Izabela Kuprys-Lipinska

Lipoxin A4 generation is decreased in aspirin‐sensitive patients in lysine‐aspirin nasal challenge in vivo model

Background:  Lipoxins represent a group of lipoxygenase derived eicosanoids which, in contrast to leukotrienes, are potent anti‐inflammatory mediators. The aim of our study was to determine lipoxin A4 (LXA4) and leukotriene C4 (LTC4) levels in nasal lavages after intranasal challenge with aspirin in aspirin intolerant (AIA) in comparison to aspirin tolerant (ATA) asthmatics and after allergen challenge in patients suffering from allergic rhinitis.

Perennial is more effective than preseasonal subcutaneous immunotherapy in the treatment of seasonal allergic rhinoconjunctivitis.

Background Two different regimens of subcutaneous immunotherapy (IT), perennial or preseasonal, may be used in the treatment of seasonal allergy. The aim of this study was to compare the efficacy and safety of perennial IT (PIT) and preseasonal IT (PSIT) in patients suffering from seasonal rhinoconjunctivitis. Methods The study was planned as a randomized, double-blind, comparative study on the efficacy and safety of PIT and PSIT. The study group comprised 120 patients allergic to grass and rye pollen. After the observational season they were randomized to receive PIT or PSIT for 3 years. The effect of IT was assessed based on symptom severity and medication use recorded in diaries. Results Ninety-nine patients completed the study. No difference was seen between the groups regarding combined symptom medication score (SMS) in the first season of IT. During the second season, the difference between PIT and PSIT regarding combined SMS was 27.9% (p = 0.063) and reached 42.7% (p = 0.012) in favor of PIT in the third season. Both treatments had a similar safety profile. Conclusion PIT was more effective than PSIT in the treatment of rhinoconjunctivitis in patients allergic to grass and rye pollens. Clinicaltrials.gov registration number NCT01555736.

Two patterns of changes in nasal nitric oxide after lysine aspirin nasal challenge in patients with aspirin-exacerbated respiratory disease.

Background Nasal nitric oxide (nNO) levels after nasal lysine acetylsalicylic acid (lys-ASA) challenge have not been determined. This study was designed to determine a pattern of changes after lys-ASA challenge in aspirin-exacerbated respiratory disease (AERD) patients and to evaluate the usefulness of nNO measurements in the assessment of lys-ASA nasal challenge outcome. Methods Eighteen patients with aspirin hypersensitivity, nasal polyps, and asthma were included. Aspirin-tolerant control groups consisted of 10 healthy volunteers without asthma and nasal polyps and 10 patients with nasal polyps without asthma. All subjects underwent nasal challenge with lys-ASA. nNO was measured before and 1, 2, 4, and 24 hours after control solution and lys-ASA administration. Results A significant fall in nNO levels was noted in AERD patients with a positive result to challenges at time points 1 hour (p = 0.0033), 2 hours (p = 0.0033), and 3 hours (p = 0.026) after lys-ASA. A trend toward higher nNO concentrations was observed after lys-ASA challenge at the 2-hour (p = 0.018) and 4-hour (p = 0.018) time points compared with baseline in subjects with AERD and a clinically negative re to the challenge. No significant changes in nNO levels after the challenge were observed in control groups. The combined increase and decrease in nNO levels gave the sensitivity as 0.94 and specificity 1.00 at best. Conclusion nNO levels decrease after lys-ASA nasal challenge in subjects with AERD and a clinically positive result of the challenge. An unexpected trend toward an increase in nNO levels is observed in subjects with AERD and a clinically negative result of the challenge.

Budesonide/formoterol for maintenance and reliever therapy: new quality in asthma management

Asthma is a chronic inflammatory disease of the airways with variable symptoms and airway obstruction. The strategy of asthma management aims to prevent and relieve acute attacks and achieve long-term control of symptoms. Symbicort® is a fixed combination of the corticosteroid budesonide and the long-acting β2-agonist formoterol – the first component treats inflammation, the second provides rapid and long-term smooth muscle relaxation. These two components make budesonide/formoterol suitable for both maintenance and reliever asthma therapy (Symbicort SMART®). There is increasing evidence from clinical trials that such a regimen is an effective and safe treatment option. The patient taking budesonide/formoterol for symptom relief simultaneously increases the dose of inhaled corticosteroids. Therefore, the pharmacological intervention provides an earlier step up in controller therapy, just prior to asthma deterioration, and thus prevents exacerbations. Such a regimen better reflects the nature of asthma and...

