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Asthma is one of the most common chronic diseases in children and adults. Cocaine is associated with asthma exacerbations. In Denmark, the prevalence of cocaine use has been increasing in recent years. This is a case report of a 47-year-old male with acute asthma exacerbation after cocaine use. Cocaine use is probably an underestimated reason for acute asthma exacerbations.

The anti-inflammatory effect of systemic corticosteroid (CS) on obstructive lung diseases and seasonal allergic rhinitis is well known. So are the physiological side-effects of CS. A major development in inhalation and biologic treatment as well as hyposensibilisation has taken place in recent years and evidence of personalized use of CS in acute exacerbations increases. We review the side effects of CS and the rationale for use of systemic CS in treatment of obstructive lung diseases as asthma and COPD, as well as seasonal allergic rhinitis.

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Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

INTRODUCTION: Clinical trials have shown oral corticosteroid (OCS) sparing effects of anti-IL5/anti-IL5-receptor treatments. The generalisability of these clinical trials may be limited, due to the rigid inclusion and exclusion criteria, and the short tapering duration. Real-world evidence is needed to bridge the gap between the clinical trials and the clinical practice. With this study we present real-life data on the OCS sparing effects of anti-IL5/anti-IL5-receptor treatments after 12 and 24 months of treatment.METHODS: Severe, eosinophilic asthma patients treated with mepolizumab, reslizumab or benralizumab for 24 months were included in this observational study. Data on OCS-dose, FEV1, ACT/ACQ score and blood eosinophils were obtained from the patients records before anti-IL5/anti-IL5-receptor treatment, and after 12 and 24 months of treatment.RESULTS: At baseline 75% of patients were on daily OCS. This number was reduced to 50% after one year of treatment, p < 0.001, and 28% after two years of treatment, p < 0.001. Within the group on daily OCS the median daily dose was reduced from 10 mg of Prednisolone at baseline (IQR 5-20) to 3.75 mg Prednisolone (IQR 0-10) after 12 months, and 0 mg Prednisolone (IQR 0-7.5) after 24 months, p < 0.001.CONCLUSIONS: The findings in this study add to the generalisability of the clinical studies, showing significant OCS sparing effects of anti-IL5/anti-IL5-receptor treatment in a real-life setting. Furthermore, these findings add to the understanding of the long-term effects of anti-IL5/anti-IL5-receptor treatment, showing an even further and persistent OCS reduction after two years of treatment.

Background: Impulse Oscillometry (IOS) is a novel tool that may be to comparable to spirometry. In asthmatics, differences in the resistance at low frequencies and high frequencies can indicate small airway involvement. The aim of this study was to assess the reproducibility of IOS measurements in healthy subjects and well-controlled asthmatics. Methods: In 24 healthy controls and 13 patients with well-controlled asthma, IOS and spirometry was performed at baseline and within 4 weeks. The reproducibility explored in Bland-Altman plots, expressed as bias with lower and higher limits of agreements (B; LLOA, ULOA). The relationship of IOS and spirometry was assessed by correlation. Results: In healthy subjects, the resistance at 5Hz and at 20Hz increased after 4 weeks (p=0.01) but remained in the normal range. For healthy controls, the reproducibility of FEV1 (-0.8%; -15.3%, 13.3%) and FVC (1.1%; -16.3%, 18.4%) and FEV1/FVC with (-1.6%; -11.8%, 8.6%) was better than that of X5 (-5.2%; -148.4%, 138%) and R5 (3,8%; -24%, 31,5%). For patients with well controlled asthma, the reproducibility of FEV1 at (-1,1% ; -12,9%; 10,7%), FVC at (-3.2%; -15.3%; 9.1%) and FEV1/FVC at (0.4%; -7.1%; 7.8%) was comparable with that of X5 at (1.3%; -23.5%; 26%) and R5 at -4.9%; -22.2%; 12.4%). There was no sign of a trend in any plot. X5 and R5 of controls (Spearmans R>0.59, p 0.79, p Conclusion: IOS measurements within a 4-week interval were reproducible in healthy controls and well-controlled asthmatics and correlated with spirometric data.

