M Kraft

..The distal lung is an important site of inflammation in asthma. Maximal midexpiratory flows and the ratio of maximal:partial flows are purported to reflect distal lung function...

..Many questions remain, but the ground is fertile for continued investigation...

..To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS)...

..M. (r = 0.71, p = 0.004) and 4:00 A.M. (r = 0.59, p = 0.03). We conclude that the distal lung units, specifically the collateral channels, and may be functionally altered at night in NA...

..We conclude that the airway macrophage may be the airway inflammatory cell driving the reduction in steroid responsiveness at night in NA, and this function is modulated by IL-13...

..However, they have not been evaluated chronotherapeutically. This article addresses the roles of corticosteroids and leukotrienes in nocturnal asthma and their position as therapeutic agents or targets for therapy...

..Therefore, serum levels of cortisol may not be the appropriate measurement to assess the role of cortisol in nocturnal asthma...

..pneumoniae (p = 0.05). M. pneumoniae was present in the lower airways of chronic, stable asthmatics with greater frequency than control subjects, and may play a role in the pathogenesis of chronic asthma...

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..Clarithromycin treatment in asthmatic patients could reduce the edematous area as identified by alpha(2)-macroglobulin staining, which may lead to airway tissue shrinkage and cause an artificial increase in the number of blood vessels...

..Although obesity has been hypothesized to worsen asthma, data from studies of subjects with well-characterized asthma are lacking...

..These findings need further delineation but may help us to understand the pathophysiology of asthma and new treatment options...

..02; 10(-8) mol/L, P =.02). IFN-gamma did not significantly alter airway fibroblast proliferation. CONCLUSION: IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma...

..IV magnesium (Mg2+) has been proposed as an emergent treatment for acute asthma exacerbations. Recent studies have focused on the effects of Mg2+ on bronchial smooth muscle, yet asthma is primarily an inflammatory disease...

..The examples given in this report demonstrate how various aspects of our investigation are performed...

..In contrast to substance P, the substance P receptor neurokinin 1 has not been examined at the protein level in asthmatic airways...

..Thus, all biologic functions, from those of the cell, the tissue, the organs, and the entire body, run on a cycle of altering activity and function.(ABSTRACT TRUNCATED AT 400 WORDS)..

..However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial...

..Although inhaled corticosteroids (ICSs) are effective in preventing deterioration in asthma control, at least half of subjects with mild-to-moderate asthma will remain stable when these agents are discontinued...

..Further studies are required to determine whether this novel approach to treatment should be recommended...

..CONCLUSION: This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States...

..The elements of asthma control achieved by LABAs (improved lung function) and leukotriene receptor antagonists (LTRAs; protection against exacerbations) may be complementary as well...

..The fraction of exhaled nitric oxide as a measure of inflammation is suggested as offering the best combination of disease evaluation and practical implementation for improved asthma outcomes...

..We hypothesized that treatment with montelukast, an oral cysteinyl-leukotriene receptor antagonist, would improve both proximal and distal lung physiology in patients with mild asthma...

..One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control...

..Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids...

..Due to their highly targeted delivery systems, newer HFA-based formulations have the potential to effectively treat asthma at reduced doses...

..Several studies suggest that patients with asthma who are homozygous for arginine at the 16th position of the beta2-adrenergic receptor may not benefit from short-acting beta-agonists...

..The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma...

..This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis...

..CONCLUSIONS: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae...

..M., suggesting chronic overstimulation in vivo. These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma...

..CONCLUSIONS: Our results from these two pilot studies suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to reduced elastin density...

..It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations...

..CONCLUSIONS: Nocturnal asthma is associated with elevation and phase delay of peak serum melatonin levels. Elevated melatonin levels might contribute to the pathogenesis of nocturnal asthma...

..Conversely, adrenal response to corticotropin might be enhanced in nonnocturnal asthma, attenuating nocturnal worsening of airway inflammation...

..These results suggest that M. pneumoniae infection may contribute to the pathogenesis of chronic asthma at different levels of the airways, by inducing TGF-beta1 in large airways and the chemokine RANTES in small airways...

..Platelet-derived growth factor (PDGF) may have a significant role in airway remodeling in asthma, because it is a powerful inductor of many airway fibroblast activities such as collagen synthesis...

..The mechanism of action of LTRAs leads to their effects on systemic allergic inflammatory processes...

..The frequent coexpression of these disorders and their shared pathophysiology suggests that these are similar disorders affecting the upper and lower airways...

..Although steroid therapy is helpful in symptomatic control, it does not remedy structural alterations or many aspects of the inflammatory milieu. This article discusses several studies and supports the need for further investigation...

..The analysis of data collected from epidemiologic studies continues to be a critical part of enhancing the understanding of the pathophysiology of asthma, which will lead to improved patient outcomes...