Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jan 2002
Randomized Controlled Trial Clinical TrialEffects of inhaled furosemide on CO(2) ventilatory responsiveness in humans.
We previously showed that inhaled furosemide improves experimentally induced dyspnea. In order to test the possibility that inhaled furosemide may alter the CO(2) chemosensitivity and thereby reduce the dyspneic sensation, the effect of inhaled furosemide on CO(2) chemosensitivity was evaluated with a double-blinded, randomized crossover design in 10 healthy subjects. ⋯ Our results showed that (1) inhaled furosemide does not affect the breathing patterns of resting breathing, (2) inhaled furosemide does not affect the slope and intercept of the CO(2) response curve, regardless of whether the CO(2) chemosensitivity is measured by the steady-state technique or rebreathing technique and (3) inhaled furosemide improves the dyspneic sensation produced during hypercapnic hyperpnea. These results suggest that the mechanism of the improvement of dyspnea by inhaling furosemide is not associated with the decrease in the ventilatory drive to CO(2).
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The mucus lining of the respiratory tract originates from products of secretory cells interspersed among mucosal cells or within submucosal glands and protects the underlying mucosa from dehydration. Current understanding is that the lining is a two-fluid model in which the upper layer is a viscoelastic gel (mucus, cross-linked glycoproteins) that overlies a sol layer (serous). Thus mucus propelled by ciliary beating, flows above the sol layer and contains sloughed cells and xenobiotic materials that come into contact with it. ⋯ If high velocity of expiratory airflow is preserved then even with chronic exposure to respiratory irritants and cigarette smoke, mucus clearance remains effective due to cough and two-phase, gas-liquid interactions. However, in patients with advanced airway obstruction and incapable of generating forceful expiratory flows, cough and shearing are ineffective and mucociliary clearance is disparate with markedly slowed mucus layer transport within central airways. Mucolytic therapy for patients with advanced airway obstruction improves ventilation and reduces the frequency of exacerbation.
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Pulm Pharmacol Ther · Jan 2002
ReviewDelta-opioid receptor antagonists as a new concept for central acting antitussive drugs.
Our recent findings indicated that mu- and kappa-opioid receptors enhance each other's antitussive processes. However, delta-opioid receptors played an inhibitory role in antitussive processes mediated by the mu- and kappa-opioid receptors. ⋯ These delta-opioid receptor-mediated antitussive effects may be mediated by the antagonism of delta(1)-, but not delta(2)-opioid receptors. In this review, we study the possibility of the delta-opioid receptor antagonist as a new concept for central acting antitussive drugs.
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Pulm Pharmacol Ther · Jan 2002
Comparative Study Clinical TrialA widely available method for the assessment of aerosol delivery in cystic fibrosis.
Whilst nebulisers are commonly used in the treatment of cystic fibrosis (CF), nebulised aerosol lung deposition in individual patients is not routinely assessed in clinical practice. The present study was designed to evaluate whether a comparative measurement of aerosol lung deposition from nebulisers using a widely available scintigraphic method could be employed to assist the selection of the best system for individual patients. Lung deposition of the radiolabelled aerosol from the Pari LC Plus (Pari Medical Ltd) nebuliser and the HaloLite Adaptive Aerosol Delivery (AAD) system (Profile Therapeutics Ltd) was measured using planar scintigraphy in 10 healthy volunteers and 6 CF patients. ⋯ The aerosol deposition from HaloLite AAD had higher central distribution than that obtained with the Pari LC Plus. The overall intersubject variability of the delivered dose was 56% with Pari LC Plus and 24% with HaloLite AAD (P<0.05). The measurement of aerosol deposition from nebulisers can be performed using a simple and widely available methodology, and may improve nebuliser selection in CF patients.