S E Wenzel

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..These results support the concept that interactions of innate and adaptive immune systems may be important in promoting the tissue eosinophilia of asthma, particularly in those with more severe disease...

..However, 5-lipoxygenase inhibitors, anti-IgE, and immunomodulatory drugs are also likely to have a place in treatment. Improving therapy in this disease will require a better understanding of the phenotypes involved...

..Recent studies suggest that response to therapy in severe asthma may depend on the phenotype...

..While an anti-inflammatory effect is suggested, longer-term, earlier intervention, studies are needed to determine whether these compounds will have any effect on the natural history of the disease...

..Treatment remains problematic and likely will remain so until a better understanding of this disease develops...

..Treatment is problematic and will probably remain so until a better understanding of this disease develops...

..This Review analyses some of the methods that have been used to define asthma phenotypes and proposes an integrated method of classification to improve our understanding of these phenotypes...

..Understanding the commonalities of the pathology of severe asthma should, however, lead to the development of improved therapies...

..Treatment remains problematic and likely will remain so until a better understanding of this disease develops...

..In addition, five patients were completely weaned off oral steroids...

..These results suggest that two distinct pathologic, physiologic, and clinical subtypes of severe asthma exist, with implications for further research and treatment...

..While long term studies will be helpful in determining the 'disease modifying' effects of these drugs, data suggest that these drugs are useful in the treatment of a broad range of asthmatic patients...

..These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors...

..These results suggest that although increased collagen deposition in the SBM at the large airway level is a characteristic of asthma, it may not explain the differences in severity of asthma...

..05) were also increased in WC compared with NC, whereas PGD(2) and beta-tryptase were not. This study confirms that inflammation is present in the airways of very young WC and may differ from patterns seen in adults with asthma...

..001). There were no significant changes among the four groups after allergen challenge in 6-keto-PGF1 alpha or PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)..

..After allergen challenge, the best correlation was found between the levels in BALF for the prostanoids PGD2 and TxB2 (r = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS)..

..Further, they may be considered for primary use in patients with mild, persistent asthma, especially those who are steroid-phobic or who have compliance issues...

..Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma...

..Exhaled nitric oxide (FeNO) associates with asthma and eosinophilic inflammation. However, relationships between nitric oxide synthases, arginase, FeNO, asthma severity and inflammation remain poorly understood...

..Atopic subjects with asthma and without LAR had significantly higher levels of all four mediators after challenge than atopic subjects with asthma and with LAR and atopic subjects without asthma.(ABSTRACT TRUNCATED AT 250 WORDS)..

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..This study suggests that small airway may be identified and analysed in transbronchial biopsy tissue samples and therefore transbronchial biopsy tissue samples could expand the analysis of inflammation and tissue remodelling in asthma...

..Conclusions and Clinical Relevance These data indicate that sPLA(2) -IIA and sPLA(2) -X are the major sPLA(2) s in human airways, and suggest a link between the levels of sPLA(2) -X in the airways and several features of asthma...

..Thus, the cromione, SCG and NS, are effective prophylactic drugs recommended for use in both adults and children in the management of mild persistent asthma, EIB, and potentially as modest steroid-sparing agents...

..Urinary LTE4 was also measured in healthy children (age 3-12) and found to be 103 +/- 9...

..These data suggest that CD11b(+)Gr1(int)F4/80(+) cells contribute to the protective effects of LPS in allergic asthma by tempering Th2 effector function in the tissue...

..0006). CONCLUSIONS: Mosaic pattern of attenuation, when present, is highly suggestive of BO, but SA and BO may be indistinguishable...

..Efforts are to compare tissue and lavage biomarkers with less invasive measures, such as sputum, serum, or exhaled breath, to improve the treatment and management of asthma...

..The objective of this analysis was to investigate whether patients with severe or difficult-to-treat asthma who experienced recent severe asthma exacerbations are at increased risk of future asthma exacerbations...

..Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A(4) (LXA(4)) is an arachidonic acid-derived mediator that serves as an agonist for resolution of inflammation...

..However, an effect on exacerbations and tissue inflammation has not been shown...

..A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation...

..Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important...

..Future studies will specifically evaluate the role of inflammatory/oxidative processes, infection, genetics, and the distal lung in the pathogenesis of severe asthma...

..IgE-mediated responses contribute to allergy and asthma. Little is understood regarding the relationship of tissue IgE to systemic IgE, inflammation or clinical outcomes...

..Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies...

..Although these interactions have implications for remodeling in asthma, little is understood regarding the mechanisms controlling TIMP-1 product...

..We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component...

..22). Peripheral blood neutrophil MMP-9 protein was not affected by GCs. CONCLUSIONS: BAL neutrophils contribute to BAL fluid MMP-9 protein and activity and are poorly inhibited by GCs...

..CONCLUSIONS: Differentiating severe asthma by age at onset and presence or absence of eosinophils identifies phenotypes of asthma, which could benefit subsequent genetic and therapeutic studies...

..Although IL-13 induced activation of PI3K-Akt, the activation did not contribute to the synergy observed with TGF-beta1 plus IL-13 in TIMP-1 expression and in fact may dampen it. The mechanisms behind the synergy remain to be determined...

..These data suggest that TGF-beta2 production by asthmatic bronchial epithelial cells may increase airway mucin expression. IL-13-induced mucin expression may occur in part through TGF-beta2 up-regulation...

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..Clearance of apoptotic cells is crucial to the resolution of inflammation and development of fibrosis, but the process is not well understood in normal or diseased human lungs...

..Thus, the accuracy of such assessments is essential for proper clinical management. The consistency of asthma severity assessment in patients with difficult-to-treat disease is unknown...

..The fractional concentration of exhaled nitric oxide (FENO) is increased in asthma, correlates with eosinophilic inflammation, and decreases after steroid therapy...

..Whether differing fibrotic capacities of fibroblasts from these two regions contribute to this variability is unknown...

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..Thus, our results suggest that IL-15, either alone or in combination with TNF-alpha, may perpetuate allergic inflammation by reduction of spontaneous eosinophil apoptosis through autocrine production of GM-CSF and NF-kappaB activation...

..Although MMP-9 is increased in lavage fluid and sputum in patients with asthma, controversy exists as to the role of tissue MMP-9...

..Larger-scale studies are needed...

..3%) deaths took place outside a hospital. We conclude that this population shares characteristics of severe or poorly controlled asthma, low educational and socioeconomic levels, and lack of medical care and of inhaled steroid use...

..As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation...

..Chronic rhinosinusitis with nasal polyps is generally characterized by eosinophilic infiltration and a Th2-biased cytokine profile. However, the mechanisms that lead to nasal polyps are not clear...

..001). We conclude that eicosanoids are increased in the tracheal aspirates and urine of children with bronchiolitis...

..More than 280 pulmonologist and allergist sites across the United States participated...

..Despite the critical role of allergens in the pathogenesis of these disorders, little is known about how allergens modulate the immune response. IL-13 receptor alpha2 (IL-13Ralpha2) is a decoy receptor for IL-13...

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..Asthma is a significant public health problem that results in 1.8 million annual emergency department (ED) visits. Many ED visits may be prevented with specialized asthma care...