ABSTRACT
Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.
Subject(s)
Confidentiality , Data Anonymization , Humans , PrivacyABSTRACT
The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.
Subject(s)
Hypersensitivity , Precision Medicine , Allergens , Desensitization, Immunologic , Genomics , Humans , Hypersensitivity/diagnosis , Hypersensitivity/therapyABSTRACT
INTRODUCTION: Frequently observed multiple sensitizations to several animals highlights the importance of a molecular diagnosis, distinguishing between sensitizations specific to single species and sensitizations due to cross-reactivity. OBJECTIVE: The aim of our study was to assess the usefulness of a molecular diagnosis in the description of sensitization profiles in allergy patients living in Central Europe, with a particular focus on animal-derived molecules. METHODS: The molecular diagnosis was performed using the ImmunoCAP ISAC microarray. Results of 1,255 allergy patients were subjected to statistical analysis. RESULTS: The highest sensitization rates were observed for uteroglobin Fel d 1 (31.8%) and kallikrein Can f 5 (16.4%), followed by animal lipocalins Can f 1 (13.9%), Equ c 1 (6.2%), Fel d 4 (5.3%), Can f 2 (4.2%), and Mus m 1 (4.1%). Sensitization rates to serum albumins Fel d 2, Can f 3, Equ c 3, and Bos d 6 were very low, with the highest being 3.2% to Fel d 2. Detailed subanalysis confirmed the dominant role of Fel d 1 or Can f 5 and/or Can f 1 in cat- or dog-sensitized patients, respectively. Further analysis focused on lipocalins and albumins confirmed a high rate of cosensitizations within both groups. CONCLUSION: The sensitization to animal allergen molecules is very frequent in Central Europe. The most common is sensitization to species-specific cat uteroglobin Fel d 1 and dog kallikrein Can f 5, followed by sensitizations to animal lipocalins. Our data suggest that commonly observed multiple sensitizations detected by extract approach can be explained not only by true cosensitization, but also by cross-reactivity, mainly in the frame of lipocalins. Cross-reactive serum albumins are minor sensitizers and are probably not important from this point of view.
Subject(s)
Allergens/immunology , Hypersensitivity/immunology , Adolescent , Adult , Aged , Animals , Cats , Child , Child, Preschool , Cross Reactions/immunology , Dogs , Europe , Female , Humans , Infant , Lipocalins/immunology , Male , Mice , Middle Aged , Serum Albumin/immunology , Species Specificity , Young AdultABSTRACT
Dupilumab is a monoclonal antibody against interleukin 4 (IL-4) receptor α that blocks signaling from IL-4 and IL-13, essential mediators of T helper 2 (Th2) pathway. To date, all clinical trials investigating the use of dupilumab excluded patients with human immunodeficiency virus. Herein, we describe the safe and successful use of dupilumab in a patient with atopic dermatitis, severe therapy resistant asthma, and HIV infection.
Subject(s)
Asthma , Dermatitis, Atopic , HIV Infections , Adult , Antibodies, Monoclonal, Humanized , Asthma/diagnosis , Asthma/drug therapy , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/drug therapy , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Interleukin-13 , MaleABSTRACT
BACKGROUND: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. OBJECTIVE: We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. METHODS: A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. RESULTS: Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed. CONCLUSION: This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307).
Subject(s)
Allergens/immunology , Antigens, Plant/immunology , Asthma/therapy , Betula/immunology , Conjunctivitis, Allergic/therapy , Pollen/immunology , Rhinitis, Allergic, Seasonal/therapy , Sublingual Immunotherapy , Adolescent , Adult , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Sublingual Immunotherapy/adverse effects , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet (ALK-Abelló, Hørsholm, Denmark) is developed for treatment of tree pollen-induced allergic rhinoconjunctivitis (ARC). OBJECTIVE: The aim of this pivotal phase III trial was to demonstrate the efficacy and safety of the SQ tree SLIT-tablet. METHODS: This was a randomized, double-blind, placebo-controlled trial with 634 subjects (12-65 years) with moderate-to-severe ARC despite use of symptom-relieving medication. Eligible subjects were randomized 1:1 to active or placebo treatment. The primary end point was the average daily ARC total combined score (TCS) during the birch pollen season (BPS) analyzed for subjects with diary data during the BPS. Secondary end points included average daily symptom scores (DSS) during the BPS, average TCS and DSS during the tree pollen season (TPS), and average daily medication scores (DMS) in the BPS and TPS. RESULTS: The primary and key secondary end points demonstrated statistically significant and clinically relevant effects of the SQ tree SLIT-tablet compared with placebo. For the BPS, absolute (relative) differences from placebo were 3.02 (40%) for TCS, 1.32 (37%) for DSS, and 1.58 (49%) for DMS (all P < .0001). For the TPS, absolute (relative) differences from placebo were 2.27 (37%) for TCS, 0.99 (33%) for DSS, and 1.20 (47%) for DMS (all P < .0001). Treatment was well tolerated. The most frequently reported treatment-related adverse events were mild or moderate local reactions related to sublingual administration. CONCLUSION: The trial demonstrated the efficacy and safety of the SQ tree SLIT-tablet compared with placebo during the BPS and TPS in adolescents and adults with birch pollen-induced ARC (EudraCT 2015-004821-15).
