C E Brightling

..abstract:..

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..Biologic therapies directed toward OX40/OX40L are in early phases of development, and results from these studies are eagerly awaited...

..Asthma is characterized by disordered airway physiology as a consequence of increased airway smooth muscle contractility. The underlying cause of this hypercontractility is poorly understood...

..The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFalpha, cytokines known to be important in asthma...

..In asthma interleukin (IL)-13 is increased in the airway compared with non-asthmatic eosinophilic bronchitis. Whether this differential expression is specific to the airway or is more generalised is uncertain...

..New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy...

..Nonasthmatic eosinophilic bronchitis is a newly recognized cause of chronic cough. Our objective was to review the pathogenesis, natural history, diagnosis, and treatment of this condition...

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..These results suggest that inhibition of the CXCL10/CXCR3 axis offers a novel target for the treatment of asthma...

..Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear...

..This suggests that interactions between mast cells and airway smooth muscle cells are critical for the development of the disordered airway physiology in asthma...

..Thus, it is time for sputum induction to move from the research laboratory to the clinic...

..Therefore the challenge for clinicians is to evaluate the risk/benefit ratio of these therapies in individual patients with asthma...

..In conclusion, the mannitol challenge my have potential as a novel cough challenge test and further work is required to extend our findings and to assess whether it has utility in different causes of chronic cough...

..In general, response to therapy in both conditions is very good and the limited long-term data available suggest that both usually have a benign course, although in some cases persistent airflow obstruction may occur...

..Early clinical trials of anti-IL-13 therapies in asthma have shown promise, and the results of further efficacy studies are eagerly awaited...

..Interestingly, improvement in airway remodeling in response to anti-IL5 observed using CT imaging and analysis of sub-epithelial matrix deposition does suggest that the eosinophil may play a causal role in airway remodeling...

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..As CXCR3 ligands are elevated in many pulmonary diseases, CXCR3 may be important for determining the anatomical microlocalization of mast cells within the human lung...

..In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation...

..A management strategy that aims to minimise eosinophilic airway inflammation, as well as symptoms, is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease...

..Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown...

..Eosinophilic bronchitis is an important cause of chronic cough. Treatment with inhaled corticosteroids is associated with a short-term improvement in cough and reduced sputum eosinophil count but the long-term outcome is uncertain...

..We sought to examine IL-13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL-13 localize to the airway smooth muscle bundle and bronchial glands...

..However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung...

..We tested the hypothesis that the cough and increased cough reflex sensitivity seen in patients with idiopathic pulmonary fibrosis may be due to airway inflammation in a prospective, cross-sectional study...

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..In asthma, Th2 cytokines have been implicated as playing a critical role in the development of airway inflammation and hyper-responsiveness. Whether inflammatory cells within the airway smooth muscle release these cytokines is unknown...

..CONCLUSIONS: These results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids...

..Non-asthmatic ASM releases a mediator or mediators that inhibit mast cell migration towards stimulated asthmatic ASM. Specifically targeting mast cell migration into the ASM bundle may provide a novel treatment for asthma...

..Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation...

..Whether these inflammatory phenotypes have differential cytokine and chemokine expression is unknown...

..However, the expression of GM-CSF and its receptor in airway samples in asthma and COPD across disease severity needs to be further defined...

..The IL-13 receptor, IL-13Ralpha1, is expressed on most leukocytes, except T-cells. Evidence to support IL-13Ralpha1 expression on mast cells is limited...

..Nitric oxide (NO) has potential advantages as a tool to monitor airway inflammation although little is known about the relationship between NO and eosinophilic airway inflammation and the factors which influence it...

..64 ng/ml [0.36 to 0.90] and 11-fold [3.3 to 36]), respectively. In conclusion, eosinophilic bronchitis is associated with active airway inflammation with increased release of vasoactive and bronchoconstrictor mediators...

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..An immunopathological study was undertaken to test the hypothesis that idiopathic chronic cough is associated with lymphocytic airway inflammation...

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..96. In conclusion, sputum induction is safe and the cell and fluid phase mediators repeatable in the investigation of airway inflammation in patients with COPD. VAS symptom scores and the CRQ are reproducible outcome measures in COPD...

..These findings support the hypothesis that immunoglobulin E loading of mast cells within the asthmatic airway contributes to the disordered airway physiology of this disease...

