Prevention of Exercise-Induced Bronchoconstriction by Inhaled Frusemide

Bianco, S.; Robuschi, M.; Vaghi, Adriano; Pasargiklian, M

doi:10.1016/s0140-6736(88)92540-8

Cited by 219 publications

(109 citation statements)

References 9 publications

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“…Furosemide produced relaxation in human fetal airway after constriction by the neurotransmitter, acetylcholine, as well as by the inflammatory mediator, LTD 4 . Elevated levels of LTD 4 , Figure 1.…”

Section: Discussionmentioning

confidence: 93%

“…1A), showed significant decreases in isometric tension in response to a single 300 M dose of furosemide (n ϭ 9) compared with saline controls (n ϭ 6; p Ͻ 0.05). Airway rings constricted with an inflammatory mediator, LTD 4 (Fig. 1B), also demonstrated significant decreases in isometric tension in response to furosemide (n ϭ 6) compared with controls (n ϭ 6; p Ͻ 0.05).…”

Section: Human Fetal Airwaymentioning

confidence: 90%

“…The rings were constricted with the EC 50 concentration of acetylcholine, then 300 M furosemide (American Regent Laboratories, Inc, Shirley, NY, U.S.A.) or an equal volume of saline control was added. In a separate set of experiments, rings were constricted with EC 50 for LTD 4 (BIOMOL Research Laboratories, Plymouth Meeting, PA, U.S.A.), followed by addition of 300 M furosemide or saline control. The tissues were dried at 59°C for 5 d, then weighed.…”

Section: Methodsmentioning

confidence: 99%

“…Statistics were performed using the Sigmastat statistical package (Jandel Scientific, San Rafael, CA, U.S.A.). Relaxation is expressed as a percent decrease in isometric tension for the human fetal airway, relative to the prior constriction to acetylcholine or to LTD 4 . Human fetal airway responses to furosemide were compared with controls by unpaired t test.…”

Section: Methodsmentioning

confidence: 99%

“…Isometric tension changes were measured in human fetal (11)(12)(13)(14)(15)(16) wk) trachea and mainstem bronchus rings exposed to furosemide (300 M) or saline after acetylcholine or leukotriene D 4 constriction. Significant decreases in isometric tension to furosemide were demonstrated after constriction with acetylcholine or leukotriene D 4 . To examine the site of effect and mimic aerosolized and systemic administration, furosemide (3-300 M) and bumetanide (0.3-30 M) were applied separately to epithelial and adventitial surfaces of newborn mouse airways.…”

mentioning

confidence: 99%

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Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways

2001

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This study was designed to test the hypotheses that furosemide directly causes relaxation in human fetal airway and that delivery of loop diuretics to either the adventitial or epithelial surface of newborn mouse airway results in equivalent relaxation. Isometric tension changes were measured in human fetal (11-16 wk) trachea and mainstem bronchus rings exposed to furosemide (300 M) or saline after acetylcholine or leukotriene D 4 constriction. Significant decreases in isometric tension to furosemide were demonstrated after constriction with acetylcholine or leukotriene D 4 . To examine the site of effect and mimic aerosolized and systemic administration, furosemide (3-300 M) and bumetanide (0.3-30 M) were applied separately to epithelial and adventitial surfaces of newborn mouse airways. No differences in airway diameter changes to epithelial or adventitial furosemide or bumetanide were observed, but a 10-fold difference in potency was found. In summary, human fetal airway relaxed to furosemide when constricted with either neurotransmitter or inflammatory mediator in vitro. Further, no differences in relaxation to equimolar epithelial and adventitial furosemide were observed in isolated newborn mouse airway. Taken together, this provides evidence that furosemide has a direct, nonepithelial-dependent effect on airway smooth muscle tone. Systemically administered furosemide improves pulmonary mechanics and gas exchange in infants with chronic lung disease independent of its diuretic effects (1, 2). Studies demonstrating a reduction of bronchoconstrictive responses in pediatric (3) and adult asthmatics (4, 5) with aerosolized furosemide further support the notion that a nondiuretic effect may produce improvements in pulmonary function. Indeed, the in vitro airway relaxation to furosemide that is observed in animal models (6 -8) suggests that there may be a direct effect on airway smooth muscle.However, a bronchodilatory response to inhaled furosemide is not consistently observed in infants with chronic lung disease (9, 10). Although aerosolized administration of furosemide could minimize systemic effects while producing localized bronchodilation, it is not widely accepted that inhaled furosemide has therapeutic efficacy during acute bronchoconstriction. Taken together, it is presently unclear whether these inconsistent results are because of species differences or inadequate concentrations of drug that reach the airway with aerosolized treatment, or because furosemide in fact does not act via a mechanism of direct airway smooth muscle relaxation (11). Therefore, the potential relevance of previous in vitro animal findings requires validation by the study of human airway response (12), with the first objective to test the hypothesis that furosemide causes direct relaxation of human fetal airway.In addition to demonstrating a direct relaxing effect on airway smooth muscle, further support for the bronchodilatory response to furosemide via aerosolization would require evidence that mechanisms can be activated from th...

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Section: Discussionmentioning

confidence: 93%

Section: Human Fetal Airwaymentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways

2001

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Asthma and Sports

Orenstein¹

2007

The Young Athlete

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Air Quality and Temperature Effects on Exercise‐Induced Bronchoconstriction

Rundell

Anderson

Sue‐Chu

et al. 2015

Comprehensive Physiology

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Exercise-induced bronchoconstriction (EIB) is exaggerated constriction of the airways usually soon after cessation of exercise. This is most often a response to airway dehydration in the presence of airway inflammation in a person with a responsive bronchial smooth muscle. Severity is related to water content of inspired air and level of ventilation achieved and sustained. Repetitive hyperpnea of dry air during training is associated with airway inflammatory changes and remodeling. A response during exercise that is related to pollution or allergen is considered EIB. Ozone and particulate matter are the most widespread pollutants of concern for the exercising population; chronic exposure can lead to new-onset asthma and EIB. Freshly generated emissions particulate matter less than 100 nm is most harmful. Evidence for acute and long-term effects from exercise while inhaling high levels of ozone and/or particulate matter exists. Much evidence supports a relationship between development of airway disorders and exercise in the chlorinated pool. Swimmers typically do not respond in the pool; however, a large percentage responds to a dry air exercise challenge. Studies support oxidative stress mediated pathology for pollutants and a more severe acute response occurs in the asthmatic. Winter sport athletes and swimmers have a higher prevalence of EIB, asthma and airway remodeling than other athletes and the general population. Because of fossil fuel powered ice resurfacers in ice rinks, ice rink athletes have shown high rates of EIB and asthma. For the athlete training in the urban environment, training during low traffic hours and in low traffic areas is suggested.

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Prevention of Exercise-Induced Bronchoconstriction by Inhaled Frusemide

Cited by 219 publications

References 9 publications

Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways

Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways

Asthma and Sports

Air Quality and Temperature Effects on Exercise‐Induced Bronchoconstriction

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