Pulmonary pharmacology & therapeutics
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Chronic and uncontrollable cough is one of the most common and debilitating symptoms found in patients with chronic airway diseases. The physical trauma and stresses of chronic cough on the airway mucosa and respiratory muscles can further worsen the deteriorating process of the airway diseases. ⋯ A number of new and important questions concerning the physiological and pharmacological mechanisms underlying chronic cough have emerged in these presentations. Further studies are required to answer these questions, which should bring a better understanding of the pathogenic mechanisms of chronic cough and lead to the development of new therapeutic strategies.
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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.
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Stimulation of laryngeal receptors is the natural starting point of defensive airway reflexes including the cough reflex, expiration reflex, spasmodic panting, and apnoea with laryngospasm. Although several different types of laryngeal receptors have been reported, the laryngeal irritant receptors are considered to play the most essential role in elicitation of defensive airway reflexes. Based on the knowledge that the laryngeal irritant receptors are stimulated by water solutions lacking chloride anions, we have developed an experimental method to elicit defensive airway reflexes with a direct instillation of distilled water onto the laryngeal mucosa in humans. ⋯ The reflex responses to water stimulation observed in these patients were characterized by apnoea with laryngospasm while the cough reflex was never elicited. Endoscopic images of the larynx in these patients were also characterized by laryngeal oedema. Considering the pathological changes occurring in the central nervous system and the laryngeal mucosa, it is possible that the defensive airway reflexes may be modified by central and/or peripheral mechanisms in patients with MSA.
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Pulm Pharmacol Ther · Jan 2004
Randomized Controlled Trial Clinical TrialRelationship between neutrophil elastase and acute lung injury in humans.
We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating as the primary endpoint, and the weaning rate from mechanical ventilator, the discharge rate from intensive care unit (ICU), and the survival rate as secondary endpoints. ⋯ VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup, and increase in VFD value correlated with PFI rating and increase in ICU free days. It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans.
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Pulm Pharmacol Ther · Jan 2004
Comparative StudyComparative effects of dopamine and dobutamine on hypercapnic depression of diaphragmatic contractility in dogs.
The present study was undertaken to evaluate the effects of dopamine and dobutamine on diaphragmatic contractility in dogs with induced hypercapnia. Animals were divided into three groups of ten each. In each group, hypercapnia (80-90 mmHg) was produced by adding 10% CO2 to the inspired gas. ⋯ The increase in Pdi was more than in Group III than in Group II (P<0.05). In Group I, Pdi to each stimulus did not change from hypercapnia-induced values. In conclusion, compared with dopamine, dobutamine is effective in improving hypercapnic depression of diaphragmatic contractility in dogs.