Aspects of Bronchial Reactivity to Prostaglandins and Aspirin in Asthmatic Patients

Pasargiklian, M; Bianco, S.; Allegra, L.; Moavero, N E; Pannone, Giuseppe; Robuschi, M.; Grugni, A.

doi:10.1159/000193780

Cited by 52 publications

(23 citation statements)

References 4 publications

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“…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].…”

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confidence: 99%

Prostaglandin E₂in the expired breath condensate of patients with asthma

Κostikas

Papatheodorou²,

Psathakis³

et al. 2003

Eur Respir J

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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...

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Prostaglandin E₂in the expired breath condensate of patients with asthma

Κostikas

Papatheodorou²,

Psathakis³

et al. 2003

Eur Respir J

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“…The short duration of the protective effect of frusemide was completely missed in another study, conducted without randomization and with a period of observation limited to 30 min [9]. Although, in practice, the bronchial response to LASA is normally evaluated 60 min after challenge, often terminating the reaction with an inhaled bronchodilator [6,7,10,12,13,17], the time course of the reaction is known to be longer [6,7], and such a short observation period is unsuitable for evaluating the effect of pharmacological agents on the bronchial response to LASA.…”

Section: Discussionmentioning

confidence: 99%

“…Inhaled prostaglandin E (PGE) has previously been reported to efficiently protect against aspirin-induced asthma [12], and might act by inhibiting mediator releasing cells [35], affecting leukotriene metabolism [22,26], or simply counteracting the inhibitory effect of LASA.…”

Section: Discussionmentioning

confidence: 99%

“…Bronchial challenge with LASA was performed using two different techniques, which are progressive modifcations of the inhalation challenge originally described [10,12,13]. In a first group of patients (Study 1), we used a method of continuous aerosol generation with a jet nebulizer (Nebula, Markos, Monza, Italy) during tidal breathing inhalation for drug delivery.…”

Section: Methodsmentioning

confidence: 99%

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Time-limited protective effect of inhaled frusemide against aspirin-induced bronchoconstriction in aspirin-sensitive asthmatics

Sestini

Pieroni²,

Refini³

et al. 1994

Eur Respir J

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Inhaled frusemide effectively prevents the bronchial obstructive response to allergens and to a number of nonallergic stimuli. In most of the experimental models in which it has been tested, the protective effect of frusemide has been evaluated for only a short time after administration. In aspirin-sensitive patients, acetylsalicylic acid causes an asthmatic reaction which typically lasts for 2 h or more after exposure. We investigated the presence and duration of the protective effect of inhaled frusemide against the bronchial response to aspirin in sensitive patients, using a specific inhalation challenge with lysine acetylsalicylate (LASA). In the first study, eight subjects with aspirin-asthma underwent two bronchial challenges with a single dose of lysine acetylsalicylate administered through a jet nebulizer, after treatment with 40 mg inhaled frusemide or placebo, according to a randomized, double-blind protocol. Forced expiratory volume in one second (FEV1) was monitored for 120 min after challenge. In the second study in eight patients, the protocol was modified by the use of a dosimeter for delivery of lysine acetylsalicylate, by reducing the dose of lysine acetylsalicylate to avoid intense reactions, and by extending the follow-up to 4 h. In the first study, after placebo, FEV1 gradually decreased, reaching a maximum decrement of 39 +/- 3% at 120min. Inhaled frusemide exerted a significant protection at all time-points, although this activity appeared to decrease with time. In the second study, after placebo, inhaled lysine acetylsalicylate caused a gradual decrease in FEV1, which reached a maximum decrement at 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…None of the numerous new compounds demonstrated any real thera peutic value [18][19][20], PGU is less effective than PGE|_2 from a bronchial point of view in spite of its po tent vasodilatory activity and one of its analogues, 6-oxo-PGF|" was found by us to be devoid of any antireactive activity [21].…”

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Perspectives in the Treatment of Reversible Airway Obstruction

Pasargiklian¹,

Bianco²

1986

Respiration

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The pharmacological therapy of asthmatic syndromes is based essentially on the programmed use of disodium cromoglycate, beta-2-stimulants, antimuscarinics, theophyllines and corticosteroids. However, the continual progress being made in pathogenesis and pharmacology suggests, to an ever-increasing extent, the application of new therapeutic approaches for these diseases, some of which are fairly interesting from a speculative point of view although they are as yet of limited practical value. Calcium antagonists and alpha-blockers have a mild anti-reactive effect but this is not sufficiently potent to justify use of these products in the treatment of asthma unless there are also cardiovascular disorders for which these drugs are particularly indicated. Despite the initial promising prospects, all attempts to obtain PGE analogues of therapeutic value as antiasthmatics have proved fruitless. Research into orally active chromone derivatives has proved equally unproductive. On the other hand, certain new inhalatory chromones are decidedly more promising. Specific antagonization of mediators (histamine, prostaglandin, leukotrienes) did not produce the effect hoped for in asthma, but this was foreseeable insofar as the major pathogenic mediators are too vast in number (and no doubt there are still many more to be discovered) to allow one to conceive it possible to achieve a satisfactory therapeutic effect by merely blocking some of them. Inflammation of the bronchial wall is currently considered to be one of the basic pathogenic factors provoking the recurrence of asthma: this is proved indirectly by the potent antiasthmatic effect of corticosteroids which are the most effective anti-inflammatory agents. As regards nonsteroidal anti-inflammatory drugs (NSAID), however, matters are more complicated. Some patients (approximately 10% of all adult asthmatics) suffer from violent asthmatic attacks after taking NSAIDs. For this reason the possibility of desensitization treatment was suggested whereby gradually increasing doses of aspirin (ASA) or another NSAID are given. However, the results proved negative insofar as only the rhinitic component showed any real improvement while the asthma remained more or less unchanged. In a low percentage of asthmatic patients (less than 1 %) NSAIDs lead to sudden and extensive bronchodilatation. However, if they are administered repeatedly, this effect tends to wear off quickly: thus, the possibility of using these for long-term treatment on a regular basis can be excluded.

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Aspects of Bronchial Reactivity to Prostaglandins and Aspirin in Asthmatic Patients

Cited by 52 publications

References 4 publications

Prostaglandin E₂in the expired breath condensate of patients with asthma

Prostaglandin E₂in the expired breath condensate of patients with asthma

Time-limited protective effect of inhaled frusemide against aspirin-induced bronchoconstriction in aspirin-sensitive asthmatics

Perspectives in the Treatment of Reversible Airway Obstruction

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Aspects of Bronchial Reactivity to Prostaglandins and Aspirin in Asthmatic Patients

Cited by 52 publications

References 4 publications

Prostaglandin E2in the expired breath condensate of patients with asthma

Prostaglandin E2in the expired breath condensate of patients with asthma

Time-limited protective effect of inhaled frusemide against aspirin-induced bronchoconstriction in aspirin-sensitive asthmatics

Perspectives in the Treatment of Reversible Airway Obstruction

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Product

Resources

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Prostaglandin E₂in the expired breath condensate of patients with asthma

Prostaglandin E₂in the expired breath condensate of patients with asthma