thomy; Turner, Steve; Wooler, Edwina; Lødrup Carlsen, Karin C

    2015-04-01

    The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence. PMID:25745042

  15. Perimenstrual asthma: from pathophysiology to treatment strategies.

    PubMed

    Graziottin, Alessandra; Serafini, Audrey

    2016-01-01

    The prevalence of asthma is about 9,7 % in women and 5,5 % in men. Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity. PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations. It is hypothesized that hormonal status may influence asthma in women, focusing on the role of sex hormones, and specifically on the impact of estrogens' fluctuations at ovulation and before periods. This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI). Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed. PMID:27482380

  16. Prenatal Stress, Prematurity, and Asthma.

    PubMed

    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C

    2015-12-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health. PMID:26676148

  17. Adoption of a Portal for the Primary Care Management of Pediatric Asthma: A Mixed-Methods Implementation Study

    PubMed Central

    DuRivage, Nathalie; Mayne, Stephanie L; Finch, Stacia; Ross, Michelle E; Giacomini, Kelli; Suh, Andrew; McCarn, Banita; Brandt, Elias; Karavite, Dean; Staton, Elizabeth W; Shone, Laura P; McGoldrick, Valerie; Noonan, Kathleen; Miller, Dorothy; Lehmann, Christoph U; Pace, Wilson D; Grundmeier, Robert W

    2016-01-01

    Background Patient portals may improve communication between families of children with asthma and their primary care providers and improve outcomes. However, the feasibility of using portals to collect patient-reported outcomes from families and the barriers and facilitators of portal implementation across diverse pediatric primary care settings have not been established. Objective We evaluated the feasibility of using a patient portal for pediatric asthma in primary care, its impact on management, and barriers and facilitators of implementation success. Methods We conducted a mixed-methods implementation study in 20 practices (11 states). Using the portal, parents of children with asthma aged 6-12 years completed monthly surveys to communicate treatment concerns, treatment goals, symptom control, medication use, and side effects. We used logistic regression to evaluate the association of portal use with child characteristics and changes to asthma management. Ten clinician focus groups and 22 semistructured parent interviews explored barriers and facilitators of use in the context of an evidence-based implementation framework. Results We invited 9133 families to enroll and 237 (2.59%) used the portal (range by practice, 0.6%-13.6%). Children of parents or guardians who used the portal were significantly more likely than nonusers to be aged 6-9 years (vs 10-12, P=.02), have mild or moderate/severe persistent asthma (P=.009 and P=.04), have a prescription of a controller medication (P<.001), and have private insurance (P=.002). Portal users with uncontrolled asthma had significantly more medication changes and primary care asthma visits after using the portal relative to the year earlier (increases of 14% and 16%, respectively). Qualitative results revealed the importance of practice organization (coordinated workflows) as well as family (asthma severity) and innovation (facilitated communication and ease of use) characteristics for implementation success

  18. [Oxidation phenotype as a risk factor for development of allergic diseases].

    PubMed

    Niewiński, P; Orzechowska-Juzwenko, K; Patkowski, J; Wolańczyk-Medrala, A; Nittner-Marszalska, M; Rzemisławska, Z

    1999-01-01

    The relationship between genetically determined polymorphic metabolism and susceptibility to allergic diseases has aroused much interest. The aim of our study was to evaluate whether patients with allergic diseases, like atopic asthma and allergic rhinitis differ from healthy persons in their ability to oxidize sparteine as a model drug. The study was completed by 200 persons, 40 patients with allergic diseases--20 with atopic asthma and 20 with allergic rhinitis and 160 healthy volunteers as a control group. The results of our study revealed a predominance of very extensive metabolizers of sparteine among patients with allergic diseases in comparison with healthy volunteers. The difference in the oxidation metabolic ratio (MR) frequency distribution between patients with allergic diseases and healthy persons was statistically significant. Relative risk (odds ratio) of development of atopic asthma was 3.29 times higher, and that of allergic rhinitis 2.94 times higher for persons with very extensive oxidation phenotype. Our results represent some evidence for a possible relationship between extensive, rapid oxidation phenotype and the higher susceptibility to development of atopic asthma and allergic rhinitis. PMID:10592724

  19. Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

    PubMed Central

    Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

    2012-01-01

    Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

  20. Asthma & Allergy Development: Contrasting Influences of Yeasts & Other Fungal Exposures

    PubMed Central

    Behbod, Behrooz; Sordillo, Joanne E.; Hoffman, Elaine B.; Datta, Soma; Webb, Tara E.; Kwan, Doris L.; Kamel, Jimmy A.; Muilenberg, Michael L.; Scott, James A.; Chew, Ginger L.; Platts-Mills, Thomas A.E.; Schwartz, Joel; Coull, Brent; Burge, Harriet; Gold, Diane R.

    2016-01-01

    Background Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants’ bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. Objective We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. Methods In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2–3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. Results Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. Conclusions and Clinical Relevance Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for

  1. Scientists find link between allergic and autoimmune diseases in mouse study

    Cancer.gov

    Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such as multiple sclerosis, asthma, Crohn's disease, ce

  2. Risk factors for atopic and non-atopic asthma in a rural area of Ecuador

    PubMed Central

    Vaca, Maritza; Oviedo, Gisela; Erazo, Silvia; Quinzo, Isabel; Fiaccone, Rosemeire L; Chico, Martha E; Barreto, Mauricio L; Cooper, Philip J

    2010-01-01

    Background Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children. Methods A cross-sectional study was conducted among 3960 children aged 6–16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity. Results A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/day)) but inversely associated with age and birth order. Conclusions The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze. PMID:20435862

  3. Occupational asthma.

    PubMed

    Kenyon, Nicholas J; Morrissey, Brian M; Schivo, Michael; Albertson, Timothy E

    2012-08-01

    Occupational asthma is the most common occupational lung disease. Work-aggravated asthma and occupational asthma are two forms of asthma causally related to the workplace, while reactive airways dysfunction syndrome is a separate entity and a subtype of occupational asthma. The diagnosis of occupational asthma is most often made on clinical grounds. The gold standard test, specific inhalation challenge, is rarely used. Low molecular weight isocyanates are the most common compounds that cause occupational asthma. Workers with occupational asthma secondary to low molecular weight agents may not have elevated specific IgE levels. The mechanisms of occupational asthma associated with these compounds are partially described. Not all patients with occupational asthma will improve after removal from the workplace. PMID:21573916

