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Biomedical subjects

L Mastalerz

Publications and source records attributed to L Mastalerz.

10 recordsLinked to original sources
PubMed2000

Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics.

Asthma is characterized by chronic airway inflammation resulting from overproduction of pro-inflammatory mediators, such as leukotrienes (LT). The authors questioned the biosynthetic capacity of asthmatic patients for lipoxins (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory responses that inhibit pro-inflammatory events. Levels of LXA4, 15-epi-LXA4 and LTC4 were determined in 14 clinically characterized aspirin-intolerant asthmatics (AIA), 11 aspirin-tolerant asthmatics (ATA) and eight healthy volunteers using a stimulated whole blood protocol. Both LXA4 and 15-epi-LXA4 were generated in whole blood activated by the divalent cation ionophore, A23187. Higher levels of LXA4 were produced in ATA than either AIA or healthy volunteers. Exposure of AIA whole blood to interleukin-3 prior to A23187 did not elevate their reduced capacity to generate LXA4. Generation of a bronchoconstrictor, LTC4, was similar in both AIA and ATA. Consequently, the ratio of LXA4:LTC4 quantitatively favoured the bronchoconstrictor for AIA and differed from both ATA and healthy subjects. In addition, the capacity for 15-epi-LXA4 generation was also diminished in AIA, since whole blood stimulated in the presence of aspirin gave increased levels only in samples from ATA. The present results indicate that asthmatics possess the capacity to generate both lipoxins and 15-epimer-lipoxins, but aspirin-intolerant asthmatics display a lower biosynthetic capacity than aspirin-tolerant asthmatics for these potentially protective lipid mediators. This previously unappreciated, diminished capacity for lipoxin formation by aspirin-intolerant asthmatic patients may contribute to their more severe clinical phenotype, and represents a novel paradigm for the development of chronic inflammatory disorders.

Adult↗
PubMed1999

[Extramedullary hemopoiesis presenting as a tumor of the posterior mediastinum in a patient with hemolytic anemia].

Extramedullary hemopoietic focus is a rare cause of tuberous enlargement of the posterior mediastinum. A 62-year-old man who had been diagnosed as having congenital spherocytic anemia 20 years ago, was admitted to hospital with initial diagnosis of pneumonia. Chest X-ray disclosed inflammatory infiltration in the lower lobe of the right lung and a tumor in the posterior mediastinum. Pneumonia subsided following treatment with antibiotics. Spiral computer tomography with concomitant transthoracic biopsy of the lesion, confirmed the presence of tumor located on the right side of the spinal column, as well as the presence of two minor focci on its opposite side. Cytological examination revealed extramedullary hemopoiesis. Differential diagnosis of tumor in posterior mediastinum, should take into consideration the possibility of extramedullary hemopoietic focci.

Anemia, Hemolytic↗
PubMed1998

Nasal provocation test with lysine-aspirin for diagnosis of aspirin-sensitive asthma.

Nasal provocation tests (NPTs) with lysine-aspirin (L-ASA) have been recently introduced for assessment of aspirin-induced asthma (AIA). They differ in dose and means of aspirin instillation, duration of observation period, and criteria for positivity. Thus far they have not become a routine part of clinical diagnosis. Fifty-one patients with AIA, confirmed by oral challenge test, were recruited to undergo diagnostic NPTs with L-ASA. In 10 of these patients (19.6%), NPTs could not be performed because of total obstruction of at least one nostril or marked fluctuations in nasal flows, leaving 41 patients with AIA for the study. Control groups consisted of 13 aspirin-tolerant asthmatic patients and 10 healthy subjects. L-ASA at a total dose of 16 mg of acetylsalicylic acid applied bilaterally into the inferior nasal conchae caused significant fall in inspiratory nasal flow in at least one nostril (>40%), which was measured by anterior rhinomanometry, and clinical symptoms of watery discharge and nasal blockage in 35 of 41 patients with AIA, one of 10 healthy subjects, and none of 13 aspirin-tolerant asthmatic patients. No relationship was found between the baseline nasal flow values and the intensity of response to L-ASA. No systemic reactions, including bronchospasm, were noticed, even in patients whose initial FEV1 was lower than 70% of predicted value. This test is highly specific (95.7%) and sensitive (86.7%), but negative results do not exclude possible intolerance to aspirin (predictive value of a negative result 78.6%). In conclusion, the NPT described is a simple, safe, and quick test for diagnosis of AIA. It can be used in patients with unstable asthma. It may be a method of choice to confirm hypersensitivity to aspirin manifested only by symptoms from the upper respiratory tract. Patients suspected of aspirin intolerance who have negative NPT results should undergo bronchial or oral challenge tests with aspirin.

Adult↗
PubMed1998

Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics.

