Indomethacin Blocks Airway Tolerance to Repetitive Exercise but Not to Eucapnic Hyperpnea in Asthmatic Subjects

Margolskee, Dorothy J.; Bigby, Barbara G.; Boushey, Homer A.

doi:10.1164/ajrccm/137.4.842

Cited by 53 publications

(23 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be further supported by two of the subjects, Nos 6 and 8, whose EIA was not blocked by the warm-humid conditions during Ch1 indomethacin trials while they had a mean negative protection index of 5% following Ch2 indomethacin trials. This may explain why indomethacin does not appear to be effective in blocking the refractory period for hyperventilation-induced asthma [21]. Similar results could occur if the synthesis of prostaglandin was not effectively inhibited, however this is unlikely at the doses chosen [22].…”

Section: Discussionmentioning

confidence: 97%

The effects of indomethacin on refractoriness following exercise both with and without a bronchoconstrictor response

Wilson¹,

Bar‐Or²,

O'Byrne³

1994

Eur Respir J

View full text Add to dashboard Cite

T Th he e e ef ff fe ec ct ts s o of f i in nd do om me et th ha ac ci in n o on n r re ef fr ra ac ct to or ri in ne es ss s f fo ol ll lo ow wi in ng g e ex xe er rc ci is se e b bo ot th h w wi it th h a an nd d w wi it th ho ou ut t a a b br ro on nc ch ho oc co on ns st tr ri ic ct to or r r re es sp po on ns se e ABSTRACT: Repeated exercise tests demonstrate refractoriness to the development of exercise-induced asthma (EIA). It is unclear whether it is the initial exercise per se or the resulting bronchoconstriction that causes the attenuated response to the second exercise challenge. This study was designed to determine whether the reported blocking of the refractory period by indomethacin requires a significant bronchoconstriction following the primary exercise challenge.Thirteen asthmatic teenagers (aged 12-16 yrs) were tested on four visits. Each visit included two 7 min treadmill exercise challenges at 80% maximum heart rate, separated by a 30 min rest. Conditions for the second exercise challenge (Ch2) were always thermoneutral (20-22°C and 25-35% relative humidity (RH); whilst challenge one (Ch1) was completed twice in thermoneutral and twice in warm-humid breathing conditions (33-35°C and 90-95% RH). A pretreatment for 3 days in a double-blind design with either placebo or indomethacin was completed. Forced expiratory volume in one second (FEV 1 ) was measured before and repeatedly following each challenge. The % fall in FEV 1 following Ch1 of the placebo thermoneutral trial was taken as reference. "Percent protection" at each visit was expressed as the decrease in EIA following Ch2, compared to reference.Warm-humid breathing reduced the EIA post Ch1 by 75%, whilst providing similar protection to thermoneutral conditions. Indomethacin had no significant effect on EIA after Ch1, but reduced "percent protection" for both warm-humid (from 67 to 16%) and thermoneutral (from 70 to 26%) conditions.The data indicate that inhibitory prostaglandins play a major role in EIA refractoriness and suggest that the release of these prostaglandins is initiated by some exercise factor, independent of the development of bronchoconstriction.

show abstract

Section: Discussionmentioning

confidence: 97%

The effects of indomethacin on refractoriness following exercise both with and without a bronchoconstrictor response

Wilson¹,

Bar‐Or²,

O'Byrne³

1994

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Attenuation of airway obstruction with multiple exercise challenges has been carefully described in the literature, and large interindividual variability has been reported [5,10,12,13,18,21,23,26,28,32,33]. Many factors are known that may contribute to the variability of exercise-induced refractoriness between subjects with bronchial asthma.…”

Section: Discussionmentioning

confidence: 99%

“…Refractoriness has been shown to be influenced by a variety of factors such as type of exercise [35], time between serial tests [10], cooling and drying of airways [34], release of mediators [23], and, more recently, the responsivity of bronchial microcirculation [13].…”

