Effect of inhaled prostaglandin E2 on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.

Pavord, Ian D.; Wisniewski, A; Mathur, Ruchi; Wahedna, I; Knox, Alan J.; Tattersfield, AE

doi:10.1136/thx.46.9.633

Cited by 66 publications

(32 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of significant correlation might be based on the fact that PGE 2 inhibits challenges that work indirectly via neural pathways or mediator release but not those that act predominantly via a direct action on airway smooth muscle, such as histamine and metacholine [2,3]. The above theory is partially supported by previous observations that PGE 2 inhibits acetylcholine release from cholinergic nerves [25], represents the ultimate mediator of airway smooth muscle relaxation produced by activation of sensory nerve inhibitory system [26], but fails to protect against bronchoconstriction induced by methacholine [27]. Another plausible explanation might be based on the theory that the inhibitory effect of PGE 2 in histamine-induced contraction appears to be concentration-dependent [28].…”

Section: Discussionmentioning

confidence: 90%

Prostaglandin E₂in the expired breath condensate of patients with asthma

Κostikas

Papatheodorou²,

Psathakis³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

Inhaled prostaglandin (PG)E 2 has been found to cause bronchodilation in asthmatics, although it does not have bronchodilative effects in normal subjects. The aim of this study was to investigate the levels of PGE 2 in the expired breath condensate of patients with asthma, the possible contribution of smoking habit to its levels and the possible relationship between PGE 2 and the degree of bronchial hyperresponsiveness, as assessed by the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20).A total of 30 mild asthmatics (15 smokers, all steroid-naive, FEV1 88¡6 (%¡SD)) and 20 healthy control subjects (10 smokers) were studied. Histamine challenge testing was performed in all subjects and the PD20 was determined.The results showed that asthmatic smokers had significantly higher values of PGE 2 compared to asthmatic nonsmokers and control subjects (40¡21 versus 14.5¡4.5 versus 11.7¡3 pg?mL -1 , respectively). Further analysis showed that PGE 2 levels were significantly higher in asthmatic smokers compared to smoker and nonsmoker controls (40¡21 versus 11.6¡2 versus 11.7¡4 pg?mL -1 , respectively). No significant difference was observed between asthmatic nonsmokers and both control smokers and control nonsmokers. No significant correlation was found between PGE 2 levels and PD20 in all groups of asthmatics, irrespective of smoking habit.In conclusion, the elevation of prostaglandin E 2 in the expired breath condensate of patients with asthma is mainly attributed to smoking habit and prostaglandin E 2 levels do not predict the degree of bronchial hyperresponsiveness. Eicosanoids are important inflammatory mediators in asthma. These lipid mediators include leukotrienes, prostaglandins and thromboxanes. Prostaglandin (PG)E 2 is a dominant cyclooxygenase product of airway epithelium and smooth muscle, and is considered to be immunomodulatory and predominantly bronchoprotective [1]. PGE 2 inhibits both exercise-induced bronchoconstriction [2] and allergen-induced early and late asthmatic responses [3], and also prevents aspirin-induced bronchoconstriction in aspirin-sensitive asthma [4]. PGE 2 has also been shown to decrease exhaled nitric oxide [5] and to prevent the induction of inducible NO synthase in certain cell lines [6]. In vitro studies have shown that PGE 2 inhibits many inflammatory events, including mast cell mediator release and eosinophil activation [7].The measurement of markers in the expired breath condensate (EBC) has proven to be a useful noninvasive method for the assessment and monitoring of airway inflammation [8]. EBC is a simple, noninvasive technique for monitoring airway inflammation. It reflects abnormalities in markers obtained bronchoscopically, in sputum and in exhaled air [8]. Measurement of PGE 2 in EBC of asthmatic patients, when compared to normal subjects, has not shown any significant differences [9,10]. However, recent evidence suggests that cigarette smoke stimulates the formation of PGE 2 in airway macrophages [11].Despi...

