Ewa Nizankowska

Safety of a specific COX‐2 inhibitor in aspirin‐induced asthma

In a subset of patients with asthma, aspirin and several other non‐steroidal anti‐inflammatory drugs (NSAID) that inhibit simultaneously cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) precipitate dangerous asthmatic attacks.

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.

The atopy trait in hypersensitivity to nonsteroidal anti-inflammatory drugs

The prevalence of atopy was evaluated in two groups of subjects with hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAID):

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.

Plasma 9α,11β-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma

Background: Prostaglandin D2 (PGD2) is a major cyclooxygenase product generated by activated mast cells during an allergic response. Assessment of PGD2 and its metabolites in patients with asthma has mostly been performed in urine, bronchoalveolar lavage fluid and induced sputum, whereas human plasma determinations have been performed only sporadically. Methods: In 32 patients with allergic asthma and 50 healthy non-allergic controls, baseline plasma and urinary levels of 9α,11β-PGF2, a primary PGD2 metabolite, were assessed by gas chromatography/mass spectrometry. Serum tryptase levels were measured by fluoroenzyme immunoassay and urinary leukotriene E4 (LTE4) by ELISA. In a subgroup of 10 asthmatics (randomly selected from the 32 study patients) in whom bronchial allergen challenges with specific allergens (Dermatophagoides pteronyssinus, n = 4, mixed grass pollens, n = 6) were carried out, measurements were taken both before and after provocation. Results: At baseline no significant differences between mean plasma and urinary levels of the PGD2 metabolite and serum tryptase levels were found in asthmatics or controls. Asthmatic patients had significantly higher urinary LTE4 levels. Allergen challenge resulted in a significant early increase in the mean plasma 9α,11β-PGF2 level and only a borderline but significant increase in the urinary 9α,11β-PGF2 level within 2 hours after provocation. The challenge did not produce statistically significant changes in serum tryptase levels. Urinary LTE4 levels remained significantly increased 4 hours after provocation. Conclusions: PGD2 is actively involved in the early asthmatic response to allergens. Measurement of 9α,11β-PGF2 release into plasma rather than urine following allergen challenge is a sensitive marker of enhanced PGD2 synthesis, most probably due to mast cell activation.

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 L‐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.

Clinical and genetic features underlying the response of patients with bronchial asthma to treatment with a leukotriene receptor antagonist.

Background Treatment with antileukotriene drugs results in clinical improvement in many, though not all, patients with asthma. It can be hypothesized that the subpopulation of asthmatic patients, characterized by aspirin intolerance and cysteinyl‐leukotriene overproduction, might profit most from antileukotriene treatment.

Hydrocortisone and airflow impairment in aspirin-induced asthma

We studied the effects of intravenous injection of hydrocortisone, as compared to its solvent, in 31 patients with aspirin-induced asthma. Mean FEV1 fell significantly 5 minutes after an intravenous bolus of 300 mg of hydrocortisone, but not after the solvent, and returned to the initial values 1 hour later. Only three of 31 patients displayed at this time clinical signs of increased impairment of airflow that resolved spontaneously. Neither in these three patients nor in another patient known already to respond with bronchoconstriction to 30 to 50 mg of hydrocortisone did intravenous injections of 20 mg of methylprednisolone, 4 mg of dexamethasone, or 4 mg of betamethasone produce any signs of bronchial obstruction. In the whole group of patients, mean FEV1 increased significantly 3 to 5 hours after hydrocortisone injection. It is hypothesized that hydrocortisone might induce early bronchoconstriction in patients with aspirin-induced asthma through its inhibitory effects on prostanoid biosynthesis. Use of intravenous steroids other than hydrocortisone is advisable in patients with aspirin-induced asthma.

The α-chain of high-affinity receptor for IgE (FcɛRIα) gene polymorphisms and serum IgE levels

Background:  The high‐affinity receptor for immunoglobulin‐E (IgE) (FcɛRI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its α subunit (FcɛRIα) genetic variability in allergic diseases.

Protection against exercise‐induced bronchoconstriction by montelukast in aspirin‐sensitive and aspirin‐tolerant patients with asthma

Background Montelukast, a cysteinyl‐leukotriene receptor antagonist, was reported to have a protective effect against exercise‐induced bronchoconstriction (EIB). Aspirin‐induced asthma (AIA) is characterized by overproduction of cysteinyl‐leukotrienes.