Subject(s)
Allergens/immunology , Betula/immunology , Conjunctivitis, Allergic/therapy , Pollen/immunology , Rhinitis, Allergic, Seasonal/therapy , Sublingual Immunotherapy/methods , Adolescent , Adult , Aged , Child , Double-Blind Method , Humans , Middle Aged , Tablets , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
Subject(s)
Anti-Allergic Agents/therapeutic use , Asthma/prevention & control , Histamine H1 Antagonists/therapeutic use , Rhinitis, Allergic/drug therapy , Animals , Child , Clinical Decision-Making , Evidence-Based Practice , Humans , Quality of Life , Rhinitis, Allergic/epidemiologyABSTRACT
BACKGROUND: A diagnosis of Hymenoptera venom allergy is based on clinical history and the results of skin tests and/or laboratory methods. OBJECTIVE: To analyze the utility of available laboratory tests in diagnosing Hymenoptera venom allergy. METHODS: Ninety-five patients with Hymenoptera venom allergy with a history of bee (35) or wasp (60) anaphylactic sting reaction and positive skin test with bee or wasp venom were included in this analysis. Specific immunoglobulin E (to bee venom extract, wasp venom extract, available recombinant molecules, and a basophil activation test with venom extracts were assessed in all the patients. Test sensitivity and specificity were calculated by using standard threshold values; then, receiver operating characteristic curve analysis was performed to compute optimal threshold values. Also, statistical analysis of the utility of different combinations of laboratory tests was performed. RESULTS: The optimal threshold values were revealed to be the following: 1.0 kIU/L for bee venom extract (sensitivity, 97.14%; specificity, 100%), 0.35 kIU/L for rApi m 1 (sensitivity, 68.57%; specificity, 100%), 1.22 kIU/L for wasp venom extract (sensitivity, 88.33%; specificity, 95.45%), 0.7 kIU/L for rVes v 5 (sensitivity, 86.67%; specificity, 95.45%), 1.0 kIU/L for rVes v 1 (sensitivity, 56.67%; specificity, 95.45%), 6.5% for basophil activation test with bee venom extract (sensitivity, 80%; specificity, 95.45%), and 4.5% for basophil activation test with wasp venom extract (sensitivity, 91.53%; specificity, 95.45%). The best test combinations were found to be the following: bee venom extract plus rApi m 1 (sensitivity, 97.14%; specificity, 95.45%) in bee and either wasp venom extract plus rVes v 5, or rVes v 5 plus rVes v 1 (both sensitivity, 98.33%; specificity, 95.45%) in patients with wasp venom allergy. CONCLUSION: Our analysis confirmed that currently used laboratory tests represent effective tools in diagnosing Hymenoptera venom allergy. Moreover, our probabilistic approach offered another way to interpret concrete values of laboratory test results and opened possible direction on how to optimize the laboratory diagnostic procedure.
