Grażyna Bochenek

Certain subphenotypes of aspirin-exacerbated respiratory disease distinguished by latent class analysis

BACKGROUND Aspirin-exacerbated respiratory disease (AERD) is recognized as a distinct asthma phenotype. It usually has a severe course accompanied by chronic hyperplastic eosinophilic sinusitis with nasal polyps, blood eosinophilia, and increased concentrations of urinary leukotriene E4 (LTE4). More insightful analysis of individual patients shows this group to be nonhomogeneous. OBJECTIVE We sought to identify any likely subphenotypes in a cohort of patients with AERD through the application of latent class analysis (LCA). METHODS Clinical data from 201 patients with AERD (134 women) were collected from questionnaires. Standard spirometry, atopy traits, blood eosinophilia, and urinary LTE4 concentrations were evaluated. LCA was applied to identify possible AERD subphenotypes. RESULTS Four classes (subphenotypes) within the AERD phenotype were identified as follows: class 1, asthma with a moderate course, intensive upper airway symptoms, and blood eosinophilia (18.9% of patients); class 2, asthma with a mild course, relatively well controlled, and with low health care use (34.8% of patients); class 3, asthma with a severe course, poorly controlled, and with severe exacerbations and airway obstruction (41.3% of patients); and class 4, poorly controlled asthma with frequent and severe exacerbations in female subjects (5.0% of patients). Atopic status did not affect class membership. Patients with particularly intensive upper airway symptoms had the highest levels of blood eosinophilia and the highest concentrations of urinary LTE4. CONCLUSIONS LCA revealed unique AERD subphenotypes, thus corroborating the heterogeneity of this population. Such discrimination might facilitate more individualized treatment in difficult-to-treat patients.

Aspirin-exacerbated respiratory disease: clinical disease and diagnosis.

This article summarizes the current knowledge in the field of clinical presentation and diagnosis of aspirin-exacerbated respiratory disease (AERD). The definition, prevalence, natural history, and clinical presentation of this distinct clinical syndrome are described. The classification and tolerance of particular groups of cyclooxygenase inhibitors by patients with AERD are presented. The authors comprehensively discuss provocation tests with aspirin as the most reliable method to confirm the diagnosis of AERD.

Elevated urinary leukotriene E4 excretion in asthma: a comparison of HPLC-mass spectrometry and ELISA

allergic to argan oil or a control serum. Bound IgEs were detected by peroxidase-conjugated goat anti-human IgEs (KPL), using ECL Plus western blotting kit (GE Healthcare Europe GmbH, Saclay, France). Immunoblotting analysis shows IgE reactivity to one band of about 10 kDa. This band disappears after inhibition with 1mg/ml of proteins extracted from argan nuts (Fig. 1C). During the last 20 years, argan oil became an expensive oil, consumption of which extended to western and Far Eastern countries because of its fatty acids profile (3). It is expected that new cases of allergy to argan oil could appear. The identified allergen is a protein of 10 kDa, persistent in oil. This protein could belong to the family of oleosins which are known to be potent allergens as described for peanut and sesame (4, 5). The ability to induce severe reaction at low doses is underlined by the systemic reaction induced by prick-test and the low reactogenic dose. It must be taken in consideration by oil producers that allergenicity of argan oil could be suppressed by step of refining (6). We thank the Dr Abdellah Harguil (Agadir, Morocco) who has kindly provided us the serum of the patient allergic to argan oil studied here.

Use of Sensitive, Broad-Spectrum Molecular Assays and Human Airway Epithelium Cultures for Detection of Respiratory Pathogens

Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ∼30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1–10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ∼76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.

Factors associated with asthma control in patients with aspirin-exacerbated respiratory disease ☆

BACKGROUND Effective control of asthma is the primary goal of its treatment. Despite an improved understanding of asthma pathogenesis and accessibility of novel therapies, the rate of uncontrolled asthma remains high. OBJECTIVE To find potential factors associated with asthma control in patients with aspirin-exacerbated respiratory disease (AERD). METHODS Clinical data were collected from a specifically structured questionnaire. Demographics, a history of upper airway symptoms, asthma course, exacerbations expressed as emergency department (ED) visits/hospitalizations, and asthma treatment were considered. Spirometry, skin prick tests, total IgE concentration, and blood eosinophil count were evaluated. Asthma control was assessed through the Asthma Control Test (ACT). RESULTS Out of 201 AERD patients, 41 (20.4%), 69 (34.3%), and 91 (45.3%) had controlled, partially controlled, and uncontrolled asthma, respectively. A multivariate ordered logistic regression analysis revealed that hospitalizations for asthma in the previous 12 months (OR 2.88; 95%CI, 1.11-7.46), ED visits for asthma throughout its duration (OR 1.05; 95%CI, 1.004-1.10), and total IgE concentration (OR 1.28; 95%CI, 1.02-1.60) were positively associated with poor asthma control, whereas FEV1 values (OR 0.98; 95%CI, 0.96-0.99) and medical care at a referential specialty clinic (OR 0.50; 95%CI, 0.27-0.95) were positively associated with good asthma control. CONCLUSIONS The prevalence of uncontrolled asthma in AERD patients is high and similar to that observed in different asthmatic populations. Owing both to the specificity and complexity of the disease, AERD patients should stay under regular care of well experienced referential medical centers to ensure that this asthma phenotype is dealt with effectively.

