Izabela Kupryś-Lipińska

Loss of asthma control after cessation of omalizumab treatment: real life data.

Introduction Many clinical and observational studies have demonstrated effectiveness of omalizumab (OMA) in the treatment of severe asthma, but the optimal duration of the therapy remains unknown. Aim The article presents the authors’ clinical experience on OMA cessation in routine practice. Material and methods Due to new reimbursement criteria, OMA therapy has been interrupted in 11 subjects (6 women/5 men). The mean age of patients was 50.73 ±14.16 years, the mean time of severe asthma duration was 13.54 ±6.05 years. All of them had an excellent/good response to OMA. The duration of OMA therapy was 67.73 ±11.64 months. Results Nine out of 11 patients had severe asthma exacerbation within the first 5 months after the OMA withdrawal. The mean time to the first severe exacerbation was 7.56 ±2.67 weeks. Between the time of OMA cessation and the time of reassessment, the mean score of Asthma Control Questionnaire increased from 2.58 ±0.71 to 3.63 ±1.26 points and the mean score of Asthma Quality of Life Questionnaire decreased from 4.3 ±1.91 to 3.18 ±1.17 points. The mean oral corticosteroids (OCS) dose increased from 4.61 ±3.0 mg/day to 33.33 ±13.12 mg/day. The number of exacerbations within the last 12 months increased from 1.6 ±0.67 to 5.2 ±1.4, and the number of hospitalizations or emergency room (ER) attendence increased from 0.11 ±0.31 to 1.56 ±1.26. Conclusions These data indicate that the withdrawal of OMA therapy after the successful long-term therapy may cause severe asthma exacerbations. Therefore, the decision regarding cessation of OMA treatment should be undertaken individually after careful weighing benefits and risks, especially in patients with a long history of severe asthma, treated with high doses of OCS before OMA introduction, near-fatal asthma events and/or aggravation of asthma during previous episodes of interruptions in OMA treatment.

Effectiveness of omalizumab in a patient with a life-threatening episode of bronchospasm and larynx angioedema after exposure to house dust

Omalizumab is a monoclonal antibody against IgE, nowadays approved for the treatment of persistent severe (EU) or moderate-to severe (USA) IgE-mediated asthma but there is also some evidence (case reports and four published clinical trials) on the effectiveness of this medication in urticaria and angioedema. The case of a 42-year-old woman suffering from severe allergic asthma and severe chronic urticaria with concomitant angioedema is presented in the article. She had a life-threatening episode of bronchospasm and larynx edema after exposure to house dust recorded in her medical history. The patient did not respond to standard therapy. The improvement in asthma control and remission of chronic urticaria and angioedema was achieved after introducing the therapy with omalizumab.

Omalizumab in pregnant women treated due to severe asthma: two case reports of good outcomes of pregnancies

The article presents case reports of 2 women who became pregnant during therapy with omalizumab. Both subjects suffered from very severe asthma and were treated chronically with all available medications including systemic steroids (first – 20 mg prednisolone/day, second – 40 mg prednisolone/day). Both were enrolled into treatment with omalizumab and started regular therapy in 2007. The course of asthma significantly improved in both cases (withdrawal of oral steroids or significant reduction of their dose, better asthma control). The first woman, 32-year-old, became pregnant in 2010 and gave birth in Oct 2010 – it was her 3rd pregnancy, and 3rd labor. The second woman, 31-year-old, also became pregnant in 2010 and gave birth in Jan 2011 – it was her 5th pregnancy and 2nd labor. Both had severe asthma exacerbations during previous pregnancies and labors, and decided to continue therapy with omalizumab. The first woman, besides omalizumab, was treated with high doses of inhaled corticosteroids (ICS) and long-acting β agonists (LABA) while the second one was treated with high doses of ICS, LABA and 2.5 mg to 5 mg prednisone/day. The pregnancies proceeded without asthma exacerbations. The first woman delivered a healthy girl (Apgar 9, weight 3200 g, length 56 cm) in the 40th week of pregnancy by caesarean section due to the narrow pelvis. The second one delivered a healthy boy (Apgar 9, weight 3800 g, length 56 cm) in week 40 by caesarean section due to the aggravating obstetrical history. In both cases, treatment with omalizumab did not affect pregnancies and newborns.

The step further to understand the role of cytosolic phospholipase A2 alpha and group X secretory phospholipase A2 in allergic inflammation: pilot study.

Allergens, viral, and bacterial infections are responsible for asthma exacerbations that occur with progression of airway inflammation. cPLA2 α and sPLA2X are responsible for delivery of arachidonic acid for production of eicosanoids—one of the key mediators of airway inflammation. However, cPLA2 α and sPLA2X role in allergic inflammation has not been fully elucidated. The aim of this study was to analyze the influence of rDer p1 and rFel d1 and lipopolysaccharide (LPS) on cPLA2 α expression and sPLA2X secretion in PBMC of asthmatics and in A549 cell line. PBMC isolated from 14 subjects, as well as A549 cells, were stimulated with rDer p1, rFel d1, and LPS. Immunoblotting technique was used to study the changes in cPLA2 α protein expression and ELISA was used to analyze the release of sPLA2X. PBMC of asthmatics released more sPLA2X than those from healthy controls in the steady state. rDer p1 induced more sPLA2X secretion than cPLA2 α protein expression. rFel d1 caused decrease in cPLA2 α relative expression in PBMC of asthmatics and in A549 cells. Summarizing, Der p1 and Fel d1 involve phospholipase A2 enzymes in their action. sPLA2X seems to be one of important PLA2 isoform in allergic inflammation, especially caused by house dust mite allergens.