Prevalence, risk factors and underdiagnosis of asthma in the general population aged over 60 years

Introduction Bronchial asthma is one of the frequent chronic diseases in elderly persons. Global data show that 6.5–17% of the elderly suffer from asthma. However, there are no Polish data available on asthma prevalence in this group. Aim This article is a retrospective analysis of the Polish Multicentre Study of Epidemiology of Allergic Diseases (PMSEAD) results aimed at assessing prevalence and clinical characteristics in the elderly. Material and methods The study was conducted in 1998–1999 in 11 research centres in Poland, including the Lodz centre. The study included randomly selected subjects of both sexes. Demographics and prevalence were assessed among adults (aged 16–80 years) based on the nationwide database and the detailed clinical analysis was based on the Lodz centre database. Results Nationwide data were obtained from 12 970 adults, including 1057 respondents in the Lodz Province; 20.3% of respondents in Poland and 23.6% in the Lodz Province were over 60 years of age. In both groups, elderly participants significantly more frequently suffered from asthma (asthma prevalence in this group was 6.7% for Poland and 12.0% for the Lodz Province). The multivariate analysis demonstrated that age over 60 years (OR = 2.08), residence in the city centre (OR = 3.30), and occurrence of seasonal allergic rhinitis (OR = 3.11) were significant risk factors for asthma occurrence among the residents of the Lodz Province. Among the elderly in Lodz, almost 50% of patients with asthma had not had a proper diagnosis made despite reporting clinical symptoms. Conclusions In Poland asthma is a common and frequently underdiagnosed disease in the elderly.

Differences in response to Der p1 and bacterial lipopolysaccharide in peripheral blood mononuclear cells from severe and non-severe asthmatics

Background: Asthma is heterogeneous disease with many phenotypes. Phospholipases A 2 (PLA 2 ) participate in production of eicosanoids–lipid mediators that modulate the chronic inflammation in asthmatics. Histone modification is a mechanism that controls the transcription of many inflammatory genes. Aim: The aim of the study was to compare the response of PBMC isolated from severe, non-severe and healthy controls to nDer p1 and LPS in relation to changes in PLA 2 , histone acetylases (HAT) and deacetylases (HDAC) genes expression. Methods: Twelve severe, 15 non-severe asthmatics atopic to Der p1 and 15 healthy controls were enrolled to the study. The expression of PLA 2 , HAT and HDAC were assessed in PBMC before and after stimulation with nDer p1 and bacterial lipopolysacharide. The qRT-PCR was run with TaqMan Low Density Array Cards. 2 -ΔΔCt was used to calculate changes in gene expression. Results: Patients with severe asthma characterized the increased expression of HDAC1 and PLA2G4C as well as decreased expression of EP300 and PLA2G12 in response to nDer p1. Likewise the same profile of PLA2G4C and EP300 expression was observed in severe asthmatics after LPS stimulation. Non-severe asthmatics showed decreased expression of HDAC2 and PLA2G15 in response to LPS. Conclusions: PBMC from severe and non-severe asthmatics differently response to environmental factors. Der p1 and LPS influence the expression of selected phospholipases A 2 , HAT and HDAC genes in PBMC from asthmatics. Funded by Polish National Science Center grant: DEC-2012/05/N/NZ5/02630.

Effectiveness and adverse events of plasmapheresis and immunoglobulin G infusion in patient with resistant chronic urticaria and angioedema - a case report

Aim Here is presented a case of 54 years old woman with the history of severe chronic urticaria from over 30 yrs resistant to nsAnti-H1 and treated with plasmapheresis and intravenous immunoglobulin G. Results In this patient urticaria with angioedema eruptions were induced by cold, pressure, NSAID, antibiotics, but mainly appeared spontaneous, and were aggravated before menstruation. She was twice hospitalized due to the severe angioedema. nsAnti-H1 in standard and high doses were ineffective, and caused the drowsiness. Concomitant treatment with LTRA, anti-H2 and sAnti-H1 as well as diet were also ineffective. Only high doses of oral corticosteroids (oCS) partly controlled the clinical symptoms. Autologous serum skin test was positive, skin biopsy revealed oedema of derma and infiltration by eosinophils and lymphocytes. She had also the history of thyroid gland disorder. Due to autoimmunologic background plasmapheresis was applied. During first cycle adverse event (AE) – eruption of urticaria with angioedema developed. AE was treated with intravenous CS (ivCS) and Anti-H1. Next cycles with CS premedication proceeded without AE. Remission of urticaria lasted 6 month, and then symptoms relapsed. Second series of plasmapheresis and plasmapheresis booster preceeded CS premedication passed without AE, but during intravenous immunoglobulin G infusion, applied for continuation, urtical reaction with angioedema again appeared and disappeared after treatment with ivCS. Patient was again free from symptoms through 6 months. Then symptoms turn back but they could be control by low doses of oCS with nsAnti-H1. In 2008 she had hysterectomy due to cervical cancer (in situ). Nowadays she is still symptomatic despite treatment but symptoms are mild and tolerated. She refused anti-IgE therapy due to cancerophobia. Conclusion In some patients suffering from severe chronic urticaria a compromise in symptoms control and therapy intensity need to be obtain and accepted by a patient and a physician.