  4. The Study Team for Early Life Asthma Research (STELAR) consortium ‘Asthma e-lab’: team science bringing data, methods and investigators together

    PubMed Central

    Custovic, Adnan; Ainsworth, John; Arshad, Hasan; Bishop, Christopher; Buchan, Iain; Cullinan, Paul; Devereux, Graham; Henderson, John; Holloway, John; Roberts, Graham; Turner, Steve; Woodcock, Ashley; Simpson, Angela

    2015-01-01

    We created Asthma e-Lab, a secure web-based research environment to support consistent recording, description and sharing of data, computational/statistical methods and emerging findings across the five UK birth cohorts. The e-Lab serves as a data repository for our unified dataset and provides the computational resources and a scientific social network to support collaborative research. All activities are transparent, and emerging findings are shared via the e-Lab, linked to explanations of analytical methods, thus enabling knowledge transfer. eLab facilitates the iterative interdisciplinary dialogue between clinicians, statisticians, computer scientists, mathematicians, geneticists and basic scientists, capturing collective thought behind the interpretations of findings. PMID:25805205

  5. The Study Team for Early Life Asthma Research (STELAR) consortium 'Asthma e-lab': team science bringing data, methods and investigators together.

    PubMed

    Custovic, Adnan; Ainsworth, John; Arshad, Hasan; Bishop, Christopher; Buchan, Iain; Cullinan, Paul; Devereux, Graham; Henderson, John; Holloway, John; Roberts, Graham; Turner, Steve; Woodcock, Ashley; Simpson, Angela

    2015-08-01

    We created Asthma e-Lab, a secure web-based research environment to support consistent recording, description and sharing of data, computational/statistical methods and emerging findings across the five UK birth cohorts. The e-Lab serves as a data repository for our unified dataset and provides the computational resources and a scientific social network to support collaborative research. All activities are transparent, and emerging findings are shared via the e-Lab, linked to explanations of analytical methods, thus enabling knowledge transfer. eLab facilitates the iterative interdisciplinary dialogue between clinicians, statisticians, computer scientists, mathematicians, geneticists and basic scientists, capturing collective thought behind the interpretations of findings. PMID:25805205

  6. Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice

    PubMed Central

    Clement, Cecilia G; Tuvim, Michael J; Evans, Christopher M; Tuvin, Daniel M; Dickey, Burton F; Evans, Scott E

    2009-01-01

    Background Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria. Methods To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days. Results We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic

  7. The role of anti-infectives in the treatment of refractory asthma.

    PubMed

    Maselli, Diego Jose; Adams, Sandra; Peters, Jay

    2011-12-01

    Refractory asthma not only has a significant effect on quality of life, but also imposes an economic burden on society. Increasing evidence suggests that there is a pathophysiologic interaction between infection and allergic disease in patients with severe or refractory asthma. Therapeutic trials of macrolides and azoles are being utilized in some patients with refractory asthma who fail to respond to standard therapy. In this article we review the definition of refractory asthma and the potential pathophysiologic interactions between infection and allergic disease. Emerging data suggest that microorganisms and their byproducts may be a therapeutic target in the therapy of patients with severe or refractory asthma. PMID:21459926

  8. CRAC ion channels and airway defense reflexes in experimental allergic inflammation.

    PubMed

    Sutovska, M; Adamkov, M; Kocmalova, M; Mesarosova, L; Oravec, M; Franova, S

    2013-01-01

    Calcium release-activated calcium channels (CRAC) play unambiguous role in secretory functions of mast cells, T cells, and eosinophils. Less knowledge exists about the role of CRAC, widely distributed in airway smooth muscle (ASM) cells, in airway contractility. The presented study seeks to determine the possible participation of CRAC in ASM-based inflammatory airway disorders in guinea pigs. The acute and long-term administration (14 days) of the CRAC antagonist 3-fluoropyridine-4-carboxylic acid was used to examine the ASM contractility and associated reflexes in the guinea pig model of allergic airway inflammation by the following methods: (i) evaluation of specific airway resistance in vivo; (ii) evaluation of the contractile response of isolated ASM strips in vitro; and (iii) citric acid-induced cough reflex; (iv) measurement of exhaled NO levels (E(NO)). Allergic airway inflammation was induced by repetitive exposure of guinea pigs to ovalbumin (10(-6) M). The CRAC antagonist administered in a single dose to guinea pigs with confirmed allergic inflammation significantly reduced the cough response and the airway resistance, which corresponded with the findings in vitro. Long-term application of the CRAC antagonist had more strongly expressed effects. The results confirm the role of CRAC in the pathophysiology of experimental animal asthma and have a potential meaning for anti-asthma therapy. PMID:22836617

  9. Acute and chronic exposure to Tyrophagus putrescentiae induces allergic pulmonary response in a murine model

    PubMed Central

    Nuñez, Nailê Karine; dos Santos Dutra, Moisés; Barbosa, Gustavo Leivas; Morassutti, Alessandra Loureiro; de Souza, Rodrigo Godinho; Vargas, Mauro Henrique Moraes; Antunes, Géssica Luana; Silveira, Josiane Silva; da Silva, Guilherme Liberato; Pitrez, Paulo Márcio

    2016-01-01

    Background Tyrophagus putrescentiae (Tp) is a source of aeroallergen that causes allergic diseases. Objective To describe an acute and chronic murine model of allergic asthma with Tp extract with no systemic sensitization and no use of adjuvant. Methods Mites from dust sample were cultured and a raw extract was produced. Female BALB/c mice (6-8 weeks) were challenged intranasally with Tp extract or Dulbecco's phosphate-buffered saline, for 10 consecutive days (acute protocol) or for 6 weeks (chronic protocol). Twenty-four hours after the last intranasal challenge, bronchoalveolar lavage fluid (BALF) was performed for total and differential cells count, cytokine analysis, and eosinophil peroxidase activity. Lung tissue was also removed for histopathologic analysis. Results Tp extract has shown a significant increase in total cells count from BALF as well as an increase in absolute eosinophils count, eosinophil peroxidase activity, interleukin (IL)-5 and IL-13 levels, in both acute and chronic protocols. Peribronchovascular infiltrate, goblet cells hyperplasia and collagen deposition were shown in the airways of acute and chronic Tp-exposed mice. Conclusion Our data suggest that the intranasal exposure to Tp extract, with no systemic sensitization and no use of adjuvants, induces a robust allergic inflammation in the lungs of mice, in both acute and chronic models. Our Tp extract seems to be a potent allergen extract which may be used in asthma model studies. PMID:26844220

  10. 10. Occupational asthma.