The effect of omalizumab on eosinophilic inflammation of the respiratory tract in patients with allergic asthma

Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab - an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

Exacerbating Factors Induce Different Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Asthmatics, Patients with Chronic Obstructive Pulmonary Disease and Healthy Subjects

Background: Despite several common phenotypic features, chronic obstructive pulmonary disease (COPD) and severe asthma differ with regard to their causative factors and pathophysiology. Both diseases may be exacerbated by environmental factors, however, the molecular profiles of disease episodes have not been comprehensively studied. We identified differences in gene and protein expression profiles expressed by peripheral blood mononuclear cells (PBMC) of COPD patients, patients with atopic asthma and healthy subjects when challenged with exacerbating factors in vitro: lipopolysaccharide (LPS), house dust mite (HDM) and cat allergen. Methods: PBMC isolated from patients with severe atopic asthma and COPD, as well as healthy subjects were stimulated with rDer p 1 DG, rFel d 1 DG and LPS. The changes in the expression of 47 genes belonging to five groups (phospholipase A2, eicosanoids, transcription factors, cytokines and airway remodeling) were studied using TaqMan low density array cards. Immunoblotting was used to study relative protein expression. Results: rDer p 1 significantly up-regulated the expression of PLA2G4A, PLA2G6, PLA2G15, CYSLTR1, LB4R2, PTGS1, PTGS2, FOXP1, GATA3, HDAC2, IREB2, PPARG, STAT4, TSLP and CHI3L1 genes in asthmatics in comparison to healthy subjects. LPS induced significant expression of ANXA1 and LTA4H in asthmatics when compared to COPD patients and healthy subjects. SOX6,STAT4 and IL1RL1 were induced in COPD after LPS stimulation. Analysis of protein expression revealed a pattern similar to mRNA expression. Conclusions: LPS-induced exacerbation of asthma and COPD is characterized by differential expression of selected genes in PBMC. HDM allergen changed the expression profile of inflammatory genes between patients with asthma of atopic origin and healthy controls.

Omalizumab therapy in a patient with severe asthma and co-existing chronic obstructive pulmonary disease

Address for correspondence: Izabela Kupryś-Lipińska MD, PhD, Department of Internal Medicine, Asthma and Allergy, Norbert Barlicki Memorial University Hospital No. 1, Medical University of Lodz, 22 Kopcinskiego St, 90-153 Lodz, Poland, phone: +48 606 819 702, fax: +48 42 678 11 76, e-mail: ikuprys@wp.pl Received: 4.12.2017, accepted: 13.12.2017. Omalizumab therapy in a patient with severe asthma and co-existing chronic obstructive pulmonary disease

The Position Paper of the Polish Society of Allergologyon climate changes, natural disasters and allergyand asthma

The observed global climate change is an indisputable cause of the increased frequency of extreme weather events and related natural disasters. This phenomenon is observed all over the world including Poland. Moreover, Polish citizens as tourists are also exposed to climate phenomena that do not occur in our climate zone. Extreme weather events and related disasters can have a significant impact on people with allergic diseases, including asthma. These effects may be associated with the exposure to air pollution, allergens, and specific microclimate conditions. Under the auspices of the Polish Society of Allergology, experts in the field of environmental allergy prepared a statement on climate changes, natural disasters and allergy and asthma to reduce the risk of adverse health events provoked by climate and weather factors. The guidelines contain the description of the factors related to climate changes and natural disasters affecting the course of allergic diseases, the specific microclimate conditions and the recommendations of the Polish Society of Allergology for vulnerable population, patients suffering from asthma and allergy diseases, allergologists and authorities in the event of climate and weather hazards.

Effectiveness of omalizumab in an asthmatic patient with severe airway and blood eosinophilia

Omalizumab is a monoclonal antibody raised against class E immunoglobulin (IgE), approved for the treatment of chronic severe (in the EU) or moderate-to-severe (in the USA) IgE-mediated asthma. Omalizumab is effective in reducing asthma exacerbations, hospitalizations and emergency visits due to exacerbations as well as in improving patients’ quality of life (QoL) [1–3].

The prevalence of asthma work relatedness: Preliminary data

OBJECTIVES About 5-10% of asthmatics do not respond well to standard treatment plan. Occupational exposure may be one of the factors that can be linked with treatment failure. The aim of the study was to assess the prevalence of work-related asthma (WRA) among adult asthmatics under follow up in an outpatient allergy clinic and to create a useful tool for detecting individuals with possible WRA. MATERIAL AND METHODS Preliminary 5-question questionnaire designed to recognize WRA was presented to 300 asthmatics. All patients with positive preliminary verification along with 50 subjects from control group were asked to fill up a detailed questionnaire. The WRA was diagnosed by positive match for asthma symptoms in combination with workplace exposure indicated in the detailed WRA questionnaire followed by confirmation of each WRA case by detailed exposure analysis. RESULTS Work-related asthma was recognized in 63 subjects (21% of study group). The preliminary questionnaire has 76.9% sensitivity and 94% specificity in recognition of WRA. Occupational exposure to irritants is a risk factor of WRA recognition (relative risk (RR) = 2.09 (1.44:3.03)). Working in exposure-free environment is a factor against WRA recognition (RR = 0.38 (0.24:0.61)). Among subjects with work-related asthma, the uncontrolled course of the disease is significantly more frequent (p = 0.012). Subjects with WRA more often report sickness absenteeism due to asthma than those without WRA (9.6% vs. 3.2%, respectively), but the observed differences did not reach the statistical significance. CONCLUSIONS Short 5-question questionnaire seems to be a promising tool to detect individuals with possible work-related asthma in the outpatient setting for further evaluation and additional attention.