Background: Measuring FeNO is an convenient, non-invasive method to assess airway inflammation. In asthmatics, elevated FeNO can predict treatment response to inhaled corticosteroids (ICS), can be used to monitor treatment adherence and guide step-up or step-down of ICS treatment. The aim of this study was to investigate, whether spirometry, IOS or walking affected FeNO measurement. Methods: FeNO was measured twice at baseline in 25 healthy controls and 21 patients with well-controlled asthma, and was repeated after performing IOS, spirometry and after walking 400 m. Reproducibility was assessed with a Bland-Altman test where the bias(B), upper limits of agreement (ULOA) and lower limits (LLOA) of agreement are calculated as % mean of collected data. These calculations will be written to as [B;ULOA;LLOA]. Results: At baseline mean FeNO was 16.0 (95% CI 12.3-19.8) in the healthy subjects and 20.2 (14.9-25.6) ppb in the asthmatics. There was no significant change in FeNO at baseline [0.258; 74.2;-74.8], after IOS [-9.21; 56.4;-74.9], spirometry [-3.65; 75.8;-83.1] or after walking [-4.18; 92.5;-84.1]. The limits of agreement in a Bland-Altman plot were 12 ppb, less than the clinically significant difference. There was no trend to bias in the Bland-Altman plots. Conclusion: Measurement of FeNO in healthy subjects and well-controlled asthmatics is not affected by performing IOS, spirometry, or exercise.

Background: MicroRNAs (miRNAs) represent important post-transcriptional regulators with a dynamic expression profile during health and disease. Objectives: We explored the miRNA profile of human mast cells (MCs) during sen­sitization with IgE, during activation through IgE, and relat ed it to prostaglandin D2 synthesis and histamine release. Method: We investigated the expression pattern of 762 miRNAs during the IgE-mediated sensitization and activation of MCs cultured from CD133+ stem cells that were isolated from allergic asthmatic patients and nonatopic controls. Results: IgE-mediated sensitization increased the expression of miRNA-210 eight-fold. This increase was sustained during IgE-mediated MC activation. Furthermore, we confirmed the increase of the miRNA-132/212 cluster after MC activation. Predicted target genes of miRNA-210/132/212 were enriched in several pathways known to be involved in MC activation. Histamine release was significantly higher in MCs from allergic patients when compared to controls, and a number of miRNAs correlated with histamine release and prostaglandin D2 synthesis during MC activation. Conclusion: The miRNAs and analysis presented here can help to elucidate the role of miRNAs in mediator release during MC activation. We speculate that miRNA-210 could be important in MC sensitization that leads to allergic symptoms.

Background: Allergic rhinoconjunctivitis is a global health problem. Different allergen immunotherapy regimes are marketed but have low adherence because they are expensive, complex, and time-consuming. New allergen immunotherapy forms are needed. Objective: In a 3-year follow-up double-blind randomized placebo-controlled trial, we aimed to investigate the effect of intralymphatic allergen immunotherapy (ILIT). Methods: Patients with grass pollen rhinoconjunctivitis were treated with 3 ILIT injections and an ILIT booster 1 year later, 3 ILIT injections and a placebo booster, or 3 placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score (cSMS). A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen. Results: A total of 36 patients were included. Log 10-transformed cSMS was reduced by 0.30 (95% CI, 0.11-0.49; P =.002), equaling 48.5% (95% CI, 24.5%-62%), in the entire 3-year follow-up period, significant only in the first follow-up season but not in the second and third seasons. The regression model showed a 37% (P 4 to grass showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test results was found. Conclusions: ILIT gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.