    PubMed

    Bardana, Emil J

    2008-02-01

    A diversity of airborne dusts, gases, fumes, and vapors can induce dose-related respiratory symptoms in individuals exposed in the workplace. These agents can cause annoyance reactions, irritational effects, sensitization, or the induction of corrosive changes in the respiratory tract, depending on their composition, concentration, and duration of exposure. The prevalence of occupational asthma (OA) ranges from 9% to 15% of the asthmatic population. Factors that might influence the development of OA include the work environment, climatic conditions, genetic proclivities, tobacco and recreational drug use, respiratory infection, bronchial hyperresponsiveness, and endotoxin exposure. Pathogenetically, new-onset OA can be allergic or nonallergic in origin. The allergic variants are usually caused by high-molecular-weight allergens, such as grain dust and animal or fish protein. Selected low-molecular-weight agents are also capable of inducing allergic OA. Symptoms ensue after a latent period of months to years. Nonallergic OA can be precipitated by a brief high-level exposure to a potent irritant. Symptoms occur immediately or within a few hours of the exposure. Once the diagnosis of allergic OA is established, the worker should be removed from further exposure in the workplace. In nonallergic OA the worker can return to work if the exposure was clearly a nonrecurring event. If the diagnosis is made in a timely fashion, most workers experience improvement. Prevention is the best therapeutic intervention. PMID:18241692

  11. Dendritic cells in asthma.

    PubMed

    van Helden, Mary J; Lambrecht, Bart N

    2013-12-01

    The lungs are constantly exposed to antigens, most of which are non-pathogenic and do not require the induction of an immune response. Dendritic cells (DCs) are situated at the basolateral site of the lungs and continuously scan the environment to detect the presence of pathogens and subsequently initiate an immune response. They are a heterogeneous population of antigen-presenting cells that exert specific functions. Compelling evidence is now provided that DCs are both sufficient and necessary to induce allergic responses against several inhaled harmless allergens. How various DC subsets exactly contribute to the induction of allergic asthma is currently a subject of intense investigation. We here review the current progress in this field. PMID:24455765

  12. Allergens in household dust and serological indicators of atopy and sensitization in Detroit children with history--based eivdence of asthma

    EPA Science Inventory

    BACKGROUND: Home exposure to allergens is an important factor in the development of sensitization and subsequent exacerbations of allergic asthma. We investigated linkages among allergen exposure, immunological measurements, and asthma by examining (1) reservoir dust allergen lev...

  13. Advances in asthma 2015: Across the lifespan.

    PubMed

    Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

    2016-08-01

    In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. PMID:27497278

  14. Allergic Aspergillus sinusitis and its association with allergic bronchopulmonary aspergillosis

    PubMed Central

    Panjabi, Chandramani

    2011-01-01

    Allergic Aspergillus sinusitis (AAS) is a three decade old clinicopathologic entity in which mucoid impaction akin to that of allergic bronchopulmonary aspergillosis (ABPA) occurs in the paranasal sinuses. Features such as radiographic evidence of pansinusitis, passage of nasal plugs and recurrent nasal polyposis in patients with an atopic background is suggestive of AAS. Histopathlogic confirmation from the inspissated mucus is a sine qua non for the diagnosis. Heterogeneous densities on computed tomography of the paranasal sinuses are caused by the 'allergic mucin' in the sinuses. Many patients give a history of having undergone multiple surgical procedures for symptomatic relief. The current approach to treatment appears to include an initial surgical debridement followed by postoperative oral corticosteroids for long durations. Although both ABPA and AAS are classified as Aspergillus-related hypersensitivity respiratory disorders, their co-occurrence appears to be an infrequently recognised phenomenon. This could perhaps be attributed to the fact that these two diseases are often treated by two different specialties. A high index of suspicion is required to establish the diagnoses of ABPA and AAS. All patients with asthma and/or rhinosinusitis along with sensitisation to Aspergillus antigens are at an increased risk of developing ABPA and/or AAS. ABPA must be excluded in all patients with AAS and vice versa. Early diagnosis and initiation of appropriate therapy could plausibly alter the course of the disease processes and prevent the possible development of long term sequelae. PMID:22053309

  15. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  16. Long-Acting Beta Agonists Enhance Allergic Airway Disease.

    PubMed

    Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  17. [Persulfate asthma in hairdressers].

    PubMed

    Pankow, W; Hein, H; Bittner, K; Wichert, P

    1989-03-01

    At the a two-year apprenticeship, a young female hairdresser developed rhinoconjunctivitis and bronchial asthma, induced by a hair bleach containing the substance persulphate. On each occasion, her symptoms occurred in the form of an immediate reaction. The causative role of the bleach was demonstrated with the aid of an inhalation challenge test. In addition, the prick test produced a positive reaction vis-a-vis persulphate. The long latency period and the positive prick test might militate in favour of an allergic pathomechanism. PMID:2710769

  18. Beta-escin has potent anti-allergic efficacy and reduces allergic airway inflammation

    PubMed Central

    2010-01-01

    Background Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects. Results In the course of a routine in vitro screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect in vivo. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone. Conclusions We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases. PMID:20487574

  19. Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study

    PubMed Central

    2012-01-01

    Background The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is now the most common chronic disease of children in the United States. The rapidity of the increase strongly suggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of allergic manifestations suggests that these exposures may act on the prenatal development of the immune system. We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes the development of allergic asthma in a mouse model. The current study was designed to identify a critical period of BPA exposure and to begin elucidating the mechanisms for this susceptibility. Methods Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before pregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPA-loaded mother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the experimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups were challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and hyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic expression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various ages. Results Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype in response to their "suboptimal" allergic sensitization, whereas, pups only exposed to BPA postnatally from breast milk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse fetuses and newborn pups, but increased

  20. Mouse Models of Asthma.

    PubMed

    Debeuf, Nincy; Haspeslagh, Eline; van Helden, Mary; Hammad, Hamida; Lambrecht, Bart N

