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Biomedical subjects

E Nizankowska

Publications and source records attributed to E Nizankowska.

At least 55 records · Page 3Linked to original sources
PubMed1995

Autoimmune phenomena in bronchial asthma with special reference to aspirin intolerance.

We assessed the autoimmune status of 185 adult patients with bronchial asthma and 46 healthy subjects of similar sex and age. The patients were divided into groups with: (1) aspirin-induced asthma (AIA) (n = 80); (2) intrinsic asthma with good aspirin tolerance (n = 46); and (3) atopic asthma (n = 59). Antinuclear antibodies (ANA) at a titer of > or = 1:40 were present in the serum of 55% of the patients with AIA, 41% of those with intrinsic asthma, 39% of those with atopic asthma, and 11% of the healthy subjects, with the difference between each patient group and the healthy subjects being statistically significant (p < 0.05). The fluorescence staining pattern of ANA on Hep-2 cells was mainly speckled, but the precise antigen specificity of the antibodies could not be identified with reference sera against extractable nuclear antigens. None of the subjects exhibited anti-double stranded deoxyribonucleic acid (anti-ds-DNA) or anti-neurtrophil cytoplasmic antibodies (ANCA). Positive ANA were associated with signs of complement activation, the presence of rheumatoid factor, and circulating immune complexes. Clinical signs of autoimmunity, evidenced by rheumatic symptoms, cold sensitivity, and Raynaud's phenomenon, were more common among the patients who tested positively for ANA. The assessment of autoimmunity may help in better characterizing patients with asthma and understanding various symptoms of the disease. Any causal relationship between asthma and autoimmunity remains to be established.

Adolescent↗
PubMed1995

Treatment of steroid-dependent bronchial asthma with cyclosporin.

The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.

Adult↗
PubMed1994

Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge.

We have recently shown that oral aspirin provocation leads to an increase in LTE4 and a reduction in 11-dehydro-TXB2 levels in urine of patients with aspirin induced-asthma (AIA). To test the hypothesis that cyclooxygenase inhibition and an enhancement of cysteinyl-leukotriene production occurs in the lungs of patients with AIA, we examined the eicosanoid levels in bronchoalveolar lavage fluid obtained 30 min after lysine-aspirin or placebo inhalation in 10 patients with AIA. Eosinophil cationic protein (ECP) levels were determined to evaluate eosinophil activation. Six asthmatics nonsensitive to aspirin (NA) underwent challenge with placebo. The dose of lysine-aspirin inhaled by patients with AIA was equal to that which had produced > or = 20% fall in FEV1. Compared with NA, patients with AIA had: (1) eicosanoid levels, particularly PGE2 and TXB2, elevated and (2) higher number of eosinophils and ECP. The overproduction of eicosanoids could be related to a distinct eosinophilic inflammation in airways of patients with AIA. Inhalation of lysine-aspirin had no effects on 12-HETE and 15-HETE levels, but it markedly depressed cyclooxygenase products and significantly enhanced leukotriene production in the lungs of patients with AIA.

Adult↗
PubMed1992

Altered distribution of IgG subclasses in aspirin-induced asthma: high IgG4, low IgG1.

We have determined IgG subclass concentrations in 100 patients with aspirin-induced asthma and 80 healthy controls. Patients on chronic corticotherapy (n = 64) had significantly lower total IgG levels than patients not receiving steroids (n = 36) or controls. Corticotherapy was not associated with changes in the subclass distributions. In patients, the most striking finding was elevation of IgG4. It was not related to corticotherapy or serum IgE levels. The rise in IgG4 was accompanied by a modest, though statistically significant, depression of IgG1. No changes of IgG2 and IgG3 concentrations were observed. Thus, aspirin-induced asthma is characterized by a distinct pattern of distributions of IgG subclasses. It is suggested that in aspirin-induced asthma elevation of IgG4 might result from chronic antigenic stimulation, of viral origin, and that determination of IgG subclass distribution might be of clinical interest.

Aspirin↗
PubMed1991

Cyclosporin for steroid-dependent asthma.

We used cyclosporin to treat 12 adult patients with severe bronchial asthma who had been on systemic steroids for an average of 16 years. During the baseline period, lasting 4-6 months, therapy with high doses of inhaled beclamethasone, aminophylline and salbutamol was standardized and a minimum necessary dose of systemic steroids was established. After 9 months' treatment with low-dose cyclosporin (average whole-blood trough levels of 105 ng/ml), in six patients the daily dose of oral prednisone could be reduced from mean 30 mg to mean 11 mg, while daily symptom scores and peak expiratory flows improved significantly. This was accompanied by a reduction in exacerbations of asthma. However, in six other patients attempts to taper the steroid doses were unsuccessful, and cyclosporin was stopped after 4 to 7 months. These preliminary results suggest that cyclosporin might be of benefit in some patients with steroid-dependent asthma.

Adult↗
PubMed1990

Salicylate pre-treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin-intolerant patients.

Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA-induced asthma. We performed a double-blind, placebo-controlled, randomized cross-over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre-treatment on ASA-induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA-induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P less than 0.02 and P less than 0.002, respectively) after trilisate pre-treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients.

Adult↗
PubMed1990

Choline magnesium trisalicylate in patients with aspirin-induced asthma.

Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity.

Adult↗
PubMed1989

Glucocorticosteroids attenuate aspirin-precipitated adverse reactions in aspirin-intolerant patients with asthma.

We evaluated the effects of corticosteroid pretreatment on the intensity of adverse reactions to aspirin during carefully controlled aspirin challenges in 13 aspirin-sensitive asthmatics. Two studies were performed. First, using a double-blind crossover design, we administered to five patients 75 mg prednisone daily or placebo for two days preceding the challenge. No consistent protection against adverse reactions was achieved. In the second study, a 10-day pretreatment with 15 mg oral prednisolone and topical intrabronchial and intranasal beclomethasone offered total clinical protection against bronchospasm produced by threshold doses of aspirin in five of eight patients. In two others, the bronchospasm provoked was less severe, and only in one patient did its intensity remained unchanged. There was a significant reduction in fall of mean pulmonary function tests following the second aspirin challenge, which was performed after ten days of steroid treatment. Steroids given for ten days also prevented significantly nasal discharge and nasal blockade. When diagnostic challenge tests with aspirin are carried out in asthmatic patients on long-term corticosteroid therapy, there is an increased possibility of false negative results.

Adult↗
PubMed1988

An abnormality of arachidonic acid metabolism is not a generalized phenomenon in patients with aspirin-induced asthma.

Aspirin (ASA)-induced asthma is a distinct clinical syndrome in which bronchoconstrictive response to nonsteroidal anti-inflammatory drugs can be predicted on the basis of their in vitro activity as inhibitors of cyclooxygenase. In ten ASA-sensitive asthmatics and ten matched healthy controls we measured 12-hydroxy-eicosatetraenoic acid (12-HETE) production by platelets and 5-hydroxy-eicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) production by polymorphonuclear leucocytes. The blood cells were obtained before administration of the threshold doses of ASA and during the ASA-induced reactions. Initial levels of eicosanoids determined did not differ between the two groups. In both groups, after ASA challenge, 12-HETE rose to similar levels while 5-HETE and LTB4 remained unchanged. These data do not support the concept that an abnormality in the regulation of arachidonic acid oxidative pathways in ASA-sensitive asthmatics is a generalized phenomenon which embraces the platelets and leucocytes; rather it is inhibition of cyclo-oxygenase within the tissues of the respiratory tract that triggers asthmatic attacks in the sensitive patients.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Bleeding time and PAF-acether-induced platelet aggregation in atopy.

In a double-blind cross-over study 20 mg of aspirin or placebo were administered to 18 patients with respiratory atopy without eczema and to 12 healthy controls. Mean bleeding time before administration of either aspirin or placebo was on average about 1 min. longer in atopics than in the controls, and this difference was significant (p 0.05). Atopics' platelets also aggregated less well in response to arachidonic acid in comparison to controls. On the contrary, no difference in platelet aggregability was detected in response to either PAF-acether alone or to combination of subthreshold, synergistic concentrations of PAF-acether and collagen. Aspirin at a dose used did not affect either bleeding time or platelet aggregability. Thus, in respiratory atopy there exists a moderate hemostatic imbalance, the reason of which remains to be established.

Adult↗
PubMed1987

Effects of inhibition of thromboxane A2 synthesis in aspirin-induced asthma.

Since inhibition of cyclooxygenase precipitates asthmatic attacks in patients with aspirin idiosyncrasy, we have evaluated the effects of pharmacologic inhibition of thromboxane A2 (TXA2) synthetase, next to cyclooxygenase enzyme in arachidonic acid cascade. Sixteen patients with aspirin-induced asthma received increasing doses on 3 days (25 to 400 mg) of an imidazole derivative, OKY-046, which specifically blocks TXA2 synthetase. Twenty-three healthy control subjects received a single dose of 400 mg of OKY-046. In both patients and control subjects, the inhibitor at a dose of 400 mg produced (1) a pronounced fall in thromboxane B2 serum levels, (2) a rise in serum 6-keto-prostaglandin F1 alpha, and (3) a depression in platelet aggregability to arachidonic acid and adenosine diphosphate. The drug, however, neither precipitated attacks of asthma nor impaired pulmonary function tests throughout a 24-hour observation period. Five patients, but none of the control subjects, developed transient nasal congestion about 1 hour after taking the drug. Thus, inhibition of TXA2 synthetase, contrary to inhibition of cyclooxygenase, does not affect bronchopulmonary function in patients with asthma and aspirin intolerance.

Acrylates↗
PubMed1987

Effects of inhibition of thromboxane A2 synthesis in aspirin-induced asthma.