Background Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established. Methods Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing allergen concentrations. At each step basophil activation (CD193 + CD63+ ) was monitored with and without (background activation) allergen challenge at optimal concentration. The sequential desensitization protocol was compared to two single-dose desensitization protocols with threshold and subthreshold allergen concentrations. Incubation intervals and allergen concentrations were varied in order to optimise the protocol. Results Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocol did not reduce basophil activation with optimal allergen challenge from a mean 57.1 (95% CI: 32.7 - 81.5) to 50.4% (95% CI: 16.3 - 84.4; n = 5; P = 0.43) and 45.0% (95% CI: 23.1 - 66.9; P = 0.14) respectively, while the sequential desensitization protocol reduced activation to a mean 37.2% (95% CI: 16.3 - 58.1; P = 0.018). Reducing incubation time from 10 to 5 minutes increased mean background activation from 22.4 (95% CI: 11.7 - 33.1) to 30.0% (95% CI: 19.7 - 40.3; n = 5; P = 0.026). Increasing time intervals from 10 to 20 minutes reduced background activation from 30.9 (95% CI: 22.8 - 39.0) to 21.9% (95% CI: 16.0 - 27.7; n = 5; P = 0.020). Increasing allergen concentration intervals from 2-fold to 5- and 10-fold did not have significant effect on basophil activation. Conclusions Sequential desensitization ex vivo effectively attenuates the basophil response to allergen. Increasing the time spent at each step improves desensitization. This protocol could be valuable for investigation the mechanism of desensitization. © 2016 International Clinical Cytometry Society.

Summary Background The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and airway remodelling. Methods We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 15 centres across the UK, Denmark, and Canada. We enrolled participants of either sex aged 18–75 years with inadequately controlled moderate-to-severe asthma for 12 months or more, requiring treatment with inhaled corticosteroids at a stable dose. We randomly assigned participants (1:1) to receive tralokinumab (300 mg) or placebo by an interactive web-based system or voice response system. Participants and study personnel were masked to treatment allocation. Both tralokinumab and placebo were administered subcutaneously every 2 weeks. The primary outcome measure was change from baseline to week 12 in bronchial biopsy eosinophil count. Secondary outcome measures included change in blood and sputum eosinophil counts. Exploratory outcomes included fractional exhaled nitric oxide (FENO) and blood IgE concentrations. Safety analyses were carried out in all participants who received study drug. This trial is registered with ClinicalTrials.gov, number NCT02449473, and with the European Clinical Trials Database, EudraCT 2015-000857-19. Findings Between Sept 25, 2015, and June 21, 2017, 224 participants were enrolled and screened. Of these participants, 79 were randomly assigned to receive tralokinumab (n=39) or placebo (n=40). Tralokinumab did not significantly affect bronchial eosinophil count compared with placebo at week 12 (treatment effect ratio 1·43, 95% CI 0·63–3·27; p=0·39). Compared with placebo, tralokinumab did not significantly affect blood eosinophil count (treatment effect ratio 1·21, 95% CI 1·00–1·48; p=0·055) or sputum eosinophil count (0·57, 0·06–6·00; p=0·63), but FENO concentration (0·78, 0·63–0·96; p=0·023) and total blood IgE concentration (0·86, 0·77–0·97; p=0·014) were significantly reduced. 33 (85%) of 39 patients receiving tralokinumab and 32 (80%) of 40 receiving placebo reported at least one adverse event during the treatment period. No deaths in either treatment group were observed. Treatment-related adverse events occurred more frequently in the tralokinumab group than in the placebo group (11 [28%] of 39 vs seven [18%] of 40). Interpretation Tralokinumab did not significantly affect eosinophilic inflammation in bronchial submucosa, blood, or sputum compared with placebo, but did reduce FENO and IgE concentrations. These results suggest interleukin 13 is not crucial for eosinophilic airway inflammation control in moderate-to-severe asthma. Funding AstraZeneca.

Introduction: Mepolizumab is a novel treatment for severe eosinophilic asthma. The effects of mepolizumab have been examined in tightly controlled studies with rigid inclusion and exclusion criteria resulting in homogenous baseline characteristics. However, baseline characteristics of the eosinophilic asthma patients, and thus the effects of mepolizumab, may differ in real-world clinical practice. Methods: Baseline characteristics of patients treated with mepolizumab (at a dose of 100 mg administered subcutaneously every 4th week) were drawn from a prospective database and from patient records. Results: From June 2016 to January 2017 36 patients initiated mepolizumab treatment. All patients were treated with high-dose inhaled corticosteroids and a second controller. 50% of patients were female sex. Mean age at baseline was 54 years CI (50-57). Baseline mean FEV1 of expected was 65% CI(58-72) and baseline mean blood eosinophilic count was 514 /µl CI(385- 643). 89% of patients were treated with maintenance oral corticosteroids (OCS). A mean daily OCS dose was 13 mg Prednisolone CI(11-15). 25% of patients were additionally treated with immunosuppressive agents. Conclusion: Compared with studies like MENSA, DREAM and SIRIUS, patients in our cohort have higher blood eosinophilic counts and they are more heavily treated with immunosuppressive agents. Thereto, compared with DREAM and MENSA the percent of patients taking OCS is higher. The age and the mean FEV1 of expected, however, is comparable. Significant baseline characteristics in this real-world database differed from previous clinical trials. We need further studies to evaluate the effects of mepolizumab in real-world clinical settings.