    2016-01-01

    Allergic asthma is a chronic inflammatory disease of the conducting airways characterized by the presence of allergen-specific IgE, Th2 cytokine production, eosinophilic airway inflammation, bronchial hyperreactivity, mucus overproduction, and structural changes in the airways. Investigators have tried to mimic these features of human allergic asthma in murine models. Whereas the surrogate allergen ovalbumin has been extremely valuable for unravelling underlying mechanisms of the disease, murine asthma models depend nowadays on naturally occurring allergens, such as house dust mite (HDM), cockroach, and Alternaria alternata. Here we describe a physiologically relevant model of acute allergic asthma based on sensitization and challenge with HDM extracts, and compare it with the ovalbumin/alum-induced asthma model. Moreover, we propose a detailed readout of the asthma phenotype, determining the degree of eosinophilia in bronchoalveolar lavage fluids by flow cytometry, visualizing goblet cell metaplasia, and measuring Th cytokine production by lung-draining mediastinal lymph node cells restimulated with HDM. © 2016 by John Wiley & Sons, Inc. PMID:27248433

  1. Bronchial hyperresponsiveness to mannitol, airway inflammation and Asthma Control Test in atopic asthmatic children

    PubMed Central

    Consilvio, Nicola P.; Rapino, Daniele; Nicola, Marta Di; Scaparrotta, Alessandra; Cingolani, Anna; Petrosino, Marianna I.; Filippo, Paola Di; Pillo, Sabrina Di; Chiarelli, Francesco

    2016-01-01

    Introduction The aim of this study was to evaluate the relationship between airway hyperresponsiveness (AHR) to mannitol and bronchial inflammation measured as exhaled nitric oxide (FeNO) and to assess whether asthma control correlates with AHR to mannitol and FeNO in atopic asthmatic children. Material and methods Allergy evaluation, the mannitol challenge test, FeNO levels and the Asthma Control Test (ACT) questionnaire were assessed in 40 children with intermittent and mild persistent allergic asthma. Results All the subjects showed positive AHR to mannitol. Pearson's correlation test revealed a significant inverse correlation between AHR (mannitol PD15) and FeNO (p = 0.020). There was also a significant positive correlation between ACT and PD15 (p = 0.020) and a significant negative correlation between ACT and FeNO levels (p = 0.003). The study population was divided into two groups according to FeNO levels (group A ≥ 16 ppb vs. group B < 16 ppb). In group A mannitol PD15 was significantly lower (p = 0.040) and ACT score values were significantly lower (p = 0.001) compared to group B. In group A, the ACT showed that 13.3% of subjects had well-controlled asthma, 80% had partially controlled asthma and 6.7% had uncontrolled asthma. In group B, the ACT showed that 72% of subjects had well-controlled asthma and 28% had partially controlled asthma. Conclusions Our findings indicate that the degree of AHR to mannitol correlates with the degree of airway inflammation in asthmatic atopic children; moreover, better control of asthma correlates with a lower degree of AHR to both mannitol and FeNO. PMID:26925129

  2. [Asthma and aspirin].

    PubMed

    Schiappoli, Michele; Gani, Federica; Frati, Francesco; Marcucci, Francesco; Senna, Gianenrico

    2003-02-01

    Aspirin (ASA) is an important cause of asthma so that ASA induced asthma (AIA) is considered a disease. Its prevalence is of 0.3-0.6 in the general population but it raises to 21% in the asthmatic one. Middle aged female are the most affected. AIA generally begins with a non allergic rhinitis, complicated sometimes with polyps, that evolves secondarily in asthma. The disease is often so severe to need oral corticosteroids to be controlled. It persists independently to the intake of ASA. From a pathogenetic point of view the interaction of ASA with the arachidonic acid metabolism seems to be important. The inhibition of cyclo-oxygenase (COX) induces an activation of lypo-oxygenase with an increased synthesis of leukotrienes. In ASA intolerant patients there is also an activation of LTC4 synthetase, enzyme responsible for the synthesis of leukotrienes. Clinical history is very important to diagnose the disease but to confirm the diagnosis sometimes the provocation test is mandatory. Oral and bronchial challenges can be dangerous, while nasal challenge is safer even if must be better standardized. Patients must not use antiinflammatory drugs with the same mechanism of action of ASA; COX-2 inhibitors are generally well tolerated. Antileukotrienes are useful to treat asthma, in association with steroids. Desensitization can be used in very selected patients. PMID:12908375

  3. Occupational allergies and asthma.

    PubMed Central

    Tarlo, S. M.

    1999-01-01

    OBJECTIVE: To review aspects of occupational allergies and asthma for primary care physicians recognizing, diagnosing, and managing patients with these conditions. QUALITY OF EVIDENCE: Studies in the medical literature mainly provide level 2 evidence, that is, from at least one well-designed clinical trial without randomization, from cohort or case-control analytical studies, from multiple time series, or from dramatic results in uncontrolled experiments. MAIN MESSAGE: Occupational allergies and asthma have the best prognosis with an early, accurate diagnosis and subsequent avoidance of exposure to the relevant sensitizer. These diagnoses can normally be suspected from the clinical history. Primary care physicians can also initiate investigations to make an objective diagnosis, can assess workplace exposure agents from the history, and can review appropriate data sheets on material safety. Specialist evaluation is likely to be needed for skin tests, however, and for other specialized tests (such as pulmonary function assessments at work and off work or specific challenges with the suspected workplace agent). Patients with a confirmed diagnosis need appropriate medical management of their allergic manifestations or asthma, but also often require psychosocial support during the period of investigation and management, especially in relation to required changes in their work and to compensation or insurance claims. CONCLUSIONS: Consider workplace exposure as a source of patients' allergies or asthma and aim to make an early, accurate diagnosis. PMID:10386216

  4. Allergic Skin Conditions

    MedlinePlus

    American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

  5. Allergic Bronchopulmonary Aspergillosis (ABPA)

    MedlinePlus

    American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

  6. The receptor for advanced glycation end products is a central mediator of asthma pathogenesis.

    PubMed

    Milutinovic, Pavle S; Alcorn, John F; Englert, Judson M; Crum, Lauren T; Oury, Tim D

