Disease relevance of Asthm1

• CONTEXT: Asthma and obesity incidence is increasing worldwide, and asthma is often more severe in the obese [1].
• Though more complete examination of functional association is required, results have potential implications for the role of these candidate genes in the pathogenesis of human pulmonary diseases including asthma, acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and emphysema [2].
• BACKGROUND: Asthma is associated with recruitment of eosinophils, accumulation of chronic inflammatory cells in the airway walls, subepithelial fibrosis and other structural changes of airway wall remodelling [3].
• We recently reported on the effects of nicotine on human DCs and proposed a possible mechanism that links cigarette smoke to higher incidences of respiratory tract infection and asthma [4].
• Angiogenesis is a feature of chronic lung diseases such as asthma and pulmonary fibrosis; however, the pathways controlling pathological angiogenesis during lung disease are not completely understood [5].

Psychiatry related information on Asthm1

• Early-Life Psychological Stress Exacerbates Adult Mouse Asthma via the Hypothalamus-Pituitary-Adrenal Axis [6].

High impact information on Asthm1

• Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease [7].
• Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility [7].
• Specifically, neonatal CD25(high) T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers [7].
• Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups [7].
• Modulation of Airway Remodeling and Airway Inflammation by Peroxisome Proliferator-Activated Receptor {gamma} in a Murine Model of Toluene Diisocyanate-Induced Asthma [8].

Biological context of Asthm1

• BACKGROUND: Asthma functional genomics studies are challenging because it is difficult to relate gene expression changes to specific disease mechanisms or pathophysiologic features [9].
• BACKGROUND: Asthma is a major public health problem worldwide, and the morbidity and mortality of asthma have increased in the past two decades [10].
• Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology [11].
• Since asthma is a disease that is associated with increased oxidative stress and altered antioxidant defenses, we investigated the expression of GRX in a murine model of allergic airway disease [12].
• RESULTS: Asthma phenotype was totally abrogated in alpha4- or beta2-deficient mice [13].

Anatomical context of Asthm1

• BACKGROUND: Asthma is characterized by allergen-induced airway inflammation orchestrated by TH2 cells [14].
• BACKGROUND: Asthma is an acute-on-chronic inflammatory disease of the airways characterized by recruitment of eosinophils into the epithelial layer, chronic inflammation in the lamina propria, as well as variable accumulation of mast cells in the airway wall [15].
• Bone marrow eosinophilopoiesis induced by interleukin (IL)-5 is a major contributor to eosinophilic airway inflammation in asthma [16].

Associations of Asthm1 with chemical compounds

• METHODS: A subset of 608 homes from the National Cooperative Inner-City Asthma Study population had dust samples adequate for analysis of mouse allergen [17].
• Moreover, pretreatment with RU-486, a glucocorticoid receptor antagonist, before ovalbumin challenge completely inhibited a psychological stress-induced exacerbation of asthma [6].
• Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model [18].
• Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain [19].
• To provide further insight into the role of alpha4beta1/VCAM-1 pathway and to compare this to the role of beta2 integrin in the development of acute asthma phenotype, we used genetically deficient mice, in contrast to previous studies with anti-functional antibodies yielding ambiguous results [13].

Regulatory relationships of Asthm1

• Results reported here show that blocking of IL-5Ralpha expression through RNA interference can enhance effective treatment of asthma, and that bone marrow can be used as a key targeted organ in the treatment of asthmatic mice [16].
• Recently, it has been reported that acidic mammalian chitinase is expressed in the setting of T helper-2-associated inflammation and subsequently induces airway hyperresponsiveness in allergic asthma patients [20].

Other interactions of Asthm1

• Our data suggest that simvastatin may be used as a therapeutic agent in asthma, based on reductions of various allergic responses via regulating small G proteins/MAP kinases/NF-kappaB in mouse allergic asthma [21].
• BACKGROUND: Asthma is associated with airway hyperresponsiveness and enhanced T-cell number/activity on one hand and increased levels of exhaled nitric oxide (NO) with expression of inducible NO synthase (iNOS) on the other hand [22].
• These findings suggest that inhibiting D6 function might be a novel means to attenuate airway responses in individuals with allergic asthma [23].
• As2O3 likely exerts its broad anti-inflammatory effects by suppression of NF-kappaB activation through augmentation of IkappaBalpha expression in asthma [24].
• BACKGROUND: Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of allergic inflammation and bronchial hyperresponsiveness (BHR) [25].

Analytical, diagnostic and therapeutic context of Asthm1

• Rationale: Epidemiological studies suggest that infections with helminths protect from the development of asthma [26].
• METHODS: We developed a new monoclonal-based ELISA to determine the prevalence of rat allergen in dust samples from inner-city homes of the National Cooperative Inner-City Asthma Study population [27].
• 1. Asthma research is arguably limited by an absence of appropriate animal models to study the pharmacology of inflammatory mediators that affect airway hyperresponsiveness and remodelling [28].
• METHODS: We conducted an ongoing prospective birth cohort study of 498 children with a history of allergy or asthma in at least 1 parent living in metropolitan Boston (the Home Allergens and Asthma Study) [29].
• DESIGN: A cross-sectional survey of parents of elementary school children, using a self-administered questionnaire with a 12-month recall on asthma symptoms based on the International Study of Asthma and Allergies in Childhood [30].

References