Subject(s)
Anaphylaxis/diagnosis , Arthropod Venoms/immunology , Clinical Laboratory Techniques/methods , Hymenoptera , Hypersensitivity/diagnosis , Adult , Animals , Basophils , Bee Venoms/immunology , Humans , Immunoglobulin E/analysis , Immunoglobulin E/immunology , ROC Curve , Sensitivity and Specificity , Wasp Venoms/immunologySubject(s)
Allergens/immunology , Bee Venoms/immunology , Hypersensitivity/diagnosis , Immunoglobulin E/blood , Immunologic Tests , Insect Bites and Stings/diagnosis , Insect Proteins/immunology , Phospholipases A/immunology , Wasp Venoms/immunology , Adolescent , Adult , Aged , Allergens/administration & dosage , Biomarkers/blood , Child , Czech Republic , Female , Humans , Hypersensitivity/immunology , Insect Bites and Stings/immunology , Insect Proteins/administration & dosage , Male , Middle Aged , Phospholipases A/administration & dosage , Predictive Value of Tests , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology , Retrospective Studies , Slovenia , Young AdultABSTRACT
Molecular diagnosis of allergy and microarray technology have opened a completely new avenue of insight into sensitization profiles from both the clinical and the epidemiological point of view. We used this innovative tool in the description of sensitization patterns in pollen-sensitized patients in Middle Europe. Immunoglobulin E detection using 112 different allergenic molecules was carried out employing the ImmunoCAP ISAC microarray system. Sera from 826 patients sensitized to at least one pollen-derived molecule were subjected to analysis. The highest observed sensitization rate was 81.0% to grass-specific molecules (the most frequent being Phl p 1; 69.6%). The second most frequent sensitization was 54.8% to Betulaceae-specific molecules (Bet v 1; 54.2%). Together, grasses and Betulaceae components (and their cosensitizations with other components) comprised the vast majority of pollen sensitizations. Unexpectedly frequently observed sensitizations were those to Cupressaceae-specific molecules (14.1%), Oleaceae-specific molecules (10.8%), and the plane tree-derived molecule Pla a 2 (15.5%). The sensitization rates for all other molecules were within the expected range (Art v 1, 13.6%; Pla l 1, 9.6%; Che a 1, 8.4%; Par j 2, 0.9%; Amb a 1, 0.8%, and Sal k 1, 0.5%). Cross-reacting molecule sensitization rates were found to be 12.4% for profilins, 5.0% for polcalcins, and 6.4% for lipid transfer proteins. Molecular diagnosis of allergy gives a more precise and comprehensive insight into pollen sensitization patterns than extract-based testing, allowing a better understanding of the sensitization process and regional differences. The data presented here may help to improve the diagnostic and allergen-specific treatment procedures in the respective region.
Subject(s)
Allergens/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/epidemiology , Cross Reactions , Europe/epidemiology , Humans , Immunoassay , Microarray Analysis , Retrospective Studies , Rhinitis, Allergic, Seasonal/etiology , Rhinitis, Allergic, Seasonal/immunologyABSTRACT
The aim of this study was to confirm or refute the difference between efficacy of long-term specific immunotherapy (SIT) with standardized allergen vaccine consisting of six grass pollens (oat grass, orchard grass, fescue, rye grass, timothy grass, and rye) administered either by sublingual or by supralingual route. To investigate clinical and immunologic changes, 51 patients of a previous 1-year double-blind, placebo-controlled, randomized study were enrolled in an open randomized study that continued over the next 3 years. Sublingual or supralingual immunotherapy (SLIT) was performed in the same way, keeping the drops under or on the tongue, respectively, for 1-2 minutes before swallowing them. Data about symptoms scores and rescue medication intake during grass pollen seasons, as well as skin-prick test results, levels of specific IgG, and IgE antibodies were collected after each pollen season. It was clearly shown that both routes of administration were effective, leading to a significant decrease of clinical symptoms of grass pollen allergy after SIT lasting 3-4 years. No statistically significant difference between sublingually and supralingually treated patients was observed at the end of the study. Adverse effects were limited to a small number of generally mild local and/or systemic reactions with no significant difference between both administration ways of SIT. The significant therapeutic effect of both SLIT and supralingual immunotherapy lasting 3-4 years was clearly achieved. Despite no significant difference between efficacy of both administration ways of SIT, the onset of sublingual SIT effect seems to be slightly faster than that of supralingual SIT.