    2012-10-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been shown to contribute to the pathogenesis of diabetes, atherosclerosis, and neurodegeneration. However, its role in asthma and allergic airway disease is largely unknown. These studies use a house dust mite (HDM) mouse model of asthma/allergic airway disease. Respiratory mechanics were assessed and compared between wild-type and RAGE knockout mice. Bronchovascular architecture was assessed with quantitative scoring, and expression of RAGE, immunoglobulins, and relevant cytokines was assessed by standard protein detection methods and/or quantitative RT-PCR. The absence of RAGE abolishes most assessed measures of pathology, including airway hypersensitivity (resistance, tissue damping, and elastance), eosinophilic inflammation, and airway remodeling. IL-4 secretion, isotype class switching, and antigen recognition are intact in the absence of RAGE. In contrast, normal increases in IL-5, IL-13, eotaxin, and eotaxin-2 production are abrogated in the RAGE knockouts. IL-17 indicates complex regulation, with elevated baseline expression in RAGE knockouts, but no induction in response to allergen. Treatment of WT mice with an inhibitor of RAGE markedly reduces inflammation in the HDM model, suggesting that RAGE inhibition may serve as a promising therapeutic strategy. Finally, the results in the HDM model are recapitulated in an ovalbumin model of asthma, suggesting that RAGE plays a role in asthma irrespective of the identity of the allergens involved. PMID:22889845

  7. 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

  8. Management of asthma with anti-immunoglobulin E: a review of clinical trials of omalizumab.

    PubMed

    Nowak, Dennis

    2006-11-01

    Immunoglobulin E (IgE) is a key mediator of the inflammatory reactions that are central to the pathogenesis of allergic diseases such as asthma and rhinitis. The recognition of the importance of IgE in allergic disease led to the development of omalizumab, a humanized monoclonal anti-IgE antibody that binds free circulating IgE and prevents the interaction between IgE and high-affinity (FcepsilonRI) and low-affinity (FcepsilonRII) IgE receptors on inflammatory cells. By removing free IgE, omalizumab also markedly downregulates the expression of high-affinity receptors on basophils, mast cells and dendritic cells. Several studies have shown that omalizumab effectively reduces the risk of exacerbations and hospitalization and improves symptom control, lung function and quality of life in patients with severe persistent allergic asthma. Importantly, omalizumab has been shown to be effective in patients with poorly controlled severe persistent allergic asthma, a group of patients with few effective additional treatment options. In addition, omalizumab has been shown to provide effective relief from the symptoms of allergic rhinitis (including patients with concomitant asthma). Patients with uncontrolled severe persistent allergic asthma are a challenging and difficult-to-treat population for whom omalizumab might represent an important new treatment option. In addition, omalizumab may provide a means to address comorbid allergic disease in patients with asthma. Further investigation is also warranted to explore potential applications of omalizumab in occupational asthma. PMID:16949266

  9. The Role of Allergen Exposure and Avoidance in Asthma

    PubMed Central

    Baxi, Sachin N.; Phipatanakul, Wanda

    2010-01-01

    Allergy testing and avoidance of allergens plays an important role in asthma control. Increased allergen exposure, in genetically susceptible individuals, can lead to allergic sensitization. Continued allergen exposure can increase the risk of asthma and other allergic diseases. In a patient with persistent asthma, identification of indoor and outdoor allergens and subsequent avoidance can improve symptoms. Often times, a patient will have multiple allergies and the avoidance plan should target all positive allergens. Several studies have shown that successful allergen remediation includes a comprehensive approach including education, cleaning, physical barriers and maintaining these practices. PMID:20568555

  10. [Impact of air pollution on the development of asthma].

    PubMed

    Sánchez, Jorge; Caraballo, Luis

    2015-01-01

    Air pollution affects the origin and evolution of respiratory diseases. The increased frequency of asthma in recent years has been associated with growth air pollutants and small particles produced from the combustion of petroleum or cigarette smoke. Some mechanisms of how these contaminants can influence asthma and other allergic diseases are known: 1) acting as irritating on alveolar epithelial cells, 2) actin as adjuvant for allergens inflammation, 3) and epigenetic mechanisms. In this review, we discuss the pathophysiological mechanisms by which air pollutants become risk factors for the development of asthma and other allergic diseases. PMID:26556664

  11. Nasal hyperreactivity and inflammation in allergic rhinitis

    PubMed Central

    Veld, C. de Graaf-in't; Wijk, R. Gerth van; Zijlstra, F. J.

    1996-01-01

    The history of allergic disease goes back to 1819, when Bostock described his own ‘periodical affection of the eyes and chest’, which he called ‘summer catarrh’. Since they thought it was produced by the effluvium of new hay, this condition was also called hay fever. Later, in 1873, Blackley established that pollen played an important role in the causation of hay fever. Nowadays, the definition of allergy is ‘An untoward physiologic event mediated by a variety of different immunologic reactions’. In this review, the term allergy will be restricted to the IgE-dependent reactions. The most important clinical manifestations of IgE-dependent reactions are allergic conjunctivitis, allergic rhinitis, allergic asthma and atopic dermatitis. However, this review will be restricted to allergic rhinitis. The histopathological features of allergic inflammation involve an increase in blood flow and vascular permeability, leading to plasma exudation and the formation of oedema. In addition, a cascade of events occurs which involves a variety of inflammatory cells. These inflammatory cells migrate under the influence of chemotactic agents to the site of injury and induce the process of repair. Several types of inflammatory cells have been implicated in the pathogenesis of allergic rhinitis. After specific or nonspecific stimuli, inflammatory mediators are generated from cells normally found in the nose, such as mast cells, antigen-presenting cells and epithelial cells (primary effector cells) and from cells recruited into the nose, such as basophils, eosinophils, lymphocytes, platelets and neutrophils (secondary effector cells). This review describes the identification of each of the inflammatory cells and their mediators which play a role in the perennial allergic processes in the nose of rhinitis patients. PMID:18475703

  12. Airway Fibrinogenolysis and the Initiation of Allergic Inflammation

    PubMed Central

    Millien, Valentine Ongeri; Lu, Wen; Mak, Garbo; Yuan, Xiaoyi; Knight, J. Morgan; Porter, Paul; Kheradmand, Farrah

    2014-01-01

    The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention. PMID:25525732

  13. Allergic Bronchopulmonary Aspergillosis

    PubMed Central

    Greenberger, Paul A.; Bush, Robert K.; Demain, Jeffrey G.; Luong, Amber; Slavin, Raymond G.; Knutsen, Alan P.