Eicosanoid biosynthesis during mucociliary and mucous metaplastic differentiation of bronchial epithelial cells

The purpose of this study was to examine the profile of eicosanoids secreted by human bronchial epithelial cells (HBEC) during their in vitro differentiation toward mucociliary or mucous metaplastic phenotype. Eicosanoids were measured in supernatants by mass spectrometry, and corresponding gene expression by real-time PCR. Primary HBEC produced mainly prostaglandins (PGE2, PGD2) and epoxides (e.g. 14,15-EET), but during further mucociliary differentiation we observed a gradual increase in secretion of lipoxygenase derived HETEs. Treatment with IL-13 and IL-4 induced mucous metaplasia and resulted in downregulation of PG pathway, and potent induction of 15-lipoxygenase (marked release of 15-HETE). The deficiency in PG production sustained during long term culture of mucous metaplastic epithelia. In conclusions, Th2-type cytokines induce changes in eicosanoid metabolism of airway epithelial cells, resulting in an immense induction of 15-lipoxygenase pathway, and inhibition of PG pathways. Deficient production of immunomodulatory PGs may promote chronic inflammation and airway remodeling.

Mast cell activation after adenosine inhalation challenge in patients with bronchial asthma

A total of 7.5% of the males and 2.2% of the females had persistent wheezing complaints. Wheezing symptoms were found to be significantly high among males and smokers. The prevalence of allergic rhinitis and dermatitis were 24.1% and 6.8% respectively. Rhinitis rates were 16.5% among males and 7.6% among females. The eczema rate was 5.2% among males and 1.6% among females. Prevalence of having a pet at home was 11.7% and family history of atopy was 11.9%. Pet ownership [OR: 1.25 (0.94–1.65)] and family history of atopy [(OR: 3.77(2.88–4.94)] were significantly associated with rhinitis. Smoking rate was 23.3% in the whole group, 20.3% in males and 3.0% in females. Wheezing, asthma-like symptoms, cumulative asthma, current asthma and rhinitis were less common related in students who did not smoke. The rates of asthma, and asthma-like symptoms were found to be higher among smoking students than in non-smoking students, statistically. The low prevalence of asthma in our low-income population may depend on geographical and climatic variation, as well as to the low socioeconomic status of our population. The higher prevalence of rhinitis may depend on that some students may have confused the question about rhinitis and some with sinusitis or other nonallergic rhinitis complaints may have answered the same question with yes , because nonallergic rhinitis patients may have the same complaints like allergic rhinitis patients (5). In conclusion, asthma and/or asthmalike symptoms among university students in the eastern region of Turkey are lower than the developed countries, and habitual smoking is an important risk factor for allergic diseases.

The role of questionnaires in the assessment of asthma control

The achievement and the maintenance of asthma control is currently considered the main goal of asthma treatment. Recent guidelines recommend regular assessment of asthma control and indicate questionnaires as important tools that can facilitate its evaluation. Questionnaires relate to GINA or NAEPP guidelines. Questionnaires constitute complex numerical or categorical scales and consist of several to over a dozen questions relating to the patients symptoms of asthma, limitations in daily activities and usage of rescue medications within a period of time. Each questionnaire is characterized by the features that affect its reliability and usefulness. In the following paper we discuss most of the questionnaires which assess asthma control. We focus on the items they include and present the results of studies that prove the effectiveness of individual questionnaires in assessment of asthma control. Attention was drawn to the patient groups to which the questionnaires are addressed. We list the features of the questionnaire which should be considered before choosing a test, so that it satisfies both the doctors and the patients needs. The role of questionnaires as the easy-to-use tools is growing steadily. Unfortunately, not all are available in Polish language. Conducting appropriate validation studies may allow to use many of them in Polish conditions.

Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper

NSAID‐exacerbated respiratory disease (N‐ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence‐based recommendations for the diagnosis and management of N‐ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N‐ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N‐ERD. Recommendations for the most effective management of a patient with N‐ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub‐phenotypes and emerging sub‐endotypes of N‐ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N‐ERD and unmet needs, which should be addressed in the future.

Management of suspected drug hypersensitivity reactions. Guidelines of the Section of Drug Hypersensitivity of the Polish Society of Allergology

1Klinika Immunologii, Reumatologii i Alergii, Uniwersytet Medyczny w Łodzi 2 Klinika Pulmonologii, II Katedra Chorób Wewnętrznych im. Prof. Andrzeja Szczeklika, Uniwersytet Jagielloński Collegium Medicum w Krakowie 3Klinika Alergologii i Chorób Wewnętrznych, Uniwersytet Medyczny w Białymstoku 4 Katedra i Klinika Chorób Wewnętrznych, Alergologii i Immunologii Klinicznej, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach 5Zakład Alergologii Klinicznej, Pomorski Uniwersytet Medyczny w Szczecinie 6Katedra i Klinika Chorób Wewnętrznych i Alergologii, Uniwersytet Medyczny we Wrocławiu 7Zakład Alergologii Klinicznej i Środowiskowej, Uniwersytet Jagielloński Collegium Medicum w Krakowie 8Poradnia Alergologiczna i Poradnia Alergologiczna dla Dzieci w Starachowicach 9 Poradnia Alergologiczna, Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie 10Klinika Reumatologii, Uniwersytet Medyczny w Łodzi