Introduction: Systematic assessment of patients with severe asthma is pivotal to decide which patients are eligible to new biological therapies. However, the level of diagnostic work -up in patients with severe asthma is only poorly investigated.Aims & objectives: To describe the diagnostic work -up in a complete population of patients with severe asthma including: objective confirmation of the asthma diagnosis, and identification of potential treatment barriers, such as poor adherence and poor inhaler technique.Methods: A retrospective cross-sectional multicenter study was performed in 2013. We evaluated patient record forms of all patients (aged 18-65 years) consecutively referred with asthma to one of five respiratory outpatient clinics over two years. Patients were included in the study, if they fulfilled ERS/ATS guidelines for having severe asthma.Results: Among 1563 patients with asthma, 98 (6.3%) patients fulfilled the criteria for having severe asthma. The diagnosis of asthma was confirmed objectively in 53/98 patients (54.1%). In total, 83.7% underwent at least one diagnostic test for asthma: reversibility test: 63.3%, PEF: 52% and bronchial challenge test: 21.4%. Among patients eligible for a bronchial challenge test (FEV1 > 70%; negative PEF measurement/reversibility test), only 23.1% had such a test performed. Inhalation technique and adherence were assessed in 19.4 and 30.6% of patients, respectively.Conclusion: Among patients managed for severe asthma in a specialist setting, only half had the asthma diagnosis confirmed objectively, and adherence and inhaler technique were infrequently assessed. (C) 2017 Elsevier Ltd. All rights reserved.

Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established.Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing allergen concentrations. At each step basophil activation (CD193Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocol did not reduce basophil activation with optimal allergen challenge from a mean 57.1 (95% CI: 32.7 - 81.5) to 50.4% (95% CI: 16.3 - 84.4; n = 5; P = 0.43) and 45.0% (95% CI: 23.1 - 66.9; P = 0.14) respectively, while the sequential desensitization protocol reduced activation to a mean 37.2% (95% CI: 16.3 - 58.1; P = 0.018). Reducing incubation time from 10 to 5 minutes increased mean background activation from 22.4 (95% CI: 11.7 - 33.1) to 30.0% (95% CI: 19.7 - 40.3; n = 5; P = 0.026). Increasing time intervals from 10 to 20 minutes reduced background activation from 30.9 (95% CI: 22.8 - 39.0) to 21.9% (95% CI: 16.0 - 27.7; n = 5; P = 0.020). Increasing allergen concentration intervals from 2-fold to 5- and 10-fold did not have significant effect on basophil activation.Sequential desensitization ex vivo effectively attenuates the basophil response to allergen. Increasing the time spent at each step improves desensitization. This protocol could be valuable for investigation the mechanism of desensitization. © 2016 International Clinical Cytometry Society.

Organic acid anhydrides (OAA) are widely used in the chemical industry. They are irritants and can cause sensitization and asthma. We describe the first documented case of occupational asthma caused by the OAA maleic anhydride (MA) in the production of insecticides. A 60-year-old man developed work-related respiratory symptoms after eight years of intermittent exposure to MA. Peak expiratory flow measurements showed greater variance on work days than on days off. Both a basophilic activation test and determination of the MA-specific IgE level in serum showed sensitization to MA.

BACKGROUND: Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.METHODS: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with 2-2.5-fold increasing allergen doses in 10 steps starting at 1/1,000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 minutes of allergen stimulation (n=7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n=10).RESULTS: Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, p0.79, pCONCLUSION: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. This article is protected by copyright. All rights reserved.