    2014-01-01

    There remains lack of agreement on diagnostic criteria and approaches to treatment of patients with Allergic Bronchopulmonary Aspergillosis (ABPA). The results of a survey of AAAAI members regarding these 2 issues are presented and compared for concordance with published recommendations. The literature was reviewed for pertinent reports and an electronic survey was conducted of AAAAI members and fellows regarding diagnostic criteria, numbers of patients evaluated for ABPA, and treatment approaches. From 508 respondents to the survey sent to 5155 U. S. physicians in the AAAAI database of members and fellows, 245 (48%) health professionals had treated at least 1 patient with ABPA in the previous year. For the diagnosis of ABPA, there was a difference in the threshold concentration of total serum IgE as 44.9% used ≥ 417 kU/L whereas 42.0% used ≥ 1000 kU/L. These findings suggest that ABPA might be underdiagnosed. Regarding pharmacotherapy, oral steroids were recommended for 97.1% of patients and oral steroids + inhaled corticosteroids + anti-fungal agent were utilized in 41.2% of patients. The armamentarium for treatment of ABPA includes oral corticosteroids as the initial treatment with inhaled corticosteroids used for management of persistent asthma. Azoles remain adjunctive. Published experience with omalizumab has been limited. PMID:25439360

  14. Optimal management of allergic rhinitis.

    PubMed

    Scadding, Glenis K

    2015-06-01

    Allergic rhinitis (AR), the most common chronic disease in childhood is often ignored, misdiagnosed and/or mistreated. Undertreated AR impairs quality of life, exacerbates asthma and is a major factor in asthma development. It can involve the nose itself, as well as the organs connected with the nose manifesting a variety of symptoms. Evidence-based guidelines for AR therapy improve disease control. Recently, paediatric AR guidelines have been published by the European Academy of Allergy and Clinical Immunology and are available online, as are a patient care pathway for children with AR and asthma from the Royal College of Paediatrics and Child Health. Management involves diagnosis, followed by avoidance of relevant allergens, with additional pharmacotherapy needed for most sufferers. This ranges, according to severity, from saline sprays, through non-sedating antihistamines, oral or topical, with minimally bioavailable intranasal corticosteroids for moderate/severe disease, possibly plus additional antihistamine or antileukotriene. The concept of rhinitis control is emerging, but there is no universally accepted definition. Where pharmacotherapy fails, allergen-specific immunotherapy, which is uniquely able to alter long-term disease outcomes, should be considered. The subcutaneous form (subcutaneous immunotherapy) in children has been underused because of concerns regarding safety and acceptability of injections. Sublingual immunotherapy is both efficacious and safe for grass pollen allergy. Further studies on other allergens in children are needed. Patient, carer and practitioner education into AR and its treatment are a vital part of management. PMID:25838332

  15. Prevalence and triggers of allergic rhinitis in the United Arab Emirates

    PubMed Central

    2014-01-01

    Background and objectives Allergic rhinitis is a morbid condition that is frequently overlooked by patients and physicians. This type of atopy has not been adequately investigated in the United Arab Emirates. Methods This cross-sectional, population-based observational study was conducted in the seven Emirates (Abu Dhabi, Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah). It used the European Community Respiratory Health Survey (ECRHS II) to screen for allergic rhinitis in people living in this region. Results Symptoms of allergic rhinitis were present in 85 (7%) of the 1,229 study population. Only 33 (39%) patients received treatment. Seventy-six (89%) patients had asthma. Thirty-seven (44%) patients were poly-sensitized. Symptoms were aggravated by dust (59%), grass/pollens (44%) and proximity to animals (21%). Winter was the peak season (37%), followed by spring (30%), autumn (18%) and summer (15%). Grass/pollen allergies were clustered in the winter, spring and summer (p ≤ 0.001). Dust was non-seasonal (p ≥ 0.121) and animal allergy was worse in the winter (p = 0.024) and spring (p = 0.044). Spring symptoms were less common in people living in the inner city (p = 0.003). Conclusions At least 7% of the studied population had allergic rhinitis. Most (71%) of these patients had environmental triggers and remained untreated. Allergic rhinitis awareness and measures to control allergens and dust are needed. The impact of preventing allergic rhinitis on other common atopies in the region deserves future studies. PMID:25097721

  16. Latex Hypersensitivity among Allergic Egyptian Children: Relation to Parental/Self Reports

    PubMed Central

    El-Sayed, Zeinab A.; El-Sayed, Shereen S.; Zaki, Rehab M.; Salama, Mervat A.

    2014-01-01

    Background. Latex allergy is one of the major health concerns and allergic reactions to latex may be serious and fatal. Purpose. In this study, we sought to determine the frequency of latex hypersensitivity in a group of allergic Egyptian infants and children and its relation to the history provided by the patients or caregivers. Methods. We consecutively enrolled 400 patients with physician diagnosed allergic diseases. The study measurements included clinical evaluation for the site and duration of allergy, history suggestive of latex allergy, family history of allergy, and skin prick testing (SPT) using a commercial latex extract. Results. The study revealed that 16/400 (4%) patients had positive SPT; 11 of them only had positive history of sensitivity to latex. Positive latex SPT was reported in 3.4% (11/326) of patients with bronchial asthma, 5.9% (7/118) of patients with skin allergy, and 4.5% (2/44) of patients with allergic rhinitis. SPT was positive in 7.4% (4/54) of patients with concomitant respiratory and skin allergy. Latex SPT was more specific than sensitive (97.69% and 77.77%, resp.) with a negative predictive value of 99.47%. Conclusion. Although underrecognized, latex is an important allergen in the pediatric age group with a sensitization frequency of 4% among allergic children. It was observed to be especially associated with multiple allergic diseases coexisting in the same patient. Pediatric allergologists should educate their patients on latex allergy and encourage the use of latex-free products. PMID:25505988

  17. Immunologic principles of allergic disease.

    PubMed

    Averbeck, Marco; Gebhardt, Carl; Emmrich, Frank; Treudler, Regina; Simon, Jan C

    2007-11-01

    Allergy either results from a pathological excessive immune reaction, or from the defective induction of tolerance to otherwise harmless antigens. Allergic reactions are mounted by mechanisms of innate and adaptive immunity. The development of an allergic response can be divided in sensitization and elicitation phases. Immediate type allergic reactions (e.g. anaphylaxis, urticaria, rhinoconjunctivitis allergica, allergic asthma) are mediated by IgE antibodies which are produced by B cells stimulated by allergen-specific Th2 cells. Crosslinking of allergen-specific IgE on membrane surfaces of mast cells and basophilic granulocytes leads to release of soluble mediators which may cause systemic symptoms within minutes to hours. The following infiltration of eosinophilic granulocytes and Th2 cells directs chronic inflammation. Humoral cytotoxic immune reactions (e.g. drug induced cytopenia) are mediated by IgG and IgM antibodies which are directed against membrane associated antigens. IgG and IgM antibodies directed against soluble antigens elicit immune complex mediated cytotoxicity (e.g.drug induced vasculitis). Delayed type immune reactions (e.g.contact dermatitis) are based on the activation of antigen specific CD4(+) and CD8(+) T cells and need 24 h to 48 h to develop. Upon recurrent contact with identical antigens, recruitment of CD4(+) and CD8(+) T cells cause inflammation and cytotoxic induced apoptosis in target cells as well as cytokine mediated leukocyte infiltration. Subsequent immigration of CD4(+) Th2 cells provides anti-inflammatory mechanisms leading to resolution of the inflammatory response and tissue repair. PMID:17976144