..The importance of IL-13 in the asthma paradigm is supported by increased expression in human subjects, particularly in patients with mild-to-moderate asthma. However, the role of IL-13 in severe asthma needs to be further defined...

..CONCLUSION: We conclude that methacholine airway responsiveness and the sputum differential eosinophil count are the most useful objective tests in patients with mild asthma...

..Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown...

..Chemokines and their receptors could play key roles in the recruitment of T cells to the asthmatic lung. CCR8 is preferentially expressed on T-helper type 2 cells, and is thought to play a role in the pathogenesis of human asthma...

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..A study was undertaken to test the hypothesis that blockade of K(Ca)3.1 would attenuate HLMC proliferation and migration...

..T cells and eosinophils were not usually seen in the airway smooth muscle in any of the groups. CONCLUSIONS: The infiltration of airway smooth muscle by mast cells is associated with the disordered airway function found in asthma...

..Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation...

..007). CONCLUSION: In subjects with eosinophilic bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway secretions. These chemokines may play a key role in mast cell recruitment to the superficial airway in this condition...

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..All features improved markedly on a gluten free diet, suggesting a causal relationship between coeliac disease, cough, and lymphocytic bronchoalveolitis...

..Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations...

..02). CONCLUSION: The increased expression of IL-13 in asthma compared with eosinophilic bronchitis supports the concept that IL-13 may play a critical role in the pathophysiology of asthma...

..Further study of this interesting condition may shed light on the relationship between airway inflammation and airway responsiveness, leading to a greater understanding of both eosinophilic bronchitis and asthma...

..038) in matched controls. Therefore, AHR was increased in women who have had pre-eclampsia. This association and its possible mechanisms warrant further investigation...

..We hypothesized that this results from migration of ASM or progenitors in response to chemokines derived from ASM or mast cells within the ASM bundle...

..We sought to describe the HRCT scan abnormalities of a large severe asthma cohort and to determine the utility of clinical features to direct the use of HRCT scanning in this group of patients...

..08 to 0.55; P=0.01). CONCLUSIONS: Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.)...

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..Hip bone marrow could provide a more convenient less invasive source of mast cell progenitors...

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..Our findings support the view that there is release of inflammatory and tussive mediators in patients with chronic cough and suggest that there might be similarities in the mechanism of cough in a diverse range of conditions...

..INTERPRETATION: A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment...

..001). Organ-specific autoantibodies were present in a significantly higher proportion of cases than controls (40% vs. 13%; P = 0.047). These findings suggest a relationship between idiopathic chronic cough and organ-specific autoimmunity...

..Further study of this interesting condition will increase our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutics for both eosinophilic bronchitis and asthma...

..This supports the hypothesis that adhesion is important in the recruitment and retention of HLMC by the ASM in asthma, and for the functional interaction of these cells...

..Further investigation of this group may disclose novel mechanisms of fixed airflow obstruction...

..Chronic inflammation is assumed to be important, although there is limited and contradictory information about the relationship between airway inflammation and postbronchodilator FEV1...

..Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model...

..The importance of Aspergillus fumigatus sensitization and colonization of the airways in patients with asthma is unclear. Objectives: To define the relationship between the clinical and laboratory features of A. fumigatus-associated asthma...

..The aim of this study was to assess whether airway remodelling is restricted to specific subphenotypes of severe asthma...

..Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction...

..Targeting these interactions in asthma might offer a new strategy for the treatment of this common disease...

..1, providing a clearly defined mechanism by which adenosine inhibits HLMC migration and degranulation. A2A receptor agonists with channel-modulating function may be useful for the treatment of mast cell-mediated disease...

..Epithelial dysfunction has been implicated in asthma pathophysiology, but no studies have directly assessed ciliary function in asthma...

..We conclude that the addition of simultaneous pulse oximetry with ELCS will identify rogue measurements in about 8% of cases highlighting the need for repeat samples and thus increasing the accuracy of the measurement of PaO2 by ELCS...

..We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD...

..Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease...

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

..Review the literature to provide a comprehensive approach, including algorithms for the clinician to follow in evaluating and treating the patient with acute, subacute, and chronic cough...

..Thus, inflammatory responses to pathogens are regulated by networks in which patterns of TLR expression and colocalization of tissue cells and leukocytes are critical...