From bronchoprovocation studies and investigations of the acute effects of drugs that inhibit leukotrienes (LT), the hypothesis has emerged that leukotrienes are important mediators of airway obstruction and other symptoms in aspirin-intolerant asthma (AIA). However, it has yet not been shown if subjects with AIA respond favorably to clinical treatment with leukotriene inhibitors. Therefore, in a double-blind placebo-controlled crossover study, we examined the effects of 6 wk of treatment with the leukotriene-pathway inhibitor zileuton (600 mg, four times daily) in 40 patients with well-characterized AIA. The treatment was added to existing therapy, which included medium to high doses of inhaled (average daily dose 1,030 microg of beclomethasone or budesonide) or oral glucocorticosteroids (4 to 25 mg/d) for all but one of the patients. On top of this treated baseline, there were no significant effects of adding placebo, indicating that their asthma was kept relatively stable. However, there was an acute and chronic improvement in pulmonary function after treatment with zileuton, expressed both as increased FEV1 from baseline compared with placebo, and higher morning and evening peak expiratory flow rate (PEFR) values on zileuton treatment compared with placebo. The improvements occurred despite lower use of rescue bronchodilator with zileuton. Zileuton also diminished nasal dysfunction, which is one of the cardinal signs of AIA. There was a remarkable return of smell, less rhinorrhea, and a trend for less stuffiness and higher nasal inspiratory flow during treatment with zileuton. Zileuton caused a small but distinct reduction of bronchial hyperresponsiveness to histamine and inhibited aspirin-induced bronchoconstriction. Zileuton inhibited urinary excretion of LTE4 but did not change airway reactivity to inhaled LTD4, supporting that zileuton specifically inhibited leukotriene biosynthesis. The findings indicate that leukotrienes are important mediators of persistent airway obstruction and chronic nasal dysfunction in AIA. The study also suggests that addition of a leukotriene pathway inhibitor such as zileuton may bring about greater control of asthma than what is achieved by treatment with medium to high doses of glucocorticosteroids alone.

Adrenergic beta-Agonists↗
PubMed1998

Salmeterol prevents aspirin-induced attacks of asthma and interferes with eicosanoid metabolism.

We determined the effect of a long acting beta2-agonist, salmeterol, on aspirin-induced asthma (AIA) attacks and urinary release of eicosanoids in a double-blind, placebo-controlled, crossover study in 10 asthmatics sensitive to aspirin. The patients inhaled 50 microgram of salmeterol or placebo 15 min prior to a cumulative challenge with increasing doses of lysine-aspirin (L-ASA) (Part I), and before a single, predetermined dose of L-ASA that caused a 20% fall in FEV1 (PD20) (Part II). Salmeterol significantly attenuated aspirin-precipitated bronchoconstriction and the increase in urinary LTE4. Salmeterol also prevented the decrease in blood eosinophils, and abolished the correlation between the urinary levels of LTE4 and provocative doses of aspirin. In addition, PGD-M, the major urinary metabolite of PGD2, increased after L-ASA inhalation in six of nine subjects; this increase was blocked in all six by salmeterol. The protective effect of salmeterol on aspirin-induced attacks and mediator release suggests that it may be efficacious in aspirin-sensitive asthma.

Administration, Inhalation↗
PubMed1997

Intranasal fluticasone propionate for chronic eosinophilic rhinitis in patients with aspirin-induced asthma.

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32-60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with E-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects (P = 0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.

Administration, Intranasal↗
PubMed1996

Protective and bronchodilator effects of prostaglandin E and salbutamol in aspirin-induced asthma.

We performed a double-blind, two-phase study on protective and bronchodilator effects of prostaglandins E2 and E1 (PGE2, PGE1) and salbutamol in patients with aspirin-induced asthma (AIA). In phase 1 we assessed the effects of pretreatment with PGE2, salbutamol, or the PGE1-analogue, misoprostol, on bronchoconstriction precipitated by inhalation of L-lysine aspirin in 11 patients with AIA. PGE2 and salbutamol were inhaled at equimolar concentrations of 0.25 mumol, 5 min before the aspirin challenge, while 400 micrograms misoprostol was administered orally 1 h before challenge. PGE2 attenuated the bronchoconstrictive reactions in 10 patients, salbutamol in eight, and misoprostol in seven. The mean provocative dose of aspirin causing a 20% fall in FEV1 (PD20) decreased after PGE2 (p = 0.04) and salbutamol (p = 0.06), but only marginally after misoprostol (p = 0.25). There was a positive correlation between magnitude of the protection offered by the three compounds in individual subjects. In phase 2, we examined bronchial response to inhaled PGE2, PGE1, salbutamol, and 2% ethanol in 12 AIA patients compared with 10 aspirin-tolerant patients with asthma. AIA subjects were characterized by less pronounced and shorter bronchodilator responses. There was no correlation between the protective and bronchodilator actions of the compounds used in individual patients. Thus, inhaled PGE2 and salbutamol protect against aspirin-induced attacks of asthma through mechanisms unrelated to their bronchodilator properties. Airways of aspirin-sensitive patients with asthma demonstrate distinct bronchial reactivity.

Administration, Inhalation↗
PubMed1995

[Role of prostaglandins F and E in regulation of bronchial activity].

Prostaglandins (PGs) belong to the family of eicosanoids. A main substrate in their biosynthesis is arachidonic acid. Involvement of PGs in regulation of bronchial activity is a complex process and far from being fully understood. In 1968 it was shown that prostaglandins E1 and E2 cause bronchodilation, while prostaglandin F2a constricts an isolated human smooth muscle. The recent studies which revealed protective effects of PGE2 on bronchial reaction induced in patients by ultrasonically nebulized distilled water, allergen, metabisulfite, or exercise, revitalized interest among clinicians. Reports that PGE2 inhibits airways response in bronchial provocation with lysine aspirin, allow to believe that PGE2 plays a role in pathogenesis of aspirin induced asthma.

Aspirin↗