Since inhibition of cyclo-oxygenase precipitates asthmatic attacks in patients with aspirin idiosyncrasy, we have evaluated the effects of pharmacological inhibition of the next enzyme in arachidonic acid cascade, i.e., thromboxane synthetase. Twelve patients with aspirin-induced asthma received on 3 days increasing doses (25-400 mg) of an imidazole derivative, OKY-046, which specifically blocks TXA2 synthetase. Twelve healthy controls received a single dose of 400 mg OKY-046. The drug neither precipitated asthmatic attacks nor altered pulmonary function tests throughout a 24-hr observation period. Five of 12 patients, but none of the controls, developed nasal congestion, approximately 1 hr after ingestion of the inhibitor. Though initial platelet aggregation evoked by arachidonic acid or ADP did not differ between the two groups, inhibitory effects of 400 mg OKY-046 on the aggregability were more pronounced in the patients than in the controls. Thus, inhibition of TXA2 synthetase, contrary to inhibition of cyclo-oxygenase, does not affect bronchopulmonary function in patients with asthma and aspirin intolerance. It does, however, often produce nasal congestion, possibly through reorientation of prostanoid synthesis from TXA2 to PGD2. It remains to be established whether pronounced depressive effects of a TXA2 synthetase inhibitor on platelet aggregability constitute a treat of aspirin idiosyncrasy or is a more general phenomenon associated with bronchial asthma.

Adult↗
PubMed1987

The effect of prostacyclin on asthma precipitated by aspirin.

Inhibition of prostacyclin biosynthesis by aspirin might be expected to promote asthmatic attacks in aspirin-intolerant patients. In vitro, prostacyclin inhibits generation of leukotrienes and opposes their bronchoconstrictive action. In a double-blind study we compared the effects of intravenous infusions of prostacyclin with those of its solvent on bronchoconstriction provoked by threshold doses of aspirin in 9 known aspirin-sensitive asthmatics. The intensity of bronchial obstruction precipitated by aspirin was similar during prostacyclin and placebo infusions. There was no difference in other symptoms of intolerance, except for rhinorrhea which seemed accentuated by prostacyclin (possibly because of nasal vasodilatation). Our results suggest that either the inhibitory effects of prostacyclin on leukotrienes described in vitro do not apply in vivo, or the importance of leukotrienes have been overestimated in this type of asthma. Idiosyncrasy to aspirin, which affects 5-10% of adult asthmatics, was thought several decades to be of allergic background, while in fact numerous and extensive immunological studies ruled out typical IgE--mediated allergic mechanisms for aspirin--induced asthma. In 1974, at the Department of Allergy and Clinical Immunology in Cracow, a novel hypothesis was put forward. If stated that in sensitive patients, precipitation of asthmatic attacks by aspirin and by certain nonsteroidal antiinflammatory drugs (NSAID) results from inhibition of specific enzyme in the bronchi, cyclooxygenase, leading to an imbalance of prostanoids in the respiratory tract. Over the years which followed evidence has been accumulated which strongly support this hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Lack of effect of i.v. prostacyclin on aspirin-induced asthma.

Inhibition of prostacyclin biosynthesis by aspirin might be expected to promote asthmatic attacks in aspirin-intolerant patients. In vitro, prostacyclin impedes generation of leukotrienes and opposes their bronchoconstrictive action. In a double-blind study we compared the effects of intravenous infusions of prostacyclin with those of its solvent on bronchoconstriction provoked by threshold doses of aspirin in nine known aspirin-sensitive asthmatics. The intensity of bronchial obstruction precipitated by aspirin was similar during prostacyclin and placebo infusions. There was no difference in other symptoms of intolerance, except for rhinorrhea which seemed accentuated by prostacyclin (possibly because of nasal vasodilatation). Our results suggest that either the inhibitory effects of prostacyclin on leukotrienes described in vitro do not apply in vivo, or the importance of leukotrienes has been overestimated in this type of asthma.

Adult↗
PubMed1985

Bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1.

We evaluated in a double-blind study the bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1 (PGE1-carbinol), described recently as a nonirritant bronchodilator in animals. Fifteen asthmatic patients received by inhalation single doses of 1, 10, and 30 micrograms PGE1-carbinol, 55 micrograms PGE2, and placebo (10% ethanol in normal saline, which was also used as diluent for the PGs). Such pulmonary function tests as forced expiratory volume in 1 second, forced vital capacity, and maximal expiratory flow were monitored during 2 hours following inhalation of each compound. 10 and 30 micrograms PGE1-carbinol produced significant but short-acting bronchodilation, similar to that caused by 55 micrograms PGE2. One-third of the patients reported mild cough and throat irritation during and shortly after inhalation of 30 micrograms PGE1-carbinol or 55 micrograms PGE2. Placebo and 1 microgram PGE1-carbinol produced minimal side effects, but neither agent caused bronchodilation. In an adjunctive, unblinded trial, the same patients received 400 micrograms fenoterol. Fenoterol caused greater bronchodilation 15 and 30 minutes after inhalation than did the PGs in the double-blind study.

Adult↗