Predictors of excessive short-acting ß2-agonist use and asthma exacerbations: a retrospective analysis of a Polish prescription database.

Introduction: Despite being linked to unfavourable outcomes, short-acting ß2-agonists (SABAs) are still overused by a substantial proportion of patients with asthma. Aim: To analyse the prevalence and predictors of SABA overuse and exacerbations in patients with asthma in a nationwide database of prescription purchase records. Material and methods: The prevalence of excessive SABA use (≥ 12 canisters) and overuse (≥ 3 canisters) was analysed among patients aged 18-64 years who purchased asthma medications in 2018. Predictors of excessive SABA use and SABA overuse were examined by quasi-Poisson regression. Negative binomial regression was used to study the association of excessive SABA use or overuse to the risk of asthma exacerbation defined as a prescription for oral corticosteroids. Results: Of 91,763 patients with asthma, 42,189 (46%) were SABA users (mean age, 47 years; 58% female). Among them, 34% purchased ≥ 3 SABA canisters, and 6% purchased ≥ 12 canisters. The risk (risk ratio, 95% CI) of excessive SABA use was lower in patients with concomitant prescriptions for inhaled corticosteroids (0.41, 0.34-0.48) or inhaled corticosteroids and long-acting ß2-agonists (0.52, 0.47-0.56), women (0.63, 0.58-0.68), and those in secondary care (0.60, 0.44-0.66); older age was associated with a higher risk of excessive SABA use (1.06, 1.03-1.10). Excessive SABA use was the strongest predictor of asthma exacerbations among all patients (3.24, 2.84-3.70) and in those with ≥ 1 exacerbation (1.60, 1.50-1.71). Conclusions: Excessive SABA use is highly prevalent in asthma management, is associated with lack of prescriptions for inhaled corticosteroids, and substantially increases the exacerbation risk.

Biomarkers for predicting response to aspirin therapy in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To assess clinical features as well as genetic, immune, cytological and biochemical biomarkers that might predict a positive response to high-dose aspirin therapy in AERD. METHODS: We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52-week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high-dose aspirin were defined as patients with improvement in 5-item Asthma Control Questionnaire score, 22-item Sino-Nasal Outcome Test (SNOT-22) score and forced expiratory volume in 1 second at 52 weeks. RESULTS: There were 28 responders (82%). Positive baseline predictors of response included female sex (p = .002), higher SNOT-22 score (p = .03), higher blood eosinophil count (p = .01), lower neutrophil percentage in induced sputum (p = .003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (p = .004) and lower expression of the proteoglycan 2 gene, PRG2 (p = .01). The best prediction model included Asthma Control Test and SNOT-22 scores, blood eosinophils and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. CONCLUSIONS AND CLINICAL RELEVANCE: Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression and low PRG2 expression may predict a positive response to long-term high-dose aspirin therapy in patients with AERD.

Artificial neural network identifies nonsteroidal anti-inflammatory drugs exacerbated respiratory disease (N-ERD) cohort.

BACKGROUND: To date, there has been no reliable in vitro test to either diagnose or differentiate nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD). The aim of the present study was to develop and validate an artificial neural network (ANN) for the prediction of N-ERD in patients with asthma. METHODS: This study used a prospective database of patients with N-ERD (n = 121) and aspirin-tolerant (n = 82) who underwent aspirin challenge from May 2014 to May 2018. Eighteen parameters, including clinical characteristics, inflammatory phenotypes based on sputum cells, as well as eicosanoid levels in induced sputum supernatant (ISS) and urine were extracted for the ANN. RESULTS: The validation sensitivity of ANN was 94.12% (80.32%-99.28%), specificity was 73.08% (52.21%-88.43%), and accuracy was 85.00% (77.43%-92.90%) for the prediction of N-ERD. The area under the receiver operating curve was 0.83 (0.71-0.90). CONCLUSIONS: The designed ANN model seems to have powerful prediction capabilities to provide diagnosis of N-ERD. Although it cannot replace the gold-standard aspirin challenge test, the implementation of the ANN might provide an added value for identification of patients with N-ERD. External validation in a large cohort is needed to confirm our results.

The effect of levocetirizine and montelukast on clinical symptoms, serum level and skin expression of COX-1 and COX-2 enzymes in patients suffering from chronic autoimmune urticaria - a pilot study.

