R J Martin

..We conclude that, in normal persons, rIFN-gamma can be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma appear to be warranted for certain pulmonary diseases...

..Current studies will further define the role of macrolide antibiotics in the treatment of stable patients with asthma, ultimately determining whether these therapeutic agents have a place in asthma management...

..A bacterial infection in asthmatic subjects with weakened TLR2-IFN-gamma signaling may result in an exaggerated airway mucin production...

..Dry powder inhalers (DPIs) generate a larger particle size compared with metered-dose inhalers (MDIs), which affects pulmonary deposition, bioavailability, and subsequent systemic effects of fluticasone propionate (fluticasone)...

..Although asthma is considered an airway disease, the location of the inflammatory response may be greater in the alveolar tissue area. If correct, this could alter the therapeutic approach to this disease...

..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...

..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...

..This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations...

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

..50, P = 0.022). Thus, M. pneumoniae respiratory infection is associated with BHR in this murine model. It appears that acute mycoplasma infection suppresses IFN-gamma, which may be a pivotal factor in the control of BHR...

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..Most recently, studies are also invoking atypical bacterial infections, Mycoplasma pneumoniae and Chlamydia pneumoniae, as factors in both acute exacerbation and chronic asthma...

..Therefore, we investigated whether 4-week treatment with ipratropium bromide inhalation solution 0.02% (qid) could improve sleep characteristics in COPD...

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..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...

..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...

..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...

..We examined repeated measurements of the fractional concentration of exhaled nitric oxide (FENO) and the correlation with cells and mediators in induced sputum (IS) from patients with COPD...

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..07 +/- 0.03 vs. 0.04 +/- 0.02 mg/ml, respectively. Thus the fall in lung volume during sleep in the nocturnal asthmatic patient is a result, not a cause, of the overnight worsening of lung function...

..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...

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

..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, the role of such a low-level Mp infection in the regulation of allergic inflammation remains unknown...

..Exhaled nitric oxide (ENO) is a noninvasive marker of airway inflammation. The purpose of this study was to compare a standardized offline ENO measurement apparatus with a validated on-line method...

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

..Mast cells have previously been shown to promote mycoplasma clearance in mice; however, it is unknown whether mast cells would aid Mp clearance under allergic conditions...

..However, the role of inhaled corticosteroids in the treatment of COPD is controversial. We hypothesised that inhaled corticosteroids reduce the progression of airflow limitation in COPD...

..Selected macrolide antibiotics have steroid-sparing effects in patients with steroid-dependent asthma. In addition to inhibiting methylprednisolone clearance, macrolides may also display anti-inflammatory effects...

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

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

..However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present...

..These results suggest that endothelin-1 release may cause ventilatory depression mediated through endothelin-A receptors located in the chemosensitive areas of the ventrolateral medulla...

..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)..

..A protocol for sputum induction which restricts the use of hypertonic saline based on lung function is both safe and effective in subjects with moderate to severe COPD...

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..This will be particularly true if the cost of the medication is reduced in the future. Asthma control, morbidity, and mortality will improve with a careful and comprehensive medical regimen using the current multiple treatment options...

..We investigated whether a subset of IL-13-producing BLT1-positive CD8 T lymphocytes are present in asthmatic airways and are associated with impaired lung function...

..Our results suggest that hosts with different genetic background may have different susceptibility to repeated respiratory Mp infections along with inflammatory responses...

..We conducted a double-blind, randomized, placebo-controlled study to evaluate the efficacy of telithromycin in patients with acute exacerbations of asthma...

..m. (r = 0.94; 0.93, 0.95); every 2 hours (r = 0. 96; 0.96, 0.97); and every 3 hours (r = 0. 91, 0.91, 0.93). The two-sample alternatives (10 p.m/8 a.m. and 9 p.m/7 a.m.) are accurate, as well as more convenient, economical, and practical...

..Glucocorticoids (GCs) are highly effective in the treatment of asthma. However, some individuals have GC-insensitive asthma...

..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...

..Mounting evidence indicates that recognition and treatment of distal lung inflammation may be key components of appropriate asthma pharmacotherapy...

..The cause of corticosteroid-resistant (CR) asthma is unknown...

..This represents a potentially important model to investigate the mechanisms involved in airway hyperreactivity induced by neonatal lung injury...

..Steroid-resistant (SR) asthma is characterized by airway inflammation that fails to resolve despite treatment with corticosteroids, raising concerns that resistance to steroid therapy in asthma could lead to airway remodeling...

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..In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial...

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

..These results demonstrate that IL-17/IL-17F production is IL-23-dependent in an acute Mp infection, and contributes to neutrophil recruitment and activity in the lung defense against the infection...

..Objectives: To test whether the established allergic airway inflammation compromises host innate immunity (e.g., Toll-like receptor 2 [TLR2]) to hinder the elimination of Mp from the lungs...

..These studies suggest that M. pneumoniae infection synergizes with ETS and suppresses the lung's ability to respond appropriately to environmental challenges leading to enhanced oxidative stress...

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

..These results clearly demonstrate that respiratory Mp infection increases airway mucin expression, which is dependent on the activation of TLR2 signaling...

..Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed...

..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...

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

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

..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...

..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...

..The possible role of antibacterial therapy in the management of asthma and the need for well-designed studies to investigate this is also discussed...

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..Our animal models may also provide a new means to understand the role of infection in asthma pathogenesis and give evidence for the asthma hygiene hypothesis...

..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...

..Regardless of what treatment regimen a physician chooses to prescribe, the choice of medication depends on many factors, including patient preference, physician comfort with the regimen, and cost...

..The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy...

..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...

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

..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...

..Our results suggest that Mp infections could modulate airway collagen deposition in a murine model of allergic airway inflammation with TGF-beta1 involved in the collagen deposition process...

..Prospective studies are warranted to more fully evaluate the importance of atypical bacterial pneumonia as an asthma risk factor...

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

..The Childhood Asthma Management Program (CAMP) study was designed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers...

..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...

..Differential susceptibility to asthma among preterm children may relate to exposures that operate in the in utero and early postnatal environment to accelerate lung development, alter innate immunity, or both...

..pneumoniae by up to 20-fold in lung tissue but not in BALF. CONCLUSION: Inhaled FP suppresses airway inflammation and BHR, which may be caused, in part, by its ability to reduce concentrations of M. pneumoniae in lung tissue...

..By extending the delivery of anti-inflammatory medication to the distal lung, the new HFA-based corticosteroids have the potential to treat asthma more effectively and at reduced steroid doses...

..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...

..We speculate that activation of the NO/cGMP pathway during cholinergic stimulation plays an important role in modulating peripheral as well as central contractile elements in the developing lung...

..This mechanism might contribute to increased ASM reactivity seen in bronchopulmonary dysplasia...

..2% (95% CI, 1.2%, 3.2%). CONCLUSIONS: SDB is a relatively common condition in 8- to 11-year-old children. Potentially vulnerable subgroups, black children, and former preterm infants, are at increased risk...

..0625 for mask vs albuterol, p = 0.0625 for mask vs unprotected exercise). CONCLUSIONS: This heat exchanger mask blocks cold exercise-induced decline in lung function at least as effectively as albuterol pretreatment...

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..The ability to predict who will and will not respond to corticosteroids and additive therapy will greatly improve our ability to treat asthma effectively. ..