(Chest 1994; 106:244-49) [PGE.
(Chest 1994; 106:244-49)
[PGE.sub.2]=prostaglandin [Esub2];
[PGF.sub.2[alpha]]=prostaglandin [F.sub.2[alpha]]
In 1988 Bianco and colleagues(1) not past nor futureed the first data indicating that inhaled furosemide has a protective import in exercise-induced bronchoconstriction. Since this seminal article, there has been a growing interest in the issue of furosemide on airway physiology and pathophysiology. The greatest insights into the mechanisms of action of furosemide have been obtained from studies in the kidney. Since the major propos gradation of action of furosemide in this design is on ion transport in renal epithelial small cavitys it is tempting to speculate that the site of action of furosemide in asthma may be the airway epithelial small room This hypothesis is intriguing and may provide of recent origin insight into the biology of asthma because, at at hand there are few data suggesting that epithelial (ion) transport plays a major part in asthma. The purpose of this short review is to summarize data published since 1988 forward the protective effect of bend diuretics against bronchial hyperresponsiveness in human asthma and discuss possible mechanisms for this protective effect
PROTECTIVE event OF FUROSEMIDE IN ASTHMA
Pretreatment of asthmatic controls with inhaled furosemide has been shown to have a protective efficiency against bronchial responses to indirectly acting bronchial provocants of that kind as exercise or isocapnic hyperventilation,(1)(2)(3)(4)(5)(6) inhalation of nebulized distilled water,(7)(8)(9) adenosine 5'-monophosphate,(10)(11) inhaled lysine aspirin,(12) sodium metabisulfite,(13)(14) and inhaled allergens.(15)(16) by conversion inhaled furosemide has, at best, a moderate tenor against pharmacologic challenges such as histamine- and methacholine-induced bronchoconstriction.(3)(10)(11)(13)(17) The protective purport of furosemide against physiologic challenges is dose dependent(1) has marked intersubject variability, and have the appearances to be more marked than that of other link diuretics,(9)(11)(14) although this should be qualified in view of the small number of make subordinates studied and the single doses of diuretics used.
MECHANISMS OF THE PROTECTIVE tenor OF FUROSEMIDE
The mechanisms of the protective event of furosemide in asthma are poorly understood and may be multifactorial. The profile of activity of furosemide is to a high degree similar to that of cromoglycate and indicates that its protective effect is not fit to a direct effect forward airway smooth muscle and is best explained by means of inhibition of the release of paracrine mediators evok on physiologic stimuli.
Indeed, furosemide is not a bronchodilator agent. In vitro studies have shown that furosemide does not inhibit acetylcholine-, histamine-, or tachykinin-induced contraction of airway glossy muscle in vitro.(18)(19) Most studies in asthmatic make liables have shown that it has little, if any, force on baseline lung function,(1)(3)(4)(7)(10)(11)(12)(13)(15) although a slight incrase in [FEVsub1] has been raise in some studies with high doses of inhaled furosemide.(2)(5)(20)
Furosemide probably has about effect on airway nerves, if it be not that whether this effect plays a part in its protective effect in human asthma is debatable. In vitro, furosemide inhibits the two cholinergic and nonadrenergic, noncholinergic contraction of airway flat muscle. This suggests furosemide inhibits the release of tachykinins on C-fibers, an effect which was, in this preparation, independent of the neighborhood of epithelium.(18) Furosemide also inhibits neural function in a variety of hypothesiss outside the lung, but there are no direct recordings of potential issues of furosemide on neural traffic in afferent firmness fibers innervating the lungs and airways.(21) Studies forward cough induced by different stimuli have attempted to demonstrate an inhibitory drift of furosemide on airway endurances in man. Inhaled furosemide restores the cough response to nebulized low-chloride, hypoosmolar solutions in normal enslaves and, to a lesser bulk in asthmatic subjects,(21)(22)(23) but has no power on both capsaicin-induced(22) and metabisulfite-induced cough(23) Cough owing to inhalation of nebulized hypoosmolar solutions is owing to the stimulation of afferent pluck endings in human airways since it is abolished through administration of the aerosol to the central airways in lung transplant recipients.(24) There is circumstantial evidence, however, that the prevention of low-chloride-induced cough is not mediated from a direct inhibitory effect of furosemide forward nerve endings in the airways. First, inhaled furosemide does not thwart capsaicin-induced cough, which involves release of tachykinins by the agency of C-fiber endings, at least in the guinea pig.(25) inferior the protective effect of furosemide against cough induced through nebulized low-chloride solutions may be befitting to modifications of the ionic composition of the microenvironment of the cough receptors(26) rather than to a direct tenor of furosemide on the fortitude endings. Whatever its mode of action, the preventive validity of acutely induced cough by way of furosemide raises two questions. First, whether the antitussive properties of furosemide also apply to spontaneous cough is unknown since we are not aware of controll therapeutic trials of furosemide in patients suffering from cough other whether this effect is relevant to the protective consequence of furosemide against bronchial challenges is debatable, since it has been shown that the rejoinders of cough and bronchoconstriction to inhaled aerosols may be mediated at separate mechanisms.(27)
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