  18. Childhood Asthma

    MedlinePlus

    ... Share your child's asthma management plan with the school nurse and any coaches who oversee your child. With the approval of physicians and parents, school-age children with asthma should be allowed to ...

  19. Sputum RNA signature in allergic asthmatics following allergen bronchoprovocation test

    PubMed Central

    Zuiker, Rob G.J.A.; Tribouley, Catherine; Diamant, Zuzana; Boot, J. Diderik; Cohen, Adam F.; Van Dyck, K.; De Lepeleire, I.; Rivas, Veronica M.; Malkov, Vladislav A.; Burggraaf, Jacobus; Ruddy, Marcella K.

    2016-01-01

    Background Inhaled allergen challenge is a validated disease model of allergic asthma offering useful pharmacodynamic assessment of pharmacotherapeutic effects in a limited number of subjects. Objectives To evaluate whether an RNA signature can be identified from induced sputum following an inhaled allergen challenge, whether a RNA signature could be modulated by limited doses of inhaled fluticasone, and whether these gene expression profiles would correlate with the clinical endpoints measured in this study. Methods Thirteen non-smoking, allergic subjects with mild-to-moderate asthma participated in a randomised, placebo-controlled, 2-period cross-over study following a single-blind placebo run-in period. Each period consisted of three consecutive days, separated by a wash-out period of at least 3 weeks. Subjects randomly received inhaled fluticasone ((FP) MDI; 500 mcg BID×5 doses in total) or placebo. On day 2, house dust mite extract was inhaled and airway response was measured by FEV1 at predefined time points until 7 h post-allergen. Sputum was induced by NaCl 4.5%, processed and analysed at 24 h pre-allergen and 7 and 24 h post-allergen. RNA was isolated from eligible sputum cell pellets (<80% squamous of 500 cells), amplified according to NuGEN technology, and profiled on Affymetrix arrays. Gene expression changes from baseline and fluticasone treatment effects were evaluated using a mixed effects ANCOVA model at 7 and at 24 h post-allergen challenge. Results Inhaled allergen-induced statistically significant gene expression changes in sputum, which were effectively blunted by fluticasone (adjusted p<0.025). Forty-seven RNA signatures were selected from these responses for correlation analyses and further validation. This included Th2 mRNA levels for cytokines, chemokines, high-affinity IgE receptor FCER1A, histamine receptor HRH4, and enzymes and receptors in the arachidonic pathway. Individual messengers from the 47 RNA signatures correlated significantly

  20. First report of asthma prevalence in Afghanistan using international standardized methods.

    PubMed

    Bemanin, M H; Fallahpour, M; Arshi, S; Nabavi, M; Yousofi, T; Shariatifar, A

    2015-03-01

    No data on the prevalence of asthma in Afghanistan have been published before. In a school-based survey in 2010-2011 the wheezing section of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was completed by a random sample of 1500 children aged 6-7 years and 1500 adolescents aged 13-14 years old. The prevalence of physician-diagnosed asthma was 12.5% in 6-7-year-olds and 17.3% in 13-14-year-olds (P = 0.002). The prevalence of wheeze in the last 12 months was similar in children and adolescents (19.2% and 21.7% respectively). The prevalence of ever wheezing, night attacks, speech-limiting wheeze and exercise-induced wheeze was 23.1%, 4.8%, 12.2% and 9.6% respectively in children and 30.5%, 4.4%, 13.0% and 13.6% respectively in adolescents. These rates are higher than those in neighbouring countries. This first epidemiological survey of asthma in Afghanistan shows that asthma and wheezing are common in Kabul students. PMID:26074219

  1. Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood

    PubMed Central

    Strachan, D P; Aït-Khaled, N; Foliaki, S; Mallol, J; Odhiambo, J; Pearce, N; Williams, H C

    2015-01-01

    Background Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. Methods Questionnaire data for 210 200 children aged 6–7 years from 31 countries, and 337 226 children aged 13–14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. Results In both age groups, inverse trends (P < 0.0001) were observed for reported ‘hay fever ever’ and ‘eczema ever’ with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. Conclusions These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the ‘hygiene hypothesis’ for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread. PMID:24912652

  2. The childhood asthma prevention study (CAPS): design and research protocol of a randomized trial for the primary prevention of asthma.

    PubMed

    Mihrshahi, S; Peat, J K; Webb, K; Tovey, E R; Marks, G B; Mellis, C M; Leeder, S R

    2001-06-01

    The Childhood Asthma Prevention Study is a randomized controlled trial to measure whether the incidence of atopy and asthma can be reduced by house dust mite allergen reduction, a diet supplemented with omega-3 fatty acids, or a combination of both interventions. Six hundred and sixteen pregnant women whose unborn children were at high risk of developing asthma because of a family history were randomized prenatally. Study groups are as follows: Group A (placebo diet intervention, no house dust mite reduction), Group B (placebo diet intervention, active house dust mite reduction), Group C (active diet intervention, no house dust mite reduction), and Group D (active diet intervention, active house dust mite reduction). The house dust mite reduction intervention comprises use of physical and chemical methods to reduce allergen contact. The dietary intervention comprises use of a daily oil supplement from 6 months or at onset of bottle-feeding, and use of margarine and cooking oils based on sunflower or canola oils to increase omega-3 dietary intake. Data is collected quarterly until the infant is 1 year old and then half yearly until age 5 years. Questionnaires are used to collect respiratory illness history and information about diet and home environment. Dust is collected from the child's bed and bedroom and playroom floors. Blinded assessments are conducted at 18 months, 3 years, and 5 years. Skin prick tests to common allergens, blood tests, and detailed illness, medication use, and vaccination histories are collected. Primary outcomes will be the development of allergic sensitization and the presence and severity of asthma. This study is designed to measure the effectiveness of allergen reduction and dietary supplementation, both separately and in combination, for the primary prevention of atopy and asthma. The results of this study may have important implications for public health policies to reduce the incidence of childhood asthma. Control Clin Trials 2001