Section: Introductionmentioning

confidence: 99%

Influence of exercise-induced bronchoconstriction on refractoriness

Nowak

Jörres

Magnussen

1992

Lung

View full text Add to dashboard Cite

This study determined if the degree of exercise-induced refractoriness is determined by the degree of exercise-induced bronchoconstriction. In 12 patients with exercise-induced asthma (mean [SEM] age 27 [3] years) we performed 2 pairs of exercise challenges 45 min apart at different work loads on 2 days. Mean (SEM) total respiratory heat loss during low and high work loads was 3.4 (0.2) and 5.1 (0.4) kcal, respectively. After the first and second exercise challenge at low work loads, mean (SEM) SRaw increased by 107 (15) and 73 (16)% (n.s.), as compared to 361 (40) and 98 (25)% at high work loads (p less than 0.005). We found a correlation between the initial airways response and refractoriness (r = 0.58, p less than 0.005) and conclude that the degree of refractoriness after exercise-induced bronchoconstriction is in part dependent on the severity of exercise-induced bronchoconstriction.

show abstract

“…The presence of a refractory period appears to be independent of the magnitude of obstruction provoked by the first challenge [129], and inversely related to the time separating any two consecutive challenges [31]. Studies examining the effect of indomethacin in man [43,44] and sensitized rabbit [17] suggest that refractoriness to repeated bouts of exercise and hyperpnoea, respectively, is dependent on the generation of bronchodilating prostaglandins. However, indomethacin appears to be ineffective in blocking refractoriness to hyperpnoea in asthmatic subjects [44].…”

Section: The Refractory Periodmentioning

confidence: 99%

“…Studies examining the effect of indomethacin in man [43,44] and sensitized rabbit [17] suggest that refractoriness to repeated bouts of exercise and hyperpnoea, respectively, is dependent on the generation of bronchodilating prostaglandins. However, indomethacin appears to be ineffective in blocking refractoriness to hyperpnoea in asthmatic subjects [44]. This is one of the few inconsistencies that distinguish exercise-from hyperpnoea-induced responses in man; the other being the ability of antihistamine to inhibit exercise-but not hyperpnoea-induced airway obstruction [87].…”

Section: The Refractory Periodmentioning

confidence: 99%

Models and mechanisms of exercise-induced asthma

An¹

1995

Eur Respir J

View full text Add to dashboard Cite

M Mo od de el ls s a an nd d m me ec ch ha an ni is sm ms s o of f e ex xe er rc ci is se e--i in nd du uc ce ed d a as st th hm ma a A.N. FreedModels and mechanisms of exercise-induced asthma. A.N. Freed. ERS Journals Ltd 1995. ABSTRACT: Airflow-induced bronchoconstriction (AIB) in mammals can be broadly categorized as either vagal-dependent or vagal-independent. Among mammals, rabbits and cats belong to the former and guinea-pigs belong to the latter categories. Although insufficient data are available to classify monkeys, dogs and man appear to occupy the middle ground in which a small but significant parasympathetic component modulates airflow-induced bronchoconstriction. The fact that vagal activity can only partially account for airflow-induced bronchoconstriction in some asthmatic subjects suggests that vagal-dependent models may be of limited value in studying the human condition, but should prove valuable in elucidating the parasympathetic component of this mechanism. Although airflow-induced bronchoconstriction appears to be remarkably similar in guinea-pigs, dogs and humans, there are important differences concerning the potential role of specific mediators in producing airflow limitation. Concordant data from animal models and man suggest that: 1) airflow-induced bronchoconstriction is a basic mammalian response to airway desiccation; 2) airway drying stimulates and cooling inhibits this response; 3) hyperpnoea with dry air may damage the bronchial mucosa and contribute to this response; 4) biochemical mediators contribute to the development of this response; 5) vascular engorgement and airway oedema do not appear to be the primary effectors of this response, and in fact may antagonize it; 6) airway smooth muscle constriction is involved in the production of airflow-induced bronchoconstriction, and airway oedema may enhance its effect; and 7) airway and vascular responses to dehydration may protect against acute dry air-induced mucosal injury.Finally, although one must be cautious in extrapolating results from animals to humans, the similarities that do exist suggest that the investigation of airflow-induced bronchoconstriction in carefully selected animal models will continue to provide new insights concerning its development in humans.

show abstract

Indomethacin Blocks Airway Tolerance to Repetitive Exercise but Not to Eucapnic Hyperpnea in Asthmatic Subjects

Cited by 53 publications

References 13 publications

The effects of indomethacin on refractoriness following exercise both with and without a bronchoconstrictor response

The effects of indomethacin on refractoriness following exercise both with and without a bronchoconstrictor response

Influence of exercise-induced bronchoconstriction on refractoriness

Models and mechanisms of exercise-induced asthma

Contact Info

Product

Resources

About