Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jan 2008
Randomized Controlled Trial Multicenter StudyComparable long-term safety and efficacy of a novel budesonide/formoterol pressurized metered-dose inhaler versus budesonide/formoterol Turbuhaler in adolescents and adults with asthma.
Budesonide/formoterol in one inhaler is an established therapy for asthma and chronic obstructive pulmonary disease. The long-term safety and efficacy profile of a novel hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation of budesonide/formoterol was compared with that of budesonide/formoterol in a dry powder inhaler (DPI; Turbuhaler). This multinational, 52-week, randomized, open, parallel-group study included patients aged > or = 12 years with asthma who had a forced expiratory volume in 1s (FEV1)> or = 50% of predicted normal; all patients used inhaled corticosteroids (400-1200 microg/day) and needed additional short-acting beta 2-agonist therapy. ⋯ The proportion of patients discontinuing as a result of adverse events was low in both groups (pMDI 12/446 [3%], DPI 2/227 [1%]). Lung function was improved to a similar extent in both groups and there was no detectable difference in time to first severe asthma exacerbation. The novel HFA pMDI formulation of budesonide/formoterol is an equally well tolerated and effective treatment for adults and adolescents with asthma as the budesonide/formoterol DPI.
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Pulm Pharmacol Ther · Jan 2008
Randomized Controlled TrialChronic inhalation of nebulized levalbuterol does not increase mucociliary clearance in healthy subjects.
Acute inhalations of beta 2-adrenergic receptor agonists increase mucociliary clearance (MCC). Less is known about the effect of long-term inhalations of these agents on MCC, or cough clearance (CC). We hypothesized that chronic inhalations of nebulized levalbuterol, the R-isomer of albuterol, would enhance MCC and/or CC in healthy subjects, compared to albuterol or placebo. ⋯ MCC averaged (+/-SD) 12.3+/-8.3%, 9.2+/-4.7% and 10.0+/-9.6% with placebo, albuterol and levalbuterol, respectively. CC averaged 3.9+/-6.8%, 4.9+/-4.3% and 3.8+/-6.4% with placebo, albuterol and levalbuterol, respectively. These results indicate that chronic inhalations of nebulized levalbuterol for 1 week do not increase MCC or CC in healthy subjects, compared to albuterol or placebo.
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Pulm Pharmacol Ther · Jan 2008
Randomized Controlled TrialAcute effects of sildenafil on exercise pulmonary hemodynamics and capacity in patients with COPD.
We investigated in chronic obstructive pulmonary disease (COPD) patients whether a single dose of sildenafil can attenuate the exercise-induced increase in pulmonary artery pressure, thereby allowing augmentation of stroke volume (SV), and improving maximal exercise capacity. ⋯ Regardless of mPpa at rest, sildenafil attenuates the increase in mPpa during submaximal exercise in COPD. This attenuated increase is neither accompanied by enhanced SV and CO, nor by improved maximal exercise capacity.
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Pulm Pharmacol Ther · Jan 2008
Randomized Controlled TrialEffects of airway anesthesia on dyspnea and ventilatory response to intravenous injection of adenosine in healthy human subjects.
We have recently shown that intravenous injection of adenosine causes dyspnea and hyperventilation in man, and we suggested that stimulation of vagal C-fibers in the airways and lungs is involved. To test this hypothesis further, the present study was performed in healthy subjects (n=12; age 32.4+/-10.2 yrs, 7 females) to determine if the effect of adenosine could be attenuated by blocking the airway sensory receptors by inhalation of aerosolized lidocaine, a local anesthetic. In each subject, the effects of intravenous injection of adenosine (10mg) on dyspneic sensation, minute ventilation, airway resistance and heart rate were measured after the subject inhaled lidocaine or placebo aerosol on two separate days. ⋯ The intensity of adenosine-induced dyspnea was markedly reduced after the lidocaine pretreatment compared to placebo. In a sharp contrast, the VE and heart rate responses to adenosine were not affected by lidocaine. These results lend further support to our previous studies indicating that the origin of the dyspnogenic action of intravenous adenosine is most likely vagal bronchopulmonary C-fiber sensory nerves.
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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.