Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jan 2005
Clinical TrialReproducibility and validity of a Yan-style portable citric acid cough challenge.
Although many different methods of measuring cough reflex sensitivity have been published, few are simple enough to use outside of a hospital or laboratory environment. The aim of this study was to develop a simple, quick, and portable cough challenge, assess its reproducibility, and compare its results with those measured by an existing established hospital protocol. Twenty-five volunteers performed cough challenges based on an established hospital dosimeter protocol, and, on a separate occasion, by a protocol inhaling citric acid from DeVilbiss 40 hand-held nebulisers (citric acid concentrations of 10-3000 mM). ⋯ The coefficient of repeatability for the hand-held method was 0.40 log mM. Administering citric acid from DeVilbiss 40 hand-held nebulisers offers a rapid, portable, and reproducible cough challenge in healthy volunteers. The results correlate well with an existing Mefar dosimeter challenge, but give two to three times greater cough thresholds.
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Pulm Pharmacol Ther · Jan 2005
Effect of histamine, albuterol and deep inspiration on airway and lung tissue mechanics in cynomolgus monkeys.
Forced oscillation is a technique that has been used to measure airway and lung tissue impedance. To evaluate airway and lung tissue impedance in a colony of cynomolgus monkeys housed at Schering-Plough Research Institute, a forced oscillation technique was used to measure Newtonian resistance (R(N)), tissue damping (G), tissue elastance (H) and lung hysteresivity (eta). Functional residual capacity (FRC) was also measured to correlate the lung impedance data with FRC. ⋯ Aerosolized albuterol (0.003-3mg/ml) produced a concentration-dependent reversal of the increases in R(N), G, H and eta induced by histamine with the greatest reversal seen on R(N). Deep inspiration, performed after the aerosolized albuterol exposure, also reversed the histamine-induced changes in R(N), G, and H with the complete reversal seen on the increase in H. These results demonstrate that significant correlations exist between airway and lung tissue impedance and FRC and that airway and lung tissue mechanics contribute significantly to inherent bronchoconstrictor reactivity and to the bronchodilator response to a beta-adrenergic agonist and deep inspiration in cynomolgus monkeys.
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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.
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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
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.