Good outcomes of pregnancy in two cases of women treated with omalizumab due to the severe asthma

The prevalence of asthma during pregnancy is estimated on 4%. Uncontrolled, severe asthma is a risk for both a mother and an unborn child. Therefore, optimization of asthma treatment during pregnancy is vital in achieving good outcomes. Physicians and their patients may have some doubts about safety of anti-asthmatic medications, especially if drugs are new. Omalizumab is a humanized recombinant anti-IgE monoclonal antibody recommended for the treatment of chronic severe IgE-mediated asthma. Clinical and observational studies confirmed its effectiveness in improving asthma control, reducing severe exacerbations and improving quality of life. The safety data concerning pregnancy come from the experimental studies on animals and they show no teratogenic effect. We present case reports of two women who became pregnant during the treatment with omalizumab. Both with very severe asthma treated chronically with all available medication including systemic steroids (first – 20 mg prednisolone/day, second – 40 mg prednisolone/day). Both started their regular treatment with omalizumab in 2007 and have significant improvement (withdrawal of oral steroids or significant reduction of their dose, better asthma control) . First, 32-year old woman became pregnant in 2010 and gave birth in Oct 2010 - it was her 3rd pregnancy, and 3rd labor , second 31-year old – also became pregnant in 2010 and gave birth in Jan 2011 - it was her 5th pregnancy and 2nd labor. Both had complications during previous pregnancies and labors and decided to continue therapy with omalizumab. First woman, besides omalizumab, was treated with high doses of ICS and LABA, second - high doses of ICS, LABA and 5 mg prednisone/day. The pregnancies proceeded without asthma exacerbations and other complications. First woman delivered healthy girl (Apgar 9, weight 3200 g, length 56 cm) in 40 week of pregnancy by caesarean section due to the narrow pelvis, second - health boy (Apgar 9, weight 3800 g, length 56 cm) in 40 week by caesarean section due to the aggravating obstetrical history. In both cases treatment with omalizumab did not affect pregnancies and newborns.

287 Nasal Nitric Oxide Levels after Lysine Aspirin Nasal Challenge in Subjects with Aspirin Induced Asthma.

Background Changes in nasal nitric oxide (nNO) levels after nasal lysine aspirin (lys-ASA) challenge have not been determined. Methods Fourteen patients with aspirin induced asthma (AIA) with or without nasal polyps with aspirin were included to the study. Hypersensitivity had to be confirmed by positive result of oral aspirin challenge Ten healthy subjects served as the control group. 12 mg of lys-ASA were applied unilaterally. Nasal symptoms were assessed using visual analogue scale (VAS) and nNO and peak nasal inspiratory flow (PNIF) measurements were performed before and 1, 2, 4 and 24 hours after the challenge. The result of the challenge was considered as positive when at least 20% fall of PNIF as well as 20% increase of total VAS score were observed. Results Ten patients (71.4%) had clinically positive result of the challenge. We observed significant fall in nNO levels in AIA patients after 1 and 2 hours after the challenge (653. 1 ± 420. 2 at baseline versus 490. 3 ± 456. 0; P = 0.0029 and 439. 9 ± 556. 4 ppb; P = 0.0076; respectively). The decrease in nNO level was more pronounced in patients with clinically positive result of the challenge (510. 1 ± 212. 5 at baseline versus 283. 3 ± 173. 4; P = 0.005; 159, 6 ± 166,1; P = 0.005 and 331. 0 ± 312.0 ppb; P = 0.037 after 1, 2 and 3 hours, respectively). In 4 subjects with clinically negative result of the challenge we noticed a trend towards higher nNO concentrations after lys-ASA challenge (1010. 8 ± 625. 2 at baseline vs 1341. 3 ± 670. 5 ppb after 4 hours). No significant changes in nNO levels after the challenge were observed in healthy controls. Conclusions NO levels decrease after lys-ASA nasal challenge in subjects with AIA and clinically positive nasal provocation. An unexpected trend towards increase in nNO levels was observed in subjects with AIA and clinically negative provocation Potential usefulness of nNO measurement in aspirin nasal provocation needs further evaluation.