Udgivelsesdato: 2008-Aug The aim of the current study was to describe the incidence of respiratory symptoms and allergic sensitisation and the sequence of events leading to respiratory symptoms among Danish baker apprentices (BA). A total of 114 BA were surveyed over a 20-month period. Questionnaires were completed along with spirometric analysis and skin-prick tests to common and work-related allergens. Bronchial hyperresponsiveness (BHR) was determined at baseline and at the end of the follow-up period. The incidences of work-related rhinitis and asthma-like symptoms were 22.1 and 10.0 cases.100 person-yrs(-1), respectively. At 20 months the cumulative incidence proportion was 40.2 and 20.5% for rhinitis and asthma-like symptoms, respectively. The cumulative incidence of occupational sensitisation was 6.1%. An increased risk of asthma-like symptoms was found in both atopic subjects and in females. In the BA with new onset respiratory symptoms, an increase in BHR from baseline was observed. Forced expiratory volume in one second and forced vital capacity did not change during the follow-up period. No relationship was observed between new sensitisation and new symptoms. In conclusion rhinitis- and asthma-like symptoms were found to develop commonly in Danish baker apprentices. The mechanism by which symptoms arose was perceived to reflect the development of an inflammation rather than the production of a specific immunoglobulin E pathway, as sensitisation to occupational allergens was rarely observed. Hence, respiratory symptoms and allergy may develop through separate pathways.

FcεRI, the high–affinity receptor for IgE, and eosinophils are thought to be key components of the allergic reaction underlying asthma and rhinitis. We provide evidence at the protein level that FcεRI is expressed in human blood eosinophils, and that the synthesis of FcεRI in purified human blood eosinophils is regulated by fibronectin in combination with IgE, IL–4, both involved in allergic reactions, and by RANTES, a strong chemotactic agent for eosinophils. This provides further evidence for a regulatory effect of IgE on human eosinophils in allergic disease.

Introduction Many conditions may mimic severe asthma. Therefore, patients with asthma who receive high dose asthma therapy are recommended to undergo systematic evaluation in order to objectively confirm the diagnosis of asthma. Aims and objectives To evaluate to which extent patients treated by respiratory specialists for severe asthma had the diagnosis of asthma verified by the demonstration of variable airflow obstruction. Methods A retrospective cross-sectional study was performed in 2013. Patient record forms of all patients (18–65 years) newly referred to one of five respiratory outpatient clinics in Denmark in the period of 2009–2010 with a diagnose of asthma (ICD-10: DJ45-DJ459) were screened after a two-year observation period for having severe asthma. Patients were included in the study, if they had a doctors diagnosis of asthma and received inhaled corticosteroids equivalent to ≥1600 μg budesonide and a second controller (long acting beta-2-agonist, theophylline or leukotriene-antagonist) for a minimum of twelve months or were treated with oral prednisolone (minimum six months). Diagnostic tests for asthma were registered: Day-to-day PEF monitoring, reversibility test (short-acting beta-2-agonist or prednisolone) and bronchial challenge test (methacholine, mannitol, exercise test, eucapnic voluntary hyperpnoea test). Results A total of 1417 newly referred subjects were screened, of whom 98 patients fulfilled the above criteria of having severe asthma. Overall, 84% were assessed with at least one diagnostic test: Reversibility test 63%, PEF monitoring 57% and bronchial challenge test 21%. In total, 50% of the study population had at least one positive diagnostic test; 37% had a positive reversibility test, 17% had significant peak flow variation and 12% had a positive bronchial challenge test. Among those having negative reversibility test or negative peak flow measurements with FEV1≥70%, only 30% had a bronchial challenge test performed. Conclusion Among patients managed for severe asthma in five specialist hospital clinics in Denmark, only half had the asthma diagnosis confirmed objectively. This indicates a substantial room for improvement in order to ensure that patients receiving high dose asthma therapy truly have asthma.