  3. Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis

    PubMed Central

    Saulyte, Jurgita; Regueira, Carlos; Montes-Martínez, Agustín; Khudyakov, Polyna; Takkouche, Bahi

    2014-01-01

    Background Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions. Methods and Findings We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children. We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92–1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06–1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14–1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03–1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24–1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04–1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17–1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01–1

  4. Polycyclic aromatic hydrocarbons and childhood asthma.

    PubMed

    Karimi, Parisa; Peters, Kamau O; Bidad, Katayoon; Strickland, Paul T

    2015-02-01

    Asthma is the most common chronic illness in children living in developed countries and the leading cause of childhood hospitalization and school absenteeism. Prevalence rates of asthma are increasing and show disparities across gender, geographic regions, and ethnic/racial groups. Common risk factors for developing childhood asthma include exposure to tobacco smoke, previous allergic reactions, a family history of asthma, allergic rhinitis or eczema, living in an urban environment, obesity and lack of physical exercise, severe lower respiratory tract infections, and male gender. Asthma exacerbation in children can be triggered by a variety of factors, including allergens (e.g., pollen, dust mites, and animal dander), viral and bacterial infections, exercise, and exposure to airway irritants. Recent studies have shown that exposure to polycyclic aromatic hydrocarbons (PAHs), a major component of fine particulate matter from combustion sources, is also associated with onset of asthma, and increasing asthmatic symptoms. In this paper, we review sources of childhood PAH exposure and the association between airborne PAH exposure and childhood asthma prevalence and exacerbation. PMID:25600297

  5. Asthma and anaphylactoid reactions to food additives.

    PubMed Central

    Tarlo, S. M.; Sussman, G. L.

    1993-01-01

    Presumed allergic reactions to hidden food additives are both controversial and important. Clinical manifestations include asthma, urticaria, angioedema, and anaphylactic-anaphylactoid events. Most adverse reactions are caused by just a few additives, such as sulfites and monosodium glutamate. Diagnosis is suspected from the history and confirmed by specific challenge. The treatment is specific avoidance. PMID:8499792

  6. Cockroach allergen exposure and risk of asthma.

    PubMed

    Do, D C; Zhao, Y; Gao, P

    2016-04-01

    Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins have provided a basis for studying the mechanisms regarding cockroach allergen-induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen-presenting cell (APC) function in T-cell polarization, and cytokine production. Environmental pollutants, which often coexist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergen-induced innate immune responses, and the genetic basis for cockroach sensitization. PMID:26706467

  7. Allergic diseases and risk of hematopoietic malignancies in a cohort of postmenopausal women: A report from the Iowa Women’s Health Study

    PubMed Central

    Linabery, Amy M.; Prizment, Anna E.; Anderson, Kristin E.; Cerhan, James R.; Poynter, Jenny N.; Ross, Julie A.

    2014-01-01

    Background Allergic diseases signify immune dysregulation attributable to underlying genetics and environmental exposures. Associations between various allergies and hematopoietic cancers have been observed, albeit inconsistently, however few prospective studies have examined the risk, and even fewer among older adults. Methods We examined risk of incident hematopoietic cancers in those reporting allergic diseases in a population-based cohort of 22,601 older women (Iowa Women’s Health Study). Self-reported allergic status, including asthma, hay fever, eczema and/or other allergies, was determined via questionnaire in 1997 (mean age=72 years, range 63–81 years). Incident cancers were ascertained by linkage with the Iowa Cancer Registry from 1997–2011. Cox proportional hazards regression was performed to estimate multivariate-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for myeloid (N=177) and lymphoid (N=437) malignancies, respectively. Results Allergic diseases were not associated with risk of myeloid (HR=1.00, 95% CI: 0.72–1.37) or lymphoid (HR=0.99, 95% CI: 0.81–1.22) malignancies overall, or for most allergic and malignant subtypes examined. Self-reported asthma was positively associated with development of myelodysplastic syndrome (MDS, HR=2.00, 95% CI: 0.93–4.32). In addition, there was a 30–40% decrease in risk of both lymphoid and myeloid cancers in those reporting rural residences but no association in those reporting urban residences; the interaction between residence and allergy was statistically significant for lymphoid malignancies (Pinteraction=0.05). Conclusions and Impact These results suggest asthma may contribute to the pathogenesis of MDS, a finding consistent with the chronic antigen stimulation hypothesis. Susceptibility differences by location of residence are concordant with the hygiene hypothesis and merit additional exploration. PMID:24962839

  8. Estrogen effects in allergy and asthma

    PubMed Central

    Bonds, Rana S.; Midoro-Horiuti, Terumi

    2012-01-01

    Purpose of review Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Of these, estrogen has been the subject of much study. This review highlights recent research exploring the effects of estrogen in allergic disease. Recent findings Estrogen receptors are found on numerous immunoregulatory cells and estrogen’s actions skew immune responses toward allergy. It may act directly to create deleterious effects in asthma, or indirectly via modulation of various pathways including secretory leukoprotease inhibitor, transient receptor potential vanilloid type 1 ion channel and nitric oxide production to exert effects on lung mechanics and inflammation. Not only do endogenous estrogens appear to play a role, but environmental estrogens have also been implicated. Environmental estrogens (xenoestrogens) including bisphenol A and phthalates enhance allergic sensitization in animal models and may enhance development of atopic disorders like asthma in humans. Summary Estrogen’s role in allergic disease remains complex. As allergic diseases continue to increase in prevalence and affect women disproportionately, gaining a fuller understanding of its effects in these disorders will be essential. Of particular importance may be effects of xenoestrogens on allergic disease. PMID:23090385

  9. ASSESSMENT OF ALLERGIC IMMUNE RESPONSES TO INDOOR AIR FUNGAL CONTAMINANTS

    EPA Science Inventory

    We are using a mouse model to assess immune and inflammatory responses as well as changes in respiratory function and pathology characteristic of allergic asthma to fungal extracts M. anisopliae (MACA), S. chartarum (SCE), and P. chrysogenum (PCE). This model will be useful to a...