Subject(s)
Administration, Sublingual , Allergens/administration & dosage , Desensitization, Immunologic/methods , Poaceae/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/therapy , Adolescent , Adult , Child , Dosage Forms , Double-Blind Method , Drug Administration Schedule , Female , Humans , Immunoglobulin E/blood , Immunoglobulin G/blood , Male , Middle Aged , Placebos , Rhinitis, Allergic, Seasonal/immunology , Skin Tests , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The major sources of allergens in the indoor air include house dust mites, dander derived from domestic animals and rodents, cockroach, and several fungi. Mites are the main cause of allergies in some countries with a warmer climate, but the epidemiological significance of mite and cockroach allergens in Central Europe has not been established yet. METHODS: We assessed sensitization profiles of allergy patients in a Central European region in regard to sensitization to mites and cockroach. We used molecular diagnosis by means of the microarray ISAC, and we investigated 1766 patients with clinical suspicion to an allergic disorder. 1255 of them were positive to at least one allergen component, and this group was subjected to statistical analysis. RESULTS: The sensitization to at least one mite-specific molecule (Der p 1, 2, Der f 1, 2) was observed relatively frequently in 32.7% of patients. Specific IgE to mite group 2 molecules is almost fully cross-reactive. Group 1 allergens are also cross-reactive, but in some patients, a species-specific response was observed. Relatively high rate of sensitization both to group 1 and 2 allergens in our patients indicates the greater role of co-sensitizations. Isolated sensitizations to molecules derived from glyciphagid mites Lep d 2 and/or Blo t 5 without sensitization to other mite-derived molecules were observed only exceptionally (in 0.6% of cases). True sensitization to at least one cockroach-specific molecule (Bla g 1, 2, 5) was very rare (in 0.6% of cases), and nearly all of them were co-sensitizations with other noncockroach-derived molecules. Sensitization to an inhaled tropomyosin was observed rarely in 2.2% of patients (Der p 10 in 1.9% and Bla g 7 in 1.5%). Co-sensitization of inhaled tropomyosins with the respective mite- or cockroach-specific molecules was observed only in the minority of patients suggesting the different route of sensitization being more frequent. CONCLUSIONS: The majority of patients are co-sensitized to several molecules of the respective allergen source. The knowledge of this molecular spectrum of sensitization is important for optimal diagnosis and treatment in respect to allergen content in mite extracts used for diagnostic and therapeutic purposes. In regard to the sensitization patterns of Central European patients, it is necessary to point out the importance of quantifying at least three major mite components Der f 1, Der p 1 and Der f 2 (or Der p 2).
Subject(s)
Asthma , General Practitioners , Humans , Paramedics , Asthma/diagnosis , Asthma/therapy , Educational Status , PatientsABSTRACT
Immediate and delayed hypersensitivity reactions can play a role in the pathogenesis of atopic dermatitis (AD). We tested 71 patients (median age 5 years) with AD for hypersensitivity to grass and birch pollen, Dermatophagoides pteronyssinus, and Dermatophagoides farinae using atopy patch test (APT), skin prick test (SPT), and specific IgE measurement. The sensitivity (SE) and specificity (SP) of the tests were calculated on the basis of personal history of AD exacerbation, clinical AD score (SCORAD) changes, and the number of days with need for topical anti-inflammatory treatment (AITD) in relation to exposure to the allergens being tested. APT was positive in 45 patients, mostly to D. farinae (n=37). SPT and/or specific IgE were positive in 42 subjects, in most cases to grass and birch pollen (n=29). SE of APT reached 33%-56% for history, 33% for SCORAD, and 0%-60% for AITD; SP of APT was comparable for all three assessment standards (history, SCORAD, and AITD) (48%-67%). SE of SPT/specific IgE was higher for history (26%-63%) than for the other two standards of assessment (0%-67%); SP of SPT/specific IgE was also highest for history (69%-91%), and lower for SCORAD (59%-87%) and AITD (65%-80%). AD is often associated with hypersensitivity; its influence on AD, however, is clinically significant only in a minor group of patients. While personal history and SCORAD changes present themselves as possible standards in the evaluation of clinically relevant hypersensitivity in AD patients, the anti-inflammatory treatment days (AITD) appears to be unsuitable for this purpose.
ABSTRACT
BACKGROUND: Adherence to allergen immunotherapy is important for its effectiveness. There is currently limited data available on allergen immunotherapy adherence outside of clinical trials i.e. in real-life clinical practice. As part of a European Academy of Allergy and Clinical Immunology Immunotherapy Interest group initiative, we endeavoured to design a survey in order to prospectively evaluate adherence to subcutaneous and sublingual immunotherapy across different European countries. METHOD/DESIGN: The inclusion criteria for this prospective, multi-country survey were set as: adults, starting clinically indicated allergen immunotherapy for respiratory allergic disorders or Hymenoptera venom allergy. An online survey was designed in order to enrol participants and assess adherence to immunotherapy. Eight countries (Czech Republic, Georgia, Germany, Greece, Italy, Poland, Portugal, Spain) were selected to reflect different parts of Europe and differences in allergens and routes of immunotherapy administration. Each country has an allocated National co-ordinator that has identified local Allergy departments willing to enrol participants in this survey. Each participant will be followed up for a total of three years. In order to assess adherence, a 4-monthly follow-up form detailing any missed doses and reasons will be completed online. In case of a participant discontinuing treatment, reasons for this will be recorded. DISCUSSION: The use of online survey software has enabled us to make this survey a reality and reach clinicians in different countries. Forty-five centres have enrolled a total of over 1,350 participants. It is hoped that this prospective real life survey will enable us to gain a better understanding of reasons that affect adherence to subcutaneous and sublingual immunotherapy and assist in developing ways to improve this.