INTRODUCTION: Chronic autoimmune urticaria (CAU) lasts over 6 weeks and is characterized by circulating IgE autoantibodies or IgG against IgE or IgE receptor. AIM: To assess the clinical, laboratory and histological effects of 4-week levocetirizine and montelukast therapy in patients suffering from CAU. MATERIAL AND METHODS: Of 296 tested patients with chronic urticaria 40 had a positive ASST test. Only 17 (16 female/1 male; medium age: 44 years) fulfilled all study inclusion/exclusion criteria. The study was designed as an open, randomized trial with two arms: levocetirizine or montelukast treatment for 4 weeks following a 2-week wash-out period. All participants completed urticaria activity score (UAS) and visual analogue scale (VAS) questionnaires before and after both therapies. Blood samples and skin bioptats were obtained before and after treatment to evaluate COX-1 and COX-2 serum concentrations and skin expression. RESULTS: Clinical response to therapy measured with the UAS and VAS was better in the levocetirizine group. Both drugs caused a significant decrease in COX-1 and COX-2 serum level. COX-1 and COX-2 expression in epidermal and dermal inflammatory infiltration did not change significantly in either study group, but a significant decrease of COX-1 expression was observed when the groups were combined for analysis, and the decrease in COX-2 expression in the epidermis was of borderline significance. CONCLUSIONS: The effectiveness of levocetirizine and montelukast in treating CAU may be partly related to the reduction of COX-1 and COX-2 serum level and tissue expression, but further studies on a larger group of patients are needed to support this observation.

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.

Polish Society of Allergology statement on the diagnosis and treatment of severe, difficult-to-control bronchial asthma.

Severe asthma requires at least high doses of inhaled corticosteroids (ICS) in combination with a long-acting ß-agonist (LABA) or systemic corticosteroids (SCS) for more than 50% of days/year to avoid loss of control, or remains uncontrolled despite the treatment described above. The diagnosis of severe asthma should be confirmed in a reference centre as it requires careful differential diagnosis and the exclusion of factors hindering the achievement of optimal control. Severe asthma represents a significant burden for the patient, their family and the healthcare system. This is due to the severity of the symptoms, drug costs, significant impairment of everyday functioning and life quality, and limitation in the professional work. In the case of ineffectiveness of the step 4 GINA treatment, the patient should be referred to a specialist centre to consider additional treatment, including anti-IgE receptor (omalizumab), anti-IL-5 receptor (mepolizumab), or an antibody directed against the α-subunit of receptor for IL-5 (benralizumab). In the case of severe asthma, intensification of therapy should first of all include biological therapy and not the use of SCS. Biological drugs are available in Poland as a part of the therapeutic programme for the treatment of severe asthma. In practice, the therapeutic programme may change with subsequent notices of the Ministry of Health and does not have to be consistent with the Summary of Product Characteristics for individual preparations. The current review presents the basic principles of differential diagnosis of severe asthma and the selection of the optimal biological therapy in Polish conditions.

The position paper of the Polish Society of Allergology on climate changes, natural disasters and allergy and 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 the Polish program for the treatment of severe allergic asthma with omalizumab: a single-center experience.

BACKGROUND: A national program for the treatment of severe allergic (IgE-dependent) asthma with omalizumab (OMA) was implemented in Poland in 2013. This observational study evaluated the effectiveness of the Polish OMA program and monitored asthma control after treatment discontinuation. METHODS: In the first year of the program, 53 patients (23 new/30 continuing treatment) received OMA in the Barlicki Hospital, Poland. Patients were evaluated at baseline and after 16 weeks of OMA treatment by spirometry, mean dose of inhaled corticosteroids (ICS) and oral corticosteroids (OCS), number of asthma exacerbations, the Asthma Control Questionnaire (ACQ), and the Asthma Quality of Life Questionnaire (AQLQ). OMA treatment responses were determined using the global effectiveness of treatment evaluation scale. Fourteen patients ceased OMA treatment following ≥36 months of therapy and entered follow up. RESULTS: All patients treated with OMA de novo for at least 16 weeks had a decrease in asthma exacerbations and showed a good (15/16, 94 %) or an excellent (1/16, 6 %) response to treatment. We observed a reduction in OCS dose (≥5 mg/day) in 14/16 (88 %) patients. ACQ and AQLQ scores improved by ≥0.5 points in 15/16 (94 %) and 14/16 (88 %) patients, respectively. After OMA cessation, 11/14 (79 %) patients showed worsening of asthma control and severe exacerbations. CONCLUSIONS: Patients in the OMA program show significant benefits, including reduced use of OCS, improved asthma control and quality of life. After OMA discontinuation, frequent severe exacerbations were observed primarily in patients whose asthma was previously uncontrolled by high OCS doses.

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.

Clinical and biochemical factors for response to aspirin desensitization in aspirin-induced asthma patients ­ pilot study.

Aspirin desensitization is considered to be an effective and well-tolerated therapy for patients with Non-steroidal anti-inflammatory(NSAIDs)-Exacerbated Respiratory Disease (NERD). The aim of the present study was to investigate the influence of aspirin desensitization on inflammatory cell count in induced sputum and nasal lavage in fifteen NERD individuals subjected to one-year aspirin therapy. The decrease in induced sputum count of eosinophils and macrophages was observed. Clinical efficacy of aspirin therapy in improving nasal symptoms and quality of life in NERD patients was also confirmed.

