Tracheal mucous transport in experimental canine asthma

Wanner, Adam; Zarzecki, S.; Hirsch, John D.; Epstein, Scott K.

doi:10.1152/jappl.1975.39.6.950

Cited by 78 publications

(9 citation statements)

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“…It is only recently that the aerosol route of administration has been explored with this compound. For example, it has been shown that an aerosol formulation of FPL before and during antigen challenge of dogs [9] or ragweed sensitive human patients 110], prevented antigen-induced decreases in tracheal mucous velocity. This response was shown to be indepen dent of anaphylactic bronchoconstriction, however.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic properties of FPL 55712 administered by aerosol

O’Donnell

Welton

1984

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FPL 55712 was investigated by the aerosol route of administration for efficacy at protecting against leukotriene-induced bronchoconstrictions in guinea pigs and for mediator release inhibitory activity in passively sensitized rats. In the studies to investigate leukotriene antagonism; anesthetized, spontaneously breathing guinea pigs were pretreated with propranolol and were exposed via tracheal cannula to aerosols generated by a Monaghan nebulizer. Subsequently, the animals were artificially ventilated and challenged with LTD4 or LTE4 (25 micrograms/kg, i.v.). FPL 55712 produced a concentration-dependent inhibition of LTD4 and LTE4-induced bronchoconstriction (IC50's 0.5% and 0.8%, respectively). Although the biologic half-life of FPL 55712, administered intravenously, was very short (1.7 minutes against LTD4 and 1.2 minutes against LTE4) after aerosol administration the biological half-life was surprisingly long (120 minutes against LTD4 and 90 minutes against LTE4). Aerosolized FPL 55712 also possessed weak antiallergic activity in comparison to disodium cromoglycate when measured as an inhibitor of IgE-mediated anaphylactic bronchoconstriction in rats (IC50's of 2.0% and 0.01%, respectively). Thus, these studies demonstrate that, when administered by aerosol, FPL 55712 is effective at protecting against leukotriene-induced bronchoconstrictions, exhibits a long duration of action and also possesses weak antiallergic activity.

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Section: Introductionmentioning

confidence: 99%

Pharmacologic properties of FPL 55712 administered by aerosol

O’Donnell

Welton

1984

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“…larger doses of ipratropium bro mide might have produced a fall in tracheal mucous velocity. Nevertheless, the doses of the drugs employed are those recommended from clinical studies which presumably would result in a similar degree of bronchodilatation in patients [12], Thus, these studies suggest that ipratropium bromide in thera peutic doses ought not to depress mucociliary transport.…”

Section: Discussionmentioning

confidence: 89%

Effects of Nebulized Ipratropium Bromide and Atropine Sulfate on Tracheal Mucous Velocity and Lung Mechanics in Anesthetized Dogs

Sackner¹,

Chapman²,

Dougherty³

1977

Respiration

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Ipratropium bromide is an anticholinergic agent, which, when administered by inhalation, is an effective bronchodilator in patients with chronic bronchitis and bronchial asthma. Since other parasympatholytic agents such as atropine and hyoscine depress mucociliary clearance, a potentially deleterious side effect, ipratropium bromide was tested for its effect on this function. We found that ipratropium bromide in therapeutic doses for humans, did not slow tracheal mucous velocity in anesthetized dogs.

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“…Using an inhalation challenge model that used ragweed extract, Mezey et al [5] showed impairment in mucus transport in asymptomatic ragweed‐sensitive asthmatics both immediately and 1 h after challenge. Allergen challenge in animal models of allergic airways disease also shows decreased TMV for several days [6, 7, 30] with no clear linkage to the time course of bronchoconstriction in the animals. Thus, the observations presented in this report are consistent with earlier animal and human studies as well as those seen in naturally occurring disease.…”

Section: Discussionmentioning

confidence: 99%

Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics

Bennett

Herbst

Alexis

et al. 2011

Clin Experimental Allergy

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Background Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity. Objective The purpose of this study was to determine the effect of inhaled house dust mite challenge on regional deposition of inhaled particles and mucociliary clearance (MCC) in allergic asthmatics. Methods We used gamma scintigraphy (inhalation of 99mTc -sulfur colloid particles) to measure regional particle deposition and MCC in allergic asthmatics (n=12) 4hr following an inhaled dust mite allergen challenge (Dermatophagoides farinae extract; PDmax = fall in FEV1 of 10%) for comparison to baseline non-challenge measures. Results In responders (n=9 PDmax dose), lung function returned to pre-challenge values by 3 hours but was significantly decreased at 6 and 24 hours in 3 of the responders (i.e. late phase response) and induced sputum eosinophils were increased at 24 hours post-challenge (p < 0.05). Responders showed enhanced bronchial airway deposition of inhaled particles (p < 0.05) and slowed clearance from the central lung zone (p < 0.01) at 4 hrs post-challenge compared to baseline (no allergen challenge) that was predicted by the PDmax allergen concentration (r = − 0.70, p < 0.05). The fall in lung function at 24 hours post challenge correlated with reduced MCC from the central lung zone (r = − 0.78, p < 0.02) and PDmax. Non-responders (n=3) had no change in lung function, regional deposition or MCC post-challenge vs. baseline. Conclusions and clinical relevance These data suggest that regional deposition and clearance of inhaled particles may be sensitive for detecting mild airway obstruction associated with early and late-phase allergen-induced effects on mucus secretions. The study was listed on clinicaltrials.gov (NCT00448851).

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Tracheal mucous transport in experimental canine asthma

Cited by 78 publications

References 0 publications

Pharmacologic properties of FPL 55712 administered by aerosol

Pharmacologic properties of FPL 55712 administered by aerosol

Effects of Nebulized Ipratropium Bromide and Atropine Sulfate on Tracheal Mucous Velocity and Lung Mechanics in Anesthetized Dogs

Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics

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