Pulmonary pharmacology & therapeutics
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Cigarette smoking has been associated with impaired endothelium-dependent relaxation responses in the brachial and coronary arteries (endothelial dysfunction). The aim of the present study was to determine if the airway circulation is also affected and if airway treatment has an effect on endothelial function. Airway blood flow (Q(aw)) responses to inhaled albuterol as an index of endothelial function were measured in age-matched healthy current smokers, healthy ex-smokers, ex-smokers with COPD and healthy lifetime non-smokers; in the ex-smokers with COPD, the albuterol responsiveness was repeated after a 4-week treatment with an inhaled glucocorticoid/beta(2)-adrenergic agonist combination drug. ⋯ While drug treatment per se did not change Q(aw) significantly, it restored albuterol responsiveness (+67.6+/-11.1%; p<0.05) in the ex-smokers with COPD. Thus, cigarette smoking is associated with endothelial dysfunction in the airway, with a partial recovery of endothelial function after smoking cessation in healthy ex-smokers but not in ex-smokers with COPD. In the latter, combined glucocorticoid/beta(2)-adrenergic agonist treatment restores albuterol responsiveness.
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Pulm Pharmacol Ther · Jan 2007
Randomized Controlled TrialCapsaicin exposure elicits complex airway defensive motor patterns in normal humans in a concentration-dependent manner.
The airway defensive response to tussive agents, such as capsaicin, is frequently assessed by counting the number of cough sounds, or expulsive events. This method does not identify or differentiate important respiratory events that occur in the respiratory muscles and lungs, which are critical in assessing airway defensive responses. The purpose of this study was to characterize the airway defensive behaviours (cough and expiration reflex) to capsaicin exposure in humans. ⋯ At higher concentrations (>50 microM) ER's with one or more expulsive events (ER1) appeared, and the number of CR's with three or more expulsive events (CR3) increased. The decrease in EMG activation and airflow measurements with each successive expulsive event suggests a decline in power and shear force as the number of expulsive events increased. Therefore, the airway defensive response to capsaicin is a complex motor pattern that functions to coordinate ER's and CR's with differing numbers of expulsive events possibly to prevent aspirations and keep air moving to promote clearance.
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Pulm Pharmacol Ther · Jan 2006
Randomized Controlled TrialBimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial.
Asthma is characterized by increased recruitment of inflammatory cells from the circulation into the airways. As selectins mediate tethering and rolling of leukocytes on the vascular endothelium, they constitute a promising target for the therapeutic modulation of inflammation. We evaluated the effect of inhaled bimosiamose (TBC1269), a synthetic pan-selectin antagonist, on allergen-induced late asthmatic reactions (LAR) in mild asthmatics. ⋯ Administration of the pan-selectin antagonist bimosiamose is effective in a human allergen challenge model of asthma. The result of this proof-of-concept exploratory trial is the first study that demonstrates clinical efficacy of selectin-antagonists as novel therapeutic strategy in asthma.
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Pulm Pharmacol Ther · Jan 2005
Randomized Controlled TrialA randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks.
Although it is well known that intravenous administration of MgSO4 as an adjunct to conventional therapy is effective in treating asthma attacks, the effect of nebulized MgSO4 as a vehicle for salbutamol has been less evaluated. The aim of this study was to compare the effects of nebulized salbutamol administrated through either MgSO4 or isotonic saline solution on the 'peak expiratory flow rate' (PEFR), other respiratory and clinical parameters, and hospitalization rate of patients suffering from moderate to severe asthma attacks. Twenty-six patients with asthma attack were enrolled in the study in a randomized single blind fashion. ⋯ When the treatment response was evaluated within the groups, group 2 showed statistically significant increase in PEFR (% of predicted) 1h earlier than group 1 (60th vs 120th minute, p=0.003 vs p=0.007). The mean duration of achieving target-PEFRs was 105.7+/-72.1 min for group 1 and 118.3+/-96.7 min for group 2 (p>0.05). This study suggested that the additional usage of MgSO4 to nebulized salbutamol has no beneficial effect on the treatment of asthma attacks.
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Pulm Pharmacol Ther · Jan 2004
Randomized Controlled Trial Comparative Study Clinical TrialBudesonide/formoterol in a single inhaler rapidly relieves methacholine-induced moderate-to-severe bronchoconstriction.
Inhalers containing corticosteroids and long-acting beta2-agonists are becoming increasingly important in asthma management. A rapid effect is important to patients, particularly during exacerbations. We compared the onset of bronchodilation and patient-perceived relief from dyspnoea following single-inhaler budesonide/formoterol or salmeterol/fluticasone in a model of acute bronchoconstriction. ⋯ Median recovery times to 85% of baseline FEV1 were shorter for budesonide/formoterol (1 or 2 inhalations: 3.3 and 2.8 min, respectively) than salmeterol/fluticasone (8.9 min; P < 0.001) and placebo (> 30 min). One min after budesonide/formoterol, dyspnoea was significantly reduced (Borg score -0.86 units, both doses) compared with salmeterol/fluticasone (-0.55 units; P < 0.05) and placebo (-0.23 units; P < 0.001). Budesonide/formoterol provides immediate bronchodilation, faster than salmeterol/fluticasone, which patients can feel during acute methacholine-induced bronchoconstriction.