The whole-genome expression analysis of peripheral blood mononuclear cells from aspirin sensitive asthmatics versus aspirin tolerant patients and healthy donors after in vitro aspirin challenge.

BACKGROUND: Up to 30% of adults with severe asthma are hypersensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients. Therefore, the aim of this study was to compare the AIA expression profile against aspirin tolerant asthma (ATA) and healthy volunteers (HV) profile in peripheral blood mononuclear cells (PBMCs) after in vitro aspirin challenge in Caucasian population. METHODS: PBMCs were separated from blood of three groups of subjects--11 AIA, 7 ATA and 15 HV and then stimulated by either 2 µM lysine aspirin or 20 µM lysine as a control. Subsequently, RNA was isolated, transcribed into cDNA and subjected to microarray and qPCR studies. Simultaneously, protein was extracted from PBMCs and used in further immunoblotting analysis. RESULTS: The validation of results at mRNA level has shown only three genes, whose expression was significantly altered between comprising groups. mRNA expression of CNPY3 in PBMCs in AIA was significantly lower (-0.41 ± 2.67) than in HV (1.04 ± 2.69), (p = 0.02); mRNA expression of FOSL1 in PBMCs in AIA was also significantly decreased (-0.66 ± 2.97) as opposed to HV (0.31 ± 4.83), (p = 0.02). While mRNA expression of ERAS in PBMCs was increased (1.15 ± 0.23) in AIA in comparison to HV (-1.32 ± 0.41), (p = 0.03). At protein level the changed expression of one protein was confirmed. Protein expression of FOSL1 in PBMCs in AIA was both significantly lower (-0.86 ± 0.08) than in ATA (0.39 ± 0.42), (p = 0.046) and in HV (0.9 ± 0.27), (p = 0.007). CONCLUSIONS: This pilot study implies a positive association between CNPY3, ERAS, FOSL1 and aspirin-intolerant asthma, suggesting that these findings would be useful for further investigations of NSAIDs mechanism.

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.

Impact of chronic obstructive pulmonary disease (COPD) on patient's life and his family.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is one of the most common chronic diseases of adults and is a major cause of chronic morbidity and mortality throughout the world. It is the cause of physical and mental suffering for the patient, significantly impairs quality of life, reduces the vital activity and affects the patient's life in its various aspects. In 2012, the nationwide survey was conducted in COPD outpatients with a history of smoking exploring the various factors of the disease and its effects on the health and life of the patient. The purpose of the analysis presented here is to assess the impact of COPD and tobacco smoking on the patient's health and life. MATERIAL AND METHODS: Data were collected from patients by their physicians during routine visit with usage of specifically prepared questionnaire for this study. Patients over 35 years of age, with diagnosed COPD, current or past smokers were recruited from outpatients settings. The study involved 10,365 patients with COPD. Representative sample of 2,967 questionnaires were randomly drawn for the statistical analysis. RESULTS: The mean age of responders was 61.15 ± 10.25 years, 33.98% of participants were women, 56.73% were current smokers and 43.37% declared smoking in the past. The largest number of patients had COPD in a moderate degree (II - acc. to GOLD 2010) - 55.38%, sequentially mild (I) - 21.40%, and severe (III) - 19.96%, the smallest group were people with very severe degree of disease (IV) - 3.27%. Using the new classification of the COPD severity (acc. to GOLD 2013), the largest group of patients were less symptomatic (mMRC ) subjects who had a low risk (A) - 52.67%, but in fact a second group of patients were subjects with severe symptoms and a high risk (D) - 20 45% , sequentially - patients with low severity of symptoms, but a high risk (C) - 16.16% , and severe symptoms and a low risk - 10.72% (B). Patients most often reported that COPD affects their activity in sport (83.45% of respondents), than in living activity (82.78%) and family life (79.3%). COPD had significant (moderate or severe) effect on sport (60.85%) and life activity (38.44%), as well as on work (34.9%), but the greatest impact, leading up to the resignation of the activity: on sport practice (21.75%), sexual intercourse (12.6%) and hobbies (11.49%). The disease severity (GOLD 2013 C/D) was the independent factor which reduced all forms of activity. In patients' opinion smoking had negative impact on their health (52,65%) and the family budget (41.83%). The negative impact of smoking on family relations was declared by 16.38% of respondents. Among the factors which favor effective quit from addiction were: age ≥ 65 years and more seere degree of obturation (III/IV GOLD 2010). CONCLUSIONS: The results of the study confirmed the significant impact of the disease and addiction to smoking not only on patients' life but also on their families.

POLASTMA--the Polish National Programme of Early Diagnosis and Therapy of Asthma.

