Models and mechanisms of exercise-induced asthma

An, Freed

doi:10.1183/09031936.95.08101770

Cited by 69 publications

(53 citation statements)

References 99 publications

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“…Previous studies have demonstrated hyperosmolar insults may result in increased airway responsiveness in rabbits (25) and increased vascular permeability (and possibly neuropeptide release) in rats (26). In addition, intracellular fluid loss in lung epithelial cells (as could occur after instillation of the rats with a hyperosmolar salt solution) is thought to contribute to exercise-induced bronchoconstriction, late-phase asthmatic responses (27), and increased chemokine expression in airway epithelial cells (28).…”

Section: Discussionmentioning

confidence: 99%

Acute pulmonary toxicity of particulate matter filter extracts in rats: coherence with epidemiologic studies in Utah Valley residents.

Dye

Lehmann

McGee

et al. 2001

Environ Health Perspect

130

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Epidemiologic reports by C.A. Pope III et. al. demonstrated that in the Utah Valley, closure of an open-hearth steel mill over the winter of 1987 was associated with reductions in respiratory disease and related hospital admissions in valley residents. To better examine the relationship between plant-associated changes in ambient particulate matter (PM) and respiratory health effects, we obtained total suspended particulate filters originally collected near the steel mill during the winter of 1986 (before closure), 1987 (during closure), and 1988 (after plant reopening). PM subcomponents were water-extracted from these filters and Sprague-Dawley rats were intratracheally instilled with equivalent masses of extract. Data indicated that 24 hr later, rats exposed to 1986 or 1988 extracts developed significant pulmonary injury and neutrophilic inflammation. Additionally, 50% of rats exposed to 1986 or 1988 extracts had increased airway responsiveness to acetylcholine, compared to 17 and 25% of rats exposed to saline or the 1987 extract, respectively. By 96 hr, these effects were largely resolved except for increases in lung lavage fluid neutrophils and lymphocytes in 1986 extract-exposed rats. Analogous effects were observed with lung histologic assessment. Extract analysis using inductively coupled plasma-mass spectroscopy demonstrated in all three extracts nearly 70% of the mass appeared to be sodium-based salts derived from the glass filter matrix. Interestingly, relative to the 1987 extract, the 1986/1988 extracts contained more sulfate, cationic salts (i.e., calcium, potassium, magnesium), and certain metals (i.e., copper, zinc, iron, lead, strontium, arsenic, manganese, nickel). Although total metal content was (3/4) 1% of the extracts by mass, the greater quantity detected in the 1986 and 1988 extracts suggests metals may be important determinants of the pulmonary toxicity observed. In conclusion, the pulmonary effects induced by exposure of rats to water-based extracts of local ambient PM filters were in good accord with the cross-sectional epidemiologic reports of adverse respiratory health effects in Utah Valley residents.

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Section: Discussionmentioning

confidence: 99%

Acute pulmonary toxicity of particulate matter filter extracts in rats: coherence with epidemiologic studies in Utah Valley residents.

Dye

Lehmann

McGee

et al. 2001

Environ Health Perspect

130

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“…The urinary excretion (mean±SE) of 9α,11β-PGF 2 Eur Respir J 1998;12: 345-350. and N τ -methylhistamine, was measured before and after exercise challenge in a group of asthmatics with a history of EIB. The major cyclooxygenase product of mast cells PGD 2 , is metabolized in the lung, via the action of the reduced nicotinamide adeine dinucleotide phosphate (NADPH)-dependent enzyme 11-ketoreductase to 9α, 11β-PGF 2 , and is excreted intact into the urine [24].…”

Section: Aamentioning

confidence: 99%

“…It is characterized by transient airflow obstruction resulting in a Š15% decrease in forced expiratory volume in one second (FEV1) following 5-8 min of exercise. The fall in FEV1 reaches a maximum approximately 10 min after exercise and gradually normalizes over the next hour [2]. The precise pathophysiology of EIB remains unclear, although it is widely accepted that during exercise the upper airways are unable to adequately warm and humidify the increased volumes of inspired air.…”

mentioning

confidence: 99%

Evidence for mast cell activation during exercise-induced bronchoconstriction

O’Sullivan¹,

Roquet²,

Dahlén³

et al. 1998

Eur Respir J

126

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Exercise-induced bronchoconstriction (EIB) is thought to occur in 70-80% of asthmatics, most commonly amongst those with moderate-to-severe airway hyperresponsiveness [1]. It is characterized by transient airflow obstruction resulting in a Š15% decrease in forced expiratory volume in one second (FEV1) following 5-8 min of exercise. The fall in FEV1 reaches a maximum approximately 10 min after exercise and gradually normalizes over the next hour [2]. The precise pathophysiology of EIB remains unclear, although it is widely accepted that during exercise the upper airways are unable to adequately warm and humidify the increased volumes of inspired air. This results in airway cooling and increased airway fluid osmolality in the lower airways [3,4]. One hypothesis suggests that hyperosmolar triggering of mast cells and possibly other inflammatory cells results in the release of bronchoconstricting mediators, e.g. cysteinyl-leukotrienes (cys-LTs), histamine and prostaglandin (PG)D 2 [5].Previous indications for the participation of mast cell mediators in the pathogenesis of EIB are based on pharmacological data. For example, disodium cromoglycate (DSCG), a drug which stabilizes mast cell membranes, is effective in blunting exercise-induced asthma [6,7]. Pretreatment with a number of H 1 receptor antagonists has been shown to attenuate EIB [8][9][10]; however, the degree of protection afforded by this class of drugs has been modest. More recently, studies employing leukotriene receptor antagonists [11,12] and biosynthesis inhibitors [13] have implicated leukotrienes in the airway bronchoconstrictor response to exercise.The direct approach of measuring mast cell mediator release in response to exercise challenge has yielded ambiguous results. Some studies have reported an elevation in plasma and whole blood histamine concentrations following EIB [14,15], while other studies have failed to verify those findings [16,17]. Apart from the methodological problems encountered when sampling plasma histamine [18] and its short half-life in the circulation, approximately 1 min [19], it has been suggested that elevations in plasma histamine mainly reflect the basophilia which normally accompanies exercise [20]. Increases in the levels of tryptase and PGD 2 , both specific mast cell markers, have been detected in nasal lavage following nasal provocation with cold dry air [21], but not after exercise [22,23].The purpose of this study was to provide evidence to establish mast cell activation as a feature of EIB. To this end, a combination of mast cell markers, 9α,11β-PGF 2 Sullivan, A. Roquet, B. Dahlén, F. Larsen, A. Eklund, M. Kumlin, P.M. O'Byrne, S-E. Dahlén. ©ERS Journals 1998. ABSTRACT: Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Evidence for mast cell activation during exercise-induced bronchoconstriction....

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“…23 It causes transient dehydration of the bronchial mucosa due to the low water content of the air, leading to a hyperosmolarity of the mucosal fluid of the airway surface lining, which may damage bronchial epithelial cells. 1,14 The hyperosmolarity of the mucosal fluid alters the osmotic gradient throughout the mucosa and sub-mucosa, resulting in the activation and degranulation of mast cells in the sub-mucosa. Degranulation of these mast cells results in the release of pro-inflammatory mediators and the activation of cholinergic receptors.…”

Section: Dry Cold Airmentioning

confidence: 99%