show abstract

Section: Discussionmentioning

confidence: 90%

Prostaglandin E₂in the expired breath condensate of patients with asthma

Κostikas

Papatheodorou²,

Psathakis³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Under different circumstances COX products may have a protective role. PGE 2 has been shown to have a potential bronchoprotective role both in vitro [6,7] and in vivo [8,9]. Studies showing that oral indomethacin inhibits refractoriness to repeated bronchoconstriction challenge suggest that endogenous PGE 2 may be involved in this protective response [10,11].…”

mentioning

confidence: 99%

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells

Range¹,

Pang²,

Holland³

et al. 2000

Eur Respir J

View full text Add to dashboard Cite

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells. S.P. Range, L. Pang, E. Holland, A.J. Knox. #ERS Journals Ltd 2000. ABSTRACT: Cyclo-oxygenase (COX) inhibitors may have a role in reducing inflammation in asthma and other pulmonary diseases. COX inhibitors have different selectivities for the two COX isoenzymes (COX 1 and COX 2) which vary between purified enzyme and intact cell preparations. The relative selectivity of COX inhibitors has not been studied in human airway cells.A number of COX inhibitors in cultured human airway cells were compared which exclusively express either COX 1 (primary degree cultured human airway smooth muscle (HASM) cells) or COX 2 (A549 pulmonary epithelial cell-line) as measured by Western blotting. COX activity was assayed by prostaglandin (PG)E 2 production following 30 min incubation with 5 mM arachidonic acid.COX activity in both cell types was similar; HASM cells 92. -5 M for aspirin. Sodium valerate had no effect in either HASM or A549 cells. The COX 2:COX 1 selectivity ratio (COX 2 IC50/COX 1 IC50) was <0.0001 for nimesulide, 0.001 for NS398, 0.03 for flurbiprofen and 1.9 for indomethacin.In conclusion the present study has shown that cyclo-oxygenase inhibitors have a range of selectivities for cyclo-oxygenase 1 and cyclo-oxygenase 2 in intact human airway cells. The relative cyclo-oxygenase 2 selectivity of N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulphonamide and nimesulide may have implications for the treatment of asthma and other inflammatory pulmonary diseases. Recent studies have suggested that cyclo-oxygenase (COX) products may be involved in the pathophysiology of several pulmonary diseases: COX products have been implicated in the inflammation found in asthmatic airways, with different COX products exerting differential effects in different situations in vivo [1±3]. Inhaled indomethacin and aspirin protect against indirect bronchoconstrictor challenges in asthma [4,5] suggesting that release of constrictor prostaglandins such as prostaglandin (PG)D 2 and PGF 2a may contribute to the mechanisms of action of these stimuli. Under different circumstances COX products may have a protective role. PGE 2 has been shown to have a potential bronchoprotective role both in vitro [6,7] and in vivo [8,9]. Studies showing that oral indomethacin inhibits refractoriness to repeated bronchoconstriction challenge suggest that endogenous PGE 2 may be involved in this protective response [10,11]. A small number of patients with asthma exhibit aspirin sensitivity, whereby oral aspirin and other COX inhibitors produce bronchochoconstriction. This bronchoconstriction can be prevented by inhalation of PGE 2 [12,13]. Collectively these studies implicate COX products in several aspects of asthma pathophysiology, but it is clear that the responses to COX inhibition depend on the inhibitor studied, the route of administration, the circumstances of use and the type of patients studied. Studies in cultured airway smooth muscle cells in vitro have sug...

show abstract

“…In two of the three separate experiments performed with PF-5212372, no apparent inhibition was observed with up to 1 M PF-5212372. This is of great interest because of the apparent bronchoprotective effects of PGE 2 in the lung (Pavord et al, 1991;Sestini et al, 1996;Szczeklik et al, 1996;Vancheri et al, 2004). If PF-5212372 is able to spare lung inhibition of PGE 2 in a clinical setting, this may be of great benefit (Mathison and Koziol, 2002).…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of an Inhibitor of Cytosolic Phospholipase A₂α for the Treatment of Asthma

Hewson¹,

Patel²,

Calzetta³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

Effect of inhaled prostaglandin E2 on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.

Cited by 66 publications

References 28 publications

Prostaglandin E₂in the expired breath condensate of patients with asthma

Prostaglandin E₂in the expired breath condensate of patients with asthma

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells

Preclinical Evaluation of an Inhibitor of Cytosolic Phospholipase A₂α for the Treatment of Asthma

Contact Info

Product

Resources

About

Effect of inhaled prostaglandin E2 on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.

Cited by 66 publications

References 28 publications

Prostaglandin E2in the expired breath condensate of patients with asthma

Prostaglandin E2in the expired breath condensate of patients with asthma

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells

Preclinical Evaluation of an Inhibitor of Cytosolic Phospholipase A2α for the Treatment of Asthma

Contact Info

Product

Resources

About

Prostaglandin E₂in the expired breath condensate of patients with asthma

Prostaglandin E₂in the expired breath condensate of patients with asthma

Preclinical Evaluation of an Inhibitor of Cytosolic Phospholipase A₂α for the Treatment of Asthma