Asthma represents a growing health, social, and economic issue as it affects a considerable part of the population, adversely affecting patients' quality of life, while its chronic character and severity of symptoms impair family life. It has been estimated that 12% of the population of Poland (4.5 million) suffer from asthma and 16% report wheezes (5.7 million). In order to improve asthma care and patient outcomes, evidence-based recommendations must not only be developed, but also disseminated and implemented at a national and local level, which is key for integration into clinical practice. For these reasons, the Polish Society of Allergology (PSA) has decided to undertake actions, leading to some improvement of the epidemiological situation in Poland. The Polish National Programme of Early Diagnosis and Therapy of Asthma has been developed. This initiative is a response to the demand for medical care improvement in patients with asthma. Its goals include early diagnosis of asthma and improved control in the course of the disease, a reduction in the number of subjects with asthma-associated disability for work, an increased use of anti-inflammatory agents vs. rescue medications, a reduced number of patients with severe, uncontrolled bronchial asthma and prevention of complications of the disease and of adverse effects of applied therapy, an increase in social awareness regarding the bulk of problems associated with asthma, and reduction of the total costs of the care of patients suffering from asthma. Details regarding programme assumptions, goals, target groups, and modes of implementation are described in the document.

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.

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 3(rd) pregnancy, and 3(rd) labor. The second woman, 31-year-old, also became pregnant in 2010 and gave birth in Jan 2011 - it was her 5(th) pregnancy and 2(nd) 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 ß 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 40(th) 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.

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.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Efficacy and safety of a 12-week therapy with a new formulation of fluticasone propionate at doses of 125 and 250 µg administered through a new generation cyclohaler twice daily, in comparison to fluticasone propionate 500 µg dry powder inhaler twice daily in patients with moderate asthma.

INTRODUCTION: Inhaled fluticasone is used in the treatment of chronic bronchial asthma. Its high efficacy and good safety profile have been proven by clinical trials and observations. Its unique pharmacokinetic properties make it distinguishable from other drugs from this group. In vitro tests run on an artificial model of the airways and pharmacokinetic studies conducted on healthy volunteers have shown that the new formulation of this drug is outstanding due a twofold better lung deposition, compared to the reference medicine. The aim of this study was to evaluate the efficacy and safety of the new formulation of fluticasone propionate administered through new generation cyclohaler (CNG), compared to original fluticasone administered through dry powder inhaler (DPI) in patients with chronic moderate asthma. MATERIAL END METHODS: The study included 457 patients. 376 subjects were randomized to one out of the three groups: 127 subjects--to the group treated with the new formulation of fluticasone at a dose of 125 µg BID, 125 subjects--to the group treated with new formulation of fluticasone at a dose of 250 µg BID, and 124 subjects--to the group treated with the reference drug--fluticasone DPI 500 µg BID. At the beginning of the study, the groups did not differ in demographical or clinical aspects. Active therapy lasted 12 weeks. The primary endpoint was a mean change in morning PEF during a 12-week course of therapy (ΔmPEF of 15 L/min was considered as statistically significant). Additionally, other functional parameters of the respiratory system--clinical symptoms and the use of rescue drugs were studied. During the whole study the safety of patients was monitored by recording adverse events; in addition, a systemic exposure to fluticasone was evaluated by testing the changes of cortisol in serum and in a 24-hour collection of urine in a subgroup consisting of 45 patients. Statistical analysis was conducted on both groups: intention-to-treat (ITT) and per protocol (PP). RESULTS: In PP as well as in ITT analysis, a mean change in morning PEF at the end of the therapy in comparison with the initial period was statistically significant in all therapeutic groups. The efficacy of the treatment with fluticasone at doses of 125 µg BID and 250 µg and the reference medicines did not differ statistically significantly after a 12-week course of therapy or during the whole period of treatment. During the study, significant improvement in the range of other functional parameters such as evening PEF, FEV1, clinical symptoms and the use of rescue drugs was observed in all therapeutic groups, without significant differences in efficacy between the study groups. The comparison of efficacy of fluticasone at a dose of 125 µg BID with the generic product at a dose of 250 µg BID showed a weak dose-response relationship concerning the change in morning PEF, which arises from the almost flat dose-response curve in the range of medium and high doses for this drug. No significant quantitative or qualitative differences were shown between the groups in the recorded adverse events, qualified as related to treatment with fluticasone. There were no significant changes revealed in cortisol concentration in serum or in a 24-hour collection of urine between the initial level and the final visit in any of the groups. CONCLUSIONS: Fluticasone administered through the new generation cyclohaler, compared to original fluticasone DPI, allows a twofold reduction in drug dose, retaining in new formulation clinical efficacy that corresponds to the reference drug at twice the dose. New formulation of fluticasone administered through the new generation cyclohaler has a safety profile clinically comparable to the reference drug.