ABSTRACT
The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
Subject(s)
Humans , Rhinitis, Allergic, Seasonal/prevention & control , Treatment Outcome , Anti-Allergic Agents/therapeutic use , Rhinitis, Allergic/prevention & control , Rhinitis, Allergic/drug therapyABSTRACT
STUDY OBJECTIVE: To examine the differences in the inflammatory cell and cytokine profile between patients with chronic bronchitis (CB) with and without airway obstruction compared to control subjects. DESIGN: We used bronchial biopsy samples from the patients and control subjects and analyzed them for the presence of CD3 T cells, CD68, major basic protein (MBP), elastase, and tryptase, as well as expression of messenger RNA (mRNA) coding for interleukin (IL)-4, IL-5, interferon (IFN)-gamma, IL-9, eotaxin, and IFN-gamma-inducible protein (IP)-10. The techniques of immunocytochemistry and in situ hybridization were used. Results were expressed as the number of immunoreactive and mRNA-positive cells per field. RESULTS: Increased number of elastase, CD68, and MBP-positive cells (n = 9, p < 0.01) was demonstrated in both groups of patients with CB compared to control subjects. In patients with CB and obstruction, the number of elastase, CD68, and the number of CD3-positive cells was significantly increased compared to patients with CB without obstruction (n = 9, p < 0.01). IFN-gamma mRNA expression was increased in both groups of patients with CB compared to control subjects (n = 9, p < 0.01). IL-9 mRNA was significantly increased only in patients with CB and obstruction (n = 9, p < 0.01). Co-localization studies demonstrated > 80% of all IL-9-positive cells to be CD3-positive T cells. IP-10 mRNA was significantly increased in both groups of patients with CB compared to control subjects (n = 9, p < 0.01). CONCLUSIONS: These results indicate a differential expression of inflammatory markers and cytokine mRNA in patients with obstructive CB. Increased presence of T lymphocytes and up-regulation of IL-9 and IP-10 mRNA expression in the bronchial biopsy samples may contribute to the airway obstruction in these patients.
Subject(s)
Bronchi/pathology , Bronchitis, Chronic/metabolism , Interleukin-9/biosynthesis , Pulmonary Disease, Chronic Obstructive/metabolism , T-Lymphocytes/metabolism , Up-Regulation , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Biopsy, Needle , Blood Proteins/metabolism , Bronchitis, Chronic/complications , Bronchitis, Chronic/pathology , CD3 Complex/analysis , Chemokine CCL11 , Chemokines, CC/metabolism , Cytokines/metabolism , Eosinophil Granule Proteins , Eosinophils/pathology , Female , Humans , Immunohistochemistry , In Situ Hybridization , Inflammation , Macrophages/pathology , Male , Middle Aged , Neutrophils/pathology , Pancreatic Elastase/metabolism , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/pathology , Ribonucleases/metabolismABSTRACT
BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate AD, especially in a subset of patients with head and neck type AD (HNAD). In the present study, the relationship between AD and sensitization to Malassezia antigens was investigated. METHODS: We assessed 173 patients with AD. The severity of eczema was determined with Eczema Area and Severity Index (EASI); the type of AD, namely, head and neck type, was reported as well. The total serum IgE and specific IgE to Malassezia were determined and correlated with clinical picture of AD, sex, age, and the EASI. RESULTS: Total IgE was elevated in 77.7% of patients. Specific IgE to Malassezia was positive (≥0.35 kU/L) in 49.1% of patients. Men were significantly more often sensitized to Malassezia antigen (58% of men vs 42% of women; P value, 0.04). Concurrently, 58% of patients with HNAD versus 42% non-HNAD patients had higher levels of specific IgE to Malassezia, this difference being nearly significant (P value, 0.06). Patients with atopy were also more frequently sensitized to Malassezia. No significant relationship between EASI and the level of total IgE or specific IgE to Malassezia was observed. CONCLUSIONS: In our population, IgE-mediated sensitization was found in up to 49% of all patients with AD, most common in men and in head and neck type.