Udgivelsesdato: Okt 5 Objective To describe the prevalence of atopy and respiratory symptoms among baker apprentices at the start of the education and factors associated with non-participation in the study. Methods A total of 346 students, 22.1(0.6) years of age, mean (SD), from the food production programme of technical colleges in Denmark were invited to participate in a 3 year study. Of the students, 187 agreed to participate and filled in a physician-administered questionnaire. The presence of atopy was determined by skin prick test (SPT) and serum allergen specific IgE (SpIgE). Bronchial hyper responsiveness to methacholine (PD20 ≤ 1,440 μg) was determined. Results Prevalence of atopy was 32%. The prevalence of symptoms from the lungs and nose was 19.8 and 25.5%, respectively. Significantly, more SPT reactions were seen in males compared to females (39 vs. 22%, P < 0.05). Sensitization towards flour was significantly more frequent if determined as SpIgE (7.3%) compared to SPT (0.5%). We found a positive association between atopy and lung symptoms OR 6.1 (2.8-13.2 SD) and nasal symptoms OR 3.7 (1.8-7.5 SD). The major reason for non-participation was fear of blood sampling (25.5%). Conclusion The prevalence of atopy in bakers' apprentices was of the same magnitude in the general Danish population. Significantly, more male bakers' apprentices had atopy. This finding has major impact on the diagnostic procedures of occupational allergy in bakery workers emphasizing the need for standardization of the clinical tests. The main reasons for non-participation were, fear of blood-sampling (57%) and the 3 years commitment to the follow-up study (39%).

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Background: A number of occupational respiratory allergens are food related, and little is known about the responses these allergens elicit in sensitized persons that ingest them. Methods: Nine respiratory flour-allergic volunteers were exposed in a double-blind placebo-controlled food challenge with flour. Responses were monitored by spirometry, acoustic rhinometry, determination of urinary methyl histamine and tryptase and flow cytometric evaluation of basophil, dendritic and T cell numbers and markers. Results: Significant increases in serum tryptase (compared with placebo post-exposure levels) and methyl histamine and a coordinated decrease in blood basophils and nasal volume after ingestion of allergen compared with placebo suggest an allergic response to ingested allergen. There was no change in forced expiratory volume in 1 s. The number of blood plasmacytoid dendritic cells (DC), but not of myeloid DC, decreased after exposure (p = 0.001). DC HLA DR was reduced after both exposures (p < 0.001). Expression of CXCR4 on DC was reduced after allergen (p = 0.033) but not after placebo exposure. CD4+ T cell expression of CD25 was elevated after placebo (p = 0.021) but reduced after allergen provocation. The reduction in CD25 expression after allergen compared with placebo was significant (p = 0.024). CD152 was downregulated on these cells after allergen (p = 0.039) but less so after placebo exposure. Conclusion: Persons with respiratory allergy respond after ingestion of the relevant allergen. Response to this allergen challenge may selectively recruit plasmacytoid DC through CXCR4 and T cells expressing CD25 and CD152, which may be a regulatory phenotype.

A single-blind imipramine dose titration study was conducted in 15 diabetic patients with neuropathy symptoms. The effect of treatment was evaluated by use of visual analog scales. Imipramine doses were individually adjusted until doses yielded plasma concentrations of imipramine plus desipramine that were well above 400 nmol/L or until all neuropathy symptoms had vanished. In all except one patient, there was marked relief of symptoms. In the responding patients (n = 14), much of the effect occurred at plasma levels of imipramine plus desipramine below 100 nmol/L, but a considerable interindividual variation was observed. Concentrations above 400 to 500 nmol/L were required to ensure maximal effect in all patients, and we did not find any indication of a decreased effect at high drug levels. The dose-dependent kinetics of imipramine was confirmed, and dose increments should therefore be carried out in small steps and preferably with monitoring of drug levels. Clinical Pharmacology and Therapeutics (1990) 47, 509–515; doi:10.1038/clpt.1990.65

Asthma is one of the most common chronic diseases in children and adults. Cocaine is associated with asthmaexacerbations. In Denmark, the prevalence of cocaine use has been increasing in recent years. This is a casereport of a 47-year-old male with acute asthma exacerbation after cocaine use. Cocaine use is probably anunderestimated reason for acute asthma exacerbations. Asthma is one of the most common chronic diseases in children and adults. Cocaine is associated with asthma exacerbations. In Denmark, the prevalence of cocaine use has been increasing in recent years. This is a case report of a 47-year-old male with acute asthma exacerbation after cocaine use. Cocaine use is probably an underestimated reason for acute asthma exacerbations.