Paul M O'Byrne

..New treatment approaches developed to manage some of the phenotypes of severe refractory asthma have included humanized monoclonal antibodies (hMabs)...

..The maintenance of asthma control has significant advantages to patients and greatly outweighs the potential risks of treatment side effects...

..A recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls...

..Patients with severe refractory asthma have not achieved asthma control, even with high doses of ICS, usually in combination with LABAs and other maintenance treatments...

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..An emerging role for measurements of AHR is in the evaluation of the optimal treatment for patients with asthma...

..Asthmatic patients lose lung function faster than normal subjects. The effectiveness of early intervention with inhaled corticosteroids on this decline in lung function is not established in recent-onset disease...

..Inhaled corticosteroid/long-acting inhaled beta(2)-agonist combinations may not be as effective in children as in they are adults in improving asthma control and reducing asthma exacerbations...

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..For patients who do not achieve asthma control despite taking drugs, measurement of the inflammatory response in the airway in induced sputum could provide further information to guide treatment...

..Long-acting ss(2)-agonists are an established controller medication in asthma. BI 1744 is a novel L\long-acting ss(2)-agonist with a preclinical profile that suggests 24-hour bronchodilation and bronchoprotection may be achieved...

..The benefit was seen in patients of all ages. Subsequent studies have revealed that this beneficial effect of budesonide/formoterol as maintenance and reliever requires both components of the combination...

..The similarities and differences between exacerbations asthma and COPD with an emphasis on epidemiology and clinical presentation are discussed and compared in this chapter...

..However, it is not known which of these treatment options is more effective in sustaining asthma control...

..The objective of this post hoc study was to study the effects of low-dose inhaled budesonide on lung function in smokers and nonsmokers with mild persistent asthma...

..Leukotriene receptor antagonists have an excellent safety profile...

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..There was an additional focus on the indirect measurement of airway inflammation and its interaction with airway hyperresponsiveness, as well as the role of measuring airway inflammation in the management of asthma...

..GINA Controlled/Partly Controlled and GOAL Totally Controlled/Well-Controlled correspond to ACQ-5 <1.00. The ACQ-5 is more responsive to change in a clinical trial setting than a categorical scale...

..In addition, treatment of patients with severe asthma with an anti-IL-5 mAb also reduces the number of severe asthma exacerbations, demonstrating a central role of eosinophils in many exacerbations...

..Nevertheless, because IL-4 is required for IgE production and IL-5 is required for eosinophilopoesis, these Th2 cytokines must remain important candidates for a role in the pathogenesis of allergic asthma...

..To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma...

..001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens...

..Studies in chronic obstructive pulmonary disease reported increased rates of pneumonia with ICS. Concerns exist about an increased pneumonia risk in patients with asthma taking ICS...

..For this reason, pharmacologic treatment to reduce airway inflammation is currently the cornerstone of therapy for most individuals who have asthma...

..Treatment with either leukotriene receptor antagonists or anti-IgE also reduces the risks of asthma exacerbations, but the magnitude of the benefit compared with the combination of ICS and long-acting beta(2)-agonists is not yet known...

..Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood, symptoms, and airflow limitation...

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..However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma...

..The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined...

..The present analysis compared the efficacy of early intervention with inhaled budesonide in Caucasian and Asian patients over the first 3 years of the inhaled Steroid Treatment As Regular Therapy in early asthma study...

..The use of combination inhaled budesonide and formoterol as maintenance and reliever therapy significantly improves the risk and the time to exacerbations in asthma...

..The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge...

..However, the duration of the protective effects of inhaled steroids after discontinuation of therapy has not been established...

..Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects...

..Extensive evidence in animal models supports a role for IL-13 in the pathobiology of asthma. IMA-638 and IMA-026 are fully humanized IgG(1) antibodies that bind to different epitopes and neutralize IL-13 bioactivity...

..We have previously shown that inhibiting allergen (Ag)-induced recruitment of EPC in sensitized mice attenuated increased bronchial vascularity and development of airway hyperresponsiveness...

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..Understanding the mechanisms regulating progenitor cell mobilization and trafficking to the peripheral circulation might be important for the development of effective asthma therapies...

..Objectives: To determine the safety of long-acting beta-agonists among patients with asthma using corticosteroids...

..However, they do not normalize lung function and prevent structural changes in the airway wall in all asthmatic patients...

..Thus, the proinflammatory environment established during an acute influenza A infection enhances Th2-polarized immunity to a low dose of HDM and precipitates marked lung dysfunction...

..In animal models, the induction and maintenance of allergic airway inflammation is primarily a function of myeloid dendritic cells, whereas the tolerization to inhaled allergens is likely a function of plasmacytoid dendritic cells...

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..This review examines the newer information on the pathophysiologic characteristics of asthma and focuses on papers published over the past 3 years that have helped to improve current levels of understanding...

..We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype...

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..IL-13 can promote airway smooth muscle migration through Src-kinase and leukotriene-dependent pathways. This may contribute to the accumulation of smooth muscle cells in remodeled airway submucosa...

..Both ventilation (V) and perfusion (Q) of the lungs are altered in asthma, but their relationships with allergen-induced airway responses and gas exchange are not well described...

..We examined changes in the cellular nature of airway inflammation between consecutive exacerbations and their predictors in individual patients...

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..Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity...

..The mechanisms of the transient allergen-induced airway hyperresponsiveness are not likely to fully explain the underlying mechanisms of the persistent airway hyperresponsiveness in asthmatic patients...

..Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency...

..We conclude that, the cysteinyl leukotriene receptor antagonist, pranlukast, attenuates allergen-induced increase in airway eosinophils by decreasing bone marrow eosinophilopoiesis and airway chemotactic and eosinophilopoietic cytokines...

..Exacerbations of airway disease are eosinophilic, neutrophilic, both or neither. The primary objective of the present study was to identify whether the treatment of a neutrophilic bronchitis can unmask an associated eosinophilia...

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..In an effort to remain current, a yearly update, based on an extensive review of the previous year's peer-reviewed literature on asthma management, is available on the web version of the GINA guidelines...

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..CONCLUSION: Pretreatment with pranlukast attenuated allergen-induced airway responses and the decrease in circulating myeloid dendritic cells, demonstrating a novel role of cysteinyl leukotrienes in dendritic cell trafficking...

..The phosphatidylinositol-3 kinase pathway is a key signaling mechanism in the chemotactic migration of ASM cells in response to cysteinyl leukotrienes...

..The amplitude, frequency, or localization of Ca(2+) oscillations in the smooth muscle may determine the degree of airway sensitivity and reactivity, which are characteristic features of asthma...

..Fibrocytes are circulating mesenchymal cell progenitors that are involved in tissue repair and fibrosis...

..Thus, the intertwined relationship of ASM and ECM and their response to stimuli such as chronic inflammation in diseases such as asthma and COPD contribute to the remodeling seen in airways of patients with these diseases...

..Our findings reveal biological roles for LXR in ASM cells and suggest that modulation of LXR activity offers prospects for new therapeutic approaches in the treatment of asthma and other inflammatory respiratory diseases...

..The suppressive effect by montelukast demonstrates that this is a cysLT(1) receptor-mediated effect...